Methods and bioavailable highly permeable compounds for diseases treatment

Abstract

Methods and compositions are provided for treating diseases by administering bioavailable, highly permeable API-based non-covalent complexes, solid dispersions or conjugates. The compounds, compositions and methods are particularly useful for treating diseases.

Description

METHODS AND BIOA VAILABLE HIGHLY PERMEABLE COMPOUNDS FOR DISEASES TREATMENTFIELD OF THE INVENTION

[0001] The invention relates generally to methods and compounds for treating diseases, particularly methods and compounds based on APIs for treating diseases.BACKGROUND OF THE INVENTION

[0002] Infectious diseases pose a significant threat to public health worldwide, causing substantial damage both in terms of human suffering and economic burden. These diseases, ranging from common colds to more severe conditions like HIV / AIDS and Ebola, have the potential to wreak havoc on communities and healthcare systems. The damage inflicted by infectious diseases extends beyond the direct effects on individual health, impacting productivity, socioeconomic stability, and healthcare infrastructure.

[0003] One of the primary ways infectious diseases cause harm is through their ability to spread rapidly within populations, leading to outbreaks and pandemics. Such events can overwhelm healthcare systems, strain resources, and result in significant morbidity and mortality. Additionally, infectious diseases can have long-term consequences, including chronic health conditions and disabilities, further exacerbating the burden on individuals and society as a whole.

[0004] Moreover, the economic toll of infectious diseases is profound, encompassing direct healthcare costs, lost productivity, and investments in prevention and control measures. In regions with limited resources and inadequate healthcare infrastructure, the impact of infectious diseases can be particularly devastating, perpetuating cycles of poverty and inequality. Addressing the damage caused by infectious diseases requires a comprehensive approach that encompasses prevention, surveillance, early detection, and access to effective treatments and vaccines.

[0005] Metabolic diseases, such as diabetes, obesity, and metabolic syndrome, inflict significant damage on both individual health and society at large. These conditions disrupt the body's normal metabolic processes, leading to complications that affect various organs and systems. For instance, diabetes can result in cardiovascular diseases, kidney failure, blindness, and nerve damage, significantly reducing quality of life and life expectancy forthose affected.

[0006] Furthermore, the economic burden of metabolic diseases is staggering, encompassing direct healthcare costs, loss of productivity, and expenses related to managing complications. The prevalence of these conditions is on the rise globally, driven by factors such as sedentary lifestyles, unhealthy diets, and aging populations. Addressing the damage caused by metabolic diseases requires a multifaceted approach, including public health interventions to promote healthier lifestyles, improved access to healthcare services, andresearch into new treatments and preventive strategies.

[0007] Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's, inflict profound damage on individuals and society, both in terms of human suffering and economic burden. These diseases gradually impair cognitive function, motor skills, and overall neurological health, leading to progressive disability and dependency. Beyond the personal toll on affected individuals and their families, neurodegenerative diseases strain healthcare systems, require extensive caregiving resources, and diminish productivity. Moreover, as populations age worldwide, the prevalence of these conditions is expected to increase, highlighting the urgent need for innovative treatments, better support services, and enhanced public awareness and education initiatives.

[0008] Cardiovascular diseases exact a heavy toll on both individuals and society, manifesting in a range of conditions such as coronary artery disease, stroke, and hypertension. These diseases not only contribute to significant morbidity and mortality but also impose substantial economic burdens through healthcare costs and lost productivity. The damage caused by cardiovascular diseases extends beyond the physical realm, impacting emotional well-being, social dynamics, and overall quality of life for affected individuals and their families. Effective prevention strategies, early detection, and comprehensive management approaches are crucial in mitigating the devastating effects of cardiovascular diseases and reducing their societal impact.

[0009] Diseases inflict damage not only on individuals but also on society as a whole, posing significant challenges to healthcare systems, economies, and overall well-being. Whether they are infectious, metabolic, neurodegenerative, or cardiovascular in nature, diseases disrupt normal physiological functions, impairing physical health, mental health, or both. Beyond the immediate health consequences, they often lead to financial strain, decreased productivity, and social disruption. Highly effective medications play a pivotal role in the treatment of diseases by providing targeted and potent therapeutic interventions that can significantly improve patient outcomes and quality of life. These medications are often the result of rigorous scientific research and development processes, leveraging advancements in pharmacology, biotechnology, and medical innovation. By targeting specific disease mechanisms, reducing symptoms, and preventing complications, highly effective drugs not only alleviate suffering but also contribute to the overall reduction of disease burden on individuals and society. Furthermore, they enable healthcare providers to offer personalized treatment approaches, tailored to individual patient needs, leading to more precise and efficient healthcare delivery. Overall, the availability and utilization of high-efficacy medications represent a cornerstone in modem medicine's ability to combat various diseases and enhance patient care.SUMMARY OF THE INVENTIONTechnical Problem

[0010] The transition from in vitro studies to clinical trials often reveals a significant efficacy gap in drug delivery systems. While in vitro studies provide valuable insights into the mechanisms and potential efficacy of a drug, translating these results into clinical settings presents considerable challenges. Factors such as physiological barriers, systemic clearance, and biodistribution dynamics can drastically alter the performance of a drug in vivo compared to the controlled conditions of a laboratory environment.

[0011] Addressing the efficacy gap between in vitro studies and clinical trials necessitates the development of sophisticated drug delivery systems. These systems aim to bridge the disparity by ensuring that the drug reaches the targeted sites in the body at levels comparable to those observed in vitro. Various approaches, including nanoparticles, liposomes, and microparticles, have been explored to enhance drug delivery efficiency and efficacy.

[0012] Furthermore, the design of drug delivery systems must consider factors such as stability, biocompatibility, and controlled release kinetics to optimize therapeutic outcomes. By employing innovative technologies and leveraging our understanding of biological systems, researchers strive to narrow the efficacy gap and facilitate the successful translation of promising drug candidates from the laboratory bench to the patient bedside.

[0013] Therefore, there is an efficacy gap between in vitro studies and clinical trials requires a drug delivery system with which to achieve the in vitro levels.Solution to Problem

[0014] The present invention proposes to destroy the crystallinity of the phase, the phase itself and the phase boundaries of API and to form chemical bonds (including hydrogen bonding, van der Waals bonding, donor-acceptor bonding, 71-71 bonding, Ion-dipole bonding and ion-induced dipole bonding, ionic bonding, hydrophobic bonding and others) between API molecules and the carrier and thereby change the properties of API by forming new compounds from it. In this invention, it is found that during solvation, the carrier molecules (as part of non-covalent or inclusion or supramolecular complex with API) can in some cases modify the biological / cell membrane by adhesion or by insertion into the lipid membrane or using other transport mechanism and promote the transport (permeability) of API or change in hydrophilicity and hydrophobicity, due to which changes in the paracellular transport. That changes in permeability can occur due to:1) as a consequence of blocking / reducing the activity of CYP3A4 and / or P-gly coproteins, blocking / reducing the activity of other transmembrane carrier proteins, transporters, enzymes, etc., by membrane interacting with carrier substance molecules;2) due to blocking / reduction of CYP3A4 and / or P-glycoprotein activity, blocking / reduction of activity of other transmembrane protein transporters, transporters, enzymes, etc., by carrier substance molecules interacting with the membrane due to adhesion of carrier substance molecules to the cellular layer. Such adhesion can lead to interaction with transporters domains located on the outer part of the cell membrane and block the action of the transmembrane transporter protein;3) due to a change in the structure of the cell membrane after the incorporation of carrier substance molecules into this membrane, rather than due to adhesion;4) due to the direct effect of carrier substance molecules on the intestinal epithelium cell membrane: it may consist in alteration of lipid bilayer properties, density of intercellular contacts or inhibition of trans-membrane proteins of multi drug resistance;5) due to changes in hydrophilicity and hydrophobicity due to which changes in the paracellular transport of the non-covalent complex may occur6) other changes in the structure and properties of the membrane, through other mechanisms that contribute to an increase in its permeability;7) due to the use of various transmembrane transport mechanisms.

[0015] A number of methods to destroy the crystallinity of the phase are generally referred to as "Molecular / Solid Dispersion Methods" and subdivided into a number of submethods, all of which involve molecular mixing and disordered phase processes of the components at the molecular level and create a homogeneous / highly dispersed phase with many chemical interactions between the API and the carrier.

[0016] Molecular / Solid dispersions of the present inventions includes inclusion complexes and supramolecular complexes (that can present in solid phase) that can present in form of solid solution in which molecules of one compound (API, carrier) occupy places in the crystal lattice of another compound (API, carrier) or in which one compound (carrier) spatially encloses another (API). Thus in solid dispersions of the invention not only mixing at the molecular level but also complexation can take place.

[0017] Molecular / Solid dispersion methods such as the solvent evaporation, cryogenic methods, melting methods and hot-stage extrusion methods are used to create compounds with the described properties. In contrast to melting methods in the method of milling with high-energy input / stress, the required processes take place locally in places of excess energy created by mechanical forces (e.g. at the moment of collision of balls there are shear, compression and impact). The processes of milling withhigh energyinput / stress are cumulative processes: a) destruction of the structure of the initial phases; b) solid-state formation of chemical bonds between invermectin and the carrier; c) solid-state phase transformations including solid-phase fusion with formation of fusion phases (including nonequilibrium); d) accumulation of structural defects; e) dispersion, disarrangement and homogenization; and the result is a gradual synthesis of the necessary compounds.

[0018] It should be understood that milling in high-energy conditions is not done for grinding, but for energy impact, which provides the formation of new melting phases, and the size of the particles can increase, not decrease. During high-energy milling the powder particles are repeatedly flattened, cold welded, fractured and rewelded. Whenever two steel balls collide, some powder is trapped between them. Typically, around 1000 particles with an aggregate weight of about 0.2 mg are trapped during each collision. The force of the impact plastically deforms the powder particles, leading to work hardening and fracture. The new surfaces thus created enable the particles to weld together; this leads to an increase in particle size. Since in the early stages of milling, the particles are soft (if using either ductile -ductile or ductile -brittle material combination), their tendency to weld together and form large particles is high. A broad range of particle sizes develops, with some as large as three times larger than the starting particles.

[0019] The present invention discloses that the molecular / solid dispersion treatment of API acquires new molecular properties that are not identical to the pharmaceutical composition. When combined into a pharmaceutical composition, each of the substances retains its molecular properties in the same form as they were before being combined into the pharmaceutical composition and does not change its molecular composition. At the same time, obtaining a solid dispersion produces a qualitatively different molecular substance that permanently changes its basic molecular properties due to the formation of chemical bonds between the molecules of the carrier and API. Because API and the carrier together form a new single structure, the properties of the API solid dispersion method are different from and not equivalent to a mixture of API with any other substance. The use of solid dispersion method involves difficulties in selecting the carrier, solvent and processing conditions, it is necessary to achieve processing parameters in which the substances do not disintegrate or degrade, it is necessary to control the toxicity of the resulting compounds, since in some cases using some carriers, the toxicity of the resulting compounds may increase. In general, using the solid dispersion method is a complex process with many factors.

[0020] When treated by the solid dispersion method, API acquires new molecular properties that are not identical to the pharmaceutical composition, namely modified pharmacokinetic parameters, different system bioavailability, in vivo permeability, reduced by 3-5 times the toxicity, the treatment time of the infection is reduced to 1-2 days at a single dose, the new compounds have different spectra from the simple mixture. Compounds obtained by solid dispersion methods can have any size (like alloys), can be dissolved in solvents, can be made into various compositions and formulations, can be combined with other preparations, i.e. have all the properties of a separate substance per se.

[0021] Provided are methods and compounds for the disease treatment. Provided are methods (co-treating methods / solid dispersion techniques) for modifying the properties of a compound (API) by creating a molecular / solid dispersion or inclusion complex (compound of Formula II, using as precursors API, host substance and, if necessary, other compounds) with properties of increased bioavailability and permeability and using compounds obtained by this methods (or aqueous solutions or suspensions thereof) to manufacture a pharmaceutical dosage form to treat cancer in a human in need thereof (by administering a therapeutically effective amount) or to treat a cancer wherein the host substance is selected from: a) polymers and oligomers, predominantly organic polymers and oligomers, even more predominantly polysaccharides and oligosaccharides, hemicelluloses, storage polysaccharides, sulfated polysaccharides and oligosaccharides, pectins, gums, mucilages, or mixtures thereof; b) substances that may contain in significant amounts polysaccharides and oligosaccharides, hemicelluloses, storage polysaccharides, sulfated polysaccharides and oligosaccharides, pectins, gums, mucilages, which may be (but are not limited to) plants or algae or animal or fungi, parts of plants or algae or animal or fungi, processed plants or algae or animal or fungi, processed parts of plants or algae or animal or fungi containing in significant amounts the substances specified in paragraph a), or mixtures thereof; c) syntetic polymers, predominantly water-soluble polymers or mixtures thereof; d) polyols or mixtures thereof; e) saccharides or mixtures thereof; f) surfactants or mixtures thereof; g) acids or mixtures thereof; h) oxides and salts based on these oxides or mixtures thereof; i) copolymers of the polymers listed in paragraph a) and c); j) methoxylated, ethoxylated, esterificated, carboxylated, alkoxylated, acetylated, hydroxylated, hydrated, decarboxylated, amide, oxidized, sulfated, aminoacid derivatives, fermented, thermally modified, chemically modified, acid modified derivatives of the substances specified in a)-i), and their esters, salts, and any other chemical derivatives, and mixtures thereof; k) any combination of substances specified in paragraph a)-j); wherein co-treating method is selected from: a) grinding / milling with high energy stress method; b) grinding / milling with high energy stress and solvent method; c) media milling method; d) kneading method; e) hot-melt method / melting method / fusion method; f) hot-melt extrusion / hot-stage extrusion method; g) meltrex method; h) melt agglomeration method; i) high-pressure homogenization method; j) solvent evaporation method; k) spin-coated films method; 1) spray-drying method; m) supercritical fluid (SCF) process method; n) cryogenic techniques method; o) lyophilization / freeze-drying technique method; p) spray freezing onto cryogenic fluids method; q) spray freezing into cryogenic liquids (SFL) method; r) spray freezing into vapor over liquid (SFV / L) method; s) ultra-rapid freezing method; t) precipitation / co-precipitation method; u) microwave irradiation method; v) energy input method; w) heat / shear energy input method; x) combined method.Advantageous Effects of Invention

[0022] When treated by the solid dispersion method, API acquires new molecular properties that are not identical to the pharmaceutical composition, namely modified pharmacokinetic parameters, increased bioavailability, permeability, reduced by 3-5 times the toxicity.BRIEF DESCRIPTION OF DRAWINGS

[0023] Fig. 1 Polymer repeat units.Fig.2 Polymer repeat units.Fig.3 Polymer repeat units.Fig.4 Polymer repeat units.Fig.5 Polymer repeat units.Fig. 6 Monosaccharides.Fig. 7 Monosaccharides.Fig. 8 Radicals.Fig. 9 NCC examples.Fig. 10 NCC examples.Fig. 11 NCC examples.Fig. 12-72 APIs used for NCC, SD, conjugates.DETAILED DESCRIPTION OF THE INVENTION

[0024] The following description is presented to enable any person skilled in the art to make and use the invention, and is provided in the context of a particular application and its requirements. Various modifications to the disclosed embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be applied to other embodiments and applications without departing from the spirit and scope of the present invention. Thus, the present invention is not limited to the embodiments shown, but is to be accorded the widest scope consistent with the claims.I. DEFINITIONS OF THE PRESENT INVENTION

[0025] The term “Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism”, as used herein, means any disease of the blood and blood-forming organs and certain disorders involving the immune mechanism listed in The International Statistical Classification of Diseases and Related Health Problems (including ICD-9, ICD-10 (Chapter III Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism (D50-D89)), ICD-10-CM, ICD-11 (03 Diseases of the blood or blood-forming organs and 04 Diseases of the immune system), ICD- 11-CM, and others);The term “Endocrine, nutritional and metabolic diseases”, as used herein, means any endocrine, nutritional and metabolic disease listed in The International Statistical Classification of Diseases and Related Health Problems (including ICD-9, ICD-10 (Chapter IV Endocrine, nutritional and metabolic diseases (E00-E90)), ICD-10-CM, ICD-11 (05 Endocrine, nutritional or metabolic diseases), ICD-l l-CM, and others);The term “Mental and behavioural disorders”, as used herein, means any mental and behavioural disorders listed in The International Statistical Classification of Diseases and Related Health Problems (including ICD-9, ICD-10 (Chapter V Mental and behavioural disorders (F00-F99)), ICD-10-CM, ICD-11 (06 Mental, behavioural or neurodevelopmental disorders and 07 Sleep-wake disorders), ICD-l l-CM, and others) or any disorder or condition listed in The Diagnostic and Statistical Manual of Mental Disorders, Fifth or IV Edition (DSM-5, DSM-5-TR, DSM-IV-TR);The term “Diseases of the nervous system”, as used herein, means any disease of the nervous system listed in The International Statistical Classification of Diseases and Related Health Problems (including ICD-9, ICD-10 (Chapter VI Diseases of the nervous system (G00- G99)), ICD-10-CM, ICD-11 (08 Diseases of the nervous system), ICD-l l-CM, and others);The term “Diseases of the eye and adnexa”, as used herein, means any disease of the eye and adnexa listed in The International Statistical Classification of Diseases and Related Health Problems (including ICD-9, ICD-10 (Chapter VII Diseases of the eye and adnexa (H00- H59)), ICD-10-CM, ICD-11 (09 Diseases of the visual system), ICD-l l-CM, and others);The term “Diseases of the ear and mastoid process”, as used herein, means any diseases of the ear and mastoid process listed in The International Statistical Classification of Diseases and Related Health Problems (including ICD-9, ICD-10 (Chapter VIII Diseases of the ear and mastoid process (H60-H95)), ICD-10-CM, ICD-11, ICD-11-CM, and others);The term “Diseases of the circulatory system”, as used herein, means any disease of the circulatory system listed in The International Statistical Classification of Diseases and Related Health Problems (including ICD-9, ICD-10 (Chapter IX Diseases of the circulatory system (100-199)), ICD-10-CM, ICD-11 (11 Diseases of the circulatory system), ICD-11- CM, and others);The term “Diseases of the respiratory system”, as used herein, means any disease of the respiratory system listed in The International Statistical Classification of Diseases and Related Health Problems (including ICD-9, ICD-10 (Chapter X Diseases of the respiratory system (J00-J99)), ICD-10-CM, ICD-11, ICD-11-CM, and others);The term “Diseases of the digestive system”, as used herein, means any disease of the digestive system listed in The International Statistical Classification of Diseases and Related Health Problems (including ICD-9, ICD-10 (Chapter XI Diseases of the digestive system (K00-K93)), ICD-10-CM, ICD-11, ICD-11-CM, and others);The term “Diseases of the skin and subcutaneous tissue”, as used herein, means any disease of the skin and subcutaneous tissue listed in The International Statistical Classification of Diseases and Related Health Problems (including ICD-9, ICD-10 (Chapter XII Diseases of the skin and subcutaneous tissue (L00-L99)), ICD-10-CM, ICD-11, ICD-11-CM, and others);The term “Diseases of the musculoskeletal system and connective tissue”, as used herein, means any disease of the musculoskeletal system and connective tissue listed in The International Statistical Classification of Diseases and Related Health Problems (including ICD-9, ICD-10 (Chapter XIII Diseases of the musculoskeletal system and connective tissue (M00-M99)), ICD-10-CM, ICD-11, ICD-11-CM, and others);The term “Diseases of the genitourinary system “, as used herein, means any disease of the genitourinary system listed in The International Statistical Classification of Diseases and Related Health Problems (including ICD-9, ICD-10 (Chapter XIV Diseases of the genitourinary system (N00-N99)), ICD-10-CM, ICD-11, ICD-11-CM, and others);

[0026] The term “parasitic diseases”, as used herein, means any protozoa, unicellular, apicomplexa, algae parasites, macroparasites (worms, helminths, flukes, etc), ectoparasites and arthropods parasitic diseases listed in The International Statistical Classification of Diseases and Related Health Problems (including ICD-9, ICD-10 (Chapter I Certain infectious and parasitic diseases (A00-B99)), ICD-10-CM, ICD-11 (01 Certain infectious or parasitic diseases), ICD-11-CM, and others) and includes case of Disease vector control. Non-limiting examples: Onchocerciasis (due to Onchocerca volvulus), Lymphatic filariasis (due to Wuchereriabancrofti), Strongyloidiasis (due to Strongyloidesstercoralis), Scabies (due to Sarcoptesscabiei), Crusted scabies (Norwegian Scabies), Pediculosis (due to Pediculuscapitis, Pediculuscorporis, Pediculus pubis), Demodicosis (due to Demodexfolliculorum and Demodexbrevis), Demodicosis (due to Demodexfolliculorum and Demodexbrevis), Filariasis (due to Mansonellaozzardi), Filariasis (due to Mansonellastreptocerca), Gnathostomiasis (due to Gnathostomaspinigerum), Cutaneous larva migrans (due to Ancylostomabraziliense), Trichuriasis (due to Trichuristrichiura), Ascariasis (due to Ascarislumbricoides, Enterobiasis (due to Enterobiusvermicularis), Myiasis, Trichinosis, Schistosomiasis, Bedbugs, Rosacea, Buruli ulcer, and for Disease vector control(non limiting example): Malaria, Dengue, Leishmaniasis, African trypanosomiasis (sleeping sickness), American trypanosomiasis (Chagas disease).

[0027] The term “fungal diseases”, as used herein, means any fungal medical conditions or diseases or disorders or syndromes or infections caused by fungi, including listed in The International Statistical Classification of Diseases and Related Health Problems (including ICD-9, ICD-10 (Chapter I Certain infectious and parasitic diseases (A00-B99)), ICD-10-CM, ICD-11 (01 Certain infectious or parasitic diseases), ICD-l l-CM, and others). Non-limiting examples: Aspergillosis; Basidiobolomycosis; Blastomycosis; Candidosis; Chromoblastomycosis; Coccidioidomycosis; Conidiobolomycosis; Cryptococcosis; Dermatophytosis; Eumycetoma; Histoplasmosis; Lobomycosis; Mucormycosis; Nondermatophyte superficial dermatomycoses; Paracoccidioidomycosis; Phaeohyphomycosis; Pneumocystosis; Scedosporiosis; Sporotrichosis; Talaromycosis; Emmonsiosis;And those fungal disease caused by fungi belonging to the order Mucorales or genus Acremonium; Aspergillus; Aspergillus; Candida; Cladophialophora; Coccidioides; Cryptococcus; Cryptococcus; Curvularia; Cylindrocarpon; Exophiala; Falciformispora; Fusarium; Glenospora; Histoplasma; Leptosphaeria; Lomentospora; Madurella; Microsporum; Nakaseomyces; Neotestudina; Paracoccidioides; Phaeoacremonium; Phialophora; Pichia; Pneumocystis; Pyrenochaeta; Scedosporium; Talaromyces; Trichophyton; Zopfia. And those fungal disease caused by fungi belonging to the species (non-limiting example): Cryptococcus neoformans; Candida auris; Aspergillus fumigatus; Candida albicans; Nakaseomyces glabrata (formerly Candida glabrata); Histoplasma capsulatum; Histoplasma capsulatum var. capsulatum; Histoplasma capsulatum var. duboisii; Histoplasma capsulatum var. farciminosum; Histoplasma duboisii; Histoplasma muris; Acremonium falciform; Acremonium kiliense; Acremonium recifei; Aspergillus flavus; Aspergillus nidulans; Cladophialophora bantiana; Cladophialophora mycetomatis; Curvularia geniculata; Curvularia lunata; Cylindrocarpon cyanescens; Exophiala jeanselmei; Falciformispora senegalensi; Fusarium moniliforme; Fusarium solani; Glenospora clapieri; Leptosphaeria senegalensis; Leptosphaeria tompkinsii; Madurella grisea; Madurella mycetomatis; Microsporum audouinii; Microsporum canis; Neotestudina rosatii; Phaeoacremonium parasiticum; Phialophora cyanescens; Phialophora verrucosa; Scedosporium (ex. Pseudoalleschia) boydii; Pyrenochaeta mackinonii; Pyrenochaeta romeroi; Trichophyton rubrum; Zopfia rosatii; Candida tropicalis; Candida parapsilosis; Scedosporium americanum; Scedosporium apiospermum; Scedosporium aurantiacum; Scedosporium boydii; Scedosporium cereisporum; Scedosporium deficiens; Scedosporium dehoogii; Scedosporium desertorum; Scedosporium magalhaesii; Scedosporium minutisporum; Scedosporium prolificans; Scedosporium rarisporum; Scedosporium sanyaense; Coccidioides immitis; Coccidioides posadasii; Lomentospora prolificans; Pichia kudriavzeveii (formerly Candida krusei); Cryptococcus gattii; Talaromyces mameffei; Pneumocystis jirovecii; Paracoccidioides americana; Paracoccidioides brasiliensis; Paracoccidioides cerebriformis; Paracoccidioides ceti; Paracoccidioides lutzii; Paracoccidioides restrepoana; Paracoccidioides venezuelensis.

[0028] The term “bacterial diseases”, as used herein, means any bacterial medical conditions or diseases or disorders or syndromes or infections caused by bacteria, including those caused by bacteria belonging to the genus: Abiotrophia; Acetobacter; Acholeplasma; Achromobacter; Acidaminococcus; Acidomonas; Acidovorax; Acinetobacter; Actinobacillus; Actinobaculum; Actinomadura; Actinomyces; Actinotignum; Advenella; Aerococcus; Aeromonas; Afipia; Aggregatibacter; Agrobacterium; Alcaligenes; Alistipes; Alkanindiges; Alloiococcus; Alloprevotella; Alloscardovia; Amycolatopsis;Anaerobiospirillum; Anaerococcus; Anaeroglobus; Anaerostipes; Anaplasma; Aquimonas; Arcanobacterium; Arcobacter; Arthrobacter; Asaia; Atlantibacter; Atopobium; Atopobium ; Aureimonas; Auritidibacter; Bacillus; Bacteroides; Balneatrix; Bartonella; Bergeyella; Bifidobacterium; Bilophila; Bisgaardia; Bordetella; Borrelia; Brachybacterium; Brachyspira; Branchiibius; Brevibacillus; Brevibacterium; Brevundimonas; Brucella; Budvicia; Bulleidia; Burkholderia; Buttiauxella; Butyricimonas; Campylobacter; Canibacter; Capnocytophaga; Cardiobacterium; Catabacter; Catonella; Cedecea; Cellulomonas; Cellulosimicrobium; Centipeda; Chitinophaga; Chlamydia; Chlamydophila; Chromobacterium; Chryseobacterium; Citrobacter; Clostridioides; Clostridium; Collinsella; Comamonas; Coprobacillus; Corynebacterium; Coxiella; Cronobacter; Cruoricaptor; Cryptobacterium; Cupriavidus; Curtobacterium; Cutibacterium; Delftia; Dermabacter; Dermacoccus; Dermatophilus; Desmospora; Desulfomicrobium; Desulfovibrio; Dialister; Dichelobacter; Dietzia; Diplorickettsia; Dokdonella; Dolosigranulum; Dyella; Dysgonomonas; Edwardsiella; Effusibacillus; Eggerthella; Eggerthia; Ehrlichia; Eikenella; Eisenbergiella; Elizabethkingia; Empedobacter; Enterobacter; Enterococcus; Erwinia; Erysipelatoclostridium; Erysipelothrix; Escherichia; Eubacterium; Ewingella;Exiguobacterium; Facklamia; Faecalicatena contorta; Fastidiosipila; Fenollaria; Fibrobacter; Filifactor; Finegoldia; Flavobacterium; Fluoribacter; Francisella; Frederiksenia; Fretibacterium; Fusobacterium; Gallibacterium; Gardnerella; Gemella; Globicatella; Gordonia; Gordonibacter; Granulibacter; Granulicatella; Haematobacter; Haematomicrobium; Haematospirillum; Haemophilus; Hafnia; Halomonas; Hathewaya; Hazenella; Helcobacillus; Helcococcus; Helicobacter; Herbaspirillum; Hungatella; Ignatzschineria; Ignavigranum; Inquilinus; Janibacter; Jonquetella; Kerstersia; Kingella; Klebsiella; Kluyvera; Kocuria; Kosakonia; Kytococcus; Lachnoanaerobaculum; Lactobacillus; Lactococcus; Laribacter; Lawsonella; Leclercia; Legionella; Leifsonia; Lelliottia; Leminorella; Leptospira; Leptotrichia; Leuconostoc; Listeria; Luteibacter; Luteococcus; Lysinibacillus; Malacobacter; Mannheimia; Massilia; Megamonas; Megasphaera; Metamycoplasma; Methylobacterium; Microbacterium; Micrococcus; Microvirgula; Mobiluncus; Moellerella; Mogibacterium; Moraxella; Morganella; Moryella; Murdochiella; Mycobacterium; Mycoplasma; Mycoplasmoides; Mycoplasmopsis; Myroides; Necropsobacter; Negativicoccus; Neisseria; Neisseria ; Neoehrlichia; Neorickettsia; Nocardia; Nocardiopsis; Oblitimonas; Ochrobactrum; Odoribacter; Oerskovia; Oligella; Oribacterium; Orientia; Orientia ; Oscillibacter; Paenalcaligenes; Paenibacillus; Pandoraea; Pantoea; Parabacteroides; Paraclostridium; Paracoccus; Paraeggerthella; Parapseudoflavitalea; Parvimonas; Pasteurella; Peptococcus; Peptoniphilus; Peptostreptococcus; Phocaeicola; Photobacterium; Photorhabdus; Plesiomonas; Pluralibacter; Pontibacter; Porphyromonas; Prescottia; Prevotella; Propionibacterium; Proteus; Providencia; Pseudoclavibacter; Pseudomonas; Pseudonocardia; Pseudopropionibacterium; Pseudoramibacter; Pseudoxanthomonas; Psychrobacter; Pyramidobacter; Rahnella; Ralstonia; Raoultella; Rhizobium; Rhodococcus; Rickettsia; Robinsoniella; Rodentibacter; Roseomonas; Rothia; Ruminococcus; Saccharomonospora; Saccharopolyspora; Saezia; Salmonella; Scandinavium; Scardovia; Sciscionella; Sebaldella; Sedimentibacter; Segniliparus; Selenomonas; Serratia; Shewanella; Shigella; Shuttleworthia; Simkania; Slackia; Sneathia; Sodalis; Solobacterium; Sphingobacterium; Sphingomonas; Spiroplasma; Staphylococcus; Stenotrophomonas; Stomatobaculum; Streptobacillus; Streptococcus; Streptomyces; Sutterella; Suttonella; Tannerella; Tatlockia; Tatumella; Tepidimonas; Terrisporobacter; Tissierella; Treponema; Tropheryma; Trueperella; Tsukamurella; Turicella; Turicibacter; Ureaplasma; Vagococcus; Varibaculum; Veillonella; Vibrio; Waddlia; Wautersiella; Weeksella; Weissella; Williamsia; Wohlfahrtiimonas; Wolinella; Xenophilus; Yersinia; Yokenella;a comprehensive list of bacterial pathogens species can be found in “A comprehensive list of bacterial pathogens infecting humans”, Bartlett et al., Microbiology 2022; 168:001269, DOI 10. 1099 / MIC.0.001269, DOI: 10.5281 / ZENODO.7337535, but not excluding other bacteria; and are selected from those listed in The International Statistical Classification of Diseases and Related Health Problems (including ICD-9, ICD-10 (Chapter I Certain infectious and parasitic diseases (A00-B99)), ICD-10-CM, ICD-11 (01 Certain infectious or parasitic diseases), ICD- 11-CM, and others); and / or wherein a person's medical conditions / diseases / disorders / syndromes are selected from those listed in The Diagnostic and Statistical Manual of Mental Disorders, including DSM-IV, DSM-5, DSM-5-TR, and others; and / or wherein a person's medical conditions / diseases / disorders / syndromes are selected from those listed in the Medical Subject Headings and beginning with MeSH codes C01-C25; and / or wherein a person's medical conditions / diseases / disorders / syndromes are selected from conditions that are published in the Genetic and Rare Diseases (GARD) Information Center;

[0029] The term “viral diseases”, as used herein, means any viral medical conditions or diseases or disorders or syndromes or infections caused by viruses, including those caused by RNA viruses, DNA viruses and reverse transcribing viruses; including those caused by viruses belonging to the realm Duplodnaviria, Monodnaviria, Adnaviria, Ribozyviria, Riboviria, and Varidnaviria; including those caused by dsDNA viruses, ssDNA viruses, dsRNA viruses, (+)ssRNA viruses, (-)ssRNA viruses, ssRNA-RT viruses, dsDNA-RT viruses; including viral infections or viral diseases caused by viruses included in the families Coronaviridae, Flaviviridae, Herpesviridae, Orthomyxoviridae, Paramyxoviridae, Polyomaviridae, Retroviridae, Togaviridae, but not excluding other viruses families; including viral infections or viral diseases caused by Human SARS coronavirus, SARS coronavirus 2, Dengue virus, West Nile virus, Yellow fever virus, Zika virus, Bovine alphaherpesvirus 1, Influenza A virus, Hendra virus, BK polyomavirus, Human immunodeficiency virus type 1, Chikungunya virus, Semliki forest virus, Sindbis virus, Venezuelan equine encephalitis virus, Human adenovirus, Junin arenavirus, Lassa virus, Lymphocytic choriomeningitis virus, Machupo virus, Pichinde virus, Porcine reproductive and respiratory syndrome virus (PRRSV) / Betaarterivirus suid 1 , Human astrovirus, Hantaan virus, Crimean-Congo hemorrhagic fever virus, Dugbe virus, Bunyamwera virus, Bunyavirus La Crosse, Bunyavirus snowshoe hare, Punta toro phlebovirus, Rift valley fever virus, Sandfly fever Naples phlebovirus (Toscana virus), Sandfly fever Sicilian virus, Uukuniemi virus, Norwalk virus, Southampton virus, Sapporo virus, porcine circovirus 2 , Human coronavirus, MERS coronavirus, Human torovirus, Ebola virus, Lake Victoria marburg virus, Japanese encephalitis virus, Langat virus, Louping ill virus, St. louis encephalitis virus, Tick-borne powassan virus, TBE virus, Hepatitis C virus, GB virus C / Hepatitis G virus, Hepatitis B virus, Hepatitis E virus, Human cytomegalovirus, Cercopithecine herpesvirus, Epstein-Barr virus, Human herpesvirus 8, Human herpesvirus 6, Human herpesvirus 7, Human herpesvirus 1, Human herpesvirus 2, Varicella-zoster virus, Bovine alphaherpesvirus 1 , Equine herpesvirus type 1 (EHV-1) , Pseudorabies virus, Rubella virus, Influenza B virus, Influenza C virus, Influenza A virus, Dhori virus, Human papillomavirus (16,18), Human papillomavirus 2, Human papillomavirus 1, Nipah virus, Measles virus, Human parainfluenza, Mammalian orthorubulavirus 5 (Simian virus 5), Mumps virus, Newcastle, Adeno-associated virus, Human parvovirus Bl 9, Encephalomyocarditis virus, Cosavirus A, Coxsackievirus, Echovirus, Human enterovirus (68, 70), Poliovirus, Hepatitis Avirus, Aichi virus, Rosavirus A, Rhinovirus, Salivirus A, Human respiratory syncytial virus, JC polyomavirus, KI Polyomavirus, Merkel cell polyomavirus, WU polyomavirus, BK polyomavirus, Molluscum contagiosum virus, Cowpox virus, Horsepox virus, Vaccinia virus, Variola virus, Yaba monkey tumor virus, Yaba-like disease virus, Smallpox, Orf virus, Rotavirus A, Rotavirus B, Orbivirus, Coltivirus, Rotavirus C, Banna virus, Human T- lymphotropic virus, Human immunodeficiency virus, Eastern chimpanzee simian foamy virus, Simian foamy virus, Human immunodeficiency virus type 1 / 2, Australian bat lyssavirus, Duvenhage virus, Lagos bat virus, Mokola virus, Rabies virus, Chandipura virus, Isfahan virus, Vesicular stomatitis virus, European bat lyssavirus, Barmah forest virus, Eastern equine encephalitis virus, Mayaro virus, O'nyong-nyong virus, Ross river virus, Sagiyama virus, Western equine encephalitis virus, Rubella virus, Hepatitis delta virus, Hepatitis E virus, Torque teno virus, Human rhinovirus, Murray valley encephalitis virus, Oropouche virus, Monkeypox virus, New York virus, Puumala virus, Seoul virus, but not excluding other viruses; and are selected from those listed in The International Statistical Classification of Diseases and Related Health Problems (including ICD-9, ICD-10 (Chapter I Certain infectious and parasitic diseases (A00-B99)), ICD-10-CM, ICD-11 (01 Certain infectious or parasitic diseases), ICD- 11-CM, and others); and / or wherein a person's medical conditions / diseases / disorders / syndromes are selected from those listed in The Diagnostic and Statistical Manual of Mental Disorders, including DSM-IV, DSM-5, DSM-5-TR, and others; and / or wherein a person's medical conditions / diseases / disorders / syndromes are selected from those listed in the Medical Subject Headings and beginning with MeSH codes C01-C25; and / or wherein a person's medical conditions / diseases / disorders / syndromes are selected from conditions that are published in the Genetic and Rare Diseases (GARD) Information Center;

[0030] The term “cancer”, as used herein, means any cancer (tumor, neoplasm), Bone and muscle sarcoma cancers; Chondrosarcoma; Ewing's sarcoma; Malignant fibrous histiocytoma of bone / osteosarcoma; Osteosarcoma; Rhabdomyosarcoma; Leiomyosarcoma; Myxosarcoma; Fibrocartilaginous mesenchymoma of bone; Brain and nervous system cancers; Astrocytoma; Brainstem glioma; Pilocytic astrocytoma; Ependymoma; Primitive neuroectodermal tumor; Cerebellar astrocytoma; Cerebral astrocytoma; Glioblastoma; Glioma; Medulloblastoma; Neuroblastoma; Oligodendroglioma; Pineal astrocytoma; Pituitary adenoma; Visual pathway and hypothalamic glioma; Breast cancers; Breast cancer; Inflammatory breast cancer; Invasive lobular carcinoma; Tubular carcinoma; Invasive cribriform carcinoma of the breast (also termed invasive cribriform carcinoma); Medullary carcinoma; Male breast cancer; Phyllodes tumor; Mammary secretory carcinoma; Papillary carcinomas of the breast; Endocrine system cancers; Adrenocortical carcinoma; Islet cell carcinoma (endocrine pancreas); Multiple endocrine neoplasia syndrome; Pancreatic Cancer; Parathyroid cancer; Pheochromocytoma; Thyroid cancer; Merkel cell carcinoma; Eye cancers; Uveal melanoma; Retinoblastoma; Optic nerve glioma; Gastrointestinal cancers; Anal cancer; Appendix cancer; Cholangiocarcinoma; Carcinoid tumor, gastrointestinal; Colon cancer; Duodenal cancer; Extrahepatic bile duct cancer; Gallbladder cancer; Gastric (stomach) cancer; Gastrointestinal carcinoid tumor; Gastrointestinal stromal tumor (GIST); Hepatocellular cancer; Pancreatic cancer, islet cell; Rectal cancer; Small intestine cancer;Genitourinary and gynecologic cancers; Bladder cancer; Cervical cancer; Endometrial cancer; Extragonadal germ cell tumor; Ovarian cancer; Ovarian epithelial cancer (surface epithelial-stromal tumor); Ovarian germ cell tumor; Penile cancer; Kidney cancer; Renal cell carcinoma; Renal pelvis and ureter, transitional cell cancer; Prostate cancer; Testicular cancer; Gestational trophoblastic tumor; Ureter and renal pelvis; transitional cell cancer(urothelial carcinoma); Urethral cancer; Uterine sarcoma; Vaginal cancer; Vulvar cancer; Wilms tumor (nephroblastoma); Head and neck cancers; Esophageal cancer; Head and neck cancer; Nasopharyngeal carcinoma; Oral cancer; Oropharyngeal cancer; Paranasal sinus and nasal cavity cancer; Pharyngeal cancer; Salivary gland cancer; Hypopharyngeal cancer; Hematopoietic cancers; Acute biphenotypic leukemia; Acute eosinophilic leukemia; Acute lymphoblastic leukemia; Acute myeloid leukemia; Acute myeloid dendritic cell leukemia; AIDS-related lymphoma; Anaplastic large cell lymphoma; Angioimmunoblastic T-cell lymphoma; B-cell prolymphocytic leukemia; Burkitt's lymphoma; Chronic lymphocytic leukemia; Chronic myelogenous leukemia; Cutaneous T-cell lymphoma; Diffuse large B-cell lymphoma; Follicular lymphoma; Hairy cell leukemia; Hepatosplenic T- cell lymphoma; Hodgkin's lymphoma; Intravascular large B-cell lymphoma; Large granular lymphocytic leukemia; Lymphoplasmacytic lymphoma; Lymphomatoid granulomatosis; Mantle cell lymphoma; Marginal zone B-cell lymphoma; Mast cell leukemia; Mediastinal large B cell lymphoma; Multiple myeloma / plasma cell neoplasm; Myelodysplastic syndromes; Mucosa-associated lymphoid tissue lymphoma; Mycosis fungoides; Nodal marginal zone B cell lymphoma; Non-Hodgkin lymphoma; Precursor B lymphoblastic leukemia; Primary central nervous system lymphoma; Primary cutaneous follicular lymphoma; Primary cutaneous immunocytoma; Primary effusion lymphoma; Plasmablastic lymphoma; Sezary syndrome; Splenic marginal zone lymphoma; T-cell prolymphocytic leukemia; Skin cancers; Basal cell carcinoma; Squamous cell carcinoma; Squamous cell skin cancer; Skin adnexal tumors (e.g. sebaceous carcinoma); Melanoma; Merkel cell carcinoma; Keratoacanthoma; Sarcomas of primary cutaneous origin (e.g. dermatofibrosarcoma protuberans); Lymphomas of primary cutaneous origin (e.g. mycosis fungoides); Thoracic and respiratory cancers; Adenocarcinoma of the lung; Basaloid squamous cell lung carcinoma; Bronchial adenomas / carcinoids; Small cell lung cancer; Mesothelioma; Nonsmall cell lung cancer; Non-small cell lung carcinoma; Pleuropulmonary blastoma; Laryngeal cancer; Thymoma and thymic carcinoma; Squamous-cell carcinoma of the lung; HIV / AIDS related cancers; AIDS-related cancers; Kaposi sarcoma; Epithelioid hemangioendothelioma (EHE); Desmoplastic small round cell tumor; Liposarcoma; and any malignant tumors such as Carcinoma, Sarcoma, Lymphoma, Leukemia, Germ cell tumor, Blastoma (e.g. neuroblastoma, retinoblastoma, nephroblastoma, hepatoblastoma, medulloblastoma, etc.), Melanoma, Endothelioma, Glioma of tissues, organs, parts of organs, parts of the body, skin, muscles, bones, connective tissue, internal organs, organs of vision, speech, hearing, smell, taste: a. skin; b. head; eye; ear; nose; mouth; tongue; teeth; lower jaw; face; cheek; c. neck; throat; Adam's apple; shoulders; d. hand; elbow; wrist; hand; fingers; thumb; e. spine; breast; mammary gland; rib cage; f. abdomen; navel; genitals (penis / scrotum or clitoris / vagina); perineum; anus; g. leg; pelvis; thigh; buttock; knee; shin; calf; foot - toes; h. hair, nails;i. pituitary; duodenum; stomach; gallbladder; intestines; lungs; uterus; bladder; adrenals; parathyroid; liver; pancreas; kidneys; prostate; esophagus; spleen; heart; thymus; worm gland; thyroid; testes; ovaries; j . brain; k. anatomical parts included in “Terminologia Anatomica The Second Edition”, Parts I- V, Chapters 1-16, which is the international standard for human anatomical terminology; and any person's cancer medical conditions or diseases or disorders or syndromes are selected from those listed in The International Statistical Classification of Diseases and Related Health Problems (including ICD-9, ICD-10 (Chapter II Neoplasms (C00-D48)), ICD-10-CM, ICD-11 (02 Neoplasms), ICD-l l-CM, and others); and any person's cancer medical conditions or diseases or disorders or syndromes are selected from those listed in The Diagnostic and Statistical Manual of Mental Disorders, including DSM-IV, DSM-5, DSM-5-TR, and others; and any person's cancer medical conditions or diseases or disorders or syndromes are selected from those listed in the Medical Subject Headings 2023 and its MeSH TreeNumber code starts with MeSH codes C01-C25; and any person's cancer medical conditions or diseases or disorders or syndromes are selected from conditions that are published in the Genetic and Rare Diseases (GARD) Information Center.

[0031] The term "treatment" as used herein, unless otherwise specified, means the abolition, relief, inhibition of the progression or prevention of the disorder or condition to which the term applies, or one or more symptoms of such disorder or condition. The term "treatment", as used herein, refers to the action of treatment as "treating" is defined directly above. Treatment also means "for use in manufacturing a pharmaceutical dosage form to treat".

[0032] The term "therapeutically effective amount", as used herein, is the amount of a compound of Formula I-V present in a composition described herein that is necessary to provide the desired level of the drug in the secretions and tissues of the respiratory tract and lungs or, alternatively, in the bloodstream of the subject to be treated to produce the expected physiological response or desired biological effect when such composition is administered in the selected route of administration.The exact amount depends on a variety of factors, such as the specific compound of Formula I-V, the specific activity of the composition, the delivery device used, the physical characteristics of the composition, its intended use, and patient considerations such as severity of the disease state, patient cooperation, etc., and can be readily determined by a person skilled in the art based on the information provided herein.

[0033] The term “active pharmaceutical ingredient” (API, guest, guest drug, guest drug compound, guest compound, guest extract, guest biologically active extract) is pharmaceutically active and bioactive compound; if the selected guest drug is in the form of a free base - the pharmaceutical salts of that base and the pharmaceutical ester or ether are also included; if the guest drug is in the form of a pharmaceutical salt - the free base of thatsalt, the pharmaceutical ester or ether, and other pharmaceutical salts of that free base are also included; also include racemate, enantiomer, diastereomer, tautomer, polymorph, pseudopolymorph, hydrate, isotopically labeled forms, prodrugs thereof or mixtures thereof.

[0034] The term "additional active pharmaceutical ingredient" (AAPI, guest, guest drug, guest drug compound, guest compound, guest extract, guest biologically active extract) is a pharmaceutically active and biologically active compound that is administered with an API to produce an additional therapeutic effect.

[0035] The term “additional active natural pharmaceutical ingredienf’(AANPI, guest, guest drug, guest drug compound, guest compound, guest extract, guest biologically active extract) is pharmaceutically active and bioactive compound from natural sources, primary or secondary metabolite that is administered with an API to produce an additional therapeutic effect. AANPI may be in the form of a pure substance isolated from a natural source, in the form of an extract, a dried extract, or in the form of a processed natral source, such as a powder and any other form in which it is contained.

[0036] The term “derivative” of active pharmaceutical ingredient (of API, AAPI, AANPI, guest, guest drug, guest drug compound, guest compound) means derivatives such as racemate, enantiomer, diastereomer, tautomer, polymorph, pseudopolymorph, hydrate, isotopically labeled forms, prodrugs, pharmaceutical salts, pharmaceutical ester or ether. If the API in the form of a free base, the derivatives are the pharmaceutical salts of that base and the pharmaceutical ester or ether. If the API is in the form of a pharmaceutical salt - the free base of that salt, the pharmaceutical ester or ether, and other pharmaceutical salts of that free base are also derivatives. Derivatives can also be other obvious derivatives - chemical and phisical derivatives (see below).

[0037] The term “prodrug” is defined in the pharmaceutical field as a biologically inactive derivative of a drug that, when introduced into the human body, is transformed into a biologically active parent drug according to some chemical or enzymatic pathway.

[0038] The term “solvent”, as used herein, means organic and inorganic solvents which may be (but are not limited to): water, hydrocarbons and their halogen derivatives, alcohols, esters and ethers, ketones, nitro compounds: 1,1,1 -trichloroethane, 1,1,2- trichloroethene, 1,1 -dichloroethene, 1,2-dichloroethane, 1,2-dichloroethene, 1,2- dimethoxyethane, 1,2-propanedioi, 1,4-dioxane, 1 -butanol, 1 -pentanol, 1 -propanol, 2- butanol, 2-butanone, 2-ethoxyethanol, 2-methoxyethanol, 2 -methyl- 1 -propanol, 2- methylpyridine, 2-methyltetrahydrofuran, 2-nitropropane, 2-propanol, 3 -methyl- 1 -butanol, 4- methyl-2-pentanone, acetic acid, acetic anhydride, acetone, acetonitrile, acetophenone, ammonia, aniline, anisole, benzene, benzonitrile, benzylalcohol, bromoethane, bromoform, bromooctane, butanol, butanone, butylacetate, butylbenzene, carbon disulfide, carbontetrachloride, carbontet, cellosolve acetate, cetic acid, chlorobenzene, chloroform, chloroform, chlorohexane, cumene, cyclohexanes cyclohexane, cyclohexanol, cyclohexanone, cyclopentane, cyclopentanes, decalin, decane, decanol, dibromoethane, dibutylether, dichlorobenzene, difluorobenzene, dichloroethane, dichloromethane, diethyleneglycol, diethylether, diglyme (diethylene glycoldimethyl ether), diisopropylether, dimethoxyethane, dimethyl acetate, dimethyl sulfoxide, dimethylacetamide, dimethylformamide, dimethylpyridine, dimethylsulfoxide, dioxane, di oxanes (1.4 dioxane), dodecane, esters, etbe, ethanediol, ethanol, ether(s), ethoxybenzene, ethyl acetate, ethyl acetoacetate, ethyl alcohol, ethylacetate, ethylbenzene, ethylene glycol ethyl ether, ethyleneglycol methyl ether , ethylene glycol monobutyl ether, ethyleneglycol, ethylether, ethylformate, fluorobenzene, fluoroctane, formamide, formic acid, freon, furfuraldehyde, glacial acetic acid, glycerin, glycol ethers, halobenzenes, heptane, heptanes, heptanol, hexadecane, hexadecyliodide, hexamethylphosphoramide, hexamethylphosphorous triamide (hmpt), hexane, hexanes, hexanol, i-amyl alcohol, iodobenzene, isobutanol, isobutyl acetate, isooctane, isopropanol, isopropyl acetate, isopropylbenzene, isopropyltoluene, mcresol, mesitylene, methanoic acid, methanol, methoxyethanol, methyl acetate, methyl ethyl ketone, methyl t-butyl ether, methyl tert butyl ether, methylbutyl ketone, methylcyclohexane, methylenechloride, methylethyl ketone, methylformamide, methylisobutyl ketone, miscellaneous solvents, monochlorobenzene, morpholine, m-xylene, n,n-dimethylacetamide, n,n-dimethylformamide, n-amyl alcohol, n-butyl acetate, nitrobenzene, nitroethane, nitromethane, n-methyl-2-pyrrolidinone(nmp), n-methylpyrrolidone, n-octanol, nonane, nonanol, octane, octanol, odichlorobenzene, onitrotoluene, o-xylene, pentadecane, pentane, pentanes, pentanol, perchloroethylene, perfluorobenzene, petroleum ether (ligroine), phenol, phenylether, propanol, propoxypropane, propyl acetate, propylene glycol methyl ether , p- xylene, pyridine, secbutanol, secbutylbenzene, sulfolane, t-butanol, t-butyl alcohol, tbutylbenzene, tert-butylmethylether, tetrachloroethane, tetrachloroethylene, tetrachloromethane, tetrahydrofuran, tetrahydrothiophenedioxide, tetralin, toluene, tributylphosphate, trichloroethane, trifluoromethylbenzene , trichloroethylene, triethylamine, trimethylbenzene, trimethylpentane, undecane, xylene, xylenes, 2,2,4-trimethyl pentane, and mixtures thereof. The term "physiologically accepted solvent" typically refers to a solvent that is considered safe for use in biological and physiological systems. In various scientific and medical applications, solvents are used for dissolving or diluting substances, and it's important that these solvents do not cause harm to living organisms. Here are some common examples: a. Water: Water is the most fundamental and widely used solvent in biological systems. It is essential for various physiological processes and is the basis for many biological fluids. b. Saline Solution: Saline solution is a mixture of salt (sodium chloride) dissolved in water. It is commonly used as an intravenous fluid to replenish electrolytes and maintain hydration. c. Ethanol and other alchohols: Ethanol, or ethyl alcohol, is a type of alcohol that is sometimes used in medical and laboratory settings. It is commonly used as a disinfectant and can be used in certain pharmaceutical preparations. d. Glycerol: Glycerol, also known as glycerin, is a colorless and odorless liquid that is often used as a solvent in pharmaceuticals, cosmetics, and food. It is considered safe for use in various physiological applications. e. Propylene Glycol: Propylene glycol is a synthetic liquid that is commonly used in the pharmaceutical and food industries. It is used as a solvent in oral, injectable, and topical drug formulations. f. Dimethyl Sulfoxide (DMSO): DMSO is a solvent that is known for its ability to penetrate biological tissues. It is used in medical and laboratory settings for certain applications, such as cryopreservation of cells.

[0039] The term “physically modified” or “physical derivative” means use of physical methods for modification of involves use of mechanical forces, sound, ultrasound, dry heat, microwave technology, UV and gamma radiations. Generally natural carriers on modification using heating method (thermally modified derivative) will leads to change in its physical characteristics like viscosity, density, swelling index, water holding capacity, flowproperties etc. Due to changes in these characteristics the improved results were obtained in case of modified natural carriers.

[0040] The term “chemically modified” or “chemical derivative” means use of chemical methods for modification. Non-limiting examples:A. Methoxylated, ethoxylated, esterificated, carboxylated, alkoxylated, acetylated, hydroxylated, hydrated, hydrolyzed, decarboxylated, amide, oxidized, sulfated, aminoacid derivatives, fermented derivatives, acid modified derivatives, and their esters, salts , and the like;B. Acetyl; Anhydro, D-alanyl; N-acetyl-D-alanyl; N-acetimidoyl; N-(N-methyl- acetimidoyl); N-(N,N-dimethyl-acetimidoyl); formyl; glycolyl; N-acetyl-glutaminyl; N- methyl-5-glutamyl; glycyl; glyceryl; 2,3-di-O-methyl-glyceryl; 4-hydroxybutyryl; 3,4- dihydroxybutyryl; (R)-3-hydroxybutyryl; (S)-3-hydroxybutyryl; lactyl; methyl; amino; N- acetyl; phosphate; pyruvyl; 1-carboxyethylidene; sulfate; tauryl derivatives; Alkyl derivatives: Methyl, ethyl, . . . dodecyl derivatives; Aliphatic carboxylic acids derivatives: Formyl, acetyl, glycoloyl, propionyl; Butyryl, valeryl; Hexanoyl, heptanoyl, octanoyl; Nonanoyl, decanoyl, undecanoyl; Lauroyl, myristoyl, palmitoyl; Stearoyl, eleostearoyl, linoleoyl, arachidonoyl; Glycerol derivatives and its oxidation products:Glycerol, glyceraldehyde, glycerone, glyceric acid; Glycosyl derivatives: Glucose, galactose, fucose, and the like; Gluconic acid, glucuronic acid; Glucosaminef, N- acetylglucosamine; Neuraminic, sialic, muramic acids; N-Acetylneuraminic acid, N- glycoloylneuraminic acid; Other derivatives: Ceramide, choline, ethanolamine; Inositol, serine, other aminoacids; Phosphatidyl, sphingosine, sphingoid, Phosphoric derivatives, and the like;C. any other chemically modified derivativeswhich are described in the scientific and patent literature.Others non-limiting examples: a) Carboxymethylation / carbomoylethylation in which free -OH groups replacement were done which leads to improved aqueous drug solubility. Carboxymethylation of natural carriers increases their hydrophilicity and makes them more soluble in aqueous systems. b) Modification, such as the removal of a terminal sialic acid to expose glucose, fucose, mannose, galactose and the like; c) Starting with an polysaccharide, acid catalyzed, base catalyzed or enzyme catalyzed hydrolysis may be used to produce lower molecular weight polysaccharides; d) Embodiments of the invention also include derivatives of polymer, such as fragments, dimers, trimers, and polymers of polymer; e) These derivatives provide a substrate for attaching therapeutic agents through attachment to the amino, carboxyl, sulfhydryl, phosphoryl or other functional groups of the derivative. The carboxyl groups that naturally occur on the terminal glycoside of polymer can be used to attach other molecules through the use of carbodiimides or other agents. Amine derivatives can also be used to attach therapeutic agents by a variety of reactions. Alternatively, dextran or poly-L-lysine can be attached to the polymer carrier to provide an increased number of sites of attachment for the therapeutic agent.

[0041] The term “avermectin”, as used herein, means avermectins and their derivatives such as: Avermectins; Avermectin Ala; Avermectin Alb; Avermectin A2a; Avermectin A2b; Avermectin Bia; Avermectin Bib; Avermectin B2a; Avermectin B2b; Ivermectins; IvermectinBia; Ivermectin Bib; Ivermectin Ala; Ivermectin Alb; Milbemycins; Milbemycin A3; Milbemycin A4; Milbemycin D; Milbemycin B2; Milbemycin B3; Milbemycin G; Nemadectins; Nemadectin; Meilingmycins; Meilingmycin A; Milbemectins; Milbemectin; Milbemycin oxime; Moxidectins; Moxidectin; Doramectins; Doramectin; Selamectins; Selamectin; Eprinomectins; Eprinomectin Bia; Eprinomectin Bib; Emamectins; Emamectin Bia; Emamectin Bib; Tenvermectins; Tenvermectin B; Tenvermectin A and the like; or derivatives thereof such as racemate, enantiomer, diastereomer, tautomer, polymorph, pseudopolymorph, hydride or solvate thereof; or a pharmaceutically acceptable salt or ester or ether thereof; or prodrug thereof; or methabolite thereof; or aglycone thereof; or derivatives which may be obtained by gene replacement processes in genetically engineered strains, or / and by fermentation, or / and by chemical modifications and the like, which are described in the scientific and patent literature; or mixtures thereof.

[0042] The term “disease” is mean any disease a medical conditions or diseases or disorders or syndromes or infections of a human or mammal or animal or bird has at least one of the following characteristics:A. it is a medical condition in which functions are impaired or that is caused by impaired function at the organism level, including such functions as: a. sleep b. sexual reproduction c. thinking, speech, reading, writing, behavior d. observation, hearing, smell, sensory abilities e. exchange with the environment, including impaired functions: e.1 nutrition e.2 respiration e.3 excretion f. locomotion, operation of limbs and body parts g. othersB. it is a medical condition in which processes are disturbed or caused by disturbances in such systems and supra-systems of the body as: a. Musculoskeletal system b. Circulatory system, Cardiovascular system, Lymphatic system c. Nervous system d. Integumentary system e. Haematopoietic and immune systems f. Respiratory system g. Digestive system h. Urinary system i. Reproductive system j. Endocrine systemC. it is a medical condition in which processes are disrupted or caused by disruption of processes at the tissue / cell system level including: a. cell reproduction, division, differentiation, atypia, signaling, such as: a.1 cancer, malignant tumors such as Carcinoma, Sarcoma, Lymphoma, leukemia, Germ cell tumor, Blastoma (e.g. neuroblastoma, retinoblastoma, nephroblastoma, hepatoblastoma, medulloblastoma, etc.), Melanoma, endothelioma of tissues, organs, parts of organs, parts of the body specified in Section G; b. metabolism of cells and tissues i. cellular uptake of nutrientsii. sensitivity to the action of hormones, transmitters, neurotransmitters, etc., such as insulin, cortisol, dopamine, and others;D. it is a genetic diseases, chromosomal disorder or genetic syndrome;E. it is a medical condition that is caused or accompanied by morphological changes such as: tumor, metastases, cysts, necrosis, inflammation, accumulation of mineral salts, metabolites and etc.F. it is a medical condition that is caused by or accompanied by: a. lesion or involvement or presence of infectious agents, which may be: i. viruses ii. bacteria; iii. fungi iv. parasites; v. ectoparasitoses; vi. protozoa; vii. prions; b. by lesion or involvement or presence of toxic agents; c. by lesion or involvement or presence of allergic agents, including Systemic allergic diseases; d. excessive / insufficient energy and other influences, such as: i. kinetic exposures and kinetic injuries; ii. thermal injuries; iii. radiation injuries; iv. barotraumas; v. other injuries; e. external factors: i. war, disasters; ii. violence; iii. stresses; iv. overwork; v. mistreatment and upbringing; vi. other factors;G. it is a medical condition that affect body parts, organs, and tissues, such as parts of the body, skin, muscles, bones, connective tissue, internal organs, organs of vision, speech, hearing, smell, taste: a. skin; b. head - eye - ear - nose - mouth - tongue - teeth - lower jaw - face - cheek; c. neck - throat - Adam's apple - shoulders; d. hand - elbow - wrist - hand - fingers - thumb; e. spine - breast - mammary gland - rib cage; f. abdomen - navel - genitals (penis / scrotum or clitoris / vagina) - perineum - anus; g. leg - pelvis - thigh - buttock - knee - shin - calf - foot - toes; h. hair, nails; i. pituitary - duodenum - stomach - gallbladder - intestines - lungs - uterus - bladder - adrenals - parathyroid - liver - pancreas - kidneys - prostate - esophagus - spleen - heart - thymus - worm gland - thyroid - testes - ovaries; j. brain; k. anatomical parts included in “Terminologia Anatomica The Second Edition”, Parts I- V, Chapters 1-16, which is the international standard for human anatomical terminology;H. it is a medical condition in which the body is in the state or age of: a. embryo b. fetus c. infantile age d. childhood e. adulthoodf. old age g. pregnancy and childbirth h. disability i. coma j. anesthesia k. sleep i. during medical procedures, diagnostics and surgeries; or the term “disease” is mean any human medical conditions / diseases / disorders / syndromes are selected from:For animal diseases, corresponding classifications can be found in recognized catalogs such as the World Organisation for Animal Health (WOAH, formerly OIE) disease list, the Veterinary extension of the ICD (VetICD-10), SNOMED CT veterinary terminology, NADIS (UK), VeNom Coding Group, Vet-ICD-O-Canine-1, the USDA Animal Disease Information System, or other comparable classifications, each of which is incorporated herein by reference.

[0043] Terms described in the scientific and patent literature may be used to define the terms of the invention more broadly.II. COMPOUNDS OF THE PRESENT INVENTION.

[0044] Reference will now be made in detail to certain embodiments of the invention, examples of which are shown in the accompanying description, structures, and formulas. Although the invention will be described in connection with the embodiments listed, it will be understood that they are not intended to limit the invention to these embodiments. Rather, the invention is intended to encompass all alternatives, modifications, and equivalents that may be included within the scope of the present invention.

[0045] The compounds of the present invention may also exist in the form of physiologically acceptable salts. Examples of physiologically acceptable salts include salts derived from an appropriate base such as an alkali metal or alkaline earth metal (e.g., Na+, K+, Ca+2, Mg+2, Li+), ammonium and NR4+ (where R is defined herein). Physiologically acceptable salts of a nitrogen atom or amino group include (a) acid accession salts formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, sulfamic acid, phosphoric acid, nitric acid and the like; (b) salts formed by organic acids, such as, for example, acetic acidtartaric acid, maleic acid, fumaric acid, lysine, arginine, glutamic acid, glycine, serine, threonine, alanine, iso-leucine, leucine and the like, oxalic acid, salicylic acid, gluconic acid, citric acid, malic acid ascorbic acid, benzoic acid, succinic acid, isethionic acid, lactobionic acid, tannic acid, palmitic acid, alginic acid, malonic acid, naphthalenesulfonic acid, methane sulfonic acid, p-toluenesulfonic acid, naphthalenedisulfonic acid, polygalacturonic acid, sulfosalicylic acid, glycolic acid, 2- hydroxy-3 -naphthoate, pamoate, stearic acid, phthalic acid, mandelic acid, lactic acid, ethane sulfonic acid,; and (c) salts formed from element anions, e.g., chlorine, bromine, and iodine. Physiologically acceptable salts of a hydroxy group compound include the anion of said compound in combination with a suitable cation such as Na+ and NR4+. All such forms are contemplated within the scope of the invention.

[0046] Compounds of the invention have the ability to exist as various polymorphs or pseudopolymorphs. As used in this document, crystalline polymorphism refers to the ability of a crystalline compound to exist in different crystal structures. Crystalline polymorphism can result from differences in crystal packing (packing polymorphism) or from differences in packing between different conformers of the same molecule (conformational polymorphism). As used herein, crystalline pseudopolymorphism refers to the ability of a compound hydrate or solvate to exist in different crystal structures. Pseudopolymorphs of the present invention may exist because of differences in crystal packing (packing pseudopolymorphism) or because of differences in packing between different conformers of the same molecule (conformational pseudopolymorphism). All such forms are considered to be within the scope of the invention.

[0047] The compounds of the invention can also exist as amorphous solids. As used herein, an amorphous solid is a solid in which there is no long-range ordering of atoms in the solid. This definition also applies when the crystal size is two nanometers or less. Additives, including solvents, can be used to create the amorphous forms of the present invention. All such forms are contemplated within the scope of the invention.

[0048] For therapeutic use, the active ingredients of the compounds of the invention will be physiologically acceptable. Ingredients that are not physiologically acceptable, however, may also find use, such as in the preparation or purification of a physiologicallyacceptable compound.

[0049] Lastly, it is to be expected that the compositions presented herein include the compounds of the invention in their non-ionized as well as zwitterionic forms, and combinations with stoichiometric amounts of water, as in hydrates. All such forms are contemplated within the scope of the invention.

[0050] It should be noted that all enantiomers, diastereomers and racemic mixtures, tautomers, polymorphs, pseudopolymorphs of compounds are included in the scope of the present invention. All mixtures of such enantiomers and diastereomers are included in the scope of the present invention.

[0051] The compounds of the invention can have chiral centers, such as chiral carbon or phosphorus atoms. Thus, the compounds of the invention include racemic mixtures of all stereoisomers, including enantiomers, diastereomers, and atropisomers. Additionally, the compounds of the invention include enriched or resolved optical isomers on any or all asymmetric chiral atoms. Other words, the chiral centers evident from the figures are presented as chiral isomers or racemic mixtures. Racemic and diastereomeric mixtures as well as individual optical isomers isolated or synthesized essentially free from their enantiomeric or diastereomeric partners are within the scope of the invention. Racemic mixtures are divided into their individual, essentially optically pure isomers by well-known methods, such as, for example, separation of diastereomeric salts formed with optically active excipients, such as acids or bases, followed by conversion back to optically active substances. In most cases, the desired optical isomer is synthesized by stereospecific reactions starting from the corresponding stereoisomer of the desired starting substance. All such forms are provided within the scope of the invention.

[0052] The compounds of the invention may in some cases exist as tautomeric isomers. While only one delocalized resonance structure may be depicted, all such forms are considered within the scope of the invention.

[0053] Any formula or structure herein is also intended to represent unlabeled forms and isotopically labeled forms of compounds. Isotopically labeled compounds have the structures represented in the formulas provided herein except that one or more atoms are replaced with an atom of a selected atomic mass or mass number. Examples of isotopes that may be included in the compounds of the disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine and chlorine such as 2H (deuterium, D), 3H (tritium), SS, 13C, 14C, 1SN, 18F, 3 IP, 32P, 35S, 36C1 and 1251, but without limitation. Different isotopically labeled compounds of the present disclosure, such as those incorporating radioactive isotopes such as 3H, 13C and 14C. All such forms are provided within the scope of the invention. Such isotopically labeled compounds can be useful in metabolic studies, reaction kinetic studies, detection or imaging techniques such as positron emission tomography (PET) or single photon emission computed tomography (SPECT), including tissue distribution analyses of drugs or substrates, or in the radioactive treatment of patients. The disclosure also includes compounds of Formula I in which 1 to n hydrogens attached to the carbon atom are substituted with deuterium, where n is the number of hydrogens in the molecule. These compounds exhibit increased resistance to metabolism and thus are useful for increasing the half-life of any compound of formula I when administered to a mammal, particularly a human.

[0054] The compounds of the present invention may also exist in the form which described in the scientific and patent literature.III. KEY METHODS AND CONCEPTS OF THE PRESENT INVENTION

[0055] A key part of the invention is to modify the properties of API by creating an API -carrier system (non-exclusive examples of such systems include: solid dispersion of API-carrier, solution of API-carrier, emulsion (microemulsion) of API-carrier ( when API and carrier are in co- or different phases), gel of API-carrier, non-covalent complex of API- carrier, inclusion complex of API-carrier, supramolecular complex of API-carrier, conjugate of API-carrier, etc. in which occurs: a. increasing the solubility of the API by homogenizing and dispersing it in the carrier; b. creation or strengthening of non-covalent interaction and / or intercalation between API and carrier, including by organizing additional (excessive) non-covalent interaction (including non-equilibrium) or creating supramolecular or inclusion complex bonds; c. organization of covalent interaction between API and carrier - conjugation of carrier API; d. increasing the permeability of the API-carrier system due to one of several possible mechanisms; and associated changes in biophysical, pharmacological, toxicological and therapeutic properties of the API-carrier system compared to API, including due to formation of new non-covalent or conjugated molecular structures between API and carrier.

[0056] Carriers plays major role in formulation of solid dispersion. They can be hydrophilic or hydrophobic or water swellable. Depending on their characteristics they can be used as release retardant or release enhancers. Also the dissolution characteristics of drug molecules are depend on nature of carriers. The criteria for selection of best carrier: a. It should be water soluble or swellable, soluble in variety of solvents. b. It should be economical, pharmacologically inert, non-toxic. c. It should be heat stable. d. Chemically compatible with drug. e. Water soluble and non-water soluble carriers must prevent the recrystallization trend and help to maintain the supersaturation state after dissolution (spring and parachute effect) via hydrogen bonding interaction f. It should form a non-viscous solution, as the most commonly used polymers tend to form viscous solutions after dissolution in water, which delays the release of the drug from their matrix. Moreover, these polymers are metabolized in the gastrointestinal tract and release the drug primarily in the colon (Sinh V. R. et al., 2001).

[0057] Polymers those are derived from plant origin are used in the current invention because of their diverse pharmaceutical applications and also easy availability, biocompatibility, non-toxic nature, chemically inertness they are preferred over the synthetic ones. Polysaccharide, one of the most abundant industrial raw materials are used because of their sustainability, bio-safety and bio-degradability. The natural gums are metabolic byproducts of plants obtained from various parts of plant like seed, fruit, incised trunk (gummy exudate), etc. Natural polysaccharides are biodegradable, biocompatible materials for use in drug delivery systems. However, these materials have certain limitations, like uncontrolled rate of hydration, change in viscosity during shelf life, microbial contamination. Therefore to overcome this problems some modification have done. Modifications can be done in terms of physical modifications and chemical modifications.Molecular / Solid dispersions (SD)

[0058] Molecular / Solid dispersion of the invention can be defined as the dispersion of one or more active ingredients in an inert carrier or matrix at solid state prepared by the melting / fusion, solvent, melting-solvent method, mechanochemical treatment and other methods. The drug is hydrophobic in nature whereas matrix is hydrophilic. Solid dispersions of the present invention may be in the form of molecular dispersions, simple eutectic mixtures, solid solutions, glass solutions and glass suspensions, mechanochemically obtained solid dispersions (including solid dispersions in the form of micro- mechanocomposites in which solid-phase fusion, mechanosynthesis, mechanoactivation processes have occurred), amorphous precipitation in a crystalline carrier, compound or complex formations. Solid dispersions of the present invention may be in the form of first generation solid dispersions; second generation solid dispersions; third generation solid dispersions; fourth generation solid dispersions. Solid dispersions of the present invention may be in the form of: Class C-C, Class C-A, Class A-C, Class A-A, Class M-C, Class M-A based on physical state and molecular arrangement of both API and carrier. Molecular / Solid dispersions of the present inventions includes inclusion complexes and supramolecular complexes (that can present in solid phase) that can present in form of solid solution in which molecules of one compound (API, carrier) occupy places in the crystal lattice of another compound (API, carrier) or in which one compound (carrier) spatially encloses another (API). Thus in solid dispersions of the invention not only mixing at the molecular level but also complexation can take place.Table 3. Classification According to Physical State and Molecular Arrangement of API and CarrierClass API (active pharmacal ingredient) CarrierC-C Crystalline CrystallineC-A Crystalline AmorphousA-C Amorphous CrystallineA-A Amorphous AmorphousM-C Molecularly dispersed CrystallineM-A Molecularly dispersed Amorphous

[0059] Many analytical and instrumental technique are used to characterize solid dispersions. Techniques used for characterization are can be thermal methods, spectroscopic methods, microscopic methods, microthermal analysis, macroscopic techniques, etc. Just a mixture of substances, without treatment of the active pharmaceutical ingredient and carrier, does not lead to the results that solid dispersion leads to. Solid dispersion is not a mixture of synergists that amplify each other's effects. Solid dispersion is not a type of nanoparticle.

[0060] The present invention proposes to destroy the crystallinity of the phase, the phase itself and the phase boundaries of API and to form chemical bonds (including hydrogen bonding, van der Waals bonding, donor-acceptor bonding, 71-71 bonding, Iondipole bonding and ion-induced dipole bonding, ionic bonding, hydrophobic bonding and others) between API molecules and the carrier or by creating supramolecular or inclusion complex bonds between API molecules and the carrier and thereby change the properties ofAPI by forming new compounds from it. A number of methods are used for this, generally referred to as "Solid Dispersion Methods" and subdivided into a number of sub-methods, all of which involve molecular mixing and disordered phase processes of the components at the molecular level and create a homogeneous / highly dispersed phase with many chemical interactions between the API and the carrier. All of these processes are described in the literature.

[0061] The methods for obtaining molecular / solid dispersions of the present invention include 1) solvent evaporation and cryogenic methods; 2) melting methods andhot-stage extrusion methods; 3) mechanochemical methods (but not excluding other methods). Particle size of solid dispersion may vary and depends on the equipment device (e.g. nozzle size), equipment operation parameters, the degree of grinding of the finished product. The usual particle size is 0.5-1000 microns, but can exceed 1000 microns, and the resulting solid dispersion can also be ground to submicron size after it is obtained.

[0062] The solvent evaporation method consists of the solubilization of the drug and carrier in a volatile solvent that is later evaporated. In this method, the thermal decomposition of drugs or carriers can be prevented, since organic solvent evaporation occurs at low temperature. Differences in solvent evaporation processes are related to the solvent evaporation procedure, which usually include vacuum drying, heating of the mixture on a hot plate, slow evaporation of the solvent at low temperature, the use of a rotary evaporator, a stream of nitrogen, spray-drying, freeze-drying, the use of supercritical fluids (SCF) and other types of solvent evaporation.

[0063] Melting method consisting of melting the drug within the carrier followed by cooling and pulverization of the obtained product. In the melting process, the molecular mobility of carrier is high enough to change the drug’s incorporation. A common adaptation to the melting phase consists of suspending the active drug in a previously melted carrier, instead of using both drug and carrier in the melted state, reducing, therefore, the process temperature. To cool and solidify the melted mixture, several processes such as ice bath agitation, stainless steel thin layer spreading followed by a cold draught, solidification on petri dishes at room temperature inside a dessicator, spreading on plates placed over dry ice, immersion in liquid nitrogen or stored in a dessicator, and other types of cooling were used. After cooling, the mixture must be pulverized regarding its handling. However, the use of high temperatures, and the fact that several drugs can be degraded by the melting process, can be a limitation of this method. The incomplete miscibility between drug and carrier that may occur, because of the high viscosity of a polymeric carrier in the molten state, is another limitation of this process. To avoid the melting method limitations, several modifications, like hot-stage extrusion, Meltrex, melt agglomeration or other were introduced to the original method.

[0064] The mechanochemical method of obtaining molecular / solid dispersions consists in intensive mechanical processing (for example, in planetary or other types of mills) under conditions where the processes of solid-phase fusion, mechanosynthesis, mechanoactivation occur between the components, including the formation of microcomposites, in which the processes of mechanochemical solid-phase fusion / melting of the guest substance with the host substance, mechanosynthesis, mechanoactivation have occurred, when the mixing of components results in a reaction in the solid phase, forming products that have high contact surface and extremely high concentration of defects of various kinds. The formation of the interfacial surface, which is necessary for the realizationof physic-chemical interaction, takes place. Under these conditions, the characteristic time of mass transfer of reagents to each other for the passage of the physio-chemical reaction decreases. Simultaneously with comminution and formation of mechanochemically obtained solid dispersions, additional structural defects are created in the mixture components. In the macroscopic approximation, the activation barrier of chemical interaction decreases. As a rule, the longer the mechanical processing time, the higher the bioavailability and permeabilityof the resulting solid dispersions, while the particle size can remain practically unchanged.

[0065] At the initial stage of mechanochemical processing the initial collisions of powder particles with balls lead to plastic deformation of particles and their flattening. Continued plastic deformation is accompanied by an increase in the ratio of the surface area of the particles to their volume. In the process of deformation of the particles the pure inner layers of the active pharmaceutical ingredient are opened, which come into close contact with the pure layers of the other component, causing the process of welding. The accompanying plastic deformation hardening reaches a critical value and the formed object is destroyed. The three processes - plastic deformation, welding and fracture of the machined particles - are then repeated many times in parallel. In the process, the material acquires a layered, twisted structure. At the end of the initial fusion stage, a mixed heterophase system called a mechanocomposite is formed. The mechanocomposite has a morphologically metastable structure with a high density of interphase boundaries between the initial components, which provide a developed contact surface and a high concentration of defects due to the large number of atoms on the surfaces and in the near-surface layers. Such a system has a large stored energy, which, together with the extremely large contact surface between the components, provides a high reactivity of the system. At the same time, despite the almost perfect contact surface of the reagents in the matrix, large inclusions of the more brittle component in contact with the plastic reagent can be observed in the volume of the mechanocomposite.

[0066] The method of mechanochemical processing leads to the same results as the other methods, but excludes toxic solvents or thermal degradation processes of the active pharmaceutical ingredient.

[0067] Solid dispersions of the invention include solid phase inclusion complexes and solid-state supramolecular inclusion complexesin which API molecules are intercalated into the cavity.

[0068] Co-treating method of solid dispersion of the present invention can be selected from (but not excluding other methods, which should lead to the formation of the bioavailable solid dispersion):Method 1 (Mechanochemical Method; Grinding / Milling With High Energy Stress): “guest drug” and the “host substance” are milled in a roller, ball, planetary, vibratory, jet, drum, medium-speed, impact-jet, centrifugal countercurrent, rotary, disintegrator, and other types of mills or other grinders with controlled energy stress. The grinding process may produce particles of a size of mainly 0.5 to 1000 microns, which are powders. Grinding should be carried out to such a state that there are changes in the structure and properties of the ground substance so that it has increased bioavailability and permeability and bioavailable highlypermeable molecular / solid dispersion or solid phase non-covalent, inclusion, supramolecular complex is formed. Grinding should cause structural changes such as defects, increased deformation, associates. In the grinding process any of the processes of solid-phase fusion, mechanochemical synthesis, mechanosynthesis, mechanoactivation must occur and including the formation of microcomposites in which the processes of mechanochemical solid-phase fusion of the guest substance with the host substance, mechanosynthesis, mechanoactivation have occurred, when the mixing of components occurs reaction in the solid phase, forming products (including solid phase non-covalent, inclusion, supramolecular complexes) that have high contact surface and extremely high concentration of defects of various kinds. The solvent(s) may be added to the grinding process.Method 2 (Grinding / Milling With High Energy Stress and Solvent; Mechanochemical Method With Solvent): “guest drug” and the “host substance” are wetted with a solvent, the wetted mass is dried and then ground in the same manner as described in Method 1. The list of solvents used is the same as the solvents listed in Method 1 ;Method 3 (Media Milling): The solid dispersion is prepared by using high-shear media mills. The milling chamber charged with milling media, solvent, “guest drug”, and “host substance” is rotated at a very high-shear rate under controlled temperatures. The milling medium is composed of glass, zirconium oxide, highly cross-linked polystyrene resin or other standart milling medium. High energy shear forces are generated as a result of the impaction of the milling media with the “guest drug” and “host substance”. The list of solvents used is the same as the solvents listed in Method 1;Method 4 (Kneading Method): This method is based on impregnating the “host substance” with a little amount of water or hydroalcoholic solutions to convert it into a paste. The «guest drug» is then added to the above paste and kneaded for a specified time. The kneaded mixture is then dried and passed through a sieve if required. On a laboratory scale, kneading can be achieved by using a mortar and pestle. On large scale, kneading can be done by utilizing extruders and other machines;Method 5 (Hot-Melt Method, Melting Method, Fusion Method): In this method, the physical mixture of «guest drug» and a “host substance” are heated directly until the two melt. The melted mixture is then cooled and solidified rapidly with rigorous stirring. The final solid mass is then crushed, pulverized, and sieved. The melting method consists of melting the «guest drug» within the “host substance” followed by cooling and pulverization of the obtained product. A common adaptation to the melting phase consists of suspending the «guest drug» in a previously melted “host substance”, instead of using both «guest drug» and “host substance” in the melted state, reducing, therefore, the process temperature. To cool and solidify the melted mixture, several processes such as ice bath agitation, stainless steel thin layer spreading followed by a cold draught, solidification on petri dishes at room temperature inside a desiccator, spreading on plates placed over dry ice, immersion in liquid nitrogen or stored in a desiccators or other cooling method were used. After cooling, the mixture must be pulverized regarding its handling. KinetiSol® dispersing technology also can be used;Method 6 (Hot-Melt Extrusion, Hot-stage extrusion): Hot-Melt Extrusion is a modification of the Melting Method. Hot-melt extrusion is essentially the same as the melting method except that intense mixing of the components is induced by the extruder. Hot-stageextrusion consists of the extrusion, at high rotational speed, of the «guest drug» and “host substance”, previously mixed, at melting temperature for a small period of time. The resulting product is then collected after cooling at room temperature and milled. A reduction in processing temperature can be achieved by the association of hot-stage extrusion with the use of carbon dioxide as a plasticizer;Method 7 (Meltrex Method): Meltrex is a modification of the Melting Method. Meltrex is a patented solid dispersion manufacturing process, also based on the melting process. The crucial elements in the Meltrex technology are the use of a special twin screw extruder and the presence of two independent hoppers in which the temperature can vary over a broad temperature range;Method 8 (Melt agglomeration Method): Melt agglomeration is a modification of the Melting Method. Melt agglomeration allows the preparation of solid dispersions in conventional high shear mixers. It is made by adding the molten “host substance” containing the «guest drug» to the heated excipients, by adding the molten “host substance” to a heated mixture of «guest drug» and excipients, or by heating a mixture of the «guest drug», “host substance” and excipients to a temperature within or above the melting range of the “host substance”. It is also possible to produce stable solid dispersions by melt agglomeration in a rotary processor;Method 9 (High-Pressure Homogenization): In this method, the suspension of an «guest drug» and “host substance” is forced under pressure through a micro- or submicro- sized aperture valve of a high-pressure homogenizer;Method 10 (Solvent Evaporation Method): In this method dissolved both the «guest drug» and the “host substance” in a common solvent and then evaporate the solvent to produce a solid solution. A basic process of preparing solid dispersions of this type consists of dissolving the «guest drug» and the polymeric “host substance” in a common solvent or solvents mixture (the list of solvents used is the same as the solvents listed in Method 1). Normally, the resulting films are pulverized and / or milled. The use of the “host substances” partially suspended, instead of dissolved, was also can be used. Solvent evaporation procedure usually include vacuum drying, heating of the mixture on a hot plate, slow evaporation of the solvent at low temperature, the use of a rotary evaporator, a stream of nitrogen, or other drying procedure;Method 11 (Spin-coated films Method): Spin-coated films method is a modification of the Solvent Evaporation Method, which consists of dissolving «guest drug» and “host substance” in a common solvent that is dropped onto a clean substrate highly spinned. The solvent is evaporated during spinning;Method 12 (Spray-drying Method): Spray-drying is a modification of the Solvent Evaporation Method. It consists of dissolving or suspending the «guest drug» and “host substance”, then spraying it into a stream of heated airflow to remove the solvent;Method 13 (Supercritical Fluid (SCF) Process): Supercritical Fluid Process is a modification of the Solvent Evaporation Method. In this method, the «guest drug» particles are solubilized within the SCF (usually carbon dioxide). Several methods of SCF processing can be used to address individual aspects, such as precipitation with a compressed antisolvent process (PCA), solution enhanced dispersion by SCF (SEDS), supercriticalantisolvent processes (SAS), the rapid expansion of supercritical solutions (RESS), gas antisolvent recrystallization (GAS), and aerosol supercritical extraction system (ASES). In this method modification, the technique consists of dissolving the «guest drug» and the “host substance” in a common solvent that is introduced into a particle formation vessel through a nozzle, simultaneously with CO2. When the solution is sprayed, the solvent is rapidly extracted by the SCF, resulting in the precipitation of solid dispersion particles on the walls and bottom of the vessel;Method 14 (Cryogenic Techniques): Cryogenic methods are methods in which a solution of «guest drug» and “host substance” in a common solvent is frozen before a low-temperature solvent evaporation procedure. The common solvent can be the same as in the Solvent Evaporation Method. Freezing of the solution can occur after injection. The type of injection device can be a capillary, rotary, pneumatic, ultrasonic nozzle, or other types of the injection device. The location of the nozzle can be above or under the cryogenic liquid level. The composition of cryogenic liquid can be hydrofluoroalkanes, fluorocarbons, N2, Ar, 02, organic solvents, or other types of cryogenic liquid. After cryogenic processing, dry powder can be obtained by various drying processes like spray freeze drying, atmospheric freeze drying, vacuum freeze drying, lyophilization, or other low-temperature drying processes. The list of common solvents used is the same as the solvents listed in Method 1;Method 15 (Lyophilization / Freeze-Drying Technique): Lyophilization Method is a modification of the Cryogenic Techniques. In this technique, the common solvent from the solution is eliminated through a primary freezing and subsequent drying of the solution containing both «guest drug» and “host substance” at reduced pressure. The basic freeze- drying process consists of dissolving the «guest drug» and “host substance” in a common solvent, which is immersed in cryogenic liquid until it is fully frozen. Then, the frozen solution is further lyophilized;Method 16 (Spray Freezing onto Cryogenic Fluids): This Method is a modification of the Cryogenic Techniques. In this technique, the «guest drug» and the “host substance” were dissolved in a common solvent and atomized above the surface of a boiling agitated cryogenic liquid refrigerant;Method 17 (Spray Freezing into Cryogenic Liquids (SFL)): This Method is a modification of the Cryogenic Techniques. It incorporates direct liquid-liquid impingement (by spraying) between the solution and cryogenic liquid to provide intense atomization into microdroplets. The frozen particles are then lyophilized to obtain dry and free-flowing micronized powders.Method 18 (Spray Freezing into Vapor over Liquid (SFV / L)): This Method is a modification of the Cryogenic Techniques. Freezing of «guest drug» solutions in cryogenic fluid vapors and subsequent removal of frozen solvent. During SFV / L the atomized droplets typically start to freeze in the vapor phase before they contact the cryogenic liquid. As the solvent freezes, the «guest drug» becomes supersaturated in the unfrozen regions of the atomized droplet.Method 19 (Ultra-Rapid Freezing): This Method is a modification of the Cryogenic Techniques. Application of «guest drug» solution to the solid surface of the cryogenic substrate leads to instantaneous freezing and subsequent lyophilization.Method 20 (Precipitation Technique, Co-precipitation Method): In the precipitation methodthe «guest drug» is dissolved in a solvent, which is then added to Non-solvent to precipitate the crystals. Non-solvent is added dropwise to the «guest drug» and “host substance” solution, under constant stirring. In the course of the non-solvent addition, the «guest drug» and “host substance” are co-precipitated to form micro-particles. In the end, the resulted micro-particle suspension is filtered and dried. The list of solvents used is the same as the solvents listed in Method 1.Method 21 (Microwave Irradiation Method): This method involves the microwave irradiation reaction between «guest drug» and complexing agent using a micro wave oven. The «guest drug» and “host substance” in a definite molar ratio are dissolved in a mixture of water and / or organic solvent in a specified proportion into a container. The mixture is reacted in the microwave oven. After the reaction completes, an adequate amount of solvent mixture is added to the above reaction mixture to remove the residual uncomplexed free «guest drug» and “host substance”. The precipitate so obtained is separated using a filter, and dried. The list of solvents used is the same as the solvents listed in Method 1.Method 22 (Energy Input Method): Method comprises the step of exposing a host substance and a «guest drug» to an energy input until a bioavailable highly permeable solid dispersion is formed of the «guest drug» as amorphous material entrapped in the host substance.Method 23 (Heat / Shear Energy Input Method): Method comprises the step of exposing a host substance and a «guest drug» to an energy input, whereby the energy input is heat and / or shear forces, until a bioavailable highly permeable solid dispersion is formed of the «guest drug» as amorphous material entrapped in the host substance.Method 24: Other methods - electrostatic spinning, electrostatic blowing, electrospraying film casting; gel entrapment technique, KinetiSol dispersing (KSD), drum drying, freeze- drying (FD), rotary evaporation (RE), spray congealing, co-precipitation (CP), co-grinding, spin-coated film (SCF), centrifuge vacuum drying (CVD), melt cooling and the like;Method 25: A method comprising - contacting an active pharmaceutical ingredient and a matrix “host substance” to form a solid dispersion under conditions sufficient to form a solid dispersion;Method 26 (Combined method): This method includes any combination of Methods 1-25.Methods 1-26 should lead to the formation of the bioavailable solid dispersion.

[0069] Others methods of obtaining of SD are described in the scientific and patent literature.Non-covalent complexes (NCC)

[0070] Non-covalent complex of the invention are molecular ensembles that, as a whole, have specific properties that differ from the environment and whose internal structure and form are determined by non-covalent interactions of atoms. This distinguishes noncovalent systems from molecular systems in which the structure is determined mainly by covalent interactions. Noncovalent complex are molecular complexes of two or more cationic, anionic or neutral molecules held together in a single system by hydrogen bonding, van der Waals interactions, donor-acceptor interactions, 71-71 interactions, ionic interactions, hydrophobic interactions. Noncovalent complex have the ability to form different architectures while the chemical composition of the system remains unchanged. Noncovalent complex of the invention consisting of at least two different components, generally a matrix (“host”, “host substance”, “carrier”, etc.) and a therapeutic agent (API, active pharmaceutical ingredient, drug, guest, “guest drug”, “guest drug compound”, “guest substance”, etc.). Many analytical and instrumental technique are used to characterize noncovalent complexes (spectroscopic methods, etc.). Noncovalent complexes play a particularly important role in biological systems, such as the transfer of molecules and ions across biological membranes. The rate of release of active pharmaceutical ingredient molecules from noncovalent complexes or conjugate can play a significant role in increasing bioavailability.

[0071] Non-covalent complexes of the invention include inclusion complexes in which API molecules are intercalated into the cavity, host-guest complexes, and supramolecular complexes.

[0072] Method of preparation of non-covalent active pharmaceutical ingredientcarrier complex of the present invention is selected from (but not excluding other methods, which should lead to the formation of the bioavailable non-covalent complex and which are described in the scientific and patent literature): a) Dissolving solid dispersion in solvent (usually water) to form the liquid solubilized noncovalent complex (to form solutions, gels, colloids, sols, suspensions, etc.) under conditions sufficient to form the liquid solubilized noncovalent complex; b) Liquid-phase method for obtaining a complex of carrier with API: a pre-prepared aqueous solution of the corresponding starting carrier and a solution of API in an organic solvent miscible with water, such as acetone, are mixed under stirring and heating to a temperature not exceeding 70°C, followed by holding under stirring at said temperature until a homogeneous solution is obtained with isolation of the obtained complex, possibly in the form of a crystalline solid suspension, which, if necessary, is further ground to obtain the product; c) Dissolving host substance and guest drug in solvent (usually ethanol or acetone) to form the liquid solubilized noncovalent complex; d) Host substance is placed in a flask and completely dissolved in ethanol. Then a guest drug is added to the flask. Water is slowly added to the solution and stirred for several hours;e) (a-d) when energy is supplied by any other means, such as (but not limited to)electromagnetic radiation, heat, mechanical action, sound, ultrasound, or in any of the ways described in the scientific and patent literature. As a non-limiting example, an example of exposure by mechanical and acoustic influence is given. Or non- covalent complex obtained by the interaction of aqueous or non-aqueous solutions of host substance and guest drug under conditions of mechano-acoustic and precipitation of the resulting complex with ethyl alcohol.

[0073] Others methods of obtaining of NCCare described in the scientific and patent literature.Conjugates (CON)

[0074] Another approach of the invention to improving drug performance and reducing toxicity is the conjugation to a polymeric carrier. Chemical conjugation of API to a water-soluble, biodegradable, and biocompatible polymer could present many advantages over presently available API formulations. Conjugation of an insoluble drug to a water- soluble biodegradable polymer may increase the water solubility of the drug, drug circulation time, and accumulation in the diseased tissue, resulting in an improved therapeutic effect and reduced toxicity.

[0075] Polysaccharides have high chemical stability. Because of the stability of polysaccharides, covalent linkages between therapeutic agents and polysaccharides can be achieved in organic solvents. This is a considerable advantage since some therapeutic agents have low water solubility. Working in nonaqueous media, water-labile linkages (e.g., esters) can be created between the therapeutic agent and the polysaccharide. In addition, polysaccharides do not denature at high temperature, and tolerate extremes of pH or in organic solvents.

[0076] Methods of preparation of conjugate of active pharmaceutical ingredient and carrier is selected from (but not excluding other methods, which should lead to the formation of the bioavailable CON):Method 1. API was conjugated to oxidized carrier in borate buffer solution, pH ~11, for 2- 48 h at room temperature. Pure water-soluble conjugates were obtained as lyophilized powder. The reduced conjugate where the drug is attached by a stable amine bond can be prepared by reducing the imine bond of the derivative using sodium borohydride. API was conjugated carrier in two steps: first, carrier was oxidized to dialdehyde carrier with potassium periodate in water at 25 °C and purified from the interfering oxidative anions (periodate and iodate) by passage through an ion-exchange column of Dowex-1 (Aldrich, Milwaukee, Wis.) in acetate form. Dowex-1 acetate was obtained by pretreating the commercial anion exchanger with 1 M acetic acid. The purified oxidized carrier solution was dialyzed through a 12,000-molecular-weight cutoff dialysis tubing (Medicell International, London, United Kingdom) against deionized water for 48 h at 4°C andlyophilized to dryness. In the next step, API was bound to the oxidized carrier by the formation of an imine bond between the primary amine bond of API and the aldehydes of the oxidized carrier. Conjugation occurred in 0.1 M borate buffer solution, pH 11, for 48 h under constant stirring. The imine conjugate was purified by dialysis and lyophilized to dryness. The imine (unreduced) conjugate was reduced to a more stable amine form by the addition of sodium borohydride powder (1.1 M NaBH-i / mol of saccharide units in the polymer) to the imine conjugate solution, with overnight stirring at room temperature. The amine (reduced) conjugate obtained was purified by dialysis and lyophylized as described above for the imine conjugate.Method 2. This method demonstrates the attachment of a API to a hydrolysis product of carrier.Preparation of the carrier Hydrolysis Product. Carrier (100 g) was dissolved in 37C water to give a 20% solution. In a separate container, NaOH (200 g) was dissolved in 37C water (5 L). Sodium borohydride (20 g) was dissolved in the NaOH solution, and the carrier solution was then added to this solution. Another 20 g of sodium borohydride was added to the reaction, and the reaction mixture was stirred at 37C for 15 min, whereupon the mixture was brought to pH 8.6 by the addition of concentrated cold HC1 4 °C.The solution was extensively dialyzed using 3000 molecular weight cut-off dialysis tubing. The dialysate was filtered through an 0.22 micron filter and lyophylized to give the carrier hydrolysis product as a white crystalline solid.Preparation of Carboxymethyl Carrier Hydrolysis Product. Fifty grams of the carrier hydrolysis product was dissolved in 200 mb of water. To this solution was added one mole of NaOH, followed by bromoacetic acid (70-275 mmols). The reaction was allowed to run for 90 min at 30C. At the end of the reaction, the solution was neutralized by the addition of 6N HC1. The product was then purified with extensive ultrafiltration using an appropriate filter, then lyophilized.Attaching the Therapeutic Agent. The coupling of API to the carboxymethyl hydrolysis product of carrier was performed in a two step process. To a mixture of ethylene diamine (2.5 mb), adenosine5-monophosphate (10 g), and 1 -hydroxybenzotriazole (HOBt, 3.7Eg) was added l-ethyl-3 -(3 -dimethylaminopropyl) carbodiimide (EDC, 15 g) over 3.5 h at 40C in 4 portions. The water was removed under vacuum and the product triturated with 50 mb of 2: 1 CH3CN / MeOH. The solid was washed with an additional 100 mb of acetonitrile and dried under vacuum at 50C. The solid was passed through a 2.5 cm x 25 cm column containing 100 mb of wet volume Amberlite IR- 120 (Na form) ion exchange resin. The fractions containing the product, ethylenediamine -APIwere combined and the water was removed under vacuum. The product was again triturated with 2: 1 acetone / MeOH, and washed with 100 mb of acetone. The product was dried under vacuum for 2 h at 50C.Bioavailability and permeability

[0077] In the present invention, bioavailable solid dispersions, bioavailable noncovalent complexes and conjugates are obtained and used. Bioavailable with respect to the solid dispersions, noncovalent complexes, or conjugat means at least one of the following:1) absolute, relative bioavailability of the solid dispersion, noncovalent complex, or conjugate of the active pharmaceutical ingredient is higher than that of the active pharmaceutical ingredient itself;2) concentrations, Cmax, AUC and other pharmokinetic parameters of active pharmaceutical ingredient and / or its metabolites in blood, plasma, organs, or tissues for the solid dispersion, noncovalent complex, or conjugate of the active pharmaceutical ingredient is higher than that of the active pharmaceutical ingredient itself.

[0078] Highly permeable solid dispersions, noncovalent complexes, or conjugates are obtained and used in the current invention. Highly permeable with respect to the solid dispersions, the noncovalent complexes, or conjugate of the present invention means at least one of them:1) the transfer of molecules, ions, metabolites of active pharmaceutical ingredient across the biological / cell membrane is improved for the solid dispersion or the noncovalent complex or conjugate of active pharmaceutical ingredient than for theactive pharmaceutical ingredient itself is presented;2) the transfer of molecules, ions, metabolites of active pharmaceutical ingredient across the Caco-2 cell line layer or other cell line layer (the intestinal epithelium cells layer, etc.) is improved for the solid dispersion, the noncovalent complex, or conjugate of active pharmaceutical ingredient than for theactive pharmaceutical ingredient itself is presented;3) intestinal permeabilityis improved for the solid dispersion, the noncovalent complex, or conjugate of active pharmaceutical ingredient than for theactive pharmaceutical ingredient itself is presented;4) reverse transport of API is impeded;5) metabolism is blocked and API accumulates in tissues;6) increase in permeability according to the methods used to determine permeability in The Biopharmaceutics Classification System.

[0079] Within the scope of the current invention, an increase in permeability, an increase in absorption, increase a concentration of an API in cells, tissues from solid dispersions, noncovalent complexes, or conjugates is achieved through the following mechanisms (but not excluding other mechanisms for increasing permeability):8) as a consequence of blocking / reducing the activity of CYP3A4 and / or P- glycoproteins, blocking / reducing the activity of other transmembrane carrier proteins, transporters, ABC transporters, enzymes, etc., by membrane interacting with carrier substance molecules (or carrier molecular part of NCC or conjugate);9) due to blocking / reduction of CYP3A4 and / or P-glycoprotein activity, blocking / reduction of activity of other transmembrane protein transporters, transporters, enzymes, etc., by carrier substance molecules interacting with the membrane due to adhesion of carrier substance molecules (or carrier molecular part of NCC or conjugate) tothe cellular layer. Such adhesion can lead to interaction with transporters domains located on the outer part of the cell membrane and block the action of the transmembrane transporter protein;10) due to a change in the structure of the cell membrane after the incorporation of carrier substance molecules(or carrier molecular part of NCC or conjugate) into this membrane, rather than due to adhesion;11) due to the direct effect of carrier substance molecules (or carrier molecular part of NCC or conjugate) on the intestinal epithelium cell membrane: it may consist in alteration of lipid bilayer properties, density of intercellular contacts or inhibition of transmembrane proteins of multidrug resistance;12) due to changes in hydrophilicity, hydrophobicity, or other biophysical properties of the non-covalent complex, or conjugate due to which changes in the parace llular transport of the non-covalent complex, or conjugates may occur;13) due to changes in hydrophilicity, hydrophobicity or other biophysical properties of the non-covalent complex, or conjugate due to which changes in the transmembrane transport of the non-covalent complex, or conjugates may occur (passive, active transport);14) due to adhesion to mucin. Carrier may form sufficiently strong bonds with mucin, which was demonstrated in an in vitro experiment using mucin from pig stomach. When comparing the adhesion index with mucin of several polysaccharides - hyaluronic acid, polysaccharide from tamarind seeds and AG, it was shown that AG has the greatest mucoadhesive property;15) other changes in the structure and properties of the membrane or other biophysical properties of the non-covalent complex, or conjugate, through other mechanisms that contribute to an increase in its permeability;16) other mechanism of increase in permeability that are described in the scientific and patent literature.Other possible formulations to increase bioavailability and permeability.

[0080] In alternative embodiments, API, AAPI, AANPI can be formulated in any way for the manufacture of drugs with enhanced bioavailability and permeability, solubility, reduced toxicity, (including drug delivery systems) and can be applied in a variety of forms including nanoparticles, microparticles, nanocomposites, microcomposites, composites, polymeric nanoparticles (PNPs), liposomes, freeze-dried liposomes, micelles, polymeric micelles, niosomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), nanoemulsions, microemulsions, emulsions, self-nanoemulsifying drug delivery systems (SNEDDS), nanocrystals, co-crystals, mesoporous silica nanoparticles (MSNs), dendrimers, ultradispersions, solid dispersions, solid amorphous dispersions, noncovalent complexes, complexes with polymer, complexes with biopolymer, host-guest complexes, inclusion complexes, solutions, solutions in fat / oil, solutions with cosolvent, solutions with surface active agent / surfactant, solutions with solubilizing agent, polymorphes, lipid-based systems, lipid-based formulations, lipid-based drug delivery systems (LBDDS), gels, colloids, sols, or in any form described in the scientific and patent literature for example or / and API, AAPI, AANPI can be obtained using methods ofPhysical A) Reduction Particle size modification a) Micronizationb) Nanosuspension,B) Modification of the crystal habitC) Solid dispersions a) Eutectic mixtures b) Solid solutions c) Amorphous solid solutions d) Glass solutions and glass suspension e) Cryogenic techniques.A) Change of pH,Chemical B) Use of buffer, modification C) Derivatization,D) Complexation,E) Salt formation.Miscellaneous A) Supercritical fluid process, methods B) Use of adjuvant like surfactant, solubilizers, cosolvency, hydrotropy, and novel excipients. and any of the ways described in the scientific and patent literature.Inflammaging as the Master Regulator of P-Catenin Fate

[0081] In particular, it concerns methods for regulating P-catenin nuclear translocation and controlling the inflammatory context (inflammaging) to:1. Treat or prevent cancer; and2. Promote cellular regeneration and epigenetic rejuvenation.P-catenin is a central component of the Wnt signaling pathway and plays a pivotal role in regulating cellular proliferation, sternness, and survival. However, hyperactivation of P- catenin can lead to oncogenesis. No unified model currently explains how P-catenin can simultaneously exhibit reparative and oncogenic effects depending on physiological conditions.The present invention is based on the discovery that the outcome of P-catenin activity — whether promoting repair / regeneration or oncogenesis — is determined by the inflammatory context (inflammaging). Factors defining inflammaging include:1. Levels of pro-inflammatory cytokines (e.g., IL-6, TNF-a, IL-11);2. Activity of TGF-p, NF-KB, STAT3 ;3. Accumulation of S A SP factors ;4. Mitochondrial dysfunction (ROS production, mtDNA leakage, cGAS-STING activation).The invention demonstrates that:1. Low inflammatory conditions: P-catenin translocates to the nucleus, activating reparative genes (Cyclin DI, survivin, Sox2, Nanog), thereby promoting cellular regeneration and rejuvenation.2. High inflammatory conditions: P-catenin switches to EMT and oncogenic programs, supporting survival of mutated cells and driving carcinogenesis.

[0082] Methods for Cancer Therapy. The invention provides methods comprising: a) Export of P-catenin from the nucleus of tumor cells using agents that inhibit its nuclear translocation, including but not limited to: ivermectin, niclosamide, and other Wnt / p-catenin inhibitors. b) Suppression of inflammaging by reducing activity of at least one of the following: TGF-P, NF-KB, STAT3, IL-6, TNF-a, SASP factors, ROS, and mitochondrial dysfunction, using agents including but not limited to:1. TGF-P inhibitors (e.g., RepSox);2. NF-KB inhibitors (aspirin, curcumin, proteasome inhibitors);3. STAT3 inhibitors (e.g., Stattic);4. Anti-IL-6 antibodies (e.g., tocilizumab);5. Anti-TNF agents (e.g., infliximab, etanercept);6. IL- ip inhibitors (e.g., canakinumab, anakinra);7. Anti-IL-11 antibodies;8. Anti-VEGFA agents (e.g., bevacizumab);9. Senolytics (dasatinib, quercetin, navitoclax);10. Antioxidants (NAC, mitochondria-targeted ROS scavengers, CoQlO, MitoQ, SkQl);11. Mitophagy activators (metformin, SIRT activators, AMPK agonists). c) (Optional) Metabolic therapy, including methionine restriction, glucose restriction, glutamine limitation, or administration of metabolic modulators (e.g., metformin, SIRT activators, rMETase) to enhance mitochondrial function, induce autophagy, and synergize with P-catenin modulation.

[0083] Methods for Epigenetic Reprogramming and Cellular Rejuvenation. The invention further provides methods comprising: a) Preconditioning to reduce inflammaging, using TGF-P inhibitors, metformin, senolytics, anti-IL-11 antibodies, or other suitable agents. b) Controlled nuclear translocation of P-catenin to activate repair, sternness, and regenerative programs. c) Subsequent nuclear export of P-catenin to stabilize cells in an anti -oncogenic state.Inflammatory Pathways, Factors, and Cytokines defining inflammation include:1. Signaling pathways and transcription factors: TGF-p, NF-KB, STAT3, SASP, ROS, cGAS- STING pathway, NLRP3 inflammasome2. Classical pro-inflammatory cytokines: IL-1 (a, P), IL-2, IL-6, IL-8, IL-12, IL-18, TNF-a, IFN-y, MCP-1, GM-CSF3. Additional cytokines regulating inflammation: IL-11, IL-17, IL-23, IL-27, IL-35, IL-374. Tumor progression and angiogenesis factors: VEGFA, CXCL12, HMGB15. Mitochondrial dysfunction contributing to inflammation:1. mtDNA leakage —> cGAS-STING activation2. Reduced mitophagy3. Increased ROS4. ETC impairmentTechnical Effects1. Creation of a universal model to control P-catenin-dependent cellular processes.2. Effective cancer therapy via P-catenin nuclear export + inflammaging suppression.3. Safe epigenetic reprogramming enabling cellular rejuvenation and lifespan extension.Examples of Implementation1. Administration of ivermectin with metformin and TGF-P inhibitor (RepSox) to treat colorectal cancer.2. Use of niclosamide with a senolytic and anti-IL-6 antibody for treatment of metastatic tumors.3. In vivo somatic cell rejuvenation: o Pre-treatment with senolytics and metformin o Induced nuclear translocation of P-catenin (e.g., forskolin, lithium) o Subsequent nuclear export of P-catenin (e.g., ivermectin).

[0084] Provided are the method for controlling cell fate and treating diseases associated with aberrant P-catenin activity, comprising:1. modulating p-catenin nuclear localization (wherein p-catenin nuclear localization modulator can be selected from any disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system or can be selected from any other pharmacologically acceptable p-catenin nuclear localization modulator), and2. reducing inflammaging by inhibiting at least one pro-inflammatory pathway, cytokine, or mitochondrial dysfunction factor,wherein said method results in safe induction of regeneration in non-malignant tissues or inhibition of oncogenesis in malignant tissues.In another embodiment, provided are the method, wherein said inhibition of inflammaging is achieved by suppressing one or more pathways selected from the group consisting of:1. TGF-P signaling,2. NF-KB signaling,3. STAT3 signaling,4. SASP (Senescence-Associated Secretory Phenotype),5. ROS production,6. cGAS-STING activation,7. NLRP3 inflammasome activation.In another embodiment, provided are the method, wherein said inhibition of inflammaging is achieved by reducing at least one pro-inflammatory cytokine selected from the group consisting of: IL-la, IL-ip, IL-2, IL-6, IL-8, IL-11, IL-12, IL-17, IL-18, IL-23, IL-27, IL-35, IL-37, TNF-a, IFN-y, MCP-1 (CCL2), GM-CSF, VEGFA, CXCL12, and HMGBl.

[0085] In another embodiment, provided are the method, wherein said reduction of inflammation is performed by administering at least one agent selected from:1. TGF-P inhibitors (including RepSox, SB431542, LY2157299, or any other TGF-P inhibitor disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG. 12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable TGF-P inhibitor),2. NF-KB inhibitors (including aspirin, curcumin, proteasome inhibitors, or any other NF-KB inhibitor disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG. 12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable NF-KB inhibitor),3. STAT3 inhibitors (including Stattic, BP-1-102, or any other STAT3 inhibitor disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG. 12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable STAT3 inhibitor),4. Anti-IL-6 antibodies (including tocilizumab, or other pharmacologically acceptable Anti-IL-6 antibody),5. Anti-TNF agents (including infliximab, etanercept, or other pharmacologically acceptable Anti-TNF agent),6. Anti-IL-ip agents (including canakinumab, anakinra, or other pharmacologically acceptable Anti-IL-ip agent),7. Anti-IL-11, Anti-IL-17, Anti-IL-23, Anti-IL-12, Anti-VEGFA antibodies,8. Senolytics (including dasatinib, quercetin, navitoclax, or any other Senolytic disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG. 12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable Senolytic),9. Antioxidants (including N-acetylcysteine, MitoQ, SkQl, coenzyme Q10, or any other Antioxidant disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG. 12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable Antioxidant),10. AMPK activators and SIRT activators (including metformin, resveratrol, NAD+precursors, or any other AMPK activator and SIRT activator disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG. 12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable AMPK activator and SIRT activator).In another embodiment, provided are the method,, further comprising direct modulation of [3- catenin nuclear translocation, wherein such modulation comprises:1. inhibiting [3-catenin nuclear entry for cancer therapy, or2. promoting [3-catenin nuclear entry for controlled regenerative purposes wherein [3-catenin nuclear translocation modulator can be selected from any disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG. 12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system or can be selected from any other pharmacologically acceptable [3-catenin nuclear translocation modulator).

[0086] In another embodiment, provided are the method, wherein inhibition of [3-catenin nuclear translocation is achieved by administering ivermectin, niclosamide, or any other [3-catenin nuclear translocation inhibitor that can be selected from any disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG. 12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system or can be selected from any other pharmacologically acceptable [3-catenin nuclear translocation inhibitor) or functional analogs thereof.In another embodiment, provided are the method, wherein promotion of [3-catenin nuclear translocation for regenerative purposes is achieved by agents selected from:1. GSK3 inhibitors (including lithium, CHIR99021, or any other GSK3 inhibitor disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG. 12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable GSK3 inhibitor),2. Forskolin or any other cAMP pathway activator disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG. 12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable cAMP pathway activator,3. Wnt agonists (any Wnt agonist disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable Wnt agonists),4. Small molecules activating [3-catenin stability.

[0087] In another embodiment, provided are the method, wherein said regenerative or anti-aging therapy further comprises:1. induction of mitophagy and autophagy to reduce mitochondrial dysfunction,2. reduction of senescent cell burden,3. metabolic modulation to reduce insulin resistance and vascular inflammation.In another embodiment, provided are the method, wherein said therapy is applied in the context of epigenetic reprogramming, and comprises:• (i) reducing inflammaging,• (ii) transiently activating [3-catenin nuclear entry to induce regenerative gene expression,• (iii) subsequently inhibiting [3-catenin nuclear entry to minimize oncogenic risk.In another embodiment, provided are the method, wherein said method is applied for the treatment or prevention of a disease selected from:1. cancer,2. age-related degenerative disease,3. fibrosis,4. metabolic syndrome,5. neurodegenerative disease,6. cardiovascular disease,7. immune senescence,8. any other disease.

[0088] In another embodiment, provided are the method, wherein one or more agents used for modulation of [3-catenin or inhibition of inflammaging are provided in the form of:1. a non-covalent complex,2. a molecular dispersion,3. a solid dispersion,4. a conjugate with a polymer, lipid, nanoparticle, antibody, peptide, or nucleic acid, thereby enhancing solubility, bioavailability, stability, or tissue-specific delivery of said agent.The composition for use in the previous method, wherein the agents selected from ivermectin, niclosamide, metformin, RepSox, TGF-J3 inhibitors, NF-KB inhibitors, senolytics, antioxidants (selected from any TGF-P inhibitors, NF-KB inhibitors, senolytics, antioxidants disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG. 12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system or other pharmacologically acceptable TGF-P inhibitors, NF-KB inhibitors, senolytics, antioxidants), or combinations thereof are formulated as a non-covalent complex, solid dispersion, or conjugate for oral, intravenous, intranasal, or local administration.

[0089] In another embodiment, provided are the method, wherein said therapy comprises a combination of:1. (i) at least one [>-catcnin nuclear translocation inhibitor or activator (selected from any [>- catenin nuclear translocation inhibitor or activator disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG. 12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system or other pharmacologically acceptable [S-catcnin nuclear translocation inhibitor or activator), and2. (ii) at least one inflammaging-reducing agent selected from TGF-[> inhibitors, NF-KB inhibitors, STAT3 inhibitors, senolytics, anti-cytokine antibodies, antioxidants, or metabolic modulators (selected from TGF-[> inhibitors, NF-KB inhibitors, STAT3 inhibitors, senolytics, anti-cytokine antibodies, antioxidants, or metabolic modulators disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG. 12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system or other pharmacologically acceptable TGF-[3 inhibitors, NF-KB inhibitors, STAT3 inhibitors, senolytics, anti-cytokine antibodies, antioxidants, or metabolic modulators), administered simultaneously, sequentially, or as a fixed-dose combination.The composition for use in the previous method, wherein said [3-catenin modulator and inflammaging- reducing agent are co-formulated in:1. a single dosage form,2. a non-covalent complex,3. a solid dispersion,4. a nanoparticle, liposome, or polymeric conjugate, providing synergistic therapeutic effect for treatment of cancer, prevention of oncogenesis, or induction of safe regenerative programs.In another embodiment, provided are the method, wherein said therapy further comprises metabolic intervention selected from the group consisting of:1. administration of methioninase (rMETase),2. dietary methionine restriction,3. dietary glucose restriction or ketogenic diet,4. glutamine restriction,5. inhibition of glycolysis, glutaminolysis, or one-carbon metabolism, wherein such metabolic intervention synergizes with [3-catenin modulation and inflammaging reduction to suppress tumor growth and progression.

[0090] In another embodiment, provided are the method, wherein methioninase (rMETase) is administered in combination with at least one agent selected from ivermectin, niclosamide, metformin, RepSox, or a TGF- inhibitor, or any other compound disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG. 12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system to simultaneously reduce P-catenin oncogenic activity, lower inflammaging, and deprive tumor cells of metabolic substrates.The composition for use in any of methods, wherein P-catenin modulator(s), inflammaging- reducing agent(s), and metabolic therapy agent(s) are formulated as:• a co-formulated pharmaceutical composition,• a non-covalent complex, molecular or solid dispersion, or delivery system, for synergistic cancer therapy.In another embodiment, provided are the method, wherein the therapy further comprises stimulation of mitophagy and autophagy, by administering at least one agent selected from the group consisting of:1. SIRT activators (including SIRT1 activators such as resveratrol, NAD+precursors, or any other SIRT activator disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable SIRT activator),2. AMPK activators (including metformin, AICAR, or any other AMPK activator disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG. 12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable AMPK activator),3. mitophagy-inducing natural products (including urolithin A, or any other mitophagy -inducing natural product disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof,together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable mitophagy -inducing natural product), mTOR inhibitors (including rapamycin, or any other mTOR inhibitor disclosed in (

[0091] (GUESTs),

[0095] (active pharmaceutical ingredient),

[0110] (AAPIs),

[0111] (AAPIs),

[0114] (AANPIs), and those listed in from FIG. 12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable mTOR inhibitor), and pharmacologically acceptable analogs or derivatives thereof, wherein said stimulation synergizes with [3-catenin modulation and inflammaging reduction to promote safe cellular regeneration, enhance mitochondrial function, and suppress oncogenic processes.IV. NON-COVALENT COMPLEXES, SOLID DISPERSIONS AND CONJUGATESOF THE INVENTION

[0091] [Ref-0091] Provided are the non-covalent active pharmaceutical ingredientcarrier complex (of Formula I)[GUEST]k- [HOST]n-(H2O)m with enhanced permeability and / or bioavailability properties for treating diseases in a human or animal or mammal or bird as well as for manufacturing a pharmaceutical dosage form to treat disease a human or animal or mammal or bird in need thereof (by administering a therapeutically effective amount), at a dosage ranging from 0.0001 ng / kg to 100000 mg / kg (calculated for pure API) wherein said dosage provides improved therapeutic efficacy; wherein the non-covalent complex has enhanced permeability (into the internal organs and tissues of the person receiving the drug) and bioavailability properties; wherein the therapeutic efficacy of the non-covalent complex is enhanced by enhanced permeability, which allows for rapid achievement of the required concentration in the organs and tissues of the patient; wherein k is 1 to 100; wherein n is 1 to 10000; wherein m is 1 to 100000; wherein GUEST isi.e. GUEST is Ibrutinib;i.e. GUEST is Enzalutamide;i.e. GUEST is Lenvatinib;i.e. GUEST is Dasatinib;i.e. GUEST is Venetoclax;i.e. GUEST is Abiraterone acetate;wherein1) Ri is CH3 ; R2 is CH2CH3 ; X-Y is CH=CH ; (i.e. GUEST is Avermectin Ala);2) Ri is CH3 ; R2 is CH3; X-Y is CH=CH ; (i.e. GUEST is Avermectin Alb);3) Ri is CH3 ; R2 is CH2CH3 ; X-Y is CH2-CHOH ; (i.e. GUEST is Avermectin A2a);4) Ri is CH3 ; R2 is CH3; X-Y is CH2-CHOH ; (i.e. GUEST is Avermectin A2b);5) Ri is H ; R2 is CH2CH3 ; X-Y is CH=CH ; (i.e. GUEST is Avermectin Bia);6) Ri is H ; R2 is CH3; X-Y is CH=CH ; (i.e. GUEST is Avermectin Bib);7) Ri is H ; R2 is CH2CH3 ; X-Y is CH2-CHOH ; (i.e. GUEST is Avermectin B2a);8) Ri is H ; R2 is CH3; X-Y is CH2-CHOH ; (i.e. GUEST is Avermectin B2b);9) Ri is H ; R2 is CH2CH3 ; X-Y is CH2-CH2 ; (i.e. GUEST is Ivermectin Bia);10)Ri is H ; R2 is CH3; X-Y is CH2-CH2 ; (i.e. GUEST is Ivermectin Bib);11)Ri is CH3; R2is CH2CH3 ; X-Y is CH2-CH2 ; (i.e. GUEST is Ivermectin Ala);12)Ri is CH3; R2 is CH3; X-Y is CH2-CH2 ; (i.e. GUEST is Ivermectin Alb);wherein1) Ri is H ; R2is CH3 ; (i.e. GUEST is Milbemycin A3) ;2) Ri is H ; R2is CH2CH3; (i.e. GUEST is Milbemycin A4) ;3) Ri is H ; R2is CH(CH3)2; (i.e. GUEST is Milbemycin D) ;4) Ri is CH3; R2is CH3; (i.e. GUEST is Milbemycin B2) ;5) Ri is CH3; R2is CH2CH3; (i.e. GUEST is Milbemycin B3) ;6) Ri is CH3; R2is CH(CH3)2; (i.e. GUEST is Milbemycin G) ;wherein1) =R1is -H, (P)-OH ; =R2is -H, -H ; -R3is selected from -CH3, -CH2CH3(i.e. GUEST is Milbemectin);2) =R is =NOH ;=R2is -H, -H ; -R3is selected from -CH3, -CH2CH3(i.e. GUEST is Milbemycin oxime);3) =R is -H, (P)-OH ; =R2is =NOCH3; -R3is (Z)-C(CH3)=CH-CH(CH3)2; (i.e. GUEST is Moxidectin);4) =R is -H, (P)-OH ; =R2is -H, (a)-OH ; -R3is (Z)-C(CH3)=CH-CH(CH3)2; (i.e. GUEST is Nemadectin);wherein1) R is CH2CH3 ; (i.e. GUEST is TenvermectinB) ;2) R is CH3 ; (i.e. GUEST is TenvermectinA) ;(i.e. GUEST is Flubendazole);(i.e. GUEST is Oxfendazole); o)(i.e. GUEST is Mebendazole);(i.e. GUEST is Niclosamide);(i.e. GUEST is Colchicine);(i.e. GUEST is Quercetin);(i.e. GUEST is Resveratrol);(i.e. GUEST is thymoquinone);(i.e. GUEST is Pyrvinium); aa)(i.e. GUEST is Albendazole sulfoxide (S-oxide));(i.e. GUEST is Albendazole); ac) GUESTS selected from those listed in from FIG.12 to FIG.72.Below are the names of the compounds drawn on a particular page (for information purposes):FIG.12 :ABT-737; Linifanib (ABT-869); ABT-888 (Veliparib); Axitinib; Saracatinib (AZD0530); AZD6244 (Selumetinib); Nintedanib (BIBF 1120); Bosutinib (SKI-606); Dasatinib; Gefitinib (ZD 1839); Lenalidomide (CC-5013); Motesanib Diphosphate (AMG-706); Nilotinib (AMN-107); PD0325901; PI-103; Rapamycin (Sirolimus); Sorafenib Tosylate; Vorinostat (SAHA, MK0683); VX-680 (MK-0457, Tozasertib); Y-27632 2HC1; Elesclomol (STA-4783); Entinostat (MS-275, SNDX-275); Enzastaurin (LY317615); Obatoclax mesylate (GX15-070); Olaparib (AZD2281, Ku-0059436); Nutlin-3; Pictilisib (GDC-0941); SB 431542; Luminespib (AUY-922, NVP-AUY922); ZSTK474; SB 216763; MK-2206 dihydrochloride; SU11274; Vismodegib (GDC-0449); Belinostat (PXD101); Iniparib (BSI-201); Abexinostat (PCI-24781); KU-55933 (ATM Kinase Inhibitor); GSK1904529A; PF-04217903; Rucaparib (AG-014699, PF-01367338) phosphate; Vatalanib (PTK787) 2HC1; GDC-0879; LY294002; Danusertib (PHA-739358); BI 2536; JNJ-38877605; Everolimus (RAD001); TW-37; Mocetinostat (MGCD0103); SRT1720 HC1; MLN8237 (Alisertib); Andarine (GTX-007); 17-DMAG HC1 (Alvespimycin); SNS-032 (BMS-387032); Barasertib (AZD1152-HQPA); Paclitaxel (Taxol); Roscovitine (Seliciclib, CYC202) ; Capecitabine (Xeloda); ABT-751 (E7010); CYC116; JNJ 26854165 (Serdemetan); WZ4002; BIIB021; NPI-2358 (Plinabulin); XAV-939; ENMD-2076; BIBR1532; Anastrozole; Aprepitant (MK-0869)FIG.13 :Bicalutamide (Casodex); CUDC-101; Exemestane; Cladribine; Decitabine; Tivozanib (AV-951); Doxorubicin (Adriamycin) HC1; Adrucil (Fluorouracil); Abitrexate (Methotrexate); Clofarabine; OSI-930; Oxaliplatin (Eloxatin); Etoposide (VP-16)Etoposide; Ku-0063794; Evista (Raloxifene Hydrochloride); Topotecan HC1; 2 -Methoxy estradiol; Letrozole; Temozolomide; Amuvatinib (MP -470); JNJ-7706621; MDV3100 (Enzalutamide); Celecoxib; PD 173074; WYE-354; Vemurafenib (PLX4032, RG7204); Altretamine (Hexalen); Anagrelide hydrochloride ; Flutamide (Eulexin); Fluvastatin sodium (Lescol); Megestrol Acetate; Dexamethasone; Pelitinib (EKB-569); YM155 (Sepantronium Bromide); Zileuton; Ispinesib (SB-715992); Tipifamib (Zamestra); Zibotentan (ZD4054); Doxercalciferol (Hectorol); SB 525334; AEE788 (NVP-AEE788); PHA-793887; PIK-93; Ponatinib (AP24534); Mycophenolate mofetil (CellCept); SB939 (Pracinostat); MK-1775; Quizartinib (AC220); AZD7762; R406(free base); Febuxostat (Uloric); Dapagliflozin; AZD8055; EX 527; BMS 777607; KU-60019; BIRB 796 (Doramapimod); Tie2 kinase inhibitor; NVP-BSK805 2HC1; Mifepristone (Mifeprex); Ezetimibe (Zetia); Estrone; Disulfiram (Antabuse); Hydrocortisone (Cortisol); Unknown; DCC-2036(Rebastinib); Azathioprine (Azasan, Imuran); Azacitidine (Vidaza); Simvastatin (Zocor); Lomustine (CeeNU)FIG.14 :Tamoxifen Citrate (Nolvadex), Tamoxifen; Maraviroc; E7080 (Lenvatinib); LDE225 (NVP-LDE225, Erismodegib); Cyclophosphamide monohydrate; AG14361; Ixazomib Citrate (MLN9708); GSK461364; SGI- 1776 free base; BMS 794833; Formestane; DAPT (GSI-IX); Irinotecan HC1 Trihydrate (Campto); Momelotinib (CYT387); SB590885; (-)-Epigallocatechin gallate; Cyclosporin A; Phloretin; Chrysophanic acid (Chrysophanol); PCI-32765 (Ibrutinib); Turofexorate Isopropyl (XL335); AMG 900; Mitoxantrone 2HC1; Mycophenolic acid; Omipalisib (GSK2126458, GSK458); Fingolimod (FTY720) HC1; Toremifene Citrate (Fareston, Acapodene); CAL-101 (GS-1101); BI6727 (Volasertib); TAME; Telatinib (BAY 57-9352); Degrasyn (WP1130); BKM120 (NVP-BKM120); cx-4945 (Silmitasertib); GW3965 HC1; Galunisertib (LY2157299); TAK-733; MK-0752; GSK690693; LY2603618 (IC-83); GSK1120212 (Trametinib); PF-3845; PHA-665752; A-769662; KX2-391; YO-01027 (Dibenzazepine); Fedratinib (SAR302503, TG101348); AZ 3146; CH5132799; Flavopiridol (Alvocidib) HC1; PH-797804; Dacomitinib (PF299804, PF-00299804); INK 128 (MLN0128); Crenolanib (CP-868596); PAC-1; Lonidamine; AZ628; YM201636; 3 -Methyladenine (3- MA); BX-795; Unknown; RG108; Canagliflozin; Nocodazole; Tofacitinib (CP-690550, Tasocitinib); Sotrastaurin (AEB071); Sirtinol; Aminoglutethimide (Cytadren); Torin 2; CEP33779FIG. 15 :Daunorubicin HC1 (Daunomycin HC1); TPCA-1; GW 4064; Unknown; PF-562271; S-Ruxolitinib; PF 573228; SMI-4a; Unknown; OSI-906 (Linsitinib); GW9508; PF-4708671; NSC 23766; Necrostatin-1; Unknown; Sodium Phenylbutyrate; GSK3787; NU6027; SANT-1; Lomeguatrib; SKI II; Unknown; Vincristine Sulfate; FR 180204; MG149; Ruxolitinib (INCB018424); Temsirolimus (CCI-779, NSC 683864); GSK650394; Unknown; SecinH3; Crizotinib (PF-02341066); Combretastatin A4; gossypol-Acetic acid, AT101; BIX 01294; Bafetinib (INNO-406); Valproic acid sodium salt (Sodium valproate); SNS-314 Mesylate; Lapatinib (GW-572016) Ditosylate; Pazopanib HC1; AG-490 (Tyrphostin B42); NSC 74859 (S3I-201); CP- 724714; Fludarabine Phosphate (Fludara); Resveratrol; Fludarabine (Fludara); Dyphylline (Dilor); DMXAA (Vadimezan); Artesunate; Aminophylline (Truphylline); HER2 Inhibitor 1; GW788388; Lapatinib; SB- 505124; TAK-285; Istradefylline (KW-6002); WP1066; Bindarit; Tyrphostin AG 879 (AG 879); Palmatine chloride; AZD8931; Mubritinib (TAK 165); Cryptotanshinone; Hesperetin; Nobiletin (Hexamethoxyflavone); WHI-P154; Inosine; Pirfenidone; PF 477736; WZ 811; Sulfamethizole (Proklar)FIG. 16 :Pazopanib; Unknown; CGS 21680 HC1; Doxofylline; Nifuroxazide; Sulfamethoxypy ridazine; Afatinib (BIBW2992); ENMD-2076 L-(+) -Tartaric acid; AC480 (BMS-599626); Kynurenic acid; Balsalazide disodium; Nordihydroguaiaretic acid; Baohuoside I; Palmatine; 3,4',5-Trimethoxy-trans-stilbene; Alpha- Mangostin; LY2109761; Plerixafor 8HC1 (DB06809); LY364947; Chloroquine Phosphate; Unknown; Nicotinamide N-oxide; Tannic acid; Theophylline-7-acetic acid; Proxyphylline; Scutellarin; CI-1033 (Canertinib); CEP-32496; Plerixafor; Stattic; GW2580; Butein; Imiquimod; Neratinib (HKI-272); Ticlopidine hydrochloride; NLG919; Unknown; Epacadostat (INCB024360); FLLL32; Isoxazole 9 (ISX-9); BMS202 (PD-l / PD-Ll inhibitor 2); T0901317; SC144; RepSox; Dorsomorphin (Compound C) 2HC1; pimozide; K02288; LDN193189 HC1; ML347; DMH1; LDN-212854; HO-3867; SH-4-54; INCB024360 analogue; EW- 7197; Kartogenin; Hydroxychloroquine Sulfate; SB225002; Poziotinib (HM781-36B); SD-208; Indoximod (NLG-8189); BLZ945; Afatinib (BIBW2992) Dimaleate; LDN-214117; Pexidartinib (PLX3397); Dorsomorphin (Compound C); Napabucasin; Motolimod (VTX-2337); Resiquimod; SCH58261FIG. 17 :STA-21; BEC Hydrochloride; PD-l / PD-Ll inhibitor 1; Halofuginone; ZM241385; SIS3 HC1; ATI-2341; GS-9620; ZK756326 2HC1; Alantolactone; NT157; ARRY-380 (ONT-380); LM10; JNJ-42756493 (Erdafitinib); BP-1-102; eFT-508 (eFT508); SH5-07 (SH-5-07); AMD3465 hexahydrobromide; Atractylenolide I; DAPTA; AUNP-12; HJC0152; PRN1371; A2AR antagonist 1; Reparixin (Repertaxin); CA- 4948; PF-06840003; C188-9; IDO inhibitor 1; GO-203; Coptisine chloride; AS1517499; Cu-CPT22; Adenosine 5'-monophosphate monohydrate; DCC-2618; Saikosaponin D; Lanatoside C; Acetyl Resveratrol; Regadenoson; CAS: 1923833-60-6; TP0427736 HC1; Homoharringtonine; Fraxinellone; Erianin; Schaftoside; Isofraxidin; Lapatinib ditosylate monohydrate; SR1078; LY 3200882 ; LIT-927; AZ304; Unknown; Niclosamide; CCCP; AZD2098; MD2-IN-1; C-176 STING inhibitor; GSK2981278; BMS-1166; MSX-122; Danirixin (GSK1325756); AZD-5069; CPI-444; ITD-1; SR1001; IDO-IN-1; SCH-527123; PLX5622; E6446 (dihydrochloride); BIBF-0775FIG. 18 :H-151; SRI-011381; C-178; SX-682; PD 169316; STAT5-IN-1; TA-02; STING agonist-1 (G10); SB- 297006; Sulfatinib; SB?4; Tyrphostin AG-528; Ki20227; A-83-01; BMS-813160; SR 0987; SC-43; AUDA; APX-115 free base; STAT3-IN-1; SR-717?lithium; Cucurbitacin lib; Perillaldehyde; L-Quebrachitol; Kaempferol-3-O-rutinoside; Falcarindiol; TLR2-IN-C29; RCM-1; Preladenant; Cenicriviroc; 680C91; BMS- 1001; Motixafortide (BL-8040); Ticlopidine; SJ000291942; SU5204; SM 324405; Namodenoson (CF-102);AMG-9810; LY-3381916; Navoximod; Colivelin; MSA-2; CU-CPT9a; Chloroquine; BDTX-189; Canertinib dihydrochloride; AMG 487; Crizotinib hydrochloride; R243; Balsalazide; BD750; Linderalactone; MSX-127; MSX-130; SR3335; CU-CPT-8m; RS-102895 Hydrochloride; Bortezomib (Velcade); Cediranib (AZD2171); CI-1040 (PD184352); Deforolimus (MK-8669) ; Dovitinib (TKI-258, CHIR-258); Imatinib Mesylate (STI571); Panobinostat (LBH589); Dimesna; AR-42 (HDAC-42); STF-62247; Sunitinib Malate; Masitinib (AB 1010)FIG. 19 :SB 203580; SB202190 (FHPI); Brivanib (BMS-540215); NVP-ADW742; LAQ824 (Dacinostat); MLN8054; ZM-447439; BTZ043 racemate; OSU-03012 (AR-12); U0126-EtOH; Foretinib (GSK1363089, XL880); INO-1001 (3-Aminobenzamide); Cabozantinib (XL184, BMS-907351); AT9283; Malotilate; 17- AAG (Tanespimycin); Brivanib alaninate (BMS-582664); Ivacaftor (VX-770); Docetaxel (Taxotere); PLX- 4720; TGX-221; WZ3146; PD98059; Regorafenib (BAY 73-4506); WZ8040; Ritonavir; MK-2866 (GTx- 024); Fulvestrant (Faslodex); Raltitrexed (Tomudex); Dutasteride; Bendamustine HCL ; Nelarabine (Arranon); Dexrazoxane Hydrochloride; Epirubicin Hydrochloride; Agomelatine; Leflunomide; Dienogest; Nepafenac; Posaconazole; Ramelteon; AMG-073 HC1 (Cinacalcet hydrochloride); BMS-708163 (Avagacestat); Adapalene; Amisulpride; Aniracetam; Asenapine maleate; Benazepril hydrochloride; Bumetanide; Carmofur; Celastrol; Cetirizine Dihydrochloride; Diethylstilbestrol; Dapoxetine hydrochloride (Priligy); Antipyrine; Deflazacort (Calcort); Nizatidine; Valsartan (Diovan); Dipyridamole (Persantine); Hydroxyurea (Cytodrox); Nicotinamide (Vitamin B3); Diclofenac Sodium; Metronidazole (Flagyl); Sulfamethoxazole; Sulfisoxazole; Crystal violet ; Haloperidol (Haldol); Triamcinolone (Aristocort); Azilsartan Medoxomil (TAK-491); Prucalopride; CilostazolFIG. 20 :Epothilone A; Floxuridine; Tegafur (FT-207, NSC 148958); LY2886721; Ifosfamide; Mercaptopurine (6- MP); Streptozotocin (STZ); KH6425; Alizarin; Costunolide; Doxazosin mesylate; Etodolac (Lodine); Etomidate; Fluconazole; Flumazenil; Fluoxetine HC1; Flupirtine maleate; Gatifloxacin; Genistein; Ginkgolide B; Glimepiride; TG100-115; Lansoprazole; Loratadine; MGCD-265; Rigosertib (ON-01910); Ki8751; Patupilone (EPO906, Epothilone B); CHIR-99021 (CT99021) HC1; BMS-707035; Amonafide; Acitretin; Gestodene; Drospirenone; Mosapride citrate; Nafamostat mesylate; Naftopidil Dihydrochloride; Omeprazole (Prilosec); Ondansetron hydrochloride (Zofran); Pizotifen malate; Rocuronium bromide; Tenofovir (Viread); Tigecycline; Trilostane; Vecuronium Bromide; Bimatoprost; Linezolid (Zyvox); Alfuzosin hydrochloride (Uroxatral); 5 -Aminolevulinic acid hydrochloride; Droxinostat; Ranolazine dihydrochloride; Repaglinide; Rolipram; Sildenafil citrate; Sumatriptan succinate; Tianeptine sodium; Topiramate; Tranilast (SB 252218), Trans-Tranilast; Venlafaxine HC1; Voriconazole; Ziprasidone hydrochloride; Zonisamide; Aurora A Inhibitor I; PHA-680632; Thiazovivin; SP600125; Roxadustat (FG-4592); Calcitriol (Rocaltrol); Alfacalcidol; Moxifloxacin hydrochlorideFIG. 21 :Orantinib (TSU-68, SU6668); GSK429286A; Pimasertib (AS-703026); Lomibuvir (VX-222, VCH-222); LY335979 (Zosuquidar trihydrochloride); Iloperidone (Fanapt); MC1568; HMN-214; Naratriptan HC1; Betamethasone (Celestone); Aztreonam (Azactam, Cayston); Tadalafil (Cialis); Palomid 529; XL765; AT7519; Zinc Pyrithione; A-966492; Hesperadin; BIX 02188; Darifenacin HBr; 2-Thiouracil; Pimobendan (Vetmedin); Azelastine hydrochloride (Astelin); Clarithromycin (Biaxin, Klacid); PHT-427; Ampicillin sodium; KRN 633; AT7867; VX-809 (Lumacaftor); Pomalidomide; PD318088; Tazarotene (Avage); BS-181 HC1; Fasudil HC1 (HA-1077); Candesartan (Atacand); Altrenogest; Apixaban; Semagacestat (LY450139); Reserpine; Furosemide (Lasix); Cefdinir (Omnicef); Clotrimazole (Canesten); Rizatriptan Benzoate (Maxalt); Pyridostigmine Bromide (Mestinon); Riluzole (Rilutek); Artemether; Sulfameter (Bayrena); Prednisone (Adasone); Acetylcysteine; Ethinyl Estradiol; Naproxen Sodium; Nitazoxanide (Alinia, Annita); Triamcinolone Acetonide; Orlistat (Alli, Xenical); Allopurinol (Zyloprim); Allopurinol Sodium (Aloprim); Zafirlukast (Accolate); Ibuprofen (Advil); Albendazole (Albenza); Chlorothiazide; Ursodiol (Actigal Urso); Nitrofurazone (Nitrofural); Ketoprofen (Actron); Adenosine (Adenocard); Artemisinin; Zolmitriptan (Zomig); Telbivudine (Sebivo, Tyzeka); Monobenzone (Benoquin); All-trans Retinoic Acid (Tretinoin); Phenylbutazone (Butazolidin, Butatron)FIG. 22 :Dofetilide (Tikosyn); Flucytosine (Ancobon); Unknown; Pregnenolone; Unknown; Ipratropium bromide; Betamethasone Dipropionate (Diprolene); Betapar (Meprednisone); Betamethasone valerate (Betnovate); Busulfan (Myleran, Busulfex); Gemcitabine (Gemzar); Carbamazepine (Carbatrol); Desonide; Didanosine (Videx); Progesterone (Prometrium); Lamivudine (Epivir); Deferasirox (Exjade); Piroxicam (Feldene); Glipizide (Glucotrol); Adefovir Dipivoxil (Preveon, Hepsera); Indomethacin (Indocid, Indocin); Levonorgestrel (Levonelle), Norgestrel; Gemfibrozil (Lopid); Indapamide (Lozol); Methylprednisolone; Meloxicam (Mobic); Mesna (Uromitexan, Mesnex); Methocarbamol (Robaxin); Telmisartan (Micardis); Thiabendazole; Nevirapine (Viramune); Nimodipine (Nimotop); Oxybutynin (Ditropan); Pitavastatin calcium(Livalo); Quetiapine fumarate (Seroquel); Cefditoren pivoxil; Sulfadiazine; Chlorprothixene; Thioguanine; Thiotepa (Thioplex); Ethionamide; Trifluridine (Viroptic); Vidarabine (Vira-A); Teniposide (Vumon); Rifaximin (Xifaxan); Ramipril (Altace); Fenofibrate (Tricor, Trilipix); Ranolazine (Ranexa); Ranitidine Hydrochloride; Acipimox ; Nifedipine (Adalat); Amiloride HC1; Baricitinib (LY3009104); Chloroxine; Cimetidine (Tagamet); Clemastine Fumarate; Daidzein; Methylthiouracil; Isoniazid (Tubizid); Enalapril maleate (Vasotec); Menadione; Metformin hydrochloride (Glucophage); Methoxsalen (Oxsoralen); Primidone (Mysoline); Nefiracetam (TransIon); Nicorandil (Ikorel); PF 3716556; Methscopolamine (Pamine); Pyrimethamine; Sulindac (Clinoril)FIG. 23 :Silibinin (Silybin); Silymarin (Silybin B); Synephrine (Oxedrine); Tangeretin (Tangeritin); Tanshinone I; Tanshinone IIA (Tanshinone B); Tetrahydropapaverine hydrochloride; Troxerutin; Ursolic acid (Malol); Vanillylacetone; Aloin (Barbaloin); Ammonium Glycyrrhizinate (AMGZ), Ammonium Glycyrrhizate; Biochanin A (4-Methylgenistein); Butylscopolamine bromide (Scopolamine butylb; Dioscin (Collettiside III); Diosmetin (Luteolin 4-methyl ether); Gastrodin (Gastrodine); Indirubin; Lappaconite Hydrobromide; L- camitine (Levocamitine); Naringin Dihydrochalcone (Naringin DC); Polydatin(Piceid); Metoprolol tartrate; Nimesulide; Noradrenaline bitartrate monohydrate (Levoph; Pioglitazone hydrochloride (Actos); Tioconazole; AMG458; PHA-848125; Enoxacin (Penetrex); Onalespib (AT13387); CHIR-98014; Ganetespib (STA-9090); MK-8245; NVP-BGT226; PA-824; AG-1024 ; Amiodarone HC1; Pefloxacin mesylate; KW-2478; ARQ 197 (Tivantinib); BX-912; Delanzomib (CEP-18770); NVP-BVU972; PCI-34051; SB705498; CUDC-907; Dovitinib Dilactic acid (TKI258 Dilactic aci; AST-1306; BMS-265246; MK-2461; CPI-613; PF-5274857; GW-842166X; M344; RITA (NSC 652287); Vistusertib (AZD2014); A-803467; Torcetrapib (CP-529414); Ciclopirox ethanolamine; Rimonabant (SR141716); Cabazitaxel (Jevtana); Bufexamac; Lamotrigine; PMSF (Phenylmethylsulfonyl Fluoride); Piceatannol; Lonafamib (SCH66336); Synephrine HC1; Galeterone (TOK- 001); Verteporfin (Visudyne)FIG. 24 :Atazanavir sulfate; AZD4547; Ipatasertib (GDC-0068); Dabrafenib (GSK2118436); Alpelisib (BYL719); CI994 (Tacedinaline); Pravastatin sodium; NVP-TAE226; Quercetin (Sophoretin); Naringenin; Salidroside (Rhodioloside); Candesartan cilexetil (Atacand); Mestranol; Naftopidil (Flivas); S-(+)-Rolipram; Atropine sulfate monohydrate; Roflumilast (Daxas); AZD8330; Dexamethasone acetate; Ethynodiol diacetate; Atomoxetine HC1; BRL 54443; GSK1292263; Moguisteine; Nadifloxacin; Amitriptyline HC1 ; BIBR-1048 (Dabigatran); KW 2449; RAF265 (CHIR-265); ITF2357 (Givinostat); Daphnetin; Gandotinib (LY2784544); Ixazomib (MLN2238); Desloratadine ; Oxybutynin chloride; SB743921 HC1; Ivermectin; Sulfanilamide; Avasimibe (CI-1011); R406; CYT997; NVP-BHG712; OSI-420 (Desmethyl Erlotinib); AZ 960; Torkinib (PP242); (+)-Usniacin (D-Usnic acid); 4-Methylumbelliferone (4-MU); Aesculin (Esculin); Amygdalin; Unknown; Apigenin; Unknown; Ipriflavone; Asiatic acid; Baicalein; 5 -hydroxymethyl tolterodine (PNU 200577); Baicalin; Azithromycin; Belnacasan (VX-765); Bergenin (Cuscutin); Berberine chloride; Caffeic acid; Chlorogenic acid; Chrysin; Cytisine; Dihydroartemisinin (DHA); Emodin; Enoxolone (Glycyrrhetin); 10- Hydroxycamptothecin, Hydroxy Camptothecine; Fisetin (Fustel)FIG. 25 :Formononetin (Formononetol); Fumalic acid (Ferulic acid); Glycyrrhizin (Glycyrrhizic Acid); Gramme; Gynostemma Extract; Tolbutamide; Hesperidin; Honokiol; Unknown; Icariin; Unknown; Kaempferol; Limonin; Luteolin; Unknown; Matrine ((+)-Matrine); Morin hydrate (Aurantica); Myricetin (Cannabiscetin); Myricitrin (Myricitrine); Nalidixic acid (NegGram); Naringin (Naringoside); Oleanolic Acid (Caryophyllin); Oridonin (Isodonol); Orotic acid (6-Carboxyuracil); Osthole (Osthol); Oxymatrine (Matrine N-oxide); Unknown; Piperine (1-Piperoylpiperidine); Puerarin (Kakonein); Quercetin dihydrate (Sophoretin); Rutaecarpine (Rutecarpine); Rutin (Rutoside); Salicin (Salicoside, Salicine); Sclareol; Dihydromyricetin (Ampeloptin); Sodium Danshensu; Isoliquiritigenin; Sophocarpine; Curcumol; Astragaloside A; Bethanechol chloride; Chlorpromazine HC1; Clonidine hydrochloride (Catapres); Cardamonin; Dehydroepiandrosterone (DHEA); Domperidone (Motilium); Estriol; Famciclovir (Famvir); Fenbendazole (Panacur); Gallamine triethiodide (Flaxedil); Hexestrol (Bibenzyl); Imatinib (STI571) ; Loperamide hydrochloride; Manidipine (Manyper); LY411575; TAK-901; TG101209; Milrinone (Primacor); Moroxydine HC1; Nateglinide (Starlix); Novobiocin sodium (Albamycin); Olanzapine (Zyprexa); Olopatadine hydrochloride (Opatanol); Ozagrel; Pancuronium dibromide; Quinine hydrochloride dihydrate; Racecadotril (Acetorphan); Ribavirin (Copegus); Rosiglitazone maleate; Scopolamine hydrobromideFIG. 26 :Sotalol HC1; Sulfadoxine (Sulphadoxine); Vardenafil Hydrochloride Trihydrate (Vivanza; Maprotiline hydrochloride; Naphazoline hydrochloride (Naphcon); Ciclopirox (Penlac); Dopamine hydrochloride (Inotropin); L-Ascorbyl 6-palmitate; Ritodrine hydrochloride (Yutopar); Econazole nitrate (Spectazole); Miconazole (Monistat); Secnidazole (Flagentyl); Rivaroxaban (Xarelto); Tofacitinib citrate (CP-690550 citrate); PIK-294; Neohesperidin; Clomipramine hydrochloride (Anafranil); Ceftiofur hydrochloride ;Phenformin hydrochloride ; Erythromycin; AZD5438; Omecamtiv mecarbil (CK-1827452); MG-132; OSI- 027; PP-121; Trospium chloride (Sanctura); Tolterodine tartrate (Detrol LA); Clomifene citrate (Serophene); Cloxacillin sodium; Cortisone acetate (Cortone); Isoprenaline hydrochloride; Rosiglitazone (Avandia); CCT128930; R788 (Fostamatinib); A66; Edaravone (MCI-186); A-674563; AS-252424; CHIR-124; LY2608204; TAK-700 (Orteronel); PF-00562271; R547; SNX-2112; WAY-600; WYE-125132; Odanacatib (MK 0822); BMS-754807; Suplatast tosylate; TWS119; BMS-536924; Ginkgolide A; Unknown; Ciproxifan Maleate; Prednisolone acetate (Omnipred); Dimethyl Fumarate; Clinofibrate; ICG-001; PF-04929113 (SNX- 5422); ADL5859 HC1; Ciprofibrate; Geldanamycin; GSK1838705A; ZM 336372; GSK1070916; JTC-801; Apitolisib (GDC-0980, RG7422); Nepicastat hydrochloride; Brompheniramine hydrogen maleate; CarvedilolFIG. 27 :Phenylephrine hydrochloride; Medroxyprogesterone acetate; (+,-)-Octopamine HC1; Dinaciclib (SCH727965); MK-5108 (VX-689); Olmesartan medoxomil (Benicar); Tubastatin A hydrochloride; AG-1478 (Tyrphostin AG-1478); PF-04691502; Benidipine hydrochloride; Fluticasone propionate (Flonase, Veramyst); Formoterol hemifumarate; Ketotifen fumarate (Zaditor); Urapidil hydrochloride; Bifonazole; Butoconazole nitrate; Ganciclovir; Phentolamine Mesylate ; Uridine; Acemetacin (Emflex); Natamycin; Nystatin (Fungicidin); Buflomedil HC1; Clobetasol propionate; Phenacetin; Pioglitazone (Actos); Tolfenamic acid; Tolvaptan (OPC-41061); Zidovudine (Retrovir); 10-DAB (10-Deacetylbaccatin); Cephalomannine; Genipin; Geniposidic acid; Gliclazide (Diamicron); Quinapril hydrochloride (Accupril); Scopine; Captopril (Capoten); Cyproterone acetate; Cytidine; Doxifluridine; Gimeracil; ML133 HCL; CP 673451; LY2811376; Thalidomide; Finasteride; Bisoprolol fumarate; Dacarbazine (DTIC-Dome); Acarbose; Lidocaine (Alphacaine); Tioxolone; PHA-767491; Betaxolol hydrochloride (Betoptic); Unknown; Sulfamerazine; Trimethoprim; Estradiol valerate; Gliquidone; Tylosin tartrate; Betahistine 2HC1; Brinzolamide; Eletriptan HBr; Flumequine; Azlocillin sodium salt; Trifluoperazine 2HC1; Adrenalone HC1; Azacyclonol; Triflusal; AZD6482; VarlitinibFIG. 28 :Xylazine HC1; Catharanthine; Moclobemide (Ro 111163); Tideglusib; ARN-509; Sulfathiazole; Carfilzomib (PR-171); Rofecoxib (Vioxx); Azilsartan (TAK-536); BML-190; Semaxanib (SU5416); SAR131675; Equol; AM251; StemRegenin 1; Otilonium Bromide; Cyclocytidine HC1; IMD0354; ML130; T0070907; Golvatinib (E7050) ; Alverine Citrate; Forskolin; Chlorhexidine HC1; Beclomethasone dipropionate ; Dexmedetomidine; Foscamet Sodium; Acesulfame Potassium ; Apocynin (Acetovanillone); Schisandrin B; Gambogic Acid; Atovaquone (Atavaquone); Etravirine (TMC125); U-104; Camostat Mesilate (FOY-305); Rupatadine Fumarate; VU 0364770; Guanosine; IEM 1754 dihydrobroMide; A 205804; IKK-16; Indacaterol Maleate; Betulinic acid; Tempol (4-Hydroxy-TEMPO); VU 0361737; GW 441756; BI-D1870; SB-742457; Tyrphostin 9 (SF 6847); ZM 323881 HC1; ZM 306416; CCG 50014; JNJ-7777120; 4-Aminohippuric Acid; Aripiprazole (Ability); Almotriptan malate (Axert); Paroxetine HC1; Terazosin HC1 Dihydrate; Ivabradine HC1 (Procoralan); Cisatracurium besylate (Nimbex); Naltrexone HC1; GW9662; Go 6983; Dapivirine (TMC120); ML-161; IOX2; Salubrinal; Kil6198; MLN0905; IcotinibFIG. 29 :TAK 715; TDZD-8; Melatonin; Felbamate; Fluvoxamine maleate; Oxcarbazepine; H 89 2HC1; Trichlormethiazide (Achletin); Suprofen (Profenal); Pranlukast; Oxfendazole; Tizanidine HC1; Pralatrexate(Folotyn); Roxatidine acetate HC1; Tropicamide; Diclazuril; Rebamipide; Lovastatin (Mevacor); Balofloxacin; Lafutidine; Argatroban; Atorvastatin calcium (Lipitor); Famotidine (Pepcid); Clevidipine Butyrate; Adiphenine HC1; Rivastigmine tartrate (Exelon); Dexmedetomidine HC1 (Precedex); Bexarotene; Temocapril HC1; Gabexate mesylate; Rasagiline mesylate; Flunixin meglumin; Dronedarone HC1 (Multaq); Ibutilide fumarate; Probucol; Fluocinolone acetonide (Flucort-N); Phenoxybenzamine HC1; Tenoxicam(Mobiflex); Xylometazoline HC1; Clevudine (Levovir); Zaltoprofen; Amoxicillin (Amoxycillin); Aspirin (Acetylsalicylic acid); Niflumic acid; Amprenavir (Agenerase); Proparacaine HC1; Evacetrapib (LY2484595); Apoptosis Activator 2; GNF-2; Unknown; Unknown; Losartan potassium; Sparfloxacin; Tolnaftate; Ozagrel HC1 ; AICAR (Acadesine); Cobicistat (GS-9350); Cabozantinib malate; PF-4981517; UK 383367; Bazedoxifene HC1; PFI-l(PF-6405761) ; SL327; Acebutolol HC1; Ampiroxicam; Lithocholic acid; Mirabegron (YM178); Allylthiourea; Hyoscyamine (Daturine); AvanafilFIG. 30 :Probenecid (Benemid) ; Procaine (Novocaine) HC1; Sennoside A; Sennoside B; JNK-IN-8; Methazolamide; Unknown; SN-38; JZL184; Nabumetone; Sertraline HC1; Vitamin D3 (Cholecalciferol); Nafcillin Sodium; Norethindrone (Norethisterone); Olsalazine Sodium; Diphemanil Methylsulfate; Doxapram HC1; Vitamin D2 (Ergocalciferol); Desvenlafaxine; Estradiol Benzoate; Unknown; Valdecoxib; Bisacodyl; Decamethonium Bromide; Estradiol Cypionate; Griseofulvin; Guanidine (Aminoformamidine) HC1; Mefenamic Acid; Pirarubicin; Guanabenz (WY-8678) Acetate; Sulfacetamide Sodium; Ticagrelor; Triamterene; Ethambutol HC1; Homatropine Methylbromide; Homatropine Bromide; Hydroxyzine 2HC1; Histamine 2HC1; Levodropropizine; Pefloxacin Mesylate Dihydrate; Sulconazole Nitrate; Timolol Maleate; Tolazoline HC1;Azithromycin Dihydrate; Amfenac Sodium (mono hydrate); Benzydamine Hydrochloride; Carprofen; Cetylpyridinium Chloride; Chlorpropamide; Chlorquinaldol; Chlorzoxazone; Choline Chloride; Cinchophen; Clofazimine; Clorprenaline HCL; Coumarin; Cyromazine; Ethamsylate; Isovaleramide; Penciclovir; Penfluridol; Salicylanilide; Sasapyrine; Sulfaguanidine; Tiratricol; Triclabendazole; Uracil; Primaquine Diphosphate; Resminostat (RAS2410); Azaguanine-8FIG. 31 :Bemegride; Bergapten; Broxyquinoline; Cepharanthine; Deoxycorticosterone acetate; Dirithromycin; Domiphen Bromide; Doxylamine Succinate; Ethacridine lactate monohydrate; Florfenicol; Nicardipine HC1; Serotonin HC1; Sucralose; Teriflunomide; Valnemulin HC1; b-AP15; Cetrimonium Bromide; Difluprednate; Diminazene Aceturate; Eprosartan Mesylate; Fenspiride HC1Fenspiride HC1; Flumethasone; Halcinonide; Halobetasol Propionate; Loxapine Succinate; Unknown; Vitamin A Acetate; Voglibose; Benzbromarone; Benzethonium chloride; Benzocaine; Penicillin G Sodium; Bezafibrate; Chromocarb; Clofibric acid; Cysteamine HC1; Erythritol; Fidaxomicin; Liothyronine Sodium; Mevastatin; Mexiletine HC1; Montelukast Sodium; Nithiamide; Oxaprozin; Pheniramine Maleate; Pilocarpine HC1; Flopropione; Tranylcypromine (2-PCPA) HC1; Phenothiazine; Mechlorethamine HC1; Epinastine HC1; HA14-1; Latrepirdine 2HC1; Bazedoxifene Acetate; Aloe-emodin; Daidzin; VX-745; Triciribine; Quinacrine 2HC1; Unknown; Flurbiprofen; Chlorpheniramine Maleate; Idoxuridin; Mitotane; Rifabutin; Rifampin; Rifapentine; spironolactone; Taxifolin (Dihydroquercetin); Alizapride hydrochlorideFIG. 32 :Brimonidine Tartrate; Buspirone hydrochloride; Diacerein; Silodosin; Efaproxiral sodium; Flufenamic acid; Nicaraven; Tamibarotene; Vilazodone Hydrochloride; TTNPB; LX1606 hippurate; Vinorelbine Tartrate; Tenovin-6; Almorexant HC1; Oxiracetam; Tenatoprazole; Refametinib (RDEA119, Bay 86-9766); Meclofenoxate (Centrophenoxine) HC1; Ospemifene; Nelfinavir Mesylate; Carteolol HC1; Cyclobenzaprine HC1; Chloroambucil; Bambuterol HC1; MetoclopraMide HC1; Diphenidol HC1; Dicoumarol; Procainamide HC1; Labetalol HC1; Meclofenamate sodium; Aliskiren Hemifumarate; Bepotastine Besilate; Daptomycin; Nebivolol HC1; Tacrolimus (FK506); Rosuvastatin Calcium; Mupirocin; WAY-100635 Maleate; Eltrombopag olamine; Eltrombopag; Fenoprofen calcium hydrate; Sodium Nitroprusside; Quisinostat (JNJ-26481585) 2HC1; 6 -Mercaptopurine (6-MP) Monohydrate; CHIR-99021 (CT99021); Flavopiridol (Alvocidib); Vinblastine sulfate; Acetazolamide; 17-Hydroxyprogesterone; Cefotaxime sodium; Fenofibric acid; Fenbufen; Pentamidine isethionate; Esomeprazole sodium; Furazolidone; Citric acid trilithium salt tetrahydrate; 4- Aminoantipyrine; Acetylleucine; Unknown; Bithionol; Amino guanidine (hydrochloride); Diethylcarbamazine (citrate); Danthron; Pantoprazole sodium; Salicylic acid; Methylene Blue; Hexylresorcinol; Fluphenazine (dihydrochloride); (+)-Camphor, Camphor; CephalothinFIG. 33 :Chlormadinone acetate; Xylitol; Urethane; Cefixime; Cefazolin Sodium; Nitroxoline; Pentylenetetrazol; 4- Chloro-DL-phenylalanine; Succinylsulfathiazole; Butamben; Sulfabenzamide; Itopride hydrochloride; Amodiaquin (dihydrochloride dihydrate); Alcaftadine; Diazoxide; Chlorotrianisene; (+ / -)-Sulfinpyrazone; Brexpiprazole; Cyproheptadine hydrochloride; Mebendazole; Levofloxacin hydrate; Gallic acid; Diflunisal; Isosorbide Mononitrate; Parecoxib; Cefmenoxime hydrochloride; Atipamezole; Tedizolid Phosphate; Acetohydroxamic acid; Triclosan; Azelaic acid; Terazosin HC1 ; Guanfacine Hydrochloride; Sivelestat sodium tetrahydrate; Glycopyrrolate; Hydroquinidine; Etoricoxib; Ciclesonide; Loxoprofen; Protirelin; Rebeprazole sodium; Clioquinol; Efavirenz; arbinoxaMine Maleate; Benzocaine hydrochloride; Lidocaine hydrochloride; Saxagliptin hydrate ; Atazanavir; AT-406; Etonogestrel; Escin; TH-302; Cinnarizine; Esculetin; 3,3'- Diindolylmethane; Isatin; Benzamide; Palmitoylethanolamide; Acetylcholine iodide; (-)-Menthol, DL- Menthol; Benzenesulfonamide; Pantoprazole (Protonix); 2-Deoxy-D-glucose; (-)Epicatechin; Perphenazine; MPTP hydrochloride; MK-4827(Niraparib); Salvianolic acid B; Trapidil; JervineFIG. 34 :(20S)-Protopanaxadiol; Arctiin; Psoralen; Genistin (Genistoside); Wogonin; Sulfacetamide Sodium salt hydrate; Citalopram HBr; Ondansetron Hydrochloride Dihydrate; Cisapride hydrate; Imidapril HC1; Azatadine dimaleate; Cefaclor; Ganoderic acid A; Stavudine; Demethylzeylasteral (T-96); Unknown; Unknown; Unknown; Fangchinoline; N-Ethylmaleimide (NEM); Unknown; Mafenide hydrochloride; Nortriptyline hydrochloride; Benactyzine hydrochloride; Urea; 2,3 -Butanedione-2 -monoxime; Asiaticoside; Unknown; Diammonium Glycyrrhizinate; (+)-Fangchinoline; Scoparone; Unknown; Syringic acid; Unknown; Cordycepin; Pazufloxacin mesylate; Tyramine; Sesamol; Tryptamine; Unknown; Dihydrothymine; Unknown; Umbelliferone; Carbendazim; Cinnamic acid; 2-Methoxy-l,4-naphthoquinone; Thymopentin; Cefonicid sodium; Trolox; Doxepin hydrochloride; Pargyline hydrochloride; Quinestrol; ELR-510444; Tipiracil hydrochloride; Osalmid; Mafenide Acetate; Unknown; 4-Amino-5-imidazolecarboxamide; Cefepime Dihydrochloride Monohydrate; Unknown; Promestriene; O6-Benzylguanine; Unknown; Cystamine dihydrochloride; Cholic acid; Methylmalonate; Carbasalate Calcium; Spermidine trihydrochloride; Lifitegrast; Leuprorelin AcetateFIG. 35 :Unknown; Velpatasvir; Ethopabate; Calcipotriene; 4-Biphenylacetic acid; Glucosamine hydrochloride; Flavanone; Rotenone (Barbasco); Tacrine hydrochloride hydrate; Unknown; Colchicine; CAS: 118-10-5; Ilaprazole; Unknown; p-Coumaric Acid; Crocin; Tauroursodeoxycholic Acid; Bisdemethoxycurcumin; 3'- Hydroxypterostilbene; Pinocembrin; Unknown; Sinapinic Acid; Caryophyllene oxide; (+)-Bomeol; Tetramethylpyrazine; Unknown; Tubeimoside I; Mogroside V; Harmine hydrochloride; Decursinol angelate; Schisandrin A; Schizandrol A; Unknown; Hydroxytyrosol; Isoalantolactone; Amentoflavone; Loganin; 6- Gingerol; Carnosic acid; Eleutheroside B; Unknown; Gamma-Oryzanol; Histamine; Tanshinone IIA sulfonate (sodium); Stachydrine; Dehydroandrographolide Succinate Potasium Sa; Lappaconitine; Norcantharidin; Unknown; Sinomenine hydrochloride; Stachydrine hydrochloride; Obacunone; Unknown; Picroside I; Secoisolariciresinol diglucoside; Veratramine; Cephalotaxine; Unknown; Liquiritin; Astilbin; Betaine; 2'- Deoxyinosine; Echinocystic acid; Rosavin; Eupatilin; L-Cycloserine; Ginsenoside Re; Monocrotaline; Pyrogallol; L-Rhamnose monohydrateFIG. 36 :Arteether; Leonurine; Isopsoralen; Unknown; Alpinetin; Bavachinin; Protopine; Jatrorrhizine; Lycorine hydrochloride; Trigonelline Hydrochloride; Dehydroandrographolide; Mangiferin; Imperatorin; Panaxatriol; Gracillin; Macranthoidin B; Astragaloside IV; Patchouli alcohol; Methyl gallate; Palmitic acid; Lathyrol; Ginsenoside Rd; Picroside II; Betulin; (-)-Epicatechin gallate; Forsythin; Swertiamarin; Unknown; Nicergoline; Capmatinib (INCB28060); Aloperine; Leucovorin Calcium Pentahydrate; Torin 1; Ibandronate sodium; L-Arginine HC1; Palonosetron HC1; TG 100713; Solifenacin succinate; KY02111; IPA-3; Scriptaid ; PP2; PD168393; PRT062607 (P505-15, PRT2607, BIIB057) HC1; 10058-F4; Batimastat (BB-94); Ilomastat (GM6001, Galardin); EPZ004777; XL888; P276-00; PPI; CGK 733; Amprolium HC1; Ceritinib (LDK378); abemaciclib (LY2835219); TCID; IU1; Ceftriaxone Sodium Trihydrate; BAM7; CNX-2006; GZD824 Dimesylate ; LDN-57444; RKI-1447; AGI-5198; AZD3463; P5091 (P005091); Batyl alcohol; 4'- Demethylpodophyllotoxin; (-)-epigallocatechin; Ginsenoside RglFIG. 37 :4'-Demethylepipodophyllotoxin; Unknown; Methyl protocatechuate; D-Pinitol; D-Galactose; Glucosamine sulfate; Allantoin; 4-Hydroxybenzyl alcohol; Cycloastragenol; Sophoridine; (lR,2R)-trans-N-Boc-l,2- cyclohexanediamine; (-)-Arctigenin; Hederagenin; Betulonic acid; Ursonic acid; Lycorine; Isoimperatorin; Iso-Steviol; Indigo; Thymoquinone; Tectoridin; Daminozide; Menadiol Diacetate; Xanthoxyline; Benzyl isothiocyanate; Methyl syringate; L-5 -Hydroxytryptophan; Unknown; alpha- Asarone; Adrenosterone; Harmaline; Plumbagin; Protodioscin; Unknown; Unknown; Indole-3-acetic acid; Unknown; Flavone; Protocatechuic acid; Pyridoxine; Brivudine; L-Tryptophan; Unknown; Unknown; Unknown; Acotiamide hydrochloride; Delamanid; kaempferide; Anamorelin; Propacetamol hydrochloride; Elagolix Sodium; Tiamulin fumarate; AOA hemihydrochloride; TBHQ; Nadolol; Sophoricoside; Propantheline bromide; Neticonazole Hydrochloride; Nilutamide; Ibudilast; Gadopentetate Dimeglumine; Iproniazid; Teprenone; Octenidine Dihydrochloride; Crisaborole (AN2728); Levocetirizine Dihydrochloride; Unknown; Maltol; Fumaric acid; Usnic acidFIG. 38 :Euphorbiasteroid; Tolmetin; Aceclofenac; Oxindole; Taurolidine; Nikethamide; Cedrol; Glycocholic acid; 4-Methylesculetin; Fimasartan; Efonidipine; Tilorone dihydrochloride; Capsaicin; Sulfalene(SMPZ); Isoprinosine; Brassinolide; Notoginsenoside Rl; 3,4-Dihydroxybenzaldehyde; Vindoline; GW5074; Isotretinoin ; Ulipristal acetate; spiramycin; Methyl-Hesperidin; , Alogliptin; Propranolol HC1; (+)-Catechin, (+)-Catechin hydrate; Tandutinib (MLN518); Vandetanib (ZD6474); Enrofloxacin; (R)-baclofen; Miltefosine (Hexadecylphosphocholine); L-NAME HC1; NU7026; Mozavaptan; Prazosin HC1; Penicillamine (Cuprimine); Sarafloxacin HC1; Lisinopril (Zestril); Fosinopril sodium (Monopril); Vinpocetine (Cavinton); Dichlorphenamide (Diclofenamide); VE-821; Sulfapyridine (Dagenan); RGD (Arg-Gly-Asp) Peptides; GSK2636771; ACY-1215; PQ 401; Tenovin-1; AG 18 (Tyrphostin 23); Vonoprazan Fumarate (TAK-438); AP26113; Vortioxetine (Lu AA21004) hydrobromide; GW0742; AZD5363; Tyrphostin AG 1296 (AG 1296); TCS 359; Pemirolast (BMY 26517) potassium; Duvelisib (IPI-145, INK1197); UPF 1069; (+)-Bicuculline; Venetoclax (ABT-199, GDC-0199); Birinapant (TL32711); IWR-l-endo; Oprozomib (ONX 0912); VX-661; (+)-JQl; GSK J4 HC1; Tariquidar; Hexamethonium DibromideFIG. 39 :Flavoxate HC1; Succinylcholine Chloride Dihydrate; Terbutaline Sulfate; AMG-517; Macitentan; Zebularine; (-)-Blebbistatin; GDC-0349; AZD2461; Embelin; TAE684 (NVP-TAE684); SGX-523; XL147 analogue; Erlotinib(OSI-744); Pemetrexed; Gemcitabine HC1 (Gemzar); PIK-75 ; Bleomycin sulfate; Carboplatin; Perifosine (KRX-0401); Camptothecin; Oxibendazole; Danofloxacin Mesylate; Pamidronate Disodium; Ellagic acid; Galanthamine hydrobromide; Granisetron HC1; Ketoconazole; GSK1059615; Dorzolamide HCL; Varenicline tartrate; Marbofloxacin; LY2228820; Perindopril Erbumine (Aceon); Irbesartan (Avapro); Norfloxacin (Norxacin); Cidofovir (Vistide); Ibuprofen Lysine (NeoProfen);CCT129202; Tripelennamine HC1; Risperidone (Risperdal); Alendronate sodium trihydrate; Methyldopa (Aldomet); Cytarabine; Torsemide (Demadex); Eplerenone; Unknown; Deferiprone; Sodium butyrate; Sodium orthovanadate; Taurine; Rheochrysidin (Physcione); Fudosteine; Gabapentin (Neurontin); R935788 (Fostamatinib disodium); (-)-Huperzine A (HupA); Diosmin; Donepezil HC1 (Aricept); Itraconazole (Sporanox); Neostigmine bromide (Prostigmin); Salbutamol sulfate (Albuterol); Methacycline hydrochloride (Physiomycine); 7-Aminocephalosporanic acid; PTC124 (Ataluren); VX-702; Lomefloxacin hydrochloride (Maxaquin); Hydralazine hydrochloride; PF-05212384 (PKI-587); Taladegib (LY2940680); NU7441(KU- 57788)FIG. 40 :MK-8776 (SCH 900776); Meclizine dihydrochloride; Procarbazine hydrochloride (Matulane); Trazodone hydrochloride (Desyrel); Disodium Cromoglycate; Tranexamic acid (Transamin); Flubendazole (Flutelmium); Clindamycin phosphate; Etidronate (Didronel); Lomoxicam (Xefo); CCT137690; P22077; PR-619; Wnt-C59 (C59); Paromomycin Sulfate; Proflavine Hemisulfate; Sodium ascorbate; Clodronate Disodium; DBeQ; GDC- 0152; E-64; PYR-41; CPI-169; SC79; BI-847325; AZ5104; Xanthohumol; AZD3839; LRRK2-IN-1; Cyclo(RGDyK); NPS-1034; Dexamethasone Sodium Phosphate; Oseltamivir Phosphate; Histamine Phosphate; AMI-1; GDC-0623; G007-LK; AI-10-49; PF-4989216; AZD8186; Dibutyryl-cAMP (Bucladesine); UM171; Pyrilamine maleate; 8-Bromo-cAMP; BLU9931; TP -0903; TH287; GSK503; Oltipraz; Bromodeoxyuridine (BrdU); Disodium (R)-2-Hydroxyglutarate; Sodium Tauroursodeoxycholate (TUDC); GDC-0032; CPI-360; ONO-4059; Oleuropein; Monomethyl auristatin E (MMAE); Dp44mT; Vidofludimus; PF-03084014 (PF-3084014); Tiplaxtinin (PAI-039); GSK2801; SBI-0206965; MCB-613; SB239063; AZD6738; PF-04418948; DDR1-IN-1; SU5402; VR23FIG. 41 :UNC-2025; P7C3; TIC10; Akti-1 / 2; SirReal2; A-1210477; AMG319; ODM-201; Unknown; Gypenoside; BAY 1895344; Unknown; Tea polyphenol, Aprotinin, Grape Seed Extract; Elemicin; Methyl Dihydrojasmonate; Citral; Valproic acid; Olivetol; Nuciferine; L-SelenoMethionine; ONC212; Sodium Aescinate; Carvacrol; cis-Anethole; isoleucine; Perillyl alcohol; Allicin; Muscone; Bornyl acetate; DL- Glutamine; Vincamine; Savolitinib(AZD6094, HMPL-504); Sodium Houttuyfonate; Bakuchiol; WT161; BTSA1; Tetramisole HC1; Vitamin A Palmitate; Bromosporine; Minocycline HC1; NSC 405020; AZD1080; NSC319726; Apramycin Sulfate; EPZ005687; AZD3514; PD 123319; Unknown; Cephalexin (Cefalexin); Purmorphamine; Binimetinib (MEK162, ARRY-162, ARRY-438162); Brefeldin A ; GSK2334470; TIC10 analogue; I-BET-762; BIO; Fosbretabulin (Combretastatin A4 Phosphate, ; Thiamet G ; OAC1; RGFP966; Ferrostatin-1 (Fer-1); AZD2858; Unknown; ZM 39923 HC1; PluriSin #1 (NSC 14613); SGC 0946; Erastin; RI-1; Ro 31-8220 Mesylate; AZD1981FIG. 42 :Unknown; CZC24832; SGI-1027; SRPIN340; ETP-46464; Golgicide A; XL388; Rociletinib (CO-1686, AVL-301); EHop-016; KPT-185; KPT-276; Skepinone-L; 9-Aminoacridine9-AminoacridineAminoacrid; bendroflumethiazide; benzthiazide; cinoxacin; clofoctol; DicycloMine Hydrochloride; glafenine hydrochloride; isoetharine mesylate; isoxicam; mepenzolate bromide; mesoridazine besylate; metaproterenol sulfate; metaraminol bitartrate; meticrane; nialamide; nifenazone; pasiniazid; pentoxifylline; proadifen hydrochloride; procodazole; terfenadine; Thioridazine hydrochloride; tolmetin sodium; Ebastine; Unknown; BMS-833923 (XL139); Tazemetostat (EPZ-6438); I0WH 032; RVX-208(RVX-000222); XL019; trimipramine maleate; CFTRinh 172; SSR128129E (SSR); TAK-632; Tasisulam (LY573636); UNC1999; GSK2606414; JIB04 (NSC693627); ZCL 278; CC-292 (AVL-292); Mdivi-1; AZ191; MM-102; Pacritinib (SB1518); Rilpivirine; Unknown; Sorafenib; RG2833 (RGFP109); PF-562271 HC1; STF-118804; TG003; WZ4003; ID-8; Selinexor (KPT-330); NMS-873; Unknown; ASP3026; LGK-974FIG. 43 :AZ20; CNX-774; IWP L6; SGC-CBP30; UNC2250; VE-822; GSK2656157; MK8745; ZLN005; 4EGI-1; FLI-06; Ribociclib (LEE011); ME0328; Unknown; BTB06584; CW069; NH125; NSC697923; PTC -209; CK- 636; Sal003; Triapine; UNC669; CRT0044876; SKLB1002; 1-Azakenpaullone; 4ElRCat; ISRIB (transisomer); FPH1 (BRD-6125); OTX015; VGX-1027; Y-320; Nexturastat A; AGI-6780; AZD7545; ML167; VER-49009; Entospletinib (GS-9973); K-Ras(G12C) inhibitor 6; LB42708; CGP 57380; Loxistatin Acid (E- 64C); DMOG; PU-H71; NMS-E973; OG-L002; C646; UNC1215; AZD9291; MPI-0479605; CCT007093; GNF-5; KN-62; PFK15; HS-173; GSK923295; Z-FA-FMK; CH5138303; WIKI4; Losmapimod; YH239-EE; GNE-0877; ML323; IOX1; Unknown; VER-50589; Unknown; Darapladib (SB-480848); PF-543; AZD1208FIG. 44 :INH1; PTC-209 HBr; CX-6258 HC1; EHT 1864 2HC1; Tepotinib (EMD 1214063); LDC000067; FPH2 (BRD-9424); XMD8-92; IWP-2; INH6; CGI1746; PI-1840; (-)-p-Bromotetramisole Oxalate; AEBSF HC1; MI-2 (MALT1 inhibitor); TAPI-1; PF-3758309; CPI-203; FH535; Leupeptin Hemisulfate; Puromycin 2HC1; TMP269; Pritelivir (BAY 57-1293); XL413 (BMS-863233); HJC0350; GNE-7915; Pepstatin A; PD173955;BAY 87-2243; SB-3CT; K-Ras(G12C) inhibitor 9; Zotarolimus (ABT-578); PD 151746; Go6976; WH-4-023; Phosphoramidon Disodium Salt; SF1670 (PTEN inhibitor); IM-12; Deltarasin; Optovin; HSP990 (NVP- HSP990); Paliperidone; Santacruzamate A (CAY10683); 6H05; NMS-P937 (NMS1286937); ARQ 621; Sabutoclax; ESI-09; GNE-9605; Unknown; Z-DEVD-FMK; PFI-3; Glasdegib (PF-04449913); LCL161; K- Ras(G12C) inhibitor 12; Tasquinimod; AGK2; Anacardic Acid; GNF-5837; Unknown; MG-101 (ALLN); Splitomicin; LY2874455; URMC-099; UMI-77; PFI-2 HC1; MI-3 (Menin-MLL Inhibitor); Remodelin; G-749; NedaplatinFIG. 45 :VS-5584 (SB2343); Bisindolylmaleimide I (GF109203X); Ro3280; PJ34 hcl; JNK inhibitor IX; Nutlin-3b; Unknown; Cerdulatinib (PRT062070, PRT2070); CID755673; Obeticholic Acid; Idasanutlin (RG-7388); MI-2 (Menin-MLL inhibitor); LCZ696; PF-06463922; DTP3; Ledipasvir (GS5885); Verdinexor (KPT-335); RBC8; SP2509; GSK1324726A (I-BET726); Lomitapide Mesylate; EIl; ML141; BRD4770; PX-478 2HC1; Picropodophyllin (PPP); YK -4-279; Reversine; CAY10603; SU9516; Piperlongumine; AT13148; LMK-235; PF-431396; BMH-21; PND-1186 (VS-4718); Defactinib (VS-6063, PF-04554878); TAI-1; MS436; GSK2578215A; HPOB; LY2584702; ML324; 4SC-202; TH588; GSK2830371; OF-1; PI-3065; BAF312 (Siponimod); FTI 277 HC1; SBE 13 HC1; Bikinin; Salirasib; LFM-A13; CCG-1423; LDC1267; LY2584702 tosylate; RN486; Dovitinib (TKI258) Lactate; Calpeptin; LY2090314; CH5183284 (Debio-1347); UNC0379; CH-223191; GSK-LSD1 2HC1; BQU57; SB273005; GSK126; Docetaxel Trihydrate; Pemetrexed Disodium HydrateFIG. 46 :EPZ015666; ANA-12; Dasatinib Monohydrate; Sunitinib; Elacridar (GF120918); Erlotinib; LB-100; CL- 387785 (EKI-785); PD 0332991 (Palbociclib) HC1; PD 0332991 (Palbociclib) Isethionate; (S)-crizotinib; MI- 773 (SAR405838); STF-083010; FRAX597; SRT2104 (GSK2245840); Ro-3306; BRD73954; Unknown; BV- 6; Afuresertib (GSK2110183); GNE-317; CB-839; Purvalanol A; AZD2932; NU1025; Marimastat (BB-2516); Anisomycin; MHY1485; ERK5-IN-1; SU6656; KNK437; Cyclo (-RGDIK); D 4476; Pilaralisib (XL147); Gentamicin Sulfate; AT7519 HC1; VER155008; Pexmetinib (ARRY-614); Pyridostatin Trifluoroacetate Salt; LY3009120; GSK JI; BG45; HTH-01-015; Cobimetinib (GDC-0973, RG7420); Ulixertinib (BVD-523, VRT752271); Tenofovir Alafenamide (GS-7340); BPTES; Licochalcone A; E333O; Endoxifen HC1; Cilengitide trifluoroacetate; KC7F2; Favipiravir (T-705); DEL-22379; STF-31; PFI-4; L-685,458; RG7112 (RO5045337); 0412; Peficitinib (ASP015K, JNJ-54781532); Entrectinib (RXDX-101); RO5126766 (CH5126766); ABC294640; Spautin-1; GSK621; DASA-58; 6-Thio-dG; FIIN-2; Coelenterazine; Vorapaxar (SCH 530348)FIG. 47 :SKF38393 HC1; ORY-lOOl (RG-6016) 2HC1; GMX1778 (CHS828); 0411; NCT-501; EPI-001; AP-III-a4 (ENOblock); SW033291; CB-5083; Decemotinib (VX-509); VX-l le; Riociguat (BAY 63-2521); AZD3759; Voxtalisib (XL765, SAR245409); Unknown; NVP-TNKS656; D-Luciferin; LJI308; FG-2216; Radotinib; PX- 12; K03861; Ozanimod (RPC1063); SGC707; GNF-7; NSC59984; Cucurbitacin B; Z-VAD(OH)-FMK; GlyH- 101; KD025 (SLx-2119); Ro 61-8048; Mirin; GSK2879552 2HC1; Q-VD-Oph; Daprodustat (GSK1278863); MS023; CC-223; Chaetocin; Pimavanserin; AZD3965; LJH685; Uprosertib (GSK2141795); ON123300; PF- 06447475; Bay K 8644; VPS34-IN1; AZ6102; AG99; Kenpaullone; NSC348884; WZB117; MLN2480; PF- CBP1 HCL; Acalabrutinib (ACP-196); LTX-315; GSK591 (EPZ015866,GSK3203591); CAS: 1448347-49-6; Bitopertin (RG1678, RO-4917838); HLCL-61 hydrochloride; I-BRD9 (GSK602); PIK-III; SMER28; RSL3; ML264; PD0166285; CB1954; Ponesimod (ACT-128800); SGI-7079; ETC-1002; Pluripotin (SCI)FIG. 48 :AG-221 (Enasidenib); SB366791 (SB-366791); 4-Hydroxytamoxifen; BI-1347; KDM4D-IN-1; PLX7904; C-DIM12; SCR7; SBI-0640756; DEBT; BI-78D3; FCCP; Sivelestat (ONO-5046); PF-8380; IC261; BI-7273; MI-136; A-366; Tyloxapol; Halothane; AMG 337; SKF96365; Benzyl alcohol; Benzyl benzoate; Pralidoxime (chloride); NQDI-1; Tubercidin; L755507; Eflomithine hydrochloride hydrate; Folic acid; Kobe0065; MK-886 (L-663,536); Olmutinib (HM61713, BI 1482694); Glutathione; IMR-1; IQ-1; 5-Iodotubercidin; RS-1; Sildenafil; Alosetron Hydrochloride; D panthenol; TRxO237 (LMTX) mesylate; Vitamin E; Cefradine; CCF642; Emricasan (IDN-6556, PF-03491390); 7,8-Dihydroxyflavone; MK-4827(Niraparib) tosylate; ITSA-1 (ITSA1); LY3023414; SR-12813; Fatostatin; Selonsertib (GS-4997); Eugenol; Rivastigmine; HA15; Epoxomicin (BU-4061T); Saccharin 1 -methylimidazole (SMI); PRIMA-1; SQ22536; LY333531 HC1; FRAX486; NSC87877; MK-4101; VO-Ohpic trihydrate; Diethylmaleate; BI-9564; EAI045; Shikonin; KYA1797KFIG. 49 :AZD8835; Necrosulfonamide; BAY-61-3606; RK-33; WNK463; LOXO-lOl(sulfate); CeMMEC13; RHPS 4 methosulfate; APS-2-79 HC1; NSC228155; BMS-911543; LLY-507; Deguelin; 4-Aminobutyric acid; Sarcosine; Oleic Acid; Latanoprost; Voreloxin (SNS-595) hydrochloride; BAW2881 (NVP-BAW2881); Leukadherin-1; CPI-637; GGTI 298 TFA salt; Pamapimod (R-1503, Ro4402257); ML390; SKL2001; AS101;OICR-9429; BDA-366; NVP-CGM097; BFH772; CPI-1205; AZD9496; BML210 / CAY10433; BGP-15 2HC1; HPI-4 (Ciliobrevin A); CPI-455 HC1; LY2801653 (Merestinib); GDC-0084; MX69; CA-074 methyl ester (CA-074 Me); NS-398 (NS398); ML-7 HC1; UNC3866; Etomoxir (Na salt); CC-115; CZ415; XMD16-5; XMD8-87; Apoptozole; XMU-MP-1; Y-39983 HC1; APR-246 (PRIMA-1MET); ZINC00881524 (ROCK inhibitor); NSC12; SRT2183; THZ1 2HC1; UNC0638; GSK2269557; Sodium ferulate; Monastrol; LY3039478; Danshensu; EPZ020411 2HC1; Capsazepine; S49076; LCI699; Unknown; TAK-063; 1400W 2HC1; Miransertib (ARQ O92)HC1FIG. 50 :KRIBB11; OTS514 hydrochloride; SAR-020106; Importazole; MI-463; RRx-001; PNU-74654; CCT196969; LY2857785; BH3I-1; JTE-013; SKLB4771 / FLT3-IN-1; Avadomide(CC-122); BAY 1217389; Thiomyristoyl; ASP8273 (Naquotinib); LXR-623 (WAY-252623); LDC4297 (LDC044297); ONO-4059 (GS- 4059) hydrochloride; Salermide; CP21R7 (CP21); Lificiguat(YC-l); ABBV-075 (Mivebresib); Citarinostat (ACY-241); E7449; SUN11602; Bioymifi; TGR-1202; MK-8617; Nazartinib (EGF816, NVS-816); B02; OTS964; PD-166866; 10074-G5; BLU-554; LF3; NMS-P118; Troglitazone (CS-045); GSK6853; GSK180736A; GSK2256098; SRT3025 HC1; EED226; PRT-060318 (PRT318); CFI-400945; BAY-876; Cl- amidine; YU238259; VLX1570; KPT-8602; TAS-102; ARS-853 (ARS853); AZD5582; CRT0066101; LTURM34; Verubecestat (MK-8931); S7983S7983A-196; AD80; SGC2085; RXDX-106 (CEP-40783); Unknown; Senexin A; TMP195; MSC2530818; Sitravatinib (MGCD516); Tirofiban Hydrochloride; 3BDO; TPX-0005; Amcasertib (BBI503); UnknownFIG. 51 :Unknown; TAK-659; TRC051384; Marinopyrrole A (Maritoclax); Unknown; Lys05; FX1; Tofogliflozin(CSG 452); GSK'872 (GSK2399872A); Unknown; Unknown; Sodium dichloroacetate (DCA); Belizatinib (TSR-011); Autophinib; Unknown; Vorasidenib (AG-881); CZC-25146; S 38093; Gilteritinib (ASP2215); NCT-503; Tucidinostat (Chidamide); 3-TYP; PF-06726304; R-IMPP; ROC-325; Chk2 Inhibitor II (BML-277); LY3214996; ACSS2 inhibitor; Unknown; CCG-203971; PKM2 inhibitor(compound 3k); Unknown; Unknown; Ceftazidime; Pirenzepine dihydrochloride; Carmustine; Diphenyleneiodonium chloride (DPI); LYN-1604; GNF-6231; ACY-738; Boldenone Undecylenate; EAD1; COTI-2; Acamprosate CalciuM; GSK3326595 (EPZ015938); Unknown; Adenosine Dialdehyde (ADOX); Unknown; 3PO; OSS-128167; H3B- 6527; Vitamin E Acetate; Sodium Demethylcantharidate; Neferine; Protoporphyrin IX; Pyrithioxin; 2,6- Dihydroxyanthraquinone; Takinib; CA3; PTC-028; Homotaurine; Taurocholic acid sodium salt hydrate; S- allyl-L-cysteine; Sodium erythorbate; Calcium folinate; S-Methyl-L-cysteine; LLY-283; Atrazine; 7- Ethylcamptothecin; Propyl gallateFIG. 52 :7 -Methoxy coumarin; Unknown; ML204; Doxycycline; UNC0642; JQ-EZ-05 (JQEZ5); Unknown; Terconazole; Thiocolchicoside; 2-D082-D08; SHP099 hydrochloride; Nisin; Pixantrone Maleate; Lentinan; 4-Isopropylbenzaldehyde; Geranyl acetate; Diaveridine; Quinocetone; Enoxacin Sesquihydrate; Sulfamethazine Sodium Salt; 4-Aminosalicylic acid; Itacitinib (INCB39110); Brilanestrant (GDC-0810, ARN-810); IWP-01; Nomilin; Granisetron; Revaprazan Hydrochloride; Daclatasvir Digydrochloride; Argatroban Monohydrate; Regorafenib Monohydrate; 2-Acetylphenothiazine (ML171); Skp2 inhibitor Cl (SKPin Cl); SNS-314 Mesylate; Squalene; Farnesol; Linalool; KPT-9274; Agmatine sulfate; Asciminib (ABL001); Tenalisib (RP6530); Mebhydrolin napadisylate; Mebeverine Hydrochloride; Etofylline; Mephenesin; Tiamulin; PHTPP; RAF709; Vitamin K2; Methotrexate disodium; Alectinib hydrochloride; Forchlorfenuron; Metadoxine; J147; Unknown; RAD 140; 7-(Diethylamino)coumarin-3 -carboxylic acid; 4,4'-DIMETHOXYBENZIL; 3,8-Dihydroxy Urolithin; 2', 7- Dihydroxy-3,4-benzocoumarin; PRT4165; Y15; Oxidopamine (hydrobromide); Ruxolitinib Phosphate; Cisapride; UNC-926; SC66; HTHQ(l-O-Hexyl-2,3,5-trimethylhydroquinone); NU2058; UK 5099; Acacetin; DisopyramideFIG. 53 :AZD1390; A-804598; Gefitinib hydrochloride; Fenretinide; Suloctidil; Fendiline hydrochloride; RU58841; Ramatroban; Nimustine Hydrochloride; Vidarabine monohydrate; Amoxicillin trihydrate; Nerolidol; Triprolidine Hydrochloride; Cloperastine hydrochloride; Molindone hydrochloride; Econazole; Betahistine mesylate; Dehydroepiandrosterone acetate; bpV (HOpic); 79-6 (CID5721353, BCL6 inhibitor); Anlotinib (AL3818) dihydrochloride; FGF401; ISO-1; PK11007; Guggulsterone E&Z; Stevioside; Lobeline hydrochloride; Cefoxitin sodium; Dabrafenib Mesylate; O-Phospho-L-serine; Tetrahydroberberine; Nitisinone; Meisoindigo; Metroprolol succinate; alpha-Naphthoflavone; Nintedanib Ethane sulfonate Salt; Cediranib Maleate; Benproperine phosphate; Dapiprazole Hydrochloride; AWD 131-138; DY131; Fipronil; Dibutyl phthalate; UTP, Trisodium Salt; Tegaserod Maleate; 1,4-Cineole; Carbaryl; Bromopyruvic acid; Promazine hydrochloride; Quinacrine Dihydrochloride Dihydrate; Ferulic acid methyl ester; Sanguinarine chloride; Hyperoside; Isobavachalcone; Curculigoside; Verbascoside; Aucubin; Curcurbitacin IIA; Psoralidin;Bavachin; Monotropein; Nafronyl oxalate salt; Clidinium Bromide; Desipramine Hydrochloride; FluoromethoIone; Vortioxetine; Ellagic Acid hydrate; Spermine Tetrahydrochloride; Salmeterol; GalanginFIG. 54 :Tropisetron; D-Ribose; DL-Serine; 6-Paradol; Amenamevir; (-)-Sparteine Sulfate; Dapagliflozin propanediol monohydrate; Azetidine-2-carboxylic acid; Tilmicosin phosphate; Unknown; Cytarabine hydrochloride; Unknown; 3-Hydroxycinnamic acid; UM-164; Tetrahydrocurcumin; Nonivamide; Pterostilbene; Nifuratel; 2,2'-Cyclouridine; 2-Aminobenzenesulfonamide; Nilotinib hydrochloride; lenvatinib Mesylate; Selamectin; TBB; Unknown; Unknown; Ethoxyquin; Pseudolaric Acid B; ARQ 531; CID 16020046 (CID 16020046); Unknown; Atropine sulfate; Tizoxanide; Dexrazoxane; CCT245737 ; L-Omithine hydrochloride; Unknown; Tizanidine; 7-Nitroindazole; Bedaquiline; Lazertinib (YH25448,GNS-1480); Cefpiramide sodium; Unknown; Eptifibatide Acetate; Atosiban Acetate; Salmon Calcitonin Acetate; Leuprorelin Acetate; Angiotensin II human Acetate; Desmopressin Acetate; Azasetron HC1; Apremilast (CC- 10004)Apremilast (CC-10004); Edoxaban; 6-Hydroxy-4-methylcoumarin; Ethyl Coumarin-3-carboxylate; Allitol; Oxalic acid; 4-Hydroxyquinazoline; Coumarin-3 -carboxylic acid; 6-Hydroxycoumarin; 5'-Adenylic acid; ADP; Sophocarpine Monohydrate; Maackiain; Praeruptorin B; N-Benzoyl-(2R,3S)-3-phenylisoserine; Alliin; 3,6'-Disinapoyl sucrose; (20R)-Protopanaxdiol; Pristimerin; SauchinoneFIG. 55 :Angoroside C; Beta-Elemonic; Liensinine; Flavokawain B; Yangonin; Cyasterone; Triptonide; Demethylnobiletin; Diosbulbin B; Narcissoside; Trifolirhizin; Brazilin; Dehydrocorydalin; Ginkgolic Acid; Gingerol; Bergaptol; IBMX; L-Kynurenine; Palifosfamide; DKM 2-93; Unknown; 4'-Methoxychalcone; Metronidazole Benzoate; 17-Beta-Estradiol-3,17-Dipropionate; Scopolamine HBr trihydrate; Canagliflozin hemihydrate; JANEX-1; Suberohydroxamic acid; Cambinol; OAC2; GSK 5959; Solcitinib; CAY10602; KHS101 hydrochloride; CA-5f; Proguanil; Zerumbone; 4-Octyl Itaconate; PNU 282987; BQCA; K 858; Fingolimod; N-Ethyl-5-methyl-2-(l-methylethyl)-cyclohexanecarboxamide; TEPP-46 (ML265, CID- 44246499, NCGC00186528); PLX8394; PT2385; GDC-0575 (ARRY-575, RG7741); AZ31; Pamiparib (BGB-290); Derazantinib(ARQ-087); Nec-ls (7-Cl-O-Necl); ex229 (compound 991); RGX-104; EBI-2511; INCB057643; ABBV-744; Atuveciclib (BAY-1143572); AZ32; IACS-010759 (IACS-10759); Bimiralisib (PQR309); Avitinib (AC0010); PHY34; LXH254; MBQ-167; NGI-1(ML414); Alofanib(RPT835); XRK3F2; Ripretinib (DCC-2618); S55746 (S 055746, BCL201); Adavivint (SM04690)FIG. 56 :IITZ-01; Lanifibranor(IVA-337); IDF-11774; 2'-Deoxyguanosine; 20S-Ginsenoside Rh2, (20R)Ginsenoside Rh2; Gambogenic acid; 6-Shogaol; (+)-Gallocatechin; Boldine; Auraptene; Sinigrin; Gallocatechin gallate; Hydroxy safflor yellow A; Harringtonine; Songorine; Specnuezhenide; Pseudoprotodioscin; Isoxanthohumol; Sweroside; Lithospermoside; Mulberroside A; Epigoitrin; Anhydroicaritin; Anemoside B4; Manninotriose; Rhapontin; Rhoifolin; Corynoline; Dihydrocapsaicin; Calycosin-7-O-beta-D-glucoside; Corilagin; 10- Gingerol; Nardosinone; Pogostone; Senegenin; Alisol B Acetate; Ingenol; Magnolin; Eleutheroside E; Glycitein; Timosaponin A3; Morin; Isorhamnetin; Kaempferitrin; Ononin; Polyphyllin I; Wogonoside; Scutellarein; Tectorigenin; Eriodictyol; Apigetrin; Schizandrol B; Camosol; Harpagide; Chicoric acid; Artemisic acid; Neochlorogenic acid; Picfeltarraenin IA; Pulegone; Berbamine; Peiminine; Daurisoline; Betulinicaldehyde; Chelidonine; Momordin Ic; Ziyu-glycoside I; Rubimaillin; Rhapontigenin; Curdione; GriffonilideFIG. 57 :Columbin; Sinapine thiocyanate; Tussilagone; Periplocin; Crebanine; Ruscogenin; Forsythoside B; Nitidine Chloride; Oroxin A; Oroxin B; Vitexin; Oroxylin A; Eriocitrin; Complanatuside; Ferulaldehyde; Dehydroandrographolide Succinate; Indirubin-3'-monoxime; Santalol; Steviolbioside; Schisandrin C; Vaccarin; Protosappanin B; Tiliroside; Homoorientin; Securinine; Isosilybin; Oxypeucedanin; Acetylshikonin; (+)-Isocorynoline; 7-Epitaxol; Dracohodin perochlorate; Koumine; Isoguanosine; ISCK03; Alisol B; Alisol A; Demethoxycurcumin; Aloesin; Fargesin; Neobavaisoflavone; Genkwanin; Casticin; Astragalin; Isopimpinellin; Isoliquiritin; Gelsemine; Dauricine; Kirenol; Corylin; Ginsenoside Fl; Polyphyllin VI; Shanzhiside methyl ester; Cyanidin-3-O-glucoside chloride; Atractylenolide III; Atractylenolide II; (20R)- Ginsenoside Rhl; Topotecan; Octreotide Acetate; Ajmaline; Methyl Aminolevulinate Hydrochloride; Chlorprothixene hydrochloride; Parecoxib Sodium; Tobramycin sulfate; Vitamin A; Tedizolid; 10- Hydroxy decanoic acid; Moxifloxacin; 7-Hydroxy-4-chromone; Xylazine; Amsacrine hydrochlorideFIG. 58 :Mepivacaine; Lomefloxacin; Trimebutine maleate; Ethyl caffeate; Carvedilol Phosphate; Estropipate; N- Acetyl-DL-phenylalanine; Nefazodone hydrochloride; 6-Biopterin; 4-Butylresorcinol; Metyrapone; Cefoperazone sodium; Fluorescein; D-Tagatose; Flavokawain A; Gallocyanine; Tos-Arg-OMe.HCl; Sulfamide; Chicago Sky Blue 6B; Edetate Trisodium; Ropivacaine; Berberine; Leonurine Hydrochloride; Corynoxine; Calycosin; Corosolic acid; Ambroxol; AKBA; Sanguinarine; Wedelolactone; 23-Hydroxybetulinic acid; Columbianadin; Luteoloside; (20R)Ginsenoside Rg3; 20S-Ginsenoside Rg3; Maslinic acid; Minaprine dihydrochloride; Ammonium lactate; Hydroxyzine pamoate; Clodronate disodium tetrahydrate; RG 13022; Ranitidine; Orphenadrine Hydrochloride; Stearic acid; 5,6,7-Trimethoxyflavone; S-(- )-Cotinine; 3,4-Dimethoxycinnamic acid; L-serine; Anthraquinone-2-carboxylic Acid; Dihydrocoumarin; Pempidine; Fosfosal; Octyl gallate; Ethyl palmitate; Thymine; Losartan; Dasatinib hydrochloride; Delapril Hydrochloride; GI254023X; Indacaterol; Ertapenem sodium; Emedastine; Unknown; Deracoxib; lurasidone; Abemaciclib; Aceto hexamide; Verinurad (RDEA3170); Rolapitant; FruquintinibFIG. 59 :Tubastatin A; Dienestrol ; Alectinib (CH5424802); Auranofin; Bromocriptine Mesylate; Clorgyline HC1; Methoxamine HC1; Oxprenolol HC1; Thiostrepton; Suxibuzone; Digoxigenin; Pindolol; 2-Ethoxybenzamide; 6-Acetamidohexanoic acid; 8-Hydroxyquinoline; Timonacic; Osimertinib mesylate; Naproxen; Carglumic Acid; Ilaprazole sodium; Unknown; Ethacrynic Acid; Diphenylpyraline hydrochloride; Omeprazole Sodium; Drofenine Hydrochloride; Moxisylyte hydrochloride; Isoxsuprine hydrochloride; Chloropyramine hydrochloride; Xanthopterin Hydrate; Isoproterenol sulfate dihydrate; Lapachol; Tryptanthrin; JNJ0966; Ketorolac tromethamine salt; Scopolamine N-Oxide HydrobroMide Monohydrate; Pravastatin; atorvastatin; Tetryzoline; Midodrine; Diclofenac Epolamine; Palonosetron; Chlorpromazine; Setipiprant(ACT- 129968, KYTH-105); Baricitinib phosphate; Citric acid; YM 90709; Aliskiren; sulforaphane; AS-8351; Prazosin; Raloxifene; Dronedarone; Unknown; CID 2011756; Motesanib (AMG-706); Glycochenodeoxycholic acid; Rasagiline; Alda 1; Alprenolol hydrochloride; Cilostamide; HMN-176; Relugolix; Kevetrin hydrochloride; Choline Fenofibrate; cariporide; WAY-316606; GSK0660; acalisib (GS-9820); Linoleic acid; TH34FIG. 60 :HS-1371; WM-1119; Evobrutinib; SSE15206; ML385; CC-90003; MK-3903; Aristolochic acid A; Levistilide A; Urocanic acid; Isorhamnetin 3-O-neohesperoside; Mecamylamine Hydrochloride; Demecarium Bromide; Waltonitone; Praeruptorin D; Madecassic acid; Oleanonic Acid; Danazol; (?)-Norepinephrine; Protriptyline hydrochloride; Crocin I; Rotundic acid; Bakkenolide A; N-(5-Aminopentyl)acetamide; Sudan I; Allyl Methyl Sulfide; Unknown; Doxycycline monohydrate; Diclofenac acid; Quinoline-4-carboxylic acid; Unknown; Terpinen-4-ol; Ureidopropionic acid; Hexadecanedioic acid; Picolinic acid (PCL 016); 2-(4- Methoxyphenyl)acetic acid; Chlorhexidine diacetate; 2-Methoxybenzoic acid; 3-(Methylthio)propionic acid; Glycochenodeoxycholic acid sodium salt; SAR125844; dBETl; Iberdomide(CC220); dBET6; UPGL00004; AZD3229; GSK'547; PFK158; DC661; SPHINX31; Creatine monohydrate; Aminomalonic acid; Chelerythrine Chloride; Ofloxacin; Bestatin; Acetylcholine Chloride; Clofibrate; Seratrodast(AA-2414, ABT- 001); BGJ398 (NVP-BGJ398|Infigratinib); HS-10296; SEL120(SEL120-34,SEL120-34A); compound 3i (666- 15); Polyphyllin VII; Abiraterone Acetate; Unknown; Rheic Acid; Tetrandrine; Ethisterone; CX-5461; I-BET151 (GSK1210151A)FIG. 61 :Daporinad (FK866, APO866); Clopamide; Dolutegravir Sodium; Dimenhydrinate; Anethole trithione; Vanoxerine dihydrochloride; Rabeprazole Related Compound E; Hodostin; Bendamustine; Glucosamine; Unknown; Salicylamide; Tulobuterol hydrochloride; Zucapsaicin; Clemizole; Nimorazole; fexaramine; Apilimod; GK921; AGI 10674 ; TAS-301; AZ876; Ufiprazole; Riboflavin Tetrabutyrate; Chlorophyllin (sodium copper salt); SR4370; Bicyclol ; Clebopride (malate); Glycyrrhetinic acid; Flurbiprofen Axetil; Nifurtimox; Lucanthone; Eicosapentaenoic Acid; GLPG0634 analogue; GSK343; SR9243; Brigatinib (AP26113); MK-8353 (SCH900353); PLX51107; BAY-8002; Unknown; Tinostamustine(EDO-SlOl); CH7057288; Zanubrutinib (BGB-3111); ULK-101; FDL169; AZD1480; Altiratinib; uridine triacetate; Gadoxetate sodium; 6-Bromo-2-hydroxy-3-methoxybenzaldehyde; Genz-123346 free base; SMI-16a; T56- LIMKi; PF-6260933; KX1-004; NVP 231; X-376; Compound 401; Mitapivat; AG 494; RIPA-56; HG-14-10- 04; GNE-477; Desmethylanethol trithione; R112; WHI-P180; WHI-P258; ST 271; RG14620FIG. 62 :NSC 42834; AG 555; Kobe2602; NIH-12848; kb-NB77-78; Briciclib; SU1498; TTP 22; CVT-313; B-Raf IN 1; MTX-211; ZD-4190; SR-3029; URB602; 4-IBP; JK184; NSC23005 Sodium; Src Inhibitor 1; VUF10460; BQR695; Longdaysin; Methylprednisolone hemisuccinate; Hydrocortisone butyrate; Unknown; AR7; Fursultiamine; T-3775440 HC1; Glumetinib; iCRT14; BI-3812; SKLB-23bb; H3B-5942; V-9302; BAY- 293; BAY-218; JNJ-38877618(OMO-1); ZT-12-037-01; Bentamapimod; GSK8612; G1T38; AM580; Ensartinib (X-396) dihydrochloride; Josamycin; SKLB 610; EBE-A22; Bohemine; CZC-54252; ASP5878; NG 52; PD153035; CYM5541; Irosustat (STX64, BN83495); ML348; ML346; ML335; Norethisterone Enanthate; Unknown; THZ531; AG-126; IRAK-1-4 Inhibitor I; KM11060; TB5; YL-109; ETC-159; ABT 702 dihydrochloride; APY29; Temsavir (BMS-626529); Brequinar; E7820; GNE-617FIG. 63 :Belotecan (CKD-602) hydrochloride; AM 095; HC-067047; R-7050; WM-8014; SGC-GAK-1; IQ-1S; Unknown; YHO-13177; NSC 185058; TCS-OX2-29; MKT-077; LXS-196; MK1064; AX-024 HC1; CC-401 Hydrochloride; 7ACC2; PF-670462; JD-5037; C7280948; MN 64; DB07268; Etofenamate; Inauhzin; JW55;APD668; SW-044248; ML364; ASP-9521; Brevianamide F; Y16; Siramesine HC1; I-CBP112; TAS-116; Talabostat (Val-boroPro, PT-100); DT-061(SMAP); Selpercatinib (LOXO-292, ARRY-192); TAS6417; PTC596; Gboxin; Borussertib; AZD7648; BAY 2402234; TAS-120; Belvarafenib(GDC5573, HM95573, RG6185); PDD00017273; BA ; NG25; Imidazole ketone erastin; NDI-091143; Ziritaxestat (GLPG1690); FF-10101; DS-6051b; Fadrozole; Lasofoxifene Tartrate; Branaplam (LMI070); Somatostatin Acetate; Goserelin Acetate; Sodium Hyaluronate; WDR5-0103; Sphingosine; AIM-100; SU5408; NKL 22; Bardoxolone; E7046?; G15; ETC-206; B-Raf inhibitor 1 dihydrochlorid; AST-487FIG. 64 :FT113; CCG-222740; Cytosporone B; Ebselen; L-779450; Merimepodib; TOFA(RMI14514; MDL14514); BAY1125976; ODM-203; USP25 / 28 inhibitor AZ1; UBCS039; Olutasidenib (FT-2102); Ginsenoside F2; Chikusetsusaponin Iva; (20S)Ginsenoside Rg2; Punicalagin; Solasonine; Solamargine; Didymin; Toosendanin; Indoprofen; Roquinimex; Tirapazamine; Estramustine phosphate sodium; CPI- 1189; 4-IPP; Triglycidyl Isocyanurate (Teroxirone); 2'-Deoxy-5-Fluorocytidine; SR-4835; SR18662 ; Unknown; ONO-7475; VLX600; BAY-1816032; ASP4132; Alobresib (GS-5829); HLM006474; BAY 2416964; RN-1734; NSC95397; TM5441; DIM-C-pPhOH; Mobocertinib (TAK788); Luminol; Vipivotide tetraxetan (PSMA-617); RK- 287107; C75; L 189; ML327; AZ-33; MMAF; ML216; ML210; Ansamitocin P-3; Seclidemstat; Ellipticine hydrochloride; BCI-121; BCTC; Vorolanib; 3'-Fluoro-3'-deoxythymidine (Alovudine); Bufalin; Rottierin; THZ2; PQR620; UT-34; MZ 1( MZ-1); JHU395; JMS-17-2; IMR-1A; XCT790FIG. 65 :Indibulin; CADD522; 6-Methoxydihydrosanguinarine; Navitoclax (ABT-263); Vindesine sulfate; Unknown; Cinobufagin; 5,7-Dimethoxyflavone; Sinapine; Resibufogenin; H3B-120; Nodakenetin; Picfeltarraenin IB; Hypericin; Polyphyllin B (Formosanin C); Daphnoretin; Hispidulin; Demethyleneberberine; Desoxyrhaponticin; Stylopine (Trahydocoptisine); TPI-1; Dimethylcurcumin (ASC- J9); Bozitinib (PLB-1001); NE 52-QQ57; RA-190; Gossypol; ONC206; Ningetinib; EOAI3402143; SRT- 1460; HI-TOPK-032; BCH; MCP110; CDKI-73; GSK484 HC1; ARN-3236; BI 894999; GSK 2837808A; 6- Diazo-5-oxo-L-norleucine; BAY 1251152; JSH-150; EMD638683; GSK3145095; JH-RE-06; MYC1361; MYCi975; BI-3406; MS1943; GCN2iB; BO-264; CC-92480; RBN012759; 9-ing-41; IM156; ABTL-0812; Donafenib (Sorafenib D3); Phenoxodiol (Haginin E); VX-803 (M4344); NEO2734; Acelarin (NUC-1031); SP-146; Irinotecan; Solanesol (Nonaisoprenol); MAZ51; PACAP 1-38; Prim-o-glucosylcimifugin; Tenacissoside H; Buddlejasaponin IVb; Chonglou Saponin VII; NotopterolFIG. 66 :Ginsenoside Rb3; Ginsenoside Rkl; Berberrubine; Isoliensinine; Raddeanin A; Ginsenoside Rc; Epmedin C; Methylprotodioscin; Tubeimoside II; Pentostatin; Lanreotide acetate; (E / Z)-BCI; KS176; HAMNO; C- DIM5; TRi-1; COH-29; Antineoplaston A10; Y06036; Alsterpaullone; ML281; Oncrasin-1; RA-9; TBOPP; ML-180; Amarogentin; L-2-Hydroxyglutaric acid disodium; Calcium Levofolinate; SYP-5; NP-G2-044; 9- Methoxycanthin-6-one; L-DAB HBR; Itaconic acid; L-Histidine monohydrochloride monohydr; Maleimide; Nudifloric Acid; L-Histidinol dihydrochloride; 1 -Methylnicotinamide chloride; Apatinib; MSAB; Lanreotide; Unknown; Treosulfan; PT2399; RBN-2397; DRB18; CBR-5884; NCGC00378430; FDI-6; iHAPl; Ezatiostat; IACS-13909; Fluzoparib (SHR-3162); TK216; CB-103; BSO (L-Buthionine-(S,R)-sulfoximine); Fatostatin; Gallein; SAR439859; (Rac)-JBJ-04-125-02; CCS-1477 (CBP-IN-1); SZL Pl-41; SRX3207; 6- Aminonicotinamide; Phenol Red sodium salt; Megestrol; TMPyP4 tosylate; CDDO-Im; Tetraethylammonium chloride; PKR-IN-C16FIG. 67 : cis-Resveratrol; EN4; Rhosin hydrochloride; Neticonazole; CPI-0610; Ceritinib dihydrochloride; Metarrestin (ML246); 4-Hydroxyphenylpyruvic acid; 6-Iodopravadoline (AM630); Indisulam; CC-90010; KB-R7943 mesylate; Elimusertib (BAY-1895344); Estrogen receptor modulator 1; Metformin; CTPI-2; (Z)-4- Hydroxytamoxifen; CM10; DTHIB; Zoledronic Acid; Remdesivir (GS-5734); BOS 172722; A939572; AG- 636; Emavusertib (CA-4948); Hypocrellin A; Ophiopogonin D; CP-31398 Dihydrochloride; EC33O; SKI-V; NPD8733; HPK1-IN-2; YUM70; ARV-110; Lucitanib (E3810) hydrochloride; OSMI-1; BSJ-4-116; BTYNB; MS 140; PFI-90; MYLS22; JNJ-63576253 (TRC-253); Pimonidazole; Paeoniflorin; 4-Hydroxyphenylacetic acid; Unknown; L-Leucine; Carbenoxolone disodiuM; Molidustat(BAY 85-3934); STO-609; Isosorbide dinitrate; 2',5'-Dihydroxyacetophenone; Diphenylamine Hydrochloride; Deferoxamine mesylate; Unknown; N- Acetylcysteine amide; Methyl cinnamate; ABX-1431; Vadadustat; CP 640186; GPNA; ND-630; ligustroflavone; IOX4; SBI-797812; S-Gboxin; BMS303141; Unknown; Pteryxin; Tenovin-3FIG. 68 :Myrislignan; Senkyunolide I; Cynarin; Sodium oxamate; VH298; Cyclosporine (Neoral); MPEP; Neohesperidin dihydrochalcone (Nhdc); Prucalopride Succinat; Fosaprepitant dimeglumine salt; Medroxyprogesterone; Catalpol; Epalrestat; Cinnamaldehyde; Amifostine; Fumagillin; Squalane; Nafarelin Acetate; L-Fucose; Catharanthine hemitartrate; D-Mannose; pyrvinium; (S)-(?)-Limonene; Unknown; Rubitecan; Pemigatinib (INCB054828); Staurosporine; Folinic acid; Rucaparib; Pipobroman; Palbociclib;Irinotecan hydrochloride; Trametinib DMSO solvate; Ribociclib hydrochloride; Larotrectinib; Ixazomib Citrate (MLN9708); Pemetrexed; Ribociclib succinate; Dexamethasone palmitate; Enasidenib Mesylate; Rucaparib Camsylate; Regorafenib Hydrochloride; Nilotinib hydrochloride monohydrate; ad)The sequence number is used to abbreviate the guest drug, and InChKey is used to obtain molecular information about the guest drug. So for example for GUEST29917 - “29917” is the sequential number of compound Zuclopenthixol dihydrochloride, and GUEST29917 means Zuclopenthixol dihydrochloride for which InChlKey is LPWNZMIBFHMYMX- MHKBYHAFSA-N. Based on this InChlKey the molecular inormation InChi for Zuclopenthixol dihydrochloride (GUEST29917) can be derived: InChI=lS / C22H25ClN2OS.2ClH / c23-17-7-8-22-20(16-17)18(194-l-2-6-21(19)27-22)5-3-9- 24-10-12-25(13-l l-24)14-15-26;; / hl-2,4-8,16,26H,3,9-15H2;2*lH / bl8-5-;;Accordingly, GUEST29917-GUEST29919 means all the guest drug having sequence numbers 29917-29919, that is: GUEST29917, GUEST29918, GUEST29919; that is, the result GUEST29917-GUEST29919 means guest drugs: Zuclopenthixol dihydrochloride (LPWNZMIBFHMYMX-MHKBYHAFSA-N), Zunsemetinib (FQPQMJULRZINPV- UHFFFAOYSA-N), Zuranolone (HARRKNSQXBRBGZ-GVKWWOCJSA-N).If the selected guest drug is in the form of a free base - the pharmaceutical salts of that base and the pharmaceutical ester or ether are also included. If the guest drag is in the form of a pharmaceutical salt - the free base of that salt, the pharmaceutical ester or ether, and other pharmaceutical salts of that free base are also included. Also include racemate, enantiomer, diastereomer, tautomer, polymorph, pseudopolymorph, hydrate or prodrug thereof or mixtures thereof.Thus guest drug is selected from GUEST1-29924.derivatives of compounds specified in (a)-(ad) such as racemate, enantiomer, diastereomer,tautomer, polymorph, pseudopolymorph, hydride or solvate thereof; or a pharmaceutically acceptable salt or ester or ether thereof; or prodrug thereof; or methabolite thereof; or aglycone thereof; or derivatives thereof (including chemical and physical); or derivatives which may be obtained by gene replacement processes in genetically engineered strains, or / and by fermentation, or / and by chemical modifications and the like, or / and which are described in the scientific and patent literature, for example (non-limited examples) in:wherein [HOST]nis (satisfies at least one of (A) to (H)):A)R is H, MeororB) Chemically modified derivatives of (A) where any -OH can be replaced by R, wherein R is H, halogen, F, Cl, Br, I, OH, Me, Et, Ac, OMe, OEt, OAc, ORA, N(RA)2,N3, CN, NO2, S(O)ZRA, (Ci-Ci5)alkyl, (C4-C8)carbocyclylalkyl, (Ci-Cx)substitutcd alkyl, (Ci-Cxjalkcnvl. (C2- Cxjsubstitutcd alkenyl, (C’2-Cx)alkynyl. (C2-C8)substituted alkynyl, — C(=O)RA, — C(=O)ORA, — C(=O)NRARB, — C(=O)SRA, — S(O)RA, — S(O)2RA, — S(O)(ORA), — S(O)2(ORA), — SO2NRARB, (C6-C2o)aiyl(Ci-C8)alkyl, — PO(OH)2, — PO(OH)OPO(OH)2,— PO(OH)OPO(OH)O PO(OH)2, — PO(ORA)2, — PORARB, phenyl, 1-naphthyl, 2-naphthyl, benzyl, (Cf-G,)cycloalkyl. — CH2 — (C3- Csjcycloalkyl. — O — ( Ci-Cs) alkyl, — O-benzyl, — O — CH2 — (Cs-Gjcycloalkyl. CF3, C(halogen)3, — C(=Q)RA, — C(=Q)ORA, — C(=Q)N(RA), — NRARB, —+N(RA)3, — SRA, — S(O)RA, — S(O)2RA, — S(O)(ORA), — S(O)2(ORA), — OC(=Q)RA, — OC(=Q)ORA, — OC(=Q)(N(RA)2), — SC(=Q)RA, — SC(=Q)ORA, — SC(=Q)(N(RA)2), — N(RA)C(=Q)RA, — N(RA)C(=Q)ORA, — N(RA)C(=Q)N(RA)2, — SO2NRA2, — CN,— N3, — NO2, — ORA, NRARB, N(RA)ORB, NRANRB, N3, NO, NO2, CHO, CN, — CH(=NRA),— CH=NNHRA, — CH=N(ORA), — CH(ORA)2, — C(=O)NRBRA, — C(=S)NRBRA, — C(=O)ORA, (C6-C2o)optionally substituted aryl, optionally substituted heteroaryl, — C(=O)(Ci- Cs)alkyl, — S(O)n(Ci-Cs)alkyl, SRA,or selected from radicals obtained by removal of a hydrogen atom from the compounds shown in FIG. 8 wherein Q is O, S, NRA, ^(O)^), N(ORA), ^(OXOR^, or N— NRA2;wherein RA, RBis H, halogen, F, Cl, Br, I, OH, Et, Me, Ac, ORC, N(RC)2,N3, CN, NO2, S(O)ZRC, (Ci-Ci3)alkyl, (C4-C8)carbocyclylalkyl, (Ci-C«)substitutcd alkyl, (C2-C8)alkenyl, (C2- C8)substituted alkenyl, (C2-Cs)alkynyl, (C2-C8)substituted alkynyl, — C(=O)Rc, — C(=O)ORc, — C(=O)NRcRc, — C(=O)SRc, — S(O)RC, — S(O)2RC, — S(O)(ORC), — S(O)2(ORC), — SO2NRCRC, (C6-C2o)aryl(Ci-C8)alkyl, — PO(OH)2, — PO(OH)OPO(OH)2,— PO(OH)OPO(OH)OPO(OH)2, — PO(ORC)2, — PORCRC, phenyl, 1 -naphthyl, 2-naphthyl, benzyl, (Cs-Csjcycloalkyl, — CH2— (Cs-Csjcycloalkyl, — O — ( Ci-C8) alkyl, — O-benzyl, — O — CH2— (C3-C6)cycloalkyl, CF3, C(halogen)3, — C(O) Rc, — C(O)ORc, — C(O)N(Rc), — NRCRC,CH=N(ORc), — CH(ORC)2, — C(=O)NRCRC, — C(=S)NRCRC, — C(=O)ORC, (C6-C20)optionally substituted aryl, optionally substituted heteroaryl, — C(=O)(Ci-C8)alkyl, — S(O)z(Ci-C8)alkyl, or SRC; wherein Rcis H, OH, F, Cl, Br, I, Me, Et, Ac, OMe, OEt, or OAc,or selected from radicals obtained by removal of a hydrogen atom from the compounds shown in FIG. 8; whereinz is from 1 to 10.D) wherein [HOST]nisand continue on FIG.l, FIG.2, FIGG, FIG.4, FIGG, and the likewherein xl, x2, x3, x4, x5, x6 is from 1 to 108; whereinwherein at least one of Ml, M2, M3, M3, M4, M5, M6is a repeat unit(s) or terminal residue formed from this monomers: a) 4-epi-Legionaminic acid; 6-Deoxy-L-altrose; N-Acetyl-6-deoxy-L-altrosamine; 6- Deoxy-D-gulose; 6-Deoxy-D-talose; N-Acetyl-6-deoxy-D-talosamine; 8-epi- Acinetaminic acid; 8-epi-Legionaminic acid; Abequose; Acinetaminic acid; D-Allose; D-Alluronic acid; D-Allosamine; N-Acetyl-D-allosamine; L-Altrose; L-Altruronic acid; L-Altrosamine; N-Acetyl-L-altrosamine; L-Apiose; L-Arabinose; Bacillosamine; Colitose; D-glycero-D-manno-Heptose; 3-Deoxy-D-lyxo-heptulosaric acid; D- Digitoxose; D-Fructose; L-Fucose; N-Acetyl-L-fucosamine; D-Galactose; D- Galacturonic acid; D-Galactosamine; N-Acetyl-D-galactosamine; D-Glucose; D- Glucuronic acid; D-Glucosamine; N-Acetyl-D-glucosamine; D-Gulose; D-Guluronic acid; D-Gulosamine; N-Acetyl-D-gulosamine; L-Idose; L-Iduronic acid; L-Idosamine; N-Acetyl-L-idosamine; 2-Keto-3-deoxy-nononic acid; 3-Deoxy-D-manno-octulosonic acid; Legionaminic acid; L-glycero-D-manno-Heptose; D-Lyxose; D-Mannose; D- Mannuronic acid; D-Mannosamine; N-Acetyl-D-mannosamine; Muramic acid; N- Acetylmuramic acid; N-Glycolylmuramic acid; Neuraminic acid; N-Acetylneuraminic acid; N-Glycolylneuraminic acid; Olivose; Paratose; Pseudaminic acid; D-Psicose; D- Quinovose; N-Acetyl-D-quinovosamine; L-Rhamnose; N-Acetyl-L-rhamnosamine; D-Ribose; Sialic acid; L-Sorbose; D-Tagatose; D-Talose; D-Taluronic acid; D- Talosamine; N-Acetyl-D-talosamine; Tyvelose; D-XyloseDioses; Aldodiose; Glycolaldehyde; Trioses; Aldotriose; Glyceraldehyde; Ketotriose; Dihydroxyacetone; Tetroses; Aldotetroses; Erythrose Threose; Ketotetrose; Erythrulose; Pentoses; Aldopentoses; Arabinose; Lyxose; Ribose; Xylose; Ketopentoses; Ribulose; Xylulose; Deoxy sugars; Deoxyribose; Hexoses; Aldohexoses; Allose; Altrose; Galactose; Glucose; Gulose; Idose; Mannose; Talose; Ketohexoses; Fructose; Psicose; Sorbose; Tagatose; Fucose; Fuculose; Rhamnose; Heptoses; Ketoheptoses; Mannoheptulose; Sedoheptulose; Octoses; Nonoses; Neuraminic acid; galactosamine, N- acetylgalactosamine, N-formylgalactosamine, N-propionylgalactosamine, N-n- butanoylgalactosamine, N-iso-butanoylgalactosamine, lactose, lactobionic acid, mannose, aminoacids, nucleosides, folate, folic acid, y-FBA-folate, and a-FBA-folate, and other folic acid chemical derivatives; and (using IUPAC nomenclature of organic chemistry, IUPAC Condensed code system) from this monomers:1,4-Anhydro-Gal; 1,4-Anhydro-Gal; 1,4-Anhydro-Kdo; IdAlt-ol; IdEry-ol; 2,3- Anhydro-All; 2,3-Anhydro-Man; 2,3-Anhydro-Rib; 2,5-Anhydro-D-Alt; 2,5-Anhydro-D-AltOS; 2,5-Anhydro-L-Man; 2,5-Anhydro-Man; 2,5-Anhydro-Man-ol; 2,5- Anhydro-ManOS; 2,5-Anhydro-Tal-ol; 2,5-Anhydro-TalOP; 2,7-Anhydro-Kdo; 2,7- Anhydro-Kdof; 3,6-Anhydro-Fruf; 3,6-Anhydro-Gal; 3,6-Anhydro-GalOS; 3,6- Anhydro-Glc; 3,6-Anhydro-L-Gal; 3,6-Anhydro-L-GalOMe; 3dLyxHepUlosaric; 4,7- Anhydro-KdoOPEtn; 4,8-Anhydro-DDGlcOct; 4,8-Anhydro-Kdo; 4,8-Anhydro- LDGlcOct; 4dAraHex; 4dEry-ol; 4eLeg5Ac7Ac; 6dAlt; 6dAltNAc; 6dAltOAc; 6dAltf; 6dAltfOAc; 6dGul; 6dManHep; 6dTal; 6dTalNAc; 6dTalNAcOAc; 6dTalOAc; 6dTalOAcOAc; 6dTalOAcOMe; 6dTalOMe; 6dTalOMe-ol; 6dTalf; 8eAciNAcNAc; 8eLeg; 8eLeg5Ac7Ac; 8eLeg5Ac7AcGro; 8eLegNAc; 8eLegNAcNBut; Abe; AbeOAc; AcefA; AciNAcNAc; Aco; AcoNAc; A11N; AllOAc; AllOMe; Alt; AltA; AltAN; AltNAcA; AltOMeA; Altf; AltfOAc; Ami; ApiOAc; ApiOMe-ol; Apif; Ara; Ara-ol; AraGlc; AraHepUloNAc-onic; AraHepUloNAcN- onic; AraHepUloNGc-onic; AraHexA; AraN; AraNMeOMe; AraOAc; AraOAcOP-ol; AraOMe; AraOPN; Araf; ArafGro; ArafOCoum; ArafOFer; ArafOMe; ArafOS; Asc; Bac; BacNAc; BoiOMe; Col; D-2dAraHex; D-2dAraHexA; D-3dAraHepUlosonic; D- 3dLyxHepUlosaric; D-3dThrHexUlosonic; D-3dThrPen; D-3dXylHexOMe; D- 4dAraHex; D-4dEryHexOAcN4en; D-4dLyxHex; D-4dLyxHexOMe; D- 4dThrHexA4en; D-4dThrHexAN4en; D-4dThrHexOAcN4en; D-4dXylHex; D- 6dA110Me; D-6dAlt; D-6dAltHep; D-6dAltHepOMe; D-6dAltHepf; D-6dAraHex; D- 6dAraHexN; D-6dAraHexNAc; D-6dAraHexOMe; D-6dLyxHexOMe; D-6dManHep; D-6dManHepOAc; D-6dManHepOP; D-6dTal; D-6dTalHep; D-6dTalOAc; D- 6dTalOAcOMe; D-6dTalOMe; D-6dXylHex; D-6dXylHexN4Ulo; D- 6dXylHexNAc4Ulo; D-6dXylHexOMe; D-7dLyxOctUlosonic; D-9dThrAltNon-onic; D-Alt; D-Apif; D-ApifOAc; D-ApifOMe; D-Ara; D-Ara-ol; D-AraHepUlo-onic; D- AraHex; D-AraHexUloOMe; D-AraN; D-AraOS; D-Araf; D-ArafN; D-Fuc; D-Fuc-ol; D-FucN; D-FucNAc; D-FucNAc-ol; D-FucNAcN; D-FucNAcNMe; D- FucNAcNMeN; D-FucNAcOAc; D-FucNAcOMe; D-FucNAcOP; D-FucNAcOPEtn; D-FucNAlaAc; D-FucNAsp; D-FucNBut; D-FucNButGro; D-FucNFo; D-FucNLac; D-FucNMeN; D-FucNN; D-FucNThrAc; D-FucOAc; D-FucOAcN; D-FucOAcNBut; D-FucOAcNGroA; D-FucOAcOBut; D-FucOAcOMe; D-FucOBut; D-FucOEtn; D- FucOMe; D-FucOMeN; D-FucOMeOCoum; D-FucOMeOFer; D-FucOMeOSin; D- FucOS; D-Fucf; D-FucfNAc; D-FucfOAc; D-Ido; D-IdoA; D-IdoOSA; D-Rha; D- Rha-ol; D-RhaCMe; D-RhaGro; D-RhaN; D-RhaNAc; D-RhaNAcOAc; D-RhaNBut; D-RhaNButOMe; D-RhaNFo; D-RhaOFoN; D-RhaOMe; D-RhaOMeN; D-RhaOP; D-RhaOS; D-RibHex; D-RibHexNAc; D-Sor; D-ThrHexA4en; D-ThrHexAN4en; D- ThrHexfNAc2en; D-ThrPen; D-Thre-ol; DDAltHep; DDAltHepOMe; DDGalHep; DDGalHepOMe; DDGlcHep; DDManHep; DDManHepGroPA; DDManHepOBut; DDManHepOEtn; DDManHepOMe; DDManHepOP; DDManHepOPEtn; DDManNonUloNAcOFoN-onic; DLAltNonUloNAc-onic; DLGalNonUloNAc-onic; DLGalNonUloNAcN; DLGalNonUloNAcN-onic; DLGlcHepOMe; DLHepGlcOMe; DLManHep; DLManHepOPEtn; Dha; Dig; DigCMe; DigOAc; DigOFo; DigOMe; Ery; Ery-L-GlcNonUloNAcOAcOMeSH-onic; Ery-ol; Ery-onic; EryHex; EryHex2en; EryHexA3en; EryOMe-onic; Fru; Fruf; FrufF; FrufI; FrufN; FrufNAc; FrufOAc; FrufOAcOBzOCoum; FrufOAcOFer; FrufOBzOCin; FrufOBzOCoum; FrufOBzOFer; FrufOFer; FrufOLau; Fuc; Fuc-ol; FucN; FucNAc; FucNAcA; FucNAcGroP; FucNAcN; FucNAcNMe; FucNAcOAc; FucNAcOMe; FucNAla; FucNAm; FucNBut; FucNFo; FucNProp; FucNThrAc; FucOAc; FucOAcNAm; FucOAcNBut; FucOAcOMe; FucOAcOSOMe; FucOMe; FucOMeOPam; FucOMeOVac; FucOP; FucOPOMe; FucOS; FucOSOMe; Fucf; Gal; Gal-ol; Gal6Ulo; GalA; GalA-ol; GalAAla; GalAAlaLys; GalAGroN; GalALys; GalAN; GalANCys; GalANCysAc;GalANSerAc; GalAOLac; GalAOPyr; GalASer; GalAThr; GalAThrAc; GalCl; GalF; GalGro; GalGroN; GalGroP; GalN; GalNAc; GalNAc-ol; GalNAc-onic; GalNAcA; GalNAcAAla; GalNAcAN; GalNAcASer; GalNAcGro; GalNAcGroP; GalNAcGroPAN; GalNAcN; GalNAcOAc; GalNAcOAcA; GalNAcOAcAN; GalNAcOAcGroP; GalNAcOAcOMeA; GalNAcOAcOP; GalNAcOMe; GalNAcOP; GalNAcOPCho; GalNAcOPEtn; GalNAcOPyr; GalNAcOS; GalNAla; GalNAmA; GalNCysGly; GalNFoA; GalNFoAN; GalNOPCho; GalNSuc; GalNonUloNAc-onic; GalOAc; GalOAcA; GalOAcAGroN; GalOAcAOLac; GalOAcAThr; GalOAcGroP; GalOAcN; GalOAcNAla; GalOAcNAmA; GalOAcNFoA; GalOAcNFoAN; GalOAcOFoA; GalOAcOMe; GalOAcOP; GalOAcOPyr; GalOFoAN; GalOFoNAN; GalOLac; GalOLac-ol; GalOMe; GalOMeA; GalOMeCl; GalOMeF; GalOMeNAla; GalOP; GalOPA; GalOPAEtn; GalOPAN; GalOPCho; GalOPEtn; GalOPEtnA; GalOPEtnN; GalOPy; GalOPyr; GalOS; GalOSA; GalOSOEt; GalOSOMeA; GalOctUloNAc-onic; Galf; GalfGro; GalfGroP; GalfNAc; GalfOAc; GalfOAcGro; GalfOAcGroP; GalfOAcOLac; GalfOLac; GalfOMe; GalfOP; GalfOPCho; GalfOPyr; Gl; Glc; Glc-ol; Glc6Ulo; GlcA; GlcAAla; GlcAAlaLys; GlcAGlu; GlcAGly; GlcAGro; GlcAGroN; GlcALys; GlcAN; GlcAOLac; GlcAOPy; GlcAOPyr; GlcASer; GlcAThr; GlcAThrAc; GlcCho; GlcF; GlcGro; GlcGroA; GlcGroP; GlcGroPA; GlcI; GlcN; GlcN-ol; GlcNAc; GlcNAc-ol; GlcNAcA; GlcNAcAAla; GlcNAcAN; GlcNAcANAla; GlcNAcANAlaAc; GlcNAcANAlaFo; GlcNAcAla; GlcNAcCl; GlcNAcGlu; GlcNAcGly; GlcNAcGro; GlcNAcGroP; GlcNAcGroPA; GlcNAcI; GlcNAcN; GlcNAcN-ol; GlcNAcNAla; GlcNAcNAlaFo; GlcNAcNAmA; GlcNAcNButA; GlcNAcOAc; GlcNAcOAcA; GlcNAcOAcN; GlcNAcOAcNAla; GlcNAcOAcOCmOOle; GlcNAcOAcOCmOPam; GlcNAcOAcOCmOVac; GlcNAcOAcOLac; GlcNAcOAcOOle; GlcNAcOAcOPam; GlcNAcOAcOPyr; GlcNAcOAcOS-ol; GlcNAcOAcOVac; GlcNAcOGc; GlcNAcOLac; GlcNAcOLacAla; GlcNAcOLacGro; GlcNAcOMe; GlcNAcOMeA; GlcNAcOP; GlcNAcOPCho; GlcNAcOPEtg; GlcNAcOPEtn; GlcNAcOPOAch; GlcNAcOPyr; GlcNAcOS; GlcNAcOS-ol; GlcNAcOSA; GlcNAm; GlcNAmA; GlcNBut; GlcNButAN; GlcNButOAc; GlcNCmOCm; GlcNCmOCmOOle; GlcNCmOCmOVac; GlcNCmOVac; GlcNGc; GlcNGly; GlcNMe; GlcNMeOCm; GlcNMeOCmOPam; GlcNMeOCmOSte; GlcNMeOCmOVac; GlcNMeOSte; GlcNMeOVac; GlcNN; GlcNOAep; GlcNOCmOAch; GlcNOCmOVac; GlcNOMar; GlcNOMe; GlcNOMyr; GlcNOOle; GlcNOPam; GlcNOPyr; GlcNOSte; GlcNOVac; GlcNS; GlcNSOS; GlcNSOSOMe; GlcNSuc; GlcOAc; GlcOAcA; GlcOAcGro; GlcOAcGroA; GlcOAcGroP; GlcOAcN; GlcOAcNBut; GlcOAcNCmOOle; GlcOAcNCmOPam; GlcOAcNCmOVac; GlcOAcNMeOCm; GlcOAcNMeOCmOVac;GlcOAcNMeOVac; GlcOAcNOCmOVac; GlcOAcNOOle; GlcOAcNOPam; GlcOAcNOVac; GlcOAcOCoum; GlcOAcOFer; GlcOAcOOle; GlcOAcOP; GlcOAcOPam; GlcOAcOS; GlcOAcOSA; GlcOAcOSte; GlcOButA; GlcOBz; GlcOCoum; GlcOEt; GlcOEtn; GlcOEtnA; GlcOEtnN; GlcOFer; GlcOFoN; GlcOGc; GlcOLac; GlcOMal; GlcOMe; GlcOMe-ol; GlcOMeA; GlcOMeAN; GlcOMeN; GlcOMeNOMyr; GlcOMeOFoA; GlcOMeOPyr; GlcOOle; GlcOP; GlcOP-ol; GlcOPA; GlcOPCho; GlcOPChoGro; GlcOPEtn; GlcOPEtnGro; GlcOPEtnN; GlcOPGroP; GlcOPN; GlcOPNOMyr; GlcOPNOPam; GlcOPOOle; GlcOPPEtn; GlcOPPEtnN; GlcOPam; GlcOPyr; GlcOS; GlcOSA; GlcOSN; GlcOSNMeOCm; GlcOSOEt; GlcOSOMe; GlcOSOMeA; GlcOSin; GlcS; GlcSH; GlcThr; Glcf; Gro; Gro-ol; Gul; GulAN; GulNAcA; GulNAcAN; GulNAcNAmA; GulNAcOAcA; Hep; HepOP; HepOPEtn; HepOPPEtn; Hex; HexA; HexN; HexNAc; HexOMeOFo; Hexf; Ido; IdoA; IdoN; IdoNAc; IdoOAcA; IdoOAcOSA; IdoOMeA; IdoOS; IdoOSA;IdoOSOEtA; IdoOSOMeA; Kdn; KdnOAc; KdnOMe; KdnOPyr; Kdo; Kdo-ol; KdoGroP; KdoN; KdoOAc; KdoOAcOS; KdoOMe; KdoOP; KdoOPEtn; KdoOPN; KdoOPOEtn; KdoOPOPEtn; KdoOPPEtn; KdoOPPEtnN; KdoOPyr; KdoOS; Kdof; Ko; KoOMe; KoOPEtn; L-4dEryHexAN4en; L-4dThrHex4en; L-4dThrHexA4en; L- 4dThrHexA4enAla; L-4dThrHexAN4en; L-4dThre-ol; L-6dAraHex; L- 6dAraHexOMe; L-6dGalHep; L-6dGalHepOP; L-6dGulHep; L-6dGulHepOMe; L- 6dGulHepOP; L-6dXylHexNAc4Ulo; L-Aco; L-AcoOMe; L-AcoOMeOFo; L- BoiOMe; L-Cym; L-CymOAc; L-DigOMe; L-Ery; L-EryCMeOH; L-EryHexA4en; L- Fru; L-Fruf; L-Gal; L-GalAN; L-GalNAc; L-GalNAc-onic; L-GalNAcA; L- GalNAcAN; L-GalNAcOAcA; L-GalNAmA; L-GalOAcNAmA; L-GalOS; L-Glc; L- GlcA; L-GlcNAc; L-GlcOMe; L-Gro-onic; L-GroHexUlo; L-Gul; L-Gul-onic; L- GulA; L-GulAN; L-GulHep; L-GulNAc; L-GulNAcA; L-GulNAcAGly; L- GulNAcAN; L-GulNAcANEtn; L-GulNAcNAmA; L-GulNAcNEtnA; L- GulNAcOAc; L-GulNAcOAcA; L-GulNAcOAcAN; L-GulNAcOEtA; L- GulNAcOEtnA; L-GulOAcA; L-Lyx; L-LyxHex; L-LyxHexNMe; L-LyxHexOMe; L- Man; L-ManOMe; L-ManOctUlo-onic; L-Ole; L-OleOAc; L-Oli; L-OliOMe; L-Qui; L-QuiN; L-QuiNAc; L-QuiNAcOMe; L-QuiNAcOP; L-QuiOMeN; L-RibHex; L- Ribf; L-Tal; L-The; L-TheOAc; L-Thr; L-ThrHexA4en; L-ThrHexAN4en; L- ThrHexOMe4en; L-ThrHexOMeA4en; L-ThrHexOSA4en; L-Xyl; L-XylHex; L- XylOMe; LDGalHep; LDGalNonUloNAc-onic; LDGlcHep; LDIdoHep; LDIdoHepPro; LDManHep; LDManHepGroN; LDManHepGroPA; LDManHepOAc; LDManHepOCm; LDManHepOEtn; LDManHepOMe; LDManHepOP; LDManHepOPEtn; LDManHepOPEtnOEtn; LDManHepOPOCm;LDManHepOPOMe; LDManHepOPOPEtn; LDManHepOPOPPEtn;LDManHepOPPEtn; LDManHepOPPEtnOPyrP; LDManHepOPyrP;LDManNonUloNAcOFoN-onic; LDManNonUloOFoNN-onic; LLManNonUloOFoN- onic; Leg; Leg5Ac7Ac; LegNAc; LegNAcAla; LegNAcNAla; LegNAcNAm; LegNAcNBut; LegNFo; Lyx; LyxHex; LyxHexOMe; LyxOMe; LyxOctUlo-onic; Lyxf; Man; Man-ol; ManA; ManCMe; ManF; ManGroP; ManN; ManNAc; ManNAcA; ManNAcAAla; ManNAcAGro; ManNAcAN; ManNAcANOOm; ManNAcASer; ManNAcAThr; ManNAcGroA; ManNAcGroP; ManNAcGroPA; ManNAcNAmA; ManNAcNEtnA; ManNAcOAc; ManNAcOAcA; ManNAcOLac; ManNAcOMe; ManNAcOMeAN; ManNAcOPEtn; ManNAcOPyr; ManNBut; ManNGroP; ManNonUloNAc-onic; ManOAc; ManOAcA; ManOAcN; ManOAcOMe; ManOAcOPyr; ManOAep; ManOBut; ManOEtn; ManOLac; ManOMe; ManOMeA; ManOP; ManOP-ol; ManOPCho; ManOPEtn; ManOPOMe; ManOPOPyr-ol; ManOPy; ManOPyr; ManOS; ManOctUlo; ManSH; Manf; Mur; MurNAc; MurNAcAla; MurNAcOP; MurNAcSer; Neu; Neu5Ac; Neu5AcN; Neu5AcNAc; Neu5AcNMe; Neu5AcOAc; Neu5AcOAcOMe; Neu5AcOGc; Neu5AcOMe; Neu5AcOS; Neu5Gc; Neu5GcA; Neu5GcN; Neu5GcOMe; Neu5GcOS; NeuOFo; NeuOMe; OLac; Ole; Oli; OliN; OliNAc; OliOMe; Par; Parf; PerNAc; Pse; Pse5Ac7Ac; Pse5Ac7AcNBut; Pse5Ac7AcOBut; PseNAc; PseNAcNAm; PseNAcNBut; PseNAcNFo; PseNAcNGro; PseNAcOAcNBut; PseNAcOBut; PseNButNFo; PseNGcNAm; PseOAc; PseOAcOFo; PseOFo; Qui; QuiN; QuiNAc; QuiNAc-ol; QuiNAcGro; QuiNAcGroP; QuiNAcN; QuiNAcNAlaAc; QuiNAcNAm; QuiNAcNAspAc; QuiNAcNBut; QuiNAcNButGro; QuiNAcNGroA; QuiNAcOAc; QuiNAcOBut; QuiNAcOMe; QuiNAcOP; QuiNAla; QuiNAlaAc; QuiNAlaAcGro; QuiNAlaBut; QuiNAlaButGro; QuiNAspAc; QuiNBut; QuiNButAla; QuiNButOMe; QuiNFo; QuiNGlyAc; QuiNHse; QuiNHseGro; QuiNLac; QuiNMal; QuiNSerAc; QuiNThrAc; QuiOMe; QuiOMeN; QuiOS;QuiOSN; QuiOSNBut; Rha; Rha-ol; RhaCMe; RhaCl; RhaGro; RhaGroA; RhaGroP; RhaNAc; RhaNAcNBut; RhaNAcNFo; RhaNAcOAc; RhaNPro; RhaOAc; RhaOAcOLac; RhaOAcOMe; RhaOBut; RhaOFer; RhaOLac; RhaOMe; RhaOMeCMeNLac; RhaOMeCMeOFo; RhaOP; RhaOPEtn; RhaOPOMe; RhaOProp; RhaOPyr; RhaOS; Rhaf; Rib; Rib-ol; RibGroP-ol; RibOAc; RibOAcOP-ol; RibOP-ol; RibOPEtn-ol; RibOPGroP-ol; Ribf; Ribf-uronic; RibfOAc; Sed; Sedf; Sor; Sorf; Sue; Sug; SugOAc; Tag; Tai; The; Thr; Thre-ol; Thre-onic; Tyv; VioNAc; Xluf; XlufOMe; Xyl; Xyl-ol; Xyl-onic; XylHex; XylHexNAc; XylHexUlo; XylHexUloN; XylHexUloNAc; XylNAc; XylNMe; XylOAc; XylOBz; XylOMe; XylOP; XylOS; Xylf; Yer; YerOAc; a-Tri-ol; a-Tri-onic; aldehyde-2,5-Anhydro-L-Man; aldehyde-2,5- Anhydro-Tal; aldehyde-Gro; aldehyde-Hex; aldehyde-L-Gro; aldehyde -L-GroN; aldehyde-QuiNAc; aldehyde-Rib; aldehyde-a-Tri-ol; aldehyde-b-Tri-ol; b-Tri-N-ol; b- Tri-OP-ol; b-Tri-ol; b-Tri-onic; bl-4Glc; cNeu5Ac; b) and from monomers listed in FIG.6, 7 and the like, and chemical derivatives thereof; c) deoxysugars of (a) , (b) (Deoxyribose, Rhamnose, Fuculose, Fucose, and the like); d) uronic acids of (a), (b), (c) - (glucuronic acid, iduronic acid, etc), which may be methoxylated, ethoxylated or acetylated; e) (a), (b), (c), (d) in which a hydroxyl group has been replaced with an amine group - amino sugars (galactosamine, glucosamine, sialic acid, N-acetylglucosamine, N- acetylgalactosamine, N-acetylneuraminic acid and the like (more then 60 aminosugars)); f) sulfonic acid derivatives of (a), (b), (c), (d), (e) - sulfosugars (O-, N- sulfated, and the like); g) acetyl; Anhydro, D-alanyl; N-acetyl-D-alanyl; N-acetimidoyl; N-(N-methyl- acetimidoyl); N-(N,N-dimethyl-acetimidoyl); formyl; glycolyl; N-acetyl-glutaminyl; N-methyl-5-glutamyl; glycyl; glyceryl; 2,3-di-O-methyl-glyceryl; 4-hydroxybutyryl; 3,4-dihydroxybutyryl; (R)-3 -hydroxybutyryl; (S)-3 -hydroxybutyryl; lactyl; methyl; amino; N-acetyl; phosphate; pyruvyl; 1-carboxyethylidene; sulfate; tauryl; Me; Et; Pr; Bu; Pe; Hx; Hp; Oc; Nn; Dec; Und; Dod; Acyl; RCO-; Fo (or HCO); Ac; Gc; Pp; Br (Butyryl); VI (valeryl); Hxo; Hpo; Oco; Nno; Deo; Udo; Lau; Myr; Pam; Ste; eSte; Lin; D4Ach; ; Gro; Gra; Gm; Gri; Ose; Glcd; Gal; Fuc; GlcA; GlcUe; GlcN; GlcNAc; Neu; Sia; Mur; NeuAcg; NeuGc; Cer; Cho; Etnh; Ins; Ser; Ptd; Sph; Spd; P (Phosphoric residue) derivatives of (a), (b), (c), (d), (e), (f); h) (a), (b), (c), (d), (e), (f), (g) salts (gum, gummi, and the like); i) compounds of formula:CH(ORA)2, — C(=O)NRBRA, — C(=S)NRBRA, — C(=O)ORA, (C6-C20)optionally substituted aryl, optionally substituted heteroaryl, — C(=O)(Ci-Cs)alkyl, — S(O)z(Ci-Cs)alkyl, SRA, or selected from radicals obtained by removal of a hydrogen atom from the compounds shown in FIG.8; wherein Q is O, S, NRA,+N(O)(RA), N(ORA), ^(OXOR^, or N— NRA2; wherein RA, RBis H, halogen, F, Cl, Br, I, OH, Et, Me, Ac, ORC, N(RC)2,N3, CN, NO2, S(O)ZRC, (Ci-Ci5)alkyl, (C4-C8)carbocyclylalkyl, (Ci-C8)substituted alkyl, (C2-Cs)alkenyl, (C2-C8)substituted alkenyl, (C2-Cs)alkynyl, (C2-Cs)substituted alkynyl, — C(=O)Rc, — C(=O)ORc, — C(=O)NRcRc, — C(=O)SRc, — S(O)RC, — S(O)2RC, — S(O)(ORC), — S(O)2(ORC), — SO2NRCRC, (C6-C20)aiyl(Ci-C8)alkyl, — PO(OH)2, — PO(OH)OPO(OH)2,— PO(OH)OPO(OH)OPO(OH)2, — PO(ORC)2, — PORCRC, phenyl, 1 -naphthyl, 2-naphthyl, benzyl, (C3-C6)cycloalkyl, — CH2— (C3-C6)cycloalkyl, — O — ( Ci-Cs) alkyl, — O-benzyl, — O— CH2— (C3-C6)cycloalkyl, CF3, C(halogen)3, — C(O) Rc, — C(O)ORc, — C(O)N(Rc), — NRCRC, —+N(RC)3, — SRC, — S(O) Rc, — S(O)2RC, — S(O)(ORC), — S(O)2(ORC), — OC(O) Rc, — OC(O)ORc, — OC(O)(N(RC)2), — SC(=Q)RC, — SC(=Q)ORC, — SC(=Q)(N(RC)2), — N(RC)C(=Q)RC, — N(RC)C(=Q)ORC, — N(RC)C(=Q)N(RC)2, — SO2NRC2, — CN,— N3, — NO2, — ORC, NRCRC, N(RC)ORC, NRCNRC, N3, NO, NO2, CHO, CN, — CH(=NRc) ,— CH=NNHRc, — CH=N(ORc), — CH(ORc)2, — C(=O)NRcRc, — C(=S)NRcRc, — C(=O)ORc, (C6-C2o)optionally substituted aryl, optionally substituted heteroaryl, — C(=O)(Ci-C8)alkyl, — S(O)z(Ci-C8)alkyl, or SRC;wherein Rcis H, OH, F, Cl, Br, I, Me, Et, Ac, OMe, OEt, or OAc, or selected from radicals obtained by removal of a hydrogen atom from the compounds shown in FIG. 8; wherein z is from 1 to 10; and structural isomers thereof; and stereoisomers thereof; and the like;|||||Conjugates of (DI) bound (O-, N-, P-, C-, S-linked, and the like) to any Protein, Peptide, Low molecular weight compound, Lipid, Aptamer, Antibody, Affibody, Avimer, or Nanobody, etc., that may include, but are not limited to:Glycated derivatives (O-, N-, P-, C-, S-linked); glycoconjugates, glycoproteins (O-, N-, P-, C-, S-linked), neoglycoproteins, glycolipids, glycopeptides, proteoglycans, peptidoglycans, glycosides, lipopolysaccharides, and mixtures thereof; and wherein bonds may be covalent bonds, al-1, al-2, al-3, al-4, al-5, al-6, al-7, al-8, a2-l, a2-2, a2-3, a2-4, a2-5, a2-6, al-1, a2-8, a2-9, a6-6, pi-1, pi-2, pi-3, pi-4, pi-5, pi-6, Pl-7, pi-8, pi-9, P2-1, P2-2, P2-3, P2-4, P2-5, P2-6, P2-7, P2-8, P3-3, al-2, and the like, aq- w, Pq-w, wherein q and w are independently from 1 to 9;E) wherein [HOST]nis[X]nwherein X is selected from:wherein R described 11111111;F) Conjugates of (A)-(E) bound (O-, N-, P-, C-, S-linked, and the like) to any Protein, Peptide, Low molecular weight compound, Lipid, Aptamer, Antibody, Affibody, Avimer, or Nanobody, etc., that may include, but are not limited to:Glycated derivatives (O-, N-, P-, C-, S-linked), glycoconjugates, glycoproteins (O-, N-, P-, C-, S-linked), neoglycoproteins, glycolipids, glycopeptides, proteoglycans, peptidoglycans, glycosides, lipopolysaccharides, and mixtures thereof; and wherein bonds may be covalent bonds, al-1, al-2, al-3, al-4, al-5, al-6, al-7, al-8, a2-l, a2-2, a2-3, a2-4, a2-5, a2-6, a2-7, a2-8, a2-9, a6-6, pi-1, pi-2, pi-3, pi-4, pi-5, pi-6, Pl-7, pi-8, pi-9, P2-1, P2-2, P2-3, P2-4, P2-5, P2-6, P2-7, P2-8, P3-3, al-2, and the like, aq- w, Pq-w, wherein q and w are independently from 1 to 9;G) Polymers and oligomers, copolymers, biopolymers (natural, obtained by chemical or physical modification of natural polymers (chemical or physical derivatives), or synthesized specifically), or their Conjugates (like in (F)) that under at least one of the following conditions:1. co-occurring in physiologic body fluids, plasma, intercellular fluid together with APIs;2. by non-covalent binding to API;3. by covalent binding to API into a conjugate; result in at least one of the following: a. an increase in the permeability of the API, API-carrier system (solution, non- covalent complex, conjugate, and the like); b. an increase in the concentration of API, API-carrier system in cells and tissues; for at least one of the following reasons: i. inhibition or modulation of multi drug resistance (MDR), predominantly mediated by efflux transporters of the ATP-binding cassette (ABC) superfamily including P-glycoprotein (P-gp); ii. induction, inhibition or modulation of CYP1, CYP2, CYP3 enzymes (non limiting examples: CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4 enzymes); iii. due to a change in the structure of the cell membrane, change in lipid biolayer properties after the incorporation of carrier substance molecules (or carrier molecular part of NCC or conjugate) into this membrane or due adhesion to this membrane; iv. due to changes in charge, hydrophilicity, hydrophobicity or other biophysical properties of the non-covalent complex, or conjugate due to which changes in the transmembrane (passive, active) or paracellular transport of the non-covalent complex, or conjugates; v. for other reasons e.g., by the introduction or presence in the carrier of targeted fragments capable of selectively interacting with the receptor, cell surface receptors, membrane receptors, transmembrane receptors, etc. Such targeted fragments may include, but are not limited to, Proteins, Peptides, Low molecular weight compounds, Lipids, Aptamers, Antibodies, Affibodies, Avimers, Nanobodies, or any other targeted fragments, which are used as vector molecules and are described in patent or scientific literature; or for other reasons disclosed in patent or scientific literature.H) chemical or phisical derivatives of A-G, structural isomers thereof; and stereoisomers thereof; and the like.[End-0091]

[0092] [Ref-0092] In another embodiment, provided are the non-covalent active pharmaceutical ingredient-carrier complex wherein the carrier is selected from (satisfies at least one of (A) to (H)):A. Polymers and oligomers, predominantly organic polymers and oligomers, predominantly water-soluble organic polymers and oligomers, natural polymers and oligomers, biopolymers and biooligomers even more predominantly polysaccharides, homopolysaccharides, heteropolysaccharides, oligosaccharides, glycoconjugates,glycoproteins (O-, N-, P-, C-, S- linked), neoglycoproteins, glycolipids, glycopeptides, proteoglycans, peptidoglycans, glycolipids, glycosides, lipopolysaccharides, hemicelluloses, storage polysaccharides, sulfated polysaccharides and oligosaccharides, pectins, gums, mucilages, which may be (but are not exclusive to):A.l. Polyelectrolites and non-polyelectrolites;A.2. Polymers and oligomers, which can be obtained from animal, nonanimal, natural (i.e., microbiological or plant) sources: a) from plants, higher plants (non-limiting examples): Starch; Cellulose; Guar gum; Gum arable; Locust beanvgum; Pectin ; Acacia gum ; Gum arabic ; Arabinogalactan ; Costus glucans ; Xylan ; Glucomannan ; Xyloglucan ; Inulin ; beta-glucan ; Guar gum ; Karaya gum ; Tara gum ; Fenugreek gum ; Locust bean gum; Tragacanth gum ; Cassia tor a gum; and the like; b) from mushrooms (non-limiting examples): Polysaccharide -K (Krestin, PSK), betaglucans, Polysaccharide peptide (PSP);and the like; c) from Algae (non-limiting examples): Alginates; Galactans; Carrageenan; Alginate ; Agar ; Carrageenan ; Fucoidan; Ulvan ; Laminarin; Angelan ; Porphyran ; Spirulan ; Agarose ; Rhodymenan; and the like; d) from animal origin (non-limiting examples): Glycosaminoglycans(GAGs); Hyaluronic acid; Glycogen; Hyaluronan ; Chitin; Chitosan; Heparin; Chondroitin sulphate; Keratan sulphate; Dermatan sulphate; Asialofetuin; fetuin;and the like; e) from microbial origin (non-limiting examples): Dextran; Gellan gum; Pullulan; Xanthan gum; Curdlan; Scleroglucan; Pullulan; Dextran; Xanthan; Levan; Gellan; Emulsan; Schizophyllan; Glucuronan; Succinoglycan; Nigcran ;and the like;A.3. Hemicelluloses, which can be arabanes, arabinans, galactans (galactosans), glucans, xylans, mannans, fructans, xyloglucans, arabinogalactans, arabinoxylans, glucomannans, galactomannans, galactoglucomannans, beta-glucans, galactogens, and the like, their mixtures, but not excluding other hemicelluloses, and mixtures thereof;A.4. Sulfated polysaccharides and oligosaccharides which may be fucoidans, carrageenans or carrageenins, agaropectins, sea cucumber sulfated polysaccharides (SCSP), chondroitin sulfate, keratan sulfate, and the like, their mixtures, but not excluding other sulfated polysaccharides and oligosaccharides, and mixtures thereof;A.5. Oligosaccharides, fructooligosaccharides, galactooligosaccharides (oligogalactosyllactose, oligogalactose, oligolactose, transgalactooligosaccharides), xylooligosaccharides, isomaltooligosaccharides and the like, but not excluding other oligosaccharides and mixtures thereof;A.6. Polysaccharides and oligosaccharides, storage polysaccharides, sulfated polysaccharides and oligosaccharides, pectins, gums, mucilages which may be (but are notexclusive to others): polyuronic acids and esters; gum(s), gum arabic, xanthan gum, oat gum, gellan gum, guar gum, carob gum, karaya gum, dammar gum, gummiarabica, tara gum, ghatti gum, british gum, agar, agar-agar, tragakant gum, conjac gum, velan gum, dutan gum; galacturonic acid-based polysaccharides with side chains of rhamnose, arabinose, xylose and fructose and their salts (pectins, pectates, pectinates); pectin, pectins of beets, carrots, peppers, pumpkins, eggplant, sunflower, apples, quinces, cherries, plums, pears, citrus, zosterin; modified pectins, modified citrus pectin; acidic polysaccharides - i.e. e. polysaccharides containing carboxyl groups and / or phosphate groups and / or sulfuric ester groups; plantain husk, psyllium; soybean hemicellulose; galacturones, homogalacturones, polygalacturonic acids and their salts, rhamnogalacturonan, rhamnogalactans; calloses, laminarins, chrysolaminarins, curdlans; inulins, guars, dextrans, pullulans; agaroses; alginic acid and its salts alginates, propylene glycol alginate; arabin, arabic acid and its salts, and the like, but not excluding other, and mixtures thereof;A.7. Cellulose, cellulosic polymers, methylcellulose, ethylcellulose, hydroxypropylcellulose(s) (HPC), hydroxypropylmethylcellulose acetate succinate, hypromellose(s), hydroxypropylmethylcellulose(s) (HPMC), methylethylcellulose, ethylhydroxyethylcellulose, croscaramellose, carboxymethylcellulose and its salts; starch, starch(es), starch 1500G, soluble starch, modified starches, hydroxyethyl starch, cationic starch, acid-treated starch, alkaline modified starch, bleached starch, oxidized starch, enzyme treated starch, monostarch phosphate, distarch glycerol, distarch phosphate, phosphated distarch phosphate, acetylated distarch phosphate, starch acetate esterified with acetic anhydride, starch acetate esterified with vinyl acetate, acetylated distarch adipate, acetylated distarch glycerol, distarch glycerine, hydroxy propyl starch, hydroxy propyl distarch glycerine, hydroxy propyl distarch phosphate, hydroxy propyl distarch glycerol, starch sodium octenyl succinate, acetylated oxidised starch, and the like;A.8. Dextrin(s), maltodextrins, amylodextrins, polydextroses; amylopectin, amylose, glycogen;chitosan, chitins ;pullulans, glucuronoaraboxylans, methyl- glucuronoaraboxylans, glycosaminoglycans, mucopolysaccharides, heparin / heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, hyaluronan, hyaluronic acid, and the like; and mixtures thereof;A.9. Glycated derivatives of these polymers and oligomers (O-, N-, P-, C-, S-linked); but not excluding other polymers and oligomers, biopolymers and biooligomers even more predominantly polysaccharides, homopolysaccharides, heteropolysaccharides, oligosaccharides, glycoconjugates, glycoproteins (O-, N-, P-, C-, S- linked), neoglycoproteins, glycolipids, glycopeptides, proteoglycans, peptidoglycans, glycolipids, glycosides, lipopolysaccharides, hemicelluloses, storage polysaccharides, sulfated polysaccharides and oligosaccharides, pectins, gums, mucilagesand mixtures thereof;B. Polymers, syntetic polymers, predominantly water-soluble polymers which may be (but are not limited to):polymers and copolymers formed from acrylic acid, methacrylic acid, and / or esters thereof; polymethacrylates, Eudragit and their salts; polyacrylamides; poly(amidoamine)s, poly(propyleneimine)s, polyethylene glycols; polyvinyl alcohol; polyvinylpyrrolidone; acrylic polymers, cellulose acetate phthalate(s), copovidone(s), ethyl oleate, glycerol derivatives, glyceryl triacetate, polyethylene glycol(s) (PEG), PEGderivatives, polymethacrylates, propylene glycol, propylene glycol derivatives, povidone(s), polyvinylpyrrolidone (s) (PVP), polyvinyl acetate phthalate(s) (PVAP), hypromellose acetate succinate(s) (HPMCAS), hydroxypropyl methylcellulose acetate succinate (HPMCAS), hypromellose phthalate(s) (HPMCP), cellulose butyrate phthalate, cellulose hydrogen phthalate, cellulose proprionate phthalate, polyvinyl acetate phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate, dioxypropyl methylcellulose succinate, carboxymethyl ethylcellulose, hydroxypropyl methylcellulose acetate succinate, Avicel(s), Avicel PH101, Avicel PH102, Benecel(s), Brij(s), Brij 30, Brij 35, Capryol(s), Cavamax(s), Cavasol(s) and Cavitron(s) HPpCD cyclodextrins, Compritol 888 ATO, Cremophor(s), Cremophor EL, Cremophor REMO, DiCai Dihydrate, epoxidized palm oil (Epo), Eudragit(s), Eudragit E, Eudragit EPO, Eudragit L100, Eudragit L100-55, Eudragit S100, Gelucire(s), Gelucire 44 / 14, HP-50 AAS-LF, HP-55 AAS-MF, HPMC(p-606), HPMC-E, HPMC-F, HPMC-K, HPMCAS-H, HPMCAS-L, HPMCAS-M, HPMCAS SDD, HPMCAS(AS-MG), HPMCAS-M SDDs, HPMCAS-MG, HPMCP (HP 55), HPMCP-HP55, HPMCPh, hypromellose phthalate HP-50, Imwitor(s), Imwitor 742, Klucel HPC, Kolhdon 17 PF, Kollicoat(s), Kollicoat IR, Kollicoat MAE, Kollicoat MAE 100, Kollicoat MAE 100P , Kollicoat Protect, Kollidon(s) (povidone(s)), Kolhdon 12 pf, Kolhdon 12 / 17PF, Kolhdon 30, Kollidon 30 / 90, Kollidon 90, Kollidon CL-F, Kollidon CL-SF, Kollidon K30, Kolhdon SR, Kolhdon SR, Kollidon SR(PVAc), Kolhdon V64 / Fine, Kolhdon VA 64, Kollidon VA 64 (copovidone), Kollidon VA64, Kolliphor(s), Kolliphor EL, Kolliphor EL / ELP, Kolliphor HS15, Kolliphor P 188, Kolliphor P 188 / 407, Kolliphor P 188 / micro, Kolliphor P 407 , Kolliphor P 407 / micro, Kolliphor PS 20, Kolliphor PS 60, Kolliphor PS 80, Kolliphor RH 40, Kolliphor SLS, Kolliphor SLS / fine, Kollisolv(s), Kollisolv GTA, Kollisolv PEG 1450, Kollisolv PEG 300, Kollisolv PEG 3350, Kollisolv PEG 400, Kollisolv PEG E 300, Kollisolv PEG E 400, Kollisolv PEG grades (polyethylene glycol), Kolliwax(s), Kolliwax GMS II, Kolliwax SA, Labrasol(s), Lactose 310 Mono, Lactose FF316, Laurogucol(s), Maisine(s), Miglyol(s), Myq(s), Myrj 52, PEG 1000, PEG 10000, PEG 1500, PEG 2000, PEG 20000, PEG 3000, PEG 400, PEG 4000, PEG 600, PEG 6000, PEG 800 , PEG 8000 , Pharmacoat(s), PVP K-12 , PVP K-120 , PVP K-15, PVP K-17, PVP K-30, PVP K-60, PVP K-90, PVP SDD, PVP VA64 SDDs, PVP-VA, PVP-VA 64, PVP-VA SDD, Palm stearin based polyesteramide (PSPEA), Peceol(s), pectin(s), Plasdone(s), Plasdone K povidone, Plasdone K-12 povidone, Plasdone K-29 / 32 povidone, Plasdone K-90 povidone, Plasdone S, Plasdone S-630 copovidone, poly(2-ethyl-2-oxazoline), polyethylene oxide) (PEG) (3400, 10000, 20000), polyoxyethylene stearate, Shin-Etsu AQOAT(s), Soluplus(es), Solutol(s), sucrose laurate, tocopheryl PEG 1000-succinate (TPGS), vitamin E TPGS, d-a-tocopherol polyethylene glycol 1000 succinate (TPGS), Isomalt (Galen IQ 810), galactosylated Polymers; galactosylated ciclodextrins; cationic glycopolymers; block and statistical carbohydrate-based galactosylated copolymers; galactosylated albumin(s), galactosylated bovine serum albumin; Statistical Cationic Glycopolymer of 2-aminoethyl methacrylamide (AEMA) and 2-lactobionamidoethyl methacrylamide (LAEMA) P(AEMA n -st-LAEMA m) (m,n from 1 to 1000); Cationic Block Glycopolymer of 2-aminoethyl methacrylamide (AEMA) and 2-lactobionamidoethyl methacrylamide; p-Vinylbenzyl galactoside (VBG); galactosylated N-3-guanidinopropyl methacrylamide-co-poly (ethylene glycol) methacrylatecopolymers; galactosylated amphiphilic graft copolymer (PHEA-g-BIB-pButMA-g-PEG- GAL); (cholesteryloxy carbonylamino) ethylamine-a,P-polyasparthydrazied (CHE-PAHy- Lacs); PLGA-di-GAL; and the like, and others which are described in the scientific and patent literature (for example: Macro-Glycoligands. Methods and Protocols, Editors: Xue- Long Sun); and the like; but not excluding other synthetic polymers and mixtures thereof;C. Copolymers is made from monomers of the polymers listed in paragraph A, B including alternating copolymers, random copolymers, block copolymers, graft copolymers, crosslinked modifications which may be (but are not limited to): methacrylic acid and ethyl acrylate copolymers; methacrylic acid copolymers; vinylpyrrolidone-vinyl acetate copolymers (PVPVA); polyvinylpolypyrrolidone (PVPP); PVA-PEG graft co-polymers; HPMC and PVA-PEG grafted copolymers; polyvinylpyrrolidone-arabinogalactan copolymers; grafted polyvinylpyrrolidone-arabinogalactan copolymers; the graft copolymer has a) poly(vinyl acetate) and / or poly (vinyl alcohol) and / or poly(vinyl chloride) and poly(vinyl ester) on b) a polymer chain of polyethylene glycols, polyalkylene glycols, polypropylene glycols, polyisobutylene glycols orpolymethylpentene glycols; graft copolymer polyvinyl acetate and / or hydrolysed polyvinyl acetate (polyvinyl alcohol) groups on a polyalkylene oxide (preferably polyethylene oxide); vinylpyrrolidone-vinyl acetate copolymers; vinylpyrrolidone-vinyl acetate copolymer-64+; vinylpyrrolidone -vinyl acetate VA 64; polymethacrylate-based copolymers includes anionic, cationic, and neutral copolymers based on methacrylic acid and methacrylic / acrylic esters their salts, esters or other derivatives and mixtures thereofand the like;D. Polymers and oligomers, copolymers, biopolymers (natural, obtained by chemical or physical modification of natural polymers (chemical or physical derivatives), or synthesized specifically) that under at least one of the following conditions:1. co-occurring in physiologic body fluids, plasma, intercellular fluid together with APIs;2. by non-covalent binding to API;3. by covalent binding to API into a conjugate; result in at least one of the following: a. an increase in the permeability of the API, API-carrier system (solution, non- covalent complex, conjugate, and the like); b. an increase in the concentration of API, API-carrier system in cells and tissues; for at least one of the following reasons: i. inhibition or modulation of multidrug resistance (MDR), predominantly mediated by efflux transporters of the ATP-binding cassette (ABC) superfamily including P-glycoprotein (P-gp);ii. induction, inhibition or modulation of CYP1, CYP2, CYP3 enzymes (non limiting examples: CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4 enzymes); iii. due to a change in the structure of the cell membrane, change in lipid biolayer properties after the incorporation of carrier substance molecules (or carrier molecular part of NCC or conjugate) into this membrane or due adhesion to this membrane; iv. due to changes in charge, hydrophilicity, hydrophobicity or other biophysical properties of the non-covalent complex, or conjugate due to which changes in the transmembrane (passive, active) or parace llular transport of the non-covalent complex, or conjugates;E. Other carriers:El. Macrocyclic hosts which may be (but are not exclusive to others): cyclodextrins, cucurbit[n]urils, and calix [ n | arenes, pillarenes, crown ethers, cyclophanes, cryptands;E2. Acids and salts based on these acids which may be (but are not limited to): citric acid, tartaric acid, succinic acid, phosphoric acid, aminoacids, acetate(s), sodium acetate, alginate(s), sodium alginate, glycyrrhizic acid and their salts, and mixtures thereof;8E3. Polyols which may be (but are not limited to): ethylene glycol, glycerol, erythritol, threitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, iditol, inositol, volemitol, isomalt, maltitol, lactitol, maltotriitol, maltotetraitol, polyglycitol, and mixtures thereof;E4. Monosaccharides, disaccharides, trisaccharides, tetrasaccharides, pentaccharides, hectaccharides and the like mixtures thereof;E5. Surfactants which may be (but are not limited to): anionic surfactants contained anionic functional groups at their head, such as sulfate, sulfonate, phosphate, carboxylates, carboxylate salts; alkyl sulfates; alkyl-ether sulfates; carboxylate -based fluorosurfactants; cationic surfactants; primary, secondary, or tertiary amines; permanently charged quaternary ammonium salts; zwitterionic (amphoteric) surfactants; zwitterionic surfactants which cationic part is based on primary, secondary, or tertiary amines or quaternary ammonium cations; sultaines; betaines; phospholipids; zwitterionic surfactants of the tertiary amine oxides structural type; non-ionic surfactants; ethoxylates; fatty alcohol ethoxylates; alkylphenol ethoxylates (apes or apeos); fatty acid ethoxylates; special ethoxylated fatty esters and oils; ethoxylated amines and / or fatty acid amides; terminally blocked ethoxylates; fatty acidesters of polyhydroxy compounds; fatty acid esters of glycerol; fatty acid esters of sorbitol; fatty acid esters of sucrose; alkyl polyglucosides; ammonium lauryl sulfate; sodium lauryl sulfate; sodium dodecyl sulfate; sodium laureth sulfate; sodium lauryl ether sulfate; sodium myreth sulfate; docusate (dioctyl sodium sulfosuccinate) and their salts; perfluorooctanesulfonate (pfos); perfluorobutanesulfonate; alkyl-aryl ether phosphates; alkyl ether phosphates; sodium stearate; sodium lauroyl sarcosinate; perfluorononanoate; perfluorooctanoate; octenidine dihydrochloride; cetrimonium bromide (ctab); cetylpyridinium chloride (cpc); benzalkonium chloride (bac); benzethonium chloride (bzt); dimethyldioctadecylammonium chloride; dioctadecyldimethylammonium bromide (dodab); chaps (3-[(3- cholamidopropyl)dimethylammonio]-l-propanesulfonate); cocamidopropyl hydroxy sultaine; cocamidopropyl betaine; phosphatidylserine; phosphatidylethanolamine; phosphatidylcholine; sphingomyelins; lauryldimethylamine oxide; myristamine oxide; narrow-range ethoxylates; octaethylene glycol monododecyl ether; pentaethylene glycol monododecyl ether; nonoxynols; triton x-100; polyethoxylated tallow amine; cocamide monoethanolamine; cocamide diethanolamine; poloxamers; glycerol monostearate; glycerol monolaurate; sorbitan monolaurate; sorbitan monostearate; sorbitan tristearate; tween(s), tween 20; tween 40; tween 60; tween 80; decyl glucoside; span(s), span 20, span 40, span 80; lauryl glucoside; octyl glucoside; poloxamer(s), poloxamer 188, poloxamer 407, polyoxyethylene stearate, myrj 52, deoxycholic acid, bile acids, pluronic(s), pluronic F-127, pluronic P85, pluronic f68, gelucire(s), gelucire 44 / 14, lecithins, polysorbates, polysorbate 80, plasdone-s630, pluronic-f68, inutec spl, compritol 888 ato, tocopherol polyethylene glycol succinate, polyoxyethylated castor oil, polyoxyethylated glycerides, lauroyl macroglycerides, and mono- and di-fatty acid esters of low molecular weight polyethylene glycols; and mixtures thereof;F. Methoxylated, ethoxylated, esterificated, carboxylated, alkoxylated, acetylated, hydroxylated, hydrated, decarboxylated, amide, oxidized, sulfated, aminoacid derivatives, fermented, thermally modified, chemically modified, acid modified derivatives of the substances specified in A-E, and their esters, salts, and any other chemical derivatives, and mixtures thereof or / and which are described in the scientific and patent literature;Alternatively, dextran or poly-L-lysine can be attached to the gum arabic carrier to provide an increased number of sites of attachment for the therapeutic agent.G. Conjugates of || || bound (O-, N-, P-, C-, S-linked, and the like) to any Protein, Peptide, Low molecular weight compound, Lipid, Aptamer, Antibody, Affibody, Avimer, or Nanobody, etc., that may include, but are not limited to:Glycated derivatives (O-, N-, P-, C-, S-linked), glycoconjugates, glycoproteins (O-, N-, P-, C-, S-linked), neoglycoproteins, glycolipids, glycopeptides, proteoglycans, peptidoglycans, glycosides, lipopolysaccharides, and mixtures thereof; and wherein bonds may be covalent bonds, al-1, al-2, al-3, al-4, al-5, al-6, al-7, al-8,a2-l, a2-2, a2-3, a2-4, a2-5, a2-6, a2-7, a2-8, a2-9, a6-6, [31-1, [31-2, [31-3, [31-4, [31-5, [31-6, pi-7, pi-8, pi-9, 32-1, 2-2, P2-3, P2-4, P2-5, P2-6, P2-7, P2-8, 33-3, al-2, and the like, aq-w, Pq-w, wherein q and w are independently from 1 to 9;H. Any combination of substances specified in items A-G.[End-0092]

[0093] In another embodiment, provided are the non-covalent complex when dissolved in a physiologically acceptable solvent other than water.

[0094] In another embodiment, the non-covalent complex is selected from inclusion complexes, including partial inclusion complexes, and supramolecular complexes.

[0095] [Ref-0095] Provided are the methods (co-treating methods / solid dispersion techniques) for modifying the properties of an active pharmaceutical ingredient (API) by creating a molecular / solid dispersion, solid phase inclusion or supramolecular complex (both of Formula II) using API, host substance (and, if necessary, other compounds) with properties of increased bioavailability and / or permeability and using Formula II compounds obtained by this methods (or aqueous solutions or suspensions thereof) to treat a disease in humans or animal or mammal or bird and / or to manufacture a pharmaceutical dosage form to treat disease in a human or animal or mammal or bird in need thereof (by administering a therapeutically effective amount) ), at a dosage ranging from 0.0001 ng / kg to 100000 mg / kg (calculated for pure API) wherein said dosage provides improved therapeutic efficacy; wherein the described compounds has enhanced permeability (into the internal organs and tissues of the person receiving the drug) and bioavailability properties; wherein the therapeutic efficacy of the described compounds is enhanced by enhanced permeability, which allows for rapid achievement of the required concentration in the organs and tissues of the patient; wherein active pharmaceutical ingredient is selected from:Milbemycins; Milbemycin A3; Milbemycin A4; Milbemycin D; Milbemycin B2; Milbemycin B3; Milbemycin G; Nemadectins; Nemadectin; Meilingmycins; Meilingmycin A; Milbemectins; Milbemectin; Milbemycin oxime; Moxidectins; Moxidectin; Doramectins; Doramectin; Selamectins; Selamectin; Eprinomectins; Eprinomectin Bia; Eprinomectin Bib; Emamectins; Emamectin Bia; Emamectin Bib; Tenvermectins; Tenvermectin B; Tenvermectin A; Avermectins; Avermectin Ala; Avermectin Alb; Avermectin A2a; Avermectin A2b; Avermectin Bia; Avermectin Bib; Avermectin B2a; Avermectin B2b; Ivermectins; Ivermectin Bia; Ivermectin Bib; Ivermectin Ala; Ivermectin Alb; Fenbendazole; Flubendazole; Thiabendazole; Oxfendazole; Triclabendazole; Mebendazole; Oxyclozanide; Niclosamide; Nitazoxanide; Colchicine; Artemisinin; Quercetin; Curcumin; Resveratrol; thymoquinone; Pyrvinium; Albendazole sulfoxide; Albendazole or compounds selected from those listed in from FIG.12 to FIG.72; or compounds (API, AAPI, AANPI) selected from thosederivatives thereof such as racemate, enantiomer, diastereomer, tautomer, polymorph, pseudopolymorph, hydride or solvate thereof; or a pharmaceutically acceptable salt or ester or ether thereof; or prodrug thereof; or methabolite thereof; or aglycone thereof;or derivatives which may be obtained by gene replacement processes in genetically engineered strains, or / and by fermentation, or / and by chemical modifications and the like, which are described in the scientific and patent literature;or mixtures thereof; wherein the host substance is selected fromA. Polymers and oligomers, predominantly organic polymers and oligomers, even more predominantly polysaccharides and oligosaccharides, hemicelluloses, storage polysaccharides, sulfated polysaccharides and oligosaccharides, pectins, gums, mucilages, which may be (but are not exclusive to):A. l. Hemicelluloses, which can be arabanes, arabinans, galactans (galactosans), glucans, xylans, mannans, fructans, xyloglucans, arabinogalactans, arabinoxylans, glucomannans, galactomannans, galactoglucomannans, beta-glucans, galactogens, their mixtures, but not excluding other hemicelluloses, and mixtures thereof;A.2. Sulfated polysaccharides and oligosaccharides which may be fucoidans, carrageenans or carrageenins, agaropectins, sea cucumber sulfated polysaccharides (SCSP), chondroitin sulfate, keratan sulfate, their mixtures, but not excluding other sulfated polysaccharides and oligosaccharides, and mixtures thereof;A.3. Polysaccharides and oligosaccharides, storage polysaccharides, sulfated polysaccharides and oligosaccharides, pectins, gums, mucilages which may be (but are not exclusive to others): polysaccharides based on glucose, dextrose, galactose, mannose, arabinose, rhamnose, sucrose, maltose, lactose and their uronic acids, which may be methoxylated or acetylated, and their salts (gum, gummi); polyuronic acids and esters; gum, xanthan gum, oat gum, gellan gum, guar gum, carob gum, karaya gum, dammar gum, gummiarabica, tara gum, ghatti gum, british gum, agar, agar-agar, tragakant gum, conjac gum, velan gum, dutan gum; galacturonic acid-based polysaccharides with side chains of rhamnose, arabinose, xylose and fructose and their salts (pectins, pectates, pectinates); pectin, pectins of beets, carrots, peppers, pumpkins, eggplant, sunflower, apples, quinces, cherries, plums, pears, citrus, zosterin; modified pectins, modified citrus pectin; acidic polysaccharides - i.e. e. polysaccharides containing carboxyl groups, phosphate groups and / or sulfuric ester groups; plantain husk, psyllium; soybean hemicellulose; galacturones, homogalacturones, polygalacturonic acids and their salts, rhamnogalacturonan, rhamnogalactans; calloses, laminarins, chrysolaminarins, curdlans; inulins, guars, dextrans, pullulans; agaroses, galactooligosaccharides (oligogalactosyllactose, oligogalactose, oligolactose or transgalactooligosaccharides), xylooligosaccharides, fructooligosaccharides, isomaltooligosaccharide; alginic acid and its salts alginates, propylene glycol alginate; arabin, arabic acid and its salts; cellulose, cellulosic polymers, methylcellulose, ethylcellulose, hydroxypropylcellulose(s) (HPC), hydroxypropylmethylcellulose acetate succinate, hypromellose(s), hydroxypropylmethylcellulose(s), (HPMC), methylethylcellulose, ethylhydroxyethylcellulose, croscaramellose, carboxymethylcellulose and its salts; starch, starch(es), starch 1500G, soluble starch, modified starches, hydroxyethyl starch, cationic starch, acid-treated starch, alkaline modified starch, bleached starch, oxidized starch, enzyme treated starch, monostarch phosphate, distarch glycerol, distarch phosphate, phosphated distarch phosphate, acetylated distarch phosphate, starch acetate esterified with acetic anhydride, starch acetate esterified with vinyl acetate, acetylated distarch adipate, acetylated distarch glycerol,distarch glycerine, hydroxy propyl starch, hydroxy propyl distarch glycerine, hydroxy propyl distarch phosphate, hydroxy propyl distarch glycerol, starch sodium octenyl succinate, acetylated oxidised starch; dextrin(s), maltodextrins, cyclodextrins, amylodextrins, polydextroses; amylopectin, amylose, glycogen;chitosan, chitins;pullulans, glucuronoaraboxylans, methyl- glucuronoaraboxylans, glycosaminoglycans, mucopolysaccharides, heparin / heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, hyaluronan, hyaluronic acid and mixtures thereof, but not excluding other polysaccharides and oligosaccharides, hemicelluloses, stored polysaccharides, sulfated polysaccharides and oligosaccharides, mucilages and mixtures thereof;A.4. Macrocyclic hosts which may be (but are not exclusive to others): cyclodextrins, cucurbit[n]urils, and calixfn] arenes, pillarenes, crown ethers, cyclophanes, cryptands;B. Substances that may contain in significant amounts (more than 5% wt.) polysaccharides and oligosaccharides, hemicelluloses, storage polysaccharides, sulfated polysaccharides and oligosaccharides, pectins, gums, mucilages, which may be (but are not limited to) plants or algae or animal or fungi, parts of plants or algae or animal or fungi, processed plants or algae or animal or fungi, processed parts of plants or algae or animal or fungi containing in significant amounts the substances specified in paragraph A, and mixtures thereof. A frequent but non-limiting example is dried brown or red algae such as kelp or focus;C. Syntetic polymers, predominantly water-soluble polymers which may be (but are not limited to):polymers and copolymers formed from acrylic acid, methacrylic acid, and / or esters thereof; polymethacrylates, Eudragit and their salts; polyacrylamides; poly(amidoamine)s, poly (propyleneimine) s, polyethylene glycols; polyvinyl alcohol; polyvinylpyrrolidone; acrylic polymers, cellulose acetate phthalate(s), copovidone(s), ethyl oleate, glycerol derivatives, glyceryl triacetate, polyethylene glycol(s) (PEG), PEG derivatives, polymethacrylates, propylene glycol, propylene glycol derivatives, povidone(s), polyvinylpyrrolidone(s) (PVP), polyvinyl acetate phthalate(s) (PVAP), hypromellose acetate succinate(s) (HPMCAS), hydroxypropyl methylcellulose acetate succinate (HPMCAS), hypromellose phthalate(s) (HPMCP), cellulose butyrate phthalate, cellulose hydrogen phthalate, cellulose proprionate phthalate, polyvinyl acetate phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate, dioxypropyl methylcellulose succinate, carboxymethyl ethylcellulose, hydroxypropyl methylcellulose acetate succinate, Avicel(s), Avicel PH101, Avicel PH 102, Benecel(s), Brij(s), Brij 30, Brij 35, Capryol(s), Cavamax(s), Cavasol(s) and Cavitron(s) HPpCD cyclodextrins, Compritol 888 ATO, Cremophor(s), Cremophor EL, Cremophor RH40, DiCai Dihydrate, epoxidized palm oil (Epo), Eudragit(s), Eudragit E, Eudragit EPO, Eudragit L100, Eudragit L100-55, Eudragit S100, Gelucire(s), Gelucire 44 / 14, HP-50 AAS-LF, HP-55 AAS-MF, HPMC(p-606), HPMC-E, HPMC-F, HPMC-K, HPMCAS- H, HPMCAS-L, HPMCAS-M, HPMCAS SDD, HPMCAS(AS-MG), HPMCAS-M SDDs, HPMCAS-MG, HPMCP (HP 55), HPMCP-HP55, HPMCPh, hypromellose phthalate HP-50, Imwitor(s), Imwitor 742, Klucel HPC, Kolhdon 17 PF, Kollicoat(s), Kollicoat IR, Kollicoat MAE, Kollicoat MAE 100, Kollicoat MAE 100P , Kollicoat Protect, Kollidon(s) (povidone(s)), Kollidon 12 pf, Kollidon 12 / 17PF, Kolhdon 30, Kollidon 30 / 90, Kolhdon 90, Kollidon CL-F, Kollidon CL-SF, Kollidon K30, KollidonSR, Kollidon SR, Kollidon SR(PVAc), Kollidon V64 / Fine, Kollidon VA 64, Kollidon VA 64 (copovidone), Kollidon VA64, Kolliphor(s), Kolliphor EL, Kolliphor EL / ELP, Kolliphor HS15, Kolliphor P 188, Kolliphor P 188 / 407, Kolliphor P 188 / micro, Kolliphor P 407 , Kolliphor P 407 / micro, Kolliphor PS 20, Kolliphor PS 60, Kolliphor PS 80, Kolliphor RH 40, Kolliphor SLS, Kolliphor SLS / fine, Kollisolv(s), Kollisolv GTA, Kollisolv PEG 1450, Kollisolv PEG 300, Kollisolv PEG 3350, Kollisolv PEG 400, Kollisolv PEG E 300, Kollisolv PEG E 400, Kollisolv PEG grades (polyethylene glycol), Kolliwax(s), Kolliwax GMS II, Kolliwax SA, Labrasol(s), Lactose 310 Mono, Lactose FF316, Laurogucol(s), Maisine(s), Miglyol(s), Myrj(s). Myrj 52, PEG 1000, PEG 10000, PEG 1500, PEG 2000, PEG 20000, PEG 3000, PEG 400, PEG 4000, PEG 600, PEG 6000, PEG 800 , PEG 8000 , Pharmacoat(s), PVP K-12 , PVP K-120 , PVP K-15, PVP K-17, PVP K-30, PVP K-60, PVP K-90, PVP SDD, PVP VA64 SDDs, PVP-VA, PVP-VA 64, PVP-VA SDD, Palm stearin based polyesteramide (PSPEA), Peceol(s), pectin(s), Plasdone(s), Plasdone K povidone, Plasdone K-12 povidone, Plasdone K-29 / 32 povidone, Plasdone K-90 povidone, Plasdone S, Plasdone S-630 copovidone, poly(2-ethyl-2-oxazoline), poly(ethylene oxide) (PEG) (3400, 10000, 20000), polyoxyethylene stearate, Shin-Etsu AQOAT(s), Soluplus(es), Solutol(s), sucrose laurate, tocopheryl PEG 1000-succinate (TPGS), vitamin E TPGS, d-a- tocopherol polyethylene glycol 1000 succinate (TPGS), Isomalt (Galen IQ 810), but not excluding other synthetic polymers and mixtures thereof;D. Polyols which may be (but are not limited to): ethylene glycol, glycerol, erythritol, threitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, iditol, inositol, volemitol, isomalt, maltitol, lactitol, maltotriitol, maltotetraitol, polyglycitol, and mixtures thereof;E. Saccharides which may be glucose, dextrose, galactose, mannose, arabinose, rhamnose, sucrose, maltose, lactose, ribose, and mixtures thereof;F. Surfactants which may be (but are not limited to): anionic surfactants contained anionic functional groups at their head, such as sulfate, sulfonate, phosphate, carboxylates, carboxylate salts; alkyl sulfates; alkyl-ether sulfates; carboxylate -based fluorosurfactants; cationic surfactants; primary, secondary, or tertiary amines; permanently charged quaternary ammonium salts; zwitterionic (amphoteric) surfactants; zwitterionic surfactants which cationic part is based on primary, secondary, or tertiary amines or quaternary ammonium cations; sultaines; betaines; phospholipids; zwitterionic surfactants of the tertiary amine oxides structural type; non-ionic surfactants; ethoxylates; fatty alcohol ethoxylates; alkylphenol ethoxylates (apes or apeos); fatty acid ethoxylates; special ethoxylated fatty esters and oils; ethoxylated amines and / or fatty acid amides; terminally blocked ethoxylates; fatty acid esters of polyhydroxy compounds; fatty acid esters of glycerol; fatty acid esters of sorbitol; fatty acid esters of sucrose; alkyl polyglucosides; ammonium lauryl sulfate; sodium lauryl sulfate; sodium dodecyl sulfate; sodium laureth sulfate; sodium lauryl ether sulfate; sodium myreth sulfate; docusate (dioctyl sodium sulfosuccinate) and their salts; perfluorooctanesulfonate (pfos); perfluorobutanesulfonate; alkyl-aryl ether phosphates; alkyl ether phosphates; sodium stearate; sodium lauroyl sarcosinate; perfluorononanoate; perfluorooctanoate; octenidine dihydrochloride; cetrimonium bromide (ctab); cetylpyridinium chloride (cpc); benzalkonium chloride (bac); benzethonium chloride (bzt); dimethyldioctadecylammonium chloride; dioctadecyldimethylammonium bromide (dodab); chaps (3-[(3-cholamidopropyl)dimethylammonio]-l-propanesulfonate); cocamidopropyl hydroxy sultaine; cocamidopropyl betaine; phosphatidylserine; phosphatidylethanolamine; phosphatidylcholine; sphingomyelins; lauryldimethylamine oxide; myristamine oxide; narrow-range ethoxylates; octaethylene glycol monododecyl ether; pentaethylene glycol monododecyl ether; nonoxynols; triton x-100; polyethoxylated tallow amine; cocamide monoethanolamine; cocamide diethanolamine; poloxamers; glycerol monostearate; glycerol monolaurate; sorbitan monolaurate; sorbitan monostearate; sorbitan tristearate; tween(s), tween 20; tween 40; tween 60; tween 80; decyl glucoside; span(s), span 20, span 40, span 80; lauryl glucoside; octyl glucoside; poloxamer(s), poloxamer 188, poloxamer 407, polyoxyethylene stearate, myrj 52, deoxycholic acid, bile acids, pluronic(s), pluronic F-127, pluronic P85, pluronic f68, gelucire(s), gelucire 44 / 14, lecithins, polysorbates, polysorbate 80, plasdone-s630, pluronic-f68, inutec spl, compritol 888 ato, tocopherol polyethylene glycol succinate, polyoxyethylated castor oil, polyoxyethylated glycerides, lauroyl macroglycerides, and mono- and di-fatty acid esters of low molecular weight polyethylene glycols; and mixtures thereof;G. Acids and salts based on these acids which may be (but are not limited to): citric acid, tartaric acid, succinic acid, phosphoric acid, aminoacids, acetate(s), sodium acetate, alginate(s), sodium alginate, glycyrrhizic acid and their salts, and mixtures thereof;H. Oxides and salts based on these oxides which may be (but are not limited to): silicon dioxide, silicates, titanium dioxide, and mixtures thereof;I. Copolymers of the polymers listed in paragraph A, C including alternating copolymers, random copolymers, block copolymers, graft copolymers, cross-linked modifications which may be (but are not limited to): methacrylic acid and ethyl acrylate copolymers; methacrylic acid copolymers; vinylpyrrolidone-vinyl acetate copolymers (PVPVA); polyvinylpolypyrrolidone (PVPP); PVA-PEG graft copolymers; HPMC and PVA-PEG grafted copolymers; grafted polyvinylpyrrolidone- arabinogalactan copolymers; the graft copolymer has a) poly(vinyl acetate) and / or poly (vinyl alcohol) and / or poly( vinyl chloride) and poly(vinyl ester) on b) a polymer chain of polyethylene glycols, polyalkylene glycols, polypropylene glycols, polyisobutylene glycols orpolymethylpentene glycols; graft copolymer polyvinyl acetate and / or hydrolysed polyvinyl acetate (polyvinyl alcohol) groups on a polyalkylene oxide (preferably polyethylene oxide); vinylpyrrolidone -vinyl acetate copolymers; vinylpyrrolidone -vinyl acetate copolymer-64+; vinylpyrrolidone-vinyl acetate VA 64; polymethacrylate-based copolymers includes anionic, cationic, and neutral copolymers based on methacrylic acid and methacrylic / acrylic esters their salts, esters or other derivatives and mixtures thereof;J. Carriers listedK. Polymers and oligomers, copolymers, biopolymers (natural, obtained by chemical or physical modification of natural polymers (chemical or physical derivatives), or synthesized specifically) that under at least one of the following conditions:1. co-occurring in physiologic body fluids, plasma, intercellular fluid together with APIs;2. by non-covalent binding to API;3. by covalent binding to API into a conjugate; result in at least one of the following: a. an increase in the permeability of the API, API-carrier system (solution, non- covalent complex, conjugate, and the like); b. an increase in the concentration of API, API-carrier system in cells and tissues; for at least one of the following reasons: i. inhibition or modulation of multidrug resistance (MDR), predominantly mediated by efflux transporters of the ATP-binding cassette (ABC) superfamily including P-glycoprotein (P-gp); ii. induction, inhibition or modulation of CYP1, CYP2, CYP3 enzymes (non limiting examples: CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4 enzymes); iii. due to a change in the structure of the cell membrane, change in lipid biolayer properties after the incorporation of carrier substance molecules (or carrier molecular part of NCC or conjugate) into this membrane or due adhesion to this membrane; iv. due to changes in charge, hydrophilicity, hydrophobicity or other biophysical properties of the non-covalent complex, or conjugate due to which changes in the transmembrane (passive, active) or paracellular transport of the non- covalent complex, or conjugates;L. Conjugates of (A)-(K) bound (O-, N-, P-, C-, S-linked, and the like) to any Protein, Peptide, Low molecular weight compound, Lipid, Aptamer, Antibody, Affibody, Avimer, or Nanobody, etc., that may include, but are not limited to:Glycated derivatives (O-, N-, P-, C-, S-linked), glycoconjugates, glycoproteins (O-, N-, P-, C-, S-linked), neoglycoproteins, glycolipids, glycopeptides, proteoglycans, peptidoglycans, glycosides, lipopolysaccharides, and mixtures thereof;and wherein bonds may be covalent bonds, al-1, al-2, al-3, al-4, al-5, al-6, al-7, al-8, a2-l, a2-2, a2-3, a2-4, a2-5, a2-6, a2-7. a2-8, a2-9, a6-6, pi-1, [31-2, [31-3, [31- 4, pi-5, pi-6, pi-7, pi-8, pi-9, P2-1, [32-2, [32-3, [32-4, [32-5, [32-6, [32-7, [32-8, |33-3, al-2, and the like, aq-w, Pq-w, wherein q and w are independently from 1 to 9;M. Methoxylated, ethoxylated, esterificated, carboxylated, alkoxylated, acetylated, hydroxylated, hydrated, decarboxylated, amide, oxidized, sulfated, aminoacid derivatives, fermented, thermally modified, chemically modified, acid modified derivatives of the substances specifiedand their esters, salts, and any other chemical derivatives, and mixtures thereof;N. Any combination of substances specified in items A-M; wherein co-treating method (solid dispersion preparation method) is selected from: a) mechanochemical method; grinding / milling with high energy stress method; b) mechanochemical method with solvent; grinding / milling with high energy stress and solvent method; c) media milling method; d) kneading method; e) hot-melt method / melting method / fusion method; f) hot-melt extrusion / hot-stage extrusion method; g) meltrex method; h) melt agglomeration method; i) high-pressure homogenization method; j) solvent evaporation method; k) spin-coated films method; electrostatic spinning, electrostatic blowing, electrospraying film casting; l) spray-drying method; m) supercritical fluid (SCF) process method; n) cryogenic techniques method; o) lyophilization / freeze-drying technique method; p) spray freezing onto cryogenic fluids method; q) spray freezing into cryogenic liquids (SFL) method; r) spray freezing into vapor over liquid (SFV / L) method; s) ultra-rapid freezing method; t) precipitation / co-precipitation method; u) microwave irradiation method; v) energy input method; w) heat / shear energy input method; x) gel entrapment technique; y) a method comprising: contacting an active pharmaceutical ingredient and a matrix “host substance” to form a solid dispersion under conditions sufficient to form a solid dispersion; x) combined method.: !?nd-0095j

[0096] In another embodiment, provided are the the methods and the complex wheninstead of non-covalent complexes, conjugates (of Formula III) are administered, obtained by the methods described in this invention and in the patent and scientific literature.V. Combination Therapy / Fherapeutic Combinations of NCC, SD, Conjugate

[0100] The compound of Formula I-III of the invention are also used in combination with other active ingredients. The compounds and compositions of the present invention are also intended for use in the general care of patients with disease, including nutritionand / or antifungal prophylaxis, antipyretics and analgesics, antiemetics (such as metoclopramide) and / or anti-diarrheals vitamin and mineral supplements (including vitamin K), antiinflammatories (such as ibuprofen), pain medications, and medications for other common conditions in the patient population, such as antimalarials (including artemether and artesunate-lumefantrine combination therapy), typhoid or shigellosis.

[0101] It is also possible to combine any compound of the invention with one or more additional active therapeutic agents in a unitary dosage form for simultaneous or sequential administration to a patient. The combination therapy may be administered as simultaneous or sequential administration. In case of sequential administration the combination may be administered in two or more injections.

[0102] Co-administration of a compound of the invention with one or more other active therapeutic agents generally refers to the simultaneous or sequential administration of a compound of the invention and one or more other active therapeutic agents such that therapeutically effective amounts of the compound of the invention and one or more other active therapeutic agents are simultaneously present in the patient.

[0103] Co-administration comprises administering single doses of the compounds of theinvention before or after administering single doses of one or more other active therapeutic agents, for example, administering the compounds of the invention within seconds, minutes or hours after administering one or more other active therapeutic agents. For example, a single dose of the compound of the invention may be administered first, followed by a single dose of one or more other active therapeutic agents within seconds or minutes. Alternatively, a single dose of one or more other therapeutic agents may be administered first, followed by a single dose of the compound of the invention within seconds or minutes. In some cases, it may be desirable to first administer a single dose of the compound of the invention and then, after a few hours (e.g., 1-12 hours), administer a single dose of one or more other active therapeutic agents. In other cases, it may be desirable to first administer a single dose of one or more other active therapeutic agents and then administer a single dose of the compound of the invention a few hours later (e.g., 1-12 hours).

[0104] Combination therapy can provide "synergism" and "synergy", i.e., the effect achieved when the active ingredients are used together is greater than the sum of the effects occurring when the compounds are used separately. Synergistic effects can be achieved when the active ingredients are (1) combined and administered or delivered simultaneously in a combination drug; (2) delivered alternately or in parallel as separate drugs; or (3) by some other scheme. When drugs are alternated, a synergistic effect may be achieved when the compounds are administered or delivered sequentially, for example, in separate tablets, pills, or capsules, or when different injections are given in separate syringes. In general, in alternation, the effective dose of each active ingredient is administered sequentially, that is, serially, whereas in combination therapy the effective doses of two or more active ingredients are administered together. Synergistic effect means ancancer effect that exceeds the predictedpurely additive effect of the individual compounds of the combination.

[0105] A kit comprising a compound of Formula I-IV is also provided. In some embodiments of the invention, individual kits are provided comprising a compound selected from the group of each of the formulas provided herein and each subgroup and embodiments thereof, including Formula II, Formula II, Formula I. In one aspect, the kit includes a compound of Formula I. Each of the individual kits described herein may include a label and / or instructions for administering the compound to treat a disease or condition in a subject (e.g., human) in need thereof. In some embodiments of the invention, the disease or condition is a “diseases of the invention”. In other embodiments of the invention, each individual kit may also contain instructions for administering additional medical agents in combination with a compound of Formula I to treat a disease or condition in a subject (e.g., human) in need thereof.. In each of the embodiments presented herein, there is another embodiment in which the kit includes individual dosage units of the compound described herein. Examples of individual doses may include tablets, tablets, capsules, fdled syringes or syringe cartridges, IV bags, etc., each containing a therapeutically effective amount of the compound in question. In some embodiments, the kit may contain a single dosage unit, and in other embodiments, the kit may contain multiple dosage units, such as the number of dosage units required for a particular regimen or period.

[0106] In certain embodiments, the product container may be a vial, jar, ampule, preloaded syringe, blister pack, tin, can, bottle, box, or intravenous bag.

[0107] Also, certain embodiments of the invention provide for the use of a compound selected from each of claims herein in the preparation of a medicament for use in the treatment of ‘diseases of the invention” in humans.

[0108] In another embodiment, the method of treating a “diseases of the invention” in a human in need thereof comprises administering a therapeutically effective amount of a pharmaceutical composition comprising an effective amount of a Formula I-III compound in combination with at least one additional therapeutic agent.

[0109] In another embodiment, a method of treating “diseases of the invention” in a person in need thereof includes administering a therapeutically effective amount of a pharmaceutical composition comprising an effective amount of compound of Formula I-III in combination with at least one additional therapeutic agent such as (but not limited to) intravenous or intramuscular forms of thiamine, vitamin C, vitamin D, glutanione, S- adenosylmethionine, cysteine, N-acetylcysteine.

[0110] [Ref-0110] In another embodiment, the method comprises administering a therapeutically effective amount of a combination pharmaceutical agent (of Formula I-III) comprising: a) a first pharmaceutical agent - compound of Formula I-III (is 0.01-99.99% of the total weight of the Formula I-III), and b) a second pharmaceutical agent / agents ( AAPI, AAPI(s)) comprising at least one additional therapeutic agent active “diseases of the invention” of the Formula I-III component, or decreases the hepatotoxicity of the Formula I-III component, or increases the stability of the Formula I-III component (0.01-99.99% of the total weight of the composition) which may be(but are not limited to): niclosamide, nitazoxanide, chloroquine, lopinavir, ritonavir, hydroxychloroquine, vegetable or animal fats, ethyl alcohol, water, glycerin, propylene glycol, triethylene glycol, dimethylsulfoxide, solvents, betaine hydrochloride, caprilic acid, monolauric acid, monolaurin (glyceryl monolaurate), undecenoic acid (undecylenic acid), pau p'arco bark extract, cat's claw extract, garlic extract, black walnut shell extract, catalase enzyme, lipase, glucoamylase, pectinase, beta-glucanase, cellulase, alpha-galactosidase, amylase, invertase, xylanase, hemicellulase, or other enzymes, black cumin oil, nigella sativa, oregano oil, essential oils, lactoferrin, colloid silver, vitamin C, thiamine, benfothiamine, sulbutiamine, allithiamine, vitamin D, vitamin A, zinc salts, iodine, melatonin, phenofibrate, curcumin, quercetin, resveratrol, lysine, glycine, glutathione, N- acetylcysteine, cysteine, lipoic acid, S-adenosyl-L-methionine, milk thistle extract, grape seed extract, carnitine, antiandrogens, aspirin, bromhexine, budesonide, cannabidiol, colchicine, convalescent plasma, ensovibep, famotidine, favipiravir, fluvoxamine, iota- carrageenan, metformin, molnupiravir, bamlanivimab / etesevimab, bebtelovimab, casirivimab / imdevimab, sotrovimab, tixagevimab / cilgavimab, nitric oxide, paxlovid, peginterferon lambda, povidone-iodine, proxalutamide, camostat (camostat mesilate, camostat mesylate), foistar, glycyrrhiza glabra, liquorice, glycyrrhizic acid, amantadine, artemisia annua, amodiaquine, artemisinin, rutin, hesperidin, hesperetin, luteolin, baricitinib, arbidol, umifenovir, fluoxetine, kaempferol, kaempferol 3-o-rutinoside, catechin, epigallocatechin, epigallocatechin gallate, epigallocatechin-3 -gallate, myricetin, andrographolide, atorvastatin, indomethacin, nafamostat, nafamostat mesilate, nafamostat mesylate, omega 3, dha / epa, xylitol, xlear, ellagic acid, apnOl, alunacedase alfa, soluble ace2, rhace2-apn01, azelastine, baicalin, cetylpyridinium chloride, estradiol, hydrogen peroxide, loratadine, methylene blue, monolaurin, propolis, sofosbuvir, darunavir, galidesivir, cepharanthine, hypericin, spironolactone, apigenin, emodin, apilimod, atovaquone, ciclesonide, daclatasvir, fenofibrate, fucoidan, hypochlorous acid, methotrexate, nicotine, pomegranate, punica granatum, punicalagin, punicalan, urolithin a, rosuvastatin, selenium, theaflavin-3, 3 ’-digallate, dexamethasone, boceprevir, paritaprevir, cryptoquindoline, losartan, myricitrin, amiodarone, simeprevir, berberine, chrysin, digoxin, atazanavir, azvudine, ro-0622, azd7442, tixagevimab, cilgavimab, azithromycin, carvedilol, cetirizine, ct-p59, disulfiram, darolutamide, doxycycline, fostamatinib, masitinib, naproxen, neem, azadirachta indica a. juss, regdanvimab, ruxolitinib, saline, selamectin, silmitasertib, suramin, tannic acid, tenofovir disoproxil, valproic acid, amentoflavone, pristimerin, ribavirin, indinavir, saquinavir, cryptospirolepine, rhoifolin, pectolinarin, tamoxifen, 6- gingerol, theaflavin, oleuropein, etoposide, genistein, ibuprofen, paclitaxel, sertraline, tacrolimus, puerarin, limonin, obacunone, amprenavir, velpatasvir, ursolic acid, daidzein, sesamin, astragalin, gilteritinib, baicalein, caffeic acid, amitriptyline, apalutamide, apixaban, aframomum melegueta, aprotinin, ashwagandha, withania somnifera, bedaquiline, bergamottin, boswellic acids, calpeptin, canakinumab, chlorpheniramine, chlorphenamine, chlorhexidine, desloratadine, clarinex, diphenhydramine, doramectin, doxazosin, echinacea purpurea, enzalutamide, forsythoside a, glycine, griffithsin, hydroxyurea, huashibaidu, jing si herbal tea, jinhua qinggan, jtOOl (vvl l6), lenzilumab, lianhua qingwen, nelfmavir, noql9, panobinostat, paroxetine, phosphodiesterase enzyme type 5 inhibitors, pleurotus ostreatus, rheum palmatum, s-217622, tafenoquine, tofacitinib, virgin coconut oil, xuanfeibaidu, zinc pyrithione, berbamine, moxidectin, thymoquinone, xanthoangelol e, tingenone, iguesterin, micafungin, ombitasvir, tipranavir, glecaprevir, emetine, colistin, ebselen, lonafamib, glycyrrhizin, crocin, cryptomisrine, biscryptolepine, herbacetin, cycloeucalenol, campesterol, cyanidin-3-o-glucoside, afatinib, nilotinib, scedapin c, quinadoline b, decitabine, gemcitabine, afzelin, rhein, artesunate, bufalin, camptothecin, capsaicin, chlorpromazine, cyclophosphamide, dasatinib, doxorubicin, flutamide, folic acid, hydralazine, isotretinoin,leflunomide, morin, naringenin, phenytoin, propylthiouracil, pterostilbene, reserpine, simvastatin, sirolimus, sorafenib, sulindac, tretinoin, verapamil, vincristine, bicuculline, ledipasvir, tideglusib, bemcentinib, ergotamine, taraxerol, diosbulbinoside d, estrone-2,3- quinone, hinokiflavone, ginkgetin, norquinadoline a, natamycin, raltegravir, dolutegravir, cyanidin 3-o-rutinoside, quercetin 3-o-rutinoside, magnolol, phillyrin, conivaptan, aloesin, gingerol, tinocordiside, sesaminol, sesamolin, ephedrine, solanine, donepezil, vby-825,, omipalisib, psoralidin, cryptotanshinone, tetrandrine, fangchinoline, z-fa-fmk, imatinib, duloxetine, allicin, ezetimibe, pravastatin, ramipril, abemaciclib, dihydromyricetin, scutellarein, corilagin, ouabain, isorhamnetin, nystatin, sunitinib, anakinra, eculizumab, dieckol, sinigrin, glabridin, gimsilumab, kinl901, infliximab, leronlimab, pal4, pro-140, vyrologix, tocilizumab, procyanidin, a-hederin, ferulic acid, cyanidin, cyanidin 5-o-P-d- glucoside, cyanidin 3-o-glucoside, chlorogenic acid, gallic acid, Z-carragccnan. 4'- fluorouridine, 76clabs, 8g3, a6-001, agp-14, agp-15, amodiaquine, acarbose, ard-61, arq ajib, arylazothiazolimines, aviptadil, ayurcov, beauvericin, bifonazole, bismuth subsalicylate, bis- thiadiazoles, blue light, brazilin, breathing exercises, brii-196 / brii-198, bromelain, bucillamine, c60 fullerene, camellia sinensis, cd24fc, chlorine dioxide, chyawanprash, clevudine, clitoria tematea, asian pigeonwings, bluebellvine, blue pea, butterfly pea, cordofan pea, darwin pea, clofoctol, codivir, copper(ii) gluconate, clsp-2, ctb-ace2 gum, cysteamine, d-a-tocopherol polyethylene glycol succinate, tpgs, dfo, diammonium glycyrrhizinate, dimethyl sulfoxide, darunavir ethanolate, ebastine, eklc4, engineered ace2, enoxaparin, epicatechin, fbr-002, estrogen, ethoxzolamide, ethyl lauroyl arginine, exo-cd24, evusheld, tixagevimab, cilgavimab, ferrocene derivatives, flovid-20, gancao-banxia, gb-1, green tea, hanshi zufei, heparin, hinokitiol, homo-harringtonine, honey, hydroxyzine, inm005, intcrfcron-Z (interferon lamba), isoprinosine, js016, kabasura kudineer, kalmegh, kinetin, led spirulina, levamisole, levilimab, 1-glutamine, ly2835219, manidipine, manuka honey, maoto, mesencure, metformin glycinate, mi- 1851, monte lukast, multimeric soluble ace2, n-acetylglucosamine, natto extract, naphthoquine, niacinamide, nicotinamide mononucleotide, opaganib, oseltamivir, oxygen-ozone immunoceutical therapy, palmitoylated ace2, pamapimod, pegylated interferon alpha-2b, peg ifh-a2b, pentosan polysulfate, pioglitazone, phoxwell, phthalocyanine, porphyridium sp., pranayama, probenecid, propolis sulabiroin-a, pyramax, pyronaridine-artesunate, pyrimidine, pyronaridine, q34, quinine, raloxifene, rd-xl9, rejuveinix, riboflavin, sabizabulin, saliravira, sarbd-1, sars-block, schafloside, sea cucumber sulfated polysaccharide, scsp, seraph 100 microbind affinity filter, serratiopeptidase, serratia e-15 protease, serralysin, serratiaprotease, serrapeptase, shallot, si-f019, silibinin, sngOOl, spirulina, sodium bicarbonate, stenoparib, sti-9167, thymic peptides, tollovir, toremifene, tpntl, tranilast, trisb92, urtica dioica agglutinin, zinv03977803, znonps, znsec-humicin, z-veid-fmk, minocycline, coclobine, dieckol 1, celastrol, 3-isotheaflavin-3 gallate, dihydrotanshinone i, citriquinochroman, holyrine b, proximicin c, pityriacitrin b, anthrabenzoxocinone, penimethavone a, maraviroc, valrubicin, icatibant, bepotastine, epirubicin, epoprostenol, vapreotide, aprepitant, caspofungin, perphenazine, hrsace2, tegobuvir, olysio, filibuvir, alisporivir, allyl disulphide, allyl trisulphide, digitoxigenin, tenufolin, pavetannin cl, lianhuaqingwen, dorzolamide, deptropine, neostigmine bromide, ethotoin, hydrocotamine, ampyrone, withanolide b, lurasidone, lumacaftor, perfenazine, benserazide, isocarboxazide, cryptophycin 1, cryptophycin 52, deoxycylindrospermopsin, anatibant, pilaralisib, zabofoxacin, tiracizine, picotamide, cilazapril, indisulam, ziprasidone, propadimine, phenformin, torososide b, covitris2020, chlovid2020, silybin, licoleafol, mitomycin c, gardenin a, 6-paradol, psiadia punctulata, tanshinone-i, mangiferin, y-mangostin, 3,3'-diindolylmethane, 4-hydroxy-2- nonenal, acetaldehyde, aflatoxin-bl, aica-ribonucleotide, alitretinoin, alpha-tocopherol, azacitidine, azathioprine, belinostat, benazepril, benzopyrene, bezafibrate, bisphenol-a,bortezomib, bucladesine, buspirone, buthionine-sulfoximine, cadmium-chloride, caffeine, carbamazepine, carbon-tetrachloride, celecoxib, ciglitazone, cisplatin, clodronic-acid, clofibrate, clozapine, colforsin, corticosterone, coumestrol, cycloheximide, cytarabine, dactinomycin, daunorubicin, deguelin, dichloroacetic-acid, diclofenac, dieldrin, diethylstilbestrol, dimethylnitrosamine, dinoprost, entinostat, estriol, ethinyl-estradiol, fenretinide, fluorouracil, fulvestrant, fumonisin-bl, furan, gefitinib, glafenine, glucosamine, haloperidol, ifosfamide, indole-3-carbinol, ionomycin, irinotecan, levofloxacin, lithiumchloride, mercaptopurine, methapyrilene, methimazole, methoxychlor, mevalonic acid, mifepristone, nimesulide, norepinephrine, ochratoxin-a, olanzapine, omeprazole, orphenadrine, oxidopamine, pentachlorophenol, phenethyl-isothiocyanate, pifithrin, pilocarpine, pirinixic acid, piroxicam, progesterone, pyrazolanthrone, ranitidine, rimonabant, rosiglitazone, rotenone, sulfasalazine, tamibarotene, testosterone, tetrachloroethylene, tetracycline, thapsigargin, theophylline, topotecan, tributyltin, trichloroethylene, trichostatin- a, triclosan, troglitazone, tunicamycin, tyrphostin-ag-1478, urethane, valdecoxib, vancomycin, vorinostat, wortmannin, zearalenone, zidovudine, zinc32960814, zincl2006217, zinc03231196, nigricanoside a, nigricanoside b, callophysin a, gallocatechin, hyperin, lupinifolin, viomycin, capastat, demethoxycurcumin, bisdemethoxycurcumin, scutellarin, alloyohimbine gummadiol, asparagamine a, vincapusine, oxytetracycline, naringin, kanamycin, cefpiramide, salvianolic acid b, teniposide, benzoylgedunin, 6- deaminosinefungin, unii-o9h5kyl Isv, cephalosporin derivatives, neomycin, tcm5280805, tcm5280445, tcm5280343, tcm5280863, tcm5458190, quinadoline, polyketide isochaetochromin dl, O-hydroxyusambarensine, 6-oxoisoiguesterin, 22-hydroxyhopan3-one, grazopavir, mfcd00832476, mfcd02180753, pacritinib, a3659, a3777, leucopelargonidin, taxifolin, eriodictyol, enterodiol, naringen, flemiflavanone d, euchrestaflavanone a, triamterene, estrone, azadirachtin-h, azadirachtin-i, azadirachtin-q, sn00334175, snOO 162745, alphaspinasterol, gycyrrhizin, azadirachtani, mycophenolic acid, kushenol-w, 6-azauridine, cyanidin 5-o-P-d-glucoside, morelloflavone, methylochnaflavon, isoginkget, sciadopitysin, podocarpusflavone a, cryptomerin, cytochalasin z8, leucal, zanamivir, penciclovir, etravirine, p-coumaric acid, ketazolam, methylnaltrexone, ethynodiol diacetate, petunidin 3,5-odiglucoside, delphinidin 3-o-rutinoside, grazoprevir, las 51620435, las 51620429, rosoxacin, levomefolic, etodolac, tenofovir, tinofoviralafenamide, omipressin, otosiban, lanreotide, argiprestocin, demoxytocin, carbetocin, lypressin, examorelin, polymyxin bl, verbascoside, abrisapogenol g, kaempferol-3-o-rutinoside, hederagenin, abrusoside a, robustaflavone, agathisflavone, swertianolin, ononin, pedunculoside, imperialine, peimisine, batatasin i, pomiferin, coumarin, rhodionin, aloin, sarsasapogenin, silydianin, rutaecarpine, morusin, a-mangostin, yohimibine, coclaurine, strychnine, myristicin, medicarpin, coptisine, tiliroside, glabrone, lignans, gastrodin, cordycepin, ajugol, evodiamine, nuciferine, cynarin, betulin, gramine, narciclasine, vitexin, protopanaxatriol, karanjin, gigantol, harsingar, nictoflorin, lupeol, aloevera, aloenin, giloy, sitosterol, nimbin, ginger, shogaol, cyanin, medicagol, faradiol, flavanthrin, withanoside v, somniferine, vicenin, isorientin, sesamolinol, ellipticine, ecteinascidin, homoharringtonine, dolastatin, halichondrin, plicamycin, arvoside, nicotiflorin, kaempferol sulphates, quercetin-3-o- glucuronide, isorhamnetin-3-o-glucoside, narcissin, calendula glycoside b, lauruside, miricetine-3 -glucoside, cordifoliside, anthraquinones, emodine 8-glucosides, acetoside, lisinopril, deoxynortryptoquivaline, thalimonine, sophaline, tomatidine, 10- hydroxyusambarensine, stychnopentamine, usambarensine, vanillin, crambescidin 786, crambescidin 826, sepiapterin, tetrodotoxin, caulerpin, lutein, galanthamine, nomilin, deacetylnomilin, ichangin, amyrin, 24-dimethylene cycloartenol, isoiguesterin, lentinula edodes, agaricus bisporus, jmx0286, jmx0301, jmx0941, erythromycin, chloramphenicol, mpi43, mpi44, mpi46, keigairengyoto, shosaikotokakikyosekko, kakkontokasenkyushin'i,vuwcov059, vwcov267, vuwcov270, 4-hydroxycordoin, mallotophilippen d, 3 '-(3 -methyl -2- butenyl)-4'-o-P-d-glucopyranosyl-4,2'-dihydroxychalcone, lefamulin, cefixime, cefpodoxime, ciprofloxacin, sparfloxacin, moxifloxacin, tbaj-876, (s)-crizotinib, spermidine, spermine, mk-2206, saffron, mdl-28170, z Ivg chn2, ono 5334, mln-3897, tipifamib, salinomycin, bavachin, tanshinone iia, isobavachalcone, lycorine hydrochloride, lycorine, bufotaline, cinobufagin, periplocoside, veratridine, coniferyl aldehyde, comuside, brusatol, momordinic, roburicacid, hruceine a, isoalantolactone, oridonin, dehydrocostus lactone, alantolactone, dehydrodiisoeugenol, liensinine, isoliensinine, vps34-inl, stf-62247, mcoppb, gw 803430, amodiaquine dihydrochloride, n-methylspiperone, clemastine fumarate, gmc 2- 29, lu ae58054, chlorprothixene, methdilazine, methotrimeprazine maleate, piperacetazine, difeterol, loperamide, naltrindole isothiocyanate, aml241, cpdd, sb 271046, gmc 2-113, caa- 0225, cathepsin inhibitor 1, z-gly-leu-phechloromethyl ketone, balicatib, calpain inhibitor i, berzosertib, ikk-2 inhibitor viii, nsc 33994, alpha-l-arabinopyranose, ml414, itlt dihydrochloride, s-15176 difumarate, jtv519 hemifumarate, rescimetol, trifluomeprazine 2- butenedioate, asteriscunolide d, genz-123346, maprotiline, deserpidine, melitracen, dlunarizine, proglumetacin, dmp 777, dexanabinol, trifluoperazine 2hcl, thioridazine hcl, bicalutamide, cinnamaldehyde, piperine, zingeberene, gr 127935, diazepam, levetiracetam, sotalol, tolterodine, oxazepam, thiamazole, hydroxycarbamide, clonazepam, meloxicam, temazepam, anastrozole, rivaroxaban, perindopril, silodosin, lorazepam, pramipexole, bupropion, venlafaxine, bisoprolol, aripiprazole, linagliptin, clopidogrel, allopurinol, indapamide, chlortalidone, nifedipine, warfarin, phylloflavan, milk thistle, ilexin b, isosilybin b, spiperone, vitamin bl2, vitamin b9, vitamin kl, vitamin k2, vitamin e, oleanderolide, proceragenin a, balsaminone a, anacardic acid, aloeresin d, tcid, dihydrokaempferol, dihydroquercetin, myricentin, isoquercitrin, pc000550, pc000361, pc000558, pc000573, grl0617, mefloquine, brequinar, dipyridamole, quercetagetin, glycycrrhizin, 59- tetrahydrocannabinol, arteether, dihydroartemisinin, arteannuin, cannabidinol, punicalin, panduratin a, andrographis paniculata, zingiber officinale, boesenbergia rotunda, Scutellaria baicalensis, pomegranate peel extract, zinc000013444414, zinc000137976768, zincOOO 143375720, diosmin, apiin, okadaic acid, p-57as3, concanamycin a, amphotericin b, oleandrin, gitoformate, eprinomectin, beta-escin, fusicoccin, perilla aldehyde, perillyl alcohol, cidofovir, valaciclovir, tazarotene, hydroquinone, bromocriptine, acyclovir, finasteride, betamethasone, clonidine, somatotropin, nitisinone, tadalafil, vinblastine, pyrimethamine, pentamidine, etacrynic acid, proguanil, everolimus, tamsulosin, rifapentine, terbinafine, fluvastatin, cyclosporine, hydrocortisone, pentoxifylline, nitrogen, arginine, abatacept, interferon beta- la, thalidomide, crizanlizumab, nitroglycerin, fluorescein, captopril, brexanolone, omalizumab, siltuximab, propranolol, interferon beta- lb, prednisone, prednisolone, methylprednisolone, torin-2, rapamycin, radotinib, thiostrepton, cl-amidine, bb-cl-amidine, broussoflavan a, hygromycin b, nabiximols, abyssinone ii, procynidin bl, indigo blue, crytospirolepine, lO'-hydroxyusambaresine, strychnopentamine, usararotenoid a, 12a-epi-milletosin, torchnil, febcin, pibrentasvir, 5 -chloro-omega-hydroxy- l-o- methylemodin, cystodion e, jql, zbc260, zafirlukast, pranlukast, canderastan cilexetil, saquanivir, boron citrate, oleoylethanolamide, liquiritin, laminarin, eckol, trifucol, -d- galactose, K-carrageenan, cl35-ls / cl44-ls, sab-185, vir-783 l / vir-7832, covi-amg / covi-drops, covi-guard, 2-deoxy-d-glucose, dnl758, lanadelumab, abivertinib, bld-2660, pemziviptadil, artesunate / pyronaridine, carragelose, at-527, ptc299, brilacidin, saracatinib, erlotinib, osimertinib, pictilisib, dinaciclib, cigb-325, sb203580, ralimetinib, mapkl3-in-l, arry-797, tofacitinibfedratinib, mpro 13b, gc-373, gc-376, mpro n3, bosutinib, clofazimine, domperidone, entecavir, fedratinib, ipratropium bromide, lomitapide, metoclopramide, slra, thioguanine, sitagliptin, dihydroergotamine, crinine, ilexsaponin b2, strictinin, zinc000027215482, zinc000252515584, loniflavone, 2'-o-ribose methyltransferase, tirucallina, zinc000253504770, zinc000253504766, triamcinolone, amoxicillin, hydrochlorothiazide, terflavin a, chebulagic acid, chebulinic acid, coumaroylquinic acids, sinapoyl d glucoside, tetra-o-galloyl-P-d-glucose, methyl rosmarinates, cosmosiin, dihydronitidine, lectin, digitoxigenine, calarene, amaranthin, diarylheptanoids, indigo, aloe emodin, dihydrocelastrol, phyllaemblinol, isocolumbin, magnoflorine, piperolactam a, withanone, biflavone, cinnamic amides, agomelatine, ramelteon, immunoglobulin, ifn-pia, ifn-pib, interleukin -2, cynk-001, baloxavir marboxil, asc09, danoprevir, cobicistat, carrimycin, dihydroartemisinine, piperaquine, fingolimod, piclidenoson, cflOl, nivolumab, obtivo, meplazumab, jakotinib, tj003234, tozumab, adamumab, ravulizumab, alxnl210, clazakizumab, avdoralimab, iph5401, ly3127804, ifx-1, bevacizumab, valsartan, 7- hydroxystaurosporine, bafetinib, emtricitabine, adefovir, tenofovir alafenamide, abacavir, ganciclovir, didanosine, delavirdine, pirfenidone, P-glucan, p-coumaroyltriacetic acid lactone, zinc02111387, zinc02122196, sn00074072, zinc04090608, xuebijing, lung cleansing and detoxifying decoction, etanercept, ibrutinib, enalapril, telmisartan, oroxylin a, irisolidone, anhydrosafflor yellow b, euchrenone, uncaric acid, demethylzeylasteral, maslinic acid, atractylenolide iii, astragaloside iv, daturaolone, cucurbitacin g 2-glucoside, citronellol, limonene, salvianolic acid, neochlorogenic acid, kobophenol a, bis-demethoxycurcumin, 5- viniferin, pseudoephedrine, methylephedrine, speciophylline, uncarine f, anisodamine, forsythoside i, amygdalin, urso-deoxycholic acid, withanolide a, P-sitosterol, famesiferol b, amlodipine, dexchlorpheniramine, tanshinones, isatis indigotica root, rhizoma cibotii, torreya nucifera, shuang huang lian, estragole, eugenol, ubiquinone, flecainide, polymethoxyflavones, poly-hydroxyflavones, meamsitrin, 3-o-P-d-glucoside, benzoic acid, biorobin, delphinidin, galangin, isoferulic acid, dithymoquinone, negillicine, negillidine, mucl, a-lactalbumin, or mixtures thereof.[End-0110]

[0111] iRsf Olllj In another embodiment, provided are the method when the non- covalent complex, molecular / solid dispersion or conjugate is combined with at least one additional active pharmaceutical ingredient (AAPI) active (in vitro, in vivo, ex vivo, in silico) against disease (non limiting example: cancer, etc) and selected from: 5 -Fluorouracil; Abarelix; Abiraterone; Acetaminophen; Acetaminophen or paracetamol; Acetazolamide; Actiq; Ad...

Claims

CLAIMSWhat is claimed is:

1. Non-covalent active pharmaceutical ingredient-carrier complex (of Formula I)[GUEST]k« [H0ST]n«(H20)m with enhanced permeability and / or bioavailability properties for treating cancer in a human as well as for manufacturing a pharmaceutical dosage form to treat cancer in a human in need thereof (by administering a therapeutically effective amount), at a dosage ranging from 0.0001 ng / kg to 100000 mg / kg (calculated for pure API) wherein k is 1 to 100; wherein n is 1 to 10000; wherein m is 1 to 100000; wherein non-covalent complex is obtained by:1) dissolution in water of solid-phase non-covalent complex or inclusion complex or molecular dispersion obtained by mechanochemical method or any method selected from: a) grinding / milling with high energy stress method; b) grinding / milling with high energy stress and solvent method; c) media milling method; d) kneading method; e) hot-melt method / melting method / fusion method; f) hot-melt extrusion / hot-stage extrusion method; g) meltrex method; h) melt agglomeration method; i) high-pressure homogenization method; j) solvent evaporation method; k) spin-coated films method; electrostatic spinning, electrostatic blowing, electrospraying film casting; l) spray -drying method; m) supercritical fluid (SCF) process method; n) cryogenic techniques method; o) lyophilization / freeze-drying technique method; p) spray freezing onto cryogenic fluids method; q) spray freezing into cryogenic liquids (SFL) method;r) spray freezing into vapor over liquid (SFV / L) method; s) ultra-rapid freezing method; t) precipitation / co-precipitation method; u) microwave irradiation method; v) energy input method; w) heat / shear energy input method; x) gel entrapment technique; y) a method comprising: contacting an active pharmaceutical ingredient and a matrix “host substance” to form a solid dispersion under conditions sufficient to form a solid dispersion; z) combined method.2) any other method described in description of the patent application; wherein the non-covalent complex has enhanced permeability (into the internal organs and tissues of the person receiving the drug) and / or bioavailability properties; wherein the therapeutic efficacy of the non-covalent complex can be (or is) enhanced by enhanced permeability and / or bioavailability, which allows for rapid achievement of the required concentration in the organs and tissues of the patient; wherein enhanced permeability and / or bioavailability results in at least one of the following: a. an increase in the permeability of the API, API-carrier system (solution, non-covalent complex, and the like); b. an increase in the concentration of API, API-carrier system in cells and tissues; for at least one of the following reasons: i. inhibition or modulation of multidrug resistance (MDR), predominantly mediated by efflux transporters of the ATP -binding cassette (ABC) superfamily including P-glycoprotein (P-gp); ii. induction, inhibition or modulation of CYP1, CYP2, CYP3 enzymes (non limiting examples: CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4 enzymes); iii. due to a change in the structure of the cell membrane, change in lipid biolayer properties after the incorporation of carrier substance molecules (or carrier molecular part of NCC or conjugate) into this membrane or due adhesion to this membrane; iv. due to changes in charge, hydrophilicity, hydrophobicity or other biophysical properties of the non- covalent complex due to which changes in the transmembrane (passive, active) or paracellular transport of the non-covalent complex;wherein GUEST isi.e. GUEST is Lenalidomide;i.e. GUEST is Osimertinib;i.e. GUEST is Enzalutamide;i.e. GUEST is Pomalidomide;i.e. GUEST is Lenvatinib;i.e. GUEST is Dasatinib;i.e. GUEST is Venetoclax;i.e. GUEST is Apalutamide;i.e. GUEST is Abiraterone acetate;wherein1) Ri is H R2 is CH3 ; (i.e. GUEST is Milbemycin A3) ;2) Ri is H R2is CH2CH3; (i.e. GUEST is Milbemycin A4) ;3) Ri is H R2is CH(CH3)2; (i.e. GUEST is Milbemycin D) ;4) Ri is CH3R2is CH3; (i.e. GUEST is Milbemycin B2) ;5) Ri is CH3R2is CH2CH3; (i.e. GUEST is Milbemycin B3) ;6) Ri is CH3R2is CH(CH3)2; (i.e. GUEST is Milbemycin G) ;b)(i.e. GUEST is Nemadectin); c)wherein1) =R3is -H, (P)-OH;=R2is -H, -H ; -R3is selected from -CH3, -CH2CH3; (i.e. GUEST is Milbemectin);2) =R]is =NOH ;=R2is -H, -H ; -R3is selected from -CH3, -CH2CH3; (i.e. GUEST is Milbemycin oxime);3) =R3is -H, (P)-OH;=R2is =NOCH3; -R3is (Z)-C(CH3)=CH-CH(CH3)2;(i.e. GUEST is Moxidectin);4) =R3is -H, (P)-OH;=R2is -H, (a)-OH ; -R3is (Z)-C(CH3)=CH-CH(CH3)2;(i.e. GUEST is Nemadectin);wherein1) R is CH2CH3 ; (i.e. GUEST is Emamectin Bia) ;2) R is CH3 ; (i.e. GUEST is Emamectin Bib) ;(i.e. GUEST is Thiabendazole (Tiabendazole));(i.e. GUEST is Oxfendazole);(i.e. GUEST is Nitazoxanide);(i.e. GUEST is Artemisinin);(i.e. GUEST is Resveratrol);(i.e. GUEST is Pyrvinium);(i.e. GUEST is Albendazole sulfoxide (S-oxide)); ab) GUESTS selected from those listed in from FIG. 12 to FIG.72.; ac)by skilled in the art; ad) derivatives of compounds specified in (a)-(ac) such as racemate, enantiomer, diastereomer, tautomer, polymorph, pseudopolymorph, hydride or solvate thereof; or a pharmaceutically acceptable salt or ester or ether thereof; or prodrug thereof; or methabolite thereof; or aglycone thereof; or derivative thereof (see “DEFINITIONS OFor derivatives which may be obtained by gene replacement processes in genetically engineered strains, or / and by fermentation, or / and by chemical modifications and the like, or / and which are described in the scientific and patentliterature; wherein [HOST]n isA) selected from:ElB) Chemically modified derivatives of (A) where any -OH, H can be replaced by R, wherein R is H, halogen, F, Cl, Br, I, OH, Me, Et, Ac, OMe, OEt, OAc, ORA, N(RA)2,N3, CN, NO2, S(O)ZRA, (Ci-Ci5)alkyl, (C4-Cs)carbocyclylalkyl, (Ci-C8)substituted alkyl, (C2-Cs)alkenyl, (C2- C8)substituted alkenyl, (C2-C8)alkynyl, (C2-C8)substituted alkynyl, — C(=O)RA, — C(=O)ORA, — C(=O)NRARB, — C(=O)SRA, — S(O)RA, — S(O)2RA, — S(O)(ORA), — S(O)2(ORA), — SO2NRARB, (C6-C2o)aryl(Ci-C8)alkyl, — PO(OH)2, — PO(OH)OPO(OH)2,— PO(OH)OPO(OH)O PO(OH)2, — PO(ORA)2, — PORARB, phenyl, 1-naphthyl, 2-naphthyl, benzyl, (C3-C6)cycloalkyl, — CH2— (C3- C6)cycloalkyl, — O — ( Ci-Cs) alkyl, — O-benzyl, — O — CH2— (C3-C6)cycloalkyl, CF3, C(halogen)3, — C(=Q)RA, — C(=Q)ORA, — C(=Q)N(RA), — NRARB, —+N(RA)3, — SRA, — S(O)RA, — S(O)2RA, — S(O)(ORA), — S(O)2(ORA), — OC(=Q)RA, — OC(=Q)ORA, — OC(=Q)(N(RA)2), — SC(=Q)RA, — SC(=Q)ORA, — SC(=Q)(N(RA)2), — N(RA)C(=Q)RA, — N(RA)C(=Q)ORA, — N(RA)C(=Q)N(RA)2, — SO2NRA2, — CN — N3, — NO2, — ORA, NRARB, N(RA)ORB, NRANRB, N3, NO, NO2, CHO, CN, — CH(=NRA) ,— CH=NNHRA, — CH=N(ORA), — CH(ORA)2, — C(=O)NRBRA, — C(=S)NRBRA, — C(=O)ORA, (C6-C2o)optionally substituted aryl, optionally substituted heteroaryl, — C(=O)(Ci- C8)alkyl, — S(O)n(Ci-C8)alkyl, SRA,or selected from radicals obtained by removal of a hydrogen atom from the compounds shown in FIG. 8 wherein Q is O, S, NRA,+N(O)(RA), N(ORA),+N(O)(ORA), or N— NRA2; wherein RA, RBis H, halogen, F, Cl, Br, I, OH, Et, Me, Ac, ORC, N(RC)2,N3, CN, NO2, S(O)ZRC, (Ci-Ci5)alkyl, (C4-C8)carbocyclylalkyl, (Ci-C8)substituted alkyl, (C2-C8)alkenyl, (C2-C8)substituted alkenyl, (CS-Gjalkynyl. (C2-C8)substituted alkynyl, — C(=O)Rc, — C(=O)ORC, — C(=O)NRCRC, — C(=O)SRc, — S(O)RC, — S(O)2RC, — S(O)(ORC), — S(0)2(ORC), — SO2NRCRC, (C6-C2o)aryl(Ci-C8)alkyl, — PO(OH)2, — PO(OH)OPO(OH)2— PO(OH)OPO(OH)OPO(OH)2, — PO(ORC)2, — PORCRC, phenyl, 1 -naphthyl, 2-naphthyl, benzyl, (C3-C6)cycloalkyl, — CH2— (C3-C6)cycloalkyl, — O — ( Ci-Cs) alkyl, — O-benzyl, — O — CH2— (C3-C6)cycloalkyl, CF3, C(halogen)3, — C(O) Rc, — C(O)ORC, — C(O)N(RC), — NRCRC, —+N(RC)3, — SRC, — S(O) Rc, — S(O)2RC, — S(O)(ORC), — S(O)2(ORC), — OC(O) Rc, — OC(O)ORC, — OC(O)(N(RC)2), — SC(=Q)RC, — SC(=Q)ORC, — SC(=Q)(N(RC)2), — N(Rc)C(=Q)Rc, — N(Rc)C(=Q)ORc, — N(Rc)C(=Q)N(Rc)2, — SO2NRC2, — CN ,— N3, — NO2, — ORC, NRCRC, N(RC)ORC, NRCNRC, N3, NO, NO2, CHO, CN, — CH(=NRC) — CH=NNHRC, — CH=N(ORc), — CH(ORC)2, — C(=O)NRCRC, — C(=S)NRCRC, — C(=O)ORc, (C6-C2o)optionally substituted aryl, optionally substituted heteroaryl, — C(=O)(Ci-C8)alkyl, — S(O)z(Ci-C8)alkyl, or SRC; wherein Rcis H, OH, F, Cl, Br, I, Me, Et, Ac, OMe, OEt, or OAc,or selected from radicals obtained by removal of a hydrogen atom from the compounds shown in FIG. 8; wherein z is from 1 to 10. wherein [HOST]nisD1) — [M 1]n— — [M 1xi-M2x2]n— — [M 1xi-M2x2-M3x3]n— — [M 1xi-M2X2-M3x3-M4x4]n— , — [M 1xi-M2X2-M3X3-M4x4-M5X5]n— — [M 1xi-M2x2-M3x3-M4x4-M5x5-M6x6]rl— [M1]n— I [M 1xr M2X2]n — f , [M 1xi-M2x2-M3x3]n— f, [M 1xi-M2x2-M3x3-M4x4]n— f, [M 1xi-M2x2-M3x3-M4x4-M5xs]n — f, [M 1xi- M 2x2“ M 3x3- M 4X4- M 5XS- M 6xe]n — f,and continue on FIG.1 , FIG.2, FIG.3, FIG.4, FIG.5, and the like wherein x1, x2, x3, x4, x5, x6 is from 1 to 108; whereinwherein at least one of M1 , M2, M3, M3, M4, M5, M6 is a repeat unit(s) or terminal residue formed from this monomers: a) 4-epi-Legionaminic acid; 6-Deoxy-L-altrose; N-Acetyl-6-deoxy-L-altrosamine; 6-Deoxy-D- gulose; 6-Deoxy-D-talose; N-Acetyl-6-deoxy-D-talosamine; 8-epi-Acinetaminic acid; 8-epi- Legionaminic acid; Abequose; Acinetaminic acid; D-Allose; D-Alluronic acid; D-Allosamine; N-Acetyl-D-allosamine; L-Altrose; L-Altruronic acid; L-Altrosamine; N-Acetyl-L- altrosamine; L-Apiose; L-Arabinose; Bacillosamine; Colitose; D-glycero-D-manno-Heptose; 3-Deoxy-D-lyxo-heptulosaric acid; D-Digitoxose; D-Fructose; L-Fucose; N-Acetyl-L- fucosamine; D-Galactose; D-Galacturonic acid; D-Galactosamine; N-Acetyl-D-galactosamine; D-Glucose; D-Glucuronic acid; D-Glucosamine; N-Acetyl-D-glucosamine; D-Gulose; D- Guluronic acid; D-Gulosamine; N-Acetyl-D-gulosamine; L-Idose; L-Iduronic acid; L- Idosamine; N-Acetyl-L-idosamine; 2-Keto-3-deoxy-nononic acid; 3-Deoxy-D-manno- octulosonic acid; Legionaminic acid; L-glycero-D-manno-Heptose; D-Lyxose; D-Mannose; D- Mannuronic acid; D-Mannosamine; N-Acetyl-D-mannosamine; Muramic acid; N-Acetylmuramic acid; N-Glycolylmuramic acid; Neuraminic acid; N-Acetylneuraminic acid; N- Glycolylneuraminic acid; Olivose; Paratose; Pseudaminic acid; D-Psicose; D-Quinovose; N- Acetyl-D-quinovosamine; L-Rhamnose; N-Acetyl-L-rhamnosamine; D-Ribose; Sialic acid; L- Sorbose; D-Tagatose; D-Talose; D-Taluronic acid; D-Talosamine; N-Acetyl-D-talosamine; Tyvelose; D-XyloseDioses; Aldodiose; Glycolaldehyde; Trioses; Aldotriose; Glyceraldehyde; Ketotriose; Dihydroxy acetone; Tetroses; Aldotetroses; Erythrose Threose; Ketotetrose; Erythrulose; Pentoses; Aldopentoses; Arabinose; Lyxose; Ribose; Xylose; Ketopentoses; Ribulose; Xylulose; Deoxy sugars; Deoxyribose; Hexoses; Aldohexoses; Allose; Altrose; Galactose; Glucose; Gulose; Idose; Mannose; Talose; Ketohexoses; Fructose; Psicose; Sorbose; Tagatose; Fucose; Fuculose; Rhamnose; Heptoses; Ketoheptoses; Mannoheptulose; Sedoheptulose; Octoses; Nonoses; Neuraminic acid; galactosamine, N-acetylgalactosamine, N- formylgalactosamine, N-propionylgalactosamine, N-n-butanoylgalactosamine, N-iso- butanoylgalactosamine, lactose, lactobionic acid, mannose, aminoacids, nucleosides, folate, folic acid, y-FBA-folate, and a-FBA -folate, and other folic acid chemical derivatives; and (using IUPAC nomenclature of organic chemistry, IUPAC Condensed code system) from this monomers:1,4-Anhydro-Gal; 1,4-Anhydro-Gal; 1,4-Anhydro-Kdo; IdAlt-ol; IdEry-ol; 2,3-Anhydro-All; 2,3-Anhydro-Man; 2,3-Anhydro-Rib; 2,5-Anhydro-D-Alt; 2,5-Anhydro-D-AltOS; 2,5- Anhydro-L-Man; 2,5-Anhydro-Man; 2,5-Anhydro-Man-ol; 2,5-Anhydro-ManOS; 2,5- Anhydro-Tal-ol; 2,5-Anhydro-TalOP; 2,7-Anhydro-Kdo; 2,7-Anhydro-Kdof; 3,6-Anhydro- Fruf; 3,6-Anhydro-Gal; 3,6-Anhydro-GalOS; 3,6-Anhydro-Glc; 3,6-Anhydro-L-Gal; 3,6- Anhydro-L-GalOMe; 3dLyxHepUlosaric; 4,7-Anhydro-KdoOPEtn; 4,8-Anhydro-DDGlcOct; 4,8-Anhydro-Kdo; 4,8-Anhydro-LDGlcOct; 4dAraHex; 4dEry-ol; 4eLeg5Ac7Ac; 6dAlt; 6dAltNAc; 6dAltOAc; 6dAltf; 6dAltfOAc; 6dGul; 6dManHep; 6dTal; 6dTalNAc; 6dTalNAcOAc; 6dTalOAc; 6dTalOAcOAc; 6dTalOAcOMe; 6dTalOMe; 6dTalOMe-ol; 6dTalf; 8eAciNAcNAc; 8eLeg; 8eLeg5Ac7Ac; 8eLeg5Ac7AcGro; 8eLegNAc; 8eLegNAcNBut; Abe; AbeOAc; AcefA; AciNAcNAc; Aco; AcoNAc; A11N; AllOAc; AllOMe; Alt; AltA; AltAN; AltNAcA; AltOMeA; Altf; AltfOAc; Ami; ApiOAc; ApiOMe-ol; Apif; Ara; Ara-ol; AraGlc; AraHepUloNAc-onic; AraHepUloNAcN-onic; AraHepUloNGc-onic; AraHexA; AraN; AraNMeOMe; AraOAc; AraOAcOP-ol; AraOMe; AraOPN; Araf; ArafGro; ArafOCoum; ArafOFer; ArafOMe; ArafOS; Asc; Bac; BacNAc; BoiOMe; Col; D-2dAraHex; D-2dAraHexA; D-3dAraHepUlosonic; D-3dLyxHepUlosaric; D-3dThrHexUlosonic; D- 3dThrPen; D-3dXylHexOMe; D-4dAraHex; D-4dEryHexOAcN4en; D-4dLyxHex; D-4dLyxHexOMe; D-4dThrHexA4en; D-4dThrHexAN4en; D-4dThrHexOAcN4en; D- 4dXylHex; D-6dA110Me; D-6dAlt; D-6dAltHep; D-6dAltHepOMe; D-6dAltHepf; D- 6dAraHex; D-6dAraHexN; D-6dAraHexNAc; D-6dAraHexOMe; D-6dLyxHexOMe; D- 6dManHep; D-6dManHepOAc; D-6dManHepOP; D-6dTal; D-6dTalHep; D-6dTalOAc; D- 6dTalOAcOMe; D-6dTalOMe; D-6dXylHex; D-6dXylHexN4Ulo; D-6dXylHexNAc4Ulo; D- 6dXylHexOMe; D-7dLyxOctUlosonic; D-9dThrAltNon-onic; D-Alt; D-Apif; D-ApifOAc; D- ApifOMe; D-Ara; D-Ara-ol; D-AraHepUlo-onic; D-AraHex; D-AraHexUloOMe; D-AraN; D- AraOS; D-Araf; D-ArafN; D-Fuc; D-Fuc-ol; D-FucN; D-FucNAc; D-FucNAc-ol; D-FucNAcN; D-FucNAcNMe; D-FucNAcNMeN; D-FucNAcOAc; D-FucNAcOMe; D-FucNAcOP; D- FucNAcOPEtn; D-FucNAlaAc; D-FucNAsp; D-FucNBut; D-FucNButGro; D-FucNFo; D- FucNLac; D-FucNMeN; D-FucNN; D-FucNThrAc; D-FucOAc; D-FucOAcN; D- FucOAcNBut; D-FucOAcNGroA; D-FucOAcOBut; D-FucOAcOMe; D-FucOBut; D- FucOEtn; D-FucOMe; D-FucOMeN; D-FucOMeOCoum; D-FucOMeOFer; D-FucOMeOSin; D-FucOS; D-Fucf; D-FucfNAc; D-FucfOAc; D-Ido; D-IdoA; D-IdoOSA; D-Rha; D-Rha-ol; D- RhaCMe; D-RhaGro; D-RhaN; D-RhaNAc; D-RhaNAcOAc; D-RhaNBut; D-RhaNButOMe; D-RhaNFo; D-RhaOFoN; D-RhaOMe; D-RhaOMeN; D-RhaOP; D-RhaOS; D-RibHex; D- RibHexNAc; D-Sor; D-ThrHexA4en; D-ThrHexAN4en; D-ThrHexfNAc2en; D-ThrPen; D- Thre-ol; DDAltHep; DDAltHepOMe; DDGalHep; DDGalHepOMe; DDGlcHep; DDManHep; DDManHepGroPA; DDManHepOBut; DDManHepOEtn; DDManHepOMe; DDManHepOP; DDManHepOPEtn; DDManNonUloNAcOFoN-onic; DLAltNonUloNAc-onic; DLGalNonUloNAc-onic; DLGalNonUloNAcN; DLGalNonUloNAcN-onic; DLGlcHepOMe; DLHepGlcOMe; DLManHep; DLManHepOPEtn; Dha; Dig; DigCMe; DigOAc; DigOFo; DigOMe; Ery; Ery-L-GlcNonUloNAcOAcOMeSH-onic; Ery-ol; Ery-onic; EryHex; EryHex2en; EryHexA3en; EryOMe-onic; Fru; Fruf; FrufF; FrufI; FrufN; FrufNAc; FrufOAc; FrufOAcOBzOCoum; FrufOAcOFer; FrufOBzOCin; FrufOBzOCoum; FrufOBzOFer; FrufOFer; FrufOLau; Fuc; Fuc-ol; FucN; FucNAc; FucNAcA; FucNAcGroP; FucNAcN; FucNAcNMe; FucNAcOAc; FucNAcOMe; FucNAla; FucNAm; FucNBut; FucNFo; FucNProp; FucNThrAc; FucOAc; FucOAcNAm; FucOAcNBut; FucOAcOMe; FucOAcOSOMe; FucOMe; FucOMeOPam; FucOMeOVac; FucOP; FucOPOMe; FucOS; FucOSOMe; Fucf; Gal; Gal-ol; Gal6Ulo; GalA; GalA-ol; GalAAla; GalAAlaLys; GalAGroN; GalALys; GalAN; GalANCys; GalANCysAc; GalANSerAc; GalAOLac; GalAOPyr; GalASer; GalAThr; GalAThrAc; GalCl; GalF; GalGro; GalGroN; GalGroP; GalN; GalNAc; GalNAc-ol; GalNAc-onic; GalNAcA; GalNAcAAla; GalNAcAN; GalNAcASer; GalNAcGro; GalNAcGroP; GalNAcGroPAN; GalNAcN; GalNAcOAc; GalNAcOAcA; GalNAcOAcAN; GalNAcOAcGroP; GalNAcOAcOMeA; GalNAcOAcOP; GalNAcOMe; GalNAcOP;GalNAcOPCho; GalNAcOPEtn; GalNAcOPyr; GalNAcOS; GalNAla; GalNAmA; GalNCysGly; GalNFoA; GalNFoAN; GalNOPCho; GalNSuc; GalNonUloNAc-onic; GalOAc; GalOAcA; GalOAcAGroN; GalOAcAOLac; GalOAcAThr; GalOAcGroP; GalOAcN; GalOAcNAla; GalOAcNAmA; GalOAcNFoA; GalOAcNFoAN; GalOAcOFoA; GalOAcOMe; GalOAcOP; GalOAcOPyr; GalOFoAN; GalOFoNAN; GalOLac; GalOLac-ol; GalOMe; GalOMeA; GalOMeCl; GalOMeF; GalOMeNAla; GalOP; GalOPA; GalOPAEtn; GalOPAN; GalOPCho; GalOPEtn; GalOPEtnA; GalOPEtnN; GalOPy; GalOPyr; GalOS; GalOSA; GalOSOEt; GalOSOMeA; GalOctUloNAc-onic; Galf; GalfGro; GalfGroP; Gal IN Ac: GalfOAc; GalfOAcGro; GalfOAcGroP; GalfOAcOLac; GalfOLac; GalfOMe; GalfOP; GalfOPCho; GalfOPyr; Gl; Glc; Glc-ol; Glc6Ulo; GlcA; GlcAAla; GlcAAlaLys; GlcAGlu; GlcAGly; GlcAGro; GlcAGroN; GlcALys; GlcAN; GlcAOLac; GlcAOPy; GlcAOPyr; GlcASer; GlcAThr; GlcAThrAc; GlcCho; GlcF; GlcGro; GlcGroA; GlcGroP; GlcGroPA; GlcI; GlcN; GlcN-ol; GlcNAc; GlcNAc-ol; GlcNAcA; GlcNAcAAla; GlcNAcAN; GlcNAcANAla; GlcNAcANAlaAc; GlcNAcANAlaFo; GlcNAcAla; GlcNAcCl; GlcNAcGlu; GlcNAcGly; GlcNAcGro; GlcNAcGroP; GlcNAcGroPA; GlcNAcI; GlcNAcN; GlcNAcN-ol; GlcNAcNAla; GlcNAcNAlaFo; GlcNAcNAmA; GlcNAcNButA; GlcNAcOAc; GlcNAcOAcA; GlcNAcOAcN; GlcNAcOAcNAla; GlcNAcOAcOCmOOle; GlcNAcOAcOCmOPam; GlcNAcOAcOCmOVac; GlcNAcOAcOLac; GlcNAcOAcOOle; GlcNAcOAcOPam; GlcNAcOAcOPyr; GlcNAcOAcOS-ol; GlcNAcOAcOVac; GlcNAcOGc; GlcNAcOLac; GlcNAcOLacAla; GlcNAcOLacGro; GlcNAcOMe; GlcNAcOMeA; GlcNAcOP; GlcNAcOPCho; GlcNAcOPEtg; GlcNAcOPEtn; GlcNAcOPOAch; GlcNAcOPyr; GlcNAcOS; GlcNAcOS-ol; GlcNAcOSA; GlcNAm; GlcNAmA; GlcNBut; GlcNButAN; GlcNButOAc; GlcNCmOCm; GlcNCmOCmOOle; GlcNCmOCmOVac; GlcNCmOVac; GlcNGc; GlcNGly; GlcNMe; GlcNMeOCm; GlcNMeOCmOPam; GlcNMeOCmOSte; GlcNMeOCmOVac; GlcNMeOSte; GlcNMeOVac; GlcNN; GlcNOAep; GlcNOCmOAch; GlcNOCmOVac; GlcNOMar; GlcNOMe; GlcNOMyr; GlcNOOle; GlcNOPam; GlcNOPyr; GlcNOSte; GlcNOVac; GlcNS; GlcNSOS; GlcNSOSOMe; GlcNSuc; GlcOAc; GlcOAcA; GlcOAcGro; GlcOAcGroA; GlcOAcGroP; GlcOAcN; GlcOAcNBut; GlcOAcNCmOOle; GlcOAcNCmOPam; GlcOAcNCmOVac; GlcOAcNMeOCm; GlcOAcNMeOCmOVac; GlcOAcNMeOVac; GlcOAcNOCmOVac; GlcOAcNOOle; GlcOAcNOPam; GlcOAcNOVac; GlcOAcOCoum; GlcOAcOFer; GlcOAcOOle; GlcOAcOP; GlcOAcOPam; GlcOAcOS; GlcOAcOSA; GlcOAcOSte; GlcOButA; GlcOBz; GlcOCoum; GlcOEt; GlcOEtn; GlcOEtnA; GlcOEtnN; GlcOFer; GlcOFoN; GlcOGc; GlcOLac; GlcOMal; GlcOMe; GlcOMe-ol; GlcOMeA; GlcOMeAN; GlcOMeN; GlcOMeNOMyr; GlcOMeOFoA; GlcOMeOPyr; GlcOOle; GlcOP; GlcOP-ol; GlcOPA; GlcOPCho; GlcOPChoGro; GlcOPEtn; GlcOPEtnGro;GlcOPEtnN; GlcOPGroP; GlcOPN; GlcOPNOMyr; GlcOPNOPam; GlcOPOOle; GlcOPPEtn; GlcOPPEtnN; GlcOPam; GlcOPyr; GlcOS; GlcOSA; GlcOSN; GlcOSNMeOCm; GlcOSOEt; GlcOSOMe; GlcOSOMeA; GlcOSin; GlcS; GlcSH; GlcThr; Glcf; Gro; Gro-ol; Gul; GulAN; GulNAcA; GulNAcAN; GulNAcNAmA; GulNAcOAcA; Hep; HepOP; HepOPEtn; HepOPPEtn; Hex; HexA; HexN; HexNAc; HexOMeOFo; Hexf; Ido; IdoA; IdoN; IdoNAc; IdoOAcA; IdoOAcOSA; IdoOMeA; IdoOS; IdoOSA; IdoOSOEtA; IdoOSOMeA; Kdn; KdnOAc; KdnOMe; KdnOPyr; Kdo; Kdo-ol; KdoGroP; KdoN; KdoOAc; KdoOAcOS; KdoOMe; KdoOP; KdoOPEtn; KdoOPN; KdoOPOEtn; KdoOPOPEtn; KdoOPPEtn; KdoOPPEtnN; KdoOPyr; KdoOS; Kdof; Ko; KoOMe; KoOPEtn; L-4dEryHexAN4en; L- 4dThrHex4en; L-4dThrHexA4en; L-4dThrHexA4enAla; L-4dThrHexAN4en; L-4dThre-ol; L- 6dAraHex; L-6dAraHexOMe; L-6dGalHep; L-6dGalHepOP; L-6dGulHep; L-6dGulHepOMe; L-6dGulHepOP; L-6dXylHexNAc4Ulo; L-Aco; L-AcoOMe; L-AcoOMeOFo; L-BoiOMe; L- Cym; L-CymOAc; L-DigOMe; L-Ery; L-EryCMeOH; L-EryHexA4en; L-Fru; L-Fruf; L-Gal; L-GalAN; L-GalNAc; L-GalNAc-onic; L-GalNAcA; L-GalNAcAN; L-GalNAcOAcA; L- GalNAmA; L-GalOAcNAmA; L-GalOS; L-Glc; L-GlcA; L-GlcNAc; L-GlcOMe; L-Gro-onic; L-GroHexUlo; L-Gul; L-Gul-onic; L-GulA; L-GulAN; L-GulHep; L-GulNAc; L-GulNAcA; L- GulNAcAGly; L-GulNAcAN; L-GulNAcANEtn; L-GulNAcNAmA; L-GulNAcNEtnA; L- GulNAcOAc; L-GulNAcOAcA; L-GulNAcOAcAN; L-GulNAcOEtA; L-GulNAcOEtnA; L- GulOAcA; L-Lyx; L-LyxHex; L-LyxHexNMe; L-LyxHexOMe; L-Man; L-ManOMe; L- ManOctUlo-onic; L-Ole; L-OleOAc; L-Oli; L-OliOMe; L-Qui; L-QuiN; L-QuiNAc; L- QuiNAcOMe; L-QuiNAcOP; L-QuiOMeN; L-RibHex; L-Ribf; L-Tal; L-The; L-TheOAc; L- Thr; L-ThrHexA4en; L-ThrHexAN4en; L-ThrHexOMe4en; L-ThrHexOMeA4en; L- ThrHexOSA4en; L-Xyl; L-XylHex; L-XylOMe; LDGalHep; LDGalNonUloNAc-onic; LDGlcHep; LDIdoHep; LDIdoHepPro; LDManHep; LDManHepGroN; LDManHepGroPA; LDManHepOAc; LDManHepOCm; LDManHepOEtn; LDManHepOMe; LDManHepOP; LDManHepOPEtn; LDManHepOPEtnOEtn; LDManHepOPOCm; LDManHepOPOMe; LDManHepOPOPEtn; LDManHepOPOPPEtn; LDManHepOPPEtn;LDManHepOPPEtnOPyrP; LDManHepOPyrP; LDManNonUloNAcOFoN-onic; LDManNonUloOFoNN-onic; LLManNonUloOFoN-onic; Leg; Leg5Ac7Ac; LegNAc; LegNAcAla; LegNAcNAla; LegNAcNAm; LegNAcNBut; LegNFo; Lyx; LyxHex; LyxHexOMe; LyxOMe; LyxOctUlo-onic; Lyxf; Man; Man-ol; ManA; ManCMe; ManF; ManGroP; ManN; ManNAc; ManNAcA; ManNAcAAla; ManNAcAGro; ManNAcAN; ManNAcANOOm; ManNAcASer; ManNAcAThr; ManNAcGroA; ManNAcGroP; ManNAcGroPA; ManNAcNAmA; ManNAcNEtnA; ManNAcOAc; ManNAcOAcA; ManNAcOLac; ManNAcOMe; ManNAcOMeAN; ManNAcOPEtn; ManNAcOPyr; ManNBut;ManNGroP; ManNonUloNAc-onic; ManOAc; ManOAcA; ManOAcN; ManOAcOMe; ManOAcOPyr; ManOAep; ManOBut; ManOEtn; ManOLac; ManOMe; ManOMeA; ManOP; ManOP -ol; ManOPCho; ManOPEtn; ManOPOMe; ManOPOPyr-ol; ManOPy; ManOPyr; ManOS; ManOctUlo; ManSH; Manf; Mur; MurNAc; MurNAcAla; MurNAcOP; MurNAcSer; Neu; Neu5Ac; Neu5AcN; Neu5AcNAc; Neu5AcNMe; Neu5AcOAc; Neu5AcOAcOMe; Neu5AcOGc; Neu5AcOMe; Neu5AcOS; Neu5Gc; Neu5GcA; Neu5GcN; Neu5GcOMe; Neu5GcOS; NeuOFo; NeuOMe; OLac; Ole; Oli; OliN; OliNAc; OliOMe; Par; Parf; PerNAc; Pse; Pse5Ac7Ac; Pse5Ac7AcNBut; Pse5Ac7AcOBut; PseNAc; PseNAcNAm; PseNAcNBut; PseNAcNFo; PseNAcNGro; PseNAcOAcNBut; PseNAcOBut; PseNButNFo; PseNGcNAm; PseOAc; PseOAcOFo; PseOFo; Qui; QuiN; QuiNAc; QuiNAc-ol; QuiNAcGro; QuiNAcGroP; QuiNAcN; QuiNAcNAlaAc; QuiNAcNAm; QuiNAcNAspAc; QuiNAcNBut; QuiNAcNButGro; QuiNAcNGroA; QuiNAcOAc; QuiNAcOBut; QuiNAcOMe; QuiNAcOP; QuiNAla; QuiNAlaAc; QuiNAlaAcGro; QuiNAlaBut; QuiNAlaButGro; QuiNAspAc; QuiNBut; QuiNButAla; QuiNButOMe; QuiNFo; QuiNGlyAc; QuiNHse; QuiNHseGro; QuiNLac; QuiNMal; QuiNSerAc; QuiNThrAc; QuiOMe; QuiOMeN; QuiOS; QuiOSN; QuiOSNBut; Rha; Rha-ol; RhaCMe; RhaCl; RhaGro; RhaGroA; RhaGroP; RhaNAc; RhaNAcNBut; RhaNAcNFo; RhaNAcOAc; RhaNPro; RhaOAc; RhaOAcOLac; RhaOAcOMe; RhaOBut; RhaOFer; RhaOLac; RhaOMe; RhaOMeCMeNLac; RhaOMeCMeOFo; RhaOP; RhaOPEtn; RhaOPOMe; RhaOProp; RhaOPyr; RhaOS; Rhaf; Rib; Rib-ol; RibGroP-ol; RibOAc; RibOAcOP-ol; RibOP-ol; RibOPEtn-ol; RibOPGroP-ol; Ribf; Ribf-uronic; RibfOAc; Sed; Sedf; Sor; Sorf; Sue; Sug; SugOAc; Tag; Tai; The; Thr; Thre-ol; Thre-onic; Tyv; VioNAc; Xluf; XlufOMe; Xyl; Xyl-ol; Xyl-onic; XylHex; XylHexNAc; XylHexUlo; XylHexUloN; XylHexUloNAc; XylNAc; XylNMe; XylOAc; XylOBz; XylOMe; XylOP; XylOS; Xylf; Yer; YerOAc; a-Tri-ol; a-Tri-onic; aldehyde-2,5-Anhydro-L-Man; aldehyde-2,5-Anhydro-Tal; aldehyde-Gro; aldehyde-Hex; aldehyde-L-Gro; aldehyde-L-GroN; aldehyde-QuiNAc; aldehyde-Rib; aldehyde-a-Tri-ol; aldehyde-b-Tri-ol; b-Tri-N-ol; b-Tri-OP-ol; b-Tri-ol; b-Tri- onic; bl-4Glc; cNeu5Ac; b) and from monomers listed in FIG.6,7 and the like, and chemical derivatives thereof; c) deoxysugars of (a) , (b) (Deoxyribose, Rhamnose, Fuculose, Fucose, and the like); d) uronic acids of (a), (b), (c) - (glucuronic acid, iduronic acid, etc), which may be methoxylated, ethoxylated or acetylated; e) (a), (b), (c), (d) in which a hydroxyl group has been replaced with an amine group - amino sugars (galactosamine, glucosamine, sialic acid, N-acetylglucosamine, N-acetylgalactosamine,N-acetylneuraminic acid and the like (more then 60 aminosugars)); f) sulfonic acid derivatives of (a), (b), (c), (d), (e) - sulfosugars (O-, N- sulfated, and the like); g) acetyl; Anhydro, D-alanyl; N-acetyl-D-alanyl; N-acetimidoyl; N-(N-methyl-acetimidoyl); N- (N,N-dimethyl-acetimidoyl); formyl; glycolyl; N-acetyl-glutaminyl; N-methyl-5-glutamyl; glycyl; glyceryl; 2,3-di-O-methyl-glyceryl; 4-hydroxybutyryl; 3,4-dihydroxybutyryl; (R)-3- hydroxybutyryl; (S)-3 -hydroxybutyryl; lactyl; methyl; amino; N-acetyl; phosphate; pyruvyl; 1- carboxyethylidene; sulfate; tauryl; Me; Et; Pr; Bu; Pe; Hx; Hp; Oc; Nn; Dec; Und; Dod; Acyl; RCO-; Fo (or HCO); Ac; Gc; Pp; Br (Butyryl); VI (valeryl); Hxo; Hpo; Oco; Nno; Deo; Udo; Lau; Myr; Pam; Ste; eSte; Lin; D4Ach; ; Gro; Gra; Gm; Gri; Ose; Glcd; Gal; Fuc; GlcA; GlcUe; GlcN; GlcNAc; Neu; Sia; Mur; NeuAcg; NeuGc; Cer; Cho; Etnh; Ins; Ser; Ptd; Sph; Spd; P (Phosphoric residue) derivatives of (a), (b), (c), (d), (e), (f); h) (a), (b), (c), (d), (e), (f), (g) salts (gum, gummi, and the like); i) compounds of formula:and structural isomers, anomers thereof; and stereoisomers thereof; and the like; wherein R1-R5 is H, halogen, F, Cl, Br, I, OH, Me, Et, Ac, OMe, OEt, OAc, ORA, N(RA)2,N3, CN, NO2, S(O)ZRA, (Ci-Ci5)alkyl, (C4-C8)carbocyclylalkyl, (Ci-C8)substituted alkyl, (C2- C8)alkenyl, (C2-C8)substituted alkenyl, (C2-C8)alkynyl, (C2-C8)substituted alkynyl, — )SRA, — S(O)RA, — S(O)2RA, —aryl(Ci-C8)alkyl, — PO(OH)2, — PO(OH)OPO(OH)2— PO(OH)OPO(OH)O PO(OH)2, — PO(ORA)2, — PORARB, phenyl, 1- naphthyl, 2-naphthyl, benzyl, (C3-C6)cycloalkyl, — CH2— (C3-C6)cycloalkyl, — O — ( Ci-Cs) alkyl, — O-benzyl, cycloalkyl, CF3, C(halogen)3, — C(=Q)RA, — C(=Q)ORA, — C(= —+N(RA)3, — SRA, — S(O)RA, — S(O)2RA, — S(O)(ORA), — S(O) — OC(=Q)ORA, — OC(=Q)(N(RA)2), — SC(=Q)RA, — SC(=Q)ORA, — N(RA)C(=Q)RA, — N(RA)C(=Q)ORA, —N(RA)C(=Q)N(RA)2N3, — NO2, — ORA, NRARB, N(RA)ORB, NRANRB, N3, NO, NO2, CHO, CN, — CH(=NRA) — CH=NNHRA, — CH=N(ORA), — CH(ORA)2, — C(=O)NRBRA, — C(=S)NRBRA, — C(=O)ORA, (C6-C2o)optionally substituted aryl, optionally substituted heteroaryl, — C(=O)(Ci-C8)alkyl, — S(O)z(Ci-C8)alkyl, SRA, or selected from radicals obtained by removal of a hydrogen atom from the compounds shown in FIG.8; wherein Q is O, S, NRA,+N(O)(RA), N(ORA),+N(O)(ORA), or N— NRA2; wherein RA, RBis H, halogen, F, Cl, Br, I, OH, Et, Me, Ac, ORC, N(RC)2,N3, CN, NO2, S(O)ZRC, (Ci-Ci5)alkyl, (C4-C8)carbocyclylalkyl, (Ci-C8)substituted alkyl, (C2-C8)alkenyl, (C2-C8)substituted alkenyl, (C2-C8)alkynyl, (C2-C8)substituted alkynyl, — C(=O)Rc, — C(=O)ORC, — C(=O)NRCRC, — C(=O)SRc, — S(O)RC, — S(O)2RC, — S(O)(ORC), — S(O)2(ORC), — SO2NRCRC, (C6-C2o)aryl(Ci-C8)alkyl, — PO(OH)2, — PO(OH)OPO(OH)2,— PO(OH)OPO(OH)OPO(OH)2, — PO(ORC)2, — PORCRC, phenyl, 1 -naphthyl, 2-naphthyl, benzyl, (C3-C6)cycloalkyl, — CH2— (C3-C6)cycloalkyl, — O — ( Ci-Cs) alkyl, — O-benzyl, — O— CH2— (C3-C6)cycloalkyl, CF3, C(halogen)3, — C(O) Rc, — C(O)ORC, — C(O)N(RC), —NRCRC, —+N(RC)3, — SRC, — S(0) Rc, — S(O)2RC, — S(O)(ORC), — S(O)2(ORC), — 0C(0) Rc, — OC(O)ORC, — OC(O)(N(RC)2), — SC(=Q)RC, — SC(=Q)ORC, — SC(=Q)(N(RC)2), — N(Rc)C(=Q)Rc, — N(Rc)C(=Q)ORc, — N(Rc)C(=Q)N(Rc)2, — SO2NRC2, — CN — N3, — N02, — ORC, NRCRC, N(RC)ORC, NRCNRC, N3, NO, NO2, CHO, CN, — CH(=NRC) CH=NNHRC, — CH=N(ORc), — CH(ORC)2, — C(=O)NRCRC, — C(=S)NRCRC, — C(=O)ORC, (C6-C2o)optionally substituted aryl, optionally substituted heteroaryl, — C(=O)(Ci-C8)alkyl, — S(O)z(Ci-C8)alkyl, or SRC; wherein Rcis H, OH, F, Cl, Br, I, Me, Et, Ac, OMe, OEt, or OAc, or selected from radicals obtained by removal of a hydrogen atom from the compounds shown in FIG. 8; wherein z is from 1 to 10; and structural isomers thereof; and stereoisomers thereof; and the like;D2) Conjugates of (DI) bound (O-, N-, P-, C-, S-linked, and the like) to any Protein, Peptide, Low molecular weight compound, Lipid, Aptamer, Antibody, Affibody, Avimer, or Nanobody, etc., that may include, but are not limited to:Glycated derivatives (O-, N-, P-, C-, S-linked); glycoconjugates, glycoproteins (O-, N-, P-, C-, S-linked), neoglycoproteins, glycolipids, glycopeptides, proteoglycans, peptidoglycans, glycosides, lipopolysaccharides, and mixtures thereof; and wherein bonds may be covalent bonds, al-1, al-2, al-3, al-4, al-5, al-6, al-7, al-8, a2-l, a2-2, a2-3, a2-4, a2-5, a2-6, a2-7, a2-8, a2-9, a6-6, pi-1, 1-2, 01-3, 01-4, 01-5, 01-6, 01-7, 01-8, 01-9, 02-1, 02-2, 02-3, 02-4, 02-5, 02-6, 02-7, 02-8, 03-3, al-2, and the like, aq- w, 0q-w, wherein q and w are independently from 1 to 9;E) wherein [HOST]nis[X]nwherein X is selected from:wherein R describedF) Conjugates of (A)-(E) bound (O-, N-, P-, C-, S-linked, and the like) to any Protein, Peptide, Low molecular weight compound, Lipid, Aptamer, Antibody, Affibody, Avimer, or Nanobody, etc., that may include, but are not limited to:Glycated derivatives (O-, N-, P-, C-, S-linked), glycoconjugates, glycoproteins (O-, N-, P-, C- , S-linked), neoglycoproteins, glycolipids, glycopeptides, proteoglycans, peptidoglycans, glycosides, lipopolysaccharides, and mixtures thereof; and wherein bonds may be covalent bonds, al-1, al-2, al-3, al-4, al-5, al-6, al-7, al-8, a2-l, a2-2, a2-3, a2-4, a2-5, a2-6, a2-7, a2-8, a2-9, a6-6, pi-1, 1-2, 01-3, 01-4, 01-5, 01-6, 01-7, 01-8, 01-9, 02-1, 02-2, 02-3, 02-4, 02-5, 02-6, 02-7, 02-8, 03-3, al-2, and the like, aq-w, Pq-w, wherein q and w are independently from 1 to 9;G) Polymers and oligomers, copolymers, biopolymers (natural, obtained by chemical or physical modification of natural polymers (chemical or physical derivatives), or synthesized specifically), or their Conjugates (like in (F)) that under at least one of the following conditions:

1. co-occurring in physiologic body fluids, plasma, intercellular fluid together with APIs;2. by non-covalent binding to API;3. by covalent binding to API into a conjugate; result in at least one of the following: a. an increase in the permeability of the API, API-carrier system (solution, non-covalent complex, conjugate, and the like); b. an increase in the concentration of API, API-carrier system in cells and tissues; for at least one of the following reasons: i. inhibition or modulation of multidrug resistance (MDR), predominantly mediated by efflux transporters of the ATP-binding cassette (ABC) superfamily including P-glycoprotein (P-gp); ii. induction, inhibition or modulation of CYP1, CYP2, CYP3 enzymes (non limiting examples: CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4 enzymes); iii. due to a change in the structure of the cell membrane, change in lipid biolayer properties after the incorporation of carrier substance molecules (or carrier molecular part of NCC or conjugate) into this membrane or due adhesion to this membrane; iv. due to changes in charge, hydrophilicity, hydrophobicity or other biophysical properties of the non-covalent complex, or conjugate due to which changes in the transmembrane (passive, active) or paracellular transport of the non-covalent complex, or conjugates;2. The methods and the complex of claim 1 wherein GUEST is(i.e. GUEST is Albendazole); c)(i.e. GUEST is Triclabendazole); d)(i.e. GUEST is Mebendazole);(i.e. GUEST is Quercetin);(i.e. GUEST is Curcumin);But excluding combinations with cyclodextrins in the treatment of cancer (at a dosage of approximately 20 to 400 micrograms per kilogram), but not excluded in the treatment of non- cancerous diseases.

3. The methods and the complex of claim 1 or 2 wherein carrier for non-covalent active pharmaceutical ingredient-carrier complex is selected from (satisfies at least one of):A. Polymers and oligomers, predominantly organic polymers and oligomers, predominantly watersoluble organic polymers and oligomers, natural polymers and oligomers, biopolymers and biooligomers even more predominantly polysaccharides, homopolysaccharides, heteropolysaccharides, oligosaccharides, glycoconjugates, glycoproteins (O-, N-, P-, C-, S- linked), neoglycoproteins, glycolipids, glycopeptides, proteoglycans, peptidoglycans, glycolipids, glycosides, lipopolysaccharides, hemicelluloses, storage polysaccharides, sulfated polysaccharides and oligosaccharides, pectins, gums, mucilages, which may be (but are not exclusive to):A. l. Polyelectrolites and non-polyelectrolites;A.

2. Polymers and oligomers, which can be obtained from animal, nonanimal, natural (i.e., microbiologicalor plant) sources: a) from plants, higher plants (non-limiting examples): Starch; Cellulose; Guar gum; Gum arable; Locust beanvgum; Pectin ; Acacia gum ; Gum arabic ; Arabinogalactan ; Costus glucans ; Xylan ; Glucomannan ; Xyloglucan ; Inulin ; beta-glucan ; Guar gum ; Karaya gum ; Tara gum ; Fenugreek gum ; Locust bean gum; Tragacanth gum ; Cassia tor a gum; and the like; b) from mushrooms (non-limiting examples): Polysaccharide-K (Krestin, PSK), beta-glucans, Polysaccharide peptide (PSP); and the like; c) from Algae (non-limiting examples): Alginates; Galactans; Carrageenan; Alginate ; Agar ; Carrageenan ; Fucoidan; Ulvan ; Laminarin; Angelan ; Porphyran ; Spirulan ; Agarose ; Rhodymenan; and the like; d) from animal origin (non-limiting examples): Glycosaminoglycans(GAGs); Hyaluronic acid; Glycogen; Hyaluronan ; Chitin; Chitosan; Heparin; Chondroitin sulphate; Keratan sulphate; Dermatan sulphate; Asialofetuin; fetuin; and the like; e) from microbial origin (non-limiting examples): Dextran; Gellan gum; Pullulan; Xanthan gum; Curdlan; Scleroglucan; Pullulan; Dextran; Xanthan; Levan; Gellan; Emulsan; Schizophyllan; Glucuronan; Succinoglycan; Nigcran ;and the like;A.

3. Hemicelluloses, which can be arabanes, arabinans, galactans (galactosans), glucans, xylans, mannans, fructans, xyloglucans, arabinogalactans, arabinoxylans, glucomannans, galactomannans, galactoglucomannans, beta-glucans, galactogens, and the like, their mixtures, but not excluding other hemicelluloses, and mixtures thereof;A.

4. Sulfated polysaccharides and oligosaccharides which may be fucoidans, carrageenans or carrageenins, agaropectins, sea cucumber sulfated polysaccharides (SCSP), chondroitin sulfate, keratan sulfate, and the like, their mixtures, but not excluding other sulfated polysaccharides and oligosaccharides, and mixtures thereof;A.

5. Oligosaccharides, fructooligosaccharides, galactooligosaccharides (oligogalactosyllactose, oligogalactose, oligolactose, transgalactooligosaccharides), xylooligosaccharides, isomaltooligosaccharides and the like, but not excluding other oligosaccharides and mixtures thereof;A.

6. Polysaccharides and oligosaccharides, storage polysaccharides, sulfated polysaccharides and oligosaccharides, pectins, gums, mucilages which may be (but are not exclusive to others): polyuronic acids and esters; gum(s), gum arabic, xanthan gum, oat gum, gellan gum, guar gum, carob gum, karaya gum,dammar gum, gummiarabica, tara gum, ghatti gum, british gum, agar, agar-agar, tragakant gum, conjac gum, velan gum, dutan gum; galacturonic acid-based polysaccharides with side chains of rhamnose, arabinose, xylose and fructose and their salts (pectins, pectates, pectinates); pectin, pectins of beets, carrots, peppers, pumpkins, eggplant, sunflower, apples, quinces, cherries, plums, pears, citrus, zosterin; modified pectins, modified citrus pectin; acidic polysaccharides - i.e. e. polysaccharides containing carboxyl groups and / or phosphate groups and / or sulfuric ester groups; plantain husk, psyllium; soybean hemicellulose; galacturones, homogalacturones, polygalacturonic acids and their salts, rhamnogalacturonan, rhamnogalactans; calloses, laminarins, chrysolaminarins, curdlans; inulins, guars, dextrans, pullulans; agaroses; alginic acid and its salts alginates, propylene glycol alginate; arabin, arabic acid and its salts, and the like, but not excluding other, and mixtures thereof;A.

7. Cellulose, cellulosic polymers, methylcellulose, ethylcellulose, hydroxypropylcellulose(s) (HPC), hydroxypropylmethylcellulose acetate succinate, hypromellose(s), hydroxypropylmethylcellulose(s) (HPMC), methylethylcellulose, ethylhydroxyethylcellulose, croscaramellose, carboxymethylcellulose and its salts; starch, starch(es), starch 1500G, soluble starch, modified starches, hydroxyethyl starch, cationic starch, acid-treated starch, alkaline modified starch, bleached starch, oxidized starch, enzyme treated starch, monostarch phosphate, distarch glycerol, distarch phosphate, phosphated distarch phosphate, acetylated distarch phosphate, starch acetate esterified with acetic anhydride, starch acetate esterified with vinyl acetate, acetylated distarch adipate, acetylated distarch glycerol, distarch glycerine, hydroxy propyl starch, hydroxy propyl distarch glycerine, hydroxy propyl distarch phosphate, hydroxy propyl distarch glycerol, starch sodium octenyl succinate, acetylated oxidised starch, and the like;A.

8. Dextrin(s), maltodextrins, amylodextrins, poly dextroses; amylopectin, amylose, glycogen;chitosan, chitins;pullulans, glucuronoaraboxylans, methyl-glucuronoaraboxylans, glycosaminoglycans, mucopolysaccharides, heparin / heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, hyaluronan, hyaluronic acid, and the like; and mixtures thereof;A.

9. Glycated derivatives of these polymers and oligomers (O-, N-, P-, C-, S-linked); but not excluding other polymers and oligomers, biopolymers and biooligomers even more predominantly polysaccharides, homopolysaccharides, heteropolysaccharides, oligosaccharides, glycoconjugates, glycoproteins (O-, N-, P-, C-, S- linked), neoglycoproteins, glycolipids, glycopeptides, proteoglycans, peptidoglycans, glycolipids, glycosides, lipopolysaccharides, hemicelluloses, storage polysaccharides, sulfated polysaccharides and oligosaccharides, pectins, gums, mucilagesand mixtures thereof;B. Polymers, syntetic polymers, predominantly water-soluble polymers which may be (but are not limited to):polymers and copolymers formed from acrylic acid, methacrylic acid, and / or esters thereof;polymethacrylates, Eudragit and their salts; polyacrylamides; poly(amidoamine)s, poly(propyleneimine)s, polyethylene glycols; polyvinyl alcohol; polyvinylpyrrolidone; acrylic polymers, cellulose acetate phthalate(s), copovidone(s), ethyl oleate, glycerol derivatives, glyceryl triacetate, polyethylene glycol(s) (PEG), PEG derivatives, polymethacrylates, propylene glycol, propylene glycol derivatives, povidone(s), polyvinylpyrrolidone(s) (PVP), polyvinyl acetate phthalate(s) (PVAP), hypromellose acetate succinate(s) (HPMCAS), hydroxypropyl methylcellulose acetate succinate (HPMCAS), hypromellose phthalate(s) (HPMCP), cellulose butyrate phthalate, cellulose hydrogen phthalate, cellulose proprionate phthalate, polyvinyl acetate phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate, dioxypropyl methylcellulose succinate, carboxymethyl ethylcellulose, hydroxypropyl methylcellulose acetate succinate, Avicel(s), Avicel PH101, Avicel PH102, Benecel(s), Brij(s), Brij 30, Brij 35, Capryol(s), Cavamax(s), Cavasol(s) and Cavitron(s) HPpCD cyclodextrins, Compritol 888 ATO, Cremophor(s), Cremophor EL, Cremophor REMO, DiCai Dihydrate, epoxidized palm oil (Epo), Eudragit(s), Eudragit E, Eudragit EPO, Eudragit L100, Eudragit LI GO- 55, Eudragit S100, Gelucire(s), Gelucire 44 / 14, HP-50 AAS- LF, HP-55 AAS-MF, HPMC(p-606), HPMC-E, HPMC-F, HPMC-K, HPMCAS-H, HPMCAS-L, HPMCAS-M, HPMCAS SDD, HPMCAS(AS-MG), HPMCAS-M SDDs, HPMCAS-MG, HPMCP (HP 55), HPMCP-HP55, HPMCPh, hypromellose phthalate HP- 50, Imwitor(s), Imwitor 742, Klucel HPC, Kolhdon 17 PF, Kollicoat(s), Kollicoat IR, Kollicoat MAE, Kollicoat MAE 100, Kollicoat MAE 100P , Kollicoat Protect, Kollidon(s) (povidone(s)), Kollidon 12 pf, Kolhdon 12 / 17PF, Kollidon 30, Kolhdon 30 / 90, Kolhdon 90, Kolhdon CL-F, Kollidon CL-SF, Kollidon K30, Kolhdon SR, Kollidon SR, Kolhdon SR(PVAc), Kolhdon V64 / Fine, Kollidon VA 64, Kolhdon VA 64 (copovidone), Kolhdon VA64, Kolliphor(s), Kolliphor EL, Kolliphor EL / ELP, Kolliphor HS15, Kolliphor P 188, Kolliphor P 188 / 407, Kolliphor P 188 / micro, Kolliphor P 407 , Kolliphor P 407 / micro, Kolliphor PS 20, Kolliphor PS 60, Kolliphor PS 80, Kolliphor RH 40, Kolliphor SLS, Kolliphor SLS / fine, Kollisolv(s), Kollisolv GTA, Kollisolv PEG 1450, Kollisolv PEG 300, Kollisolv PEG 3350, Kollisolv PEG 400, Kollisolv PEG E 300, Kollisolv PEG E 400, Kollisolv PEG grades (polyethylene glycol), Kolliwax(s), Kolliwax GMS II, Kolliwax SA, Labrasol(s), Lactose 310 Mono, Lactose FF316, Laurogucol(s), Maisine(s), Miglyol(s), Myrj(s), Myrj 52, PEG 1000, PEG 10000, PEG 1500, PEG 2000, PEG 20000, PEG 3000, PEG 400, PEG 4000, PEG 600, PEG 6000, PEG 800 , PEG 8000 , Pharmacoat(s), PVP K-12 , PVP K-120 , PVP K-15, PVP K-17, PVP K-30, PVP K-60, PVP K-90, PVP SDD, PVP VA64 SDDs, PVP-VA, PVP- VA 64, PVP-VA SDD, Palm stearin based polyesteramide (PSPEA), Peceol(s), pectin(s), Plasdone(s), Plasdone K povidone, Plasdone K- 12 povidone, Plasdone K-29 / 32 povidone, Plasdone K-90 povidone, Plasdone S, Plasdone S-630 copovidone, poly(2-ethyl-2-oxazoline), poly(ethylene oxide) (PEG) (3400, 10000, 20000), polyoxyethylene stearate, Shin- Etsu AQOAT(s), Soluplus(es), Solutol(s), sucrose laurate, tocopheryl PEG 1000-succinate (TPGS), vitamin E TPGS, d-a-tocopherol polyethylene glycol 1000 succinate (TPGS), Isomalt (Galen IQ 810), galactosylated Polymers; galactosylated ciclodextrins; cationic glycopolymers; block and statistical carbohydrate-basedgalactosylated copolymers; galactosylated albumin(s), galactosylated bovine serum albumin; Statistical Cationic Glycopolymer of 2-aminoethyl methacrylamide (AEMA) and 2-lactobionamidoethyl methacrylamide (LAEMA) P(AEMA n -st- LAEMA m) (m,n from 1 to 1000); Cationic Block Glycopolymer of 2-aminoethyl methacrylamide (AEMA) and 2-lactobionamidoethyl methacrylamide; p-Vinylbenzyl galactoside (VBG); galactosylated N-3-guanidinopropyl methacrylamide-co-poly (ethylene glycol) methacrylate copolymers; galactosylated amphiphilic graft copolymer (PHEA-g-BIB-pButMA-g-PEG-GAL); (cholesteryloxycarbonylamino) ethylamine-a,P-polyasparthydrazied (CHE-PAHy-Lacs); PLGA- di-GAL; and the like, and others which are described in the scientific and patent literature (for example: Macro-Glycoligands. Methods and Protocols, Editors: Xue-Long Sun); and the like; but not excluding other synthetic polymers and mixtures thereof;C. Copolymers is made from monomers of the polymers listed in paragraph A, B including alternating copolymers, random copolymers, block copolymers, graft copolymers, cross-linked modifications which may be (but are not limited to): methacrylic acid and ethyl acrylate copolymers; methacrylic acid copolymers; vinylpyrrolidone-vinyl acetate copolymers (PVPVA); polyvinylpolypyrrolidone (PVPP); PVA-PEG graft copolymers; HPMC and PVA-PEG grafted copolymers; polyvinylpyrrolidone-arabinogalactan copolymers; grafted polyvinylpyrrolidone- arabinogalactan copolymers; the graft copolymer has a) poly(vinyl acetate) and / or poly (vinyl alcohol) and / or poly(vinyl chloride) and poly(vinyl ester) on b) a polymer chain of polyethylene glycols, polyalkylene glycols, polypropylene glycols, polyisobutylene glycols orpolymethylpentene glycols; graft copolymer polyvinyl acetate and / or hydrolysed polyvinyl acetate (polyvinyl alcohol) groups on a polyalkylene oxide (preferably polyethylene oxide); vinylpyrrolidone-vinyl acetate copolymers; vinylpyrrolidone-vinyl acetate copolymer-64+; vinylpyrrolidone-vinyl acetate VA 64; polymethacrylate-based copolymers includes anionic, cationic, and neutral copolymers based on methacrylic acid and methacrylic / acrylic esters their salts, esters or other derivatives and mixtures thereofand the like;D. Polymers and oligomers, copolymers, biopolymers (natural, obtained by chemical or physical modification of natural polymers (chemical or physical derivatives), or synthesized specifically) that under at least one of the following conditions:

1. co-occurring in physiologic body fluids, plasma, intercellular fluid together with APIs;2. by non-covalent binding to API;3. by covalent binding to API into a conjugate; result in at least one of the following: a. an increase in the permeability of the API, API-carrier system (solution, non-covalent complex, conjugate, and the like);b. an increase in the concentration of API, API-carrier system in cells and tissues; for at least one of the following reasons: i. inhibition or modulation of multidrug resistance (MDR), predominantly mediated by efflux transporters of the ATP-binding cassette (ABC) superfamily including P-glycoprotein (P-gp); ii. induction, inhibition or modulation of CYP1, CYP2, CYP3 enzymes (non limiting examples: CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4 enzymes); iii. due to a change in the structure of the cell membrane, change in lipid biolayer properties after the incorporation of carrier substance molecules (or carrier molecular part of NCC or conjugate) into this membrane or due adhesion to this membrane; iv. due to changes in charge, hydrophilicity, hydrophobicity or other biophysical properties of the non-covalent complex, or conjugate due to which changes in the transmembrane (passive, active) or paracellular transport of the non-covalent complex, or conjugates; for other reasons e.g., by the introduction or presence in the carrier of targeted fragments capable of selectively interacting with the receptor, cell surface receptors, membrane receptors, transmembrane receptors, etc. Such targeted fragments may include, but are not limited to, Proteins, Peptides, Low molecular weight compounds, Lipids, Aptamers, Antibodies, Affibodies, Avimers, Nanobodies, or any other targeted fragments, which are used as vector molecules and are described in patent or scientific literature; or for other reasons disclosed in patent or scientific literature;E. Other carriers:EL Macrocyclic hosts which may be (but are not exclusive to others): cyclodextrins, cucurbit[n]urils, and calix[n] arenes, pillarenes, crown ethers, cyclophanes, cryptands;E2. Acids and salts based on these acids which may be (but are not limited to): citric acid, tartaric acid, succinic acid, phosphoric acid, aminoacids, acetate(s), sodium acetate, alginate(s), sodium alginate, glycyrrhizic acid and their salts, and mixtures thereof;8E3. Polyols which may be (but are not limited to): ethylene glycol, glycerol, erythritol, threitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, iditol, inositol, volemitol, isomalt, maltitol, lactitol, maltotriitol, maltotetraitol, polyglycitol, and mixtures thereof;E4. Monosaccharides, disaccharides, trisaccharides, tetrasaccharides, pentaccharides, hectaccharides and the like mixtures thereof;E5. Surfactants which may be (but are not limited to): anionic surfactants contained anionic functional groups at their head, such as sulfate, sulfonate, phosphate, carboxylates, carboxylate salts; alkyl sulfates; alkyl-ether sulfates; carboxylate-based fluorosurfactants; cationic surfactants; primary, secondary, ortertiary amines; permanently charged quaternary ammonium salts; zwitterionic (amphoteric) surfactants; zwitterionic surfactants which cationic part is based on primary, secondary, or tertiary amines or quaternary ammonium cations; sultaines; betaines; phospholipids; zwitterionic surfactants of the tertiary amine oxides structural type; non-ionic surfactants; ethoxylates; fatty alcohol ethoxylates; alkylphenol ethoxylates (apes or apeos); fatty acid ethoxylates; special ethoxylated fatty esters and oils; ethoxylated amines and / or fatty acid amides; terminally blocked ethoxylates; fatty acid esters of polyhydroxy compounds; fatty acid esters of glycerol; fatty acid esters of sorbitol; fatty acid esters of sucrose; alkyl polyglucosides; ammonium lauryl sulfate; sodium lauryl sulfate; sodium dodecyl sulfate; sodium laureth sulfate; sodium lauryl ether sulfate; sodium myreth sulfate; docusate (dioctyl sodium sulfosuccinate) and their salts; perfluorooctanesulfonate (pfos); perfluorobutanesulfonate; alkyl-aryl ether phosphates; alkyl ether phosphates; sodium stearate; sodium lauroyl sarcosinate; perfluorononanoate; perfluorooctanoate; octenidine dihydrochloride; cetrimonium bromide (ctab); cetylpyridinium chloride (cpc); benzalkonium chloride (bac); benzethonium chloride (bzt); dimethyldioctadecylammonium chloride; dioctadecyldimethylammonium bromide (dodab); chaps (3-[(3-cholamidopropyl)dimethylammonio]-l- propanesulfonate); cocamidopropyl hydroxysultaine; cocamidopropyl betaine; phosphatidylserine; phosphatidylethanolamine; phosphatidylcholine; sphingomyelins; lauryldimethylamine oxide; myristamine oxide; narrow-range ethoxylates; octaethylene glycol monododecyl ether; pentaethylene glycol monododecyl ether; nonoxynols; triton x-100; polyethoxylated tallow amine; cocamide monoethanolamine; cocamide diethanolamine; poloxamers; glycerol monostearate; glycerol monolaurate; sorbitan monolaurate; sorbitan monostearate; sorbitan tristearate; tween(s), tween 20; tween 40; tween 60; tween 80; decyl glucoside; span(s), span 20, span 40, span 80; lauryl glucoside; octyl glucoside; poloxamer(s), poloxamer 188, poloxamer 407, polyoxyethylene stearate, myrj 52, deoxycholic acid, bile acids, pluronic(s), pluronic F-127, pluronic P85, pluronic f68, gelucire(s), gelucire 44 / 14, lecithins, polysorbates, polysorbate 80, plasdone-s630, pluronic-f68, inutec spl, compritol 888 ato, tocopherol polyethylene glycol succinate, polyoxyethylated castor oil, polyoxyethylated glycerides, lauroyl macroglycerides, and mono- and di-fatty acid esters of low molecular weight polyethylene glycols; and mixtures thereof;F. Methoxylated, ethoxylated, esterificated, carboxylated, alkoxylated, acetylated, hydroxylated, hydrated, decarboxylated, amide, oxidized, sulfated, aminoacid derivatives, fermented, thermally modified, chemically modified, acid modified derivatives of the substances specified in A-E, and their esters, salts, and any other chemical derivatives, and mixtures thereof or / and which are described in the scientific and patent literature; Alternatively, dextran or poly-L-lysine can be attached to the gum arabic carrier to provide an increased number of sites of attachment for the therapeutic agent.G. Conjugates of (A)-(F) bound (O-, N-, P-, C-, S-linked, and the like) to any Protein, Peptide, Lowmolecular weight compound, Lipid, Aptamer, Antibody, Affibody, Avimer, or Nanobody, etc., that may include, but are not limited to:Glycated derivatives (O-, N-, P-, C-, S-linked), glycoconjugates, glycoproteins (O-, N-, P-, C-, S- linked), neoglycoproteins, glycolipids, glycopeptides, proteoglycans, peptidoglycans, glycosides, lipopolysaccharides, and mixtures thereof; and wherein bonds may be covalent bonds, al-1, al-2, al-3, al-4, al-5, al-6, al-7, al-8, a2-l, a2-2, a2-3, a2-4, a2-5, a2-6, a2-7, a2-8, a2-9, a6-6, pi-1 , 1-2, 01-3, 01-4, 01-5, 01-6, 01-7, 01-8, 01-9, 02-1, 02-2, 02-3, 02-4, 02-5, 02-6, 02-7, 02-8, 03-3, al-2, and the like, aq-w, 0q-w, wherein q and w are independently from 1 to 9;E. Any combination of substances specified in items A-G.

4. The methods and the complex of claims 1-3 when non-covalent complex when dissolved in a physiologically acceptable solvent other than water.

5. The methods and the complex of claims 1-4 when the non-covalent complex is selected from inclusion complexes, including partial inclusion complexes, and supramole cular complexes.

6. The methods (co-treating methods / solid dispersion techniques) for modifying the properties of an active pharmaceutical ingredient (API) by creating a solid phase inclusion complex or molecular / solid dispersion(both of Formula II) using API, host substance (and, if necessary, other compounds) with properties of increased bioavailabilify and / or permeability and using Formula II compounds obtained by this methods (or aqueous solutions or suspensions thereof) to treat a cancer in humans and / or to manufacture a pharmaceutical dosage form to treat cancer in a human in need thereof (by administering a therapeutically effective amount)), at a dosage ranging from 0.0001 ng / kg to 100000 mg / kg (calculated for pure API) wherein active pharmaceutical ingredient is selected from:Milbemycins; Milbemycin A3; Milbemycin A4; Milbemycin D; Milbemycin B2; Milbemycin B3; Milbemycin G; Nemadectins; Nemadectin; Meilingmycins; Meilingmycin A; Milbemectins; Milbemectin; Milbemycin oxime; Moxidectins; Moxidectin; Doramectins; Doramectin; Selamectins; Selamectin; Eprinomectins; Eprinomectin Bia; Eprinomectin Bib; Emamectins; Emamectin Bia; Emamectin Bib; Tenvermectins; Tenvermectin B; Tenvermectin A; Avermectins; Avermectin Ala; Avermectin Alb; Avermectin A2a; Avermectin A2b; Avermectin Bia; Avermectin Bib; Avermectin B2a; Avermectin B2b; Ivermectins; Ivermectin Bia; Ivermectin Bib; Ivermectin Ala; Ivermectin Alb; Fenbendazole; Flubendazole; Thiabendazole; Oxfendazole; Triclabendazole; Mebendazole; Oxyclozanide; Niclosamide;Nitazoxanide; Colchicine; Artemisinin; Quercetin; Curcumin; Resveratrol; thymoquinone; Pyrvinium;Albendazole sulfoxide; Albendazole; or compounds selected from those listed in from FIG. 12 to FIG.72; or compoundsor derivatives thereof such as racemate, enantiomer, diastereomer, tautomer, polymorph, pseudopolymorph, hydride or solvate thereof; or a pharmaceutically acceptable salt or ester or ether thereof; or prodrug thereof; or methabolite thereof; or aglycone thereof; or derivatives which may be obtained by gene replacement processes in genetically engineered strains, or / and by fermentation, or / and by chemical modifications and the like, which are described in the scientific and patent literature;or mixtures thereof; wherein the host substance is selected from:A. Polymers and oligomers, predominantly organic polymers and oligomers, even more predominantly polysaccharides and oligosaccharides, hemicelluloses, storage polysaccharides, sulfated polysaccharides and oligosaccharides, pectins, gums, mucilages, which may be (but are not exclusive to):A. l. Hemicelluloses, which can be arabanes, arabinans, galactans (galactosans), glucans, xylans, mannans, fructans, xyloglucans, arabinogalactans, arabinoxylans, glucomannans, galactomannans, galactoglucomannans, beta-glucans, galactogens, their mixtures, but not excluding other hemicelluloses, and mixtures thereof;A.

2. Sulfated polysaccharides and oligosaccharides which may be fucoidans, carrageenans or carrageenins, agaropectins, sea cucumber sulfated polysaccharides (SCSP), chondroitin sulfate, keratan sulfate, their mixtures, but not excluding other sulfated polysaccharides and oligosaccharides, and mixtures thereof;A.

3. Polysaccharides and oligosaccharides, storage polysaccharides, sulfated polysaccharides and oligosaccharides, pectins, gums, mucilages which may be (but are not exclusive to others): polysaccharides based on glucose, dextrose, galactose, mannose, arabinose, rhamnose, sucrose, maltose, lactose and their uronic acids, which may be methoxylated or acetylated, and their salts (gum, gummi); polyuronic acids and esters; gum, xanthan gum, oat gum, gellan gum, guar gum, carob gum, karaya gum, dammar gum, gummiarabica, tara gum, ghatti gum, british gum, agar, agar-agar, fragakant gum, conjac gum, velan gum, dutan gum; galacturonic acid-based polysaccharides with side chains of rhamnose, arabinose, xylose and fructose and their salts (pectins, pectates, pectinates); pectin, pectins of beets, carrots, peppers, pumpkins, eggplant, sunflower, apples, quinces, cherries, plums, pears, citrus, zosterin; modified pectins, modified citrus pectin; acidic polysaccharides - i.e. e. polysaccharides containing carboxyl groups, phosphate groups and / or sulfuric ester groups; plantain husk, psyllium; soybean hemicellulose;galacturones, homogalacturones, polygalacturonic acids and their salts, rhamnogalacturonan, rhamnogalactans; calloses, laminarins, chrysolaminarins, curdlans; inulins, guars, dextrans, pullulans; agaroses, galacto-oligosaccharides (oligogalactosyllactose, oligogalactose, oligolactose or transgalactooligosaccharides), xylooligosaccharides, fructooligosaccharides, isomaltooligosaccharide; alginic acid and its salts alginates, propylene glycol alginate; arabin, arabic acid and its salts; cellulose, cellulosic polymers, methylcellulose, ethylcellulose, hydroxypropylcellulose(s) (HPC), hydroxypropylmethylcellulose acetate succinate, hypromellose(s), hydroxypropylmethylcellulose(s), (HPMC), methylethylcellulose, ethylhydroxyethylcellulose, croscaramellose, carboxymethylcellulose and its salts; starch, starch(es), starch 1500G, soluble starch, modified starches, hydroxyethyl starch, cationic starch, acid-treated starch, alkaline modified starch, bleached starch, oxidized starch, enzyme treated starch, monostarch phosphate, distarch glycerol, distarch phosphate, phosphated distarch phosphate, acetylated distarch phosphate, starch acetate esterified with acetic anhydride, starch acetate esterified with vinyl acetate, acetylated distarch adipate, acetylated distarch glycerol, distarch glycerine, hydroxy propyl starch, hydroxy propyl distarch glycerine, hydroxy propyl distarch phosphate, hydroxy propyl distarch glycerol, starch sodium octenyl succinate, acetylated oxidised starch; dextrin(s), maltodextrins, cyclodextrins, amylodextrins, polydextroses; amylopectin, amylose, glycogen;chitosan, chitins;pullulans, glucuronoaraboxylans, methyl- glucuronoaraboxylans, glycosaminoglycans, mucopolysaccharides, heparin / heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, hyaluronan, hyaluronic acid and mixtures thereof, but not excluding other polysaccharides and oligosaccharides, hemicelluloses, stored polysaccharides, sulfated polysaccharides and oligosaccharides, mucilages and mixtures thereof;A.

4. Macrocyclic hosts which may be (but are not exclusive to others): cyclodextrins, cucurbit[n]urils, and calix[n] arenes, pillarenes, crown ethers, cyclophanes, cryptands;B. Substances that may contain in significant amounts (more than 5% wt.) polysaccharides and oligosaccharides, hemicelluloses, storage polysaccharides, sulfated polysaccharides and oligosaccharides, pectins, gums, mucilages, which may be (but are not limited to) plants or algae or animal or fungi, parts of plants or algae or animal or fungi, processed plants or algae or animal or fungi, processed parts of plants or algae or animal or fungi containing in significant amounts the substances specified in paragraph A, and mixtures thereof. A frequent but non-limiting example is dried brown or red algae such as kelp or focus;C. Syntetic polymers, predominantly water-soluble polymers which may be (but are not limited to):polymers and copolymers formed from acrylic acid, methacrylic acid, and / or esters thereof; polymethacrylates, Eudragit and their salts; polyacrylamides; poly(amidoamine)s,poly (propyleneimine) s, polyethylene glycols; polyvinyl alcohol; polyvinylpyrrolidone; acrylic polymers, cellulose acetate phthalate(s), copovidone(s), ethyl oleate, glycerol derivatives, glyceryl triacetate, polyethylene glycol(s) (PEG), PEG derivatives, polymethacrylates, propylene glycol, propylene glycol derivatives, povidone(s), polyvinylpyrrolidone(s) (PVP), polyvinyl acetate phthalate(s) (PVAP), hypromellose acetate succinate(s) (HPMCAS), hydroxypropyl methylcellulose acetate succinate (HPMCAS), hypromellose phthalate(s) (HPMCP), cellulose butyrate phthalate, cellulose hydrogen phthalate, cellulose proprionate phthalate, polyvinyl acetate phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate, dioxypropyl methylcellulose succinate, carboxymethyl ethylcellulose, hydroxypropyl methylcellulose acetate succinate, Avicel(s), Avicel PH 101, Avicel PH102, Benecel(s), Brij(s), Brij 30, Brij 35, Capryol(s), Cavamax(s), Cavasol(s) and Cavitron(s) HPpCD cyclodextrins, Compritol 888 ATO, Cremophor(s), Cremophor EL, Cremophor RH40, DiCai Dihydrate, epoxidized palm oil (Epo), Eudragit(s), Eudragit E, Eudragit EPO, Eudragit LI 00, Eudragit L 100-55, Eudragit S100, Gelucire(s), Gelucire 44 / 14, HP-50 AAS-LF, HP-55 AAS-MF, HPMC(p- 606), HPMC-E, HPMC-F, HPMC-K, HPMCAS-H, HPMCAS-L, HPMCAS-M, HPMCAS SDD, HPMCAS(AS-MG), HPMCAS-M SDDs, HPMCAS-MG, HPMCP (HP 55), HPMCP-HP55, HPMCPh, hypromellose phthalate HP-50, Imwitor(s), Imwitor 742, Klucel HPC, Kolhdon 17 PF, Kollicoat(s), Kollicoat IR, Kollicoat MAE, Kollicoat MAE 100, Kollicoat MAE 100P , Kollicoat Protect, Kollidon(s) (povidone(s)), Kolhdon 12 pf, Kolhdon 12 / 17PF, Kollidon 30, Kolhdon 30 / 90, Kolhdon 90, Kollidon CL-F, Kolhdon CL-SF, Kollidon K30, Kolhdon SR, Kolhdon SR, Kolhdon SR(PVAc), Kolhdon V64 / Fine, Kolhdon VA 64, Kolhdon VA 64 (copovidone), Kollidon VA64, Kolliphor(s), Kolliphor EL, Kolliphor EL / ELP, Kolliphor HS15, Kolliphor P 188, Kolliphor P 188 / 407, Kolliphor P 188 / micro, Kolliphor P 407 , Kolliphor P 407 / micro, Kolliphor PS 20, Kolliphor PS 60, Kolliphor PS 80, Kolliphor RH 40, Kolliphor SLS, Kolliphor SLS / fine, Kollisolv(s), Kollisolv GTA, Kollisolv PEG 1450, Kollisolv PEG 300, Kollisolv PEG 3350, Kollisolv PEG 400, Kollisolv PEG E 300, Kollisolv PEG E 400, Kollisolv PEG grades (polyethylene glycol), Kolliwax(s), Kolliwax GMS II, Kolliwax SA, Labrasol(s), Lactose 310 Mono, Lactose FF316, Laurogucol(s), Maisine(s), Miglyol(s), Myrj(s), Myrj 52, PEG 1000, PEG 10000, PEG 1500, PEG 2000, PEG 20000, PEG 3000, PEG 400, PEG 4000, PEG 600, PEG 6000, PEG 800 , PEG 8000 , Pharmacoat(s), PVP K-12 , PVP K- 120 , PVP K-15, PVP K-17, PVP K-30, PVP K-60, PVP K-90, PVP SDD, PVP VA64 SDDs, PVP- VA, PVP-VA 64, PVP-VA SDD, Palm stearin based polyesteramide (PSPEA), Peceol(s), pectin(s), Plasdone(s), Plasdone K povidone, Plasdone K-12 povidone, Plasdone K-29 / 32 povidone, Plasdone K- 90 povidone, Plasdone S, Plasdone S-630 copovidone, poly(2-ethyl-2-oxazoline), polyethylene oxide) (PEG) (3400, 10000, 20000), polyoxyethylene stearate, Shin-Etsu AQOAT(s), Soluplus(es), Solutol(s), sucrose laurate, tocopheryl PEG 1000-succinate (TPGS), vitamin E TPGS, d-a-tocopherol polyethylene glycol 1000 succinate (TPGS), Isomalt (Galen IQ 810), but not excluding other syntheticpolymers and mixtures thereof;D. Polyols which may be (but are not limited to): ethylene glycol, glycerol, erythritol, threitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, iditol, inositol, volemitol, isomalt, maltitol, lactitol, maltotriitol, maltotetraitol, polyglycitol, and mixtures thereof;E. Saccharides which may be glucose, dextrose, galactose, mannose, arabinose, rhamnose, sucrose, maltose, lactose, ribose, and mixtures thereof;F. Surfactants which may be (but are not limited to): anionic surfactants contained anionic functional groups at their head, such as sulfate, sulfonate, phosphate, carboxylates, carboxylate salts; alkyl sulfates; alkyl-ether sulfates; carboxylate-based fluorosurfactants; cationic surfactants; primary, secondary, or tertiary amines; permanently charged quaternary ammonium salts; zwitterionic (amphoteric) surfactants; zwitterionic surfactants which cationic part is based on primary, secondary, or tertiary amines or quaternary ammonium cations; sultaines; betaines; phospholipids; zwitterionic surfactants of the tertiary amine oxides structural type; non-ionic surfactants; ethoxylates; fatty alcohol ethoxylates; alkylphenol ethoxylates (apes or apeos); fatty acid ethoxylates; special ethoxylated fatty esters and oils; ethoxylated amines and / or fatty acid amides; terminally blocked ethoxylates; fatty acid esters of polyhydroxy compounds; fatty acid esters of glycerol; fatty acid esters of sorbitol; fatty acid esters of sucrose; alkyl polyglucosides; ammonium lauryl sulfate; sodium lauryl sulfate; sodium dodecyl sulfate; sodium laureth sulfate; sodium lauryl ether sulfate; sodium myreth sulfate; docusate (dioctyl sodium sulfosuccinate) and their salts; perfluorooctanesulfonate (pfos); perfluorobutanesulfonate; alkyl-aryl ether phosphates; alkyl ether phosphates; sodium stearate; sodium lauroyl sarcosinate; perfluorononanoate; perfluorooctanoate; octenidine dihydrochloride; cetrimonium bromide (ctab); cetylpyridinium chloride (cpc); benzalkonium chloride (bac); benzethonium chloride (bzt); dimethyldioctadecylammonium chloride; dioctadecyldimethylammonium bromide (dodab); chaps (3-[(3-cholamidopropyl)dimethylammonio]-l-propanesulfonate); cocamidopropyl hydroxysultaine; cocamidopropyl betaine; phosphatidylserine; phosphatidylethanolamine; phosphatidylcholine; sphingomyelins; lauryldimethylamine oxide; myristamine oxide; narrow-range ethoxylates; octaethylene glycol monododecyl ether; pentaethylene glycol monododecyl ether; nonoxynols; triton x-100; polyethoxylated tallow amine; cocamide monoethanolamine; cocamide diethanolamine; poloxamers; glycerol monostearate; glycerol monolaurate; sorbitan monolaurate; sorbitan monostearate; sorbitan tristearate; tween(s), tween 20; tween 40; tween 60; tween 80; decyl glucoside; span(s), span 20, span 40, span 80; lauryl glucoside; octyl glucoside; poloxamer(s), poloxamer 188, poloxamer 407, polyoxyethylene stearate, myrj 52, deoxycholic acid, bile acids, pluronic(s), pluronic F-127, pluronic P85, pluronic f68, gelucire(s), gelucire 44 / 14, lecithins, polysorbates, polysorbate 80, plasdone-s630, pluronic-f68, inutec spl, compritol 888 ato, tocopherolpolyethylene glycol succinate, polyoxyethylated castor oil, polyoxyethylated glycerides, lauroyl macroglycerides, and mono- and di-fatty acid esters of low molecular weight polyethylene glycols; and mixtures thereof;G. Acids and salts based on these acids which may be (but are not limited to): citric acid, tartaric acid, succinic acid, phosphoric acid, aminoacids, acetate(s), sodium acetate, alginate(s), sodium alginate, glycyrrhizic acid and their salts, and mixtures thereof;H. Oxides and salts based on these oxides which may be (but are not limited to): silicon dioxide, silicates, titanium dioxide, and mixtures thereof;I. Copolymers of the polymers listed in paragraph A, C including alternating copolymers, random copolymers, block copolymers, graft copolymers, cross-linked modifications which may be (but are not limited to): methacrylic acid and ethyl acrylate copolymers; methacrylic acid copolymers; vinylpyrrolidone-vinyl acetate copolymers (PVPVA); polyvinylpolypyrrolidone (PVPP); PVA-PEG graft co-polymers; HPMC and PVA-PEG grafted copolymers; grafted polyvinylpyrrolidone- arabinogalactan copolymers; the graft copolymer has a) poly(vinyl acetate) and / or poly (vinyl alcohol) and / or poly(vinyl chloride) and poly(vinyl ester) on b) a polymer chain of polyethylene glycols, polyalkylene glycols, polypropylene glycols, polyisobutylene glycols orpolymeth- ylpentene glycols; graft copolymer polyvinyl acetate and / or hydrolysed polyvinyl acetate (polyvinyl alcohol) groups on a polyalkylene oxide (preferably polyethylene oxide); vinylpyrrolidone-vinyl acetate copolymers; vinylpyrrolidone-vinyl acetate copolymer-64+; vinylpyrrolidone -vinyl acetate VA 64; polymethacrylate -based copolymers includes anionic, cationic, and neutral copolymers based on methacrylic acid and methacrylic / acrylic esters their salts, esters or other derivatives and mixtures thereof;J. Gamers listedK. Methoxylated, ethoxylated, esterificated, carboxylated, alkoxylated, acetylated, hydroxylated, hydrated, decarboxylated, amide, oxidized, sulfated, aminoacid derivatives, fermented, thermally modified, chemically modified, acid modified derivatives of the substances specified in A-J, and their esters, salts, and any other chemical derivatives, and mixtures thereof;L. Polymers and oligomers, copolymers, biopolymers (natural, obtained by chemical or physical modification of natural polymers (chemical or physical derivatives), or synthesized specifically) that under at least one of the following conditions:

1. co-occurring in physiologic body fluids, plasma, intercellular fluid together with APIs;2. by non-covalent binding to API;3. by covalent binding to API into a conjugate; result in at least one of the following: a. an increase in the permeability of the API, API-carrier system (solution, non-covalent complex, conjugate, and the like); b. an increase in the concentration of API, API-carrier system in cells and tissues; for at least one of the following reasons: i. inhibition or modulation of multidrug resistance (MDR), predominantly mediated by efflux transporters of the ATP-binding cassette (ABC) superfamily including P-glycoprotein (P-gp); ii. induction, inhibition or modulation of CYP1, CYP2, CYP3 enzymes (non limiting examples: CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4 enzymes); iii. due to a change in the structure of the cell membrane, change in lipid biolayer properties after the incorporation of carrier substance molecules (or carrier molecular part of NCC or conjugate) into this membrane or due adhesion to this membrane; iv. due to changes in charge, hydrophilicity, hydrophobicity or other biophysical properties of the non-covalent complex, or conjugate due to which changes in the transmembrane (passive, active) or paracellular transport of the non-covalent complex, or conjugates;M. Conjugates of (A)-(K) bound (O-, N-, P-, C-, S-linked, and the like) to any Protein, Peptide, Low molecular weight compound, Lipid, Aptamer, Antibody, Affibody, Avimer, or Nanobody, etc., that may include, but are not limited to:Glycated derivatives (O-, N-, P-, C-, S-linked), glycoconjugates, glycoproteins (O-, N-, P-, C- , S-linked), neoglycoproteins, glycolipids, glycopeptides, proteoglycans, peptidoglycans, glycosides, lipopolysaccharides, and mixtures thereof; and wherein bonds may be covalent bonds, al-1, al-2, al-3, al-4, al-5, al-6, al-7, al-8, a2- 1, a2-2, a2-3, a2-4, a2-5, a2-6, a2-7, a2-8, a2-9, a6-6, pi-1, 1-2, 01-3, 01-4, 01-5, 01-6, 01- 7, 01-8, 01-9, 02-1, 02-2, 02-3, 02-4, 02-5, 02-6, 02-7, 02-8, 03-3, al-2, and the like, aq-w, 0q-w, wherein q and w are independently from 1 to 9;N. Any combination of substances specified in items A-M; wherein co-treating method (solid dispersion preparation method) is selected from:a) grinding / milling with high energy stress method; b) grinding / milling with high energy stress and solvent method; c) media milling method; d) kneading method; e) hot-melt method / melting method / fusion method; f) hot-melt extrusion / hot-stage extrusion method; g) meltrex method; h) melt agglomeration method; i) high-pressure homogenization method; j) solvent evaporation method; k) spin-coated films method; electrostatic spinning, electrostatic blowing, electrospraying film casting; l) spray -drying method; m) supercritical fluid (SCF) process method; n) cryogenic techniques method; o) lyophilization / freeze-drying technique method; p) spray freezing onto cryogenic fluids method; q) spray freezing into cryogenic liquids (SFL) method; r) spray freezing into vapor over liquid (SFV / L) method; s) ultra-rapid freezing method; t) precipitation / co-precipitation method; u) microwave irradiation method; v) energy input method; w) heat / shear energy input method; x) gel entrapment technique; y) a method comprising: contacting an active pharmaceutical ingredient and a matrix “host substance” to form a solid dispersion under conditions sufficient to form a solid dispersion; z) combined method.

7. The methods of claims 1-6 when instead of non-covalent complex, solid phase inclusion complex or molecular / solid dispersion or conjugate (of Formula III) are administered and obtained by the methods and techniques described in this invention (i.e., when instead of API being used AAPI or AANPI) and in the patent and scientific literature.

8. The methods of claims 1-7 when the non-covalent complex, molecular / solid dispersion or conjugate is combined with at least one additional active pharmaceutical ingredient (AAPI) active (in vitro, in vivo, exvivo, in silico) against cancer and selected from: 5 -Fluorouracil; Abarelix; Abiraterone; Acetaminophen; Acetaminophen or paracetamol; Acetazolamide; Actiq; Adcretris; Adriamycin RDF; Afinitor; Agomelatine; Agrylin; Albendazole; Aldara; Aldesleukin; Alemtuzumab; Alfuzosin; Alimta; Aliskiren; Alitretinoin; Alkeran; All-trans retinoic acid or tretinoin; Allopurinol; Aloxi; Alpha-Lipoic Acid; Altretamine; Amantadine; Amifostine; Amiloride; Aminoglutethimide; Aminolevulinic Acid; Amiodarone; Amitriptyline; Amlodipine; Amodiaquine; Amsacrine; Anagrelide; Anakinra; Anastrozole; Anexsia; Anzemet; Aprepitant; Aprotinin; Arava; Aredia; Arginine; Arimidex; Aripiprazole; Aromasin; Arranon; Arsenic Trioxide; Artesunate; Arzerra; Asparaginase Erwinia Chrysanthemi; Aspirin; Atenolol; Atorvastatin; Atovaquone; Atrial Natriuretic Peptide; 7Bendamustine; Benserazide; Bepridil; Bevacizumab; Bexarotene; Bexxar; Bezafibrate; BiCNU; Bicalutamide; Biperiden; Blenoxane; Bleomycin; Bortezomib; Bosentan; Bosulif; Bosutinib; Brentuximab Vedotin; Bromfenac; Bromocriptine; Busulfan; Cabazitaxel; Cabergoline; Cabozantinib; Caffeine; Calcitriol; Campath; Camptosar; Candesartan; Capecitabine; Captopril; Carbimazole; Carboplatin; Carfilzomib; Carglumic acid; Carmustine; Carvedilol; Casodex; CeeNU; Celebrex; Celecoxib; Cephalexin; Cerubidine; Cetuximab; Chlorambucil; Chloroquine; Chlorpromazine; Cholecalciferol; Cidofovir; Cilnidipine; Cimetidine; Cinacalcet; Ciprofloxacine; Cisplatin; Citalopram; Cladribine; Clarithromycin; Clofarabine; Clofoctol; Clolar; Clomifene; Clomipramine; Clotrimazole; Colchicine; Cometriq; Conjugated Estrogens; Cosmegen; Crizotinib; Cyclophosphamide; Cytabarine; Cytadren; Cytarabine; Cytosar-U; Cytoxan; DES; DTIC-Dome; Dacarbazine; Dactinomycin; Dalteparin; Danazol; Dapsone; Dasatinib; Daunorubicin; Deferoxamine; Degarelix; Denosumab; Desmopressin; Diclofenac; Diethylstilbestrol; Diflunisal; Digitoxin; Digoxin; Dimethyl Fumarate; Dipyridamole; Disulfiram; Docetaxel; Dolasetron; Donepezil; Doxazosin; Doxorubicin; Doxycycline; Ebastine; Efavirenz; Eflomithine; Elitek; Ellence; Eloxatin; Emcyt; Emend; Enalapril; Enoxaparin; Enzalutamide; Epalrestat; Epirubicin; Erbitux; Eribulin; Erivedge; Erlotinib; Erwinaze; Esomeprazole; Estramustine; Ethacrynic acid; Ethyol; Etodolac; Etoposide; Eulexin; Everolimus; Evista; Exemestane; FOLFIRI; FOLFIRI- Bevacizumab; FOLFIRI-Cetuximab; FOLFIRINOX; FOLFOX; Famotidine; Fareston; Faslodex; Fasudil; Felodipine; Femara; Fenofibrate; Fentanyl; Fingolimob; Fish oil (EPA / DHA); Flubendazole; Fludara; Fludarabine; Fluorouracil; Fluoxetine; Fluspirilene; Flutamide; Fluvastatin; Fluvoxamine; Folinic Acid; Folotyn; Fulvestrant; Fusilev; Gardasil; Gefitinib; Gemcitabine; Gemtuzumab Ozogamicin; Gemzar; Gleevec; Glipizide; Glucarpidase; Glutamine; Goserelin; Granisetron; Griseofulvin; Halaven; Haloperidol; Herceptin; Hexalen; Hycamtin; Hydralazine; Hydrocodone; Hydroxychloroquine; Hymecromone; Ibandronate; Ibritumomab Tiuxetan; Ibuprofen; Iclusig; Idamycin; Idarubicin; Ifex; Ifosfamide; Imatinib; Imipramine; Imiquimod; Imuran; Indomethacin; Ingenol Mebutate; Inlyta; Interferon Alfa-2b; Intron A; lodixanol; Ipilimumab; Irbesartan; Iressa; Irinotecan; Irinotecan); Istodax; Itraconazole; Ixabepilone; Ixempra; Jakafi; Jevtana; Kadian; Kepivance; Ketoconazole; Ketorolac; Kyprolis; Kytril; Lanreotide; Lansoprazole; Lapatinib; Leflunomide; Letrozole; Leucovorin; Leukeran; Leukine; Leuprolide; Leustatin; Levetiracetam; Levofloxacin; Levulan; Licofelone; Lidocaine; Lithium; Lomustine; Loperamide; Loratadine; Losartan; Lovastatin; Loxoprofen; Lupon Depot; Lysodren; Macitentan; Manidipine;Maraviroc; Masoprocol; Matulane; Mebendazole; Mechlorethamine; Mechloroethamine; Meclofenamate; Mefloquine; Megace; Megestrol; Megestrol acetate; Melatonin; Meloxicam; Melphalan; Memantine; Mepacrine or Quinacrine; Mercaptopurine; Mesna; Metformin; Methazolamide; Methimazole; Methotrexate; Methoxsalen; Methyl Aminolevulinate; Methylnaltrexone; Methylprednisolone; Metoclopramide; Metvixia; Mifepristone; Minocycline; Mirtazapine; Mitomycin; Mitotane; Mitoxantrone; Montelukast; Morphine; Mozobil; Mutamycin; Mycophenolate; Mycophenolic Acid; Myfortic; Myleran; Mylotarg; Nadroparin; Naltrexone; Naproxen; Navelbine; Nelarabine; Nelfmavir; Neulasta; Neumega; Neutroval; Nexavar; Niclosamide; Nifedipine; Nifurtimox; Nilandron; Nilotinib; Nilutamide; Nimodipine; Nipent; Nisodilpine; Nitazoxanide; Nitisinone; Nitroglycerine; Nitroxoline; Nolvadex; Norethandrolone; Noscapine; Novantrone; Nplate; Octreotide; Ofatumumab; Olanzapine; Olsalazine; Omacetaxine; Omeprazole; Oncaspar; Oncovin; Ondansetron; Oprelvekin; Orlistat; Ormeloxifene; Oseltamivir; Ouabain; Oxaliplatin; Oxcarbazepine; Paclitaxel; Palifermin; Palonosetron; Pamidronate; Panitumumab; Pantoprazole; Paraplatin; Pazopanib; Pegaspargase; Pegfilgrastim; Peginterferon Alfa-2b; Pemetrexed; Penfluridol; Pentamidine; Pentostatin; Pentoxifylline; Perjeta; Perphenazine; Pertuzumab; Phentolamine; Phenylbutyrate; Phenytoin; Photofrin; Picato; Pimozide; Pioglitazone; Pipobroman; Pirfenidone; Platinol; Plenaxis; Plerixafor; Ponatinib; Porfimer; Pralatrexate; Pravastatin; Prazosin; Prednisone; Pregabalin; Premarin; Procarbazine; Progesterone; Prograf; Proleukin; Promethazine; Prometrium; Propranolol; Provenge; Purinethol; Pyrimethamine; Pyrvinium pamoate; Quadramet; Quadrivalent Human Papillomavirus Vaccine; Quetiapine; Rabeprazole; Raloxifene; Raltitrexed; Ranolazine; Rapamune; Rasburicase; Regorafenib; Repaglinide; Ribavirin; Rifabutin; Riluzole; Risperidone; Ritonavir; Rituxan; Rituximab; Roflumilast; Romidepsin; Romiplostim; Rosuvastatin; Ruxolitinib; Samarium Sm 153 Lexidronam; Sargramostim; SecreFlo; Secretin; Sensipar; Sertraline; Sildenafil; Simvastatin; Sipuleucel-T; Sirolimus; Sodium Bicarbonate; Sodium Oxybate; Sorafenib; Spironolactone; Sprycel; Stivarga; Streptozocin; Sulfasalazine; Sulindac; Sunitinib; Sutent; Sylatron; Synribo; Tacrolimus; Tadalafil; Tamoxifen; Tarceva; Targretin; Tasigna; Taxol; Taxotere; Telmisartan; Temodar; Temozolomide; Temsirolimus; Teniposide; Terbinafine; Tetrathiomolybdate; Thalidomide; Thalomid; Thiabendazole; Thioguanine; Thioridazine; Ticagrelor; Ticlopidine; Tigecycline; Timolol; Tinzaparin; Tolfenamic acid; Tomudex; Topiramate; Topotecan; Toremifene; Torisel; Tositumomab; Tranexamic acid; Trastuzumab; Trazodone; Treanda; Trelstar Depot; Triamterene; Trifluoperazine; Triptorelin; Trisenox; Tykerb; Ulinastatin; UroXatral; Urokinase; Uvadex; Valproic acid; Valrubicin; Valsartan; Valstar; Vandetanib; VePesid; Vectibix; Velban; Velcade; Vemurafenib; Verapamil; Vercyte; Vinblastine; Vincristine; Vindesine; Vinorelbine; Visipaque; Vismodegib; Voraxaze; Vorinostat; Votrient; Vumon; Warfarin; Xalkori; Xeloda; Xgeva; Xibrom; Xtandi; Yervoy; Zanosar; Zelboraf; Zevalin; Zofiran; Zoladex; Zoledronate; Zoledronic Acid; Zolinza; Zometa; Zytiga; tbo-Filgrastim,9. The methods of claims 1-8 when the non-covalent complex or molecular / solid dispersion or conjugate is combined with at least one additional active pharmaceutical ingredient (AAPI) selected from:A. inductor, inhibitor or modulator of P-glycoprotein / BCRP / MRP2 / MCT1 / SNAT2 / PEPT1 / ABC- transporters which are described in the scientific and patent literature, for example (non-limited examples): Curcumin, Demethoxycurcumin, Bisdemethoxycurcumin, and the like;B . inductor, inhibitor or modulator of CYP1, CYP2, CYP3 enzymes (non limiting examples: CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4 enzymes) which are described in the scientific and patent literature, for example (non-limited examples for CYP3A4): sulphaphenazole, quinidine, furafylline, troleandomycin (TAO) and diethyldithiocarbamate (DDC), and the like; c. dipole modifiers that are able to incorporate into lipid membranes and modify their physicochemical properties, phase segregation character, dipole potentialwhich are described in the scientific and patent literature, for example (non-limited examples): flavanoids,phloretin, floricin, biochanin A, myricetin, quercetin, taxifolin, genistin, genistein, daidzein, catechin, 2,4,6-trihydroxyacetophenone (THAP), floxin B and erythrosine, dihydroquercetin, and the like with or whithout vitamin C;D . Hepatoprotective agent which are described in the scientific and patent literature, for example (nonlimited examples): according to the different mechanism of action, it can be roughly divided into detoxification drugs (eg. N-acetylcysteine, S-adenosylmethionine and Glutathione), anti-inflammatory drugs (eg. Glycyrrhizic acid preparation, magnesium isoglycyrrhizinate), hepatocyte membrane protector (eg. Polyene phosphatidylcholine), antioxidant drugs (eg. Bicyclol, Silymarin), anticholestatic drug (Ursodeoxycholic acid, Cholestyramine), immunosuppressants (Glucocorticoids) and specific treatment agents (L- carnitine, Anticoagulants), and the like.

10. The methods of claims 1-9 when the non-covalent complex or molecular / solid dispersion or conjugateis combined with at least one additional active pharmaceutical ingredient (AAPI) selected from:A. autophagy inductor, inhibitor or modulatorwhich are described in the scientific and patent literature, for example (non-limited examples): lithium; carbamazepine; Rapamyrin; Temsirolimus; Everolimm; Oeforolimus; PP242; Torin 1; Metformin; 15132799; GDC-0980; 501-0941; Perifosine; Fluspirilene; CCE779; Pimozide; Trifluoperazine; Nicardipine; Lithium; L-690330; Carbamazepine; Xmtospongin B; Minoxidil; Clonidine; Verapamil; Loperamide; Amiodarone; Nimodipine; Nitrendipine; Rilmenidine; Bromperidol; Metergoline; Thioridazine; Chlorpromazine; Fludroconisone; Noscapine; Oemastine; Tat — beclin 1 peptide, and the like;B. apoptosis inductor, inhibitor or modulator which are described in the scientific and patent literature;C. autoptosis inductor, inhibitor or modulator which are described in the scientific and patent literature;D. ferroptosis inductor, inhibitor or modulator which are described in the scientific and patent literature;E. pyroptosis inductor, inhibitor or modulator which are described in the scientific and patent literature;F. cell reprogramming agent which are described in the scientific and patent literature;G. SCOT inductor, inhibitor or modulator which are described in the scientific and patent literature;H. senolitic agent which are described in the scientific and patent literature;I. inductor, inhibitor or modulator of ABCA1; ABCB1; AHR; AIFM1; AKR1C3; AKT1; ALOX12; ALOX5; ALPP; ANXA1; APAF1; AR; ATF2; ATF3; AURKB; BAD; BAK1; BAX; BBC3; BCL2; BCL2L1; BCL2L11; BCL2L2; BECN1; BID; BIRC2; BIRC3; birc5a; BNIP3; CALR; CASP12; CASP2; CASP3; CASP6; CASP7; CASP8; CASP9; CCNB1; CCND1; CCND2; CCND3; CCNE1; CD80; CDC25C; CDC42; CDH1; CDH2; CDK1; CDK2; CDK4; CDK6; CDK7; CDK9; CDKN1A; CDKN1B; CDKN1C; CDKN2B; CFLAR; CHEK-2; CHUK; COX-1; COX-2; CSN2; CTNNBIP1; CYC3B; CycA; CycB; CYCS; CYP19A1; CYP1A1; CYP1A2; CYP1B1; CYP2B6; CYP2C8; CYPIA1; DDIT3; DIABLO; Dox; DUSP10; E2F1; EBV-EA; EDN1; EGF; EGFR; EGR1; ENDOG; ERBB2; ERBB3; ERK1 / 2; ERP29; ESRI; FADD; Fas; FASLG; FGF2; FN1; FOS; FOXM1; GADD45A; GATA1; GATA2; GCLC; GGT1; GLI1; GPT; GPX1; GRB2; GSK3B; GSTM1; HBG1; HIF1A; HMBS; HNRNPA2B1; HSPA4; HSPA5; HSPB2; ICAM1; IFNG; IGF1; IGF1R; IGF2; IKBKB; IKBKE; IL1B; IL2 ; IL4; IL6; IL8; ITGA2; ITGAV; ITGB3; JAK1; JAK2; JUN; JUNB; KDR; KLK3; LDHB; LOX; LTA; LTA4H; MAP2; MAP2K1; MAP2K4; MAPK1; MAPK3; MAPK7; MAPK8; MCL1; MDM2; MMP1; MMP14; MMP15; MMP2; MMP3; MMP7; MMP9; MTOR; MYC; MYLK; NDUFS1; NFATC1; NFE2; NFKB1; NFKBIA; NOS2; NOXI; NQO1; NR1H3; ODC1; PARP1; PCNA; PDIA3; PHB; PIK3CA; PIM2; PLAU; PLCG1; PLK1; PMAIP1; POR; PPARG; PRKAB1; PRKACA; PRKCA; PRKCG; PROMI; Proteasome; PSMD9; PTCHI; PTGER3; PTK2; PTPN1; RAC1; RADU; RAFI; RAP1A; RBI; RELA; RHOA; RHOB; ROCK1; ROS1; RPS6KA3; RPS6KA5; RPS6KB1; SLC2A1; SNAI1; SOD1; S0S1; SP1; SP3; SP4; SPDEF; SRC; STAT3; STAT5B; SULT1A3; Telomerase; TFDP1; TFF1; TGFBR1; TGFBR2; TGFBR3; TIMP1; TIMP2; TNF; TNFRSF10A; TNFRSF10B; TNFRSF1A; TNFRSF1B; TOP1MT; TOP2A; TOP2B; TP53; TP63; TRADD; TUBB3; TUBG1; TWIST1; UCP2; UGT1A; V-ATPases; VCAM1; VEGFA; WEE1; WSB1; XIAP; XIAP.

11. The methods of claims 1-10 when the non-covalent complex or molecular / solid dispersion or conjugate is combined with a) at least one additional active natutral pharmaceutical ingredient (AANPI) selected from:Terpenoids; Flavonoids; Alkaloids; Polyketides; Polycyclic aromatic natural products; Steroids; Saponin;Oxygen heterocycles; Benzopyranoids; Benzofuranoids; Aliphatic natural products; Aminoacids and peptides;Polypyrroles; T annins; and compounds listedAANPI may be in the form of a pure substance isolated from a natural source, in the form of an extract, a dried extract, or in the form of a processed nafral source, such as a powder and any other form in which it is contained; b) at least one additional active natutral pharmaceutical ingredient (AANPI) selected from: folate, glycyrrhizic acid, P-sitosterol-P-D-glucoside (Sito-G), asialoorosomucoid, and asialofetuin;c) at least one of: radiation therapy; photodynamic therapy; photoimmunotherapy; surgery; chemotherapy, cytotoxic chemotherapy; Immunotherapy, immunotherapy with modified gamma delta T cells; hormonal therapy; oncolytic virus therapy; ketogenic diet plus dexamethasone; and the like.

12. The methods of claims 1-11 when active pharmaceutical ingredient (API) and / or additional active pharmaceutical ingredient (AAPI) and / or additional active natutral pharmaceutical ingredient (AANPI) is formulated in form of:A) a stabilized aqueous formulation which comprises API and / or AAPI and / or AANPI, solvent, surface active agent and cosolvent or a stabilized formulation which comprises API and / or AAPI and / or AANPI solutions in fat / oil or API and / or AAPI and / or AANPI emulsion;B) Th emethod of claim 10, 11 wherein the compound is a compound of Formula IV in the form of solution / emulsion / suspension comprising: a) a first pharmaceutical composition comprising a compound of Formula I -III, and; b) at least one of the following components:(1) oil phase containing vegetable or / and animal fats;(2) one or more surfactants;(3) one or more solvents;(4) one or more gelling agents;C) nanoparticles, microparticles, nanocomposites, microcomposites, composites, polymeric nanoparticles (PNPs), liposomes, freeze-dried liposomes, micelles, polymeric micelles, niosomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), nanoemulsions, microemulsions, emulsions, self-emulsifying (nano or micro) drug delivery systems (SNEDDS, SMEDDS, SEDDS), nanocrystals, co-crystals, mesoporous silica nanoparticles (MSNs), dendrimers, ultradispersions, solid dispersions, solid amorphous dispersions, noncovalent complexes, complexes with polymer, complexes with biopolymer, host-guest complexes, inclusion complexes, solutions, solutions in fat / oil, solutions with cosolvent, solutions with surface active agent / surfactant, solutions with solubilizing agent, polymorphes, lipid-based systems, lipid-based formulations, lipid-based drug delivery systems (LBDDS), gels, colloids, sols, and the like, or in any form described in the scientific and patent literature for example;D) a food product or beverage, or dietary supplement;E) wherein API, AAPI, AANPI can be obtained using methods of: A) Reduction Particle size: a) Micronization; b) Nanosuspension; B) Modification of the crystal habit; C) Solid dispersions: a) Eutectic mixtures; b) Solid solutions; c) Amorphous solid solutions; d) Glass solutions and glass suspension; e)Cryogenic techniques; A) Change of pH ; B) Use of buffer; C) Derivatization; D) Complexation,; E) Salt formation; A) Supercritical fluid process ; B) Use of adjuvant like surfactant, solubilizers, cosolvency, hydrotropy, and novel excipients.

13. The methods of claims 1-12 when non-covalent complexes or molecular / solid dispersions or conjugates are used as anticancer pharmaceutical agent, antitumor pharmaceutical agent, antineoplastic pharmaceutical agent, chemotherapeutic agent, or agent that is inductor, inhibitor or modulator of:1) cell death in cancer cell lines;2) cell death in senescent cell lines;3) immunogenic cell death;4) PAK1 -mediated cytostatic autophagy;5) caspase-dependent apoptosis;6) WNT-T cell factor (TCF), Hippo and Akt / mTOR pathways;7) growth and proliferation of cancer cells;8) cancer stem-like cells.

14. The methods of claims 1-13 when the dosage of the non-covalent complex or molecular / solid dispersion or conjugate a) exceeds EC 1 (1% of maximal effective concentration for API) for the respective cancer cell line; b) exceeds EC 5 (5% of maximal effective concentration for API) for the respective cancer cell line; c) exceeds EC 50 (half maximal effective concentration for API) for the cancer cell line; d) exceeds EC 90 (90% of maximal effective concentration for API) for the cancer cell line.

15. The method of treatment of the cancer and / or method of manufacture a pharmaceutical dosage form to treat cancer in a human or a mammal or an animal or a bird by administering a therapeutically effective amount of the solid dispersion or the noncovalent complex or congugate to a human or a mammal or an animal or a bird in need thereof wherein the "carrier (host)" molecule of the solid dispersion, "carrier (host)" molecular part of non-covalent complex or conjugate interacts with the biological membranes of the organism in such a way that the transfer of molecules, ions or metabolites of API, AAPI, AANPI across this biological membrane is improved. Thus, the scope of the invention includes solid dispersions and non- covalent complexes and conjugates with special permeability properties (highly permeable solid dispersions and non-covalent complexes and conjugates).

16. The methods of claims 1-15 when the complex, the molecular / solid dispersion, the conjugatehas at least one of the altered properties compared to pure API, AAPI, AANPI:1) The non-covalent complex, the solid dispersion, the conjugatehas a higher bioavailability than pure API, AAPI, AANPI;2) The non-covalent complex, the solid dispersion, the conjugatehas a higher permeability than pure API, AAPI, AANPI;3) The non-covalent complex, the solid dispersion, the conjugate has a lower toxicity or cytotoxicity than pure API, AAPI, AANPI;4) The non-covalent complex, the solid dispersion, the conjugatehas a different pharmokinetic parameters than API, AAPI, AANPI;5) The non-covalent complex, the solid dispersion, the conjugatehas a improved solubility than API, AAPI, AANPI.

17. The methods of claims 1-16 when The methods of claims 1-16 wherein (at least one of the following): a) the carrier chemically modified. I.e. carrier is a polymer, biopolymer or synthetic polymer, or methoxylated, ethoxylated, esterificated, carboxylated, alkoxylated, acetylated, hydroxylated, hydrated, decarboxylated, amide, oxidized, sulfated, aminoacid derivatives, fermented, thermally modified, chemically modified, acid modified, esters and ethers, salts, and any other chemical derivatives thereof; b) the method of preparation of non-covalent complex, molecular / solid dispersion, or conjugateis selected from listed in the present invention; c) the complex, the molecular / solid dispersion, the conjugate use for directing a therapeutic agent to a selected cell target in a subject; d) the therapeutic agent is covalently linked to the carrier; e) the carrier has a plurality of carboxymethyl functional groups suitable for covalent linkage to the therapeutic agent; f) the carrier is covalently linked to the therapeutic agent by a phosphoramidate linkage; g) the carrier is covalently linked to the therapeutic agent by a ethylenediamine linkage; h) the mass ratio of API, AAPI, AANPI to polymer or carrier is from 1 : 1 to 1 : 10000; i) additional active pharmaceutical ingredient (AAPI) or additional active natutral pharmaceutical ingredient (AANPI) are co-processed with the API to form their joint non-covalent complex or molecular / solid dispersion or conjugate; j) non-covalent complex or molecular / solid dispersion is obtained by any of the methods described in the description of the invention.

18. The methods of claims 1-17 wherein disease is selected from “Diseases of the blood and bloodforming organs and certain disorders involving the immune mechanism”, “Endocrine, nutritional and metabolic diseases”, “Mental and behavioural disorders”, “Diseases of the nervous system”, “Diseases of the eye andadnexa”, “Diseases of the ear and mastoid process”, “Diseases of the circulatory system”, “Diseases of the respiratory system”, “Diseases of the digestive system”, “Diseases of the skin and subcutaneous tissue”, “Diseases of the musculoskeletal system and connective tissue” , “Diseases of the genitourinary system“, “fungal diseases”, “bacterial diseases”, “viral diseases”, “parasitic diseases”, or any other disease or medical condition of official, traditional or alternative medicine.

19. The methods of claims 1-18 when non-covalent complexes or molecular / solid dispersions or conjugates (alone or in combination with AAPI, AANPI) may be used for a wide range of active agents of the group of ACE inhibitors, adenohypophoseal hormones, adrenergic neuron blocking agents, adrenocortical steroids, inhibitors of the biosynthesis of adrenocortical steroids, alpha- adrenergic agonists, alpha-adrenergic antagonists, selective alpha 2-adrenergic agonists, analgesics, antipyretics and anti-inflammatory agents, androgens, anesthetics, antiaddictive agents, antiandrogens, antiarrhythmic agents, antiasthmatic agents, anticholinergic agents, anticholinesterase agents, anticoagulants, antidiabetic agents, antidiarrheal agents, antidiuretics, antiemetic and prokinetic agents, antiepileptic agents, antiestrogens, antifungal agents, antihypertensive agents, antimicrobial agents, antimigraine agents, antimuscarinic agents, antineoplastic agents, antiparasitic agents, antiparkinsons agents, antiplatelet agents, antiprogestins, antithyroid agents, anti- tussives, antiviral agents, antidepressant, a typical antidepressants, azaspirodecanediones, barbituates, benzodiazepines, benzothiadiazides, beta-adrenergic agonists, beta-adrenergic antagonists, selective beta 1- adrenergic antagonists, selective beta 2-adrenergic agonists, bile salts, agents affecting volume and composition of body fluids, butyrophenones, agents affecting calcification, calcium channel blockers, cardiovascular drugs, catecholamines and sympathomimetic drugs, cholinergic agonists, cholinesterase reactivators, dermatological agents, diphenylbutylpiperidines, diuretics, ergot alkaloids, estrogens, ganglionic blocking agents, ganglionic stimulating agents, hydantoins, agents for control of gastric acidity and treatment of peptic ulcers, haematopoietic agents, histamines, histamine antagonists, 5 -hydroxy tryptamine antagonists, drugs for the treatment of hyperlipoproteinemia, hypnotics and sedatives, immunosuppressive agents, laxatives, methylxanthines, monoamine oxidase inhibitors, neuromuscular blocking agents, organic nitrates, opiod analgesics and antagonists, pancreatic enzymes, pheno thiazines, progestins, prostaglandins, agents for the treatment of psychiatric disorders, retinoids, sodium channel blockers, agents for spasticity and acute muscle spasms, succinimides, thioxanthines, thrombolytic agents, thyroid agents, tricyclic antidepressants, inhibitors of tubular transport of organic compounds, drugs affecting uterine motility, vasodilators, vitamins, hormones, steroids, nucleic acids, antibodies, enzymes, chemoprotective agents and radioprotecting agents; and (as agent or agent for):Abortifacient, Acaricidal, Allelopathic, Allergenic, Amnestic, Analgesic, Anesthetic, Anthelmintic,Antiallergic, Antiamebic, Antianemic, Anti-anxiety, Antiarrhythmic, Antiarthritic, Antiasthmatic, Antibacterial, Anticancer, Anticholinergic, Anticholinesterase, Anticonvulsant, Antidementic, Antidepressant, Antidermatitic, Antidiabetic, Antidiarrheic, Antidote, Antiedemic, Antiemetic, Antifertility, Antifungal, Antigout, Antihepatitic, Antihepatotoxic, Anti-HIV, Anti-HSV, Antihyperlipidemic, Antihypertensive, Antiinflammatory, Antileishmanial, Antileprotic, Antimalarial, Antimicrobial, Antimigraine, Anti-muscle regidity, Antimutagenic, Antimyasthenic, Antineoplastic, Antioxidant, Antiparkinson, Antiprotozoal, Antipsychotic, Antipyretic, Antiseptic, Antispasmodic, Antithrombotic, Anti-tremor, Antitrypanosomal, Antituberculotic, Antitumor, Antitussive, Antiulcerogenic, Antiviral, Anxiogenic, Attractant, Biomarker, Cardiotonic, Carminative, Choleretic, CNS stimulant, Convulsant, Cytotoxic, Defense, Dental, Depilatory, Dermatitic, Diaphoretic, Diuretic, Edematous, Emetic, Emulsifying agent, Enhance flowering, Enhance fruiting, Enhance germination, Enhance leaf growth, Enhance plant growth, Enhance plant growth, Enhance root growth, Enhance stem growth, Essential amino acid, Expectorant, Feeding attractant, Feeding deterrent, Flavor, Genotoxic, Hallucinogenic, Hemolytic, Hemostatic, Hepatotoxic, Herbicidal, Hormonal, Hypnotic, Immunomodulative, Immunostimulant, Immunosuppressant, Induce tremor, Inhibit CYP, Inhibit flowering, Inhibit fruiting, Inhibit germination, Inhibit leaf growth, Inhibit plant growth, Inhibit root growth, Inhibit spore germination, Inhibit stem growth, Insecticidal, Irritant, Laxative, Molluscicidal, Muscle relaxant, Mutagenic, Narcotic, Nematocidal, Neurotoxic, Nonessential amino acid, Nucleic acid, Nutrient, Odor, Other cardiovascular agent, Other digestive organ agent, Other genitourinary agent, Other health agent, Other nervous system agent, Other respiratory tract agent, Oviposition attractant, Oviposition deterrent, Oxytocic, Pediculicidal, Phototoxic, Phytoalexin, Phytotoxic, Pigment, Piscicidal, Pneumotoxic, Pollinator attractant, Psychotomimetic, Repellent, Sedative, Sex attractant, Solvent, Stomachic, Teratogenic, Tonic, Toxic, Tumorigenic, UV shield, Vitamin agent. Supplements Agent, life-extending agent, longevity enhancing agent, Anti-Age Agent, blood thinning agent, Nootropic agent, psychoactive agent, antipsychotic agent; and (as agent or agent for): sleep agent; sexual reproduction agent; Reproductive Control Agent; Abortifacient Agent; Abortifacient Agent, Nonsteroidal; Abortifacient Agent, Steroidal; Contraceptive Agent; Contraceptive Agent, Female; Contraceptives, Oral; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Contraceptives, Oral, Sequential; Contraceptives, Oral, Synthetic; Contraceptives, Postcoital; Contraceptives, Postcoital, Hormonal; Contraceptives, Postcoital, Synthetic; Luteolytic Agent; Menstruation-Inducing Agent; Sperm Immobilizing Agent; Spermatocidal Agent; Contraceptive Agent, Hormonal; Contraceptive Agent, Male; Antispermatogenic Agent; Spermatogenesis-Blocking Agent; Fertility Agent; Fertility Agent, Female; Fertility Agent, Male; Oxytocics; Tocolytic Agent; thinking, speech, reading, writing, behavior agent; observation, hearing, smell, sensory abilities agent; nutrition agent; respiration agent; excretion agent; locomotion, operation of limbs and body parts agent; Musculoskeletal system agent; Circulatory system, Cardiovascular system, Lymphatic system agent; Cardiovascular Agent; Anti-Arrhythmia Agent; Antihypertensive Agent; Calcium ChannelBlockers; Cardioplegic Solutions; Cardiotonic Agent; Fibrinolytic Agent; Natriuretic Agent; Nitric Oxide Donors; Potassium Channel Blockers; Sclerosing Solutions; Sodium Channel Blockers; Voltage-Gated Sodium Channel Blockers; Vasoconstrictor Agent; Calcium Channel Agonists; Nasal Decongestants; Vasodilator Agent; Endothelium-Dependent Relaxing Factors; Nervous system agent; Central Nervous System Agent; Abuse-Deterrent Formulations; Aversive Agent; Adjuvants, Anesthesia; Alcohol Deterrents; Analgesics; Analgesics, Non-Narcotic; Analgesics, Short-Acting; Calcitonin Gene-Related Peptide Receptor Antagonists; Dentin Desensitizing Agent; Narcotics; Analgesics, Opioid; Anticonvulsants; Anti-Dyskinesia Agent; Antiparkinson Agent; Aromatic Amino Acid Decarboxylase Inhibitors; Catechol O-Methyltransferase Inhibitors; Antiemetics; Antitussive Agent; Central Nervous System Depressants; Anesthetics; Anesthetics, Combined; Anesthetics, General; Anesthetics, Inhalation; Anesthetics, Intravenous; Anesthetics, Dissociative; Anesthetics, Local; Hypnotics and Sedatives; Sleep Aids, Pharmaceutical; Orexin Receptor Antagonists; Tranquilizing Agent; Anti-Anxiety Agent; Antimanic Agent; Antipsychotic Agent; Central Nervous System Stimulants; Aphrodisiacs; Appetite Stimulants; Appetite Depressants ;Convulsants; WakefulnessPromoting Agent; Emetics; Muscle Relaxants, Central; Narcotic Antagonists; Neuroprotective Agent; Nootropic Agent; Psychotropic Agent; Antidepressive Agent; Antidepressive Agent, Second- Generation; Antidepressive Agent, Tricyclic; Hallucinogens; Integumentary system agent; Dermatologic Agent; Antipruritics; Astringents; Emollients; Keratolytic Agent; Photosensitizing Agent; Sunscreening Agent; Haematopoietic and immune systems agent; Blood Agent; Lymphocyte Activation Agent; Lymphocyte Cooperation Agent; Neutrophil Activation Agent; Neutrophil Infiltration Agent; Hematologic Agent; Anticoagulants; Antithrombins; Factor Xa Inhibitors; Antisickling Agent; Blood Substitutes; Plasma Substitutes; Coagulants; Agglutinins; Hemagglutinins; Hemostatics; Anticoagulant Reversal Agent; Antifibrinolytic Agent; Heparin Antagonists; Hematinics; Platelet Aggregation Inhibitors; Immune System Agent; Immunomodulation Agent; Neuroimmunomodulation Agent; Immune Tolerance Agent; Clonal Anergy Agent; Clonal Deletion Agent; Endotoxin Tolerance Agent; Immune Privilege Agent; Self Tolerance Agent; Tachyphylaxis Agent; Transplantation Tolerance Agent; Immunosuppressant; Immunogenetic Agent; Cytokine Agent; AntiCytokine Agent; Seroconversion Agent; Immunocompetence Agent; Immune Evasion Agent; Immune Reconstitution Agent; Complement Activation Agent; Complement Pathway, Alternative Agent; Complement Pathway, Classical Agent; Complement Pathway, Mannose-Binding Lectin Agent; Blood Group Incompatibility Agent; Antigen- Antibody Reactions Agent; Antibody-Dependent Enhancement Agent; Anti- Allergic Agent; Mast Cell Stabilizers; Respiratory system agent; Respiratory System Agent; Anti-Asthmatic Agent; Bronchodilator Agent; Bronchoconstrictor Agent; Expectorants; Pulmonary Surfactants; Digestive system agent; Urinary system agent; Reproductive system agent; Endocrine system agent; cell reproduction, division, differentiation, atypia, such as: agent; cancer, malignant tumors such as Carcinoma, Sarcoma, Lymphoma, leukemia, Germ cell tumor, Blastoma (e.g. neuroblastoma, retinoblastoma, nephroblastoma, hepatoblastoma, medulloblastoma, etc.), Melanoma, endothelioma of tissues, organs, parts of organs agent; Antineoplastic Agent; Angiogenesis Inhibitors; Antibiotics, Antineoplastic; Anticarcinogenic Agent;Antimetabolites, Antineoplastic; Antimitotic Agent; Antineoplastic Agent, Alkylating; Antineoplastic Agent, Hormonal; Antineoplastic Agent, Phytogenic; Antineoplastic Agent, Immunological; Immune Checkpoint Inhibitors; MTOR Inhibitors; Myeloablative Agonists; Poly(ADP -ribose) Polymerase Inhibitors; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Topoisomerase II Inhibitors; cell death, apoptosis, autophagy agent; cellular signaling agent; metabolism of cells and tissues agent; cellular uptake of nutrients agent; sensitivity to the action of hormones, transmitters, neurotransmitters, etc., such as insulin, cortisol, dopamine, and others agent; genetic diseases, chromosomal disorder or genetic syndrome agent; Anti- Inflammatory Agent; Anti-Inflammatory Agent, Non-Steroidal; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Antifibrotic Agent; Demulcents; Tumor Necrosis Factor Inhibitors; Antiviral Agent; Anti- Retroviral Agent; Anti-HIV Agent; CCR5 Receptor Antagonists; HIV Fusion Inhibitors; HIV Integrase Inhibitors; HIV Protease Inhibitors; Reverse Transcriptase Inhibitors; Viral Fusion Protein Inhibitors; Viral Protease Inhibitors; Coronavirus Protease Inhibitors; HCV NS3-4A Protease Inhibitors; anti-bacterial agent; anti-fungi agent; anti-parasites agent; anti-ectoparasitose agent; Antiprotozoal Agent; Amebicides; Antimalarials; Antitrichomonal Agent; Coccidiostats; Trypanocidal Agent; anti prions agent; anti-toxic agent; anti-allergic agents, including Systemic allergic diseases agent; kinetic exposures and kinetic injuries agent; thermal injuries agent; radiation injuries agent; barotraumas agent; other injuries agent; anti-stress agent; Radiation-Sensitizing Agent; Diagnostic Uses Agent; Prophylaxis Agent; Pre-exposure prophylaxis Agent; Therapeutic Uses Agent; Antiglaucoma Agent; Anti-Infective Agent; Anti-Bacterial Agent; Antitreponemal Agent; Antitubercular Agent; Antibiotics, Antitubercular; beta-Lactamase Inhibitors; Leprostatic Agent; Antifungal Agent; Anti-Infective Agent, Local; Hand Sanitizers; Anti- Infective Agent, Urinary; Antiparasitic Agent; Anthelmintic; Antinematodal Agent; Filaricides; Antiplatyhelmintic Agent; Anticestodal Agent; Schistosomicides; Disinfectants; Contact Lens Solutions; Dental Disinfectants; Root Canal Irrigants; AntiObesity Agent; Appetite Depressants; Antirheumatic Agent; Gout Suppressants; Uricosuric Agent; Gastrointestinal Agent; Antacids; Antidiarrheals; Anti-Ulcer Agent; Cathartics; Cholagogues and Choleretics; Guanylyl Cyclase C Agonists; Laxatives; Lipotropic Agent; Genitourinary Agent; Renal Agent; Urological Agent; Lipid Regulating Agent; Hypolipidemic Agent; Anticholesteremic Agent; Hydroxymethylglutaryl- CoA Reductase Inhibitors; PCSK9 Inhibitors; Lipoprotein Lipase Activators; Pharmaceutical Solutions; Dialysis Solutions; Hemodialysis Solutions; Ophthalmic Solutions; Lubricant Eye Drops; Parenteral Nutrition Solutions; Fat Emulsions, Intravenous; Senotherapeutics; Smoking Cessation Agent; Physiological & Psychological Effect Agent; Physiological & Psychological Adaptation Agent; Adaptogen; Nootropic Agent; Psychotropic Drug; Psychoactive Agent; Physiological / Biological Effect Agent; Physiological Adaptation Agent; Acclimatization Agent; Body Temperature Regulation Agent; Sweating Regulation Agent; Thermogenesis Regulation Agent; Shivering Regulation Agent; Torpor Regulation Agent; Estivation Agent; Hibernation Agent; Tissue Survival Agent; Recovery of Function Agent; Regeneration Agent; Bone Regeneration Agent; Brain Regeneration Agent; Liver Regeneration Agent; Nerve Regeneration Agent; Wound Healing Agent; Tissue Regeneration Agent; Organ Regeneration Agent; Aging Agent; Anti-AgingAgent; Skin Aging Agent; Skin Anti-Aging Agent; Immunosenescence Agent; Anti-Immunosenescence Agent; Transplantation Immunology Agent; Graft vs Host Reaction Agent; Host vs Graft Reaction Agent; Histocompatibility Agent; Toxic Agent; Toxicant; Toxin; Cytotoxicity; Antitoxin; Antidote; Antivenin; Cytotoxicity; Pigmentation Agent; and (as agent or agent for):ACE inhibitors; Inhibitors Of The Biosynthesis Of Adrenocortical Steroids; Monoamine Oxidase Inhibitors; Inhibitors Of Tubular Transport Of Organic Compounds; Alpha-Adrenergic Antagonists; Beta-Adrenergic Antagonists; Selective Beta 1-Adrenergic Antagonists; Histamine Antagonists; 5- Hydroxytryptamine Antagonists; Opiod Analgesics And Antagonists; Calcium Channel Blockers; Sodium Channel Blockers; Beta Blocking Agent; Calc. Chan. Blocker; Alpha-Adrenergic Agonists; Selective Alpha 2-Adrenergic Agonists; Beta-Adrenergic Agonists; Selective Beta 2-AdrenergicAgonists; Cholinergic Agonists; Leukocyte Growth Factor Agent; Cytolytic Antibody; Small Molecule Agent; Fluorinated Agent; Sulfur Containing Agent; Chlorinated Agent; Oncological Agent; Myeloid Leukemia Agent; Breast Cancer Agent; Colorectal Cancer Agent; Multiple Myeloma Agent; Testicular Cancer Agent; Hodgkin Lymphoma Agent; Graft-Versus-Host-Disease Agent; Brain Tumors Agent; Melanoma Agent; Lymphoblastic Leukemia Agent; Prostate Cancer Agent; Small Cell Lung Cancer Agent; Ovarian Cancer Agent; Hairy Cell Leukemia Agent; Skin Cancer Agent; Graft-Versus-Host Disease Agent; Chem. Ind. Nausea & Vomiting Agent; Esophageal Cancer Agent; Opiod Analgesic Agent; Hypercalcemia Agent; Non-Small Cell Lung Carcin Agent; Basal Cell Carcinoma Agent; Thrombocytopenia Agent; Non Hodgkin Lymphoma Agent; Bone Cancer Agent; Opioid Analgesic Agent; Bladder Cancer Agent; T-Cell Lymphoma Agent; Lymphocytic Leukemia Agent; Pancreatic Cancer Agent; Parathyroid Carcinoma Agent; Graft-Versus Host Disease Agent; Kidney Cancer Agent; Tumor Lysis Syndrome Agent; Bone Marrow Cancer Agent; Thyroid Cancer Agent; Anal Cancer Agent; Basophilic Leukemia Agent; Bihary Tract Cancer Agent; Blood Cancer Agent; Breast Tumors Agent; Cervical Cancer Agent; Colorectal Tumors Agent; Endometerial Cancer Agent; Eosinophilic Leukemia Agent; Gastric Cancer Agent; Gastrointestinal Tumors Agent; Head Cancer Agent; Lymphoblastic Lymphoma Agent; Mantle Cell Lymphoma Agent; Mesothelioma Agent; Neck Cancer Agent; Neutrophilic Leukemia Agent; Non Small Cell Lung Carcinoma Agent; Pancreatic Tumors Agent; Mineral Supplement; Vitamin; Alimentary Tract Agent; Metabolism Agent; Laxative Agent; Gastrointestinal Agent; Antidiar., Antiinfla., Antiinf. Agent; Stomatological Prep; Antidiabetic Agent; Anti-Obesity Agent; Anabolic Agent; Acid Related Disorders Agent; Antiemetic Agent; Antinauseant Agent; Anti-Infective Agent; Antibacterial Agent; Antimycobacterial Agent; Antiviral Agent; Antimycotic Agent; Anti-Parasitic Agent; Anti-Bacterial Agent; Anti-Fungal Agent; Blood And Blood Forming Organ Agent; Antithrombotic Agent; Antihemorrhagic Agent; Blood Subs. & Perfusion Sins.; Lipid Modifying Agent; Antianemic Agent;Anticoagulant; Antileukemic Agent; Chemotherapeutic Agent; Cardiovascular Agent; Vasoprotective Agent; Cardiac Therapy Agent; Antihypertensive Agent; Peripheral Vasodilator Agent; Diuretic; Renin- Angiotensin Agent; RAS-acting agents; Endocrine System Agent; Endocrine Therapy Agent; Thyroid Therapy Agent; Corticosteroid; Immunosuppressive Agent; Pituit. & Hypoth. Hormones; Calcium Homeostasis Agent; Genitourinary And Sex Hormone Agent; Sex Hormones & Modulators Agent; Gynecological Antiinfective Agent; Antiseptic Agent; Urological Agent; Gynecologicals Agent; Musculo-Skeletal Agent; Muscle Relaxant; Topical Products; Other Disorders Of Musculo-Skeletal System Agent; Antiinflammatory Agent; Antirheumatic Agent; Antigout Agent; Treatment Of Bone Diseases Agent; Nervous System Agent; Anesthetic Agent; Analgesic Agent; Psychoanaleptic Agent; Antiepileptic Agent; Misc. Nervous Agent; Anti-Parkinson Agent; Psycholeptic Agent; Antidepressant; Respiratory System Agent; Cough & Cold Prep; Throat Prep; Obstructive Airway Diseases Agent; Antihistamine Agent; Nasal Prep; Other Respir. System Prods; Sensory Organ Agent; Ophthalmological Agent; Otological Agent; Ophthalmol. & Otol. Prep; Alimentary Tract & Metabolism Agent; Anti-Infective Agent; Blood & Blood Forming Organs Agent; Cardiovascular System Agent; Dermatological Agent; Endocrine System Agent; Genito-Urinary & Sex Hormones Agent; Musculo- Skeletal System Agent; Nervous System Agent; Oncological Agent; Respiratory System Agent; Sensory Organs Agent; Nervous System' Agent; Genito-Urinary & Sex Horomone; Blood & Blood Forming Organ Agent; Cardiovascular Agent; Genito-Urinary & Sex Hormone Agent; Sensory Organ Agent; Musculo- Skeletal; Alimentary Tract & Metabolism Agent; Reproductive Agent; Endocrine Agent; Antiinflammatory; Skeletomuscular; hnmulogical; Contrast Agent; Alimentary Agent; Antidote; Nsaid; Cardiovascular Diseases Agent; Oncology Agent; Infectious Diseases Agent; Diabetes Agent; Genetic Disorders Agent; Neurology Agent; Respiratory Disorders Agent; Immunology Agent; Dermatology; Rare Disorders Agent; Hematology Agent; Nephrology; Urology; Sleep; Women's Healthcare Agent; Hormonal Disorders Agent; Ophthalmology; Diagnostics; Miscellanious Agent; Diagnostic Contrast Agent; Veterinary Agent; Adeno-Hypophoseal Hormones; Adrenergic Neuron Blocking Agent; Adrenocortical Steroids; Analgesics; Antipyretics And Anti- Inflammatory Agent; Androgens; Anesthetics; Antiaddictive Agent; Antiandrogens; Antiarrhythmic Agent; Antiasthmatic Agent; Anticholinergic Agent; Anticholinesterase Agent; Anticoagulants; Antidiabetic Agent; Antidiarrheal Agent; Antidiuretics; Antiemetic And Prokinetic Agent; Antiepileptic Agent; Antiestrogens; Antifungal Agent; Antihypertensive Agent; Antimicrobial Agent; Antimigraine Agent; Antimuscarinic Agent; Antineoplastic Agent; Antiparasitic Agent; Antiparkinsons Agent; Antiplatelet Agent; Antiprogestins; Antithyroid Agent; Anti-Tussives; Antiviral Agent; A Typical Antidepressants; Azaspirodecanediones; Barbituates; Benzodiazepines; Benzothiadiazides; Bile Salts; Agent Affecting Volume And Composition Of Body Fluids; Butyrophenones; Agent Affecting Calcification; Catecholamines And Sympathomimetic Agent; Cholinesterase Reactivators; Dermatological Agent; Diphenylbutylpiperidines; Diuretics; Ergot Alkaloids; Estrogens; Ganglionic Blocking Agent; Ganglionic Stimulating Agent; Hydantoins; Agent For Control Of Gastric Acidity And Treatment Of Peptic Ulcers; Haematopoietic Agent; Histamines; Agent For The Treatment Of Hyperlipoproteinemia; Hypnotics And Sedatives; Immunosuppressive Agent; Laxatives;Methylxanthines; Neu-Romuscular Blocking Agent; Organic Nitrates; Pancreatic Enzymes; Pheno Thiazines; Progestins; Prostaglandins; Agent For The Treatment Of Psychiatric Disorders; Retinoids; Agent For Spasticity And Acute Muscle Spasms; Succinimides; Thioxanthines; Thrombolytic Agent; Thyroid Agent; Tricyclic Antidepressants; Agent Affecting Uterine Motility; Vasodilators and agent for support health of: a. skin; b. head - eye - ear - nose - mouth - tongue - teeth - lower jaw - face - cheek; c. neck - throat - Adam's apple - shoulders; d. hand - elbow - wrist - hand - fingers - thumb; e. spine - breast - mammary gland - rib cage; f. abdomen - navel - genitals (penis / scrotum or clitoris / vagina) - perineum - anus; g. leg - pelvis - thigh - buttock - knee - shin - calf - foot; h. hair, nails; i. pituitary - duodenum - stomach - gallbladder - intestines - lungs - uterus - bladder - adrenals - parathyroid - liver - pancreas - kidneys - prostate - esophagus - spleen - heart - thymus - worm gland - thyroid - testes - ovaries; j . brain; k. anatomical parts included in YT erminologia Anatomica The Second Edition Parts I-V, Chapters 1-16, which is the international standard for human anatomical terminology; 1. other anatomical parts included in MESH terminology; and agent for a medical condition like: a. embryo agent; b. fetus agent; c. infantile age agent; d. childhood agent; e. adulthood agent; f. old age agent; g. pregnancy and childbirth agent; h. disability agent; i. coma agent; j. anesthesia agent; k. sleep agent; 1. during medical procedures, diagnostics and surgeries; m. other agent for a medical condition included in MESH terminology and the like, alone or in combination. Although extensive, this list is not intended to be comprehensive.

20. The methods of claims 1-19 wherein is used for an animal or mammal or bird.

21. A method for controlling cell fate and treating diseases associated with aberrant P-catenin activity, comprising:

1. modulating P-catenin nuclear localization (wherein P-catenin nuclear localization modulator can be selected from any disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG. 12 to FIG.72), or a non-co valent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system or can be selected from any other pharmacologically acceptable P-catenin nuclear localization modulator), and2. reducing inflammaging by inhibiting at least one pro-inflammatory pathway, cytokine, or mitochondrial dysfunction factor,wherein said method results in safe induction of regeneration in non-malignant tissues or inhibition of oncogenesis in malignant tissues.

22. The method of Claim 21, wherein said inhibition of inflammaging is achieved by suppressing one or more pathways selected from the group consisting of:

1. TGF-0 signaling,2. NF-KB signaling,3. STAT3 signaling,4. SASP (Senescence- Associated Secretory Phenotype),5. ROS production,6. cGAS-STING activation,7. NLRP3 inflammasome activation.

23. The method of Claim 21, wherein said inhibition of inflammaging is achieved by reducing at least one pro-inflammatory cytokine selected from the group consisting of:IL-la, IL-10, IL-2, IL-6, IL-8, IL-11, IL-12, IL-17, IL-18, IL-23, IL-27, IL-35, IL-37, TNF-a, IFN- y, MCP-1 (CCL2), GM-CSF, VEGFA, CXCL12, and HMGBl.

24. The method of any of Claims 21-23, wherein said reduction of inflammation is performed by administering at least one agent selected from:

1. TGF-0 inhibitors (including RepSox, SB431542, LY2157299, or any other TGF-P inhibitor disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non- covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable TGF-P inhibitor),2. NF-KB inhibitors (including aspirin, curcumin, proteasome inhibitors, or any other NF-KB inhibitor disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable NF-KB inhibitor),3. STAT3 inhibitors (including Stattic, BP-1-102, or any other STAT3 inhibitor disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable STAT3 inhibitor),4. Anti-IL-6 antibodies (including tocilizumab, or other pharmacologically acceptable Anti-IL- 6 antibody),5. Anti-TNF agents (including infliximab, etanercept, or other pharmacologically acceptable Anti-TNF agent),6. Anti-IL-10 agents (including canakinumab, anakinra, or other pharmacologically acceptable Anti-IL-ip agent),7. Anti-IL-11, Anti-IL-17, Anti-IL-23, Anti-IL-12, Anti-VEGFA antibodies,8. Senolytics (including dasatinib, quercetin, navitoclax, or any other Senolytic disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable Senolytic),9. Antioxidants (including N-acetyl cysteine, MitoQ, SkQl, coenzyme Q10, or any other Antioxidant disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable Antioxidant),10. AMPK activators and SIRT activators (including metformin, resveratrol, NAD+precursors, or any other AMPK activator and SIRT activator disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable AMPK activator and SIRT activator).

25. The method of any of Claims 21-24, further comprising direct modulation of P-catenin nuclear translocation, wherein such modulation comprises:

1. inhibiting P-catenin nuclear entry for cancer therapy, or2. promoting P-catenin nuclear entry for controlled regenerative purposes wherein P-catenin nuclear translocation modulator can be selected from any disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system or can be selected from any other pharmacologically acceptable P-catenin nuclear translocation modulator).

26. The method of Claim 25, wherein inhibition of P-catenin nuclear translocation is achieved by administering ivermectin, niclosamide, or any other P-catenin nuclear translocation inhibitor that can be selected from any disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system or can be selected from any otherpharmacologically acceptable [3-catenin nuclear translocation inhibitor) or functional analogs thereof.

27. The method of Claim 25, wherein promotion of [3-catenin nuclear translocation for regenerative purposes is achieved by agents selected from:

1. GSK3 inhibitors (including lithium, CHIR99021, or any other GSK3 inhibitor disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable GSK3 inhibitor),2. Forskolin or any other cAMP pathway activator disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable cAMP pathway activator,3. Wnt agonists (any Wnt agonist disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable Wnt agonists),4. Small molecules activating [3-catenin stability.

28. The method of any of Claims 21-27, wherein said regenerative or anti-aging therapy further comprises:

1. induction of mitophagy and autophagy to reduce mitochondrial dysfunction,2. reduction of senescent cell burden,3. metabolic modulation to reduce insulin resistance and vascular inflammation.

29. The method of any of Claims 21-28, wherein said therapy is applied in the context of epigenetic reprogramming, and comprises:• (i) reducing inflammaging,• (ii) transiently activating [3-catenin nuclear entry to induce regenerative gene expression,• (iii) subsequently inhibiting [3-catenin nuclear entry to minimize oncogenic risk.

30. The method of any of Claims 21-29, wherein said method is applied for the treatment or prevention of a disease selected from:

1. cancer,2. age-related degenerative disease,3. fibrosis,4. metabolic syndrome,5. neurodegenerative disease,6. cardiovascular disease,7. immune senescence,8. any other disease.

31. The method of any of Claims 21-30, wherein one or more agents used for modulation of 0- catenin or inhibition of inflammaging are provided in the form of:

1. a non-covalent complex,2. a molecular dispersion,3. a solid dispersion,4. a conjugate with a polymer, lipid, nanoparticle, antibody, peptide, or nucleic acid, thereby enhancing solubility, bioavailability, stability, or tissue-specific delivery of said agent.

32. The composition for use in the method of Claim 31, wherein the agents selected from ivermectin, niclosamide, metformin, RepSox, TGF-0 inhibitors, NF-KB inhibitors, senolytics, antioxidants (selected from any TGF-0 inhibitors, NF-KB inhibitors, senolytics, antioxidants disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system or other pharmacologically acceptable TGF-0 inhibitors, NF-KB inhibitors, senolytics, antioxidants), or combinations thereof are formulated as a non-covalent complex, solid dispersion, or conjugate for oral, intravenous, intranasal, or local administration.

33. The method of any of Claims 21-32, wherein said therapy comprises a combination of:

1. (i) at least one 0-catenin nuclear translocation inhibitor or activator (selected from any flea ten in nuclear translocation inhibitor or activator disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system or other pharmacologically acceptable 0-catenin nuclear translocation inhibitor or activator), and2. (ii) at least one inflammaging-reducing agent selected from TGF-0 inhibitors, NF-KB inhibitors, STAT3 inhibitors, senolytics, anti-cytokine antibodies, antioxidants, or metabolic modulators (selected from TGF-0 inhibitors, NF-KB inhibitors, STAT3 inhibitors, senolytics, anti-cytokine antibodies, antioxidants, or metabolic modulators disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system or other pharmacologically acceptable TGF-0 inhibitors, NF-KB inhibitors, STAT3 inhibitors, senolytics, anti-cytokine antibodies, antioxidants, or metabolic modulators), administered simultaneously, sequentially, or as a fixed-dose combination.

34. The composition for use in the method of Claim 33, wherein said P-catenin modulator and inflammaging-reducing agent are co-formulated in:

1. a single dosage form,2. a non-covalent complex,3. a solid dispersion,4. a nanoparticle, liposome, or polymeric conjugate, providing synergistic therapeutic effect for treatment of cancer, prevention of oncogenesis, or induction of safe regenerative programs.

35. The method of any of Claims 21-34, wherein said therapy further comprises metabolic intervention selected from the group consisting of:

1. administration of methioninase (rMETase),2. dietary methionine restriction,3. dietary glucose restriction or ketogenic diet,4. glutamine restriction,5. inhibition of glycolysis, glutaminolysis, or one-carbon metabolism, wherein such metabolic intervention synergizes with P-catenin modulation and inflammaging reduction to suppress tumor growth and progression.

36. The method of Claim 35, wherein methioninase (rMETase) is administered in combination with at least one agent selected from ivermectin, niclosamide, metformin, RepSox, or a TGF-P inhibitor, or any other compound disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system to simultaneously reduce P-catenin oncogenic activity, lower inflammaging, and deprive tumor cells of metabolic substrates.

37. The composition for use in any of Claims 35-36, wherein P-catenin modulator(s), inflammaging-reducing agent(s), and metabolic therapy agent(s) are formulated as:• a co-formulated pharmaceutical composition,• a non-covalent complex, molecular or solid dispersion, or delivery system, for synergistic cancer therapy.

38. The method of any of Claims 21-37, wherein the therapy further comprises stimulation of mitophagy and autophagy, by administering at least one agent selected from the group consisting of:

1. SIRT activators (including SIRT1 activators such as resveratrol, NAD+precursors, or any other SIRT activator disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable SIRT activator),2. AMPK activators (including metformin, AICAR, or any other AMPK activator disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable AMPK activator),3. mitophagy-inducing natural products (including urolithin A, or any other mitophagy- inducing natural product disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable mitophagy-inducing natural product),4. mTOR inhibitors (including rapamycin, or any other mTOR inhibitor disclosed in ([0091] (GUESTs), [0095] (active pharmaceutical ingredient), [0110] (AAPIs), [0111] (AAPIs), [0114] (AANPIs), and those listed in from FIG.12 to FIG.72), or a non-covalent complex, molecular dispersion, solid dispersion, or a conjugate (with a polymer, lipid, nanoparticle, peptide, antibody, or nucleic acid, etc) thereof, together with a pharmaceutically acceptable carrier, excipient, or delivery system; or other pharmacologically acceptable mTOR inhibitor),5. and pharmacologically acceptable analogs or derivatives thereof, wherein said stimulation synergizes with 0-catenin modulation and inflammaging reduction to promote safe cellular regeneration, enhance mitochondrial function, and suppress oncogenic processes.

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