Composition for treating local bacterial skin diseases

Abstract

The present disclosure provides a hydrogel formulation comprising a therapeutically effective amount of an extract of the Croton lechleri ​​tree. The present disclosure also provides a method of treating a dermatological condition in a subject via topical administration of a hydrogel formulation comprising a therapeutically effective amount of an extract of the Croton lechleri ​​tree.

Description

[Technical field]

[0001] Cross-reference to related applications This application claims the benefit of U.S. Provisional Application No. 63 / 153,864, filed February 25, 2021, and U.S. Provisional Application No. 63 / 189,276, filed May 17, 2021, the disclosures of each of which are incorporated herein by reference. Summary of the Invention [Means for solving the problem]

[0002] The present invention generally relates to hydrogel formulations comprising a therapeutically effective amount of Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg. filtered latex, the therapeutically effective amount including at least the component concentrations of the reference standard. The component concentrations and performance standards of the reference standard Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg. filtered latex, are found in Tables 1a-e. [Brief description of the drawings]

[0003] [Figure 1] FIG. 1 shows a representative total ion chromatogram and additional spectra from multiple reaction monitoring identifying marker compounds in the AB-101 composition. [Figure 2A] Figure 2A shows the NMR spectra of three lots of AB-101 in D2O: the top spectrum is from lot 00, the middle spectrum is from lot 01, and the bottom spectrum is from lot 02. [Figure 2B] Figure 2B shows an overlay of NMR spectra of AB-101 lots 00, 01, and 02 in D2O. [Figure 3A] Figure 3A shows the nuclear magnetic resonance (NMR) spectra of three lots of AB-101 in d4-methanol: the top spectrum is from lot 00, the middle spectrum is from lot 01, and the bottom spectrum is from lot 02. [Figure 3B] FIG. 3B shows an overlay of NMR spectra of AB-101 lots 00, 01, and 02 in d4-methanol. [Figure 4A] Figure 4A shows the NMR spectra of four lots of AB-101 in d4-methanol: the top spectrum is from lot 00, the top middle spectrum is from lot 01, the bottom middle spectrum is from lot 02, and the bottom spectrum is from lot X. [Figure 4B] FIG. 4B is an overlay of NMR spectra of AB-101 lots 00, 01, 02, and X in d4-methanol. [Diagram 5] FIG. 5 is a bar graph comparing the results of analysis of AB-101 lots for A) gallocatechin B) epigallocatechin C) catechin D) epicatechin E) taspine. [Figure 6] FIG. 6 is a representative total ion chromatogram of dimethylcedrusin. [Figure 7] FIG. 7 is a liquid dressing of a film-forming hydrogel containing 50% AB-101. [Figure 8] FIG. 8 shows the hydrogel where dimethicone was added after the hydrogel was formed. [Figure 9] FIG. 9 shows the hydrogel when dimethicone is added before the hydrogel is formed. [Figure 10] FIG. 10 is a micrograph of the addition of dimethicone after hydrogel formation, showing a brown color indicating that AB-101 was incorporated into the hydrogel matrix. [Figure 11]FIG. 11 is a micrograph of the case where dimethicone was added before the hydrogel was formed, showing a blue color indicating air entrapment between the AB-101 and the hydrogel matrix. [Figure 12] FIG. 12 shows air entrapped in the formulation by high shear. [Figure 13] FIG. 13 shows the rupture of the emulsion when AB-101 was added to water before the hydrogel formed. [Figure 14] FIG. 14 shows the gel permeation chromatograms of three PMMA standards. [Figure 15] FIG. 15 shows an overlay of gel permeation chromatograms of three PMMA standards. [Figure 16] FIG. 16 shows the chromatogram of AB-101 Lot 01 at a concentration of 1.25 mg / mL. [Figure 17A] FIG. 17A shows the calibration curve of Mw. [Figure 17B] FIG. 17B shows the calibration curve for Mn. [Figure 18] FIG. 18 shows the particle size distribution analysis results for the AB-101 lot. [Figure 19] FIG. 19 shows the mobility distribution of the zeta potential of the pharmaceutical AB-101 extract. [Figure 20] FIG. 20 shows the mobility distribution of the zeta potential of AB-101 hydrogel. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0004] Before describing the compositions and methods, it should be understood that the present invention is not limited to the specific processes, compositions, or methodologies described. It should also be understood that the terms used herein are only for the purpose of describing the specific versions or embodiments, and are not intended to limit the scope of the embodiments herein, which are limited only by the appended claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the embodiments herein, the preferred methods, devices, and materials are described herein. All publications mentioned herein are incorporated by reference in their entirety. Nothing herein should be construed as an admission that the embodiments herein are not entitled to antedate such disclosure by prior invention.

[0005] As used herein, the following terms have the meanings indicated.

[0006] It should also be noted that as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise.

[0007] The term "about" as used herein is intended to modify the numerical value it modifies, indicating that such numerical value varies within a margin of error. When no specific error, such as standard deviation for the average value shown in a graph or table of data, is described, the term "about" should be understood to mean plus or minus 10% of the numerical value with which it is used. Thus, about 50% means a range of 45% to 55%.

[0008] As used herein, the term "AB-101" may be used interchangeably with Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg. filtered latex and vegetable raw materials. The latex is an excreta from wounded trunks of Croton lechleri, preferably Croton lechleri ​​Mull.Arg. In such cases, the latex is whole latex. In all cases, the latex is unfractionated.

[0009] As used herein, the term "acute bacterial skin or skin structure infection" is defined as a bacterial infection of the skin, including but not limited to bacterial skin infection, drug-resistant bacterial skin infection, or multi-drug resistant bacterial skin infection. Moreover, such infections may be uncomplicated or complicated, and may be mild or severe. Such infections may be without lesions, abscesses, or wounds (e.g., primary infections such as all forms of impetigo, including but not limited to mupirocin-resistant impetigo), or with lesions, abscesses, or wounds. Moreover, such infections may be of any size, including lesions of 75 cm2 or more (often referred to as acute bacterial skin and skin structure infections (or ABSSSIs)), or skin infections of lesser size (often referred to as secondary infected traumatic lesions (or SITLs), skin and soft tissue infections (or SSTIs)).

[0010] "Administering", when used in conjunction with a therapeutic agent such as AB-101, means administering the therapeutic agent directly to a target tissue, or administering the therapeutic agent to a patient, where the therapeutic agent positively affects the target tissue. Thus, as used herein, the term "administering", when used in conjunction with the compositions of the embodiments herein, includes, but is not limited to, providing the composition in or on the target tissue; providing the composition to a patient, for example, by topical application, so that the therapeutic agent reaches the target tissue. "Administering" the composition may be accomplished topically or in conjunction with other known techniques.

[0011] As used herein, the term "cellulitis / erysipelas" is defined as a diffuse bacterial skin infection characterized by widespread areas of redness, edema, and / or induration.

[0012] The transitional term "comprising" is synonymous with "including," "containing," or "characterized by" and is inclusive or open-ended and does not exclude additional, unrepresented elements or method steps.

[0013] In embodiments or claims where the term "comprising" is used as a transitional phrase, such embodiments can also be envisioned by replacing the term "comprising" with the term "consisting of" or "consisting essentially of."

[0014] As used herein, the term "consisting of" or "consisting of" means that the hydrogel formulation, pharmaceutical composition, composition, or method includes only those elements, steps, or ingredients specifically recited in a particular claimed embodiment or claim.

[0015] As used herein, the term "substantially consisting of" or "substantially consisting of" means that the hydrogel formulation or method includes only those elements, steps, or ingredients specifically recited in a particular claimed embodiment or claim, and may optionally include additional elements, steps, or ingredients that do not materially affect the basic and novel characteristics of the particular embodiment or claim. For example, the only active ingredient(s) in a composition or method for treating a particular condition (e.g., nutrient depletion) is the therapeutic agent(s) specifically recited in a particular embodiment or claim.

[0016] The term "combination therapy" refers to the administration of two or more therapeutic agents to treat a therapeutic condition or disorder described in this disclosure. Such administration includes the co-administration of these therapeutic agents in a substantially simultaneous manner, such as in a single capsule having a fixed ratio of active ingredients, or in multiple separate capsules for each active ingredient. Furthermore, such administration also includes the sequential use of each type of therapeutic agent. In either case, the treatment regimen provides the beneficial effect of the combination of agents in the treatment of a condition or disorder described herein.

[0017] The term "disease" as used herein is generally intended to be synonymous with and used interchangeably with the terms "disorder," "syndrome," and "condition" (in medical conditions), i.e., all of which reflect an abnormal condition of the human or animal body or parts thereof that impairs normal functioning, typically manifested by characteristic signs and symptoms, and that reduces the duration or quality of the human or animal's life.

[0018] As used herein, the terms "excipient" and "pharmaceutically acceptable excipient" are intended to be generally synonymous and are used interchangeably with the terms "carrier," "pharmaceutically acceptable carrier," "diluent," and "pharmaceutically acceptable diluent."

[0019] As used herein, the term "extract" refers to the unfractionated liquid that resides between the bark and wood of the tree.

[0020] As used herein, the term "major skin abscess" is defined as a bacterial infection characterized by a collection of pus within the dermis or deeper, accompanied by redness, swelling, and / or induration.

[0021] The term "patient" is generally synonymous with the term "subject" and includes all mammals, including humans. Examples of patients include humans, domestic animals such as cows, goats, sheep, pigs, rabbits, and companion animals such as dogs, cats, rabbits, and horses. Preferably, the patient is a human.

[0022] As used herein, the term "pharmaceutically acceptable salts" refers to salts prepared from bases or acids that are acceptable for administration to patients, such as mammals. The term "pharmaceutically acceptable salts" embraces salts commonly used to form alkali metal salts and to form addition salts of free acids or free bases. The nature of the salt is not critical, provided that it is pharmaceutically acceptable. Such salts can be derived from pharmaceutically acceptable inorganic or organic bases and pharmaceutically acceptable inorganic or organic acids.

[0023] As used in embodiments herein, sap includes sap, latex, resin, extract, or any combination thereof.

[0024] As used herein, the term "therapeutic agent" or "therapeutic agent" or "pharmaceutical active agent" means an agent utilized to treat, combat, ameliorate, prevent or ameliorate an unwanted condition or disease in a patient.

[0025] The term "therapeutically acceptable" refers to a composition that is suitable for use in contact with the tissues of a patient without undue toxicity, irritation, or allergic response, is commensurate with a reasonable benefit / risk ratio, and is effective for its intended use.

[0026] The term "therapeutically acceptable salts" as used herein refers to water- or oil-soluble or dispersible salts or zwitterionic forms of the compounds disclosed herein that are therapeutically acceptable as defined herein. The salts can be prepared during the final isolation and purification of the compounds, or can be prepared separately by reacting the appropriate compound in the form of a free base with a suitable acid.

[0027] The phrase "therapeutically effective" is intended to modify the amount of active ingredient used to treat a disease or disorder or affect a clinical endpoint.

[0028] A "therapeutically effective amount" or "effective amount" of a composition is a predetermined amount calculated to achieve the desired effect, i.e., inhibiting, blocking, or reversing cell activation, migration, or proliferation. The activity contemplated by the present method includes both medical and / or prophylactic treatment, as appropriate. The particular dose of a compound administered in accordance with the present invention to obtain a therapeutic and / or prophylactic effect will, of course, be determined by the particular circumstances surrounding the case, including, for example, the compound administered, the route of administration, and the condition being treated. The compounds are effective over a wide dosage range, for example, the dosage per application will usually fall within the range of 0.001-10 mg / kg, more usually within the range of 0.01-1 mg / kg. However, it will be understood that the effective amount administered will be determined by the physician in light of the relevant circumstances, including the condition being treated, the choice of compound to be administered, and the chosen route of administration, and thus the above dosage ranges are not intended to limit the scope of the present invention in any way. A therapeutically effective amount of a composition of the invention is typically that amount which, when administered in a physiologically acceptable excipient composition, is sufficient to achieve an effective systemic concentration or local concentration in a tissue.

[0029] The terms "treat", "treated", "treat" or "treatment" as used herein refer to both therapeutic treatment and prophylactic or preventative measures, the purpose of which is to prevent or delay (alleviate) an undesirable physiological condition, disorder or disease, or to obtain a beneficial or desired clinical outcome. For purposes of the present invention, beneficial or desired clinical outcomes include, but are not limited to, alleviation of symptoms, reduction in the extent of the condition, disorder or disease; stabilization (i.e., not worsening) of the pathology, disorder or disease state, delay in onset or slowing of progression of the pathology, disorder or disease, improvement of the pathology, disorder or disease state, and remission (whether partial or total), whether detectable or undetectable, or enhancement or amelioration of the pathology, disorder or disease. Treatment includes eliciting a clinically significant response without undue side effects. Treatment also includes prolonging survival compared to the expected survival in the absence of treatment. Treatment may also be preemptive in nature, i.e., includes prevention of disease. Prevention of a disease may include complete protection from a disease, such as preventing infection with a pathogen, or may include preventing the progression of a disease. For example, prevention of a disease may not mean a complete blockage of all effects associated with the disease at any level, but instead may mean preventing symptoms of the disease to a clinically significant or detectable level. Prevention of a disease may also mean preventing the progression of a disease to a later stage.

[0030] The term "topical" includes administration to or suitable for administration to any skin or mucosal surface. In some embodiments, "topical" can be a skin surface. Skin surfaces include any part of the body, including but not limited to the face, hands, legs, neck, abdomen, eyes, nose, and chest. Mucosal surfaces include, but are not limited to, the mucosa of the mouth or buccal mucosa, lips, tongue, nose, buccal mucosa, palate, gums, nasopharynx, respiratory epithelium, conjunctiva, vagina, cervix, and urethral mucosa.

[0031] As used herein, the term "wound" is defined as damage to living tissue caused by a cut, blow or other impact.

[0032] The term "wound infection" is defined herein as a bacterial infection characterized by purulent drainage from the wound accompanied by surrounding redness, edema, pain, tenderness and / or induration.

[0033] Also provided are embodiments in which any embodiment herein may be combined with any one or more of the other embodiments, unless otherwise specified, and provided that the combinations are not mutually exclusive.

[0034] detail The chemical defense of plants involves a complex mixture of organic compounds, usually without the participation of individual substances; these compounds appear in different concentrations (majority or minority) in various products derived from natural species. The biological activity of these products is found to derive from their ability to interact with themselves and with other substances, through synergistic, additive or antagonistic effects, and can be optimized through the modification of the pharmacokinetics and / or pharmacodynamics of the constituent substances. The biological effect may result from the interaction with all the organic compounds or from the interaction between certain components. Thus, as described herein, AB101 consists of the whole latex obtained from Croton lechleri ​​trees, which is unfractionated, but selected based on the presence of selected components that meet the reference criteria, as described herein.

[0035] In the study of natural products, the role and mechanism of the main compounds in relation to their biological activity are generally studied. Thus, the scientific literature is filled with countless studies in which the main components were found to be responsible for these activities. However, this ignores the interactions of the whole set of compounds that may be present in low concentrations in natural products. In a study carried out with the essential oil Thymus vulgaris and its main component thymol, the effects of the oil's components were not phytotoxic to lettuce seeds, but the action of thymol alone caused a significant inhibitory effect on seed germination, raising the possibility of partial inhibition of thymol activity by other components of the oil. This shows the importance of considering the interactions between all the components of a product.

[0036] For example, the activity of the sap and three active components of Dracaena cochinchinensis was evaluated for analgesic activity via inhibition of capsaicin-induced TRPV1 channel currents. The authors found that the combination of the three active components of the sap was responsible for the analgesic activity of the species and that these components acted synergistically.

[0037] Another consideration regarding interactions between active ingredients of natural products is the ability to alter the pharmacokinetics of the ingredients compared to when these molecules are administered alone. This can be achieved by modifying the absorption, distribution, metabolism, and excretion profiles. One study reported the pharmacokinetic profile of chlorogenic acid and corilloin alone compared to DA-9701, a product formed with hydroalcoholic extracts of Pharbitis nil and Corydalis tubers. The results showed that when DA-9701 was administered orally, the AUC of corilloin was significantly increased compared to when the two compounds were administered orally alone. This increase in AUC could be explained by a reduced hepatic and / or gastrointestinal first-pass metabolism compared to pure corilloin. In addition, there may be an inhibition of presystemic metabolism of corticosteroids by other components of DA-9701.

[0038] Another example is the complexity of metabolic pathways, which may be directly related to the biological effects recorded in essential oils, extracts and herbal products. In a study with the essential oil of Eucalyptus tereticornis and its main components, it was observed that all three main components enhanced the contractile action of acetylcholine in rat trachea, whereas upon potassium stimulation the essential oil showed a relaxant effect, which may be due to the inhibition of acetylcholinesterase activity.

[0039] Croton lecleri (a member of the Euphorbiaceae family, commonly called the Euphorbiaceae) includes approximately 1,300 species of plants that may be herbaceous (plants with no woody stems above ground), shrubs (woody plants smaller than trees, with several main stems at or near the ground), arborescent (perennial plants with long slender stems or trunks supporting foliage in most species), or liana (a variety of long-stemmed woody climbing plants that are rooted in the soil above ground and use trees or other vertical means to climb up into the canopy to access lighter areas of the forest). The genus Croton is a diverse and complex group of flowering plants that range from herbs and shrubs to trees. Croton is widespread in tropical and subtropical regions around the world.

[0040] Dragon's blood is a deep red resin obtained from different species of several different plant genera: Croton, Dracaena, Daemonorops, Calamus lotan, Pterocarpus, etc. This red resin has been used since ancient times as a varnish, medicine, incense, and dye. The name Dragon's blood is used to refer to all the above plant genera, often without distinction of genus or species. Plants of the same genus have different therapeutic and nutritional properties depending on the soil, rainfall, humidity, sunshine, fauna, etc. However, the red resins of Croton and Daemonorops (a genus of rattan palm in the Arecaceae family found mainly in the tropical and subtropical regions of southeastern Asia, with a few species found in southern China and the Himalayas) are very different. As the genera Croton and Daemonorops are native to opposite ends of the globe, their composition is different and therefore the specificity of the original plant is important to obtain the desired medicinal properties or to avoid undesirable toxic consequences. For example, the milky latex is often toxic or at least irritating to the skin, which is common among plants in the Euphorbiaceae family, so the selection of specific genera, species and regions of Euphorbiaceae and Euphorbiaceae is essential to ensure that the latex has the potential to repeatedly exert a specific medicinal effect.

[0041] Croton species found in the rainforests of South America (Bolivia, Brazil, Colombia, Ecuador, Peru), Central America, and Mexico produce a red latex commonly known as dragon's blood, which has medicinal properties. Dragon's blood trees cultivated in these regions include Croton lecleri, Croton draco, Croton paranostigma, Croton sordidus, Croton ulculana, and Croton cisarapenesis.

[0042] In a particular embodiment, the particular dragon's blood tree of the present invention is Croton lechleri ​​Mull. Arg: Euphorbiaceae. Dragon's blood is also called Sangre de drago (Peru) and Sangre de grado (Ecuador).

[0043] The desired medicinal properties can be found by extracting the composition from either the leaves or the bark, but in a preferred embodiment, it comprises the crimson latex of Croton lechleri, preferably the filtered latex of Croton lechleri, preferably Croton lechleri ​​Mull.Arg, where the composition comprises at least the concentration of the components of the reference standard Croton lechleri ​​latex, also referred to as the utilized latex, preferably the concentration of the components of the filtered latex of Croton lechleri, preferably the concentration of the components of the filtered latex of Croton lechleri ​​Mull.Arg. According to Langenheim (2003), resin is a lipophilic mixture of volatile and non-volatile terpenoid and / or phenolic secondary compounds, usually secreted into specialized structures located within or on the surface of the plant, and has potential importance in ecological interactions. In contrast, latex is a mixture of terpenoids, phenolic compounds, acids, and carbohydrates that has a protective role (Lewisohn 1991) and is produced in specialized cells called laticifers (Fahn 1979). The chemical properties of dragon blood are species-specific and have been studied by many authors. For example, dragon blood used in art can be differentiated from several individual species, as it has been sold as a coloring agent for centuries (Baumer and Dietemann 2010). Dragon blood of the genus Croton is usually called latex, because it is secreted and stored by zooxanthellae, and its main components are polymeric anthocyanidins, coexisting with many minor components such as diterpenes and simple phenols (Salatino et al. 2007). Dragon's blood, secreted from the stems of Pterocarpus officinalis, is also called latex (Weaver 1997; Guerrero and Guzman 2004), but little information is known about the chemical composition of the exudate or its ecological function.Dragon's blood, from species of Dracaena and Daemonorops, is a phenolic resin (Langenheim 2003) whose chemical composition is well known (e.g. Gonzalez et al. 2000; Shen et al. 2007; Sousa et al. 2008). Dragon's blood is sometimes called latex (e.g. Philipson 2001). However, this is confusing because plants also produce other exudates that go by this name, such as xylem latex and stem latex, which are quite different in location, chemical composition, and function. The resin is obtained by tapping the tree or by other common drainage extraction methods. Drainage extraction of tree latex also has the advantage that it is not necessary to use complex and expensive extraction techniques to obtain the desired composition from leaves and bark. The Croton lechleri ​​Mull.Arg. latex of this application is then filtered through a 30 micron filter to remove plant debris and thick resinous material. The chemical characterization of Dragon's Blood is specific to the region and has not been performed by previous authors.

[0044] The medicinal and toxicological properties of various species of Croton are attributed to a wide variety of chemical compounds, such as terpenoids and steroids, alkaloids, and phenolic compounds, the latter mainly including flavonoids, lignans, and proanthocyanidins. In some embodiments of the present application, the whole latex is utilized to exploit the "organic" synergistic effects of all latex components as nature intended. The molecular classes found in the latex of Croton lechleri ​​Mull.Arg. of the present invention that provide the desired medicinal properties of Croton lechleri ​​Mull.Arg. are: alkaloids, diterpenes, lignins, phenols, phytosterols, proanthocyanidins, sterols, and tannins.

[0045] Hydrogel formulations must have a safety profile for use in topical applications that results in low systemic blood absorption (i.e., passage into the bloodstream) of the composition and a low partition coefficient, measured by LogP, for the absorbed composition. LogP represents the concentration of a solute in organic and aqueous partitioning. A lower LogP means a higher partition or concentration of aqueous solutes. This is desirable from a safety perspective. A higher LogP indicates that the composition is more likely to be absorbed and retained in the body via organs and tissues, whereas a lower LogP indicates a higher safety profile as the composition is not absorbed and retained but rather naturally excreted, which can lead to the accumulation of toxic compounds.

[0046] AB-101 is a novel dermatological agent derived from Croton lechleri ​​Mull.Arg. The novelty of this invention is the identification of a pharmaceutical AB-101 composition that has all of the performance characteristics described above to treat dermatological conditions and promote healing with an appropriate safety profile. This is a complex multivariate solution of optimizing multiple performance characteristics, the solution of which is not obvious to one of skill in the art.

[0047] In the embodiments disclosed herein, the Croton lechleri ​​latex utilized, preferably the filtered Croton lechleri ​​latex, preferably the filtered Croton lechleri ​​Mull.Arg. latex, is not fractionated but contains at least the concentrations of the specific components of the reference standard and performance standard as specified in Tables 1a-e.

[0048] AB-101 is a first-in-class broad-spectrum topical antibiotic in a new class of drugs called multi-targeted therapeutics (MTTs). The AB-101 platform utilizes the latex of Croton lechleri ​​(Mul.Arg), a plant native to the Amazon forest. This extract, or AB-101 botanical drug (BDS), contains multiple bioactive compounds.

[0049] Skin diseases in the general dermatology field include the treatment of skin and skin structure infections (SSSIs), also known as skin and soft tissue infections (SSTIs) and acute bacterial skin and skin structure infections (ABSSSIs). The pathogens involved are often bacteria and require antibiotic treatment. These skin infections can be acute or chronic, primary or secondary.

[0050] Common skin conditions include, but are not limited to, atopic dermatitis (AD), also known as atopic eczema or eczema, impetigo, and infections associated with complications of epidermolysis bullosa (EB). These are examples where bacterial pathogens are either the primary cause of the skin condition or are associated as a secondary complication. In each case, topical treatment to address bacterial pathogen skin conditions is the focus of the pharmaceutical grade AB-101 composition.

[0051] The need for more effective antibiotics stems from the problem of resistance to current antibiotic treatments. This is problematic for the two most commonly used topical antibiotics: mupirocin and fusidic acid. Increased use of mupirocin is associated with increased susceptibility to mupirocin resistance, which is significantly associated with persistent MRSA colonization. Mupirocin resistance has been reported to be as high as 81%. (T.Poovelikunnel et al.Mupirocin resistance: clinical implications and potential alternatives for the eradication of MRSA.J Antimicrob Chemother 2015; 70:2681-2692 doi:10.1093 / jac / dkv169 Advance Access publication July 3, 2015) Antibiotic resistance is a significant problem in both hospitals and the community. Topical antibiotics are widely used for dermatological conditions, which may lead to the emergence of resistance. (High levels of fusidic acid resistance in dermatology patients. Br J Dermatol.2003 May;148(5):1018-20.doi: 10.1046 / j.1365-2133.2003.05291.x.) Shah et al. reported that 50% of S. aureus isolated from dermatology patients were resistant to fusidic acid. This figure rose to 78% in patients with atopic eczema. Of patients from whom fusidic acid-resistant S. aureus was isolated, 96% had used fusidic acid-containing preparations within the past 6 months. The level of fusidic acid resistance in S. aureus cultured from nondermatology patients was only 9.6%, a level significantly lower than that of dermatology patients (P<0.001).

[0052] Eczema (infected and non-infected): A paper by Ogonowska, including many of the scholars he cites, sheds light on the role that the pathogen Staphylococcus aureus plays in exacerbating eczema. (Staphylococcus aureus colonization in patients with atopic dermatitis: an attempt to reveal the unknown. Frontiers in Microbiology. January 2021. Vol. 11. doi:10.3389 / fmicb.2020.567090.eCollection 2020). Some of the key issues regarding the treatment of atopic dermatitis (AD) / eczema highlighted by Ogonowska include: A chronic, relapsing inflammatory skin disease that may persist or emerge during adolescence or adulthood. AD is common in 15-30% of children and 2-10% of adults worldwide. Patients harbor a high burden of Staphylococcus aureus (S. aureus) in lesional and non-lesional skin. If left untreated, skin infections can spread throughout the body. Interestingly, the incidence of multidrug-resistant Staphylococcus aureus (MRSA) is higher in AD patients than in healthy individuals, making treatment even more challenging. High colonization rates of S. aureus were observed in both pediatric and adult groups, which increased with the severity of AD and acted as an exacerbating factor for inflammation. Among S. aureus isolates, methicillin-resistant S. aureus (MRSA) is a key group that deserves special attention. MRSA is a group of strains that are resistant to multiple β-lactam antibiotics (cephalosporins, carbapenems, monobactams, and penicillins). This phenotype limits treatment options, including for skin infections. It has been demonstrated that the proportion of MRSA among S. aureus strains colonizing AD patients is 4-13 times higher than in healthy controls. Carrying MRSA is the most well-known risk factor for developing infection, and the bacteria spreads further because MRSA is easily transmitted by direct skin contact in public places such as gyms. One of the main factors favoring the colonization of S. aureus is the change in the lipid and fatty acid composition of the skin. A significant decrease in ceramides and an increase in cholesterol were observed in the epidermis (especially in the stratum corneum). The decrease in lipid levels in the skin could explain the role of these components in maintaining skin moisture. To restore the proper barrier function of damaged skin, it is essential to maintain disturbed hydration of the epidermis. To this end, moisturizers containing emollients and humectants have been shown to reduce itching and inflammation, and even the need for anti-inflammatory agents.

[0053] Impetigo (infectious and non-infectious): Impetigo is the most common bacterial infection in children. This acute, highly contagious infection of the superficial layers of the epidermis is caused primarily by Streptococcus pyogenes or Staphylococcus aureus. Secondary infection from pre-existing skin lesions (cuts, abrasions, insect bites, chickenpox, etc.) can also occur. (Moulin F, Quinet B, Raymond J, Gillet Y, Cohen R. Managing children skin and soft tissue infections. Arch Pediatr.) These infections include methicillin-resistant Staphylococcus aureus (MRSA) (Moran GJ, Amii RN, Abrahamian FM, Talan DA. Methicillin-resistant Staphylococcus aureus in community-acquired skin infections. Emerg Infect Dis. 2005 Jun. 11(6):928-30). Impetigo is classified into non-bullous (impetigo) (about 70%) and bullous (Cole C, Gazewood J.Diagnosis and Treatment of impetigo.Am Fam Physician.2007 Mar 15.75(6):859-64) as shown in the figure below.

[0054] Topical antibiotics such as mupirocin and fusidic acid are commonly prescribed, but there are growing concerns that they contribute to antimicrobial resistance.

[0055] Epidermolysis Bullosa: EB is a rare genetic connective tissue disorder that affects 1 in 20,000 births in the United States (approximately 200 children are born with EB each year). Although there are many genetic and symptomatic variations of EB, all patients share the hallmark symptom of extremely fragile skin that blister and tear with minor friction or trauma. The list of complications and secondary diseases is long, requiring multiple interventions by a variety of medical specialists. EB affects all genders, races, and ethnicities equally.

[0056] Patients with epidermolysis bullosa (EB), a genetic blistering disease, often have chronic wounds that can be colonized by a variety of bacteria, particularly the opportunistic pathogen Staphylococcus aureus. We therefore investigated the prevalence of S. aureus colonization in swabs taken from the anterior nares, pharynx, and wounds of EB patients in the Netherlands. Within approximately 2 years, more than 90% of chronic wounds from EB patients were colonized with S. aureus. Molecular typing showed that EB patients were not contaminated with a single type of S. aureus. Rather, the population structure of S. aureus in the sampled EB patients reflected the population structure of S. aureus in the Netherlands. (Magdalena M. van der Kooi-Pola et al., Host-pathogen interactions in epidermolysis bullosa patients contaminated with S. aureus, J Med Microbiol.2014 Mar;304(2):195-203)

[0057] Although EB is a more severe and specific skin disease than eczema or impetigo, they share the need to fight bacterial infection. Treatment with topical antibiotics, particularly those highly effective against Staphylococcus aureus and MRSA, is effective in treating infections in all three of these life-threatening skin diseases.

[0058] Psoriasis is a skin disease that causes red, itchy, scaly patches, commonly found on the knees, elbows, trunk, and scalp. As defined by the Mayo Clinic, psoriasis is a common, long-term (chronic) disease with no cure. Most cases of psoriasis occur in cycles that last for weeks to months, followed by periods of relief and remission. Signs and symptoms of psoriasis vary from person to person. Common signs and symptoms include: 1. red patches of skin covered with thick, silvery scales; 2. small scaly patches (common in children); 3. dry, cracked skin that bleeds and itches; 4. itching, burning, and pain; 5. thickened, pitted, or raised nails; and 6. swollen or stiff joints. Psoriasis patches can range from a few spots with dandruff-like scales to a large rash that covers a large area. The most commonly affected areas are the hips, elbows, knees, legs, soles of the feet, scalp, face, and palms.

[0059] Secondary bacterial infections can complicate psoriatic lesions, as reported by S.Lafi et al. Such infections can progress rapidly and become life-threatening. Hassan studied the current prevalence of secondary bacterial infections in psoriasis and also highlighted new trends related to antimicrobial resistance. (Lafi, S., Hasan, A., Al-Alowssi, M. (2010). Secondary bacterial infections complicating psoriasis. Egyptian Academic Journal of Biological Sciences, G. Microbiology, 2(2), 37-42).

[0060] Another study by Eva Marcus showed that nearly half of the patients surveyed had psoriatic plaques colonized with pathogenic bacteria. Examination of the bacterial flora in psoriasis has focused on the demonstration of Staphylococcus aureus, with a prevalence of up to 64% in the lesional skin of patients with psoriasis vulgaris. Correspondingly, Staphylococcus aureus has also been found as the most common bacterium in patients with hyperinfective pustular psoriasis. In this study, 31% of the bacteria were gram-positive and 9% were gram-negative. (Marcus, E., Demmler, D., Rudolph, A., & Fischer, M. (2011). Bacterial colonization of psoriatic plaques. Is there a connection? Dermatology reports, 3(2)).

[0061] AB-101 is an important topical treatment to reduce and cure psoriasis symptoms. Staphylococcus aureus is the most commonly isolated pathogen in psoriatic lesions, and AB-101 has been shown to be highly effective. Furthermore, with the increase in multidrug resistance, especially S. aureus, the presence of MRSA is also on the rise. Its effectiveness against gram-negative bacteria also contributes to the positive role of AB-101. With new MDR topical treatments against secondary bacterial invasion to prevent the development of fatal systemic infections, AB-101 will be an excellent antibiotic treatment for psoriasis.

[0062] Pathogen colonization has been described in detail by Sunhyo Ryu (Syu, P.I. Song, CH.Seo, H.Cheong and Y.Park, Colonization and Infection of the Skin by S.aureus: Immune System Evasion and Response to Cationic Antimicrobial Peptides, Int.J.Mol.Sci.2014,15,8753-8772). The colonizing pathogens are mainly related to Staphylococcus aureus and MRSA, and AB-101 is an effective and novel therapeutic agent against these pathogens.

[0063] Ryu details the causes, mechanisms, and risks of E. coli-infected S. aureus and MRSA. Specifically, S. aureus is a widespread skin pathogen that accounts for the majority of human skin bacterial infections. The incidence of S. aureus-induced skin infections reflects the competition between the host's skin immune defenses and S. aureus' virulence factors. S. aureus inhabits the skin, nose, and pharynx as a commensal flora. Approximately 30% of healthy individuals are asymptomatically contaminated with S. aureus, of which 10%-20% are contaminated permanently in the anterior nares, 30%-50% are contaminated intermittently, and the rest of the population is never contaminated. Importantly, S. aureus causes a variety of infections ranging from mild skin infections to abscesses, endocarditis, and sepsis, making it a major cause of hospital-acquired infections. Furthermore, several cases of community-acquired methicillin-resistant S. aureus (CA-MRSA) infections have been reported recently. These reports have described severe and even fatal infections with highly virulent S. aureus in immunocompromised patients.

[0064] MRSA infections are caused by strains of Staphylococcus aureus that have become resistant to antibiotics commonly used to treat routine infections. Most MRSA infections occur in hospitals and other healthcare settings, such as nursing homes and dialysis centers. When they occur in these settings, they are called healthcare-associated MRSA (HA-MRSA). HA-MRSA infections are usually associated with invasive procedures and devices, such as surgery, IV tubing, and artificial joints. However, another type of MRSA infection occurs in the wider community, among healthy people. Community-acquired MRSA (CA-MRSA) is transmitted by skin-to-skin contact. It often begins as a painful skin swelling and typically causes skin and soft tissue infections, but can also cause invasive diseases such as endocarditis, necrotizing pneumonia, and sepsis. HA-MRSA, in contrast, is considered a hospital-acquired pathogen that is usually associated with invasive diseases, such as bloodstream infections, pneumonia, surgical site infections, and urinary tract infections.

[0065] AB-101 with MTT is a novel and important antibiotic to combat colonizing S. aureus and MRSA, as associated with disorders caused by S. aureus and MRSA nasal passages or ear canals, as a pre-operative irrigant to prevent the occurrence of SSTI or sepsis, and in any other application to those skilled in the art related to conditions that can prevent the spread and clearance of colonizing S. aureus and MRSA.

[0066] AB-101 is an effective treatment for wounds, including superficial cuts and abrasions, as well as chronic infections. Chronic infections and wounds include, but are not limited to, diabetic ulcers, arterial ulcers, venous ulcers, mixed arterial-venous ulcers, and pressure ulcers. Those familiar with these infections and wounds are well aware that they are infected by gram-positive pathogens related to Staphylococcus aureus (S. aureus), Methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes (S. pyogenes), and Pseudomonas aeruginosa (P. aeruginosa) gram-negative pathogens. Furthermore, chronic wounds are very complex and difficult to heal. Killing bacteria is a critical component to allow the healing process. The fact that AB-101 is effective against both gram-positive and gram-negative pathogens, along with AB-101's MTT properties, provide it with unique efficacy as a drug compound.

[0067] AB-101 is a first-in-class broad-spectrum topical antibiotic in a new class called Multi-Targeted Therapeutics (MTT). AB-101 Botanical Drug (BDS) extract has multiple bioactive compounds, making it a highly effective antibiotic ideal for treating topical skin infections. An overview of indications for which AB-101 is effective is provided in Table A along with relevant pathogens and detailed diseases causing SSTIs and wound infections. [Table 1]

[0068] AB-101 exhibited an unexpected and unique safety profile based on its physical properties, allowing for maximization of drug delivery while enhancing the safety profile. This unexpected discovery is contrary to common understanding in the art. It is a common belief in the art that to formulate a safe and effective drug, the dosage should be as low as possible while still achieving the desired efficacy. This is the exact opposite with AB-101. By maximizing dosage, safety is also synergistically maximized. This, combined with the fact that the lipophilic components of AB-101 are absorbed through the skin and only the hydrophilic components are likely available for bloodstream absorption, enhances the safety of AB-101. As a result, any AB-101 absorbed into the bloodstream is naturally and easily eliminated by normal bodily functions. There is also negligible systemic absorption, reducing safety risks. This makes AB-101 a highly potent and highly effective antibiotic designed for the treatment of local skin symptoms of SSTIs.

[0069] Some embodiments herein are directed to a method for identifying a composition of Croton lechleri ​​latex, preferably a composition of Croton lechleri ​​filtered latex, preferably a composition of Croton lechleri ​​Mull.Arg filtered latex, comprising the steps of: (a) determining the concentration of a component of Croton lechleri ​​latex, preferably a component of Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg; (b) comparing the concentration of the component with the concentration of the component of a reference standard; and c) determining the composition of Croton lechleri ​​latex, preferably a composition of Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg, wherein the composition is at least equal to the concentration of a component of Croton lechleri ​​latex, preferably a component of Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg, of the reference standard. Contains the concentrations of components of filtered latex from Mull.Arg.

[0070] Some embodiments herein are directed to a method of identifying a Croton lekreri latex composition, preferably a Croton lekreri filtered latex composition, preferably a Croton lekreri Mull.Arg filtered latex composition, for use in treating a dermatological condition in a subject, comprising the steps of: (a) determining the concentration of a component of the Croton lekreri latex, preferably the concentration of a component of the Croton lekreri filtered latex, preferably the concentration of a component of the Croton lekreri Mull.Arg filtered latex; (b) comparing the concentration of the component of the Croton lekreri latex to the concentration of the component of a reference standard; and (c) identifying the Croton lekreri latex composition, preferably the Croton lekreri Mull.Arg filtered latex composition. Arg; (b) comparing the concentrations of the components with the concentrations of the components of a reference standard; and (c) a composition of Croton lechleri ​​latex, preferably a composition of filtered Croton lechleri ​​latex, preferably Croton lechleri ​​Mull.Arg, which composition comprises at least the concentrations of the components of the Croton lechleri ​​latex of the reference standard, preferably the concentrations of the components of the filtered Croton lechleri ​​latex, preferably the concentrations of the components of the filtered Croton lechleri ​​Mull.Arg.

[0071] Some embodiments herein include a composition of Croton lechleri ​​latex, preferably a composition of filtered Croton lechleri ​​latex, preferably Croton lechleri ​​Mull.Arg, comprising the steps of: (a) determining the concentrations of components of the Croton lechleri ​​latex, preferably the concentrations of components of the filtered Croton lechleri ​​latex, preferably Croton lechleri ​​Mull.Arg; (b) comparing the concentrations of the components with the concentrations of the components of a reference standard; and (c) determining the concentrations of the components of the Croton lechleri ​​latex, preferably the composition of filtered Croton lechleri ​​latex, preferably Croton lechleri ​​Mull.Arg, comprising the steps of: (a) determining the concentrations of the components of the Croton lechleri ​​latex, preferably the concentrations of the components of the filtered Croton lechleri ​​latex, preferably Croton lechleri ​​Mull.Arg; (b) comparing the concentrations of the components with the concentrations of the components of a reference standard; and Identifying a composition of filtered latex of Mull.Arg. A composition for use in treating or preventing or reducing the risk of a dermatological condition in a subject, the composition comprising at least a concentration of a component of Croton lechleri ​​latex of a reference standard, preferably a concentration of a component of Croton lechleri ​​filtered latex, preferably a concentration of a component of Croton lechleri ​​Mull.Arg filtered latex.

[0072] In certain embodiments, the particular dragon's blood tree of the present invention is Croton lechleri ​​Mull.Arg: Euphorbiaceae. Dragon's blood is also called Sangre de drago (Peru) and Sangre de grado (Ecuador). Embodiments of the present invention are directed to hydrogel formulations of Croton lechleri ​​latex, preferably filtered Croton lechleri ​​latex, preferably filtered Croton lechleri ​​Mull.Arg. and a pharmaceutically acceptable excipient. Such hydrogel formulations have been found to be useful in the successful treatment of dermatological conditions therewith. In some embodiments, the hydrogel formulations are administered topically. In some embodiments, the hydrogel formulations are administered intranasally. The embodiments relate to the method of making and using the compounds and compositions, which are Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg, and the composition comprises at least the concentration of the components of the reference standard Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg filtered latex, disclosed herein, together with a pharma- ceutically acceptable carrier. Particular embodiments are directed to a method for inhibiting a dermatological condition. Other embodiments are directed to a method for treating a dermatological condition in a patient in need of such treatment, comprising administering to said patient a therapeutically effective amount of a composition according to the invention. Also provided is the use of a particular extract of Croton lechleri ​​disclosed herein in the manufacture of a medicament for the treatment of a dermatological condition.

[0073] Hydrogel formulation Embodiments herein are directed to a hydrogel formulation comprising Croton lekreli latex, preferably Croton lekreli filtered latex, preferably Croton lekreli Mull.Arg filtered latex, wherein the composition comprises at least the concentrations of the components of the Croton lekreli latex of a reference standard, preferably the concentrations of the components of the Croton lekreli filtered latex, preferably the concentrations of the components of the Croton lekreli Mull.Arg filtered latex.

[0074] The preferred therapeutic agent should be potent and have the ability to readily deliver broad spectrum antibiotic activity including Staphylococcus aureus, MRSA, and Streptococcus pyogenes. The antibiotic should be readily released from the carrier, and the carrier should aid in retaining the antibiotic active ingredient on the skin. The amount of antibiotic should be at a substantial high level to achieve complete kill, to minimize the development of antimicrobial resistant organisms. The carrier should moisturize the affected area and help the skin return to a normal state. The IDEA delivery system seals in moisture like a liquid bandage, protecting the injured area. The AB-101 topical antibiotic delivery system was developed to provide a combination of these novel and unexpected performance properties in one product to promote healing and resolution of these dermatological skin conditions.

[0075] The AB-101 topical antibiotic carrier system uses hydrogel therapeutic carriers and structures and can be incorporated into, but not limited to, ointments, gels, mousses, creams and spray forms. Hydrogels containing AB-101 can be incorporated into dressings, sponges, tapes, patches or bandages. AB-101 can be delivered via, but not limited to, tubes, pumps, jars, manual / mechanical sprays or aerosol packaging and delivery systems. The hydrogel delivery system is designed to rapidly release AB-101 pharmaceutical grade antibiotic, with maximum delivery to ensure efficacy and safety. Hydrogels are effective moisturizers due to their high water content, and the combination of the film-forming properties of AB-101 with the hydrogel facilitates the formation of a liquid bandage.

[0076] AB-101 can be used neat or undiluted as a topical antibiotic to treat skin conditions. In this form, AB-101 is thin and watery. The benefits of converting and formulating AB-101 into a hydrogel provide the known benefits of hydration along with unexpected novel benefits related to performance efficacy, improved safety profile, improved application, ease of administration, and promotion of protective liquid dressing properties.

[0077] Dosing to maximize the effectiveness of AB-101 is a key requirement to ensure optimal performance. Eradication of all targeted bacteria is essential to avoid or at least minimize the promotion of antibiotic resistance. Specifically, antibiotic doses are designed to eradicate the entire population of pathogens. If antibiotics are not taken for the entire prescribed course, pathogenic bacteria can adapt to the presence of low doses of antibiotics and eventually form populations that are completely resistant to the antibiotic regardless of the dose. This means that the design of the hydrogel carrier must incorporate the maximum thermodynamically stable level of AB-101 pharmaceutical grade. This requires clear formulation techniques in the art and intensive experimentation to identify the ideal formulation.

[0078] The final pH of hydrogels containing AB-101 is in the range of 4.0 to 6.7, a range that provides both skin health and antimicrobial benefits.

[0079] All hydrogel components and additives used in AB-101 formulations must meet specifications appropriate for cosmetic grade or pharmaceutical grade carriers suitable for dermatological applications. Additionally, to ensure that AB-101 hydrogel is mild, it does not use more than about 2 wt% monohydroxy alcohols, including but not limited to methanol, ethanol, propanol, denatured alcohol, and alkoxylated cetyl alcohol. The antibiotic activity of AB-101 hydrogel formulations depends primarily on the level of AB-101, not at initial levels where all formulations have levels of AB-101 ranging from 5% to 50%. AB-101 hydrogel formulations do not rely on cromoglycic acid or its salts as the active ingredient to treat dermatitis. Secondary antibiotic components can also be included in the formulation, as well as ingredients that help promote skin health, such as vitamins, emollients, hyaluronic acid, propylene glycol, proteins, and urea, and ingredients that lock in moisture, such as lanolin, mineral oil, and petrolatum.

[0080] Croton lechleri, Sangre de Drago, Dragons Blood, etc. are used and formulated into hydrogels. Vasquez studied the wound healing effect of Sepigel-based hydrogels. The levels of Croton lechleri ​​used were 0.5% to 2%. (Guillermo Jose Gallardo Vasquez, Bach.Laura Barboza Mejia, Healing effect of the gel made from the latex of Croton lechleri"Blood of Drago",Rev Cient Cienc Med 2015;18(1):10-16). This gel cannot be used for eczema. The Croton lechleri ​​content is too low and the pH of these formulations is 6.8-6.9. Also, the gel is formulated with ethyl alcohol, which may reduce its mildness. Vasquez does not mention antibiotic activity. The levels of Croton lekleri from an antibiotic standpoint are considered to be early or ineffective levels that are not effective in eradicating bacterial infections and possibly allowing for antibiotic resistance. The pH levels are too high and do not promote the ideal levels for skin health, while actually promoting an environment favorable for the growth of Staphylococcus aureus and MRSA.

[0081] Bobrowski (US 7,883,727) describes the use of CGO 110, an extract of Croton lechleri, as a treatment for vomiting and itching. CGO 110 has a reduced proanthocyanidin content to eliminate the reddish-brown color and is therefore structurally different from AB-101 via its reduced proanthocyanidin levels. CGO 110 is formulated in "Aloe barbadensis gel for topical application for various inflammatory, itchy and inflammatory dermatological uses." Aloe barbadensis gel is similar in nature to Aloe vera gel and is not considered a hydrogel (https: / / puracy.com / blogs / ingredients / aloe-barbadensis, February 2021). The level of CGO 110, an extract of Croton lechleri, is less than 2% in Aloe barbadensis gel. The topical gel described by Bobrowski should not be confused with hydrogels designed to deliver AB-101.

[0082] Palacios Pelaez et al. (US 2019 / 0240193) formulated aloe vera gel for the skin treatment of atopic dermatitis, finding an unexpected synergy between low levels of croton lekleri and panthenol and a sodium cromoglycate formulation using alkoxylated cetyl alcohol as an essential ingredient. The croton lekleri used is in the form of a hydroglycolic solution (water and propylene glycol), with the croton lekleri already diluted to 1% to 5% by weight. This solution is further diluted in Pelaez's embodiments, so that the croton lekleri is significantly less than 2% of the total formulation when the composition uses aloe vera gel. These embodiments rely on the synergistic effect of sodium cromoglycate, which is not present in the AB-101 hydrogel composition.

[0083] The pharmaceutical AB-101 composition utilizes Croton lechleri ​​Mull.Arg latex. There are many examples in the art where Croton lechleri ​​Mull.Arg latex has been fractionated and individual components isolated or individual components minimized or removed. This may be the result of the specific application. For pharmaceutical grades of AB-101, it is preferable to use the whole extract to take advantage of the synergistic effects associated with all of the active compounds.

[0084] Importantly, the variability of all compounds varies greatly depending on geography, environment, soil, altitude, age of the tree, etc. These variations are highlighted by Thiago Vaz Lopes, Dragon's blood (Croton lechleri ​​MUll.Arg; An Update on the Chemical Composition and Medical Applications of This Natural Plant Extract, Revista Brasileira de Higiene and Animal Health (v.7,n2) p.167-192 (2013)).

[0085] The novelty of AB-101 is based on the in vitro confirmation by bioassays of the association of specific compounds in AB-101 with their concentration levels, and the confirmation by human trials that they are effective therapeutic agents for wound healing, bleeding treatment, and infection control. The utility of this new discovery is the basis for the development of medicines and drugs that meet FDA standards.

[0086] The FDA requires bioassays to be conducted that correlate the performance of the botanical material, based on the chemical properties of the composition and changes therein, with its effectiveness in treating wounds, treating bleeding, and fighting infections.

[0087] Croton lechleri ​​MUll.Arg latex is complex, difficult to define and tricky to understand because its composition uses a full accompaniment of all the bioactive substances that make up Croton lechleri ​​MUll.Arg latex. Net, new discoveries are needed to find important activity markers and performance and safety tests.

[0088] "The FDA requires the identification of important biomarkers or active ingredients that drive biological activity. Therefore, important biomarkers and their associated concentrations for AB-101 have never been published, defined, or identified as they relate to wound healing properties, antimicrobial activity, wound treatment, bleeding treatment, or infection control safety. Without this information, the FDA would not grant drug status, which is the core of what makes a drug."

[0089] "Drug" means any product, compound, drug or therapeutic agent that is regulated as a drug or controlled substance by a foreign equivalent of the U.S. Food and Drug Administration (FDA).

[0090] The FDA's botanical drug guidance states: Due to the heterogeneous nature of botanical medicines and potential uncertainty about their active ingredients, one of the key issues with botanical medicines is ensuring consistency of therapeutic effect among marketed drug batches. In general, consistency of therapeutic effect is supported by a "total of evidence" approach that includes consideration of the following: -Management of plant materials (e.g. agricultural practices, collection, etc.). -Quality control through chemical testing (e.g. analytical tests such as spectroscopic and / or chromatographic methods that capture the active chemical components of the botanical medicine) and manufacturing controls (e.g. process validation). - Biological test methods (e.g., biological test methods that reflect the drug's known or intended mechanism of action) and clinical data (for details on the use of clinical data to ensure consistency of treatment).

[0091] Using whole Croton lechleri ​​MUll.Arg latex provides unique synergistic benefits across the entire composition to meet specific bioassay performance goals. Table B shows the 16 bioactives contained in the pharmaceutical grade of AB-101. These bioactive compounds provide benefits including antibacterial, antiviral, anti-inflammatory, cell proliferation to promote healing, anticancer, hemostatic, antioxidant, and fibroblast stimulating properties to promote healing. Maintaining the latex of Croton lechleri ​​MUll.Arg provides significant synergistic benefits in wound healing and infection prevention.

[0092] Table B shows the Croton lechleri ​​MUll.AB-101 Arg latex and its properties. [Table 2]

[0093] Some embodiments herein are directed to hydrogel formulations comprising Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg. filtered latex, wherein the composition comprises at least the Croton lechleri ​​latex component concentrations of the reference standard, preferably Croton lechleri ​​filtered latex component concentrations, preferably Croton lechleri ​​Mull.Arg. filtered latex component concentrations, and pharma- ceutically acceptable excipients, of the embodiments herein. Optionally, the hydrogel formulation may further comprise one or more other therapeutic components. In an embodiment, the hydrogel formulation comprises a therapeutically effective amount of Croton lekleri latex, preferably Croton lekleri filtered latex, preferably Croton lekleri Mull.Arg filtered latex, and the composition comprises at least the concentration of the components of the Croton lekleri latex of a reference standard, preferably the concentration of the components of the Croton lekleri filtered latex, preferably the concentration of the components of the Croton lekleri Mull.Arg filtered latex. In an embodiment, the hydrogel formulation is suitable for topical administration or is a topical hydrogel formulation. In some embodiments, the Croton lekleri latex, preferably Croton lekleri filtered latex, preferably Croton lekleri Mull.Arg filtered latex, has a PDI of the embodiments disclosed herein.

[0094] Embodiments herein are directed to hydrogel formulations comprising: comprising Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg filtered latex, wherein the composition comprises at least the concentrations of components of the Croton lechleri ​​latex, preferably the concentrations of components of the Croton lechleri ​​filtered latex, preferably the concentrations of components of the Croton lechleri ​​Mull.Arg filtered latex of a reference standard; water; one or more preservative enhancing humectants; one or more chelating agents; one or more dispersing agents / co-emulsifiers; one or more preservatives; one or more emollients; one or more de-flocculating agents; one or more thickening / stabilizing / emulsifying / texturing agents; and Optionally, one or more pH adjusters.

[0095] Embodiments herein are directed to a hydrogel formulation comprising Croton lekleri latex, preferably Croton lekleri filtered latex, preferably Croton lekleri Mull.Arg filtered latex, wherein the composition comprises at least a concentration of components of Croton lekleri latex, preferably a concentration of components of Croton lekleri filtered latex, preferably a concentration of components of Croton lekleri Mull.Arg filtered latex, reference standard Arg, propanediol, disodium edetate dihydrate, methylparaben, propylparaben, water, dimethicone, caprylic / capric triglyceride, SEPINEO™ P600 (acrylamide / sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80).

[0096] Embodiments herein are directed to a hydrogel formulation comprising Croton lekleri latex, preferably Croton lekleri filtered latex, preferably Croton lekleri filtered latex Mull.Arg., the composition comprising at least the concentration of the components of Croton lekleri latex, preferably the concentration of the components of Croton lekleri filtered latex, preferably the concentration of the components of Croton lekleri filtered latex, preferably the concentration of the components of Croton lekleri filtered latex, preferably the concentration of the components of Croton lekleri filtered latex, preferably the concentration of the components of Croton lekleri filtered latex, Hydrate, PHOSAL® 50PG (Phosphatidylcholine, Lysophosphatidylcholine, Propylene Glycol, Sunflower Seed Oil Glycerides, Ethanol, Soybean Fatty Acids, Ascorbyl Palmitate, D,L-α-Tocopherol), Methylparaben, Propylparaben, Water, Dimethicone, Caprylic / Capric Triglyceride, SEPINEO™ P600 (Acrylamide / Sodium Acryloyldimethyltaurate Copolymer / Isohexadecane / Polysorbate 80), Sodium Benzoate, Potassium Sorbate, Trollamine.

[0097] Embodiments herein are directed to a hydrogel formulation comprising Croton lekleri latex, preferably Croton lekleri filtered latex, preferably Croton lekleri filtered latex Mull.Arg., the composition comprising at least the concentration of the components of Croton lekleri latex, preferably the concentration of the components of Croton lekleri filtered latex, preferably the concentration of the components of Croton lekleri filtered latex, preferably the concentration of the components of Croton lekleri filtered latex, preferably the concentration of the components of Croton lekleri filtered latex, preferably the concentration of the components of Croton lekleri filtered latex, Ingredients include: sodium dihydrate, PHOSAL® 50PG (phosphatidylcholine, lysophosphatidylcholine, propylene glycol, sunflower seed oil glycerides, ethanol, soybean fatty acids, ascorbyl palmitate, D,L-alpha-tocopherol), methylparaben, propylparaben, water, dimethicone, caprylic / capric triglyceride, SEPINEO™ P600 (acrylamide / sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80), sodium benzoate, potassium sorbate.

[0098] Embodiments herein are directed to a hydrogel formulation comprising a latex of Croton lekleri, preferably a filtered latex of Croton lekleri, preferably a filtered latex of Croton lekleri Mull.Arg, wherein the composition comprises at least the concentrations of the components of the latex of Croton lekleri, preferably the concentrations of the components of the filtered latex of Croton lekleri, preferably the concentrations of the components of the filtered latex of Croton lekleri Mull.Arg, reference standard, propanediol, disodium edetate dihydrate, methylparaben, propylparaben, water, dimethicone. , caprylic / capric triglyceride, SEPINEO™ P600 (acrylamide / sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80), where the Croton lecleri contains at least about 110 PPM gallocatechin, at least about 780 PPM epigallocatechin, at least about 1.6 PPM catechin, at least about 2 PPM epicatechin, at least about 45 PPM taspine, and at least about 0.1 PPM dimethylcedrusine, and where the Croton lecleri has a polydispersity index of about 0.5 to about 0.85.

[0099] Embodiments herein are directed to a hydrogel formulation comprising Croton lekleri latex, preferably Croton lekleri filtered latex, preferably Croton lekleri filtered latex Mull.Arg., the composition comprising at least the concentrations of the components of Croton lekleri latex, preferably the concentrations of the components of Croton lekleri filtered latex, preferably the concentrations of the components of Croton lekleri filtered latex, preferably the concentrations of the components of Croton lekleri filtered latex, preferably the concentrations of the components of Croton lekleri filtered latex, preferably the concentrations of the components of Croton lekleri filtered latex, Ingredients include: PG (phosphatidylcholine, lysophosphatidylcholine, propylene glycol, sunflower seed oil glyceride, ethanol, soybean fatty acid, ascorbyl palmitate, D,L-α-tocopherol), methylparaben, propylparaben, water, dimethicone, caprylic / capric triglyceride, SEPINEO™ P600 (acrylamide / sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80), sodium benzoate, potassium sorbate, trolamine, wherein the croton reclary is at least about 110% by weight. at least about 780 PPM gallocatechin, at least about 780 PPM epigallocatechin, at least about 1.6 PPM catechin, at least about 2 PPM epicatechin, at least about 45 PPM taspine, and at least about 0.1 PPM dimethylcedrusine, and has a polydispersity index of about 0.5 to about 0.85.

[0100] Embodiments herein are directed to a hydrogel formulation comprising Croton lekleri latex, preferably Croton lekleri filtered latex, preferably Croton lekleri filtered latex Mull. Arg., the composition comprising at least a concentration of Croton lekleri latex components, preferably a concentration of Croton lekleri filtered latex components, preferably a concentration of Croton lekleri filtered latex components, preferably a concentration of Croton lekleri filtered latex components, preferably a concentration of Croton lekleri filtered latex components, preferably a concentration of Croton lekleri filtered latex components, preferably a concentration of Croton lekleri filtered latex components, preferably a concentration of Croton lekleri filtered latex components, , ascorbyl palmitate, D,L-α-tocopherol), methylparaben, propylparaben, water, dimethicone, caprylic / capric triglyceride, SEPINEO™ P600 (acrylamide / sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80), sodium benzoate, potassium sorbate, wherein the Croton lecleri contains at least about 110 PPM gallocatechin, at least about 780 PPM epigallocatechin, at least about 1.6 PPM catechin, at least about 2 PPM epicatechin, at least about 45 PPM taspine, and at least about 0.1 PPM dimethylcedrusin, and wherein the Croton lecleri has a polydispersity index of from about 0.5 to about 0.85.

[0101] Embodiments herein are directed to a hydrogel formulation comprising Croton lekleri latex, preferably Croton lekleri filtered latex, preferably Croton lekleri filtered latex Mull.Arg., wherein the composition comprises at least a concentration of the components of Croton lekleri latex, preferably a concentration of the components of Croton lekleri filtered latex, preferably a concentration of the components of Croton lekleri filtered latex, preferably a concentration of the components of Croton lekleri filtered latex Mull.Arg., a reference standard, glycerin, methylparaben, propylparaben, water, sodium phosphate dibasic Heptahydrate, Sodium Phosphate Monobasic, Sodium Hexametaphosphate, Medium Chain Triglycerides, SEPINEO™ P600 (Acrylamide / Sodium Acryloyldimethyltaurate Copolymer / Isohexadecane / Polysorbate 80), wherein the Croton lecleri contains at least about 110 PPM gallocatechin, at least about 780 PPM epigallocatechin, at least about 1.6 PPM catechin, at least about 2 PPM epicatechin, at least about 45 PPM taspine, at least about 0.1 PPM dimethylcedrusine, and wherein the Croton lecleri has a polydispersity index of about 0.5 to about 0.85.

[0102] In some embodiments of the hydrogel formulation, the filtered latex of Croton lechleri ​​is filtered latex of Croton lechleri ​​Mull.Arg.

[0103] In certain embodiments, the Croton lechleri ​​latex, preferably the Croton lechleri ​​filtered latex, preferably the Croton lechleri ​​Mull.Arg. filtered latex, comprises one or more compounds selected from gallocatechin, epigallocatechin, catechin, epicatechin, taspine, and dimethylcedrusin, and combinations thereof.

[0104] Each of gallocatechin, epigallocatechin, catechin, epicatechin, taspine, and dimethylcedrusine may be present in the Croton lechleri ​​latex, preferably the filtered Croton lechleri ​​latex, preferably the filtered Croton lechleri ​​Mull.Arg. latex, in at least the amounts found in Table 1a, or any combination of such amounts.

[0105] Embodiments herein are directed to a hydrogel formulation comprising Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg. filtered latex, and a pharma- ceutically acceptable excipient. In certain embodiments, Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg. filtered latex, comprises one or more compounds selected from gallocatechin, epigallocatechin, catechin, epicatechin, taspine, and dimethylcedrusin, and combinations thereof. Each of gallocatechin, epigallocatechin, catechin, epicatechin, taspine and dimethylcedrusine may be present in the Croton lechleri ​​latex, preferably the Croton lechleri ​​filtered latex, preferably the Croton lechleri ​​Mull.Arg. filtered latex, in at least the amounts found in Table 1a or any combination of such amounts.

[0106] As shown in Table B, AB-101 contains a broad range of compounds. The primary bioactive reference compounds in pharmaceutical grade AB-101 are gallocatechin, epigallocatechin, catechin, epicatechin, taspine, and dimethylcedrutin. Of particular importance is a secondary set of polyphenol bioactivities consisting of the gallates, including catechin gallate (CG), epicatechin gallate (ECG), gallocatechin gallate (GCG), and epigallocatechin gallate (EGCG). The gallate bioactivity profile of particular importance in AB-101 is antimicrobial and antioxidant activity. These properties are Rahardiyan, Dino. (2018), Antibacterial potential of catechin of tea(Camellia sinensis) and its applications, Food Research.3.1-6, and Multifunctional Antioxidant Activities of Alkyl Gallates The Open Bioactive Compounds Journal,2010,3:1-11 Isao Kubo, Noriyoshi Masuoka, Tae Joung Ha, Kuniyoshi Shimizu, Ken-ichi Nihei.

[0107] From a composition standpoint, the primary and secondary bioactives make up 80% to 99% of the pharmaceutical grade concentration composition of AB-101, with the remaining uncharacterized compounds making up the entire remainder of AB-101. Of these, the gallate bioactive family accounts for 1% to 20% of the bioactivity. For AB-101 Lot 01, the reference range for primary bioactivity is 85% to 90%, the secondary reference range is 3% to 4%, and the total uncharacterized compounds in AB-101 is 7% to 11%.

[0108] Croton lechleri ​​Mull.Arg latex exerts unique synergistic effects across the composition to achieve specific bioassay performance goals. The primary reference standard is the main focus of the pharmaceutical grade of AB-101 bioactivity, while the secondary reference standard demonstrates the biodiversity, polydispersity, and synergistic composition within AB-101 that also contribute to AB-101 efficacy.

[0109] [Table 3]

[0110] [Table 4]

[0111] [Table 5]

[0112] [Table 6]

[0113] [Table 7]

[0114] If the Croton lechleri ​​latex, preferably the filtered Croton lechleri ​​latex, preferably the filtered Croton lechleri ​​Mull.Arg. latex does not contain at least the amounts of gallocatechin, epigallocatechin, catechin, epicatechin, taspine and dimethylcedrusine set forth in Table 1a, it is not suitable for use in the hydrogel formulations and methods of use described herein.

[0115] In some embodiments, the gallocatechins present in the latex are in an amount of at least about 110 PPM, at least about 115 PPM, at least about 120 PPM, at least about 125 PPM, at least about 130 PPM, at least about 135 PPM, at least about 140 PPM, at least about 145 PPM, at least about 150 PPM, at least about 155 PPM, at least about 160 PPM, at least about 165 PPM, at least about 170 PPM, at least about 175 PPM, at least about 180 PPM, at least about 185 PPM, at least about 190 PPM, at least about 195 PPM, at least about 200 PPM, or a range between any two of these values.

[0116] In some embodiments, epigallocatechin is present in the latex in an amount of at least about 780 PPM, at least about 790 PPM, at least about 800 PPM, at least about 810 PPM, at least about 820 PPM, at least about 830 PPM, at least about 840 PPM, at least about 850 PPM, at least about 860 PPM, at least about 870 PPM, at least about 880 PPM, at least about 890 PPM, at least about 900 PPM, at least about 910 PPM, at least about 920 PPM, at least about 930 PPM, at least about 940 PPM, at least about 950 PPM, at least about 960 PPM, at least about 970 PPM, at least about 980 PPM, at least about 990 PPM, at least about 1000 PPM, at least about 1010 PPM, at least about 1020 PPM, at least about 1030 PPM, at least about 1040 PPM, at least about 1050 PPM, at least about 1060 PPM, at least about 1070 PPM, at least about 1080 PPM, at least about 1090 PPM, at least about 1100 PPM, at least about 1110 PPM, about 1120 PPM, at least about 1130 PPM, at least about 1140 PPM, at least about 1150 PPM, at least about 1160 PPM, at least about 1170 PPM, at least about 1180 PPM, at least about 1190 PPM, at least about 1200 PPM, at least about 1210 PPM, at least about 1220 PPM, at least about 1230 PPM, at least about 1240 PPM, at least about 1250 PPM, at least about 1260 PPM, at least about 1270 PPM, at least about 1280 PPM, at least about 1290 PPM, at least about 1300 PPM, at least about 1310 PPM, at least about 1320 PPM, at least about 1330 PPM, at least about 1340 PPM, at least about 1350 PPM, at least about 1360 PPM, at least about 1370 PPM, at least about 1380 PPM, at least about 1390 PPM, at least about 1400 PPM, at least about 1410 PPM, at least about 1420 PPM, at least about 1430 PPM, at least about 1440 PPM, at least about 1450 PPM, at least about 1460 PPM, at least about 1470 PPM,At least about 1480 PPM, at least about 1490 PPM, at least about 1500 PPM, at least about 1510 PPM, at least about 1520 PPM, at least about 1530 PPM, at least about 1540 PPM, at least about 1550 PPM, at least about 1560 PPM, at least about 1570 PPM, at least about 1580 PPM, at least about 1590 PPM, at least about 1600 PPM, at least about 1610 PPM, at least about 1620 PPM, at least about 1630 PPM, at least about 1640 PPM, at least about 1650 PPM, at least about 1660 PPM, at least about 1670 PPM, at least about 1680 PPM, at least about 1690 PPM, at least about 1700 PPM, or a range between any two of these values.

[0117] In some embodiments, the catechins present in the latex are at least about 1.6 PPM, at least about 1.7 PPM, at least about 1.8 PPM, at least about 1.9 PPM, at least about 2.0 PPM, at least about 2.1 PPM, at least about 2.2 PPM, at least about 2.3 PPM, at least about 2.4 PPM, at least about 2.5 PPM, at least about 2.6 PPM, at least about 2.7 PPM, at least about 2.8 PPM, at least about 2.9 PPM, at least about 3.0 PPM, at least about 3.1 PPM, at least about 3.2 PPM, M, at least about 3.3 PPM, at least about 3.4 PPM, at least about 3.5 PPM, at least about 3.6 PPM, at least about 3.7 PPM, at least about 3.8 PPM, at least about 3.9 PPM, at least about 4.0 PPM, at least about 4.1 PPM, at least about 4.2 PPM, at least about 4.3 PPM, at least about 4.4 PPM, at least about 4.5 PPM, at least about 4.6 PPM, at least about 4.7 PPM, at least about 4.8 PPM, at least about 4.9 PPM, at least about 5.0 PPM, at least about 5.1 PPM, at least about 5.2 PPM, at least about 5.3 PPM, at least about 5.4 PPM, at least about 5.5 PPM, at least about 5.6 PPM, at least about 5.7 PPM, at least about 5.8 PPM, at least about 5.9 PPM, at least about 6.0 PPM, at least about 6.1 PPM, at least about 6.2 PPM, at least about 6.3 PPM, at least about 6.4 PPM, at least about 6.5 PPM, at least about 6.6 PPM, at least about 6.7 PPM, at least about 6.8 PPM, at least about 6.9 PPM, at least about 7.0 PPM, at least Also about 7.1 PPM, at least about 7.2 PPM, at least about 7.3 PPM, at least about 7.4 PPM, at least about 7.5 PPM, at least about 7.6 PPM, at least about 7.7 PPM, at least about 7.8 PPM, at least about 7.9 PPM, at least about 8.0 PPM, at least about 8.1 PPM, at least about 8.2 PPM, at least about 8.3 PPM, at least about 8.4 PPM, at least about 8.5 PPM, at least about 8.6 PPM, at least about 8.7 PPM, at least about 8.8 PPM, at least about 8.9 PPM, at least about 9.0 PPM, at least about 9.1 PPM, at least about 9.2 PPM, at least about 9.3 PPM, at least about 9.4 PPM, at least about 9.5 PPM, at least about 9.6 PPM, at least about 9.7 PPM, at least about 9.8 PPM, at least about 9.9 PPM, at least about 10.0 PPM, at least about 10.1 PPM, at least about 10.2 PPM, at least about 10.3 PPM, at least about 10.4 PPM, at least about 10.5 PPM, at least about 10.6 PPM, at least about 10.7 PPM, at least about 10.8 PPM, at least about 10.9 PPM, at least about 11.0 PPM, or a range between any two of these values.

[0118] In some embodiments, the epicatechin present in the latex is at least about 2.0 PPM, at least about 2.1 PPM, at least about 2.2 PPM, at least about 2.3 PPM, at least about 2.4 PPM, at least about 2.5 PPM, at least about 2.6 PPM, at least about 2.7 PPM, at least about 2.8 PPM, at least about 2.9 PPM, at least about 3.0 PPM, at least about 3.1 PPM, at least about 3.2 PPM, at least about 3.3 PPM, at least about 3.4 PPM, at least about 3.5 PPM, at least about 3.6 PPM, at least about 3.7 PPM, at least about 3.8 PPM, at least about 3.9 PPM, at least about 4.0 PPM, at least about 4.1 PPM, at least about 4.2 PPM, at least about 4.3 PPM, at least about 4.4 PPM, at least about 4.5 PPM, at least about 4.6 PPM, at least about 4.7 PPM, at least about 4.8 PPM, at least about 4.9 PPM, at least about 5.0 PPM, at least about 5.1 PPM, at least about 5.2 PPM, at least about 5.3 PPM, at least about 5.4 PPM, at least about 5 0.5 PPM, at least about 5.6 PPM, at least about 5.7 PPM, at least about 5.8 PPM, at least about 5.9 PPM, at least about 6.0 PPM, at least about 6.1 PPM, at least about 6.2 PPM, at least about 6.3 PPM, at least about 6.4 PPM, at least about 6.5 PPM, at least about 6.6 PPM, at least about 6.7 PPM, at least about 6.8 PPM, at least about 6.9 PPM, at least about 7.0 PPM, at least about 7.1 PPM, at least about 7.2 PPM, at least about 7.3 PPM, at least about 7.4 PPM, .4 PPM, at least about 7.5 PPM, at least about 7.6 PPM, at least about 7.7 PPM, at least about 7.8 PPM, at least about 7.9 PPM, at least about 8.0 PPM, at least about 8.1 PPM, at least about 8.2 PPM, at least about 8.3 PPM, at least about 8.4 PPM, at least about 8.5 PPM, at least about 8.6 PPM, at least about 8.7 PPM, at least about 8.8 PPM, at least about 8.9 PPM, at least about 9.0 PPM, at least about 9.1 PPM, at least about 9.2 PPM, at least about 9.3 PPM, at least about 9.4 PPM, at least about 9.5 PPM, at least about 9.6 PPM, at least about 9.7 PPM, at least about 9.8 PPM, at least about 9.9 PPM, at least about 10.0 PPM, or a range between any two of these values.

[0119] In some embodiments, the taspine is present in the latex in an amount of at least about 45 PPM, at least about 46 PPM, at least about 47 PPM, at least about 48 PPM, at least about 49 PPM, at least about 50 PPM, at least about 51 PPM, at least about 52 PPM, at least about 53 PPM, at least about 54 PPM, at least about 55 PPM, at least about 56 PPM, at least about 57 PPM, at least about 58 PPM, at least about 59 PPM, at least about 60 PPM, at least about 61 PPM, at least about 62 PPM, at least about 63 PPM, at least about 64 PPM, at least about 65 PPM, or a range between any two of these values.

[0120] In some embodiments, the dimethylhydrin present in the latex is at least about 0.1 mg dimethylhydrin / kg latex, at least about 0.11 PPM, at least about 0.12 PPM, at least about 0.13 PPM, at least about 0.14 PPM, at least about 0.15 PPM, at least about 0.16 PPM, at least about 0.17 PPM, at least about 0.18 PPM, at least about 0.19 PPM, at least about 0.20 PPM, at least about 0.21 PPM, at least about 0.22 PPM, at least about 0.23 PPM, at least about 0.24 PPM, at least about 0.25 PPM, at least about 0.26 PPM, at least about 0.27 PPM, at least about 0.28 PPM, at least about 0.29 PPM, at least about 0.30 PPM, at least about 0.31 PPM, at least about 0.32 PPM, at least about 0.33 PPM, at least about 0.34 PPM, at least about 0.35 PPM, at least about 0.36 PPM, at least about 0.37 PPM, at least about 0.38 PPM, at least about 0.39 PPM, at least about 0.40 PPM, at least about 0.41 PPM, at least about 0.42 PPM, at least about 0.43 PPM, at least about 0.44 PPM, at least about 0.45 PPM, at least about 0.46 PPM, at least about 0.47 PPM, at least about 0.48 PPM, at least about 0.49 PPM, at least about 0.50 PPM, at least about 0.51 PPM, at least about 0.52 PPM, at least about 0.53 PPM, at least about 0. at least about 0.24 PPM, at least about 0.25 PPM, at least about 0.26 PPM, at least about 0.27 PPM, at least about 0.28 PPM, at least about 0.29 PPM, at least about 0.30 PPM, at least about 0.31 PPM, at least about 0.32 PPM, at least about 0.33 PPM, at least about 0.34 PPM, at least about 0.35 PPM, at least about 0.36 PPM, at least about 0.37 PPM, at least about 0.38 PPM, at least about 0.39 PPM, about 0.40 PPM, at least about 0.41 PPM, at least about 0.42 PPM, at least about 0.43 PPM, at least about 0.44 PPM, at least about 0.45 PPM, at least about 0.46 PPM, at least about 0.47 PPM, at least about 0.48 PPM, at least about 0.49 PPM, at least about 0.5 PPM, at least about 0.6 PPM, at least about 0.7 PPM, at least about 0.8 PPM, at least about 0.9 PPM, at least about 1.0 PPM, at least about 1.1 PPM, at least about 1.2 PPM, at least about 1.3 PPM, at least about 1.4 PPM, at least about 1. .5 PPM, at least about 1.6 PPM, at least about 1.7 PPM, at least about 1.8 PPM, at least about 1.9 PPM, at least about 2.0 PPM, at least about 2.1 PPM, at least about 2.2 PPM, at least about 2.3 PPM, at least about 2.4 PPM, at least about 2.5 PPM, at least about 2.6 PPM, at least about 2.7 PPM, at least about 2.8 PPM, at least about 2.9 PPM, at least about 3.0 PPM, at least about 3.1 PPM, at least about 3.2 PPM, at least about 3.3 PPM, at least about 3.4 PPM, at least about 3.5 PPM, at least about 3.6 PPM, at least about 3.7 PPM, at least about 3.8 PPM, at least about 3.9 PPM, at least about 4.0 PPM, at least about 4.1 PPM, at least about 4.2 PPM, at least about 4.3 PPM, at least about 4.4 PPM, at least about 4.5 PPM, at least about 4.6 PPM, at least about 4.7 PPM, at least about 4.8 PPM, at least about 4.9 PPM, at least about 5.0 PPM, at least about 5. 1 PPM, at least about 5.2 PPM, at least about 5.3 PPM, at least about 5.4 PPM, at least about 5.5 PPM, at least about 5.6 PPM, at least about 5.7 PPM, at least about 5.8 PPM, at least about 5.9 PPM, at least about 6.0 PPM, at least about 6.1 PPM, at least about 6.2 PPM, at least about 6.3 PPM, at least about 6.4 PPM, at least about 6.5 PPM, at least about 6.6 PPM, at least about 6.7 PPM, at least about 6.8 PPM, at least about 6.9 PPM, at least about 7.0 PPM, at least about 7.1 PPM, at least about 7.2 PPM, at least about 7.3 PPM, at least about 7.4 PPM, at least about 7.5 PPM, at least about 7.6 PPM, at least about 7.7 PPM, at least about 7.8 PPM, at least about 7.9 PPM, at least about 8.0 PPM, at least about 8.1 PPM, at least about 8.2 PPM, at least about 8.3 PPM, at least about 8.4 PPM, at least about 8.5 PPM PM, at least about 8.6 PPM, at least about 8.7 PPM, at least about 8.8 PPM, at least about 8.9 PPM, at least about 9.0 PPM, at least about 9.1 PPM, at least about 9.2 PPM, at least about 9.3 PPM, at least about 9.4 PPM, at least about 9.5 PPM, at least about 9.6 PPM, at least about 9.7 PPM, at least about 9.8 PPM, at least about 9.9 PPM, at least about 10.0 PPM, or a range between any two of these values.

[0121] In some embodiments, the hydrogel formulations are suitable for topical administration (including, for example, dermal, oral mucosal, buccal, sublingual, intraocular, and wound cavities).

[0122] In some embodiments of the hydrogel formulation, the composition comprises Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​filtered latex Mull.Arg., and the composition comprises at least a concentration of Croton lechleri ​​latex components, preferably Croton lechleri ​​filtered latex components, preferably Croton lechleri ​​filtered latex components, preferably Croton lechleri ​​Mull. The concentration of the reference standard is about 5% to about 80%, about 10% to about 80%, about 15% to about 80%, about 20% to about 80%, about 25% to about 80%, about 80% to about 80%, about 30% to about 80%, about 35% to about 80%. About 40% to about 80%, about 45% to about 80%, about 50% to about 80%, about 55% to about 80%, about 60% to about 80%, about 65% to about 80%, about 70% to about 80%, about 75% to about 80%, about 5% to about 75%, about 5% to about 70%, about 5% to about 65%, about 5% to about 60%, about 5% to about 55%, about 5% to about 50%, about 5% to about 45%, about 5% to about 40%, about 5% to about 35%, about 5% to about 30%, about 5% to about 25%, about 5% to about 20%. About 5% to about 15%, about 5% to about 10%, about 10% to about 75%, about 15% to about 70%, about 20% to about 65%, about 25% to about 60%, about 30% to about 55%, about 35% to about 55%, about 40% to about 50%, or values ​​within these ranges.Specific examples include about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, or a range between these two values. Certain embodiments of the hydrogel formulation include Croton lekreli latex, preferably Croton lekreli filtered latex, preferably Croton lekreli filtered latex Mul Arg., and the composition has a concentration of at least the components of Croton lekreli latex, preferably the concentration of the components of Croton lekreli filtered latex, preferably the concentration of the components of Croton lekreli filtered latex Mul Arg. Reference Standard, in an amount of about 40%.In certain embodiments of the hydrogel formulation, the composition comprises Croton lekleri latex, preferably Croton lekleri filtered latex, preferably Croton lekleri filtered latex Mul. Arg., wherein the composition comprises at least a concentration of the components of the Croton lekleri latex reference standard, preferably a concentration of the components of the Croton lekleri filtered latex, preferably a concentration of the components of the Croton lekleri filtered latex Mull.Arg. in an amount of about 50%. In certain embodiments of the hydrogel formulation, the composition comprises Croton lekleri latex, preferably Croton lekleri filtered latex, preferably Croton lekleri Mull.Arg., wherein the composition comprises at least a concentration of the components of the Croton lekleri latex, preferably a concentration of the components of the Croton lekleri filtered latex, preferably a concentration of the components of the Croton lekleri Mull. Arg. reference standard in an amount of about 43%. In certain embodiments of the hydrogel formulation, the composition comprises Croton lekleri latex, preferably Croton lekleri filtered latex, preferably Croton lekleri filtered latex Mull.Arg., at least a concentration of Croton lekleri latex components, preferably a concentration of Croton lekleri filtered latex components, preferably a concentration of Croton lekleri filtered latex components, preferably a concentration of Croton lekleri filtered latex components, preferably a concentration of Croton lekleri filtered latex components, preferably a concentration of Croton lekleri filtered latex components, preferably a concentration of Croton lekleri filtered latex components, preferably a concentration of Croton lekleri filtered latex components, preferably a concentration of Croton lekleri filtered latex components, preferably a concentration of Croton lekleri filtered latex components. The Arg of the standard is about 45%.

[0123] In some embodiments of the hydrogel formulation, the one or more preservative-enhanced moisturizers are selected from the group consisting of ZEMEA® USP, propanediol, and combinations thereof.

[0124] In some embodiments of the hydrogel formulation, the one or more preservative-enhanced humectants are in an amount of about 1% to about 10%, about 2% to about 10%, about 3% to about 10%, about 4% to about 10%, about 5% to about 10%, about 6% to about 10%, about 7% to about 10%, about 8% to about 10%, about 9% to about 10%, about 1% to about 9%, about 1% to about 8%, about 1% to about 7%, about 1% to about 6%, about 1% to about 5%, about 1% to about 4%, about 1% to about 3%, about 1% to about 2%, about 2% to about 9%, about 3% to about 8%, about 4% to about 7%, about 5% to about 6%, or a value within one of these ranges. Specific examples may include about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, or a range between any two of these values. In certain embodiments of the hydrogel formulation, the one or more preservation-promoting humectants are in an amount of about 5%. In certain embodiments of the hydrogel formulation, the one or more preservation-promoting humectants are in an amount of about 4%. All of the above represent weight percent of embodiments of the hydrogel formulation. All of the above represent weight percent of embodiments of the hydrogel formulation.

[0125] In some embodiments of the hydrogel formulation, the one or more chelating agents are selected from the group consisting of edetate disodium dihydrate, disodium EDTA, and combinations thereof.

[0126] In some embodiments of the hydrogel formulation, the one or more chelating agents may be from about 0.05% to about 0.5%, from about 0.1% to about 0.5%, from about 0.15% to about 0.5%, from about 0.2% to about 0.5%, from about 0.25% to about 0.5%, from about 0.3% to about 0.5%, from about 0.35% to about 0.5%, from about 0.4% to about 0.5%, from about 0.45% to about 0.5%, from about 0.05% to about 0.45%, from about 0.05% to about 0.4%, from about 0.05% to about 0.35%, from about 0.0 5% to about 0.3%, about 0.05% to about 0.25%, about 0.05% to about 0.2%, about 0.05% to about 0.15%, about 0.05% to about 0.1%, about 0.1% to about 0.45%, about 0.15% to about 0.4%, about 0.2% to about 0.35%, about 0.25% to about 0.30%, about 0.05% to about 0.25%, about 0.075% to about 0.225%, about 0.1% to about 0.2%, about 0.125% to about 0.175%, or a value within these ranges. Specific examples include about 0.05%, about 0.1%, about 0.15%, about 0.2%, about 0.25%, about 0.3%, about 0.35%, about 0.4%, about 0.45%, about 0.5%, about 0.2%, about 0.225%, about 0.25%, about 0.275%, about 0.3%, or a range between any two of these values. In certain embodiments of the hydrogel formulation, the one or more chelating agents are in an amount of about 0.15%. In certain embodiments of the hydrogel formulation, the one or more chelating agents are in an amount of about 0.10%. All of the above represent weight percent of the hydrogel formulation embodiment.

[0127] In some embodiments of the hydrogel formulation, the one or more dispersing agents / co-emulsifiers are selected from the group consisting of PHOSAL® 50PG, phosphatidylcholine, lysophosphatidylcholine, propylene glycol, sunflower seed oil glycerides, ethanol, soybean fatty acids, ascorbyl palmitate, D,L-α-tocopherol, and combinations thereof.

[0128] In some embodiments of the hydrogel formulation, the one or more dispersing agents / co-emulsifiers are in an amount of about 0.5% to about 5%, about 1% to about 3%, about 0.5% to about 2%, about 0.05% to about 0.2%, about 0.25% to about 1.25%, about 0.01% to about 0.1%, about 0.001% to about 0.01%, about 0.005% to about 0.02%, or a value within one of these ranges. Specific examples include about 0.001%, about 0.004%, about 0.005%, about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.1%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, or a range between any two of these values. In certain embodiments of the hydrogel formulation, the one or more dispersing agents / co-emulsifiers are in an amount of about 2%. In certain embodiments of the hydrogel formulation, the one or more dispersing agents / co-emulsifiers are in an amount of about 1%. In certain embodiments of the hydrogel formulation, the one or more dispersing agents / co-emulsifiers are in an amount of about 0.824%. In certain embodiments of the hydrogel formulation, the one or more dispersing agents / co-emulsifiers are in an amount of about 0.676%. In certain embodiments of the hydrogel formulation, the one or more dispersing agents / co-emulsifiers are in an amount of about 0.12%. In certain embodiments of the hydrogel formulation, the one or more dispersing agents / co-emulsifiers are in an amount of about 0.05%. In certain embodiments of the hydrogel formulation, the one or more dispersing agents / co-emulsifiers are in an amount of about 0.03%. In certain embodiments of the hydrogel formulation, the one or more dispersing agents / co-emulsifiers are in an amount of about 0.01%. In certain embodiments of the hydrogel formulation, the one or more dispersing agents / co-emulsifiers are in an amount of about 0.004%. In certain embodiments of the hydrogel formulation, the one or more dispersing agents / co-emulsifiers are in an amount of about 0.8%. In certain embodiments of the hydrogel formulation, the one or more dispersing agents / co-emulsifiers are in an amount of about 0.7%. In certain embodiments of the hydrogel formulation, the one or more dispersing agents / co-emulsifiers are in an amount of about 0.1%. All of the above represent weight % of the hydrogel formulation embodiment.

[0129] In some embodiments of the hydrogel formulation, the one or more preservatives are selected from the group consisting of methylparaben, propylparaben, sodium benzoate, potassium sorbate, and combinations thereof.

[0130] In some embodiments of the hydrogel formulation, the one or more preservatives are present in an amount of about 0.005% to about 0.1%, about 0.1% to about 1%, about 0.05% to about 0.5%, or a value within one of these ranges. Specific examples include about 0.005%, about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.1%, about 0.4%, about 0.45%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, or a range between any two of these values. In certain embodiments of the hydrogel formulation, the one or more preservatives are present in an amount of about 0.45%. In certain embodiments of the hydrogel formulation, the one or more preservatives are present in an amount of about 0.4%. In certain embodiments of the hydrogel formulation, the one or more preservatives are present in an amount of about 0.1%. In certain embodiments of the hydrogel formulation, the one or more preservatives are in an amount of about 0.02%. In certain embodiments of the hydrogel formulation, the one or more preservatives are in an amount of about 0.5%. All of the above represent weight percent of the hydrogel formulation embodiment.

[0131] In some embodiments of the hydrogel formulation, the one or more emollients are selected from the group consisting of DOW CORNING® Q7 9120 (PHARMACEUTICAL GRADE), Dow Corning® 200 Fluid 350 cSt, LABRAFAC™ WL1349, dimethicone, medium chain triglycerides, and combinations thereof.

[0132] In some embodiments of the hydrogel formulation, the one or more emollients may be from about 0.5% to about 10%, from about 1% to about 10%, from about 1.5% to about 10%, from about 2% to about 10%, from about 2.5% to about 10%, from about 3% to about 10%, from about 3.5% to about 10%, from about 4% to about 10%, from about 4.5% to about 10%, from about 5% to about 10%, or from about 5.5% to about 10%. ~ about 10%, about 6% to about 10%, about 6.5% to about 10%, about 7% to about 10%, about 7.5% to about 10%, about 8% to about 10%, about 8.5% to about 10%, about 9% to about 10%, about 9.5% to about 10%, about 0.5% to about 9.5%, about 0.5% to about 9%, about 0.5% to about 8.5%, about 0.5% to about 8%, about 0.5% to about 7. 5%, about 0.5% to about 7%, about 0.5% to about 6%, about 0.5% to about 5.5%, about 0.5% to about 5%, about 0.5% to about 4.5%, about 0.5% to about 4%, about 0.5% to about 3.5%, about 0.5% to about 3%, about 0.5% to about 2.5%, about 0.5% to about 2%, about 0.5% to about 1.5%, about 0.5% to about 1%, about 1% to about 9 0.5%, about 1.5% to about 9%, about 2% to about 8.5%, about 0.5% to about 8%, about 3% to about 7.5%, about 3.5% to about 7%, about 4% to about 6.5%, about 4.5% to about 6%, about 5% to about 5.5%, about 1% to about 5%, about 1.5% to about 4.5%, about 2% to about 4%, about 2.5% to about 3.5%, or a value within these ranges. Specific examples include about 0.5%, about 1%, about 1.5%, about 2%, about 2.5%, about 3%, about 3.5%, about 4%, about 4.5%, about 5%, about 5.5%, about 6%, about 6.5%, about 7%, about 7.5%, about 8%, about 8.5%, about 9%, about 9.5%, about 10%, or a range between any two of these values. In certain embodiments of the hydrogel formulation, the one or more emollients are in an amount of about 2%. In certain embodiments of the hydrogel formulation, the one or more emollients are in an amount of about 2.5%. In certain embodiments of the hydrogel formulation, the one or more emollients are in an amount of about 5%. In certain embodiments of the hydrogel formulation, the one or more emollients are in an amount of about 7%. All of the above represent weight percent of the hydrogel formulation embodiment.

[0133] In some embodiments of the hydrogel formulation, the one or more thickening / stabilizing / emulsifying / texturing agents are selected from the group consisting of SEPINEO™ P600 (acrylamide / sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80), acrylamide / sodium acryloyldimethyltaurate copolymer, isohexadecane, polysorbate 80, and combinations thereof.

[0134] In some embodiments of the hydrogel formulation, the one or more thickening / stabilizing / emulsifying / texturing agents are in an amount of about 0.05% to about 10%, about 0.05% to about 5%, about 0.05% to about 1%, about 0.5% to about 3%, about 0.5% to about 2%, about 0.5% to about 1.5%, about 0.5% to about 1%, about 2% to about 6%, or a value within one of these ranges. Specific examples include about 0.05%, about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 1.5%, about 2%, about 2.5%, about 3%, about 3.5%, about 4%, about 4.5%, about 5%, about 5.5%, about 6%, or a range between any two of these values. In certain embodiments of the hydrogel formulation, the one or more thickening / stabilizing / emulsifying / texturing agents are in an amount of about 4%. In certain embodiments of the hydrogel formulation, the one or more thickening / stabilizing / emulsifying / texturing agents are in an amount of about 1.4%. In certain embodiments of the hydrogel formulation, the one or more thickening / stabilizing / emulsifying / texturing agents are in an amount of about 1.6%. In certain embodiments of the hydrogel formulation, the one or more thickening / stabilizing / emulsifying / texturing agents are in an amount of about 0.8%. In certain embodiments of the hydrogel formulation, the one or more thickening / stabilizing / emulsifying / texturing agents are in an amount of about 1%. In certain embodiments of the hydrogel formulation, the one or more thickening / stabilizing / emulsifying / texturing agents are in an amount of about 0.2%. In certain embodiments of the hydrogel formulation, the one or more thickening / stabilizing / emulsifying / texturing agents are in an amount of about 0.4%. In certain embodiments of the hydrogel formulation, the one or more thickening / stabilizing / emulsifying / texturing agents are in an amount of about 1.3%. All of the above represent weight % of the hydrogel formulation embodiments.

[0135] In some embodiments of the hydrogel formulation, the one or more pH adjusting agents is trolamine.

[0136] In some embodiments of the hydrogel formulation, the one or more pH adjusting agents are from about 0.05% to about 0.5%, from about 0.1% to about 0.5%, from about 0.15% to about 0.5%, from about 0.2% to about 0.5%, from about 0.25% to about 0.5%, from about 0.3% to about 0.5%, from about 0.35% to about 0.5%, from about 0.4% to about 0.5%, from about 0.45% to about 0.5%, from about 0.05% to about 0.45%, from about 0.05% to about 0.4%, from about 0.05% to about 0.35%, from about 0. 05% to about 0.3%, about 0.05% to about 0.25%, about 0.05% to about 0.2%, about 0.05% to about 0.15%, about 0.05% to about 0.1%, about 0.1% to about 0.45%, about 0.15% to about 0.4%, about 0.2% to about 0.35%, about 0.25% to about 0.30%, about 0.05% to about 0.25%, about 0.075% to about 0.225%, about 0.1% to about 0.2%, about 0.125% to about 0.175%, or a value within these ranges. Specific examples include about 0.05%, about 0.1%, about 0.15%, about 0.2%, about 0.25%, about 0.3%, about 0.35%, about 0.4%, about 0.45%, about 0.5%, about 0.2%, about 0.225%, about 0.25%, about 0.275%, about 0.3%, about 0.325%, about 0.35%, about 0.375%, about 0.4%, about 0.425%, about 0.45%, about 0.475%, about 0.5%, or a range between any two of these values. In certain embodiments of the hydrogel formulation, the one or more pH adjusting agents are in an amount of about 0.26%. All of the above represent weight percent of the hydrogel formulation embodiment.

[0137] In some embodiments of the hydrogel formulation, propanediol is in an amount of about 1% to about 10%, about 2% to about 10%, about 3% to about 10%, about 4% to about 10%, about 5% to about 10%, about 6% to about 10%, about 7% to about 10%, about 8% to about 10%, about 9% to about 10%, about 1% to about 9%, about 1% to about 8%, about 1% to about 7%, about 1% to about 6%, about 1% to about 5%, about 1% to about 4%, about 1% to about 3%, about 1% to about 2%, about 2% to about 9%, about 3% to about 8%, about 4% to about 7%, about 5% to about 6%, or a value within one of these ranges. Specific examples include about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, or a range between any two of these values. In certain embodiments of the hydrogel formulation, the propanediol is in an amount of about 5%. In certain embodiments of the hydrogel formulation, the propanediol is in an amount of about 4%. All of the above represent weight percent of the hydrogel formulation embodiment.

[0138] In some embodiments of the hydrogel formulation, edetate disodium dihydrate is from about 0.05% to about 0.5%, from about 0.1% to about 0.5%, from about 0.15% to about 0.5%, from about 0.2% to about 0.5%, from about 0.25% to about 0.5%, from about 0.3% to about 0.5%, from about 0.35% to about 0.5%, from about 0.4% to about 0.5%, from about 0.45% to about 0.5%, from about 0.05% to about 0.45%, from about 0.05% to about 0.4%, from about 0.05% to about 0.35%, from about 0.05% to about 0. ... 0.05% to about 0.3%, about 0.05% to about 0.25%, about 0.05% to about 0.2%, about 0.05% to about 0.15%, about 0.05% to about 0.1%, about 0.1% to about 0.45%, about 0.15% to about 0.4%, about 0.2% to about 0.35%, about 0.25% to about 0.30%, about 0.05% to about 0.25%, about 0.075% to about 0.225%, about 0.1% to about 0.2%, about 0.125% to about 0.175%, or a value within these ranges. Specific examples include about 0.05%, about 0.1%, about 0.15%, about 0.2%, about 0.25%, about 0.3%, about 0.35%, about 0.4%, about 0.45%, about 0.5%, about 0.2%, about 0.225%, about 0.25%, about 0.275%, about 0.3%, or ranges between any two of these values. In certain embodiments of the hydrogel formulation, the edetate disodium dihydrate is in an amount of about 0.15%. In certain embodiments of the hydrogel formulation, the edetate disodium dihydrate is in an amount of about 0.10%. All of the above represent weight percent of the hydrogel formulation embodiment.

[0139] In some embodiments of the hydrogel formulation, PHOSAL® 50 PG (phosphatidylcholine, lysophosphatidylcholine, propylene glycol, sunflower seed oil glycerides, ethanol, soybean fatty acids, ascorbyl palmitate, D,L-α-tocopherol) is about 0.5% to about 5%, about 1% to about 3%, 0.5% to about 2%, about 0.05% to about 0.2%, about 0.25% to about 1.25%, about 0.01% to about 0.1%, about 0.001% to about 0.01%, about 0.005% to about 0.02%, or values ​​within these ranges. Specific examples include about 0.001%, about 0.004%, about 0.005%, about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.1%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, or a range between any two of these values. In a particular embodiment of the hydrogel formulation, PHOSAL® 50PG (phosphatidylcholine, lysophosphatidylcholine, propylene glycol, sunflower seed oil glyceride, ethanol, soybean fatty acid, ascorbyl palmitate, D,L-α-tocopherol) is in an amount of about 2%. All of the above represent weight percent of the hydrogel formulation embodiment.

[0140] In some embodiments of the hydrogel formulation, methylparaben is from about 0.05% to about 0.5%, from about 0.1% to about 0.5%, from about 0.15% to about 0.5%, from about 0.2% to about 0.5%, from about 0.25% to about 0.5%, from about 0.3% to about 0.5%, from about 0.35% to about 0.5%, from about 0.4% to about 0.5%, from about 0.45% to about 0.5%, from about 0.05% to about 0.45%, from about 0.05% to about 0.4%, from about 0.05% to about 0.35%, from about 0.0 5% to about 0.3%, about 0.05% to about 0.25%, about 0.05% to about 0.2%, about 0.05% to about 0.15%, about 0.05% to about 0.1%, about 0.1% to about 0.45%, about 0.15% to about 0.4%, about 0.2% to about 0.35%, about 0.25% to about 0.30%, about 0.05% to about 0.25%, about 0.075% to about 0.225%, about 0.1% to about 0.2%, about 0.125% to about 0.175%, or a value within these ranges. Specific examples include about 0.05%, about 0.1%, about 0.15%, about 0.2%, about 0.25%, about 0.3%, about 0.35%, about 0.4%, about 0.45%, about 0.5%, about 0.2%, about 0.225%, about 0.25%, about 0.275%, about 0.3%, or a range between any two of these values. In certain embodiments of the hydrogel formulation, methylparaben is in an amount of about 0.15%. In certain embodiments of the hydrogel formulation, methylparaben is in an amount of about 0.1%. All of the above represent weight percent of the hydrogel formulation embodiment.

[0141] In some embodiments of the hydrogel formulation, propylparaben is present in an amount of about 0.005% to about 0.05%, about 0.01% to about 0.05%, about 0.015% to about 0.05%, about 0.02% to about 0.05%, about 0.025% to about 0.05%, about 0.03% to about 0.05%, about 0.035% to about 0.05%, about 0.04% to about 0.05%, about 0.045 ... 0.005% to about 0.045%, about 0.005% to about 0.045%, about 0.005% to about 0.04%, about 0.005% to about 0.035%, about 0.005% to about 0.03%, about 0.005% to about 0.02%, about 0.005% to about 0.015%, about 0.005% to about 0.01%, about 0.01% to about 0.045%, about 0.02% to about 0.04%, about 0.025% to about 0.035%, about 0.02% to about 0.04%, about 0.015% to about 0.045%, or values ​​within these ranges. Specific examples include about 0.005%, about 0.01%, about 0.02%, about 0.025%, about 0.03%, about 0.035%, about 0.04%, about 0.045%, about 0.05%, or a range between any two of these values. In certain embodiments of the hydrogel formulation, propylparaben is in an amount of about 0.02%. All of the above represent weight percent of the hydrogel formulation embodiment.

[0142] In some embodiments of the hydrogel formulation, sodium benzoate is present in an amount of about 0.005% to about 0.1%, about 0.1% to about 1%, about 0.05% to about 0.5%, or any value within these ranges. Specific examples include about 0.005%, about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.1%, about 0.4%, about 0.45%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, or a range between any two of these values. In certain embodiments of the hydrogel formulation, sodium benzoate is present in an amount of about 0.40%. In certain embodiments of the hydrogel formulation, sodium benzoate is present in an amount of about 0.45%. All of the above represent weight percent of the hydrogel formulation embodiment.

[0143] In some embodiments of the hydrogel formulation, potassium sorbate is present in an amount of about 0.005% to about 0.1%, about 0.1% to about 1%, about 0.05% to about 0.5%, or any value within these ranges. Specific examples include about 0.005%, about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.1%, about 0.4%, about 0.45%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, or a range between any two of these values. In certain embodiments of the hydrogel formulation, potassium sorbate is present in an amount of about 0.45%. All of the above represent weight percent of the hydrogel formulation embodiment.

[0144] In some embodiments of the hydrogel formulation, the water is about 20% to about 80%, about 25% to about 80%, about 30% to about 80%, about 35% to about 80%, about 40% to about 80%, about 45% to about 80%, about 50% to about 80%, about 55% to about 80%, about 60% to about 80%, about 65% to about 80%, about 70% to about 80%, about 75% to about 80%, about 20% to about 75%, about 20% about 70%, about 20% to about 65%, about 20% to about 60%, about 20% to about 55%, about 20% to about 50%, about 20% to about 45%, about 20% to about 40%, about 20% to about 35%, about 20% to about 30%, about 20% to about 25%, about 25% to about 75%, about 30% to about 70%, about 35% to about 65%, about 40% to about 60%, about 45% to about 55%, or values ​​within these ranges. Specific examples include about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 60%, about 75%, about 80%, or a range between any two of these values. In certain embodiments of the hydrogel formulation, water is in an amount of about 43.38%. In certain embodiments of the hydrogel formulation, water is in an amount of about 33.38%. In certain embodiments of the hydrogel formulation, water is in an amount of about 40.38%. In certain embodiments of the hydrogel formulation, water is in an amount of about 38.38%. In certain embodiments of the hydrogel formulation, water is in an amount of about 40.7%. In certain embodiments of the hydrogel formulation, water is in an amount of about 39%. All of the above represent weight % of the hydrogel formulation embodiments.

[0145] In some embodiments of the hydrogel formulation, dimethicone is from about 0.5% to about 10%, from about 1% to about 10%, from about 1.5% to about 10%, from about 2% to about 10%, from about 2.5% to about 10%, from about 3% to about 10%, from about 3.5% to about 10%, from about 4% to about 10%, from about 4.5% to about 10%, from about 5% to about 10%, from about 5.5% to about 10%, 0%, about 6% to about 10%, about 6.5% to about 10%, about 7% to about 10%, about 7.5% to about 10%, about 8% to about 10%, about 8.5% to about 10%, about 9% to about 10%, about 9.5% to about 10%, about 0.5% to about 9.5%, about 0.5% to about 8.5%, about 0.5% to about 7.5%, about 0.5% to about 7%, about 0.5% to about 6.5%, about 0.5% to about 6%, about 0.5% to about 5.5%, about 0.5% to about 5%, about 0.5% to about 4.5%, about 0.5% to about 4%, about 0.5% to about 3.5%, about 0.5% to about 3%, about 0.5% to about 2.5%, about 0.5% to about 2%, about 0.5% to about 1.5%, about 0.5% to about 1%, about 1% to about 9.5%, It is about 1.5% to about 9%, about 2% to about 8.5%, about 0.5% to about 8%, about 3% to about 7.5%, about 3.5% to about 7%, about 4% to about 6.5%, about 4.5% to about 6%, about 5% to about 5.5%, about 1% to about 5%, about 1.5% to about 4.5%, about 2% to about 4%, about 2.5% to about 3.5%, or a value within these ranges. Specific examples include about 0.5%, about 1%, about 1.5%, about 2%, about 2.5%, about 3%, about 3.5%, about 4%, about 4.5%, about 5%, about 5.5%, about 6%, about 6.5%, about 7%, about 7.5%, about 8%, about 8.5%, about 9%, about 9.5%, about 10%, or a range between any two of these values. In certain embodiments of the hydrogel formulation, dimethicone is in an amount of about 2%. In certain embodiments of the hydrogel formulation, dimethicone is in an amount of about 2.5%. In certain embodiments of the hydrogel formulation, dimethicone is in an amount of about 3%. All of the above represent weight percentages of the hydrogel formulation embodiments.

[0146] In some embodiments of the hydrogel formulation, dimethicone may be from about 175 cSt to about 525 cSt, from about 200 cSt to about 525 cSt, from about 225 cSt to about 525 cSt, from about 250 cSt to about 525 cSt, from about 275 cSt to about 525 cSt, from about 300 cSt to about 525 cSt, from about 325 cSt to about 525 cSt, from about 350 cSt to about 525 cSt, from about 375 cSt to about 525 cSt, from about 400 cSt to about 525 cSt, from about 425 cSt to about 525 cSt, from about 450 cSt to about 525 cSt, from about 475 cSt to about 525 cSt, from about 500 cSt to about 525 cSt, from about 175 cSt to about 500 cSt, from about 175 cSt to about 475 cSt, About 175cSt to about 450cSt, about 175cSt to about 425cSt, about 175cSt to about 400cSt, about 175cSt to about 375cSt, about 175cSt to about 350cSt, about 175cSt to about 325cSt, about 175cSt to about 300cSt, about 175cSt to about 275cSt, about 175cSt to about 250cSt, about 175cSt to about 225cSt, about 175cSt to about 200cSt, about 200cSt to about 500cSt, about 225cSt to about 475cSt, about 250cSt to about 450cSt, about 275cSt to about 425cSt, about 300cSt to about 400cSt, about 325cSt to about 375cSt, or values ​​within these ranges. Specific examples may include about 175 cSt, about 200 cSt, about 225 cSt, about 250 cSt, about 275 cSt, about 300 cSt, about 325 cSt, about 350 cSt, about 375 cSt, about 400 cSt, about 425 cSt, about 450 cSt, about 475 cSt, about 500 cSt, about 525 cSt, or a range between any two of these values. In certain embodiments of the hydrogel formulation, dimethicone has a viscosity of about 350 cSt.

[0147] In some embodiments of the hydrogel formulation, caprylic / capric triglyceride is in an amount of about 1% to about 10%, about 2% to about 10%, about 3% to about 10%, about 4% to about 10%, about 5% to about 10%, about 6% to about 10%, about 7% to about 10%, about 8% to about 10%, about 9% to about 10%, about 1% to about 9%, about 1% to about 8%, about 1% to about 7%, about 1% to about 6%, about 1% to about 5%, about 1% to about 4%, about 1% to about 3%, about 1% to about 2%, about 2% to about 9%, about 3% to about 8%, about 4% to about 7%, about 5% to about 6%, or a value within one of these ranges. Specific examples include about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, or ranges between any two of these values. In certain embodiments of the hydrogel formulation, the caprylic / capric triglyceride is in an amount of about 5%. In certain embodiments of the hydrogel formulation, the caprylic / capric triglyceride is in an amount of about 7%. All of the above represent weight percentages of the hydrogel formulation embodiments.

[0148] In some embodiments of the hydrogel formulation, SEPINEO™ P600 (acrylamide / sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80) is present in an amount of about 0.5% to about 10%, about 1% to about 10%, about 1.5% to about 10%, about 2% to about 10%, about 2.5% to about 10%, about 3% to about 10%, about 3.5% to about 10%, about 4% to about 10%, about 4.5% to about 10%, about 5% to about 10%, about 5.5% to about 10%, about 6% to about 10%, about 6.5% to about 10%, about 7% to about 10%, about 7.5% to about 10%, about 8% to about 10%, about 8.5% to about 10%, about 9% to about 10%, about 9.5% to about 10%, about 0.5% to about 9.5%, about 0.5% to about 8.5 %, about 0.5% to about 8%, about 0.5% to about 7.5%, about 0.5% to about 7%, about 0.5% to about 6.5%, about 0.5% to about 6%, about 0.5% to about 5.5%, about 0.5% to about 4.5%, about 0.5% to about 4%, about 0.5% to about 3.5%, about 0.5% to about 3%, about 0.5% to about 2.5%, about 0.5% to about 2%, about 0.5% to about 1.5%, about 0. 5% to about 1%, about 1% to about 9.5%, about 1.5% to about 9%, about 2% to about 8.5%, about 0.5% to about 8%, about 3% to about 7.5%, about 3.5% to about 7%, about 4% to about 6.5%, about 4.5% to about 6%, about 5% to about 5.5%, about 1% to about 5%, about 1.5% to about 4.5%, about 2% to about 4%, about 2.5% to about 3.5%, or a value within these ranges. Specific examples include about 0.5%, about 1%, about 1.5%, about 2%, about 2.5%, about 3%, about 3.5%, about 4%, about 4.5%, about 5%, about 5.5%, about 6%, about 6.5%, about 7%, about 7.5%, about 8%, about 8.5%, about 9%, about 9.5%, about 10%, or a range between any two of these values. In a particular embodiment of the hydrogel formulation, SEPINEO™ P600 (acrylamide / sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80) is in an amount of about 3.3%. In a particular embodiment of the hydrogel formulation, SEPINEO™ P600 (acrylamide / sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80) is in an amount of about 4.0%. All of the above represent weight percent of the hydrogel formulation embodiment.

[0149] In some embodiments of the hydrogel formulation, trolamine is from about 0.05% to about 0.5%, from about 0.1% to about 0.5%, from about 0.15% to about 0.5%, from about 0.2% to about 0.5%, from about 0.25% to about 0.5%, from about 0.3% to about 0.5%, from about 0.35% to about 0.5%, from about 0.4% to about 0.5%, from about 0.45% to about 0.5%, from about 0.05% to about 0.45%, from about 0.05% to about 0.4%, from about 0.05% to about 0.35%, from about 0.05% to about 0.5% % to about 0.3%, about 0.05% to about 0.25%, about 0.05% to about 0.2%, about 0.05% to about 0.15%, about 0.05% to about 0.1%, about 0.1% to about 0.45%, about 0.15% to about 0.4%, about 0.2% to about 0.35%, about 0.25% to about 0.30%, about 0.05% to about 0.25%, about 0.075% to about 0.225%, about 0.1% to about 0.2%, about 0.125% to about 0.175%, or a value within these ranges. Specific examples include about 0.05%, about 0.1%, about 0.15%, about 0.2%, about 0.25%, about 0.3%, about 0.35%, about 0.4%, about 0.45%, about 0.5%, about 0.2%, about 0.225%, about 0.25%, about 0.275%, about 0.3%, about 0.325%, about 0.35%, about 0.375%, about 0.4%, about 0.425%, about 0.45%, about 0.475%, about 0.5%, or a range between any two of these values. In certain embodiments of the hydrogel formulation, the trolamine is in an amount of about 0.26%. All of the above represent weight percent of the hydrogel formulation embodiment.

[0150] In some embodiments of the hydrogel formulation, the hydrogel formulation has a viscosity of about 3.0 to about 7.0, about 3.5 to about 7.0, about 4.0 to about 7.0, about 4.5 to about 7.0, about 5.0 to about 7.0, about 5.5 to about 7.0, about 6.0 to about 7.0, about 6.5 to about 7.0, about 3.0 to about 6.5, about 3.0 to about 6.0, about 3.0 to about 5, about 3.0 to about 4.5, about 3.0 to about 4, about 3.0 to about 3.5, about 3.0, about 3.1, about 3.2, about 3.3, about 3.4, about 3.5, The pH range is about 3.6, about 3.7, about 3.8, about 3.9, about 4.0, about 4.1, about 4.2, about 4.3, about 4.4, about 4.5, about 4.6, about 4.7, about 4.8, about 4.9, about 5.0, about 5.1, about 5.2, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6.0, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, about 7.0, or a range between any two of these values. In certain embodiments of the hydrogel formulation, the hydrogel formulation has a pH of about 4.0 to about 6.7. In certain embodiments of the hydrogel formulation, the hydrogel formulation has a pH of about 3.0 to about 4.0. In certain embodiments of the hydrogel formulation, the hydrogel formulation has a pH of about 5.5 to about 6.5.

[0151] In some embodiments, the hydrogel formulation does not contain more than about 2 wt% monohydroxy alcohol.

[0152] In some embodiments, the hydrogel formulation does not include sodium cromoglycate.

[0153] In some embodiments of the hydrogel formulation, glycerin is about 1% to about 5%, about 1.5% to about 5%, about 2% to about 5%, about 2.5% to about 5%, about 3% to about 5%, about 3.5% to about 5%, about 4% to about 5%, about 4.5% to about 5%, about 1% to about 4.5%, about 1% to about 4%, about 1% to about 3.5%, about 1% to about 3%, about 1% to about 2.5%, about 1% to about 2%, about 1% to about 1.5%, about 1.5% to about 4.5%, about 2% to about 4%, about 2.5% to about 3.5%, or values ​​within these ranges. Specific examples include about 1%, about 1.5%, about 2%, about 2.5%, about 3%, about 3.5%, about 4%, about 4.5%, about 5%, or ranges between any two of these values. In certain embodiments of the hydrogel formulation, glycerin is in an amount of about 3%. All of the above represent weight percentages of the hydrogel formulation embodiments.

[0154] In some embodiments of the hydrogel formulation, sodium phosphate dibasic heptahydrate is in an amount of about 1% to about 3%, about 1.5% to about 3%, about 2% to about 3%, about 2.5% to about 3%, about 1% to about 2.5%, about 1% to about 2%, about 1% to about 1.5%, about 1.5% to about 2.5%, or a value within one of these ranges. Specific examples include about 1%, about 1.5%, about 2%, about 2.5%, about 3%, or a range between any two of these values. In certain embodiments of the hydrogel formulation, sodium phosphate dibasic heptahydrate is in an amount of about 2%. All of the above represent weight percent of the hydrogel formulation embodiment.

[0155] In some embodiments of the hydrogel formulation, the monobasic sodium phosphate is about 0.1% to about 0.4%, about 0.15% to about 0.4%, about 0.2% to about 0.4%, about 0.25% to about 0.4%, about 0.3% to about 0.4%, about 0.35% to about 0.4%, about 0.1% to about 0.35%, about 0.1% to about 0.3%, about 0.1% to about 0.25%, about 0.1% to about 0.2%, about 0.1% to about 0.15%, about 0.15% to about 0.35%, about 0.2% to about 0.3%, or a value within these ranges. Specific examples include about 0.1%, about 0.15%, about 0.2%, about 0.25%, about 0.3%, about 0.35%, about 0.4%, or a range between any two of these values. In a particular embodiment of the hydrogel formulation, sodium phosphate monobasic is in an amount of about 0.26%. All of the above represent weight percent of the hydrogel formulation embodiment.

[0156] In some embodiments of the hydrogel formulation, sodium hexametaphosphate is in an amount of about 0.005% to about 0.02%, about 0.01% to about 0.02%, about 0.015% to about 0.02%, about 0.005% to about 0.015%, about 0.005% to about 0.01%, about 0.01% to about 0.015%, or a value within one of these ranges. Specific examples include about 0.005%, about 0.01%, about 0.015%, about 0.02%, or a range between any two of these values. In certain embodiments of the hydrogel formulation, sodium hexametaphosphate is in an amount of about 0.01%. All of the above represent weight percent of the hydrogel formulation embodiment.

[0157] In some embodiments of the hydrogel formulation, the medium chain triglycerides are from about 1% to about 6%, from about 1.5% to about 6%, from about 2% to about 6%, from about 2.5% to about 6%, from about 3% to about 6%, from about 3.5% to about 6%, from about 4% to about 6%, from about 4.5% to about 6%, from about 5% to about 6%, from about 5.5% to about 6%, from about 1% to about 5.5%, from about 1% to about 5%, from about 1% to about 4.5%, from about 1% to about 4%, from about 1% to about 3.5%, from about 1% to about 3%, from about 1% to about 2.5%, from about 1% to about 1.5%, from about 1.5% to about 4.5%, from about 2% to about 4%, from about 2.5% to about 3.5%, or values ​​within these ranges. Specific examples include about 1%, about 1.5%, about 2%, about 2.5%, about 3%, about 3.5%, about 4%, about 4.5%, about 5%, about 5.5%, about 6%, or a range between any two of these values. In certain embodiments of the hydrogel formulation, the medium chain triglycerides are in an amount of about 4%. All of the above represent weight percentages of the hydrogel formulation embodiments.

[0158] Polydispersity Index (PDI) is used to measure the breadth of molecular weight distribution of AB-101. PDI is used to indicate the distribution of polymer chain molecular weights in a given polymer, and as the PDI value increases, there is an increase in crosslinking, network formation, heterogeneity in chain length, branching, hyperbranching, and a more random arrangement. PDI is an important measure to characterize the unique compositional properties of AB-101 or other Croton lechleri ​​derived compositions. In any of the embodiments disclosed herein, the Croton lechleri ​​latex, preferably the filtered Croton lechleri ​​latex, preferably the filtered Croton lechleri ​​Mull.Arg latex, has a PDI of about 0.5 to about 0.85, about 0.55 to about 0.85, about 0.6 to about 0.85, about 0.65 to about 0.85, about 0.7 to about 0.85, about 0.75 to about 0.85, about 0.8 to about 0.85, about 0.5 to about 0.8, about 0.5 to about 0.75, about 0.5 to about 0.7, about 0.5 to about 0.65, about 0.5 to about 0.6, about 0.5 to about 0.55, or values ​​within these ranges. Specific examples include about 0.5, about 0.55, about 0.6, about 0.65, about 0.7, about 0.75, about 0.8, about 0.85, or a range between any two of these values. In some embodiments, the Croton lechleri ​​latex, preferably the Croton lechleri ​​filtered latex, preferably the Croton lechleri ​​Mull.Arg filtered latex, has a PDI of about 0.81.

[0159] In some embodiments, the hydrogel formulation is as described in Table C: [Table 8]

[0160] In some embodiments, the hydrogel formulation is as set forth in Table D: [Table 9]

[0161] In some embodiments, the hydrogel formulation is as set forth in Table E: [Table 10]

[0162] In some embodiments, the hydrogel formulation is as set forth in Table F: [Table 11]

[0163] The hydrogel formulation of AB-101 described and claimed herein is a plant-derived material that meets the criteria of being consistently reproducible from batch to batch and reliably providing the desired health benefits via topical application that may be used in hydrogel formulations. It can be used to treat dermatological conditions. Plant-derived raw materials face the challenge of varying plant characteristics that can affect quality due to changes in environmental weather, climate, rainfall, harvest time (by season, time of day, month), geographical changes, longitude location, latitudinal location, altitude, changes in soil conditions, harvesting protocols, and many other conditions. This can affect the bioactivity of the plant, resulting in inconsistencies in achieving the desired performance. This creates a challenge in defining a pharmaceutical grade of Dragon's Blood to provide a consistent and reproducible therapeutic effect. This is further complicated by the wide variety of species referred to as Dragon's Blood. For example, the phytochemical and anti-staphylococcal biofilm evaluation of Dracaena draco L.Spp. draco resin, referred to as Dragon's Blood, is "inactive against free-living Staphylococcus aureus at the maximum tested concentration of 1000mcg / ml." In contrast, AB-101 (latex of Croton lechleri, preferably filtered latex of Croton lechleri, preferably filtered latex of Croton lechleri ​​Mull.Arg with appropriate levels of gallocatechin, epigallocatechin, catechin, epicatechin, taspine, and dimethylcedrucin) is effective against Staphylococci, especially Methicillin-susceptible Staphylococcus aureus (MSSA) or Staphylococcus aureus in the shortened nomenclature, especially Methicillin-resistant Staphylococcus aureus (MRSA), especially Mupirocin-resistant MRSA. The common name of Croton lechleri ​​resin, i.e. Dragon's Blood (Sangre de grado), has led to confusion in defining plant-derived medicines, indicating that not all Croton lechleri ​​plants are the same or produce similar effects.

[0164] The advantage of AB-101 (filtered or unfiltered latex of Croton lechleri, preferably filtered latex of Croton lechleri, preferably filtered latex of Croton lechleri ​​Mull.Arg.) is its ability to provide consistent results for treating pathogens from batch to batch despite all confounding conditions. The challenge with using whole latex is identifying compounds that perform based on the many bioactive compounds that make up the latex. Even from the same species and grown in similar locations, there is variability in the chemical content and bioactivity of whole latex, resulting in unexpectedly different abilities to fight and kill pathogens.

[0165] A methodology that can identify the entire latex is useful in having an assay that determines when a batch meets predefined performance criteria. Having proprietary analytical and microbiological assays allows the ability to identify which batches of Croton lechleri ​​filtered or unfiltered latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​filtered latex Mull.Arg, have the combination of ingredients that consistently deliver the desired results.

[0166] AB-101 Plant Raw Material (BRM) is a composite plant product that contains specific amounts of specific marker compounds (catechin, gallocatechin, epicatechin, epigallocatechin, taspine, and dimethylcedrusine) (see Table 1a). Liquid chromatography with tandem mass spectrometry (LC-MS / MS) can be utilized to characterize the presence and levels of such marker compounds for consistent and reproducible performance between batches of AB-101. Marker compounds in AB-101 BRM include proanthocyanidins: catechin, gallocatechin, epicatechin, epigallocatechin, the alkaloid taspine, and the lignin dimethylcedrusine.

[0167] The taxonomic classification of Croton lechleri ​​Mull.Arg. is as follows (van Ee & Berry, 2011, Riina et al, 2009, The Plant List, 2012, The Angiosperm Phylogeny Group, 2009): Phylum Gymnosperms Class Angiosperms Subclass: Magnoliaceae Order Malpighiformes Euphorbiaceae Euphorbiaceae Genus Croton Subgenus Adenophili Section Cyclostigma Subsection Cyclostigma Species: Croton lechleri ​​Mull.Arg.

[0168] Plant biodiversity plays a key role in the characterization of the constituent chemical compounds. Chemical compounds utilized to ensure critical batch-to-batch consistency of AB-101 must 1) exhibit antimicrobial or scar-forming properties, 2) be present in AB-101, and 3) be detectable by analytical techniques. Using these criteria, the analytical work focused on three classes of compounds: polyphenols (proanthocyanidins), alkaloids (taspines), and lignins (dimethylcedrusin). In the proanthocyanidin class, four compounds were noted: catechin, epicatechin, gallocatechin, and epigallocatechin. In the alkaloid class, a key compound is taspine. Finally, in the lignin class, a key compound is dimethylcedrusin. Each of these compounds fulfills the three required elements detailed above. Below are the chemical structures of the six compounds utilized as critical markers of batch-to-batch consistency of AB-101.

[0169] Proanthocyanidins [ka]

[0170] For characterization studies, AB-101 extracts were freeze-dried and the freeze-dried powder was subjected to three different extraction methods.

[0171] Method 1 - Ultrasonic polyphenol extraction. Freeze-dried AB-101 extract was dissolved in methanol. The resulting emulsion was sonicated for 10 min and then centrifuged to remove particulates for 5 min. The supernatant was subjected to LC-MS / MS analysis.

[0172] Method 2 - Soxhlet extraction. The freeze-dried AB-101 extract was subjected to Soxhlet extraction with 80% ethanol. The ethanol was removed by rotary evaporation. The resulting material was resuspended in ethanol and subjected to LC-MS / MS analysis.

[0173] Method 3 - Polyphenol extraction. Lyophilized AB-101 extract was incubated with methanol overnight at room temperature in the dark. The supernatant was filtered through a Whatman filter, dried, and then resuspended in methanol. The resulting material was subjected to LC-MS / MS analysis.

[0174] Figure 1 shows a representative total ion chromatogram and additional multiple reaction monitoring spectra identifying key marker compounds in the AB-101 extract. Figure 6 shows a representative total ion chromatogram of dimethylcedrusin, a compound that is detectable using all three extraction methods.

[0175] Biodiversity introduces a huge amount of variability. To capture this variation, NMR techniques using "spectral fingerprints" were used with overlapping reference standards. These fingerprints capture most of the components within AB-101 and can be quantified using nuclear magnetic resonance (NMR). Examples of NMR spectra using three different lots of AB-101 (lots 00, 01, and 02, respectively) and two different deuterated solvents (D2O and d4-methanol, respectively) are shown in Figures 2A and 3A, and spectral overlays of each solvent are shown in Figures 2B and 3B, showing no significant variation.

[0176] In a separate NMR analysis using d4-methanol as the solvent, four different lots of AB-101 (Lots 00, 01, 02, and X, respectively) were compared. The NMR spectrum of each lot is shown in Figure 4A, with the spectra of each lot overlaid in Figure 4B. Although the fingerprints of the four lots appear similar, there are important differences. This is shown by comparing the concentration levels in ppm based on the LC-MS / MS quantitative and qualitative NMR "fingerprints" for the marker compounds catechin, epicatechin, gallocatechin, epigallocatechin, taspine, and dimethylcedrusine. The results are shown in Table 2, showing that lots 1 and 2 are more similar, while lots X and 0 have the greatest differences. [Table 12]

[0177] 5A-E are bar graphs comparing the results of AB-101 lot analyses of five marker compounds.

[0178] Lot 00 is an example of a lot that is not suitable for use with the hydrogel formulations and methods of use described herein. Lots X, 01, and 02 are examples of lots that are suitable for use with the hydrogel formulations and methods of use described herein.

[0179] Zheng-Ping Chen's publication (Studies on the Anti-Tumour, Anti-Bacterial and Wound-Healing Properties of Dragon's Blood, Planta Med. 60 (1994)) shows the non-obviousness of identifying the optimal properties of pharmaceutical grade AB-101. Chen uses a bioassay that measures the rate of incorporation of H-thymidine into the DNA of cells in the presence of a test sample. This bioassay allows the wound-healing properties of the "sap" to be measured. Chen used latex from Croton lechleri ​​MUll.Arg from Ecuador. The assay showed that the uptake rates of the dried sap and MeOH extract were 68±12 and 88±5. According to Chen, the dried sap and MeOH were found to be highly inhibitory to wound healing properties. One skilled in the art would not expect the entire Croton lechleri ​​MUll.Arg latex extract to be effective in wound healing. Chen further stated that the Ecuadorian sap only contained trace amounts of taspine. Chen wanted to minimize or remove taspine entirely due to concerns about its cytotoxicity. Chen evaluated certain compounds through extraction. In particular, gallocatechin and epigallocatechin were evaluated to slightly stimulate cell proliferation, while catechin and epicatechin showed little effect. Furthermore, taspine and dimethylcedrusine showed little healing effect in the Ecuadorian sap.

[0180] Pharmaceutical grade AB-101 identified a unique composition that maximizes healing properties while maintaining film forming, low LogP, and antibiotic activity. Chen maintained Croton lechleri ​​Mull.AB-101 Pharmaceutical Grade uses whole Arg latex, including taspine and dimethyl cedrusine. Arg latex is a medicinal ingredient associated with localized wound healing effects. Taspine has antibiotic, antiviral, and anti-inflammatory properties. Dimethyl cedrusine has unique fibroblast stimulating properties that promote healing. Gallocatechin and epigallocatechin were optimized to be at least approximately 60% of the total of the four catechins, and epigallocatechin was optimized to be at least approximately 45% of the total of the four catechins.

[0181] In some embodiments, the Croton lechleri ​​latex, preferably the filtered Croton lechleri ​​latex, preferably the filtered Croton lechleri ​​latex Mull.Arg., has a minimum bactericidal concentration (MBC) of about 6.25 (% vol. / vol.), about 12.5 (% vol. / vol.), about 25 (% vol. / vol.), about 50 (% vol. / vol.), or a range between any two of these values. In some embodiments, the Croton lechleri ​​latex, preferably the filtered Croton lechleri ​​latex, preferably the filtered Croton lechleri ​​Mull.Arg. latex, has an MBC of about 6.25 (% vol. / vol.) to about 50 (% vol. / vol.).

[0182] Some embodiments of the present disclosure are directed to hydrogel formulations that further comprise one or more other therapeutic components. In embodiments, the hydrogel formulation comprises a therapeutically effective amount of latex of Croton lekleri, preferably filtered latex of Croton lekleri, preferably filtered latex of Croton lekleri Mull.Arg. In embodiments, the hydrogel formulation is suitable for topical administration or is a topical hydrogel formulation.

[0183] The excipients must be "acceptable" in the sense that they are compatible with the other components of the formulation and are not harmful to the recipient of the formulation. The excipients utilize a small number of known, well-characterized excipient components that are not irritating or sensitizing when used topically or on a wound and do not reduce the efficacy of AB-101. The appropriate formulation of the hydrogel formulation depends on the selected route of administration. Any of the well-known techniques and excipients may be suitably used as understood in the art. The hydrogel formulations disclosed herein may be manufactured by any method known in the art.

[0184] Some examples of suitable excipients include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, and methylcellulose, including eutectic solvents, eutectic-based ionic liquids, or ionic liquids. Hydrogel formulations can further include lubricants such as talc, magnesium stearate, mineral oil, wetting agents, emulsifying and suspending agents, and preservatives such as methyl- and propylhydroxy-benzoates.

[0185] Compositions include those suitable for topical (e.g., cutaneous, oral mucosal, buccal, sublingual, intraocular, and wound cavity) administration, although the most suitable route may depend, for example, on the condition and disorder of the recipient. The compositions may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. Typically, these methods include the step of associating Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg. filtered latex, where the composition contains at least the concentration of the Croton lechleri ​​latex component of the reference standard ("active ingredient") disclosed herein, preferably the concentration of the Croton lechleri ​​filtered latex component, preferably the concentration of the Croton lechleri ​​Mull.Arg filtered latex component, and a carrier constituting one or more accessory ingredients. In general, the compositions are prepared by uniformly and intimately bringing into association the active ingredients with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product into the desired composition.

[0186] The hydrogel formulations disclosed herein may be administered topically, i.e., by non-systemic administration. This includes applying the compounds disclosed herein externally to the surface of the skin and / or wound cavity to achieve a therapeutically effective amount in the skin, such as the epidermis, dermis, and / or wound cavity. In embodiments, topical administration or topical hydrogel formulations do not result in systemic administration or exposure of Croton lekleri to the patient.

[0187] Preferred unit dosage pharmaceutical compositions are those containing an effective amount, as herein below recited, or an appropriate fraction thereof.

[0188] The hydrogel formulations can be formulated in unit dosage form. The term "unit dosage form" refers to physically discrete units suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined amount of active material calculated to produce a desired therapeutic effect, in association with a suitable pharmaceutical excipient.

[0189] An active hydrogel formulation comprising Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg filtered latex, wherein the composition comprises at least the concentration of the components of the Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, of a reference standard, and can be effective over a wide dosage range and generally administered in a therapeutically effective amount. However, the amount of the hydrogel formulation comprising Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg filtered latex. wherein the composition comprises at least the concentration of the components of a reference standard Croton lechreri latex, preferably the concentration of the components of a filtered latex of Croton lechreri, preferably the concentration of the components of a filtered latex of Croton lechreri Mull.Arg., the latex actually administered will usually be determined by a physician depending on the relevant circumstances including the condition to be treated, the selected route of administration, the compound actually administered, the individual patient's age, weight, response, severity of the patient's symptoms, etc.

[0190] The pharma- ceutically acceptable excipients may be selected from one or more cream bases, one or more emulsifiers, one or more preservatives, one or more humectants, one or more diluents, and latex of Croton lechleri, preferably filtered latex of Croton lechleri, preferably filtered latex of Croton lechleri ​​Mull.Arg.

[0191] In some embodiments, the therapeutically effective amount may vary, for example, according to the specific application to be treated, the method of administration of the compound, the health and condition of the patient, and the judgment of the prescribing physician.The proportion or concentration of Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg filtered latex, is as follows, where the composition contains at least the concentration of Croton lechleri ​​latex components of the reference standard, preferably Croton lechleri ​​filtered latex components, preferably Croton lechleri ​​filtered latex Mull.Arg components, in the hydrogel formulation, and may vary depending on many factors, including dosage, chemical properties (e.g., hydrophobicity), and route of administration. For example, the compounds may be provided in a physiologically buffered aqueous solution containing about 0.1 to about 10% w / v of the compound for parenteral administration. Some typical dose ranges of the compounds are about 1 μg / kg to about 1 g / kg of body weight per day. In some embodiments, the dose range is about 0.01 mg / kg to about 100 mg / kg of body weight per day. The dosage will depend on variables such as the type and extent of progression of the disease or disorder, the overall health of the particular patient, the relative biological potency of the selected compound, the composition of the excipients, and its route of administration. Effective amounts can be extrapolated from dose-response curves derived from in vitro or animal model test systems.

[0192] The amount of the composition administered to a patient will vary depending on what is being administered, the purpose of the administration, such as prophylaxis or treatment, the condition of the patient, the method of administration, etc. In therapeutic applications, compositions can be administered to a patient already suffering from a disease in an amount sufficient to cure or at least partially arrest the symptoms of the disease and its complications.

[0193] Methods for preparing hydrogel formulations The present invention relates to a method for preparing a hydrogel formulation comprising the steps of: 1) preparing phase A by combining propanediol, methylparaben, and propylparaben to form phase A, then mixing phase A and heating at an initial temperature of about 40° C. to about 70° C. until phase A becomes clear, at which point heating is stopped; 2) Combine edetate disodium dihydrate, water, sodium benzoate, and potassium sorbate to form phase B, then mix phase B and stir for approximately 40 minutes until phase B is clear. o Prepare phase B by heating from C to a second temperature of about 70°C, stopping heating when clear; 3) adding phase B to phase A to form phase C, and stirring at a first stirring speed of about 500 rpm to about 1000 rpm; 4) PHOSAL® 50PG (phosphatidylcholine, lysophosphatidylcholine, propylene glycol, sunflower seed oil glycerides, ethanol, soybean fatty acids, ascorbyl palmitate, D,L-α-tocopherol) is added to the stirred phase C to form phase D and stirred at a second stirring speed of about 500 rpm to about 1000 rpm, for example, for about 3 minutes; 5) Prepare Phase E by combining Caprylic / Capric Triglyceride and SEPINEO™ P600 (Acrylamide / Sodium Acryloyldimethyltaurate Copolymer / Isohexadecane / Polysorbate 80) and mixing until uniform; 6) Add Phase E to Phase D to form Phase F and stir at a third stirring speed of about 500 rpm to about 1000 rpm, for example, for about 3 minutes; 7) cooling Phase F to a third temperature of about 45° C. or less; 8) adding Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​filtered latex Mull.Arg., where the composition comprises at least a concentration of the Croton lechleri ​​latex component, preferably a concentration of the Croton lechleri ​​filtered latex component, preferably a concentration of the Croton lechleri ​​filtered latex component Mull.Arg., and stirring at a fourth stirring speed of about 500 rpm to about 1000 rpm, for example for about 5 minutes; 9) Add dimethicone to Phase G and stir at a fifth stirring speed of about 500 rpm to about 1000 rpm for about 2 minutes to form the hydrogel formulation.

[0194] In some embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation comprises propanediol in an amount of about 1% to about 10%, about 2% to about 10%, about 3% to about 10%, about 4% to about 10%, about 5% to about 10%, about 6% to about 10%, about 7% to about 10%, about 8% to about 10%, about 9% to about 10%, about 1% to about 9%, about 1% to about 8%, about 1% to about 7%, about 1% to about 6%, about 1% to about 5%, about 1% to about 4%, about 1% to about 3%, about 1% to about 2%, about 2% to about 9%, about 3% to about 8%, about 4% to about 7%, about 5% to about 6%, or a value within one of these ranges. Specific examples include about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, or a range between any two of these values. In certain embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation comprises propanediol in an amount of about 5%. In certain embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation comprises propanediol in an amount of about 4%. All of the above represent weight percentages of the resulting hydrogel formulation embodiments.

[0195] In some embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation may comprise from about 0.05% to about 0.5%, about 0.1% to about 0.5%, about 0.15% to about 0.5%, about 0.2% to about 0.5%, about 0.25% to about 0.5%, about 0.3% to about 0.5%, about 0.35% to about 0.5%, about 0.4% to about 0.5%, about 0.45% to about 0.5%, about 0.05% to about 0.45%, about 0.05% to about 0.4%, about 0.05% to about 0.35%, about 0.05% to about 0.3%, about 0.05% to about 0.25%, about 0.05% to about 0.2%, about 0.05% to about 0.15%, about 0.05% to about 0.1%, about 0.1% to about 0.45%, about 0.15% to about 0.4%, about 0.2% to about 0.35%, about 0.25% to about 0.30%, about 0.05% to about 0.25%, about 0.075% to about 0.225%, about 0.1% to about 0.2%, about 0.125% to about 0.175%, or a value within these ranges. Specific examples include about 0.05%, about 0.1%, about 0.15%, about 0.2%, about 0.25%, about 0.3%, about 0.35%, about 0.4%, about 0.45%, about 0.5%, about 0.2%, about 0.225%, about 0.25%, about 0.275%, about 0.3%, or a range between any two of these values. In certain embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation comprises methylparaben in an amount of about 0.15%. In certain embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation comprises methylparaben in an amount of about 0.1%. All of the above represent weight percent of the resulting hydrogel formulation embodiment.

[0196] In some embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation comprises propylparaben in an amount of about 0.005% to about 0.05%, about 0.01% to about 0.05%, about 0.025% to about 0.05%, about 0.025% to about 0.05%, about 0.03% to about 0.05%, about 0.015% to about 0.05%, about 0.02% to about 0.05%, about 0.025% to about 0.05%, about 0.03% to about 0.05%, about 0.035% to about 0.05%, about 0.04% to about 0.05%, about 0.045% to about 0.05%, about 0.005% to about 0.045%, about 0.005% to about 0.035%, about 0.005% About 0.03%, about 0.005% to about 0.02%, about 0.005% to about 0.015%, about 0.005% to about 0.01%, about 0.01% to about 0.045%, about 0.02% to about 0.04%, about 0.025% to about 0.035%, about 0.02% to about 0.04%, about 0.015% to about 0.045%, or values ​​within these ranges. Specific examples include about 0.005%, about 0.01%, about 0.02%, about 0.025%, about 0.03%, about 0.035%, about 0.04%, about 0.045%, about 0.05%, or a range between any two of these values. In certain embodiments of the methods of preparing a hydrogel formulation, the resulting hydrogel formulation comprises propylparaben in an amount of about 0.02%. All of the above represent weight percentages of the resulting hydrogel formulation embodiment.

[0197] In certain embodiments of the method of preparing a hydrogel formulation, the first temperature is about 40° C. to about 70° C., about 45° C. to about 65° C., about 50° C. to about 60° C., or a value within one of these ranges. In certain embodiments of the method of preparing a hydrogel formulation, the first temperature is about 55° C.

[0198] In some embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation has a hydrogel concentration of about 0.05% to about 0.5%, about 0.1% to about 0.5%, about 0.15% to about 0.5%, about 0.2% to about 0.5%, about 0.25% to about 0.5%, about 0.3% to about 0.5%, about 0.35% to about 0.5%, about 0.4% to about 0.5%, about 0.45% to about 0.5%, about 0.05% to about 0.45%, about 0.05% to about 0.4%, about 0.05% to about 0.35% , about 0.05% to about 0.3%, about 0.05% to about 0.25%, about 0.05% to about 0.2%, about 0.05% to about 0.15%, about 0.05% to about 0.1%, about 0.1% to about 0.45%, about 0.15% to about 0.4%, about 0.2% to about 0.35%, about 0.25% to about 0.30%, about 0.05% to about 0.25%, about 0.075% to about 0.225%, about 0.1% to about 0.2%, about 0.125% to about 0.175%, or a value within these ranges. Specific examples include about 0.05%, about 0.1%, about 0.15%, about 0.2%, about 0.25%, about 0.3%, about 0.35%, about 0.4%, about 0.45%, about 0.5%, about 0.2%, about 0.225%, about 0.25%, about 0.275%, about 0.3%, or ranges between any two of these values. In certain embodiments of the method for preparing a hydrogel formulation, the resulting hydrogel formulation comprises edetate disodium dihydrate in an amount of about 0.15%. In certain embodiments of the method for preparing a hydrogel formulation, the resulting hydrogel formulation comprises edetate disodium dihydrate in an amount of about 0.10%. All of the above represent weight percent of the resulting hydrogel formulation embodiment.

[0199] In some embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation contains water in an amount of about 20% to about 80%, about 25% to about 80%, about 30% to about 80%, about 35% to about 80%, about 40% to about 80%, about 45% to about 80%, about 50% to about 80%, about 55% to about 80%, about 60% to about 80%, about 65% to about 80%, about 70% to about 80%, about 75% to about 80%, ...25% to about 80%, about 25% to about 80%, about 25% to about 80%, about 25% to about 80%, about 25% to about 80%, about 25% to about 80%, about 25% to about 80%, about 25% to about 80%, about 25% to about 80%, about 25% to about 80%, about 25% to about 80%, about 25% to about 80%, about 25% to about 80%, about 25% to about 80%, about 25% to about 80%, about 25% to about 80%, about 25% to about 80%, about 25% to about 80%, about 2 0% to about 75%, about 20% to about 70%, about 20% to about 65%, about 20% to about 60%, about 20% to about 55%, about 20% to about 50%, about 20% to about 45%, about 20% to about 40%, about 20% to about 35%, about 20% to about 30%, about 20% to about 25%, about 25% to about 75%, about 30% to about 70%, about 35% to about 65%, about 40% to about 60%, about 45% to about 55%, or values ​​within these ranges. Specific examples include about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 60%, about 75%, about 80%, or a range between any two of these values. In certain embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation comprises water in an amount of about 43.38%. In certain embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation comprises water in an amount of about 33.38%. In certain embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation comprises water in an amount of about 40.38%. In certain embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation comprises water in an amount of about 38.38%. In certain embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation comprises water in an amount of about 40.7%. In certain embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation comprises water in an amount of about 39%. All of the above represent weight % of the resulting hydrogel formulation embodiment.

[0200] In some embodiments of the method for preparing a hydrogel formulation, the resulting hydrogel formulation comprises sodium benzoate in an amount of about 0.005% to about 0.1%, about 0.1% to about 1%, about 0.05% to about 0.5%, or a value within one of these ranges. Specific examples include about 0.005%, about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.1%, about 0.4%, about 0.45%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, or a range between any two of these values. In certain embodiments of the method for preparing a hydrogel formulation, the resulting hydrogel formulation comprises sodium benzoate in an amount of about 0.40%. In certain embodiments of the methods of preparing a hydrogel formulation, the resulting hydrogel formulation comprises sodium benzoate in an amount of about 0.45%, all of which represent weight percentages of the resulting hydrogel formulation embodiment.

[0201] In some embodiments of the method for preparing a hydrogel formulation, the resulting hydrogel formulation comprises potassium sorbate in an amount of about 0.005% to about 0.1%, about 0.1% to about 1%, about 0.05% to about 0.5%, or a value within one of these ranges. Specific examples include about 0.005%, about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.1%, about 0.4%, about 0.45%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, or a range between any two of these values. In certain embodiments of the method for preparing a hydrogel formulation, the resulting hydrogel formulation comprises potassium sorbate in an amount of about 0.45%. All of the above represent weight percent of the resulting hydrogel formulation embodiment.

[0202] In certain embodiments of the method of preparing a hydrogel formulation, the second temperature is about 40 o C ~ about 70 o C, about 45 o C~about 65 o C, about 50 o C~about 60 oC, or a value within one of these ranges. In certain embodiments of the method of preparing a hydrogel formulation, the second temperature is about 55° C.

[0203] In certain embodiments of the method of preparing a hydrogel formulation, the first stirring speed is about 500 rpm to about 1000 rpm, about 500 rpm to about 900 rpm, about 500 rpm to about 800 rpm, about 500 rpm to about 700 rpm, about 500 rpm to about 600 rpm, about 600 rpm to about 700 rpm, about 600 rpm to about 800 rpm, about 600 rpm to about 900 rpm, about 600 rpm to about 1000 rpm, or a value within one of these ranges. In certain embodiments of the method of preparing a hydrogel formulation, the first stirring speed is about 600 rpm.

[0204] In some embodiments of the method for preparing a hydrogel formulation, the resulting hydrogel formulation contains PHOSAL® 50PG (phosphatidylcholine, lysophosphatidylcholine, propylene glycol, sunflower seed oil glycerides, ethanol, soybean fatty acids, ascorbyl palmitate, D,L-α-tocopherol) at about 0.5% to about 5%, about 1% to about 3%, 0.5% to about 2%, about 0.05% to about 0.2%, about 0.25% to about 1.25%, about 0.01% to about 0.1%, about 0.001% to about 0.01%, about 0.005% to about 0.02%, or values ​​within these ranges. Specific examples include about 0.001%, about 0.004%, about 0.005%, about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.1%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, or a range between any two of these values. In a particular embodiment of the method for preparing a hydrogel formulation, the resulting hydrogel formulation comprises PHOSAL® 50PG (phosphatidylcholine, lysophosphatidylcholine, propylene glycol, sunflower seed oil glyceride, ethanol, soybean fatty acid, ascorbyl palmitate, D,L-α-tocopherol) in an amount of about 2%. All of the above represent weight percent of the resulting hydrogel formulation embodiment.

[0205] In certain embodiments of the method of preparing a hydrogel formulation, the second stirring speed is about 500 rpm to about 1000 rpm, about 500 rpm to about 900 rpm, about 500 rpm to about 800 rpm, about 500 rpm to about 700 rpm, about 500 rpm to about 600 rpm, about 600 rpm to about 700 rpm, about 600 rpm to about 800 rpm, about 600 rpm to about 900 rpm, about 600 rpm to about 1000 rpm, or a value within one of these ranges. In certain embodiments of the method of preparing a hydrogel formulation, the second stirring speed is about 600 rpm.

[0206] In some embodiments of the methods of preparing a hydrogel formulation, the resulting hydrogel formulation comprises caprylic / capric triglyceride in an amount of about 1% to about 10%, about 2% to about 10%, about 3% to about 10%, about 4% to about 10%, about 5% to about 10%, about 6% to about 10%, about 7% to about 10%, about 8% to about 10%, about 9% to about 10%, about 1% to about 9%, about 1% to about 8%, about 1% to about 7%, about 1% to about 6%, about 1% to about 5%, about 1% to about 4%, about 1% to about 3%, about 1% to about 2%, about 2% to about 9%, about 3% to about 8%, about 4% to about 7%, about 5% to about 6%, or a value within one of these ranges. Specific examples include about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, or ranges between any two of these values. In certain embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation comprises caprylic / capric triglyceride in an amount of about 5%. In certain embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation comprises caprylic / capric triglyceride in an amount of about 7%. All of the above represent weight percentages of the resulting hydrogel formulation embodiments.

[0207] In some embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation comprises SEPINEO™ P 600 (acrylamide / sodium acrylonitrile dimethyl taurate copolymer / isohexadecane / polysorbate 80) in an amount of about 0.5% to about 10%, 0.5% to about 10%, about 1% to about 10%, about 1.5% to about 10%, about 2% to about 10%, about 2.5% to about 10%, about 3% to about 10%, about 3.5% to about 10%, about 4% to about 10%, or about 5% to about 10%. 0%, about 4.5% to about 10%, about 5% to about 10%, about 5.5% to about 10%, about 6% to about 10%, about 6.5% to about 10%, about 7% to about 10%, about 7.5% to about 10%, about 8% to about 10%, about 8.5% to about 10%, about 9% to about 10%, about 9.5% to about 10%, about 0.5% to about 9.5%, about 0.5% to about 9%, about 0.5% to about 8.5%, about 0.5% to about 8%, about 0.5% to about 7.5%, about 0.5% to about 7%, about 0.5% to about 6.5%, about 0.5% to about 5.5%, about 0.5% to about 5%, about 0.5% to about 4.5%, about 0.5% to about 4%, about 0.5% to about 3.5%, about 0.5% to about 3%, about 0.5% to about 2.5%, about 0.5% to about 2%, about 0.5% to about 1.5%, about 0.5% to about 1%, about 1% to about 9.5%, about 1.5% to about 9%, about 2% to about 8.5%, about 0.5% to about 8%, about 3% to about 7.5%, about 3.5% to about 7%, about 4% to about 6.5%, about 4.5% to about 6%, about 5% to about 5.5%, about 1% to about 5%, about 1.5% to about 4.5%, about 2% to about 4%, about 2.5% to about 3.5%, or a value within these ranges. Specific examples include about 0.5%, about 1%, about 1.5%, about 2%, about 2.5%, about 3%, about 3.5%, about 4%, about 4.5%, about 5%, about 5.5%, about 6%, about 6.5%, about 7%, about 7.5%, about 8%, about 8.5%, about 9%, about 9.5%, about 10%, or a range between any two of these values. In certain embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation comprises SEPINEO™ P600 (acrylamide / sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80) in an amount of about 3.3%.In certain embodiments of the methods of preparing a hydrogel formulation, the resulting hydrogel formulation comprises SEPINEO™ P600 (acrylamide / sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80) in an amount of about 4.0%, all of which represent weight % of the resulting hydrogel formulation embodiment.

[0208] In certain embodiments of the method of preparing a hydrogel formulation, the third stirring speed is about 500 rpm to about 1000 rpm, about 500 rpm to about 900 rpm, about 500 rpm to about 800 rpm, about 500 rpm to about 700 rpm, about 600 rpm to about 700 rpm, about 600 rpm to about 800 rpm, about 600 rpm to about 900 rpm, about 600 rpm to about 1000 rpm, or a value within one of these ranges. In certain embodiments of the method of preparing a hydrogel formulation, the third stirring speed is about 700 rpm to about 1000 rpm. In certain embodiments of the method of preparing a hydrogel formulation, the third stirring speed is about 700 rpm.

[0209] In certain embodiments of the method of preparing a hydrogel formulation, the third temperature is less than about 25° C., less than about 30° C., less than about 35° C., less than about 40° C., less than about 45° C., or a value within one of these ranges. In certain embodiments of the method of preparing a hydrogel formulation, the third temperature is less than about 25° C. In certain embodiments of the method of preparing a hydrogel formulation, the third temperature is less than about 30° C. In certain embodiments of the method of preparing a hydrogel formulation, the third temperature is less than about 35° C. In certain embodiments of the method of preparing a hydrogel formulation, the third temperature is less than about 40° C. In certain embodiments of the method of preparing a hydrogel formulation, the third temperature is less than about 45° C. In certain embodiments of the method of preparing a hydrogel formulation, the third temperature is about 20° C.

[0210] In some embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation comprises Croton lekleri latex, preferably Croton lekleri filtered latex, preferably Croton lekleri filtered latex Mull.Arg., wherein the composition comprises at least a concentration of a component of Croton lekleri latex, preferably Croton lekleri filtered latex Mull.Arg., and the amount of the reference standard is about 5% to about 80%, about 10% to about 80%, about 15% to about 80%, about 20% to about 80%, about 25% to about 80%, about 30% to about 80%, about 35% to about 80%, about 40% to about 80%, about 45% to about 80%, about 46% to about 80%, about 47% to about 80%, about 48% to about 80%, about 49% to about 90%, about 50% to about 90%, about 51% to about 90%, about 52% to about 90%, about 53% to about 90%, about 54% to about 90%, about 55% to about 90%, about 56% to about 90%, about 57% to about 90%, about 58% to about 90%, about 59% to about 90%, about 60% to about 90%, about 61% to about 90%, about 62% to about 90%, about 63% to about 90%, about 64% to about 90%, about 65% to about 90%, about 66% to about 90%, about 67% to about 90%, about 68% to about 90%, about 69% to about 90%, about 70% to about 90%, about 71% to about 90%, about 72% to about 90%, about 73% to about 9 Arg of reference standard substance in an amount of about 80%, about 45% to about 80%, about 50% to about 80%, about 55% to about 80%, about 60% to about 80%, about 65% to about 80%, about 70% to about 80%, about 75% to about 80%, about 5% to about 75%, about 5% to about 70%, about 5% to about 65%, about 5% to about 60%, about 5% to about 55%, about 5% to about 50%, about 5% to about 45% , about 5% to about 40%, about 5% to about 35%, about 5% to about 30%, about 5% to about 25%, about 5% to about 20%, about 5% to about 15%, about 5% to about 10%, about 10% to about 75%, about 15% to about 70%, about 20% to about 65%, about 25% to about 60%, about 30% to about 55%, about 35% to about 55%, about 40% to about 50%, or a value within one of these ranges. Specific examples can include about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, or a range between any two of these values.In certain embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation comprises Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg filtered latex, wherein the composition comprises at least the concentration of components of the Croton lechleri ​​latex, preferably the concentration of components of the Croton lechleri ​​filtered latex, preferably the concentration of components of the Croton lechleri ​​Mull.Arg filtered latex, of a reference standard in an amount of at least about 40%. In certain embodiments of the method for preparing a hydrogel formulation, the resulting hydrogel formulation comprises Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​filtered latex Mull.Arg, wherein the composition comprises at least the concentration of the components of the Croton lechleri ​​latex of the reference standard, preferably the concentration of the components of the Croton lechleri ​​filtered latex, preferably the concentration of the components of the Croton lechleri ​​Mull.Arg filtered latex, in an amount of about 50%. In certain embodiments of the method for preparing a hydrogel formulation, the resulting hydrogel formulation comprises Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​filtered latex Mull.Arg. Here, the composition comprises at least the concentration of components of the reference standard Croton lechleri ​​latex, preferably the concentration of components of the filtered Croton lechleri ​​latex, preferably the concentration of components of the filtered Croton lechleri ​​Mull.Arg latex in an amount of about 43%.In certain embodiments of the method for preparing a hydrogel formulation, the resulting hydrogel formulation comprises Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​filtered latex Mull.Arg., wherein the composition comprises at least the concentration of the components of the Croton lechleri ​​latex of the reference standard, preferably the concentration of the components of the Croton lechleri ​​filtered latex, preferably the concentration of the components of the Croton lechleri ​​filtered latex Mull.Arg., in an amount of about 45%. The aforementioned percentages are for compost made from AB-101 having exemplary amounts of marker compounds present in the latex as disclosed in Table 1a. To illustrate, a pharmaceutical composition containing 100% AB-101 contains at least about 110 PPM of gallocatechins, and a pharmaceutical composition containing 200% AB-101 contains at least about 220 PPM of gallocatechins, all of which represent weight percentages of the resulting hydrogel formulation embodiment.

[0211] In certain embodiments of the method of preparing a hydrogel formulation, the fourth stirring speed is about 500 rpm to about 1000 rpm, about 500 rpm to about 900 rpm, about 500 rpm to about 800 rpm, about 500 rpm to about 700 rpm, about 600 rpm to about 700 rpm, about 600 rpm to about 800 rpm, about 600 rpm to about 900 rpm, about 600 rpm to about 1000 rpm, or a value within one of these ranges. In certain embodiments of the method of preparing a hydrogel formulation, the fourth stirring speed is about 700 rpm.

[0212] In some embodiments of the method of preparing a hydrogel formulation, the resulting hydrogel formulation may be from about 0.5% to about 10%, about 1% to about 10%, about 1.5% to about 10%, about 2% to about 10%, about 2.5% to about 10%, about 3% to about 10%, about 3.5% to about 10%, about 4% to about 10%, about 4.5% to about 10%, about 5% to about 10%, about 5.5% to about 10%, about 6% to about 10%, about 6.5% to about 10%, about 7% to about 10%, about 7.5% to about 10%, about 8% to about 10%, about 8.5% to about 10%, about 9% to about 10%, about 9.5% to about 10%, about 0.5% to about 9.5%, about 0.5% to about 8.5%, about 0.5% to about 7.5%. , about 0.5% to about 7%, about 0.5% to about 6.5%, about 0.5% to about 6%, about 0.5% to about 5.5%, about 0.5% to about 4.5%, about 0.5% to about 4%, about 0.5% to about 3.5%, about 0.5% to about 2.5%, about 0.5% to about 2%, about 0.5% to about 1.5%, about 0.5% to about 1%, about 1% to about 9.5%, about 1.5% to about 9%, about 2% to about 8.5%, about 0.5% to about 8%, about 3% to about 7.5%, about 3.5% to about 7%, about 4% to about 6.5%, about 4.5% to about 6%, about 5% to about 5.5%, about 1% to about 5%, about 1.5% to about 4.5%, about 2% to about 4%, about 2.5% to about 3.5%, or values ​​within these ranges. Specific examples include about 0.5%, about 1%, about 1.5%, about 2%, about 2.5%, about 3%, about 3.5%, about 4%, about 4.5%, about 5%, about 5.5%, about 6%, about 6.5%, about 7%, about 7.5%, about 8%, about 8.5%, about 9%, about 9.5%, about 10%, or a range between any two of these values. In certain embodiments of the method for preparing a hydrogel formulation, the resulting hydrogel formulation comprises dimethicone in an amount of about 2%. In certain embodiments of the method for preparing a hydrogel formulation, the resulting hydrogel formulation comprises dimethicone in an amount of about 2.5%. In certain embodiments of the method for preparing a hydrogel formulation, the resulting hydrogel formulation comprises dimethicone in an amount of about 3%. All of the above represent weight percentages of the resulting hydrogel formulation embodiment.

[0213] In some embodiments of the method of preparing a hydrogel formulation, dimethicone is from about 175 cSt to about 525 cSt, from about 200 cSt to about 525 cSt, from about 225 cSt to about 525 cSt, from about 250 cSt to about 525 cSt, from about 275 cSt to about 525 cSt, from about 300 cSt to about 525 cSt, from about 325 cSt to about 525 cSt, from about 350 cSt to about 525 cSt, from about 375 cSt to about 525 cSt, from about 400 cSt to about 525 cSt, from about 425 cSt to about 525 cSt, from about 450 cSt to about 525 cSt, from about 475 cSt to about 525 cSt, from about 500 cSt to about 525 cSt, from about 175 cSt to about 500 cSt, from about 175 cSt to about 475 cSt, approx. 175cSt ~ approx. 450cSt, approx. 175cSt ~ approx. 425cSt, approx. 175cSt ~ approx. 400cSt, approx. 175cSt ~ approx. 375cSt, approx. 175 cSt ~ approx. 350cSt, approx. 175cSt ~ approx. 325cSt, approx. 175cSt ~ approx. 300cSt, approx. 175cSt ~ approx. 275cSt, approx. 175cSt ~ approx. 250 cSt, approx. 175cSt ~ approx. 225cSt, approx. 175cSt ~ approx. 200cSt, approx. 200cSt ~ approx. 500cSt, approx. 225cSt ~ approx. 475cSt, approx. 250 cSt ~ about 450cSt, about 275cSt - about 425cSt, about 300cSt - about 400cSt, about 325cSt - about 375cSt, or a value within these ranges. Specific examples include about 175 cSt, about 200 cSt, about 225 cSt, about 250 cSt, about 275 cSt, about 300 cSt, about 325 cSt, about 350 cSt, about 375 cSt, about 400 cSt, about 425 cSt, about 450 cSt, about 475 cSt, about 500 cSt, about 525 cSt, or a range between any two of these values. In certain embodiments of the method of preparing a hydrogel formulation, the dimethicone has a viscosity of about 350 cSt.

[0214] In certain embodiments of the method of preparing a hydrogel formulation, the fifth stirring speed is about 500 rpm to about 1000 rpm, about 500 rpm to about 900 rpm, about 600 rpm to about 1000 rpm, about 700 rpm to about 1000 rpm, about 800 rpm to about 1000 rpm, about 900 rpm to about 1000 rpm, or a value within one of these ranges. In certain embodiments of the method of preparing a hydrogel formulation, the fifth stirring speed is about 900 rpm.

[0215] In some embodiments of the method for preparing a hydrogel formulation, the resulting hydrogel formulation has a viscosity of about 3.0 to about 7.0, about 3.5 to about 7.0, about 4.0 to about 7.0, about 4.5 to about 7.0, about 5.0 to about 7.0, about 5.5 to about 7.0, about 6.0 to about 7.0, about 6.5 to about 7.0, about 3.0 to about 6.5, about 3.0 to about 5.5, about 3.0 to about 5, about 3.0 to about 4.5, about 3.0 to about 3.5, about 3.0, about 3.1, about 3.2, about 3.3, about 3.4, about 3.5 , about 3.6, about 3.7, about 3.8, about 3.9, about 4.0, about 4.1, about 4.2, about 4.3, about 4.4, about 4.5, about 4.6, about 4.7, about 4.8, about 4.9, about 5.0, about 5.1, about 5.2, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6.0, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, about 7.0, or a range between any two of these values. In certain embodiments of the methods of preparing a hydrogel formulation, the resulting hydrogel formulation has a pH of about 4.0 to about 6.7. In certain embodiments of the methods of preparing a hydrogel formulation, the resulting hydrogel formulation has a pH of about 3.0 to about 4.0. In certain embodiments of the methods of preparing a hydrogel formulation, the resulting hydrogel formulation has a pH of about 5.5 to about 6.5.

[0216] How to use The present invention relates to a method of treating a dermatological condition in a subject, comprising topically administering to the subject a therapeutically effective amount of the hydrogel formulation disclosed herein.

[0217] The present invention also relates to a method of treating a skin condition in a subject, comprising topically administering to the subject a therapeutically effective amount of a hydrogel formulation disclosed herein, wherein the therapeutically effective amount comprises at least a concentration of a component of the latex of Croton lechleri, preferably a concentration of a component of the filtered latex of Croton lechleri, preferably a concentration of a component of the filtered latex of Croton lechleri ​​Mull.Arg., a standard disclosed herein.

[0218] The present invention also relates to a method of treating a dermatological condition in a subject comprising topically administering a therapeutically effective amount of the hydrogel formulation disclosed herein, wherein the hydrogel formulation of Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg, comprises one or more compounds selected from gallocatechin, epigallocatechin, catechin, epicatechin, taspine, and dimethycedrusine, and combinations thereof. Each of gallocatechin, epigallocatechin, catechin, epicatechin, taspine, and dimethycedrusine is administered in the amount found in Table 1a or in paragraphs

[0134] to

[0139] of the latex of Croton lechleri, preferably Croton lechleri ​​filtered latex. lechleri ​​Mull.Arg. filtered latex, preferably Croton lechleri ​​Mull.Arg. filtered latex, or any combination of such amounts. In some embodiments, the Croton lechleri ​​latex, preferably Croton lechleri ​​Mull.Arg. filtered latex, preferably Croton lechleri ​​Mull.Arg. filtered latex, has a PDI of the embodiments disclosed herein.

[0219] Also provided herein is a hydrogel formulation as disclosed herein for use as a pharmaceutical.In some embodiments, the latex of Croton lechleri, preferably the filtered latex of Croton lechleri, preferably the filtered latex of Croton lechleri ​​Mull.Arg., has a PDI of the embodiment disclosed herein.

[0220] Also provided herein are hydrogel formulations as disclosed herein for use as a medicament for the treatment of a dermatological condition.

[0221] Also provided is the use of a hydrogel formulation as disclosed herein as a pharmaceutical for the treatment of a dermatological condition.

[0222] Also, the hydrogel formulation of Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​filtered latex Mul.Arg, comprises concentrations of the components of the Croton lechleri ​​latex, preferably Croton lechleri ​​Mul.Arg latex, as disclosed herein for use in the manufacture of a medicament for the treatment of a dermatological condition, the concentrations of the components of the Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mul.Arg filtered latex, are reference standard concentrations. In some embodiments, the Croton lechreri latex, preferably the Croton lechreri filtered latex, preferably the Croton lechreri filtered latex Mull. Arg., has a PDI of the embodiments disclosed herein.

[0223] The concentrations of the components of the Croton lekleri latex, preferably the filtered Croton lekleri latex, of the hydrogel formulation include the concentrations of the components of the Croton lekleri latex, preferably the filtered Croton lekleri latex, of the reference standard, as disclosed herein for the treatment of a dermatological condition. In some embodiments, the Croton lekleri latex, preferably the filtered Croton lekleri latex, preferably the filtered Croton lekleri latex Mull.Arg., has a PDI of the embodiments disclosed herein.

[0224] Also provided is the use of a hydrogel formulation as disclosed herein, wherein the hydrogel formulation comprises a Croton lekleri latex, preferably a Croton lekleri filtered latex, preferably a Croton lekleri filtered latex Mull.Arg., comprising a concentration of a component of the Croton lekleri latex, preferably a Croton lekleri filtered latex Mull.Arg., which is a reference standard concentration as disclosed herein for the treatment of a dermatological condition. In some embodiments, the Croton lekleri latex, preferably a Croton lekleri filtered latex, preferably a Croton lekleri filtered latex Mull.Arg., has a PDI of an embodiment disclosed herein.

[0225] Also provided herein is a method for achieving a therapeutic effect in a patient comprising administering a therapeutically effective amount of a hydrogel formulation as disclosed herein, wherein the hydrogel formulation of Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg. hydrogel formulation comprises a concentration of a component of Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​filtered latex Mull.Arg., in a reference standard concentration. In some embodiments, the Croton lechleri ​​latex, preferably Croton lechleri ​​filtered latex, preferably Croton lechleri ​​Mull.Arg. filtered latex has a PDI of an embodiment disclosed herein.

[0226] In some embodiments, the dermatological condition is selected from the group consisting of atopic dermatitis, epidermolysis bullosa, impetigo, psoriasis, wounds, pathogen-contaminated skin, atopic dermatitis in patients with Staphylococcus aureus infection, atopic dermatitis in patients with Methicillin-resistant Staphylococcus aureus (MRSA) infection, atopic dermatitis in patients with mupirocin-resistant MRSA infection, epidermolysis bullosa in patients with Staphylococcus aureus infection, epidermolysis bullosa in patients with Methicillin-resistant Staphylococcus aureus (MRSA) infection, epidermolysis bullosa in patients with mupirocin-resistant MRSA infection, epidermolysis bullosa in patients with Streptococcus pyogenes infection, epidermolysis bullosa in patients with Pseudomonas aeruginosa infection. impetigo in patients with Staphylococcus aureus infection, impetigo in patients with Methicillin-resistant Staphylococcus aureus (MRSA) infection, impetigo in patients with mupirocin-resistant MRSA infection, impetigo in patients with Streptococcus pyogenes infection, psoriasis in patients with Staphylococcus aureus infection, psoriasis in patients with Methicillin-resistant Staphylococcus aureus (MRSA) infection, psoriasis in patients with mupirocin-resistant MRSA infection, wounds in patients with Staphylococcus aureus infection, wounds in patients with Methicillin-resistant Staphylococcus aureus (MRSA) infection, wounds in patients with mupirocin-resistant MRSA infection, wounds in patients with Streptococcus pyogenes infection, wounds in patients with Pseudomonas aeruginosa infection, and combinations thereof.

[0227] In some embodiments, the skin condition is atopic dermatitis.

[0228] In some embodiments, the dermatological condition is epidermolysis bullosa.

[0229] In some embodiments, the skin condition is impetigo.

[0230] In some embodiments, the skin condition is psoriasis.

[0231] In some embodiments, the skin condition is a wound.

[0232] In some embodiments, the skin condition is pathogen-infested skin.

[0233] In some embodiments, the pathogen is selected from the group consisting of Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), mupirocin-resistant MRSA, and combinations thereof.

[0234] In some embodiments, the pathogen is Staphylococcus aureus.

[0235] In some embodiments, the pathogen is methicillin-resistant Staphylococcus aureus (MRSA).

[0236] 254 In some embodiments, the pathogen is mupirocin-resistant MRSA.

[0237] In some embodiments, the skin condition is atopic dermatitis in a patient with Staphylococcus aureus infection.

[0238] In some embodiments, the skin condition is atopic dermatitis in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection.

[0239] In some embodiments, the skin condition is atopic dermatitis in a patient with mupirocin-resistant MRSA infection.

[0240] In some embodiments, the skin condition is epidermolysis bullosa in a patient with Staphylococcus aureus infection.

[0241] In some embodiments, the dermatological condition is epidermolysis bullosa in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection.

[0242] In some embodiments, the skin condition is epidermolysis bullosa in patients with mupirocin-resistant MRSA infection.

[0243] In some embodiments, the skin condition is epidermolysis bullosa and the patient has a Streptococcus pyogenes infection.

[0244] In some embodiments, the skin condition is epidermolysis bullosa in a patient infected with Pseudomonas aeruginosa.

[0245] In some embodiments, the skin condition is impetigo in a patient with Staphylococcus aureus infection.

[0246] In some embodiments, the skin condition is impetigo in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection.

[0247] In some embodiments, the skin condition is impetigo in patients with mupirocin-resistant MRSA infection.

[0248] In some embodiments, the skin condition is impetigo in patients with Streptococcus pyogenes infection.

[0249] In some embodiments, the skin condition is psoriasis in patients with Staphylococcus aureus infection.

[0250] In some embodiments, the dermatological condition is psoriasis in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection.

[0251] In some embodiments, the skin condition is psoriasis in a patient with mupirocin-resistant MRSA infection.

[0252] In some embodiments, the skin condition is a wound in a patient with Staphylococcus aureus infection.

[0253] In some embodiments, the skin condition is a wound in a patient with a methicillin-resistant Staphylococcus aureus (MRSA) infection.

[0254] In some embodiments, the skin condition is a wound in a patient with mupirocin-resistant MRSA infection.

[0255] In some embodiments, the skin condition is a wound in a patient with Streptococcus pyogenes infection.

[0256] In some embodiments, the skin condition is a wound in a patient with Pseudomonas aeruginosa infection.

[0257] Also provided herein is a method of preventing a dermatological condition in a subject in need thereof comprising contacting the skin of the subject with a hydrogel formulation as disclosed herein, wherein the hydrogel formulation of Croton lekleri latex, preferably Croton lekleri filtered latex, preferably Croton lekleri filtered latex Mull.Arg. comprises a concentration of a component of a reference standard Croton lekleri latex, preferably Croton lekleri filtered latex, preferably Croton lekleri filtered latex Mull.Arg., as disclosed herein. In some embodiments, the Croton lekleri latex, preferably Croton lekleri filtered latex, preferably Croton lekleri Mull.Arg. filtered latex has a PDI of an embodiment disclosed herein.

[0258] Also provided herein is a method of maintaining overall skin health of a subject comprising contacting the skin of a subject in need thereof with a hydrogel formulation as disclosed herein, wherein the hydrogel formulation's Croton lekleri latex, preferably Croton lekleri filtered latex, preferably Croton lekleri filtered latex Mull.Arg., comprises a concentration of Croton lekleri latex components as disclosed herein, preferably Croton lekleri filtered latex components, preferably Croton lekleri filtered latex components Mull.Arg., comprises a concentration of Croton lekleri filtered latex components as disclosed herein, preferably Croton lekleri filtered latex components, preferably Croton lekleri filtered latex components Mull.Arg., comprises a concentration of Croton lekleri filtered latex components of a reference standard as disclosed herein. In some embodiments, the Croton lekleri latex, preferably Croton lekleri filtered latex, preferably Croton lekleri filtered latex Mull.Arg., has a PDI of an embodiment disclosed herein.

[0259] The hydrogel formulations can be administered in a variety of ways, including topically (including, for example, dermal, oral mucosal, buccal, sublingual, and intraocular), and the route of administration can vary depending on the condition and its severity.

[0260] The hydrogel formulations can be administered in a variety of ways, including topically (e.g., to the skin, oral mucosa, buccal, sublingual, intraocular, and wound cavities). The specific dosage level for a particular patient will depend on a variety of factors, including the activity of the particular compound employed, age, body weight, general health, sex, diet, time of administration, route of administration, excretion rate, drug combination, the exact disorder being treated, and the severity of the indication or condition being treated. The route of administration will also vary depending on the condition and its severity.

[0261] The hydrogel formulations of the present invention can be administered once a day, twice a day, three times a day, four times a day, five times a day, six times a day, seven times a day, eight times a day, nine times a day, ten times a day, or ranges between these values. In some embodiments, the hydrogel formulation is administered once a day. In some embodiments, the hydrogel formulation is administered twice a day. In some embodiments, the hydrogel formulation is administered three times a day. In some embodiments, the hydrogel formulation is administered three times a day. In some embodiments, the hydrogel formulation is administered one to three times a day. In some embodiments, the hydrogel formulation is administered until the dermatological condition is resolved, cleared, or treated.

[0262] The hydrogel formulations of the present invention may be administered continuously, every 15 minutes and 30 minutes, hourly, hour and a half, 2 hours, 21 / 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 ​​hours, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, 56 weeks, 57 weeks, 58 weeks, 59 weeks, 60 weeks, 61 weeks, 62 weeks, 63 weeks, 64 weeks, 65 weeks, 66 weeks, 67 weeks, 68 weeks, 69 weeks, 70 weeks, 71 weeks, 72 weeks, 73 weeks, 74 weeks, 75 weeks, 76 weeks, 77 weeks, 78 weeks, 79 weeks, 80 weeks, 81 weeks, 82 weeks, 83 weeks, 84 weeks, 85 weeks weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, or ranges between these values. In some embodiments, administration continues for 24 weeks. In certain embodiments, administration continues for 2 weeks. In certain embodiments, administration continues for 4 weeks. In some embodiments, administration continues until the dermatological symptoms are resolved, eliminated, or treated.

[0263] The treatment duration for dermatological diseases was 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, 56 weeks, 57 weeks, 58 weeks, 59 weeks, 60 weeks, 61 weeks, 62 weeks, 63 weeks, 64 weeks, 65 weeks, 66 weeks, 67 weeks, 68 weeks, 69 weeks, 70 weeks, 71 weeks, 72 weeks, 73 weeks, 74 weeks, 75 weeks, 76 weeks, 77 weeks, 78 weeks, 79 weeks, 80 weeks, 81 weeks, 82 weeks, 83 weeks, 84 weeks, 85 weeks, 86 weeks, 87 weeks, 88 weeks, 89 weeks, 90 weeks, 91 weeks, 92 weeks, 93 weeks, 94 weeks, 95 weeks, 96 weeks, 97 weeks, 98 weeks, 99 weeks, 100 weeks, 101 weeks, 10 4 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, or ranges between these values. In some embodiments, the treatment lasts for 2 weeks. In some embodiments, the treatment lasts until the dermatological symptoms are resolved, disappeared, or treated.

[0264] Treatment of skin diseases can be continued until the targeted lesions have completely disappeared.

[0265] Treatment of the skin condition may be continued at the discretion of the prescribing physician.

[0266] In certain embodiments, the hydrogel formulations of the present invention may be applied topically directly to the skin condition.

[0267] In certain embodiments, the hydrogel formulations of the present invention may be applied topically directly to lesions resulting from dermatological conditions.

[0268] In certain embodiments, the dosage is an appropriate amount of the hydrogel formulation of the present invention to cover the target area of ​​the dermatological condition. The hydrogel formulation is applied to each dermatological condition once, twice, or more times per day. Multiple dabs may be applied to the crop of lesions. The hydrogel formulation is gently rubbed (for about 15 seconds) onto the skin condition until the hydrogel formulation forms a thin layer.

[0269] In certain embodiments, the hydrogel formulation of the present invention is first applied to a dressing (e.g., gauze), which is then applied to the skin lesion. A treated dressing is applied to each lesion. If the dressing is detached from the lesion or if the dressing has been worn for 24 hours, a new treated dressing can be applied. A new dressing is generally, but not always, applied daily, and can be applied up to once per week or longer. In one embodiment, the composition is administered until symptoms (e.g., skin lesions) disappear or become less noticeable, or until problematic side effects occur.

[0270] In some embodiments, the hydrogel formulation is at least about 0.01%, at least about 0.05%, at least about 0.1%, at least about 0.25%, at least about 0.5%, at least about 0.75%, at least about 1%, at least about 3%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 100%.

[0271] Example Section - AB-101 Hydrogel Formulation and Performance For the drug to be effective, it must be readily released from the hydrogel carrier, and the hydrogel carrier should not increase the penetration or penetration of the bioactive ingredient into the skin. Minimizing penetration into the skin allows the maximum amount of AB-101 to remain in the affected area of ​​the skin, resolving the skin condition. The active pharmaceutical ingredient (CPL) of AB-101 should have a low partitioning potential to minimize systemic absorption and maximize safety when using AB-101.

[0272] A series of hydrogel formulations containing pharmaceutical grade AB-101 were prepared as shown in Table 3a, and the pH of each formulation is shown in Table 3b. The hydrogel formulations used Dow Corning 200® fluid, 350CST dimethicone, caprylic / capric triglyceride, and SEPINEO™ P600 copolymer to form the gel, and the AB-101 dosage range included loading levels of 20%, 30%, 40%, and 50%, with reduced purified water in the formulation as the level of AB-101 increased. The AB-101 used in the formulations was mechanically filtered and not fractionated, thus maintaining the proanthocyanidin and taspine composition detailed in the AB-101 fingerprint.

[0273] [Table 13]

[0274] [Table 14] EXAMPLES

[0275] Example 1 - Release Test of AB-101 from Carriers: In Vitro Franz Diffusion Cells The Franz diffusion cell in vitro drug release test (IVRT) used here is recognized as the industry standard method for measuring the release of topically applied drugs from carriers (USP Chapter 1724, USP 36 / NF31, 2013, Ueda et al, 2009; Li & Rahn, 1993). The test used Versapore® membranes (Pall Corporation SKU 66394), which have been shown to be effective in indicating the in vivo release of drugs from carriers (Thakker KD, Chern WH. 2003. Development and validation of in vitro release tests for semi-solid dosage forms - A case study. Dissolution Technologies. May;10(2):10-6). To measure the carrier release flux (amount of permeant or test substance that passes through the membrane per unit area per unit time) of AB-101 PACs (catechin, epicatechin, gallocatechin, epigallocatechin) and taspine, an existing analytical LC-MS / MS method was used to quantify the amount of each PAC and taspine that diffused through the membrane, i.e., the flux. [Table 15] EXAMPLES

[0276] Example 2 - AB-101 Skin Permeation Test: In Vitro Franz Diffusion Cell The in vitro drug permeation test (IVPT) using Franz diffusion cells used here is recognized as the industry standard method for measuring the skin permeability of topical products (USP Chapter 1724, USP 36 / NF31, 2013 and Ueda et al., 2009; Li & Rahn, 1993). Additionally, this study used a Strat-M membrane (Millipore Sigma SKU SKBM02560), which has been shown to be predictive of in vivo skin permeation outcomes (Flaten GE, Palac Z, Engesland A, Filipovic-Grcic J, Vanic Z, Skalko-Basnet N. 2015. In vitro skin models as a tool in optimization of drug formulation. 75:10-24. To measure the transdermal flux (amount of permeant or test substance that passes through the membrane per unit area per unit time) of AB-101's PACs (catechin, epicatechin, gallocatechin, epigallocatechin) and taspine, an existing analytical LC-MS / MS method was used to quantify the amount of each PAC and taspine that diffused through the membrane, i.e., the flux.

[0277] Franz diffusion cell in-vitro drug permeation study data (Table 5) showed low flux or diffusion of AB-101 PAC and taspine compared to the total amount of these compounds in AB-101, 100% liquid. Low flux or diffusion of AB-101 PAC and taspine was demonstrated for all AB-101 foams tested; AB-101, 100%, liquid, and each of the four AB-101 hydrogel formulations tested (20%, 30%, 40%, and 50% AB-101 concentration in the hydrogel delivery material). These Franz diffusion cell in-vitro drug permeation results are predictive of low in-vivo skin permeation for AB-101. [Table 16]

[0278] As a result, the PAC of AB-101 and taspine exhibited low flux and diffusion across intact synthetic membranes, predicting low permeability through human skin and therefore low transdermal delivery levels of AB-101.

[0279] Table 5 shows novel and unexpected results that enhance both the efficacy and safety of hydrogels containing AB-101. Increasing the amount of AB-101 actually decreases the permeation of AB-101 transdermal flux. This is unexpected. Conventional expectation would be that as the dose of AB-101 increases, the permeation would also increase. This is evidence that the transdermal flux or permeation level is highest at 100% AB-101 dose. In fact, at the highest dose level of 50%, the PAC permeation level was the lowest, with negligible permeation. The inverse relationship between high dose and low transdermal flux also holds for the alkaloid taspine, where permeation decreased by 81% when the dose of AB-101 was increased to 50%.

[0280] The hydrogel completely transforms the efficacy of AB-101. This has significant performance advantages. The low permeability means that a significantly higher amount of AB-101 is available to treat skin conditions while maximizing delivery of AB-101, increasing its efficacy. This minimizes the potential for causing antimicrobial resistance by maximizing exposure to pathogens, particularly MRSA, as shown in time-kill kinetic assays. Time-kill kinetic assays showed that maximum pathogen kill was achieved at the 50% dose level. In addition to the safety benefits associated with minimizing the potential for causing antimicrobial resistance, safety is further enhanced at higher dose levels of AB-101, as the low transdermal flux of AB-101 indicates that AB-101 is maintained on the skin rather than being absorbed systemically. EXAMPLES

[0281] Example 3 - AB-101 Split Study - IN VITRO LOG P LogP evaluates the lipophilicity of a compound and indicates how easily a mixture can be distributed between the aqueous and organic phases. The in vitro LogP test utilized here is recognized as the industry standard method for evaluating the lipophilicity of a compound, in this case for compounds that are applied topically to the skin (Pollastri MP. 2010. Summary of the Rule of Five. Current protocols in pharmacology. Jun; 49(1): 9-12). If a topical drug has low lipophilicity and a LogP between -1 and 2 (Table 6), it will not penetrate or disperse well into the skin when applied to the skin (Tshepelevitsh S, Kadam SA, Darnell A, Bobacka J, Rutel A, Haljasorg T, Leito I. 2020. LogP Determination of Highly Lipophilic Hydrogen-Bonded Anion Receptor Molecules. Analytica Chimica Acta. July 30). To achieve high systemic concentrations, topical drugs must have sufficient permeability. This is defined as being lipophilic enough to migrate into the skin lipid bilayer, but not so lipophilic that it remains sequestered there once inside the skin bilayer (Weng Z,Wang K,Li H,Shi Q. 2015. A comprehensive study of drug hepatotoxicity in relation to daily dose, hepatic metabolism, and lipophilicity using 975 oral drugs. Oncotarget. July 10;6(19):17031). Lipophilicity plays a major role in determining where drugs are distributed in the body after absorption into tissues, and therefore how quickly they are metabolized and excreted (Lipinski CA. 2000. Drug-like properties and the causes of poor solubility and poor permeability. Journal of pharmacological and toxicological methods. July 1;44(1):235-49). [Table 17]

[0282] To evaluate the LogP partition coefficient of the entire AB-101 100% drug substance, a standard LogP partition coefficient test was performed on the AB-101 100% drug substance in its liquid form (CPL). In addition, LogP partition coefficient tests were performed on the five major components that affect the antibacterial activity of the AB-101 drug substance in four different forms: (1) AB-101 100% drug substance in its liquid form, (2) AB-101 100% lyophilized powder suspended in water, (3) AB-101 20% hydrogel formulation, and (4) AB-101 50% hydrogel formulation.

[0283] The following LogP partition coefficient test method was utilized: (a) a glass separatory funnel (GSF) was charged with water and n-octanol; (b) the amount of each test substance identified in the previous section was measured and charged to the GSF; (c) the GSF was charged to a vortex mixer to mix and disperse the test substance in water or n-octanol; (d) the GSF was then allowed to stand overnight to allow re-separation into the original two phases of water and n-octanol; (e) for the raw liquid AB-101 100% drug, the aqueous layer was collected and analyzed by LCMS; the aqueous layer was then collected and analyzed by LCMS and the LCMS results were compared to the known LCMS results for each test substance in the AB-101 total components to determine the amount of test substance in water and n-octanol. (f) For all other forms, the aqueous layer was collected, lyophilized, and the remaining powder was weighed and compared to the total amount of powder in AB-101 to determine the amount of powder in the aqueous layer and subtracted to determine the amount of powder in the n-octanol layer.

[0284] AB-101, 100%, LogP of drug substance (CPL).

[0285] The partition assay reported below (Table 7) measured the in vitro partition and release of AB-101, 100%, bulk drug (CPL) tested in triplicate at three different doses. These data report low lipophilicity of AB-101, 100%, liquid drug (CPL) as defined by LogP analysis. Because skin is lipophilic, these data indicate that AB-101 has poor lipophilicity and will not readily penetrate or disperse through the skin when applied directly to the skin (Mtewa AG, Ngwira K, Lampiao F, Weisheit A, Tolo CU. 2018. Fundamental Methods in Drug Permeability, pKa, LogP and LogDx Determination. J Drug Res Dev. 4(2):2470-1009; Rolland, Y. 2011. Naturals-the return of the dragon. The Medicinal Chemist. 15-JUL-1; Martin, KR (2009). Polyphenols as dietary supplements: a double-edged sword. Nutrition and Dietary Supplements, 1. doi:10.2147 / nds.s6422). The lack of lipophilicity further indicates that AB-101 will not translocate from the skin to underlying tissues or the systemic circulation. The poor skin and tissue permeability of AB-101 indicates its limited ability to be absorbed through the skin, which in turn makes it less likely to penetrate the skin and reach the systemic circulation or other tissues and organs. Even if AB-101 does reach the systemic circulation, its poor tissue permeability means that it will not accumulate in tissues and will be excreted from the body. [Table 18]

[0286] LogP of the main component of AB-101 and other compounds

[0287] The LogP of five major components affecting the antibacterial activity of AB-101 bulk drug substance (CPL) and the remaining unidentified compounds in AB-101 were tested in four different forms: 100% bulk liquid of AB-101 (CPL), 100% of AB-101 (CPL) lyophilized and resuspended, a 20% hydrogel formulation of AB-101, and a 50% hydrogel formulation of AB-101.

[0288] In the partitioning assay reported here (Table 8), we determined the in vitro partitioning and release of five major components of AB-101 that affect antibacterial activity (the four PACs catechin, epicatechin, epigallocatechin, gallocatechin, plus taspine) and the remaining components of AB-101 from four different AB-101 forms: (1) AB-101 100% liquid (CPL) from AB-101 batches 0, 1, 2 and X, (2) AB-101 100% liquid (CPL) from batches 0, 1, 2 and X were lyophilized and resuspended in water to investigate the impact on partitioning if lyophilization and resuspension steps were utilized for commercial production, and (3&4) the remaining components of AB-101 obtained from the four different forms of AB-101; and 4) two AB-101 hydrogel formulations (AB-101 20% and AB-101 50%) obtained from AB-101 batch 1. These data report low lipophilicity of the five major components of AB-101 (PAC and taspine) and other compounds of AB-101 that influence antibacterial activity. Because skin is lipophilic, PAC and taspine and other compounds of AB-101 are poorly lipophilic and do not easily penetrate or disperse in the skin when applied directly to the skin. The lack of lipophilicity further indicates that AB-101 PAC and taspine and other compounds of AB-101 do not pass through the skin to the underlying tissues or systemic circulation. The poor skin and tissue permeability of AB-101 PAC, taspine and other compounds of AB-101 indicate their limited ability to be absorbed by the skin, which in turn makes them even less likely to pass through the skin and reach the systemic circulation or other tissues or organs. Even if any of the PAC, taspine and other compounds of AB-101 reach the systemic circulation, their poor tissue permeability means that they do not accumulate in the tissues and are excreted from the body. [Table 19]

[0289] The data for AB-101 100%, AB-101 PAC, AB-101 Taspine, and AB-101 hydrogel formulations support the conclusion that it is highly unlikely that AB-101 will penetrate the skin. The data also support the conclusion that any AB-101 that does penetrate the skin is likely to be metabolized / biotransformed within the skin before it has an opportunity for systemic absorption. Furthermore, if AB-101 does penetrate the skin, it is also unlikely to be absorbed systemically given the logP results which predict little to no penetration. The hydrogel logP data indicate that there are no adverse performance factors that would alter the logP partition coefficient of AB-101 within the hydrogel matrix.

[0290] The effectiveness of AB-101 in the hydrogel in irradiating harmful pathogens was confirmed by a well diffusion assay test measuring the zone of inhibition (ZOI) and a bridging test comparing the minimum inhibitory concentration (MIC) with the level of AB-101 (50%) contained in the hydrogel.

[0291] Agar diffusion assay (Remel Tryptic Soy Agar-TSA) tests were performed with hydrogel carrier containing AB-101. TSA plates were smeared with a lawn of S. aureus ATCC 29213 or P. aeruginosa ATCC 27853. Two 4 mm holes were punched into each plate using a biopsy punch. The agar plates were then tilted on an analytical balance, and a small amount (approximately 10 mg) of hydrogel containing AB-101 was dispensed into one well. The concentration of AB-101 Lot 1 is 100 μL = 102.4 mg, but for practical purposes, 100 μL = 100 mg was used. AB-101 Lot 1 was diluted 1:1 with sterile pure water to prepare a 50% solution with the same concentration of AB-101 in the gel. An equivalent amount of this 50% AB-101 was dispensed into the second well of the agar medium, the TSA plate was incubated overnight, and the ZOI was measured the next day with a ruler. [Table 20]

[0292] The results shown in Table 9 indicate that the ZOIs of the 50% Lot 1 (control) and AB-101 hydrogels were comparable, indicating that the hydrogels are comparable to AB-101 and that the hydrogels did not inhibit the growth inhibitory effect of AB-101 on the two pathogens.

[0293] A bridging study was performed to compare the MIC of AB-101 with that of hydrogels containing AB-101. The aim of this study was to show that the hydrogel does not interfere with or affect the MIC performance of AB-101 after it is released from the carrier. A 50% solution was used to match the AB-101 concentration in the gel.

[0294] Four strains of S. aureus, four strains of P. aeruginosa, and four strains of S. pyogenes were tested against AB-101 Lot 1 50% and hydrogel 50% using the well diffusion method. The MIC values ​​of the strains and AB-101 Lot 1 are shown in Table 10. For the bridging test, the weight (mg) of hydrogel dispensed into one well on the agar medium was measured using an analytical balance. The amount of 50% AB-101 Lot 1 to be added was determined by normalizing it to the density of AB-101 Lot 1 (i.e., 1.02 mg / μL). For example, if 17.4 mg of hydrogel was dispensed into the first well, 17.1 μL of 50% AB-101 Lot 1 was dispensed into the second well of the plate. TSA plates were used for S. aureus and P. aeruginosa, and TSA + 5% delipidated sheep blood was used for S. pyogenes. [Table 21]

[0295] Table 10 shows that the hydrogel does not interfere with or alter the performance of AB-101. At the AB-101 MIC levels, the hydrogel ZOI was essentially indistinguishable from pure 50% diluted AB-101 for S. aureus, P. aeruginosa, and S. pyogenes. EXAMPLES

[0296] Example 4 - Liquid Bandages and Protection The hydrogel containing 50% AB-101 is reddish-brown in color before application. Upon application, the hydrogel becomes translucent and light in color with a slight reddish-brown tint. It takes approximately 3-4 minutes for the film to dry. Once the hydrogel dries, it becomes a shiny film, recognizable as a liquid bandage. This liquid bandage helps to trap moisture from the hydrogel and provide a protective layer. Moisture retention is especially beneficial for both eczema and EB. The protective film of the liquid bandage helps to protect the skin from impurities. Figure 7 shows the properties of the film-forming liquid bandage after application to the inner forearm. EXAMPLES

[0297] Example 5 - Preparation of AB-101 Hydrogel Formulation The following procedure highlights the steps required for the manufacture of AB-101 hydrogel formulations: 1) Combine propanediol, methylparaben, and propylparaben to form phase A, mix to prepare phase A, and heat at 55°C until phase A becomes clear; 2) Prepare phase B by mixing edetate disodium dihydrate, water, sodium benzoate, and potassium sorbate, and heat at 55°C until phase B becomes transparent; 3) Add phase B to phase A to make phase C, and stir at 600 rpm; 4) Add PHOSAL® 50PG (phosphatidylcholine, lysophosphatidylcholine, propylene glycol, sunflower seed oil glyceride, ethanol, soybean fatty acid, ascorbyl palmitate, D,L-α-tocopherol) to the stirred phase C to form phase D, and stir at 600 rpm for about 3 minutes; 5) Prepare Phase E by combining Caprylic / Capric Triglyceride and SEPINEO™ P600 (Acrylamide / Sodium Acryloyldimethyltaurate Copolymer / Isohexadecane / Polysorbate 80) and mixing until uniform; 6) Add phase E to phase D to make phase F, and stir at 700 rpm for about 3 minutes; 7) Cool phase F to below 45°C; 8) Add AB-101 to phase F to make phase G, and stir at 700 rpm for approximately 5 minutes. 9) Add dimethicone to Phase G and stir at 900 rpm for approximately 2 minutes to form the AB-101 hydrogel formulation.

[0298] Adding dimethicone at the last step after the hydrogel is formed results in a stable and homogenous product, as shown in Figure 8. If dimethicone is added before the hydrogel is formed, the resulting product will suffer from air entrapment, as shown in Figure 9). The necessity of adding dimethicone after the hydrogel is formed is further demonstrated by the photomicrograph of the hydrogel formulation (Figure 10). However, when dimethicone is added before the hydrogel is formed, the photomicrograph of the hydrogel formulation (Figure 11) shows a blue color, indicating air entrapment between the AB-101 and the hydrogel matrix.

[0299] When adding AB-101, too much shear can trap air in the formulation (Figure 12), but not enough shear can prevent hydrogel formation.

[0300] AB-101 should be added in the G phase, as adding it first (Figure 13) prevents hydrogel formation.

[0301] Hydrogel formulations are best stored in airless pump bottles to minimize exposure to air. EXAMPLES

[0302] Example 6: Testing AB-101 in patients with mild to moderate atopic dermatitis with or without secondary infection A randomized, double-blind, multicenter study to evaluate the safety and efficacy of topical AB-101 versus a hydrogel vehicle in treating mild to moderate atopic dermatitis, with or without secondary infection, in male or female participants with mild to moderate infectious or non-infectious AD.

[0303] The study objectives and endpoints are shown in Table 11. [Table 22]

[0304] The overall study design is shown in Table 12. [Table 23]

[0305] Study Participants Approximately 60 men and women aged 2 years or older with mild to moderate AD, with or without secondary infection, will be enrolled in the study.

[0306] The intervention groups and study periods are summarized in Table 13. [Table 24]

[0307] Inclusion Criteria-Participants will be included in the study only if they meet all the following criteria: Male / female participants aged 2 years or older on the day they provide written informed consent / assent. Clinical diagnosis of AD confirmed according to the criteria of Hanifin and Rajka (1980) for at least 3 months at the screening visit. Mild to moderate AD as indicated by an IGA score of 2 (mild) or 3 (moderate) at screening and on Day 1 prior to study intervention. AD in the head (including face but excluding hairy scalp), neck, trunk (excluding groin and genitalia), or extremities, occupying at least 5% of total BSA at screening and on Day 1 (Visit 1). EASI score ≥3 and ≤21 at screening and on Day 1. SIRS score ≥8 (Cohort 1) or <8 (Cohort 2). Participants using a stable regimen (consistent use from 14 days prior to the first day) of all permitted oral and topical medications. Willing to refrain from using topical medications, cosmetics, and skin cleansers on the target lesions during the application of the study intervention. Willing to refrain from applying the study intervention to skin other than the target lesions. Participants who are willing and able to comply with all scheduled visits, treatment plans, clinical tests, lifestyle considerations, and other study procedures. Female participants are eligible to participate if they are not pregnant, not breastfeeding, and meet at least one of the following conditions: are not women of childbearing potential (WOCBP) or are WOCBP who agree to follow contraceptive instructions. Participant (or legally recognized representative, if applicable) provides written informed consent / assent for the study.

[0308] Exclusion Criteria-Participants will be excluded from the study if they meet any of the following criteria: Unstable AD or consistent need for high-potency topical corticosteroids to manage AD signs and symptoms. Active systemic infection requiring antibiotic treatment. Recent or anticipated concomitant systemic or topical therapy that may alter the course of AD. Fitzpatrick skin score of 6. Prior treatment with monoclonal antibodies, TYK2 inhibitors and / or JAK inhibitors within 6 months or 5 half-lives (whichever is shorter) prior to Day 1. Previous treatment for any cancer (except squamous cell carcinoma, basal cell carcinoma, or non-invasive carcinoma of the skin that has been curatively treated with cryosurgery or surgical excision alone). Potentially active or recurrent skin disease other than AD that may confound the assessment. Current or recent (within approximately 3 months) history of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular, or neurological disease. History of lymphoproliferative disease (e.g., Epstein Barr Virus-associated lymphoproliferative disease), lymphoma, leukemia, or malignancy, or signs or symptoms suggestive of current lymphatic disease (Note: Adults with adequately treated or excised nonmetastatic basal or squamous cell carcinoma of the skin or cervical carcinoma in situ are permitted). History of systemic (within approximately 3 months), chronic, or acute skin infection (within approximately 2 weeks) requiring hospitalization or parenteral antibacterial, antiviral, antiparasitic, antiparasitic, or antifungal treatment, or if deemed clinically significant by the investigator. Use of systemic antibiotics or systemic corticosteroids within 28 days prior to screening. Use of topical antiviral, antibacterial, antifungal, or corticosteroid medications within 14 days prior to Day 1. Known inherited immunodeficiency. Major trauma or surgery within 1 month prior to screening, as determined by the investigator. Known hypersensitivity to any component of AB-101 or the carrier.Recent (within the past year) acute or chronic medical or psychiatric conditions, including suicidal ideation or active suicidal behavior, or abnormal laboratory findings, that may increase the risks associated with study participation or investigational drug administration or may interfere with the interpretation of study results, in the investigator's judgment, making the participant unsuitable for participation in the study. WOCBP with a positive urine pregnancy test within 24 hours prior to randomization or treatment assignment. A serum pregnancy test is required if the urine test is positive or cannot be confirmed as negative (Note: If 24 hours have elapsed between the screening pregnancy test and the first dose of study intervention, a repeat pregnancy test (urine or serum) must be performed and be negative in order for the participant to begin administration of the study intervention). Vaccines and mRNA vaccines are available. Within 28 days prior to the first dose of study intervention. Receipt of a live or attenuated vaccine within 30 days prior to the first dose of study intervention. Death, currently participating or having participated in a study of an investigational drug or use of an investigational device. Have a history of HIV, Hepatitis B or Hepatitis C (Note: HIV, Hepatitis B or Hepatitis C testing is not required unless mandated by local health authorities). Investigator site staff and their families directly involved in the conduct of the study, and other site staff under the supervision of the Investigator, are excluded. Have a history of alcohol or drug abuse within 6 months prior to screening that, in the Investigator's opinion, would prevent them from participating in the study. Have a history or current evidence of a condition, treatment, or test abnormality that, in the Investigator's opinion, may confound the results of the study, prevent the participant's participation for the full duration of the study, or be not in the participant's best interest.

[0309] Discussion of study design The Phase 2a multicenter, randomized, double-blind, vehicle-controlled, parallel-group study will evaluate the safety and efficacy of topical AB-101 hydrogel applied twice daily in patients with mild or moderate AD, with or without secondary infection.

[0310] 327 Participants will be screened within 14 days prior to the first day of study intervention administration to ensure they meet the inclusion criteria for the study. Screening and first day administration may be combined. Treatment with the study intervention will be administered BID for up to 4 weeks (28 days), followed by a follow-up visit 1 week (7 days) later as outlined in the SoA. Participants' total study duration will be approximately 5 weeks.

[0311] Pediatric and adult participants aged 2 years and older with mild or moderate AD dermatitis as determined by the IGA scale, with or without secondary infection as determined by the investigator and confirmed by the SIRS scale, will be enrolled. The study will consist of two cohorts with two arms. Cohort 1 will enroll 20 evaluable patients, and Cohort 2 will enroll 40 evaluable patients. Participants will be randomized in a 1:1 ratio to receive either the active study intervention or the control intervention: Cohort 1: Mild or moderate AD with secondary infection Cohort 2: Mild or moderate AD without secondary infection

[0312] Participants will enter the screening period once they agree to participate and sign the informed consent / assent form. Participants with mild to moderate AD according to the IGA scale, involvement of 5% or more of the total body surface area (BSA), including involvement of the skin target site, meeting all inclusion criteria and no exclusion criteria, and successfully completing the screening process are eligible for enrollment.

[0313] After enrollment, participants will be randomized to receive either AB-101 or a hydrogel vehicle (2:1 ratio) applied topically to the target AD. The first dose will be administered in the clinic. Participants will be asked to complete a diary and follow-up for up to 28 days. 8 Participants will be given printed instructions on how to administer the study intervention BID, spaced at least 18 hours apart. Participants will return to the clinic for five study efficacy assessments after screening: days 4, 8, 15, 22, and 29. All participants will also return for a follow-up visit on day 36, or 7 days after the last dose.

[0314] Microbiology, IGA, EASI, SIRS, and BSA lesion assessments will be performed on day 1 and at each efficacy study visit (days 4, 8, 15, 22, and 29). Photographs of lesions will be performed at selected sites at these visits.

[0315] Participants in Cohort 1 who, as determined by the investigator, have AD showing clinical progression of pre-existing infection in the AD-involved skin at the study site will be discontinued from the study intervention and treated with end-of-treatment procedures.

[0316] Cohort 2 participants whose AD has progressed clinically and who, as determined by the investigator, have clinically evident infection of AD-infected skin at study sites will have the study intervention discontinued and will undergo treatment termination.

[0317] Early discontinuations from Cohort 1 and Cohort 2 will continue study participation for 7 days to obtain follow-up outcome data.

[0318] Assuming a dropout rate of 20%, a total of approximately 72 participants (24 per cohort 1 and 48 per cohort 2) will be randomized and approximately 60 participants (20 per cohort 1 and 40 per cohort 2) will complete.

[0319] Investigators, participants, and the sponsoring research team will be blinded to the study intervention.

[0320] All primary and secondary endpoints will be achieved. EXAMPLES

[0321] Example 7 - Polydispersity Index Analysis of AB-101 To measure the PDI, an HPLC-UV method using gel permeation chromatography (GPC) and / or size exclusion (SEC) chromatography for the analysis of this polymer was developed. The particle size distribution of the polymer is calculated by the following equation: PDI=M / M wn , where Mw is the weight average molecular weight, M n is the number of average molecular weights.

[0322] Sample preparation: AB-101 was prepared by dispensing 5 mL samples and lyophilizing overnight. The samples were then weighed and resuspended in water at a concentration of 5 mg / mL. The samples were then diluted with water prior to GPC-UV / CAD analysis for PDI measurement. The HPLC method details are as follows: Column: Jordi Resolve column 5μm (inner diameter 7.8mm x length 300mm), porosity 500A HPLC conditions: Isocratic dimethylformamide (DMF) ·Flow rate 0.7mL / min ·Injection volume: 20μL Column temperature: 40℃ ·Detection CAD Standard Polymethyl Methacrylate (PMMA) Easy Vial (Agilent)

[0323] Figures 14 and 15 show the gel permeation chromatograms of the three PMMA standards that were analyzed and are currently detected. The top line is the standard yellow. The thick middle line is the standard red. The bottom dashed line is the standard green. These standards were analyzed at 2 mg / mL. The chromatographs showed that peaks could be identified that allowed the calculation of the PDI. Figure 16 is the chromatogram of AB-101 Lot01 at a concentration of 1.25 mg / mL.

[0324] Calculation of polydispersity index: Sample analysis of AB-101 Lot01 was performed using the developed method. The calibration curve was w vs. Retention time and LogM n The calibration curves are shown in Figures 17A and 17B. Using the calibration curves, the PDI was calculated based on the retention time of the peaks and the M w and M. n The results are shown in Table 14. [Table 25]

[0325] The PDI of AB-101 Lot 01 is 0.81, in contrast to the PDI of 0.9-1.2 for crofelemer disclosed in WO2012 / 101008. The higher PDI of crofelemer indicates that it has undergone purification and fractionation steps resulting in greater heterogeneity in crosslinking, network formation, chain length, and branching than AB-101. EXAMPLES

[0326] Example 8 - Particle Size Analysis of AB-101 AB-101 is a colloidal suspension by particle size analysis. This makes it inherently difficult to formulate since colloidal suspensions are inherently unstable. What has been shown for the first time in hydrogels is a method to significantly improve the stability of hydrogels containing pharmaceutical grade AB-101.

[0327] One of the main factors in the stability of a colloidal suspension is the particle size distribution. AB-101, a natural plant extract, has a large particle size distribution. The particle size distribution of AB-101 was measured by Particle Testing Authority, a division of Micromeritics Instrument Corporation, using a Saturn DigiSizer Model 5205 Laser Particle Size Analyzer. The results of the particle size distribution analysis are shown in Figure 18.

[0328] The particle size distribution of pharmaceutical grade AB-101 is very broad. The mean particle size (μm) ranges from 0.040 μm to 150.335 μm. At the lower end of the range, which comprises 19.6% of the particles, the particle distribution ranges from 0.040 μm to 0.142 μm. At the upper end of the range, which comprises 19.5% of the particles, the particle distribution ranges from 2.249 μm to 150.335 μm. This is a very large particle distribution. Products with smaller, more uniform particle sizes are more stable and less likely to separate. This broad colloidal particle distribution presents unique challenges for maintaining the stability of hydrogels containing AB-101. EXAMPLES

[0329] Example 9 - Zeta potential of AB-101 Zeta potential is an important and easily measurable indicator of the stability of colloidal dispersions. The magnitude of the zeta potential indicates the degree of electrostatic repulsion between adjacent, similarly charged particles in a dispersion. If the molecules or particles are small enough, a high zeta potential increases stability and makes the solution or suspension less likely to aggregate. If the zeta potential is low, the forces of attraction exceed the repulsion and the dispersion will coagulate, flocculate, and eventually solidify. Thus, colloids with a high zeta potential (negative or positive) are electrically stabilized, while colloids with a low zeta potential tend to coagulate or aggregate as outlined in Table 15. [Table 26]

[0330] The zeta potential of pharmaceutical grade AB-101 whole extract was measured by Particle Testing Authority using NanoPlus HD Zeta Potential and Nano Particle Analyzer. As shown in Figure 19, the zeta potential result of AB-101 was 8.93mV. Table 15 characterizes the properties of AB-101 to exhibit "rapid aggregation to destabilization" behavior. Hydrogels formulated with pharmaceutical grade AB-101 will form hydrogels that lack stability. This results in a formulation that does not meet the FDA requirements to provide a reliable drug delivery system.

[0331] Formulating a physically stable hydrogel with high concentrations of AB-101 is a significant achievement. The challenge is to maintain the pharmaceutical bioactivity of the drug substance, sufficient release of AB-101 from the hydrogel, and the malleability of the hydrogel, while maintaining the pH target. The physical stability of the formulated hydrogel requires preventing the hydrogel from coagulating, aggregating, or solidifying over time and at elevated temperatures.

[0332] Now, for the first time, pharmaceutical grade AB-101 has been formulated into a novel long-term physically stable hydrogel using a disaggregating agent, which represents the first major advance in improving formulation stability by increasing the zeta potential while maintaining the pharmaceutical and aesthetic properties of AB-101 hydrogel.

[0333] The deaggregating agents used, as shown in Table F, are sodium phosphate dibasic heptahydrate, sodium phosphate monobasic anhydrous, and sodium hexametaphosphate. These deaggregating agents release negatively charged phosphate groups, electrostatically stabilizing the particles adsorbed on the surface of AB-101 and increasing the zeta potential. This causes the particles to repel each other, minimizing clumping and aggregation. The first two deaggregating agents (sodium phosphate dibasic heptahydrate and sodium phosphate monobasic anhydrous) belong to the phosphate-based deaggregating agents, which provide electrostatic stabilization by quickly dissociating into charged anions. Sodium hexametaphosphate is a long-chain polyphosphate that dissociates over time or when exposed to high temperatures, releasing phosphate groups and providing long-term electrostatic stabilization. Figure 20 shows the zeta potential measurements of the hydrogel formulations in Table F. The phosphates and hexametaphosphates increase the pH of the hydrogel to near neutral (≈6), making them ideal for skin wound healing applications.

[0334] The improved stability can be seen by comparing the zeta potential of the pharmaceutical AB-101 extract in FIG. 19 with the zeta potential of the AB-101 hydrogel formulation in Table F shown in FIG.

[0335] The zeta potential of the AB-101 hydrogel in Table F with the disaggregating agent shown in Figure 20 is -59.92 mV. This represents a significant improvement over the zeta potential of the pharmaceutical AB-101 extract of 8.93 mV. Table 15 characterizes the properties of the AB-101 hydrogel as exhibiting "good stability" behavior. This hydrogel formulation would be one that meets FDA requirements for reliable drug delivery.

Claims

1. 1. A hydrogel formulation comprising: Contains Croton lecleri filtered latex, glycerin, methylparaben, propylparaben, water, sodium phosphate dibasic heptahydrate, sodium phosphate monobasic, sodium hexametaphosphate, medium chain triglycerides, SEPINEO™ P600 (acrylamide / sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80), The Croton lekleri filtered latex is in an amount of about 10 wt % to about 75 wt %. Hydrogel formulation.

2. 2. The hydrogel formulation of claim 1, wherein the filtered latex of Croton lekleri is the filtered latex of Croton lekleri Mull. Arg.

3. 10. The hydrogel formulation of claim 1, wherein the filtered latex of Croton lekleri is in an amount of about 30 wt% to about 50 wt%.

4. 10. The hydrogel formulation of claim 1, wherein the glycerin is in an amount of about 1 wt % to about 5 wt %.

5. 10. The hydrogel formulation of claim 1, wherein the methylparaben is in an amount of about 0.05 wt % to about 0.5 wt %.

6. 10. The hydrogel formulation of claim 1, wherein the propylparaben is in an amount of about 0.005 wt % to about 0.05 wt %.

7. 10. The hydrogel formulation of claim 1, wherein the water is in an amount of about 20 wt % to about 80 wt %.

8. 10. The hydrogel formulation of claim 1, wherein the sodium phosphate dibasic heptahydrate is in an amount of about 1 wt % to about 3 wt %.

9. 10. The hydrogel formulation of claim 1, wherein the sodium phosphate monobasic is in an amount of about 0.1% to about 0.4%.

10. 10. The hydrogel formulation of claim 1, wherein the sodium hexametaphosphate is in an amount of about 0.005 wt % to about 0.02 wt %.

11. 10. The hydrogel formulation of claim 1, wherein the medium chain triglyceride is in an amount of about 1 wt % to about 6 wt %.

12. 10. The hydrogel formulation of claim 1, wherein the SEPINEO™ P600 (acrylamide / sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80) is in an amount of about 0.5 wt % to about 10 wt %.

13. 10. The hydrogel formulation of claim 1, wherein the hydrogel formulation has a pH of about 3.0 to about 7.

0.

14. The hydrogel formulation of claim 1 for treating a dermatological condition in a subject in need thereof, wherein a therapeutically effective amount of the hydrogel formulation is topically administered to the subject.

15. 15. The hydrogel formulation of claim 14, wherein the dermatological condition is atopic dermatitis, epidermolysis bullosa, impetigo, psoriasis, wounds, skin contaminated with pathogens, atopic dermatitis in patients with Staphylococcus aureus infection, atopic dermatitis in patients with Methicillin-resistant Staphylococcus aureus (MRSA) infection, atopic dermatitis in patients with mupirocin-resistant MRSA infection, epidermolysis bullosa in patients with Staphylococcus aureus infection, epidermolysis bullosa in patients with Methicillin-resistant Staphylococcus aureus (MRSA) infection, epidermolysis bullosa in patients with mupirocin-resistant MRSA infection, epidermolysis bullosa in patients with Streptococcus pyogenes infection, epidermolysis bullosa in patients with Pseudomonas aeruginosa infection, epidermolysis bullosa in patients with Staphylococcus aureus infection. impetigo in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection, impetigo in patients with mupirocin-resistant MRSA infection, impetigo in patients with S. pyogenes infection, psoriasis in patients with S. aureus infection, psoriasis in patients with MRSA infection, psoriasis in patients with mupirocin-resistant MRSA infection, wounds in patients with S. aureus infection, wounds in patients with MRSA infection, wounds in patients with mupirocin-resistant MRSA infection, wounds in patients with S. pyogenes infection, wounds in patients with P. aeruginosa infection, and combinations thereof.

16. 16. The hydrogel formulation of claim 15, wherein the pathogen is selected from the group consisting of Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), mupirocin-resistant MRSA, and combinations thereof.

17. 15. The hydrogel formulation of claim 14, wherein the topical administration is until the dermatological condition is treated.

18. 15. The hydrogel formulation of claim 14, wherein the topical administration is directly to a skin condition.

19. 15. The hydrogel formulation of claim 14, wherein the treatment lasts until the dermatological condition is treated.

20. The hydrogel formulation of claim 1 for preventing a dermatological condition in a subject in need thereof, wherein the hydrogel formulation is contacted with the skin of the subject.

21. The hydrogel formulation of claim 1 for maintaining overall skin health of a subject in need thereof, wherein the hydrogel formulation is contacted with the skin of the subject.

22. The hydrogel formulation of claim 1, wherein the filtered latex of Croton lecleri is in an amount of 36 wt % to 44 wt %.

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