Antimicrobial organosilane

Abstract

To provide a novel organosilicon quaternary ammonium compound that is effective in infectious disease.SOLUTION: A quaternary ammonium compound of the following formula is provided. In the formula, R2,R3, R4, R22, R23, and R24 are individually independent and selected from the group consisting of the following.SELECTED DRAWING: None

Description

Technical Field

[0001] [Cross - Reference to Related Applications] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 923,372, filed Oct. 18, 2019, and U.S. Patent Application No. 63 / 014,535, filed Apr. 23, 2020.

[0002] The present disclosure provides organosilicon quaternary ammonium compounds and compositions thereof, and their use in topical medical therapies in humans and animals, and their use for disinfecting surfaces, which include, but are not limited to, working, industrial, transportation, and household applications.

Background Art

[0003] In humans and animals, it is an urgent global responsibility to provide novel antibacterial agents, including antifungal agents and antibiotics, for treating infectious diseases, such as those that are difficult to treat and do not respond or respond inadequately to current treatments.

[0004] In September 2018, the PEW Charitable Trusts reported a critical need for new antibiotics. At that time, there were only 42 antibiotics in clinical development, and the expected approval rate was 20% or less. Of these, only 15 had the potential to treat infections caused by drug - resistant Gram - negative pathogens. Only 11 of the antibiotics in development had the potential to treat pathogens considered a serious threat by the World Health Organization.

[0005] One way that microbes evade current therapies is through the formation of biofilms. Biofilms are communities of microbes that adhere to one another and often to surrounding surfaces. Such microbes can be fungi, bacteria, yeasts, algae, or generally, mixtures thereof. The microbial community is encapsulated in extracellular polymeric substances (EPS) (see Non-Patent Document 1), and EPS is a mixture of polysaccharides, extracellular DNA (eDNA), and proteins that functions as a matrix to keep microbial cells together. The biofilm matrix contributes to the overall structure and resistant phenotype of the biofilm (see Non-Patent Documents 2 and 3). This matrix also “brings about the spatial organization of the biofilm, from which microbes derive steep gradients, high biodiversity, and complex, dynamic, and synergistic interactions, including intercellular information exchange and enhanced horizontal gene transfer” (see Non-Patent Document 4). This mode of growth protection enables microbes to survive in harsh environments and disperse seeding cells to colonize new niches under favorable conditions.

[0006] The increasing microbial resistance to current treatment regimens is due, at least in part, to the enhanced effectiveness of the primary intrinsic defense mechanisms of microbes, particularly those in biofilms. Such defenses include reduced drug uptake, efflux, enzymatic inactivation, and target modification by mutation. Microbes can also acquire resistance by sharing genetic material, which is called horizontal gene transfer (HGT) and can be a more rapid process than genetic selection involved in the development of intrinsic resistance. Concurrent or sequential multiple microbial infections can occur with similar organisms of different species or mixtures of bacteria and fungi. The available antimicrobial agents used in treatment often do not have significant overlapping activity across multiple populations of pathogen candidates (Non-Patent Document 5).

[0007] The negative consequences of such biofilm interactions are major medical It can impose a burden. Chronic wounds are defined as biological barrier defects that have not healed in three months, but their management has become a major therapeutic challenge across Western European countries, and the problem is that it is only increasing along with the rising incidence of symptoms that interfere with wound healing, such as diabetes, obesity, and vascular disorders. Ulcers last on average 12 to 13 months, recur in up to 60% - 70% of patients, can lead to functional impairment and a decline in quality of life, and are an important cause of morbidity (Non-Patent Document 6). Despite being clinically and molecularly heterogeneous, all chronic wounds generally fall into one of three main clinical classifications: leg ulcers, diabetic foot ulcers, or pressure ulcers. In the United States alone, an estimated 2.4 million to 4.5 million such wounds occur (Non-Patent Document 7). Chronic leg and foot ulcers occur in many adults with vascular disease or diabetes and are caused by chronic venous insufficiency, arterial disease, prolonged pressure, or neuropathy (Non-Patent Document 6). Diabetic foot ulcers (DFUs) are the cause of 80% of non-traumatic lower limb amputations, and the associated five-year mortality rate is 43% - 55%.

[0008] These chronic wounds are mainly thought to have severe colonization by multiple microbial communities, and this microbial community contributes to persistent inflammation and the arrest of the healing process, significantly reducing the patient's quality of life. In tissue injury, microorganisms enter the wound. In the wound, the physical environment is different from the skin surface in terms of temperature, pH, nutrient availability, and host immune effectors. In this case, microbial metabolism can change, thereby providing an opportunity for commensal microorganisms to become pathogenic and for the community composition to fluctuate in response to the host's clinical factors. Once colonization occurs, these communities form biofilms within the wound, disrupting the coordinated tissue regeneration process.

[0009] Current treatments for wounds suspected of having a biofilm mainly focus on targeting bacteria, but the skin is also a host for commensal fungi and our environment is rich in fungal diversity (Non-Patent Document 8). Patients with chronic wounds receive significantly more antibiotic prescriptions (both systemic and topical) than other patients of the same age and gender. Many human commensal fungi or yeasts are also opportunistic pathogens, and many species are known to be biofilm-prolific. There is currently sufficient evidence to conclude that an increase in the species diversity of biofilms correlates with an increase in antimicrobial resistance (Non-Patent Document 9). Moreover, the use of antibiotics targeting bacteria in mixed populations has been shown to increase fungal diversity in wound tissue and provide a microenvironment suitable for the expansion of fungi in mixed bacterial-fungal biofilms.

[0010] Biofilms are present in multiple additional conditions that can lead to or relapse into chronic infections. For example, ear infections can be the result of biofilms in humans as well as in animals such as dogs, cats, rabbits, and horses. In both animals and humans, if not properly treated, infections can cause hearing loss and other health problems.

[0011] Corneal visual impairment is a general term for symptoms resulting from various infections that damage the cornea. Effective treatment of eye infections with available medications is clearly a global health priority. Fungi alone cause over one million eye infections each year, many of which lead to blindness. The eye is particularly vulnerable to fungal infections when the anatomical barrier is breached. The host immune system often cannot fight off fungal infections to prevent vision loss (see Non-Patent Document 10). The lack of powerful fungicides and the poor intraocular penetration of existing antifungal agents have led to a significant eye morbidity rate. Bacteria are also a major global cause of eye infections. If not properly treated, eye infections can damage the structure of the eye, cause visual impairment, or lead to blindness. Bacteria, especially Gram-positive bacteria, are associated with conjunctivitis, keratitis, endophthalmitis, blepharitis, and orbital cellulitis.

[0012] As a further skin disorder that has proven difficult to treat, acne vulgaris is mentioned . Acne vulgaris is caused, at least in part, by the overgrowth of Propionibacterium acnes bacteria and the inflammation induced in response to P. acnes bacteria and / or is a common skin disease that occurs when hair follicles become clogged with dead skin cells and oil from the skin. It has been suggested that P. acnes cells that are resident in hair follicles grow as a biofilm, making treatment particularly difficult (see, for example, Non-Patent Document 11).

[0013] Biofilm formation also occurs on abiotic (i.e., inanimate) surfaces, such as residential, workplace, industrial areas including manufacturing plants, public places, bathrooms, kitchens, furniture, transportation hubs and surfaces, and other surfaces that come into contact with humans or animals.

[0014] By way of example and not limitation, the food and medical sectors pose major public health problems. Biofilms serve as persistent sources of pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, which cause serious infections such as foodborne infections and nosocomial infections. Such biofilms are also sources of material degradation and damage. Environmental conditions commonly encountered in the food and medical fields also appear to enhance biofilm formation and their resistance to disinfectants.

[0015] Biofilm-induced contamination can occur at all stages of food processing, via food handlers, contaminated equipment, and food preparation surfaces (Non-Patent Document 12). The Centers for Disease Control and Prevention (CDC) reported that in the United States, 48 million foodborne illness episodes occur each year, resulting in 128,000 hospitalizations and up to 3,000 deaths (Non-Patent Document 13). In the European Union, 5,609 cases of foodborne outbreaks were reported in 2007, involving approximately 39,727 human cases (11,283 in France), 3,291 hospitalizations, and 19 deaths (7 in France) (Non-Patent Document 14). Additionally, healthcare-associated infections (HAIs), also known as nosocomial infections, commonly occur via the hands of healthcare workers, contaminated surfaces, and devices (surgical instruments, catheters, respiratory devices, endoscopes, needles, etc.) (Non-Patent Document 15). The National Hospital Discharge Survey (NHDS) estimated that the number of HAIs occurring in US hospitals from 1990 to 2002 was up to 1.7 million, of which 98,987 were fatal (Non-Patent Document 16). In Europe, the number of HAIs is estimated to be 3.2 million per year (Non-Patent Document 17).

[0016] Worldwide, a global pandemic caused by the spread of the SARS-CoV virus has occurred in recent years and continues to afflict the world. This pandemic has raised the awareness of the general public worldwide about the importance of disinfecting surfaces.

[0017] The problem of antimicrobial resistance has been worsening over decades, with fewer antibiotics and other antimicrobial agents being developed. Many infections that were previously treatable are now much more difficult to treat with current medications and may soon become untreatable.

Prior Art Documents

Non-Patent Documents

[0018]

Non-Patent Document 1

Non-Patent Document 8

Non-Patent Document 9

Non-Patent Document 10

Non-Patent Document 11

Non-Patent Document 12

Non-Patent Document 13

Non-Patent Document 14

Non-Patent Document 15

[0019] Therefore, new antibacterial agents are still strongly needed. There is a need for new safe and effective topical medicaments for treating a wide range of microbial infections, for treating topical infections in humans and other animals, including infections involving biofilms of mixed pathogens. New effective antibacterial agents are also needed for surface disinfection in a wide range of environments, including residential, workplace, industrial areas, transportation sites, and food manufacturing and supply locations. [Means for Solving the Problems]

[0020] In one embodiment, provided is a novel organosilane quaternary ammonium compound capable of treating a wide range of infections including fungal infections, gram-positive bacterial infections, gram-negative bacterial infections, and viral infections by administering in an effective amount in a topical pharmaceutical formulation to a host in need of treatment. Fungi can appear as yeasts, molds, or a combination of both forms. The novel quaternary ammonium compounds and formulations described herein can treat microorganisms in biofilms, including mixed organisms.

[0021] As shown in the examples, the plurality of non-limiting exemplary compounds described herein (e.g., Compound 1, Compound 2, and Compound 23) have potent antibacterial activity and inhibition against a wide range of treatment-difficult microorganisms present in persistent infections, such microorganisms including a plurality of Candida species, Cladosporium herbarum, Aspergillus niger, Mycoplasma pneumoniae, Fusarium oxysporum, Staphylococcus aureus, and Enterococcus faecalis. Such microorganisms are particularly prevalent in the microbial biofilms present in chronic wounds (see, e.g., Omar et al., Microbial Biofilms and Chronic Wo unds. Microorganisms 2017, Mar; 5(1): 9).

[0022] Thus, in one aspect, the organosilane quaternary ammonium compounds described herein can be used in an effective amount in topical formulations for direct administration against infectious diseases, or can be incorporated into articles for administration to wounds, such as chronic wounds or burns, for example, dressings, bandages, surgical packings, gauzes, wrappings, conformable foams, or films. When incorporated into an article, the organosilane quaternary ammonium compounds described herein can be incorporated such that the article provides controlled release of the compound or its pharmaceutically acceptable salts or compositions into the surrounding area to provide long-term inhibition of microbial growth. In some embodiments, an effective amount of a selected compound described herein is used in the treatment of chronic wounds, such as pressure ulcers, venous ulcers, arterial wounds, neuropathic ulcers, diabetic ulcers, such as leg ulcers or foot ulcers, skin lacerations, or moisture-associated skin damage (MASD), such as incontinence-associated dermatitis. In some embodiments, the compounds described herein are used in the treatment of wounds caused by burns.

[0023] In a further aspect, the quaternary ammonium compounds described herein can be used in an effective amount in the treatment of, for example, eye infections (including bacterial or fungal infections and dry eye caused by blepharitis), ear infections, skin infections including nail bed infections, acne vulgaris, eczema, medical implant infections, oral and periodontal infections, nasal infections, vaginal infections, anal infections, and other infections for which topical or suppository formulations can be used. Additionally, the quaternary ammonium compounds described herein can be incorporated into such devices for the purpose of reducing the risk of infection associated with the use of medical implants.

[0024] Importantly, in some embodiments, the novel organosilane quaternary ammonium compounds described herein can be provided as stable powders or lyophilized materials, which can be formulated using a pharmaceutically acceptable topical carrier prior to administration. In alternative embodiments, the novel organosilane quaternary ammonium compounds described herein can be incorporated into a dressing, a conformable foam, or a polymer used in a dressing, a bandage, or a film for medical applications, such as a wound dressing or a surgical packing material, to reduce the risk of infection. In yet another alternative embodiment, the novel organosilane quaternary ammonium compounds described herein can be incorporated into a medical implant, which can be, for example, but not limited to, an orthopedic implant or a dental implant.

[0025] In some embodiments, a human or animal topical infection can be treated with a selected organosilane quaternary ammonium compound, which can be used to treat a microorganism, or a combination of microorganisms or a biofilm comprising the combination, and the microorganism can be, for example, Acinetobacter (Gram-negative), Pseudomonas (Gram-negative), Proteus (Gram-negative proteobacteria), Staphylococcus (Gram-positive), Streptococcus (Gram-positive), MRSA (methicillin-resistant S. aureus), Escherichia coli (Gram-negative), Propionibacterium (Gram-positive), Klebsiella (Gram-negative), Enterococcus (Gram-positive), Haemophilius influenzae, etc., and Fungi, such as Fusarium, Aspergillus, Cladophora, and dermatophytes such as Trichophyton, Micrococcus, and the like. These include the genera Microsporum and Epidermophyton.

[0026] In certain embodiments, the topical infection comprises a Candida fungal infection, such as, but not limited to, Candida species such as C. albicans, C. auris, or C. glabrata, or combinations thereof.

[0027] The present invention provides novel organosilicon quaternary amine compounds with pharma-ceutically acceptable charge neutralizing anion(s) (whether or not specified in formula).In certain embodiments, charge neutralizing anion is selected from chloride anion, fluoride anion, iodide anion, bromide anion, hydroxide anion, chlorite anion, chlorate anion, hydroxide anion, formate anion, acetate anion, lactate anion, benzoate anion, or salicylate anion.In typical embodiments, charge neutralizing anion is chloride anion or hydroxide anion.

[0028] In some embodiments, the quaternary ammonium compound has a negatively charged substituent that may be neutralized with a pharma- ceutically acceptable cation, such as a sodium or potassium cation.

[0029] In some embodiments, the quaternary ammonium compounds are provided as zwitterions, in which the positive charge of an internal quaternary amine is neutralized with an anion derived from a substituent in the molecule, as further described below.

[0030] The present invention also provides a method for topically administering, in an effective amount, one or more of the novel organosilicon quaternary amine compounds described herein to a host in need of treating, preventing, inhibiting, or eliminating an infectious disease, which compounds may optionally contain a pharmaceutically acceptable salt, optionally in their composition.

[0031] The present invention also includes their pharmaceutically acceptable compositions in the form of powders, lyophilized powders, or other solid stable storage forms.

[0032] The selected compounds of the present invention can also be used, in an effective amount, optionally incorporated into a liquid, gel, or solid carrier, to disinfect microbial growth or biofilm formation occurring on abiotic (i.e., inanimate) surfaces, such as industrial areas including residences, workplaces, manufacturing plants, public places, bathrooms, kitchens, furniture, transportation hubs or surfaces, or other surfaces in contact with or in the environment of humans or animals. In one embodiment, environmental surfaces commonly encountered in the food and medical fields also appear to enhance biofilm formation and their resistance to disinfectants.

[0033] In one aspect, the present invention provides a formula: [Chemical formula] (wherein, a is 1, 2, 3, 4, 5, 6, 7, or 8 (wherein the methylene can have a branched alkyl, such as a C1 - C4 alkyl including methyl, etc.), R 1 each independently is a C6 - C 22 alkyl (which is C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C19 , C 20 , C 21 , or C 22 is possible), C6 - C 22 alkenyl (which can be C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , or C 22 is possible), and C6 - C 22 alkanoyl (which can be C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , or C 22 is possible) and are selected from (where any of these methylene or aliphatic carbons can have a branched alkyl, such as C1 - C4 alkyl including methyl, etc.), R 2 , R 3 , and R 4 are each independently [Chemical formula] selected from, or C2 - C 10 alkanoic acid (which can be C2, C3, C4, C5, C6, C7, C8, C9, or C 10 is possible) or their salts, and in some embodiments, R 2 , R 3 , and R 4 are all alkanoic acids (where any of these methylene or aliphatic carbons can have a branched alkyl, such as C1 - C4 alkyl including methyl, etc.), y is 0, 1, 2, 3, or 4, p is independently selected from 1, 2, 3, and 4, R 6 is independently selected from hydrogen, alkyl, aryl, cycloalkyl, and heterocyclyl, and the alkyl, aryl, cycloalkyl, and heterocyclyl each optionally has a substituent selected from C1-C6 alkyl, hydroxyl, chloro, bromo, iodo, fluoro, N(R 7 )2, COOR 7 , C(O)R 7 , CH2OR 7 , CON(R 7 )2, and NO2, R 8 , R 9 , R 10 , R 11 , R 12 , and R 13 are independently selected from hydrogen, halogen, hydroxyl, N(R 7 )2, CH2OR 7 , CON(R 7 )2, COOR 7 , C(O)R 7 , C1-C8 alkyl, C1-C8 hydroxyalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C1-C8 alkanoyl, heterocyclyl, heteroaryl, and aryl, R 7 is independently selected from hydrogen, C1-C8 alkyl, C1-C8 hydroxyalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C1-C8 alkanoyl, heterocyclyl, heteroaryl, heterocycloalkyl, and aryl, X 1 is independently selected from NR 17 , CH2, CHOH, and C(O), X 2 is independently selected from C1-C3 alkyl and C1-C3 hydroxyalkyl, X 3are each independently hydroxyl, NO2, N(R 7 )2, CH2OR 7 , C ON(R 7 )2, COOR 7 , C(O)R 7 , C1-C 12 alkanoic acid, C1-C8 alkyl, C1-C8 hydroxyalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C1-C8 alkanoyl, heterocyclyl, heteroaryl, and aryl, and are selected from X 4 are each independently selected from X 3 , R 16 are each independently selected from C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, and C1-C4 haloalkyl, R 17 are each independently hydrogen, C1-C8 hydroxyalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C1-C8 alkanoyl, heterocyclyl, heteroaryl, heterocycloalkyl, and aryl, X - is an anion, for example, chloride anion, fluoride anion, iodide anion, bromide anion, hydroxide anion, chlorite anion, chlorate anion, formate anion, acetate anion, lactate anion, benzoate anion, or salicylate anion, and when X - is an anion having two or more negative charges, the stoichiometry of the charge must be neutralized by other cations, B + is a cation, for example, ammonium cation, potassium cation, or sodium cation, and when using B + having two or more charges, for example, calcium cation, is useful, the stoichiometry must be neutralized as appropriate, for example, [Chemical formula] To provide a quaternary ammonium compound having (as described).

[0034] In some embodiments, B + is K + or Na + Another embodiment, B + is Ca +2 or Mg +2 is.

[0035] In a particular embodiment, B + is an ammonium ion, which includes NH4 + , RNH3 + , R2NH2 + , R3NH + , or R4N + is included, where in the formula, each R is independently selected from the group consisting of C1-C8 alkyl, C1-C8 hydroxyalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, heterocyclyl, heteroaryl, heterocycloalkyl, and aryl.

[0036] In any of the formulas provided herein, where there is an alkyl or aliphatic chain of a certain length, any of these methylene or aliphatic carbons can have a branched alkyl, such as C1-C4 alkyl including methyl, etc., and each combination is considered to be specifically disclosed.

[0037] In another aspect, the present invention provides a formula: [Chemical formula] (wherein a is 1, 2, 3, 4, 5, 6, 7, or 8 (where any of these methylene can have a branched alkyl, such as C1-C4 alkyl including methyl, etc.), X -is an anion, for example, chloride anion, fluoride anion, iodide anion, bromide anion, chlorite anion, chlorate anion, hydroxide anion, formate anion, acetate anion, lactate anion, benzoate anion, or salicylate anion, and X - When is an anion with two or more negative charges, the stoichiometry must be neutralized as appropriate, R 14 and R 15 are each independently [Chemical formula] , R 2 and R 17 selected from, where all other variable terms are as defined herein), to provide a quaternary ammonium compound having

[0038] In another aspect, the present invention provides a compound of the formula: [Chemical formula] (wherein p and q are each independently selected from 1, 2, 3, and 4, R 5 are each independently R 2 , R 17 , and C2-C 10 alkanoic acid (which can be C2, C3, C4, C5, C6, C7, C8, C9, or C 10 ), where the acid is optionally a diacid or its salt (where any of these methylenes can have a branched alkyl, such as C1-C4 alkyl including methyl, etc.), R 2 are each independently [Chemical formula] selected from, or R 2 are each independently selected from C1-C8 alkanoic acids or their salts, R 8 , R9 , R 10 , R 11 , R 12 , and R 13 are each independently selected from hydrogen, halogen, hydroxyl, N(R 7 )2, CH2OR 7 , CON(R 7 )2, COOR 7 , C(O)R 7 , C1-C8 alkyl, C1-C8 hydroxyalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C1-C8 alkanoyl, heterocyclyl, heteroaryl, and aryl, R 7 are each independently selected from hydrogen, C1-C8 alkyl, C1-C8 hydroxyalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C1-C8 alkanoyl, heterocyclyl, heteroaryl, heterocycloalkyl, and aryl, X 1 are each independently selected from NR 17 , CH2, CHOH, and C(O), X 2 are each independently selected from C1-C3 alkyl and C1-C3 hydroxyalkyl, X 3 are each independently selected from hydroxyl, NO2, N(R 7 )2, CH2OR 7 , CON(R 7 )2, COOR 7 , C(O)R 7 , C1-C 12 alkanoic acid, C1-C8 alkyl, C1-C8 hydroxyalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C1-C8 alkanoyl, heterocyclyl, heteroaryl, and aryl, X 4 are each independently selected from X 3 , R 17are each independently selected from hydrogen, C1-C8 hydroxyalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C1-C8 alkanoyl, heterocyclyl, heteroaryl, heterocycloalkyl, and aryl, X - is an anion, for example, chloride anion, fluoride anion, iodide anion, bromide anion, chlorite anion, chlorate anion, hydroxide anion, formate anion, acetate anion, lactate anion, benzoate anion, or salicylate anion, and when X - is an anion with two or more negative charges, the stoichiometry of the charge is still neutralized by other cations, B + is a cation, for example, sodium cation, potassium cation, magnesium cation, calcium cation, or lithium cation, and when B + is a cation with two or more positive charges, the stoichiometry of the charge is appropriately neutralized by other anions) to provide a quaternary ammonium compound.

[0039] In certain embodiments, the quaternary ammonium compound has a negatively charged moiety that can form a pharmaceutically acceptable salt, in which case the cation is selected from sodium cation, potassium cation, magnesium cation, calcium cation, cesium cation, barium cation, and lithium cation.

[0040] In one aspect, by reacting one or more quaternary ammonium compounds of formula I, formula II, formula III, or formula IV with a polyhdroxyl compound, oligomeric or polymeric products of formula I', formula II', formula III', formula IV' are formed, and the polyhdroxyl compound is a compound selected from, for example, glycerin, or It is a glycol selected from one or more of glycidol, glycerol, glycerol-propylene oxide copolymer, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, and polyvinyl alcohol.

[0041] In one embodiment, one or more quaternary ammonium compounds of Formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL are reacted with a polyhydroxyl compound to form an oligomer or polymer product of Formula I', II', III', IV', V', VI', VII', VIII', IX', X', XI', XII', XIII', XIV', XV', XVI', XVII', XVIII', XIX', XX', XXI', XXII', XXIII', XXIV', XXV', XXVI', XXVII', XXVIII', XXIX', XXX', XXXI', XXXII', XXXIII', XXXIV', XXXV', XXXVI', XXXVII', XXXVIII', XXXIX', or XL'. The polyhydroxyl compound is, for example, a compound selected from glycerin, or a glycol selected from one or more of glycidol, glycerol, glycerol-propylene oxide copolymer, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, and polyvinyl alcohol.

[0042] In one embodiment, the present invention provides a powder formulation comprising at least one quaternary ammonium compound as described herein, or a combination thereof. In some embodiments, the powder is a lyophilized powder.

[0043] In some embodiments, there is provided a pharmaceutical composition using a quaternary ammonium compound as described herein, the pharmaceutical composition containing less than about 5%, about 4%, about 3%, about 2%, about 1%, about 0.5%, or about 0.1% methanol by weight, or methanol is absent.

[0044] In some embodiments, a quaternary ammonium compound as described herein, its pharmaceutically acceptable composition, or a combination thereof is administered as an aqueous or glycerin solution formed by reconstitution of a powder or solid formulation.

[0045] In some embodiments, any mixture of quaternary ammonium compounds as described herein, or its pharmaceutically acceptable composition is appropriate as long as the desired stability is obtained.

[0046] In some embodiments, the compounds of the present invention exist as a mixture of related structures. By way of example and not limitation, mainly the following molecules:

Chemical formula

Chemical formula

[0047] In certain embodiments, the composition of any aspect of the present invention, independently, is a mixture of any of the molecules herein, provided that the indicated structure constitutes at least 10%, 20%, 30%, 40%, 50%, 51%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% of the mixture on a molar basis or on a weight basis.

[0048] As those skilled in the art will also understand, the compounds of the present invention can exist in various forms in solution and still achieve their intended purposes. That is, in certain embodiments, the present invention is a solution of the compounds shown, provided that this solution can contain various related structures, but the overall ratio of the silicon side chain groups to the silicone is the same as that shown. For example, in some embodiments, the present invention is a solution of

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0049] In one aspect, the present invention provides the following formulas V, VI, VII, VIII, IX, X, XI, and XII:

Chemical formula

Chem.

Chem.

[0050] In certain embodiments, the compounds of the present invention are

Chem.

[0051] In certain embodiments, R 22 、R 23 、and R 24 are each independently

Chem.

[0052] In certain embodiments, R 22 、R 23 、and R 24 are each independently

Chem.

[0053] In certain embodiments, each R 36 is hydrogen.

[0054] In certain embodiments, each R 32 is -CH2-SO3H.

[0055] In one aspect of the invention, Formula XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, or XXI:

Chemical formula

Chemical formula

[0056] In certain embodiments of the quaternary ammonium compounds from Formula XIII to Formula XXI, from Formula XXIII to Formula XXXIII, and from Formula XXXV to Formula XL, the variable m is independently selected from 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 16. In certain embodiments of the quaternary ammonium compounds from Formula XIII to Formula XXI, m is 14. In certain embodiments of the quaternary ammonium compounds from Formula I to Formula XXI, m is independently selected from 12 - 16.

[0057] In certain embodiments, the ammonium compounds of Formula XIII, XIV, XV, XVI, or XVII in solution are in equilibrium with other quaternary ammonium compounds of Formula XIII, XIV, XV, XVI, or XVII. In another embodiment, the quaternary ammonium compounds of Formula XIII, XVIII, XIX, XX, and XXI are in equilibrium. For example, in one embodiment, the following compounds may be in equilibrium:

Chemical formula

[0058] Due to the instability of the silicon - oxygen bond, these structures may interconvert by breaking and forming bonds such that a mixture of Formula XIII, XIV, XV, XVI, and XVII or a mixture of Formula XIII, XVIII, XIX, XX, or XXI may be present.

[0059] In another aspect of the present invention, Formula XXII, XXIII, XXIV, XXV, XXVI, or XXVII:

Chemical formula

[0060] In one embodiment, the quaternary ammonium compound of formula XXII, XXIII, or XXIV in solution is in equilibrium with other quaternary ammonium compounds of formula XXII, XXIII, or XXIV. For example, in one embodiment, the following compounds may be in equilibrium:

Chemical formula

[0061] In one embodiment, the quaternary ammonium compound of formula XXV, XXVI, or XXVII in solution is in equilibrium with other quaternary ammonium compounds of formula XXV, XXVI, or XXVII. By way of non-limiting example, the following compounds may be in equilibrium:

Chemical formula

[0062] Due to the instability of the silicon-oxygen bond, these structures may interconvert by breaking and forming bonds such that a mixture of formula XXII, XXIII, or XXIV may be present or a mixture of formula XXV, formula XXVI, or formula XXVII may be present.

[0063] In another aspect of the invention, formula XXVIII, XXIX, or XXX:

Chemical formula

[0064] In one embodiment, the compound of formula XXVIII, XXIX, or XXX is in equilibrium with other compounds of formula XXVIII, XXIX, or XXX. For example, in one embodiment, the following compounds may be in equilibrium:

Chemical formula

[0065] Due to the instability of the silicon-oxygen bond, these structures may interconvert by breaking and forming bonds such that a mixture of formula XXVIII, formula XXIX, or formula XXX may be present.

[0066] In another aspect of the invention, formula XXXI or XXXII:

Chemical formula

Chemical formula

Chemical formula

[0067] Due to the instability of the silicon-oxygen bond, these structures may interconvert by breaking and forming bonds such that a mixture of formula XXXI or formula XXXII may be present.

[0068] In another embodiment, what the present invention provides is formula XXXIII:

Chemical formula

[0069] In one embodiment, q’, r, and s are the same.

[0070] In another aspect of the present invention, the formula XXXIV, XXXV, or XXXVI:

Chemical formula

Chemical formula

[0071] In one embodiment, the compound of formula XXXIV, XXXV, or XXXVI is in equilibrium with other compounds of formula XXXIV, XXXV, or XXXVI. For example, in one embodiment, the following equilibrium may exist:

Chemical formula

[0072] Due to the instability of the silicon-oxygen bond, these structures may interconvert by breaking and forming bonds such that a mixture of the formula XXXIV, XXXV, or XXXVI may exist.

[0073] In another aspect of the present invention, a quaternary ammonium compound of formula XXXVII, XXXVIII, or XXXIX is provided: [Chemistry]

[0074] In one embodiment, the quaternary ammonium compound of formula XXXVII, XXXVIII, or XXXIX is in equilibrium with another quaternary ammonium compound of formula XXXVII, XXXVIII, or XXXIX. For example, in one embodiment, the following compounds may be in equilibrium: [Chemistry]

[0075] Due to the instability of the silicon-oxygen bond, these structures may interconvert by breaking and forming bonds such that a mixture of formula XXXVII, XXXVIII, or XXXIX may be present.

[0076] The present invention contemplates, inter alia, an antibacterial composition containing one or more compounds of formula XXXVII, XXXVIII, or XXXIX and a suitable carrier.

[0077] The present invention also includes a method of treating an infectious disease in a host in need of treatment for the infectious disease by using an effective amount of a quaternary ammonium compound of formula XXXVII, XXXVIII, or XXXIX.

[0078] In another alternative embodiment, formula XL: [Chemistry] (wherein R A is as defined above, and t is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, and Z is, independently of each other, [Chemistry] selected from, L is, independently of each other, [Chemistry] selected from R 124 and R 125 are each independently hydrogen, ethyl,

Chemical formula

[0079] The curing agent in formula XL can be any pharmaceutically acceptable compound.

[0080] In certain embodiments, the curing agents for the oligomers or polymers as described herein are diethylenetriamine (DTA), triethylenetetramine (TTA), tetraethylenepentamine (TEPA), dipropenediamine (DPDA), diethylaminopropylamine (DEAPA), Amine 248, N-aminoethylpiperazine (N-AEP), Lamiron C-260, Araldit HY-964, me thane diamine (MDA), isophorone diamine (IPDA), S Cure 211, S Cure 212, Wonderamine HM, 1,3BAC, m-xylenediamine (m-X DA), Shoamine X, Amine Black, Shoamine Black, Shoamine N, Shoamine 1001, Shoamine 1010, Metaphenylenediamine (MPDA), Diaminodiphenylmethane (DDM), Diaminodiphenylsulfone (DDS), Piperidine, N,N-Dimethylpiperidine, Triethylenediamine, 2,4,6-Tris(dimethylaminomethyl)phenol (DMP-30), Benzyldimethylamine (BDMA), and 2-(Dimethylaminomethyl)phenol (DMP-10); Imidazoles, such as 2-Methylimidazole, 2-Ethyl-4-methylimidazole, 1-Cyanoethyl-2-undecylimidazolium trimellitate, and Epoxy-imidazole adducts, etc.; Liquid polymeric mercaptans or polysulfide resins; or Acid anhydrides, such as Phthalic anhydride, Trimellitic anhydride, Pyromellitic anhydride, Benzophenone tricarboxylic anhydride, Ethylene glycol bis trimellitate, Glycerol tritrimellitate, Maleic anhydride, Tetrahydrophthalic anhydride, Methyltetrahydrophthalic anhydride, Endomethylenetetrahydrophthalic anhydride, Methylendomethylenetetrahydrophthalic anhydride, Methylbutenyltetrahydrophthalic anhydride, Dodecenyl succinic anhydride, Hexahydrophthalic anhydride, Hexahydro-4-methylphthalic anhydride, Succinic anhydride, Methylcyclohexene dicarboxylic anhydride, Alkylstyrene-maleic anhydride copolymer, Chlorendic anhydride, and Polyazelainic polyanhydride are included.

[0081] In another aspect of the present invention, formula A:

Chemical formula

Chemical formula

[0082] In another aspect of the present invention, compound B' is provided, and this compound B' is formed by the reaction of one or more compounds of formula A and one or more compounds of formula B. In one embodiment, compound B' is an oligomeric or polymeric compound having one or more formula B units and one or more formula A units.

[0083] In another aspect of the present invention, compound C' is provided, and this compound C' is formed by the reaction of one or more compounds of formula A and one or more compounds of formula C. In one embodiment, compound C' is an oligomeric or polymeric compound having one or more formula C units and one or more formula A units.

[0084] In another aspect of the present invention, compound D' is provided, and this compound D' is formed by the reaction of one or more compounds of formula A and one or more compounds of formula D. In one embodiment, compound D' is an oligomeric or polymeric compound having one or more formula D units and one or more formula A units.

[0085] In another aspect of the present invention, compound E' is provided, and this compound E' is formed by the reaction of one or more compounds of formula A and one or more compounds of formula E. In one embodiment, compound E' is an oligomeric or polymeric compound having one or more formula E units and one or more formula A units.

[0086] In another aspect of the present invention, compound F' is provided, and this compound F' is formed by the reaction of one or more compounds of formula A and one or more compounds of formula F. In one embodiment, compound F' is an oligomeric or polymeric compound having one or more formula F units and one or more formula A units.

[0087] In another aspect of the present invention, compound G' is provided, which is formed by the reaction of one or more compounds of formula A with one or more compounds of formula G. In one embodiment, compound G' is an oligomeric or polymeric compound having one or more units of formula G and one or more units of formula A.

[0088] In another aspect of the present invention, compound H' is provided, which is formed by the reaction of one or more compounds of formula A with one or more compounds of formula H. In one embodiment, compound H' is an oligomeric or polymeric compound having one or more units of formula H and one or more units of formula A.

[0089] In another aspect of the present invention, compound J' is provided, which is formed by the reaction of one or more compounds of formula A with one or more compounds of formula J. In one embodiment, compound J' is an oligomeric or polymeric compound having one or more units of formula J and one or more units of formula A.

[0090] In another aspect of the present invention, compound K' is provided, which is formed by the reaction of one or more compounds of formula A with one or more compounds of formula K. In one embodiment, compound K' is an oligomeric or polymeric compound having one or more units of formula K and one or more units of formula A.

[0091] In another aspect of the present invention, compound L' is provided, which is formed by the reaction of one or more compounds of formula A with one or more compounds of formula L. In one embodiment, compound L' is an oligomeric or polymeric compound having one or more units of formula L and one or more units of formula A.

[0092] In another aspect of the present invention, there is provided a compound M', which is formed by the reaction of one or more compounds of formula A and one or more compounds of formula M. In one embodiment, the compound M' is an oligomeric or polymeric compound having one or more formula M units and one or more formula A units.

[0093] In another aspect, the compounds of the present invention are in the form of an oil, which can be topically administered as the pure compound. The oil is optionally mixed with excipients, carriers, or diluents described herein to maintain a long shelf life without solidifying. For example, the oil of the present invention can be mixed with an ionic liquid, an organic solvent, or an aqueous solution to maintain the oil form. By way of example and not limitation of oils that can be mixed with the compounds of the present invention, coconut oil, rice bran oil, and vegetable oils are mentioned. In certain embodiments, The mixture of the compound of the present invention and the additional oil forms a storage-stable oily composition that can be topically administered to a patient in need of administration.

[0094] In certain embodiments, the compound of the present invention (optionally as an oil) is administered directly to a wound. By way of example and not limitation of how the compound can be administered, it can be dropped, poured, gently tapped, or otherwise applied to an open wound, a covered wound, or as part of a negative pressure wound therapy. For example, the compound of the present invention can be applied to a sponge for administration and inserted into the wound, and then the surrounding skin is sealed with a film and a small suction tube is punctured to create a subatmospheric pressure with this small suction tube and draw out the exudate.

[0095] In another aspect, there is provided an anti-infective composition, which comprises one or more quaternary ammonium compounds as described herein in an amount effective for the treatment, prevention, or removal of an infection, or a pharmaceutically acceptable composition thereof, and a suitable carrier.

[0096] In certain embodiments, the pharmaceutically acceptable carrier includes an aqueous or glycerin solution, such as water, saline, or phosphate buffered saline.

[0097] In certain embodiments, the glycerin solution is selected from glycerol, glycidol, glycerol-propylene oxide copolymer, ethylene glycol, propylene glycol, polyethylene glycol, or polypropylene glycol, or combinations thereof.

[0098] In another aspect, a kit is provided, the kit including a vial containing a sterile aqueous solution, a vial containing a quaternary ammonium compound as described herein, and an applicator device.

[0099] In another aspect, a kit is provided, the kit including a powder formulation containing a quaternary ammonium compound or a pharmaceutically acceptable salt thereof as described herein, a sterile aqueous solution, and an applicator device. In some embodiments, the powder is a lyophilized powder.

[0100] In some embodiments, the applicator device is a syringe.

[0101] In another aspect, a kit is provided, the kit including a sterile aqueous solution and a quaternary ammonium compound as described herein together with one or more compounds selected from sor ketal, epichlorohydrin, and polyvinyl alcohol.

[0102] In another aspect, a kit is provided, the kit including a sterile aqueous or glycerin solution and a quaternary ammonium compound as described herein together with one or more compounds selected from glycerol, glycidol, glycerol-propylene oxide copolymer, ethylene glycol, propylene glycol, polyethylene glycol, and polypropylene glycol.

[0103] In some embodiments, the present invention provides a compound as described herein, or a pharmaceutically acceptable composition thereof, which is useful for the treatment, prevention, inhibition, or elimination of an infectious disease in a host in need thereof, in an effective amount.

[0104] In one aspect, as further described herein, a method for treating, preventing, inhibiting, or eliminating an infectious disease is provided, the method comprising administering to a host in need thereof one or more quaternary ammonium compounds as described herein, or a pharmaceutically acceptable composition thereof, in an effective amount.

[0105] In some embodiments, the host is a human.

[0106] In another embodiment, the host is a mammal, such as a dog, cat, horse, cow, or pig.

[0107] In another aspect, the present invention provides a method of administering one or more compounds of the present invention, or a pharmaceutically acceptable composition thereof, in an effective amount useful for the treatment, inhibition, elimination, or prevention of the above infectious disease.

[0108] In some embodiments, the infectious disease is a mixed infection comprising bacterial species, fungal species, and viral species.

[0109] In some embodiments, one or more quaternary ammonium compounds of the present invention, or a composition thereof, are used in a host in need thereof for treating or preventing an infectious disease in a chronic wound in an amount effective for treating or preventing the infectious disease in the chronic wound.

[0110] In some embodiments, the chronic wound is a diabetic ulcer, such as a diabetic foot ulcer or a diabetic lower extremity ulcer.

[0111] In another embodiment, the chronic wound is a pressure ulcer.

[0112] In some embodiments, the chronic wound is a pressure ulcer.

[0113] In some embodiments, the chronic wound is a venous ulcer.

[0114] In some embodiments, the chronic wound is an arterial ulcer.

[0115] In some embodiments, the chronic wound is a neuropathic ulcer.

[0116] In some embodiments, the chronic wound is a skin tear.

[0117] In some embodiments, the chronic wound is moisture-associated skin damage (MASD), such as incontinence-associated dermatitis.

[0118] In some embodiments, the compounds described herein are used in the treatment of wounds caused by burns.

[0119] In another embodiment, the infection in the chronic wound is caused by a biofilm.

[0120] In some embodiments, one or more quaternary ammonium compounds of the present invention, or a composition thereof, are used in an amount effective to treat, prevent, or eliminate an eye infection in a host in need of treating, preventing, or eliminating the eye infection.

[0121] In some embodiments, the eye infection is keratitis.

[0122] In another embodiment, the eye infection is a bacterial keratitis, such as keratitis caused by Staphylococcus aureus or Pseudomonas aeruginosa.

[0123] In another embodiment, the eye infection is a fungal keratitis, for example, keratitis caused by Fusarium species, Aspergillus species, Candida species, or Curvularia species. In some embodiments, the eye infection is Acanthamoebic keratitis.

[0124] In another embodiment, the eye infection is a viral keratitis, for example, herpes simplex virus (HSV) keratitis.

[0125] In another embodiment, the eye infection is a bacterial conjunctivitis, for example, conjunctivitis caused by Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, or Pseudomonas aeruginosa.

[0126] In another embodiment, the eye infection is a viral conjunctivitis, for example, conjunctivitis caused by adenovirus or enterovirus.

[0127] In another embodiment, the eye infection is polymicrobial, in which case diagnosis and treatment are more difficult. For example, when bacteria are associated with Acanthamoeba keratitis, the risk of angiogenesis and prolonged healing is high.

[0128] In another embodiment, the eye infection is a superinfection by one or more opportunistic organisms that can also cause the infection. For example, a herpes corneal ulcer can provide a microenvironment favorable for the establishment of bacterial or fungal pathogens.

[0129] In another aspect, an eye composition is provided, the composition comprising an effective amount of one or more quaternary ammonium compounds of the present invention and an ophthalmologically acceptable carrier.

[0130] In some embodiments, the eye composition does not contain any by-products or additives, such as alcohol, etc.

[0131] In some embodiments, the ocular composition is substantially free of methanol. In some embodiments, the infectious disease to be treated is an ocular infectious disease.

[0132] In another embodiment, the infectious disease to be treated is an ear infectious disease, such as an inner ear, outer ear, or middle ear infection.

[0133] In some embodiments, the infectious disease to be treated is a skin infectious disease.

[0134] In some embodiments, the infectious disease to be treated is a nail infectious disease, such as a fungal nail infection.

[0135] In some embodiments, the infectious disease to be treated is an infectious disease of the vaginal mucosal tissue, such as vulvovaginal candidiasis.

[0136] In some embodiments, the infectious disease is within a chronic wound or ulcer, and the ulcer is, for example, a lower limb ulcer, or a diabetic ulcer such as a diabetic lower limb ulcer or a diabetic foot ulcer, but is not limited thereto.

[0137] In another aspect, a method of treating an ear infection in a host in need thereof is provided, the method comprising administering an effective amount of one or more quaternary ammonium compounds of the present invention, or a composition thereof.

[0138] In some embodiments, one or more quaternary ammonium compounds of the present invention, or a composition thereof, are used in an amount effective to treat, prevent, or eliminate an ear infection in a host in need thereof.

[0139] In some embodiments, the ear infection is an inner ear infection (otitis interna).

[0140] In some embodiments, the ear infection is an outer ear infection (otitis externa).

[0141] In another embodiment, the ear infection is a middle ear infection (otitis media).

[0142] In some embodiments, the ear infection is caused by bacteria or fungi.

[0143] In another embodiment, the ear infection is caused by both bacteria and fungi.

[0144] In another embodiment, the infection is caused by a biofilm that may contain a combination of bacterial cells and fungal cells. In another embodiment, the infection is caused by a biofilm that may contain a combination of bacterial cells and fungal cells, and one or more viruses.

[0145] In another aspect, there is provided a method of treating an eye infection in a host in need thereof, the method comprising administering, in an effective amount, one or more quaternary ammonium compounds described herein, or a composition thereof.

[0146] In another aspect, there is provided a method of treating onychomycosis, i.e., nail fungal infection, in a host in need thereof, the method comprising administering, in an effective amount, one or more quaternary ammonium compounds described herein, or a composition thereof.

[0147] In some embodiments, one or more quaternary ammonium compounds of the present invention, or a composition thereof, are used in an amount effective to treat, prevent, or eliminate onychomycosis in a host in need thereof.

[0148] In another aspect, there is provided a formulation for treating onychomycosis in a host in need thereof, the formulation comprising administering, in an effective amount, one or more quaternary ammonium compounds described herein in a carrier suitable for delivery to the nail bed. In some embodiments, the carrier is dimethyl sulfoxide.

[0149] In some embodiments, one or more of the quaternary ammonium compounds described herein are administered as an aqueous, glycerin, or dimethyl sulfoxide solution, which is formed by reconstitution from a powder formulation of one or more quaternary ammonium compounds. In some embodiments, the powder is a lyophilized powder.

[0150] In another embodiment, a method of treating or preventing such an infection in a host in need of treatment or prevention of an infection in a chronic wound is provided, the method comprising administering an effective amount of one or more of the quaternary ammonium compounds described herein, or a composition thereof.

[0151] In another embodiment, a method of treating or preventing a vaginal infection in a host in need of treatment or prevention of a vaginal infection is provided, the method comprising administering an effective amount of one or more of the quaternary ammonium compounds described herein, or a composition thereof.

[0152] In some embodiments, one or more of the quaternary ammonium compounds of the present invention, or a composition thereof, are used in an amount effective to treat or prevent a vaginal infection in a host in need of treating or preventing a vaginal infection.

[0153] In some embodiments, the vaginal infection is vulvovaginal candidiasis.

[0154] In some embodiments, a vaginal infection, such as vulvovaginal candidiasis, is a fungal infection caused by Candida species.

[0155] In some embodiments, the vaginal infection is a bacterial vaginosis.

[0156] In some embodiments, vaginal infections, such as vulvovaginal candidiasis, are bacterial infections caused by Lactobacilli, Bacteroides, Peptostreptococcus, Fusobacterium, and / or Eubacterium. genus (Peptostreptococcus), Fusobacterium genus (Fusobacterium), and / or Euba cterium genus (Eubacterium) is a bacterial infection.

[0157] In another aspect, a method of treating a dermatological disorder in a host in need thereof is provided, the method comprising administering, in an effective amount, one or more quaternary ammonium compounds described herein, or a composition thereof.

[0158] In an alternative embodiment, the infection to be treated is a dermatological disorder.

[0159] In certain embodiments, the dermatological disorder is, for example, acne vulgaris, cystic acne, eczema, folliculitis, and skin infections.

[0160] In certain embodiments, a dermatological disorder, such as acne vulgaris, is caused by the gram-positive bacterium Propionibacterium acnes, and / or Staphylococcus epidermidis.

[0161] In certain embodiments, a dermatological disorder, such as eczema (atopic dermatitis), herpetic eczema, vaccinial eczema, or coxsackievirus eczema, is caused by a bacterial or viral infection.

[0162] In certain embodiments, a dermatological disorder, such as eczema (atopic dermatitis), is caused by bacteria, such as staphylococcal bacteria or streptococcal bacteria, such as Staphylococcus aureus.

[0163] In certain embodiments, dermatological disorders such as eczema (atopic dermatitis) are caused by viruses such as herpes simplex virus and / or molluscum contagiosum virus.

[0164] In certain embodiments, dermatological disorders such as skin infections are caused by Staphylococcus aureus (S. aureus).

[0165] In some embodiments, an effective amount of one or more quaternary ammonium compounds, or a composition thereof, of the present invention is an amount necessary to treat, prevent, or eliminate the above-described infections as described herein.

[0166] In another aspect, provided is a method for treating biofilm or microbial contamination on an abiotic (i.e., inanimate) surface, the method comprising using an effective amount of one or more quaternary ammonium compounds, or a mixture thereof, as described herein.

[0167] In some embodiments, an abiotic (i.e., inanimate) surface is directly treated with a solution containing one or more quaternary ammonium compounds, or a mixture thereof, as described herein for the removal of bacterial biofilm or bacterial contamination and / or prevention of its recurrence.

[0168] In some embodiments, the bacterial biofilm or bacterial contamination is caused by Staphylococcus aureus.

[0169] In some embodiments, the bacterial biofilm or bacterial contamination is caused by methicillin-resistant Staphylococcus aureus (MRSA).

[0170] In some embodiments, the bacterial biofilm or bacterial contamination is caused by Pseudomonas aeruginosa.

[0171] In some embodiments, an abiotic (i.e., inanimate) surface is directly treated with a solution containing one or more of the quaternary ammonium compounds described herein, or a mixture thereof, for the removal of fungal biofilm or fungal contamination and / or prevention of its recurrence.

[0172] In some embodiments, fungal biofilm or fungal contamination includes Candida spp. infections, and Candida spp. are, for example, C. albicans, C. auris, or C. glabrata, or mixtures thereof, but are not limited thereto.

[0173] In some embodiments, an abiotic (i.e., inanimate) surface is directly treated with a solution containing one or more of the quaternary ammonium compounds described herein, or a mixture thereof, for the removal of viral biofilm or viral contamination and / or prevention of its recurrence.

[0174] In some embodiments, viral biofilm or viral contamination is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (COVID-19).

[0175] In some embodiments, an abiotic (i.e., inanimate) surface is directly treated with a solution containing one or more of the quaternary ammonium compounds described herein, or a mixture thereof, for the removal of multiple microbial biofilms or multiple microbial contaminations and / or prevention of their recurrence.

[0176] In some embodiments, multiple microbial biofilms or multiple microbial contaminations include bacterial species, fungal species, and viral species.

[0177] In some embodiments, one or more of the quaternary ammonium compounds described herein, or a mixture thereof, can be formulated in an effective amount as an antibacterial hand sanitizer, or a surface disinfection spray, foam, liquid, gel, or solid.

[0178] In some embodiments, a method is provided for providing improved antibacterial activity on the skin surface, the method comprising administering an effective amount of a quaternary ammonium compound or a composition thereof as described herein.

[0179] In some embodiments, the antibacterial activity is against bacteria.

[0180] In some embodiments, the antibacterial activity is against fungi.

[0181] In some embodiments, the antibacterial activity is against viruses.

[0182] In some embodiments, the antibacterial activity is against multiple microorganisms, including combinations of bacterial, fungal, and / or viral microorganisms.

[0183] In some embodiments, the antibacterial hand sanitizer is optionally combined with a thickening agent.

[0184] In some embodiments, the antibacterial hand sanitizer is optionally combined with alcohol.

[0185] In other embodiments, the quaternary ammonium compound is provided in a carrier that does not contain any alcohol.

[0186] In some embodiments, the antibacterial hand sanitizer is optionally combined with a skin conditioner.

[0187] In some embodiments, the antibacterial hand sanitizer is optionally combined with a fragrance.

[0188] In some embodiments, a quaternary ammonium compound is provided in which at least one hydrogen is replaced by deuterium.

[0189] Accordingly, the present invention includes at least the following features: (a) A quaternary ammonium compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL; (b) A quaternary ammonium compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL used for the treatment of bacterial, fungal, and / or viral infections; (c) Use of one or more quaternary ammonium compounds of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL in the manufacture of a medicament for the treatment of bacterial, fungal, and / or viral infections; (d) A method for manufacturing a medicament for the purpose of therapeutic use in treating bacterial, fungal, and / or viral infections, comprising a quaternary ammonium compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, A method for use in production, characterized by using an effective amount of one or more quaternary ammonium compounds of XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL. (e) A method for treating a bacterial, fungal, and / or viral infection, comprising administering to a host in need of treatment for a bacterial, fungal, and / or viral infection an effective amount of one or more quaternary ammonium compounds of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL. (f) A method for treating a bacterial, fungal, and / or viral infection, comprising administering to a host in need of treatment for a bacterial, fungal, and / or viral infection an effective amount of one or more quaternary ammonium compounds of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL. (g) An antibacterial composition comprising an effective amount of one or more quaternary ammonium compounds of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL and a pharmaceutically acceptable excipient. (h) A powder or solid preparation, including a lyophilized powder preparation, containing one or more quaternary ammonium compounds of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL (i) A kit comprising a powder or solid preparation containing a lyophilized powder of one or more quaternary ammonium compounds of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL, a sterile aqueous solution, and a dosing device (j) A kit comprising a sterile aqueous solution containing one or more quaternary ammonium compounds of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL, and a dosing device (k) A process for synthesizing a quaternary ammonium compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL (l) A quaternary ammonium compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL as a mixture of enantiomers or diastereomers (where relevant) containing a racemate, (m) An enantiomerically enriched form of a quaternary ammonium compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL containing an isolated enantiomer or diastereomer (i.e., with a purity greater than 85%, 90%, 95%, 97%, or 99%), (n) A process for preparing a therapeutic product containing, in an effective amount, one or more quaternary ammonium compounds of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL, A product formed by reacting a quaternary ammonium compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL with one or more compounds selected from glycerol, glycerol-propylene oxide copolymer, sor ketal, glycidol, or epichlorohydrin. A product formed by reacting a quaternary ammonium compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL with one or more compounds selected from glycerol-propylene oxide copolymer, sor ketal, glycidol, or epichlorohydrin, which is used for the treatment of bacterial, fungal, and / or viral infections. Use of a product formed by reacting a quaternary ammonium compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL with one or more compounds selected from glycerol, glycerol-propylene oxide copolymer, sor ketal, glycidol, or epichlorohydrin in the manufacture of a medicament for the treatment of bacterial, fungal, and / or viral infections. A method for manufacturing a medicament for therapeutic use in treating (r) bacterial, fungal, and / or viral infections, comprising using, in an effective amount, a product formed by reacting a compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL with one or more compounds selected from glycerol, glycerol-propylene oxide copolymer, solketal, glycidol, or epichlorohydrin, A method for treating (s) bacterial, fungal, and / or viral infections, comprising administering, in an effective amount, a product formed by reacting a quaternary ammonium compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL with one or more compounds selected from glycerol, glycerol-propylene oxide copolymer, solketal, glycidol, or epichlorohydrin to a patient in need of treatment for bacterial, fungal, and / or viral infections, (t)A method for treating a bacterial, fungal, and / or viral infection, comprising administering to a patient in need of treatment for a bacterial, fungal, and / or viral infection an effective amount of a product formed by reacting a quaternary ammonium compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL with one or more compounds selected from glycerol, glycerol-propylene oxide copolymer, solketal, glycidol, or epichlorohydrin. (u)An antibacterial composition comprising an effective amount of a product formed by reacting a quaternary ammonium compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL with one or more compounds selected from glycerol, glycerol-propylene oxide copolymer, solketal, glycidol, or epichlorohydrin, and a pharmaceutically acceptable excipient. A powder formulation or solid formulation comprising a lyophilized powder containing a product formed by reacting a quaternary ammonium compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL with one or more compounds selected from glycerol, glycidol, glycerol-propylene oxide copolymer, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, sor ketal, glycidol, or epichlorohydrin (w) A powder or solid formulation containing a lyophilized powder of a product formed by reacting a quaternary ammonium compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL with one or more compounds selected from glycerol, glycerol-propylene oxide copolymer, sor ketal, glycidol, or epichlorohydrin, a sterile aqueous solution, and a dispensing device A kit comprising A kit comprising a sterile aqueous or glycerin solution containing a product formed by reacting a quaternary ammonium compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL with one or more compounds of glycerol, glycerol-propylene oxide copolymer, sor ketal, glycidol, or epichlorohydrin, and a dispensing device. A process for preparing a therapeutic product formed by reacting a quaternary ammonium compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL with one or more compounds of glycerol, glycidol, glycerol-propylene oxide copolymer, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, sor ketal, glycidol, or epichlorohydrin. (z) A dressing, adhesive plaster, surgical packing material, film, packaging material, conformable foam body, or other type of material incorporating a compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL. (aa) Not limited thereto, for example, for treating skin infections, wounds, or ulcers such as lower limb ulcers, or diabetic ulcers such as diabetic lower limb ulcers or diabetic foot ulcers, dressings, band - aids, surgical packing materials, films, packaging materials, conformable foams incorporating compounds of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL , or the use of other types of materials, (bb) Oligomer or polymer products of formula I’, II’, III’, IV’, V’, VI’, VII’, VIII’, IX’, X’, XI’, XII’, XIII’, XIV’, XV’, XVI’, XVII’, XVIII’, XIX’, XX’, XXI’, XXII’, XXIII’, XXIV’, XXV’, XXVI’, XXVII’, XXVIII’, XXIX’, XXX’, XXXI’, XXXII’, XXXIII’, XXXIV’, XXXV’, XXXVI’, XXXVII’, XXXVIII’, XXXIX’, or XL’ (cc) Oligomer or polymer products of formula I’, II’, III’, IV’, V’, VI’, VII’, VIII’, IX’, X’, XI’, XII’, XIII’, XIV’, XV’, XVI’, XVII’, XVIII’, XIX’, XX’, XXI’, XXII’, XXIII’, XXIV’, XXV’, XXVI’, XXVII’, XXVIII’, XXIX’, XXX’, XXXI’, XXXII’, XXXIII’, XXXIV’, XXXV’, XXXVI’, XXXVII’, XXXVIII’, XXXIX’, or XL’ used in the treatment of bacterial, fungal, and / or viral infections (dd) In the manufacture of medicaments for the treatment of bacterial, fungal, and / or viral infections, formula I’, II’, III’, IV’, V’, VI’, VII’, VIII’, IX’, X’, X Use in an effective amount of an oligomer or polymer product of I’, XII’, XIII’, XIV’, XV’, XVI’, XVII’, XVIII’, XIX’, XX’, XXI’, XXII’, XXIII’, XXIV’, XXV’, XXVI’, XXVII’, XXVIII’, XXIX’, XXX’, XXXI’, XXXII’, XXXIII’, XXXIV’, XXXV’, XXXVI’, XXXVII’, XXXVIII’, XXXIX’, or XL’ (ee) A method for manufacturing a medicament for therapeutic use for treating bacterial, fungal, and / or viral infections, which comprises using an oligomer or polymer product of formula I’, II’, III’, IV’, V’, VI’, VII’, VIII’, IX’, X’, XI’, XII’, XIII’, XIV’, XV’, XVI’, XVII’, XVIII’, XIX’, XX’, XXI’, XXII’, XXIII’, XXIV’, XXV’, XXVI’, XXVII’, XXVIII’, XXIX’, XXX’, XXXI’, XXXII’, XXXIII’, XXXIV’, XXXV’, XXXVI’, XXXVII’, XXXVIII’, XXXIX’, or XL’ in the manufacture. (ff) A method for treating bacterial, fungal, and / or viral infections, which comprises administering to a host in need of treatment of a bacterial, fungal, and / or viral infection an effective amount of an oligomer or polymer product of formula I’, II’, III’, IV’, V’, VI’, VII’, VIII’, IX’, X’, XI’, XII’, XIII’, XIV’, XV’, XVI’, XVII’, XVIII’, XIX’, XX’, XXI’, XXII’, XXIII’, XXIV’, XXV’, XXVI’, XXVII’, XXVIII’, XXIX’, XXX’, XXXI’, XXXII’, XXXIII’, XXXIV’, XXXV’, XXXVI’, XXXVII’, XXXVIII’, XXXIX’, or XL’. An antibacterial composition comprising an effective amount of an oligomer or polymer product of formula I’, II’, III’, IV’, V’, VI’, VII’, VIII’, IX’, X’, XI’, XII’, XIII’, XIV’, XV’, XVI’, XVII’, XVIII’, XIX’, XX’, XXI’, XXII’, XXIII’, XXIV’, XXV’, XXVI’, XXVII’, XXVIII’, XXIX’, XXX’, XXXI’, XXXII’, XXXIII’, XXXIV’, XXXV’, XXXVI’, XXXVII’, XXXVIII’, XXXIX’, or XL’ and comprising a pharmaceutically acceptable excipient. (hh) A powder or solid preparation comprising a lyophilized powder, comprising an oligomer or polymer product of formula I’, II’, III’, IV’, V’, VI’, VII’, VIII’, IX’, X’, XI’, XII’, XIII’, XIV’, XV’, XVI’, XVII’, XVIII’, XIX’, XX’, XXI’, XXII’, XXIII’, XXIV’, XXV’, XXVI’, XXVII’, XXVIII’, XXIX’, XXX’, XXXI’, XXXII’, XXXIII’, XXXIV’, XXXV’, XXXVI’, XXXVII’, XXXVIII’, XXXIX’, or XL’ or a combination thereof. (ii) A kit comprising a powder or solid preparation comprising a lyophilized powder of an oligomer or polymer product of formula I’, II’, III’, IV’, V’, VI’, VII’, VIII’, IX’, X’, XI’, XII’, XIII’, XIV’, XV’, XVI’, XVII’, XVIII’, XIX’, XX’, XXI’, XXII’, XXIII’, XXIV’, XXV’, XXVI’, XXVII’, XXVIII’, XXIX’, XXX’, XXXI’, XXXII’, XXXIII’, XXXIV’, XXXV’, XXXVI’, XXXVII’, XXXVIII’, XXXIX’, or XL’, a sterile aqueous solution, and a dispensing device. (jj) A kit comprising a sterile aqueous or glycerin solution containing an oligomer or polymer product of formula I', II', III', IV', V', VI', VII', VIII', IX', X', XI', XII', XIII', XIV', XV', XVI', XVII', XVIII', XIX', XX', XXI', XXII', XXIII', XXIV', XXV', XXVI', XXVII', XXVIII', XXIX', XXX', XXXI', XXXII', XXXIII', XXXIV', XXXV', XXXVI', XXXVII', XXXVIII', XXXIX', or XL', and a dispensing device. (kk) A process for preparing a therapeutic product containing an oligomer or polymer product of formula I', II', III', IV', V', VI', VII', VIII', IX', X', XI', XII', XIII', XIV', XV', XVI', XVII', XVIII', XIX', XX', XXI', XXII', XXIII', XXIV', XXV', XXVI', XXVII', XXVIII', XXIX', XXX', XXXI', XXXII', XXXIII', XXXIV', XXXV', XXXVI', XXXVII', XXXVIII', XXXIX', or XL'. (ll) A dressing, plaster, surgical packing, film, packaging material, conformable foam, or other type of material incorporating a compound of formula I', II', III', IV', V', VI', VII', VIII', IX', X', XI', XII', XIII', XIV', XV', XVI', XVII', XVIII', XIX', XX', XXI', XXII', XXIII', XXIV', XXV', XXVI', XXVII', XXVIII', XXIX', XXX', XXXI', XXXII', XXXIII', XXXIV', XXXV', XXXVI', XXXVII', XXXVIII', XXXIX', or XL'. (mm)Not limited thereto, for example, for treating skin infections, wounds, or ulcers such as lower limb ulcers, or diabetic ulcers such as diabetic lower limb ulcers or diabetic foot ulcers, bandages, plasters, surgical packing materials, films, packaging materials, conformable foams incorporating a compound of formula I', II', III', IV', V', VI', VII', VIII', IX', X', XI', XII', XIII', XIV', XV', XVI', XVII', XVIII', XIX', XX', XXI', XXII', XXIII', XXIV', XXV', XXVI', XXVII', XXVIII', XXIX', XXX', XXXI', XXXII', XXXIII', XXXIV', XXXV', XXXVI', XXXVII', XXXVIII', XXXIX', or XL' , or the use of other types of materials, and (nn)medical or dental implants incorporating a compound of formula I', II', III', IV', V', VI', VII', VIII', IX', X', XI', XII', XIII', XIV', XV', XVI', XVII', XVIII', XIX', XX', XXI', XXII', XXIII', XXIV', XXV', XXVI', XXVII', XXVIII', XXIX', XXX', XXXI', XXXII', XXXIII', XXXIV', XXXV', XXXVI', XXXVII', XXXVIII', XXXIX', or XL' (oo)A method for treating biofilms or microbial contamination by administering an effective amount of one or more quaternary ammonium compounds of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL to an abiotic (i.e., inanimate) surface, and (pp)Although not limited thereto, the antibacterial quaternary compound of the present invention is used as a disinfectant for inanimate surfaces including home surfaces, workplaces, industrial areas, transportation areas or carriers, kitchens, bathrooms, furniture, etc., and is optionally placed in a suitable carrier according to appropriate uses.

Brief Description of the Drawings

[0190]

Figure 1

Figure 2

Modes for Carrying Out the Invention

[0191] In one embodiment, a novel organosilane quaternary ammonium compound is provided that can be administered in an effective amount in a topical formulation to a host in need of treatment to treat a wide range of infectious diseases including fungal infections, as well as Gram-positive bacterial infections, Gram-negative bacterial infections, and viral infections. Fungi can appear as yeasts, molds, or a combination of both forms. The novel quaternary ammonium compounds and formulations described herein can treat microorganisms in biofilms including mixed organisms.

[0192] Thus, in one aspect, the organosilane quaternary ammonium compounds described herein can be used in an effective amount in topical formulations for direct administration against infectious diseases or incorporated into articles for application to wounds, such as chronic wounds or burns, for example, dressings, bandages, surgical packings, gauzes, wrappings, conformable foams, or films. When incorporated into an article, the organosilane quaternary ammonium compounds described herein can be incorporated such that the article provides controlled release of the compound or its pharmaceutically acceptable salt or composition into the surrounding area to provide long-term inhibition of microbial growth. In some embodiments, an effective amount of a selected compound described herein is used for the treatment of chronic wounds, such as pressure ulcers, venous ulcers, arterial wounds, neuropathic ulcers, diabetic ulcers, such as lower extremity ulcers or foot ulcers, skin lacerations, or moisture-associated skin damage (MASD), such as incontinence-associated dermatitis. In some embodiments, the compounds described herein are used for the treatment of wounds caused by burns.

[0193] Importantly, in some embodiments, the novel organosilane quaternary ammonium compounds described herein can be provided as stable powders or lyophilized materials, which can be formulated using pharmaceutically acceptable topical carriers prior to administration. In alternative embodiments, the novel organosilane quaternary ammonium compounds described herein can reduce the risk of infection by being incorporated into dressings, conformable foams, or polymers used in dressings, bandages, or films for medical use, such as wound dressings or surgical packings. In yet another alternative embodiment, the novel organosilane quaternary ammonium compounds described herein can be incorporated into medical implants, such as, but not limited to, orthopedic implants or dental implants.

[0194] In some embodiments, topical infections in humans or animals can be treated with selected organosilane quaternary ammonium compounds, which can be used to treat microorganisms or biofilms containing combinations or combinations of microorganisms, such as Acinetobacter (gram negative), Pseudomonas (gram negative), Proteus (gram negative proteobacteria), Staphylococcus (gram positive), Streptococcus (gram positive), MRSA (methicillin resistant S. aureus), Escherichia coli (gram negative), Propionibacterium (gram positive), Chlamydia trachomatis (gram positive), Chlamydia trachomatis (gram negative ... negative), Chlamydia trachomatis (gram positive), Chlamydia trachomatis ( Klebsiella (gram-negative), Enterococcus (gram-positive), Haemophilus influenzae, etc., Fungi, such as Fusarium, Aspergillus, Cladophora and dermatophytes such as Trichophyton, Microsporum, and the like. These include the genera Microsporum and Epidermophyton.

[0195] The selected compounds of the present invention can be used, in an effective amount and optionally incorporated into a liquid, gel, or solid carrier, to disinfect microbial growth or biofilm formation occurring on abiotic (i.e., inanimate) surfaces, such as industrial areas including residences, workplaces, manufacturing plants, public places, bathrooms, kitchens, furniture, transportation depots or surfaces, or other surfaces in contact with humans or animals or in the environment of humans or animals. In one embodiment, environmental surfaces commonly found in the food and medical fields also appear to enhance biofilm formation and their resistance to disinfectants.

[0196] Definitions Compounds are described using their official names. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0197] For any of the formulas described herein, the quaternary ammonium compounds include isomers such as racemates, enantiomers, enantiomer mixtures, diastereomers, diastereomer mixtures, tautomers, rotational isomers, etc., as if each were specifically described.

[0198] The terms "a" and "an" do not denote a limitation of quantity, but rather the presence of at least one of the items being referred to. The term "or" means "and / or". The recitation of a range of values is intended, unless otherwise specified herein, merely as a convenient method of referring individually to each separate value falling within the range, and each separate value is incorporated herein by reference as if it were individually recited herein. All endpoints of all ranges are included within the range and can be combined independently. All methods described herein can be performed in a suitable order, unless otherwise specified herein or clearly precluded by the context. The use of examples or illustrative language (e.g., "such as") is merely intended to better illustrate the invention This is not intended to limit the scope of the present invention unless otherwise claimed. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0199] The present invention includes a quaternary ammonium compound of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL, in which at least one atom is replaced with a desired isotope and the compound has the isotope in an amount exceeding its natural abundance, i.e., is enriched. An isotope is an atom having the same atomic number but a different mass number, i.e., having the same number of protons but a different number of neutrons.

[0200] Examples of isotopes incorporable into the quaternary ammonium compounds of the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, fluorine, chlorine, and iodine, for example, 2 H, 3 H, 11 C, 13 C, 14 C, 15 N, 17 O, 18 O, 18 F, 36 Cl, and 125 I. In one non-limiting embodiment, the isotope-labeled quaternary ammonium compound can be used in metabolic studies ( 14 using 2 C), reaction rate studies (e.g., 3 using H or 18The F-labeled compounds may be particularly desirable for PET or SPECT studies. The isotope-labeled quaternary ammonium compounds of the invention and their prodrugs can generally be prepared by replacing the non-isotope-labeled reagents with isotope-labeled reagents readily available from the procedures disclosed in the schemes or in the examples and preparations described below.

[0201] By way of general example and not limitation, isotopes of hydrogen, such as deuterium ( 2 H) and tritium ( 3 H), may be used anywhere in the structures described where a desired result is to be achieved. Alternatively or in addition, isotopes of carbon, such as 13 C and 14 C, may be used.

[0202] Isotope substitution, such as deuterium substitution, can be partial or complete. Partial deuterium substitution means that at least one hydrogen is replaced by deuterium. In certain embodiments, the isotope is enriched to at least about 90%, 95%, or 99%, or more, with respect to the isotope, anywhere in the area of interest. In one non-limiting embodiment, deuterium is enriched to at least about 90%, 95%, or 99% at the desired location.

[0203] In one non-limiting embodiment, substitution of one or more hydrogen atoms with deuterium atoms can be provided in any of Formulas I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL. In one non-limiting embodiment, the substitution of hydrogen atoms with deuterium atoms is R 1 、R 2 、R 3 、R 4, R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , X 1 , X 2 , X 3 , X 4 is selected from any of the groups, or occurs within any other variable defined herein. For example, any of these groups is methyl, ethyl, or methoxy, or for example, when having methyl, ethyl, or methoxy through substitution, this alkyl residue is deuteratable (in non-limiting embodiments, CDH2, CD2H, CD3, CH2CD3, CD2CD3, CHDCH2D, CH2CD3, CHDCHD2, OCDH2, OCD2H, or OCD3, etc.). In certain other embodiments, when two substituents combine to form a ring, the unsubstituted carbon is deuteratable.

[0204] The quaternary ammonium compounds of the present invention can be provided in any suitable form, for example, in liquid, gel, aerosol, or solid form, or in a form adsorbed on a carrier.

[0205] The quaternary ammonium compounds of the present invention may or may not form a solvate with a solvent (including water). Thus, in one non-limiting embodiment, the present invention includes solvated compounds. The term "solvate" refers to a molecular complex of a compound of the present invention (including its salts) with one or more solvent molecules. By way of example and not limitation, solvents include water, ethanol, physiological saline, dimethyl sulfoxide (DMSO), glycols (including propylene glycol), acetone, and other common organic solvents. The term "hydrate" refers to a molecular complex containing a quaternary ammonium compound of the present invention and water. Pharmaceutically acceptable solvates according to the present invention include those in which the solvent may be isotopically substituted, such as D2O, d6-acetone, d6-DMSO, etc. Solvates can be either liquid or solid.

[0206] A dash symbol ("-") not between two letters or symbols is used to indicate the point of attachment of a substituent. For example, -(C=O)NH2 is attached through the carbon of the keto (C=O) group.

[0207] The term "Group I" as used herein refers to Group I alkali metals and specifically includes lithium (Li), sodium (Na), potassium (K), rubidium (Rb), cesium (Cs), and francium (Fr). "Group II" as used herein refers to Group II alkaline earth metals and specifically includes beryllium (Be), magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba), and radium (Ra). "Group III" as used herein refers to aluminum. "Transition metals" as used herein refers to any element included in the d-block, f-block lanthanides, and actinides of the periodic table. Also included are post-transition metals, specifically gallium, indium, tin, thallium, and lead.

[0208] "Aryl" refers to an aromatic group having only carbon in one or more aromatic rings. In some embodiments, the aryl group has one to three separate or fused rings and has from 6 to about 14 or 18 ring atoms and has no hetero atoms as ring members. When shown, the aryl group may be further substituted with carbon or non-carbon atoms or groups. Such substitution may include fusion with a 3- to 7-membered saturated cyclic group, which optionally has one or two hetero atoms independently selected from N, O, and S, and the fusion forms, for example, a 3,4-methylenedioxyphenyl group. Examples of aryl groups include, for example, phenyl and naphthyl, and naphthyl includes 1-naphthyl and 2-naphthyl. In some embodiments, the aryl group is a pendant group. An example of a pendant ring is a phenyl group substituted with a phenyl group. In some embodiments, the aryl group is optionally substituted as described above.

[0209] "Alkyl" is a branched or straight-chain saturated aliphatic hydrocarbon group. In a non-limiting embodiment, the alkyl group contains from 1 to about 12 carbon atoms, more typically from 1 to about 6 carbon atoms, or from 1 to about 4 carbon atoms. In a non-limiting embodiment, alkyl contains from 1 to about 8 carbon atoms. In certain embodiments, alkyl is C1-C2, C1-C3, C1-C4, C1-C5, or C1-C6. The specified ranges used herein indicate alkyl groups having each member of the range described as a separate species. For example, the term C1-C6 alkyl as used herein refers to straight-chain or branched-chain alkyl groups having 1, 2, 3, 4, 5, or 6 carbon atoms, each of which is intended to be described as a separate species. For example, the term C1-C4 alkyl as used herein refers to straight-chain or branched-chain alkyl groups having 1, 2, 3, or 4 carbon atoms, each of which is intended to be described as a separate species. Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, tert-pentyl, neopentyl, n-hexyl, 2-methylpentane, 3-methylpentane, 2,2-dimethylbutane, and 2,3-dimethylbutane. In alternative embodiments, the alkyl group is optionally substituted. The term "alkyl" also encompasses cycloalkyl or carbocyclic groups. For example, when terms containing "alk" are used, "cycloalkyl" or "carbocyclic(al)" may be part of its definition, unless clearly excluded by the context. For example, without limitation, terms such as alkyl, haloalkyl, etc. may be considered to include the cyclic forms of alkyl, unless clearly excluded by the context. Cycloalkyl" or "carbocyclic" may be part of its definition. For example, without limitation, terms such as alkyl, haloalkyl, etc. may be considered to include the cyclic forms of alkyl, unless clearly excluded by the context.

[0210] "Hydroxyalkyl" as used herein refers to any of the alkyl groups described above substituted with at least one hydroxyl substituent.

[0211] "Alkanoic acid" herein refers to any carboxylic acid in which R is alkyl, where alkyl is as defined herein. Further, the alkanoic acid can be a diacid and / or can have one or more substituents selected from halogens such as chloride, bromide, fluoride, iodide, hydroxyl, N(R 7 )2, NO2, alkyl, alkenyl, etc.

[0212] "Alkenyl" is a linear or branched aliphatic hydrocarbon group having one or more carbon-carbon double bonds that can occur at stable points along the chain. The specified ranges used herein refer to alkenyl groups having each member of the ranges described as independent species as above for the alkyl portion. Examples of alkenyl radicals include, but are not limited to, ethenyl, propenyl, allyl, propenyl, butenyl, and 4-methylbutenyl. The term "alkenyl" also includes "cis" and "trans" alkenyl configurations, or alternatively "E" and "Z" alkenyl configurations. In alternative embodiments, the alkenyl group is optionally substituted. The term "alkenyl" also encompasses cycloalkyl or carbocyclic groups having at least one point of unsaturation.

[0213] "Alkynyl" is a branched or linear aliphatic hydrocarbon group having one or more carbon-carbon triple bonds that can occur at any stable point along the chain. The specified ranges used herein refer to alkynyl groups having each member of the ranges described as independent species as above for the alkyl portion. Examples of alkynyl include, but are not limited to, ethynyl, propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, and 5-hexynyl. In alternative embodiments, the alkynyl group is optionally substituted. The term "alkynyl" also encompasses cycloalkyl or carbocyclic groups having at least one point of unsaturation.

[0214] "Halo" and "halogen" are fluorine, chlorine, bromine or iodine.

[0215] "Haloalkyl" is a branched or straight-chain alkyl group substituted with one or more halogen atoms up to the maximum allowable number of halogen atoms. Examples of haloalkyl groups include, but are not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl. "Perhaloalkyl" means an alkyl group in which all hydrogen atoms are replaced by halogen atoms. Examples include, but are not limited to, trifluoromethyl and pentafluoroethyl.

[0216] As used herein, the terms "heterocyclyl" or "heterocyclic" refer to a saturated or partially unsaturated (i.e., having one or more double and / or triple bonds in the ring without aromaticity) carbocyclic radical of 3 to about 12, more typically 3, 5, 6, 7 to 10 ring atoms, wherein at least one ring atom is a heteroatom selected from nitrogen, oxygen, phosphorus and sulfur, the remaining ring atoms are C, and one or more ring atoms are optionally substituted independently with one or more of the above substituents. The heterocycle can be a monocyclic ring having 3 to 7 ring members (2 to 6 carbon atoms and 1 to 4 heteroatoms selected from N, O, P and S), or a bicyclic ring having 6 to 10 ring members (4 to 9 carbon atoms and 1 to 6 heteroatoms selected from N, O, P and S), for example, a bicyclo[4,5], [5,5], 5,6] or [6,6] system. In some embodiments, the heteroatom is nitrogen only It is. In some embodiments, the heteroatom is only oxygen. In some embodiments, the heteroatom is only sulfur. Heterocyclic rings are described in Paquette, Leo A., "Principles of Modern Heterocyclic Chemistry" (W. A. Benjamin, New York, 1968), particularly Chapters 1, 3, 4, 6, 7, and 9, "The Chemistry of Heterocyclic Compounds, A series of Monographs" (John Wiley & Sons, New York, 1950 to present), particularly Volumes 13, 14, 16, 19, and 28, and J. Am. Chem. Soc. (1960) 82:5566. Examples of heterocyclic rings include pyrrolidinyl, dihydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidino, piperidonyl, morpholino, thiomorpholino, thioxanyl, piperazinyl, homopiperazinyl, azetidinyl, oxetanyl, thietanyl, homopiperidinyl, oxepanyl, thiepanyl, oxazepinyl, diazepinyl, thiazepinyl, 2-pyrrolinyl, 3-pyrrolinyl, indolinyl, 2H-pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl, pyrazolinyl, dithianyl, dithiolanyl, dihydropyranyl, dihydrothienyl, dihydrofuranyl, dihydroisoquinolinyl, tetrahydroisoquinolinyl, pyrazolidinylimidazolinyl, imidazolidinyl, 2-oxa-5-azabicyclo[2.2.2]octane, 3-oxa-8-azabicyclo[3.2.1]octane, 8-oxa-3-azabicyclo[3.2.1]octane, 6-oxa-3-azabicyclo[3.1.1]heptane, 2-oxa-5-azabicyclo[2.2.1]heptane, 3-azabicyco[3.1.0]hexanyl, 3-azabicyclo[4.1.0]heptanyl, azabicy Examples include, but are not limited to, cro[2.2.2]hexanyl, 3H-indolyl, quinolidinyl, N-pyridylurea, and pyrrolopyrimidine. The spiro moiety is also included within the scope of this definition. Examples of heterocyclic groups in which one or two ring carbon atoms are substituted with an oxo (=O) moiety are pyrimidinonyl and 1,1-dioxo-thiomorpholinyl. The heterocyclyl groups herein are optionally and independently substituted with one or more substituents described herein.

[0217] "Heterocycloalkyl" is a saturated ring group. It may have, for example, 1, 2, 3, or 4 heteroatoms independently selected from N, S, and O, and the remaining ring atoms are carbon. In a typical embodiment, nitrogen is the heteroatom. Monocyclic heterocycloalkyl groups typically have from 3 to about 8 ring atoms or from 4 to 6 ring atoms. Examples of heterocycloalkyl groups include morpholinyl, piperazinyl, piperidinyl, and pyrrolinyl.

[0218] The term "carrier", as applied to the compositions / combinations of the present invention, refers to a diluent, excipient, or vehicle provided together with the active compound.

[0219] "Patient" or "host" or "subject" is a human or non-human animal in need of treatment or prevention of any of the infectious diseases as described herein. In some embodiments, the host is human. "Patient" or "host" or "subject" also includes, for example, mammals, primates (e.g., humans), cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice, fish, birds, etc.

[0220] A "therapeutically effective amount" of the compositions / combinations of the present invention means an amount effective to provide a therapeutic effect, e.g., alleviation of symptoms or reduction or decrease of the disease itself, when administered to a host. In some embodiments, a therapeutically effective amount is an amount sufficient to bring about, in a host in need thereof, prevention of worsening, induction of regression, induction of cure, or inhibition, elimination, or prevention of an infectious disease.

[0221] As used herein, "salt" refers to a derivative of a disclosed compound, in which the parent compound is modified by forming its own inorganic or organic, non-toxic, acid or base addition salt. The salts of the compounds of the present invention are from parent compounds having basic or acidic moieties and can be synthesized by conventional chemical methods. Generally, such salts can be prepared by reacting a compound in free acid form with a stoichiometric amount of an appropriate base (e.g., hydroxides, carbonates, bicarbonates of Na, Ca, Mg, or K, etc.), or by reacting a compound in free base form with a stoichiometric amount of an appropriate acid. Such reactions are typically carried out in water, or in an organic solvent, or in a mixture of these two. Generally, non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile, etc., are typical if there is no problem. The salts of the compounds of the present invention further include solvates of the compounds and compound salts.

[0222] Examples of salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines, and alkali or organic salts of acidic residues such as carboxylic acids. Salts include, for example, conventional non-toxic salts of the parent compound formed from non-toxic inorganic or organic acids and quaternary ammonium salts. For example, conventional non-toxic acid salts include those derived from inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, sulfamic acid, phosphoric acid, nitric acid, etc., and organic acids such as acetic acid, propionic acid, succinic acid, glycolic acid, stearic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, pamoic acid, maleic acid, hydroxymaleic acid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid, mesylic acid, esylic acid, besylic acid, sulfanilic acid, 2-acetoxybenzoic acid, fumaric acid, toluenesulfonic acid, methanesulfonic acid, ethanedisulfonic acid, oxalic acid, isethionic acid, HOOC-(CH2) n’ -COOH (wherein n' is from 0 to 4), etc., or salts prepared using different acids that produce the same counterion. A further list of suitable salts can be found, for example, in Remington's Pharmaceutical Sciences, 17th It can be found in the 20th ed., Mack Publishing Company, Easton, Pa., p. 1418 (1985).

[0223] In typical embodiments, the positive charge in the formulas described herein forms a pair with one or more negatively charged ions, such as chloride ions.

[0224] Chemistry Embodiments of "alkyl" In some embodiments, "alkyl" is C1-C 10 alkyl, C1-C9 alkyl, C1-C8 alkyl, C1-C7 alkyl, C1-C6 alkyl, C1-C5 alkyl, C1-C4 alkyl, C1-C3 alkyl, or C1-C2 alkyl.

[0225] In some embodiments, "alkyl" has one carbon.

[0226] In some embodiments, "alkyl" has two carbons.

[0227] In some embodiments, "alkyl" has three carbons.

[0228] In some embodiments, "alkyl" has four carbons.

[0229] In some embodiments, "alkyl" has five carbons.

[0230] In some embodiments, "alkyl" has six carbons.

[0231] Non-limiting examples of "alkyl" include methyl, ethyl, propyl, butyl, pentyl, and hexyl.

[0232] Further non-limiting examples of "alkyl" include isopropyl, isobutyl, isopentyl, and isohexyl.

[0233] Further non-limiting examples of "alkyl" include sec-butyl, sec-pentyl, and sec-hexyl.

[0234] Further non-limiting examples of "alkyl" include tert-butyl, tert-pentyl, and tert-hexyl.

[0235] Further non-limiting examples of "alkyl" include neopentyl, 3-pentyl, and active pentyl.

[0236] In some embodiments, "alkyl" is "substituted alkyl".

[0237] In some embodiments, "alkenyl" is "substituted alkenyl".

[0238] In some embodiments, "alkynyl" is "substituted alkynyl".

[0239] Embodiments of "haloalkyl" In some embodiments, "haloalkyl" is C1-C 10 haloalkyl, C1-C9 haloalkyl, C1-C8 haloalkyl, C1-C7 haloalkyl, C1-C6 haloalkyl, C1-C5 haloalkyl, C1-C4 haloalkyl, C1-C3 haloalkyl, and C1-C2 haloalkyl.

[0240] In some embodiments, "haloalkyl" has one carbon.

[0241] In some embodiments, "haloalkyl" has one carbon and one halogen.

[0242] In some embodiments, "haloalkyl" has one carbon and two halogens.

[0243] In some embodiments, "haloalkyl" has one carbon and three halogens.

[0244] In some embodiments, "haloalkyl" has two carbons.

[0245] In some embodiments, "haloalkyl" has three carbons.

[0246] In some embodiments, "haloalkyl" has four carbons.

[0247] In some embodiments, "haloalkyl" has five carbons.

[0248] In some embodiments, "haloalkyl" has six carbons.

[0249] Non-limiting examples of "haloalkyl" include [Chemical formula] are as follows.

[0250] Further non-limiting examples of "haloalkyl" include [Chemical formula] are as follows.

[0251] Further non-limiting examples of "haloalkyl" include [Chemical formula] are as follows.

[0252] Further non-limiting examples of "haloalkyl" include [Chemical formula] are as follows.

[0253] Silane quaternary amine compounds have been previously described for biocidal uses, but their use has been limited to industrial, agricultural uses such as, inter alia, textile products, clothing, building materials, food packaging containers, adhesives, roofing sheets, fiberglass, plastics, agricultural products, paints, coating agents and surface treatment agents, carpets, wood, water purification systems, and laundry additives, and medical uses such as medical supplies and surgical gloves. Further, many of these silane quaternary amine compounds are typically sold in methanol and are thus potentially toxic for pharmaceutical and other medical uses (U.S. Pat. Nos. 3,560,385, 3,794,736, 5,954,869, and 8,999,357).

[0254] These quaternary ammonium compounds do not decompose to form components that are overly toxic to the host. They can be used to treat people and animals in remote locations who are not currently receiving an appropriate antibacterial health management approach.

[0255] The quaternary ammonium compounds described herein have improved stability compared to other organosilanes such as 3-(trihydroxysilyl)-N-propyl-N,N-dimethyloctadecylammonium chloride, and also have reduced levels of polymerization and subsequent formation of insoluble polysilsequioxane materials in both solid and solution form, resulting in improved shelf life. In addition, the formulations of the present invention are substantially free of alcohols such as methanol, ethanol, etc., and / or other undesirable minor volatile organic compounds. The quaternary ammonium compounds of the present invention do not produce by-products such as methanol by hydrolysis. The powders or other solid formulations of the present invention, such as lyophilized powders, are substantially free of methanol, ethanol, and / or other undesirable minor volatile organic compounds, which

[0256] is , either (i) not using such compounds in manufacturing or (ii) using vacuum drying during processing, which is a much better improvement than commercially available aqueous solutions of other organosilane antibacterial agents, such as 3-(trihydroxysilyl)-N-propyl-N,N-dimethyloctadecylammonium chloride. 3-(trihydroxysilyl)-N-propyl-N,N-dimethyloctadecylammonium chloride often contains a significant amount of methanol as a byproduct of its synthesis.

[0257] These molecules are small enough to quickly perfuse biofilms and can do so even as oligomer species, and are stable enough to cross the small channels of biofilms even in aqueous or glycerol solutions, resulting in increased penetration into biofilms with the effectiveness of removing the entire biofilm containing viable bacterial cells.

[0258] The efficacy is maintained after interaction with and killing of microorganisms because organosilane molecules are not consumed by such interactions and can continue to be lethal to active microorganisms. Moreover, the killing mechanism of these compounds reduces the likelihood of resistance developing in the targeted organisms compared to other topical infection treatments using antibiotics and antifungal agents.

[0259] Organosilane quaternary compounds forming sulfonates have also been reported before, but their uses were dedicated to industrial and agricultural uses only and did not have the medical uses as described above. The molecule is thought to be toxic for medical uses, such as for eye and ear treatments. These organosilanes have organic sulfates, which are both harmful and toxic to the eyes and ears (U.S. Patent No. 5,954,869).

[0260] Other organosilane quaternary compounds, such as 3-(trimethoxysilyl)-N-propyl-N,N-dimethyloctadecyl=ammonium=chloride and related trialkoxysilanes, have been used in the treatment of infections including wounds (see U.S. Patent Nos. 4,865,844; 4,908,355; U.S. Patent Application Publication Nos. 2011 / 0293681; 2012 / 0052106; 2013 / 0231599; 2014 / 0100504; 2016 / 0346193; 2017 / 0094974; and International Publication Nos. 2000 / 54587; 2004 / 004793). However, the compounds hydrolyze to release methanol both in the aqueous environment of biological systems and when forming aqueous compositions, and this methanol can be toxic to organisms and can be as toxic as digestion even when absorbed in tissues (see Ind. Eng. Chem. 1931, 23, 931-936). The production of toxic methanol as a byproduct significantly limits or largely precludes their use in pharmaceuticals and medical applications There is no known stable form of a silane quaternary ammonium compound that does not use additives that are considered inappropriate for medical use.

[0261] In some embodiments, the quaternary ammonium compound of the present invention is a solid compound that readily dissolves in water to form a stable aqueous solution. For example, the quaternary ammonium compound can be dissolved in saline, deionized water, or a buffer to form a visually clear aqueous solution. In some embodiments, the aqueous solution can be stored at room temperature without turbidity for at least 1, 2, 3, 4, 5, 6, 8, 12, 16 days, or longer. In another embodiment, the quaternary ammonium compound can be made more soluble by first forming a powder using a lyophilizer.

[0262] In another embodiment, the quaternary ammonium compound of the present invention forms a solution that is neutral or nearly neutral when dissolved in water. For example, the aqueous solution has a pH of about 6.4, 6.8, 7. It can have a pH of 0, 7.2, 7.4, 7.6, 7.8, or 8.0.

[0263] In some embodiments, the above solution has a concentration of the quaternary ammonium compound of the present invention of at least 0.2%, 0.4%, 0.6%, 0.8%, 1%, 1.2%, 1.4%, 1.6%, 1.8%, or 2.0%.

[0264] The zwitterion of the present invention In certain alternative embodiments, the quaternary ammonium compound of the present invention is a zwitterion. In these embodiments, X - may be absent and the quaternary amine is neutralized with an internal anion. One non-limiting example is the compound of formula I below:

Chemical formula

[0265] In other embodiments, the quaternary ammonium compound of the present invention is not a zwitterion. In this embodiment, the quaternary amine is neutralized with X - . For example, the compounds of formula I can be the following:

Chemical formula

[0266] In some embodiments, the zwitterionic quaternary ammonium compound has higher solubility in an aqueous medium than its non-zwitterionic form. In yet another embodiment, the zwitterionic compound has higher stability in an aqueous solution than its non-zwitterionic form. In some embodiments, the zwitterionic compound has higher solubility in an aqueous medium than its non-zwitterionic form. In yet another embodiment, the zwitterionic compound has higher stability in an aqueous solution than its non-zwitterionic form. In certain embodiments, sodium chloride (NaCl) salt can be replaced with another salt described herein.

[0267] In an alternative embodiment, the quaternary ammonium compound of formula I is a zwitterion and X - ions are absent. For example, in some embodiments, formula I is

Chem.

Chem.

[0268] In an alternative embodiment, the quaternary ammonium compound of formula III is a zwitterion and X - ions are absent. For example, in some embodiments, formula III is

Chem.

Chem.

[0269] In an alternative embodiment, the quaternary ammonium compound of formula IV is a zwitterion and X - ions are absent. For example, in some embodiments, formula IV is

Chem.

Chem.

[0270] Representative compounds of the present invention In some embodiments, the quaternary ammonium compound of the present invention is

Chem.

[0271] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] as follows.

[0272] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] as follows.

[0273] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] as follows.

[0274] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] as follows.

[0275] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] as follows.

[0276] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] as follows.

[0277] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] as follows.

[0278] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] .

[0279] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] .

[0280] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] .

[0281] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] .

[0282] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] .

[0283] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] .

[0284] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] .

[0285] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] .

[0286] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] .

[0287] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] .

[0288] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] .

[0289] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] .

[0290] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] .

[0291] In some embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] .

[0292] Representative compounds of the present invention In certain embodiments, the quaternary ammonium compound of the present invention is

Chemical formula

[0293] In certain embodiments, the compound of the present invention is

Chemical formula

[0294] In certain embodiments, the compound of the present invention is

Chemical formula

[0295] In certain embodiments, the compound of the present invention is

Chemical formula

[0296] In certain embodiments, the compound of the present invention is

Chemical formula

[0297] In certain embodiments, the compounds of the invention

Chemical formula

[0298] In certain embodiments, the compounds of the invention

Chemical formula

[0299] In certain embodiments, the compounds of the invention

Chemical formula

[0300] In certain embodiments, the compounds of the invention

Chemical formula

[0301] In certain embodiments, the compounds of the invention are

Chemical formula

[0302] In certain embodiments, the compounds of the invention are

Chemical formula

[0303] In certain embodiments, the compounds of the invention are

Chemical formula

[0304] In certain embodiments, the compounds of the invention are

Chemical formula

[0305] In certain embodiments, the compounds of the invention are

Chemical formula

[0306] In certain embodiments, the compounds of the invention are

Chemical formula

[0307] In certain embodiments, the compounds of the invention are

Chemical formula

[0308] In certain embodiments, the compounds of the invention are

Chemical formula

[0309] In certain embodiments, the compounds of the invention are

Chemical formula

[0310] In certain embodiments, the compounds of the invention are

Chemical formula

[0311] In certain embodiments, the compounds of the invention are

Chemical formula

[0312] In certain embodiments, the compounds of the invention are

Chemical formula

[0313] In certain embodiments, the compounds of the invention are

Chemical formula

[0314] In certain embodiments, the compounds of the present invention

Chemical formula

[0315] In certain embodiments, the compounds of the present invention

Chemical formula

[0316] In certain embodiments, the compounds of the present invention

Chemical formula

[0317] In certain embodiments, the compounds of the present invention

Chemical formula

[0318] In certain embodiments, the compounds of the present invention

Chemical formula

[0319] In certain embodiments, the compounds of the present invention are

Chemical formula

[0320] In certain embodiments, the compounds of the present invention are

Chemical formula

[0321] In certain embodiments, the compounds of the present invention are

Chemical formula

[0322] In certain embodiments, the compounds of the present invention are

Chemical formula

[0323] In certain embodiments, the compounds of the present invention are

Chemical formula

[0324] In certain embodiments, the compounds of the present invention are

Chemical formula

[0325] In certain embodiments, the compounds of the present invention are

Chemical formula

[0326] In certain embodiments, the compounds of the present invention are

Chemical formula

[0327] In certain embodiments, the compounds of the present invention are

Chemical formula

[0328] In certain embodiments, the compounds of the present invention are

Chemical formula

[0329] In certain embodiments, the compounds of the present invention are

Chemical formula

[0330] In some embodiments, the present invention provides a quaternary ammonium compound having the following formula:

Chemical formula

[0331] In certain embodiments of Formula I, R 2 , R 3 , and R 4 are independently

Chemical formula

[0332] In certain embodiments, R 8 and R 9 are independently selected from hydrogen, hydroxyl, C1-C8 alkyl, and C1-C8 hydroxyalkyl.

[0333] In certain embodiments, X 1 is NH.

[0334] In certain embodiments, X 1 is NR 17 , wherein R 17 is C1-C8 hydroxyalkyl.

[0335] In certain embodiments, X 1 is CH2.

[0336] In certain embodiments, X 2 is C1-C3 alkyl.

[0337] In certain embodiments, X 2 is C1-C3 hydroxyalkyl.

[0338] In certain embodiments of formula I,

Chemical formula

Chemical formula

[0339] In certain embodiments of formula I,

Chemical formula

Chemical formula

[0340] In certain embodiments of formula I,

Chemical formula

Chemical formula

[0341] In certain embodiments of Formula I,

Chemical formula

Chemical formula

[0342] In certain embodiments of Formula I,

Chemical formula

Chemical formula

[0343] In certain embodiments of Formula I,

Chemical formula

Chemical formula

[0344] In certain embodiments of Formula I, [Chemical Formula] is independently [Chemical Formula] selected from, wherein B + is optionally H + and can be replaced by, or B + is absent and this moiety is anionic.

[0345] In certain embodiments of Formula I, [Chemical Formula] is independently [Chemical Formula] selected from, wherein B + is optionally H + and can be replaced by, or B + is absent and this moiety is anionic.

[0346] In certain embodiments of Formula I, [Chemical Formula] is independently [Chemical Formula] selected from, wherein B + is optionally H + and can be replaced by, or B + is absent and this moiety is anionic.

[0347] In certain embodiments of Formula I, [Chemical Formula] is independently [Chemical formula] selected from, wherein B + is optionally H + and can be replaced by, or B + does not exist and this part is anionic.

[0348] In certain embodiments of Formula I, [Chemical formula] are independently [Chemical formula] selected from TIFF2025108581000197.tif217170, wherein B + is optionally H + and can be replaced by, or B + does not exist and this part is anionic.

[0349] In certain embodiments of Formula I, [Chemical formula] are independently [Chemical formula] selected from TIFF2025108581000200.tif208170 TIFF2025108581000201.tif57170, wherein B + is optionally H + and can be replaced by, or B + does not exist and this part is anionic.

[0350] In certain embodiments of Formula I, [Chemical formula] are independently [Chemistry] Selected from TIFF2025108581000204.tif227170 and TIFF2025108581000205.tif125170, where B + is optionally H + and can be replaced by, or B + is absent and this part is anionic.

[0351] In certain embodiments of Formula I, R 2 , R 3 , and R 4 are independently [Chemistry] (wherein R 10 , R 11 , R 12 , R 13 , and X 3 are as defined herein).

[0352] In certain embodiments, R 10 and R 11 are independently selected from hydrogen and C1-C8 alkyl.

[0353] In certain embodiments, R 12 and R 13 are independently selected from hydrogen, hydroxyl, C1-C8 alkyl, COOH, and C1-C8 hydroxyalkyl.

[0354] In certain embodiments, X 3 is independently selected from hydroxyl, C1-C8 alkyl, and C1-C8 hydroxyalkyl.

[0355] In certain embodiments of Formula I, [Chemistry] is [Chemical formula] It is selected from TIFF2025108581000209.tif226170.

[0356] In a certain specific embodiment of Formula I, [Chemical formula] is [Chemical formula] It is selected from TIFF2025108581000212.tif241170.

[0357] In a certain specific embodiment of Formula I, [Chemical formula] is [Chemical formula] It is selected from TIFF2025108581000215.tif210170 and TIFF2025108581000216.tif202170.

[0358] In a certain specific embodiment of Formula I, [Chemical formula] is [Chemical formula] selected from

[0359] In a certain specific embodiment of Formula I, R 2 , R 3 , and R 4 are independently [Chemical formula] (wherein R 8 , R 9 , X1 and X 4 is selected from (as defined herein).

[0360] In certain embodiments,

Chemical Structure

Chemical Structure

[0361] In certain embodiments,

Chemical Structure

Chemical Structure

[0362] In certain embodiments,

Chemical Structure

Chemical Structure

[0363] In certain embodiments,

Chemical Structure

Chemical Structure

[0364] In certain embodiments, [Chemistry] is selected from [Chemistry] In a certain specific embodiment,

[0365] In a certain specific embodiment, [Chemistry] is selected from [Chemistry] In a certain specific embodiment,

[0366] In a certain specific embodiment, [Chemistry] is selected from [Chemistry] In a certain specific embodiment,

[0367] In a certain specific embodiment, [Chemistry] is selected from [Chemistry] In a certain specific embodiment,

[0368] In a certain specific embodiment, [Chemistry] is selected from [Chemistry] In a certain specific embodiment,

[0369] In a certain specific embodiment, [Chemical formula] is selected from [Chemical formula] .

[0370] In a particular embodiment, [Chemical formula] is selected from [Chemical formula] .

[0371] In a particular embodiment, [Chemical formula] is selected from [Chemical formula] .

[0372] In a particular embodiment, [Chemical formula] is selected from [Chemical formula] .

[0373] In a particular embodiment, [Chemical formula] is selected from [Chemical formula] .

[0374] In a particular embodiment, R 8 and R9 is independently selected from hydrogen, hydroxyl, C1-C8 alkyl, and C1-C8 hydroxyalkyl.

[0375] In certain embodiments, X 1 is NH.

[0376] In certain embodiments, X 1 is NR 17 wherein R 17 is independently selected from hydrogen, C1-C8 hydroxyalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C1-C8 alkanoyl, heterocyclyl, heteroaryl, heterocycloalkyl, and aryl.

[0377] In certain embodiments, X 1 is CH2.

[0378] In certain embodiments, X 4 is NH2.

[0379] In certain embodiments, X 4 is N(R 7 )2 wherein R 7 is independently selected from hydrogen, C1-C8 alkyl, C1-C8 hydroxyalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C1-C8 alkanoyl, he terocyclyl, heteroaryl, heterocycloalkyl, and aryl.

[0380] In certain embodiments, X 4 is C1-C 12 alkanoic acid.

[0381] In certain embodiments of Formula I,

Chemical Formula

[0382] In certain embodiments of Formula I, [Chemical formula] is [Chemical formula] selected from TIFF2025108581000254.tif34170.

[0383] In certain embodiments of Formula I, [Chemical formula] is [Chemical formula] selected from the following.

[0384] In certain embodiments of Formula I, [Chemical formula] is [Chemical formula] selected from the following.

[0385] In certain embodiments, the quaternary ammonium compound of Formula I is [Chemical formula] Selected from TIFF2025108581000260.tif 163170, TIFF2025108581000261.tif 156170, TIFF2025108581000262.tif 226170, TIFF2025108581000263.tif 227170, TIFF2025108581000264.tif 233170, TIFF2025108581000265.tif 225170, TIFF2025108581000266.tif 152170, wherein B + is optionally H + and can be replaced by, or B + is absent and this moiety is anionic.

[0386] In certain embodiments, the quaternary ammonium compound of Formula I is

Chemical formula

[0387] In another aspect of the invention, the quaternary ammonium compound of Formula I is

Chemical formula

[0388] In another aspect of the invention, the quaternary ammonium compound of Formula I is

Chemical formula

[0389] In another aspect of the present invention, the quaternary ammonium compound of formula I is

Chemical formula

[0390] In another aspect of the present invention, the quaternary ammonium compound of formula I is

Chemical formula

[0391] In another aspect of the present invention, the quaternary ammonium compound of formula I is

Chemical formula

[0392] In another aspect of the present invention, the quaternary ammonium compound of formula I is

Chemical formula

[0393] In another aspect of the present invention, the quaternary ammonium compound of formula I is [Chemical formula] selected from

[0394] In another aspect of the present invention, the quaternary ammonium compound of formula I is [Chemical formula] selected from

[0395] In another aspect of the present invention, the quaternary ammonium compound of formula I is [Chemical formula] selected from

[0396] In another aspect of the present invention, the quaternary ammonium compound of formula I is [Chemical formula] selected from

[0397] In another aspect of the present invention, the quaternary ammonium compound of formula I is [Chemical formula] selected from

[0398] In another aspect of the present invention, the quaternary ammonium compound of formula I is [Chemical formula] selected from

[0399] In another aspect of the present invention, the quaternary ammonium compound of formula I is [Chemical formula] selected from

[0400] In another aspect of the present invention, the quaternary ammonium compound of formula I is [Chem.] selected from

[0401] In another aspect of the present invention, the quaternary ammonium compound of formula I is [Chem.] selected from

[0402] In another aspect of the present invention, the quaternary ammonium compound of formula I is [Chem.] selected from

[0403] In another aspect of the present invention, the quaternary ammonium compound of formula I is [Chem.] selected from

[0404] In some embodiments, the present invention provides a quaternary ammonium compound having the following formula: [Chem.] (wherein a, R 1 , R 14 , R 15 , R 16 , and X - are as defined herein), or a salt thereof or a pharmaceutically acceptable composition thereof.

[0405] In certain embodiments of formula II, R 14 and R 15 are each independently [Chem.] , R 2 , and R 17 selected from

[0406] In certain embodiments of Formula II, R 14 and R 15 are each independently

Chemical formula

[0407] In certain embodiments of Formula II, R 14 and R 15 are each independently selected from R 2 .

[0408] In certain embodiments of Formula II, R 14 and R 15 are each independently selected from R 17 .

[0409] In certain embodiments, the quaternary ammonium compound of Formula II is

Chemical formula

[0410] In another aspect of the present invention, the quaternary ammonium compound of Formula II is

Chemical formula

[0411] In another aspect, the present invention provides the following formula:

Chemical formula

[0412] In certain embodiments of Formula III, R 5 is independently

Chemical formula

[0413] In certain embodiments of Formula III, R 5 is independently

Chemical formula

[0414] In certain embodiments of Formula III, R 5 is independently

Chemical formula

[0415] In certain embodiments of Formula III, R 5 is independently selected from R 17 , and R 17 is independently selected from hydrogen, C1-C8 hydroxyalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C1-C8 alkanoyl, heterocyclyl, heteroaryl, heterocycloalkyl, and aryl.

[0416] In certain embodiments of Formula III or Formula IV, R 6 is independently selected from alkyl, aryl, cycloalkyl, and heterocyclyl, and each of said alkyl, aryl, cycloalkyl, and heterocyclyl is optionally substituted with a substituent selected from C1-C6 alkyl, hydroxyl, halogen, NH2, NHR 7 , N(R 7 )2, C(O)OH, C(O)R 7 , C(O)H, CH2OR 7 , C(O)OR 7 , CONH2, CONHR 7 , CON(R 7 )2, and NO2.

[0417] In certain embodiments of Formula III, R 5 is independently selected from

Chemical formula

[0418] In certain embodiments of Formula III,

Chemical formula

Chemical formula

[0419] In certain embodiments of Formula III,

Chemical formula

Chemical formula

[0420] In certain embodiments of Formula III, R 5 is, independently of each other, selected from C1-C 12 alkanoic acids or is a salt thereof, and R 5 forms a bond with this alkanoic acid at any carbon atom available for the formation of a C-O bond on the hydrocarbon chain.

[0421] For example, R 5 is

Chemical formula

[0422] In certain embodiments of Formula III, R 5 is C1-C 12 alkanoic acid, which is optionally a diacid, wherein R 5 forms a bond with this alkanoic acid at any carbon atom available for the formation of a C-O bond on the hydrocarbon chain.

[0423] For example, when the alkanoic acid is a diacid, R 5 is

Chemical formula

[0424] In certain embodiments of Formula III, R 5 is C1-C 12It is an alkanoic acid, and this acid optionally has one or more substituents on the hydrocarbon chain. The substituents are, inter alia, hydrogen, halogen, hydroxyl, N(R 7 )2 selected from.

[0425] For example, when the alkanoic acid has one or more substituents, R 5 is

Chemical formula

[0426] In a certain specific embodiment of formula III, R 5 is

Chemical formula

[0427] In a certain specific embodiment of formula III, R 5 is

Chemical formula

[0428] In a certain specific embodiment of formula III, R 5 is

Chemical formula

[0429] In certain specific embodiments, y is 0. In certain specific embodiments, y is 1. In certain specific embodiments, y is 2. In certain specific embodiments, y is 3. In certain specific embodiments, y is 4.

[0430] In certain embodiments, p is 0. In certain embodiments, p is 1. In certain embodiments, p is 2. In certain embodiments, p is 3. In certain embodiments, p is 4.

[0431] In certain embodiments, q is 0. In certain embodiments, q is 1. In certain embodiments, q is 2. In certain embodiments, q is 3. In certain embodiments, q is 4.

[0432] In certain embodiments, a is 1. In certain embodiments, a is 2. In certain embodiments, a is 3. In certain embodiments, a is 4. In certain embodiments, a is 5. In certain embodiments, a is 6. In certain embodiments, a is 7. In certain embodiments, a is 8.

[0433] In certain embodiments of Formula III,

Chemical formula

Chemical formula

[0434] In certain embodiments of Formula III,

Chemical formula

Chemical formula

[0435] In certain embodiments of Formula III,

Chemical formula

Chem.

[0436] In certain embodiments of Formula III,

Chem.

Chem.

[0437] In certain embodiments of Formula III,

Chem.

Chem.

[0438] In certain embodiments of Formula III,

Chem.

Chem.

[0439] In certain embodiments of Formula III,

Chem.

Chem.

[0440] In certain embodiments of Formula III,

Chemical formula

Chemical formula

[0441] In certain embodiments of Formula III,

Chemical formula

Chemical formula

[0442] In certain embodiments of Formula III,

Chemical formula

Chemical formula

[0443] In certain embodiments of Formula IV,

Chemical formula

Chemical formula

[0444] In certain embodiments of Formula IV, [Chemistry] is selected from [Chemistry] In certain embodiments of Formula IV,

[0445] is selected from [Chemistry] is selected from [Chemistry] TIFF2025108581000356.tif226170.

[0446] In certain embodiments of Formula IV, [Chemistry] is selected from [Chemistry] In certain embodiments of Formula IV,

[0447] is selected from [Chemistry] is selected from [Chemistry] In certain embodiments of Formula IV,

[0448] In some embodiments of Formula IV, [Chemistry] is selected from [Chemistry] In some embodiments of Formula IV,

[0449] In some embodiments of Formula IV,

Chemical formula

Chemical formula

[0450] In some embodiments of Formula IV,

Chemical formula

Chemical formula

[0451] In some embodiments of Formula IV,

Chemical formula

Chemical formula

[0452] In some embodiments of Formula IV,

Chemical formula

Chemical formula

[0453] In another aspect of the present invention, the quaternary ammonium compound of formula III is

Chemical formula

[0454] In another aspect of the present invention, the quaternary ammonium compound of formula III is

Chemical formula

[0455] In another aspect of the present invention, the quaternary ammonium compound of formula IV is

Chemical formula

[0456] In certain embodiments, the quaternary ammonium compound of the present invention is

Chemical formula

[0457] In certain embodiments, the quaternary ammonium compound of the present invention is

Chemical formula

[0458] In certain embodiments, the quaternary ammonium compound of the present invention is

Chemical formula

[0459] In certain embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] selected from

[0460] In certain embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] selected from

[0461] In certain embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] selected from TIFF2025108581000388.tif194170

[0462] In certain embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] selected from

[0463] In certain embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] selected from

[0464] In certain embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] selected from TIFF2025108581000392.tif184170

[0465] In certain embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] selected from

[0466] In certain specific embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] selected from

[0467] In certain specific embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] selected from

[0468] In certain specific embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] selected from

[0469] In certain specific embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] selected from

[0470] In certain specific embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] selected from

[0471] In certain specific embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] selected from

[0472] In certain embodiments, the quaternary ammonium compound of the present invention is

Chemical formula

[0473] In certain embodiments, the quaternary ammonium compound of the present invention is

Chemical formula

[0474] In certain embodiments, the quaternary ammonium compound of the present invention is

Chemical formula

[0475] In certain embodiments, the quaternary ammonium compound of the present invention is

Chemical formula

[0476] In certain embodiments, the quaternary ammonium compound of the present invention is

Chemical formula

[0477] In certain embodiments, the quaternary ammonium compound of the present invention is

Chemical formula

[0478] In certain embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] selected from the following.

[0479] In certain embodiments, the quaternary ammonium compound of the present invention is [Chemical formula] selected from TIFF2025108581000410.tif138170.

[0480] mixture In certain embodiments, a mixture of quaternary ammonium compounds is provided, the mixture comprising: (1) 0.01% to 99.9% of the compound of the present invention; (2) 0.01% to 99.9% alkyl (C14, 50%, C12, 40%, C16, 10%) dimethylbenzylammonium chloride; and (3) 0.01% to 99.9% dioctyldimethylammonium chloride; and an optional solvent mixture, with or without a thickening agent (e.g., guar gum or PVA).

[0481] In certain embodiments, a mixture of quaternary ammonium compounds is provided, the mixture comprising: (1) 0.01% to 99.9% of the compound of the present invention; (2) 0.01% to 99.9% of another compound of the present invention; (3) 0.01% to 99.9% alkyl (C14, 50%, C12, 40%, C16, 10%) dimethylbenzylammonium chloride; and (4) 0.01% to 99.9% dioctyldimethylammonium chloride; and an optional solvent mixture, with or without a thickening agent (e.g., guar gum or PVA).

[0482] In certain embodiments, a mixture of quaternary ammonium compounds is provided, the mixture comprising: (1) 0.01% to 99.9% of the compound of formula I; (2) 0.01% to 99.9% of the compound of formula XII; (3) 0.01% to 99.9% alkyl (C14, 50%, C12, 40%, C16, 10%) dimethylbenzylammonium chloride; and (4) 0. 01 to 99.9% of dioctyldimethylammonium chloride; and an optional solvent mixture, with or without a thickening agent (e.g., guar gum or PVA).

[0483] In certain embodiments, a mixture of quaternary ammonium compounds is provided, the mixture comprising (1) 0.01% to 99.9% of a compound of the present invention; and (2) 0.01% to 99.9% of another compound of the present invention; and an optional solvent mixture, with or without a thickening agent (e.g., guar gum or PVA).

[0484] In certain embodiments, a mixture of quaternary ammonium compounds is provided, the mixture comprising (1) 0.01% to 99.9% of a compound of formula I; and (2) 0.01% to 99.9% of another compound of the present invention; and an optional solvent mixture, with or without a thickening agent (e.g., guar gum or PVA).

[0485] In certain embodiments, a mixture of quaternary ammonium compounds is provided, the mixture comprising (1) 0.01% to 99.9% of a compound of formula I; and (2) 0.01% to 99.9% of a compound of formula XII; and an optional solvent mixture, with or without a thickening agent (e.g., guar gum or PVA).

[0486] In certain embodiments, a mixture of quaternary ammonium compounds is provided, the mixture comprising (1) 0.01% to 99.9% of a compound of the present invention; and (2) 0.01% to 99.9% of alkyl (C14, 50%, C12, 40%, C16, 10%) dimethylbenzylammonium chloride; and an optional solvent mixture, with or without a thickening agent (e.g., guar gum or PVA).

[0487] In certain embodiments, a mixture of quaternary ammonium compounds is provided, the mixture comprising (1) from 0.01% to 99.9% of the compound of the present invention; and (2) from 0.01% to 99.9% of dodecyl dimethyl ammonium chloride; and any desired solvent mixture, with or without a thickening agent (e.g., guar gum or PVA).

[0488] In certain embodiments, a mixture of quaternary ammonium compounds is provided, the mixture comprising (1) from 0.01% to 99.9% of the compound of the present invention; and (2) from 0.01% to 99.9% of dioctyl dimethyl ammonium chloride; and any desired solvent mixture, with or without a thickening agent (e.g., guar gum or PVA).

[0489] In certain embodiments, there is provided one of the mixtures of the above components, wherein the quaternary ammonium compound (1) has a concentration of about 5% to 99%.

[0490] In certain embodiments, there is provided one of the mixtures of the above components, wherein the quaternary ammonium compound (1) has a concentration of about 10% to 99%.

[0491] In certain embodiments, there is provided one of the mixtures of the above components, wherein the quaternary ammonium compound (1) has a concentration of about 20% to 99%.

[0492] In certain embodiments, there is provided one of the mixtures of the above components, wherein the quaternary ammonium compound (1) has a concentration of about 30% to 99%.

[0493] In certain embodiments, there is provided one of the mixtures of the above components, wherein the quaternary ammonium compound (1) has a concentration of about 5% to 90%.

[0494] In certain embodiments, one of the mixtures of the above components, wherein the quaternary ammonium... A compound containing monium (1) with a concentration of about 10% to 80% is provided.

[0495] In a certain specific embodiment, a mixture of the above components, which is a quaternary ammonium compound (1) with a concentration of about 20% to 70%, is provided.

[0496] In a certain specific embodiment, a mixture of the above components, which is a quaternary ammonium compound (1) with a concentration of about 30% to 60%, is provided.

[0497] In a certain specific embodiment, a mixture of the above components, which is a quaternary ammonium compound (1) with a concentration of about 40% to 60%, is provided.

[0498] In a certain specific embodiment, a mixture of the above components, which is a quaternary ammonium compound (2) with a concentration of about 5% to 99%, is provided.

[0499] In a certain specific embodiment, a mixture of the above components, which is a quaternary ammonium compound (2) with a concentration of about 10% to 99%, is provided.

[0500] In a certain specific embodiment, a mixture of the above components, which is a quaternary ammonium compound (2) with a concentration of about 20% to 99%, is provided.

[0501] In a certain specific embodiment, a mixture of the above components, which is a quaternary ammonium compound (2) with a concentration of about 30% to 99%, is provided.

[0502] In a certain specific embodiment, a mixture of the above components, which is a quaternary ammonium compound (2) with a concentration of about 5% to 90%, is provided.

[0503] In certain embodiments, there is provided one of the mixtures of the above components in which the quaternary ammonium compound (2) has a concentration of about 10% to 80%.

[0504] In certain embodiments, there is provided one of the mixtures of the above components in which the quaternary ammonium compound (2) has a concentration of about 20% to 70%.

[0505] In certain embodiments, there is provided one of the mixtures of the above components in which the quaternary ammonium compound (2) has a concentration of about 30% to 60%.

[0506] In certain embodiments, there is provided one of the mixtures of the above components in which the quaternary ammonium compound (2) has a concentration of about 40% to 60%.

[0507] In certain embodiments, there is provided one of the mixtures of the above components in which the quaternary ammonium compound (3) has a concentration of about 5% to 99%.

[0508] In certain embodiments, there is provided one of the mixtures of the above components in which the quaternary ammonium compound (3) has a concentration of about 10% to 99%.

[0509] In certain embodiments, there is provided one of the mixtures of the above components in which the quaternary ammonium compound (3) has a concentration of about 20% to 99%.

[0510] In certain embodiments, there is provided one of the mixtures of the above components in which the quaternary ammonium compound (3) has a concentration of about 30% to 99%.

[0511] In certain embodiments, there is provided one of the mixtures of the above components in which the quaternary ammonium compound (3) has a concentration of about 5% to 90%.

[0512] In certain embodiments, there is provided one of the mixtures of the above components, in which the quaternary ammonium compound (3) has a concentration of about 10% to 80%.

[0513] In certain embodiments, there is provided one of the mixtures of the above components, in which the quaternary ammonium compound (3) has a concentration of about 20% to 70%.

[0514] In certain embodiments, there is provided one of the mixtures of the above components, in which the quaternary ammonium compound (3) has a concentration of about 30% to 60%.

[0515] In certain embodiments, there is provided one of the mixtures of the above components, in which the quaternary ammonium compound (3) has a concentration of about 40% to 60%.

[0516] In certain embodiments, there is provided one of the mixtures of the above components, in which the quaternary ammonium compound (4) has a concentration of about 5% to 99%.

[0517] In certain embodiments, there is provided one of the mixtures of the above components, in which the quaternary ammonium compound (4) has a concentration of about 10% to 99%.

[0518] In certain embodiments, there is provided one of the mixtures of the above components, in which the quaternary ammonium compound (4) has a concentration of about 20% to 99%.

[0519] In certain embodiments, there is provided one of the mixtures of the above components, in which the quaternary ammonium compound (4) has a concentration of about 30% to 99%.

[0520] In certain embodiments, there is provided one of the mixtures of the above components, in which the quaternary ammonium compound (4) has a concentration of about 5% to 90%.

[0521] In certain embodiments, provided is one of the mixtures of the above components, in which the quaternary ammonium compound (4) has a concentration of about 10% to 80%.

[0522] In certain embodiments, provided is one of the mixtures of the above components, in which the quaternary ammonium compound (4) has a concentration of about 20% to 70%.

[0523] In certain embodiments, provided is one of the mixtures of the above components, in which the quaternary ammonium compound (4) has a concentration of about 30% to 60%.

[0524] In certain embodiments, provided is one of the mixtures of the above components, in which the quaternary ammonium compound (4) has a concentration of about 40% to 60%.

[0525] In certain embodiments, the above concentration is calculated by dividing the mass of compound (1), (2), (3), or (4) by the total mass of compound (1), (2), (3), or (4). In other embodiments, the above concentration is measured as a percentage in mol / L units.

[0526] In certain embodiments, the above mixture is provided as a blend with another of the above mixtures.

[0527] Non-limiting examples of solvents include water, ethanol, physiological saline, DMSO, and glycols (e.g., propylene glycol).

[0528] Non-limiting examples of thickeners, wetting agents, and / or gelling agents include guar gum, PVA, PVP, starch, and xanthan gum.

[0529] Methods for treating infectious diseases The present invention includes a method for treating an infectious disease in a host using a quaternary ammonium compound or product or a mixture thereof described herein.

[0530] In some embodiments, the infectious disease is treated directly with a solution (typically reconstituted from a sterile powder or solid) containing one or more quaternary ammonium compounds of the present invention.

[0531] In some embodiments, the infectious disease is treated directly with a solution containing one or more quaternary ammonium compounds of the present invention on a biological surface. Representative biological surfaces include, but are not limited to, oral regions such as teeth, gums, gingival sulcus, periodontal pockets, ear regions such as the outer ear, middle ear (tympanic cavity), inner ear (labyrinth), female genital system (e.g., vagina, cervix, uterus, fallopian tubes), male genital system (e.g., penis, scrotum, testes, epididymis), anus, perineum, rectum, peritoneum, prostate, urinary tract, intima of blood vessels, conjunctiva, corneal tissue, airways, lung tissue (e.g., bronchi and alveoli), heart valves, gastrointestinal tract, skin, scalp, any surface of nails, and the surface of wounds, particularly chronic wounds, where the wounds can be either local or internal.

[0532] Biofilm Biofilms can occur in many environments, such as on the surfaces of healthcare settings, devices, and medical devices, and particularly importantly, on the skin, ears, wounds, and other in vivo local areas of humans and animals. These sessile microbial communities are very different from their corresponding planktonic communities. Although the estimates vary, up to 40% of bacterial genes may be up- or down-regulated during the transition from the planktonic to the biofilm state for the purpose of acquiring specialized functions (see Davies D.G., Parsek M.R., Pearson J.P., Iglewski B.H., Costerton J.W., Greenberg E.P. "The involvement of cell-to-cell signals in the development of a bacterial biofilm" Science.1998, 280, 295-298; and Hall-Stoodley L., Costerton J.W., Stoodley P. "Bacterial biofilms: From the natural environment to infectious diseases" Nat. Rev. 2004, 2, 95-108). "The formation of a community of microorganisms attached to a surface once defined as such has come to be recognized as a complex developmental process with multifaceted and dynamic properties." (See Kostakioti M., Hadjifrangiskou M., Hultgren, S. "Bacterial Biofilms: Development, Dispersal, and Therapeutic Strategies in the Dawn of the Postantibiotic Era" Cold Spring Harb Perspect Med 2013, 3:a010306. http: / / dx.doi.org / 10.1101 / cshperspect.a010306).

[0533] Up to 80% of human bacterial infections are associated with biofilms. Biofilm communities can cause "persistent infections that are resistant to conventional antimicrobial therapy" and are "a major cause of today's treatment failures" (see Roemling, U., Balsalobre, C. "Biofilm infections, their resilience to therapy and innovative treatment strategies." Journal of Internal Medicine, 2004, 272: 541-561). When microorganisms form biofilms in vivo, they can acquire resistance not only to antimicrobial drugs but also to the host's own immune defenses. Antibiotics designed to combat infections have traditionally been developed to kill planktonic bacteria under the assumption that such drugs would kill the same bacteria regardless of their different forms. However, even the same bacteria in a biofilm state are different from those in a planktonic state due to a dramatic shift in gene expression. These changes in gene expression have emergent properties that cannot be predicted based on studies of planktonic cells alone. Bacteria protected within biofilms have up to 1000-fold higher antibiotic resistance than when the bacteria are in a planktonic form (see Rasmussen TB, Givskov M. Int J Med Microbiol. 2006, 296(2-3):149-161). When they form biofilms, they can acquire resistance not only to antimicrobial drugs but also to the host's own immune defenses. Antibiotics designed to combat infections have traditionally been developed to kill planktonic bacteria under the assumption that such drugs would kill the same bacteria regardless of their different forms. However, even the same bacteria in a biofilm state are different from those in a planktonic state due to a dramatic shift in gene expression. These changes in gene expression have emergent properties that cannot be predicted based on studies of planktonic cells alone. Bacteria protected within biofilms have up to 1000-fold higher antibiotic resistance than when the bacteria are in a planktonic form (see Rasmussen TB, Givskov M. Int J Med Microbiol. 2006, 296(2-3):149-161). When they form biofilms, they can acquire resistance not only to antimicrobial drugs but also to the host's own immune defenses. Antibiotics designed to combat infections have traditionally been developed to kill planktonic bacteria under the assumption that such drugs would kill the same bacteria regardless of their different forms. However, even the same bacteria in a biofilm state are different from those in a planktonic state due to a dramatic shift in gene expression. These changes in gene expression have emergent properties that cannot be predicted based on studies of planktonic cells alone. Bacteria protected within biofilms have up to 1000-fold higher antibiotic resistance than when the bacteria are in a planktonic form (see Rasmussen TB, Givskov M. Int J Med Microbiol. 2006, 296(2-3):149-161).

[0534] Clinically, biofilms are responsible for many common persistent and chronic infections in humans and animals due to their acquired and intrinsic resistance to antimicrobial agents and the selection of phenotypic variants. Such resistance tends to be multifactorial, and biofilms typically contain a mixture of fungal / bacterial species that may enhance the rejection of antimicrobial agents. (See Non-Patent Document 4 and Al-Fattani M.A and Douglas L.J. "Biofilm matrix of Candida albicans and Candida tripicalis: chemical composition and role in drug resistance" Journal of Medical Microbiology 2006; 55:999-1008).

[0535] Biofilms often consist of multiple cell layers. The layered nature of biofilms makes the exposure of individual organisms to oxygen and nutrients non-uniform, and the deeper the organisms are, the more non-uniform it becomes, leading to an environment that may cause changes in metabolic activity. In many cases, such deep-layer organisms are known as "persister cells" and are in a stationary phase. These stationary cells are often more resistant to chemical agents due to the cell layers above them, and thus are exposed to a smaller amount of treatment than those on the surface of the biofilm. For example, the effectiveness of antibiotics often decreases with the depth of the biofilm because most of the antibiotics are consumed by the upper-layer cells before they can diffuse to the lower layers, resulting in insufficient concentrations reaching the deeper layers (Roemling and Balsalobre, 551). This phenomenon leads to incomplete removal of biofilms in many antimicrobial treatment regimens, and as a result, the survival of resistant cells can be confirmed, thus creating a situation of chronic or persistent infections (Musk, Jr. D. and Hergenrother, P. "Chemical Countermeasures for the Control of Bacterial Biofilms: Effective Compounds and Promising Targets" Current Medicinal Chemistry 2006, 13, 2163-2177).

[0536] By encoding the information that identifies the antibiotics encountered in genes, surviving bacterial cells can, in the future, enable new colonies to recognize and resist such treatment regimens. This genetic information can be transmitted and shared with other microorganisms in multiple ways, such as through electrical signaling, conjugation, mutation, and heterologous expression, thus exponentially expanding "antibiotic resistance" to a wide range of available drugs and leading to the emergence of "super-resistant" strains of pathogenic organisms (Davies, J and Davies, D. "Origins and Evolution of Antibiotic Resistance" Microbiology and Molecular Biology Reviews 2010, 417-433; and Humphries, J., Xiong, L., Liu, J., Prindle, A., Yuan, F., Arjes, H.A., Tsimring, L. and Gurol, S. "Species-Independent Attraction to Biofilms through Electrical Signaling" Cell 2017, 168, 200-209).

[0537] The formation and maintenance of mature biofilms are closely related to the production of extracellular matrix. Multiple layers of cells and EPS can form a complex and dense structure, within which it is difficult for biocides to penetrate and reach the inner layers, thus indicating that the effectiveness of biocides is hindered (see Bridier, et. al. "Resistance of bacterial biofilms to disinfectants: a review" Biofouling 2011, Vol. 27). Biocides are often highly chemically reactive molecules, so the presence of organic substances, such as proteins, nucleic acids, or carbohydrates, etc., may greatly reduce the effectiveness of biocides, and potential interactions between antibacterial agents and biofilm components may also contribute to limiting the penetration of antibacterial agents into biofilms. Since biocides are often highly chemically reactive molecules, the presence of organic substances, such as proteins, nucleic acids, or carbohydrates, etc., may greatly reduce the effectiveness of biocides, and potential interactions between antibacterial agents and biofilm components may also contribute to limiting the penetration of antibacterial agents into biofilms.

[0538] "In the United States, more than five million central venous catheters are inserted each year, and biofilm infections occur in more than 50% of these catheters. In the United States alone, this results in approximately 100,000 deaths and an excess expenditure of $6.5 billion annually" (ibid.). Biofilms are also a major problem associated with implant devices. "Fungal biofilms are often resistant to known antifungal drugs" (ibid.). "Removal of some of these devices... can be costly and, in some cases, dangerous to the patient, and administering high doses of antifungal agents... can lead to further complications including kidney and liver damage. Such treatment is often not even possible, as many critically ill patients cannot tolerate such treatment, leaving few options available to such patients, and the need to find better therapeutic and diagnostic therapies to combat such biofilms is emphasized" (ibid.). Gulati, M. and Nobile, C., "Candida albicans biofilms: development, regulation, and molecular mechanisms." Microbes Infect 2016, 18(5), 310-321; Doi: 10.101 / j.mocomf.2016.01.002). In certain embodiments In certain embodiments, the compounds described herein are useful for the treatment, prevention, or removal of biofilms.

[0539] The most frequent eye infections include eye redness, bacterial or viral conjunctivitis (pink eye), corneal ulcers, keratitis, bacterial, fungal, herpal infectious keratitis, endophthalmitic, and blepharitis (eyelid infection). Conjunctivitis is the most common eye It is an infectious disease, and viral conjunctivitis is its most common form. The most common causes of bacterial conjunctivitis are Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus (Antibiotics versus placebo for acute bacterial conjunctivitis. Sheikh A, Hurwitz B., Cochrane Database Syst Rev. 2006 Apr 19; (2):CD001211;). Both viral conjunctivitis and bacterial conjunctivitis present with eye redness and are highly infectious (https: / / www.ncbi.nlm.nih.gov / pmc / articles / PMC6003010 / ). presented Blepharitis is an inflammation of the eyelid. Blepharitis is a common cause of pain, red eyelids, and hard eyelashes. The eyelid margin can be infected by bacteria or fungal infections, and their accumulation forms a biofilm. Parasitic eyelid mites called Demodex feed on the biofilm, which leads to an overgrowth of mites that causes the worsening of eyelid margin inflammation (https: / / www.allaboutvision.com / conditions / bleparitis.htm, https: / / www.reviewofoptometry.com / article / ro1117-could-eyelids-be-the-key-to-ded).

[0540] Bacterial infection is the most common cause of infectious keratitis. Common bacteria include S. aureus, coagulase-negative staphylococci, S. pneumoniae, and Pseudomonas aeruginosa (Sharma A, Taniguchi J. Review: Emerging strategies for antimicrobial drug delivery to the ocular surface: Implications for infectious keratitis. Ocul Surf 2017, 15, 670-9.; Green M, Apel A, Stapleton F. Risk factors and causative organisms in microbial keratitis. Cornea 2008, 27, 22-7)。 P. aeruginosa is the most common microorganism associated with bacterial keratitis among contact lens wearers. Acanthamoeba spp. are suspected when patients swim or visit a spa while wearing contact lenses (Stapleton F, Dart JK, Seal DV, Matheson M. Epidemiology of Pseudomonas aeruginosa keratitis in contact lens wearers. Epidemiol Infect 1995, 114, 395-402).

[0541] Dry eye syndrome or dry eye disease (DED) is one of the most common eye conditions worldwide. Often, dry eye is associated with eyelid margin inflammation, although it is relatively unlikely that this inflammation is noted as a cause rather than a result of dry eye. Blepharitis is often treated with an ointment (most often erythromycin), which seems to help. Dry eye syndrome has been suggested to have four stages. Stage 1 involves the eyelash follicles, where a biofilm can establish its place. Stage 2 Both the eyelash follicles and the meibomian glands are involved and can explain self - evident vs. non - self - evident meibomian gland dysfunction (MGD). This is because the biofilm blocks the large meibomian gland orifices (the combination of biofilm and poor or modified meibum). It takes more time to reach stage 2. Stage 3 involves the follicles, meibomian glands, and the Krause and Wolfring accessory lacrimal glands. Distance, tube narrowness, and a constant tear flow function to protect these glands over decades, and due to this function, these glands are the last glands to be affected by biofilm formation. Stage 4 occurs when the structural integrity of the eyelid is finally disrupted due to chronic inflammation, which can manifest clinically, for example, as eyelid laxity, floppy eyelid syndrome, ectropion, and entropion (Rynerson JM, Perry HD. DEBS - a unification theory for dry eye and blepharitis. Clin Ophthalmol. 2016, 10, 2455 - 67; Baudouin C. Ocular surface and external filtration surgery: mutual relationships. Dev Ophthalmol. 2012, 50, 64 - 78; Baudouin C, Messmer EM, Aragona P, et al. Revisiting the vicious circle of dry eye disease: a focus on the pathophysiology of meibomian gland dysfunction. Br J Ophthalmol. 2016, 100(3)300 - 6).

[0542] Ear infections can occur in the outer ear canal (otitis externa), inner ear (otitis interna), or middle ear canal (otitis media). Most ear infections occur in the middle ear and cause fluid buildup, swelling, and inflammation when bacteria or viruses multiply. Ear infections can become chronic, which is generally likely due to biofilm accumulation. From recent clinical trials, evidence has been obtained that in almost all cases of chronic OM, bacterial biofilms are associated behind the tympanic membrane (eardrum) and within the middle ear. Biofilms are typically extremely thin and cannot be recognized using a normal otoscope. Otitis media (OM) is the most common disease in children in the United States, and 3 / 4 of children under 3 years old will have OM at least once. Despite most cases being chronic infections, long-term or permanent damage to the ear can still occur. Acute otitis media may disappear after 1 to 2 weeks without treatment, but may also require treatment with antibiotics. Approximately 50% of antibiotic prescriptions for children under 3 years old are issued for ear infections. However, in the case of chronic OM, antibiotics may no longer be useful, and surgery is usually required to install tympanostomy tubes in the eardrum of the middle ear. (https: / / biophotonics.illinois.edu / sites / default / files / BOE-LCI_Biofilms_0.pdf).

[0543] Vulvovaginal candidiasis occurs when Candida species enter the superficial layer of the vaginal mucosal lining and cause an inflammatory reaction. The main inflammatory cells are typically polymorphonuclear cells and macrophages. Patients may present with discharge (which is typically viscous and sticky or accompanied by epidermal exfoliation), "external" dysuria, vaginal itching, vaginal burning, dyspareunia, or swelling.

[0544] Periodontal or gum disease is a pathological inflammatory condition of the gums and bone support structures (periodontal tissues) surrounding the teeth. The two most common periodontal diseases are gingivitis, which is inflammation of the gums at the tooth neck, and periodontitis, which is inflammation that affects the bone and tissues of the teeth.

[0545] The biofilms formed by pathogenic fungi have attracted attention in recent years, and several species among filamentous fungi, yeasts, and dimorphic fungi have been described as being able to develop into communities. A biofilm is a sessile microbial community that adheres strongly to surfaces and to each other and is protected by a polymeric extracellular matrix (ECM) mainly composed of polysaccharides. Cells in this case exhibit improved resistance and different phenotypes compared to planktonic or free cells and are associated with the persistence of infections (Costa-Orlandi et al., "Fungal Biofilms and Polymicrobial Diseases", J. Fungi, 2017, 3, 22; doi:10.3390 / jof3020022).

[0546] Species of Candida, including the emerging pathogen Candida dubliniensis, are currently an emerging force among the major pathogens of nosocomial infections. Many of these occurrences of infections associated with the formation of Candida biofilms include those that occur in devices such as intravascular indwelling catheters. Fungal biofilm-related infections are often refractory to conventional therapies due to antimicrobial resistance.

[0547] ​Candida species associated with biofilms show uniform resistance to a wide range of currently available conventional antifungal agents, suggesting the need for antibacterial agents that specifically target biofilm-related infections. New classes of antifungal agents, amphotericin lipid formulations, and echinocandins have demonstrated unique antifungal activity against resistant Candida biofilms and provide a breakthrough in the treatment of life-threatening invasive systemic fungal infections. The use of effective drugs in combating biofilm-related infections may lead to significant developments in the treatment of fungal implant infections (Jabra-Rizk et al., "Fungal biofilm and Drug resistance." (2004). Fungal Biofilms and Drug Resistance, Emerging infectious diseases, 2004, 10, 14-9; 10.3201 / eid1001.030119).

[0548] Pathogenic fungi can also adhere to abiotic surfaces, such as prostheses and catheters. In particular, yeasts take advantage of this situation to gain access to the bloodstream and reach the patient's internal organs. This must be guarded against, as disseminated fungal infections have a high mortality rate (Verstrepen K.J., Klis F.M. Flocculation, adhesion and biofilm formation in yeasts. Mol. Microbiol. 2006, 60, 5-15; doi: 10.1111 / j.1365-2958.2006.05072.x).

[0549] Candida albicans is the most studied model of biofilm formation and exhibits individual developmental stages similar to those of bacterial biofilms. Paracoccidioides brasiliensis is endemic to Central and South America and causes systemic It is a dimorphic fungus that causes paracoccidioidomycosis, a systemic mycosis. Sardi et al. (Sardi Jde C., Pitangui Nde S., Voltan A.R., Braz J.D., Machado M.P., Fusco Almeida A.M., Mendes Giannini M.J. In vitro Paracoccidioides brasiliensis biofilm and gene expression of adhesins and hydrolytic enzymes. Virulence. 2015, 6, 642-651. doi: 10.1080 / 21505594.2015.1031437.). The biofilm of Histoplasma capsulatum was first described by Pitangui et al. This fungus is also characterized by thermodimorphism and causes histoplasmosis. Histoplasmosis is a respiratory and systemic mycosis, and its manifestation depends on the survival and replication of yeasts in alveolar macrophages (Pitangui N.S., Sardi J.C., Silva J.F., Benaducci T., Moraes da Silva R.A., Rodriguez-Arellanes G., Taylor M.L., Mendes-Giannini M.J., Fusco-Almeida A.M. Adhesion of Histoplasma capsulatum to pneumocytes and biofilm formation on an abiotic surface. Biofouling. 2012, 28, 711-718. doi: 10.1080 / 08927014.2012.703659).

[0550] Dermatophytes are fungi that invade keratinized tissues, causing dermatophytosis, which is one of the most common cutaneous mycoses in humans and animals (Weitzman I., Summerbell R.C. The dermatophytes. Clin. Microbiol. Rev. 1995, 8, 240-259. doi: 10.1016 / S0733-8635(05)70320-X). Among dermatophytoses, onychomycosis is often accompanied by recurrence and long-term treatment, and may be ineffective in some cases. Considering the hypothesis of Burkhart et al. that this situation and biofilm formation by dermatophytes can explain the formation of dermatophyte balls, Costa-Orlandi et al. confirmed in vitro biofilm formation by two of the most widespread species in the world, Trichophyton rubrum and T. mentagrophytes (Burkhart C.N., Burkhart C.G., Gupta A.K. vitro biofilm formation was confirmed (Burkhart C.N., Burkhart C.G., Gupta A.K. Dermatophytoma: Recalcitrance to treatment because of existence of fungal biofilm. J. Am. Acad. Dermatol. 2002, 47, 629-631. doi: 10.1067 / mjd.2002.124699; Costa-Orlandi C.B., Sardi J.C., Santos C.T., Fusco-Almeida A.M., Mendes-Giannini M.J . In vitro characterization of Trichophyton rubrum and T. mentagrophytes biofilms. Biofouling. 2014, 30, 719-727. doi: 10.1080 / 08927014.2014.919282).

[0551] Candida auris is an emerging yeast that causes healthcare-associated infections It is a fungus. This can be misidentified in tests and is often resistant to antifungal drugs. An explosive spread of C. auris infections in healthcare facilities has been reported in New York City, New York, USA (Adams et al., Candida auris in Healthcare Facilities, New York, USA, 2013 - 2017, Emerg Infect Dis. 2018, 24(10), 1816 - 1824. https: / / dx.doi.org / 10.3201 / eid2410.180649). In another embodiment, the infectious disease is treated by applying a dressing containing one or more quaternary ammonium compounds of the present invention as an antibacterial composition to the infected site, and this dressing releases one or more quaternary ammonium compounds of the present invention to the infected site. The infectious disease may involve the presence of bacteria, fungi, viruses, amoebas, or combinations of these infectious species.

[0552] Topical application also includes the treatment of the oral cavity including teeth and gums. Gingivitis occurs in both chronic and acute forms. Acute gingivitis is usually associated with a specific infectious disease, microorganism, or trauma. Chronic inflammation of the gum tissue surrounding the teeth is associated with the bacterial biofilm (plaque) covering the teeth and gums (https: / / www.dentalhealth.ie / dentalhealth / causes / Periodontaldisease.html). The organosilicon quaternary ammonium compounds of the present invention can be used as oral health management agents, for example, in the control of dental plaque, for example, in plaque removal, or plaque reduction, or in the prevention, reduction, or delay of plaque formation. These compounds can also be used for the treatment and prevention of infectious diseases or infectious disorders that may occur in the oral cavity, such as gingivitis and periodontitis. The organosilicon quaternary ammonium compounds of the present invention can also be formulated as components in oral health management agents (e.g., toothpaste) to prevent dental caries (tooth decay) and gingivitis.

[0553] Topical application also includes the treatment of oral / lip care, oral ulcers, and herpes simplex. Herpes simplex is contagious, and if an individual is infected, strict hygiene measures must be adopted. Primary oral infection is caused by the herpes simplex virus (HSV), the causative virus of oral herpes. After primary oral infection, HSV remains in an inactive state and may only become activated later as the more common oral herpes, i.e., "herpes simplex". The triggers for reactivation are known and include sunlight, trauma, fatigue, stress, and menstruation (https: / / www.dentalhealth.ie / dentalhealth / causes / coldsores.html). The most common form of oral ulcer is called a minor aphthous ulcer. Usually, one to five small ulcers (less than 1 mm in diameter) appear on the lips or inside the cheeks, the floor of the mouth, or the tongue. The ulcers tend to concentrate towards the front of the mouth. Other more serious causes of oral ulcers include herpes infections (https: / / www.dentalhealth.ie / dentalhealth / causes / mouthulcers.html).

[0554] In some embodiments, the treatment of an infection comprises placing a dressing containing an antimicrobial composition as described herein in or on the infected site.

[0555] In another embodiment, the treatment of an infection comprises placing an antimicrobial composition containing one or more quaternary ammonium compounds of the present invention at the infected site. The quaternary ammonium compound, or the length of time the composition is administered, is such that the antimicrobial treatment remains effective or the infection is resolved. The treatment may be applied continuously, provide sequential applications after an appropriate time frame, or alternate with another infection treatment after an appropriate time frame. The quaternary ammonium compounds described herein can be administered to the host's infected site at appropriate intervals as determined by a healthcare provider.

[0556] In some embodiments, the quaternary ammonium compounds described herein are once a day It is placed at the site of infection for a period of less than [specific time]. In other embodiments, the quaternary ammonium compound described herein is placed at the site of infection for a period of one week or more.

[0557] An effective amount of the antimicrobial composition as described herein, or used in combination or alternation with another active pharmaceutical agent, or the antimicrobial composition described herein used with a prior, simultaneous, or subsequent use of another active pharmaceutical agent, inhibits the progression of a disorder (e.g., an infection) caused by the presence of an infectious organism in or on a host; causes regression of a disorder caused by the presence of an infectious organism in or on a host; causes cure of a disorder caused by the presence of an infectious organism in or on a host; or is used in an amount sufficient to inhibit or prevent the occurrence of a disorder caused by the presence of an infectious organism near, in, or on a host. The treatment method can be administered once a day (q.d.), twice a day (b.i.d.), three times a day (t.i.d.), four times a day (q.i.d.), once every two days (Q2d), once every three days (Q3d), as needed, or using any dosing schedule that provides treatment of an infection as described herein.

[0558] In some embodiments, a method of treating and / or preventing an infection includes placing a dressing saturated with the antimicrobial composition at the wound and / or site of infection. The dressing may be directly saturated with the antimicrobial composition before being placed at the wound and / or site of infection, i.e., pre-saturated and manufactured and packaged. In other embodiments, a method of treating and / or preventing an infection includes placing a dressing at the wound and / or site of infection and subsequently post-saturating the dressing with the antimicrobial composition. The antimicrobial composition may be added by a dropper, syringe, or other suitable means after placement of the dressing.

[0559] In some embodiments, one or more quaternary ammonium compounds or pharmaceutical compositions as described herein are used to treat or prevent a medical disorder mediated by the presence of bacteria, e.g., a bacterial infection.

[0560] In some embodiments, the quaternary ammonium compound of the present invention can be used to treat disorders caused by pathogenic bacteria, typically infectious diseases.

[0561] In some embodiments, provided is a method comprising administering to a subject an effective amount of the quaternary ammonium compound or composition thereof described herein for treating a bacterial infection.

[0562] In some embodiments, one or more quaternary ammonium compounds of the present invention can be used to treat disorders caused by Gram-positive bacteria, typically infectious diseases.

[0563] In some embodiments, provided is a method comprising administering to a subject an effective amount of the quaternary ammonium compound or composition thereof as described herein for treating a Gram-positive bacterial infection.

[0564] Non-limiting examples of Gram-positive bacteria that may be treated by the quaternary ammonium compound of the present invention, either alone or in combination with another therapeutic agent, include: Actinomyces species, including Actinomyces israelii, Actinomyces naeslundii, Actinomyces viscosus, Actinomyces odontolyticus, and Actinomyces pyogenes; Bacillus species, including Bacillus anthracis, Bacillus cereus, and Bacillus subtilis israelii), Actinomyces naeslundii), Actinomyces viscosus), Actinomyces odontolyticus), and Actinomyces pyogenes); Bacillus species, including Bacillus anthracis, Bacillus cereus, and Bacillus subtilis containing Bacillus subtilis; Clostridium species, including Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium sordellii, and Clostridium tetani; Corynebacterium species, including Corynebacterium diphtheriae, Corynebacterium jeikeium, Corynebacterium minutissimum, Corynebacterium mucifaciens, Corynebacterium pseudotuberculosis, Corynebacterium striatum, Corynebacterium tenuis, and Corynebacterium ulcerans; Enterococcus species, including Enterococcus casseliflavus, Enterococcus faecalis, Enterococcus faecium, Enterococcus raffinosus, and Enterococcus hirae; Leuconostoc ; Clostridium difficile, Clostridium perfringens ; Clostridium sordellii, and Clostridium tetani; Corynebacterium species, including Corynebacterium diphtheriae, Corynebacterium jeikeium, Corynebacterium minutissimum, Corynebacterium mucifaciens, Corynebacterium pseudotuberculosis, Corynebacterium striatum, Corynebacterium tenuis, and Corynebacterium ulcerans; Enterococcus species, including Enterococcus casseliflavus, Enterococcus faecalis, Enterococcus faecium, Enterococcus raffinosus, and Enterococcus hirae; Leuconostoc ; Clostridium tetani; Corynebacterium species, including Corynebacterium diphtheriae, Corynebacterium jeikeium, Corynebacterium minutissimum, Corynebacterium mucifaciens, Corynebacterium pseudotuberculosis, Corynebacterium striatum, Corynebacterium tenuis, and Corynebacterium ulcerans; Enterococcus species, including Enterococcus casseliflavus, Enterococcus faecalis, Enterococcus faecium, Enterococcus raffinosus, and Enterococcus hirae; Leuconostoc ; Corynebacterium pseudotuberculosis, Corynebacterium striatum, Corynebacterium tenuis, and Corynebacterium ulcerans; Enterococcus species, including Enterococcus casseliflavus, Enterococcus faecalis, Enterococcus faecium, Enterococcus raffinosus, and Enterococcus hirae; Leuconostoc ; Enterococcus casseliflavus, Enterococcus faecalis, Enterococcus faecium, Enterococcus raffinosus, and Enterococcus hirae; Leuconostoc Leuconostoc species, including Leuconostoc pseudomesenteroides; Micrococcus species, such as , Micrococcus luteus, etc.; Nocardia species, including Nocardia asteroides; Propio nibacterium species, including Propionibacterium acnes ; Staphylococcus species, including Staphylococcus aureus, Staphylococcus capitis, Staphylococcus epidermidis, Staphylococcus haemolyticus, St aphylococcus hominis, Staphylococcus lugdunensis, Staphylococcus pasteuri, and Staphylococcus saprophyticus; and Streptococcus species, including Streptococc us agalactiae, Streptococcus anginosus, Streptococcus bovis, Streptococcus dysgalactiae, Streptococcus mitis, Streptococcus muta Streptococcus mutans, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus sanguinis, Streptococcus suis, and Streptococcus viridans are included. is included.

[0565] In some embodiments, the quaternary ammonium compounds of the present invention can be used to treat disorders caused by Gram-negative bacteria, typically infections.

[0566] In some embodiments, provided is a method comprising administering an effective amount of the quaternary ammonium compound or composition thereof described herein to treat an infection caused by a Gram-negative bacteria.

[0567] Non-limiting examples of Gram-negative bacteria that may be treated by the quaternary ammonium compounds of the present invention, either alone or in combination with another therapeutic agent, include: Acinetobacter species, including Acinetobacter baumannii and Acinetobacter iwoffii; Aeromonas species, including Aeromonas veronii biovar sobria (formerly Aeromonas sobria), Aeromonas caviae, and Aeromonas hydrophila; Alcaligenes / Achromobacter species, including; Aeromonas species, which includes Aeromonas veronii subspecies sobria (formerly Aeromonas sobria), Aeromonas caviae, and Aeromonas hydrophila; Alcaligenes / Achromobacter species, including Aeromonas veronii biovar sobria (formerly Aeromonas sobria), Aeromonas caviae, and Aeromonas hydrophila; Alcaligenes / Achromobacter species, including; Aeromonas species, which includes Aeromonas veronii subspecies sobria Achromobacter species, including Alcaligenes faecalis and Alcaligenes xylosoxidans ; Bacteroides species, including Bacteroides fragilis; Bartonella species, including Bartonella bacilliformis, Bartonella clarridgeiae, Bartonella elizabethae, Bartonella henselae, Bartonella koehlerae, Ba rtonalla naantalienis, Bartonella quintana, Bartonella rochalimae, Bartonella vinsonii, and Bartonella washoensis; Bordetella species, including Bordetella bronchispetica, Bordetella pertussis, and Bordetella parapertussis ; Borrelia species, including Borrelia afzelii, Borrelia burgdorferi, Borrelia crocidurae, Borrelia duttoni, Borrelia garinii, Borrelia hermsii, Borrelia hispanica ; and Borrelia turicatae, Borrelia valaisiana, Borrelia venezuelensis, and Borrelia yangtzensis ; Borrelia turicatae, Borrelia valaisiana, Borrelia venezuelensis, and Borrelia yangtzensis (Borrelia hispanica), Borrelia miyamotoi, Borrelia parkeri, Borrelia persica, Borrelia recurrentis, Borrelia turicatae, and Borrelia venezuelensis; Brevundimonas species, including Brevundimonas diminuta and Brevundimonas vesicularis; Brucella species, including Brucella abortus, Brucella canis, Brucella melitensis, and Brucella suis; Burkholderia species, including Burkholderia cepacia, Burkholderia mallei, and Burkholderia pseudomallei; Campylobacter species, including Campylobacter jejuni, Campylobacter coli, Campylobacter upsaliensis, Campylobacter lari, and Campylobacter ; and · contains coliforms; Chlamydia / Chlamidophila species, including Chlamidophila pneumoniae, Chlamidophila psittaci, Chlamidophila pecorum, and Chlamydia trachomatis; Citrobacter species, including Citrobacter amalonaticus, Citrobacter freundii, Citrobacter koseri, and Citrobacter diversus; Coxiella burnetti; Ehrlichia species, including Ehrlichia canis and Ehrlichia chaffeensis; Enterobacter species, including Enterobacter aerogenes and Enterobacter cloacae; Escherichia species, including Escherichia coli; Francisella species, including Francisella novicida, Francisella philomiragia, and Francisella tularensis; Haemophilus species, including Haemophilus influenzae and Haemophilus ducreyi; ​​​Contained; Helicobacter species, including Helicobacter pylori; Klebsiella species, including Klebsiella · granulomatis, Klebsiella oxytoca, and Klebsiella pneumoniae; Leclercia adecarboxylata; Legionella species, including Legionella pneumophila; Leptospira species, including Leptospira interrogans, Leptospira noguchii, Lept ospira santarosai, and Leptospira weilii; Listeria species, including Listeria monocytogenes; Moraxella species, including Moraxella catarrhalis, Moraxella lacunata, and Moraxella bovis; Moraxella bovoculi; Morganella species, including Morganella morganii; Mycoplasma ) species, including Mycoplasma amphoriforme, M Mycoplasma buccale, Mycoplasma faucium, Mycoplasma fermentans, M Mycoplasma genitalium, Mycoplasma hominis, Mycoplasma lipophilum, Mycoplasma orale, Mycoplasma penetrans, Mycoplasma pirum, Mycoplasma pneumoniae, Mycoplasma primatum, Mycoplasma salivarium, and Mycoplas ma spermatophilum; Neisseria species, including Neisseria meningitidis and Neisseria gonorrhoeae; Orientia species, including Orientia tsutsugamushi and Orientia chuto; Pantoea species, including Pan toea agglomerans; Paracoccus species, including Paracoccus yeei; Prevotella species, including Prevotella intermedia and Prevotella melaninogenica; Proteus (Proteus) species, including Proteus mirabilis, Proteus penneri, and Proteus vulgaris ; Providencia species, including Providencia rettgeri and Providencia stuartii ; Pseudomonas species, including Pseudomonas aeruginosa, Pseudomonas oryzihabitans, Pseudomonas plecoglossidica, and Pseudomonas stutzeri ; Ralstonia species, including Ralstonia pickettii and Ralstonia insidiosa; Rickettsia species, including Rickettsia africae, Rickettsia akari, Rickettsia australis, Rickettsia conorii, Rickettsia felis, Rickettsia japonica, Rickettsia prowazekii, Rickettsia rickettsia, Rickettsia sibirica, and Rickettsia typhi ; Roseomonas species, including Roseomonas gilardii Species of Salmonella, including Salmonella bongori, Salmonella enterica, Salmonella paratyphi, Salmonella typhi, and Salmonella typhimurium; Species of Serratia, including Serratia marcescens, Serratia liquefaciens, Serratia rubidaea, and Serratia odoriferae; Species of Shigella, including Shigella dysenteriae and Shigella sonnei; Species of Sphingomonas, including Sphingomonas mucosissima and Sphingomonas paucimobilus; Species of Stenotrophomas, including Stenotrophomas maltophilia; Including Treponema paraluiscuniculi and Treponema pallidum; Ureaplasma species, including Ureaplasma urealyticum; Vibrio species, including Vibrio cholera, Vibrio parahaemolyticus, and Vibrio vulnificus; and Yersinia species, including Yersinia enterocolitica, Yersinia pestis, and Yersinia pseudotuberculosis are included.

[0568] In some embodiments, the quaternary ammonium compounds of the present invention can be used to treat disorders caused by Mycobacterium, typically infections.

[0569] In some embodiments, there is provided a method comprising administering an effective amount of a quaternary ammonium compound or a composition thereof as described herein for treating an infection caused by Mycobacterium.

[0570] Non-limiting examples of Mycobacterium that may be treated by the quaternary ammonium compounds of the present invention, either alone or in combination with another therapeutic agent, include: Mycobacterium abcessus, Mycobacterium africanum, Mycobacterium agri agri), Mycobacterium aichiense, Mycobacterium alvei, Mycobacterium arabiense, Mycobacterium aromaticivorans, Mycobacterium arosiense, Mycobacterium arupense, Mycobacterium aquaticum, Mycobacterium asiaticum, Mycobacterium aubagnese, Mycobacterium aurum, Mycobacterium austroafricanum, Mycobacterium a vium, Mycobacterium avium subspecies paratuberculosis , Mycobacterium avium subspecies silvaticum, Mycobacterium avium subspecies hominussuis, Mycobacterium bacteremicum , Mycobacterium barrassiae, Mycobacterium boenickei , Mycobacterium bohemicum, Mycobacterium · Mycobacterium bolletii, Mycobacterium botniense, Mycobacterium bovis, Mycobacterium branderi, Mycobacterium brisbanense, Mycobacterium brumae, Mycobacterium canariasense, Mycobacterium canettii, Mycobacterium caprae, Mycobacterium chimaera, Mycobacterium chelonae, Mycobacterium chitae, Mycobacterium chubuense, Mycobacterium colombiense, Mycobacterium conceptionense, Mycobacterium confluentis, Mycobacterium · conspicuum, Mycobacterium cookii, Mycobacterium cosmeticum, Mycobacterium diernhoferi, Mycobacterium doricum, Mycobacterium dubarryi (Mycobacterium duvalii), Mycobacterium elephantis, Mycobacterium fallax, Mycobac terium farcinogenes, Mycobacterium flavescens, Mycobacterium florentinum, Mycobacterium fortuitum, Mycobacterium frederikbergense, Mycobacterium gadium, Mycobacterium gastri, Mycobacterium genavense, Mycobacterium gilvum, M ycobacterium gordonae, Mycobacterium haemophilum, Mycobacterium hassiacum, Mycobacterium heidelbergense, Mycobacterium heckshornense , Mycobacterium hiberniae, Mycobacterium Mycobacterium hodleri, Mycobacterium holsaticum, Mycobacterium houstonense, Mycobacterium icosiumassilensis, Mycobacterium immunogenum, Mycobacterium indicus pranii, Mycobacterium intacellulare, Mycobacterium intacellulare, Mycobacterium interjectum, Mycobacterium intermedium, Mycobacterium iranicum, Mycobacterium kansasii, Mycobacterium komossense, Mycobacterium kubicae, Mycobac terium lentiflavum, Mycobacterium le prae, Mycobacterium lepraemurium, Mycobacterium lepromatosis, Mycobacterium liflandii, Mycobac terium llatzerense, Mycobacterium mad agascariense, Mycobacterium majerite Mycobacterium mageritense, Mycobacterium malmoense, Mycobacterium marinum, Mycoba cterium massiliense, Mycoba cterium massilipolynesiensis, Mycobacterium microti, Mycobacterium monacense, Mycobacterium monacense, Mycobacterium montfiorense, Mycobacterium morokaense, Mycobacterium mucogenicum, Mycobacterium mungi, Mycobacterium murale, Mycobacterium nebraskense, Mycobacterium neoaurum, Mycobacterium neworleansense, Mycobacterium nonchromogenicum, Mycobacterium obuense, Mycobacterium orygis, Mycobacterium Mycobacterium palustre, Mycobacterium parascofulaceum, Mycobacterium parafortuitum, Mycobacterium perigrinum, Mycobacterium phlei, Mycobacterium phocaicum, Mycobacterium pinnipedii, Mycobacterium porcinum, Mycobacterium pseudoshottsii, Mycobacterium psychotolerans, Mycobacterium pulveris, Mycobacterium pyrenivorans, Mycobacterium saskatchewanense, Mycobacterium sediminis, Mycobacterium senegalense, Mycobacterium septicum, Mycobacterium shimoidei, Mycobacterium shottsii, Mycobacterium simiae, Mycobacterium smegmatis, Mycobacterium sphag Mycobacterium sphagni, Mycobacterium stephanolepidis, Mycobacterium suricattae, Mycobacterium szulgai, Mycobacterium talmoniae, Mycobacterium terrae, Mycobacterium thermoresistibile, Mycobacterium triplex, Mycobacterium triviale, Mycobacterium tuberculosis, Mycobacterium tusciae, Mycobacterium ulcerans, Mycobacterium vaccae, Mycobacterium vanbaalenii, Mycobacterium xenopi, and Mycobacterium yongonense.

[0571] Non-limiting examples of bacterial-mediated disorders that may be treated by the quaternary ammonium compounds of the present invention, either alone or in combination with another therapeutic agent, include: actinomycosis, anaplasmosis, anthrax, bacterial angioma, actinomycoma, bacterial conjunctivitis, bacterial pneumonia, bacterial vaginal disease, bacterial endocarditis, bartonellosis, botulinum poisoning, boutonneuse )Heat, brucellosis, bejel, brucella spondylitis, bubonic plague, Buruli ulcer, Burnsdale ulcer, bacillary dysentery, campylobacteriosis, Carrion's disease, cat scratch disease, cellulitis, chancroid, chlamydia, chlamydia conjunctivitis, clostridial myonecrosis, cholera, Clostridium difficile colitis, diphtheria, Dainty tree ulcer, donovanosis, dysentery, ehrlichiosis, typhus exanthematicus, fried rice syndrome, five-day fever (five-day fever), floppy baby syndrome, Far East scarlet-like fever, gas gangrene, glanders, gonorrhea, granuloma inguinale, human necrobacillosis, necrotizing fasciitis, hemolytic uremic syndrome, human ewingii ehrlichiosis, human monocytic ehrlichiosis, human granulocytic anaplasmosis, infant botulism, fountain fever, Kawasaki disease, Kumoji ulcer , lymphogranuloma inguinale, Lemierre's syndrome, legionellosis, leptospirosis, Lyme disease, lymphogranuloma inguinale, Malta fever, Mediterranean fever, myonecrosis, mycoburuli ulcer, mucocutaneous lymph node syndrome, melioidosis, meningococcal disease, exanthematous fever, mycoplasma pneumonia, mycetoma, neonatal conjunctivitis, nocardiosis, Oroya fever, neonatal ophthalmia, ornithosis, Pontiac fever, hepatic periostitis, pulmonary plague, angina pectoris shock including sepsis, pasteurellosis, pelvic inflammatory disease, pertussis, plague, pneumococcal infection, pneumonia, parrot fever, parrot fever, pseudotuberculosis, Q fever, quintan fever, rabbit fever, relapsing fever , rickettsialpox, Rocky Mountain spotted fever, rat bite fever, Reiter's syndrome, rheumatic fever, salmonellosis, scarlet fever, sepsis, septicemic plague, Salls ulcer, bacillary dysentery, chancroid, syphilis, streptobacillus fever, scrub typhus, Taiwan acute respiratory pathogen, trench fever, trachoma, tuberculosis, tularemia, enteric typhoid fever, typhoid, tetanus, toxic shock syndrome, undulant fever, papular chancroid, Vibrio parahemolyticus enteritis, Whitmore's disease, walking pneumonia , Waterhouse-Friderichsen syndrome, strawberry swelling, and yersiniosis. ​

[0572] In some embodiments, one or more quaternary ammonium compounds or pharmaceutical compositions thereof as described herein are used to treat or prevent medical disorders mediated by the presence of fungi, such as fungal infections.

[0573] In some embodiments, the quaternary ammonium compounds of the present invention can be used to treat disorders caused by pathogenic fungi, typically infections.

[0574] In some embodiments, provided is a method for treating a fungal infection in a subject, the method comprising administering to the subject an effective amount of a quaternary ammonium compound or composition thereof as described herein.

[0575] Non-limiting examples of fungi that may be treated by the quaternary ammonium compounds of the present invention, either alone or in combination with another therapeutic agent, include: Absidia species, including Absidia corymbifera; Alternaria species, including Alternaria alternate; Aspergillus species, including Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, As including Aspergillus sydowii, Aspergillus terreus, Aspergillus versicolor, and Aspergillus verrucaria; Aureobasidium species, including Aureobasidium pullans; Batrachochytrium species, including Batrachochytrium dendrobatidis and Batrachochytrium salamandrivorans; Blastomyces species, including Blastomyces dermatitidis; Candida species, including Candida albicans, Candida auris, Candida dubliniensis, Candida glabrata, Candida parapsilosis, Candida rugosa, and Candida tropicalis; Chaetomium species, including Chaetomium globosum; Cladosporium species, including Cladosporium cladosporioides; Coccidioides species Blastomyces species, including Blastomyces dermatitidis; Candida species, including Candida albicans, Candida auris , Candida dubliniensis, Candida glabrata, Candida parapsilosis, Candida rugosa, and Candida tropicalis; Chaetomium species, including Chaetomium globosum; Cladosporium species, including Cladosporium cladosporioides (Cladosporium cladosporioides); Coccidioides species This includes Coccidioides immitis and Coccidioides posadasii; Cryptococcus species, including Cryptococcus albidus, Cryptococcus gattii, Cryptococcus laurentii, Cryptococcus neoformans, and Cryptococcus uniguttulatus; Cunninghamella species; Curvularia species, including Curvularia brachyspora, Curvularia clavata, Curvularia geniculata, Curvularia lunata, Curvularia pallescens, Curvularia senegalensis, and Curvularia verruculosa; Dreschslera species, including Dreschslera australiensis; Epidermophyton species, including Epidermophyton floccosum; Fonsecaea species, including Fonsecaea compacta and Fonsecaea pedrosoi; Fusarium species; Species, including Fusarium solani, Fusarium oxysporum, and Fusarium chlamydosporum; Geotrichum species, including Geotrichum capitatum, Geotrichum candidum, and Geotricum clavatum; Gliomastix species, including Gliomastix cerealis ; Gloeophyllum species, including Gloeophyllum trabeum; Histoplasma species, including Histoplasma capsulatum and Histoplasma capsulatum var. faciminosum; Malassezia species, including Malassezia furfur and Malassezia globosa; Microsporum species; Monilia species, including Monilia grisea; Mucor species, including Mucor indicus ; Paracoccidioides species, including Paracoccidioides brasiliensis; Penicillium species ; Piedraia species, including Piedraia hortae and Piedraia quintanilhae (Mucor indicus); Paracoccidioides species, including Paracoccidioides brasiliensis ; Penicillium species ; Piedraia species, including Piedraia hortae ) and Piedraia quintanilhae; Phialophora Phialophora species, including Phialophora verrucosa; Phoma species, including Phoma fimeti; Pithomyces species, including Pithomyces chartarum; Pneumocystis species, including Pneumocystis carinii and Pneumocystis jirovecii; Poria species, including Poria placenta; Rhizopus species, including Rhizopus microspores, Rhizopus oryzae, and Rhizopus stolonifer; Scolecobasidium species, including Scolecobasidium humicola; Sporothrix species, including Sporothrix brasiliensis, Sporothrix globosa, and Sporothrix schenckii; and Trichoderma species, including Trichoderma viride; and Trichophyton species, including Trichosporon beigelii, Trichophyton concentricum ) Trichophyton interdigitale, Trichophyton mentagrophytes, Trichophyton rubrum, and Trichophyton tonsurans are included.

[0576] Non-limiting examples of fungal-mediated disorders that may be treated either alone or in combination with another therapeutic agent with the quaternary ammonium compounds of the present invention include the following: invasive aspergillosis, black piedra, blastomycosis, oropharyngeal candidiasis, vulvovaginal candidiasis, phaeohyphomycosis, tinea corporis, coccidioimycosis, cryptococcosis, dermatophytosis, fusariosus, geotrichosis, histoplasmosis, mucormycosis, mycetoma, paracoccidioimycosis, pneumocystis pneumonia, sporotrichosis, tinea barbae, tinea capitis, tinea corporis, tinea cruris, Tinea manum, black piedra , onychomycosis, vitiligo, white piedra, and zygomycosis.

[0577] In some embodiments, the quaternary ammonium compounds of the present invention can be used to treat disorders caused by viruses, typically infectious diseases.

[0578] In some embodiments, provided is a method comprising administering an effective amount of a quaternary ammonium compound or a composition thereof as described herein for treating a viral infectious disease.

[0579] ​Non-limiting examples of viruses that may be treated by any of the quaternary ammonium compounds of the present invention alone or in combination with another therapeutic agent include the following: adeno-associated virus, astrovirus, BK polyomavirus, coxsackievirus A, coxsackievirus, echovirus, Epstein-Barr virus, GB virus C, human adenovirus, human coronavirus, human cytomegalovirus, human herpesvirus (1, 2, 6, 7, and 8), human papillomavirus (1, 2, 16, and 18), human parainfluenza virus, human parvovirus, human respiratory syncytial virus, human rhinovirus, human SARS coronavirus, influenza virus (A, B, and C), infectious molluscum virus, norovirus, rotavirus (A, B, and C), rubella virus, SARS coronavirus 2, vaccinia virus, and varicella-zoster virus.

[0580] Non-limiting examples of virus-mediated disorders that may be treated by any of the quaternary ammonium compounds of the present invention alone or in combination with another therapeutic agent include the following: influenza, colds, respiratory syncytial virus infection, adenovirus infection, parainfluenza virus infection, severe acute respiratory syndrome (SARS), norovirus infection, rotavirus infection, astrovirus infection, measles, rubella, chickenpox / zoster, roseola, smallpox, fifth disease, human papillomavirus (HPV), warts including genital warts, oral herpes, genital herpes, labial herpes, herpes simplex virus keratitis, and infectious molluscum.

[0581] In some embodiments, one or more quaternary ammonium compounds or pharmaceutical compositions thereof as described herein are used to treat or prevent medical disorders mediated by the presence of amoeba, such as amoeba infections.

[0582] In some embodiments, the quaternary ammonium compounds of the present invention can be used to treat disorders caused by pathogenic amoeba, typically infections.

[0583] In one embodiment, a method is provided that includes administering to a subject an effective amount of a quaternary ammonium compound or a composition thereof as described herein for treating an infection caused by amoeba.

[0584] Non-limiting examples of amoeba that may be treated by the quaternary ammonium compound of the present invention, either alone or in combination with another therapeutic agent, include the following: Acanthamoeba species; Balamuthia species, including Balamuthia mandrillaris; Dientamoeba species, including Dientamoeba fragilis; Endolimax species, including Endolimax nana; Entamoeba species, including Entamoeba Bangladeshi, Entamoeba coli, Entamoeba dispar, Entamoeba gingivalis, Entamoeba hartmanni, Entamoeba histolytica, Entamoeba moshkovskii, and Entamoeba polecki; Iodamoeba species, including Iodamoeba butschlii; Naegleria species, including Naegleria fowleri; and Sappinia species, including Sappinia diploidea and Sappinia pedata.

[0585] Non-limiting examples of amoeba-mediated disorders that may be treated by either the quaternary ammonium compound of the present invention alone or in combination with another therapeutic agent include the following: amoebiasis, amoebic dysentery, amoebic liver abscess, cutaneous amoebiasis, amoebic brain abscess, amebiasis cutis, acanthamoeba keratitis, cutaneous acanthamoebiasis, granulomatous amoebic encephalitis, balamuthia amoebic encephalitis, and Sappinia amoebic encephalitis. In some embodiments, the infectious disease is caused by Acinetobacter species, Aspergillus species, Burkholderia cepacia complex, Campylobacter species, Candida species, Clostridium difficile, Coccidioides species, Cryptococcus species, Enterobacteriaceae, Enterococcus species, Helicobacter pylori, Mycobacterium tuberculosis complex, Neisseria gonorrhoeae, Neisseria meningitidis, nontuberculous mycobacteria species, Pseudomonas species, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, and Vibrio cholerae.

[0586]

[0587] In certain alternative embodiments, the infectious disease is caused by Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes, Candida albicans, Candida auris, Cladosporium herbarum, Aspergillus niger, Proteus mirabilis, Klebsiella pneumoniae, Acinetobacter baumannii, Enterobacter species, or Fusarium species.

[0588] In some embodiments, the quaternary ammonium compound of the present invention can be used to treat inflammatory disorders caused by the presence of infectious organisms as described herein, such as bacteria, fungi, viruses, or amoebas.

[0589] Non-limiting examples of such inflammatory disorders include: adenoid pharyngitis, appendicitis, arteritis, ascending cholangitis, balanitis, blepharitis, bronchitis, bursitis, cellulitis, cerebral vasculitis, cervicitis, chemosis, cholecystitis, chondritis, chorioamnionitis, colitis, conjunctivitis, constrictive pericarditis, cryptitis, dacryadenitis, dermatitis, diabetic ulcer, duodenal lymphocytosis, encephalitis, endocarditis, endometritis, endotheliitis, enteritis, enterocolitis, eosinophilic fasciitis, epididymitis, esophagitis, folliculitis, gastritis, gingivitis, glomerulonephritis, glossitis, hepatitis, infectious arthritis, ileitis, intertrigo, keratitis, keratoconjunctivitis, labyrithitis, lymphadenitis, mastitis, mastoiditis, myocarditis, myopericarditis, myositis, necrotizing fasciitis, nephritis, omaphalitis, ovarian itis, panophthalmitis, orchitis, osteitis, osteomyelitis, pancreatitis, paraproctitis, parotitis, pericarditis, perichondritis, perifolliculitis, periodontitis, peritonitis, pharyngitis, phlebitis, pleurisy, interstitial pneumonia, pulmonitis, proctitis, prostatitis, pulpitis, pyelonephritis, purulent myositis, retinal vasculitis, rheumatic fever, rhinitis, scleritis, salpingitis, sialadenitis, sinusitis, stomatitis, synovitis, sepsis, tenosynovitis, thyroiditis, tonsillitis, tularemia, urethritis, uveitis, vaginitis, vasculitis, and vulvitus.

[0590] In some embodiments, the quaternary ammonium compound of the invention is used to treat skin infections in a host, such as a human. The infection may be caused by the presence of bacteria, fungi, amoebas, or viruses as described herein.

[0591] In some embodiments, provided is a method for treating a skin infection, the method comprising administering to a host, such as a human, an effective amount of a quaternary ammonium compound or composition thereof as described herein.

[0592] In another embodiment, the method is used to treat skin infections in another mammal, such as a cat, dog, cow, pig, or horse.

[0593] Examples of bacterial skin infections that may be treated with the quaternary ammonium compounds of the present invention include, but are not limited to: acne vulgaris, African tick bite fever; American tick bite fever (Rickettsia parkeri infection); bacterial angioma; bejel (endemic syphilis); blastomycosis-like pyoderma (proliferative pyoderma); vesicular pustulosis of the hands and feet; botryomycosis; Brill-Zinsser disease; brucellosis (Bang's disease, Malta fever, undulant fever); bubonic plague; bullous impetigo; Campylobacter jejuni; cat scratch disease (cat scratch fever, English-Wear infection, inoculation lymphoreticulosis, subacute localized lymphadenitis ); cellulitis; chancre; chancroid (soft chancre, papular chancroid); chronic lymphangitis; chronic recurrent erysipelas; chronic undermining burrowing ulcer (Meleney's gangrene ); condyloma latum; cutaneous actinomycosis; gangrenous dermatitis (gangrene of the skin); pustule; gangrenous pustule; elephantiasis; endemic typhus (exanthematous fever); exanthematous typhus (lice-borne exanthematous typhus); erysipelas (St. Anthony's fire, holy fire); Rosenbach's erysipeloid; erythema annulare; tinea rubra; carbuncle; mite-borne erysipelas; Flinders Island spotted fever; Musa sabificus (Flying squirrel typhus); folliculitis; Fournier's gangrene (Fournier's gangrene of the penis and scrotum); Furuncle (boil); gas gangrene (clostridial myonecrosis, myonecrosis); glanders (equinia, farcy, malleus); gonococcal sepsis (arthritis-dermatitis syndrome, disseminated gonococcal infection Infections); Gonorrhea (Clap); Gram-negative folliculitis; Gram-negative interdigital infection; Inguinal granuloma (Donovanosis, Genital inguinal granuloma, Tropical inguinal granuloma, Venereal granuloma, Venereal genital inguinal granuloma, Lupoid type of inguinal ulceration, Serpiginous ulceration of the groin, Ulcerated granuloma of the vulva, Ulcerated sclerosing granuloma); Green nail syndrome; Nosocomial Flunke disease; Hot tub folliculitis (Pseudomonas aeruginosa folliculitis); Human granulocytotropic anaplasmosis; Human mon ocytotropic ehrlichiosis; Contagious pustular dermatitis; Japanese spotted fever; Leptospirosis (Fort Bragg fever, Pretibial fever, Weil's disease); Listeriosis; Sublingual cellulitis; Lupus vulgaris; Lyme disease (Afzelius' disease, Lyme borreliosis); Inguinal lymph granulomatosis (Climatic bubo, Durand-Nicolas-Favre disease, Inguinal lymphogranuloma, Poradenitis inguinale, Strumous bubo); Malakoplakia (malacoplakia (malacoplakia)) ); Mediterranean spotted fever (Button fever); Melioidosis (Whitmore's disease); Meningococcemia; Missouri Lyme disease; Necrotizing fasciitis (Carnivorous bacteria syndrome); Neonatal toxic shock-like rash syndrome; Neonatal necrotizing stomatitis; North Asian tick typhus; Neonatal ophthalmia; Oroya fever (Carrion's disease); Perianal cellulitis (Perineal dermatitis, Streptococcal perianal disease); Apical abscess; Pinta; Punctate keratolysis (keratolysis pl antare sulcatum, Keratoma plantare sulcatum, Annular keratolysis); Plague; Primary gonococcal dermatitis; Pseudomonas pyoderma; Pseudomonas hot-foot syndrome; Suppurative paronychia; Suppurative myositis; Q fever; Queensland tick typhus Scarlet fever; Recurrent toxin-mediated perineal erythema; Nasal induration; Rocky Mountain spotted fever; Scarlet fever; Scrub typhus (scrub fever); Bacillary dysentery; Staphylococcal scalded skin syndrome (neonatal pemphigus, Ritter disease); Streptococcal intertrigo; Superficial pustular folliculitis (Bockhart impetigo, superficial folliculitis); Impetigo vulgaris (barber's itch, sycosis barbae); Syphilid; Syphilis (lues)); Tick-borne lymphadenopathy; Toxic shock syndrome (including streptococcal toxic shock syndrome, streptococcal toxic shock-like syndrome, toxic streptococcal syndrome); Trench fever (five-day fever, quintan fever, urban trench fever); Tropical ulcer (aden ulcer, jungle rot, Malabar ulcer, tropical phagedena)); Rabbit fever (deer farm fever, Ohara disease, Pervan Valley pest, rabbit fever); Peruvian warts; And yaws (bouba, framboesie, parangi, pian). Examples of mycobacterial skin infections that may be treated with the quaternary ammonium compounds of the present invention include, but are not limited to: Aquarium granuloma (fish tank granuloma, swimming pool granuloma); Borderline leproid type leprosy; Borderline leprosy; Borderline tuberculoid type leprosy; Buruli ulcer (Burns Dayle ulcer, Searl ulcer, Searl's ulcer); Erythema induratum (Bazin disease); Histoid leprosy; Lepromatous type leprosy; Leprosy (Hansen's disease); Lupus vulgaris (lupus tuberculosis); Miliary tuberculosis (disseminated tuberculosis, acute generalized cutaneous tuberculosis (tuberculosis cutis acuta generalisata), disseminated cutaneous tuberculosis (tuberculosis cutis disseminata)); Necrotic papular tuberculid; Primary inoculation tuberculosis (initial cutaneous change group, initial tuberculous change ).

[0594] Examples of mycobacterial skin infections that may be treated with the quaternary ammonium compounds of the present invention include, but are not limited to: Aquarium granuloma (fish tank granuloma, swimming pool granuloma); Borderline leproid type leprosy; Borderline leprosy; Borderline tuberculoid type leprosy; Buruli ulcer (Burns Dayle ulcer, Searl ulcer, Searl's ulcer); Erythema induratum (Bazin disease); Histoid leprosy; Lepromatous type leprosy; Leprosy (Hansen's disease); Lupus vulgaris (lupus tuberculosis); Miliary tuberculosis (disseminated tuberculosis, acute generalized cutaneous tuberculosis (tuberculosis cutis acuta generalisata), disseminated cutaneous tuberculosis (tuberculosis cutis disseminata)); Necrotic papular tuberculid; Primary inoculation tuberculosis (initial cutaneous change group, initial tuberculous change Group, chancre tuberculide); cutaneous adenopathy (scrofuloderma); tuberculosis of the mucocutaneous junction (acute tuberculous ulcer, orificial tuberculosis); verrucous tuberculosis of the skin (lupus vulgaris, necrotic verrucous vegetations, verrucous tuberculosis of the skin); tuberculous cellulitis; tuberculous gumma (metastatic tuberculous abscess, metastatic tuberculous ulcer); and tuberculoid leprosy.

[0595] Examples of fungal skin infections that may be treated with the quaternary ammonium compounds of the present invention include, but are not limited to: African histoplasmosis; Alternaria; Antibiotic candidiasis (iatrogenic candidiasis); black piedra; Candida auris, candidal intertrigo; candidal onychomycosis; candidal paronychia; candidal vulvovaginitis; candidal rash; chromoblastomycosis (black fungus, Cladosporium, Fonseca's disease, Pedroso's disease, Phaeosporotrichum, verrucous dermatitis); chronic mucocutaneous candidiasis; Coccidioides (California disease, desert rheumatism, San Joaquin Valley fever, valley fever); congenital cutaneous candidiasis; Cryptococcus; dermatophytid; diaper candidiasis; disseminated coccidioidomycosis (coccidioidal granuloma); distal subungual onychomycosis; Entomophthora; candidal interdigital erosions; favus; fungal folliculitis (Majocchi granuloma); Fusarium; Geotrichum; granuloma gluteale infantum; Histoplasma (cavernal disease, Darling's disease, Ohio Valley disease, reticuloendotheliosis); hyalohyphomycosis; tinea capitis; Loboa (keloidal blastomycosis, Lacaziosis, Lobo's disease); Mucor; mycetoma (Madura foot, Madura mycosis); North American blastomycosis (blastomycetic dermatitis, blastomycosis, Gilchrist's disease); onychomycosis (dermatophytic onychomycosis, ringworm of the nail, tinea unguium); oral candidiasis (thrush); otomycosis; perianal candidiasis; angular cheilitis (angular cheilosis); Phaeohyphomycosis; piedra (trichosporosis); Pityrosporum folliculitis; primary cutaneous aspergillosis; primary cutaneous coccidioidomycosis; primary cutaneous histoplasmosis; primary pulmonary coccidioidomycosis; primary pulmonary histoplasmosis; progressive disseminated histoplasmosis; proximal subungual onychomycosis; Rhinospodium; South American blastomycosis (Brazillian blastomycosis, paracoccidioidal granuloma, paracoccidioidomycosis); Sporotrichum (rose gardener's disease); systemic candidiasis; tinea barbae (barber's itch, tinea sycosis, tinea barbae); Tinea capitis (herpes tonsurans, ringworm of the scalp, scalp tinea, scalp ringworm, tinea tonsurans); Tinea corporis (ringworm, tinea circinata, tinea barbae ); Tinea gladiatorum; Tinea cruris (jock itch, tinea inguinalis, gym itch, rider's itch, tinea inguinalis); Tinea faciei; Tinea imbricata (tokelau); Tinea incognito; Tinea manuum; Tinea nigra (superficial phaeohyphomycosis, tinea nigra palmaris et plantaris); Tinea pedis (athlete's foot, foot ringworm); Dermatomycosis furfuracea (pityriasis versicolor, tinea flava); White piedra; Superficial white onychomycosis; And Zygomycosis (Phycomycosis).

[0596] In some embodiments, the quaternary ammonium compound of the present invention can be used to treat eye infections in a host, such as a human. Examples of eye infections that may be treated by the quaternary ammonium compound of the present invention include, but are not limited to: conjunctivitis, uveitis, hordeolum, blepharitis, chalazion, corneal ulcers and infections, dacryoadenitis, scleritis, keratitis, and iritis. In some embodiments, a method is provided that includes administering to a subject, such as a human, an effective amount of the quaternary ammonium compound or composition thereof described herein to treat an eye infection. In another embodiment, the method is used to treat eye infections in another mammal, such as a cat, dog, cow, pig, or horse.

[0597] In some embodiments, the quaternary ammonium compounds of the present invention can be used to treat keratitis in a host, such as a human. Keratitis can be caused by a plurality of infectious organisms, such organisms including the following: bacteria, such as Staphylococcus aureus and Pseudomonas aeruginosa; fungi, such as species of Fusarium, Candida, Aspergillus, and Curvularia; viruses, such as herpes simplex virus and varicella zoster virus; and amoebae, such as Acanthamoeba species, or combinations thereof. In some embodiments, the quaternary ammonium compounds of the present invention are used to treat bacterial keratitis in a host, such as a human.

[0598] In another embodiment, the quaternary ammonium compounds of the present invention are used to treat fungal keratitis in a host, such as a human. In another embodiment, the quaternary ammonium compounds of the present invention are used to treat viral keratitis in a host, such as a human. In another embodiment, the quaternary ammonium compounds of the present invention are used to treat Acanthamoeba keratitis in a host, such as a human. In another embodiment, the method is used to treat keratitis in another mammal, such as a cat, dog, cow, pig, or horse.

[0599] In some embodiments, the quaternary ammonium compounds of the present invention can be used to treat conjunctivitis in a host, such as a human. Conjunctivitis can be caused by a plurality of infectious organisms, such as the following: bacteria, such as Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, and Pseudomonas aeruginosa; and viruses, such as adenovirus and enterovirus. In some embodiments, the quaternary ammonium compounds of the present invention are used to treat bacterial conjunctivitis in a host, such as a human. In some embodiments, the quaternary ammonium compounds of the present invention are used to treat viral conjunctivitis in a host, such as a human. In another embodiment, the method is used to treat conjunctivitis in another mammal, such as a cat, dog, cow, pig, or horse.

[0600] In some embodiments, the quaternary ammonium compounds of the present invention are in a host, such as a human and can be used to treat ear infections. Ear infections can be present in the outer ear and / or ear canal (otitis externa), middle ear (otitis media), or inner ear (labyrinthitis). In some embodiments, provided is a method for treating an ear infection, the method comprising administering to a subject an effective amount of the quaternary ammonium compound or composition thereof described herein. In another embodiment, the method is used to treat ear infections in another animal, such as a cat, dog, cow, pig, or horse.

[0601] In some embodiments, the treatment method comprises applying a dressing material containing the quaternary ammonium compound of the present invention in an effective amount, either alone or as a pharmaceutical composition, to the infected site of a host in need of treatment. The dressing material is preferably shaped to fit within the space provided by the ear canal. The dressing material may be malleable, in which case it is possible to compress the dressing material and shape it to fit within the ear canal, or the dressing material may be rigid, in which case it is ensured that it rests against the ear canal wall and ensures proper contact and transfer of the antibacterial composition.

[0602] In some embodiments, the dressing material is placed in the ear canal for no more than one day. In other embodiments, the dressing material is placed in the ear canal for at least one week.

[0603] In some embodiments, a method of treating an infection in the ear canal of a host in need of treatment for an infectious disease comprises applying a dressing material to the host's ear canal and subsequently saturating the dressing material with an antibacterial composition. This method is thought to allow for sequential or continuous administration of the antibacterial composition while the dressing material is in place.

[0604] In some embodiments, the dressing material is composed of a soluble material that needs to be placed in the ear canal before being saturated with the antibacterial composition. In another embodiment, the dressing material is composed of a polymeric foam that expands when subsequently wetted with the antibacterial composition.

[0605] In some embodiments, a method of treating or preventing an infection in a chronic wound is provided, the method comprising administering, in an effective amount, the quaternary ammonium compound of the present invention alone or included in an antibacterial composition, to a host in need of such a method, for example, a human chronic wound. Types of chronic wounds include venous ulcers, diabetic ulcers, and pressure ulcers.

[0606] In some embodiments, a method of treating or preventing an infection in a chronic wound is provided, the method comprising applying a dressing containing one or more quaternary ammonium compounds of the present invention alone or in a composition to an infected site of a host in need of such a method.

[0607] In some embodiments, the quaternary ammonium compounds of the present invention can be used to treat fungal nail infections, i.e., onychomycosis, in a host, such as a human. A formulation for treating a nail infection must be able to penetrate deep into the nail bed.

[0608] In such embodiments, the antimicrobial composition is formulated using a solvent that can penetrate the host's nail bed, such as dimethyl sulfoxide.

[0609] In some embodiments, a method is provided for treating a fungal nail infection in a subject, the method comprising administering to the subject an effective amount of a quaternary ammonium compound or composition thereof described herein.

[0610] In some embodiments, the quaternary ammonium compounds of the present invention can be used to treat fungal vaginal infections, i.e., vulvovaginal candidiasis, in a host, such as a human. can be

[0611] In some embodiments, the antimicrobial composition is formulated as a vaginal suppository.

[0612] In some embodiments, a method is provided for treating a fungal vaginal infection in a subject, the method comprising administering to the subject an effective amount of a quaternary ammonium compound or composition thereof described herein.

[0613] Method for treating biofilms on abiotic surfaces The present invention includes a method of treating a biofilm on an abiotic surface with a quaternary ammonium compound or product or a mixture thereof described herein.

[0614] In some embodiments, the abiotic surface is treated directly with a solution containing one or more quaternary ammonium compounds of the invention (typically reconstituted from a sterile powder or solid).

[0615] In some embodiments, the abiotic surface is treated directly with a solution containing one or more quaternary ammonium compounds of the invention to remove and / or prevent the recurrence of a bacterial biofilm.

[0616] In some embodiments, the abiotic surface is treated directly with a solution containing one or more quaternary ammonium compounds of the invention to remove and / or prevent the recurrence of a fungal biofilm.

[0617] In some embodiments, the abiotic surface is treated directly with a solution containing one or more quaternary ammonium compounds of the invention to remove and / or prevent the recurrence of a viral contamination. In some embodiments, the abiotic surface is treated directly with a solution containing one or more quaternary ammonium compounds of the invention to prevent the transmission of SARS-CoV-2 from the treated surface to a host.

[0618] Abiotic surfaces can potentially harbor human pathogenic viruses or bacteria in both the intestine and the respiratory tract. Frequently touched abiotic surfaces can serve as points of transmission for bacterial, fungal, or viral contamination. Biofilms can be present on abiotic surfaces. Viral contamination can be present on abiotic surfaces. The abiotic surfaces are not particularly limited and include any surface where microorganisms can occur, or any such surface that can be exposed to microorganism or virus contact or contamination. By way of example and not limitation of the abiotic surfaces, there are surfaces present in hospitals, surgical centers, examination rooms, imaging centers, dental facilities, nursing homes, retirement homes, arena locker rooms, mass transportation vehicles (e.g., airplanes, trains, buses, and commercial vehicles), airports, railway stations, bus stops, public toilets, food or beverage processing facilities, manufacturing facilities, schools, dormitories, furniture, tables, desks, walls, atrium staircases, elevators, machine surfaces, surfaces exposed to water, such as private spas, hot tubs, saunas, bathtubs, or any surface exposed to the external environment, etc. Medical or surgical instruments or devices represent a special class of surfaces where biofilm formation can occur. This class can include any type of line, such as catheters (e.g., central venous catheters and urinary catheters), prostheses, such as heart valves, artificial joints, dentures, crowns, caps, and soft tissue implants (e.g., breast, buttock, and lip implants). Any type of implanted medical device is included (e.g., stents, intrauterine devices, pacemakers, cannulas for insertion, appliances or prostheses, lines or catheters). "Indwelling" medical devices can include devices where any part of the device is contained within the body, i.e., the device can be fully indwelling or partially indwelling.

[0619] The surface can be made of any material. By way of example and not limitation, metals such as aluminum, copper, nickel plating, gold plating, steel, stainless steel, chromium, titanium, iron, and alloys, etc. can be mentioned. As examples of surfaces which are not additional limitations, plastics such as polyolefins (e.g., polyethylene, (ultra-high molecular weight) polyethylene, polypropylene, polystyrene, poly(meth)acrylate, acrylonitrile, butadiene, ABS, acrylonitrile butadiene, etc.), polyesters (e.g., polyethylene terephthalate, etc.), and polyamides (e.g., nylon), or combinations thereof, etc. can be mentioned. As other examples, acetal copolymers, polyphenyl sulfone, polysulfone, polyether imide, polycarbonate, polyvinylidene fluoride, poly(methyl methacrylate), and poly(tetrafluoroethylene) can be mentioned. The surface can also be brick, glass, Formica, tile, pottery, porcelain, wood, vinyl, linoleum, or carpet, or combinations thereof.

[0620] Powder formulations for use in the present invention In some embodiments, one or more of the active quaternary ammonium compounds of the present invention can be provided as a powder formulation. The powder formulation can be prepared by removing any residual solvents, for example, by sublimation or boiling. In one embodiment, lyophilization is utilized to create the powder for the formulation. This is because the integrity of the product is typically maintained due to the low temperature used in the process. Additionally, the lyophilized solid can be more rapidly and easily reconstituted due to the presence of microscopic pores formed during the process. The high vacuum used during lyophilization ensures the thorough removal of any undesirable volatile components, such as methanol, ethanol, or other volatile organic substances. In some embodiments, the powder formulations of the quaternary ammonium compounds and products described herein contain less than about 5%, about 4%, about 3%, about 2%, about 1%, about 0.5%, or about 0.01% methanol by weight. The lyophilization method for solids, especially sensitive materials, used in pharmaceutical applications is known in the art. Lyophilization can be performed using any commercially available device, such as a shelf / cabinet type, contact type, radiant type, or microwave-assisted lyophilizer.

[0621] A typical lyophilization procedure consists of four steps. In the first step (pretreatment), the active quaternary ammonium compound is dissolved in a suitable solvent, and, if necessary for improving stability, preserving appearance, or enhancing subsequent processing, additional excipients are optionally added. Further, the solution of the active quaternary ammonium compound can be concentrated to be suitable for assisting in the freezing and subsequent sublimation processes. Additionally, each component can be initially individually instantaneously frozen to ensure that a free-flowing solid is formed upon completion of lyophilization.

[0622] In the second step (freezing), in the container, the solution of the active quaternary ammonium compound is frozen at a temperature lower than the triple point of the solution to ensure that sublimation, rather than melting, occurs. Optionally, this material can be subjected to a cycle of raising and lowering the temperature in a process called annealing. If the quaternary ammonium compound to be lyophilized is an amorphous solid, this compound may not have a triple point, but instead has a critical point. The amorphous solid must be maintained at a temperature lower than the critical point throughout the lyophilization process to prevent the solid from remelting or collapsing during subsequent drying steps. In the case of sensitive materials, the freezing step is often carried out rapidly by lowering the material temperature to about -50°C to -80°C. This prevents the formation of large solvent crystals that could reduce the structural integrity of the material being lyophilized and lead to a defective structure.

[0623] In the third step (primary drying), the pressure in the container is reduced (typically in the range of a few millibars), and a minimum amount of heat is applied to the material to allow the solvent to sublime. The pressure is typically controlled by the application of a partial vacuum. A small amount of heat can be applied to facilitate the sublimation of the solvent molecules. Due to the low air density inside the container, typically this heat is applied via conduction or radiation.

[0624] In the fourth step (secondary drying), the temperature is raised to a higher temperature than in the primary drying stage to remove any remaining unfrozen solvent molecules. A temperature increase is necessary to break any possible physicochemical interactions that may have formed between the solvent molecules and the frozen material. Further, typically the pressure is reduced compared to the primary drying step to facilitate desorption.

[0625] Upon completion of the lyophilization process, the vacuum is typically released with an inert gas, such as nitrogen, and sealed in a suitable container. Examples of typical containers include sealed ampoules containing a sealed glass that is broken open at the desired time of use. The active material can subsequently be reconstituted at the time of use with a suitable carrier, which can be, for example, those described herein, such as sterile water or glycerin.

[0626] Antibacterial composition The active quaternary ammonium compounds described herein can be administered as a pure chemical substance to a host in need thereof, but more typically are administered as an antibacterial composition containing the active quaternary ammonium compound or combination thereof as described herein in an amount effective for a host in need of such treatment, typically a human.

[0627] In some embodiments, the present disclosure provides an antibacterial composition comprising an effective amount of a quaternary ammonium compound together with at least one pharmaceutically acceptable carrier for any of the uses described herein. The pharmaceutical composition may contain the quaternary ammonium compound as the sole active agent.

[0628] In alternative embodiments, a quaternary ammonium compound and at least one additional active agent. In typical formulations, the selected quaternary ammonium compound of the invention is provided as a sterile powder or solid that is reconstituted at the time of use.

[0629] The effective amount of the active quaternary ammonium compound as described herein, or used in combination or alternately with another active agent, or the active quaternary ammonium compound as described herein when used prior to, simultaneously with, or subsequent to another active agent, is such that it (a) inhibits the progression of the infectious diseases described herein; (b) causes regression of the infectious diseases described herein; (c) causes cure of the infectious diseases described herein; or can be used in an amount sufficient to inhibit or prevent the onset of the infectious diseases described herein. Thus, the effective amount of the active quaternary ammonium compound or composition described herein, when administered to a patient to provide a clinical benefit, will provide the active agent in a sufficient amount.

[0630] The exact amount of the active quaternary ammonium compound or antimicrobial composition described herein that is to be delivered to the required host, typically a human, will be determined by a healthcare provider so as to achieve the desired clinical benefit.

[0631] In certain embodiments, the antimicrobial composition is in unit dosage form and contains from about 0.1 mg to about 2000 mg, from about 10 mg to about 1000 mg, from about 100 mg to about 800 mg, or from about 200 mg to about 600 mg of the active quaternary ammonium compound, and optionally from about 0.1 mg to about 2000 mg, from about 10 mg to about 1000 mg, from about 100 mg to about 800 mg, or from about 200 mg to about 600 mg of an additional active agent.

[0632] By way of example, dosage forms exist that contain at least about 0.5 mg, 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1250 mg, 1300 mg, 1400 mg, 1500 mg, or 1600 mg of the active quaternary ammonium compound. In some embodiments, the dosage form contains at least about 1 mg, 5 mg, 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 200 mg, 400 mg, 500 mg, 600 mg, 1000 mg, 1200 mg, or 1600 mg of the active quaternary ammonium compound. The dosage form can be administered, as needed, for example, once a day (q.d.), twice a day (b.i.d.), three times a day (t.i.d.), four times a day (q.i.d.), once every two days (Q2d), once every three days (Q3d), or any dosing schedule that provides treatment of the disorders described herein.

[0633] The antimicrobial composition can contain, for example, an active quaternary ammonium compound and an additional active agent in a molar ratio to achieve the desired result. For example, the pharmaceutical composition can contain the additional active agent in combination with the active quaternary ammonium compound described herein in a molar ratio of at least about 0.5:1, at least about 1:1, at least about 2:1, at least about 3:1, or about 1.5:1 to about 4:1 (additional active agent:active compound).

[0634] The quaternary ammonium compounds disclosed herein or used as described herein can be administered topically, by spray, cream, gel, foam, suppository, via an implant including an ocular implant, transdermally, in a dermatological formulation, or as an eye drop, in a unit dosage form formulation containing a conventional pharmaceutically acceptable carrier. In the case of ocular delivery, the quaternary ammonium compound can be provided, if desired, in an immediate or controlled release mode, for example, as a solution, suspension, or other formulation, or via an ocular device, or as a solution or suspension provided as a formulation for topical administration, for example, as an eye drop.

[0635] The antimicrobial composition can be formulated in any pharmaceutically useful form, for example, as an aerosol, cream, gel, foam, microparticles, nanoparticles, injectable or infusion solution, transdermal patch, subcutaneous patch, suppository, dry powder, incorporated into a medical device, and formulated as a parenteral formulation, a dermatological formulation, or an eye drop or suspension. Some dosage forms can be further divided into unit dosages of appropriate size containing the active ingredient in an appropriate amount, for example, an effective amount to achieve the desired purpose.

[0636] Compositions suitable for administration as contemplated herein and methods for manufacturing such compositions are known in the art. Examples of known techniques include, for example, U.S. Patent Nos. 5,723,269 and 9,060,938, which are hereby incorporated by reference in their entirety.

[0637] The antimicrobial compositions contemplated herein can optionally include a carrier. The carrier must be of sufficiently high purity and sufficiently low toxicity to be suitable for administration to the patient being treated. The carrier may be inert or may itself have a pharmaceutical benefit. The amount of carrier used in combination with the quaternary ammonium compound is an amount sufficient to provide a practical amount of material per unit dose of the compound for administration.

[0638] Examples of classes of carriers include, but are not limited to, binders, buffers, coloring agents, diluents, disintegrants, emulsifiers, fillers, flavoring agents, fluidizing agents, lubricants, pH adjusters, preservatives, stabilizers (e.g., xanthan gum, polyvinylpyrrolidone (PVP), guar gum, polyvinyl alcohol (PVA), etc.), surfactants, solubilizing agents, tabletting agents, thickeners (e.g., xanthan gum, polyvinylpyrrolidone (PVP), guar gum, polyvinyl alcohol (PVA), etc.), gelling agents, and wetting agents (e.g., urea, etc.).

[0639] Some carriers may be listed in more than one class; for example, vegetable oils may be used as lubricants in some formulations and as diluents in other formulations. Examples of pharmaceutically acceptable carriers include sugars, starches, celluloses, powdered tragacanth, malt, gelatin, talc, and vegetable oils. Examples of other matrix materials, fillers, or diluents include lactose, mannitol, xylitol, crystalline cellulose, calcium phosphate dibasic, and starch. Examples of surfactants include sodium lauryl sulfate and polysorbate 80.

[0640] Examples of drug complexing or solubilizing agents include polyethylene glycol, caffeine, xanthine, gentisic acid, and cyclodextrins.

[0641] Examples of disintegrants include sodium starch glycolate, sodium alginate, sodium carboxymethyl cellulose, methyl cellulose, colloidal silicon dioxide, and croscarmellose sodium. Examples of binders include methyl cellulose, crystalline cellulose, starch, and gums such as guar gum and tragacanth.

[0642] Examples of lubricants include magnesium stearate and calcium stearate.

[0643] Examples of pH adjusters include acids such as citric acid, acetic acid, ascorbic acid, lactic acid, aspartic acid, succinic acid, phosphoric acid, etc.; bases such as sodium acetate, potassium acetate, calcium oxide, magnesium oxide, trisodium phosphate, sodium hydroxide, calcium hydroxide, aluminum hydroxide, etc., and buffers generally containing a mixture of an acid and a salt of the acid. Other optional active agents that do not substantially interfere with the activity of the quaternary ammonium compounds of the present invention can also be included in the pharmaceutical composition.

[0644] Examples, not limitations, of aqueous solutions that can be used as carriers include distilled water, physiological saline, plasma, bone marrow aspirate, buffer solutions such as Hank's balanced salt solution (HBSS), HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), Ringer's buffer, ProVisc™, diluted ProVisc™, ProVisc™ diluted with PBS, Krebs buffer, Dulbecco's PBS, normal PBS, sodium hyaluronate solution, simulated body fluid, concentrated plasma platelets, tissue culture medium, aqueous solutions containing organic solvents, and mixtures thereof. In all cases, the solution can be sterilized in a manner appropriate and known to those skilled in the art.

[0645] In certain embodiments, the antimicrobial composition contains a polymeric material. The polymeric material must be biocompatible so that it can be administered to a patient without undesirable effects. Polymers are known in the art and are the subject of extensive literature and patents. In certain embodiments, the polymer is present in an amount effective to provide the desired viscosity and wettability for the desired application, for example, in the treatment of infected wounds. The specific amount of polymer used depends on a number of factors, such as, by way of example and not limitation, the specific chemical composition of the polymer used, the molecular weight of the specific polymer used, the viscosity of the desired antimicrobial composition, and the level of water retention and release desired for the particular polymer.

[0646] In certain embodiments, the antimicrobial composition is used in a polymeric material for medical, personal, or industrial use. Examples of medical uses include wound healing materials, medical devices, appropriate protective gear, artificial cartilage, biomaterials, catheters, other implantable and non-implantable devices (e.g., surgical sponges, and packaging), medical patches or devices, such as orthopedic or dental patches or devices, eye drops or suspensions, short-term wound packing, direct application to eye tissue drugs, hydrophilic coating agents for catheters, lead wires, etc., or vascular embolization agents, etc., but are not limited thereto.

[0647] In certain embodiments, the antimicrobial composition is used in polymeric materials for medical devices, pacemakers, contact lenses, dentures, prostheses, heart valves, and covers for preventing medical device infections such as joints; biomaterials, implantable devices, non-implantable devices, wound healing materials, personal protective materials, such as gloves, face masks, surgical / hospital gowns, clothing, sheets, woven or non-woven materials, sponges; medical devices, such as orthopedic or dental devices, eye drops or suspensions, intraocular inserts, ophthalmic films, selective eye delivery, short-term wound packing, direct application to eye tissue, hydrophilic coating agents for catheters, lead wires, etc., or vascular embolization agents, etc.

[0648] In certain embodiments, the polymeric material includes a polymer, a thermoplastic polymer, a thermosetting polymer, a biodegradable polymer, a modified polymer, a crosslinked polymer, a polymer for controlled delivery, a hydrogel, a hydrophilic colloid, a liquid-forming polymer, a gel-forming polymer, a silicone-based polymeric material, a film-forming polymer, a polymeric adhesive, a copolymer for controlled delivery, a medical polymer, a copolymer, or a mixture thereof, etc.

[0649] In certain embodiments, the silane quaternary ammonium compound and the polymeric material described herein are in a ratio of at least 1:1000:1000:1; 1:500:500:1, 1:300:300:1, 1:250:250:1; 1:200:200:1; 1:150:150:1; 1:100:100:1; 1:75:75:1; 1:50:50:1; 1:40:40:1; 1:30:30:1, 1:25:25:1; 1:20:20:1; 2:25:15:1; 1:10:10:1; 1:5:5:1; 1:3:3:1; 1:2:2:1; or 1:1.

[0650] In certain embodiments, the composition of the silane quaternary ammonium compound and the polymeric material forms a solid stable composition.

[0651] In certain embodiments, the composition forms a clear stable solution. In certain embodiments, the composition is stable for at least one month. In certain embodiments, the composition is stable for at least two months. In certain embodiments, the composition is stable for at least three months.

[0652] In certain embodiments, the silane quaternary ammonium compound described herein is mixed with the polymer described herein to form a flexible film. In certain embodiments, the film exists at various thickness levels suitable for the specific applications described herein.

[0653] In certain embodiments, the silane quaternary ammonium compounds described herein are incorporated into polyvinyl alcohol. In certain embodiments, the resulting product is used in medical applications and devices such as soft contact lenses, eye drops, embolization particles, tissue adhesion barriers, and as artificial cartilage and menisci. In certain embodiments, the resulting product is a medical device implant material for cartilage replacement surgery. In certain embodiments, the resulting product is transiently used as a short-term wound packing material, a direct patch to eye tissue, a catheter, a hydrophilic coating agent for lead wires, or an embolization agent for blood vessels. See, for example, Baker, M., et al., "A review of polyvinyl alcohol and it uses in cartilage and orthopedic applications", Wiley Online Library. DOI: 10.1002 / jbm.b.32694 (2012), which is incorporated herein by reference in its entirety.

[0654] In certain embodiments, the polymer is a polyvinyl alcohol hydrogel. In certain embodiments, polyvinyl alcohol hydrogen is useful for drug delivery systems. In certain embodiments, the drug delivery systems include, for example, ocular inserts, ophthalmic films, nanoparticles, microspheres, floating microspheres, mucoadhesive agents, or selective drug delivery agents. In certain embodiments, the drug delivery system is an ocular insert, an ophthalmic film, a microsphere, a floating microsphere, or a selective drug delivery agent.

[0655] Polyvinyl alcohol hydrogel is a polymer used as a matrix for sustained-release hydrogel drug delivery systems in solid, liquid, and semi-solid forms that are biocompatible and toxicologically safe. Polyvinyl alcohol hydrogel has excellent physical properties like a mucoadhesive and, by swelling, it becomes suitable for various drug delivery applications. For example, see Gajra, Balaram & Pandya et al., "Poly vinyl alcohol Hydrogel and its Pharmaceutical and Biomedical Applications: A Review", International Journal of Pharmaceutical Research, 2011, 4. 20-26, which is hereby incorporated by reference and made a part of this specification.

[0656] In some examples, the antimicrobial composition contains a hydrogel. The hydrogel must be biocompatible so that it can be administered to a patient without undesirable effects. Hydrogels are known in the art and are the subject of a wide range of literature and patents. The hydrogel is present in an effective amount to provide the desired viscosity and wetness as required for the desired application, for example, in the treatment of infected wounds. The specific amount of hydrogel used depends on a plurality of factors, such as, by way of example and not limitation, the specific chemical composition of the hydrogel used, the molecular weight of the specific hydrogel used, the viscosity of the desired antimicrobial composition, and the level of water retention and release desired for the particular hydrogel.

[0657] In some embodiments, the hydrogel controls the release rate of one or more quaternary ammonium compounds of the present invention. In some embodiments, the hydrogel is biodegradable. Examples of useful hydrogel carriers include, but are not limited to, poly(vinyl alcohol), sodium polyacrylate, poly(acrylamide), poly(N-vinyl-2-pyrrolidone), poly(N-isopropylacrylamide), cross-linked carboxymethyl cellulose, cross-linked polyethylene glycol, poly(lactic acid), hyaluronic acid, sodium alginate, agarose, starch, chitosan, methyl cellulose, polyethylene oxide, amorphous hydrogel, cross-linked polymer gel with high water content, copolymers thereof, derivatives thereof, mixtures thereof, etc.

[0658] In some examples, the antimicrobial composition contains a hydrophilic colloid. In some embodiments, the hydrophilic colloid can interact with the infection site by forming a gel. The hydrophilic colloid can be present to provide a combination of moisture and absorbency at the site where it is deemed necessary. Examples of hydrophilic colloids include natural gums such as gum arabic, ghatti gum, karaya gum, tragacanth gum, guar gum, locust bean gum, acacia gum, etc.; seaweed extracts such as agar, algin, alginates, and carrageenan, etc., cereal gums, starch, microbial gums such as dextran gum and xanthan gum, etc., pectin, gelatin, casein, collagen, polyvinyl pyrrolidone, low methoxyl pectin, propylene glycol alginate, carboxymethyl locust bean gum, carboxymethyl guar gum, and modified forms that are oxidized, acetylated, carboxylated, esterified, methylated, aminated, etherified, sulfated, borated, or phosphorylated, absorbent colloidal materials having elastomers coated with polyurethane, etc., but are not limited to these.

[0659] In certain embodiments, the antimicrobial composition for administration further comprises a quaternary ammonium compound as described herein, and optionally, a phospholipid; phosphatidylcholine; dipalmitoyl phosphatidylcholine (DPPC); dioleoyl phosphatidylethanolamine (DOPE); dioleoyl oxypropyltriethylammonium (DOTMA); dioleoyl phosphatidylcholine; cholesterol; cholesterol ester; diacylglycerol; diacylglycerol succinate; diphosphatidylglycerol (DPPG); hexadecanol; a fatty alcohol such as polyethylene glycol (PEG); polyoxyethylene-9-lauryl ether; a surfactant fatty acid such as palmitic acid or oleic acid; a fatty acid; a fatty acid monoglyceride; a fatty acid diglyceride; a fatty acid amide; sorbitan trioleate (Span™ 85) glycocholate; sorbitan monolaurate (Span™ 20); polysorbate 20 (Tween™ 20); polysorbate 60 (Tween™ 60); polysorbate 65 (Tween™ 65); polysorbate 80 (Tween™ 80); polysorbate 85 (Tween™ 85); polyoxyethylene monostearate; surfactin; a poloxomer; a sorbitan fatty acid ester such as sorbitan trioleate ; lecithin; lysophosphatidylcholine; phosphatidylserine; phosphatidylinositol; sphingomyelin; phosphatidylethanolamine (cephalin); cardiolipin; phosphatidic acid; cerebroside; dicetyl phosphate; dipalmitoyl phosphatidylglycerol; stearylamine; dodecylamine; hexadecylamine; acetyl palmitate; glycerol ricinoleate; hexadecyl stearate; isopropyl myristate; tyloxapol; poly(ethylene gly Call) 5000 - phosphatidylethanolamine; poly(ethylene glycol) 400 - monostearate; phospholipid; synthetic and / or natural detergents having high surfactant properties; deoxycholate; cyclodextrin; chaotropic salts; ion pairing agent; glucose, fructose, galactose, ribose, lactose, su crose, maltose, trehalose, cellobiose, mannose, xy lose, arabinose, glucoronic acid, galactoronic acid, mannuronic acid, glucosamine, galatosamine and neuramic acid; pullulan, cellulose, microcrystalline cellulose, hydroxyprop Hypromellose (HPMC), hydroxycellulose (HC), methylcellulose (MC), dextran, cyclodextran, glycogen, hydroxyethyl starch, carrageenan, glycon, amylose, chitosan, N,O-carboxymethyl chitosan, algin and alginic acid, starch, chitin, inulin, konjac, glucomannan, pustulan, heparin, hyaluronic acid, curdlan and xanthan, mannitol, sorbitol, xylitol, erythritol, maltitol and lactitol, pluronic polymer, polyethylene, polycarbonate (e.g., poly(1,3-dioxan-2-one)), polyanhydride (e.g., poly(sebacic anhydride)), polypropyl fumarate, polyamide (e.g., polycaprolactam), polyacetal, polyether, polyester (e.g., polylactide, polyglycolide, polylactide-co-glycolide, polycaprolactone, polyhydroxy acid (e.g., poly((β-hydroxyalkanoate))), poly(orthoester), polycyanoacrylate, polyvinyl alcohol, polyurethane, polyphosphazene, polyacrylate, polymethacrylate, polyurea, polystyrene and polyamine, polylysine, polylysine-PEG copolymer and poly(ethyleneimine), poly(ethyleneimine)-PEG copolymer, glycerol monocaprylocaprate, propylene glycol, vitamin E TPGS (also known as d-α-tocopheryl polyethylene glycol 1000 succinate), gelatin, titanium dioxide, polyvinyl pyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), hydroxypropyl Cellulose (HPC), methylcellulose (MC), block copolymer of ethylene oxide and propylene oxide (PEO / PPO), polyethylene glycol (PEG), sodium carboxymethyl cellulose (NaCMC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), containing one or more of them.

[0660] In some embodiments, the antimicrobial composition can include a polymer for the controlled delivery of the described compounds, and such polymers include Pluronic polymers, polyesters (e.g., polylactic acid, poly(lactic-co-glycolic acid), polyethylene terephthalate (PET), glycol-modified polyethylene terephthalate (PETG), polybutylene terephthalate (PBT), polycyclohexylene dimethylene terephthalate (PCT), polycyclohexylene dimethylene terephthalate glycol (PCTG), acid-modified polycyclohexylene dimethylene terephthalate (PCTA), polytrimethylene terephthalate (PTT), woven and non-woven polyethylene terephthalate (PET), spunbond, spunlace, embossed polyethylene terephthalate, LDPE non-woven polyethylene terephthalate, glycol-modified polyethylene terephthalate (PETG), or another type of polyester that can include monomers or comonomers having other carboxylic acid or alcohol functional groups), polycaprolactone, polyvalerolactone, poly(1,3-dioxan-2-one)); polyanhydrides (e.g., poly(sebacic anhydride)); polyethers (e.g., polyethylene glycol); polyurethanes; polymethacrylates; polyacrylates; and polycyanoacrylates, but are not limited thereto.

[0661] In some embodiments, the polymer can be modified using polyethylene glycol (PEG), using carbohydrates, and / or using acyclic polyacetals derived from polysaccharides. See, for example, Papisov, 2001, ACS Symposium Series, 786:301, which is hereby incorporated by reference in its entirety.

[0662] In certain embodiments, additional polymers include polyolefins (including cyclic polyolefins), which include polypropylene and polyethylene; polyvinyl chloride; polystyrene; polyvinylidene chloride; polynorbornene; polyimide; polyamide; polyurethane; polystyrene; polyvinylidene chloride; polyvinyl chloride; polylactic acid; or combinations of one or more thereof, but are not limited thereto.

[0663] In some embodiments, the antimicrobial composition contains a biodegradable polymer. The biodegradable polymer must be biocompatible so that it can be administered to a patient without undesirable effects. Biodegradable polymers are known in the art and are the subject of a wide range of literature and patents. The biodegradable polymer or combination of polymers can be selected to provide desirable properties for the selected application, such as an appropriate mix of hydrophobic and hydrophilic qualities, half-life and degradation rate, compatibility with one or more of the quaternary ammonium compounds of the present invention to be delivered, and appropriate behavior at the site of application, but are not limited thereto.

[0664] In some embodiments, the biodegradable polymer gels in the presence of an aqueous solution, such as that present at a wound or infection site.

[0665] In some embodiments, the biodegradable polymer carrier provides release of one or more of the quaternary ammonium compounds of the present invention to the site of infection at a desired rate. Examples of useful biodegradable polymers include poly(lactic acid), polyglycolic acid, poly(D,L-lactide-co-glycolide), poly(D,L-lactic acid), polyester, poly(caprolactone), poly(3-hydroxybutyrate), poly(s-caproic acid), poly(p-dioxanone), poly(propylene fumarate), poly(ether (orther) ester), polyol / diketone acetal Examples include, but are not limited to, lauryl, poly(sebacic anhydride), poly(maleic anhydride), poly(carboxybis-carboxyphenoxyphosphazene), poly[bis(p-carboxyphenoxy)methane], poly(amino acids), or copolymers thereof.

[0666] Optional active ingredients that do not substantially interfere with the activity of one or more of the quaternary ammonium compounds of the present invention used in the present invention can be included in the antibacterial composition. In certain embodiments, two or more carrier components can be combined if considered necessary for a particular application.

[0667] In some embodiments, the antibacterial composition further comprises one or more additional additives, such as urea and / or DMSO. These quaternary ammonium compounds can be included to enhance the effectiveness of the desired antibacterial composition in penetrating the site of infection, to assist if considered necessary in tissue healing or symptom relief at the site of infection, or to extend the effective shelf life of the antibacterial composition either alone or in combination with other active agents.

[0668] In some embodiments, the antimicrobial composition further comprises a surfactant. By adding a surfactant, the complex hydrophobic / hydrophilic interactions between the biofilm layers can be disrupted, thereby facilitating the penetration of one or more quaternary ammonium compounds of the present invention into the subsurface layer of the biofilm present at the site of infection. The addition is made when it is shown that one or more quaternary ammonium compounds of the present invention are insufficient for this purpose alone. The selected surfactant additive can be selected to provide the desired properties to the antimicrobial composition, and the desired properties are, for example, the stability of the surfactant and one or more quaternary ammonium compounds of the present invention in a suitable carrier, the desired level of penetration into the biofilm, and the level of reactivity with other components in the composition. Suitable surfactants are believed to be selectable by those skilled in the art. In some embodiments, the surfactant can facilitate the leaching of one or more quaternary ammonium compounds of the present invention from the selected carrier.

[0669] In some embodiments, the surfactant can facilitate the leaching of one or more quaternary ammonium compounds of the present invention from either the formulated microparticles or the polymeric nanoparticles. Examples of suitable surfactants include, but are not limited to, octenidine dihydrochloride, cetrimonium bromide (CTAB), cetylpyridinium chloride (CPC), benzalkonium chloride (BAC), benzethonium chloride (BZT), dimethyldioctadecylammonium chloride, dioctadecyldimethylammonium bromide (DODAB), cocamidopropyl hydroxysultaine (CAHS), cocamidopropyl betaine (CAPB), cocamide MEA, sodium oxyclorosen, and combinations thereof.

[0670] In some embodiments, the antimicrobial composition further comprises a buffering agent. Some of the other additive candidates for the antimicrobial composition (e.g., urea and / or DMSO) may require a very narrow pH range to function optimally. The buffering agent can be provided at an appropriate concentration to maintain the optimal pH range. Buffering agents optimized for specific desired applications would be known to those skilled in the art. Examples of suitable buffering agents include, but are not limited to, citrate, sulfonate, carbonate, acetate, borate, gluconate, phosphate, or combinations thereof.

[0671] In some embodiments, the antimicrobial composition further comprises a suitable enzyme. Adding an enzyme can assist in disrupting an established biofilm, either by degradation of extracellular polymeric substances (EPS) or by suppressing intercellular communication sent via ion channels in the form of electrical signals to coordinate cell behavior. In some embodiments, the enzyme may be a protease. The protease may be able to act on some of the polymeric materials present in the EPS, thereby improving the penetration of the antimicrobial composition. Examples of proteases include, but are not limited to, collagenase, cellulase, keratinase, papain, bromelain, trypsin, thermolysin, and combinations thereof.

[0672] In some embodiments, the antimicrobial composition further comprises a suitable tissue growth promoter. In some applications, the biofilm-induced infection being treated is present within a wound. Inclusion of a suitable tissue growth promoter may help to promote the regrowth of the tissue within the existing wound during the time of treating the infection with a dressing. Examples of suitable tissue growth promoters include, but are not limited to, endothelial cell growth factor (ECGF), epithelial growth factor (EGF), fibroblast growth factor (FGF), hepatocyte growth factor (HGF), nerve growth factor (NGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF), or combinations thereof.

[0673] In some embodiments, the antimicrobial composition further comprises a preservative. Although one or more of the quaternary ammonium compounds of the present invention are antibacterial in nature, an additional preservative can optionally be included depending on the desired shelf life of the antimicrobial composition. Examples of suitable preservatives include, but are not limited to, methylparaben, propylparaben, benzyl alcohol, benzalkonium chloride, sorbic acid, phenol, phenylethyl alcohol, BHA, BHT, or combinations thereof.

[0674] In some embodiments, the antimicrobial composition further comprises an antioxidant. Antioxidants may be necessary to stabilize any other additives present in the antimicrobial composition against air oxidation over a suitable shelf life. Examples of suitable antioxidants include, but are not limited to, ascorbic acid, BHA, BHT, sodium bisulfite, vitamin E, sodium metabisulfite, propyl gallate, or combinations thereof.

[0675] In some embodiments, the antimicrobial composition further comprises an astringent. Adding an astringent to the antimicrobial composition may desirably cause contraction of the surface tissue having an infection, thereby facilitating penetration of the antimicrobial composition into the infected space. Examples of suitable astringents include, but are not limited to, zinc oxide, ferric oxide, zinc sulfate, silver nitrate, potassium permanganate, aluminum chloride, aluminum acetate, formaldehyde, blow liquid, benzoin tincture, or combinations thereof.

[0676] An antimicrobial composition suitable for topical application to the skin preferably takes the form of an ointment, cream, lotion, foam, paste, gel, spray, aerosol, or oil. Usable carriers include petrolatum, lanolin, polyethylene glycol, alcohol, transdermal enhancers, and combinations of two or more thereof.

[0677] Antibacterial compositions suitable for transdermal administration can be provided as discrete patches configured to maintain intimate contact with the recipient's epidermis for an extended period. Antibacterial compositions suitable for transdermal administration can also be delivered by iontophoresis (see, e.g., Pharmaceutical Research 3(6):318 (1986)), which typically takes the form of an optionally buffered aqueous solution of an active quaternary ammonium compound. In some embodiments, a microneedle patch or device for delivering a drug across or into living tissue, particularly skin, is provided. The microneedle patch or device enables delivery of a drug across or into skin or other tissue barriers at clinically relevant rates with minimal or no tissue damage, pain, or irritation.

[0678] Many methods and devices for drug delivery to the eye are known in the art. Non-limiting examples are described in the following patents and patent applications (which are hereby incorporated by reference in their entirety). Examples include U.S. Patent No. 8,192,408 to Psivida Us, Inc. entitled "Ocular trocar assembly"; U.S. Patent No. 7,585,517 to Macusight, Inc. entitled "Transcleral delivery"; U.S. Patents Nos. 5,710,182 and 5,795,913 to Santen OY entitled "Ophthalmic composition"; U.S. Patent No. 8,66 3,639 entitled "Formulations for treating ocular diseases and conditions"; and U.S. Patent No. 8,663,639 "Formulations and methods for vascular permeability-related diseases or conditions" entitled U.S. Patent No. 8,486,960, "Liquid formulations for treatment of diseases or conditions"; U.S. Patent No. 8,3 67,097; and U.S. Patent No. 8,927,005, "Delivering substance and drug delivery system using the same" (Santen Pharmaceutical Co., Ltd.); "Conformable Therapeutic Shield For Vision and Pain", International Publication No. WO 2011 / 050365; and "Therapeutic Device for Pain Management and Vision", International Publication No. WO 2009 / 145842 (Forsight Labs, LLC); "Implantable therapeutic device", U.S. Patent No. 9,066,779 and U.S. Patent No. 8,623,395; "Ophthalmic Implant for Delivering Therapeutic Substances", International Publication No. WO 2014 / 160884; "Posterior segment drug delivery", International Publication No. U.S. Patent No. 8,399,006, U.S. Patent No. 8,277,830, U.S. Patent No. 8,795,712, U.S. Patent No. 8,808,727, U.S. Patent No. 8,298,578, and International Publication No. 2010 / 088548, International Publication No. 2014 / 152959 entitled "Systems for Sustained Intraocular Delivery of Low Solubility Compounds from a Port Delivery System Implant," and U.S. Patent Application Publication No. 20140276482 entitled "Injector apparatus and method for drug delivery," U.S. U.S. Patent No. 8,905,963 and U.S. Patent No. 9,033,911, International Publication No. 2015 / 057554 entitled "Formulations and Methods for Increasing or Reducing Mucus," U.S. Patent No. 8,715,712 and U.S. Patent No. 8,939,948 entitled "Ocular insert apparatus and methods," International Publication No. entitled "Insertion and Removal Methods and Apparatus for Therapeutic Devices" International Publication No. 2014 / 066775 entitled "Ophthalmic System for Sustained Release of Drug to the Eye", International Publication No. 2015 / 085234 and International Publication No. 2012 / 019176 entitled "Implantable Therapeutic Device", International Publication No. 2012 / 065006 entitled "Methods and Apparatus to determine Porous Structures for Drug Delivery", International Publication No. 2010 / 141729 entitled "Anterior Segment Drug Delivery", International Publication No. 2011 / 050327 entitled "Corneal Denervation for Treatment of Ocular Pain", International Publication No. 2013 / 022801 entitled "Small Molecule Delivery with Implantable Therapeutic Device", International Publication No. 2012 / 019047 entitled "Subconjunctival Implant for Posterior Segment Drug Delivery", International Publication No. 2012 / 068549 entitled "Therapeutic Agent Formulations for Implanted Devices", International Publication No. 2012 / 019139 entitled "Combined Delivery Methods and Apparatus", International Publication No. 2012 / 019139 entitled "Ocular Insert Apparatus and Methods", International Publication No. 20 ​​​​International Publication No. WO 2012 / 019136, titled "Injector Apparatus and Method for Drug Delivery", and International Publication No. WO 2013 / 040247, titled "Fluid Exchange Apparatus and Methods" (ForSight Vision4, Inc.). Additional non-limiting examples of methods for delivering active quaternary ammonium compounds include International Publication No. WO 2015 / 085251, titled "Intracameral Implant for Treatment of an Ocular Condition" (Envisia Therapeutics, Inc.); International Publication No. WO 2011 / 008737, titled "Engineered Aerosol Particles, and Associated Methods"; International Publication No. WO 2013 / 082111, titled "Geometrically Engineered Particles and Methods for Modulating Macrophage or Immune Responses"; International Publication No. WO 2009 / 132265, titled "Degradable compounds and methods of use thereof, particularly with particle replication in non-wetting templates"; International Publication No. WO 2010 / 111832, titled "Interventional drug delivery systems and related methods";

[0679] and International Publication No. WO 2013 / 142021, titled "Methods and compositions for treating a disease or condition using a quaternary ammonium compound and a targeting agent". systems and related methods"; International Publication No. WO 2010 / 099321 entitled "System and Associated Methods", International Publication No. WO 2008 / 100304 entitled "Polymer particle composite having high fidelity order, size, and shape particles", International Publication No. WO 2007 / 024323 entitled "Nanoparticle fabrication methods, systems, and materials" (Liquidia Technologies, Inc. and the University of North Carolina at Chapel Hill); International Publication No. WO 2010 / 009087 entitled "Iontophoretic Delivery of a Controlled-Release Formulation in the Eye" (Liquidia Technologies, Inc. and Eyegate Pharmaceuticals, Inc.) and "Compositions and Methods for Intracellular Delivery and Release of Cargo International Publication No. WO 2009 / 132206 entitled "Delivery and Release of Cargo", International Publication No. WO 2007 / 133808 entitled "Nano-particles for cosmetic applications", International Publication No. WO 2007 / 056561 entitled "Medical device, materials, and methods", International Publication No. WO 2010 / 065748 entitled "Method for producing patterned materials", International Publication No. WO 2007 / 081876 (Liquidia Technologies, Inc.) entitled "Nanostructured surfaces for biomedical / biomaterial applications and processes thereof".

[0680] Additional non-limiting examples of methods and devices for drug delivery to the eye include, for example, International Publication No. WO 2011 / 106702 and U.S. Patent No. 8,889,193 entitled "Sustained delivery of therapeutic agents to an eye compartment", International Publication No. WO 2013 / 138343 and U.S. Patent No. 8,962,577 entitled "Controlled release formulations for the delivery of HIF-1 inhibitors", International Publication No. WO 2013 / 138 entitled "Non-Linear Multiblock Copolymer-Drug Conjugates for the Delivery of Active Agents". No. 346 and US Patent Application Publication No. 2013 / 0272994, International Publication No. 2005 / 072710 entitled "Drug and Gene Carrier Particles that Rapidly Move Through Mucus Barriers" and US Patent No. 8,957,034, "Compositions and Methods for Enhancing Transport Through Mucous" entitled International Publication No. 200 8 / 030557, US Patent Application Publication No. 2010 / 0215580, US Patent Application Publication No. 2013 / 0164343, International Publication No. 2012 / 061703, US Patent Application Publication No. 2012 / 0121718 and US Patent Application Publication No. 2013 / 0236556, "Rapid Diffusion of Large Polymeric Nanoparticles in the Mammalian Brain " entitled International Publication No. 2012 / 039979 and US Patent Application Publication No. 2013 / 0183244, "Mucus Penetrating Gene Carriers" entitled International Publication No. 2012 / 109363 and US Patent Application Publication No. 2013 / 0323313, "Nanoparticles with enhanced mucosal penetration or decreased inflammation" entitled International Publication No. 2013 No. 090804 and US Patent Application Publication No. 2014 / 0329913, International Publication No. 2013 / 110028 entitled "Nanoparticle formulations with enhanced mucosal penetration", "Rapid penetration through the mucus inner layer" International Publication No. 2013 / 166498 entitled "Lipid-based drug carriers for rapid penetration through mucus linings" and US Patent Application Publication No. 2015 / 0086484 (Johns Hopkins University); International Publication No. 2013 / 166385 entitled "Pharmaceutical Nanoparticles Showing Improved Mucosal Transport", "Nanocrystals, Compositions, And Methods that Aid Particle Transport in Mucus" US Patent Application Publication No. 2013 / 0323179 (Johns Hopkins University and Kala Pharmaceuticals, Inc.); International Publication No. 2015 / 066444 entitled "Compositions and methods for ophthalmic and / or other applications", "Pharmaceutical nanoparticles showing improved mucosal transport" International Publication No. 2014 / 020210 and International Publication No. 2013 / 16 6408 (Kala Pharmaceuticals, Inc.); "Ophthalmic injection device including dosage control device" entitled U.S. Patent No. 9,022,970, "Ophthalmic compositions comprising pbo-peo-pbo block copolymers" International Publication No. WO 2011 / 153349 entitled "Stabilized ophthalmic galactomannan formulations", International Publication No. WO 2011 / 140203 entitled "Ophthalmic emulsion", International Publication No. WO 2011 / 068955 entitled "Injectable aqueous ophthalmic composition and method of use therefor", U.S. Patent Application Publication No. 2007 / 0149593 entitled "Pharmaceutical Formulation for Delivery of Receptor Tyrosine Kinase Inhibiting (RTKi) Compounds to the Eye", U.S. Patent No. 8,632,809 (Alcon, Inc.) entitled "Water insoluble polymer matrix for drug delivery" may be mentioned.

[0681] In another aspect, an ocular formulation is provided that comprises one or more of the quaternary ammonium compounds described herein in a carrier suitable for the eye. A suitable carrier must prevent the quaternary ammonium compound from being toxic or irritating to the eye and prevent unwanted side effects or damage to the eye. Examples of components not suitable for use in an ocular formulation include corrosive agents such as strong alkali or strong acid substances, for example, urea or ammonia, strong surfactants, and substances with known ocular toxicity, for example, methanol and hydrogen peroxide, etc. include.

[0682] In another aspect, there is also provided a preparation for treating onychomycosis, which preparation comprises one or more quaternary ammonium compounds described herein in a carrier capable of penetrating the nail bed and delivering the active quaternary ammonium compound to the nail bed. One representative example of a carrier capable of penetrating the nail bed is dimethyl sulfoxide.

[0683] Additional non-limiting examples of drug delivery devices and methods include, for example, U.S. Patent Application Publication No. 20050009910 entitled "Delivery of an active drug to the posterior part of the eye via subconjunctival or periocular delivery of a prodrug", "lowering intraocular pressure U.S. Patent No. 20130071349 entitled "Biodegradable polymers for lowering intraocular pressure", U.S. Patent No. 8,481,069 entitled "Tyrosine kinase microspheres", U.S. Patent No. 8,465,778 entitled "Method of making tyrosine kinase microspheres", "containing a tyrosine kinase inhibitor U.S. Patent No. 8,409,607 entitled "Sustained release intraocular implants containing tyrosine kinase inhibitors and related methods", U.S. Patent No. 8,512,738 entitled "Biodegradable intravitreal tyrosine kinase implants" U.S. Patent No. 2014 / 0031408, and U.S. Patent No. 2014 / 0294986 entitled "Microsphere Drug Delivery System for Sustained Intraocular Release", "Methods For Treating Retinopathy With Extended Therapeutic Effect" U.S. Patent No. 8,911,768 (Allergan, Inc.) entitled " "; U.S. Patent No. 6,495,164 (Alkermes Controlled Therapeutics, Inc.) entitled "Preparation of injectable suspensions having improved injectability"; International Publication No. 2014 / 047439 (Akina, Inc.) entitled "Biodegradable Microcapsules Containing Filling Material"; International Publication No. 2010 / 132664 (Baxter International Inc., Baxter Healthcare SA) entitled "Compositions And Methods For Drug Delivery"; "Polymeric nanoparticles with enhanced drugloading and methods of use thereof" U.S. Patent Application Publication No. 20120052041 (The Brigham and Women’s Hospital, Inc.) entitled " "; Therapeutic nanoparticles containing a therapeutic agent, and methods of making and using the same U.S. Patent Application Publication No. 20140178475 entitled "Therapeutic Nanoparticles Comprising a Therapeutic Agent and Methods of Making and Using Same", U.S. Patent Application Publication No. 20140248358 and U.S. Patent Application Publication No. 20140249158 (BIND Therapeutics, Inc.); U.S. Patent No. 5,869,103 entitled "Polymer microparticles for drug delivery" (Danbiosyst UK Ltd.); U.S. Patent No. 8628801 entitled "Pegylated Nanoparticles" (University of Navarra); U.S. Patent Application Publication No. 2014 / 0107025 entitled "Ocular drug delivery system" (Jade Therapeutics, LLC); "Microparticles having an improved release profile and an agent delivery system composed of a biodegradable gel, and a method of using the same" U.S. Patent No. 6,287,588; "Bioactive agent delivering system composed of microparticles in a biodegradable material to improve release profiles" U.S. Patent No. 6,589,549 (Macromed, In c.); U.S. Patent No. 6,007,845 and U.S. Patent No. 5,578,325 entitled "Nanoparticles and microparticles of non-linear hydrophilic / hydrophobic multiblock copolymers" (Massachusetts Institute of Technology); for periocular or subconjunctival administration U.S. Patent Application Publication No. 20040234611, U.S. Patent Application Publication No. 20080305172, U.S. Patent Application Publication No. 20120269894, and U.S. Patent Application Publication No. 20130122064 entitled "Ophthalmic depot formulations for periocular or subconjunctival administration" (Novartis Ag); "Block polymer" U.S. Patent No. 6,413,539 (Poly-Med, Inc.); U.S. Patent Application Publication No. 20070071756 entitled "Delivery of an agent to ameliorate inflammation" (Peyman); "Methods and compositions for enhanced delivery of bioactive molecules" U.S. Patent No. 6,706,289 (PR Pharmaceuticals, Inc.); and U.S. Patent No. 8,663,674 entitled "Microparticle containing matrices for drug delivery" (Surmodics).

[0684] Dressings, etc. In some embodiments, the antimicrobial composition containing one or more quaternary ammonium compounds of the present invention is dispersed in a suitable dressing material. The selected dressing material must be able to release the desired antimicrobial composition over a certain period according to the desired use. The dressing material can be wetted by saturating it with the antimicrobial composition before installation at the infection site, even if it may be further wetted by exudates at the infection site. Alternatively, the dressing material can be installed at the wound and / or infection site and subsequently saturated with the antimicrobial composition, for example, by applying the antimicrobial composition with a dropper or syringe or by other suitable means.

[0685] In another embodiment, an infectious disease is treated by applying a dressing material containing one or more quaternary ammonium compounds of the present invention as the antimicrobial composition to the infection site, and this dressing material releases one or more quaternary ammonium compounds of the present invention to the infection site. Infectious diseases may involve the presence of bacteria, fungi, viruses, amoebas, or combinations of these infectious specie...

Claims

1. The following formula: 【Chemical Formula 1】 (wherein, a is 1, 2, 3, 4, 5, 6, 7, or 8, y is 0, 1, 2, 3, or 4, p and q are each independently selected from 1, 2, 3, and 4, R １ is, independently of each other, C ６ -C ２２ alkyl (and C ７ , C ８ , C ９ , C １０ , C １１ , C １２ , C １３ , C １４ , C １５ , C １６ , C １７ , C １８ , C １９ , C ２０ , C ２１ , or C ２２ is possible), C ６ -C ２２ alkenyl (and C ７ , C ８ , C ９ , C １０ , C １１ , C １２ , C １３ , C １４ , C １５ , C １６ , C １７ , C １８ , C １９ , C ２０ , C ２１ , or C ２２ is possible), and C ６ -C ２２ alkanoyl (and C ７ , C ８ , C ９ , C １０ , C １１ , C １２ , C １３ , C １４ , C １５ , C １６ , C １７ , C １８ , C １９ , C ２０ , C ２１ , or C ２２ is possible) and is selected from R ２ , R ３ , and R ４ are each independently 【Chemical Formula 2】 selected from, or C ２ ~C １０ alkanoic acid (which can be C ２ C ３ C ４ C ５ C ６ C ７ C ８ C ９ or C １０ ), or a salt thereof. In some embodiments, R ２ R ３ and R ４ are all alkanoic acids, R ５ is, independently of each other, R ２ , R １７ , and C ２ to C １０ alkanoic acid (which may be C ２ , C ３ , C ４ , C ５ , C ６ , C ７ , C ８ , C ９ , or C １０ ), and the acid is optionally a diacid or a salt thereof, R ６ is independently selected from hydrogen, alkyl, aryl, cycloalkyl, and heterocyclyl, and each of said alkyl, aryl, cycloalkyl, and heterocyclyl is optionally C １ -C ６ alkyl, hydroxyl, halogen, N(R ７ ), COOR ２ , C(O)R ７ , CH ７ OR ２ , CON(R ７ ), and NO ７ ), and has a substituent selected from ２ , and NO ２ ; R ７ is, independently of each other, hydrogen, C １ -C ８ alkyl, C １ -C ８ hydroxyalkyl, C ２ -C ８ alkenyl, C ２ -C ８ alkynyl, C １ -C ８ haloalkyl, C １ -C ８ alkanoyl, heterocyclyl, heteroaryl, heterocycloalkyl, and aryl, and is selected from R ８ 、 R ９ 、 R １０ 、 R １１ 、 R １２ 、 and R １３ are each independently selected from hydrogen, halogen, hydroxyl, N(R ７ ), CH ２ OR ２ OR ７ 、 CON(R ７ ), COOR ２ 、 C(O)R ７ 、 C ７ ~C １ ~C ８ alkyl, C １ ~C ８ hydroxyalkyl, C ２ ~C ８ alkenyl, C ２ ~C ８ alkynyl, C １ ~C ８ haloalkyl, C １ ~C ８ alkanoyl, heterocyclyl, heteroaryl, and aryl, X １ is, independently of each other, NR １７ CH ２ CHOH, and C(O), and is selected from X ２ is, independently of each other, C １ to C ３ alkyl, and C １ to C ３ selected from hydroxyalkyl, X ３ is, independently of each other, hydroxyl, NO ２ , N(R ７ ), ２ CH ２ OR ７ ), CON(R ７ ), ２ COOR ７ ), C(O)R ７ C １ ~C ８ alkyl, C １ ~C ８ hydroxyalkyl, C ２ ~C ８ alkenyl, C ２ ~C ８ alkynyl, C １ ~C ８ haloalkyl, C １ ~C ８ alkanoyl, heterocyclyl, heteroaryl, and aryl, and is selected from X ４ is, independently of each other, X ３ selected from, R １４ and R １５ are each independently 【Chemical Formula 3】 , R ２ , and R １７ selected from R １６ is, independently of each other, C １ to C ４ alkyl, C ２ to C ４ alkenyl, C ２ to C ４ alkynyl, and C １ to C ４ selected from haloalkyl, R １７ is, independently of each other, hydrogen, C １ -C ８ hydroxyalkyl, C ２ -C ８ alkenyl, C ２ -C ８ alkynyl, C １ -C ８ haloalkyl, C １ -C ８ alkanoyl, heterocyclyl, heteroaryl, heterocycloalkyl, and aryl, and is selected from X － is an anion, B ＋ is a quaternary ammonium compound (which is a cation), or a pharmaceutically acceptable salt or composition thereof.

2. The quaternary ammonium compound according to claim 1, wherein the anion is selected from the group consisting of chloride anion, fluoride anion, iodide anion, bromide anion, hydroxide anion, chlorite anion, chlorate anion, hydroxide anion, formate anion, acetate anion, lactate anion, benzoate anion, and salicylate anion.

3. The quaternary ammonium compound according to claim 1, wherein the quaternary ammonium compound has a negatively charged substituent.

4. The quaternary ammonium compound according to claim 3, wherein the negatively charged substituent is neutralized with a pharmaceutically acceptable cation.

5. The quaternary ammonium compound according to claim 4, wherein the cation is selected from potassium cation, sodium cation, and calcium cation.

6. The quaternary ammonium compound according to claim 1, wherein the pharmaceutically acceptable composition contains at least 50% less of the quaternary ammonium compound in moles compared to other quaternary ammonium compounds in the composition.

7. The quaternary ammonium compound according to claim 1, wherein the compound is zwitterionic.

8. R ２ , R ３ , and R ４ are C １ to C １２ alkanic acids, the quaternary ammonium compound according to claim 1.

9. R ２ , R ３ , and R ４ are 【Chemical Formula 4】 The quaternary ammonium compound according to claim 1, which is selected from the group consisting of

10. R ２ 、R ３ 、and R ４ are [Chemical Formula 5] The compound according to claim 1, which is selected from the group consisting of

11. R ５ is 【Chemical Formula 6】 The quaternary ammonium compound according to claim 1, which is selected from the group consisting of

12. R ５ is selected from the group consisting of hydrogen, C １ to C ８ hydroxyalkyl, C ２ to C ８ alkenyl, C ２ to C ８ alkynyl, and C １ to C ８ The quaternary ammonium compound according to claim 1, selected from the group consisting of haloalkyl.

13. X １ The compound according to any one of claims 9 to 11, wherein X is NH.

14. X １ is NR １７ wherein R １７ is C １ -C ８ hydroxyalkyl, the quaternary ammonium compound according to any one of claims 9 to 11.

15. X ２ is C １ to C ３ alkyl, the quaternary ammonium compound according to claim 9 or 11.

16. X ２ is C １ to C ３ a hydroxyalkyl, the quaternary ammonium compound according to claim 9 or 11.

17. X ３ is selected from hydroxyl, N(R ７ ), ２ CH ２ OR ７ COOR ７ C １ -C ８ alkyl, and C １ -C ８ hydroxyalkyl, and is the quaternary ammonium compound according to claim 10 or 11.

18. X ４ is selected from the group consisting of N(R ７ ), C ２ to C １ alkyl, C ８ to C １ hydroxyalkyl, and C ８ to C １ alkanecarboxylic acid, and is the quaternary ammonium compound according to claim 10 or 11. １２ ​

19. The following: 【Chemical Formula 7】 【Chem.】 【Chem.】 [Chemical] [Chemical] The quaternary ammonium compound according to claim 7, which is selected from the group consisting of

20. The following: 【Chemical 8】 The quaternary ammonium compound according to claim 1, which is selected from the group consisting of

21. The quaternary ammonium compound according to claim 19, which exists as a monocationic form or a dicationic form compound.

22. The quaternary ammonium compound according to any one of claims 1 to 21, which is a powder or a solid.

23. A pharmaceutical composition comprising the compound according to any one of claims 1 to 21 and optionally a pharmaceutically acceptable carrier.

24. The pharmaceutical composition according to claim 23, which is suitable for local delivery.

25. The pharmaceutical composition according to any one of claims 22 to 24, which is in a form selected from the group consisting of a liquid, a cream, a gel, a spray, a foam, a wipe, a powder, a paste, and a solid.

26. A method for treating a local infection in a host, the treatment comprising administering to the host in need of treatment an effective amount of the compound according to any one of claims 1 to 21 or the pharmaceutical composition according to any one of claims 22 to 25.

27. A method for treating a host having an infection selected from the group consisting of an eye infection, an ear infection, a skin infection, and a nail infection, the treatment comprising administering to the host an effective amount of the compound according to any one of claims 1 to 21 or the pharmaceutical composition according to any one of claims 22 to 25.

28. The method according to claim 26 or 27, wherein the infection is caused by a bacterial infection, a fungal infection, an amoeba infection, a viral infection, or a combination thereof.

29. The method according to claim 26 or 27, wherein the infection is caused by Staphylococcus aureus, Pseudomonas aeruginosa, Fusarium spp., Aspergillus spp., Candida albicans, Candida auris, Curvularia spp., Haemophilus influenzae, or Acanthamoeba keratitis, or a combination thereof.

30. The method according to any one of claims 26 to 29, wherein the infection is an eye infection.

31. The method according to any one of claims 26 to 29, wherein the infection is an ear infection, and the infection is present in the outer ear (otitis externa), the middle ear (otitis media), or the inner ear (otitis interna).

32. The method according to any one of claims 26 to 29, wherein the infection is a nail infection.

33. The method according to any one of claims 26 to 29, wherein the infection is a chronic wound.

34. The method according to any one of claims 26 to 29, wherein the infection causes periodontal disease.

35. The method according to claim 30, wherein the eye infection is selected from the group consisting of bacterial or viral conjunctivitis (pink eye), corneal ulcer, keratitis, bacterial, fungal, herpes infectious keratitis, endophthalmitis, and blepharitis.

36. A method for treating a dermatological disorder in a host in need of treatment for the dermatological disorder, the method comprising administering to the host an effective amount of the compound according to any one of claims 1 to 21.

37. The method according to claim 36, wherein the dermatological disorder is selected from the group consisting of acne vulgaris, cystic acne, eczema, folliculitis, and skin infections.

38. The method according to claim 37, wherein the dermatological disorder is acne vulgaris.

39. The method according to claim 37, wherein the dermatological disorder is selected from the group consisting of eczema, herpes eczema, vaccinia eczema, and coxsackie eczema.

40. The method according to claim 37, wherein the dermatological disorder is cystic acne.

41. The method according to claim 37, wherein the dermatological disorder is a skin infection.

42. The method according to any one of claims 36 to 41, wherein the dermatological disorder is caused by a pathogen selected from the group consisting of gram-positive bacteria, gram-negative bacteria, fungi, and viruses.

43. The method according to any one of claims 36 to 41, wherein the dermatological disorder is caused by a pathogen selected from the group consisting of Propionibacterium acnes, Staphylococcus epidermidis, staphylococcal bacteria such as Staphylococcus aureus, or streptococcal bacteria.

44. The method according to claim 42, wherein the virus is selected from the group consisting of herpes simplex virus and molluscum contagiosum virus.

45. The method according to claim 36, wherein the dermatological disorder is a skin infection caused by Staphylococcus aureus.

46. The method according to any one of claims 26 to 45, wherein the host is a human.

47. The method according to any one of claims 26 to 45, wherein the host is a mammal.

48. The method according to any one of claims 26 to 45, wherein the host is a dog, cat, rabbit, horse, pig, or cow.

49. An antibacterial composition for treating an infection in a host in need of treatment for the infection, the composition comprising an effective amount of the compound according to any one of claims 1 to 21 in combination with one or more of glycerol, glycerol-propylene oxide copolymer, sor ketal, glycidol, or epichlorohydrin, and optionally further comprising another pharmaceutically acceptable excipient.

50. The antimicrobial composition according to claim 49, wherein the infectious disease is an eye infectious disease.

51. The antimicrobial composition according to claim 49, wherein the infectious disease is an ear infectious disease selected from the group consisting of an outer ear (otitis externa) infectious disease, a middle ear (otitis media) infectious disease, or an inner ear (otitis interna) infectious disease.

52. The antimicrobial composition according to claim 49, wherein the infectious disease is a nail infectious disease.

53. The antimicrobial composition according to claim 49, wherein the infectious disease is a chronic wound.

54. The antimicrobial composition according to claim 49, wherein the infectious disease causes periodontal disease.

55. The antimicrobial composition according to claim 50, wherein the eye infectious disease is selected from the group consisting of bacterial or viral conjunctivitis (pink eye), corneal ulcer, keratitis, bacterial, fungal, herpes infectious keratitis, endophthalmitis, or blepharitis.

56. The antimicrobial composition according to claim 49, wherein the infectious disease causes a dermatological disorder.

57. The antimicrobial composition according to claim 56, wherein the dermatological disorder is selected from the group consisting of acne vulgaris, cystic acne, eczema, folliculitis, and skin infectious diseases.

58. The antimicrobial composition according to claim 57, wherein the dermatological disorder is acne vulgaris.

59. The antimicrobial composition according to claim 56, wherein the dermatological disorder is selected from the group consisting of eczema, herpes eczema, vaccinia eczema, or coxsackie eczema.

60. The antimicrobial composition according to claim 57, wherein the dermatological disorder is cystic acne.

61. The antimicrobial composition according to claim 57, wherein the dermatological disorder is a skin infectious disease.

62. The antimicrobial composition according to claim 56, wherein the dermatological disorder is a chronic wound.

63. The antimicrobial composition according to any one of claims 56 to 62, wherein the dermatological disorder is caused by Gram-positive bacteria, Gram-negative bacteria, fungi, or viruses, or a combination thereof.

64. The antimicrobial composition according to any one of claims 56 to 62, wherein the dermatological disorder is caused by Propionibacterium acnes, Staphylococcus epidermidis, staphylococcal bacteria such as Staphylococcus aureus, or streptococcal bacteria, or a combination thereof.

65. The antimicrobial composition according to claim 63, wherein the virus includes herpes simplex virus or molluscum contagiosum virus.

66. The antimicrobial composition according to claim 61, wherein the skin infectious disease is caused by Staphylococcus aureus.

67. The antibacterial composition according to claim 49, wherein the infectious disease is caused by biofilm formation.

68. The antibacterial composition according to any one of claims 49 to 67, which is in the form of a spray, cream, gel, foam, dry powder, wipe, paste, solid, transdermal patch, skin solution, subcutaneous patch, eye drop, or suspension.

69. The antibacterial composition according to any one of claims 49 to 68, wherein the antibacterial composition is added to a polymeric material.

70. The polymeric material according to claim 69, wherein the polymeric material is selected from the group consisting of a thermoplastic polymer, a thermosetting polymer, a biodegradable polymer, a modified polymer, a crosslinked polymer, a polymer for controlled delivery, a hydrogel, a hydrophilic colloid, a liquid-forming polymer, a gel-forming polymer, a silicone-based polymeric material, a film-forming polymer, a polymer adhesive, a copolymer, and a medical polymer, and mixtures thereof.

71. The antibacterial composition according to claim 70, wherein the polymer is a hydrogel.

72. The antibacterial composition according to claim 70, wherein the polymer is a gel-forming polymer.

73. The antibacterial composition according to claim 70, wherein the polymer is a film-forming polymer.

74. The antibacterial composition according to claim 70, wherein the polymer is a hydrophilic colloid.

75. The antibacterial composition according to claim 70, wherein the polymer is a silicone-based polymeric material.

76. The antibacterial composition according to claim 70, wherein the polymer is an adhesive.

77. The antibacterial composition according to any one of claims 70 to 76, wherein the polymer is a modified polymer, a copolymer, or a mixture thereof.

78. The antibacterial composition according to any one of claims 70 to 77, wherein the polymer is a biodegradable polymer.

79. The antibacterial composition according to any one of claims 70 to 78, wherein the polymer is a soluble polymer.

80. The antibacterial composition according to any one of claims 70 to 79, comprising one or more additional additives.

81. The antibacterial composition according to claim 80, wherein the additional additives include a surfactant, a buffer, an enzyme, a tissue growth promoter, a preservative, an antioxidant, an astringent, a topical carrier, or a pharmaceutically acceptable carrier.

82. Applied to a surface, said surface being selected from the group consisting of a medical device, a coating material for a medical device, a pacemaker, a contact lens, a denture, a prosthesis, a heart valve, and a heart graft; a biomaterial, an implantable device, a non-implantable device, a wound healing material, a personal protective material, a glove, a face mask, a surgical or hospital gown, clothing, a sheet, a sponge, a woven or non-woven material, an ocular implant, an ophthalmic film, a short-term wound filler, a catheter hydrophilic coating, a catheter lead wire, and an embolization agent, the compound according to any one of claims 1 to 21.

83. A method for treating an infectious disease in a host, comprising: a) applying a dressing containing the antibacterial composition according to any one of claims 49 or 69 to 81 to the infected site of the host, and the dressing releases one or more compounds according to claims 1 to 21 to the infected site; b) covering the wound, infection, or skin exposure with the dressing.

84. The method according to claim 83, wherein the dressing is in the form of a spray, cream, gel, foam, film, dry powder, wipe, paste, solid, suspension, solution, or solid material.

85. The method according to claim 83 or 84, wherein the dressing comprises a material selected from the group consisting of a thermoplastic polymer, a thermosetting polymer, a biodegradable polymer, a modified polymer, a cross-linked polymer, a polymer for controlled delivery, a hydrogel, a hydrophilic colloid, a liquid-forming polymer, a gel-forming polymer, a silicone-based polymer material, a film-forming polymer, a polymer adhesive, a copolymer, a polymer material containing a medical polymer, a cloth material, a non-adherent dressing material, and a hydrofiber, or a combination thereof.

86. The method according to claim 85, wherein the dressing is a film-forming polymer.

87. The method according to claim 85, wherein the dressing is a polymer adhesive.

88. The method according to claim 85, wherein the dressing is a gel-forming polymer.

89. The method according to claim 85, wherein the dressing is a silicone-based polymer or material.

90. The method according to claim 85, wherein the dressing is a hydrogel.

91. The method according to claim 85, wherein the dressing is a hydrophilic colloid.

92. The method according to any one of claims 83 to 91, wherein the dressing is a modified polymer, a copolymer, or a mixture thereof.

93. The method according to any one of claims 83 to 92, wherein the dressing material is a biodegradable polymer.

94. The method according to any one of claims 83 to 93, wherein the dressing material is a soluble polymer.

95. The method according to any one of claims 83 to 94, comprising one or more additional additives including a penetration enhancer, a tissue adhesive, an adhesion preventer, or a plasticizer.

96. The method according to any one of claims 83 to 95, wherein the dressing material comprises a composite material.

97. The method according to claim 83, wherein the dressing material is a cloth material.

98. The method according to claim 97, wherein the cloth material comprises natural fibers, synthetic fibers, cellulose, woven or non-woven fabric materials, or mixtures thereof.

99. The method according to claim 83, wherein the infectious disease is caused by Gram-positive bacteria, Gram-negative bacteria, fungi, viruses, amoebas, or combinations of their infectious species, or biofilm formation.

100. The method according to claim 83, wherein the infectious disease is a chronic wound.

101. The method according to claim 83, wherein the infectious disease is due to biofilm formation.

102. The method according to claim 83, wherein the dressing material is useful for covering a wound or skin exposure.

103. The wound is an infectious disease, burn, skin exposure, open wound, skin laceration, abrasion, puncture, avulsion, scab, surgical wound, abscess, skin tear, skin ulcer or lesion, damaged tissue, bite, water-related skin injury, foot ulcer, necrosis, susceptible skin graft or flap, acute wound, chronic wound, trauma, diabetes, pressure ulcer, venous ulcer, arterial wound, neuropathic ulcer, diabetic ulcer, lower extremity ulcer, skin tear, water-related skin injury (MASD), and other skin exposure-related injuries, or is caused by them. The method according to claim 102.

104. A compound of the following formula: 【Chemical Formula 9】 【Chem.】 [Chemical] 【Chem.】 [Chemical] 【Chem.】 【Chem.】 【Chem.】 [Chemical] [Chemical] (wherein, a is 1, 2, 3, 4, 5, 6, 7, or 8, y is 0, 1, 2, 3, or 4, p and q are each independently selected from 1, 2, 3, and 4, R １ is, independently of each other, C ６ to C ２２ alkyl (and C ７ , C ８ , C ９ , C １０ , C １１ , C １２ , C １３ , C １４ , C １５ , C １６ , C １７ , C １８ , C １９ , C ２０ , C ２１ , or C ２２ is possible), C ６ to C ２２ alkenyl (and C ７ , C ８ , C ９ , C １０ , C １１ , C １２ , C １３ , C １４ , C １５ , C １６ , C １７ , C １８ , C １９ , C ２０ , C ２１ , or C ２２ can be), and C ６ to C ２２ alkanoyl (and C ７ , C ８ , C ９ , C １０ , C １１ , C １２ , C １３ , C １４ , C １５ , C １６ , C １７ , C １８ , C １９ , C ２０ , C ２１ , or C ２２ can be) selected from, Each R ２１ is independently C １ to C ２２ alkyl (and C １ , C ２ , C ３ , C ４ , C ５ , C ６ , C ７ , C ８ , C ９ , C １０ , C １１ , C １２ , C １３ , C １４ , C １５ , C １６ , C １７ , C １８ , C １９ , C ２０ , C ２１ , or C ２２ is possible), C ２ to C ２２ alkenyl (and C ２ , C ３ , C ４ , C ５ , C ６ , C ７ , C ８ , C ９ , C １０ , C １１ , C １２ , C １３ , C １４ , C １５ , C １６ , C １７ , C １８ , C １９ , C ２０ , C ２１ , or C ２２ is possible), C ２ to C ２２ alkanoyl (and C ２ , C ３ , C ４ , C ５ , C ６ , C ７ , C ８ , C ９ , C １０ , C １１ , C １２ , C １３ , C １４ , C １５ , C １６ , C １７ , C １８ , C １９ , C ２０ , C ２１ , or C ２２ is possible), and is selected from -alkyl-aryl, and each of R ２１ is optionally substituted with 1, 2, or 3 substituents, and the substituents are independently C １ to C ６ alkyl, halogen, and 【Chemical Formula 10】 selected from, R ２２ , R ２３ , and R ２４ are each independently 【Chemical 11】 selected from, R ２５ is, independently of one another, R ２２ R １７ and C ２ to C １０ alkanoic acid (which may be C ２ C ３ C ４ C ５ C ６ C ７ C ８ C ９ or C １０ ), where the acid is optionally a diacid or a salt thereof, R ３１ is C ６ -C ２２ alkyl (and C ６ , C ７ , C ８ , C ９ , C １０ , C １１ , C １２ , C １３ , C １４ , C １５ , C １６ , C １７ , C １８ , C １９ , C ２０ , C ２１ , or C ２２ is possible), C ６ -C ２２ alkenyl (and C ６ , C ７ , C ８ , C ９ , C １０ , C １１ , C １２ , C １３ , C １４ , C １５ , C １６ , C １７ , C １８ , C １９ , C ２０ , C ２１ , or C ２２ is possible), C ６ -C ２２ alkynyl (and C ６ , C ７ , C ８ , C ９ , C １０ , C １１ , C １２ , C １３ , C １４ , C １５ , C １６ , C １７ , C １８ , C １９ , C ２０ , C ２１ , or C ２２ is possible), and C ６ -C ２２ alkenylalkynyl (and C ６ , C ７ , C ８ , C ９ , C １０ , C １１ , C １２ , C １３ , C １４ , C １５ , C １６ , C １７ , C １８ , C １９ , C ２０ , C ２１ , or C ２２ and can be selected from), Each R ３２ independently represents hydrogen, 【Chemical Formula 12】 selected from, R ３３ each independently is selected from hydroxyl, hydrogen, C １ to C ６ alkyl, and halogen R ３４ and R ３５ are each independently 【Chemical Formula 13】 , R ２２ , and R １７ selected from Each R ３６ independently represents hydrogen, 【Chemical Formula 14】 selected from, X １ is, independently of each other, NR １７ , CH ２ , CHOH, and C(O), and is selected from X ２ is, independently of each other, C １ to C ３ alkyl, and C １ to C ３ selected from hydroxyalkyl, X ３ is, independently of each other, hydroxyl, NO ２ , N(R ７ ), ２ , CH ２ OR ７ , CON(R ７ ), ２ , COOR ７ , C(O)R ７ , C １ -C １２ alkanic acid, C １ -C ８ alkyl, C １ -C ８ hydroxyalkyl, C ２ -C ８ alkenyl, C ２ -C ８ alkynyl, C １ -C ８ haloalkyl, C １ -C ８ alkanoyl, heterocyclyl, heteroaryl, and aryl, and is selected from X ４ is, independently of each other, X ３ selected from, X ５ is selected from a complex ring, cycloalkyl, alkyl, aryl, heteroaryl, alkenyl, haloalkyl, and alkynyl, R ６ is independently selected from hydrogen, alkyl, aryl, cycloalkyl, and heterocyclyl, each of said alkyl, aryl, cycloalkyl, and heterocyclyl being optionally C １ to C ６ alkyl, hydroxyl, chloro, bromo, iodo, fluoro, N(R ７ ), ２ COOR ７ C(O)R ７ CH ２ OR ７ CON(R ７ ), ２ and NO ２ and having substituents selected from, R ７ is, independently of each other, hydrogen, C １ to C ８ alkyl, C １ to C ８ hydroxyalkyl, C ２ to C ８ alkenyl, C ２ to C ８ alkynyl, C １ to C ８ haloalkyl, C １ to C ８ alkanoyl, heterocyclyl, heteroaryl, heterocycloalkyl, and aryl, and is selected from R ８ 、R ９ 、R １０ 、R １１ 、R １２ 、and R １３ are each independently selected from hydrogen, halogen, hydroxyl, N(R ７ ), CH ２ OR ２ OR ７ ), CON(R ７ ), COOR ２ ), C(O)R ７ ), C ７ ~C １ ~C ８ alkyl, C １ ~C ８ hydroxyalkyl, C ２ ~C ８ alkenyl, C ２ ~C ８ alkynyl, C １ ~C ８ haloalkyl, C １ ~C ８ alkanoyl, heterocyclyl, heteroaryl, and aryl, R １７ is, independently of each other, hydrogen, C １ -C ８ hydroxyalkyl, C ２ -C ８ alkenyl, C ２ -C ８ alkynyl, C １ -C ８ haloalkyl, C １ -C ８ alkanoyl, heterocyclyl, heteroaryl, heterocycloalkyl, and aryl, and is selected from X － is an anion, for example, chloride anion, fluoride anion, iodide anion, bromide anion, hydroxide anion, chlorite anion, chlorate anion, formate anion, acetate anion, lactate anion, benzoate anion, or salicylate anion; and B ＋ is a cation, for example, ammonium, potassium, or sodium, and o is 1 or 2, n is each independently selected from 0, 1, and 2, m is each independently selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20. m' is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22, Q is -CR １０４ R １０４ - and R １０１ and R １０２ both are hydrogen, or In an alternative embodiment, R １０１ and R １０２ are each independently selected from hydrogen and ethyl, R １０３ are each independently 【Chemical Formula 15】 selected from Each R １０４ is independently selected from hydrogen, alkyl, alkenyl, alkynyl, halogen, and haloalkyl, R １０５ is hydrogen or -CH ２ CH ２ OH, and R １０６ is, independently of each other, hydrogen, hydroxy, and C １ to C ６ alkoxy selected from, R １０７ and R １０８ are each independently selected from C １ to C ６ alkyl, R Ａ is 【Chemical 16】 and A is each independently 【Chemical 17】 selected from p' is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, q', r, and s are each independently selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, X is 【Chemical Formula 18】 selected from M is selected from hydrogen, sodium, potassium, cesium, or lithium, t is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, Z is each independently 【Chemical Formula 19】 selected from L is each independently 【Chemical 20】 selected from R １２４ and R １２５ each independently represents hydrogen, ethyl, 【Chemical 21】 selected from T is a monovalent capping group, which group can optionally be derived from a curing agent, wherein the curing agent can be any pharmaceutically acceptable compound, X － is an anion, and when X － is an anion with two or more negative charges, the charge stoichiometry must be neutralized by other cations).

105. A compound formed by reacting a quaternary ammonium compound of formula A with one or more compounds of formula B, C, D, E, F, G, H, J, K, L, or M: 【Chemical 22】 (wherein Q is -CR １０４ R １０４ and is - X is 【Chemical 23】 selected from M is selected from hydrogen, sodium, potassium, cesium, or lithium, m is each independently selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20, m' is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22, n is each independently selected from 0, 1, and 2, o is 1 or 2, R １０４ is independently selected from hydrogen, alkyl, alkenyl, alkynyl, halogen, and haloalkyl, R １０６ is, independently of each other, hydrogen, hydroxy, and C １ to C ６ selected from alkoxy, R １０７ and R １０８ are each independently selected from C １ to C ６ alkyl, Each R １０９ is independently selected from halo, hydroxyl, and alkoxy, X － is an anion, and when X － is an anion with two or more negative charges, the charge stoichiometry must be neutralized by other cations).

106. A pharmaceutical composition comprising the compound according to claim 104 or 105 and optionally a pharmaceutically acceptable carrier.

107. A compound or pharmaceutical composition according to claim 104 or 105 or the pharmaceutical composition according to claim 106, which is used for the treatment of an infectious disease in a host, wherein the infectious disease is of the eye, ear, skin, or nail.

108. A method for treating a local infectious disease in a host in need thereof, the method comprising administering to the host in need thereof an effective amount of the compound according to claim 104 or 105.

109. A method for manufacturing a medicament for therapeutic use in treating local infection, wherein the treatment comprises administering an effective amount of the compound according to claim 104 or 105 to a host in need of said treatment.

110. A method for treating a dermatological disorder in a host, wherein the treatment comprises administering an effective amount of the compound according to claim 104 or 105 to a host in need of said treatment.

111. A method for manufacturing a medicament for the therapeutic treatment of a dermatological disorder, wherein the treatment comprises administering an effective amount of the compound according to claim 104 or 105 to a host in need of said treatment.

112. An antibacterial composition for treating an infectious disease in a host in need thereof, comprising an effective amount of the compound according to claim 104 or 105 in combination with one or more of glycerol, glycerol-propylene oxide copolymer, sor ketal, glycidol, or epichlorohydrin, optionally with the addition of another pharmaceutically acceptable excipient.

113. A method for treating an infectious disease in a host in need thereof, comprising: a) applying a dressing material comprising the antibacterial composition according to claim 112 to the site of infection, wherein the dressing material releases one or more compounds according to claim 104 or 105 to the site of infection of the host; and b) covering the wound, infection, or skin exposure with the dressing material.

114. Use of a product formed by reacting the compound according to claim 104 or 105 with one or more compounds selected from glycerol, glycerol-propylene oxide copolymer, sor ketal, glycidol, or epichlorohydrin in the manufacture of a medicament for the treatment of bacterial, fungal, viral infections, or combinations of these species.

115. A method for disinfecting a surface, comprising applying the compound according to any one of claims 1 to 21, 104, or 105, or a mixture thereof, to the surface.

Images