Antibacterial 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 of related applications] This application claims the benefits of U.S. Provisional Patent Application No. 62 / 923,372, filed on 18 October 2019, and U.S. Patent Application No. 63 / 014,535, filed on 23 April 2020.

[0002] This disclosure provides organosilicon quaternary ammonium compounds and compositions thereof, as well as their use in topical medical treatments in humans and animals, and their use for disinfecting surfaces, including, but not limited to, work, industrial, transportation, and household applications. [Background technology]

[0003] Providing novel antimicrobial agents, including antifungals and antibiotics, for treating difficult-to-treat infections in humans and animals that do not respond or respond inadequately to current treatments is an urgent global responsibility.

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

[0005] One way microorganisms evade current therapies is through the formation of biofilms. Biofilms consist of communities of microorganisms that adhere to each other and, often, to surrounding surfaces. These microorganisms may be fungi, bacteria, yeasts, algae, or generally mixtures thereof. The microbial community is encased in an extracellular macromolecule (EPS) (see Non-Patent Literature 1), a mixture of polysaccharides, extracellular DNA (eDNA), and proteins that functions as a matrix holding the microbial cells together. The biofilm matrix contributes to the overall structure and resistance phenotype of the biofilm (see Non-Patent Literature 2 and Non-Patent Literature 3). This matrix also "results in the spatial organization of the biofilm, from which the microorganisms derive steep, high biodiversity, and complex, dynamic, and synergistic interactions, including intercellular communication and enhanced horizontal gene transfer" (see Non-Patent Literature 4). This mode of protection of growth allows microorganisms to survive in harsh environments and disperse seeded cells to colonize new microenvironments under desirable conditions.

[0006] The rise in microbial resistance to current treatment regimens is at least partially due to increased effectiveness of primary endogenous defense mechanisms in microorganisms, particularly those in biofilms. These defenses include reduced drug uptake, efflux, enzyme inactivation, and target alteration through mutation. Microorganisms can also acquire resistance by sharing genetic material, a process called horizontal gene transfer (HGT), which may be a more rapid process than gene selection involved in the development of endogenous resistance. Simultaneous or sequential multiple microbial infections can occur in similar organisms of different species or in mixtures of bacteria and fungi. Available antimicrobial agents used for treatment often lack significant overlapping activity across multiple populations of candidate pathogens (Non-Patent Literature 5).

[0007] The negative consequences of these biofilm interactions include major medical issues such as non-healing or chronic wounds. It can be burdensome. Chronic wounds are defined as biological barrier defects that do not heal within three months, but their management is a major treatment challenge across Western countries, and the problem is that it only increases with the rising incidence of conditions that interfere with wound healing, such as diabetes, obesity, and vascular disorders. Ulcers last an average of 12 to 13 months, recur in up to 60% to 70% of patients, and can lead to functional impairment and a reduced quality of life, making them a significant cause of morbidity (Non-Patent Literature 6). Regardless of whether they are clinically and molecularly heterogeneous, all chronic wounds generally belong to one of three main clinical classifications: lower extremity ulcers, diabetic foot ulcers, or pressure ulcers. In the United States alone, it is estimated that 2.4 million to 4.5 million people suffer from these wounds (Non-Patent Literature 7). Chronic lower extremity and foot ulcers occur in many adults with vascular disease or diabetes and are caused by chronic venous insufficiency, arterial disease, long-term compression, or neuropathy (Non-Patent Literature 6). Diabetic foot ulcers (DFUs) account for 80% of non-traumatic lower limb amputations, and the associated 5-year mortality rate is 43% to 55%.

[0008] These chronic wounds are primarily thought to involve serious colonization by multiple microbial communities, which contribute to persistent inflammation and cessation of the healing process, significantly reducing the patient's quality of life. In tissue injury, microorganisms enter the wound. The physical environment in a wound differs from that of the skin surface in terms of temperature, pH, nutrient availability, and host immune effectors. In this case, microbial metabolism may change, providing an opportunity for symbiotic microorganisms to become pathogenic and for the community composition to fluctuate in response to host 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. However, 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-producing species. 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 fungal expansion of mixed bacterial-fungal biofilms.

[0010] Biofilms are present in multiple additional conditions that can lead to chronic infections or recurrent 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 every 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 fungal infections to prevent vision loss (see Non-Patent Document 10). The lack of potent 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, leading to visual impairment or blindness. Bacteria, especially gram-positive bacteria, are associated with conjunctivitis, keratitis, endophthalmitis, blepharitis, and orbital cellulitis.

[0012] As a further skin disorder that has been proven to be 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 when hair follicles become clogged with dead skin cells and oil from the skin. It is a common skin disease. It has been suggested that P. acnes cells that normally inhabit hair follicles grow as a biofilm, making treatment particularly difficult (see, for example, Non-Patent Document 11). Biofilm formation also occurs on abiotic (i.e., inanimate) surfaces, such as residential areas, workplaces, industrial areas including manufacturing plants, public places, bathrooms, kitchens, furniture, transportation bases and surfaces, and other surfaces that come into contact with humans or animals.

[0013] <XXX By way of example and not limitation, the food and medical sectors pose major public health problems. Biofilms serve as a persistent source of pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, which can lead to serious infections such as foodborne infections and nosocomial infections. Such biofilms are also a source of material degradation and damage. Environmental conditions commonly found in the food and medical fields also appear to enhance biofilm formation and their resistance to disinfectants.

[0014]

[0015] It should be noted that there seems to be an issue with the "XXX" in the tag at line 9 in the original text. If this is an error, please correct it for a more accurate translation. Also, the tags are preserved as per the requirements, even if there are potential issues with some of them in the original.​Contamination caused by biofilms can occur at any stage of food processing, through food handlers, contaminated equipment, and food preparation surfaces (Non-Patent Literature 12). The Centers for Disease Control and Prevention (CDC) reported that there are 48 million food poisoning episodes in the United States each year, resulting in 128,000 hospitalizations and up to 3,000 deaths (Non-Patent Literature 13). In the European Union, 5,609 outbreaks of food poisoning 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 Literature 14). In addition, healthcare-associated infections (HAIs), also known as hospital-acquired infections, commonly occur through the hands of healthcare workers, contaminated surfaces, and equipment (surgical instruments, catheters, respiratory devices, endoscopes, needles, etc.) (Non-Patent Literature 15). The National Hospital Discharge Study (NHDS) estimated that there were a peak of 1.7 million cases of HAI in US hospitals between 1990 and 2002, of which 98,987 were fatal (Non-Patent Literature 16). In Europe, the number of HAI cases is estimated at 3.2 million per year (Non-Patent Literature 17).

[0016] Globally, the SARS-CoV virus has caused a global pandemic in recent years, continuing to plague the world. This pandemic has raised public awareness worldwide about the importance of disinfecting surfaces.

[0017] The problem of antibiotic resistance has worsened over decades, yet fewer antibiotics and other antimicrobial agents are being developed. Many infections that were once treatable are now far more difficult to treat with the current pool of medicines and may soon become untreatable. [Prior art documents] [Non-patent literature]

[0018] [Non-Patent Document 1] Karatan E., Watnick P. "Signals, regulatory networks, and materials that build and break bacterial biofilms" Microbiol. Mol. Biol Rev. 2009, 73:310-347 [Non-Patent Document 2] Sutherland IW "The biofilm matrix-An immobilized but dynamic microbial environment" Trends Microbiol. 2001, 9:222-227 [Non-Patent Document 3] Branda SS, Vik S., Friedman L., Kolter R. "Biofilms: The matrix revisited" Trends Microbiol. 2005, 13:20-26 [Non-Patent Document 4] Flemming H.-C., Wingender J., Szewzyk U. Steinberg, P., Rice SA, Kjelleberg, S. "Biofilms: An emergent form of bacterial life" Nature Reviews Microbiology 2016, 14:563-575 [Non-Patent Document 5] Tuft, S. "Polymicrobial infection and the eye" Br J Ophthalmol. 2006, 90(3):257-258 [Non-Patent Document 6] Richmond NA, Maderal AD, Vivas AC. Evidence-based management of common chronic lower extremity ulcers. Dermatol Ther 2013; 26:187-196 [Non-Patent Document 7] Evidence-based management of PAD & the diabetic foot. Brownrigg JR et al., Eur J Vasc Endovasc Surg. 2013 Jun; 45(6):673-81 [Non-licensed document 8] Percival SL, McCarty SM, Lipsky B. 2015. Biofilms and wounds: an overview of the evidence. Adv Wound Care (New Rochelle) 4: 373-381

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

[0020] In one embodiment, there is provided a novel organosilane quaternary ammonium compound that can be administered in an effective amount in a topical pharmaceutical formulation to a host in need of treatment to treat a wide range of infections, including fungal infections, 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.

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

[0022] Accordingly, in one embodiment, the organosilane quaternary ammonium compounds described herein can be used in effective amounts in topical formulations for direct administration to infections, or incorporated into, for example, bandages, adhesive bandages, surgical packing materials, gauze, packaging materials, shape-adjustable foams, or films for administration to wounds, such as chronic wounds or burns. When incorporated into articles, the organosilane quaternary ammonium compounds described herein can be incorporated such that the article controls the release of the compound or a pharmaceutically acceptable salt or composition thereof into the surrounding area to provide long-term inhibition of microbial growth. In some embodiments, an effective amount of selected compounds 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 or foot ulcers, skin lacerations, or moisture-related skin injuries (MASD), such as incontinence-related dermatitis. In some embodiments, the compounds described herein are used for the treatment of burn-induced wounds.

[0023] In further embodiments, the quaternary ammonium compounds described herein can be used in effective amounts, for example, for the treatment of 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 are available. Furthermore, the quaternary ammonium compounds described herein can be incorporated into medical implants for the purpose of reducing the risk of infection associated with the use of such devices.

[0024] Importantly, in some embodiments, the novel organosilane quaternary ammonium compounds described herein can be provided as a stable powder or lyophilized material, which can be formulated with a pharmaceutically acceptable topical carrier before administration. In alternative embodiments, the novel organosilane quaternary ammonium compounds described herein can be incorporated into bandages, shape-adjustable foams, polymers used in bandages, adhesive bandages, or films for medical applications, such as wound dressings or surgical packing materials, to reduce the risk of infection. 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.

[0025] In some embodiments, localized infections in humans or animals are treatable with selected organosilane quaternary ammonium compounds, which can be used to treat microorganisms, combinations of microorganisms, or biofilms containing such combinations, and the microorganisms include, 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), This includes species such as Klebsiella (Gram-negative), Enterococcus (Gram-positive), Haemophilus influenzae, and others. Fungi, such as Fusarium, Aspergillus, and Cryptocoryne. This includes genera such as Cladosporium, Curvularia, and Candida, as well as dermatophytes, such as Trichophyton and Microsporum. These include genera such as Microsporum and Epidermophyton.

[0026] In certain embodiments, the local infection includes, but is not limited to, Candida fungal infections, such as C. albicans, C. auris, or C. glabrata, or combinations thereof.

[0027] The present invention provides novel organosilicon quaternary amine compounds having (whether or not explicitly stated in the formula) a pharmaceutically acceptable charge-neutralizing anion (one or more). In certain embodiments, the charge-neutralizing anion is selected from chloride anions, fluoride anions, iodide anions, bromide anions, hydroxide anions, chlorite anions, chlorate anions, hydroxide anions, formate anions, acetate anions, lactate anions, benzoate anions, or salicylate anions. In typical embodiments, the charge-neutralizing anion is a chloride anion or a hydroxide anion.

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

[0029] In some embodiments, the quaternary ammonium compound is provided as a zwitterion, and the positive charge of the internal quaternary amine in the compound is neutralized by an anion derived from a substituent in the molecule, as further described below.

[0030] The present invention also provides a method for topically administering an effective amount of one or more of the novel organosilicon quaternary amine compounds described herein to a host needing treatment, prevention, inhibition, or elimination of 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 depots 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 relates to 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 C1-C4 alkyl including methyl, etc.), R 1 are each independently 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 (It is possible to be), C6~C 22 Alkenyl (this is 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 It is possible for it to be, and C6~C 22 Alkanoyl (This is 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 (It is possible to be) selected from (where either these methylene or aliphatic carbons may have branched alkyl groups, such as C1-C4 alkyl groups containing methyl), R 2 , R 3 , and R 4 Each of them operates independently. [ka] Select from or C2~C 10 Alkanes (these are C2, C3, C4, C5, C6, C7, C8, C9, or C 10 It is possible to be (or a salt thereof), and in some embodiments, R 2 , R 3 , and R 4 These are all alkanates (where either these methylene or aliphatic carbons may have branched alkyl groups, such as C1-C4 alkyl groups containing methyl), y is 0, 1, 2, 3, or 4. p is independently selected from 1, 2, 3, and 4. R 6 The elements are independently selected from hydrogen, alkyl, aryl, cycloalkyl, and heterocyclyl, and each of the alkyl, aryl, cycloalkyl, and heterocyclyl elements is optionally selected from C1-C6 alkyl, hydroxyl, chloro, bromo, iodine, fluoro, and N(R) 7 )2, COOR 7 , C(O)R 7 CH2OR 7 CON(R 7 )2 and NO2 have substituents selected from NO2, R 8 , R 9 , R 10 , R 11 , R 12 , and R 13 These are, independently, hydrogen, halogen, hydroxyl, and N(R) 7 )2, CH2OR 7 CON(R 7 )2, COOR 7 , C(O)R 7 Selected from C1-C8 alkyl, C1-C8 hydroxyalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C1-C8 alkanoyl, heterocyclyl, heteroaryl, and aryl. R 7 Each of these 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 Each of them operates independently, NR 17 Selected from CH2, CHOH, and C(O), X 2 Each of these is independently selected from C1-C3 alkyl and C1-C3 hydroxyalkyl groups. X 3These are, independently, hydroxyl, NO2, and N(R) 7 )2, CH2OR 7 , C ON(R 7 )2, COOR 7 , C(O)R 7 , C1~C 12 Selected from alkanates, C1-C8 alkyl, C1-C8 hydroxyalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C1-C8 alkanoyl, heterocyclyl, heteroaryl, and aryl. X 4 Each of them is independent of X 3 Selected from, R 16 Each of these is independently selected from C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, and C1-C4 haloalkyl. R 17 Each of these 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. X - X is an anion, for example, a chloride anion, a fluoride anion, an iodide anion, a bromide anion, a hydroxide anion, a chlorite anion, a chlorate anion, a formate anion, an acetate anion, a lactate anion, a benzoate anion, or a salicylate anion. - If it is an anion with two or more negative charges, the stoichiometry of the charge must be neutralized by other cations. B + B is a cation, for example, an ammonium cation, a potassium cation, or a sodium cation, and has a charge of 2 or more. + For example, if it is useful to use calcium cations, the stoichiometry must be neutralized appropriately, for example, [ka] To provide a quaternary ammonium compound having (as described).

[0034] In some embodiments, B + is K + or Na + In another embodiment, B + is Ca +2 or Mg +2 In a certain specific embodiment, B

[0035] is an ammonium ion, which includes NH4 + , RNH3 + , R2NH2 + , R3NH + , or R4N + , 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 methylenes 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 methylenes can have a branched alkyl, such as C1-C4 alkyl including methyl, etc.), X -X is an anion, for example, a chloride anion, a fluoride anion, an iodide anion, a bromide anion, a chlorite anion, a chlorate anion, a hydroxide anion, a formate anion, an acetate anion, a lactate anion, a benzoate anion, or a salicylate anion. - If the anion has two or more negative charges, the stoichiometry must be neutralized appropriately. R 14 and R 15 Each of them operates independently. [ka] , R 2 , and R 17 The present invention provides a quaternary ammonium compound having (selected from, where all other variable terms in the formula are as defined herein).

[0038] In another embodiment, the present invention is given by formula: [ka] (In the ceremony p and q are independently selected from 1, 2, 3, and 4, respectively. R 5 Each of them is independent of R 2 , R 17 , and C2~C 10 Alkanes (these are C2, C3, C4, C5, C6, C7, C8, C9, or C 10 (It is possible to be) selected from, where the acid is optionally a diacid or a salt thereof (where any of these methylenes may have a branched alkyl, for example, a C1-C4 alkyl containing methyl), R 2 Each of them operates independently. [ka] Select from, or R 2 Each is independently selected from C1-C8 alkanates or their salts. R 8 , R9 , R 10 , R 11 , R 12 , and R 13 These are, independently, hydrogen, halogen, hydroxyl, and N(R) 7 )2, CH2OR 7 CON(R 7 )2, COOR 7 , C(O)R 7 Selected from C1-C8 alkyl, C1-C8 hydroxyalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C1-C8 alkanoyl, heterocyclyl, heteroaryl, and aryl. R 7 Each of these 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 Each of them operates independently, NR 17 Selected from CH2, CHOH, and C(O), X 2 Each of these is independently selected from C1-C3 alkyl and C1-C3 hydroxyalkyl groups. X 3 These are, independently, hydroxyl, NO2, and N(R) 7 )2, CH2OR 7 CON(R 7 )2, COOR 7 , C(O)R 7 , C1~C 12 Selected from alkanates, C1-C8 alkyl, C1-C8 hydroxyalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C1-C8 alkanoyl, heterocyclyl, heteroaryl, and aryl. X 4 Each of them is independent of X 3 Selected from, R 17Each of these 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. X - X is an anion, for example, a chloride anion, a fluoride anion, an iodide anion, a bromide anion, a chlorite anion, a chlorate anion, a hydroxide anion, a formate anion, an acetate anion, a lactate anion, a benzoate anion, or a salicylate anion. - If it is an anion with two or more negative charges, the stoichiometry of the charge is such that it is still neutralized by other cations. B + is a cation, for example, a sodium cation, a potassium cation, a magnesium cation, a calcium cation, or a lithium cation, and B + However, if the cation has two or more positive charges, the stoichiometry of the charges provides a quaternary ammonium compound (where the charge is appropriately neutralized by other anions).

[0039] In certain embodiments, the quaternary ammonium compound has a negatively charged portion capable of forming 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 embodiment, by reacting one or more quaternary ammonium compounds of formula I, formula II, formula III, or formula IV with a polyhydroxyl compound, Oligomers or polymer products of formulas I', II', III', and IV' are formed, and the polyhydroxyl compound is, for example, a compound selected from glycerol, This is a glycol selected from one or more of the following: glycidol, glycerol, glycerol-propylene oxide copolymer, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, and polyvinyl alcohol.

[0041] In one aspect, one or more quaternary ammonium compounds 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 are reacted with a polyhydroxyl compound to produce compounds of formulas I', II', III', IV', V', VI', VII', VIII', IX', X', XI', XII', XIII', XIV', XV', XVI', XVII', XV Oligomers or polymer products of III', XIX', XX', XXI', XXII', XXIII', XXIV', XXV', XXVI', XXVII', XXVIII', XXIX', XXX', XXXI', XXXII', XXXIII', XXXIV', XXXV', XXXVI', XXXVII', XXXVIII', XXXIX', or XL' are formed, and 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, a pharmaceutical composition is provided using a quaternary ammonium compound as described herein, which contains about 5%, about 4%, about 3%, about 2%, about 1%, about 0.5%, or less than about 0.1% by weight of methanol, or which contains no methanol.

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

[0045] In some embodiments, any mixture of quaternary ammonium compounds as described herein, or pharmaceutically acceptable compositions thereof, is suitable, provided that the desired stability is achieved.

[0046] In some embodiments, the compounds of the present invention exist as a mixture of related structures. As examples, rather than being limited to one, the following molecules are primarily included: [ka] The composition consists of: [ka] These molecules may also contain some of the related structures. These related structures can be interconverted in solution.

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

[0048] As those skilled in the art will also understand, the compounds of the present invention may 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 indicated compound, although this solution may contain various related structures, the overall ratio of silicon side chain groups to silicone is as indicated. It is identical to the one described. For example, in some embodiments, the present invention is [ka] It is a solution of, however this solution contains various related molecules, [ka] Total number of parts [ka] The ratio of the parts is about 3 to 1 in terms of ratio (i.e., on a molar basis). In certain embodiments, about 3 to 1 includes any ratio from 2.6:1 to 3.4:1. In other embodiments, about 3 to 1 includes any ratio from 2.8:1 to 3.2:1. In certain embodiments, the sodium chloride (NaCl) salt can be replaced with another salt described herein. And in other embodiments, the present invention is [ka] It is a solution of, however this solution contains various related molecules, [ka] Total number of parts [ka] The ratio of the parts is about 2:1 in proportion (i.e., on a molar basis). In certain embodiments, about 2:1 includes any ratio from 1.6:1 to 2.4:1. In other embodiments, about 2:1 includes any ratio from 1.8:1 to 2.2:1. In certain embodiments, the sodium chloride (NaCl) salt can be replaced with another salt described herein.

[0049] In one embodiment, the present invention relates to the following formulas V, VI, VII, VIII, IX, X, XI, and XII: [ka] TIFF0007912110000017.tif185170 (in the formula, Each R 21 These are, independently, C1~C 22 Alkyl (this includes C1, C2, C3, C4, C5, C6, 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 (It is possible to be), C2~C 22 Alkenyl (this is C2, C3, C4, C5, C6, 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 (It is possible to be), C2~C 22 Alkanoyl (This is C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , or C 22 It is possible that this R is selected from (and alkyl-aryl), 21 Each of these is optionally substituted with one, two, or three substituents, and the substituents are independently C1-C6 alkyl, halogen, and [ka] Selected from, R 22 , R 23 , and R 24 Each of them operates independently. [ka] Selected from, R 25 Each of them is independent of R 22 , R 17 , and C2~C 10 Alkanes (these are C2, C3, C4, C5, C6, C7, C8, C9, or C 10 (It is possible to be) selected from, where the acid is optionally a diacid or a salt thereof. R 31 C6~C 22 Alkyl (this includes C6, 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 (It is possible to be), C6~C 22 Alkenyl (this is C6, C7, C8, C9, C10 , 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 (It is possible to be), C6~C 22 Alkinyl (this is C6, 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 It is possible for it to be, and C6~C 22 Alkenylalkynyl (this is C6, 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 (It is possible to be) selected from, Each R 32 Independently, hydrogen, [ka] Selected from, In a particular embodiment, each R 32 Independently, hydrogen, [ka] Selected from, R 33Each of these is independently selected from hydroxyl, hydrogen, C1-C6 alkyl, and halogen. R 34 and R 35 Each of them operates independently. [ka] , R 22 , and R 17 Selected from, Each R 36 Independently, hydrogen, [ka] Selected from, X 5 These are selected from heterocyclic, cycloalkyl, alkyl, aryl, heteroaryl, alkenyl, haloalkyl, and alkynyl compounds. The formula provides a quaternary ammonium compound selected from (wherein the remaining variable terms are as defined herein).

[0050] In a particular embodiment, the compound of the present invention is [ka] or a pharmaceutically acceptable salt thereof.

[0051] In a particular embodiment, R 22 , R 23 , and R 24 Each of them operates independently. [ka] Selected from.

[0052] In a particular embodiment, R 22 , R 23 , and R 24 Each of them operates independently. [ka] Selected from.

[0053] In a particular embodiment, each R 36 It is hydrogen.

[0054] In a particular embodiment, each R 32 It is -CH2-SO3H.

[0055] In one embodiment of the present invention, formulas XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, or XXI: [ka] TIFF0007912110000028.tif174170TIFF0007912110000029.tif184170 (in the formula, o is either 1 or 2. n is independently selected from 0, 1, and 2. m is 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 the alternative embodiment, R 101 and R 102 These are independently selected from hydrogen and ethyl, R 103 Each of them operates independently. [ka] Selected from, Each R 104 Each of these is independently selected from hydrogen, alkyl, alkenyl, alkynyl, halogen, and haloalkyl; R 105 Compounds of hydrogen (or -CH2CH2OH) are provided.

[0056] In certain embodiments of the quaternary ammonium compounds from formulas XIII to XXI, from formulas XXIII to XXXIII, and from formulas XXXV to 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 formulas XIII to XXI, m is 14. In certain embodiments of the quaternary ammonium compounds from formulas I to XXI, m is independently selected from 12 to 16.

[0057] In a particular embodiment, an ammonium compound of formula XIII, XIV, XV, XVI, or XVII in solution is in equilibrium with other quaternary ammonium compounds of formula XIII, XIV, XV, XVI, or XVII. In another embodiment, 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: [ka]

[0058] Due to the instability of the silicon-oxygen bond, these structures may interconvert by cleaving and forming bonds, potentially resulting in mixtures of formulas XIII, XIV, XV, XVI, and XVII, or mixtures of formulas XIII, XVIII, XIX, XX, or XXI.

[0059] Another aspect of the present invention, formulas XXII, XXIII, XXIV, XXV, XXVI, or XXVII: [ka] TIFF0007912110000033.tif194170 (in the formula, R106 The following are provided: each is independently selected from hydrogen, hydroxyl, and C1-C6 alkoxy, and all other variable items are as defined herein) a quaternary ammonium compound.

[0060] In one embodiment, a 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: [ka]

[0061] In one embodiment, a 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. As an example, but not limited to one, the following compounds may be in equilibrium: [ka]

[0062] Due to the instability of the silicon-oxygen bond, these structures may interconvert by cleaving and forming bonds, such that mixtures of formulas XXII, XXIII, or XXIV may exist, or mixtures of formulas XXV, XXVI, or XXVII may exist.

[0063] In another aspect of the present invention, formulas XXVIII, XXIX, or XXX: [ka] (In the formula, R 107 and R 108 Each of these is independently selected from C1-C6 alkoxys, and all other variable items are as defined herein, and a quaternary ammonium compound is provided.

[0064] In one embodiment, a 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: [ka]

[0065] Due to the instability of the silicon-oxygen bond, these structures can interconvert by cleaving and forming the bond, so that mixtures of formulas XXVIII, XXIX, or XXX may exist.

[0066] In another embodiment of the present invention, formula XXXI or XXXII: [ka] (In the formula, R A teeth, [ka] And, A is independent of each other, [ka] Selected from, p' is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. Quaternary ammonium compounds are provided (all other variable items are as defined herein).

[0067] Due to the instability of the silicon-oxygen bond, these structures can interconvert by cleaving and forming the bond, so that mixtures of formula XXXI or formula XXXII may exist.

[0068] In another embodiment, the present invention provides formula XXXIII: [ka] (All other variable terms in the formula are as defined herein, q', r, and s are each independently selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, which are quaternary ammonium compounds.

[0069] In one embodiment, q', r, and s are identical.

[0070] In another embodiment of the present invention, formulas XXXIV, XXXV, or XXXVI: [ka] (In the formula, X is [ka] Selected from, A quaternary ammonium compound is provided (where M is selected from hydrogen, sodium, potassium, cesium, or lithium, and all other variable items are as defined herein).

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

[0072] Due to the instability of the silicon-oxygen bond, these structures can interconvert by cleaving and forming the bond, so that mixtures of formulas XXXIV, XXXV, or XXXVI may exist.

[0073] In another aspect of the present invention, quaternary ammonium compounds of formulas XXXVII, XXXVIII, or XXXIX are provided: [ka]

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

[0075] Due to the instability of the silicon-oxygen bond, these structures can interconvert by cleaving and forming the bond, so that mixtures of formulas XXXVII, XXXVIII, or XXXIX may exist.

[0076] The present invention particularly aims to provide an antimicrobial composition containing one or more compounds of formula XXXVII, XXXVIII, or XXXIX, and a suitable carrier.

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

[0078] In another alternative embodiment, formula XL: [ka] (In the formula, R A As defined above, t is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. Each Z is independent of the others. [ka] Selected from, Each L is independent of the others. [ka] Selected from, R 124 and R 125 These are, independently, hydrogen, ethyl, [ka] Selected from, An oligomer or polymeric quaternary ammonium compound is provided, in which T is a monovalent capping group, which may optionally be derived from a curing agent, and in the formula all other variable items are as defined herein.

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

[0080] In certain embodiments, the curing agents for oligomers or polymers as described herein include diethylenetriamine (DTA), triethylenetetramine (TTA), tetraethylenepentamine (TEPA), dipropenediamine (DPDA), diethylaminopropylamine (DEAPA), amine 248, N-aminoethylpiperazine (N-AEP), Lamiron C-260, Araldite HY-964, and others. Intanedaamine (MDA), Isophoronediamine (IPDA), S Cure 211, S Cure 212, Wandamin HM, 1,3BAC, m-Xylenediamine (mX DA), Showamine X, Amine Black, Showamine Black, Showamine N, Showamine 1001, Showamine 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, e.g., 2-Methylimidazole, 2-Ethyl-4-Methylimidazole, 1-Cyanoethyl-2-Undecylimidazolium Trimelitate, and Epoxy-Imidazole Adducts, etc.; Liquid Polymercaptan or Polysulfide Refined Cells Lipids; or acid anhydrides, including, for example, phthalic anhydride, trimellitic anhydride, pyromellitic anhydride, benzophenone tricarboxylic acid anhydride, ethylene glycol bistrimellitate, glycerol tritrimellitate, maleic anhydride, tetrahydrophthalic anhydride, methyltetrahydrophthalic anhydride, endomethylene tetrahydrophthalic anhydride, methylendomethylene tetrahydrophthalic anhydride, methylbutenyl tetrahydrophthalic anhydride, dodecenyl succinic anhydride, hexahydrophthalic anhydride, hexahydrophthalic anhydride, hexahydro-4-methylphthalic anhydride, succinic anhydride, methylcyclohexenedicarboxylic acid anhydride, alkylstyrene-maleic acid anhydride copolymer, chloridenic acid anhydride, and polyazelaic acid polyanhydride.

[0081] In another embodiment of the present invention, formula A: [ka] (In the formula, Each R 109 Each of these is independently selected from halo, hydroxyl, and alkoxy, and all other variable items are as defined herein) a quaternary ammonium compound, Formulas B, C, D, E, F, G, H, or J: [ka] (wherein the formula, all other variable items are as defined herein) one or more compounds of, A product formed by reacting the two is provided.

[0082] In another embodiment of the present invention, compound B' is provided, which 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 oligomer or polymer compound having one or more formula B units and one or more formula A units.

[0083] In another embodiment of the present invention, compound C' is provided, which 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 oligomer or polymer compound having one or more formula C units and one or more formula A units.

[0084] In another embodiment of the present invention, compound D' is provided, which is one or more formulas It is formed by the reaction of compound A with one or more compounds of formula D. In one embodiment, compound D' is an oligomer or polymer compound having one or more formula D units and one or more formula A units.

[0085] In another embodiment of the present invention, compound E' is provided, which 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 oligomer or polymer compound having one or more formula E units and one or more formula A units.

[0086] In another embodiment of the present invention, compound F' is provided, which 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 oligomer or polymer compound having one or more formula F units and one or more formula A units.

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

[0088] In another embodiment of the present invention, a 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 oligomer or polymer compound having one or more formula H units and one or more formula A units.

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

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

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

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

[0093] In another embodiment, the compounds of the present invention are oily substances that can be administered topically as pure compounds. The oily substances are optionally mixed with excipients, carriers, or diluents described herein to maintain a long shelf life without solidification. For example, the oily substances of the present invention can be mixed with ionic liquids, organic solvents, or aqueous solutions to maintain their oily form. Examples of oily substances that can be mixed with the compounds of the present invention, but are not limited to, include coconut oil, rice bran oil, and vegetable oils. In certain particular embodiments, A mixture of the compound of the present invention and an additional oily substance forms a storage-stable oily composition that can be administered topically to patients who require such administration.

[0094] In certain embodiments, the compound of the present invention (optionally as an oil) is administered directly to a wound. Examples of how the compound can be administered include, but are not limited, dropping, pouring, tapping, or otherwise administering it to an open wound, a covered wound, or as part of a negative pressure wound treatment. For example, the compound of the present invention can be administered and inserted into a wound in the form of a sponge, after which the surrounding skin is sealed with a membrane, and a small suction tube is used to create a pressure below atmospheric pressure and to draw out the exudate.

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

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

[0097] In a particular embodiment, the glycerin solution is selected from glycerol, glycidol, glycerol-propylene oxide copolymer, ethylene glycol, propylene glycol, polyethylene glycol, or polypropylene glycol, or a combination thereof.

[0098] In another embodiment, a kit is provided, which comprises a vial containing a sterile aqueous solution, a vial containing a quaternary ammonium compound as described herein, and a dispensing device.

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

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

[0101] In another embodiment, a kit is provided which comprises a sterile aqueous solution and a quaternary ammonium compound as described herein, together with one or more compounds selected from solketal, epichlorohydrin, and polyvinyl alcohol.

[0102] In another embodiment, a kit is provided which comprises 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 compounds as described herein, or pharmaceutically acceptable compositions thereof, which are useful in effective amounts for treating, preventing, inhibiting, or eliminating infections in a host where there is a need for treatment, prevention, inhibition, or elimination of an infection.

[0104] In one embodiment, a method is provided, as further described herein, for treating, preventing, inhibiting or eliminating an infectious disease, wherein the method involves providing a host that needs to be treated, prevented, inhibited or eliminated with one or more quaternary ammonium compounds, as described herein. Or, it includes administering an effective amount of the pharmaceutically acceptable composition.

[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 embodiment, the present invention provides a method for administering one or more compounds of the present invention, or a pharmaceutically acceptable composition thereof, in an effective amount useful for treating, inhibiting, eliminating, or preventing the above-mentioned infection.

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

[0109] In some embodiments, one or more quaternary ammonium compounds or compositions thereof of the present invention are used in a host that needs to be treated or prevented from having an infection in a chronic wound, in an amount effective for treating or preventing an infection in a chronic wound.

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

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

[0118] In some embodiments, the compounds described herein are used to treat wounds caused by burns.

[0119] In another embodiment, infection in chronic wounds is caused by biofilms.

[0120] In some embodiments, one or more quaternary ammonium compounds of the present invention, or a composition thereof, are used in an amount effective for treating, preventing, or eliminating an eye infection in a host that needs to be treated, prevented, or eliminated for an eye infection.

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

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

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

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

[0125] In another embodiment, the eye infection is bacterial conjunctivitis, such as conjunctivitis caused by Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, or Pseudomonas erginosa.

[0126] In another embodiment, the eye infection is viral conjunctivitis, such as conjunctivitis caused by adenovirus or enterovirus.

[0127] In another embodiment, eye infections are multimicrobial in origin, making diagnosis and treatment more difficult. For example, when bacteria are involved in Acanthamoeba keratitis, there is a high risk of prolonged angiogenesis and healing.

[0128] In another embodiment, an eye infection is a sequential infection by one or more opportunistic organisms that may also cause infection. For example, a herpetic corneal ulcer may provide a suitable microenvironment for the establishment of bacterial or fungal pathogens.

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

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

[0131] In some embodiments, the eye composition is substantially methanol-free. In some embodiments, the infection to be treated is an eye infection.

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

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

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

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

[0136] In some embodiments, the infection is located 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 to these.

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

[0138] In some embodiments, one or more quaternary ammonium compounds or compositions thereof of the present invention are used in an amount effective for treating, preventing, or eliminating an ear infection in a host that needs to be treated, prevented, or eliminated for an ear infection.

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

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

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

[0142] In some embodiments, ear infections are caused by bacteria or fungi.

[0143] In another embodiment, ear infections are caused by both bacteria and fungi.

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

[0145] In another embodiment, a method is provided for treating an eye infection in a host that requires treatment for an eye infection, the method comprising administering an effective amount of one or more quaternary ammonium compounds or compositions thereof as described herein.

[0146] In another embodiment, a method is provided for treating onychomycosis, i.e., a fungal infection of the nail, in a host that needs treatment for the onychomycosis, the method comprising administering one or more quaternary ammonium compounds or compositions thereof as described herein in an effective amount.

[0147] In some embodiments, one or more quaternary ammonium compounds or compositions thereof of the present invention are used in an amount effective for treating, preventing, or eliminating onychomycosis in a host that needs to be treated, prevented, or eliminated.

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

[0149] In some embodiments, one or more quaternary ammonium compounds described herein are administered as aqueous, glycerin, or dimethyl sulfoxide solutions, which are formed by reconstructing 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 is provided for treating or preventing infections in a host requiring treatment or prevention of infections in chronic wounds, the method comprising administering an effective amount of one or more quaternary ammonium compounds or compositions thereof as described herein.

[0151] In another embodiment, a method is provided for treating or preventing a vaginal infection in a host requiring treatment or prevention of a vaginal infection, the method relating to one or more of the following four types described herein. This includes administering an effective amount of a ammonium compound or a composition thereof.

[0152] In some embodiments, one or more quaternary ammonium compounds of the present invention, or a composition thereof, are used in a host that needs to be treated or prevented from having a vaginal infection, in an amount effective for treating or preventing the 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 a Candida species.

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

[0156] In some embodiments, vaginal infections, such as vulvovaginal candidiasis, are caused by Lactobacillus, Bacteroides, and Peptostreptococcus. The genus Peptostreptococcus, the genus Fusobacterium, and / or Euba It is a bacterial infection caused by bacteria of the genus Eubacterium.

[0157] In another embodiment, a method is provided for treating a dermatological disorder in a host requiring treatment of a dermatological disorder, the method comprising administering an effective amount of one or more quaternary ammonium compounds or compositions thereof as described herein.

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

[0159] In certain embodiments, dermatological disorders include, for example, acne vulgaris, cystic acne, eczema, folliculitis, and skin infections.

[0160] In certain embodiments, dermatological disorders, such as acne vulgaris, are caused by the Gram-positive bacteria Propionibacterium acnes and / or Staphylococcus epidermidis.

[0161] In certain embodiments, dermatological disorders, such as eczema (atopic dermatitis), herpetic eczema, vaccinia eczema, or coxsackielic eczema, are caused by bacterial or viral infections.

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

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

[0164] In a particular embodiment, a dermatological disorder, such as a skin infection, is caused by Staphylococcus aureus (S. aureus).

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

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

[0167] In some embodiments, a non-living (i.e., abiotic) surface is directly treated with a solution containing one or more quaternary ammonium compounds described herein, or a mixture thereof, 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 erginosa.

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

[0172] In some embodiments, the fungal biofilm or fungal contamination includes a Candida fungal infection, where the Candida species are, for example, C. albicans, C. auris, or C. glabrata, or a mixture thereof.

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

[0174] In some embodiments, the viral biofilm or viral contamination is caused by SARS coronavirus 2 (COVID-19).

[0175] In some embodiments, a non-living (i.e., abiotic) surface is directly treated with a solution containing one or more quaternary ammonium compounds described herein, or a mixture thereof, for the removal of a multimicrobial biofilm or multimicrobial contamination and / or prevention of its recurrence.

[0176] In some embodiments, the multiple microbial biofilm or multiple microbial contamination includes bacterial species, fungal species, and viral species.

[0177] In some embodiments, one or more quaternary ammonium compounds described herein, or mixtures thereof, may be incorporated in effective amounts as an antimicrobial hand sanitizer or surface disinfectant spray, foam, liquid, gel, or solid.

[0178] In some embodiments, a method is provided for providing enhanced antimicrobial activity to the skin surface, which includes 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 antimicrobial activity is against fungi.

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

[0182] In some embodiments, the antimicrobial activity is against multiple microorganisms, including combinations of bacteria, fungi, 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 atom is substituted with deuterium.

[0189] Therefore, the present invention includes at least the following features: (a) 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, Quaternary ammonium compounds of XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL, (b) Quaternary ammonium compounds 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, XXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL used in 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, XXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL in the manufacture of pharmaceuticals for the treatment of bacterial, fungal, and / or viral infections. (d) A method for manufacturing a pharmaceutical product intended for therapeutic use to treat bacterial, fungal, and / or viral infections, comprising 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, A method characterized by using an effective amount of one or more quaternary ammonium compounds, namely XXVIII, XXIX, XXX, XXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL, in the production process. (e) A method for treating a bacterial, fungal, and / or viral infection, comprising administering to a host in need of treatment for the bacterial, fungal, and / or viral infection 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, XXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL in an effective amount. (f) A method for treating a bacterial, fungal, and / or viral infection, comprising administering to a host in need of treatment for the bacterial, fungal, and / or viral infection 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 an effective amount. (g) An antimicrobial composition comprising an effective amount of one or more quaternary ammonium compounds 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, and comprising a pharmaceutically acceptable excipient, (h) Powder or solid preparations, including lyophilized powder preparations 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, XXI, 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, XXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL, a sterile aqueous solution, and a dispensing 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, XXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL, and a dispensing device. (k) A process for synthesizing quaternary ammonium compounds 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, XXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL. (l) Quaternary ammonium compounds 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 as mixtures of enantiomers or diastereomers (if applicable), including racemates. (m) Quaternary ammonium compounds 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, XXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL in enantiomeric or diastereomeric (where applicable) forms, including isolated enantiomers or diastereomers (i.e., with 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 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, XXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL. (o) Products 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, XXI, 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. (p) Products 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, XXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL with one or more compounds selected from glycerol-propylene oxide copolymer, solketal, glycidol, or epichlorohydrin, used for the treatment of bacterial, fungal, and / or viral infections. (q) 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, XXI, 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 in the manufacture of a pharmaceutical product for the treatment of bacterial, fungal, and / or viral infections. (r) A method for manufacturing a pharmaceutical product intended for therapeutic use to treat bacterial, fungal, and / or viral infections, wherein the formula is 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, XXI, XXXII, XXXIII, XXXIV, A method characterized by using an effective amount of a product formed by reacting a compound of XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL with one or more compounds selected from glycerol, glycerol-propylene oxide copolymer, solketal, glycidol, or epichlorohydrin in the production process. (s) A method for treating bacterial, fungal, and / or viral infections, 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. (t) A method for treating bacterial, fungal, and / or viral infections, 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 antimicrobial 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, XXI, 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 comprising a pharmaceutically acceptable excipient, (v) Powdered or solid formulations containing a freeze-dried powder, comprising 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, XXI, 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, solketal, glycidol, or epichlorohydrin. (w) A powder or solid formulation containing a freeze-dried 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, XXI, 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 sterile aqueous solution, and a dispensing device. kit including, (x) 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, XXI, 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 dispensing device. (y) A process for preparing therapeutic products 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, XXI, 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, solketal, glycidol, or epichlorohydrin. (z) Bandages, adhesive bandages, surgical packing materials, films, packaging materials, and shape-conforming (comfortable) foams incorporating compounds of formulas I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL. Body, or other types of material, (aa) Not limited to, but including, bandages, adhesive bandages, surgical packing materials, films, packaging materials, and comfortable 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 for the treatment of skin infections, wounds, or ulcers such as lower limb ulcers, or diabetic ulcers such as diabetic lower limb ulcers or diabetic foot ulcers. , or use of other types of materials, (bb) 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', oligomeric or polymeric products of XXV', XXVI', XXVII', XXVIII', XXIX', XXX', XXXI', XXXII', XXXIII', XXXIV', XXXV', XXXVI', XXXVII', XXXVIII', XXXIX', or XL'; (cc) Oligomers or polymer products 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', used for the treatment of bacterial, fungal, and / or viral infections. (dd) In the manufacture of pharmaceuticals for the treatment of bacterial, fungal, and / or viral infections, formulas I', II', III', IV', V', VI', VII', VIII', IX', X', X Use of an effective amount of the 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 pharmaceutical product intended for therapeutic use to treat bacterial, fungal, and / or viral infections, characterized in that 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' is used in the manufacturing process. (ff) A method for treating a bacterial, fungal, and / or viral infection, comprising administering 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' to a host in need of treatment for a bacterial, fungal, and / or viral infection, (gg)An antimicrobial 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, Powders or solid preparations containing lyophilized powders comprising oligomers or polymer products or combinations thereof 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', or XL', (ii) A kit comprising a powder or solid formulation containing 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) Formula I', II', III', IV', V', VI', VII', VIII', IX', X', XI', XII', XIII', XIV', XV', XVI', XVII', XVIII', XIX', XX', XX I', XXII', XXIII', XXIV', XXV', XXVI', XXVII', XXVIII', XXIX', XXX', XXXI', XXXII', XXXIII', XXXIV', XXXV', XXXVI', A kit comprising a sterile aqueous or glycerin solution containing an oligomer or polymer product of XXXVII', XXXVIII', XXXIX', or XL', and a dispensing device. 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) Bandages, adhesive bandages, surgical packing materials, films, packaging materials, and shape-conforming materials 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'. Foam, or other types of materials, (mm) Not limited to, but for example, bandages, adhesive bandages, surgical packing materials, films, packaging materials, and comfortable 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' 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. , or use of other types of materials, (nn) A medical or dental implant 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 biofilm or microbial contamination by administering an effective amount of one or more quaternary ammonium compounds 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, XXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, or XL to a non-living (i.e., abiotic) surface, and, (pp) The antimicrobial quaternary compound of the present invention, optionally encapsulated in an appropriate carrier for the appropriate application, for use as a disinfectant on living surfaces including, but not limited to, home surfaces, workplaces, industrial areas, transportation areas, or carriers, kitchens, bathrooms, furniture, etc. [Brief explanation of the drawing]

[0190] [Figure 1] This bar graph shows the results of disk diffusion susceptibility tests conducted on various microorganisms using two solutions of Compound 1. The x-axis shows the microbial strains tested under three different reaction conditions, which include two concentrations of Compound 1 and a control. The y-axis represents the inhibition zone, measured in millimeters. [Figure 2] This bar graph shows the results of disk diffusion susceptibility tests conducted on various microorganisms while broadly increasing the concentration of compound 1. The x-axis shows the microbial strains tested under five different reaction conditions, which include four concentrations of compound 1 and a control. The y-axis represents the inhibition zone, measured in millimeters. [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 dose as a topical formulation to a host in need of treatment to treat a wide range of infections, including fungal infections, as well as Gram-positive bacterial infections, Gram-negative bacterial infections, and viral infections. The fungi can appear as yeasts, molds, or a combination of both. The novel quaternary ammonium compounds and formulations described herein can treat microorganisms in biofilms, including mixed organisms.

[0192] Accordingly, in one embodiment, the organosilane quaternary ammonium compounds described herein can be used in effective amounts in topical formulations for direct administration to infections, or incorporated into, for example, bandages, adhesive bandages, surgical packing materials, gauze, packaging materials, shape-adjustable foams, or films for administration to wounds, such as chronic wounds or burns. When incorporated into articles, the organosilane quaternary ammonium compounds described herein can be incorporated such that the article controls the release of the compound or a pharmaceutically acceptable salt or composition thereof into the surrounding area to provide long-term inhibition of microbial growth. In some embodiments, an effective amount of selected compounds 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 or foot ulcers, skin lacerations, or moisture-related skin injuries (MASD), such as incontinence-related dermatitis. In some embodiments, the compounds described herein are used for the treatment of burn-induced wounds.

[0193] Importantly, in some embodiments, the novel organosilane quaternary ammonium compounds described herein can be provided as a stable powder or lyophilized material, which can be formulated with a pharmaceutically acceptable topical carrier before administration. In alternative embodiments, the novel organosilane quaternary ammonium compounds described herein can be incorporated into bandages, shape-adjustable foams, polymers used in bandages, adhesive bandages, or films for medical applications, such as wound dressings or surgical packing materials, to reduce the risk of infection. 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, local infections in humans or animals are treatable with selected organosilane quaternary ammonium compounds, which can be used to treat microorganisms, combinations of microorganisms, or biofilms containing such combinations, and the microorganisms include, 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), and others. This includes species such as Klebsiella (Gram-negative), Enterococcus (Gram-positive), Haemophilus influenzae, and others. Fungi, such as Fusarium, Aspergillus, and Cladonia genera such as Cladosporium, Curvularia, and Candida, as well as dermatophytes, such as Trichophyton and Microsporum. These include genera such as Microsporum and Epidermophyton.

[0195] The selected compounds of the present invention can also 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 non-living (i.e., abominable) surfaces, such as residences, workplaces, industrial areas including manufacturing plants, public places, bathrooms, kitchens, furniture, transportation hubs or surfaces, or other surfaces that come into contact with or are in environments with humans or animals. In one embodiment, environmental surfaces commonly found in the food and medical fields appear to also exhibit improved biofilm formation and increased resistance to disinfectants.

[0196] definition Compounds are described using their formal names. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which this invention pertains.

[0197] Any of the formulas described herein, the quaternary ammonium compound thereof, includes isomers such as racemates, enantiomers, enantiomer mixtures, diastereomers, diastereomer mixtures, tautomers, and rotational isomers, as each is specifically described.

[0198] The terms "a" and "an" do not indicate a limit on quantity, but rather indicate the presence of at least one of the items mentioned. The term "or" means "and / or". Unless otherwise specified herein, the enumeration of value ranges is intended to serve merely as a simple way to refer individually to each distinct value contained within that range, and each distinct value constitutes part of this specification by reference as if they were individually enumerated herein. The endpoints of all ranges are contained within that range and can be combined independently. All methods described herein can be performed in a preferred order unless otherwise specified herein or clearly contradicted by the context. The use of example or illustrative words (e.g., "such as") is merely intended to better illustrate the invention. This does not constitute a limitation of the scope of the invention unless otherwise stated. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art to which the invention pertains.

[0199] The present invention includes quaternary ammonium compounds 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. An isotope is an atom that has the same atomic number but a different mass number, i.e., the same number of protons but a different number of neutrons.

[0200] Examples of isotopes that can be incorporated into the quaternary ammonium compound of the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, fluorine, chlorine, and iodine, for example, respectively. 2 H, 3 H, 11 C, 13 C, 14 C, 15 N, 17 O, 18 O, 18 F, 36 Cl, and 125 I is an example. In one non-limiting embodiment, an isotope-labeled quaternary ammonium compound is subjected to metabolic testing ( 14 Using C), reaction rate tests (for example, 2 H or 3 Positron emission tomography (PEM) detection or imaging techniques, including drug or substrate tissue distribution assays (using H). It can be used in imaging techniques (PET) or single-photon emission computed tomography (SPECT), or in radiation therapy for patients. For details, 18F-labeled compounds may be particularly desirable for PET or SPECT studies. The isotope-labeled quaternary ammonium compounds of the present invention and their prodrugs can generally be prepared by replacing the unlabeled reagents with readily available isotope-labeled reagents in the procedures disclosed in the scheme or in the examples and preparations described below.

[0201] As a general example, rather than a limited one, consider hydrogen isotopes, for example, deuterium ( 2 H) and tritium ( 3 H) may be used anywhere in the described structure where the desired result is obtained. Alternatively, or in addition to it, carbon isotopes, for example, 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 atom 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, at any location of interest. In one non-limiting embodiment, deuterium is enriched to at least about 90%, 95%, or 99%, at a desired location.

[0203] In one non-limiting embodiment, the substitution of one or more hydrogen atoms to deuterium atoms can be provided by any of the 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 to 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 The group is selected from any of the following, or arises within any other variable as defined herein. For example, if any of these groups is methyl, ethyl, or methoxy, or has methyl, ethyl, or methoxy through substitution, for example, then the alkyl residue is deuterated (in a non-limiting embodiment, such as CDH2, CD2H, CD3, CH2CD3, CD2CD3, CHDCH2D, CH2CD3, CHDCHD2, OCDH2, OCD2H, or OCD3). In certain other embodiments, if two substituents together form a ring, the unsubstituted carbon is deuterated.

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

[0205] The quaternary ammonium compounds of the present invention may or may not form solvates with a solvent (including water). Therefore, in one non-limiting embodiment, the present invention includes compounds in solvated form. The term "solvate" refers to a molecular complex of the compound of the present invention (including its salts) with one or more solvent molecules. Examples of solvents, though not limiting, 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 the quaternary ammonium compound of the present invention and water. Pharmaceutically acceptable solvates according to the present invention may include those in which the solvent is isotope-substituted, such as D2O, d6-acetone, or d6-DMSO. Solvates can be liquid or solid.

[0206] A dash ("-") without a space between two letters or symbols is used to indicate a substituent bond. For example, -(C=O)NH2 is bonded through the carbon of the keto (C=O) group.

[0207] The term "Group I" as used herein refers to the alkali metals of Group I, specifically lithium (Li), sodium (Na), potassium (K), rubidium (Rb), cesium (Cs), and francium (Fr). "Group II" as used herein refers to the alkaline earth metals of Group II, specifically beryllium (Be), magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba), and radium (Ra). "Group III" as used herein refers to aluminum. "Transition metal" as used herein refers to any element contained in the lanthanides and actinides of blocks d and f 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 atoms in one or more aromatic rings. In some embodiments, the aryl group has one to three separate or fused rings with 6 to about 14 or 18 ring atoms, but no heteroatoms as ring members. Where indicated, the aryl group may be further substituted with carbon or non-carbon atoms or groups. Such substitutions may include condensation with a 3- to 7-membered saturated cyclic group, which optionally has one or two heteroatoms independently selected from N, O, and S, and which condense to form, for example, a 3,4-methylenedioxyphenyl group. Examples of aryl groups include phenyl and naphthyl, with naphthyl including 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" refers to a branched or linear saturated aliphatic hydrocarbon group. In one non-limiting embodiment, an alkyl group contains 1 to about 12 carbon atoms, more commonly 1 to about 6 carbon atoms, or 1 to about 4 carbon atoms. In one non-limiting embodiment, an alkyl group contains 1 to about 8 carbon atoms. In certain embodiments, an alkyl group is C1-C2, C1-C3, C1-C4, C1-C5, or C1-C6. The designations used herein refer to alkyl groups having members in each range that are described as independent species. For example, the term C1-C6 alkyl as used herein refers to linear or branched alkyl groups having 1, 2, 3, 4, 5, or 6 carbon atoms, and is intended to mean that these are each described as independent species. For example, the term C1-C4 alkyl as used herein refers to linear or branched alkyl groups having 1, 2, 3, or 4 carbon atoms, and is intended to mean that these are each described as independent species. Examples of alkyl groups 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, alkyl groups may be optionally substituted. The term "alkyl" also includes cycloalkyl or carbocyclic groups. For example, when a term containing "alk" is used, unless the context clearly excludes it, The terms "cycloalkyl" or "carbocyclic" may be part of its definition. For example, without limitation, terms such as alkyl and haloalkyl may all be considered to include the cyclic form of alkyl unless clearly excluded by context.

[0210] In this specification, "hydroxyalkyl" refers to any of the alkyl groups described above. This indicates a molecule substituted with at least one hydroxyl substituent.

[0211] "Alkano acid" as used herein refers to any carboxylic acid in which R is alkyl, where alkyl is as defined herein. Furthermore, alkano acids can be diacides and / or halogens such as chloride, bromide, fluoride, iodide, hydroxyl, N(R) 7 It has one or more substituents selected from )2, NO2, alkyl, alkenyl, etc.

[0212] An "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 range as used herein refers to an alkenyl group having each member in the range described above as an independent species for the alkyl moiety. 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 includes cycloalkyl or carbocyclic groups having at least one unsaturated point.

[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 designations used herein refer to alkynyl groups having each member in the range described above as an independent species for the alkyl moiety. Examples of alkynyls 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 may be optionally substituted. The term "alkynyl" also encompasses cycloalkyl or carbocyclic groups having at least one unsaturated point.

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

[0215] A "haloalkyl" is a branched or linear 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. A "perhaloalkyl" means an alkyl group in which all hydrogen atoms are replaced with halogen atoms. Examples include, but are not limited to, trifluoromethyl and pentafluoroethyl.

[0216] The terms “heterocyclyl” or “heterocyclic” as used herein 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, or 7 to 10 ring atoms, where at least one ring atom is a heteroatom selected from nitrogen, oxygen, phosphorus, and sulfur, the remaining ring atoms are carbon, and one or more ring atoms are independently optionally substituted with one or more of the above substituents. A heterocyclic is a monocyclic 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 having 6 to 10 ring members (4 to 9 carbon atoms and 1 to 6 heteroatoms selected from N, O, P, and S), e.g., bicyclo[4,5], [5,5], It may be a [5,6] or [6,6] system. In some embodiments, the heteroatom is nitrogen only. In some embodiments, the heteroatom is oxygen only. In some embodiments, the heteroatom is sulfur only. Heterocyclic compounds are described in "Principles of Modern Heterocyclic Chemistry" by Paquette, Leo A. (WA Benjamin, New York, 1968), particularly chapters 1, 3, 4, 6, 7 and 9; "The Chemistry of Heterocyclic Compounds, A series of Monographs" by 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 heterocycles 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, indlinyl, 2H-pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl, pyrazolinyl, dithianyl, dithiolanyl, di Hydropyranyl, 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-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[4.1.0]heptanyl, azabicyclo Examples include, but are not limited to, chloro[2.2.2]hexanyl, 3H-indolyl, quinolidinyl, N-pyridylurea, and pyrrolopyrimidine. Spiro moieties are also included in this definition. Examples of heterocyclic groups in which one or two ring carbon atoms are substituted with an oxo (=O) moiety are pyrimidinolyl and 1,1-dioxo-thiomorpholinyl. The heterocyclyl groups herein may be independently and optionally substituted with one or more substituents as described herein.

[0217] A "heterocycloalkyl" is a saturated ring group. It may have, for example, one, two, three, or four heteroatoms independently selected from N, S, and O, with the remaining ring atom being carbon. In a typical embodiment, nitrogen is the heteroatom. Monocyclic heterocycloalkyl groups typically have three to about eight ring atoms or four to six ring atoms. Examples of heterocycloalkyl groups include morpholinyl, piperadinyl, piperidinyl, and pyrrolinyl.

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

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

[0220] The “therapeutically effective amount” of the composition / combination of the present invention means an amount that, when administered to a host, is effective in providing a therapeutic effect, such as remission of symptoms or reduction or decrease of the disease itself. In some embodiments, the therapeutically effective amount is an amount sufficient to prevent exacerbations, induce regression, induce a cure, or inhibit, eliminate, or prevent an infection in a host where such effects are needed.

[0221] As used herein, “salt” refers to a derivative of the disclosed compound, in which the parent compound is modified by forming an inorganic or organic, non-toxic, acid or base addition salt of itself. The salts of the compounds of the present invention are derived from the parent compound having a basic or acidic moiety. These can be synthesized by conventional chemical methods. Generally, such salts can be prepared by reacting a free acidic form of the compound with a stoichiometric amount of a suitable base (e.g., hydroxide, carbonic acid, sodium bicarbonate, Ca, Mg, or K), or by reacting a free basic form of the compound with a stoichiometric amount of a suitable acid. Such reactions are typically carried out in water, an organic solvent, or a mixture of these two. Generally, non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are typical, if applicable. The salts of the compounds of the present invention further include the compounds and solvates of the 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 and quaternary ammonium salts of parent compounds formed from non-toxic inorganic or organic acids. For example, conventional non-toxic 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, ecylic acid, besylic acid, sulfanilic acid, 2-acetoxybenzoic acid, fumaric acid, toluenesulfonic acid, methanesulfonic acid, ethanedisulfonic acid, oxalic acid, isethionic acid, HOOC-(CH2) n’ Examples include salts prepared from -COOH (where n' is 0-4), 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, 17.th It can be found in the 20th ed., Mack Publishing Company, Easton, Pa., p. 1418 (1985).

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

[0224] chemistry "alkyl" embodiment In some embodiments, "alkyl" is C1-C 10 These are 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, the "alkyl" has one carbon atom.

[0226] In some embodiments, the "alkyl" has two carbon atoms.

[0227] In some embodiments, the "alkyl" has three carbon atoms.

[0228] In some embodiments, the "alkyl" has four carbon atoms.

[0229] In some embodiments, the "alkyl" has five carbon atoms.

[0230] In some embodiments, the "alkyl" has six carbon atoms.

[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 activated pentyl.

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

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

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

[0239] "Haloalkyl" embodiment In some embodiments, "haloalkyl" is C1-C 10 These include 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, the "haloalkyl" has one carbon atom.

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

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

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

[0244] In some embodiments, the "haloalkyl" has two carbon atoms.

[0245] In some embodiments, the "haloalkyl" has three carbon atoms.

[0246] In some embodiments, the "haloalkyl" has four carbon atoms.

[0247] In some embodiments, the "haloalkyl" has five carbon atoms.

[0248] In some embodiments, the "haloalkyl" has six carbon atoms.

[0249] As a non-limiting example of "haloalkyl", [ka] These are some examples.

[0250] As a further non-limiting example of "haloalkyl", [ka] These are some examples.

[0251] As a further non-limiting example of "haloalkyl", [ka] These are some examples.

[0252] As a further non-limiting example of "haloalkyl", [ka] These are some examples.

[0253] While silane quaternary amine compounds have been previously described for biocidal applications, their use has been limited to industrial and agricultural applications, such as textiles, clothing, construction materials, food packaging, adhesives, roofing materials, fiberglass, plastics, agricultural products, paints, coatings and surface treatments, carpets, wood, water purification systems, and laundry additives, as well as medical applications, such as medical supplies and surgical gloves. Furthermore, many of these silane quaternary amine compounds are typically sold in methanol, and therefore may be toxic for pharmaceutical and other medical applications (U.S. Patents 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 excessively toxic to the host. They can be used to treat people and animals in remote areas who do not currently have access to adequate antimicrobial healthcare approaches.

[0255] The quaternary ammonium compounds described herein exhibit improved stability compared to other organosilanes, such as 3-(trihydroxysilyl)-N-propyl-N,N-dimethyloctadecylammonium chloride, and also exhibit improved polymerization and subsequent formation of insoluble polysilsesquioxane materials in both solid and solution states. Because of the reduced alcohol content, it results in improved shelf life. In addition, the formulations of the present invention are substantially free of alcohols, such as methanol, ethanol, and / or other undesirable small amounts of volatile organic compounds.

[0256] The quaternary ammonium compounds of the present invention do not produce by-products, such as methanol by hydrolysis. The powder or other solid formulations of the present invention, such as the lyophilized powder, are substantially free of methanol, ethanol, and / or other undesirable small amounts of volatile organic compounds. This is achieved by either (i) not using such compounds in the manufacture, or (ii) using vacuum drying during processing, which is a far greater improvement than commercially available aqueous solutions of other organosilane antimicrobial agents, such as 3-(trihydroxysilyl)-N-propyl-N,N-dimethyloctadecylammonium chloride. 3-(trihydroxysilyl)-N-propyl-N,N-dimethyloctadecylammonium chloride often contains a considerable amount of methanol as a byproduct of its synthesis.

[0257] Because these molecules are small enough, they can quickly perfuse biofilms, even as oligomeric species, and are stable enough to cross small channels in biofilms even in aqueous or glycerin solutions, thus resulting in increased penetration into biofilms with the effectiveness of removing entire biofilms containing surviving bacterial cells.

[0258] The efficacy is maintained even after interaction with and killing of microorganisms. This is because organosilane molecules are not consumed by such interactions and can remain lethal to active microorganisms. Furthermore, the killing mechanism of these compounds reduces the likelihood of resistance developing in the targeted organism compared to other topical infection treatments using antibiotics and antifungals.

[0259] Quaternary organosilane compounds forming sulfonates have also been reported previously, but their uses were limited to industrial and agricultural applications, and there were no medical applications as described above. These molecules are considered toxic for medical use, such as in the treatment of the eyes and ears. These organosilanes contain organic sulfuric acid esters, 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 Publications 2011 / 0293681; 2012 / 0052106; 2013 / 0231599; 2014 / 0100504; 2016 / 0346193; 2017 / 0094974; and International Publications 2000 / 54587; 2004 / 004793). However, the compound hydrolyzes to release methanol, both in the aquatic environment of biological systems and when forming aqueous compositions, which can be toxic to organisms and as toxic as digestion even when absorbed by tissues (see Ind. Eng. Chem. 1931, 23, 931-936). The formation of toxic methanol as a byproduct is a concern for pharmaceutical and medical applications. Their use in this context is severely restricted or largely excluded. Furthermore, no stable form of silane quaternary ammonium compounds is known that does not use additives deemed unsuitable for medical applications.

[0261] In some embodiments, the quaternary ammonium compounds of the present invention are solid compounds that readily dissolve in water to form stable aqueous solutions. For example, the quaternary ammonium compounds can dissolve in physiological saline, deionized water, or buffer solutions to form visually clear aqueous solutions. In some embodiments, the aqueous solutions can be stored at room temperature without turbidity for at least 1, 2, 3, 4, 5, 6, 8, 12, 16 days, or longer. In other embodiments, the quaternary ammonium compounds can be made more soluble by first forming a powder using a freeze-dryer.

[0262] In another embodiment, the quaternary ammonium compound of the present invention, when dissolved in water, forms a neutral or nearly neutral solution. For example, the aqueous solution is approximately 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 - It may not be present, and the quaternary amine is neutralized by the internal anion. One non-restrictive example is the compound of formula I below: [ka]

[0265] In other embodiments, the quaternary ammonium compound of the present invention is not zwitterionic. In this embodiment, the quaternary amine is X - It is neutralized by [a certain compound]. For example, the following compounds of formula I are possible: [ka]

[0266] In some embodiments, zwitterionic quaternary ammonium compounds are more soluble in aqueous media than their non-zwitterionic forms. In yet another embodiment, zwitterionic compounds are more stable in aqueous solutions than their non-zwitterionic forms. In some embodiments, zwitterionic compounds are more soluble in aqueous media than their non-zwitterionic forms. In yet another embodiment, zwitterionic compounds are more stable in aqueous solutions than their non-zwitterionic forms. In certain embodiments, sodium chloride (NaCl) salts can be replaced with other salts described herein.

[0267] In an alternative embodiment, the quaternary ammonium compound of formula I is a zwitterion, and X - No ions exist. For example, in some embodiments, formula I is, [ka] Therefore, a representative compound of formula I is [ka] That is the case.

[0268] In an alternative embodiment, the quaternary ammonium compound of formula III is a zwitterion, and X - No ions exist. For example, in some embodiments, Equation III is, [ka] Therefore, a representative compound of formula III is, [ka] That is the case.

[0269] In an alternative embodiment, the quaternary ammonium compound of formula IV is a zwitterion, and X - No ions exist. For example, in some embodiments, formula IV is, [ka] Therefore, a representative compound of formula IV is, [ka] That is the case.

[0270] Representative compounds of the present invention In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0271] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0272] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0273] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0274] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0275] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0276] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0277] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0278] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0279] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0280] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0281] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0282] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0283] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0284] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0285] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0286] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0287] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0288] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0289] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0290] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0291] In some embodiments, the quaternary ammonium compounds of the present invention are [ka] That is the case.

[0292] Representative compounds of the present invention In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] TIFF0007912110000088.tif220170TIFF0007912110000089.tif196170TIFF0007912110000090.tif223170TIFF0007912110000091.tif230170TIFF0007912110000092.tif211170TIFF0007912110000093.tif79170.

[0293] In a particular embodiment, the compound of the present invention is [ka] Selected from.

[0294] In a particular embodiment, the compound of the present invention is [ka] Selected from.

[0295] In a particular embodiment, the compound of the present invention is [ka] Select from TIFF0007912110000097.tif202170 or TIFF0007912110000098.tif132170, or any alternative protonation state that is available at pH 6-8, with additional B as appropriate to compensate for the change in charge. + or X - It has counterions.

[0296] In a particular embodiment, the compound of the present invention is [ka] Select from TIFF0007912110000100.tif184170 or TIFF0007912110000101.tif129170, or any alternative protonation state that is available at pH 6-8, with additional B as appropriate to compensate for the change in charge. + or X - It has counterions.

[0297] In a particular embodiment, the compound of the present invention is [ka] Select from TIFF0007912110000103.tif187170 or TIFF0007912110000104.tif123170, or any alternative protonation state that is available at pH 6-8, with additional B as appropriate to compensate for the change in charge. + or X - It has counterions.

[0298] In a particular embodiment, the compound of the present invention is [ka] Selected from.

[0299] In a particular embodiment, the compound of the present invention is [ka] Selected from.

[0300] In a particular embodiment, the compound of the present invention is [ka] Select from TIFF0007912110000108.tif197170 or TIFF0007912110000109.tif174170, or any alternative protonation state that is available at pH 6-8, with additional B as appropriate to compensate for the change in charge. + or X - It has counterions.

[0301] In a particular embodiment, the compound of the present invention is [ka] Selected from.

[0302] In a particular embodiment, the compound of the present invention is [ka] Select from TIFF0007912110000112.tif192170 or TIFF0007912110000113.tif247170, or any alternative protonation state that is available at pH 6-8, with additional B as appropriate to compensate for the change in charge. + or X - counter It has ions.

[0303] In a particular embodiment, the compound of the present invention is [ka] Selected from.

[0304] In a particular embodiment, the compound of the present invention is [ka] Select from TIFF0007912110000116.tif188170 or TIFF0007912110000117.tif131170, or any alternative protonation state that is available at pH 6-8, with additional B as appropriate to compensate for the change in charge. + or X - It has counterions.

[0305] In a particular embodiment, the compound of the present invention is [ka] Selected from.

[0306] In a particular embodiment, the compound of the present invention is [ka] Selected from.

[0307] In a particular embodiment, the compound of the present invention is [ka] Selected from TIFF0007912110000121.tif181170TIFF0007912110000122.tif183170TIFF0007912110000123.tif182170TIFF0007912110000124.tif96170, or any alternative protonation state that is available at pH 6-8, with additional B as appropriate to compensate for the change in charge. + or X - It has counterions.

[0308] In a particular embodiment, the compound of the present invention is [ka] Selected from.

[0309] In a particular embodiment, the compound of the present invention is [ka] Selected from TIFF0007912110000127.tif182170TIFF0007912110000128.tif186170TIFF0007912110000129.tif186170TIFF0007912110000130.tif187170, or any alternative protonation state that is available at pH 6-8, with additional B as appropriate to compensate for the change in charge. + or X - It has counterions.

[0310] In a particular embodiment, the compound of the present invention is [ka] Selected from.

[0311] In a particular embodiment, the compound of the present invention is [ka] Selected from TIFF0007912110000133.tif182170 and TIFF0007912110000134.tif198170.

[0312] In a particular embodiment, the compound of the present invention is [ka] Selected from TIFF0007912110000136.tif196170 and TIFF0007912110000137.tif131170.

[0313] In a particular embodiment, the compound of the present invention is [ka] Selected from TIFF0007912110000139.tif228170 and TIFF0007912110000140.tif252170.

[0314] In a particular embodiment, the compound of the present invention is [ka] Selected from TIFF0007912110000142.tif177170 and TIFF0007912110000143.tif254170.

[0315] In a particular embodiment, the compound of the present invention is [ka] Selected from.

[0316] In a particular embodiment, the compound of the present invention is [ka] Selected from TIFF0007912110000146.tif216170.

[0317] In a particular embodiment, the compound of the present invention is [ka] Selected from TIFF0007912110000148.tif225170.

[0318] In a particular embodiment, the compound of the present invention is [ka] Selected from TIFF0007912110000150.tif221170.

[0319] In a particular embodiment, the compound of the present invention is [ka] Selected from TIFF0007912110000152.tif224170.

[0320] In a particular embodiment, the compound of the present invention is [ka] Selected from.

[0321] In a particular embodiment, the compound of the present invention is [ka] Selected from.

[0322] In a particular embodiment, the compound of the present invention is [ka] Selected from.

[0323] In a particular embodiment, the compound of the present invention is [ka] Selected from.

[0324] In a particular embodiment, the compound of the present invention is [ka] Selected from.

[0325] In a particular embodiment, the compound of the present invention is [ka] Selected from.

[0326] In a particular embodiment, the compound of the present invention is [ka] Select from TIFF0007912110000160.tif229170, TIFF0007912110000161.tif158170, or any alternative protonation state that is available at pH 6-8, with additional B as appropriate to compensate for the change in charge. + or X - It has counterions.

[0327] In a particular embodiment, the compound of the present invention is [ka] Select from TIFF0007912110000164.tif183170, TIFF0007912110000165.tif183170, or any alternative protonation state that is available at pH 6-8, with additional B as appropriate to compensate for the change in charge. + or X - It has counterions.

[0328] In a particular embodiment, the compound of the present invention is [ka] Selected from.

[0329] In a particular embodiment, the compound of the present invention is [ka] Select from TIFF0007912110000169.tif185170, TIFF0007912110000170, TIFF0007912110000171, and TIFF0007912110000171.tif159170.

[0330] In some embodiments, the present invention relates to the following formula: [ka] The present invention provides a quaternary ammonium compound having (wherein all variable terms are as defined herein).

[0331] In a particular embodiment of formula I, R 2 , R 3 , and R 4 Independently, [ka] (In the formula, R 8 , R 9 , X 1 , X 2 , and B + (as defined herein) is selected from.

[0332] In a particular embodiment, R 8 and R 9 These are independently selected from hydrogen, hydroxyl, C1-C8 alkyl, and C1-C8 hydroxyalkyl.

[0333] In a particular embodiment, X 1 It is NH.

[0334] In a particular embodiment, X 1 , NR 17 And in the formula, R 17 These are C1-C8 hydroxyalkyl groups.

[0335] In a particular embodiment, X 1 This is CH2.

[0336] In a particular embodiment, X 2 These are C1-C3 alkyl groups.

[0337] In a particular embodiment, X 2 These are C1-C3 hydroxyalkyl groups.

[0338] In a particular embodiment of formula I, [ka] Independently, [ka] Selected from, in the formula, B + H is optional. + It can be replaced with B + It does not exist, and this part is anionic.

[0339] In a particular embodiment of formula I, [ka] Independently, [ka] Selected from, in the formula, B + H is optional. + It can be replaced with B + It does not exist, and this part is anionic.

[0340] In a particular embodiment of formula I, [ka] Independently, [ka] Selected from, in the formula, B + H is optional. + It can be replaced with B+ It does not exist, and this part is anionic.

[0341] In a particular embodiment of formula I, [ka] Independently, [ka] Selected from, in the formula, B + H is optional. + It can be replaced with B + It does not exist, and this part is anionic.

[0342] In a particular embodiment of formula I, [ka] Independently, [ka] Selected from, in the formula, B + H is optional. + It can be replaced with B + It does not exist, and this part is anionic.

[0343] In a particular embodiment of formula I, [ka] Independently, [ka] Selected from TIFF0007912110000186.tif197170, in the formula, B + H is optional. + It can be replaced with B + It does not exist, and this part is anionic.

[0344] In a particular embodiment of formula I, [ka] Independently, [ka] Selected from, in the formula, B + H is optional. + It can be replaced with B + It does not exist, and this part is anionic.

[0345] In a particular embodiment of formula I, [ka] Independently, [ka] Selected from, in the formula, B + H is optional. + It can be replaced with B + It does not exist, and this part is anionic.

[0346] In a particular embodiment of formula I, [ka] Independently, [ka] Selected from, in the formula, B + H is optional. + It can be replaced with B + It does not exist, and this part is anionic.

[0347] In a particular embodiment of formula I, [ka] Independently, [ka] Selected from, in the formula, B + H is optional. + It can be replaced with B + It does not exist, and this part is anionic.

[0348] In a particular embodiment of formula I, [ka] Independently, [ka] Selected from TIFF0007912110000197.tif217170, in the formula, B + H is optional. + It can be replaced with B + It does not exist, and this part is anionic.

[0349] In a particular embodiment of formula I, [ka] Independently, [ka] Selected from TIFF0007912110000200.tif208170 and TIFF0007912110000201.tif57170, in the formula, B + H is optional. + It can be replaced with B + It does not exist, and this part is anionic.

[0350] In a particular embodiment of formula I, [ka] Independently, [ka] Selected from TIFF0007912110000204.tif227170 and TIFF0007912110000205.tif125170, in the formula, B + H is optional. + It can be replaced with B + It does not exist, and this part is anionic.

[0351] In a particular embodiment of formula I, R 2 , R 3 , and R 4 Independently, [ka] (In the formula, R 10 , R 11 , R 12 , R 13 , and X 3 (as defined herein) is selected from.

[0352] In a particular embodiment, R 10 and R 11 These are independently selected from hydrogen and C1-C8 alkyl groups.

[0353] In a particular embodiment, R 12 and R 13 These are independently selected from hydrogen, hydroxyl, C1-C8 alkyl, COOH, and C1-C8 hydroxyalkyl.

[0354] In a particular embodiment, X 3 These are independently selected from hydroxyl, C1-C8 alkyl, and C1-C8 hydroxyalkyl.

[0355] In a particular embodiment of formula I, [ka] teeth, [ka] Selected from TIFF0007912110000209.tif226170.

[0356] In a particular embodiment of formula I, [ka] teeth, [ka] Selected from TIFF0007912110000212.tif241170.

[0357] In a particular embodiment of formula I, [ka] teeth, [ka] Select from TIFF0007912110000215.tif210170 and TIFF0007912110000216.tif202170.

[0358] In a particular embodiment of formula I, [ka] teeth, [ka] Selected from.

[0359] In a particular embodiment of formula I, R 2 , R 3 , and R 4 Independently, [ka] (In the formula, R 8 , R 9 , X1 , and X 4 (as defined herein) is selected from.

[0360] In a particular embodiment, [ka] teeth, [ka] Select from TIFF0007912110000222.tif206170 and TIFF0007912110000223.tif108170.

[0361] In a particular embodiment, [ka] teeth, [ka] Selected from.

[0362] In a particular embodiment, [ka] teeth, [ka] Selected from.

[0363] In a particular embodiment, [ka] teeth, [ka] Selected from.

[0364] In a particular embodiment, [ka] teeth, [ka] Selected from.

[0365] In a particular embodiment, [ka] teeth, [ka] Selected from.

[0366] In a particular embodiment, [ka] teeth, [ka] Selected from.

[0367] In a particular embodiment, [ka] teeth, [ka] Selected from.

[0368] In a particular embodiment, [ka] teeth, [ka] Selected from.

[0369] In a particular embodiment, [ka] teeth, [ka] Selected from.

[0370] In a particular embodiment, [ka] teeth, [ka] Selected from.

[0371] In a particular embodiment, [ka] teeth, [ka] Selected from.

[0372] In a particular embodiment, [ka] teeth, [ka] Selected from.

[0373] In a particular embodiment, [ka] teeth, [ka] Selected from.

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

[0375] In a particular embodiment, X 1 It is NH.

[0376] In a particular embodiment, X 1 , NR 17 And in the formula, R 17 Each of these elements 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 a particular embodiment, X 1 This is CH2.

[0378] In a particular embodiment, X 4 It is NH2.

[0379] In a particular embodiment, X 4 N(R) 7 )2, and in the formula, R 7 These are, independently, hydrogen, C1-C8 alkyl, C1-C8 hydroxyalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C1-C8 alkanoyl, and he Selected from telocyclyl, heteroaryl, heterocycloalkyl, and aryl.

[0380] In a particular embodiment, X 4 C1~C 12 It is an alkanic acid.

[0381] In a particular embodiment of formula I, [ka] teeth, [ka] Selected from.

[0382] In a particular embodiment of formula I, [ka] teeth, [ka] Selected from TIFF0007912110000254.tif34170.

[0383] In a particular embodiment of formula I, [ka] teeth, [ka] Selected from.

[0384] In a particular embodiment of formula I, [ka] teeth, [ka] Selected from.

[0385] In a particular embodiment, the quaternary ammonium compound of formula I is [ka] Selected from TIFF0007912110000260.tif163170TIFF0007912110000261.tif156170TIFF0007912110000262.tif226170TIFF0007912110000263.tif227170TIFF0007912110000264.tif233170TIFF0007912110000265.tif225170TIFF0007912110000266.tif152170, in the formula, B + H is optional. + It can be replaced with B + It does not exist, and this part is anionic.

[0386] In a particular embodiment, the quaternary ammonium compound of formula I is [ka] Select from TIFF0007912110000268.tif191170, TIFF0007912110000269.tif221170, TIFF0007912110000270, TIFF0007912110000271.tif122170.

[0387] In another embodiment of the present invention, a quaternary ammonium compound of formula I is [ka] Selected from TIFF0007912110000273.tif220170 or TIFF0007912110000274.tif70170, or a salt thereof or a pharmaceutically acceptable composition thereof.

[0388] In another embodiment of the present invention, a quaternary ammonium compound of formula I is [ka] Selected from TIFF0007912110000276.tif156170, TIFF0007912110000277.tif227170, or a salt thereof or a pharmaceutically acceptable composition thereof.

[0389] In another embodiment of the present invention, a quaternary ammonium compound of formula I is [ka] Selected from TIFF0007912110000280.tif183170, TIFF0007912110000281.tif186170, or a salt thereof or a pharmaceutically acceptable composition thereof.

[0390] In another embodiment of the present invention, a quaternary ammonium compound of formula I is [ka] Selected from, or a salt thereof or a pharmaceutically acceptable composition thereof.

[0391] In another embodiment of the present invention, a quaternary ammonium compound of formula I is [ka] Selected from, or a salt thereof or a pharmaceutically acceptable composition thereof.

[0392] In another embodiment of the present invention, a quaternary ammonium compound of formula I is [ka] Selected from, or a salt thereof or a pharmaceutically acceptable composition thereof.

[0393] In another embodiment of the present invention, a quaternary ammonium compound of formula I is [ka] Selected from.

[0394] In another embodiment of the present invention, a quaternary ammonium compound of formula I is [ka] Selected from.

[0395] In another embodiment of the present invention, a quaternary ammonium compound of formula I is [ka] Selected from.

[0396] In another embodiment of the present invention, a quaternary ammonium compound of formula I is [ka] Selected from.

[0397] In another embodiment of the present invention, a quaternary ammonium compound of formula I is [ka] Selected from.

[0398] In another embodiment of the present invention, a quaternary ammonium compound of formula I is [ka] Selected from.

[0399] In another embodiment of the present invention, a quaternary ammonium compound of formula I is [ka] Selected from.

[0400] In another embodiment of the present invention, a quaternary ammonium compound of formula I is [ka] Selected from.

[0401] In another embodiment of the present invention, a quaternary ammonium compound of formula I is [ka] Selected from.

[0402] In another embodiment of the present invention, a quaternary ammonium compound of formula I is [ka] Selected from.

[0403] In another embodiment of the present invention, a quaternary ammonium compound of formula I is [ka] Selected from.

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

[0405] In a particular embodiment of formula II, R 14 and R 15 Each of them operates independently. [ka] , R 2 , and R 17 Selected from.

[0406] In a particular embodiment of formula II, R 14 and R 15 Each of them operates independently. [ka] Selected from.

[0407] In a particular embodiment of formula II, R 14 and R 15 Each of them is independent of R 2 Selected from.

[0408] In a particular embodiment of formula II, R 14 and R 15 Each of them is independent of R 17 Selected from.

[0409] In a particular embodiment, the quaternary ammonium compound of formula II is [ka] Selected from TIFF0007912110000301.tif217170TIFF0007912110000302.tif178170TIFF0007912110000303.tif217170TIFF0007912110000304.tif201170TIFF0007912110000305.tif254170, or a salt thereof or a pharmaceutically acceptable composition thereof.

[0410] In another aspect of the present invention, a quaternary ammonium compound of formula II is [ka] Selected from, or a salt thereof or a pharmaceutically acceptable composition thereof.

[0411] In another embodiment, the present invention relates to the following formula: [ka] (In the formula, a, p, q, y, R 1 , R 5 , R 6 , R 16 , and X - This is defined herein as The present invention provides a quaternary ammonium compound having ( ) or a salt thereof, or a pharmaceutically acceptable composition thereof.

[0412] In a particular embodiment of Equation III, R 5 Independently, [ka] (In the formula, R 8 , R 9 , X 1 , X 2 , and B + (as defined herein) is selected from.

[0413] In a particular embodiment of Equation III, R 5 Independently, [ka] (In the formula, R 10 , R 11 , R 12 , R 13 , and X 3 (as defined herein) is selected from.

[0414] In a particular embodiment of Equation III, R 5 Independently, [ka] (In the formula, R 8 , R 9 , X 1 , and X 4 (as defined herein) is selected from.

[0415] In a particular embodiment of Equation III, R 5 R is independent of R 17 Selected from, R 17 Each of these elements 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 a particular embodiment of Formula III or Formula IV, R 6 The elements are independently selected from alkyl, aryl, cycloalkyl, and heterocyclyl, each of which is optionally C1-C6 alkyl, hydroxyl, halogen, NH2, or 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 It has substituents selected from )2 and NO2.

[0417] In a particular embodiment of Equation III, R 5 Independently, [ka] (In the formula, p and (R 6 ) y (as defined herein) is selected from.

[0418] In a particular embodiment of Formula III, [ka] teeth, [ka] Selected from.

[0419] In a particular embodiment of Formula III, [ka] teeth, [ka] Selected from TIFF0007912110000316.tif185170.

[0420] In a particular embodiment of Equation III, R 5 These are, independently, C1~C 12 Selected from alkanic acids or their salts, R 5 This alkanoic acid forms a bond with any carbon atom on the hydrocarbon chain that is available for the formation of a CO bond.

[0421] For example, R 5 teeth, [ka] A bond can be formed in this location.

[0422] In a particular embodiment of Equation III, R 5 C1~C 12 It is an alkanoic acid, and this acid is optionally a diacid, in the formula R 5 This alkanoic acid forms a bond with any carbon atom on the hydrocarbon chain that is available for the formation of a CO bond.

[0423] For example, if the alkanoic acid is a diacid, R 5 teeth, [ka] A bond can be formed in this location.

[0424] In a particular embodiment of Equation III, R 5 C1~C 12It is an alkanoic acid, which optionally has one or more substituents on its hydrocarbon chain, the substituents being, in particular, hydrogen, halogen, hydroxyl, N(R) 7 ) Selected from 2.

[0425] For example, if an alkanoic acid has one or more substituents, R 5 teeth, [ka] A bond can be formed in this location.

[0426] In a particular embodiment of Equation III, R 5 teeth, [ka] Select C1~C 12 It is an alkanic acid.

[0427] In a particular embodiment of Equation III, R 5 teeth, [ka] Select C1~C 12 It is an alkanic acid.

[0428] In a particular embodiment of Equation III, R 5 teeth, [ka] C1~C selected from TIFF0007912110000323.tif201170 and TIFF0007912110000324.tif228170 12 It is an alkanic acid.

[0429] In a particular embodiment, y is 0. In a particular embodiment, y is 1. In a particular embodiment, y is 2. In a particular embodiment, y is 3. In a particular embodiment, y is 4.

[0430] In a particular embodiment, p is 0. In a particular embodiment, p is 1. In a particular embodiment, p is 2. In a particular embodiment, p is 3. In a particular embodiment, p is 4.

[0431] In a particular embodiment, q is 0. In a particular embodiment, q is 1. In a particular embodiment, q is 2. In a particular embodiment, q is 3. In a particular embodiment, q is 4.

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

[0433] In a particular embodiment of Formula III, [ka] teeth, [ka] Selected from.

[0434] In a particular embodiment of Formula III, [ka] teeth, [ka] Selected from.

[0435] In a particular embodiment of Formula III, [ka] teeth, [ka] Selected from.

[0436] In a particular embodiment of Formula III, [ka] teeth, [ka] Selected from.

[0437] In a particular embodiment of Formula III, [ka] teeth, [ka] Selected from.

[0438] In a particular embodiment of Formula III, [ka] teeth, [ka] Selected from.

[0439] In a particular embodiment of Formula III, [ka] teeth, [ka] Selected from TIFF0007912110000339.tif98170.

[0440] In a particular embodiment of Formula III, [ka] teeth, [ka] Selected from TIFF0007912110000342.tif213170 and TIFF0007912110000343.tif203170.

[0441] In a particular embodiment of Formula III, [ka] teeth, [ka] Selected from TIFF0007912110000346.tif163170.

[0442] In a particular embodiment of Formula III, [ka] teeth, [ka] Selected from TIFF0007912110000349.tif159170.

[0443] In a particular embodiment of formula IV, [ka] teeth, [ka] Selected from.

[0444] In a particular embodiment of formula IV, [ka] teeth, [ka] Selected from.

[0445] In a particular embodiment of formula IV, [ka] teeth, [ka] Selected from TIFF0007912110000356.tif226170.

[0446] In a particular embodiment of formula IV, [ka] teeth, [ka] Selected from.

[0447] In a particular embodiment of formula IV, [ka] teeth, [ka] Selected from.

[0448] In some embodiments of formula IV, [ka] teeth, [ka] Selected from.

[0449] In some embodiments of formula IV, [ka] teeth, [ka] Selected from TIFF0007912110000365.tif36170.

[0450] In some embodiments of formula IV, [ka] teeth, [ka] Selected from TIFF0007912110000368.tif205170 and TIFF0007912110000369.tif199170.

[0451] In some embodiments of formula IV, [ka] teeth, [ka] Selected from TIFF0007912110000372.tif145170.

[0452] In some embodiments of formula IV, [ka] teeth, [ka] Selected from TIFF0007912110000375.tif217170.

[0453] In another embodiment of the present invention, the quaternary ammonium compound of formula III is [ka] Selected from TIFF0007912110000377.tif101170.

[0454] In another embodiment of the present invention, the quaternary ammonium compound of formula III is [ka] Selected from.

[0455] In another embodiment of the present invention, a quaternary ammonium compound of formula IV is [ka] Selected from TIFF0007912110000380.tif192170.

[0456] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from TIFF0007912110000382.tif169170.

[0457] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from.

[0458] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from.

[0459] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from.

[0460] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from.

[0461] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from TIFF0007912110000388.tif194170.

[0462] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from.

[0463] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from.

[0464] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from TIFF0007912110000392.tif184170.

[0465] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from.

[0466] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from.

[0467] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from.

[0468] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from.

[0469] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from.

[0470] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from.

[0471] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from.

[0472] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from TIFF0007912110000401.tif61170.

[0473] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from TIFF0007912110000403.tif162170.

[0474] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from.

[0475] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from.

[0476] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from.

[0477] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from.

[0478] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from.

[0479] In a particular embodiment, the quaternary ammonium compound of the present invention is [ka] Selected from TIFF0007912110000410.tif138170.

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

[0481] In certain embodiments, a mixture of quaternary ammonium compounds is provided, 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% of alkyl (C14, 50%, C12, 40%, C16, 10%) dimethylbenzylammonium chloride; and (4) 0.01% to 99.9% of dioctyldimethylammonium chloride; and any desired solvent mixture, with or without a thickener (e.g., guar gum or PVA).

[0482] In a particular embodiment, 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% of alkyl (C14, 50%, C12, 40%, C16, 10%) dimethylbenzylammonium chloride; and (4) 0. The mixture comprises 0.1-99.9% dioctyldimethylammonium chloride, and any desired 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, comprising (1) 0.01% to 99.9% of the compound of the present invention; and (2) 0.01% to 99.9% of another compound of the present invention; and any desired 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, 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 any desired solvent mixture, with or without a thickening agent (e.g., guar gum or PVA).

[0485] In a particular embodiment, a mixture of quaternary ammonium compounds is provided, 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 any desired 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, comprising (1) 0.01% to 99.9% of the compounds of the present invention; and (2) 0.01% to 99.9% of alkyl (C14, 50%, C12, 40%, C16, 10%) dimethylbenzylammonium chloride; and any desired solvent mixture, with or without a thickener (e.g., guar gum or PVA).

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

[0489] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (1) is present in a concentration of approximately 5% to 99%.

[0490] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (1) is present in a concentration of approximately 10% to 99%.

[0491] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (1) is present in a concentration of approximately 20% to 99%.

[0492] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (1) is present in a concentration of approximately 30% to 99%.

[0493] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (1) is present in a concentration of approximately 5% to 90%.

[0494] In a particular embodiment, one of the mixtures of the above components is a quaternary ammonium compound. A mononium compound (1) is provided in a concentration of approximately 10% to 80%.

[0495] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (1) is present in a concentration of approximately 20% to 70%.

[0496] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (1) is present at a concentration of approximately 30% to 60%.

[0497] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (1) is present at a concentration of approximately 40% to 60%.

[0498] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (2) is present in a concentration of approximately 5% to 99%.

[0499] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (2) is present in a concentration of approximately 10% to 99%.

[0500] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (2) is present in a concentration of approximately 20% to 99%.

[0501] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (2) is present in a concentration of approximately 30% to 99%.

[0502] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (2) is present in a concentration of approximately 5% to 90%.

[0503] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (2) is present in a concentration of approximately 10% to 80%.

[0504] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (2) is present in a concentration of approximately 20% to 70%.

[0505] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (2) is present in a concentration of approximately 30% to 60%.

[0506] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (2) is present at a concentration of approximately 40% to 60%.

[0507] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (3) is present in a concentration of approximately 5% to 99%.

[0508] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (3) is present in a concentration of approximately 10% to 99%.

[0509] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (3) is present in a concentration of approximately 20% to 99%.

[0510] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (3) is present in a concentration of approximately 30% to 99%.

[0511] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (3) is present in a concentration of approximately 5% to 90%.

[0512] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (3) is present in a concentration of approximately 10% to 80%.

[0513] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (3) is present in a concentration of approximately 20% to 70%.

[0514] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (3) is present at a concentration of approximately 30% to 60%.

[0515] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (3) is present at a concentration of approximately 40% to 60%.

[0516] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (4) is present in a concentration of approximately 5% to 99%.

[0517] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (4) is present in a concentration of approximately 10% to 99%.

[0518] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (4) is present in a concentration of approximately 20% to 99%.

[0519] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (4) is present in a concentration of approximately 30% to 99%.

[0520] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (4) is present in a concentration of approximately 5% to 90%.

[0521] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (4) is present in a concentration of approximately 10% to 80%.

[0522] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (4) is present in a concentration of approximately 20% to 70%.

[0523] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (4) is present in a concentration of approximately 30% to 60%.

[0524] In a particular embodiment, a mixture of the above components is provided in which the quaternary ammonium compound (4) is present at a concentration of approximately 40% to 60%.

[0525] In a particular embodiment, the 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 concentration is measured as a percentage in mol / L units.

[0526] In a particular embodiment, 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] Treatment methods for infectious diseases The present invention includes a method for treating an infectious disease in a host using a quaternary ammonium compound or product or mixture thereof as described herein.

[0530] In some embodiments, the infection is treated directly with a solution containing one or more quaternary ammonium compounds of the present invention (typically reconstructed from sterile powders or solids).

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

[0532] Biofilm Biofilms can develop in many environments, including healthcare settings, equipment, and the surfaces of medical devices, and, most importantly, in the skin, ears, wounds, and other in vivo local areas of humans and animals. These colonized microbial communities differ significantly from their corresponding plankton communities. Although estimates vary, it is possible that as much as 40% of bacterial genes are upregulated or downregulated during the transition from planktonic to biofilm states in order to acquire specialized functions (see Davies DG, Parsek MR, Pearson JP, Iglewski BH, Costerton JW, Greenberg EP "The involvement of cell-to-cell signals in the development of a bacterial biofilm" Science. 1998, 280, 295-298; and Hall-Stoodley L., Costerton JW, Stoodley P. "Bacterial biofilms: From the natural environment to infectious diseases" Nat. Rev. 2004, 2, 95-108). "Formation of microbial communities attached to surfaces" What was once defined as such has come to be recognized as a complex developmental process with multifaceted and dynamic properties. (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. (See 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 resistant to conventional antimicrobial treatments" and are "a major cause of treatment failure today" (see Roemling, U. Balsalobre, C. "Biofilm infections, their resilience to therapy and innovative treatment strategies." Journal of Internal Medicine, 2004, 272: 541-561). Microorganisms form biofilms in vivo. When they form biofilms, they can acquire resistance not only to antibiotics but also to the host's own immune defenses. Antibiotics designed to combat infections have traditionally been developed to kill planktonic bacteria, based on the assumption that such drugs would kill the same bacteria regardless of their morphology. However, even with the same bacteria, those in a biofilm state undergo a dramatic shift in gene expression compared to those in a planktonic state. This is different. These changes in gene expression have emergent properties that cannot be predicted based on studies of plankton-like cells alone. Bacteria protected within biofilms have up to 1000 times higher antibiotic resistance than bacteria in plankton-like morphology (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, as well as 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 Literature 4 and Al-Fattani MA and Douglas LJ "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 are often composed of multiple cell layers. The layered nature of biofilms leads to heterogeneous exposure of individual organisms to oxygen and nutrients, particularly in deeper layers, creating an environment that can alter metabolic activity. Often, these deeper organisms are known as "surviving bacterial cells" and are in a quiescent state. These quiescent cells are often enhanced to chemotherapeutic agents by the cell layers above them and are therefore exposed to less treatment than those on the biofilm's surface. For example, the effectiveness of antibiotics often decreases in deeper biofilms because a large portion of the antibiotic is consumed by the cells in the upper layers before it can diffuse to the lower layers, resulting in insufficient concentrations reaching deeper levels (Roemling and Balsalobre, 551). This phenomenon leads to incomplete removal of biofilms in many antimicrobial treatment regimens, resulting in the survival of resistant cells and thus creating a situation of chronic or persistent infection (Musk, Jr. D. and Hergenrother, P. "Chemical Countermeasures for the Control of Bacterial Biofilms: Effective Compounds and Promising Current Medicinal Chemistry 2006, 13, 2163-2177).

[0536] By genetically encoding information to identify encountered antibiotics, surviving bacterial cells enable future 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, HA, 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 complex and dense structures, within which biocides have difficulty penetrating and reaching the inner layers, thus hindering the effectiveness of biocides (Bridier, et. al. "Resistance of bacterial biofilms to disinfectants: a See review "Biofouling 2011, Vol. 27". Biocides are chemically highly reactive molecules. Because of this, the presence of organic matter, such as proteins, nucleic acids, or carbohydrates, can significantly impair the effectiveness of biocides, and potential interactions between antimicrobial agents and biofilm components can also limit the penetration of antimicrobial agents into biofilms.

[0538] "In the United States, more than 5 million central venous catheters are implanted each year, and biofilm infections occur in more than 50% of these catheters. In the U.S. alone, this results in approximately 100,000 deaths and a $6.5 billion expenditure surplus 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. Often, such treatments are not even possible because many critically ill patients cannot tolerate them, leaving them with few options, which highlights the need to find better therapeutic and diagnostic therapies to combat these biofilms" (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). A certain implementation In terms of form, the compounds described herein are useful for treating, preventing, or removing biofilms.

[0539] The most common eye infections include conjunctivitis (red eye), bacterial or viral conjunctivitis (pink eye), corneal ulcer, keratitis, bacterial, fungal, and herpetic keratitis, endophthalmitis, and blepharitis (eyelid infection). Conjunctivitis is the most common eye infection. Conjunctivitis is an infectious disease, with viral conjunctivitis being 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 and bacterial conjunctivitis cause redness of the eyes. It presents with symptoms and is highly infectious (https: / / www.ncbi.nlm.nih.gov / pmc / articles / PMC6003010 / ). Eye Blepharitis is inflammation of the eyelids. Common causes of blepharitis include pain, red eyelids, and stiff eyelashes. The eyelid margins can become infected with bacterial or fungal infections, and the accumulation of these can form a biofilm. Parasitic eyelash mites called Demodex mites are a cause of blepharitis. They feed on film, which leads to an overgrowth of mites that exacerbates 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 infections are the most common cause of infectious keratitis. Common bacteria include S. aureus, coagulase-negative Staphylococcus species, S. pneumoniae, and Pseudomonas erginosa (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 in contact lens wearers. Acanthamoeba should be suspected if a patient swims or visits 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 accompanied by inflammation of the eyelid margin, but this inflammation is relatively rarely recognized as a cause rather than a consequence of dry eye. Blepharitis is often treated with ointments (often erythromycin), which appears to be helpful. It has been suggested that dry eye syndrome has four stages. Stage 1 involves the eyelash follicles, where biofilms can establish a habitat. Stage 2 This involves both the eyelash follicles and meibomian glands and can explain meibominan gland dysfunction (MGD) because biofilms block the openings of the giant meibomian glands (a combination of biofilms and poor or modified meibomian glands). It takes even longer to reach stage 2. Stage 3 involves the hair follicles, meibomian glands, and the Krause and Wolfring accessory lacrimal glands. Distance, narrow ducts, and a constant tear flow protect these glands for decades, making them the last to be affected by biofilm formation. Stage 4 occurs when the structural integrity of the eyelid is ultimately destroyed due to chronic inflammation, which can manifest clinically as, for example, eyelid laxity, hypotonia (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 external auditory canal (otitis externa), inner ear (otitis interna), or middle ear canal (otitis media). Most ear infections occur in the middle ear, causing fluid accumulation, swelling, and inflammation as bacteria or viruses multiply. Ear infections can become chronic, which is generally due to biofilm accumulation. Recent clinical trials have shown that almost all chronic omandibular malformations (OM) cases involve bacterial biofilms in the posterior tympanic membrane (eardrum) and within the middle ear. Evidence has been found to be associated with this condition. Biofilms are typically very thin and cannot be detected with a standard otoscope. Otitis media (OM) is the most common childhood illness in the United States, with three-quarters of children under three years old experiencing OM at least once. Although most cases are chronic infections, long-term or permanent damage to the ear can still occur. Acute otitis media may resolve on its own within one to two weeks, but may require treatment with antibiotics. Approximately 50% of antibiotic prescriptions for children under three years old are for ear infections. However, in cases of chronic OM, antibiotics may no longer be effective, and surgery is usually required to place a tympanostomy tube in the middle ear's tympanic membrane. (https: / / biophotonics.illinois.edu / sites / default / files / BOE-LCI_Biofilms_0.pdf).

[0543] Vulvovaginal candidiasis occurs when Candida species invade the superficial layer of the vaginal mucosa and trigger an inflammatory response. The main inflammatory cells are typically polymorphonuclear cells and macrophages. Patients may present with discharge (which is typically viscous and sticky, or accompanied by peeling), "external" dysuria, vaginal itching, vaginal burning, dyspareunia, or swelling.

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

[0545] Biofilms formed by pathogenic fungi have attracted attention in recent years, and several species of filamentous fungi, yeasts, and dimorphic fungi have been described as being capable of developing into communities. Biofilms are colonized microbial communities that adhere strongly to surfaces and to each other, and are protected by a polymeric extracellular matrix (ECM) mainly composed of polysaccharides. In this case, cells exhibit enhanced resistance and different phenotypes compared to plankton-like 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] Candida species include the novel opportunistic pathogen Candida dubliniens. Including (is), it is currently an emerging force among major pathogens causing hospital-acquired infections. Many of these infections associated with Candida biofilm formation include those occurring with devices such as intravascular catheters. Fungal biofilm-associated infections are often refractory to conventional therapy due to antibiotic resistance.

[0547] Biofilm-associated Candida species exhibit uniform resistance to a wide range of currently available conventional antifungal agents, suggesting a need for antibiotics that specifically target biofilm-associated infections. Novel classes of antifungal agents, amphotericin lipid preparations, and echinocandin have demonstrated unique antifungal activity against resistant Candida biofilms, offering a breakthrough in the treatment of life-threatening invasive systemic mycoses. The use of drugs effective in combating biofilm-associated infections could lead to significant advances 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 adhere to non-living surfaces, such as prostheses and catheters, and yeasts, in particular, can take advantage of this situation to gain access to the bloodstream and reach the patient's internal organs. This requires vigilance, as disseminated fungal infections have a high mortality rate (Verstrepen KJ, Klis FM 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, exhibiting individual developmental stages similar to those of bacterial biofilms. Paracoccidioides brasiliensis is a system endemic to Central and South America. This is a dimorphic fungus that causes paracoccidioidomycosis, a type of sexually transmitted fungal infection. Sardi et al. (Sardi Jde C., Pitangui Nde S., Voltan AR, Braz JD, Machado MP, Fusco Almeida AM, Mendes Giannini MJ In vitro Paracoccidioides brasiliensis biofilm and Gene expression of adhesins and hydrolytic enzymes. Virulence. 2015, 6, 642-651. doi: 10.1080 / 21505594.2015.1031437.). Histoplasma capsulatum biofilms were first described by Pitangui et al. This fungus is also characterized by thermodimorphism and is a cause of histoplasmosis. Histoplasmosis is a respiratory and systemic fungal infection whose manifestation depends on the survival and replication of yeast in alveolar macrophages (Pitangui NS, Sardi JC, Silva JF, Benaducci T., Moraes da Silva RA, Rodriguez-Arellanes G., Taylor ML, Mendes-Giannini MJ, Fusco-Almeida AM 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 tissue and cause dermatophytosis, which is one of the most common skin mycoses in humans and animals (Weitzman I., Summerbell RC The dermatophytes. Clin. Microbiol. Rev. 1995, 8, 240-259. doi: 10.1016 / S0733-8635(05)70320-X). Among dermatophytosis, onychomycosis is often accompanied by recurrence and long-term treatment, and in some cases treatment is ineffective. Considering this situation and the hypothesis by Burkhart et al. that dermatophytic globules can be explained by biofilm formation by dermatophytes, Costa-Orlandi et al. investigated the effects of two of the most prevalent species worldwide, Trichophyton rubrum and T. mentagrophytes, in In vitro biofilm formation was confirmed (Burkhart CN, Burkhart CG, Gupta AK) 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 CB, Sardi JC, Santos CT, Fusco-Almeida AM, Mendes-Giannini MJ 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 outbreak of C. auris infections has been reported in healthcare facilities 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 infection is treated by applying a bandage material containing one or more quaternary ammonium compounds of the present invention as an antimicrobial composition to the site of infection, the bandage material releasing one or more quaternary ammonium compounds of the present invention to the site of infection. The infection may involve the presence of bacteria, fungi, viruses, amoebas, or combinations thereof.

[0552] Topical applications include treatment of the oral cavity, including the teeth and gums. Gingivitis can occur in both chronic and acute forms. Acute gingivitis is usually associated with certain infections, microorganisms, or trauma. Chronic inflammation of the gum tissue surrounding the teeth is associated with bacterial biofilms (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, such as for plaque removal or reduction, or for the prevention, reduction, or delay of plaque formation. These compounds can also be used for the treatment and prevention of infections or infectious diseases that may occur in the oral cavity, such as gingivitis and periodontitis. The organosilicon quaternary ammonium compounds of the present invention can also be incorporated as ingredients in oral health management agents (e.g., toothpaste) to prevent dental caries (tooth decay) and gingivitis.

[0553] Topical application includes oral / lip care, treatment of oral ulcers, and herpes simplex. Herpes simplex is contagious, and if an individual becomes infected, strict hygiene measures must be taken. Primary oral infection is caused by the herpes simplex virus (HSV), the virus that causes oral herpes. After primary oral infection, HSV remains inactive and may only reactivate later as the more common oral herpes, or "herpes simplex." Triggers for reactivation are known, including sun exposure, trauma, fatigue, stress, and menstruation (https: / / www.dentalhealth.ie / dentalhealth / causes / coldsores.html). The most common form of oral ulcer is called aphthous ulcer. Typically, one to five small ulcers (less than 1 mm in diameter) appear on the inside of the lips or cheeks, or on the bottom of the mouth or tongue. The ulcers tend to concentrate towards the front of the mouth. Another more serious cause of oral ulcers is herpes infection (https: / / www.dentalhealth.ie / dentalhealth / causes / mouthulcers.html).

[0554] In some embodiments, treatment of an infection includes placing a bandage containing an antimicrobial composition as described herein in or over the site of infection.

[0555] In another embodiment, treatment of an infection includes placing an antimicrobial composition containing one or more quaternary ammonium compounds of the present invention at the site of infection. The duration of administration of the quaternary ammonium compounds or compositions is such that the antimicrobial treatment remains effective or the infection is resolved. Treatment may be applied continuously, with simultaneous sequential applications after appropriate time intervals, or alternating with treatment for another infection after appropriate time intervals. The quaternary ammonium compounds described herein may be administered to the site of infection in the host at appropriate intervals as determined by the healthcare provider.

[0556] In some embodiments, the quaternary ammonium compounds described herein are used for 1 day It is placed at the site of infection for a period of time less than or equal to a certain duration. In other embodiments, the quaternary ammonium compounds described herein are placed at the site of infection for a period of one week or more.

[0557] An effective amount of the antimicrobial composition described herein, or the antimicrobial composition described herein used in combination with or alternately with another active pharmaceutical agent, or used prior to, concurrently with, or subsequently with another active pharmaceutical agent, is used in an amount sufficient to inhibit the progression of a disorder (e.g., an infection) caused by the presence of an infectious organism in or on a host; induce regression of a disorder caused by the presence of an infectious organism in or on a host; induce healing of a disorder caused by the presence of an infectious organism in or on a host; or inhibit or prevent the occurrence of a disorder caused by the presence of an infectious organism near, in, or on a host. The treatment may be administered, as needed, once daily (qd), twice daily (bid), three times daily (tid), four times daily (qid), once every two days (Q2d), once every three days (Q3d), or using any dosing schedule that provides treatment for an infection as described herein.

[0558] In some embodiments, a method for treating and / or preventing an infection includes placing a bandage saturated with an antimicrobial composition on a wound and / or infected site. The bandage may be directly saturated with the antimicrobial composition before being placed on the wound and / or infected site, i.e., it may be manufactured and packaged in a pre-saturated state. In other embodiments, a method for treating and / or preventing an infection includes placing a bandage on the wound and / or infected site, followed by subsequent saturation of the bandage with an antimicrobial composition. The antimicrobial composition may be added after the bandage has been placed by an injector, syringe, or other suitable means.

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

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

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

[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 infections.

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

[0564] Non-limiting examples of Gram-positive bacteria that may be treated with the quaternary ammonium compounds of the present invention, either alone or in combination with other therapeutic agents, include: Actinomyces species, including Actinomyces israeri (Actinomyces Actinomyces naeslundii, Actino This includes Actinomyces viscosus, Actinomyces odontolyticus, and Actinomyces pyogenes; and Bacillus species, which include Bacillus anthracis, Bacillus cereus, and Bacillus subtilis. This includes Bacillus subtilis; Clostridium species, including Clostridium botulinum and Clostridium difficile. Clostridium difficile, Clostridium perflingens Clostridium perfringens), Clostridium sordellii, and Clostridium perfringens. This includes *Clostridium tetani*; and *Corynebacterium* species, including *Corynebacterium diphtheriae*, *Corynebacterium jeikeium*, *Corynebacterium minutissimum*, *Corynebacterium mucifaciens*, and *Corynebacterium pseudotx*. This includes Corynebacterium pseudotuberculosis, Corynebacterium striatum, Corynebacterium tenuis, and Corynebacterium ulcerans; and Enterococcus species, including Enterococcus caeseriflabus. This includes Enterococcus casseliflavus, Enterococcus faecalis, Enterococcus faecium, Enterococcus raffinosus, and Enterococcus hirae; Leuconost Leuconostoc species, which include Leuconostoc pseudomesenteroides; Micrococcus species, for example , Microccocus luteus, etc.; Nocardia species, which include Nocardia asteroides; propio The species Propionibacterium includes Propionibacterium acnes. This includes Staphylococcus species, such as Staphylococcus aureus, Staphylococcus capitis, Staphylococcus epidermidis, Staphylococcus haemolyticus, and This includes Staphylococcus hominis, Staphylococcus lugdunensis, Staphylococcus pasteuri, and Staphylococcus saprophyticus; as well as the Streptococcus species, which include Streptococcus Streptococcus agalactiae, Streptococcus anginosus, Streptococcus bovis, Streptococcus dysgalactiae, Streptococcus mitis, Streptococcus muta Streptococcus mutans, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus sanguinis, Streptococcus suis, and S This includes *Streptococcus viridans*.

[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, a method is provided for treating an infection caused by Gram-negative bacteria, comprising administering an effective amount of a quaternary ammonium compound or composition thereof as described herein.

[0567] Non-limiting examples of Gram-negative bacteria that may be treated with the quaternary ammonium compounds of the present invention, either alone or in combination with other therapeutic agents, include: Acinetobacter species, including Acinetobacter baumannii and Acinetobacter iwoffii. It is found in the Aeromonas species, including the subspecies Aeromonas veronii sobri. Aeromonas veronii biovar sobria (formerly Aeromonas s Aeromonas obriae, Aeromonas caviae, and Aeromonas hyd Includes Aeromonas hydrophila; Alcaligenes / Achilles Lomobacter species, including Alcaligenes faecalis and Alcaligenes xylosoxidans This includes; Bacteroides species, which include Bacteroides fragilis; Bartonella species, which include Bartonella bacilliformis, Bartonella clarridgeiae, Bartonella elizabethae, and Bartonella hense Bartonella henselae, Bartonella koehlerae, Bartonella Bartonalla naantalienis, Bartonalla quintana This includes Bartonella quintana, Bartonella rochalimae, Bartonella vinsonii, and Bartonella washoensis; and Bordetella species, which include Bordetella bronchispetica, Bordetella pertussis, and Bordetella parapertussis. Borrelia species include Borrelia afzelii, Borrelia burgdorferi, Borrelia crocidurae, Borrelia duttoni, Borrelia garinii, Borrelia hermsii, and Borrelia hispanica. (Borrelia hispanica), Borrelia miyamotoi, Borrelia This includes Borrelia parkeri, Borrelia persica, Borrelia recurrentis, Borrelia turicatae, and Borrelia venezuelensis; Brevundimonas species, which include Brevundimonas diminuta and Brevundimonas vesicularis; Brucella species, which include Brucella abortus, Brucella canis, Brucella melitensis, and Brucella swiss This includes the Burkholderia species, which include Burkholderia cepacia, Burkholderia mallei, and Burkholderia pseudomalle This includes Burkholderia pseudomallei; Campylobacter species, which include Campylobacter jejuni, Campylobacter coli, Campylobacter upsaliensis, Campylobacter lari, and Campylobacter • Contains: Chlamydia / Chlamydophila species, including Chlamydophila pneumoniae, Chlamydophila psittaci, Chlamydophila pecorum, and Chlamydia trachomatis; Citrobacter species, including Citrobacter amalonaticus, Citrobacter freundii, and Citrobacter This includes Citrobacter koseri and Citrobacter diversus; and Coxiella burnetti; Ehrlichia species, including Ehrlichia canis and Ehrlichia chaffeensis; Enterobacter - (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 Virus influenzae and Haemophilus ducreyi Includes; Helicobacter species, which include Helicobacter pylori; Klebsiella species, which include Klebsiella This includes Klebsiella granulomatis, Klebsiella oxytoca, and Klebsiella pneumoniae; Leclercia adecarboxylata; Legionella species, which include Legionella pneumophila; Leptospira species, which include Leptospira interrogans, Leptospira noguchii, and Leptospira This includes Leptospira santarosai and Leptospira weilii; Listeria species, which include Listeria monocytogenes; Moraxella species, This includes Moraxella catarrhalis, Moraxella lacunata, and Moraxella bovis; Moraxella bovoculi; Morganella species, which include Morganella morganii; Mycoplasma ) species, including Mycoplasma amphoriforme, Mycoplasma buccale, Mycoplasma faucium, Mycoplasma fermentans, Mycoplasma genitalium, Mycoplasma hominis, Mycoplasma lipophilum, Mycoplasma orale, Mycoplasma penetrans, Mycoplasma pirum, Mycoplasma pneumoniae, Mycoplasma primatum, Mycoplasma salivarium, and Mycoplasma This includes Mycoplasma spermatophilum; Neisseria species, which include Neisseria meningitidis and Neisseria gonorrhoeae; and Orientia. ) species, which include Orientia tsutsugamushi and Orientia chuto; Pantoea species, which include Pan This includes Pantoea agglomerans; Paracoccus species, which include Paracoccus yeei; Prevotella species, which include Prevotella intermedia and Includes Prevotella melaninogenica; Proteus The (Proteus) species includes Proteus mirabilis, Proteus penneri, and Proteus vulgaris. Commonly found; Providencia species, including Providencia rettgeri and Providencia stuartii. This includes Pseudomonas species, such as Pseudomonas erginosa, Pseudomonas oryzihabitans, and Pseudomonas plecoglossi. This includes ferns (Pseudomonas plecoglossidica) and Pseudomonas stutzeri; Ralstonia species, which include Ralstonia pickettii and Ralstonia insidiosa; Rickettsia species, which include Rickettsia africae, Rickettsia akari, Rickettsia australis, Rickettsia conorii, Rickettsia felis, Rickettsia japonica, and Rickettsia roizekii. This includes *Rickettsia prowazekii*, *Rickettsia rickettsia*, *Rickettsia sibirica*, and *Rickettsia typhi*; and the species *Roseomonas*. This includes Roseomonas gilardii; Salmon Salmonella species include Salmonella bongori, Salmonella enterica, Salmonella paratyphi, Salmonella typhi, and Salmonella typhimuri. This includes Salmonella typhimurium; and Serratia species, which include Serratia marcescens, Serratia liquefaciens, Serratia rubidaea, and Serratia ordulph. This includes Serratia odoriferae; the Shigella species, which includes Shigella de Shigella dysenteriae and Shigella sonnei Includes; Sphingomonas species, which include Sphingomonas mucosissima and Sphingomonas paucimobilus; Stenotrophomas species, which include S This includes Stenotrophomas maltophilia; Treponema species, including Treponema carateum, This includes Treponema paraluiscuniculi and Treponema pallidum; Ureaplasma species, which include Ureaplasma urealyticum; Vibrio species, which include Vibrio cholera, Vibrio parahaemolyticus, and Vibrio vulnificus; and Yersinia species, which include Yersinia enterocolitica, Yersinia pestis, and Yersinia pseudotuberculosis. ru.

[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, a method is provided for treating infections caused by Mycobacterium, comprising administering an effective amount of a quaternary ammonium compound or a composition thereof as described herein.

[0570] Non-limiting examples of mycobacteria that may be treated with the quaternary ammonium compounds of the present invention, either alone or in combination with other therapeutic agents, include: Mycobacterium abcessus, Mycobacterium africanum, and Mycobacterium agri. Mycobacterium aichiense, Mycobacterium alvei, Mycobacterium arabiense, Mycobacterium aromaticivorans, Mycobacterium arosiense, Mycobacterium arupense, Mycobacterium aquaticum, Mycobacterium asiaticum, Mycobacterium aubagnese, Mycobacterium aurum Mycobacterium austroafricanum, Mycobacterium aurum Mycobacterium avium, Mycobacterium avium subspecies Palatuber's claw Mycobacterium avium paratuberculosis, Mycobacterium avium silvaticum, Mycobacterium avium hominussuis, Mycobacterium bacterium 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 Mycobacterium conspicuum, Mycobacterium cookii, Mycobacterium cosmeticum, Mycobacterium diernhoferi, Myco Bacterium doricum, Mycobacterium dubarii (Mycobacterium duvalii), Mycobacterium elephantis, Mycobacterium fallax, Mycobacterium Mycobacterium farcinogenes, Mycobacterium flavescens, Mycobacterium florentinum, Mycobacterium fortuitum, Mycobacterium frederikbergense, Mycobacterium gadium, Mycobacterium gastri, Mycobacterium genavense, Mycobacterium gilvum, Mycobacterium 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... Intracellulare, Mycobacterium interjectum, Mycobacterium intermedium, Mycobacterium iranicum, Mycobacterium kansasii, Mycobacterium komossense, Mycobacterium kubicae, Mycobacterium Mycobacterium lentiflavum Mycobacterium leprae, Mycobacterium lepraemurium, Mycobacterium lepromatosis, Mycobacterium liflandii, Mycobacterium Mycobacterium llatzerense, Mycobacterium mada Mycobacterium madagascariense, Mycobacterium majerite Mycobacterium mageritense, Mycobacterium malmoense, Mycobacterium marinum, Mycobacterium Mycobacterium massiliense, Mycobacterium massiliense Mycobacterium massilipolynesiensis, Mycobacterium microti, Mycobacterium monacens Mycobacterium monacense, Mycobacterium montfiorense, Mycobacterium morokaense, Mycobacterium mucogenicum, Mycobacterium mungi, Mycobacterium murale, Mycobacterium nebraskense, Mycobacterium Mycobacterium neoaurum, Mycobacterium neworleansense, Mycobacterium nonchromogenicum, Mycobacterium obuense, Mycobacterium orygis, Mycobacterium Mycobacterium palustre, Mycobacterium parascofulaceum, Mycobacterium parafortuitum, Mycobacterium perigrinum, Mycobacterium phlei, Mycobacterium 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 shotsii Mycobacterium simiae, Mycobacterium shottsii Mycobacterium smegmatis, Mycobacterium sphagnum Mycobacterium sphagni, Mycobacterium stephanolepidis, Mycobacterium suricattae, Mycobacterium szulgai, Mycobacterium Mycobacterium talmoniae, Mycobacterium terrae, Mycobacterium thermoresistibile, Mycobacterium triplex, Myco 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 with the quaternary ammonium compounds of the present invention, either alone or in combination with other therapeutic agents, include: actinomycosis, anaplasmosis, anthrax, bacterial hemangioma, actinomycetoma, bacterial conjunctivitis, bacterial pneumonia, bacterial vaginal disease, bacterial endocarditis, bartonellosis, botulism, and boutenneuse. ) Fever, brucellosis, Begel, brucellobacterial spondylitis, bubonic plague, Buruli ulcer, Barnsdale ulcer, bacterial dysentery, campylobacteriosis, Callion's disease, cat scratch disease, cellulitis, chancroid, chlamydia, chlamydial conjunctivitis, Clostridium myonecrosis, cholera, Clostridium difficile colitis, diphtheria, Daintree ulcer, donavanosis, dysentery, ehrlichiosis, typhus, fried rice syndrome, quinque-day fever (Five-day fever), floppy baby syndrome, Far East scarlet-like fever, gas gangrene, glanders, gonorrhea, inguinal granuloma, human necrotizing bacilli, necrotizing fasciitis, lysis Hematologic uremic syndrome, human ehrlichiosis, human monocytic ehrlichiosis, human granulocytic anaplasmosis, infant botulism, Izumi fever, Kawasaki disease, Kumüsie's ulcer (ulder) , lymphogranulomatosis of the inguinal region, Lemier's syndrome, Legionnaires' disease, leprosy, leptospirosis, listeriosis, Lyme disease, lymphogranulomatosis of the inguinal region, Malta fever, Mediterranean fever, myonecrosis, mycoburuli ulcer, mucocutaneous lymphadenopathy, meliodosis, meningococcal disease, rash fever, mycoplasma pneumonia, mycomas, neonatal conjunctivitis, nocardiosis, Oroya fever, neonatal ophthalmitis, avian diseases, Pontiac fever, hepatic periosis, pneumonic plague, post-angina shock including sepsis, pasteurellosis, pelvic inflammatory disease, pertussis, plague, pneumococcal infection, pneumonia, psittacosis, psittacosis, pseudotuberculosis, Q fever, quintan fever, rabbit fever, relapsing fever, Rickettsial smallpox, Rocky Mountain spotted fever, raven bite fever, Reiter's syndrome, rheumatic fever, salmonellosis, scarlet fever, sepsis, septic plague, Searles' ulcer, bacterial dysentery, chancroid, syphilis, streptobacillus fever, scrub typhus, Taiwan acute respiratory pathogen, trench fever, trachoma, tuberculosis, tularemia, typhoid fever, typhoid fever, tetanus, toxic shock syndrome, undulating fever, papular chancroid (ulcus molle), Vibrio parahemorrhagicus enteritis, Whitmore's disease, walking pneumonia Waterhouse-Friedricksen syndrome, strawberry tumors, and Yersinia.

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

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

[0576] Non-limiting examples of fungal-mediated disorders that may be treated with the quaternary ammonium compounds of the present invention, either alone or in combination with other therapeutic agents, include: invasive aspergillosis, black sandy hair, blastomycosis, oropharyngeal candidiasis, vulvovaginal candidiasis, melanoma, chytridiomycosis, coccidioimycosis, cryptococcosis, dermatophytosis, fusariosis, geotrichumosis, histoplasmosis, mucormycosis, mycetoma, paracoccidioidomycosis, Pneumocystis pneumonia, sporotrichumosis, tinea folliculitis, tinea capitis, tinea corporis, tinea cruris, tinea manum, and tinea venereum. , onychomycosis, tinea versicolor, white sandy hair, and zygomycosis.

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

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

[0579] Non-limiting examples of viruses that may be treated with the quaternary ammonium compounds of the present invention, either alone or in combination with other therapeutic agents, include: adeno-associated viruses, astroviruses, BK polyomaviruses, cosavirus A, coxsackievirus, echovirus, Epstein-Barr virus, GB virus C, human adenoviruses, human coronaviruses, human cytomegaloviruses, human herpesviruses (1, 2, 6, 7, and 8), human papillomaviruses (1, 2, 16, and 18), human parainfluenza viruses, human parvoviruses, human respiratory polynuclear viruses, human rhinoviruses, human SARS coronaviruses, influenza viruses (A, B, and C), molluscum contagiosum virus, norovirus, rotaviruses (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 either alone or in combination with other therapeutic agents using the quaternary ammonium compounds of the present invention include: influenza, the common cold, polynuclear respiratory virus infections, adenovirus infections, parainfluenza virus infections, severe acute respiratory syndrome (SARS), norovirus infections, rotavirus infections, astrovirus infections, measles, rubella, varicella / shingles, roseola, smallpox, disease V, human papillomavirus (HPV), warts including genital warts, oral herpes, genital herpes, cold sores, herpes simplex virus keratitis, and molluscum contagiosum.

[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 amoebas, such as amoebic infections.

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

[0583] In some embodiments, a method is provided for treating an amoeba-induced infection, comprising administering to a subject an effective amount of a quaternary ammonium compound or a composition thereof, as described herein.

[0584] Non-limiting examples of amoebas that may be treated with the quaternary ammonium compounds of the present invention, either alone or in combination with other therapeutic agents, include: Acanthamoeba species; Balamuthia species, including Balamuthia mandrillaris; Dientamoeba species, including Dientamoeba fragilis; Endolimax species, including Endolimax nana; Ento Entamoeba species include Entamoeba Bangladeshi, Entamoeba coli, Entamoeba dispar, Entamoeba gingivalis, Entamoeba hartmanni, Entamoeba histolytica, Entamoeba moshkovskii, and E This includes Entamoeba polecki; and Iodamoeba species, which include Iodamoeba butschlii; The species Naegleria includes Naegleria fowleri; and the species Sappinia includes Sappinia diploidea and Sappinia pedata.

[0585] Non-limiting examples of amoeboid disorders that may be treated with the quaternary ammonium compounds of the present invention, either alone or in combination with other therapeutic agents, include: amoebosis, amoeboid dysentery, amoeboid liver abscess, cutaneous amoebiasis, amoeboid brain abscess, amebiasis cutis, and Acanthamoeba cornea. Inflammation, cutaneous acanthamoebiasis, granulomatous amebic encephalitis, balamutia amebic encephalitis, and sappinia amebic encephalitis.

[0586] In some embodiments, the infection is caused by Acinetobacter, Aspergillus, Burkholderia cepacia, Campylobacter, Candida, Clostridium difficile, Coccidioides, Cryptococcus, Enterobacteriaceae, Enterococcus, Helicobacter pylori, Mycobacterium tubercurosis, Neisseria gonoree, Neisseria meningitidis, nontuberculous mycobacteria, Pseudomonas, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, and Vibrio cholerae.

[0587] In certain alternative embodiments, the infection is caused by Staphylococcus aureus, Pseudomonas erginosa, 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 compounds of the present invention can be used to treat inflammatory disorders caused by the presence of infectious organisms, such as bacteria, fungi, viruses, or amoebas, as described herein.

[0589] Non-exclusive examples of such inflammatory disorders include: adenoid pharyngitis, appendicitis, arteritis, ascending cholangitis, balanitis, blepharitis, bronchitis, bursitis, cellulitis, cerebral vasculitis, cervicitis, conjunctival edema, cholecystitis, chondritis, chorioamnionitis. Colitis, conjunctivitis, constrictive pericarditis, cryptitis, dacryodenitis, dermatitis, diabetic ulcer, duodenal lymphocytosis, encephalitis, endocarditis, endometritis, endotheliitis, enteritis, colitis, eosinophilic fasciitis, epididymitis, esophagitis, folliculitis, gastritis, gingivitis, glomerulonephritis, glossitis, hepatitis, infectious arthritis, ileitis, intertrigo, keratitis, keratoconjunctivitis, labyrithitis, lymphadenitis, mastitis, mastitis Temporitis, myocarditis, myocarditis, myositis, necrotizing fasciitis, nephritis, omphalitis (omaphalitis), ovaries Inflammation, ophthalmitis, orchitis, osteitis, osteomyelitis, pancreatitis, paraproctitis, parotitis, Pericarditis, perichondritis, perifollicular inflammation, periodontitis, peritonitis, pharyngitis, phlebitis, pleurisy, interstitial pneumonia, pneumonia (pulmonitis), proctitis, prostatitis, pulpitis, pyelonephritis, suppurative myositis, retinal vasculitis, rheumatic fever, rhinitis, scleritis, salpingitis, sialadenitis, sinusitis, stomatitis, synovitis, sepsis, tenosynovitis, thyroiditis, tonsillitis, tularemia, urethritis, uveitis, vaginitis, vasculitis, and vulvitis (vulvitus).

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

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

[0592] In another embodiment, the method is used to treat a skin infection in another mammal, such as a cat, dog, cattle, 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 bites; American tick bites (Rickettsia parkeri infection); bacterial hemangioma; Begel (endemic syphilis); blastomycetic pyoderma (proliferative pyoderma); pyoderma vesicles of the hands and feet; botryomycosis; Brill-Zinser disease; brucellosis (Bang disease, Malta fever, undulating fever); bubonic plague; bullous impetigo; Campylobacter jejuni; cat scratch disease (cat scratch fever, English-Wear infection, inoculation lymphoreticulosis, subacute focal lymphadenitis) ); cellulitis; chancre; soft chancre (chancroid, papulo-chancre); chronic lymphangitis; chronic recurrent erysipelas; chronic pocket deepening (chronic undermining burrowing); ); condyloma latum; actinomycosis; necrotizing dermatitis (necrosis of the skin); pustulosis; necrotizing pustulosis; elephantiasis; endemic typhus (rash fever); epidemic typhus (lice-borne epidemic typhus); erysipelas (holy fire, St. Anthony's fire); Rosenbachian erysipelas; annular erythema; erythrorhizon; paronychia; flea-borne spotted fever; Flinders Island spotted fever; Musa Savityphus (Flying squirrel typhus); folliculitis; Fournier's gangrene (Fournier's gangrene of the penis and scrotum); furuncle syndrome; gas gangrene (Clostridium myonecrosis, myonecrosis); glanders (equinia, farcy, malleus); gonococcal sepsis (arthritis-dermatitis syndrome, disseminated gonococcal sepsis) Infections; gonorrhea (Clap); Gram-negative folliculitis; Gram-negative interdigital infection; inguinal granuloma (Donovan's disease, genital inguinal granuloma, tropical inguinal granuloma, venereal granuloma, venereal genital inguinal granuloma, lupoid-type inguinal ulcer formation, serpentine ulcer formation of the inguinal region, ulcerative granuloma of the vulva, ulcerative sclerosing granuloma); green nail syndrome; hospital-acquired furuncle syndrome; bathtub folliculitis (Pseudomonas erginosa folliculitis); human granulocytotropic anaplasmosis; human mono Monocytotropic ehrlichiosis; impetigo; Japanese spotted fever; leptospirosis (Fort Bragg fever, anterior tibial fever, Weil's disease); listeriosis; cellulitis of the floor of the mouth; lupus-like folliculitis; Lyme disease (Afzelius' disease, Lyme borreliosis); inguinal lymph node Granulomatous diseases (climatic bubo, Durand-Nicolas-Fabre disease, lymphogranuloma of the inguinal region, poradenitis inguinale, strumous bubo); malakoplakia (malacoplakia) Mediterranean spotted fever (button fever); meridianus (Whitmore's disease); meningococcal bacteremia; Missouri-Lyme disease; necrotizing fasciitis (carnivorous bacterial syndrome); neonatal toxic eruption; neonatal gangrenous stomatitis; North Asian typhus; neonatal ophthalmitis; Oroya fever (Kallion's disease); perianal cellulitis (perineal dermatitis, streptococcal perianal disease); periapical abscess; pinta; punctate keratolysis (keratolysis pluripotency) Antare sulcatum, Keratoma plantare sulcatum (ring keratolysis); plague; primary gonorrhea Pseudomonas pyoderma; Pseudomonas hot-foot syndrome; paronychia; suppurative myositis; Q fever; Queensland tick typhus Sneeze fever; Recurrent toxin-mediated perineal erythema; Nasal debilis; Rocky Mountain spotted fever; Scarlet fever; Scrub typhus; Bacterial dysentery; Staphylococcal scalded skin syndrome (neonatal pemphigus, Ritter's disease); Streptococcal intertrigo; Superficial pustular folliculitis (Bockhardt's impetigo, superficial folliculitis); Folliculitis vulgaris (barber's rash, syphilis); Syphilis (Syphilis (lues)); Tick-borne lymphadenopathy; Toxic shock syndrome ( Streptococcal toxin shock syndrome, streptococcal toxin shock-like syndrome, toxic streptococcal syndrome; trench fever (five-day fever, quintan fever, urban trench fever); tropical ulcer (adenophora) Ulcers, jungle rot, malabar ulcer, tropical phagedena); tularemia (deer turtle fever, Ohara disease, Pervant Valley plague, rabbit fever); Peruvian warts; and strawberry ulcers (bouba, framboesie, parangi, pian).

[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, the following: aquarium granuloma (fish tank granuloma, swimming pool granuloma); borderline leprosy; borderline tuberculous leprosy; Buruli ulcer (Barnsdale ulcer, Searle ulcer); indurated erythema (Bazan's disease); histological leprosy; leprosy; leprosy (Hansen's disease); lichenoid lichen (lichenoid cutaneous tuberculosis); lupus vulgaris (lupus tuberculosis); miliary tuberculosis (disseminated tuberculosis, acute systemic cutaneous tuberculosis (tuberculosis cutis acuta generalisata), disseminated cutaneous tuberculosis (tuberculosis cutis disseminata)); gangrenous papular tuberculosis; primary inoculated tuberculosis (initial cutaneous changes, initial tuberculous changes). Tuberculous chancre; cutaneous adenosis (softening cutaneous tuberculosis); mucocutaneous transitional tuberculosis (acute tuberculous ulcer, orificial tuberculosis); cutaneous verrucous tuberculosis (corticoid lupus, toxic verrucous tuberculosis); tuberculous cellulitis; tuberculous abscess (migratory tuberculous abscess, migratory tuberculous ulcer); and tuberculous rabies.

[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, the following: African histoplasmosis; alternariosis; antibiotic candidiasis (iatrogenic candidiasis); black sand hair; Candida auris; candidal intertrigo; candidal onychomycosis; candidal paronychia; candidal vulvovaginitis; candidal rash; melanomatosis (melanomatosis, cladosporium infection, Fonseca's disease, Pedroso's disease) Candidiasis (disease), pheosporotrichumosis, verrucosa); chronic mucocutaneous candidiasis; coccidioidomycosis (California disease, desert rheumatism, San Joaquin Valley fever, canyon fever); congenital cutaneous candidiasis; cryptococcosis; tinea; diaper candidiasis; disseminated coccidioidomycosis (coccidioidomycosis); distal subonychomycosis; entomophthora infection; candidiasis Dalmatian interdigital erosion; tinea; fungal folliculitis (Majocchi granuloma); Fusarium disease; geotrichumosis; infantile gluteal granuloma; histoplasmosis (cave disease, Darling disease, Ohio Valley disease, reticuloendotheliosis); achromatopsia; argynia; Loboa disease (keloid blastomycosis, lacaziosis, Lobo disease); mucormycosis; mycetoma (Mazura foot, Mazura mycosis); North American blastomycosis (Brastomyces sarcoides) Skin inflammation, blastomycosis, Gilchrist's disease; onychomycosis (dermatophytic onychomycosis, tinea unguium, nail fungus); oral candidiasis (thrush); otomycosis; perianal candidiasis; angular cheilitis (angular cheilitis); pheohypomycosis; trichosporosis; Pityrosporum folliculitis; primary cutaneous aspergillosis; primary cutaneous coccidioidomycosis Primary cutaneous histoplasmosis; Primary pulmonary coccidioidomycosis; Primary pulmonary histoplasmosis; Progressive disseminated histoplasmosis; Proximal subungual onychomycosis; Rhinosporidium; South American blastomycosis (Brazilian blastomycosis, paracoccidioidomycosis, paracoccidioidomycosis); Sporotrichosis (rose gardener's disease); Systemic candidiasis; Tinea barbae (tinea sycosis); Tinea capitis (herpes tonsurans, hair follicle tinea, scalp tinea) Tinea, tinea of ​​the scalp, tinea capitis (tinea tonsurans); tinea corporis (tinea, ringworm, tinea veitchii) ); martial artist's tinea; tinea cruris (itchy groin, tinea cruris, gym pruritus, jockey pruritus, tinea inguinalis); tinea facilitata; tinea imbricate (Tokelau's tinea); atypical tinea; tinea manuum; tinea (superficial pheohypomycosis, palmoplantar tinea nigra et plantaris); tinea pedis (athlete's foot, tinea of ​​the foot); dermatomycosis furfuracea, pityriasis versicolor, tinea flava); white sandy hair; white superficial onychomycosis; and zygomycosis (algal mycosis).

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

[0597] In some embodiments, the quaternary ammonium compounds of the present invention can be used to treat keratitis in a host, for example, a human. Keratitis can be caused by multiple infectious organisms, such as: bacteria, e.g., Staphylococcus aureus and Pseudomonas erginosa; fungi, e.g., species of Fusarium, Candida, Aspergillus, and Curvularia; viruses, e.g., herpes simplex virus and varicella virus; and amoebas, e.g., 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, for example, a human.

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

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

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

[0601] In some embodiments, the treatment involves applying a bandage containing an effective amount of the quaternary ammonium compound of the present invention, either alone or as part of a pharmaceutical composition, to the site of infection in a host requiring treatment. The bandage is preferably molded to fit into the space provided by the external auditory canal. The bandage may be malleable, so as to allow it to be compressed and molded to fit into the external auditory canal, or the bandage may be rigid, so as to ensure that it rests against the wall of the external auditory canal, thereby ensuring proper contact and movement of the antimicrobial composition.

[0602] In some embodiments, the bandage is left in the ear canal for a period of one day or less. In other embodiments, the bandage is left in the ear canal for a period of one week or more.

[0603] In some embodiments, a method for treating an infection in the external auditory canal of a host requiring treatment of the infection includes applying a bandage to the host's external auditory canal and subsequently saturating the bandage with an antimicrobial composition. This method appears to allow for sequential or continuous administration of the antimicrobial composition while the bandage remains in place.

[0604] In some embodiments, the bandage material is composed of a soluble material that needs to be placed in the external auditory canal before being saturated with an antimicrobial composition. In other embodiments, the bandage material is composed of a polymer foam that expands when subsequently wetted with an antimicrobial composition.

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

[0606] In some embodiments, a method is provided for treating or preventing infection in chronic wounds, the method comprising applying a bandage material containing one or more quaternary ammonium compounds of the present invention, either alone or in a composition, to the infected site of a host requiring 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. The therapeutic formulation for nail infections 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 fungal nail infections, comprising administering to a subject an effective amount of a quaternary ammonium compound or composition thereof as described herein.

[0610] In some embodiments, the quaternary ammonium compounds of the present invention may be used in a host, for example, a human, to treat a fungal vaginal infection, namely vulvovaginal candidiasis. can.

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

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

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

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

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

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

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

[0618] Non-living surfaces may harbor human pathogenic viruses or bacteria, both intestinal and respiratory. Multi-contact non-living surfaces can be points of transmission for bacterial, fungal, or viral contamination. Biofilms may be present on non-living surfaces. Viral contamination may be present on non-living surfaces. Non-living surfaces are not particularly limited and include any surface on which microorganisms may grow, or any such surface that may be exposed to microbial or viral contact or contamination. Examples, rather than limitations, of non-living surfaces include surfaces found in hospitals, surgical centers, examination rooms, radiography centers, dental facilities, nursing homes, elderly care facilities, stadium locker rooms, mass transit vehicles (e.g., airplanes, trains, buses, and commercial vehicles), airports, railway stations, bus stops, public restrooms, food or beverage processing facilities, manufacturing facilities, schools, dormitories, furniture, tables, desks, walls, open stairwells, elevators, machine surfaces, surfaces exposed to water, such as private spas, hot tubs, saunas, bathtubs, or any surface exposed to the external environment. Medical or surgical instruments or equipment constitute a special class of surfaces that may form biofilms. This class may include all kinds of lines, such as catheters (e.g., central venous catheters and urinary catheters), prostheses, such as heart valves, artificial joints, dentures, crowns, tooth caps, and soft tissue implants (e.g., breast, buttock, and lip implants). It includes all kinds of implantable medical devices (e.g., stents, intrauterine devices, pacemakers, intubation tubes, appliances or prostheses, lines or catheters). A “retained” medical device may include a device in which any part of the device is contained within the body, i.e., the device may be entirely retained or partially retained.

[0619] The surface can be made of any material. Examples, though not limited, include metals such as aluminum, copper, nickel plating, gold plating, steel, stainless steel, chromium, titanium, iron, and alloys. Additional examples of non-limited surfaces include 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. Other examples include acetal copolymers, polyphenylsulfone, polysulfone, polyetherimide, polycarbonate, polyvinylidene fluoride, poly(methyl methacrylate), and poly(tetrafluoroethylene). The surface can also be brick, glass, Formica, tile, ceramic, porcelain, wood, vinyl, linoleum, or carpet, or combinations thereof.

[0620] Powder formulation for use in the present invention In some embodiments, one or more active quaternary ammonium compounds of the present invention can be provided as powder formulations. Powder formulations can be prepared by removing any residual solvent, for example, by sublimation or boiling. In one embodiment, lyophilization is used to produce powders for formulations. This is because the low temperature used in the process typically maintains the integrity of the product. Furthermore, the lyophilized solids become even more rapidly and easily reconstituted due to the presence of microscopic pores formed by 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 quaternary ammonium compounds and products described herein contain methanol at about 5%, about 4%, about 3%, about 2%, about 1%, about 0.5%, or less than about 0.01% by weight. Lyophilization methods for solids used in pharmaceutical applications, particularly sensitive materials, are known in the art. Freeze-drying can be performed using any commercially available equipment, such as shelf / cabinet type, contact type, radiation type, or microwave-assisted freeze-drying machines.

[0621] A typical freeze-drying procedure consists of four steps. In the first step (pretreatment), the active quaternary ammonium compound is dissolved in a suitable solvent, and optional excipients are added as needed to improve stability, preserve appearance, or enhance subsequent processing. Furthermore, the solution of the active quaternary ammonium compound can be concentrated to be suitable for assisting the freezing and subsequent sublimation processes. In addition, each component can be initially flash-frozen to ensure the formation of a free-flowing solid upon completion of freeze-drying.

[0622] In the second step (freezing), the solution of the active quaternary ammonium compound in the container is frozen at a temperature below the triple point of the solution to ensure that sublimation occurs rather than melting. Optionally, the material can be subjected to a temperature-up and down cycle in a process called annealing. If the quaternary ammonium compound to be freeze-dried is an amorphous solid, it may not have a triple point, but instead has a critical point. Amorphous solids must be kept below the critical point throughout the freeze-drying process to prevent re-melting or disintegration of the solid during the subsequent drying process. For sensitive materials, the freezing step is often performed rapidly by lowering the material temperature to approximately -50°C to -80°C. This prevents the formation of large solvent crystals, which can reduce the structural integrity of the freeze-dried material and lead to defects.

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

[0624] In the fourth step (secondary drying), the temperature is raised higher than in the primary drying step to remove any remaining antifreeze solvent molecules. The increased temperature is necessary to break any physicochemical interactions that may have formed between the solvent molecules and the frozen material. Furthermore, the pressure is typically lowered compared to the primary drying step to facilitate desorption.

[0625] Upon completion of the freeze-drying process, the vacuum is typically released with an inert gas, such as nitrogen, and the material is sealed in a suitable container. Typical containers include sealed ampoules containing sealed glass that are broken open upon desired use. The active material can then be reconstituted upon use with a suitable carrier, such as those described herein, e.g., sterile water or glycerin.

[0626] antibacterial composition The active quaternary ammonium compounds described herein may be administered as pure chemicals to a host in need; however, more typically, they are administered as an antimicrobial composition containing the active quaternary ammonium compounds or combinations thereof as described herein in amounts effective to a host in need of such treatment, typically a human.

[0627] In some embodiments, the Disclosure provides antimicrobial compositions 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 activating agent. In a typical formulation, the selected quaternary ammonium compound of the present 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 when used in combination with or alternately with another activating agent, or when used prior, concurrently, or subsequently with another activating agent, is sufficient to (a) inhibit the progression of the infection described herein; (b) induce regression of the infection described herein; (c) induce a cure for the infection described herein; or inhibit or prevent the onset of the infection described herein. Therefore, the effective amount of the active quaternary ammonium compound or composition described herein will provide a sufficient amount of the activating agent when administered to a patient to provide a clinical benefit.

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

[0631] In a particular embodiment, the antimicrobial composition has a dosage form containing, in a unit dosage form, about 0.1 mg to about 2000 mg, about 10 mg to about 1000 mg, about 100 mg to about 800 mg, or about 200 mg to about 600 mg of an active quaternary ammonium compound, and optionally about 0.1 mg to about 2000 mg, about 10 mg to about 1000 mg, about 100 mg to about 800 mg, or about 200 mg to about 600 mg of an additional activator.

[0632] For example, at least about 0.5 mg, 1 mg, and 1.5 mg of the active quaternary ammonium compound. Dosage forms containing 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 are available. 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 may be administered as needed, for example, once daily (qd), twice daily (bid), three times daily (tid), four times daily (qid), once every two days (Q2d), once every three days (Q3d), or any dosing schedule that provides treatment for the disorders described herein.

[0633] The antimicrobial composition may contain, for example, an active quaternary ammonium compound and an additional activator in a molar ratio that achieves the desired result. For example, the pharmaceutical composition may contain the additional activator 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 activator:active compound).

[0634] Quaternary ammonium compounds disclosed herein or used as described herein may be administered topically, by spray, cream, gel, foam, or suppository, via implants including ocular implants, perdermally, as dermatological preparations, or as ophthalmic solutions, in unit dosage forms containing conventionally pharmaceutically acceptable carriers. For ocular delivery, quaternary ammonium compounds may be administered, if desired, by immediate or controlled release, for example, as a liquid, suspension, or other preparation, or via an ophthalmic device, or as a topically administered preparation, such as a liquid or suspension provided as ophthalmic solutions.

[0635] The antimicrobial composition may be formulated in any pharmaceutically useful form, for example, as an aerosol, cream, gel, foam, microparticles, nanoparticles, injectable or intravenous solutions, transdermal patches, subcutaneous patches, suppositories, dry powders, or in medical devices, as parenteral preparations, dermatological preparations, or ophthalmic solutions or suspensions. Some dosage forms may be further divided into unit doses of appropriate size containing an appropriate amount of the active ingredient, for example, an effective amount to achieve the desired purpose.

[0636] Compositions suitable for administration as intended herein and methods for producing such compositions are known in the art. Examples of known techniques include, for example, U.S. Patents 5,723,269 and 9,060,938, which are incorporated herein by reference.

[0637] The antimicrobial compositions intended herein may optionally include a carrier. The carrier must be sufficiently pure and sufficiently low in toxicity to be suitable for administration to the patient being treated. The carrier may be inert or may have its own pharmaceutically beneficial properties. The amount of carrier used in combination with the quaternary ammonium compound is sufficient to provide a practical amount of material per unit dose of the compound with respect to administration.

[0638] Carrier classes include binders, buffers, colorants, diluents, disintegrants, emulsifiers, fillers, fragrances, fluidizers, lubricants, pH adjusters, preservatives, stabilizers (e.g., xanthan gum, polyvinylpyrrolidone (PVP), guar gum, polyvinyl alcohol (PVA), etc.), and Examples of such agents include, but are not limited to, surfactants, solubilizers, tableting 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 multiple classes; for example, vegetable oils may be used as lubricants in some formulations and as diluents in others. Examples of pharmaceutically acceptable carriers include sugars, starch, cellulose, tragacanth powder, malt, gelatin, talc, and vegetable oils. Examples of other matrix materials, fillers, or diluents include lactose, mannitol, xylitol, crystalline cellulose, calcium diphosphate, and starch. Examples of surfactants include sodium lauryl sulfate and polysorbate 80.

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

[0641] Examples of disintegrants include sodium starch glycolate, sodium alginate, sodium carboxymethylcellulose, methylcellulose, colloidal silicon dioxide, and sodium croscarmellose. Examples of binders include methylcellulose, 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, and phosphoric acid; bases, such as sodium acetate, potassium acetate, calcium oxide, magnesium oxide, trisodium phosphate, sodium hydroxide, calcium hydroxide, and aluminum hydroxide; and buffers, generally comprising mixtures of acids and salts thereof. Other optional activators that do not substantially interfere with the activity of the quaternary ammonium compound of the present invention may also be included in the pharmaceutical composition.

[0644] Examples of usable aqueous solutions as carriers, though not limited to them, include distilled water, physiological saline, plasma, bone marrow aspirate, buffers such as Hanks equilibrium salt solution (HBSS), HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), Ringer's buffer, ProVisc®, diluted ProVisc®, ProVisc® diluted in PBS, Krebs buffer, Dulbecco's PBS, normal PBS, sodium hyaluronate solution, pseudo-body fluids, concentrated plasma platelets, tissue culture media, aqueous solutions containing organic solvents, and mixtures thereof. In all cases, the solutions can be sterilized in a suitable manner known to those skilled in the art.

[0645] In certain cases, the antimicrobial composition contains a polymer material. The polymer material must be biocompatible so that it can be administered to a patient without undesirable effects. The polymer is known in the art and is the subject of extensive literature and patents. In certain embodiments, the polymer is present in an amount effective to provide the desired viscosity and wetting properties as required for the desired application, for example, in the treatment of an infected wound. The specific amount of polymer used depends on several factors, including, but are not limited to, 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 desired level of water retention and release of the particular polymer.

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

[0647] In certain embodiments, antimicrobial compositions are used in polymer materials for medical devices, infection control covers for medical devices including pacemakers, contact lenses, dentures, prostheses, heart valves, and 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 nonwoven materials, sponges; medical devices such as orthopedic or dental devices, eye drops or suspensions, eye implants, ophthalmic films, selective ophthalmic deliveries, short-term wound fillers, direct patches for ophthalmic tissue, hydrophilic coatings for catheters, lead wires, etc., or vascular embolization agents.

[0648] In certain embodiments, the polymer material includes polymers such as thermoplastic polymers, thermosetting polymers, biodegradable polymers, modified polymers, crosslinked polymers, polymers for controlled delivery, hydrogels, hydrophilic colloids, liquid-forming polymers, gel-forming polymers, silicone-based polymer materials, film-forming polymers, polymer adhesives, polymer copolymers for controlled delivery, medical polymers, copolymers, or mixtures thereof.

[0649] In certain embodiments, the silane quaternary ammonium compounds and polymer materials described herein are in at least the ratios of 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, a composition of a silane quaternary ammonium compound and a polymer material forms a stable solid 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 compounds described herein are mixed with the polymers 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, embolus-forming particles, tissue adhesion barriers, and as artificial cartilage and meniscus. 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 filler, direct patch for ocular tissue, catheter, hydrophilic coating agent for lead wires, or vascular embolizer. For example, see 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 forms part of this specification.

[0654] In certain embodiments, the polymer is a polyvinyl alcohol hydrogel. In certain embodiments, polyvinyl alcohol hydrogen is useful for the drug delivery system. In certain embodiments, the drug delivery system includes an eye implant, an ophthalmic film, nanoparticles, microspheres, suspended microspheres, mucosal adhesives, or selective drug delivery products. In certain embodiments, the drug delivery system is an eye implant, an ophthalmic film, microspheres, suspended microspheres, or selective drug delivery products.

[0655] Polyvinyl alcohol hydrogels are polymers used as matrices in biocompatible and toxicologically safe sustained-release hydrogel drug delivery systems in solid, liquid, and semi-solid configurations. Polyvinyl alcohol hydrogels possess excellent properties, similar to mucosal adhesives, and their swelling ability makes them suitable for a variety of drug delivery applications. For example, see Gajra, Balaram & Pandya et al., "Poly vinyl alcohol Hydrogel and its Pharmaceutical and Biomedical..." See "Applications: A Review", International Journal of Pharmaceutical Research, 2011, 4. 20-26, which constitutes part of this specification by citation.

[0656] In some cases, 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 extensive literature and patents. The hydrogel is present in an amount effective for the desired application, for example, in the treatment of an infected wound, to provide the desired viscosity and wetting properties as required. The specific amount of hydrogel used depends on several factors, including, but are not limited to, 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 desired level of water retention and release of 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), crosslinked carboxymethylcellulose, crosslinked polyethylene glycol, poly(lactic acid), hyaluronic acid, sodium alginate, agarose, starch, chitosan, methylcellulose, polyethylene oxide, amorphous hydrogels, high-water-content crosslinked polymer gels, copolymers thereof, derivatives thereof, and mixtures thereof.

[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 needed. Examples of hydrophilic colloids include natural gums such as gum arabic, ghati gum, karaya gum, tragacanth gum, guar gum, locust bean gum, acacia gum, etc.; seaweed extracts such as agar, algin, alginate, and carrageenan, etc.; cereal gums, starch, microbial gums such as dextran gum and xanthan gum, etc.; pectin, gelatin, casein, collagen, polyvinylpyrrolidone, low-methoxyl pectin, propylene glycol alginate, carboxymethyl locust bean gum, carboxymethyl guar gum, and modified materials that have undergone oxidation, acetylation, carboxylation, esterification, methylation, amination, etherification, sulfation, borolysis, or phosphorylation, as well as absorbent colloidal materials having polyurethane-coated elastomers. This is not limited to these.

[0659] In certain embodiments, the antimicrobial composition for administration further comprises a quaternary ammonium compound as described herein, optionally including: phosphoglycerides; phosphatidylcholine; dipalmitoylphosphatidylcholine (DPPC); dioleylphosphatidylethanolamine (DOPE); dioleyloxypropyltriethylammonium (DOTMA); dioleylphosphatidylcholine; cholesterol; cholesterol esters; diacylglycerol; diacylglycerol succinate; diphosphatidylglycerol (DPPG); hexanedecanol; polyethyleneglycerol Fatty alcohols such as PEG; polyoxyethylene-9-lauryl ether; surfactant fatty acids such as palmitic acid or oleic acid; fatty acids; fatty acid monoglycerides; fatty acid diglycerides; fatty acid amides; sorbitan trioleate (Span(trademark) 85) glycocollate; sorbitan monolaurate (Span(trademark) 20); polysorbate 20 (Tween(trademark) 20); polysorbate 60 (Tween(trademark) 60); polysorbate 65 (Tween(trademark) 65); polysorbate 80 (Tween(trademark) 80); polysorbate 85 (Tween(trademark) 85); polyoxyethylene monostearate; surfactin; poloxomer; sorbitan trioleate, etc. Sorbitan fatty acid ester; lecithin; lysolecithin; phosphatidylserine; phosphatidylinositol; sphingomyelin; phosphatidylethanolamine (kephalin); cardiolipin; phosphatidic acid; cerebroside; dicetyl phosphate; dipalmitoylphosphatidylglycerol; stearylamine; dodecylamine; hexadecylamine; acetyl palmitate; glycerol ricinoleate; hexadecyl stearate; isopropyl myristate; tyroxapole; poly(ethyleneglycerin) (Col) 5000-phosphatidylethanolamine; poly(ethylene glycol) 400-monostearate; phospholipids; synthetic and / or natural detergents with high surfactant properties; deoxycholate; cyclodextrin; chaotropic salts; ion pairing agents; glucose, fructose, galactose, ribose, lactose, s Cloth, maltose, trehalose, cellbiose, mannose, xylose Rose, arabinose, glucuronic acid, galactoronic acid, mannuronic acid, glucosamine, galatosamine, and neuramic acid; pullulan, cellulose, microcrystalline cellulose, hydroxypropyl alcohol Ropilmethylcellulose (HPMC), hydroxycellulose (HC), methylcellulose (MC), dextran, cyclodextran, glycogen, hydroxyethyl starch, carrageenan, glyco, amylose, chitosan, N,O-carboxymethyl chitosan, algin and alginic acid, starch, chitin, inulin, konjac, glucomannan, pustulan, heparin, hyaluronic acid, curdlan and xanthan gum, mannitol, sorbitol, xylitol, erythritol, maltitol and lactitol, pluronic polymer, polyethylene, polycarbonate (e.g., poly(1,3-dioxan-2-one)), polyanhydride (e.g., poly(sebaci) Poly(ethyleneimine)-PEG copolymer, poly(ethyleneimine)-PEG copolymer, glycerol monocaprylate, polypropylfumerate, polyamide (e.g., polycaprolactam), polyacetal, polyether, polyester (e.g., polylactide, polyglycolide, polylactide-coglycolide, polycaprolactone), polyhydroxy acids (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)-PEG copolymer, glycerol monocaprylate, propylene glycol, vitamin E TPGS (also known as d-α-tocopheryl polyethylene glycol 1000 succinate), gelatin, titanium dioxide, polyvinylpyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), hydroxypropyl It contains one or more of the following: cellulose (HPC), methylcellulose (MC), ethylene oxide and propylene oxide block copolymer (PEO / PPO), polyethylene glycol (PEG), sodium carboxymethylcellulose (NaCMC), and hydroxypropyl methylcellulose acetate succinate (HPMCAS).

[0660] In some embodiments, the antimicrobial composition may include polymers for controlled delivery of the described compounds, such polymers being pluronic polymers, polyesters (e.g., polylactic acid, poly(lactic acid-coglycolic 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 nonwoven polyethylene terephthalates. Examples of polyesters include, but are not limited to, terephthalate (PET), spunbond, spunlace, embossed polyethylene terephthalate, LDPE nonwoven polyethylene terephthalate, glyco-modified polyethylene terephthalate (PETG), or other types of polyester that may contain monomers or comonomers having other carboxylic acid or alcohol functional groups; polycaprolactone, polyvalerolactone, poly(1,3-dioxan-2-one); polyacid anhydride (e.g., poly(sebacic anhydride)); polyether (e.g., polyethylene glycol); polyurethane; polymethacrylate; polyacrylate; and polycyanoacrylate.

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

[0662] In certain embodiments, further polymers include, but are not limited to, 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 one or more combinations thereof.

[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 extensive literature and patents. The biodegradable polymer or combination of polymers can be selected to provide desirable properties for the chosen application, including, but are not limited to, a suitable mixture of hydrophobic and hydrophilic properties, half-life and degradation rate, compatibility with one or more quaternary ammonium compounds of the present invention to be delivered, and appropriate behavior at the site of application.

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

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

[0666] The antimicrobial composition may include an optional active ingredient that does not substantially interfere with the activity of one or more quaternary ammonium compounds used in the present invention. In certain embodiments, two or more carrier components may be combined if deemed necessary for a particular application.

[0667] In some embodiments, the antimicrobial composition further comprises one or more additional additives, such as urea and / or DMSO. These quaternary ammonium compounds may be included to enhance the effectiveness of the desired antimicrobial composition in penetration into the site of infection being treated, to assist in tissue healing or symptom remission at the site of infection if deemed necessary, or to extend the effective shelf life of the antimicrobial composition, either alone or in combination with other activators.

[0668] In some embodiments, the antimicrobial composition further comprises a surfactant. The addition of a surfactant can help facilitate 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 by disrupting complex hydrophobic / hydrophilic interactions between biofilm layers, and is added when the one or more quaternary ammonium compounds of the present invention alone are insufficient for this purpose. The selected surfactant additive can be chosen to provide the antimicrobial composition with desired properties, such as the stability of the surfactant and the 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. A suitable surfactant should 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 a selected carrier.

[0669] In some embodiments, surfactants can facilitate the leaching of one or more quaternary ammonium compounds of the present invention from either the formulated microparticles or polymerizable nanoparticles. 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 oxychlorocene, and combinations thereof.

[0670] In some embodiments, the antimicrobial composition further includes a buffer. Some other candidate additives to the antimicrobial composition (e.g., urea and / or DMSO) may require a very narrow pH range to exert their maximum function. Buffers can be provided at appropriate concentrations to maintain the optimal pH range. Buffers optimized for specific desired applications are likely to be known to those skilled in the art. Examples of suitable buffers include, but are not limited to, citrates, sulfonates, carbonates, acetates, borates, glucons, phosphates, or combinations thereof.

[0671] In some embodiments, the antimicrobial composition further comprises a suitable enzyme. The addition of the enzyme can assist in the disruption of established biofilms, either by the degradation of extracellular macromolecules (EPS) or by suppressing intercellular communication, which is delivered via ion channels in the form of electrical signals to coordinate cellular behavior. In some embodiments, The enzyme may be a protease. Proteases may be able to act on some of the polymeric materials present in 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 the wound. The inclusion of a suitable tissue growth promoter may help promote the regrowth of tissue present within the wound during the time the infection is being treated with the dressing. Examples of suitable tissue growth promoters include, but are not limited to, endothelial growth factor (ECGF), epidermal 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 includes a preservative. Although one or more quaternary ammonium compounds of the present invention are antimicrobial in nature, additional preservatives may be optionally 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 includes an antioxidant. The antioxidant may be necessary to stabilize any other additives present in the antimicrobial composition from 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 be desirable to induce shrinkage in the infected surface tissue, thereby facilitating the 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, blown solution, benzoin tinky, or combinations thereof.

[0676] Antimicrobial compositions suitable for topical application to the skin preferably take the form of ointments, creams, lotions, foams, pastes, gels, sprays, aerosols, or oils. Suitable carriers include petrolatum, lanolin, polyethylene glycol, alcohol, transdermal enhancers, and combinations of two or more of these.

[0677] Antimicrobial compositions suitable for transdermal administration can be provided as isolated patches configured to maintain long-term adhesion to the recipient's epidermis. Antimicrobial 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 aqueous solution buffered with an optional active quaternary ammonium compound. In some embodiments, microneedle patches or devices are provided for delivering drugs across or into biological tissues, particularly the skin. Microneedle patches or devices allow for the delivery of drugs across or into the skin or other tissue barriers at clinically relevant rates, with minimal or no damage, pain, or irritation to the tissue.

[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 part of this specification by full reference): Examples include U.S. Patent No. 8,192,408, titled "Ocular trocar assembly" (Psivida Us, Inc.); U.S. Patent No. 7,585,517, titled "Transcleral delivery" (Macusight, Inc.); "Ophthalmic assembly" U.S. Patent Nos. 5,710,182 and 5,795,913 (Santen OY), titled "Ophthalmic composition"; U.S. Patent No. 8,662, titled "Formulations for treating ocular diseases and conditions" Publication No. 3,639, titled "Formulations and methods for vascular permeability-related diseases or conditions" U.S. Patent No. 8,486,960, titled "Liquid formulations for treatment of diseases or conditions," U.S. Patent No. 8,3 U.S. Patent No. 67,097 and U.S. Patent No. 8,927,005, U.S. Patent No. 7,455,855 (Santen Pharmaceutical Co., Ltd.) titled "Delivering substance and drug delivery system using the same"; "Visual acuity and International Publication No. 2011 / 050365 entitled "Conformable Therapeutic Shield For Vision and Pain," and a national publication entitled "Therapeutic Device for Pain Management and Vision." International Publication No. 2009 / 145842 (Forsight Labs, LLC); U.S. Patent Nos. 9,066,779 and 8,623,395 entitled “Implantable therapeutic device”, International Publication No. 2014 / 160884 entitled “Ophthalmic Implant for Delivering Therapeutic Substances”, entitled “Posterior segment drug delivery” U.S. Patent Nos. 8,399,006, 8,277,830, 8,795,712, 8,808,727, 8,298,578 and International Publication No. 2010 / 088548, titled "Systems for Sustained Intraocular Delivery of Low Solubility Compounds from a Port Delivery System Implant," International Publication No. 2014 / 152959 and U.S. Patent Application Publication No. 20140276482, titled "Injector apparatus and method for drug delivery." Japanese 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. Patents No. 8,715,712 and 8,939,948 entitled "Ocular insert apparatus and methods", International Publication No. International Publication No. 2013 / 116061, titled "Ophthalmic System for Sustained Release of Drug to the Eye" (International Publication No. 2014 / 066775), titled "Implantable Therapeutic Device" (International Publication No. 2015 / 085234 and International Publication No. 2012 / 019176), titled "Methods and Apparatus to Determine Porous Structures for Drug Delivery" (International Publication No. 2012 / 065006), titled "Anterior Segment Drug Delivery" (International Publication No. 2010 / 141729), titled "Corneal Denervation for Treatment of Ocular Pain" International Publication No. 2011 / 050327, titled "Small Molecule Delivery with Implantable Therapeutic Devices (Pain)" International Publication No. 2013 / 022801, titled "Therapeutic Devices," titled "Posterior Segment Drugs" International Publication No. 2012 / 019047, entitled "Subconjunctival Implant for Posterior Segment Drug Delivery," for implantable devices. Titled "Therapeutic Agent Formulations for Implanted Devices" International Publication No. 2012 / 068549, titled "Combined Delivery Methods and Apparatus," and International Publication No. 2012 / 019139, "Intraocular." International Publication No. 20 entitled "Ocular Insert Apparatus and Methods" Issue 13 / 040426, "Injector Apparatus and Method for Drug Delivery" International Publication No. 2012 / 019136, titled "Method for Drug Delivery," This is International Publication No. 2013 / 040247 (ForSight Vision4, Inc.), titled "Fluid Exchange Apparatus and Methods".

[0679] Additional, non-limiting examples of methods for delivering active quaternary ammonium compounds are found in International Publication No. 2015 / 085251, entitled "Intracameral Implant for Treatment of an Ocular Condition" (Envisia Therapeutics, Inc.); and International Publication No. 2011 / 008737, entitled "Engineered Aerosol Particles, and Associated Methods," concerning macrophages or This includes International Publication No. 2013 / 082111 entitled "Geometrically Engineered Particles and Methods for Modulating Macrophage or Immune Responses," International Publication No. 2009 / 132265 entitled "Degradable compounds and methods of use thereof, particularly with particle replication in non-wetting templates," and "Interventional drug delivery systems and related methods." International Publication No. 2010 / 099321, titled "System and Associated Methods"; International Publication No. 2008 / 100304, titled "Polymer particle composite having high fidelity order, size, and shape particles"; International Publication No. 2007 / 024323, titled "Nanoparticle fabrication methods, systems, and materials" (Liquidia Technologies, Inc. and the University of North Carolina at Chapel Hill); International Publication No. 2010 / 009087, entitled "Iontophoretic Delivery of a Controlled-Release Formulation in the Eye" (Liquidia Technologies, Inc. and Eyegate Pharmaceuticals, Inc.) and "Cargo Cells" Compositions and Methods for Intracellular Delivery and Release This is presented in International Publication No. 2009 / 132206 titled "Delivery and Release of Cargo," International Publication No. 2007 / 133808 titled "Nano-particles for cosmetic applications," International Publication No. 2007 / 056561 titled "Medical device, materials, and methods," International Publication No. 2010 / 065748 titled "Method for producing patterned materials," and International Publication No. 2007 / 081876 titled "Nanostructured surfaces for biomedical / biomaterial applications and processes thereof" (Liquidia Technologies, Inc.).

[0680] Additional, non-limiting examples of methods and devices for drug delivery to the eye include, for example, International Publication No. 2011 / 106702 and U.S. Patent No. 8,889,193 entitled "Sustained delivery of therapeutic agents to an eye compartment", International Publication No. 2013 / 138343 and U.S. Patent No. 8,962,577 entitled "Controlled release formulations for the delivery of HIF-1 inhibitors", and International Publication No. 2013 / 138 U.S. Patent Application Publication No. 346 and U.S. Patent Application Publication No. 2013 / 0272994, "Drug and Gene Carrier Particles that Rapidly Move Through Mucus Barriers," International Publication No. 2005 / 072710 and U.S. Patent No. 8,957,034, "Compositions and methods for improving transport through mucous membranes" International Publication No. 200 titled "and Methods for Enhancing Transport Through Mucous" U.S. Patent Application Publication No. 8 / 030557, U.S. Patent Application Publication No. 2010 / 0215580, U.S. Patent Application Publication No. 2013 / 0164343, International Publication No. 2012 titled "Compositions and Methods Relating to Reduced Mucoadhesion" U.S. Patent Application Publication No. / 061703, U.S. Patent Application Publication No. 2012 / 0121718, and U.S. Patent Application Publication No. 2013 / 0236556, "Rapid Diffusion of Large Polymeric Nanoparticles in the Mammalian Brain" International Publication No. 2012 / 039979 and U.S. Patent Application Publication No. 2013 / 0183244, titled "Mucus Penetrating Gene Carriers" International Publication No. 2012 / 109363 and U.S. Patent Application Publication No. 2013 / 0323313, titled "Nanoparticles with enhanced mucosal penetration or decreased inflammation" Patent No. / 090804 and U.S. Patent Application Publication No. 2014 / 0329913, "Nanoparticle formulations with enhanced mucosal penetration," and International Publication No. 2013 / 110028, "Rapid penetration through the mucosal inner layer." International Publication No. 2013 / 166498 and U.S. Patent Application entitled "Lipid-based drug carriers for rapid penetration through mucus linings" Publication No. 2015 / 0086484 (Johns Hopkins University); International Publication No. 2013 / 166385, titled "Pharmaceutical Nanoparticles Showing Improved Mucosal Transport," which describes how these nanoparticles assist in particle transport in mucus. U.S. Patent Application Publication No. 2013 / 0323179 (Johns Hopkins University and Kala Pharmaceuticals, Inc.) entitled "Nanocrystals, Compositions, And Methods that Aid Particle Transport in Mucus"; International Publication No. 2015 / 066444 entitled "Compositions and methods for ophthalmic and / or other applications" entitled "Aid Particle Transport in Mucus" International Publication No. 2014 / 020210 and International Publication No. 2013 / 16, entitled "Pharmaceutical nanoparticles showing improved mucosal transport" No. 6408 (Kala Pharmaceuticals, Inc.); Titled "Ophthalmic injection device including dosage control device" U.S. Patent No. 9,022,970, "Ophthalmic compositions comprising pbo-peo-pbo block copolymers" International Publication No. 2011 / 153349 titled "Stabilized ophthalmic galactomannan formulations", International Publication No. 2011 / 140203 titled "Ophthalmic emulsion" Examples include International Publication No. 2011 / 037908, entitled "Injectable aqueous ophthalmic composition and method of use therefor," Publication No. 2011 / 068955, U.S. Patent Application Publication No. 2007 / 0149593, entitled "Pharmaceutical Formulation for Delivery of Receptor Tyrosine Kinase Inhibiting (RTKi) Compounds to the Eye," and U.S. Patent No. 8,632,809 (Alcon, Inc.), entitled "Water insoluble polymer matrix for drug delivery."

[0681] In another embodiment, an ophthalmic formulation is provided, comprising one or more quaternary ammonium compounds as described herein in an ophthalmic carrier. The suitable carrier must prevent the quaternary ammonium compounds from being toxic or irritating to the eye, thereby preventing undesirable side effects or damage to the eye. Examples of components unsuitable for use in ophthalmic formulations include corrosive agents such as strong alkalis or strong acids, e.g., urea or ammonia, strong surfactants, and substances with known ophthalmic toxicity, e.g., methanol and hydrogen peroxide. These are some examples.

[0682] In another embodiment, a therapeutic formulation for onychomycosis is also provided, which 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," which aims to reduce intraocular pressure. U.S. Patent No. 20130071349, titled "Biodegradable polymers for lowering intraocular pressure", U.S. Patent No. 8,481,069, titled "Tyrosine kinase microspheres", U.S. Patent No. 8,465,778, titled "Method of making tyrosine kinase microspheres", and "containing a tyrosine kinase inhibitor U.S. Patent No. 8,409,607, titled "Sustained release intraocular implants containing tyrosine kinase inhibitors and related methods," and U.S. Patent No. 8,512,738, titled "Biodegradable intravitreal tyrosine kinase implants." U.S. Patent No. 2014 / 0031408, entitled "Microsphere Drug Delivery System for Sustained Intraocular Release," and U.S. Patent No. 2014 / 0294986, entitled "Methods for Treating Retinopathy With Extended Therapeutic Effect." U.S. Patent No. 8,911,768 (Allergan, Inc.) titled "Preparation of injectable suspensions having improved injectability" U.S. Patent No. 6,495,164 (Alkermes Controlled Therapeutics, Inc.) titled "Preparation of injectable suspensions having improved injectability" International Publication No. 2014 / 047439 (Akina, Inc.) titled "Biodegradable Microcapsules Containing Filling Material" International Publication No. 2010 / 132664 (Baxter International Inc. Baxter Healthcare SA) titled "Compositions and Methods for Drug Delivery" "Polymer nanoparticles with improved drug carrying capacity and their use U.S. Patent Application Publication No. 20120052041 (The Brigham and Women's Hospital, Inc.), entitled "Polymeric nanoparticles with enhanced drugloading and methods of use thereof"; "Therapeutic nanoparticles containing a therapeutic agent, and methods of preparing 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," National Patent Application Publication No. 20140248358 and U.S. Patent Application Publication No. 20140249158 (BIND Therapeutics, Inc.); U.S. Patent No. 5,869,103 titled "Polymer microparticles for drug delivery" (Danbiosyst UK Ltd.); U.S. Patent No. 8628801 titled "Pegylated Nanoparticles" (University of Navarra); U.S. Patent Application Publication No. 2014 / 0107025 titled "Ocular drug delivery system" (Jade Therapeutics, LLC); "Composed of microparticles and biodegradable gel having an improved release profile" U.S. Patent No. 6,287,588, titled "Agent delivering system comprised of microparticle and biodegradable gel with an improved releasing profile and methods of use thereof," and U.S. Patent No. 6,589,549, titled "Bioactive agent delivering system comprised of microparticles within a biodegradable material to improve release profiles" (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 periorbital or subconjunctival administration” U.S. Patent Application Publication Nos. 20040234611, 20080305172, 20120269894, and 20130122064 (Novartis Ag) entitled "Ophthalmic depot formulations for periocular or subconjunctival administration"; "Block polymer U.S. Patent No. 6,413,539, titled "Block polymer" (Poly-Med, Inc.); U.S. Patent Application Publication No. 20070071756 (Peyman), entitled "Delivery of an agent to ameliorate inflammation"; "Bioactive ingredients Examples include U.S. Patent No. 6,706,289 (PR Pharmaceuticals, Inc.), titled "Methods and compositions for enhanced delivery of bioactive molecules," and U.S. Patent No. 8,663,674 (Surmodics), titled "Microparticle containing matrices for drug delivery."

[0684] Bandages, etc. In some embodiments, an antimicrobial composition containing one or more quaternary ammonium compounds of the present invention is dispersed in a suitable bandage material. The selected bandage material must be able to release the desired antimicrobial composition over a period of time depending on the desired application. The bandage material can be moistened by saturating it with the antimicrobial composition before being placed on the infected site, even though it may become further moistened by exudate from the infected site. Alternatively, the bandage material can be placed on the wound and / or infected site and subsequently saturated with the antimicrobial composition, for example, by administering the antimicrobial composition using a dropper or syringe or by other suitable means.

[0685] In another embodiment, an infection is treated by applying a bandage containing one or more quaternary ammonium compounds of the present invention as an antimicrobial composition to the site of infection, the bandage releasing one or more quaternary ammonium compounds of the present invention to the site of infection. The infection may involve the presence of bacteria, fungi, viruses, amoebas, or combinations thereof.

[0686] In some embodiments, treatment of an infection includes placing a bandage containing an antimicrobial composition as described herein in or over the site of infection.

[0687] In certain embodiments, one or more quaternary ammonium compounds of the present invention can be used to treat disorders, typically infections, caused by Gram-positive bacteria, Gram-negative bacteria, Mycobacterium species, fungal species, or viral species as described herein.

[0688] In a particular embodiment, a method is provided comprising administering an effective amount of a quaternary ammonium compound or composition thereof as described herein for the treatment of an infection caused by a Gram-positive bacterium, Gram-negative bacterium, Mycobacterium species, fungal species, or viral species as described herein.

[0689] In a further embodiment, a dry powder formulation containing the quaternary ammonium compound of the present invention is impregnated into a bandage material, which is subsequently moistened at the site of infection by interaction with exudate or other bodily fluids. The bandage material can be placed in or over the site of infection in which a biofilm is involved. The bandage material may adhere to the site of the wound and / or infection to provide appropriate localization, or to the site of infection to prevent undesirable tissue damage during removal. In some cases, the bandage may not adhere properly. The rigidity of the bandage material may allow it to be held in the correct position during treatment, while its malleability may allow for placement and adhesion in the desired location.

[0690] Furthermore, the bandage material may contain additional additives (e.g., urea and / or DMSO) to ensure a moist environment at the site of infection. The bandage material must be composed of hypoallergenic and non-toxic materials for the purpose of making it acceptable for application to living hosts. In some embodiments, the bandage material is thought to absorb the antimicrobial composition and, once placed at the site of infection involving the biofilm, subsequently release the antimicrobial composition.

[0691] In certain embodiments, the bandage material has a bulk density that is low enough to allow the antimicrobial composition to be incorporated therein, but high enough to provide sufficient structural integrity. The bandage material must be porous to allow sufficient insertion of the antimicrobial composition into the material, thereby allowing the space to be sufficiently moistened with the antimicrobial composition in conjunction with runoff to the treatment site. The level of porosity of the bandage material must be high enough to allow sufficient moistening with the antimicrobial composition, but still allowing the bandage material to have sufficient material strength.

[0692] In certain embodiments, the bandage material is made from a flexible polymer material that provides sufficient porosity for the desired application while still maintaining structural integrity. In certain embodiments, two or more bandage material components can be combined to form a composite material if deemed necessary for a particular application. In some cases, the two or more components may exist in layers. In other cases, the two or more components may be impregnated or interlocked with each other. The combination of bandage material components may be necessary for structural integrity to ensure placement, positioning, and functionality at the site of infection.

[0693] In some embodiments, the bandage material includes a polymer foam, such as a shape-adaptive foam. The polymer foam can enable the release of a desired antimicrobial composition by either diffusion, ionic interaction, or decomposition of the material composition of the bandage material.

[0694] In some embodiments, the polymer foam can absorb exudates t...

Claims

1. The following quaternary ammonium compound: 【Chemistry 1】 (In the formula, a is 3 or 4, R １ C ６ ~C ２２ It is alkyl, R ２ , R ３ , and R ４ Each of them operates independently. 【Chemistry 2】 Selected from the group consisting of, R ７ It is hydrogen, R ８ and R ９ each independently represents hydrogen or CH ２ OR ７ and X １ NR １７ And, X ２ C １ ~C ３ Alkyl and C １ ~C ３ Selected from the group consisting of hydroxyalkyl groups, R １６ C １ ~C ４ It is alkyl, R １７ is hydrogen or C ２ It is a hydroxyalkyl, X － There are no cases where the quaternary ammonium compound is an anion or a zwitterion. B ＋ (It is a cation.)

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

3. The aforementioned cation B ＋ The quaternary ammonium compound according to claim 1 or 2, wherein the quaternary ammonium compound is selected from potassium cation, sodium cation, lithium cation, magnesium cation, and calcium cation.

4. The aforementioned compound is a zwitterion, X － The quaternary ammonium compound described in claim 1 does not exist.

5. X １ The quaternary ammonium compound according to claim 1 or 2, wherein is NH.

6. R １７ is C ２ A quaternary ammonium compound according to claim 1 or 2, wherein it is a hydroxyalkyl compound.

7. X ２ is C １ ~C ３ A quaternary ammonium compound according to claim 1 or 2, wherein it is alkyl.

8. X ２ CH ２ CH ２ The quaternary ammonium compound according to claim 7.

9. X ２ is C １ ~C ３ A quaternary ammonium compound according to claim 1 or 2, wherein it is a hydroxyalkyl compound.

10. X ２ CH ２ CH(OH)CH ２ The quaternary ammonium compound according to claim 9.

11. R ８ CH ２ A quaternary ammonium compound according to claim 1 or 2, wherein the OH group is OH.

12. R ９ CH ２ A quaternary ammonium compound according to claim 1 or 2, wherein the OH group is OH.

13. R １ The quaternary ammonium compound according to claim 1 or 2, wherein is octadecyl.

14. R １６ CH ３ The quaternary ammonium compound according to claim 13.

15. The quaternary ammonium compound according to claim 14, wherein a is 3.

16. below: 【Transformation 3】 【change】 A quaternary ammonium compound according to claim 1, selected from the group consisting of the following.

17. below: 【Chemistry 4】 A quaternary ammonium compound according to claim 1, selected from the group consisting of the following.

18. The following structure: 【Transformation 5】 A quaternary ammonium compound according to claim 1, having the following characteristics.

19. The following structure: 【Transformation 6】 A quaternary ammonium compound according to claim 1, having the following characteristics.

20. The following structure: 【Transformation 7】 A quaternary ammonium compound according to claim 1, having the following characteristics.

21. The following structure: 【Transformation 8】 A quaternary ammonium compound according to claim 1, having the following characteristics.

22. The following structure: 【Chemistry 9】 A quaternary ammonium compound according to claim 1, having the following characteristics.

23. The following structure: 【Chemistry 10】 A quaternary ammonium compound according to claim 1, having the following characteristics.

24. The following structure: 【Chemistry 11】 A quaternary ammonium compound according to claim 1, having the following characteristics.

25. The following structure: 【Chemistry 12】 A quaternary ammonium compound according to claim 1, having the following characteristics.

26. The following structure: 【Chemistry 13】 A quaternary ammonium compound according to claim 1, having the following characteristics.

27. The following structure: 【Chemistry 14】 A quaternary ammonium compound according to claim 1, having the following characteristics.

28. below: 【Chemistry 15】 【change】 Selected from the group consisting of, X － It is a methanesulfonate anion, B ＋ The quaternary ammonium compound according to claim 1, wherein is a sodium cation.

29. A quaternary ammonium compound according to any one of claims 1 to 28, which is in the form of a powder or a solid.

30. An antimicrobial composition for treating a local infection in a host, comprising the compound described in any one of claims 1 to 28.

31. The antimicrobial composition according to claim 30, wherein the infectious disease is selected from the group consisting of eye infections, ear infections, skin infections, and nail infections.

32. The antimicrobial composition according to claim 30 or 31, wherein the aforementioned infection is caused by a bacterial infection, a fungal infection, an amoeba infection, a viral infection, or a combination thereof.

33. The antibacterial composition according to claim 31, wherein the ear infection is an external ear (otitis externa) infection, a middle ear (otitis media) infection, or an inner ear (otitis interna) infection.

34. The antimicrobial composition according to claim 30 or 31, wherein the infection is an infection in a chronic wound.

35. The antibacterial composition according to claim 30 or 31, wherein the aforementioned infection is a periodontal infection.

36. The antimicrobial composition according to claim 31, wherein the eye infection is selected from the group consisting of bacterial or viral conjunctivitis (pink eye), corneal ulcer, keratitis, bacterial keratitis, fungal keratitis, herpes-related keratitis, endophthalmitis, and blepharitis.

37. An antimicrobial composition for treating dermatological disorders in a host, comprising a compound according to any one of claims 1 to 28.

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

39. The antibacterial composition according to claim 38, wherein the dermatological disorder is acne vulgaris.

40. The antibacterial composition according to claim 38, wherein the eczema is selected from the group consisting of herpetic eczema, vaccination eczema, and coxsackielic eczema.

41. The antibacterial composition according to claim 38, wherein the dermatological disorder is cystic acne.

42. The antibacterial composition according to claim 38, wherein the dermatological disorder is a skin infection.

43. The antimicrobial composition according to claim 37, wherein the dermatological disorder is caused by a pathogen selected from the group consisting of Gram-positive bacteria, Gram-negative bacteria, fungi, and viruses.

44. The antimicrobial composition according to claim 37, wherein the host is human.

45. The antimicrobial composition according to claim 37, wherein the host is a mammal.

46. The antimicrobial composition according to claim 37, wherein the host is a dog, cat, rabbit, horse, pig, or cattle.

47. The antimicrobial composition according to claim 38, wherein the skin infection is due to biofilm formation.

48. An antimicrobial composition comprising a quaternary ammonium compound according to any one of claims 1 to 28 in combination with a pharmaceutically acceptable carrier.

49. The aforementioned compound, 【Chemistry 16】 The antibacterial composition according to claim 48.

50. The aforementioned compound, 【Chemistry 17】 The antibacterial composition according to claim 48.

51. The aforementioned compound, [Chemistry 18] The antibacterial composition according to claim 48.

52. The aforementioned compound, 【Chemistry 19】 The antibacterial composition according to claim 48.

53. The antimicrobial composition according to any one of claims 48 to 52, wherein the pharmaceutically acceptable carrier is selected from the group consisting of alcohol, aqueous solution, and glycerin solution.

54. An antimicrobial composition according to any one of claims 48 to 52, suitable for local delivery.

55. The antimicrobial composition according to any one of claims 48 to 52, wherein the pharmaceutically acceptable carrier is an aqueous solution.

56. An antimicrobial composition according to any one of claims 48 to 52, which is in the form of a spray, cream, gel, foam, dry powder, wipe, paste, solid, transdermal patch, skin solution, subcutaneous patch, eye drops, or suspension.

57. The antimicrobial composition described above is an antimicrobial composition according to any one of claims 48 to 52, which is added to a polymer material.

58. The antimicrobial composition according to claim 57, wherein the polymer material is selected from the group consisting of thermoplastic polymers, thermosetting polymers, biodegradable polymers, modified polymers, crosslinked polymers, polymers for controlled delivery, hydrogels, hydrophilic colloids, liquid-forming polymers, gel-forming polymers, silicone polymer materials, film-forming polymers, polymer adhesives, copolymers, and medical polymers, as well as mixtures thereof.

59. The antimicrobial composition according to claim 58, wherein the polymer material is a hydrogel.

60. The antibacterial composition according to claim 58, wherein the polymer material is a gel-forming polymer.

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