Octenidine formulations and methods for wound healing

Abstract

Described herein are pharmaceutical compositions comprising a bis(pyridine) antimicrobial agent, or an octenidine-based compound, formulated as a topical ointment. Also described here are methods of use of bis(pyridine) antimicrobial agents, or an octenidine-based compounds, for use in methods of wound healing and methods of reducing or preventing infection in a subject.

Description

Attorney Docket No.67522-701.601 OCTENIDINE FORMULATIONS AND METHODS FOR WOUND HEALING CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 669,603, filed on July 10, 2024, which is incorporated by reference herein in its entirety. BACKGROUND

[0002] Open wounds, burns, and surgical incisions are susceptible to infection and require appropriate management to remain moist, clean, and heal. While many wound care ointments exist, antimicrobial resistance limits the efficacy of these products. There is a need for improved wound care ointment formulations having an active ingredient demonstrating superior antimicrobial activity, along with the incorporation of other compounds that optimize the healing response of the human body for wound care management. SUMMARY

[0003] The emergence of microbial resistance to particular antimicrobial agents such as antibiotics has led to the search for new potent antimicrobial agents and antimicrobial formulations that exhibit superior wound healing capabilities. In one aspect described herein are pharmaceutical compositions comprising a bis(pyridine) antimicrobial agent, or an octenidine- based compound, or octenidine or a pharmaceutically-acceptable salt thereof formulated as an antimicrobial topical ointment for use in wound care. In some embodiments, the pharmaceutical composition is formulated with a petroleum base. In some instances, the petroleum-based formulation has superior abilities to maintain a moist wound environment. In some instances, maintaining a moist wound environment is preferential for the effectiveness of treatment of a subject. Bis(pyridine) antimicrobial agents, including octenidine (OCT), disrupt the cell membrane of various microorganisms. This effect on member disruption across a broad range of microorganisms renders Bis(pyridine) antimicrobial agents, including OCT, as having widespread antimicrobial activity in which development of resistance unlikely by specific pathogens to treatment based on these agents. OCT acts in a detergent-like manner. On a cellular level, OCT depolarizes and changes the fluidity of the cell membrane of a pathogenic microorganism. On a molecular level, OCT induces a complete loss of the packing order of bacterial phospholipids. This effect is seen in both gram negative and gram positive bacteria.

[0004] In certain aspects, disclosed herein are pharmaceutical compositions comprising: a) a bis(pyridine) antimicrobial agent, and b) petrolatum, wherein the petrolatum is present in the composition in an amount greater than 50% weight per weight (w / w); wherein the composition isAttorney Docket No.67522-701.601 formulated for topical application in a human subject. In some embodiments, the bis(pyridine) antimicrobial agent is octenidine or one of its pharmaceutically acceptable salts. In some embodiments, the bis(pyridine) antimicrobial agent is an octenidine-based compound. In some embodiments, the octenidine-based compound comprises octenidine and an organic acid used for forming a pharmaceutically acceptable acid addition salt. In some embodiments, the organic acid used for forming the pharmaceutically acceptable acid addition salt is selected from acetic acid, 2,2-dichloroacetic acid, acrylic acid, adipic acid, ascorbic acid, aspartic acid benzenesulfonic acid, benzoic acid, 4-acetamido-benzoic acid, camphoric acid, camphor-10-sulfonic acid, capric acid, caproic acid, caprylic acid, carbonic acid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethane sulfonic acid, 2-hydroxy-ethane sulfonic acid, formic acid, fumaric acid, galactaric acid, gallic acid, gentisic acid, glocolic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glutaric acid, 2-oxo-glutaric acid, glyceric acid, glycerophosphoric acid, glycolic acid, glyoxilic acid, hippuric acid, hydrochloric acid, isobutyric acid, isocitric acid, itaconic acid, lactic acid, lactobionic acid, lauric acid, maleic acid, malic acid, malonic acid, mandelic acid, methane sulfonic acid, naphthalene- 1,5-disulfonic acid, naphthalene-2-sulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, octanoic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, phthalic acid, pimelic acid, pivalic acid, propanoic acid, propionic acid, pyroglutamic acid, pyruvic acid , salicyclic acid, 4-aminosalicyclic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, toluic acid, toluenesulfonic acid, undecylenic acid, and valeric acid. In some embodiments, the bis(pyridine) antimicrobial agent is octenidine dihydrochloride. In some embodiments, the pharmaceutical composition is formulated for topical application to prevent, treat, or reduce a symptom of a disease of the human subject arising from an infection with a pathogenic microorganism. In some embodiments, the octenidine dihydrochloride is dissolved within a non-aqueous solvent. In some embodiments, the non-aqueous solvent comprises a cosolvent. In some embodiments, the solvent comprises ethanol, propylene glycol, glycerine, glycofurol, polyethylene glycol, or ethoxydiglycol. In some embodiments, the octenidine dihydrochloride is dissolved in a hydrophilic compound. In some embodiments, the hydrophilic compound is ethoxydiglycol. In some embodiments, the pathogenic microorganism comprises a gram-negative bacterium. In some embodiments, the pathogenic microorganism comprises a gram-positive bacterium. In some embodiments, the pathogenic microorganism comprises an atypical bacterium. In some embodiments, the pathogenic microorganism comprises a fungus. In some embodiments, the pharmaceutical composition is formulated as an ointment. In some embodiments, pharmaceutical composition comprises white mineral oil. In some embodiments, pharmaceutical composition comprises ethoxydiglycol. In some embodiments, pharmaceuticalAttorney Docket No.67522-701.601 composition comprises Butyrospermum Parkii Nut Extract. In some embodiments, pharmaceutical composition comprises Euphorbia Cerifera (Candelilla) Wax. In some embodiments, pharmaceutical composition comprises glycerin. In some embodiments, pharmaceutical composition comprises Avena Sativa (Oat) Seed Extract. In some embodiments, pharmaceutical composition comprises honey. In some embodiments, pharmaceutical composition comprises tocopherol. In some embodiments, the bis(pyridine) antimicrobial agent is dissolved within a non-aqueous solvent. In some embodiments, the octenidine dihydrochloride is dissolved within a non-aqueous solvent. In some embodiments, the octenidine or PHMB is dissolved within a non-aqueous solvent. In some embodiments, the non-aqueous solvent comprises ethanol, propylene glycol, glycerine, glycofurol, polyethylene glycol, or ethoxydiglycol. In some embodiments, the pharmaceutical composition is formulated as an ointment. In some embodiments, the hydrophobic carrier suitable for topical application comprises one or more humectants, emollients, solvents, thickeners, penetration enhancers, or buffering agents, or any combination thereof. In some embodiments, the one or more humectants comprise mineral oil, petrolatum, white petrolatum, isopropyl palmitate, ammonium alkginate, butylene glycol, corn syrup solids, cyclomethicone, dipropylene glycol, glycerin, polydextrose, propylene glycol, sodium hyaluronate, sodium lactate, sorbitol, tagatose, trehalose, triacetin, triethanolamine, xylitol, sorbitol, or any combination thereof. In some embodiments, the one or more emollients comprise shea butter, cocoa butter, mineral oil, lanolin, lanolin alcohols, petrolatum, white petrolatum, paraffin, beeswax, squalene, coconut oil, jojoba oil, sesame oil, almond oil, canola oil, palm kernel oil, palm oil, safflower oil, soybean oil, sunflower oil, cetyl alcohol, cetyl palmitate, olive oil, oleyl alcohol, oleic acid, triethylhexanoin, cyclomethicone, dimethicone, sorbitol, xylitol, isopropyl palmitate, castor oil, carnauba wax, cetyl ester wax, emulsifying wax, microcrystalline wax, paraffin wax, white wax, yellow wax, polyethylene glycol, or a combination thereof. In some embodiments, the one or more solvents comprise propylene glycol, hexylene glycol, ethoxydiglycol, polyoxyethylene, polyoxypropylene, diethylene glycol monoethyl ether (DGME), glycerin, dimethyl sulfoxide (DMSO), or any combination thereof. In some embodiments, the one or more thickeners comprise agar, alginate, pectin, acacia, tragcanth, Karaya gum, guar gum, starch, cellulose, carbomer, bees wax, candelilla wax, carnauba wax, or any combination thereof. In some embodiments, the one or more penetration enhancers comprise micelles, phospholipids, propylene glycol, glycerin, ethanol, oleic acid, DMSO, isopropyl myristate, laurocapram, terpenes, urea, sodium lauryl sulfate, cetyl alcohol, stearyl alcohol, cyclodextrins, or any combination thereof. In some embodiments, the one or more buffering agents comprise sodium hydroxide, hydrochloric acid, sodium phosphate monobasic, sodium phosphate dibasic, sodium citrate, or a combinationAttorney Docket No.67522-701.601 thereof. In some embodiments, the pharmaceutical composition has a pH of from about 4.0 to about 7.0. In some embodiments, the pharmaceutical composition has a pH of about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, about 6.5, or about 7.0. In some embodiments, the pharmaceutical composition comprises from about 0.01% to about 1.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.01%, about 0.015%, about 0.02%, about 0.025%, about 0.03%, about 0.035%, about 0.04%, about 0.045%, about 0.05%, about 0.055%, about 0.06%, about 0.065%, about 0.07%, about 0.075%, about 0.08%, about 0.085%, about 0.09%, about 0.095%, about 0.10%, about 0.15%, about 0.20%, about 0.25%, about 0.30%, about 0.35%, about 0.40%, about 0.45%, about 0.50%, about 0.55%, about 0.60%, about 0.65%, about 0.70%, about 0.75%, about 0.80%, about 0.85%, about 0.90%, about 0.95%, or about 1.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.10% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises from about 1.0% to about 5.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.5%, about 1.6%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%,about 4.6%, about 4.7%, about 4.8%, about 4.9%, or about 5.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 1.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises from about 55%- 85% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at least about 55% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at least about 60% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises less than about 80% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises from about 85% - 99% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises greater than about 85% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises: (i) from about 55.0% to about 85.0% (w / w) of one or more humectants; (ii) from about 10.0% to about 25.0% (w / w) of one or more emulsifiers; (iii) from about 0.0% toAttorney Docket No.67522-701.601 about 10.0% (w / w) of one or more emollients; (iv) from about 1.0% to about 10.0% (w / w) of one or more solvents; or (v) from about 0.0% to about 1.0% (w / w) of a buffering agent; or combination thereof. In some embodiments, the pharmaceutical composition remains stable at 25±2 °C / 60% relative humidity for 6 months. In some embodiments, the one or more humectants comprise white petrolatum. In some embodiments, the one or more emulsifiers comprise white mineral oil. In some embodiments, the one or more solvents comprise ethoxydiglycol. In some embodiments, the pharmaceutical composition is formulated as a low- viscosity ointment having a centipoise (cP) value of between about 5,000-30,000 cP when measured at about room temperature. In some embodiments, the pharmaceutical composition is formulated as a medium-viscosity ointment having a centipoise (cP) value of between about 30,000-70,000 cP when measured at about room temperature. In some embodiments, the pharmaceutical composition is formulated as a high-viscosity ointment having a centipoise (cP) value of between about 70,000-100,000 cP when measured at about room temperature.

[0005] In certain aspects, disclosed herein are pharmaceutical compositions comprising: a) octenidine dihydrochloride, and b) petrolatum, wherein the petrolatum is present in the composition in an amount greater than 50% weight per weight (w / w); wherein the composition is formulated for topical application in a human subject. In some embodiments, the bis(pyridine) antimicrobial agent is octenidine dihydrochloride. In some embodiments, the pharmaceutical composition is formulated for topical application to prevent, treat, or reduce a symptom of a disease of the human subject arising from an infection with a pathogenic microorganism. In some embodiments, the octenidine dihydrochloride is dissolved within a non-aqueous solvent. In some embodiments, the non-aqueous solvent comprises a cosolvent. In some embodiments, the solvent comprises ethanol, propylene glycol, glycerine, glycofurol, polyethylene glycol, or ethoxydiglycol. In some embodiments, the octenidine dihydrochloride is dissolved in a hydrophilic compound. In some embodiments, the hydrophilic compound is ethoxydiglycol. In some embodiments, the pathogenic microorganism comprises a gram-negative bacterium. In some embodiments, the pathogenic microorganism comprises a gram-positive bacterium. In some embodiments, the pathogenic microorganism comprises an atypical bacterium. In some embodiments, the pathogenic microorganism comprises a fungus. In some embodiments, the pharmaceutical composition is formulated as an ointment. In some embodiments, pharmaceutical composition comprises white mineral oil. In some embodiments, pharmaceutical composition comprises ethoxydiglycol. In some embodiments, pharmaceutical composition comprises Butyrospermum Parkii Nut Extract. In some embodiments, pharmaceutical composition comprises Euphorbia Cerifera (Candelilla) Wax. In some embodiments, pharmaceutical composition comprises glycerin. In some embodiments, pharmaceutical composition comprisesAttorney Docket No.67522-701.601 Avena Sativa (Oat) Seed Extract. In some embodiments, pharmaceutical composition comprises honey. In some embodiments, pharmaceutical composition comprises tocopherol. In some embodiments, the bis(pyridine) antimicrobial agent is dissolved within a non-aqueous solvent. In some embodiments, the octenidine dihydrochloride is dissolved within a non-aqueous solvent. In some embodiments, the octenidine or PHMB is dissolved within a non-aqueous solvent. In some embodiments, the non-aqueous solvent comprises ethanol, propylene glycol, glycerine, glycofurol, polyethylene glycol, or ethoxydiglycol. In some embodiments, the pharmaceutical composition is formulated as an ointment. In some embodiments, the hydrophobic carrier suitable for topical application comprises one or more humectants, emollients, solvents, thickeners, penetration enhancers, or buffering agents, or any combination thereof. In some embodiments, the one or more humectants comprise mineral oil, petrolatum, white petrolatum, isopropyl palmitate, ammonium alkginate, butylene glycol, corn syrup solids, cyclomethicone, dipropylene glycol, glycerin, polydextrose, propylene glycol, sodium hyaluronate, sodium lactate, sorbitol, tagatose, trehalose, triacetin, triethanolamine, xylitol, sorbitol, or any combination thereof. In some embodiments, the one or more emollients comprise shea butter, cocoa butter, mineral oil, lanolin, lanolin alcohols, petrolatum, white petrolatum, paraffin, beeswax, squalene, coconut oil, jojoba oil, sesame oil, almond oil, canola oil, palm kernel oil, palm oil, safflower oil, soybean oil, sunflower oil, cetyl alcohol, cetyl palmitate, olive oil, oleyl alcohol, oleic acid, triethylhexanoin, cyclomethicone, dimethicone, sorbitol, xylitol, isopropyl palmitate, castor oil, carnauba wax, cetyl ester wax, emulsifying wax, microcrystalline wax, paraffin wax, white wax, yellow wax, polyethylene glycol, or a combination thereof. In some embodiments, the one or more solvents comprise propylene glycol, hexylene glycol, ethoxydiglycol, polyoxyethylene, polyoxypropylene, diethylene glycol monoethyl ether (DGME), glycerin, dimethyl sulfoxide (DMSO), or any combination thereof. In some embodiments, the one or more thickeners comprise agar, alginate, pectin, acacia, tragcanth, Karaya gum, guar gum, starch, cellulose, carbomer, bees wax, candelilla wax, carnauba wax, or any combination thereof. In some embodiments, the one or more penetration enhancers comprise micelles, phospholipids, propylene glycol, glycerin, ethanol, oleic acid, DMSO, isopropyl myristate, laurocapram, terpenes, urea, sodium lauryl sulfate, cetyl alcohol, stearyl alcohol, cyclodextrins, or any combination thereof. In some embodiments, the one or more buffering agents comprise sodium hydroxide, hydrochloric acid, sodium phosphate monobasic, sodium phosphate dibasic, sodium citrate, or a combination thereof. In some embodiments, the pharmaceutical composition has a pH of from about 4.0 to about 7.0. In some embodiments, the pharmaceutical composition has a pH of about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, about 6.5, or about 7.0. In some embodiments, the pharmaceutical composition comprises fromAttorney Docket No.67522-701.601 about 0.01% to about 1.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.01%, about 0.015%, about 0.02%, about 0.025%, about 0.03%, about 0.035%, about 0.04%, about 0.045%, about 0.05%, about 0.055%, about 0.06%, about 0.065%, about 0.07%, about 0.075%, about 0.08%, about 0.085%, about 0.09%, about 0.095%, about 0.10%, about 0.15%, about 0.20%, about 0.25%, about 0.30%, about 0.35%, about 0.40%, about 0.45%, about 0.50%, about 0.55%, about 0.60%, about 0.65%, about 0.70%, about 0.75%, about 0.80%, about 0.85%, about 0.90%, about 0.95%, or about 1.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.10% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises from about 1.0% to about 5.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.5%, about 1.6%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%,about 4.6%, about 4.7%, about 4.8%, about 4.9%, or about 5.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 1.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises from about 55%- 85% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at least about 55% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at least about 60% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises less than about 80% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises from about 85% - 99% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises greater than about 85% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises: (i) from about 55.0% to about 85.0% (w / w) of one or more humectants; (ii) from about 10.0% to about 25.0% (w / w) of one or more emulsifiers; (iii) from about 0.0% to about 10.0% (w / w) of one or more emollients; (iv) from about 1.0% to about 10.0% (w / w) of one or more solvents; or (v) from about 0.0% to about 1.0% (w / w) of a buffering agent; or combination thereof. In some embodiments, the pharmaceutical composition remains stable at 25±2 °C / 60% relative humidity for 6 months. In some embodiments, the one or moreAttorney Docket No.67522-701.601 humectants comprise white petrolatum. In some embodiments, the one or more emulsifiers comprise white mineral oil. In some embodiments, the one or more solvents comprise ethoxydiglycol. In some embodiments, the pharmaceutical composition is formulated as a low- viscosity ointment having a centipoise (cP) value of between about 5,000-30,000 cP when measured at about room temperature. In some embodiments, the pharmaceutical composition is formulated as a medium-viscosity ointment having a centipoise (cP) value of between about 30,000-70,000 cP when measured at about room temperature. In some embodiments, the pharmaceutical composition is formulated as a high-viscosity ointment having a centipoise (cP) value of between about 70,000-100,000 cP when measured at about room temperature.

[0006] In certain aspects, disclosed herein are pharmaceutical compositions comprising: a) a bis(pyridine) antimicrobial agent, and b) a hydrophobic carrier suitable for topical application, wherein the hydrophobic carrier is present in the composition in an amount greater than 50% weight per weight (w / w); wherein the composition is formulated for topical application in a human subject. In some embodiments, the bis(pyridine) antimicrobial agent comprises an octenidine-based compound. In some embodiments, the bis(pyridine) antimicrobial agent comprises octenidine or one of its pharmaceutically acceptable salts. In some embodiments, the bis(pyridine) antimicrobial agent comprises octenidine dihydrochloride. In some embodiments, the bis(pyridine) antimicrobial agent is dissolved within a non-aqueous solvent. In some embodiments, the octenidine dihydrochloride is dissolved within a non-aqueous solvent. In some embodiments, the octenidine or PHMB is dissolved within a non-aqueous solvent. In some embodiments, the non-aqueous solvent comprises ethanol, propylene glycol, glycerine, glycofurol, polyethylene glycol, or ethoxydiglycol. In some embodiments, the pharmaceutical composition is formulated as an ointment. In some embodiments, the hydrophobic carrier suitable for topical application comprises one or more humectants, emollients, solvents, thickeners, penetration enhancers, or buffering agents, or any combination thereof. In some embodiments, the one or more humectants comprise mineral oil, petrolatum, white petrolatum, isopropyl palmitate, ammonium alkginate, butylene glycol, corn syrup solids, cyclomethicone, dipropylene glycol, glycerin, polydextrose, propylene glycol, sodium hyaluronate, sodium lactate, sorbitol, tagatose, trehalose, triacetin, triethanolamine, xylitol, sorbitol, or any combination thereof. In some embodiments, the one or more emollients comprise shea butter, cocoa butter, mineral oil, lanolin, lanolin alcohols, petrolatum, white petrolatum, paraffin, beeswax, squalene, coconut oil, jojoba oil, sesame oil, almond oil, canola oil, palm kernel oil, palm oil, safflower oil, soybean oil, sunflower oil, cetyl alcohol, cetyl palmitate, olive oil, oleyl alcohol, oleic acid, triethylhexanoin, cyclomethicone, dimethicone, sorbitol, xylitol, isopropyl palmitate, castor oil, carnauba wax, cetyl ester wax, emulsifying wax, microcrystalline wax,Attorney Docket No.67522-701.601 paraffin wax, white wax, yellow wax, polyethylene glycol, or a combination thereof. In some embodiments, the one or more solvents comprise propylene glycol, hexylene glycol, ethoxydiglycol, polyoxyethylene, polyoxypropylene, diethylene glycol monoethyl ether (DGME), glycerin, dimethyl sulfoxide (DMSO), or any combination thereof. In some embodiments, the one or more thickeners comprise agar, alginate, pectin, acacia, tragcanth, Karaya gum, guar gum, starch, cellulose, carbomer, bees wax, candelilla wax, carnauba wax, or any combination thereof. In some embodiments, the one or more penetration enhancers comprise micelles, phospholipids, propylene glycol, glycerin, ethanol, oleic acid, DMSO, isopropyl myristate, laurocapram, terpenes, urea, sodium lauryl sulfate, cetyl alcohol, stearyl alcohol, cyclodextrins, or any combination thereof. In some embodiments, the one or more buffering agents comprise sodium hydroxide, hydrochloric acid, sodium phosphate monobasic, sodium phosphate dibasic, sodium citrate, or a combination thereof. In some embodiments, the pharmaceutical composition has a pH of from about 4.0 to about 7.0. In some embodiments, the pharmaceutical composition has a pH of about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, about 6.5, or about 7.0. In some embodiments, the pharmaceutical composition comprises from about 0.01% to about 1.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.01%, about 0.015%, about 0.02%, about 0.025%, about 0.03%, about 0.035%, about 0.04%, about 0.045%, about 0.05%, about 0.055%, about 0.06%, about 0.065%, about 0.07%, about 0.075%, about 0.08%, about 0.085%, about 0.09%, about 0.095%, about 0.10%, about 0.15%, about 0.20%, about 0.25%, about 0.30%, about 0.35%, about 0.40%, about 0.45%, about 0.50%, about 0.55%, about 0.60%, about 0.65%, about 0.70%, about 0.75%, about 0.80%, about 0.85%, about 0.90%, about 0.95%, or about 1.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.10% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises from about 1.0% to about 5.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.5%, about 1.6%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%,about 4.6%, about 4.7%, about 4.8%, about 4.9%, or about 5.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 1.0% (w / w) ofAttorney Docket No.67522-701.601 octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises from about 55%- 85% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at least about 55% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at least about 60% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises less than about 80% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises from about 85% - 99% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises greater than about 85% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises: (i) from about 55.0% to about 85.0% (w / w) of one or more humectants; (ii) from about 10.0% to about 25.0% (w / w) of one or more emulsifiers; (iii) from about 0.0% to about 10.0% (w / w) of one or more emollients; (iv) from about 1.0% to about 10.0% (w / w) of one or more solvents; or (v) from about 0.0% to about 1.0% (w / w) of a buffering agent; or combination thereof. In some embodiments, the pharmaceutical composition remains stable at 25±2 °C / 60% relative humidity for 6 months. In some embodiments, the one or more humectants comprise white petrolatum. In some embodiments, the one or more emulsifiers comprise white mineral oil. In some embodiments, the one or more solvents comprise ethoxydiglycol. In some embodiments, the pharmaceutical composition is formulated as a low- viscosity ointment having a centipoise (cP) value of between about 5,000-30,000 cP when measured at about room temperature. In some embodiments, the pharmaceutical composition is formulated as a medium-viscosity ointment having a centipoise (cP) value of between about 30,000-70,000 cP when measured at about room temperature. In some embodiments, the pharmaceutical composition is formulated as a high-viscosity ointment having a centipoise (cP) value of between about 70,000-100,000 cP when measured at about room temperature.

[0007] In certain aspects, disclosed herein are pharmaceutical compositions comprising: a) octenidine dihydrochloride, and b) a hydrophobic carrier suitable for topical application, wherein the hydrophobic carrier is present in the composition in an amount greater than 50% weight per weight (w / w); wherein the composition is formulated for topical application in a human subject. In some embodiments, the bis(pyridine) antimicrobial agent is dissolved within a non-aqueous solvent. In some embodiments, the octenidine dihydrochloride is dissolved within a non-aqueous solvent. In some embodiments, the octenidine or PHMB is dissolved within a non-aqueous solvent. In some embodiments, the non-aqueous solvent comprises ethanol, propylene glycol, glycerine, glycofurol, polyethylene glycol, or ethoxydiglycol. In some embodiments, the pharmaceutical composition is formulated as an ointment. In some embodiments, the hydrophobic carrier suitable for topical application comprises one or more humectants,Attorney Docket No.67522-701.601 emollients, solvents, thickeners, penetration enhancers, or buffering agents, or any combination thereof. In some embodiments, the one or more humectants comprise mineral oil, petrolatum, white petrolatum, isopropyl palmitate, ammonium alkginate, butylene glycol, corn syrup solids, cyclomethicone, dipropylene glycol, glycerin, polydextrose, propylene glycol, sodium hyaluronate, sodium lactate, sorbitol, tagatose, trehalose, triacetin, triethanolamine, xylitol, sorbitol, or any combination thereof. In some embodiments, the one or more emollients comprise shea butter, cocoa butter, mineral oil, lanolin, lanolin alcohols, petrolatum, white petrolatum, paraffin, beeswax, squalene, coconut oil, jojoba oil, sesame oil, almond oil, canola oil, palm kernel oil, palm oil, safflower oil, soybean oil, sunflower oil, cetyl alcohol, cetyl palmitate, olive oil, oleyl alcohol, oleic acid, triethylhexanoin, cyclomethicone, dimethicone, sorbitol, xylitol, isopropyl palmitate, castor oil, carnauba wax, cetyl ester wax, emulsifying wax, microcrystalline wax, paraffin wax, white wax, yellow wax, polyethylene glycol, or a combination thereof. In some embodiments, the one or more solvents comprise propylene glycol, hexylene glycol, ethoxydiglycol, polyoxyethylene, polyoxypropylene, diethylene glycol monoethyl ether (DGME), glycerin, dimethyl sulfoxide (DMSO), or any combination thereof. In some embodiments, the one or more thickeners comprise agar, alginate, pectin, acacia, tragcanth, Karaya gum, guar gum, starch, cellulose, carbomer, bees wax, candelilla wax, carnauba wax, or any combination thereof. In some embodiments, the one or more penetration enhancers comprise micelles, phospholipids, propylene glycol, glycerin, ethanol, oleic acid, DMSO, isopropyl myristate, laurocapram, terpenes, urea, sodium lauryl sulfate, cetyl alcohol, stearyl alcohol, cyclodextrins, or any combination thereof. In some embodiments, the one or more buffering agents comprise sodium hydroxide, hydrochloric acid, sodium phosphate monobasic, sodium phosphate dibasic, sodium citrate, or a combination thereof. In some embodiments, the pharmaceutical composition has a pH of from about 4.0 to about 7.0. In some embodiments, the pharmaceutical composition has a pH of about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, about 6.5, or about 7.0. In some embodiments, the pharmaceutical composition comprises from about 0.01% to about 1.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.01%, about 0.015%, about 0.02%, about 0.025%, about 0.03%, about 0.035%, about 0.04%, about 0.045%, about 0.05%, about 0.055%, about 0.06%, about 0.065%, about 0.07%, about 0.075%, about 0.08%, about 0.085%, about 0.09%, about 0.095%, about 0.10%, about 0.15%, about 0.20%, about 0.25%, about 0.30%, about 0.35%, about 0.40%, about 0.45%, about 0.50%, about 0.55%, about 0.60%, about 0.65%, about 0.70%, about 0.75%, about 0.80%, about 0.85%, about 0.90%, about 0.95%, or about 1.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises aboutAttorney Docket No.67522-701.601 0.10% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises from about 1.0% to about 5.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.5%, about 1.6%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%,about 4.6%, about 4.7%, about 4.8%, about 4.9%, or about 5.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 1.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises from about 55%- 85% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at least about 55% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at least about 60% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises less than about 80% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises from about 85% - 99% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises greater than about 85% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises: (i) from about 55.0% to about 85.0% (w / w) of one or more humectants; (ii) from about 10.0% to about 25.0% (w / w) of one or more emulsifiers; (iii) from about 0.0% to about 10.0% (w / w) of one or more emollients; (iv) from about 1.0% to about 10.0% (w / w) of one or more solvents; or (v) from about 0.0% to about 1.0% (w / w) of a buffering agent; or combination thereof. In some embodiments, the pharmaceutical composition remains stable at 25±2 °C / 60% relative humidity for 6 months. In some embodiments, the one or more humectants comprise white petrolatum. In some embodiments, the one or more emulsifiers comprise white mineral oil. In some embodiments, the one or more solvents comprise ethoxydiglycol. In some embodiments, the pharmaceutical composition is formulated as a low- viscosity ointment having a centipoise (cP) value of between about 5,000-30,000 cP when measured at about room temperature. In some embodiments, the pharmaceutical composition is formulated as a medium-viscosity ointment having a centipoise (cP) value of between about 30,000-70,000 cP when measured at about room temperature. In some embodiments, the pharmaceutical composition is formulated as a high-viscosity ointment having a centipoise (cP) value of between about 70,000-100,000 cP when measured at about room temperature.Attorney Docket No.67522-701.601

[0008] In certain aspects, disclosed herein are pharmaceutical compositions comprising: a) a cationic antimicrobial membrane disrupting agent selected from octenidine or polyhexamethylene biguanide (PHMB), and b) a hydrophobic carrier suitable for topical application, wherein the hydrophobic carrier is present in the composition in an amount greater than 50% weight per weight (w / w); wherein the composition is formulated for topical application in a human subject. In some embodiments, the bis(pyridine) antimicrobial agent is dissolved within a non-aqueous solvent. In some embodiments, the octenidine dihydrochloride is dissolved within a non-aqueous solvent. In some embodiments, the octenidine or PHMB is dissolved within a non-aqueous solvent. In some embodiments, the non-aqueous solvent comprises ethanol, propylene glycol, glycerine, glycofurol, polyethylene glycol, or ethoxydiglycol. In some embodiments, the pharmaceutical composition is formulated as an ointment. In some embodiments, the hydrophobic carrier suitable for topical application comprises one or more humectants, emollients, solvents, thickeners, penetration enhancers, or buffering agents, or any combination thereof. In some embodiments, the one or more humectants comprise mineral oil, petrolatum, white petrolatum, isopropyl palmitate, ammonium alkginate, butylene glycol, corn syrup solids, cyclomethicone, dipropylene glycol, glycerin, polydextrose, propylene glycol, sodium hyaluronate, sodium lactate, sorbitol, tagatose, trehalose, triacetin, triethanolamine, xylitol, sorbitol, or any combination thereof. In some embodiments, the one or more emollients comprise shea butter, cocoa butter, mineral oil, lanolin, lanolin alcohols, petrolatum, white petrolatum, paraffin, beeswax, squalene, coconut oil, jojoba oil, sesame oil, almond oil, canola oil, palm kernel oil, palm oil, safflower oil, soybean oil, sunflower oil, cetyl alcohol, cetyl palmitate, olive oil, oleyl alcohol, oleic acid, triethylhexanoin, cyclomethicone, dimethicone, sorbitol, xylitol, isopropyl palmitate, castor oil, carnauba wax, cetyl ester wax, emulsifying wax, microcrystalline wax, paraffin wax, white wax, yellow wax, polyethylene glycol, or a combination thereof. In some embodiments, the one or more solvents comprise propylene glycol, hexylene glycol, ethoxydiglycol, polyoxyethylene, polyoxypropylene, diethylene glycol monoethyl ether (DGME), glycerin, dimethyl sulfoxide (DMSO), or any combination thereof. In some embodiments, the one or more thickeners comprise agar, alginate, pectin, acacia, tragcanth, Karaya gum, guar gum, starch, cellulose, carbomer, bees wax, candelilla wax, carnauba wax, or any combination thereof. In some embodiments, the one or more penetration enhancers comprise micelles, phospholipids, propylene glycol, glycerin, ethanol, oleic acid, DMSO, isopropyl myristate, laurocapram, terpenes, urea, sodium lauryl sulfate, cetyl alcohol, stearyl alcohol, cyclodextrins, or any combination thereof. In some embodiments, the one or more buffering agents comprise sodium hydroxide, hydrochloric acid, sodium phosphate monobasic, sodium phosphate dibasic, sodium citrate, or a combination thereof. In some embodiments, theAttorney Docket No.67522-701.601 pharmaceutical composition has a pH of from about 4.0 to about 7.0. In some embodiments, the pharmaceutical composition has a pH of about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, about 6.5, or about 7.0. In some embodiments, the pharmaceutical composition comprises from about 0.01% to about 1.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.01%, about 0.015%, about 0.02%, about 0.025%, about 0.03%, about 0.035%, about 0.04%, about 0.045%, about 0.05%, about 0.055%, about 0.06%, about 0.065%, about 0.07%, about 0.075%, about 0.08%, about 0.085%, about 0.09%, about 0.095%, about 0.10%, about 0.15%, about 0.20%, about 0.25%, about 0.30%, about 0.35%, about 0.40%, about 0.45%, about 0.50%, about 0.55%, about 0.60%, about 0.65%, about 0.70%, about 0.75%, about 0.80%, about 0.85%, about 0.90%, about 0.95%, or about 1.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.10% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises from about 1.0% to about 5.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.5%, about 1.6%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%,about 4.6%, about 4.7%, about 4.8%, about 4.9%, or about 5.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 1.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises from about 55%- 85% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at least about 55% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at least about 60% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises less than about 80% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises from about 85% - 99% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises greater than about 85% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises: (i) from about 55.0% to about 85.0% (w / w) of one or more humectants; (ii) from about 10.0% to about 25.0% (w / w) of one or more emulsifiers; (iii) from about 0.0% to about 10.0% (w / w) of one or more emollients; (iv) from about 1.0% to aboutAttorney Docket No.67522-701.601 10.0% (w / w) of one or more solvents; or (v) from about 0.0% to about 1.0% (w / w) of a buffering agent; or combination thereof. In some embodiments, the pharmaceutical composition remains stable at 25±2 °C / 60% relative humidity for 6 months. In some embodiments, the one or more humectants comprise white petrolatum. In some embodiments, the one or more emulsifiers comprise white mineral oil. In some embodiments, the one or more solvents comprise ethoxydiglycol. In some embodiments, the pharmaceutical composition is formulated as a low- viscosity ointment having a centipoise (cP) value of between about 5,000-30,000 cP when measured at about room temperature. In some embodiments, the pharmaceutical composition is formulated as a medium-viscosity ointment having a centipoise (cP) value of between about 30,000-70,000 cP when measured at about room temperature. In some embodiments, the pharmaceutical composition is formulated as a high-viscosity ointment having a centipoise (cP) value of between about 70,000-100,000 cP when measured at about room temperature.

[0009] In certain aspects, disclosed herein are methods of reducing or preventing infection in a subject, the methods comprising administering to the patient the pharmaceutical composition described herein to the skin of the subject in need thereof; wherein the disease or condition is mediated by microbial infection. In some embodiments, the disease or condition is selected from first and second-degree burns, venous stasis ulcers, diabetic ulcers, partial and full thickness wounds, donor sites, post-surgical incisions, trauma wounds, and abrasions. In some embodiments, the microbial infection is mediated gram-negative bacteria, gram-positive bacteria, atypical bacteria, or a fungus, or any combination thereof. In some embodiments, the pharmaceutical composition is administered to the skin of the subject in need thereof once every other day, once per day, twice per day, three times per day, four times per day, five times per day, or six times per day.

[0010] In certain aspects, disclosed herein are methods of treating or preventing a disease or condition in a subject in need thereof, the methods comprising applying a viscous antimicrobial composition comprising an octenidine-based compound or octenidine dihydrochloride to one or more surgical implants, wherein the one or more surgical implants are coated with the viscous composition prior to surgical implant in the patient, thereby treating a microbial infection or preventing an extent of a microbial infection following a surgical implant procedure. In some embodiments, the one or more surgical implants comprises organic material. In some embodiments, the one or more surgical implants comprises non-organic material. In some embodiments, the one or more surgical implants comprises an orthopedic device. In some embodiments, the orthopedic device of composed of stainless steel, a cobalt-based alloy, titanium, or a titanium-based alloy. In some embodiments, the one or more surgical implants is a surgical mesh. In some embodiments, the surgical mesh is made of a synthetic polymer. In someAttorney Docket No.67522-701.601 embodiments, the synthetic polymer is polypropylene, polyglycolic acid, or polycaprolactone. In some embodiments, the surgical mesh is made of decellularized collagen. In some embodiments, the one or more surgical implants is a birth control device. In some embodiments, the one or more surgical implants is a cochlear implant device. In some embodiments, the one or more surgical implants is a cochlear implant device comprises a cerebral spinal fluid (CSF) shunt system. In some embodiments, the one or more surgical implants is a sponge comprising decellularized collagen. In some embodiments, the one or more surgical implants comprises a graft from a donor. In some embodiments, the graft from the donor comprises a ligament or tendon. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The novel features described herein are set forth with particularity in the appended claims. A better understanding of the features and advantages of the features described herein will be obtained by reference to the following detailed description that sets forth illustrative examples, in which the principles of the features described herein are utilized, and the accompanying drawings of which:

[0012] FIG.1 shows the chemical structure of octenidine dihydrochloride. DETAILED DESCRIPTION

[0013] The present disclosure is generally directed to topical pharmaceutical compositions comprising a bis(pyridine) antimicrobial agent formulated as a hydrophobic topical ointment for use in wound care, wound healing, and / or prevention or treating of microbial infection. The terms “topical pharmaceutical composition,” “topical composition,” “topical formulation,” and the like are used herein interchangeably and, as used herein, generally refer to a composition that is pharmaceutically acceptable and that is suitable for administering a bis(pyridine) antimicrobial agent to a subject. Such compositions include, but are not limited to, ointments, solutions, liquids, suspensions, oils, gels, creams, lotions, foams, or pastes. The pharmaceutical composition also comprises at least one solvent or co-solvent. In some embodiments, the bis(pyridine) antimicrobial agent is octenidine (OCT) or an octenidine-based compound. In some embodiments, the pharmaceutical composition is formulated in a petroleum-based; as opposed to an aqueous base or a water-in-oil emulsion. In some embodiments, the pharmaceutical composition comprises Butyrospermum Parkii Nut Extract. In some embodiments, the pharmaceutical composition comprises Euphorbia Cerifera (Candelilla) Wax. In some embodiments, the pharmaceutical composition comprises glycerin. In some embodiments, theAttorney Docket No.67522-701.601 pharmaceutical composition comprises ethoxydiglycol. In some embodiments, the pharmaceutical composition comprises white mineral oil. In some embodiments, the pharmaceutical composition comprises petrolatum. In some embodiments, the pharmaceutical composition comprises Avena Sativa (Oat) Seed Extract. In some embodiments, the pharmaceutical composition comprises honey. The pharmaceutical compositions may also contain one or more additional ingredients or excipients as described herein. Such topical formulations are useful in the treatment of diseases or conditions, such as a treatment or prevention of infection in wound management and / or wound care of a subject. Such topical formulations are useful in management of indications such as first and second degree burns, venous stasis ulcers, diabetic ulcers, partial and full thickness wounds, donor sites, post-surgical incisions, trauma wounds, and abrasions. Such topical formulations are useful in management of indications such as superficial wounds such as minor cuts, minor scrapes, minor irritations, minor abrasions, minor blisters, 1st degree burns including sunburns, minor skin irritations following post non-ablative laser therapy procedures, microdermabrasion therapy or superficial chemical peels. Such topical formulations are useful in management for relief of itch, pain and burning from minor skin irritations, lacerations, abrasions and minor burns. Such topical formulations are useful in management of indications such as minor abrasions, lacerations, minor cuts, minor scalds and burns. Such topical formulations are useful in management of indications such as diabetic foot ulcers, leg ulcers (venous stasis ulcers, arterial ulcers, and leg ulcers of mixed etiology, pressure ulcers, first and second degree partial thickness burns, donor sites, and traumatic and surgical wounds. Such topical formulations are useful in management of indications such as for dressing and management of wounds such as first and second-degree burns, venous stasis ulcers, diabetic ulcers, partial and full thickness wounds, donor sites, post- surgical incisions, trauma wounds, and abrasions. Such topical formulations are useful in wound dressings. In some embodiments, the wound dressing is intended for the management of first and second degree burns, venous stasis ulcers, diabetic ulcers, partial and full thickness wounds, donor sites, post-surgical incisions, trauma wounds, and abrasions. The wound dressing described herein can be used during wound dressing changes to soften encrusted wound dressings. Such topical formulations are useful in reducing or preventing infection in a subject, wherein the infection is the result of growth of one or more of gram-negative bacteria, gram- positive bacteria, or a fungus, and any combination thereof. Such topical formulations are useful in sterilizing one or more surgical implants prior to implantation within a subject in need of the surgical implantation. Such topical formulations are useful in pre-operative bacterial decolonization to reduce surgical site infection rates.Attorney Docket No.67522-701.601 Topical formulations

[0014] Described herein are pharmaceutical compositions comprising: a) a bis(pyridine) antimicrobial agent, and b) petrolatum, wherein the petrolatum is present in the composition in an amount greater than 50% weight per weight (w / w); wherein the composition is formulated for topical application in a human subject. In some embodiments, the bis(pyridine) antimicrobial agent is octenidine or one of its pharmaceutically acceptable salts. In some embodiments, the bis(pyridine) antimicrobial agent is an octenidine-based compound. In some embodiments, the octenidine-based compound comprises octenidine and an organic acid used for forming a pharmaceutically acceptable acid addition salt. In some embodiments, the organic acid used for forming the pharmaceutically acceptable acid addition salt is selected from acetic acid, 2,2- dichloroacetic acid, acrylic acid, adipic acid, ascorbic acid, aspartic acid benzenesulfonic acid, benzoic acid, 4-acetamido-benzoic acid, camphoric acid, camphor-10-sulfonic acid, capric acid, caproic acid, caprylic acid, carbonic acid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethane sulfonic acid, 2-hydroxy-ethane sulfonic acid, formic acid, fumaric acid, galactaric acid, gallic acid, gentisic acid, glocolic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glutaric acid, 2-oxo-glutaric acid, glyceric acid, glycerophosphoric acid, glycolic acid, glyoxilic acid, hippuric acid, hydrochloric acid, isobutyric acid, isocitric acid, itaconic acid, lactic acid, lactobionic acid, lauric acid, maleic acid, malic acid, malonic acid, mandelic acid, methane sulfonic acid, naphthalene- 1,5-disulfonic acid, naphthalene-2-sulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, octanoic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, phthalic acid, pimelic acid, pivalic acid, propanoic acid, propionic acid, pyroglutamic acid, pyruvic acid , salicyclic acid, 4-aminosalicyclic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, toluic acid, toluenesulfonic acid, undecylenic acid, and valeric acid. In some embodiments, the bis(pyridine) antimicrobial agent is octenidine dihydrochloride. In some embodiments, the bis(pyridine) antimicrobial agent provides superior, broad spectrum antimicrobial activity when the topical formulation is applied to a subject. In some embodiments, the octenidine-based compound provides superior, broad spectrum antimicrobial activity when the topical formulation is applied to a subject. In some embodiments, the octenidine provides superior, broad spectrum antimicrobial activity when the topical formulation is applied to a subject. In some embodiments, topical formulation in a hydrophobic ointment maintains a moist wound environment when applied to a subject in need thereof, thereby promoting treatment and / or prevention of pathogen infection and also promoting wound healing.

[0015] Described herein are pharmaceutical compositions comprising: a bis(pyridine) antimicrobial agent. Bis(pyridine) antimicrobial agents function as cationic surfactants. TheseAttorney Docket No.67522-701.601 agents are active antimicrobial agents against Gram-positive and Gram-negative bacteria and function by disrupting the cell membrane of each category of bacteria. Bis(pyridine) antimicrobial agents may be used as antiseptic agents prior to a medical procedure. Bis(pyridine) antimicrobial agents may be used as antiseptic agents following a medical procedure. Bis(pyridine) antimicrobial agents may be used as antiseptic agents may be used during to aid wound healing and prevent and / or treat infection. In vitro suspension tests have shown that a bis(pyridine) antimicrobial agents such as octenidine require lower effective concentrations that other known antimicrobial agents such as chlorhexidine to kill common bacteria like Staphylococcus aureus, Escherichia coli, Proteus mirabilis and the fungus Candida albicans. Octenidine is not efficiently absorbed by the skin, nor through mucous membranes, nor via wounds. Octenidine has also been found to not pass through the placental barrier. These features of bis(pyridine) antimicrobial agents including OCT focus the location of antimicrobial activity to the site of application on the subject.

[0016] In an aspect described herein, pharmaceutical compositions comprise a bis(pyridine) antimicrobial agent. In some embodiments, the bis(pyridine) antimicrobial agent is octenidine. In some embodiments, the bis(pyridine) antimicrobial agent is Octenidine dihydrochloride. In some embodiments, the bis(pyridine) antimicrobial agent is Octenidine dibromide. In some embodiments, the bis(pyridine) antimicrobial agent is an octenidine mono saccharine salt. In some embodiments, the bis(pyridine) antimicrobial agent is an Octenidine benzoate salt. In some embodiments, the bis(pyridine) antimicrobial agent is an Octenidine acetate salt. In some embodiments, the bis(pyridine) antimicrobial agent is an Octenidine gluconate. In some embodiments, the bis(pyridine) antimicrobial agent is an Octenidine per acetic acid salt. In some embodiments, the bis(pyridine) antimicrobial agent is an Octenidine perchloric acid. In some embodiments, the bis(pyridine) antimicrobial agent is an Octenidine perchloric salt. In some embodiments, the bis(pyridine) antimicrobial agent is an Octenidine lauric acid. In some embodiments, the bis(pyridine) antimicrobial agent is an Octenidine lauric acid salt. In some embodiments, the bis(pyridine) antimicrobial agent is an Octenidine palmitic acid. In some embodiments, the bis(pyridine) antimicrobial agent is an Octenidine palmitic acid salt. In some embodiments, the bis(pyridine) antimicrobial agent is an Octenidine methane sulfonic acid. In some embodiments, the bis(pyridine) antimicrobial agent is an Octenidine methane sulfonic acid salt. In some embodiments, the bis(pyridine) antimicrobial agent is an Octenidine and an organic acid used for forming a pharmaceutically acceptable acid addition salt wherein the organic acid used for forming the pharmaceutically acceptable acid addition salt is selected from acetic acid, 2,2-dichloroacetic acid, acrylic acid, adipic acid, ascorbic acid, aspartic acid benzenesulfonic acid, benzoic acid, 4-acetamido-benzoic acid, camphoric acid, camphor-10-sulfonic acid, capricAttorney Docket No.67522-701.601 acid, caproic acid, caprylic acid, carbonic acid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethane sulfonic acid, 2-hydroxy-ethane sulfonic acid, formic acid, fumaric acid, galactaric acid, gallic acid, gentisic acid, glocolic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glutaric acid, 2-oxo-glutaric acid, glyceric acid, glycerophosphoric acid, glycolic acid, glyoxilic acid, hippuric acid, hydrochloric acid, isobutyric acid, isocitric acid, itaconic acid, lactic acid, lactobionic acid, lauric acid, maleic acid, malic acid, malonic acid, mandelic acid, methane sulfonic acid, naphthalene- 1,5-disulfonic acid, naphthalene-2-sulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, octanoic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, phthalic acid, pimelic acid, pivalic acid, propanoic acid, propionic acid, pyroglutamic acid, pyruvic acid , salicyclic acid, 4-aminosalicyclic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, toluic acid, toluenesulfonic acid, undecylenic acid, and valeric acid.

[0017] Described herein are pharmaceutical compositions comprising: a) octenidine dihydrochloride, and b) petrolatum, wherein the petrolatum is present in the composition in an amount greater than 50% weight per weight (w / w); wherein the composition is formulated for topical application in a human subject. In some embodiments, the pharmaceutical composition is formulated for topical application to prevent, treat, or reduce a symptom of a disease of the human subject arising from an infection with a pathogenic microorganism. In some embodiments of the pharmaceutical composition, the octenidine dihydrochloride is dissolved within a non- aqueous solvent. In some embodiments, the non-aqueous solvent comprises a cosolvent. In some embodiments, the solvent comprises ethanol, propylene glycol, glycerine, glycofurol, polyethylene glycol, or ethoxydiglycol. In some embodiments, ethoxydiglycol serves as a preferred solvent. In some embodiments, thoxydiglycol may be used solvent or co-solvent, which can be utilized in hydrophilic or lipophilic state due to its solubility in ethanol, propylene glycol, vegetable oils, water, and butylene glycol. In some embodiments, the octenidine dihydrochloride is dissolved in a hydrophilic compound. In some embodiments, the hydrophilic compound is ethoxydiglycol. In some embodiments, the pharmaceutical composition is formulated as an ointment. In some embodiments, the pharmaceutical composition comprises white mineral oil. In some embodiments, the pharmaceutical composition comprises Butyrospermum Parkii Nut Extract. In some embodiments, the pharmaceutical composition comprises Euphorbia Cerifera (Candelilla) Wax. In some embodiments, the pharmaceutical composition comprises glycerin. In some embodiments, the pharmaceutical composition comprises Avena Sativa (Oat) Seed Extract. In some embodiments, the pharmaceutical composition comprises honey. In some embodiments, the pharmaceutical composition comprises tocopherol.Attorney Docket No.67522-701.601

[0018] Described herein are pharmaceutical compositions comprising: a) a bis(pyridine) antimicrobial agent, and b) a hydrophobic carrier suitable for topical application, wherein the hydrophobic carrier is present in the composition in an amount greater than 50% weight per weight (w / w); wherein the composition is formulated for topical application in a human subject. In some embodiments, the bis(pyridine) antimicrobial agent comprises an octenidine-based compound. In some embodiments, the bis(pyridine) antimicrobial agent comprises octenidine or one of its pharmaceutically acceptable salts. In some embodiments, the bis(pyridine) antimicrobial agent comprises octenidine dihydrochloride. In some embodiments, the bis(pyridine) antimicrobial agent is dissolved within a non-aqueous solvent. In some embodiments, the non-aqueous solvent comprises ethanol, propylene glycol, glycerine, glycofurol, polyethylene glycol, or ethoxydiglycol.

[0019] Described herein are pharmaceutical compositions comprising: a) a cationic antimicrobial membrane disrupting agent selected from octenidine or polyhexamethylene biguanide (PHMB), and b) a hydrophobic carrier suitable for topical application, wherein the hydrophobic carrier is present in the composition in an amount greater than 50% weight per weight (w / w); wherein the composition is formulated for topical application in a human subject. In some embodiments, the octenidine or PHMB is dissolved within a non-aqueous solvent. In some embodiments, the non-aqueous solvent comprises ethanol, propylene glycol, glycerine, glycofurol, polyethylene glycol, or ethoxydiglycol.

[0020] Described herein are pharmaceutical compositions comprising: a) octenidine dihydrochloride, and b) a hydrophobic carrier suitable for topical application, wherein the hydrophobic carrier is present in the composition in an amount greater than 50% weight per weight (w / w); wherein the composition is formulated for topical application in a human subject. In some embodiments, the octenidine dihydrochloride is dissolved within a non-aqueous solvent. In some embodiments, the non-aqueous solvent comprises ethanol, propylene glycol, glycerine, glycofurol, polyethylene glycol, or ethoxydiglycol.

[0021] In some embodiments, pharmaceutical compositions described herein are formulated as an ointment. In some embodiments, a hydrophobic carrier suitable for topical application of the ointment comprises one or more humectants, emollients, solvents, thickeners, penetration enhancers, or buffering agents, or any combination thereof. In some embodiments, the one or more humectants comprise mineral oil, petrolatum, white petrolatum, isopropyl palmitate, ammonium alkginate, butylene glycol, corn syrup solids, cyclomethicone, dipropylene glycol, glycerin, polydextrose, propylene glycol, sodium hyaluronate, sodium lactate, sorbitol, tagatose, trehalose, triacetin, triethanolamine, xylitol, sorbitol, or any combination thereof. In some embodiments, the one or more humectants comprise about 50%, about 55%, about 60%, aboutAttorney Docket No.67522-701.601 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 98% (w / w) of the pharmaceutical composition. In some embodiments, the one or more humectants comprise petrolatum. In some embodiments, the one or more humectants comprise white fonoline petrolatum. In some embodiments, the petrolatum comprises at least about 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, or 85% (w / w) of the pharmaceutical composition. In some embodiments, the petrolatum comprises less than 85% (w / w) of the pharmaceutical composition. In some embodiments, the petrolatum comprises between about 55-85% (w / w) of the pharmaceutical composition. In some embodiments, the petrolatum comprises between about 60-70% (w / w) of the pharmaceutical composition. In some embodiments, the petrolatum comprises between about 60-65% (w / w) of the pharmaceutical composition. In some embodiments, the petrolatum comprises between about 62-68% (w / w) of the pharmaceutical composition. In some embodiments, the one or more humectants comprise white mineral oil. In some embodiments, the white mineral oil comprises at least about 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25%, or more (w / w) of the pharmaceutical composition. In some embodiments, the white mineral oil comprises less than about 25% (w / w) of the pharmaceutical composition. In some embodiments, the white mineral oil comprises between about 10-25% (w / w) of the pharmaceutical composition. In some embodiments, the white mineral oil comprises between about 15-25% (w / w) of the pharmaceutical composition. In some embodiments, the white mineral oil comprises between about 18-22% (w / w) of the pharmaceutical composition. In some embodiments, the one or more humectants comprises Drakeol Mineral Oil 600 USP. In some embodiments, the one or more emollients comprise shea butter, cocoa butter, mineral oil, lanolin, lanolin alcohols, petrolatum, white petrolatum, paraffin, beeswax, squalene, coconut oil, jojoba oil, sesame oil, almond oil, canola oil, palm kernel oil, palm oil, safflower oil, soybean oil, sunflower oil, cetyl alcohol, cetyl palmitate, olive oil, oleyl alcohol, oleic acid, triethylhexanoin, cyclomethicone, dimethicone, sorbitol, xylitol, isopropyl palmitate, castor oil, carnauba wax, cetyl ester wax, emulsifying wax, microcrystalline wax, paraffin wax, white wax, yellow wax, polyethylene glycol, or a combination thereof. In some embodiments, the one or more solvents comprise propylene glycol, hexylene glycol, ethoxydiglycol, polyoxyethylene, polyoxypropylene, diethylene glycol monoethyl ether (DGME), glycerin, dimethyl sulfoxide (DMSO), or any combination thereof. In some embodiments, the one or more solvents comprise ethoxydiglycol. In some embodiments, the ethoxydiglycol is used to dissolve the bis(pyridine) antimicrobial agent. In some embodiments, the ethoxydiglycol is used to dissolve the octenidine dihydrochloride. In some embodiments, the ethoxydiglycol comprises at least about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20% or more (w / w) of the pharmaceuticalAttorney Docket No.67522-701.601 composition. In some embodiments, the ethoxydiglycol comprises less than about 15% (w / w) of the pharmaceutical composition. In some embodiments, the ethoxydiglycol comprises between about 1-10% (w / w) of the pharmaceutical composition. In some embodiments, the ethoxydiglycol comprises between about 5-15% (w / w) of the pharmaceutical composition. In some embodiments, the ethoxydiglycol comprises between about 8-12% (w / w) of the pharmaceutical composition. In some embodiments, the ethoxydiglycol comprises about 10% (w / w) of the pharmaceutical composition. In some embodiments, the one or more thickeners comprise agar, alginate, pectin, acacia, tragcanth, Karaya gum, guar gum, starch, cellulose, carbomer, bees wax, candelilla wax, carnauba wax, or any combination thereof. In some embodiments, the one or more thickeners comprise Euphoria Cerifera (Candelila) wax. In some embodiments, the one or more thickeners comprise Candelila Wax (TNB). In some embodiments, the Candelila Wax is present in the pharmaceutical composition at a (w / w) % of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments, the Candelila Wax is present in the pharmaceutical composition at a (w / w) % about between about 1-10%. In some embodiments, the Candelila Wax is present in the pharmaceutical composition at a (w / w) % about between about 0.5 – 3%. In some embodiments, the Candelila Wax is present in the pharmaceutical composition at a (w / w) % about between about 1.5 – 2.5%. In some embodiments, the Candelila Wax is present in the pharmaceutical composition at about 2% w / w. In some embodiments, the pharmaceutical composition comprises Butyrospermum Parkii Nut Extract. In some embodiments, the Butyrospermum Parkii Nut Extract is present in the pharmaceutical composition at a (w / w) % about between about 1-10%. In some embodiments, the Butyrospermum Parkii Nut Extract is present in the pharmaceutical composition at a (w / w) % about between about 2-5%. In some embodiments, the Butyrospermum Parkii Nut Extract is present in the pharmaceutical composition at a (w / w) % about between about 3-6%. In some embodiments, the Butyrospermum Parkii Nut Extract is present in the pharmaceutical composition at a (w / w) % of at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10%. In some embodiments, the Butyrospermum Parkii Nut Extract is present in the pharmaceutical composition at a (w / w) % of about 4%. In some embodiments, the pharmaceutical composition comprises honey. In some embodiments, the honey is present in the pharmaceutical composition at a (w / w) % of between about 0.001 to about 0.1%. In some embodiments, the honey is present in the pharmaceutical composition at a (w / w) % of less than about 0.05, 0.04, 0.03, 0.02, 0.01, 0.005, 0.004, 0.003, 0.002, or 0.001%. In some embodiments, the honey is present in the pharmaceutical composition at a (w / w) % of at least about 0.05, 0.04, 0.03, 0.02, 0.01, 0.005, 0.004, 0.003, 0.002, or 0.001%. In some embodiments, the honey is present in the pharmaceutical composition at a (w / w) % of about 0.01%. In some embodiments, the pharmaceuticalAttorney Docket No.67522-701.601 composition comprises oats extract. In some embodiments, the oats extract is present in the pharmaceutical composition at a (w / w) % of at least about 0.5, 0.4, 0.3, 0.2, 0.1, 0.05, 0.04, 0.03, 0.02, or 0.01%. In some embodiments, the oats extract is present in the pharmaceutical composition at a (w / w) % of about 0.1%. In some embodiments, the pharmaceutical composition comprises Avena Sativa (Oat) Kernel Extract. In some embodiments, the Avena Sativa (Oat) Kernel Extract is present in the pharmaceutical composition at a (w / w) % of at least about 0.5, 0.4, 0.3, 0.2, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.005, or 0.002%. In some embodiments, the Avena Sativa (Oat) Kernel Extract is present in the pharmaceutical composition at a (w / w) % of about 0.02%. In some embodiments, the one or more penetration enhancers comprise micelles, phospholipids, propylene glycol, glycerin, ethanol, oleic acid, DMSO, isopropyl myristate, laurocapram, terpenes, urea, sodium lauryl sulfate, cetyl alcohol, stearyl alcohol, cyclodextrins, or any combination thereof. In some embodiments, the pharmaceutical composition comprises glycerin. In some embodiments, the glycerin is present in the pharmaceutical composition at a (w / w) % of less than about 2, 1.8, 1.6, 1.4, 1.2, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.09, 0.08, 0.07, 0.06, 0.05, 0.04, 0.03, 0.02, or 0.01%. In some embodiments, the glycerin is present in the pharmaceutical composition at a (w / w) % of between about 0.05 – 0.3%. In some embodiments, the glycerin is present in the pharmaceutical composition at a (w / w) % about 0.08%. In some embodiments, the one or more buffering agents comprise sodium hydroxide, hydrochloric acid, sodium phosphate monobasic, sodium phosphate dibasic, sodium citrate, or a combination thereof. In some embodiments, the pharmaceutical composition has a pH of from about 4.0 to about 7.0. In some embodiments, the pharmaceutical composition has a pH of about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, about 6.5, or about 7.0. In some embodiments, the pharmaceutical composition has a pH of about 4.0 to about 6.0. In some embodiments, the pharmaceutical composition has a pH of about 5.0. In some embodiments, the pharmaceutical composition comprises from about 55% - 85% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises from about 50% - 90% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises from about 55% - 95% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at least about 55% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at least about 60% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at least about 65% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at least about 70% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at least about 75% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at leastAttorney Docket No.67522-701.601 about 80% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at least about 85% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at least about 90% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises at least about 95% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises less than about 55% - 95% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises less than about 95% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises less than about 90% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises less than about 85% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises less than about 80% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises less than about 75% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises less than about 70% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises less than about 65% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises less than about 60% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises less than about 55% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises from about 85% - 99% (w / w) of the hydrophobic carrier. In some embodiments, the pharmaceutical composition comprises greater than about 85% (w / w) of the hydrophobic carrier. In some embodiments, the hydrophobic carrier comprises a petroleum-base. In some embodiments, the hydrophobic carrier comprises petrolatum. In some embodiments, the hydrophobic carrier consists essentially of petrolatum. In some embodiments, the hydrophobic carrier comprises white petrolatum. In some embodiments, the hydrophobic carrier consists essentially of white petrolatum. In some embodiments, the hydrophobic carrier comprises mineral oil, petrolatum, white petrolatum, isopropyl palmitate, ammonium alkginate, butylene glycol, corn syrup solids, cyclomethicone, dipropylene glycol, glycerin, polydextrose, propylene glycol, sodium hyaluronate, sodium lactate, sorbitol, tagatose, trehalose, triacetin, triethanolamine, xylitol, sorbitol, or any combination thereof. In some embodiments, the hydrophobic carrier comprises shea butter, cocoa butter, mineral oil, lanolin, lanolin alcohols, petrolatum, white petrolatum, paraffin, beeswax, squalene, coconut oil, jojoba oil, sesame oil, almond oil, canola oil, palm kernel oil, palm oil, safflower oil, soybean oil, sunflower oil, cetyl alcohol, cetyl palmitate, olive oil, oleyl alcohol, oleic acid, triethylhexanoin, cyclomethicone, dimethicone, sorbitol, xylitol, isopropyl palmitate, castor oil, carnauba wax, cetyl ester wax, emulsifying wax, microcrystalline wax, paraffin wax, white wax, yellow wax,Attorney Docket No.67522-701.601 polyethylene glycol, or a combination thereof.

[0022] Octenidine is an organic compound containing a hydrogenated pyridine ring. Octenidine belongs to a class of molecules termed bis(pyridines). Octenidine is an investigational small molecule drug with antimicrobial properties. Octenidine has a chemical formula of C36H62N4. Octenidine has an average molecule weight of 550.92 and a monoisotopic molecular weight of 550.497448012. In some embodiments, pharmaceutical compositions described herein comprise octenidine, or pharmaceutically acceptable salt thereof as the active antimicrobial agent. In some embodiments, pharmaceutical compositions described herein comprise octenidine as the active antimicrobial agent. In some embodiments, the octenidine, or pharmaceutically acceptable salt thereof, is present in the pharmaceutical composition at a (w / w) % of between about 0.001 – 1.0 %. In some embodiments, the octenidine, or pharmaceutically acceptable salt thereof, is present in the pharmaceutical composition at a (w / w) % of between about 0.01 – 1.0 %. In some embodiments, the pharmaceutical composition comprises about 0.01%, about 0.015%, about 0.02%, about 0.025%, about 0.03%, about 0.035%, about 0.04%, about 0.045%, about 0.05%, about 0.055%, about 0.06%, about 0.065%, about 0.07%, about 0.075%, about 0.08%, about 0.085%, about 0.09%, about 0.095%, about 0.10%, about 0.15%, about 0.20%, about 0.25%, about 0.30%, about 0.35%, about 0.40%, about 0.45%, about 0.50%, about 0.55%, about 0.60%, about 0.65%, about 0.70%, about 0.75%, about 0.80%, about 0.85%, about 0.90%, about 0.95%, or about 1.0% (w / w) of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.01% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.02% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.03% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.04% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.05% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.06% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.07% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.8% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.09% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.1% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.12% of octenidine, orAttorney Docket No.67522-701.601 pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.14% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.16% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.18% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.2% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.25% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.3% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.35% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.4% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.5% of octenidine, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises PHMB. In some embodiments, the pharmaceutical composition comprises an effective amount of PHMB. In some embodiments, pharmaceutical compositions described herein comprise octenidine dihydrochloride, or pharmaceutically acceptable salt thereof as the active antimicrobial agent. The chemical structure of octenidine dihydrochloride is listed in FIG.1. The structure of octenidine dihydrochloride affords the molecule both hydrophobic and hydrophilic properties. These properties enable octenidine dihydrochloride to interact with the cell membranes of a various of microorganisms, disrupting the integrity of the membranes and thereby serving as a potent antimicrobial agent. In some embodiments, pharmaceutical compositions described herein comprise octenidine dihydrochloride as the active antimicrobial agent. In some embodiments, the octenidine dihydrochloride, or pharmaceutically acceptable salt thereof, is present in the pharmaceutical composition at a (w / w) % of between about 0.001 – 1.0 %. In some embodiments, the octenidine dihydrochloride, or pharmaceutically acceptable salt thereof, is present in the pharmaceutical composition at a (w / w) % of between about 0.01 – 1.0 %. In some embodiments, the pharmaceutical composition comprises about 0.01%, about 0.015%, about 0.02%, about 0.025%, about 0.03%, about 0.035%, about 0.04%, about 0.045%, about 0.05%, about 0.055%, about 0.06%, about 0.065%, about 0.07%, about 0.075%, about 0.08%, about 0.085%, about 0.09%, about 0.095%, about 0.10%, about 0.15%, about 0.20%, about 0.25%, about 0.30%, about 0.35%, about 0.40%, about 0.45%, about 0.50%, about 0.55%, about 0.60%, about 0.65%, about 0.70%, about 0.75%, about 0.80%, about 0.85%, about 0.90%, about 0.95%, or about 1.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In someAttorney Docket No.67522-701.601 embodiments, the pharmaceutical composition comprises greater than about 0.01% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.01% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.02% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.03% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.04% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 0.05% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.05% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.06% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.07% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.8% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 0.09% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.09% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 0.1% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.1% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.12% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.14% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 0.15% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.16% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.18% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.2% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.25% of octenidineAttorney Docket No.67522-701.601 dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 0.3% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.3% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.35% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.4% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 0.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises PHMB. In some embodiments, the pharmaceutical composition comprises an effective amount of PHMB. In some embodiments, the pharmaceutical composition comprises less than about 1.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 0.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 0.3% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 0.2% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 0.15% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 0.1% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 0.06% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises from about 1.0% to about 5.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.5%, about 1.6%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%,about 4.6%, about 4.7%, about 4.8%, about 4.9%, or about 5.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 1.0% (w / w) of octenidineAttorney Docket No.67522-701.601 dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 1.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 1.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 1.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 2.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 2.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 2.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 2.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 3.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 3.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 3.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 3.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 4.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 4.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises greater than about 4.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 4.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 5.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises at least about 0.05% to about 5.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises at least about 0.05% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises at least about 0.1% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises at least about 0.15% of octenidine dihydrochloride, orAttorney Docket No.67522-701.601 pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises at least about 0.2% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises at least about 0.25% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises at least about 0.3% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises at least about 0.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises at least about 0.75% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises at least about 1.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises at least about 1.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises at least about 2.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises at least about 2.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof In some embodiments, the pharmaceutical composition comprises at least about 3.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises at least about 3.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises at least about 4.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises at least about 4.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises at least about 5.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 0.1% to about 5.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 5.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 4.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 3.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 2.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 2.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In someAttorney Docket No.67522-701.601 embodiments, the pharmaceutical composition comprises less than about 1.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 1.0% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 0.75% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 0.5% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 0.3% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 0.2% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 0.15% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 0.1% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises less than about 0.05% of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof.

[0023] In some embodiments, pharmaceutical compositions described herein comprises: (i) from about 55.0% to about 85.0% (w / w) of one or more humectants; (ii) from about 10.0% to about 25.0% (w / w) of one or more emulsifiers; (iii) from about 0.0% to about 10.0% (w / w) of one or more emollients; (iv) from about 1.0% to about 10.0% (w / w) of one or more solvents; or (v) from about 0.0% to about 1.0% (w / w) of a buffering agent; or combination thereof. In some embodiments, pharmaceutical compositions described herein comprises: (i) from about 55.0% to about 85.0% (w / w) of one or more humectants; (ii) from about 10.0% to about 25.0% (w / w) of one or more emulsifiers; (iii) from about 0.0% to about 10.0% (w / w) of one or more emollients; (iv) from about 1.0% to about 10.0% (w / w) of one or more solvents; and (v) from about 0.0% to about 1.0% (w / w) of a buffering agent; or combination thereof. In some embodiments, the pharmaceutical composition remains stable at 25±2 °C / 60% relative humidity for 6 months. In some embodiments, the one or more humectants comprise petrolatum. In some embodiments, the one or more humectants comprise white petrolatum. In some embodiments, the one or more humectants is present in the pharmaceutical composition in a concentration of at least about 55% w / w. In some embodiments, the one or more humectants is present in the pharmaceutical composition in a concentration of at least about 60% w / w. In some embodiments, the one or more humectants is present in the pharmaceutical composition in a concentration of at least about 65% w / w. In some embodiments, the one or more humectants is present in the pharmaceutical composition in a concentration of at least about 70% w / w. In some embodiments, the one orAttorney Docket No.67522-701.601 more humectants is present in the pharmaceutical composition in a concentration of at least about 75% w / w. In some embodiments, the one or more humectants is present in the pharmaceutical composition in a concentration of at least about 80% w / w. In some embodiments, the one or more humectants is present in the pharmaceutical composition in a concentration of at least about 85% w / w. In some embodiments, petrolatum is present in the pharmaceutical composition in a concentration of at least about 55% w / w. In some embodiments, petrolatum is present in the pharmaceutical composition in a concentration of at least about 60% w / w. In some embodiments, petrolatum is present in the pharmaceutical composition in a concentration of at least about 65% w / w. In some embodiments, petrolatum is present in the pharmaceutical composition in a concentration of at least about 70% w / w. In some embodiments, petrolatum is present in the pharmaceutical composition in a concentration of at least about 75% w / w. In some embodiments, petrolatum is present in the pharmaceutical composition in a concentration of at least about 80% w / w. In some embodiments, petrolatum is present in the pharmaceutical composition in a concentration of at least about 85% w / w. In some embodiments, the one or more humectants consist essentially of white petrolatum. In some embodiments, the one or more emulsifiers comprise white mineral oil. In some embodiments, the one or more solvents comprise ethoxydiglycol. In some embodiments, the one or more solvents consists of ethoxydiglycol. In some embodiments, pharmaceutical compositions described herein comprises octenidine dihydrochloride as the active antimicrobial agent. In some embodiments, pharmaceutical compositions described herein consist essentially of octenidine dihydrochloride as the active antimicrobial agent. In some embodiments, the pharmaceutical composition comprises from about 0.01% to about 1.0% (w / w) of octenidine dihydrochloride. In some embodiments, the pharmaceutical composition comprises at least about 0.05% (w / w) of octenidine dihydrochloride. In some embodiments, the pharmaceutical composition comprises at least about 0.1% (w / w) of octenidine dihydrochloride.

[0024] In some embodiments, pharmaceutical compositions described herein comprises: (i) from about 55.0% to about 95.0% (w / w) of one or more humectants; (ii) from about 10.0% to about 25.0% (w / w) of one or more emulsifiers; (iii) from about 0.0% to about 10.0% (w / w) of one or more emollients; (iv) from about 1.0% to about 10.0% (w / w) of one or more solvents; or (v) from about 0.0% to about 1.0% (w / w) of a buffering agent; or combination thereof. In some embodiments, pharmaceutical compositions described herein comprises: (i) from about 55.0% to about 85.0% (w / w) of one or more humectants; (ii) from about 10.0% to about 25.0% (w / w) of one or more emulsifiers; (iii) from about 0.0% to about 10.0% (w / w) of one or more emollients; (iv) from about 1.0% to about 10.0% (w / w) of one or more solvents; and (v) from about 0.0% to about 1.0% (w / w) of a buffering agent; or combination thereof. In some embodiments, theAttorney Docket No.67522-701.601 pharmaceutical composition remains stable at 25±2 °C / 60% relative humidity for 6 months. In some embodiments, the one or more humectants is present in the pharmaceutical composition in a concentration of at least about 55% w / w. In some embodiments, the one or more humectants is present in the pharmaceutical composition in a concentration of at least about 60% w / w. In some embodiments, the one or more humectants is present in the pharmaceutical composition in a concentration of at least about 65% w / w. In some embodiments, the one or more humectants is present in the pharmaceutical composition in a concentration of at least about 70% w / w. In some embodiments, the one or more humectants is present in the pharmaceutical composition in a concentration of at least about 75% w / w. In some embodiments, the one or more humectants is present in the pharmaceutical composition in a concentration of at least about 80% w / w. In some embodiments, the one or more humectants is present in the pharmaceutical composition in a concentration of at least about 85% w / w. In some embodiments, the one or more humectants is present in the pharmaceutical composition in a concentration of at least about 90% w / w. In some embodiments, the one or more humectants is present in the pharmaceutical composition in a concentration of at least about 95% w / w. In some embodiments, the one or more humectants comprise petrolatum. In some embodiments, the one or more humectants comprise white petrolatum. In some embodiments, the one or more emulsifiers comprise white mineral oil. In some embodiments, the one or more solvents comprise ethoxydiglycol. In some embodiments, the one or more solvents consists of ethoxydiglycol. In some embodiments, pharmaceutical compositions described herein comprises octenidine dihydrochloride as the active antimicrobial agent. In some embodiments, pharmaceutical compositions described herein consist essentially of octenidine dihydrochloride as the active antimicrobial agent. In some embodiments, the pharmaceutical composition comprises from about 0.01% to about 1.0% (w / w) of octenidine dihydrochloride. In some embodiments, the pharmaceutical composition comprises from about 1.0% to about 5.0% (w / w) of octenidine dihydrochloride. In some embodiments, the pharmaceutical composition comprises at least about 0.05% (w / w) of octenidine dihydrochloride. In some embodiments, the pharmaceutical composition comprises at least about 0.1% (w / w) of octenidine dihydrochloride. In some embodiments, the pharmaceutical composition comprises at least about 0.5% (w / w) of octenidine dihydrochloride. In some embodiments, the pharmaceutical composition comprises at least about 1.0% (w / w) of octenidine dihydrochloride. In some embodiments, the pharmaceutical composition comprises at least about 2.5% (w / w) of octenidine dihydrochloride. In some embodiments, the pharmaceutical composition comprises at least about 5% (w / w) of octenidine dihydrochloride.

[0025] In an aspect, pharmaceutical compositions described herein are effective topical antimicrobial agents. In some embodiment, the pharmaceutical composition formulated forAttorney Docket No.67522-701.601 topical application to prevent, treat, or reduce a symptom of a disease of the human subject arising from an infection with a pathogenic microorganism. In some embodiments, the pathogenic microorganism comprises a gram-negative bacterium. In some embodiments, the pathogenic microorganism comprises a gram-positive bacterium. In some embodiments, the pathogenic microorganism comprises an atypical bacterium. In some embodiments, the pathogenic microorganism comprises Bacillus anthracis, Clostridium botulinum, Clostridium tetani, Escherichia coli, Haemophilus influenza, Legionella pneumophilia, Leptospira,Mycobacterium tuberculosis, Pseudomonas aeruginosa, Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA), Neisseria gonorrhoeae, Neisseria meningitidis, Streptococcus pneumonia, Treponema pallidum, Vibrio cholerae, or Yersinia pestis, or any combination thereof. In some embodiments, the pathogenic microorganism comprises In some embodiments, the pathogenic microorganism comprises Methicillin-resistant Staphylococcus aureus (MRSA). Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, Streptococcus pyogene, or Candida glabrata, or any combination thereof. In some embodiments, the pathogenic microorganism comprises a fungus. In some embodiments the pathogenic fungus is a species of Candida genus. In some embodiments the pathogenic fungus is Candida albicans. In some embodiments the pathogenic fungus is Candida glabrata. In some embodiments the pathogenic fungus is Candida tropicalis. In some embodiments the pathogenic fungus is a Malassezia species. In some embodiments, the cationic properties of pharmaceutical compositions described herein formulated for topical application comprising octenidine dihydrochloride are effective antiseptics having antiviral properties. In some embodiments, the pharmaceutical composition disrupts the lipid envelope of viruses upon application which thereby compromises viral integrity and potential for infectivity. In some embodiments, the pharmaceutical composition is an effective antiviral agent against enveloped viruses. In some embodiments, the pharmaceutical composition is an effective antiviral agent against Herpes simplex virus (HSV). In some embodiments, the pharmaceutical composition is an effective antiviral agent against influenza virus. In some embodiments, the pharmaceutical composition is an effective antiviral agent against Human immunodeficiency virus (HIV). In some embodiments, the pharmaceutical composition is an effective antiviral agent against coronaviruses (e.g., HCoV-NL63, HCoV-229E, HCoV-HKU1, HCoV-OC43, SARS-CoV, MERS-CoV, and SARS-CoV-2).

[0026] Pharmaceutical compositions described herein may be formulated for topical application in a number of different configurations. Topical formulations contain at least one active ingredient, and a vehicle. In some embodiments, the pharmaceutical composition is formulated as an ointment. An ointment is a semi-solid, water-free or nearly water-free (e.g., atAttorney Docket No.67522-701.601 least about 80% oil) solution. Features of an ointment are that of greasy, sticky, emollient, protective, occlusive. Generally, no need for preservative, so contact allergy is rare in a subject. Ointments maintains a moist local environment when applied to the skin, to a mucosal membrane, or to a surgical site, thereby maintaining a moist wound environment which is beneficial in wound healing. Ointments may be petroleum-based. In some embodiments, the petroleum-base is petrolatum. Ointments possess a strong emollient effect making them useful in dry skin conditions. Ointments provide occlusive effects enhancing penetration of active drug and improvement of drug efficacy. Ointments provide a protective film on the skin. Ointments are greasy, sticky, and retain sweat. The vehicle in an ointment may have a cooling, emollient, or protective action, or any combination thereof. Generally, ointments are less irritating that other topical formulations such as gels. Ointments often do not contain separate preservatives or emulsifiers, rendering them less prone to allergic reaction in the subject than a topical formulation containing a separate preservative or emulsifier. In some embodiments, the pharmaceutical composition is formulated as a hydrophobic nonaqueous ointment. In some embodiments, the pharmaceutical composition is formulated as a lotion. A lotion is usually considered thicker than a solution (a water or alcoholic lotion containing a dissolved powder) and more likely to contain oil as well as water or alcohol. In some embodiments, the pharmaceutical composition is formulated as a cream. A cream is thicker than a lotion, maintaining its shape, for example, a 50 / 50 emulsion of oil and water. Creams often have moisturizing benefits. In some embodiments, the pharmaceutical composition is formulated as a gel. Gels are aqueous or alcoholic monophasic semisolid emulsion, often based on cellulose and liquefies upon contact with skin. In some embodiments, the pharmaceutical composition is formulated as a paste. A paste is a concentrated suspension of oil, water and powder. In some embodiments, the pharmaceutical composition is formulated as an aerosol foam or spray. An aerosol foam or spray is a solution with pressurized propellant. In some embodiments, the pharmaceutical composition is formulated for delivery with a transdermal patch. A transdermal patch drug delivery system allows precise dosing and include an adhesive. Other topical formulations of pharmaceutical composition described herein include: emulsion, paint, suspension, milk, syrup, collodion, balm or mist. For dry, scaly skin conditions, an ointment formulation may be appropriate. For inflamed skin, an ointment formulation may be appropriate. When considering type of formulation, and dosage of pharmaceutical composition for use in a subject, age and body size of the subject should be taken into consideration. For instance, the surface area of a baby is proportionally much greater than that of an adult. This means topically applied medications can be more likely to result in side effects and toxicity in a baby or young child when applied at a dosage similar to that as in an adult.Attorney Docket No.67522-701.601

[0027] In some embodiments, pharmaceutical composition described herein are formulated with sufficient viscosity to remain in contact with the skin for a period of time following application. In some embodiments, the period of time is at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 hours. In some embodiments, the period of time is at least about 4 hours. In some embodiments, the period of time is at least about 6 hours. In some embodiments, the period of time is at least about 12 hours. In some embodiments, the period of time is at least about 24 hours. In some embodiments, the period of time is at least about 36 hours. In some embodiments, the period of time is at least about 48 hours. In some embodiments, the period of time is at least about 60 hours. In some embodiments, the period of time is at least about 72 hours. In some embodiments, the pharmaceutical composition is formulated as a low-viscosity ointment having a centipoise (cP) value of between about 5,000-30,000 cP when measured at about room temperature. In some embodiments, the pharmaceutical composition is formulated as a medium-viscosity ointment having a centipoise (cP) value of between about 30,000-70,000 cP when measured at about room temperature. In some embodiments, the pharmaceutical composition is formulated as a high- viscosity ointment having a centipoise (cP) value of between about 70,000-100,000 cP when measured at about room temperature. In some embodiments, the pharmaceutical composition is formulated for once every other day dosing. In some embodiments, the pharmaceutical composition is formulated for once daily dosing. In some embodiments, the pharmaceutical composition is formulated for dosing twice daily. In some embodiments, the pharmaceutical composition is formulated for dosing three times daily. In some embodiments, the pharmaceutical composition is formulated for dosing four times daily. Methods of reducing or preventing infection and methods of improved wound healing

[0028] Described herein are methods for using pharmaceutical compositions described herein for reducing or preventing infection in a subject. In aspect, the methods comprise: administering to the subject the pharmaceutical composition described herein to the skin of the subject in need thereof; wherein the disease or condition is mediated by microbial infection. Open wounds, burns, and surgical incisions are susceptible to infection and require appropriate management to remain moist, clean, and heal. Methods described herein maintain a moist environment within and surrounding the site of application of a pharmaceutical composition described herein. This moist environment is conducive to healing and effective for the antimicrobial agent or agents of aAttorney Docket No.67522-701.601 pharmaceutical composition described herein to reduce and / or prevent infection in the subject.

[0029] In another aspect described herein, are methods of treating or preventing a disease or condition in a patient in need thereof, the method comprising applying a viscous antimicrobial composition comprising an octenidine-based compound or octenidine dihydrochloride to one or more surgical implants, wherein the one or more surgical implants are coated with the viscous composition prior to surgical implant in the patient, thereby treating a microbial infection or preventing an extent of a microbial infection following a surgical implant procedure.

[0030] In one aspect, described herein is a method of treating a disease or condition by topically administering to a subject in need thereof a pharmaceutical composition comprising octenidine dihydrochloride or a pharmaceutically acceptable salt thereof. In some embodiments of methods described herein, the subject is a human. In some embodiments of methods described herein, the patient is a human. In some embodiments, the pharmaceutical composition is formulated as a petroleum-based ointment. In some embodiments, the pharmaceutical composition is nearly free of water. In some embodiments, the pharmaceutical composition is free of water. In some embodiments, the pharmaceutical composition is free of an aqueous solution component. In some embodiments, the pharmaceutical composition is formulated for topical administration. In some embodiments, the pharmaceutical composition is formulated for topical administration to the skin of the subject. In some embodiments, the pharmaceutical composition is formulated for topical administration to one or more mucosal surfaces of the subject. In some embodiments, the pharmaceutical composition is formulated for topical administration to a surgical site. In some embodiments, the pharmaceutical composition is formulated for pre-surgical administration. In some embodiments, the pharmaceutical composition is formulated for post-surgical administration. In some embodiments, the method comprises topically applying a pharmaceutical composition described herein to a skin of a subject in need thereof. In some embodiments, the method comprises topically applying a pharmaceutical composition described herein to one or more locations on the skin of a subject in need thereof. In some embodiments, the subject has an active infection in need of treatment. In some embodiments, the subject is at risk for developing an infection that may require subsequent treatment. In some embodiments, the disease or condition comprises first and second degree burns, venous stasis ulcers, diabetic ulcers, partial and full thickness wounds, donor sites, post- surgical incisions, trauma wounds, or abrasions, or any combination thereof. In some embodiments, the pharmaceutical composition is administered as a wound dressing. In some embodiments, the pharmaceutical composition is applied to a wound dressing prior to application of the wound dressing to the subject. In some embodiments, dressing and management of wounds in the subject are under the management of a healthcare professional. In some embodiments, theAttorney Docket No.67522-701.601 healthcare professional provides a prescription for use of the octenidine-containing pharmaceutical composition. In some embodiments, the application of the pharmaceutical composition maintains a moist wound environment in the subject following the administering. In some embodiments, the moist wound environment is maintained for a period of at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, or 72 hours. In some embodiments, the moist wound environment is conducive to the antimicrobial properties of OCT. In some embodiments, the subject is administered the octenidine-based pharmaceutical composition under the management of a healthcare professional according to instructions. In some embodiments, the instructions are printed on a label. In some embodiments, the instructions are included as an insert within a packaged kit. In some embodiments, the moist wound environment is conducive to improved wound healing in the subject. In some embodiments, the moist wound environment is conducive to improved wound healing in the subject by preventing skin in an area of injury from excessively drying out. In some embodiments, a wound dressing incorporating an octenidine-based pharmaceutical composition described herein provides superior infection prevention and / or bacterial decolonization than wound dressing incorporating a known formulation of antimicrobial agent. In some embodiments, the methods described herein are intended for the management of: - diabetic foot ulcers - leg ulcers (venous stasis ulcers, arterial ulcers and leg ulcers of mixed etiology) - pressure ulcers / sores (partial and full thickness) - 1stand 2nddegree partial thickness burns, - donor sites, and / or - traumatic and surgical wounds. In some embodiments, the pharmaceutical composition may also be used for dermal ulcers, including full thickness wounds and pressure sores. In some embodiments, consultation of a physician is recommended. In some embodiments, the pharmaceutical compositions are administered topically. In some embodiments, the pharmaceutical compositions are administered in a topical dosage form. In some embodiments, the pharmaceutical compositions are administered as an ointment, a gel, a cream, a lotion, a solution, an emulsion, a paste, a patch, a wipe, a swab, a pad, or any suitable form. In some embodiments, the pharmaceutical compositions are administered as a gel. In some embodiments, the pharmaceutical compositions are administered as a cream. In some embodiments, the pharmaceutical compositions are administered as an ointment. In some embodiments, the pharmaceutical composition is applied toAttorney Docket No.67522-701.601 one or more areas of skin of the subject in an amount sufficient to cover one or more wound sites and to maintain a moist environment.

[0031] In some embodiments of methods described herein, the octenidine-based pharmaceutical composition is provided over-the-counter (OTC) to a subject in need. In some embodiments, the subject self-administers the octenidine-based pharmaceutical composition according to instructions. In some embodiments, the instructions are printed on a label. In some embodiments, the instructions are included as in insert within a packaged kit. In some embodiments, the octenidine-based pharmaceutical composition comprises octenidine dihydrochloride. In some embodiments, the pharmaceutical composition is intended for the management of lacerations, minor cuts, and / or minor scalds or burns. In some embodiments, the pharmaceutical composition is intended for the management of minor cuts, minor scrapes, minor irritations, minor abrasions, minor blisters, 1st degree burns including sunburns, minor skin irritations following post non-ablative laser therapy procedures, microdermabrasion therapy or superficial chemical peels. In some embodiments, the pharmaceutical composition may also be used for relief of itch, pain and burning from minor skin irritations, lacerations, abrasions and minor burns. In some embodiments, the pharmaceutical composition may also be used for superficial wounds. In some embodiments, the pharmaceutical composition may also be used for minor abrasions. In some embodiments, the pharmaceutical composition may also be used for leg ulcers. In some embodiments, the pharmaceutical composition may also be used for donor sites. In some embodiments, the pharmaceutical composition may also be used for first and second degree burns. In some embodiments, the pharmaceutical composition may also be used for sunburns. In some embodiments, the pharmaceutical composition may also be used for radiation dermatitis.

[0032] In some embodiments of methods described herein, the methods serves as an effect treatment and / or prevention of pathogenic infection. In some embodiments, the source of the pathogenic infection is a microorganism. In some embodiments of methods described herein, the methods serves as an effect treatment and / or prevention of microbial infection. In some embodiments, the microbial infection is mediated gram-negative bacteria, gram-positive bacteria, atypical bacteria, or a fungus, or any combination thereof. In some embodiments, the microbial infection is mediated gram-negative bacteria. In some embodiments, the microbial infection is mediated gram-positive bacteria. In some embodiments, the microbial infection is mediated atypical bacteria. In some embodiments, the microbial infection is mediated a fungus.

[0033] In some embodiments, a pathogenic microorganism causes or is associated with the pathogenic infection. In some embodiments, the pathogenic microorganism is effectively decolonized by the treatment. In some embodiments, the pathogenic microorganism comprisesAttorney Docket No.67522-701.601 Bacillus anthracis, Clostridium botulinum, Clostridium tetani, Escherichia coli, Haemophilus influenza, Legionella pneumophilia, Leptospira, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA), Neisseria gonorrhoeae, Neisseria meningitidis, Streptococcus pneumonia, Treponema pallidum, Vibrio cholerae, or Yersinia pestis, or any combination thereof. In some embodiments, the pathogenic microorganism comprises Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, Streptococcus pyogene, or Candida glabrata, or any combination thereof. In some embodiments, the pathogenic microorganism comprises a fungus. In some embodiments, treatment effectiveness is determined as percent reduction of the pathogen compared to control (no treatment group). In some embodiments, percent reduction of the pathogen compared to control is at least about 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 99.1, 99.2, 99.3, 99.4, 99.5, 99.6, 99.7, 99.8, or 99.9% at a period of time following the administering. In some embodiments, the period of time is at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 minutes. In some embodiments, the period of time is at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 hours. In some embodiments, the treatment with a pharmaceutical composition described herein is more effective that treatment with Polymyxin / Bacitracin (Polysporin) in reduction infection in a subject. In some embodiments, the treatment with a pharmaceutical composition described herein is more effective that treatment with Bactroban (Mupirocin) in reduction infection in a subject. In some embodiments, the treatment with a pharmaceutical composition described herein is more effective that treatment with Silvadene in reduction infection in a subject. In some embodiments, the pharmaceutical composition is administered to the skin of the patient in need thereof once every other day, once per day, twice per day, three times per day, four times per day, five times per day, or six times per day. In some embodiments, pharmaceutical composition is part of a wound dressing that is applied to the skin of the patient in need thereof once every third day,Attorney Docket No.67522-701.601 once every other day, once per day, twice per day, or three times per day. In some embodiments, the pharmaceutical composition is administered to the skin of the patient in need thereof once every other day. In some embodiments, the pharmaceutical composition is administered to the skin of the patient in need thereof once per day. In some embodiments, the pharmaceutical composition is administered to the skin of the patient in need thereof twice per day. In some embodiments, the pharmaceutical composition is administered to the skin of the patient in need thereof three times per day. In some embodiments, the pharmaceutical composition is administered to the skin of the patient in need thereof four times per day.

[0034] In an aspect of methods described herein, an octenidine-based compound or octenidine dihydrochloride is used in a method of treating or preventing a disease or condition in a patient in need thereof, the method comprising applying a viscous antimicrobial composition described herein to one or more surgical implants, wherein the one or more surgical implants are coated with the viscous composition prior to surgical implant in the patient, thereby treating a microbial infection or preventing an extent of a microbial infection following a surgical implant procedure. In some embodiments, the one or more surgical implants comprises organic material. In some embodiments, the one or more surgical implants comprises non-organic material. In some embodiments, the one or more surgical implants comprises an orthopedic device. In some embodiments, the orthopedic device of composed of stainless steel, a cobalt-based alloy, titanium, or a titanium-based alloy. In some embodiments, the one or more surgical implants is a surgical mesh. In some embodiments, the surgical mesh is made of a synthetic polymer. In some embodiments, the synthetic polymer is polypropylene, polyglycolic acid, or polycaprolactone. In some embodiments, the surgical mesh is made of decellularized collagen. In some embodiments, the one or more surgical implants is a birth control device. In some embodiments, the one or more surgical implants is a cochlear implant device. In some embodiments, the one or more surgical implants is a cochlear implant device comprises a cerebral spinal fluid (CSF) shunt system. In some embodiments, the one or more surgical implants is a sponge comprising decellularized collagen. In some embodiments, the one or more surgical implants comprises a graft from a donor. In some embodiments, the graft from the donor comprises a ligament or tendon. Articles of Manufacture and Kits

[0035] Disclosed herein, in certain embodiments, are kits and articles of manufacture for use with one or more methods described herein. In some embodiments, the kit comprises additional components, such as a carrier, package, or container that is compartmentalized to receive one or more containers such as vials, tubes, and the like, each of the container(s) comprising one of theAttorney Docket No.67522-701.601 separate elements to be used in a method described herein. Suitable containers include, for example, bottles, vials, plates, syringes, and test tubes. In one embodiment, the containers are formed from a variety of materials such as glass or plastic.

[0036] The articles of manufacture provided herein contain packaging materials. Examples of pharmaceutical packaging materials include, but are not limited to, bottles, tubes, bags, containers, and any packaging material suitable for a selected formulation and intended mode of use.

[0037] For example, the container(s) include one or more of the crystalline or amorphous forms described herein. Such kits optionally include an identifying description or label or instructions relating to its use in the methods described herein.

[0038] A kit typically includes labels listing contents and / or instructions for use, and package inserts with instructions for use. A set of instructions are also typically included.

[0039] In one embodiment, a label is on or associated with the container. In one embodiment, a label is on a container when letters, numbers or other characters forming the label are attached, molded, or etched into the container itself; a label is associated with a container when it is present within a receptacle or carrier that also holds the container, e.g., as a package insert. In one embodiment, a label is used to indicate that the contents are to be used for a specific therapeutic application. The label also indicates directions for use of the contents, such as in the methods described herein.

[0040] In some embodiments, the kit comprises a pharmaceutical composition described herein and instructions for use. In some embodiments, the kit comprises a pharmaceutical composition described herein and a drug delivery device. In some embodiments, the instructions list primary indications for use. In some embodiments, the instructions providing dosing and administration recommendations for a healthcare profession managing care of the subject. Definitions:

[0041] In the following description, certain specific details are set forth in order to provide a thorough understanding of various embodiments. However, one skilled in the art will understand that the embodiments provided may be practiced without these details. Unless the context requires otherwise, throughout the specification and claims that follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense, that is, as “including, but not limited to.” As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise. It should also be noted that the term “or” is generally employed in its sense including “and / or” unless the content clearly dictates otherwise. Further,Attorney Docket No.67522-701.601 headings provided herein are for convenience only and do not interpret the scope or meaning of the claimed embodiments.

[0042] As used herein a pharmaceutical composition that is “consisting essentially” of the recited components is a composition that only has the recited elements as active ingredients, but can comprise other non-active components that do not appreciably modify the function or activity of the recited components. Any list disclosed herein that is recited as “comprising” can be recited as “consisting essentially,” to exclude non-recited chemical or biological components.

[0043] As used herein the term “about” refers to an amount that is near the stated amount by 10% or less.

[0044] As used herein the terms “individual” “subject,” and “patient” are interchangeable. The subject can be mammal such as a horse, cow, pig, chicken, goat, rabbit, mouse, rat, dog, or cat. In certain preferred embodiments, the subject is a human person.

[0045] The use of the term “including” as well as other forms, such as “include”, “includes,” and “included,” is not limiting. The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0046] The term “acceptable” with respect to a formulation, composition or ingredient, as used herein, means having no persistent detrimental effect on the general health of the subject being treated.

[0047] “Pharmaceutically acceptable,” as used herein, refers a material, such as a carrier or diluent, which does not abrogate the biological activity or properties of the compound, and is relatively nontoxic, i.e., the material is administered to an individual without causing undesirable biological effects or interacting in a deleterious manner with any of the components of the composition in which it is contained.

[0048] The term “pharmaceutically acceptable salt” refers to a form of a therapeutically active agent that consists of a cationic form of the therapeutically active agent in combination with a suitable anion, or in alternative embodiments, an anionic form of the therapeutically active agent in combination with a suitable cation. Handbook of Pharmaceutical Salts: Properties, Selection and Use. International Union of Pure and Applied Chemistry, Wiley-VCH 2002. S.M. Berge, L.D. Bighley, D.C. Monkhouse, J. Pharm. Sci.1977, 66, 1-19. P. H. Stahl and C. G. Wermuth, editors, Handbook of Pharmaceutical Salts: Properties, Selection and Use, Weinheim / Zürich:Wiley-VCH / VHCA, 2002. Pharmaceutical salts typically are more soluble and more rapidly soluble in stomach and intestinal juices than non-ionic species and so are useful in solid dosage forms. Furthermore, because their solubility often is a function of pH, selective dissolution in one or another part of the digestive tract is possible and this capability can be manipulated as one aspect of delayed and sustained release behaviors. Also, because the salt-Attorney Docket No.67522-701.601 forming molecule can be in equilibrium with a neutral form, passage through biological membranes can be adjusted.

[0049] It should be understood that a reference to a pharmaceutically acceptable salt includes the solvent addition forms. In some embodiments, solvates contain either stoichiometric or non- stoichiometric amounts of a solvent, and are formed during the process of crystallization with pharmaceutically acceptable solvents such as water, ethanol, and the like. Hydrates are formed when the solvent is water, or alcoholates are formed when the solvent is alcohol. Solvates of compounds described herein are conveniently prepared or formed during the processes described herein. In addition, the crystalline and amorphous forms provided herein optionally exist in unsolvated as well as solvated forms.

[0050] The terms “administer,” “administering,” “administration,” and the like, as used herein, refer to the methods that may be used to enable delivery of compounds or compositions to the desired site of biological action. Those of skill in the art are familiar with administration techniques that can be employed with the compositions and methods described herein. In some embodiments, the compounds and compositions described herein are administered topically.

[0051] The terms “effective amount” or “therapeutically effective amount,” as used herein, refer to a sufficient amount of an agent or a compound being administered, which will relieve to some extent one or more of the symptoms of the disease or condition being treated. The result includes reduction and / or alleviation of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. For example, an “effective amount” for therapeutic uses is the amount of the composition comprising a compound as disclosed herein required to provide a clinically significant decrease in disease symptoms. An appropriate “effective” amount in any individual case is optionally determined using techniques, such as a dose escalation study.

[0052] The terms “treat,” “treating,” or “treatment,” as used herein, include alleviating, abating or ameliorating at least one symptom of a disease or condition, preventing additional symptoms, inhibiting the disease or condition, e.g., arresting the development of the disease or condition, relieving the disease or condition, causing regression of the disease or condition, relieving a condition caused by the disease or condition, or stopping the symptoms of the disease or condition either prophylactically and / or therapeutically.

[0053] As used herein, the term “therapeutic” means an agent utilized to treat, combat, ameliorate, prevent or improve an unwanted condition or disease of a patient. In some embodiments, a therapeutic agent such as octenidine is directed to the treatment and / or the amelioration of, reversal of, or stabilization of the symptoms of pathogenic infection described herein.Attorney Docket No.67522-701.601 EXAMPLES

[0054] The following illustrative examples are representative of embodiments of the compositions and methods described herein and are not meant to be limiting in any way. Example 1 – – Testing of Antimicrobial Capacity of Pharmaceutical Compositions

[0055] In an example of an in vitro test, an antimicrobial suspension time-kill test was conducted to assess the efficacy of octenidine ointment formulations in achieving antimicrobial effectiveness.

[0056] Study objective: to document the antimicrobial efficacy for five test articles and one inert control against the test systems (microorganisms) listed herein and under the specified test parameters. Five antimicrobial test formulations and one inert control formulation were tested in a suspension time-kill test. Three reference products with known antimicrobial potencies were tested as part of the test formulations. Two test compound formulations (octenidine ointment formulations) were tested for antimicrobial efficacy in comparison to the reference products. Test formulations and conditions for storage prior and during the testing were:

[0057] Reference product 1: Polymyxin / Bacitracin (Polysporin). Active ingredient: Bacitracin Zinc (500 units / g), Polymyxin B Sulfate (10,000 units / g). Storage conditions: room temperature; under fluorescent lighting.

[0058] Reference product 2: Bactroban (Mupirocin). Active ingredient: Mupirocin (2%). Storage conditions: room temperature; under fluorescent lighting.

[0059] Reference product 3: Silvadene. Active ingredient: Silver Sulfadiazine (1%). Storage conditions: room temperature; under fluorescent lighting.

[0060] Test Compound – Regular. Active ingredient: Octenidine-HCl. Storage conditions: room temperature; under fluorescent lighting.

[0061] Test Compound – Extra Strength. Active ingredient: Octenidine-HCl. Storage conditions: room temperature; under fluorescent lighting.

[0062] Inert Control: Phosphate Buffered Saline (PBS). Control Active ingredient: NaCl (0.9%). Storage conditions: room temperature.

[0063] The following microorganisms were used within the test system for determining antimicrobial efficacy of the test formulations: Acinetobacter baumannii_UCLA_L001 Candida glabrata_UCLA_L008 Escherichia coli_UCLA_L006 Pseudomonas aeruginosa_UCLA_L002 Pseudomonas aeruginosa _UCLA_L009Attorney Docket No.67522-701.601 Serratia marcescens_UCLA_L005 Staphylococcus aureus_UCLA_L003 Staphylococcus aureus_UCLA_L004 Streptococcus pyogenes_UCLA_L007

[0064] Testing parameters:

[0065] Artificial Soil Load: 10% Fetal Bovine Serum Exposure (Contact) Time(s): 1 minute ± 2 seconds, 5 minutes ± 10 seconds, 10 minutes ± 30 seconds Test Temperature: Ambient (room temperature) Number of Tests Comprising the Study: 1 test per test article per test microorganism per contact time, with one control per test microorganism Control Replicates: Single replicate per control per test microorganism Test Replicates: Single replicate per test article per test microorganism per contact time Elution / Neutralization Broth: *Phosphate Buffered Saline (PBS), 9.9 mL *Dey / Engley broth, 9 mL & 19 mL Inoculation Volume: 0.1 ml Test Article Harvest Volume: 1 ml Test Culture & Enumeration Plate Incubation Conditions:

[0066] 36 ± 1˚C, aerobic: Acinetobacter baumannii_UCLA_L001 Escherichia coli_UCLA_L006 Pseudomonas aeruginosa_UCLA_L002 Pseudomonas aeruginosa _UCLA_L009 Serratia marcescens_UCLA_L005 Staphylococcus aureus_UCLA_L003 Staphylococcus aureus_UCLA_L004

[0067] 37 ± 1˚C, 5% CO2: Streptococcus pyogenes_UCLA_L007

[0068] Ambient, aerobic: Candida glabrata_UCLA_L008

[0069] Two neutralization methods were employed in this study. Test article Reference Product 2 – Bactron (Mupirocin) was diluted 1:10,000 in PBS and then filtered through a 47 mm filter with pore size of 0.45µm, which was then plated to growth supporting media. All other test articles were neutralized by 1:200 dilution in Dey / Engley broth.Attorney Docket No.67522-701.601

[0070] Efficacy Testing Plating Media: Tryptic Soy Agar: Acinetobacter baumannii_UCLA_L001 Escherichia coli_UCLA_L006 Pseudomonas aeruginosa_UCLA_L002 Pseudomonas aeruginosa _UCLA_L009 Serratia marcescens_UCLA_L005 Staphylococcus aureus_UCLA_L003 Staphylococcus aureus_UCLA_L004 Brain-Heart Infusion Agar Streptococcus pyogenes_UCLA_L007Sabouraud Dextrose Agar: Candida glabrata_UCLA_L008

[0071] Test Culture Growth Media: Tryptic Soy Broth: Acinetobacter baumannii_UCLA_L001 Escherichia coli_UCLA_L006 Pseudomonas aeruginosa_UCLA_L002 Pseudomonas aeruginosa _UCLA_L009 Serratia marcescens_UCLA_L005 Staphylococcus aureus_UCLA_L003 Staphylococcus aureus_UCLA_L004 Brain Heart Infusion Broth: Streptococcus pyogenes_UCLA_L007 Sabouraud Dextrose Agar: Candida glabrata_UCLA_L008

[0072] Test method: The test was conducted according to the below protocol except as otherwise noted in the protocol changes.

[0073] Study controls:

[0074] Neutralizer Verification Control

[0075] For the neutralization verification control, a single replicate was evaluated per test article for the test microorganisms Escherichia coli_UCLA_L006, Pseudomonas aeruginosa_UCLA_L002, Staphylococcus aureus_UCLA_L003, and Streptococcus pyogenes_UCLA_L007. Neutralization verification control test and control article harvestvolumes were identical to those used in the efficacy test for each test microorganism.Attorney Docket No.67522-701.601

[0076] The following is the procedure employed for test articles Test Compound – Regular, Test Compound – Extra Strength, Reference Product 1– Polymyxin / Bacitracin (Polysporin), Reference Product 3 – Silvadene: • To perform the neutralization verification control, a single replicate aliquot of the test article was prepared for each test microorganism. • To perform the neutralizer toxicity control, a single replicate aliquot of the control article was prepared for each test microorganism. • Aliquots of the test and control article were separately neutralized by addition of neutralizing broth.1 mL of test or control article was neutralized by serially diluting in 19 and 9 mL of Dey / Engley broth, for a total 1:200 dilution of test article in neutralizer. • For each microorganism, an aliquot of PBS was prepared of equal volume to the test article-neutralizer suspension (10 mL) as a test organism viability control, to be compared against the neutralization verification and neutralizer toxicity suspensions. • A neutralization verification test inoculum was prepared by diluting the test microorganism in sterile PBS to yield a final target concentration of 10 – 100 CFU per ml of each neutralized test or control article suspension or PBS aliquot. • Each neutralized test or control article suspension or PBS aliquot was inoculated with an appropriate volume of the test microorganism suspension. • Inoculated test and control article and PBS aliquots were vortex mixed and mixed suspensions were allowed to sit undisturbed at room temperature for a minimum of 10 minutes before aliquots were plated in duplicate to the appropriate growth supporting agar. Tryptic Soy Agar was used for plating Escherichia coli_UCLA_L006, Pseudomonas aeruginosa_UCLA_L002, and Staphylococcus aureus_UCLA_L003. Brain Heart Infusion Agar was used for plating Streptococcus pyogenes_UCLA_L007.

[0077] The following is the procedure employed for test article Reference Product 2 – Bactroban (Mupirocin), for which chemical neutralization and neutralization by dilution were not successful in neutralizing the active ingredient: • To perform the neutralization verification control, a single replicate aliquot of the test article was prepared for each test microorganism. • Aliquots of the test article were separately diluted in PBS.0.1 ml of test article was serially diluted in two 9.9 mL aliquots of PBS, for a total 1:10,000 dilution of test article in PBS. • For each microorganism, an aliquot of PBS was prepared of equal volume to the final test article-PBS suspension (10 mL) as a test organism viability control, to be comparedAttorney Docket No.67522-701.601 against the neutralization verification suspension. • Each test suspension or PBS aliquot was passed separately through a 47 mm filter with pore size 0.45µm using a vacuum filtration manifold. • Each filter was then plated to the appropriate growth supporting agar. Tryptic Soy Agar was used for filters to be inoculated with Escherichia coli_UCLA_L006, Pseudomonas aeruginosa_UCLA_L002, and Staphylococcus aureus_UCLA_L003. Brain Heart Infusion Agar was used for filters to be inoculated with Streptococcus pyogenes_UCLA_L007. • A neutralization verification test inoculum was prepared by diluting the test microorganism in sterile PBS to yield a final target concentration of 10 – 100 CFU on each filter associated with neutralized test article or PBS aliquot. • Each plated filter was inoculated with an appropriate volume of the test microorganism suspension.

[0078] Media Sterility Control:

[0079] Media sterility controls were performed on each day of testing and for each media type used in the study either by incubating an agar plate of each growth supporting medium type along with enumeration plates or plating an aliquot (e.g., 0.100 mL) to growth supporting agar.

[0080] Purity Control and Positive Growth Control:

[0081] A positive (growth) and purity control was performed for each test microorganism on the day of testing by inoculating a sterile agar plate with each test microorganism and / or performing an isolation streak on the appropriate growth supporting agar.

[0082] Study Acceptance Criteria:

[0083] The experimental success (controls) criteria follow: • The Initial Numbers Control must demonstrate >1 x 106CFU / ml for each test microorganism, and counts from the start and end of testing must not differ by more than ±0.5 log10. • The media sterility controls must be negative for growth. • The positive (growth) controls must be positive for growth and must demonstrate a pure culture of each test microorganism. • Antibiotic resistance of antibiotic resistant strains must be confirmed according to CLSI standards. • The neutralization test suspension counts must be ≥70% of that recorded for the respective neutralization control suspension count.

[0084] The product performance success criteria follow: • Performance criteria were determined by the Study Sponsor.Attorney Docket No.67522-701.601

[0085] Calculations: [(Plate Count 1 + Plate Count 2) / 2] x Dilution Factor = CFU / ml

[0086] For samples neutralized by filtration, the CFU / ml was determined as follows: Plate Count x Dilution Factor = CFU / ml*

[0087] Percent Reductions were calculated as follows: Percent Reduction (%) = 100 x (1 – 10-LR)

[0088] Log Reductions were calculated as follows: LR = mean log10(microbial population) – mean log10(surviving test population) LR = Log10Reduction relative to initial numbers control.

[0089] Neutralization Verification and Neutralizer Toxicity Control Results were calculated as follows: (Plate Count 1 + Plate Count 2) / 2 = CFU / ml Percent Recovery = (A / B) x 100 A= the mean CFU / ml recovered from test article (neutralization verification) or control article (neutralizer toxicity) suspension after a minimum of 10 minutes. B= the mean CFU / ml recovered from PBS (viability control) after a minimum of 10 minutes.

[0090] For neutralization by filtration, Neutralization Verification Results were calculated as follows: Plate Count = CFU Percent Recovery = (A / B) x 100 A= the CFU recovered from filter used for the test article (neutralization verification) suspension B= the CFU recovered from filter used for PBS (viability control)

[0091] The Dilution Factor used in CFU / mL calculations for these samples accounted for the pre-filtration dilutions, as well as the volumes of the suspensions passed through the filter.

[0092] Results:

[0093] Initial results of certain test groups are displayed in Table 1. Table 1 lists Suspension Time Kill Testing results for Reference Product 1 - Polymyxin / Bacitracin (Polysporin) (Lot: 3062LZ), Reference Product 3 – Silvadene (Lot: FK7908), Test Compound – Regular (Lot: 220025-05-01), and Test Compound - Extra Strength (Lot: 220025-04-01) evaluated after 1 minute ± 2 seconds, 5 minutes ± 10 seconds, and 10 minutes ± 30 seconds against all test microorganisms. The lower limit of detection for this study was 1.02 x 103 CFU / mL and is noted as <1.02E+03 CFU / mL in the Table 1 below.Attorney Docket No.67522-701.601 Table 1: Initial Results of antimicrobial suspension time-kill testAttorney Docket No.67522-701.601Attorney Docket No.67522-701.601Attorney Docket No.67522-701.601

[0094] Initial results of Reference Product 2 – Bactroban (Mupirocin) are displayed in Table 2. Table 2 lists Suspension Time Kill Testing results for Reference Product 2 - Bactroban (Mupirocin) (Lot: 19225293) evaluated after 1 minute ± 2 seconds, 5 minutes ± 10 seconds, and 10 minutes ± 30 seconds against all test microorganisms. Note, the upper limit of detection for this study was 3.00 x 106CFU / mL and is noted as >3.00E+06 CFU / mL in the Table 2 below. Table 2: Initial Results Part II of antimicrobial suspension time-kill testAttorney Docket No.67522-701.601Attorney Docket No.67522-701.601

[0095] Table 3 below displays Neutralization Verification and Neutralizer Toxicity control results for test articles Reference Product 1 - Polymyxin / Bacitracin (Polysporin),Reference Product 3 – Silvadene, Test Compound – Regular, and Test Compound - Extra Strength, for all representative test microorganisms. Table 3: Neutralization Verification and Neutralizer Toxicity control resultsAttorney Docket No.67522-701.601

[0096] Table 4 below displays Neutralization Verification and Neutralizer Toxicity control results Reference Product 2 - Bactroban (Mupirocin) (Lot: 19225293) for all representative test microorganisms. Table 4: Neutralization Verification and Neutralizer Toxicity control results Reference Product 2

[0097] Sterility and purity control results were determined for all test microorganisms used in Suspension Time Kill testing. Growth and purity control results were determined for all test microorganisms evaluated under Neutralizer Verification and Neutralizer Toxicity controls.Attorney Docket No.67522-701.601

[0098] Incubation times and temperature ranges for all Suspension Time Kill test enumerations are listed in Table 5. Table 5: Incubation times and temperature ranges for all Suspension Time Kill test enumerations

[0099] Refrigeration times and temperature ranges for all Suspension Time Kill test enumerations are listed in Table 6. Table 6: Refrigeration times and temperature ranges for all Suspension Time Kill test enumerationsAttorney Docket No.67522-701.601

[0100] Incubation times and temperature ranges for Neutralization Verification and Neutralizer Toxicity control enumerations are listed in Table 7. Table 7: Incubation times and temperature ranges for Neutralization Verification and Neutralizer Toxicity control enumerations

[0101] Refrigeration times and temperature ranges for Neutralization Verification and Neutralizer Toxicity control enumerations are listed in Table 8. Table 8: Refrigeration times and temperature ranges for Neutralization Verification and Neutralizer Toxicity control enumerations

[0102] Study Conclusion:

[0103] For this study, 4.5 mL aliquots of the following test articles were supplemented with 0.5 mL FBS and inoculated with 0.1 mL of each indicated test microorganism independently:Attorney Docket No.67522-701.601 Reference Product 1 - Polymyxin / Bacitracin (Polysporin) Reference Product 2 - Bactroban (Mupirocin) Reference Product 3 – Silvadene Test Compound – Regular Test Compound - Extra Strength The following test systems (microorganisms) were included in this study: Acinetobacter baumannii_UCLA_L001 Candida glabrata_UCLA_L008 Escherichia coli_UCLA_L006 Pseudomonas aeruginosa_UCLA_L002 Pseudomonas aeruginosa _UCLA_L009 Serratia marcescens_UCLA_L005 Staphylococcus aureus_UCLA_L003 Staphylococcus aureus_UCLA_L004 Streptococcus pyogenes_UCLA_L007 After the specified contact times of 1 minute ± 2 seconds, 5 minutes ± 10 seconds, and 10 minutes ± 30 seconds, test article replicates were neutralized and enumerated for surviving test systems. The test article Test Compound – Regular achieved >99.99% (>3 log10) reduction against the following test microorganisms by 10 minutes ± 30 seconds: Acinetobacter baumannii_UCLA_L001 Escherichia coli_UCLA_L006 Pseudomonas aeruginosa_UCLA_L002 Pseudomonas aeruginosa _UCLA_L009 Serratia marcescens_UCLA_L005 Staphylococcus aureus_UCLA_L004 Streptococcus pyogenes_UCLA_L007 The test article Test Compound – Regular achieved <90.0% (<1 log10) reduction against the following test microorganisms: Candida glabrata_UCLA_L008 Staphylococcus aureus_UCLA_L003Attorney Docket No.67522-701.601 The test article Test Compound – Extra Strength achieved >99.9% (>3 log10) reduction against the following test microorganisms by 10 minutes ± 30 seconds: Acinetobacter baumannii_UCLA_L001 Candida glabrata_UCLA_L008 Escherichia coli_UCLA_L006 Pseudomonas aeruginosa_UCLA_L002 Pseudomonas aeruginosa _UCLA_L009 Serratia marcescens_UCLA_L005 Staphylococcus aureus_UCLA_L004 Streptococcus pyogenes_UCLA_L007 The test article, Test Compound – Extra Strength achieved >99.0% (>2 log10) reduction against the following test microorganism by 10 minutes ± 30 seconds: Staphylococcus aureus_UCLA_L003 The test article Reference Product 1 – Polymyxin / Bacitracin (Polysporin) >99.9% (>3 log10) reduction against the following test microorganisms by 10 minutes ± 30 seconds: Acinetobacter baumannii_UCLA_L001 Escherichia coli_UCLA_L006 Pseudomonas aeruginosa _UCLA_L009 The test article Reference Product 1 – Polymyxin / Bacitracin (Polysporin) achieved >90.0% (>1 log10) reduction against the following test microorganisms by 10 minutes ± 30 seconds: Pseudomonas aeruginosa_UCLA_L002 Streptococcus pyogenes_UCLA_L007 The test article Reference Product 1 – Polymyxin / Bacitracin (Polysporin) achieved <90.0% (<1 log10) reduction against the following test microorganisms at all evaluated contact times: Candida glabrata_UCLA_L008 Serratia marcescens_UCLA_L005 Staphylococcus aureus_UCLA_L003 Staphylococcus aureus_UCLA_L004Attorney Docket No.67522-701.601 The test article Reference Product 2- Bactroban (Mupirocin) achieved >99.9% (>3 log10) reduction against the following test microorganism by 5 minutes ± 10 seconds: Pseudomonas aeruginosa_UCLA_L002 The test article Reference Product 2- Bactroban (Mupirocin) achieved >90.0% (>1 log10) reduction against the following test microorganisms at 5 minutes ± 10 seconds: Acinetobacter baumannii_UCLA_L001 Escherichia coli_UCLA_L006 Pseudomonas aeruginosa _UCLA_L009 Staphylococcus aureus_UCLA_L004 The test article Reference Product 2- Bactroban (Mupirocin) (achieved <90.0% (<1 log10) reduction against the following test microorganisms at all evaluated contact times: Candida glabrata_UCLA_L008 Serratia marcescens_UCLA_L005 Staphylococcus aureus_UCLA_L003 Streptococcus pyogenes_UCLA_L007 The test article Reference Product 3- Silvadene achieved >99.9% (>3 log10) reduction against the following test microorganism at 10 minutes ± 30 seconds: Staphylococcus aureus_UCLA_L003 The test article Reference Product 3- Silvadene achieved <90.0% (<1 log10) reduction against the following test microorganisms at all evaluated contact times: Acinetobacter baumannii_UCLA_L001 Candida glabrata_UCLA_L008 Escherichia coli_UCLA_L006 Pseudomonas aeruginosa_UCLA_L002 Pseudomonas aeruginosa _UCLA_L009 Serratia marcescens_UCLA_L005 Staphylococcus aureus_UCLA_L004 Streptococcus pyogenes_UCLA_L007

[0104] These results demonstrate efficacy of a Test Compound – Regular and Test Compound – Extra Strength as antimicrobial agents compared to reference antimicrobial formulations. Test Compound – Regular and Test Compound – Extra Strength are octenidine-Attorney Docket No.67522-701.601 based formulations described herein. Example 2: Use of a petroleum-based antimicrobial ointment with octenidine as an active agent for dressing and management of wounds

[0105] In this example, a petroleum-based ointment described herein containing octenidine as an active agent is used for dressing and management of wounds. The petroleum-based ointment is formulated for topical use and is intended to maintain a moist wound environment that is conducive to healing. The petroleum-based ointment is odorless and formulated with a concentration of octenidine sufficient to prevent microbial colonization within the dressing for wound care.

[0106] Dressing and management of wounds in a subject needing treatment such as with first and second degree burns, venous stasis ulcers, diabetic ulcers, partial and full thickness wounds, donor sites, post-surgical incisions, trauma wounds, or abrasions, or any combination thereof are selected for use of the petroleum-based antimicrobial topical ointment. This petroleum-based antimicrobial topical ointment may be used during wound dressing changes to soften encrusted wound dressings. Direction of care using the petroleum-based antimicrobial topical ointment may be under the management of a healthcare professional and determined by a prescription for use of the OCT-containing petroleum-based antimicrobial topical ointment.

[0107] In an instance of this example, the OCT-containing petroleum-based antimicrobial topical ointment may be distributed to a subject in need of treatment for over-the-counter (OTC) use. For OTC indication and usage, the OCT-containing petroleum-based antimicrobial topical ointment is indicated for management of superficial wounds such as minor cuts, minor scrapes, minor irritations, minor abrasions, minor blisters, 1st degree burns including sunburns, minor skin irritations following post non-ablative laser therapy procedures, microdermabrasion therapy or superficial chemical peels. The OCT-containing petroleum-based antimicrobial topical ointment may also be used for relief of itch, pain and burning from minor skin irritations, lacerations, abrasions and minor burns.

[0108] In this example, a wound dressing can be provided to a subject in need thereof. The wound dressing comprises an OCT-containing antimicrobial topical ointment described herein as part of the dressing to be applied to a subject in need thereof by prescription under the management of a healthcare professional. Indications for use: Under the management of a healthcare professional, the wound dressing is intended for the management of first and second degree burns, venous stasis ulcers, diabetic ulcers, partial and full thickness wounds, donor sites, post-surgical incisions, trauma wounds, and abrasions. It can be used during wound dressing changes to soften encrusted wound dressings. The wound dressing may be non-sterile, has noAttorney Docket No.67522-701.601 pre-determined shelf life, and under the management of a healthcare professional is intended for use of a duration of 72 hours or less. Wound dresses for similar use that the ones listed in this example may containing petrolatum, water, polyhexamethylene biguanide (PHMB) as an antimicrobial agent, and benzalkonium chloride (BZK) an as additional broad-spectrum antimicrobial agent against bacteria, fungi, and viruses. PHMB can bind to a bacterial phospholipid outer member and disrupt the integrity of the membrane. This disruption causes the bacterial cytoplasm to leak out thereby acting as an antimicrobial agent. BZK acts as a cationic surfactant, and similarly to PHMB, can disrupt the integrity of bacterial membranes causing the bacterial cytoplasm to leak out thereby acting as an antimicrobial agent. In this example, a wound dressing containing OCT as a preservative instead of PHMB and BZK is indicated for dressing and management of wounds such as first and second degree burns, venous stasis ulcers, diabetic ulcers, partial and full thickness wounds, donor sites, post-surgical incisions, trauma wounds, and abrasions. It can be used during wound dressing changes to soften encrusted wound dressings. In this example, the OCT-containing wound dressing device has the same indications for use and mechanism of action as the wound dressing device containing petrolatum, water, polyhexamethylene biguanide (PHMB) as an antimicrobial agent, and benzalkonium chloride (BZK). The primary difference between the OCT-containing wound dressing and the wound dressing using PHMB and BZK as preservatives are the technical characteristics in that the subject device also includes Octenidine dihydrochloride as a preservative rather than benzalkonium chloride and polyhexamethylene biguanide. The mechanism of action is to maintain a moist wound environment. This moist environment is conducive to healing. In an example, the wound dressing device may be constructed similarly to PolyPlex Wound Dressing, however, instead of having PHMB and BZK to prevent microbial colonization within the dressing, an active preservative used in the dressing is OCT, at a concentration of 0.1% or less. This OCT-containing wound dressing device is odorless, non-cytotoxic to cells of the subject, non-sensitizing, and non-irritating. The technological and formulation differences between the PolyPlex Wound Dressing and the OCT-containing wound dressing do not raise concerns regarding the safety and efficacy of the OCT-containing wound dressing. The OCT-containing wound dressing is applied to the subject as needed under the direction of a healthcare provider until the wound or wound sites show sufficient signs of healing.

[0109] Octenidine has demonstrated in vivo safety for wound care with no adverse effects on wound healing in a porcine model at concentrations up to 0.1% (Stahl J et al., The effect of a combination of 0.1% octenidine dihydrochloride and 2% 2-phenoxyethanol (octenisept) on wound healing in pigs in vivo and its in vitro percutaneous permeation through intact and barrier disrupted porcine skin. Int Wound J.2010 Feb;7(1):62-9.). Methods of use of octenidineAttorney Docket No.67522-701.601 dihydrochloride compositions described in Stahl J et al. for the treatment and prevention of infection are herein incorporated by reference.

[0110] In a further example of a wound dressing comprising an OCT-containing antimicrobial topical ointment described herein as part of the dressing to be applied to a subject in need thereof by prescription under the management of a healthcare professional, the formulation applied to or incorporated into the wound dressing includes Manuka honey to help maintain a moist environment. The concentration of Manuka honey in the OCT-containing formulation applied to or incorporated into the wound dressing is about 0.01%. This Manuka honey wound dressing may be applied to a subject in need thereof by prescription under the management of a healthcare professional. The wound dressing containing the Manuka Honey provides a moist environment conducive to wound healing and are indicated for light to moderately exuding wounds. The wound dressing for use under the supervision of a healthcare profession, provides a moist environment conducive to wound healing and is indicated for light to moderate exuding wounds. The Wound Dressings are intended for the management of the following: - diabetic foot ulcers - leg ulcers (venous stasis ulcers, arterial ulcers and leg ulcers of mixed etiology) - pressure ulcers / sores (partial and full thickness) - 1stand 2nddegree partial thickness burns - donor sites, and traumatic and surgical wounds. The mechanism of action is to maintain a moist environment conducive to wound healing. The OCT-containing wound dressing also containing Manuka Honey operate similarly to Derma Sciences Medihoney Gel Dressings. Manuka Honey is a primary ingredient in Derma Sciences Medihoney Gel Dressings, meaning that the technological and formulation differences between the Derma Sciences Medihoney Gel Dressings and the OCT-containing wound dressing do not raise concerns regarding the safety and efficacy of the OCT-containing wound dressing. The OCT-containing wound dressing is applied to the subject as needed under the direction of a healthcare provider until the wound or wound sites show sufficient signs of healing.

[0111] In a further example of a wound dressing comprising an OCT-containing antimicrobial topical ointment described herein as part of the dressing to be applied to a subject in need thereof obtained OTC and used by the subject, the formulation applied to or incorporated into the wound dressing includes Manuka honey to help maintain a moist environment. The concentration of Manuka honey in the OCT-containing formulation applied to or incorporated into the wound dressing is about 0.01%. This Manuka honey wound dressing may be applied to a subject in need thereof by prescription without the management of a healthcare professional. TheAttorney Docket No.67522-701.601 wound dressing containing the Manuka Honey provides a moist environment conducive to wound healing and are indicated for light to moderately exuding wounds. The wound dressing for use under the supervision of a healthcare profession, provides a moist environment conducive to wound healing and is indicated for light to moderate exuding wounds. The Wound Dressings are intended for the management of the following indications: Minor abrasions - lacerations - minor cuts - minor scalds and burns. The mechanism of action is to maintain a moist environment conducive to wound healing. The OCT-containing wound dressing also containing Manuka Honey operate similarly to Derma Sciences Medihoney Gel Dressings and may be distributed to the subject OTC for use by the subject without the need for prescription for use under the management of a healthcare professional. Manuka Honey is a primary ingredient in Derma Sciences Medihoney Gel Dressings, meaning that the technological and formulation differences between the Derma Sciences Medihoney Gel Dressings and the OCT-containing wound dressing do not raise concerns regarding the safety and efficacy of the OCT-containing wound dressing. The OCT- containing wound dressing is applied to the subject as needed under the direction of a healthcare provider until the wound or wound sites show sufficient signs of healing. Example 3: Use of a petroleum-based antimicrobial ointment with octenidine as an active agent for wound healing.

[0112] In this example, a petroleum-based ointment described herein containing octenidine as an active agent is used for topical application to a subject in need thereof to prevent and treating wound infection and aid in the management and heading of wounds in the subject.

[0113] The petroleum-based OCT containing ointment is formulated to topical application to the subject. The ointment is obtained by the subject without the need for prescription for use under the management of a healthcare professional. The mechanism of action of the ointment is to maintain a moist wound environment.

[0114] OTC indications and usage: petroleum-based OCT-containing topical ointment is indicated for management of superficial wounds such as minor cuts, minor scrapes, minor irritations, minor abrasions, minor blisters, 1st degree burns including sunburns, minor skin irritations following post non-ablative laser therapy procedures, microdermabrasion therapy or superficial chemical peels. The ointment may also be used for relief of itch, pain and burning from minor skin irritations, lacerations, abrasions and minor burns.

[0115] Additional OTC indications and usage: petroleum-based OCT-containing topicalAttorney Docket No.67522-701.601 ointment is indicated as a wound dressing for: • Superficial Wounds • Minor Abrasions • Leg Ulcers • Donor Sites • 1st and 2nd Degree Burns, including Sunburns • Radiation Dermatitis • For dermal ulcers, including full thickness wounds and pressure sores, consultation of a physician is recommended.

[0116] The petroleum-based ointment is formulated for topical use and is intended to maintain a moist wound environment that is conducive to healing. The petroleum-based ointment is odorless and formulated with a concentration of octenidine sufficient to prevent microbial colonization within the wounds or wound sites. The ointment functions for a similar use as BIAFINE Topical Cream, an oil in water emulsion. The mechanism of action of both the petroleum-based OCT containing ointment and BIAFINE Topical Cream are to maintain a moist wound environment. The petroleum-based OCT containing ointment differs from BIAFINE Topical Cream in formulation, the former being petroleum-based and the latter being an oil in water emulsion. A similar petroleum-based product (Aquaphor) to the petroleum-based OCT containing ointment is routinely used for the stated over the counter indications without issues. The important aspect is the maintenance of a moist environment. Example 4: Biocompatibility testing of a petroleum-based antimicrobial ointment with octenidine as an active agent.

[0117] In this example, a petroleum-based ointment described herein containing octenidine as an active agent is used for biocompatibility testing.

[0118] The document ISO 10993-1:2018; Biological evaluation of medical devices; Part 1: Evaluation and testing within a risk management process describes: • general principles governing the biological evaluation of medical devices within a risk management process; • the general categorization of medical devices based on the nature and duration of their contact with the body; • the evaluation of existing relevant data from all sources; • the identification of gaps in the available data set on the basis of a risk analysis; • the identification of additional data sets necessary to analyze the biologicalAttorney Docket No.67522-701.601 safety of the medical device; • the assessment of the biological safety of the medical device. This document applies to evaluation of materials and medical devices that are expected to have direct or indirect contact with: • the patient's body during intended use; • the user's body, if the medical device is intended for protection (e.g., surgical gloves, masks and others). This document is applicable to biological evaluation of all types of medical devices including active, non-active, implantable and non-implantable medical devices. This document also gives guidelines for the assessment of biological hazards arising from: • risks, such as changes to the medical device over time, as a part of the overall biological safety assessment.

[0119] ISO 10993-1:2018; Biological evaluation of medical devices; Part 1: Evaluation and testing within a risk management process is hereby incorporated by reference for methods describing biocompatibility testing.

[0120] Preclinical testing of petroleum-based ointment described herein containing octenidine as an active agent is undertaking to assess: -Cytotoxicity ISO 10993-5: 2009 -Sensitization ISO 10993-10:2010 -Intracutaneous reactivity ISO 10993-10:2010 -Implantation ISO 10993-6:2016 -Acute Systemic Toxicity ISO 10993-11:2017 -Pyrogenicity ISO 10993-11:2017

[0121] These tests provide a comprehensive assessment of biocompatibility of petroleum- based OCT pharmaceutical compositions described herein when used as indicated. Example 5: Manufacturing of a petroleum-based antimicrobial ointment with octenidine as an active agent.

[0122] In this example, a petroleum-based ointment described herein containing octenidine as an active agent is manufactured.Attorney Docket No.67522-701.601

[0123] Part A:

[0124] Premix Part A until clear, heat to 40-50°C if needed.

[0125] Part B:

[0126] Heat Part B to 80-85°C in a separate vessel.

[0127] Cool part B below 40 C and add Part A to Part B with mixing.

[0128] Part C:

[0129] Add Part C to Part A-B with mixing. Store petroleum-based OCT ointment until ready for use in a subject.

[0130] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention.

[0131] All publications, patent applications, issued patents, and other documents referred to in this specification are herein incorporated by reference as if each individual publication, patent application, issued patent, or other document was specifically and individually indicated to beAttorney Docket No.67522-701.601 incorporated by reference in its entirety. Definitions that are contained in text incorporated by reference are excluded to the extent that they contradict definitions in this disclosure.

Claims

Attorney Docket No.67522-701.601 CLAIMS WHAT IS CLAIMED IS:

1. A pharmaceutical composition comprising: a. a bis(pyridine) antimicrobial agent, and b. petrolatum, wherein the petrolatum is present in the composition in an amount greater than 50% weight per weight (w / w); wherein the composition is formulated for topical application in a human subject.

2. The pharmaceutical composition of claim 1, wherein the bis(pyridine) antimicrobial agent is octenidine or one of its pharmaceutically acceptable salts.

3. The pharmaceutical composition of claim 1, wherein the bis(pyridine) antimicrobial agent is an octenidine-based compound.

4. The pharmaceutical composition of claim 3, wherein the octenidine-based compound comprises octenidine and an organic acid used for forming a pharmaceutically acceptable acid addition salt.

5. The pharmaceutical composition of claim 4, wherein the organic acid used for forming the pharmaceutically acceptable acid addition salt is selected from acetic acid, 2,2-dichloroacetic acid, acrylic acid, adipic acid, ascorbic acid, aspartic acid benzenesulfonic acid, benzoic acid, 4-acetamido-benzoic acid, camphoric acid, camphor-10-sulfonic acid, capric acid, caproic acid, caprylic acid, carbonic acid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethane sulfonic acid, 2-hydroxy-ethane sulfonic acid, formic acid, fumaric acid, galactaric acid, gallic acid, gentisic acid, glocolic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glutaric acid, 2-oxo-glutaric acid, glyceric acid, glycerophosphoric acid, glycolic acid, glyoxilic acid, hippuric acid, hydrochloric acid, isobutyric acid, isocitric acid, itaconic acid, lactic acid, lactobionic acid, lauric acid, maleic acid, malic acid, malonic acid, mandelic acid, methane sulfonic acid, naphthalene-1,5- disulfonic acid, naphthalene-2-sulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, octanoic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, phthalic acid, pimelic acid, pivalic acid, propanoic acid, propionic acid, pyroglutamic acid, pyruvic acid , salicyclic acid, 4-aminosalicyclic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, toluic acid, toluenesulfonic acid, undecylenic acid, and valeric acid.

6. The pharmaceutical composition of any one of claims 1-5, wherein the bis(pyridine) antimicrobial agent is octenidine dihydrochloride.

7. A pharmaceutical composition comprising: a. octenidine dihydrochloride, andAttorney Docket No.67522-701.601 b. petrolatum, wherein the petrolatum is present in the composition in an amount greater than 50% weight per weight (w / w); wherein the composition is formulated for topical application in a human subject.

8. The pharmaceutical composition of any one of claims 1-7, formulated for topical application to prevent, treat, or reduce a symptom of a disease of the human subject arising from an infection with a pathogenic microorganism.

9. The pharmaceutical composition of any one of claims 6-8, wherein the octenidine dihydrochloride is dissolved within a non-aqueous solvent.

10. The pharmaceutical composition of claim 9, wherein the non-aqueous solvent comprises a cosolvent.

11. The pharmaceutical composition of claim 9, wherein the solvent comprises ethanol, propylene glycol, glycerine, glycofurol, polyethylene glycol, or ethoxydiglycol.

12. The pharmaceutical composition of any one of claims 6-8, wherein the octenidine dihydrochloride is dissolved in a hydrophilic compound.

13. The pharmaceutical composition of claim 12, wherein the hydrophilic compound is ethoxydiglycol.

14. The pharmaceutical composition of any one of claims 8-13, wherein the pathogenic microorganism comprises a gram-negative bacterium.

15. The pharmaceutical composition of any one of claims 8-14, wherein the pathogenic microorganism comprises a gram-positive bacterium.

16. The pharmaceutical composition of any one of claims 8-15, wherein the pathogenic microorganism comprises an atypical bacterium.

17. The pharmaceutical composition of any one of claims 8-16, wherein the pathogenic microorganism comprises a fungus.

18. The pharmaceutical composition of any one of claims 1-17, wherein the pharmaceutical composition is formulated as an ointment.

19. The pharmaceutical composition of any one of claims 1-18, comprising white mineral oil.

20. The pharmaceutical composition of any one of claims 1-19, comprising ethoxydiglycol.

21. The pharmaceutical composition of any one of claims 1-20, comprising Butyrospermum Parkii Nut Extract.

22. The pharmaceutical composition of any one of claims 1-21, comprising Euphorbia Cerifera (Candelilla) Wax.

23. The pharmaceutical composition of any one of claims 1-22, comprising glycerin.

24. The pharmaceutical composition of any one of claims 1-23, comprising Avena Sativa (Oat) Seed Extract.Attorney Docket No.67522-701.601 25. The pharmaceutical composition of any one of claims 1-24, comprising honey.

26. The pharmaceutical composition of any one of claims 1-25, comprising tocopherol.

27. A pharmaceutical composition comprising: a. a bis(pyridine) antimicrobial agent, and b. a hydrophobic carrier suitable for topical application, wherein the hydrophobic carrier is present in the composition in an amount greater than 50% weight per weight (w / w); wherein the composition is formulated for topical application in a human subject.

28. The pharmaceutical composition of claim 27, wherein the bis(pyridine) antimicrobial agent comprises an octenidine-based compound.

29. The pharmaceutical composition of claim 27, wherein the bis(pyridine) antimicrobial agent comprises octenidine or one of its pharmaceutically acceptable salts.

30. The pharmaceutical composition of claim 27, wherein the bis(pyridine) antimicrobial agent comprises octenidine dihydrochloride.

31. The pharmaceutical composition of any one of claims 1-30, wherein the bis(pyridine) antimicrobial agent is dissolved within a non-aqueous solvent.

32. A pharmaceutical composition comprising: a. octenidine dihydrochloride, and b. a hydrophobic carrier suitable for topical application, wherein the hydrophobic carrier is present in the composition in an amount greater than 50% weight per weight (w / w); wherein the composition is formulated for topical application in a human subject.

33. A pharmaceutical composition comprising: a. a cationic antimicrobial membrane disrupting agent selected from octenidine or polyhexamethylene biguanide (PHMB), and b. a hydrophobic carrier suitable for topical application, wherein the hydrophobic carrier is present in the composition in an amount greater than 50% weight per weight (w / w); wherein the composition is formulated for topical application in a human subject.

34. The pharmaceutical composition of any one of claims 32 or 33, wherein the octenidine dihydrochloride is dissolved within a non-aqueous solvent.

35. The pharmaceutical composition of any one of claims 33 or 34, wherein the octenidine or PHMB is dissolved within a non-aqueous solvent.

36. The pharmaceutical composition of any one of claims 33-35, wherein the non-aqueous solvent comprises ethanol, propylene glycol, glycerine, glycofurol, polyethylene glycol, or ethoxydiglycol.

37. The pharmaceutical composition of any one of claims 27-36, wherein the pharmaceutical composition is formulated as an ointment.Attorney Docket No.67522-701.601 38. The pharmaceutical composition of any one of claims 27-37, wherein the hydrophobic carrier suitable for topical application comprises one or more humectants, emollients, solvents, thickeners, penetration enhancers, or buffering agents, or any combination thereof.

39. The pharmaceutical composition claim 38, wherein the one or more humectants comprise mineral oil, petrolatum, white petrolatum, isopropyl palmitate, ammonium alkginate, butylene glycol, corn syrup solids, cyclomethicone, dipropylene glycol, glycerin, polydextrose, propylene glycol, sodium hyaluronate, sodium lactate, sorbitol, tagatose, trehalose, triacetin, triethanolamine, xylitol, sorbitol, or any combination thereof.

40. The pharmaceutical composition of claim 38 or 39, wherein the one or more emollients comprise shea butter, cocoa butter, mineral oil, lanolin, lanolin alcohols, petrolatum, white petrolatum, paraffin, beeswax, squalene, coconut oil, jojoba oil, sesame oil, almond oil, canola oil, palm kernel oil, palm oil, safflower oil, soybean oil, sunflower oil, cetyl alcohol, cetyl palmitate, olive oil, oleyl alcohol, oleic acid, triethylhexanoin, cyclomethicone, dimethicone, sorbitol, xylitol, isopropyl palmitate, castor oil, carnauba wax, cetyl ester wax, emulsifying wax, microcrystalline wax, paraffin wax, white wax, yellow wax, polyethylene glycol, or a combination thereof.

41. The pharmaceutical composition of any one or claims 38-40, wherein the one or more solvents comprise propylene glycol, hexylene glycol, ethoxydiglycol, polyoxyethylene, polyoxypropylene, diethylene glycol monoethyl ether (DGME), glycerin, dimethyl sulfoxide (DMSO), or any combination thereof.

42. The pharmaceutical composition of any one or claims 38-41, wherein the one or more thickeners comprise agar, alginate, pectin, acacia, tragcanth, Karaya gum, guar gum, starch, cellulose, carbomer, bees wax, candelilla wax, carnauba wax, or any combination thereof.

43. The pharmaceutical composition of any one or claims 38-42, wherein the one or more penetration enhancers comprise micelles, phospholipids, propylene glycol, glycerin, ethanol, oleic acid, DMSO, isopropyl myristate, laurocapram, terpenes, urea, sodium lauryl sulfate, cetyl alcohol, stearyl alcohol, cyclodextrins, or any combination thereof.

44. The pharmaceutical composition of any one or claims 38-43, wherein the one or more buffering agents comprise sodium hydroxide, hydrochloric acid, sodium phosphate monobasic, sodium phosphate dibasic, sodium citrate, or a combination thereof.

45. The pharmaceutical composition of any one of claims 1-44, wherein the pharmaceutical composition has a pH of from about 4.0 to about 7.

0.

46. The pharmaceutical composition of any one of claims 1-45, wherein the pharmaceutical composition has a pH of about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, about 6.5, or about 7.0.Attorney Docket No.67522-701.601 47. The pharmaceutical composition of any one of claims 1-46, wherein the pharmaceutical composition comprises from about 0.01% to about 1.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof.

48. The pharmaceutical composition of any one of claims 1-47, wherein the pharmaceutical composition comprises about 0.01%, about 0.015%, about 0.02%, about 0.025%, about 0.03%, about 0.035%, about 0.04%, about 0.045%, about 0.05%, about 0.055%, about 0.06%, about 0.065%, about 0.07%, about 0.075%, about 0.08%, about 0.085%, about 0.09%, about 0.095%, about 0.10%, about 0.15%, about 0.20%, about 0.25%, about 0.30%, about 0.35%, about 0.40%, about 0.45%, about 0.50%, about 0.55%, about 0.60%, about 0.65%, about 0.70%, about 0.75%, about 0.80%, about 0.85%, about 0.90%, about 0.95%, or about 1.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof.

49. The pharmaceutical composition of any one of claims 1-48, wherein the pharmaceutical composition comprises about 0.10% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof.

50. The pharmaceutical composition of any one of claims 1-46, wherein the pharmaceutical composition comprises from about 1.0% to about 5.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof.

51. The pharmaceutical composition of any one of claims 1-46 or 50, wherein the pharmaceutical composition comprises about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.5%, about 1.6%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%,about 4.6%, about 4.7%, about 4.8%, about 4.9%, or about 5.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof.

52. The pharmaceutical composition of any one of claims 1-46 or 50-51, wherein the pharmaceutical composition comprises greater than about 1.0% (w / w) of octenidine dihydrochloride, or pharmaceutically acceptable salt thereof.

53. The pharmaceutical composition of any one of claims 1-52, wherein the pharmaceutical composition comprises from about 55%- 85% (w / w) of the hydrophobic carrier.

54. The pharmaceutical composition of any one of claims 1-53, wherein the pharmaceutical composition comprises at least about 55% (w / w) of the hydrophobic carrier.

55. The pharmaceutical composition of any one of claims 1-54, wherein the pharmaceutical composition comprises at least about 60% (w / w) of the hydrophobic carrier.Attorney Docket No.67522-701.601 56. The pharmaceutical composition of any one of claims 1-55, wherein the pharmaceutical composition comprises less than about 80% (w / w) of the hydrophobic carrier.

57. The pharmaceutical composition of any one of claims 1-52, wherein the pharmaceutical composition comprises from about 85% - 99% (w / w) of the hydrophobic carrier.

58. The pharmaceutical composition of any one of claims 1-52 or 57, wherein the pharmaceutical composition comprises greater than about 85% (w / w) of the hydrophobic carrier.

59. The pharmaceutical composition of any one of claims 1-58, wherein the pharmaceutical composition comprises: (i) from about 55.0% to about 85.0% (w / w) of one or more humectants; (ii) from about 10.0% to about 25.0% (w / w) of one or more emulsifiers; (iii) from about 0.0% to about 10.0% (w / w) of one or more emollients; (iv) from about 1.0% to about 10.0% (w / w) of one or more solvents; or (v) from about 0.0% to about 1.0% (w / w) of a buffering agent; or combination thereof.

60. The pharmaceutical composition of any one of claims 1-59, wherein the pharmaceutical composition remains stable at 25±2 °C / 60% relative humidity for 6 months.

61. The pharmaceutical composition of any one of claims 38-60, wherein the one or more humectants comprise white petrolatum.

62. The pharmaceutical composition of any one of claims 38-61, wherein the one or more emulsifiers comprise white mineral oil.

63. The pharmaceutical composition of any one of claims 38-62, wherein the one or more solvents comprise ethoxydiglycol.

64. The pharmaceutical composition of any one of claims 1-63, wherein the pharmaceutical composition is formulated as a low-viscosity ointment having a centipoise (cP) value of between about 5,000-30,000 cP when measured at about room temperature.

65. The pharmaceutical composition of any one of claims 1-63, wherein the pharmaceutical composition is formulated as a medium-viscosity ointment having a centipoise (cP) value of between about 30,000-70,000 cP when measured at about room temperature.

66. The pharmaceutical composition of any one of claims 1-63, wherein the pharmaceutical composition is formulated as a high-viscosity ointment having a centipoise (cP) value of between about 70,000-100,000 cP when measured at about room temperature.

67. A method of reducing or preventing infection in a subject, the method comprising administering to the subject the pharmaceutical composition of any one of claims 1-66 to the skin of the subject in need thereof; wherein the disease or condition is mediated by microbial infection.Attorney Docket No.67522-701.601 68. The method of claim 67, wherein the disease or condition is selected from first and second- degree burns, venous stasis ulcers, diabetic ulcers, partial and full thickness wounds, donor sites, post-surgical incisions, trauma wounds, and abrasions.

69. The method of claim 67 or 68, wherein the microbial infection is mediated gram-negative bacteria, gram-positive bacteria, atypical bacteria, or a fungus, or any combination thereof.

70. The method of any one of claims 67-69, wherein the pharmaceutical composition is administered to the skin of the subject in need thereof once every other day, once per day, twice per day, three times per day, four times per day, five times per day, or six times per day.

71. A method of treating or preventing a disease or condition in a subject in need thereof, the method comprising applying a viscous antimicrobial composition comprising an octenidine- based compound or octenidine dihydrochloride to one or more surgical implants, wherein the one or more surgical implants are coated with the viscous composition prior to surgical implant in the patient, thereby treating a microbial infection or preventing an extent of a microbial infection following a surgical implant procedure.

72. The method of claim 71, wherein the one or more surgical implants comprises organic material.

73. The method of claim 71, wherein the one or more surgical implants comprises non-organic material.

74. The method of claim 73, wherein the one or more surgical implants comprises an orthopedic device.

75. The method of claim 73, wherein the orthopedic device of composed of stainless steel, a cobalt-based alloy, titanium, or a titanium-based alloy.

76. The method of claim 72 or 73, wherein the one or more surgical implants is a surgical mesh.

77. The method of claim 76, wherein the surgical mesh is made of a synthetic polymer.

78. The method of claim 77, wherein the synthetic polymer is polypropylene, polyglycolic acid, or polycaprolactone.

79. The method of claim 76, wherein the surgical mesh is made of decellularized collagen.

80. The method of claim 73, wherein the one or more surgical implants is a birth control device.

81. The method of claim 73, wherein the one or more surgical implants is a cochlear implant device.

82. The method of claim 73, wherein the one or more surgical implants is a cochlear implant device comprises a cerebral spinal fluid (CSF) shunt system.

83. The method of claim 72, wherein the one or more surgical implants is a sponge comprising decellularized collagen.Attorney Docket No.67522-701.601 84. The method of claim 72, wherein the one or more surgical implants comprises a graft from a donor.

85. The method of claim 84, wherein the graft from the donor comprises a ligament or tendon.

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