# US 10,245,257 B2 · Anti-infective methods, compositions, and devices > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,245,257 B2 - Document ID: US10245257B2 - Status: Granted - Kind: B2 - Application number: 14/552,307 - Filed: 2014-11-24 - Published: 2015-05-28 - Granted: 2019-04-02 - Earliest claimed: 2013-11-22 - Assignees: Dow Pharmaceutical Sciences, Inc. - Applicants: Dow Pharmaceutical Sciences, Inc. - Inventors: Radhakrishnan Pillai; Gordon Dow - Web page: https://patentgrep.com/patent/US10245257B2 ## CPC - A61K 31/454: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone - A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)} - A61K 47/06: Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/12: Carboxylic acids; Salts or anhydrides thereof - A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters - A61K 47/18: Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids - A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids - A61P 17/00: Drugs for dermatological disorders - A61P 31/10: Antimycotics - Y10T 83/0443: By fluid application - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION ## Abstract The present invention provides methods for treating onychomycosis. In certain embodiments, the methods comprise comprising applying a pharmaceutically acceptable formulation containing 10% efinaconazole once a day for a treatment period of at least 36 weeks to the treatment area of an onychomycosis patient (a) without debriding the nail or nail-associated tissue initially or during the treatment period and/or (b) without removing the formulation from the treatment area during the treatment period. In certain embodiments, the formulation also comprises, water, cyclomethicone, diisopropyl adipate, alcohol, C12-15 alkyl lactate, butylated hydroxytoluene, citric acid anhydrous, and disodium edetate. ## Claims ### Claim 1 A method of treating onychomycosis comprising applying a pharmaceutically acceptable efinaconazole formulation once a day for a treatment period of at least 36 weeks to the treatment area of an onychomycosis patient (a) without debriding the nail or nail-associated tissue in the treatment area initially or during the treatment period and/or (b) without removing the formulation from the treatment area during the treatment period, wherein the efinaconazole formulation comprises 10% w/w efinaconazole, water, cyclomethicone, diisopropyl adipate, alcohol, C12-15 alkyl lactate, butylated hydroxytoluene, citric acid anhydrous, and disodium edetate, wherein the amounts of butylated hydroxytoluene and disodium edetate are sufficient to ensure the formulation is (i) colorless upon initial manufacturing of the formulation and (ii) colorless or pale yellow after storage for three weeks at a temperature of about 40° C., wherein the average amount of efinaconazole delivered to each cm2 of the treatment area is about 0.15 mg/cm2 to about 0.45 mg/cm2, and wherein applying the formulation results in a mean plasma Cmax in a population of at least 15 adult onychomycosis patients after 28 days of once daily treatment that is less than 0.8 ng/mL. ### Claim 2 (depends on 1) The method of claim 1, wherein the method is performed (a) without debriding the nail or nail-associated tissue initially or during the treatment period and (b) without removing the formulation from the treatment area during the treatment period. ### Claim 3 (depends on 1) The method of claim 1, wherein the method is performed without occluding or without partially occluding the nail or nail-associated tissue. ### Claim 4 (depends on 1) The method of claim 1, wherein the patient waits at least 10 minutes before administering the formulation if the treatment area was previously in contact with water. ### Claim 5 (depends on 1) The method of claim 1, wherein the method includes a step of cleaning the treatment area prior to administering the efinaconazole formulation. ### Claim 6 (depends on 1) The method of claim 1, wherein the patient cleans the treatment area prior to treatment and waits for at least 10 minutes before administering the formulation if the cleaning includes wetting the treatment area with water. ### Claim 7 (depends on 1) The method of claim 1, wherein the efinaconazole is the only active pharmaceutical ingredient in the formulation. ### Claim 8 (depends on 1) The method of claim 1, wherein the treatment period is 48 weeks. ### Claim 9 (depends on 1) The method of claim 1, wherein the method comprises cutting nails once every two weeks or more frequently. ### Claim 10 (depends on 1) The method of claim 1, wherein the method does not comprise cutting nails more often than every two weeks. ### Claim 11 (depends on 1) The method of claim 1, wherein the efinaconazole formulation is not administered in an occluded or semi-occluded manner. ### Claim 12 (depends on 1) The method of claim 1, wherein the method comprises uniformly spreading the efinaconazole formulation throughout the treatment area with an applicator. ### Claim 13 (depends on 1) The method of claim 1, wherein the method comprises administering the efinaconazole formulation from a container that is in fluid communication with an applicator, loading the applicator, and applying the efinaconazole with the applicator. ### Claim 14 (depends on 1) The method of claim 1, wherein performance of the method in a patient population results in a mycological cure rate of at least about 40%, a clinical efficacy rate of at least about 20%, a complete cure rate of at least about 10%, or a combination of any or all thereof. ### Claim 15 A method of treating onychomycosis comprising applying a pharmaceutically acceptable efinaconazole formulation once a day for a treatment period of at least 36 weeks to the treatment area of an onychomycosis patient (a) without debriding the nail or nail-associated tissue in the treatment area initially or during the treatment period, (b) without removing the formulation from the treatment area during the treatment period, and (c) without occluding the treatment area; wherein the efinaconazole formulation comprises 10% w/w efinaconazole, water, cyclomethicone, diisopropyl adipate, alcohol, C12-15 alkyl lactate, butylated hydroxytoluene, citric acid anhydrous, and disodium edetate, wherein the amounts of butylated hydroxytoluene and disodium edetate are sufficient to ensure the formulation is (i) colorless upon initial manufacturing of the formulation and (ii) colorless or pale yellow after storage for three weeks at a temperature of about 40° C., wherein the average amount of efinaconazole delivered to each cm2 of the treatment area is about 0.15 mg/cm2 to about 0.45 mg/cm2, and wherein applying the formulation results in a mean plasma Cmax in a population of at least 15 adult onychomycosis patients after 28 days of once daily treatment that is less than 0.8 ng/mL. ### Claim 16 (depends on 1) The method of claim 1, wherein the amount of butylated hydroxytoluene in the formulation ranges from 0.05% (w/w) to 2% (w/w). ### Claim 17 (depends on 1) The method of claim 1, wherein the amount of disodium edetate in the formulation ranges from 0.0001% (w/w) to 0.0005% (w/w). ### Claim 18 (depends on 1) The method of claim 1, wherein the amount of citric acid in the formulation ranges from 0.02% (w/w) to 0.5% (w/w).