Compositions and methods for treating diseases of the nail

Abstract

Methods and compositions for treating disorders of the nail and nail bed. Such compositions contain a vehicle in which all components of the composition are dissolved, suspended, dispersed, or emulsified, a non-volatile solvent, a wetting agent, and a pharmaceutically active ingredient that is soluble in the non-volatile solvent and/or a mixture of the vehicle and the non-volatile solvent, which composition has a surface tension of 40 dynes/cm or less and has continuing spreadability, and which composition is effective in treating a disorder of the nail or nail bed.

1 - 63 . (canceled) 
     
     
         64 . A method for the treatment of onychomycosis comprising topically applying to the surface of the nail of an individual suffering from onychomycosis a pharmaceutical composition comprising a vehicle that is volatile and/or that rapidly penetrates a nail following application onto the surface of the nail, an antifungal active pharmaceutical ingredient, and a wetting agent, and wherein the application of the composition is in an amount and for a time sufficient to ameliorate the signs and symptoms of the onychomycosis, wherein the surface tension of the composition is 30 dynes/cm or less and wherein the composition, when applied to the surface of a nail, does not form a solid film. 
     
     
         65 . The method of  claim 64 , wherein the wetting agent is a volatile silicone. 
     
     
         66 . The method of  claim 64 , wherein the vehicle is an alcohol. 
     
     
         67 . The method of  claim 64 , wherein the pharmaceutical formulation further comprises a non-polar non-volatile solvent. 
     
     
         68 . The method of  claim 67 , wherein the non-volatile solvent is one or more esters of the formula RCO—OR′, wherein R and R′ may be identical or different and each of R and R′ represents a linear or branched chain of an alkyl, alkenyl, alkoxycarbonylalkyl, or alkoxycarbonyloxyalkyl radical having from 1 to 25 carbon atoms. 
     
     
         69 . The method of  claim 64 , wherein the antifungal active pharmaceutical ingredient is a triazole compound. 
     
     
         70 . The method of  claim 69 , wherein the triazole active pharmaceutical ingredient is (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidine-1-yl)-1-(1H-1,2,4-triazole-1-yl)butane-2-ol. 
     
     
         71 . The method of  claim 64 , wherein the antifungal active pharmaceutical ingredient selected from the group consisting of miconazole, ketoconazole, clotrimazole, econazole, bifonazole, butoconazole, fenticonazole, isoconazole, oxiconazole, sertaconazole, suconazole, tioconazole, fluconazole, itraconazole, ravuconazole, posaconazole, voriconazole, terconazole, and (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidine-1-yl)-1-(1H-1,2,4-triazole-1-yl)butane-2-ol 
     
     
         72 . The method of  claim 64 , wherein the pharmaceutical composition comprises an alcohol vehicle, a non-volatile solvent comprising one or more esters of the formula RCO—OR′, wherein R and R′ may be identical or different and each of R and R′ represents a linear or branched chain of an alkyl, alkenyl, alkoxycarbonylalkyl, or alkoxycarbonyloxyalkyl radical having from 1 to 25 carbon atoms, and a volatile silicone wetting agent. 
     
     
         73 . The method of  claim 64 , wherein the composition does not comprise a polymeric film forming compound. 
     
     
         74 . A pharmaceutical composition for the topical treatment of a disorder of the nail or nail bed comprising a volatile alcohol, a volatile silicone, an anti-oxidant, one or more esters of the formula RCO—OR′, wherein R and R′ may be identical or different and each of R and R′ represents a linear or branched chain of an alkyl, alkenyl, alkoxycarbonylalkyl, or alkoxycarbonyloxyalkyl radical having from 1 to 25 carbon atoms, and wherein the chain of R′ is at least 5 carbons, and a triazole antifungal agent, wherein the volatile silicone is present in the composition at a concentration less than 25% w/w, wherein the composition does not form a solid film when topically applied to the surface of a nail, and wherein the surface tension of the composition is 40 dynes/cm or less. 
     
     
         75 . The pharmaceutical composition of  claim 74 , wherein the ester is a combination of diisopropyl adipate and C12-15 alkyl lactate. 
     
     
         76 . The pharmaceutical composition of  claim 74 , wherein the ester is a combination of diisopropyl adipate and myristyl lactate. 
     
     
         77 . The pharmaceutical composition of  claim 74 , wherein the triazole antifungal agent is (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidine-1-yl)-1-(1H-1,2,4-triazole-1-yl)butane-2-ol. 
     
     
         78 . The pharmaceutical composition of  claim 74 , wherein the alcohol is ethanol. 
     
     
         79 . The pharmaceutical composition of  claim 74 , wherein the volatile silicone is a cyclic silicone. 
     
     
         80 . The pharmaceutical composition of  claim 79 , wherein the cyclic silicone is a cyclomethicone. 
     
     
         81 . The pharmaceutical composition of  claim 74 , wherein the concentration of volatile silicone is less than 20%. 
     
     
         82 . The pharmaceutical composition of  claim 74 , wherein the concentration of volatile silicone is less than 15%. 
     
     
         83 . The pharmaceutical composition of  claim 74 , which comprises alcohol, cyclomethicone, diisopropyl adipate, either or both of C12-15 alkyl lactate and isopropyl myristate, an antioxidant, and a triazole antifungal agent.