Compositions and methods for treating diseases of the nail
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, and which composition is effective in treating a disorder of the nail or nail bed.
1 . A method for the treatment of a disorder of the nail or nail bed comprising topically applying to the surface of the nail of an individual suffering from said disorder a pharmaceutical composition comprising a vehicle that is volatile and/or that rapidly penetrates a nail following the application onto the surface of the nail, a non-volatile solvent that is dissolved, suspended, dispersed, or emulsified within the vehicle, an active pharmaceutical ingredient (API) that is soluble in the non-volatile solvent or in a mixture of the non-volatile solvent and the vehicle, and a wetting agent, and wherein the application of the composition is in an amount and for a time sufficient to ameliorate the symptoms of the disorder.
2 . The method of claim 1 wherein the wetting agent and the vehicle are the same compound.
3 . The method of claim 1 wherein the wetting agent is a volatile silicone.
4 . The method of claim 1 wherein the vehicle is an alcohol.
5 . The method of claim 1 wherein the non-volatile solvent is non-polar.
6 . The method of claim 5 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.
7 . The method of claim 1 wherein the API is an antifungal agent.
8 . The method of claim 6 wherein the antifungal agent is a triazole compound.
9 . The method of claim 8 wherein the triazole compound is (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidine-1-yl)-1-(1H-1,2,4-triazole-1-yl)butane-2-ol.
10 . The method of claim 1 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, and wherein the composition does not form a film upon application to the nail.
11 . The method of claim 10 wherein the pharmaceutical formulation further comprises a hydrophobic API.
12 . The method of claim 11 wherein the API is an antifungal agent.
13 . The method of claim 12 wherein the antifungal agent is a triazole compound.
14 . The method of claim 13 wherein the triazole compound is (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidine-1-yl)-1-(1H-1,2,4-triazole-1-yl)butane-2-ol.
15 . The method of claim 10 wherein the alcohol is ethanol.
16 . The method of claim 10 wherein the non-volatile solvent comprises diisopropyl adipate and C12-15 alkyl lactate.
17 . The method of claim 10 wherein the volatile silicone wetting agent is cyclomethicone.
18 . The method of claim 1 wherein the disorder is onychomycosis.
19 . The method of claim 1 wherein the composition does not comprise a polymeric film forming compound.
20 . A pharmaceutical composition for the topical treatment of a disorder of the nail or nail bed comprising 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 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 film when topically applied to the surface of a nail.
21 . The pharmaceutical composition of claim 20 wherein the ester is a combination of diisopropyl adipate and C12-15 alkyl lactate.
22 . The pharmaceutical composition of claim 20 wherein the ester is a combination of diisopropyl adipate and myristyl lactate.
23 . The pharmaceutical composition of claim 20 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.
24 . The pharmaceutical composition of claim 20 wherein the alcohol is ethanol.
25 . The pharmaceutical composition of claim 20 wherein the volatile silicone is a cyclic silicone.
26 . The pharmaceutical composition of claim 25 wherein the cyclic silicone is a cyclomethicone.
27 . The pharmaceutical composition of claim 20 wherein the concentration of volatile silicone is less than 20%.
28 . The pharmaceutical composition of claim 20 wherein the concentration of volatile silicone is less than 15%.
29 . The pharmaceutical composition of claim 20 that comprises alcohol, cyclomethicone, diisopropyl adipate, either or both of C12-15 alkyl lactate and isopropyl myristate, an antioxidant, and a triazole antifungal agent.
30 . The pharmaceutical composition of claim 29 that comprises the following components in the following ranges of concentrations % w/w:
a. alcohol—10% to 80%
b. cyclomethicone—0.01% to less than 25%
c. diisopropyl adipate plus either or both of C12-15 alkyl lactate and isopropyl myristate—5% to 90%
d. antioxidant—0.001% to 0.50%
e. triazole antifungal agent—0.0001% to 30%.
31 . The pharmaceutical composition of claim 30 that comprises:
a. alchohol—50% to 70%,
b. cyclomethicone—10% to 15%
c. diisopropyl adipate—8% to 15%
d. either or both of C12-15 alkyl lactate and isopropyl myristate—8% to 15%
e. antioxidant—0.001% to 0.50%
f. triazole antifungal agent—2% to 15%.
32 . The pharmaceutical composition of claim 29 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.
33 . A pharmaceutical composition for the topical treatment of a disorder of the nail or nail bed comprising 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 a triazole antifungal agent, wherein the ratio of alcohol to volatile silicone in the composition % w/w is at least 2:3, wherein the composition does not form a film when topically applied to the surface of a nail.
34 . The pharmaceutical composition of claim 33 wherein the ester is a combination of diisopropyl adipate and C12-15 alkyl lactate.
35 . The pharmaceutical composition of claim 33 wherein the ester is a combination of diisopropyl adipate and myristyl lactate.
36 . The pharmaceutical composition of claim 33 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.
37 . The pharmaceutical composition of claim 33 wherein the alcohol is ethanol.
38 . The pharmaceutical composition of claim 33 wherein the volatile silicone is a cyclic silicone.
39 . The pharmaceutical composition of claim 38 wherein the cyclic silicone is a cyclomethicone.
40 . The pharmaceutical composition of claim 33 wherein the ratio of alcohol to volatile silicone is at least 1:1.
41 . The pharmaceutical composition of claim 33 wherein the ratio of alcohol to volatile silicone is at least 2:1.
42 . The pharmaceutical composition of claim 33 wherein the ratio of alcohol to volatile silicone is at least 3:1.
43 . The pharmaceutical composition of claim 33 that comprises alcohol, cyclomethicone, diisopropyl adipate, either or both of C12-15 alkyl lactate and isopropyl myristate, an antioxidant, and a triazole antifungal agent.
44 . The pharmaceutical composition of claim 43 that comprises the following components in the following ranges of concentrations % w/w:
a. alcohol—10% to 80%
b. cyclomethicone—0.01% to less than 25%
c. diisopropyl adipate plus either or both of C12-15 alkyl lactate and isopropyl myristate—5% to 90%
d. antioxidant—0.001% to 0.50%
e. triazole antifungal agent—0.0001% to 30%.
45 . The pharmaceutical composition of claim 44 that comprises:
a. alcohol—50% to 70%,
b. cyclomethicone—10% to 15%
c. diisopropyl adipate—8% to 15%
d. either or both of C12-15 alkyl lactate and isopropyl myristate—8% to 15%
e. antioxidant—0.001% to 0.50%
f. triazole antifungal agent—2% to 15%.
46 . The pharmaceutical composition of claim 43 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.
47 . The pharmaceutical composition of claim 20 that is free of polymeric film forming compounds.
48 . The pharmaceutical composition of claim 33 that is free of polymeric film forming compounds.