COMPOSITIONS AND METHODS FOR TREATING DISEASES OF THE NAIL

• US 20180117028A1
• Filed: 12/20/2017
• Published: 05/03/2018
• Est. Priority Date: 01/03/2008
• Status: Active Grant

• Current Assignee: Bausch Health Ireland Limited (Bausch Health Cos., Inc.)
• Original Assignee: Dow Pharmaceutical Sciences Incorporated (Bausch Health Cos., Inc.)
• Inventors: Winckle, Gareth, Fieldson, Gregory T.
• Granted Patent: US 10,512,640 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• CPC Class Codes: A61K 8/34 Alcohols
• CPC Class Codes: A61K 8/496 Triazoles or their condensed derivatives, e.g. benzotriazoles
• CPC Class Codes: 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
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics

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, and which composition is effective in treating a disorder of the nail or nail bed.

Claims

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, a triazole antifungal agent, 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 is a volatile silicone.

3. The method of claim 1 wherein the vehicle is an alcohol.

4. The method of claim 1 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.

5. The method of claim 1 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.

6. 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.

7. The method of claim 6 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.

8. The method of claim 6 wherein the alcohol is ethanol.

9. The method of claim 6 wherein the non-volatile solvent comprises diisopropyl adipate and C12-15 alkyl lactate.

10. The method of claim 6 wherein the volatile silicone wetting agent is cyclomethicone.

11. The method of claim 1 wherein the disorder is onychomycosis.

12. The method of claim 1 wherein the composition does not comprise a polymeric film forming compound.

13. 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 ethanol, diisopropyl adipate, C12-15 alkyl lactate, cyclomethicone, and a triazole antifungal agent;

wherein the composition is formulated as a solution;

wherein the ethanol is present in the composition at a concentration of at least 50% w/w;

wherein the cyclomethicone is present in the composition at a concentration less than 25% w/w;

wherein the diisopropyl adipate and C12-15 alkyl lactate are present in the composition at a total concentration between 15 and 50% w/w; and

wherein the application of the composition is in an amount and for a time sufficient to ameliorate the symptoms of the onychomycosis.

14. The method of claim 13 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.

15. The method of claim 13 wherein the composition does not comprise a polymeric film forming compound.