Compositions and methods for treating diseases of the nail

• US 8,039,494 B1
• Filed: 07/08/2010
• Issued: 10/18/2011
• Est. Priority Date: 07/08/2010
• Status: Active Grant

• Current Assignee: Bausch Health Ireland Limited (Bausch Health Cos., Inc.)
• Original Assignee: Dow Pharmaceutical Sciences Incorporated (Bausch Health Cos., Inc.)
• Inventors: Fieldson, Gregory T., Winckle, Gareth
• Primary Examiner(s): Padmanabhan; Sreeni
• Assistant Examiner(s): Ivanova; Svetlana M
• Application Number:
  US12/803,848
• Time in Patent Office: 467 Days
• Field of Search: None
• US Class Current: 514/359
• CPC Class Codes: A01N 2300/00 Combinations or mixtures of active ingredients covered by classes A01N27/00 - A01N65/48 with other active or formulation relevant ingredients, e.g. specific carrier materials or surfactants, covered by classes A01N25/00 - A01N65/48
• CPC Class Codes: A01N 25/30 characterised by the surfactants
• CPC Class Codes: A01N 43/653 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
• CPC Class Codes: A61K 31/4192 1,2,3-Triazoles
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• 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 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• 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 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/0012 Galenical forms characterised by the site of application
• 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: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• 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, 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.

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 consisting essentially of a vehicle that is volatile and/or that rapidly penetrates a nail following application onto the surface of the nail, a triazole antifungal active pharmaceutical ingredient (API), and a wetting agent, and optionally a non-volatile solvent that is dissolved, suspended, dispersed, or emulsified within the vehicle, and wherein the application of the composition is in an amount and for a time sufficient to ameliorate the signs and symptoms of the disorder, wherein the surface tension of the composition is 40 dynes/cm or less and wherein the composition, when applied to the surface of a nail, does not form a solid film.

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 pharmaceutical formulation contains a non-polar non-volatile solvent.

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 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.

8. The method of claim 1 wherein the pharmaceutical composition consists essentially of 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.

9. The method of claim 8 wherein the triazole compound is (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidine-1-yl)-1-(1′

-1-1,2,4-triazole-1-yl)butane-2-ol.

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

11. The method of claim 8 wherein the non-volatile solvent comprises diisopropyl adipate and C12-15 alkyl lactate.

12. The method of claim 8 wherein the volatile silicone wetting agent is cyclomethicone.

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

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

15. The method of claim 1 wherein the composition increases in spread on the surface of a clean dry glass slide throughout the six-minute period immediately following application of the composition to the surface of the slide.

16. The method of claim 15 wherein the spread of the composition on the surface of the slide encompasses an area of greater than 11.0 cm within 10 minutes following application of 100 microliters of the composition to the surface of the slide.

17. The method of claim 1 wherein the surface tension is 35 dynes/cm or less.

18. The method of claim 17 wherein the surface tension is 30 dynes/cm or less.

19. The method of claim 18 wherein the surface tension is 25 dynes/cm or less.