Foamable compositions, kits and methods for hyperhidrosis

• US 8,119,109 B2
• Filed: 03/13/2007
• Issued: 02/21/2012
• Est. Priority Date: 10/25/2002
• Status: Active Grant

• Current Assignee: VYNE Therapeutics, Inc.
• Original Assignee: Foamix Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Tamarkin, Dov, Eini, Meir, Zlatkis, Ella
• Primary Examiner(s): ALSTRUM ACEVEDO, JAMES HENRY
• Application Number:
  US11/717,897
• Publication Number:
  US 20070253911A1
• Time in Patent Office: 1,806 Days
• Field of Search: 424/65, 424/66, 424/67, 424/68, 424/401, 424/682
• US Class Current: 424/65
• CPC Class Codes: A01N 25/16 Foams
• CPC Class Codes: A61K 8/046 Aerosols; Foams
• CPC Class Codes: A61K 8/062 Oil-in-water emulsions
• CPC Class Codes: A61K 8/31 Hydrocarbons
• 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 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61K 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61Q 15/00 Anti-perspirants or body deodorants deodorisation of air A61L9/00
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin

Abstract

The composition of the present invention is geared towards treating hyperhidrosis or any condition involving and/or promoting excessive sweating, typically involving the whole body, include hyperthyroidism or similar endocrine disorders; endocrine treatment for prostatic cancer or other types of malignant disorder; severe psychiatric disorders; obesity and menopause. The foamable composition of the present invention is suitable for treating palmar hyperhidrosis; axillary hyperhidrosis; plantar hyperhidrosis; hyperhidrosis of the trunk and/or the thighs; and facial hyperhidrosis; and any combination of them consisting of a therapeutic foamable composition including: an active agent, suitable for the treatment or prevention of hyperhidrosis.

Claims

1. A method of treating a disorder of the skin, a body cavity or mucosal surface, wherein the disorder involves excessive sweating as one of its symptoms, comprising:

a) dispensing a foamable composition comprising a propellant and less than 5% short chain alcohols, having up to 5 carbon atoms in their carbon chain skeleton and one hydroxyl group, wherein the composition is stored in an aerosol container and upon dispensing the foamable composition forms a thermally stable breakable foam, the breakable foam composition comprising;

i. an active agent, suitable for the treatment of hyperhidrosis;

ii. about 2% to about 50% by weight of at least one carrier selected from the group consisting of a hydrophobic organic carrier, a solvent, an emollient and any mixture thereof;

iii. about 0.1% to about 5% by weight of a surface-active agent;

iv. about 0.01% to about 5% by weight of a polymeric agent selected from the group consisting of a bioadhesive agent, a gelling agent, a film forming agent and a phase change agent; and

v. water,

b) administering the resulting breakable foam topically to a subject having the disorder, wherein the foam does not collapse immediately upon exposure to skin temperature, and

c) collapsing the breakable foam by applying shear force to the administered breakable foam such that it is spread at, about and within the target site;

wherein the active agent is administered in a therapeutically effective amount; and

wherein the composition has some or partial resistance to centrifugation at 3000 rpm for 10 minutes.

2. The method of claim 1, wherein

the solvent is a polar solvent;

and

the administered breakable foam is absorbed.

3. The method of claim 1 or 2, wherein the composition further comprises about 0.1% to about 5% by weight of a foam adjuvant is selected from the group consisting of a fatty alcohol having 15 or more carbons in their carbon chain;

a fatty acid having 16 or more carbons in their carbon chain;

fatty alcohols, derived from beeswax and including a mixture of alcohols, a majority of which has at least 20 carbon atoms in their carbon chain;

a fatty alcohol having at least one double bond;

a fatty acid having at least one double bond;

a branched fatty alcohol;

a branched fatty acid;

a fatty acid substituted with a hydroxyl group;

cetyl alcohol;

stearyl alcohol;

arachidyl alcohol;

behenyl alcohol;

1-triacontanol;

hexadecanoic acid;

stearic acid;

arachidic acid;

behenic acid;

octacosanoic acid;

12-hydroxy stearic acid and any mixture thereof.

4. The method of claim 1, wherein the composition further comprises at least one component, selected from the group consisting of:

i. co-emulsifier or foam stabilizer;

ii. a viscosity, bulking or firming agent;

iii. a stabilizer;

iv. a foam adjuvant

v. a co-solvent;

vi. a penetration enhancer;

vii. an agent capable of having an occlusive effect; and

viii. a modulating agent.

5. The method of claim 1 wherein the propellant is itself a cooling agent.

6. The method of claim 1 wherein the foamed composition is flowable.

7. The method of claim 6, wherein the at least one carrier is selected from the group consisting of an oil, a silicone oil, an alcohol, a polyol, a polyethylene glycol (PEG), a propylene glycol, and a solvent, or combinations thereof.

8. The method of claim 6, wherein the sweating is reduced by at least 20% or about 20%.

9. The method of claim 6, wherein the composition further comprises a humectantat.

10. The method of claim 6, wherein the at least one carrier comprises a polar solvent.

11. The method of claim 1, wherein the foamed composition further comprises a co solvent at a concentration of about 0.1% to about 48% by weight of the total composition.

12. The method of claim 11, wherein the co solvent is at a concentration of about 0.1% to about 30% by weight of the total composition.

13. The method of claim 11, wherein the at least one carrier and the co-solvent are at a concentration of about 40% to about 90% by weight of the total composition.

14. The method of claim 1, wherein the foamed composition further comprises a second surface active agent.

15. The method of claim 1 wherein the polymeric agent is a combination of hydroxy propylmethyl cellulose and xantham gum.

16. The method of claim 1 wherein the polymeric agent is selected from the group consisting of sodium carboxymethyl-cellulose, hydroxyethyl-cellulose, microcrystalline-cellulose, aluminum starch octyl succinate, and polyacrylates;

carbopol;

hydroxy propylmethyl cellulose a hydroxypropyl-cellulose; and

xantham gum.

17. The method of claim 1, wherein the foamed composition further comprises a co-emulsifier at a concentration of about 0.05% to about 10% by weight of the total composition.

18. The method of claim 1, wherein the foamed composition further comprises a viscosity, bulking or firming agent is a concentration of about 0.1% to about 15% by weight of the total composition.

19. The method of claim 1, wherein the foamed composition further comprises a stabilizer at a concentration of about 0.1% to about 10% by weight of the total composition.

20. The method of claim 1, wherein the foamed composition further comprises a penetration enhancer at a concentration of about 0.1% to about 30% by weight of the total composition.

21. The method of claim 1, wherein the foamed composition further comprises an agent capable of having an occlusive effect at a concentration of about 45% to about 85% by weight of the total composition.

22. The method of claim 1, wherein the foamed composition further comprises an agent capable of having an occlusive effect at a concentration of about 25% to about 49% by weight of the total composition.

23. The method of claim 1, wherein the foamed composition further comprises an agent capable of having an occlusive effect at a concentration of about 10% to about 30% by weight of the total composition.

24. The method of claim 1, wherein the foam has a density of about 0.01 to about 0.2 g/ml.

25. The method of claim 1, wherein the foam is a breakable foam, which if not subjected to mechanical shear break, is capable of having a collapse time of about 50 seconds or more.

26. The method of claim 1, wherein the foam is a breakable foam, which if not subjected to mechanical shear break, is capable of having a collapse time of about 120 seconds or more.

27. The method of claim 1, wherein the foam is a breakable foam, which if not subjected to mechanical shear break, is capable of having a collapse time of about 300 seconds or more.

28. The method of claim 1, wherein the foamed composition further comprises an aliphatic alcohol and a fatty alcohol.

29. The method of claim 1, wherein the foamed composition further comprises a foam adjuvant agent, selected from the group consisting of a fatty alcohol having 15 or more carbons in its carbon chain and a fatty acid having 16 or more carbons in its carbon chain.

30. The method of claim 1, wherein the carrier is a hydrophobic organic carrier selected from the group consisting of mineral oil, silicone oil, a triglyceride, an ester of a fatty acid, and petrolatum.

31. The method of claim 30, wherein the hydrophobic organic carrier is occlusive.

32. The method of claim 30, wherein the hydrophobic organic carrier is non occlusive.

33. The method of claim 1, wherein the foamed composition comprises up to 80% water.

34. The method of claim 1, wherein the foamed composition comprises less than 2% or about 2% short chain alcohols.

35. The method of claim 1, wherein the foamed composition is alcohol free.

36. The method of claim 1, wherein the foamed composition comprises an emulsion.

37. The method of claim 36, wherein the emulsion is selected from the group consisting of an oil in water emulsion;

a water in oil emulsion;

an oleaginous emulsion;

a petrolatum in water emulsion;

a water in petrolatum emulsion;

a petrolatum in non aqueous solvent emulsion, a non aqueous solvent in petrolatum emulsion, a hydrophilic non aqueous solvent in petrolatum emulsion and a non aqueous emulsion.

38. The method of claim 1, wherein the foamed composition further comprises about 0.1% to about 5% by weight of a foam adjuvant selected from the group consisting of a fatty alcohol having 15 or more carbons in their carbon chain;

a fatty acid having 16 or more carbons in their carbon chain;

a fatty alcohol, derived from beeswax and including a mixture of alcohols, a majority of which has at least 20 carbon atoms in their carbon chain;

a fatty alcohol having at least one double bond;

a fatty acid having at least one double bond;

a branched fatty alcohol;

a branched fatty acid;

a fatty acid substituted with a hydroxyl group;

cetyl alcohol;

stearyl alcohol;

arachidyl alcohol;

behenyl alcohol;

1-triacontanol;

hexadecanoic acid;

stearic acid;

arachidic acid;

behenic acid;

octacosanoic acid;

12-hydroxy stearic acid and any mixture thereof.

39. The method of claim 1, wherein the active agent is selected from the group consisting of:

a) An anticholinergic drug;

b) An agent, selected from the group consisting of boric acid, tannic acid, resorcinol, potassium permanganate, formaldehyde, glutaraldehyde and methenamine;

c) a Lewis acid;

d) a salt or a complex of a metal ion, capable of treating hyperhidrosis;

e) a salt or a complex of a metal ion selected from the group consisting of aluminum and zirconium;

f) a salt or a complex of a metal selected from the group consisting of aluminum and zirconium;

g) a 5-alpha-reductase inhibitor;

h) an agent, selected from the group consisting of finasteride, flutamide, spironolactone, saw palmetto extract, epristeride and cholestan-3-one;

i) an agent, capable of treating hyperhidrosis, selected from the group consisting of mono- and dicarboxylic acids having 4 to 18 carbon atoms, a mercapto derivative thereof, a salt thereof, and an ester thereof;

j) botulinum toxin;

k) a 5-HT2C receptor antagonist;

l) an agent, selected from the group consisting of ketanserin, ritanserin, mianserin, mesulergine, cyproheptadine, fluoxetine, mirtazapine, olanzapine, and ziprasidone;

m) a 5-HT2C receptor modulator; and

n) an antiperspirant.

40. The method of claim 1, wherein the foamed composition further comprises

at least one additional therapeutic agent selected from the group consisting of an anti-infective, an antibiotic, an antibacterial agent, an antifungal agent, an antiviral agent, an antiparasitic agent, a steroid, a non-steroidal antiinflammatory agent, an immunosuppressive agent, an immunomodulator, an immunoregulating agent, a hormonal agent, vitamin A, a vitamin A derivative, vitamin B, a vitamin B derivative, vitamin C, a vitamin C derivative, vitamin D, a vitamin D derivative, vitamin E, a vitamin E derivative, vitamin F, a vitamin F derivative, vitamin K, a vitamin K derivative, a wound healing agent, a disinfectant, an anesthetic, an antiallergic agent, an alpha hydroxyl acid, lactic acid, glycolic acid, a beta-hydroxy acid, a protein, a peptide, a neuropeptide, an allergen, an immunogenic substance, a haptene, an oxidizing agent, an antioxidant, a dicarboxylic acid, azelaic acid, sebacic acid, adipic acid, fumaric acid, a retinoid, an antiproliferative agent, an anticancer agent, a photodynamic therapy agent, benzoyl chloride, calcium hypochlorite, magnesium hypochlorite, an anti-wrinkle agent, a radical scavenger, a metal, silver, a metal oxide, titanium dioxide, zinc oxide, zirconium oxide, iron oxide, silicone oxide, talc, carbon, an anti wrinkle agent, a skin whitening agent, a skin protective agent, a masking agent, an anti-wart agent, a refatting agent, a lubricating agent and any mixture thereof.

41. The method of claim 1, wherein the surface active agent includes a mixture of at least one non-ionic surfactant and at least one ionic surfactant in a ratio in the range of about 100:

1 to 6;

1.

42. The method of claim 1, wherein the surface active agent is non-ionic.

43. The method of claim 1, wherein the polymeric agent is selected from the group consisting of a water-soluble cellulose ether and a naturally-occurring polymeric material.

44. The method of claim 1, wherein the polymeric agent is selected from the group consisting of methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose (Methocel), hydroxyethyl cellulose, methylhydroxyethylcellulose, methylhydroxypropylcellulose, hydroxyethylcarboxymethylcellulose, carboxymethylcellulose, carboxymethylhydroxyethylcellulose, xanthan gum, guar gum, carrageenin gum, locust bean gum and tragacanth gum.

45. The method of claim 1 where the first agent is a hyperhidrosis agent and there is provided a second agent to treat another disorder, wherein the disorder is selected from the group consisting of a dermatose, a dermatitis, a vaginal disorder, a vulvar disorder, an anal disorder, a disorder of a body cavity, an ear disorder, a disorder of the nose, a disorder of the respiratory system, a bacterial infection, fungal infection, viral infection, dermatological pain, dermatological inflammation, acne, acne vulgaris, inflammatory acne, non-inflammatory acne, acne fulminans, nodular papulopustular acne, acne conglobata, dermatitis, bacterial skin infections, fungal skin infections, viral skin infections, parasitic skin infections, skin neoplasia, skin neoplasms, pruritis, cellulitis, acute lymphangitis, lymphadenitis, erysipelas, cutaneous abscesses, necrotizing subcutaneous infections, scalded skin syndrome, folliculitis, furuncles, hidradenitis suppurativa, carbuncles, paronychial infections, rashes, erythrasma, impetigo, ecthyma, yeast skin infections, warts, molluscum contagiosum, trauma or injury to the skin, post-operative or post-surgical skin conditions, scabies, pediculosis, creeping eruption, eczemas, psoriasis, pityriasis rosea, lichen planus, pityriasis rubra pilaris, edematous, erythema multiforme, erythema nodosum, grannuloma annulare, epidermal necrolysis, sunburn, photosensitivity, pemphigus, bullous pemphigoid, dermatitis herpetiformis, keratosis pilaris, callouses, corns, ichthyosis, skin ulcers, ischemic necrosis, miliaria, moles, Kaposi'"'"'s sarcoma, melanoma, malignant melanoma, basal cell carcinoma, squamous cell carcinoma, contact dermatitis, atopic dermatitis, rosacea, purpura, moniliasis, candidiasis, baldness, alopecia, Behcet'"'"'s syndrome, cholesteatoma, Dercum disease, ectodermal dysplasia, gustatory sweating, nail patella syndrome, lupus, hives, hair loss, Hailey-Hailey disease, chemical or thermal skin burns, scleroderma, aging skin, wrinkles, sun spots, necrotizing fasciitis, necrotizing myositis, gangrene, scarring, and vitiligo.