Non surface active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses

• US 9,072,667 B2
• Filed: 01/27/2012
• Issued: 07/07/2015
• Est. Priority Date: 07/29/2009
• Status: Active Grant

• Current Assignee: VYNE Therapeutics, Inc.
• Original Assignee: Foamix Pharmaceuticals, Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Tamarkin, Dov, Ziv, Enbal, Hazot, Yohan, Schuz, David
• Primary Examiner(s): Azpuru, Carlos
• Assistant Examiner(s): Browe, David
• Application Number:
  US13/359,787
• Publication Number:
  US 20120213710A1
• Time in Patent Office: 1,257 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• 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 47/12 Carboxylic acids; Salts or anhydrides thereof
• 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 8/046 Aerosols; Foams
• CPC Class Codes: A61K 8/34 Alcohols
• CPC Class Codes: A61K 8/342 Alcohols having more than seven atoms in an unbroken chain
• CPC Class Codes: A61K 9/12 Aerosols; Foams A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015
• CPC Class Codes: A61K 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin

Abstract

A substantially surface active agent-free and substantially polymeric agent-free foamable composition which includes short-chain alcohol, water, fatty alcohol or fatty acid or a combination of fatty alcohol and fatty acid and propellant. A substantially surface active agent-free and substantially polymeric agent-free foamable composition which includes water, fatty alcohol or fatty acid and propellant. A method of treatment using a substantially surface active agent-free and substantially polymeric agent-free foamable composition.

Claims

1. A foamable composition comprising a liquefied or compressed gas propellant and a carrier composition:

the carrier composition comprising;

a) a short chain alcohol having up to six carbon atoms in its carbon chain;

b) water; and

c) a foaming booster comprising at least one fatty alcohol or at least one fatty acid or a combination of fatty alcohols or a combination of fatty acids or a combination of at least one fatty alcohol and at least one fatty acid; and

wherein the liquefied or compressed gas propellant is at a concentration of about 3% to about 30% by weight of the carrier composition;

wherein the foamable composition comprises less than 0.2% by weight of the carrier composition of a polymeric agent;

wherein the foamable composition comprises 0% by weight surfactant; and

wherein upon dispensing, a foam is formed that is thermally stable at a temperature of 36°

C. and has a collapse time of about or more than 60 seconds.

2. The foamable composition of claim 1, wherein the short chain alcohol is selected from the group consisting of ethanol and isopropanol.

3. The foamable composition of claim 1, wherein the carrier composition further comprises at least one active agent.

4. The foamable of claim 3, wherein the active agent is selected from the group consisting of an active herbal extract, an acaricides, an age spot and keratose removing agent, an allergen, an alpha hydroxyl acid, an analgesic agent, an anesthetic, an immunogenic substance, an antiacne agent, an antiallergic agent, an antiaging agent, an antibacterial agent, an antibiotic, an antiburn agent, an anticancer agent, an antidandruff agent, an antidepressant, an antidermatitis agent, an antiedemic agent, an antifungal agent, an antihistamine, an antihelminth agent, an antihyperkeratolyte agent, an anti-infective agent, an anti-inflammatory agent, an antiirritant, an antilipemic agent, an antimicrobial agent, an antimycotic agent, an antioxidant, an antiparasitic agent, an anti-pigmentation agent, an antiproliferative agent, an antipruritic agent, an antipsoriatic agent, an antirosacea agent, an antiseborrheic agent, an antiseptic agent, an antiswelling agent, an antiviral agent, an anti-wart agent, an anti-wrinkle agent, an antiyeast agent, an astringent, a beta-hydroxy acid, benzoyl peroxide, a topical cardiovascular agent, a chemotherapeutic agent, a corticosteroid, an immunogenic substance, a dicarboxylic acid, a disinfectant, a fungicide, a hair growth regulator, a haptene, a hormone, a hydroxy acid, an immunosuppressant, an immunoregulating agent, an immunomodulator, an insecticide, an insect repellent, a keratolytic agent, a lactam, a local anesthetic agent, a lubricating agent, a masking agent, a metal, a metal oxide, a mitocide, a neuropeptide, a non-steroidal anti-inflammatory agent, an oxidizing agent, a pediculicide, a peptide, a protein, a photodynamic therapy agent, a radical scavenger, a refatting agent, a retinoid, a sanative, a scabicide, a self tanning agent, silicone talc, a skin protective agent, a skin whitening agent, a steroid, a steroid hormone, a steroidal anti-inflammatory agent, a vasoconstrictor, a vasodilator, a vitamin, a vitamin A, a vitamin A derivative, a vitamin B, a vitamin B derivative, a vitamin C, a vitamin C derivative, a vitamin D, a vitamin D derivative, a vitamin D analog, a vitamin F, a vitamin F derivative, a vitamin K, a vitamin K derivative, a wound healing agent, a wart remover, and mixtures of any two or more thereof.

5. The foamable composition of claim 1, wherein the foamable composition is transparent upon pressurization by the gas propellant.

6. The foamable composition of claim 1, wherein the carrier composition further includes about 0.1% to about 5% by weight of the carrier composition of a humectant.

7. The foamable composition of claim 6, wherein the humectant is selected from the group consisting of polyethylene glycol (PEG) 400, propylene glycol and glycerin.

8. The foamable composition of claim 1, wherein the composition is free of polymeric agent or contains less than 0.1% by weight of the carrier composition of the polymeric agent.

9. The foamable composition of claim 1, wherein the fatty acid or fatty alcohol is selected from the group consisting of (i) a fatty alcohol or fatty acid having 14 to 18 carbon atoms in its carbon chain and (ii) a fatty alcohol or fatty acid having 16 to 18 carbon atoms in its carbon chain.

10. The foamable composition of claim 1, wherein the foaming booster is a combination of fatty alcohols having 14 to 18 carbon atoms in their carbon chain.

11. The foamable composition of claim 1, wherein the combination of fatty alcohols is selected from the group consisting of:

(i) stearyl alcohol and cetyl alcohol, (ii) cetyl alcohol and myristyl alcohol, and (iii) stearyl alcohol, cetyl alcohol and myristyl alcohol.

12. The foamable composition of claim 1, wherein the foaming booster is between about 1% and about 10% by weight of the carrier composition.

13. The foamable composition of claim 11, wherein the combination of fatty alcohols is selected from the group consisting of:

(i) stearyl alcohol and cetyl alcohol and (ii) cetyl alcohol and myristyl alcohol and the ratio of the two fatty alcohols is between about 2;

1 and about 1;

2.

14. The foamable composition of claim 11, wherein the combination of fatty alcohols is selected from the group consisting of:

(i) stearyl alcohol and cetyl alcohol and (ii) cetyl alcohol and myristyl alcohol and the ratio of the two fatty alcohols is about 1;

1.

15. The foamable composition of claim 1, wherein the short chain alcohol is present in an amount selected from the group consisting of (i) 15% by weight of the carrier composition or at least 15% by weight of the carrier composition, (ii) between about 20% and 60% by weight of the carrier composition, (iii) between about 30% and 60% by weight of the carrier composition, and (iv) between about 40% and 60% by weight of the carrier composition.

16. The foamable composition of claim 1, wherein the foam has a collapse time of about or more than 120 seconds.

17. The foamable composition of claim 1, wherein the foam has a collapse time of about or more than 180 seconds.

18. The foamable composition of claim 1, wherein the carrier composition further comprises a hydrophilic solvent.

19. The foamable composition of claim 2, wherein the short chain alcohol comprises ethanol.

20. The foamable composition of claim 1, wherein the foam is a breakable foam that is thermally stable upon dispensing yet breaks upon application of shear force.

21. The foamable composition of claim 8, wherein the carrier composition is free of polymeric agent or contains less than 0.01% by weight of the carrier composition of the polymeric agent.

32. The foamable composition of claim 4, wherein the active agent is a steroid.

33. The foamable composition of claim 32, wherein the steroid is selected from the group consisting of hydrocortisone, hydroxyltriamcinolone, alpha-methyl dexamethasone, dexamethasone-phosphate, beclomethsone dipropionate, clobetasol valemate, desonide, desoxymethasone, desoxycorticosterone acetate, dexamethasone, dichlorisone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluclorolone acetonide, fludrocortisone, flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortine butylester, fluocortolone, fluprednidene (fluprednylidene) acetate, flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, triamcinolone acetonide, cortisone, cortodoxone, flucetonide, fludrocortisone, difluorosone diacetate, fluradrenolone acetonide, medrysone, amcinafel, amcinafide, betamethasone valerate and the balance of its esters, chloroprednisone, chlorprednisone acetate, clocortelone, clescinolone, dichlorisone, difluprednate, flucloronide, flunisolide, fluoromethalone, fluperolone, fluprednisolone, hydrocortisone valerate, hydrocortisone cyclopentylpropionate, hydrocortmate, mepreddisone, paramethasone, prednisolone, prednisone, beclomethasone dipropionate and triamcinolone.

34. The foamable composition of claim 33, wherein the steroid is betamethasone valerate.

46. The foamable composition of claim 11, wherein the foaming booster comprises cetyl alcohol and stearyl alcohol.

47. The foamable composition of claim 1, wherein the foaming booster comprises steric acid and stearyl alcohol.

48. The foamable composition of claim 1, wherein the foaming booster comprises steric acid.

49. The foamable composition of claim 1, wherein the foaming booster comprises stearyl alcohol.

22. A foamable composition comprising a liquefied or compressed gas propellant and a carrier composition:

the carrier composition comprising;

a) a short chain alcohol having up to six carbon atoms in its carbon chain;

b) water; and

c) a foaming booster comprising a combination of two or more fatty alcohols; and

wherein the liquefied or compressed gas propellant is at a concentration of about 3% to about 30% by weight of the carrier composition;

wherein the foamable composition comprises less than 0.2% by weight of the carrier composition of a polymeric agent;

wherein the foamable composition comprises 0% by weight surfactant;

wherein upon dispensing, a foam is formed that is thermally stable at a temperature of 36°

C. and has a collapse time of about or more than 60 seconds.

23. The foamable composition of claim 22, wherein the ratio of the two fatty alcohols is about 1:

1.

24. The foamable composition of claim 22, wherein the carrier composition further comprises an active agent.

25. The foamable composition of claim 22, wherein the carrier composition is free of polymeric agent or contains less than 0.1% by weight of the carrier composition of the polymeric agent.

35. The foamable composition of claim 24, wherein the active agent is a steroid.

36. The foamable composition of claim 35, wherein the steroid is selected from the group consisting of hydrocortisone, hydroxyltriamcinolone, alpha-methyl dexamethasone, dexamethasone-phosphate, beclomethsone dipropionate, clobetasol valemate, desonide, desoxymethasone, desoxycorticosterone acetate, dexamethasone, dichlorisone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluclorolone acetonide, fludrocortisone, flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortine butylester, fluocortolone, fluprednidene (fluprednylidene) acetate, flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, triamcinolone acetonide, cortisone, cortodoxone, flucetonide, fludrocortisone, difluorosone diacetate, fluradrenolone acetonide, medrysone, amcinafel, amcinafide, betamethasone valerate and the balance of its esters, chloroprednisone, chlorprednisone acetate, clocortelone, clescinolone, dichlorisone, difluprednate, flucloronide, flunisolide, fluoromethalone, fluperolone, fluprednisolone, hydrocortisone valerate, hydrocortisone cyclopentylpropionate, hydrocortmate, mepreddisone, paramethasone, prednisolone, prednisone, beclomethasone dipropionate and triamcinolone.

37. The foamable composition of claim 36, wherein the steroid is betamethasone valerate.

44. The foamable composition of claim 22, wherein the combination of the fatty alcohols is a combination of fatty alcohols having 14 to 18 carbons in their carbon chain.

26. A method of ameliorating or eliminating or treating or alleviating a dermatological or a mucosal disorder, the method comprising:

applying a foam composition to a surface having the dermatological or mucosal disorder in need of treatment, wherein the foam is formed from a foamable composition comprising a liquefied or compressed gas propellant and a carrier composition,

the carrier composition comprising;

a) a short chain alcohol having up to six carbon atoms in its carbon chain;

b) water; and

c) a foaming booster comprising at least one fatty alcohol or at least one fatty acid or combination of fatty alcohols or a combination of fatty acids or a combination of at least one fatty alcohol and at least one fatty acid; and

wherein the liquefied or compressed gas propellant is at a concentration of about 3% to about 30% by weight of the carrier composition;

wherein the foamable composition comprises less than 0.2% by weight of the carrier composition of a polymeric agent;

wherein the foamable composition comprises 0% by weight surfactant; and

wherein upon dispensing, the foam formed is thermally stable at a temperature of 36°

C. and has a collapse time of about or more than 60 seconds.

27. The method of claim 26, wherein the carrier composition further comprises at least one active agent.

28. The method of claim 26, wherein the carrier composition is free of polymeric agent or contains less than 0.1% by weight of the carrier composition of the polymeric agent.

38. The method of claim 27, wherein the active agent is a steroid.

39. The method of claim 38, wherein the steroid is selected from the group consisting of hydrocortisone, hydroxyltriamcinolone, alpha-methyl dexamethasone, dexamethasone-phosphate, beclomethsone dipropionate, clobetasol valemate, desonide, desoxymethasone, desoxycorticosterone acetate, dexamethasone, dichlorisone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluclorolone acetonide, fludrocortisone, flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortine butylester, fluocortolone, fluprednidene (fluprednylidene) acetate, flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, triamcinolone acetonide, cortisone, cortodoxone, flucetonide, fludrocortisone, difluorosone diacetate, fluradrenolone acetonide, medrysone, amcinafel, amcinafide, betamethasone valerate and the balance of its esters, chloroprednisone, chlorprednisone acetate, clocortelone, clescinolone, dichlorisone, difluprednate, flucloronide, flunisolide, fluoromethalone, fluperolone, fluprednisolone, hydrocortisone valerate, hydrocortisone cyclopentylpropionate, hydrocortmate, mepreddisone, paramethasone, prednisolone, prednisone, beclomethasone dipropionate and triamcinolone.

40. The method composition of claim 39, wherein the steroid is betamethasone valerate.

29. A method of ameliorating or eliminating or treating or alleviating a dermatological or a mucosal disorder, the method comprising:

applying a foam composition to a surface having the dermatological or mucosal disorder in need of treatment, wherein the foam is formed from a foamable composition comprising a liquefied or compressed gas propellant and a carrier composition;

carrier composition comprising;

a) a short chain alcohol having up to six carbon atoms in its carbon chain;

b) water; and

c) a foaming booster comprising a combination of two or more fatty alcohols;

wherein the liquefied or compressed gas propellant is at a concentration of about 3% to about 30% by weight of the carrier composition;

wherein the foamable composition comprises less than 0.2% by weight of the carrier composition of a polymeric agent;

wherein the foamable composition comprises 0% by weight surfactant; and

wherein upon dispensing, the foam formed is thermally stable at a temperature of 36°

C. and has a collapse time of about or more than 60 seconds.

30. The method of claim 29, wherein the carrier composition further comprises at least one active agent.

31. The method of claim 29, wherein the carrier composition is free of polymeric agent or contains less than 0.1% by weight of the carrier composition of polymeric agent.

41. The method composition of claim 30, wherein the active agent is a steroid.

42. The method of claim 41, wherein the steroid is selected from the group consisting of hydrocortisone, hydroxyltriamcinolone, alpha-methyl dexamethasone, dexamethasone-phosphate, beclomethsone dipropionate, clobetasol valemate, desonide, desoxymethasone, desoxycorticosterone acetate, dexamethasone, dichlorisone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluclorolone acetonide, fludrocortisone, flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortine butylester, fluocortolone, fluprednidene (fluprednylidene) acetate, flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, triamcinolone acetonide, cortisone, cortodoxone, flucetonide, fludrocortisone, difluorosone diacetate, fluradrenolone acetonide, medrysone, amcinafel, amcinafide, betamethasone valerate and the balance of its esters, chloroprednisone, chlorprednisone acetate, clocortelone, clescinolone, dichlorisone, difluprednate, flucloronide, flunisolide, fluoromethalone, fluperolone, fluprednisolone, hydrocortisone valerate, hydrocortisone cyclopentylpropionate, hydrocortmate, mepreddisone, paramethasone, prednisolone, prednisone, beclomethasone dipropionate and triamcinolone.

43. The method composition of claim 42, wherein the steroid is betamethasone valerate.

45. The method of claim 29, wherein the combination of the fatty alcohols is a combination of fatty alcohols having 14 to 18 carbons in their carbon chain.