Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses

• US 9,167,813 B2
• Filed: 01/27/2012
• Issued: 10/27/2015
• 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): Reddig, Peter J
• Assistant Examiner(s): CHICKOS, SARAH J
• Application Number:
  US13/359,709
• Publication Number:
  US 20120213709A1
• Time in Patent Office: 1,369 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A01N 25/16 Foams
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/327 Peroxy compounds, e.g. hydroperoxides, peroxides, peroxyacids
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/7056 containing five-membered rings with nitrogen as a ring hetero atom
• 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 47/38 Cellulose; Derivatives thereof
• 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 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders

Abstract

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

Claims

1. A foamable composition comprising:

a) a short chain alcohol;

b) water;

c) a foaming booster comprising;

i) about 0.1% to about 5% by weight of a polymer; and

ii) at least one fatty alcohol or at least one fatty acid or a combination thereof; and

d) a liquefied or compressed gas propellant,

wherein the composition is free of surfactant;

wherein the percent by weight is based on the weight of foamable composition other than propellant;

wherein the ratio of composition other than propellant to propellant ranges from about 100;

3 to about 100;

30;

wherein the foamable composition is transparent; and

wherein upon dispensing the foamable composition a foam is obtained having a collapse time at 36°

C. of about or more than 60 seconds.

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

3. The composition of claim 1, wherein the foaming booster is a combination of a polymer and at least one fatty alcohol, at least one fatty acid, or a mixture of at least one fatty alcohol and at least one fatty acid that can improve the foam quality and or thermal stability of the composition.

4. The composition of claim 1, further comprising at least one active agent.

5. The composition of claim 4, wherein the active agent is selected form 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 anent, 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 betahydroxy 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 antiinflammatory 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.

6. The composition of claim 4, wherein the active agent is selected from the group consisting of mometasone furoate, betamethasone valerate, diclofenac sodium, metronidazole, clindamycin phosphate, benzoyl peroxide, and mixtures of any two or more thereof.

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

8. The composition of claim 1, wherein the composition further includes a pH buffering agent.

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

10. The composition of claim 9, wherein the humectant is selected from the group consisting of PEG 400, propylene glycol and glycerin.

11. The composition of claim 1, wherein the polymer is a cellulose-based polymer.

12. The composition of claim 11, wherein the polymer is selected from the group consisting of hydroxypropyl methycellulose and hydroxypropyl cellulose.

13. The composition of claim 1, wherein the fatty acid or fatty alcohol is selected from the group consisting of (i) a fatty acid or alcohol having 14 carbon atoms in its carbon chain, (ii) a fatty acid or alcohol having 16 carbon atoms in its carbon chain, (iii) a fatty acid or alcohol having more than 16 carbon atoms in its carbon chain, and (iv) mixtures of any two or more thereof.

14. The composition of claim 3, where the foaming booster comprises a synergistic combination of at least two fatty alcohols.

15. The composition of claim 14, wherein the synergistic combination of fatty alcohols is selected form a group consisting of (i) stearyl alcohol and cetyl alcohol, (ii) cetyl alcohol and myristyl alcohol, (iii) stearyl alcohol and myristyl alcohol, and (iv) stearyl alcohol, cetyl alcohol, and myristyl alcohol.

16. The composition of claim 14, wherein the ratio between at least two fatty alcohols of the combination is between about 11:

5 and about 5;

11.

17. The composition of claim 14, wherein the ratio between at least two fatty alcohols of the combination is between about 1:

1 and about 5;

11.

18. The composition of claim 1, wherein the ratio of fatty alcohol/fatty acid to polymer is selected from the group consisting of a) between about 100:

1 and about 1;

50, b) between about 20;

1 and about 1;

20, and c) between about 10;

1 and about 1;

10.

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

20. The composition of claim 1, having a collapse time of about or more than 120 seconds at 36°

C.

21. The composition of claim 1, having a collapse time of about or more than 180 seconds at 36°

C.

22. The composition of claim 1, further comprising a hydrophilic solvent.

23. The composition of claim 22, wherein the short chain alcohol is more than 10% by weight.

24. The composition of claim 1, wherein the foam is a breakable foam that breaks easily upon application of shear force.

28. A method of treating, ameliorating or alleviating a dermatological or mucosal disorder on a patient in need, comprising:

1) dispensing from an aerosol packaging assembly comprising a container, suitable for containing a pressurized product, and a valve, capable of extruding a foam, the composition of claim 27;

2) directing the extruded foam on to a surface having the disorder; and

3) spreading the foam such that after a simple rub the foam is absorbed onto the surface;

wherein the foam has a collapse time at 36°

C. of about or more than 60 seconds.

29. The method of claim 28, wherein the active agent is a steroid.

30. The composition of claim 1, wherein the foamable composition is homogenous.

32. The composition of claim 1, wherein the foamable composition other than propellant is a suspension.

34. The composition of claim 4, wherein the short chain alcohol is at a concentration of about 15% to about 65% by weight of the composition, wherein the fatty alcohol is at a concentration of about 0.1% to about 15% by weight of the composition, and wherein the liquefied or compressed gas propellant is at a concentration of about 3% to about 30% by weight of the composition.

35. the composition of claim 4, wherein the short chain alcohol comprises ethanol, wherein the fatty alcohol comprises cetyl alcohol and stearyl alcohol, and wherein the polymer comprises hydroxypropyl cellulose.

36. the composition of claim 34, wherein the short chain alcohol comprises ethanol, wherein the fatty alcohol comprises cetyl alcohol and stearyl alcohol, and wherein the polymer comprises hydroxypropyl cellulose.

37. The composition of claim 4, further comprising a polar solvent at a concentration of about 2% to about 50% by weight of the composition.

38. The composition of claim 36, further comprising a polar solvent at a concentration of about 2% to about 50% by weight of the composition.

39. The composition of claim 37, wherein the polar solvent comprises propylene glycol.

40. The composition of claim 8, wherein the pH buffering agent comprises triethanolamine.

41. The composition of claim 4, further comprising a chelating agent comprising EDTA.

42. The composition of claim 38, wherein the polar solvent comprises propylene glycol, and the composition further comprises a pH buffering agent, and a chelating agent.

43. The composition of claim 42, wherein the pH buffering agent comprises triethanolamine and the chelating agent comprises EDTA.

44. The composition of claim 42, wherein the composition is suitable for the treatment of a fungal condition or a fungal infection.

45. The composition of claim 44, wherein the fungal infection involves pathogen colonization at the affected site and inflammation.

46. The composition of claim 34, wherein at least two active agents are present in a therapeutically effective concentration.

48. The composition of claim 42, wherein the at least one active agent is an antifungal agent.

49. The composition of claim 42, wherein the propellant comprises butane, propane, isobutane or mixtures thereof.

25. A foamable composition comprising:

1) a short chain alcohol;

2) water;

3) a foaming booster comprising;

(i) about 0.1% to about 5% by weight of a polymer; and

(ii) at least one fatty alcohol or at least one fatty acid or a combination thereof or a synergistic combination of two or more fatty alcohols; and

4) a liquefied or compressed gas propellant,

wherein the percent by weight is based on the weight of foamable composition other than propellant;

wherein the composition is free of surfactant;

wherein the ratio of composition other than propellant to propellant ranges from about 100;

3 to about 100;

30;

wherein the foamable composition is transparent; and

wherein the ratio between the two fatty alcohols is between about 11;

5 and about 5;

11.

26. The composition of claim 25, wherein the ratio between fatty alcohols of the synergistic combination is between about 1:

1 and about 5;

11.

27. The composition of claim 25, further comprising at least one active agent.

31. The composition of claim 25, wherein the foamable composition is homogenous.

33. The composition of claim 25, wherein the foamable composition other than propellant is a suspension.

47. The composition of claim 27, wherein the at least one active agent is an antifungal agent.