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

• US 9,572,775 B2
• Filed: 09/17/2015
• Issued: 02/21/2017
• 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): Blanchard, David J
• Assistant Examiner(s): CHICKOS, SARAH J
• Application Number:
  US14/857,282
• Publication Number:
  US 20160101051A1
• Time in Patent Office: 523 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) about 15% to about 60% by weight of a short chain alcohol;

b) a cellulose based polymer;

c) about 0.1% to about 15% by weight of at least one fatty alcohol;

d) a hydrophilic solvent;

e) at least one active agent; and

f) a liquefied or compressed gas propellant at a concentration of about 3% to about 30% by weight of the total foamable composition,

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

wherein the foamable composition comprises 0.1% or less by weight of a surfactant;

wherein the ratio range of the foamable composition other than propellant to propellant is from about 100;

3 to about 100;

30; and

wherein upon dispensing the foamable composition forms a foam having a collapse time about or more than 60 seconds at 36°

C.

2. The composition of claim 1, wherein the short chain alcohol is selected from the group consisting of ethanol, propanol, butanol, pentanol, isopropanol, and iso-butanol.

3. The composition of claim 1, wherein the hydrophilic solvent is selected from the group consisting of water, a glycol, propylene glycol, a low molecular weight polyethylene glycol, methoxyisopropanol, a PPG-2 propyl ether, a PPG-2 butyl ether, a PPG-2 methyl ether, a PPG-3 methyl ether, dipropylene glycol propyl ether, dipropylene glycol butyl ether, dipropylene glycol, methyl propanediol, propylene carbonate, a water soluble/dispersible polypropylene glycol, ethoxylated polypropylene glycol, glycerin, sorbitol, a hydrogenated starch hydrolysate, a silicone glycol, and mixtures of any two or more thereof.

4. The composition of claim 1, wherein the active agent is present at about 0.1% to about 5% by weight.

5. The composition of claim 4, wherein the active agent is selected from the group consisting of an active herbal extract, an acaricide, 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 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 an antifungal agent, 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 short chain alcohol comprises ethanol, wherein the fatty alcohol comprises cetyl alcohol and stearyl alcohol, and wherein the polymer comprises hydroxypropyl cellulose.

8. The composition of claim 1, wherein the composition further comprises a modulating agent.

9. The composition of claim 8, wherein the modulating agent is present at about 1% to about 5% by weight and is selected from the group consisting of a chelating agent, a sequestering agent, a complexing agent, a buffer agent, a pH modifying agent, an antioxidant, a radical scavenger, an ionization agent, and mixtures of any two or more thereof.

10. The composition of claim 9, wherein the hydrophilic solvent comprises about 2% to about 50% by weight of a polar solvent comprising a polyol or a glycol;

wherein the pH modifying agent comprises triethanolamine and the chelating agent comprises EDTA.

11. The composition of claim 1, wherein the cellulose based polymer is selected from the group consisting of hydroxypropyl methycellulose and hydroxypropyl cellulose;

and the foam is a breakable foam.

12. The composition of claim 1, wherein the cellulose based polymer is present in an amount of about 0.1% to about 5% by weight.

13. The composition of claim 1, further comprising a fatty acid, 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 1, comprising a combination of at least two fatty alcohols.

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

5 and about 5;

11 or between about 1;

1 and about 5;

11.

17. The composition of claim 1, wherein the composition comprises water.

18. The composition of claim 14, wherein the ratio of fatty alcohol to cellulose based 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 an amount selected from the group consisting of:

(i) between about 20% and 60% by weight, (ii) between about 30% and 60% by weight, and (iii) between about 40% and 60% by weight.

20. The composition of claim 1, wherein the hydrophilic solvent comprises about 2% to about 50% by weight of a polar solvent comprising a polyol or glycol.

21. The composition of claim 1, wherein the composition comprises 0.1% or less by weight of a surfactant or is essentially surfactant free.

24. 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 22;

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

3) spreading the foam on the surface;

wherein the foam has a collapse time at 36°

C. of about or more than 60 seconds.

25. The method of claim 24, wherein the active agent is an antifungal agent.

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

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

32. The composition of claim 10, wherein the composition is suitable for the treatment of a fungal condition or a fungal infection wherein the fungal infection may involve pathogen colonization at the affected site and inflammation.

33. The composition of claim 32, wherein the at least one active agent is an antifungal agent;

and wherein the propellant comprises butane, propane, isobutene, or mixtures thereof.

22. A foamable composition comprising:

1) about 15% to about 60% by weight of a short chain alcohol;

2) a cellulose based polymer;

3) about 1% to about 15% by weight of at least one fatty alcohol or at least one fatty acid or a combination thereof;

4) about 2% to about 50% by weight of a hydrophilic solvent;

5) a liquefied or compressed gas propellant;

6) about 0.1% to about 5% by weight of an active agent; and

7) optionally a pH modifying agent, a chelating agent or a combination thereof;

wherein the composition contains 0.1% or less by weight of a surfactant or is essentially surfactant free;

wherein if the composition comprises two fatty alcohols, the ratio between the two fatty alcohols is between about 11;

5 and about 5;

11;

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

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

3 to about 100;

30.

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

1 and about 5;

11.

27. The composition of claim 22, wherein the foamable composition is homogenous.

29. The composition of claim 22, wherein the foamable composition other than propellant is a suspension.

30. The composition of claim 22, wherein the composition comprises water.

31. The composition of claim 22, wherein the hydrophilic solvent comprises about 2% to about 50% by weight of a polar solvent comprising a polyol or a glycol.