Foamable composition combining a polar solvent and a hydrophobic carrier

• US 9,622,947 B2
• Filed: 01/08/2009
• Issued: 04/18/2017
• Est. Priority Date: 10/25/2002
• Status: Active Grant

• Current Assignee: VYNE Therapeutics, Inc.
• Original Assignee: Foamix Pharmaceuticals, Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Tamarkin, Dov, Friedman, Doron, Eini, Meir, Besonov, Alex
• Primary Examiner(s): Orwig, Kevin S
• Assistant Examiner(s): FRAZIER, BARBARA S
• Application Number:
  US12/350,854
• Publication Number:
  US 20090180970A1
• Time in Patent Office: 3,022 Days
• Field of Search: None
• CPC Class Codes: A01N 25/16 Foams
• CPC Class Codes: A61K 35/04 Tars; Bitumens; Mineral oils; Ammonium bituminosulfonate
• CPC Class Codes: A61K 47/06 Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
• 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 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• 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 8/37 Esters of carboxylic acids
• CPC Class Codes: A61K 8/375 the alcohol moiety containing more than one hydroxy group
• CPC Class Codes: A61K 8/4973 with oxygen as the only hetero atom
• CPC Class Codes: A61K 8/731 Cellulose; Quaternized cellulose derivatives
• CPC Class Codes: A61K 8/8176 Homopolymers of N-vinyl-pyrrolidones. Compositions of derivatives of such polymers
• CPC Class Codes: A61K 8/965 of inanimate origin
• 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 19/00 : Preparations for care of the skin
• CPC Class Codes: A61Q 19/02 : for chemically bleaching or whitening the skin
• CPC Class Codes: A61Q 19/08 : Anti-ageing preparations

Abstract

The present invention relates to a foamable vehicle or cosmetic or pharmaceutical composition, comprising: (1) an organic carrier, at a concentration of 10% to 70% by weight, wherein said organic carrier concurrently comprises: (i) at least one hydrophobic organic carrier, and (ii) at least one polar solvent; (2) at least one surface-active agent; (3) water; and (4) at least one liquefied or compressed gas propellant at a concentration of 3% to 25% by weight of the total composition.

The present invention further provides a method of treating, alleviating or preventing a disorder of mammalian subject, comprising administering the above-mentioned compositions to an afflicted target site.

Claims

1. A method of treating or alleviating a disorder, the method comprising:

(a) releasing a foamable composition from a pressurized container to form a breakable foam that is stable at skin temperature and breaks upon application of shear force, said foamable composition comprising at least one liquefied or compressed gas propellant and a therapeutic composition comprising;

(1) a liquid organic carrier, at a concentration of about 10% to about 70% by weight of the therapeutic composition, wherein said liquid organic carrier comprises;

i. at least one liquid hydrophobic organic carrier; and

ii. a liquid polar solvent comprising ethanol and glycerin;

wherein the hydrophobic organic carrier comprises isopropyl myristate;

wherein the weight ratio between the liquid polar solvent and the at least one liquid hydrophobic organic carrier is between about 1;

4 and about 4;

1;

(2) at least one surface-active agent selected from the group consisting of at least one non-ionic surface-active agent and a mixture of a non-ionic surface-active agent and an ionic surface-active agent, wherein the ratio of the non-ionic surface-active agent to the ionic surface-active agent is about 6;

1 or greater than 6;

1;

(3) at least one polymeric agent selected from the group consisting of a bioadhesive agent, a gelling agent, a film forming agent, a phase change agent, and any mixtures of two or more thereof;

(4) water; and

(5) an active agent comprising coal tar or a coal tar extract or a tincture dissolved in all or part of the liquid polar solvent;

wherein the at least one liquefied or compressed gas propellant is at a concentration of about 3% to about 25% by weight of the foamable composition,

(b) applying the breakable foam to a target area having a dermatological or mucosal disorder;

the disorder being selected from the group consisting of eczema, psoriasis, pruritis, dandruff, seborrhoeic dermatitis, and combinations of two or more thereof; and

(c) collapsing the breakable foam by applying shear force, wherein the foam is absorbed into the target area.

2. The method of claim 1, wherein upon release from a container, a shear-sensitive foam having a density of about 0.23 gr/mL or less is produced.

3. The method of claim 1, further comprising an additional polar solvent selected from the group consisting of a polyol, an alpha hydroxy acid, and any mixtures thereof, and wherein the polyol is selected from the group consisting of propylene glycol, butanediol, butenediol, butynediol, pentanediol, hexanediol, octanediol, neopentyl glycol, 2-methyl-1,3-propanediol, diethylene glycol, triethylene glycol, tetraethylene glycol, dipropylene glycol, dibutylene glycol, 1,2,6-hexanetriol, and any combinations of two or more thereof.

4. The method of claim 3, wherein the amount of the additional polar solvent is in the range of about 15% to about 60% by weight of the therapeutic composition.

5. The method of claim 3, wherein the hydrophobic carrier further comprises a silicone oil.

6. The method of claim 5, wherein the silicone oil is selected from the group consisting of dimethicone, cyclomethicone, and any mixtures thereof.

7. The method of claim 3, wherein the ratio of the additional polar solvent to the at least one liquid hydrophobic organic carrier is between about 3:

4 and about 5;

4.

8. The method of claim 1, wherein the therapeutic composition further comprises a mint comprising a peppermint, a spearmint, or mixtures thereof.

9. The method of claim 1, wherein the liquid organic carrier further comprises an additional hydrophobic organic carrier selected from the group consisting of an olive oil, corn oil, soybean oil, canola oil, cottonseed oil, coconut oil, sesame oil, sunflower oil, borage seed oil, syzigium aromaticum oil, hempseed oil, herring oil, cod-liver oil, salmon oil, flaxseed oil, wheat germ oil, evening primrose oils, omega-3 fatty acids, omega-6 fatty acids, linoleic acid, gamma-linoleic acid (GLA), eicosapentaenoic acid (EPA) docosahexaenoic acid (DHA), omega-3 oil, omega-6 oil, rosehip oil, tea tree oil, anise oil, basil oil, bergemont oil, camphor oil, cardamom oil, carrot oil, cassia oil, catnip oil, cedarwood oil, citronella oil, clove oil, cypress oil, eucalyptus oil, frankincense oil, garlic oil, ginger oil, grapefruit oil, hyssop oil, jasmine oil, jojova oil, lavender oil, lavandin oil, lemon oil, lime oil, mandarin oil, marjoram oil, myrrh oil, neroli oil, nutmeg oil, orange oil, peppermint oil, petitgrain oil, rosemary oil, sage oil, spearmint oil, star anise oil, tangerine oil, thyme vanilla oil, verbena oil, white clover oil, a liquid triglyceride oil, polyalkyl siloxanes, polyaryl siloxanes, polyalkylaryl siloxanes, polyether siloxane copolymers, polydimethylsiloxanes (dimethicones), poly(dimethylsiloxane)-(diphenyl-siloxane) copolymers, a silicone oil, isopropyl palmitate, isopropyl isostearate, diisopropyl adipate, diisopropyl dimerate, maleated soybean oil, octyl palmitate, cetyl lactate, cetyl ricinoleate, tocopheryl acetate, cetyl acetate, tocopheryl linoleate, wheat germ glycerides, arachidyl propionate, myristyl lactate, decyl oleate, propylene glycol ricinoleate, isopropyl lanolate, pentaerythrityl tetrastearate, neopentylglycol dicaprylate/dicaprate, isononyl isononanoate, isotridecyl isononanoate, myristyl myristate, octyl dodecanol, sucrose esters of fatty acids, octyl hydroxystearate, capric/caprylic triglycerides, and mixtures of any two or more thereof.

10. The method of claim 9, wherein the propellant is selected from the group consisting of butane, propane, isobutane, and mixtures of any two or more thereof.

11. The method of claim 9, wherein the additional hydrophobic carrier is selected from the group consisting of isopropyl palmitate, a liquid triglyceride oil, a silicone oil, and any mixtures of two or more thereof.

12. The method of claim 9, wherein the additional hydrophobic carrier comprises a liquid triglyceride oil.

13. The method of claim 12, wherein the liquid triglyceride oil is capric-caprylic triglycerides.

14. The method of claim 9, wherein the additional hydrophobic carrier comprises a mint oil.

15. The method of claim 14, wherein the mint oil comprises a peppermint oil.

16. The method of claim 1, wherein the liquid organic carrier further comprises an additional hydrophobic carrier comprising a silicone oil.

17. The method of claim 16, wherein the silicone oil is selected from the group consisting of dimethicone, cyclomethicone, and any mixtures thereof.

18. The method of claim 16, wherein the additional hydrophobic carrier further comprises a peppermint oil, a spearmint oil, or mixtures thereof.

19. The method of claim 1, further comprising an additional polar solvent comprising a polyol and an alpha hydroxy acid.

20. The method of claim 19, wherein the alpha hydroxy acid is citric acid.

21. The method of claim 1, wherein the amount of the liquid polar solvent is in the range of about 15% to about 60% by weight of the therapeutic composition.

22. The method of claim 1, wherein the ionic surface-active agent is selected from the group consisting of an anionic surfactant, a cationic surfactant, a zwitterionic surfactant, an amphoteric surfactant, an ampholytic surfactant, and any mixtures of two or more thereof.

23. The method of claim 1, wherein the surface-active agent comprises a polyethylene glycol ether.

24. The method of claim 1, wherein the at least one polymeric agent is a combination of xanthan gum and hydroxypropylmethylcellulose.

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

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

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

a fatty alcohol having an double bond;

a fatty acid having an 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 mixtures of two or more thereof.

26. The method of claim 25, wherein the combined amount of surface-active agent, gelling agent and foam adjuvant is less than about 5% by weight.

27. The method of claim 25, wherein the foam adjuvant is stearic acid.

28. The method of claim 1, wherein the therapeutic composition further comprises at least one of a fragrance agent, a masking agent, a buffering agent, a pH agent, a preservative, a chelating agent, an anti-oxidant, and any mixtures of two or more thereof.

29. The method of claim 28, wherein the fragrance agent, the additional hydrophobic organic carrier, or both, comprise a mint oil.

30. The method of claim 28, wherein the anti-oxidant is ascorbic acid.

31. The method of claim 1, wherein the ratio of the liquid polar solvent to the at least one liquid hydrophobic organic carrier is between about 3:

4 and about 5;

4.

32. The method of claim 1, wherein the liquid organic carrier is present in an amount in the range of about 10% to about 50% by weight of the therapeutic composition.

33. The method of claim 1, wherein the liquid organic carrier is present in an amount in the range of about 10% to about 39% by weight of the therapeutic composition.

34. The method of claim 1, wherein the liquid organic carrier is present in an amount in the range of about 10% to about 29% by weight of the therapeutic composition.

35. The method of claim 1, wherein the liquid organic carrier is present in an amount in the range of about 29% to about 70% by weight of the therapeutic composition.

36. The method of claim 1, wherein the liquid polar solvent is at a concentration of about 2% to about 50% by weight of the therapeutic composition.

37. The method of claim 1, wherein the surface-active agent is at a concentration of about 0.1% to about 5% by weight of the therapeutic composition.

38. The method of claim 1, wherein the at least one polymeric agent is at a concentration of about 0.01% to about 5% by weight of the therapeutic composition.

39. The method of claim 1, wherein the at least one polymeric agent is selected from the group consisting of a locust bean gum, a carrageenin gum, sodium alginate, a xanthan gum, quince seed extract, a tragacanth gum, a guar gum, a starch, chemically modified starches, cellulose ethers, a hydroxyethyl cellulose, a hydroxypropyl cellulose, a methyl cellulose, a methylhydroxyethylcellulose, a methylhydroxypropylcellulose, a hydroxypropylmethyl cellulose, a hydroxyethylcarboxymethylcellulose, a carboxymethylcellulose, a carboxymethylhydroxyethylcellulose, egg albumin, gelatin agar, a hydroxypropyl guar gum, a soluble starch, cationic celluloses, cationic guars, synthetic polymeric materials, carboxyvinyl polymers, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid polymers, polymethacrylic acid polymers, polyvinyl acetate polymers, polyvinyl chloride polymers, polyvinylidene chloride polymers, and mixtures of two or more thereof.

40. The method of claim 1, wherein a propellant is a mixture of volatile hydrocarbons, the mixture comprising one or more of butane, propane, and isobutane.

41. The method of claim 1, wherein the ratio of the non-ionic surface-active agent to the ionic surface-active agent is greater than 20:

1.

42. The method of claim 1, wherein the ratio of the non-ionic surface-active agent to the ionic surface-active agent is about 16:

1 or greater than 16;

1.

43. The method of claim 1, wherein the hydrophobic carrier is at a concentration of about 10% to about 40% by weight of the therapeutic composition.

44. The method of claim 1, wherein the liquid polar solvent is at a concentration of about 10% to about 40% by weight of the therapeutic composition.

45. The method of claim 1, wherein the ratio between the liquid polar solvent and the at least one liquid hydrophobic organic carrier is selected from the group consisting of about 1:

4, about 1;

2, about 3;

4, about 1;

1, about 5;

4, about 2;

1, about 3;

1, about 6;

4, about 7;

4, about 3;

1, about 3;

4 and about 4;

1.

46. The method of claim 1, wherein the hydrophobic carrier is at a concentration of about 15% to about 59% by weight of the therapeutic composition.

47. The method of claim 1, wherein the total amount of the hydrophobic carrier and the liquid polar solvent is selected from the group consisting of about 24% by weight of the therapeutic composition, about 29% by weight of the therapeutic composition, about 39% by weight of the therapeutic composition, about 50% by weight of the therapeutic composition, about 60% by weight of the therapeutic composition, about 68% by weight of the therapeutic composition, and about 69% by weight of the therapeutic composition.

48. The method of claim 1, wherein the total amount of the hydrophobic carrier and the liquid polar solvent is about 24% to about 69% by weight of the therapeutic composition.

49. The method of claim 1, wherein the at least one liquid hydrophobic organic carrier further comprises a triglyceride, a silicone oil, a mint oil and mixtures of any two or more thereof, wherein the at least one polymeric agent comprises a cellulose ether, a gum or both, wherein the surface-active agent comprises a polyoxyethylene alkyl ether, and wherein the therapeutic composition further comprises a foam adjuvant comprising a fatty acid having 16 or more carbons in its carbon chain.

50. The method of claim 49, wherein the triglyceride comprises caprylic/capric triglycerides, wherein the silicone oil comprises a cyclomethicone, a dimethicone, and mixtures thereof, wherein the mint oil comprises a peppermint oil, wherein the cellulose ether comprises a hydroxypropyl methylcellulose, wherein the gum comprises a xanthan gum, and wherein the fatty acid comprises stearic acid.

51. The method of claim 1, wherein the amount of the liquid polar solvent is in the range of about 15% to about 62% by weight of the therapeutic composition.