Moisturizing foam containing lanolin

• US 8,486,376 B2
• Filed: 04/06/2005
• Issued: 07/16/2013
• Est. Priority Date: 10/25/2002
• Status: Active Grant

• Current Assignee: VYNE Therapeutics, Inc.
• Original Assignee: Foamix Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Friedman, Doron, Besonov, Alex, Tamarkin, Dov, Eini, Meir
• Primary Examiner(s): Blanchard, David J
• Assistant Examiner(s): Gotfredson, Garen
• Application Number:
  US11/099,942
• Publication Number:
  US 20050244342A1
• Time in Patent Office: 3,023 Days
• Field of Search: None
• US Class Current: 424/47
• CPC Class Codes: A61K 31/575 substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 19/00 Preparations for care of the skin

Abstract

The present invention provides a highly tolerable, hydrating lanolin containing foamable composition for administration to the skin, body surface, body cavity or mucosal surface, e.g., the mucosa of the nose, mouth, eye, ear, respiratory system, vagina or rectum. The foamable composition includes lanolin, a surface-active agent, about 0.01% to about 5% by weight of at least one polymeric additive selected from the group consisting of a bioadhesive agent, a gelling agent, a film forming agent and a phase change agent, water, and a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition.

Claims

1. A hydrating foamable composition comprising an emulsion, the emulsion comprising:

i. a hydrating component comprising lanolin, wherein the lanolin is present in an amount of at least about 5% by weight of the composition emulsion;

ii. about 0.1% to about 5% of a non-ionic surface-active agent by weight of the composition emulsion;

iii. about 0.01% to about 5% by weight of the emulsion of at least one polymeric additive selected from the group consisting of a bioadhesive agent, a gelling agent, a film forming agent˜

and a phase change agent;

iv. water; and

v. at least one 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 steroidal antiinflammatory agent, an immunosuppressive agent, an immunomodulator, an immunoregulating agent, a hormonal agent, 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 E, a vitamin E derivative, a vitamin F, a vitamin F derivative, a 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, a 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, benzo1 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, a skin whitening agent, a skin protective agent, a masking agent, an anti-wart agent, a refatting agent, a lubricating agent, and mixtures of two or more thereof; and

a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition;

wherein the composition is free of ionic surface active agents; and

wherein upon release from a pressurized container the composition expands to form a breakable foam that is thermally stable and collapses upon application of shear force.

2. The foamable composition of claim 1, further comprising at least one organic carrier selected from the group consisting of a hydrophobic organic carrier, a polar solvent, an emollient, and mixtures of two or more thereof, wherein the at least one organic carrier is present in an amount selected from the group consisting of (i) about 2% to about 5% by weight of the emulsion;

(ii) about 5% to about 10% by weight of the emulsion;

(iii) about 10% to about 20% by weight of the emulsion; and

(iv) about 20% to about 50% by weight of the emulsion.

3. The foamable composition of claim 1, further comprising about 0.1% to about 5% by weight of the emulsion of a therapeutically active 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;

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; and

a fatty acid substituted with a hydroxyl group, and mixtures of two or more thereof.

4. The foamable composition of claim 1, wherein the foamable composition is substantially free of short chain alcohols.

5. The foamable composition of claim 1, wherein the lanolin is selected from the group consisting of:

i. lanolin, wool fat, lanolin wax, and a synthetic lanolin;

ii. a synthetic lanolin comprising at least one of cholesterol, isocholesterol, and analogs, derivatives, salts, and esters thereof;

iii. an oil-soluble hydrophobic derivative of lanolin;

iv. a synthetic lanolin comprising at least one of cholesterol and isocholesterol covalently linked with an organic moiety;

v. a synthetic lanolin comprising at least one of cholesterol and isocholesterol covalently linked with an aliphatic acid;

vi. a lanolin acid;

vii. an ester of lanolin acid with an aliphatic alcohol; and

viii. a compound selected from the group consisting of acetylated lanolin, isopropyl lanolate, and cetyl lanolate.

6. The foamable composition of claim 1, wherein the concentration range of lanolin is selected from the group of (i) between about 5% and about 12% by weight of the emulsion;

and (ii) between about 12% and about 24% by weight of the emulsion.

7. The foamable composition of claim 1, wherein the concentration of the non-ionic surface active agent is less than about 2% by weight of the emulsion.

8. The foamable composition of claim 1, wherein the emulsion is a water in oil emulsion.

9. The foamable composition of claim 1, wherein the emulsion is an oil in water emulsion.

10. The foamable composition of claim 1, wherein the non-ionic surface active agent comprises a combination of at least one non-ionic surfactant having HLB of less than 9 and at least one non-ionic surfactant having HLB of equal or more than 9, wherein the ratio between the at least one non-ionic surfactant having HLB of less than 9 and the at least one non-ionic surfactant having HLB of equal or more than 9, is between 1:

8 and 8;

1.

11. The foamable composition of claim 1, wherein the polymeric agent is selected from the group consisting of a water-soluble cellulose ether, a naturally-occurring polymeric material, and mixtures of two or more thereof.

12. The foamable composition 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, carrageenan gum, locust bean gum, and tragacanth gum.

35. The foamable composition of claim 1, wherein the concentration of the non-ionic surface active agent is less than about 1% by weight of the emulsion.

13. A method of treating or alleviating insufficient hydration of skin, a body cavity or a mucosal surface, comprising:

administering topically to skin, a body cavity or a mucosal surface a breakable foam that is thermally stable and collapses upon application of shear force, wherein the foam is obtained by releasing from a pressurized container a foamable composition comprising an emulsion comprising;

a) a hydrating component comprising lanolin, wherein the lanolin is present in an amount of at least about 5% by weight of the composition emulsion;

b) about 0.1% to about 5% of a non-ionic surface-active agent by weight of the composition emulsion;

c) about 0.01% to about 5% by weight of the emulsion of at least one polymeric additive selected from the group consisting of a bioadhesive agent, a gelling agent, a film forming agent˜

and a phase change agent; and

d) water; and

a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition;

wherein the non-ionic surface active agent comprises a combination of at least one non-ionic surfactant having HLB of less than 9 and at least one non-ionic surfactant having HLB of equal or more than 9, wherein the ratio between the at least one non-ionic surfactant having HLB of less than 9 and the at least one non-ionic surfactant having HLB of equal or more than 9, is between 1;

8 and 8;

1;

wherein the composition is free of ionic surface active agents.

14. The method of claim 13, wherein the composition further comprises about 0.1% to about 5% by weight of the emulsion of a therapeutically active 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;

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 and mixtures thereof˜

and mixtures of two or more thereof.

15. The method of claim 13 or 14, wherein the composition further comprises an additional active agent effective to treat a disorder of skin, a body cavity or a mucosal surface.

16. The method of claim 13, wherein the foamable composition further comprises at least one component, selected from (1) a therapeutically effective foam adjuvant and (2) an organic carrier consisting of at least one therapeutically active oil.

17. The method of claim 13, wherein the foamable composition further comprises a therapeutically effective foam adjuvant and an organic carrier consisting of at least one therapeutically active oil.

18. A hydrating foamable composition comprising an emulsion, the emulsion comprising:

i. a hydrating component comprising lanolin, wherein the lanolin is present in an amount of at least about 5% by weight of the emulsion;

ii. about 0.1% to about 5% of a non-ionic surface-active agent by weight of the emulsion;

iii. about 0.01% to about 5% by weight of the emulsion of at least one polymeric additive selected from the group consisting of a bioadhesive agent, a gelling agent, a film forming agent, and a phase change agent; and

iv. water; and

a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition;

wherein the non-ionic surface active agent comprises a combination of at least one non-ionic surfactant having HLB of less than 9 and at least one non-ionic surfactant having HLB of equal or more than 9, wherein the ratio between the at least one non-ionic surfactant having HLB of less than 9 and the at least one non-ionic surfactant having HLB of equal or more than 9, is between 1;

8 and 8;

1;

wherein the composition is free of ionic surface active agents; and

wherein upon release from a pressurized container the composition expands to form a breakable foam that is thermally stable and collapses upon application of shear force.

19. The foamable composition of claim 18, further comprising at least one organic carrier selected from the group consisting of a hydrophobic organic carrier, a polar solvent, an emollient, and mixtures of two or more thereof, wherein the at least one organic carrier is present in an amount selected from the group consisting of (i) about 2% to about 5% by weight of the emulsion;

(ii) about 5% to about 10% by weight of the emulsion;

(iii) about 10% to about 20% by weight of the emulsion; and

(iv) about 20% to about 50% by weight of the emulsion.

20. The foamable composition of claim 18, further comprising about 0.1% to about 5% by weight of the emulsion of a therapeutically active 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;

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; and

mixtures of two or more thereof.

21. The foamable composition of claim 18, wherein the foamable composition is substantially free of short chain alcohols.

22. The foamable composition of claim 18, wherein the lanolin is selected from the group consisting of:

i. lanolin, wool fat, lanolin wax, and a synthetic lanolin;

ii. a synthetic lanolin comprising at least one of cholesterol, isocholesterol, and analogs, derivatives, salts, and esters thereof;

iii. an oil-soluble hydrophobic derivative of lanolin;

iv. a synthetic lanolin comprising at least one of cholesterol and isocholesterol covalently linked with an organic moiety;

v. a synthetic lanolin comprising at least one of cholesterol and isocholesterol covalently linked with an aliphatic acid;

vi. a lanolin acid;

vii. an ester of lanolin acid with an aliphatic alcohols; and

viii. a compound selected from the group consisting of acetylated lanolin, isopropyl lanolate, and cetyl lanolate.

23. The foamable composition of claim 18, wherein the concentration range of lanolin is selected from the group of (i) between about 5% and about 12% by weight of the emulsion;

and (ii) between about 12% and about 24% by weight of the emulsion.

24. The foamable composition of claim 18, further comprising 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 steroidal antiinflammatory agent, an immunosuppressive agent, an immunomodulator, an immunoregulating agent, a hormonal agent, 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 E, a vitamin E derivative, a vitamin F, a vitamin F derivative, a 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 mixtures of two or more thereof.

25. The foamable composition of claim 18, wherein the concentration of the non-ionic surface active agent is less than about 2% by weight of the emulsion.

26. The foamable composition of claim 18, wherein the emulsion is a water in oil emulsion.

27. The foamable composition of claim 18, wherein the emulsion is an oil in water emulsion.

28. The foamable composition of claim 18, wherein the polymeric agent is selected from the group consisting of a water-soluble cellulose ether, a naturally-occurring polymeric material, and mixtures of two or more thereof.

29. The foamable composition of claim 18, 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, carrageenan gum, locust bean gum, and tragacanth gum.

36. The foamable composition of claim 18, wherein the concentration of the non-ionic surface active agent is less than about 1% by weight of the emulsion.

30. A method of administering a therapeutic agent to skin, a body cavity, or a mucosal surface comprising:

administering topically to the skin, body cavity or mucosal surface a breakable foamed composition that is thermally stable and collapses upon application of shear force, wherein the foam is obtained by, releasing from a pressurized container a foamable composition comprising an emulsion comprising;

a) a hydrating component comprising lanolin, wherein the lanolin is present in an amount of at least about 5% by weight of the emulsion;

b) about 0.1% to about 5% of a non-ionic surface-active agent by weight of the emulsion;

c) about 0.01% to about 5% by weight of the emulsion of at least one polymeric additive selected from the group consisting of a bioadhesive agent, a gelling agent, a film forming agent and a phase change agent;

d) at least one 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, an steroidal antiinflammatory agent, an immunosuppressive agent, an immunomodulator, an immunoregulating agent, a hormonal agent, 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 E, a vitamin derivative, a vitamin F, a vitamin F derivative, a 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, a 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, a skin whitening agent, a skin protective agent, a masking agent, an anti-wart agent, a refatting agent, a lubricating agent, and mixtures of two or more thereof; and

e) water; and

a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition;

wherein the composition is free of ionic surface active agents.

31. The method of claim 30, wherein the composition further comprises about 0.1% to about 5% by weight of the emulsion of a therapeutically active 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;

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; and

mixtures of two or more thereof.

32. The method of claim 30 or 31, wherein the composition further comprises an additional active agent effective to treat a disorder of skin, a body cavity or a mucosal surface.

33. The method of claim 30, wherein the foamable composition further comprises at least one component, selected from (1) a therapeutically effective foam adjuvant and (2) an organic carrier consisting of at least one therapeutically active oil.

34. The method of claim 30, wherein the foamable composition further comprises a therapeutically effective foam adjuvant and an organic carrier consisting of at least one therapeutically active oil.