Oleaginous pharmaceutical and cosmetic foam

• US 7,820,145 B2
• Filed: 04/28/2004
• Issued: 10/26/2010
• Est. Priority Date: 08/04/2003
• Status: Active Grant

• Current Assignee: VYNE Therapeutics, Inc.
• Original Assignee: Foamix Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Besonov, Alex, Friedman, Doron, Tamarkin, Dov, Eini, Meir
• Primary Examiner(s): Wax; Robert A
• Assistant Examiner(s): Mercier; Melissa S
• Application Number:
  US10/835,505
• Publication Number:
  US 20050031547A1
• Time in Patent Office: 2,372 Days
• Field of Search: None
• US Class Current: 424/45
• CPC Class Codes: A01N 25/16 Foams
• CPC Class Codes: A61K 31/351 not condensed with another ring
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 38/13 Cyclosporins
• 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 8/046 Aerosols; Foams
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• 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: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61Q 19/00 : Preparations for care of the skin

Abstract

The invention relates to stable oleaginous cosmetic or therapeutic foam compositions containing certain active agents, having unique therapeutic properties and methods of treatment using such compositions. The foamable composition includes at least one solvent selected from a hydrophobic solvent, a silicone oil, an emollient, a co-solvent, and mixtures thereof, wherein the solvent is present at a concentration of about 70% to about 96.5% by weight of the total composition, at least a non-ionic surface-active agent at a concentration of about 0.1% to less than about 10% by weight of the total composition; at least one gelling agent at a concentration of about 0.1% to about 5% by weight of the total composition; a therapeutically effective amount of at least one active agent; and at least one liquefied or compressed gas propellant, at a concentration of about 3% to about 25% by weight of the total composition.

Claims

1. An oleaginous foamable therapeutic composition, comprising:

a. about 70% to about 96.5% of a solvent phase, wherein the solvent phase comprises;

i) a hydrophobic solvent, a silicone oil, or a mixture thereof and

ii) optionally an emollient, a co-solvent, or a mixture thereof

b. at least a non-ionic surface-active agent at a concentration of about 0.1% to less than about 10% by weight of the total composition;

c. at least one gelling agent at a concentration of about 0.1% to about 5% by weight of the total composition;

d. a therapeutically effective amount of at least one active agent; and

f. at least one liquefied or compressed gas propellant, at a concentration of about 3% to about 25% by weight of the total composition,

wherein the composition forms a breakable foam upon dispensing that collapses upon application of shear force; and

wherein the specific gravity of the foam is less than about 0.5 g/mL; and

wherein the water content of the composition is less than about 30% by weight.

2. The oleaginous composition of claim 1, comprising less than about 5% of a lower alcohol, having up to 5 carbon atoms in its carbon chain skeleton.

3. The oleaginous composition of claim 1, further comprising a foam adjuvant selected from the group consisting of fatty alcohols having greater than or equal to 15 carbons and fatty acids having greater than or equal to 16 carbons.

4. The oleaginous composition of claim 1, wherein the hydrophobic solvent has solubility in distilled water at ambient temperatures of less than about one gram per 100 mL.

5. The oleaginous composition of claim 1, wherein the hydrophobic solvent is selected from the group consisting of mineral oil, triglyceride oil, an ester of a fatty acid, an ester of a decarboxylase acid, polyunsaturated oil, unsaturated oil, and an essential oil.

6. The oleaginous composition of claim 1, wherein the solvent phase comprises a mixture of at least one hydrophobic solvent and at least one co-solvent.

7. The oleaginous composition of claim 6, wherein the mixture of at least one hydrophobic solvent and the at least one co-solvent comprises a weight ratio of about 1:

8 to about 8;

1.

8. The oleaginous composition of claim 7, wherein the mixture forms an emulsion.

9. The oleaginous composition of claim 7, wherein the at least one co-solvent comprises glycerin.

10. The oleaginous composition of claim 9, wherein the mixture of at least one hydrophobic solvent and glycerin comprises a weight ratio of about 1:

4 to about 4;

1.

11. The oleaginous composition of claim 9, wherein the mixture of at least one hydrophobic solvent and glycerin comprises a weight ratio of about 1:

2 to about 2;

1.

12. The oleaginous composition of claim 1 or 6, wherein the co solvent is polyethyelene glycol.

13. The oleaginous composition of claim 1, further comprising an ionic surface-active agent, wherein the mixture of the non-ionic surface-active agent and the ionic surface-active agent is present at a weight ratio of about 20:

1 to about 1;

1 non-ionic surface-active agent to ionic surface-active agent.

14. The oleaginous foam able composition of claim 1, wherein the concentration of the nonionic surfactant is from about 0.1% to less than about 2%.

15. The oleaginous composition of claim 1, wherein the at least one gelling agent is one or more gelling agents selected from the group consisting of natural polymeric materials, semi-synthetic polymeric materials, synthetic polymeric materials, inorganic gelling agents and mixtures thereof.

16. The oleaginous composition of claim 1, wherein the water content is less than about 20% by weight.

17. The oleaginous composition of claim 1, wherein the composition is contained within a pressurized container.

18. The oleaginous composition of claim 1 wherein the specific gravity of the foam is about 0.01 gr/ml to about 0.3 gr/mL upon release from the pressurized container.

19. The oleaginous composition of claim 1, wherein the active agent is selected to treat a dermatological or mucosal disorder that is bacterial, fungal, viral, parasitic, inflammatory, autoimmune, allergic, hormonal, malignant and combinations thereof.

20. The oleaginous composition of claim 1 wherein the active agent is a component of the foamable composition selected from a solvent, a surface-active agent, a gelling agent and a foam adjuvant.

21. The oleaginous composition of claim 1, wherein the at least one active agent is selected from a therapeutic agent and a cosmetic agent.

22. The oleaginous composition of claim 21, wherein the at least one therapeutic agent is selected from an anti-infective, an antibiotic, an antibacterial agent, an antifungal agent, an antiviral agent, an antiparasitic agent, an antiinflammatory agent, an immunosuppressive agent, and immunomodulator, an immuno regulating agent, an anesthetic, an analgesic, an antiallergic agent, a corticosteroid, a retinoid, an antiproliferative agent, an anticancer agent, a photodynamic therapy agent, a lubricating agent and mixtures thereof.

23. The oleaginous composition of claim 22, wherein the therapeutic agent is selected for the treatment of a disorder of the skin, mucosal membrane, ear channel, vagina, penile urethra, colon and rectum.

24. The oleaginous composition of claim 22, wherein the cosmetic agent is selected from a retinoid, an anti-wrinkle agent, a radical scavenger, a self-tanning agent, a skin whitening agent, a skin protective agent, an anti-cellulite agent, a massaging oil and an anti-wart agent.

25. The oleaginous composition of claim 22, wherein the therapeutic agent is intended for transdermal delivery.

26. The oleaginous composition of claim 1, wherein the at least one active agent is an inorganic solid matter.

27. The oleaginous composition of claim 26, wherein the inorganic solid matter is a metal oxide for forming a protective layer on a body surface or a mucosal membrane.

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

29. The oleaginous composition of claim 28, wherein the at least one nonionic surfactant is a non-ionic lipophilic surfactant having an HLB value of about 3 to about 10.

30. The oleaginous composition of claim 29, comprising less than about 5% of a lower alcohol, having up to 5 carbon atoms in its carbon chain.

31. The oleaginous emulsion of claim 29, further comprising a foam adjuvant selected from the group consisting of fatty alcohols having greater than or equal to 15 carbons and fatty acids having greater than or equal to 16 carbons.

32. The oleaginous composition of claim 29, wherein the hydrophobic solvent has solubility in distilled water at ambient temperatures of less than about one gram per 100 mL.

33. The oleaginous composition of claim 32, wherein the hydrophobic solvent is selected from the group consisting of mineral oil, triglyceride oil, an ester of a fatty acid, an ester of a dicarboxylic acid, polyunsatured oil, unsaturated oil, and an essential oil.

34. The oleaginous emulsion of claim 29, wherein the at least one hydrophobic solvent and water are present at a weight ratio in the range of about 1:

3 to about 6;

1.

35. The oleaginous foam able composition of claim 29, wherein the concentration of the nonionic lipophilic surfactant is from about 0.1% to less than about 2%.

36. The oleaginous foam able composition of claim 35, wherein the non-ionic lipophilic surfactant is selected from the group consisting of soribitan derivatives, alkoxylated alcohols, hydroxylated derivatives of polymeric silicones, alkylated derivatives of hydroxylated polymeric silicones, glyceryl esters, beeswax derivatives, lecithin and mixtures thereof.

37. The oleaginous emulsion of claim 29, wherein the at least one gelling agent is selected from the group consisting of natural polymeric materials, semi-synthetic polymeric materials, synthetic polymeric materials, inorganic gelling agents and mixtures thereof.

38. The oleaginous emulsion of claim 37, wherein the inorganic gelling agent comprises silicone dioxide.

39. The oleaginous emulsion of claim 29, having a specific gravity of about 0.01 gr/ml to about 0.3 gr/mL, upon extrusion from a pressured container.

40. The oleaginous emulsion of claim 29, wherein the at least one active agent is a component of the foamable composition and is selected from a solvent, a surface-active agent, a gelling agent and a foam adjuvant.

41. The oleaginous emulsion of claim 29 wherein the at least one active agent is selected from an anti-infective, an antibiotic, an antibacterial agent, an antifungal agent, an antiviral agent, an antiparasitic agent, an antiinflammatory agent, an anesthetic, an analgesic, an antiallergic agent, a corticosteroid, a retinoid, an antiproliferative agent, an anticancer agent, a photodynamic therapy agent, an anti-wrinkle agent, a radical scavenger, a self-tanning agent, a skin whitening agent, a skin protective agent, an anti-cellulite agent, a massaging oil and an anti-wart agent, a refatting agent, a lubricating agent and mixtures thereof.

42. The oleaginous composition of claim 29, wherein the active agent is selected for the treatment of a disorder of the skin, mucosal membrane, ear channel, vagina, penile urethra, and rectum.

43. The oleaginous emulsion of claim 29, wherein the active agent is intended for transdermal delivery.

44. The oleaginous emulsion of claim 29, having the properties of breakable foam for treating, alleviating or preventing a dermatological or mucosal disorder.

45. The oleaginous composition of claim 44, wherein the etiology of the dermatological or mucosal disorder is bacterial, fungal, viral, parasitic, inflammatory, autoimmune, allergic, hormonal, malignant, and combinations thereof.

46. The oleaginous emulsion of claim 29, wherein the at least one active agent is an inorganic solid matter.

47. The oleaginous emulsion of claim 46, wherein the inorganic solid matter is selected to form a protective layer on a body surface or a mucosal membrane.

48. The oleaginous emulsion of claim 46, wherein the inorganic solid matter is selected to treat a skin disorder selected from sensitive skin, diaper rash and diaper dermatitis.

49. The oleaginous emulsion of claim 46, further comprising at least one active agent, selected from antibacterial agent, antifungals agent and anti-inflammatory agent.

50. A method of treating, alleviating or preventing a dermatological, cosmetic or mucosal disorder, comprising administering topically to a subject having said disorder a therapeutically effective amount of an oleaginous foam composition according to claim 1.

51. The oleaginous foam able composition of claim 1, further comprising a phospholipids non-ionic surfactant at concentration of about 0.1% to about 25% by weight of the total composition.

52. The oleaginous composition of claim 51 wherein the phospholipid comprises phosphatidylchlorine.

53. The composition of claim 51, wherein the phospholipid comprises lecithin.

54. A therapeutic device, comprising a pressurized can, equipped with a metered dose valve and an actuator capable of dispensing a foam, and containing an oleaginous foam composition according to claim 1 or claim 29.

55. The device of claim 54, wherein the metered dose valve provides a unit dose of between about 10 μ

L and about 1000 μ

L.

56. The device of claim 54, wherein the metered dose valve provides a unit dose of between about 50 μ

L and about 250 μ

L.

57. The oleaginous foamable therapeutic composition of claim 1, wherein said co-solvent is one or more co-solvents selected from the group consisting of polyols, sulfoxides, oleates, lactam compounds, esters, amides, alkanoic acids, and alkanols and admixtures thereof.

58. The oleaginous foamable therapeutic composition of claim 1, further comprising an ionic surface-active agent.

59. The oleaginous foamable therapeutic composition of claim 1, wherein said active agent is selected to treat a dermatological or mucosal disorder.

60. The oleaginous foamable therapeutic composition of claim 26, wherein the inorganic solid matter comprises a metal oxide.

61. The oleaginous foamable water-in-oil emulsion of claim 29, wherein said co-solvent is one or more co-solvents selected from the group consisting of polyols, sulfoxides, oleates, lactam compounds, esters, amides, alkanoic acids, and alkanols and admixtures thereof.

62. The oleaginous foamable water-in-oil emulsion of claim 61, wherein the gelling agent is one or more gelling agents selected from the group consisting of natural polymeric materials, semi-synthetic polymeric materials, synthetic polymeric materials, inorganic gelling agents and mixtures thereof.

63. The oleaginous foamable water-in-oil emulsion of claim 62, wherein the inorganic gelling agent comprises silicone dioxide.

64. The oleaginous foamable water-in-oil emulsion of claim 29, having a specific gravity of about 0.02 gr/ml to about 0.4 gr/mL, upon extrusion from a pressured container.

65. The oleaginous foamable water-in-oil emulsion of claim 29 comprising less than about 5% of a short chain alcohols having up to 5 carbon atoms in the short chain alcohol carbon chain.

66. The oleaginous foamable therapeutic composition of claim 51, further comprising an ionic surface-active agent.

67. The oleaginous composition of claim 1, wherein the co-solvent solubilizes the active agent substantially better than mineral oil solubilizes the active agent.