Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses

• US 9,682,021 B2
• Filed: 02/25/2014
• Issued: 06/20/2017
• Est. Priority Date: 11/14/2006
• Status: Active Grant

• Current Assignee: VYNE Therapeutics, Inc.
• Original Assignee: Foamix Pharmaceuticals, Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Tamarkin, Dov, Friedman, Doron, Eini, Meir, Keynan, Rita, Schuz, David, Ziv, Enbal, Danziger, Jorge, Berman, Tal
• Primary Examiner(s): Singh, Anoop
• Assistant Examiner(s): PHAN, DOAN THI-THUC
• Application Number:
  US14/189,559
• Publication Number:
  US 20140248219A1
• Time in Patent Office: 1,211 Days
• CPC Class Codes: A61K 2800/31 Anhydrous
• CPC Class Codes: A61K 47/06 Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
• CPC Class Codes: A61K 8/046 Aerosols; Foams
• 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: A61P 17/00 Drugs for dermatological disorders
• 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 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: A61Q 19/00 Preparations for care of the skin

Abstract

The present invention relates to stable substantially non-aqueous, non-alcoholic, non-silicone, foamable carrier compositions comprising petrolatum or mixtures thereof, at least one foam agent, at least one propellant, and with and without the addition of an active agent. The formulations may contain a solvent substantially miscible therein. The present invention further provides a method of treating, alleviating or preventing a disorder of mammalian subject in need thereof, comprising administering the above-mentioned compositions to an afflicted target site of said mammalian subject.

Claims

1. A foamable composition comprising:

a foamable carrier and at least one liquefied or compressed gas propellant, the foamable carrier comprising;

(1) a petrolatum or mixtures thereof at a concentration of about 50% to about 95% by weight of the foamable carrier;

(2) a solvent substantially miscible in the petrolatum at a concentration of 0% to about 50% by weight of the foamable carrier; and

(3) a foam adjuvant comprising a fatty alcohol and either a surfactant or a surfactant system at a concentration of about 0.1% to about 20% by weight of the foamable carrier;

wherein the surfactant is selected from the group consisting of a polyoxyethylene fatty acid ester, a polyoxyethylene alkylyl ether, a sucrose ester, a monoglyceride, a diglyceride, glucose methyl stearate, methyl glucose sesquistearate, polyglyceryl 10 laurate, sodium stearyl phtalmate and a mixture of any two or more thereof;

or

wherein the surfactant system is a combination of at least two surfactants selected from the group consisting of at least two polyoxyethylene alkyl ethers, steareth 2 and steareth 20, steareth 2 and Steareth 21, polyoxyethylene (40) stearate and polyoxyethylene (100) stearate, a combination of sucrose esters, sucrose stearate and sucrose distearate, and glyceryl stearate and PEG-100 stearate;

wherein the composition is non-aqueous;

wherein the composition does not contain a sorbitan fatty acid ester;

wherein the ratio of the foamable carrier to the propellant ranges from about 100;

10 to about 100;

35; and

wherein the composition is stored in a pressurized container and upon release expands to form a breakable foam.

2. The composition of claim 1, wherein the foamable carrier further comprises at least one active pharmaceutical agent.

3. The composition of claim 1, wherein the composition is flowable and/or is shakable or substantially so when stored in a pressurized container and upon release expands to form a breakable foam having no substantial or sustained cooling effect and having a foam hardness in the range of about 5 g to about 100 g.

4. The composition of claim 1, wherein the solvent is hydrophobic and is selected from the group consisting of an unctuous additive, an oil, a therapeutic oil, a PPG alkyl ether, or a combination of any two or more thereof.

5. The composition of claim 4, wherein the solvent comprises a PPG15 stearyl ether.

6. The composition of claim 4, wherein the solvent comprises a mineral oil.

7. The composition of claim 4, wherein the solvent comprises a medium chain triglyceride oil.

8. The composition of claim 1, wherein the carrier has a viscosity from about 12,000 cP to about 500,000 cP.

9. The composition of claim 1, wherein the propellant dissolves in the composition.

10. The composition of claim 9, wherein the propellant comprises n-butane, a mixture of n-butane, isobutane and propane, a hydrofluorocarbon or a mixture of any two or more thereof.

11. The composition of claim 1, wherein the foam adjuvant is selected from one or more of the group consisting of cetyl alcohol, stearyl alcohol, myristyl alcohol, oleyl alcohol, behenyl alcohol, and cetostearyl alcohol.

12. The composition of claim 1, wherein the foamable carrier further comprises at least one modulating agent selected from the group consisting of a pH adjuster, a buffering agent, a chelator, an antioxidant and an ionization agent a stabilizing agent, and a preservative.

13. The composition of claim 1, wherein the foamable carrier further comprises a polymeric agent, wherein the polymeric agent is 0.01% to 5% by weight of the foamable carrier and is selected from the group consisting of a bioadhesive agent, a gelling agent, a film forming agent and a phase change agent.

14. The composition of claim 1, wherein the solvent is at a concentration of not more than or about 40% by weight of the composition.

15. The composition of claim 2, wherein the active pharmaceutical agent is selected from the group consisting of an anti-infective agent, an antibiotic agent, an antibacterial agent, an antifungal agent, an antiviral agent, an antiparasitic agent, a steroidal anti-inflammatory agent, a nonsteroidal anti-inflammatory agent, an immunosuppressive agent, an immunomodulator, an immunoregulating agent, a hormonal agent, a steroid, a vasoactive agent, a vasoconstructor, a vasodilator, vitamin A, a vitamin A derivative, a retinoid, vitamin B, a vitamin B derivative, vitamin C, a vitamin C derivative, vitamin D, a vitamin D derivative,vitamin E, a vitamin E derivative, vitamin F, a vitamin F derivative, vitamin K, a vitamin K derivative, a wound healing agent, a burn 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, an insectoside, a retinoid, an antiproliferative agent, an anticancer agent, a photodynamic therapy agent, an anti-wrinkle agent, a radical scavenger, a metal oxide, silicone oxide, talc, an anti-acne agent, a skin whitening agent, a self tanning agent, an anti-cellulite agent, a skin protective agent, a masking agent, an anti-wart agent, a refatting agent, a lubricating agent and mixture of any two or more thereof at any proportion;

or

wherein the active pharmaceutical agent is selected from the group consisting of acyclovir, azelaic acid, allantoin, ammonium lactate, benzoyl peroxide, caffeine, calcipotriol, calcitriol, nicotinamide, ciclopirox olamine, clindamycin hydrochloride, clindamycin phosphate, clindamycin palmitate hydrochloride, coal tar, cyanocobalamine, diclofenac sodium, gentamycin sulphate, lactic acid, glycyrrhizinic acid, map (magnesium ascorbyl phosphate), minoxidil, mupirocin, salicylic acid, terbinafine, urea, fusidic acid, a hydrocortisone, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, a clobetasol, a halobetasol, a batamethsone;

halobetasol and clobetasol-17-propionate or 17-butyrate;

ketoconazole, lidocaine hydrochloride, metronidazole, tetracycline, tetracycline hydrochloride, meclocycline sulfosalicylate, resorcinol, chloramphenicol, erythromycin, acriflavinium monochloride, ethacridine lactate, dibrompropamidine isetionate, chlorhexidine acetate, chlorhexidine gluconate, chlorhexidine hydrochloride, hexamidine isetionate, phenol, povidone-iodine, dequalinium chloride, hydroxyquinoline sulfate, potassium hydroxyquinoline sulphate, benzalkonium chloride, cetrimonium bromide, cetylpyridinium chloride, cetrimide, phenylmercuric acetate, phenylmercuric borate, mercuric chloride, silver nitrate, potassium permanganate, tosylchloramide sodium, prednisolone sodium phosphate, betamethasone sodium phosphate, betamethasone 17-valerate, betamethasone diproprionate, demeclocycline, demeclocycline hydrochloride, chlortetracycline hydrochloride, oxytetracycline hydrochloride, neomycin sulfate, bacitracin zinc, gentamicin sulphate, amikacin, amikacin sulphate, sulfathiazole sodium, mafenide acetate, idoxuridine, fumaric acid, mepyramine maleate, tripelennamine hydrochloride, promethazine hydrochloride, dimetindene maleate, diphenhydramine hydrochloride, cinchocaine hydrochloride, oxybuprocaine hydrochloride, benzocaine, tetracaine hydrochloride, pramoxine hydrochloride, panthenol, dexpanthenol, calcium pantothenate, hyaluronic acid, trypsin, aminobenzoic acid, methylrosanilinium chloride, sodium butyl hydroxybenzoate, sodium ethyl hydroxybenzoate, sodium methyl hydroxybenzoate, sodium propyl hydroxybenzoate, terbinafine HCL, flucytosine, miconazole nitrate, clotrimazole and fluconazole and mixtures of any two or more thereof.

16. The composition of claim 15, wherein the active pharmaceutical agent is selected from the group consisting of a nonsteroidal anti-inflammatory drug, an immunosuppressive agent, an immunomodulator, an immunoregulating agent, a hormonal agent, a steroid, a steroidal anti-inflammatory agent, vitamin A, a vitamin A derivative, vitamin D, a vitamin D derivative, vitamin E, a vitamin E derivative and mixtures of any two or more thereof.

17. The composition of claim 15, wherein the active pharmaceutical agent is selected from a group consisting of zinc oxide, clindamicin phosphate, clotrimazole, diclofenace sodium, betamethasone 17 valerate micronized, caffeine, lidocaine base, terbinafine HCl, acyclovir, azelaic acid, miconazole nitrate and mixtures of any two or more thereof.

18. The composition of claim 13, wherein the polymeric agent is selected from the group consisting of aluminum starch octenyl succinate, an alkyl lactate, a cellulose ether, xantham gum and a mixture of any two or more thereof.

21. The composition of claim 15, wherein the metal oxide is selected from titanium dioxide, a zinc oxide, a zirconium oxide, an iron oxide, and a mixture of any two or more thereof.

23. The composition of claim 18, wherein the polymeric agent is selected from the group consisting of C-12 to C-15 alkyl lactate, carboxymethl cellulose sodium, microcrystalline cellulose, a cellulose ether, and a mixture of any two or more thereof.

26. The composition of claim 1, wherein the composition is substantially free of a silicone oil.

27. The composition of claim 1, wherein the composition does not contain a silicone oil.

31. The composition of claim 8, wherein the carrier has a viscosity selected from the group consisting of about 20,000 CPs to about 500,000 CPs, about 50,000 CPs to about 500,000 CPs, and about 100,000 CPs to about 500,000 CPs.

32. The composition of claim 1, wherein the carrier has a viscosity of about 125,000 CPs or less.

19. A foamable composition comprising:

a foamable carrier and at least one liquefied or compressed gas propellant, wherein the foamable carrier comprises;

(1) a petrolatum mixture at a concentration in excess of about 55% by weight of the foamable carrier;

(2) a solvent substantially miscible in the petrolatum at a concentration of about 0% to about 40% by weight of the foamable carrier;

(3) a foam adjuvant comprising a fatty alcohol and, optionally, at least one foam agent selected from the group consisting of a surfactant, a surfactant system, and combinations thereof at a concentration of about 0.1% to about 20% by weight of the foamable carrier; and

(4) an effective amount of an active pharmaceutical agent;

wherein the composition is non-aqueous;

wherein the composition does not contain a sorbitan fatty acid ester;

wherein the ratio of the foamable carrier to the propellant ranges from about 100;

10 to about 100;

35; and

wherein the composition is stored in an pressurized container and is flowable such that upon release expands to form a breakable foam.

20. The composition of claim 19, wherein the carrier further comprises at least one solvent selected from the group consisting of a hydrophilic solvent, a hydrophobic solvent, a polar solvent, a penetrating agent and mixture of any two or more thereof.

22. The composition of claim 19, wherein the breakable foam has no substantial or sustained cooling effect and has a foam hardness in the range of about 5g to about 100g.

28. The composition of claim 19, wherein the composition is substantially free of a silicone oil.

29. The composition of claim 19, wherein the composition is free of a silicone oil.

24. A foamable composition comprising:

a foamable carrier and at least one liquefied or compressed gas propellant, the foamable earner comprising;

(1) a petrolatum mixture at a concentration of about 50% to about 95% by weight of the foamable carrier;

(2) a solvent substantially miscible in the petrolatum at a concentration of 0% to about 50% by weight of the foamable carrier;

(3) a foam adjuvant comprising a fatty alcohol and either a surfactant or a surfactant system, at a concentration of about 0.1% to about 20% by weight of the foamable carrier; and

(4) a silicone oil;

wherein the surfactant is selected from the group consisting of a polyoxyethylene fatty acid ester, a polyoxyethylene alkylyl ether, a sucrose esyer, a monoglyceride, a diglyceride, glucose methyl stearate, methyl glucose sesquistearate, polyglyceryl 10 laurate, sodium stearyl phtalmate and a mixture of any two or more thereof;

or

wherein the surfactant system is a combination of at least two surfactants selected from the group consisting of at least two polyoxyethylene alkyl ethers, steareth 2 and steareth 20, steareth 2 and steareth 21, polyoxyethylene (40) stearate and poloyoxyethylene (100) stearate, a combination of sucrose esters, sucrose stearate and sucrose distearate, and glyceryl stearate and PEG-I 00 stearate;

wherein the composition is non-aqueous;

wherein the composition does not contain a sorbitan fatty acid ester;

wherein the ratio of the foamable carrier to the propellant ranges from about 100;

10 to about 100;

35; and

wherein the composition is stored in a pressurized container and upon release expands to form a breakable foam.

25. The composition of claim 24, wherein the silicone oil at a concentration of less than 5% by weight of the foamable carrier.

30. A foamable composition comprising:

a foamable carrier and at least one liquefied or compressed gas propellant, the foamable carrier comprising;

(1) a petrolatum or petrolatum mixture thereof at a concentration of about 50% to about 95% by weight of the foamable carrier;

(2) a solvent substantially miscible in the petrolatum at a concentration of 0% to about 50% by weight of the foamable carrier; and

(3) a foam adjuvant comprising a fatty alcohol and either a surfactant or a surfactant system at a concentration of about 0.1% to about 20% by weight of the foamable carrier;

wherein the composition is non-aqueous;

wherein the composition does not contain a sorbitan fatty acid ester;

wherein the ratio of the foamable carrier to the propellant ranges from about 100;

10 to about 100;

35; and

wherein the composition is stored in a pressurized container and upon release expands to form a breakable foam.