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

• US 8,795,635 B2
• Filed: 05/12/2010
• Issued: 08/05/2014
• Est. Priority Date: 11/14/2006
• Status: Active Grant

• Current Assignee: VYNE Therapeutics, Inc.
• Original Assignee: Foamix Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Tamarkin, Dov, Friedman, Doron, Ziv, Enbal, Eini, Meir, Danziger, Jorge, Keynan, Rita, Schuz, David, Berman, Tal
• Primary Examiner(s): Arnold, Ernst
• Assistant Examiner(s): Chang, Kyung Sook
• Application Number:
  US12/778,591
• Publication Number:
  US 20100221195A1
• Time in Patent Office: 1,546 Days
• Field of Search: 424/45
• US Class Current: 424/45
• 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 non-aqueous, substantially non-alcoholic 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 25% to about 95% by weight of the foamable carrier;

(2) a hydrophobic solvent at a concentration of about 1% to about 70% by weight of the foamable carrier; and

(3) at least one foam agent selected from the group consisting of a surfactant, a surfactant system, a foam adjuvant and combinations thereof;

at a concentration of about 0.1% to about 20% by weight of the foamable carrier;

wherein the amount of petrolatum is about the same as or in excess of the hydrophobic solvent and, together, the hydrophobic solvent and petrolatum are present in the foamable carrier at a concentration of at least about 80% by weight of the foamable carrier;

wherein the composition is substantially free of silicone oil;

wherein the composition is substantially free of short chain alcohols having up to 5 carbon atoms in their carbon chain skeleton and one hydroxyl group; and

wherein the composition is stored in a pressurized container and upon release expands to form a breakable foam which breaks upon application of shear force.

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

3. The composition of claim 2, wherein the composition is flowable or flowable to a degree 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 affect and having a foam hardness in the range of about 5 g to about 100 g.

4. The composition of claim 3, wherein the hydrophobic solvent is selected from the group consisting of an unctuous additive, an oil, a therapeutic oil, a PPG alkyl ether, and mixtures thereof.

5. The composition of claim 4, wherein the hydrophobic solvent comprises PPG-15 stearyl ether.

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

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

8. The composition of claim 4, wherein the hydrophobic solvent is a combination of a mineral oil, medium chain triglyceride oil and a PPG alkyl ether.

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

10. The composition of claim 4, wherein the propellant dissolves in the composition.

11. The composition of claim 10, wherein the propellant is selected from the group consisting of a propellant comprising n-butane, a propellant comprising a mixture of n-butane, isobutane and propane;

and a propellant comprising a hydrofluorocarbon.

12. The composition of claim 1, wherein the surfactant or surfactant system is selected from the group consisting of a polysorbate, polyoxyethylene (20) sorbitan monostearate, sorbitan monooleate, polyoxyethylene (20) sorbitan monooleate, a polyoxyethylene fatty acid ester, polyoxyethylene (8) stearate, polyoxyethylene (20) stearate, polyoxyethylene (40) stearate, polyoxyethylene (100) stearate, a polyoxyethylene alkyl ether, polyoxyethylene cetyl ether, polyoxyethylene (23) cetyl ether, polyoxyethylene (2) cetyl ether, polyoxyethylene (10) cetyl ether, a sucrose ester, a partial ester of sorbitol, sorbitan monolaurate, a monoglyceride, a diglyceride, isoceteth-20, ceteth 20, steareth 2, steareth 20, steareth 21, glyceryl monostearate, glucose methyl stearate, methyl glucose sesquistearate, span 20, tween 20, a mono fatty acid sucrose ester, a di fatty acid sucrose ester, a tri fatty acid sucrose ester, laureth-4, poyglyceryl 10 laurate, span 60, a sucrose stearic acid ester, isosteareth 20, and sodium stearyl phthalamate.

13. The composition of claim 12, wherein the surfactant or surfactant system comprises a combination of ceteth 20 and steareth-2 and the amount of surfactant or surfactant system is at a concentration of about 0.1% to about 10% by weight of the foamable carrier.

14. 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.

15. The composition of claim 2, 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, an ionization agent, a stabilizing agent, a preservative and mixtures thereof.

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

18. The composition of claim 3, wherein the active 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 insecticide, a retinoid, an antiproliferative agent, an anticancer agent, a photodynamic therapy agent, an anti-wrinkle agent, a radical scavenger, a metal oxide, titanium dioxide, zinc oxide, zirconium oxide, iron 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 mixtures of any two or more thereof at any proportion or wherein the active 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, magnesium ascorbyl phosphate, minoxidil, mupirocin, salicylic acid, terbinafine, urea, fusidic acid, a hydrocortisone, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, a clobetasol, a halobetasol, a betamethasone, halobetasol, clobetasol-17-propionate, clobetasol-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 dipropionate, 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, flucytosine, fluconazole and mixtures of any two or more thereof.

19. The composition of claim 18, wherein the active agent is selected from the group consisting of vitamin D, a vitamin D derivative, vitamin E, and a vitamin E derivative.

20. The composition of claim 18, wherein the active agent is a combination of calcitriol and alpha tocopherol.

23. A method of treating or alleviating acne in a mammalian subject, the method comprising administering a therapeutically effective amount of a foam produced from the composition of claim 2 to a target site of said mammalian subject having acne, wherein said active ingredient is a tetracycline antibiotic.

24. The composition of claim 1, wherein the at least one foam agent comprises one or more of the following three combinations:

i. ceteareth-6 and stearyl alcohol;

ii. cetearyl alcohol and cetearyl glucoside; and

iii. polyglyceryl-10 pentastearate and behenyl alcohol and sodium stearoyl lactylate.

25. The composition of claim 1, wherein the surfactant or 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, a combination of sorbitan esters, sorbitan monolaurate and sorbitan monooleate, sorbitan monolaurate and sorbitan monostearate, a combination of sucrose esters and sorbitan esters, sucrose stearate and sorbitan monostearate, a combination of a liquid polysorbate and a PEG compound, polyoxyethylene (20) sorbitan monooleate and PEG-40 stearate and methyl glucose sesquistearate, glyceryl stearate and PEG-100 stearate, sorbitan stearate and sucrose cocoate, and polysorbate 80 and PEG-40 stearate.

26. The composition of claim 1, wherein the surfactant or surfactant system comprises a polymeric emulsifier or an acrylates/C10-30 alkyl acrylate crosspolymer.

17. A non-aqueous, substantially non-alcoholic 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 46% to about 95% by weight of the foamable carrier;

(2) a hydrophobic solvent at a concentration of about 1% to about 45% by weight of the foamable carrier;

(3) at least one foam agent selected from the group consisting of a surfactant, a surfactant system;

a foam adjuvant and combinations thereof at a concentration of about 0.1% to about 15% by weight of the foamable carrier; and

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

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

5 to about 100;

30;

wherein the composition is substantially free of silicone oil;

wherein the composition is substantially free of short chain alcohols having up to 5 carbon atoms in their carbon chain skeleton and one hydroxyl group; and

wherein the composition is flowable or flowable to a degree and or is shakable or substantially so when stored in a pressurized container and upon release expands to form a breakable foam which breaks upon application of shear force, and having no substantial or sustained cooling affect and having a foam hardness in the range of about 5 g to about 100 g.

21. The composition of claim 17, wherein the ratio of hydrophobic solvent to petrolatum is between about 1:

1 to about 1;

10.

22. The composition of claim 17, wherein the foam agent comprises a surfactant comprising ceteth-20- or steareth-2 or both ceteth-20 and steareth-2, and a foam agent comprising behenyl alcohol or cetostearyl alcohol or both behenyl alcohol and cetostearyl alcohol.