Details for Patent: 9,539,208

Title:	Foam prepared from nanoemulsions and uses
Abstract:	The present invention provides a 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, and methods of using such a composition to treat, alleviate, or prevent a disorder of the skin, body cavity, or mucosal surface. The foamable oil in water nano emulsion composition includes: (a) a nano oil globule system, comprising substantially of sub-micron oil globules; (b) about 0.1% to about 5% by weight of at least one stabilizing agent selected from (i) a non-ionic surfactant, (ii) an ionic surfactant, or (iii) a polymeric agent; and (c) a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition, water and optional ingredients. Upon release from an aerosol container, the foamable composition forms and expanded foam suitable for topical administration.
Inventor(s):	Tamarkin; Dov (Macabim, IL), Besonov; Alex (Rehovot, IL), Eini; Meir (Ness Ziona, IL), Danziger; Jorge (Rishom Lezion, IL)
Assignee:	Foamix Pharmaceuticals Ltd. (Rehovot, IL)
Filing Date:	Feb 04, 2014
Application Number:	14/172,466
Claims:	1. A foamable nano-emulsion composition comprising a carrier and a propellant, the carrier comprising: a. a surface active agent, wherein the surface active agent consists of a non-ionic surface-active agent; b. water; c. a liquid hydrophobic organic carrier comprising a mineral oil and a liquid emollient comprising diisopropyl adipate; and d. a polymeric agent selected from the group consisting of a water-soluble cellulose ether, a naturally-occurring polymeric material, a microcrystalline cellulose, a hydrophobically-modified ethoxylated urethane, a carbomer, methylcellulose, a hydroxypropyl cellulose, a hydroxyethyl cellulose, a hydroxypropyl methylcellulose, a methylhydroxyethylcellulose, a hydroxyethyl carboxymethylcellulose, a carboxymethylcellulose, a xanthan gum, a guar gum, a carrageenan gum, a locust bean gum, a tragacanth gum and mixtures of any two or more thereof; wherein the carrier comprises sub-micron oil globules; wherein the propellant is a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the nano-emulsion composition; and wherein the composition is contained in a pressurized container and provides a breakable foam upon release. 2. The composition of claim 1, wherein the non-ionic surface-active agent has an HLB between 9 and 16; and wherein the liquid hydrophobic organic carrier has a required HLB between 7 and 11.5. 3. The composition of claim 1, wherein the carrier further comprises a diol, a triol, or mixtures thereof. 4. The composition of claim 1, wherein the carrier further comprises a foam adjuvant. 5. The composition of claim 1, wherein the non-ionic surface-active agent is about 0.05% to about 20% by weight of the carrier and is selected from the group consisting of a polysorbate, a polyoxyethylene fatty acid ester, a polyoxyethylene alkyl ether, a steareth, a sucrose ester, a partial ester of sorbitol and its anhydrides, sorbitan monolaurate, a monoglyceride, a diglyceride, isoceteth-20 and mono-, di- and tri-esters of sucrose with fatty acids, steareth 2, steareth 21, ceteth-20, sorbitan monooleate, glyceryl monostearate, PEG 40 stearate, polyoxyl 100 monostearate, methyl glucose sesquistearate, polysorbate 80 and mixtures of any two or more thereof. 6. The composition of claim 1, wherein the non-ionic surface-active agent comprises a polyoxyethylene alkyl ether. 7. The composition of claim 4, wherein the foam adjuvant is selected from the group consisting of a fatty alcohol having 15 or more carbons in its carbon chain; a fatty acid having 16 or more carbons in its carbon chain; fatty alcohols derived from beeswax and including a mixture of alcohols, a majority of which have at least 20 carbon atoms in its 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 any two or more thereof. 8. The composition of claim 7, wherein the foam adjuvant is selected from the group consisting of cetyl alcohol, stearyl alcohol, cetostearyl alcohol, and mixtures thereof. 9. The composition of claim 1, further comprising a therapeutic agent. 10. The composition of claim 9, wherein the therapeutic agent is 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 anti-inflammatory agent, an immunosuppressive agent, an immunomodulator, an immunoregulating agent, a hormonal agent, vitamin A, a vitamin A derivative, 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 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, an anti-wrinkle agent, a radical scavenger, a metal oxide, titanium dioxide, zinc oxide, zirconium oxide, iron oxide, silicone oxide, a skin whitening 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. 11. The composition of claim 1, wherein the oil globules of the carrier have a number-average size range of about 40 nm to about 1,000 nm. 12. The composition of claim 11, wherein the oil globules of the carrier have a number-average size range selected from the group consisting of (i) 40 nm to 500 nm; (ii) 40 nm to 200 nm; (iii) 40 nm to 100 nm; (iv) less than 500 nm; (v) less than 200 nm; and (vi) less than 100 nm. 13. The composition of claim 1, wherein the density of the foam is selected from the group consisting of (i) less than 0.12 g/mL; (ii) between 0.02 and 0.12 g/mL; (iii) between 0.04 and 0.10 g/mL; and (iv) between 0.06 and 0.10 g/mL. 14. The composition of claim 1, wherein the composition prior to addition of propellant is translucent with a blue tint. 15. The composition of claim 1, wherein diisopropyl adipate is present at a concentration of about 2% to about 5%, or about 5% to about 10% by weight of the carrier. 16. A foamable nano-emulsion composition comprising a carrier and a propellant, the carrier comprising: a. a surface-active agent, wherein the surface active agent consists of a non-ionic surface active agent comprising a polyoxyethylene alkyl ether having a HLB between 9 and 16; b. water; c. a liquid oil comprising a mineral oil, and a liquid emollient comprising diisopropyl adipate; d. a diol, a triol, or mixtures thereof; and e. a polymeric agent selected from the group consisting of a microcrystalline cellulose, a hydrophobically-modified ethoxylated urethane, a naturally-occurring polymeric material, a locust bean gum, a sodium alginate, a sodium caseinate, egg albumin, a gelatin agar, a carrageenin gum, a xanthan gum, a quince seed extract, a guar gum, a starch, a chemically modified starch, a semi-synthetic polymeric material, a cellulose ether, a hydroxyethyl cellulose, a methyl cellulose, a carboxymethyl cellulose, a hydroxypropyl guar gum, a soluble starch, a cationic cellulose, a cationic guar, a synthetic polymeric material, a carboxyvinyl polymer, a polyvinyl alcohol, a polyacrylic acid polymer, a polyvinyl acetate polymer, a polyvinyl chloride polymer, a polyvinylidene chloride polymer, an acrylic acid/ethyl acrylate copolymer, a water-soluble cellulose ether, a hydroxypropyl cellulose, a hydroxypropyl methylcellulose, a methylhydroxyethylcellulose, a methylhydroxypropylcellulose, a hydroxyethylcarboxymethylcellulose, a carboxymethylhydroxyethylcellulose, a silicone dioxide (fumed silica), a mucoadhesive agent, an acidic synthetic polymer, a carbomer, a poly(methylvinyl ether/maleic anhydride) copolymer, an acidic synthetically modified natural polymer, a neutral synthetically modified natural polymer, a basic amine-bearing polymer, a chitosan, an acidic polymer obtainable from natural sources, an alginic acid, a hyaluronic acid, a pectin, a gum tragacanth, a karaya gum, a neutral synthetic polymer, a natural and chemically modified cyclodextrin, a hydroxypropyl-.beta.-cyclodextrin, an acrylic acid polymer and copolymer, a film forming component, a water-insoluble alkyl cellulose, a water-insoluble hydroxyalkyl cellulose, an ethyl cellulose, a propyl cellulose, a butyl cellulose, a cellulose acetate, a hydroxybutyl cellulose, an ethylhydroxyethyl cellulose, a phase change polymer, a poly(N-isopropylamide), a silicone copolymer, a derivatized starch, a derivatized dexrin, and mixtures of any two or more thereof, wherein the propellant is a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the carrier composition; and wherein the composition is contained in a pressurized container and provides a breakable foam upon release. 17. The composition of claim 16, wherein the surface-active agent is between about 0.2% to about 8% by weight. 18. The composition of claim 16, wherein the triol is a triethanolamine. 19. The composition of claim 16, further comprising a therapeutic agent. 20. The composition of claim 19, wherein the therapeutic agent is an antifungal agent or a retinoid. 21. A method of promoting penetration of a therapeutic agent into a skin or a mucosal membrane, comprising a. releasing the nano-emulsion composition of claim 9 from the pressurized container; b. applying the resultant breakable foam obtained from the composition to a skin or mucosal membrane; and c. spreading the foam so that it is absorbed on the skin or mucosal membrane. 22. The method of claim 21, wherein the therapeutic agent comprises an antifungal agent, and wherein the skin or mucosal membrane has a fungal infection. 23. The method of claim 21, wherein the therapeutic agent comprises a retinoid, and wherein the skin or mucosal membrane has an acne disorder. 24. A method of treating or alleviating a disorder of a skin, body cavity or mucosal surface, comprising administering topically to a subject having said disorder, the breakable foam of the composition of claim 9, wherein the therapeutic agent comprises an antifungal agent and wherein the skin or mucosal membrane has an fungal infection; or wherein the therapeutic agent comprises a retinoid and wherein the skin or mucosal membrane has an acne disorder. 25. The composition of claim 6, wherein the polyoxyethylene alkyl ether comprises a cetostearyl ether and the polymeric agent comprises a hydroxypropyl cellulose. 26. The composition of claim 20, wherein the antifungal agent comprises a naftifine. 27. The composition of claim 26, wherein the polyoxyethylene alkyl ether comprises polyoxyethylene cetylstearyl ether and the polymeric agent comprises a hydroxypropyl cellulose. 28. The composition of claim 3, wherein the diol is selected from the group consisting of a propylene glycol, an ethylene glycol, a hexylene glycol, a diethylene glycol, and mixtures of any two or more thereof. 29. The composition of claim 3, wherein the triol comprises a glycerol, triethanolamine, or a mixture thereof. 30. The composition of claim 16, wherein the polymeric agent is selected from the group consisting of a water-soluble cellulose ether, a naturally-occurring polymeric material, a microcrystalline cellulose, a hydrophobically-modified ethoxylated urethane, a carbomer, a methylcellulose, a hydroxypropyl cellulose, a hydroxyethyl cellulose, a hydroxypropyl methylcellulose, a methylhydroxyethylcellulose, a hydroxyethyl carboxymethylcellulose, a carboxymethylcellulose, a xanthan gum, a guar gum, a carrageenan gum, a locust bean gum, a tragacanth gum and mixtures of any two or more thereof.