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.

1 . A foamable oil in water nano emulsion composition comprising:
 (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 the group consisting of
 i. a non-ionic surfactant, 
 ii. an ionic surfactant, and 
 iii. a polymeric agent; 
   (c) water; and   (d) a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition   wherein the oil, stabilizer and water are selected to provide a composition that is substantially homogenous and resistant to aging;   wherein the composition is contained in a pressurized container is substantially flowable and provides a breakable foam upon release, which is thermally stable, yet breaks under sheer force; and   wherein the bubble size of the resultant foam is significantly greater than the bubble size of the resultant foam from a composition with the same ingredients which has not been subject to nano processing.   
     
     
         2 - 20 . (canceled) 
     
     
         1 - 20 . (canceled) 
     
     
         21 . A foamable nano-emulsion composition comprising a carrier and a propellant, the carrier comprising:
 a. one or more of a hydrophobic solvent, a polar solvent, an emollient, and a mixture thereof, at a concentration of about 2% to about 50% by weight of the carrier;   b. a stabilizing agent selected from the group consisting of a surface-active agent, a polymeric agent and a mixture thereof, wherein the surface-active agent comprises a polyoxyethylene alkyl ether, and wherein the polymeric agent comprises a water-soluble cellulose ether;   c. water;   d. optionally a foam adjuvant; and   wherein the carrier comprises submicron 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.   
     
     
         22 . The composition of  claim 21 , wherein the polar solvent is selected from the group consisting of a polyol, glycerol, propylene glycol, hexylene glycol, diethylene glycol, propylene glycol n-alkanols, terpenes, di-terpenes, tri-terpenes, terpen-ols, limonene, terpene-ol, 1-menthol, dioxolane, ethylene glycol, a glycol, sulfoxide, dimethylsulfoxide (DMSO), dimethylformanide, methyl dodecyl sulfoxide, dimethylacetamide, monooleate of ethoxylated glycerides with 8 to 10 ethylene oxide units, azone (1-dodecylazacycloheptan-2-one), 2-(n-nonyl)-1,3-dioxolane, isopropyl myristate/palmitate, ethyl acetate, butyl acetate, methyl proprionate, capric/caprylic triglyceride, octylmyristate, dodecyl-myristate; myristyl alcohol, lauryl alcohol, lauric acid, lauryl lactate ketone, an amide, acetamide oleate, triolein, an alkanoic acid, caprylic acid, a lactam compound, azone, an alkanol, a dialkylamino acetate, a polyethylene glycol, PEG200, PEG300, PEG400, PEG600, and a mixture of any two or more thereof. 
     
     
         23 . The composition of  claim 21 , wherein the emollient is selected from the group consisting of hexyleneglycol, propylene glycol, an isostearic acid derivative, isopropyl palmitate, isopropyl isostearate, diisopropyl adipate, diisopropyl dimerate, maleated soybean oil, octyl palmitate, cetyl lactate, cetyl ricinoleate, tocopheryl acetate, acetylated oil bodies alcohol, cetyl acetate, phenyl trimethicone, glyceryl oleate, tocopheryl linoleate, a wheat germ glyceride, arachidyl propionate, myristyl lactate, decyl oleate, propylene glycol ricinoleate, isopropyl lanolate, pentaerythrityl tetrastearate, neopentylglycol dicaprylate/dicaprate, isononyl isononanoate, isotridecyl isononanoate, myristyl myristate, triisocetyl citrate, octyl dodecanol, sucrose esters of fatty acids, octyl hydroxystearate, and a mixture of any two or more thereof. 
     
     
         24 . The composition of  claim 21 , wherein the hydrophobic solvent is selected from the group consisting of liquid oil, a vegetable oil, a marine oil, an animal oil, saturated oil, unsaturated oil, polyunsaturated oil, olive oil, corn oil, soybean oil, canola oil, cottonseed oil, coconut oil, sesame oil, sunflower oil, borage seed oil, syzigium aromaticum oil, hempseed oil, herring oil, cod-liver oil, salmon oil, flaxseed oil, wheat germ oil, evening primrose oil, poly-unsaturated fatty acid, omega-3 fatty acid, omega-6 fatty acids, linoleic acid, linolenic acid, gamma-linoleic acid (GLA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), an essential oil, a therapeutically active oil, a silicone oil, a non-volatile silicone, polyalkyl siloxanes, polyaryl siloxanes, polyalkylaryl siloxanes and polyether siloxane copolymers, polydimethylsiloxanes (dimethicones) and poly(dimethylsiloxane)-(diphenyl-siloxane) copolymers, cyclic or linear polydimethylsiloxanes containing from about 3 to about 9 silicon atoms, a volatile silicone, cyclomethicone and a mixture of any two or more thereof. 
     
     
         25 . The composition of  claim 21 , wherein the surface-active agent u her comprises a non-ionic surface-active agent. 
     
     
         26 . The composition of  claim 21 , wherein the surface-active agent further comprises a surfactant 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, 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, a phospholipid, sodium lauryl sulphate, cocamidopropylbetaine, and a mixture of any two or more thereof. 
     
     
         27 . The composition of  claim 21 , wherein the polymeric agent further comprises a polymeric agent selected from the group consisting of a naturally-occurring polymeric material, microcrystalline cellulose, hydrophobically-modified ethoxylated urethane, a carbomer, methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose, methylhydroxyethylcellulose, hydroxyethyl carboxymethylcellulose, carboxymethylcellulose, xanthan gum, guar gum, carrageenin gum, locust bean gum, tragacanth gum, and a mixture of any two or more thereof. 
     
     
         28 . The composition of  claim 21 , 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; a fatty alcohol derived from beeswax; a mixture of alcohols, a majority of which have at least 20 carbon atoms in a 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 a mixture of any two or more thereof. 
     
     
         29 . The composition of  claim 28 , wherein the foam adjuvant is selected from the group consisting of cetyl alcohol, stearyl alcohol, cetostearyl alcohol, and a mixture thereof. 
     
     
         30 . The composition of  claim 21 , wherein the carrier further comprises an active agent. 
     
     
         31 . The composition of  claim 30 , wherein the active 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, an steroidal antiinflammatory 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, 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 a mixture of any two or more thereof. 
     
     
         32 . The composition of  claim 21 , wherein the oil globules have an average size selected from the group consisting of (i) about 40 nm to about 1,000 nm; (ii) about 40 nm to about 500 nm; (iii) about 40 nm to about 200 nm; (iv) about 40 nm to about 100 nm; (v) less than about 500 nm; (vi) less than about 200 nm; and (vii) less than about 100 nm. 
     
     
         33 . The composition of  claim 21 , wherein the breakable foam has a density selected from the group consisting of (i) less than about 0.12 g/mL; (ii) between about 0.02 g/mL and about 0.12 g/mL; (iii) between about 0,04 g/mL and about 0.10 g/mL; and (iv) between about 0.06 g/mL and about 0.10 g/mL. 
     
     
         34 . The composition of  claim 23 , wherein the emollient is diisopropyl adipate. 
     
     
         35 . The composition of  claim 24 , wherein the hydrophobic solvent is mineral oil. 
     
     
         36 . The composition of  claim 35 , wherein the carrier comprises a mixture of mineral oil and the emollient in a ratio between 2:8 and 8:2 on a weight basis. 
     
     
         37 . A method of promoting penetration of an active agent into a skin or a mucosal membrane, comprising
 a. releasing the nano-emulsion composition of  claim 30  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 it is absorbed into the skin or mucosal membrane.   
     
     
         38 . A method of treating or alleviating a disorder of a skin, body cavity, and/or mucosal surface, comprising topically administering a breakable foam produced from the composition of  claim 30  to a subject having said disorder, wherein:
 (a) the active agent comprises an antifungal agent and the disorder is an fungal disorder; or 
 (b) the active agent comprises a retinoid and the disease is a sebaceous gland disorder. 
 
     
     
         39 . A method of producing a foam composition having improved foam bubble size comprising: (i) providing an oil in water emulsion formulation, wherein the emulsion comprises (a) oil globules; (b) about 0.1% to about 5% by weight of at least one stabilizing agent selected from the group consisting of a non-ionic surfactant, an ionic surfactant, and a polymeric agent; and (c) water; (ii) subjecting the emulsion to high pressure mechanical stress to produce a nano emulsion; and (iii) filling a sealed pressurized container with the nano emulsion, wherein the container further comprises a liquefied hydrocarbon gas propellant at a concentration of about 3% to about 25% by weight of the composition and has an outlet capable of releasing the nano emulsion as a foam; wherein upon release of the foam, the bubble size is significantly greater than the bubble size of a foam from an oil in water emulsion formulation that is not subjected to high pressure mechanical stress to produce a nano emulsion. 
     
     
         40 . The composition of  claim 21 , wherein the carrier comprises one or more of a hydrophobic solvent, a polar solvent, an emollient, and a mixture thereof, at a concentration of about 2% to about 5% by weight of the carrier. 
     
     
         41 . The composition of  claim 21 , wherein the carrier comprises one or more of a hydrophobic solvent, a polar solvent, an emollient, and a mixture thereof, at a concentration of about 5% to about 10% by weight of the carrier. 
     
     
         42 . The composition of  claim 21 , wherein the carrier comprises one or more of a hydrophobic solvent, a polar solvent, an emollient, and a mixture thereof, at a concentration of about 10% to about 20% by weight of the carrier. 
     
     
         43 . The composition of  claim 21 , wherein the carrier comprises one or more of a hydrophobic solvent, a polar solvent, an emollient, and a mixture thereof, at a concentration of about 20% to about 50% by weight of the carrier.