Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof

Abstract

The present invention teaches a foamable pharmaceutical carrier comprising a benefit agent, selected from the group consisting of a dicarboxylic acid and a dicarboxylic acid ester; a stabilizer selected from the group consisting of at least one surface-active agent; at least one polymeric agent and mixtures thereof; a solvent selected from the group consisting of water, a hydrophilic solvent, a hydrophobic solvent, a potent solvent, a polar solvent, a silicone, an emollient, and mixtures thereof, wherein the benefit agent, stabilizer and solvent are selected to provide a composition that is substantially resistant to aging and to phase separation and or can substantially stabilize other active ingredients. The invention further relates to a foamable composition further containing a liquefied hydrocarbon gas propellant.

What is claimed is: 
     
         1 . A foamable composition comprising a carrier and a liquefied or a compressed gas propellant, the carrier comprising:
 i. a dicarboxylic acid ester;   ii. about 0.2% to about 8% by weight of the carrier of a surface-active agent;   iii. about 2% to about 75% by weight of the carrier of a hydrophobic solvent; and   iv. water,   
       wherein upon release from a foam dispenser, a foam is produced. 
     
     
         2 . The foamable composition of  claim 1 , wherein the liquefied or compressed gas propellant is present at about 3% to about 25% by weight of the carrier. 
     
     
         3 . The foamable composition of  claim 1 , wherein the carrier further comprises an active agent. 
     
     
         4 . The foamable composition of  claim 3 , wherein the active agent is selected from the group consisting of an active herbal extract, an acaricide, an age spot and keratose removing agent, an allergen, an analgesic, a local anesthetic, an antiacne agent, an antiallergic agent, an antiaging agent, an antibacterial, an antibiotic, an antibum agent, an anticancer agent, an antidandruff agent, an antidepressant, an antidermatitis agent, an antiedemic, an antihistamine, an antihelminth, an antihyperkeratolyte agent, an antiinflammatory agent, an antiirritant, an antilipemic, an antimicrobial, an antimycotic, an antiproliferative agent, an antioxidant, an anti-wrinkle agent, an antipruritic, an antipsoriatic agent, an antirosacea agent an antiseborrheic agent, an antiseptic, an antiswelling agent, an antiviral agent, an antiyeast agent, an astringent, a topical cardiovascular agent, a chemotherapeutic agent, a corticosteroid, a dicarboxylic acid, a disinfectant, a fungicide, a hair growth regulator, a hormone, a hydroxy acid, an immunosuppressant, an immunoregulating agent, an insecticide, an insect repellent, a keratolytic agent, a lactam, a metal, a metal oxide, a mitocide, a neuropeptide, a non-steroidal anti-inflammatory agent, an oxidizing agent, a pediculicide, a photodynamic therapy agent, a retinoid, a sanative, a scabicide, a self tanning agent, a skin whitening agent, a vasoconstrictor, a vasodilator, a vitamin, a vitamin D derivative, a wound healing agent, a wart remover and mixtures of any two or more thereof. 
     
     
         5 . The foamable composition of  claim 4 , wherein the active agent comprises tazarotene. 
     
     
         6 . The foamable composition of  claim 1 , wherein the carrier comprises one or more of an emulsion, a micro-emulsion, a nano-emulsion and mixtures of any two or more thereof. 
     
     
         7 . The foamable composition of  claim 6 , wherein the carrier comprises a nano-emulsion. 
     
     
         8 . The foamable composition of  claim 1 , wherein the dicarboxylic acid ester is selected from the group consisting of diisobutyl adipate, diisopropyl adipate, diisopropyl sebacate, diisostearyl dimer dilinoleate, diisostearyl fumerate, diisopropyl dimerate, diethyl adipate, diethyl sebacate, diethylhexyl adipate, diethylhexyl malate, dioctyl malate, diethyl succinate, dioctyl sebacate and mixtures of any two or more thereof. 
     
     
         9 . The foamable composition of  claim 8 , comprising about 2% to about 50% by weight of the carrier of diisopropyl adipate. 
     
     
         10 . The foamable composition of  claim 4 , wherein the active agent comprises a dicarboxylic acid selected from the group consisting of oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, dodecanedioic acid, maleic acid, fumaric acid and mixtures of any two or more thereof. 
     
     
         11 . The foamable composition of  claim 1 , wherein the hydrophobic solvent is selected from the group consisting of a mineral oil, triglycerides, a medium chain triglyceride oil, capric/caprylic triglyceride, alkyl esters of fatty acids, isopropyl palmitate, isopropyl myristate, isopropyl isostearate, polypropylene glycol 15 stearyl ether, octyl palmitate, cetyl lactate, cetyl ricinoleate, tocopheryl acetate, acetylated lanolin alcohol, cetyl acetate, phenyl trimethicone, glyceryl oleate, tocopheryl linoleate, wheat germ glycerides, arachidyl propionate, myristyl lactate, decyl oleate, ricinoleate, isopropyl lanolate, pentaerythrityl tetrastearate, neopentylglycol dicaprylate/dicaprate, isononyl isononanoate, isotridecyl isononanoate, myristyl myristate, triisocetyl citrate, octyl dodecanol, maleated soybean oil, unsaturated or polyunsaturated oils, an olive oil, a corn oil, a soybean oil, a canola oil, a cottonseed oil, a coconut oil, a sesame oil, a sunflower oil, a borage seed oil, a syzigium aromaticum oil, a hempseed oil, a herring oil, a cod-liver oil, a salmon oil, a flaxseed oil, a wheat germ oil, evening primrose oil, essential oils, silicone oils, a dimethicone, a cyclomethicone, a polyalkyl siloxane, a polyaryl siloxane, a polyalkylaryl siloxane, a polyether siloxane copolymer, a poly(dimethylsiloxane)-(diphenyl-siloxane) copolymer, and mixtures of any two or more thereof. 
     
     
         12 . The foamable composition of  claim 11 , comprising a mineral oil. 
     
     
         13 . The foamable composition of  claim 1 , wherein the surface-active agent is selected from the group consisting of a non ionic surface-active agent, a cationic surface-active agent, an amphoteric surface-active agent, an ionic surface-active agent and mixtures of any two or more thereof. 
     
     
         14 . The foamable composition of  claim 13 , wherein the surface-active agent is selected from the group consisting of a polysorbate, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene (20) sorbitan monooleate, a polyoxyethylene fatty acid ester, polyoxyethylene (8) stearate, polyoxyethylene (20) stearate, polyoxyethylene (40) stearate, a polyoxyethylene alkyl ether, polyoxyethylene cetyl ether, polyoxyethylene (23) cetyl ether, polyoxyethylene (2) cetyl ether, polyoxyethylene (20) cetyl ether, a sucrose ester, a partial ester of sorbitol, sorbitan monooleate, sorbitan monolaurate, sorbitan monostearate, a monoglyceride, a diglyceride, glyceryl monostearate, isoceteth-20, steareth 2, steareth 20, steareth 21, ceteareth 20, peg (40) stearate, polyoxyethylene (100) stearate, polysorbate 20, polysorbate 60, polysorbate 80, laureth 4, macrogol cetostearyl ether, peg (30) dipolyhydroxystearate, cetearyl glucoside, methyl glucose sequistearate, sucrose stearic acid esters, sucrose distearate, and mixtures of any two or more thereof. 
     
     
         15 . The foamable composition of  claim 14 , wherein the surface-active agent comprises a macrogol cetostearyl ether. 
     
     
         16 . The foamable composition of  claim 1 , wherein the foamable composition further comprises about 0.1% to about 5% by weight of the carrier of a foam adjuvant selected from the group consisting of a fatty alcohol, a fatty acid and mixtures thereof. 
     
     
         17 . The foamable composition of  claim 1 , wherein the foamable composition further comprises about 0.01% to about 5% by weight of the carrier of a polymeric agent selected from the group consisting of a bioadhesive agent, a gelling agent, a film forming agent, a phase change agent and mixtures of any two or more thereof. 
     
     
         18 . The foamable composition of  claim 1 , wherein the carrier further comprises an additional component selected from the group consisting of a modulating agent, a polar solvent, an anti perspirant, an anti-static agent, a buffering agent, a bulking agent, a chelating agent, a colorant, a conditioner, a deodorant, a diluent, a dye, an emollient, fragrance, a humectant, an occlusive agent, a penetration enhancer, a perfuming agent, a permeation enhancer, a pH-adjusting agent, a preservative, a skin penetration enhancer, a sunscreen, a sun blocking agent, a sunless tanning agent, a vitamin and mixtures of any two or more thereof. 
     
     
         19 . A method of treating a disorder of a mammalian subject, comprising administering the foamable composition of  claim 1  to a target site having a disorder, wherein the target site is selected from the group consisting of the skin, a body cavity, a mucosal surface, the nose, the mouth, the eye, the ear canal, the respiratory system, the vagina and the rectum. 
     
     
         20 . The method of  claim 19 , wherein the target site is the skin and the disorder is selected from the group consisting of acne, acne vulgaris, inflammatory acne, non-inflammatory acne, acne fulminans, nodular papulopustular acne, acne conglobata and mixtures of any two or more thereof.