Topical anti-inflammatory pharmaceutical composition with zileuton cream formulation

Abstract

Provided herein is a zileuton cream type topical anti-inflammatory pharmaceutical composition, and more particularly, a zileuton cream type topical anti-inflammatory pharmaceutical composition capable of retaining stability at room temperature and of being applied topically to maximize medical effects while minimizing absorption to an entirety of body, thereby minimizing toxicity caused by the compound so as to be suitable to topical treatment of skin diseases caused by leukotriene.

We claim: 
     
         1 . A cream type topical anti-inflammatory pharmaceutical composition, comprising zileuton, an aqueous solvent, an organic solvent, a thickening agent, and an emulsifier. 
     
     
         2 . The composition according to  claim 1 ,
 wherein the aqueous solvent is water or a pH buffer solution.   
     
     
         3 . The composition according to  claim 2 ,
 wherein the aqueous solution is a pH buffer solution having a pH of about 4 to about 5.   
     
     
         4 . The composition according to  claim 3 ,
 wherein the pH buffer solution is citrate buffer, acetate buffer or phthalate buffer.   
     
     
         5 . The composition according to  claim 1 ,
 wherein the organic solvent is at least one selected from the group consisting of ethanol, polyethylene glycol, hexylene glycol, propylene glycol monocaprylate, benzyl alcohol, N-methyl pyrrolidone, triacetin, isopropyl myristate, propylene glycol dicaprylocaprate, medium chain triglycerides, castor oil, olive oil, safflower oil, light mineral oil, squalane, dimethicone, cyclomethicone, polyglyceryl-6 dioleate, polyglyceryl-10 monooleate, polyglyceryl-10 dioleate, polyoxyl 40 hydrogenated castor oil, caprylocaproyl polyoxyl-8 glycerides, polyoxyethylene (20) sorbitan monolaurate, diethylene glycol monoethyl ether, and dimethyl sulfoxide.   
     
     
         6 . The composition according to  claim 5 ,
 wherein the organic solvent is propylene glycol.   
     
     
         7 . The composition according to  claim 1 ,
 wherein the thickening agent comprises at least one of white petrolatum and white wax.   
     
     
         8 . The composition according to  claim 1 ,
 wherein the emulsifier is at least one of phospholipid, stearyl alcohol and propylene glycol stearate.   
     
     
         9 . The composition according to  claim 1 , wherein the composition further comprises an emulsifier. 
     
     
         10 . The composition according to  claim 9 , wherein the emulsifier comprises hydrogenated lecithin. 
     
     
         11 . The composition according to  claim 1 , wherein the composition further comprises a preservative. 
     
     
         12 . The composition according to  claim 11 , wherein the preservative is at least one selected from a group consisting of methylparaben, ethylparaben, propylparaben, isobutylparaben, butyl paraben, 2-phenoxy ethanol, and 4-hydroxybenzoic acid. 
     
     
         13 . The composition according to  claim 11 , wherein the composition comprises zileuton of about 0.05 to about 2 weight %; water or pH buffer solution of about 30 to about 34 weight %; white petrolatum of about 36 to about 40 weight %; white wax of about 4 to about 8 weight %; propylene glycol of about 16 to about 22 weight %; phospholipid of about 2 to about 6 weight %; and preservative of about 0.005 to about 0.04 weight. 
     
     
         14 . The composition according to  claim 11 , wherein the composition comprises zileuton of about 0.1 to about 1 weight %; water or pH buffer solution of about 31 to about 33 weight %; white petrolatum of about 37 to about 39 weight %; white wax of about 5 to about 7 weight %; propylene glycol of about 18 to about 20 weight %; phospholipid of about 3 to about 5 weight %; and preservative of about 0.01 to about 0.03 weight %. 
     
     
         15 . The composition according to  claim 1 , wherein the composition is formulated for topical application to human skin. 
     
     
         16 . The composition according to  claim 1 , wherein zileuton is racemic zileuton. 
     
     
         17 . A method for relieving or treating atopic dermatitis, acne, urticaria, psoriasis, eczema, a bullous skin disease, collagenoses, Sjogren-Larsson syndrome, or acne in skin lesions of mastocytosis, wherein said method comprises administering, to a subject in need of such relief or treatment, a composition of  claim 1 . 
     
     
         18 . The method according to  17 , wherein the composition is applied topically to human skin. 
     
     
         19 . A method for preparing a cream type topical anti-inflammatory pharmaceutical composition, comprising:
 mixing zileuton, an aqueous solvent, an organic solvent, a thickening agent, and an emulsifier under a mixing condition of a temperature of about 30 to about 80° C. and about 600 to about 1200 rpm.   
     
     
         20 . The method according to  claim 19 , wherein the aqueous solvent is a water or a pH buffer solution having a pH of about 4 to about 5. 
     
     
         21 . The method according to  claim 19 , wherein, in the mixing, a preservative is further mixed. 
     
     
         22 . The method according to  claim 19 , further comprising cooling a resultant of the mixing at a temperature of about 20 to about 30° C. while stirring at about 600 rpm or less.