Antifungal formulations

Abstract

A topical composition and the method using the composition, which contains an antifungal agent and a low potency anti-inflammatory steroid which is safe and effective such as desonide or its derivative. The low potency steroid agent does not cause side effects such as skin atrophy, striae and hypopigmentation. The composition can be formulated in a dosage form such as a cream, ointment, gel, lotion, foam, powder, aerosol, spray, shampoo, or liquid solution. The composition can be used to treat a fungal disease such as tinea pedis, tinea capitis, tinea corporis, tinea versicolor, tinea cruris, and candidiasis as well as intertriginous dermatitis complicated by candidiasis.

1 - 16 . (canceled) 
     
     
         17 . A topical antifungal composition comprising:
 a) a therapeutically effective amount of an azole-containing antifungal compound for treating a fungal disease or a pharmaceutically acceptable salt thereof; and   b) a therapeutically effective amount of a low to low-medium potency steroidal anti-inflammatory causing minimal skin atrophy, striae and hypopigmentation, in a concentration between 0.01 wt % and 5.0 wt %, and having a higher potency than 1 wt % hydrocortisone, and   c) a carrier suitable for administration of the antifungal compound and the steroidal anti-inflammatory to the skin, wherein the composition does not cause the steroids to penetrate the skin and cause undesirable local side effects.   
     
     
         18 . The antifungal composition of  claim 17  wherein the steroidal anti-inflammatory has the following structure: 
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , R 3 , and R 4  taken independently can be H, C1-C10 alkyl, C1-C10 alkenyl, C3-C10 cycloalkyl, and phenyl groups; R 1  and R 2  taken together can be C3-C10 cycloalkyl; and R 3  and R 4  taken independently can be H, C1-C10 alkyl, C1-C10 alkenyl, C3-C10 cycloalkyl, phenyl, C7-C10 phenylalkyl, carboxylate, sulfonyl, phosphoryl, and phosphonyl groups. 
     
     
         19 . The composition of  claim 18  wherein R 1 , R 2 , R 3 , and R 4  groups are independently H, CH 3 , ethyl, propyl, phenyl, and phenylmethyl groups. 
     
     
         20 . The composition of  claim 17  wherein the steroidal anti-inflammatory is selected from the group consisting of Fluocinolone acetonide, Hydrocortisone valerate, Hydrocortisone butyrate, Alclometasone dipropionate, Desonide, and hydrocortisone probutate. 
     
     
         21 . The composition of  claim 17  wherein the antifungal is selected from the group consisting of Ketoconazole, Econoazole, Miconazole, Itraconazole, Fluconazole, Econazole, Clotrimazole, Oxiconazole, Terconazole, Tioconazole, and Clotrimazole. 
     
     
         22 . The composition of  claim 17 , wherein the composition is formulated as a cream, ointment, gel, lotion, foam, powder, aerosol, spray, shampoo, or liquid solution. 
     
     
         23 . The composition of  claim 17  having a pH of about 3.5 to about 7.0 further comprising: at least one solvent, at least one emollient, at least one humectant, at least one preservative, and at least one emulsifier; and optionally including an acid, base, or buffering agent to adjust the pH. 
     
     
         24 . The composition of  claim 23 , wherein the solvent is selected from the group consisting of propylene glycol, butylene glycol, hexylene glycol, polyethylene glycols, polypropylene glycols, and polyurethane compounds; the emollient is selected from the group consisting of white petrolatum, mineral oil, propylene glycol dicaprylate, lower fatty acid esters and lower alkyl ethers of propylene glycol, cetyl alcohol, cetostearyl alcohol, stearyl alcohol, stearic acid, cetyl esters wax, spermaceti wax, and white wax; the humectant is selected from the group consisting of glycerin and sorbitol; and the emulsifier is selected from the group consisting of glyceryl monostearate, glyceryl monoleate, stearic acid, polyoxyethylene cetyl ether, polyoxyethylene cetostearyl ether, polyoxyethylene stearyl ether, and polyethylene glycol stearate; wherein the optional acid is selected from the group consisting of hydrochloric acid and phosphoric acid, the optional base is chosen from diethanolamine, triethanolamine, and sodium hydroxide, the optional buffering agent is chosen from monobasic sodium phosphate and dibasic sodium phosphate, and the preservative is chosen from benzyl alcohol, sodium benzoate and parabens. 
     
     
         25 . The composition of  claim 17  wherein the antifungal is in an amount effective to treat fungal disease selected from the group consisting of tinea pedis, tinea capitis, tinea corporis, tinea versicolor, scalp disorders, tinea cruris, and candidiasis. 
     
     
         26 . A method of treating a fungal disease comprising administering to a subject in need of treatment the composition of any of  claim 17 , with a thin application of the composition two times per day to the affected areas. 
     
     
         27 . The method of  claim 26  wherein the subject is a child of under 10 years old. 
     
     
         28 . The method of  claim 26  wherein the fungal disease is selected from the group consisting of tinea pedis, tinea capitis, tinea corporis, tinea versicolor, scalp disorders, tinea cruris, and candidiasis. 
     
     
         29 . The composition of  claim 17  wherein the steroidal anti-inflammatory is not halogenated.