Compositions and methods for treating and preventing dermatoses

Abstract

The invention encompasses protectant agents including uracil or a metabolite thereof that effectively treat the cutaneous toxicities and dermatological side-effects associated with chemotherapeutic agents. Specifically, and surprisingly, the compositions of the invention including uracil or a metabolite thereof are effective for treating various dermatoses including atopic dermatitis, irritant contact dermatitis, radiation-induced dermatitis, dry skin dermatitis, papulopustular rashes, xerosis, pruritus, actinic keratosis, and genital warts.

1 - 42 . (canceled) 
     
     
         43 . A method of protecting a mucosal epithelium of a mouth of a patient from undesirable side-effects of an anticancer composition comprising 5-fluorouracil or a prodrug thereof, the method comprising:
 administering a pharmaceutical composition comprising uracil to the mucosal epithelium of the mouth of the patient so as to establish a local concentration of uracil in the mucosal epithelium sufficient to protect the mucosal epithelium from the undesirable side-effects, with a circulating concentration of uracil induced by administration of the pharmaceutical composition being insufficient to abrogate a clinical efficacy of the anticancer composition.   
     
     
         44 . The method of  claim 43 , wherein the anticancer composition comprises 5-fluorouracil. 
     
     
         45 . The method of  claim 43 , wherein the anticancer composition comprises the prodrug, wherein the prodrug is selected from the group consisting of ftorafur, doxifluridine, and capecitabine. 
     
     
         46 . The method of  claim 43 , wherein uracil is present in the pharmaceutical composition at a pharmaceutical concentration by weight of at least about 0.01%. 
     
     
         47 . The method of  claim 43 , wherein uracil is present in the pharmaceutical composition at a pharmaceutical concentration by weight of no more than about 60%. 
     
     
         48 . The method of  claim 43 , wherein the pharmaceutical composition further comprises at least one carrier generating a delivery vehicle selected from the group consisting of an oral emulsion, a magma, a gel, a swish, a lozenge, a paste, a cream, an oral solution, and a gum. 
     
     
         49 . The method of  claim 43 , wherein the undesirable side-effects comprise chemotherapy-induced stomatitis. 
     
     
         50 . The method of  claim 43 , wherein the pharmaceutical composition further comprises a gel-like vehicle such that the pharmaceutical composition is a topical gel-like formulation. 
     
     
         51 . The method of  claim 50 , wherein the gel-like vehicle comprises a water-soluble gelling agent, a humectant, and water, and wherein the gel-like vehicle has a viscosity of about 10,000 to 50,000 cps at 25° C. as measured with a Brookfield viscometer. 
     
     
         52 . The method of  claim 51 , wherein the water-soluble gelling agent is selected from the group consisting of agar, bentonite, carbomer, carbopol, a water-soluble cellulosic polymer, carboxyalkyl cellulose, hydroxyalkyl cellulose, alkyl cellulose, hydroxyalkyl alkylcellulose, povidone, kaolin, tragacanth, veegum, and hydroxypropyl methylcellulose. 
     
     
         53 . The method of  claim 51 , wherein the humectant is selected from the group consisting of glycerin, propylene glycol, and sorbitol. 
     
     
         54 . The method of  claim 51 , wherein the gel-like vehicle comprises 0.1% (w/w) to 10% (w/w) water-soluble gelling agent and 0.1% (w/w) to 20% (w/w) humectant. 
     
     
         55 . The method of  claim 50 , wherein the gel-like vehicle further comprises at least one antimicrobial preservative. 
     
     
         56 . The method of  claim 43 , wherein the pharmaceutical composition further comprises 1% (w/w) to 10% (w/w) of at least one sweetening agent. 
     
     
         57 . The method of  claim 43  further comprising the step of systemically administering the anticancer composition to the patient. 
     
     
         58 . A kit for oral delivery of an anticancer composition with protection of a mucosal epithelium of a mouth of a patient from undesirable side-effects, the kit comprising:
 at least one dose of the anticancer composition, wherein the anticancer composition comprises 5-fluorouracil or a prodrug thereof; and   at least one dose of a pharmaceutical composition comprising uracil for topical administration to the mucosal epithelium to establish a local concentration of uracil in the mucosal epithelium sufficient to protect the mucosal epithelium from the undesirable side-effects of the anticancer composition, with a circulating concentration of uracil from the pharmaceutical composition being insufficient to abrogate a clinical efficacy of the anticancer composition.   
     
     
         59 . The kit of  claim 58 , wherein the pharmaceutical composition further comprises at least one carrier generating a delivery vehicle selected from the group consisting of an oral emulsion, a magma, a gel, a swish, a lozenge, a paste, a cream, an oral solution, and a gum. 
     
     
         60 . The kit of  claim 58 , wherein the undesirable side-effects comprise chemotherapy-induced stomatitis. 
     
     
         61 . The kit of  claim 58 , wherein the pharmaceutical composition further comprises a gel-like vehicle such that the pharmaceutical composition is a topical gel-like formulation. 
     
     
         62 . The kit of  claim 58 , wherein the gel-like vehicle comprises a water-soluble gelling agent, a humectant, and water, and wherein the gel-like vehicle has a viscosity of about 10,000 to 50,000 cps at 25° C. as measured with a Brookfield viscometer. 
     
     
         63 . The kit of  claim 62 , wherein the water-soluble gelling agent is selected from the group consisting of agar, bentonite, carbomer, carbopol, a water-soluble cellulosic polymer, carboxyalkyl cellulose, hydroxyalkyl cellulose, alkyl cellulose, hydroxyalkyl alkylcellulose, povidone, kaolin, tragacanth, veegum, and hydroxypropyl methylcellulose. 
     
     
         64 . The kit of  claim 62 , wherein the humectant is selected from the group consisting of glycerin, propylene glycol, and sorbitol. 
     
     
         65 . The kit of  claim 62 , wherein the gel-like vehicle comprises 0.1% (w/w) to 10% (w/w) water-soluble gelling agent and 0.1% (w/w) to 20% (w/w) humectant. 
     
     
         66 . The kit of  claim 61 , wherein the gel-like vehicle further comprises at least one antimicrobial preservative.