Methods of Use To Orally and Topically Treat Acne and Other Skin Conditions By Administering a 19-NOR Containing Vitamin D Analog With or Without a Retinoid

Abstract

Oral and topical pharmaceutical compositions, kits and methods of treatment thereof for treating various skin disorder including acne, psoriasis, ichthyosis, photoaging, photodamaged skin, and, skin cancer. Exemplary vitamin D analogs as active pharmaceutical ingredients include 2-methylene-19-nor-20(S)-1α-hydroxy-bishomopregnacalciferol, 19-nor-26,27-dimethylene-20(S)-2-methylene-1α,25-dihydroxyvitamin D 3 , 2-methylene-1α,25-dihydroxy-(17E)-17(20)-dehydro-19-nor-vitamin D 3 , 2-methylene-19-nor-(24R)-1α,25-dihydroxyvitamin D 2 , 2-methylene-(20R,25S)-19,26-dinor-1α,25-dihydroxyvitamin D 3 , 2-methylene-19-nor-1α-hydroxy-pregnacalciferol, 1α-hydroxy-2-methylene-19-nor-homopregnacalciferol, (20R)-1α-hydroxy-2-methylene-19-nor-bishomopregnacalciferol, 2-methylene-19-nor-(20S)-1α-hydroxy-trishomopregnacalciferol, 2-methylene-23,23-difluoro-1α-hydroxy-19-nor-bishomopregnacalciferol, 2-methylene-(20S)-23,23-difluoro-1α-hydroxy-19-nor-bishomopregnancalciferol, (2-(3′ hydroxypropyl-1′,2′-idene)-19,23,24-trinor-(20S)-1α-hydroxyvitamin D 3 , 2-methylene-18,19-dinor-(20S)-1α,25-dihydroxyvitamin D 3 , a stereoisomer thereof, a prodrug thereof in oral compositions, a salt thereof, and/or a solute thereof. Compounds that activate retinoic acid receptors, such as retinoyls and retinoyl esters, include 13-cis-retinoic acid, all-trans-retinoic acid, (2E,4E,6Z,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexeneyl)nona-2,4,6,8-tetraenoic acid, 9-(4-methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethyl-nona-2,4,6,8-tetraenoic acid, 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-napthoic acid, 4-[1-(3,5,5,8,8-pentamethyl-tetralin-2-yl)ethenyl]benzoic acid, retinobenzoic acid, ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)ethynyl]pyridine-3-carboxylate, retinoyl t-butyrate, retinoyl pinacol, retinoyl cholesterol, an isomer thereof, a prodrug thereof for oral compositions, an ester thereof, a salt thereof, and/or, a solute thereof. Combinations of such active ingredients demonstrate synergistic efficacy.

1 . A method of treating a skin disorder, comprising administering an effective amount of a composition comprising a 19-nor-containing vitamin D compound, a stereoisomer thereof, a salt thereof or a solute thereof, wherein the medicament is administrable daily or intermittently and wherein the symptoms of the skin disorder are treated. 
     
     
         2 . The method of  claim 1 , wherein the 19-nor-containing vitamin D compound is selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       a stereoisomer thereof, a salt thereof, and a solute thereof. 
     
     
         3 . The method of  claim 1 , wherein the compound is 
       
         
           
           
               
               
           
         
       
       a stereoisomer thereof, a salt thereof or a solute thereof. 
     
     
         4 . The method of  claim 3 , wherein the compound is administered topically in an amount ranging from 340 mg to 0.34 μg/kg BW /day. 
     
     
         5 . The method of  claim 1 , wherein the compound is 
       
         
           
           
               
               
           
         
       
       a stereoisomer thereof, a salt thereof, or a solute thereof. 
     
     
         6 . The method of  claim 5 , wherein the compound is administered topically in an amount ranging from 340 mg to 0.34 μg/kg BW /day. 
     
     
         7 . The method of  claim 1 , wherein the compound is 
       
         
           
           
               
               
           
         
       
       a stereoisomer thereof, a salt thereof, or a solute thereof. 
     
     
         8 . The method of  claim 7  wherein the compound is administered topically in an amount ranging from 340 mg to 0.34 μg/kg BW /day. 
     
     
         9 . The method of  claim 1  wherein the compound is administered topically. 
     
     
         10 . The method of  claim 9  wherein the compound further comprises a pharmaceutically acceptable carrier system, the carrier system comprising 30% to 70% ethanol and 70% to 30% propylene glycol. 
     
     
         11 . The method of  claim 1  wherein the compound is administered orally. 
     
     
         12 . The method of  claim 1 , wherein the skin disorder is selected from the group consisting of acne, psoriasis, ichthyosis, photoaging, photodamaged skin and skin cancer. 
     
     
         13 . The method of  claim 12  wherein the skin disorder is acne and the treatment of the skin disorder comprises reducing comedone area. 
     
     
         14 . The method of  claim 1  additionally comprising the step of administering a compound or prodrug thereof that activates the retinoic acid receptor. 
     
     
         15 . The method of  claim 14  wherein the compound or prodrug thereof that activates the retinoic acid receptor is administered orally and the 19-nor containing vitamin D compound is administered topically.