Pharmaceutical spray composition comprising a vitamin d analogue and corticosteroid

Abstract

The present invention relates to a topical spray composition comprising a biologically active vitamin D derivative or analogue and a corticosteroid, and its use in the treatment of dermal diseases and conditions.

1 - 26 . (canceled) 
     
     
         27 . A sprayable, storage stable, substantially anhydrous topical composition comprising:
 (a) a therapeutically effective amount of calcipotriol or calcipotriol monohydrate, and   (b) a therapeutically effective amount of a betamethasone ester,   wherein the calcipotriol or calcipotriol monohydrate and betamethasone ester are dissolved in (i) a pharmaceutically acceptable propellant comprising dimethyl ether, or (ii) a pharmaceutically acceptable propellant mixture comprising a first propellant comprising dimethyl ether and a second propellant selected from the group consisting of C 3-5  alkanes, hydrofluoroalkanes, hydrochloroalkanes, fluoroalkanes, and chlorofluoroalkanes, and   (c) a pharmaceutically acceptable lipid carrier solubilized or suspended in the propellant or propellant mixture,   wherein the composition does not include propylene glycol.   
     
     
         28 . The composition of  claim 27 , wherein the propellant mixture comprises a C 3-5  alkane. 
     
     
         29 . The composition of  claim 28 , wherein the C 3-5  alkane is propane, isopropane, n-butane, isobutane, or mixtures thereof. 
     
     
         30 . The composition of  claim 29 , wherein the C 3-5  alkane is n-butane. 
     
     
         31 . The composition of  claim 29 , wherein the pharmaceutically acceptable propellant further comprises a pharmaceutically acceptable oily cosolvent. 
     
     
         32 . The composition of  claim 27 , wherein the pharmaceutically acceptable lipid carrier comprises petrolatum. 
     
     
         33 . The composition of  claim 32 , wherein the petrolatum is white soft paraffin. 
     
     
         34 . The composition of  claim 27 , wherein each gram of the composition, excluding any mass contributed by any pharmaceutically acceptable propellant, comprises 52.2 mcg of calcipotriol monohydrate and 0.643 mg of betamethasone dipropionate, and wherein the pharmaceutically acceptable lipid carrier comprises petrolatum, and wherein the composition further comprises a pharmaceutically acceptable oily cosolvent. 
     
     
         35 . The composition of  claim 31 , wherein
 (a) the calcipotriol or calcipotriol monohydrate comprises 0.001-0.05% w/w of the total composition,   (b) the betamethasone dipropionate comprises 0.0005-1% w/w of the total composition, and   (c) the pharmaceutically acceptable oily co-solvent comprises 0.1-10% w/w of the total composition.   
     
     
         36 . The composition of  claim 35 , wherein the composition comprises calcipotriol, and wherein
 (a) the calcipotriol is present in an amount of 0.005% w/w of the composition, excluding any mass contributed by any pharmaceutically acceptable propellant, and   (b) the betamethasone dipropionate is present in an amount of 0.064% w/w of the composition, excluding any mass contributed by any pharmaceutically acceptable propellant.   
     
     
         37 . The composition of  claim 31 , wherein the oily co-solvent comprises a compound of general formula I: H(OCH 2 C(CH 3 )H) x OR 1  wherein R 1  is a straight or branched chain C 1-20  alkyl, and x is an integer from 2 to 60 inclusive. 
     
     
         38 . The composition of  claim 37 , wherein the compound of general formula I is polyoxypropylene-15-stearyl ether, polyoxypropylene-11-stearyl ether, polyoxypropylene-14-butyl ether, polyoxypropylene-10-cetyl ether, or polyoxypropylene-3-myristyl ether. 
     
     
         39 . The composition of  claim 31 , wherein the oily co-solvent comprises an isopropyl ester of a straight or branched chain C 10-18  alkanoic or alkenoic acid. 
     
     
         40 . The composition of  claim 39 , wherein the isopropyl ester of a straight or branched chain C 10-18  alkanoic or alkenoic acid is isopropyl myristate, isopropyl palmitate, isopropyl isostearate, isopropyl linolate, or isopropyl monooleate. 
     
     
         41 . The composition of  claim 31 , wherein the oily co-solvent comprises a straight or branched C 8-24  alkanol or alkenol. 
     
     
         42 . The composition of  claim 41 , wherein (i) the straight C 8-24  alkanol is capryl alcohol, lauryl alcohol, cetyl alcohol, stearyl alcohol, or myristyl alcohol, (ii) the straight C 8-24  alkenol is oleyl alcohol or linoleyl alcohol, and/or (iii) the branched C 8-24  alkanol is a branched C 18-24  alkanol. 
     
     
         43 . The composition of  claim 42 , wherein the straight C 8-24  alkanol is myristyl alcohol. 
     
     
         44 . The composition of  claim 27 , wherein the pharmaceutically acceptable lipid carrier is a mixture of liquid paraffin and petrolatum. 
     
     
         45 . The composition of  claim 45 , further comprising a pharmaceutically acceptable oily co-solvent and the petrolatum is white soft paraffin.