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 . A sprayable, storage stable, substantially anhydrous topical composition comprising
 a therapeutically effective amount of a vitamin D derivative or analogue and a therapeutically effective amount of a corticosteroid, the vitamin D derivative or analogue and the corticosteroid being dissolved in a pharmaceutically acceptable propellant selected from the group consisting of dimethyl ether, diethyl ether and methylethyl ether or a propellant mixture comprising a first propellant selected from the group consisting of dimethyl ether, diethyl ether and methylethyl ether and a second propellant selected from the group consisting of C 3-5  alkanes, hydrofluoroalkanes, hydrochloroalkanes, fluoroalkanes and chlorofluoroalkanes,   the composition further comprising a pharmaceutically acceptable lipid carrier solubilized or suspended in said propellant or propellant mixture, the lipid carrier comprising one or more lipids which on application on skin and evaporation of the propellant form a semi-solid and occlusive layer at the site of application.   
     
     
         2 . A composition according to  claim 1 , wherein the vitamin D derivative or analogue is selected from the group consisting of calcitriol, tacalcitol, maxacalcitol, paricalcitol and alfacalcidol. 
     
     
         3 . (canceled) 
     
     
         4 . A composition according to  claim 1 , wherein the corticosteroid is selected from the group consisting of budenoside, clobetasol, clobetasone, desoximethasone, diflucortolon, diflorasone, fluocinonide, fluocinolon, halcinonide, halobetasol, hydrocortisone, mometasone, triamcinolone and pharmaceutically acceptable esters of any of the foregoing. 
     
     
         5 . A composition according to  claim 4 , wherein the corticosteroid ester is selected from betamethasone valerate, clobetasol propionate, hydrocortisone acetate, and hydrocortisone butyrate. 
     
     
         6 . A composition according to  claim 1  further comprising a non-evaporating oily cosolvent selected from at least one of the following solvent classes
 (a) a compound of general formula I
   H(OCH 2 C(CH 3 )H)OR 1    
 
 wherein R 1  is straight or branched chain C 1-20  alkyl, and x is an integer of 2-60; 
 (b) an isopropyl ester of a straight or branched chain C 10-18  alkanoic or alkenoic acid; 
 (c) a propylene glycol diester of a C 8-14  alkanoic or alkenoic acid; 
 (d) a straight or branched C 8-24  alkanol or alkenol; 
 (e) highly purified vegetable oils; and 
 (f) N-alkylpyrrolidone or N-alkylpiperidone. 
 
     
     
         7 . A composition according to  claim 6 , wherein the compound of general formula I is selected from polyoxypropylene-15-stearyl ether, polyoxypropylene-11-stearyl ether, polyoxypropylene-14-butyl ether, polyoxypropylene-10-cetyl ether, and polyoxypropylene-3-myristyl ether. 
     
     
         8 . A composition according to  claim 6 , wherein the isopropyl ester of a straight or branched chain C 10-18  alkanoic or alkenoic acid is selected from isopropyl myristate, isopropyl palmitate, isopropyl isostearate, isopropyl linolate, and isopropyl monooleate. 
     
     
         9 . A composition according to  claim 6 , wherein the propylene glycol diester of a C 8-14  alkanoic acid is propylene glycol dipelargonate. 
     
     
         10 . A composition according to  claim 6 , wherein the straight C 8-24  alkanol is selected from capryl, lauryl, cetyl, stearyl, oieyl, linoelyl, and myristyl alcohol, or wherein the branched C 8-24  alkanol is a branched C 18-24  alkanol. 
     
     
         11 . A composition according to  claim 6 , wherein the N-alkylpyrrolidone is N-methylpyrrolidone. 
     
     
         12 . A composition according to  claim 1 , wherein the propellant is dimethyl ether. 
     
     
         13 . A composition according to  claim 1 , wherein the first propellant of the propellant mixture is dimethyl ether. 
     
     
         14 . A composition according to  claim 1 , wherein the second propellant of the propellant mixture is a C 3-5 alkane, selected from the group consisting of n-propane, isopropane, n-butane and isobutane. 
     
     
         15 . A composition according to  claim 14 , wherein the C 3-5 alkane is selected from n-butane and isobutane. 
     
     
         16 . A composition according to  claim 15 , wherein the ratio of n-butane and isobutane to dimethyl ether is in the range of 6:1-0:1 v/v. 
     
     
         17 - 21 . (canceled) 
     
     
         22 . A pressurized container adapted to dispensing a topical composition on an affected skin area, the container including a container body comprising a composition according to  claim 1  and a valve assembly including an actuator for releasing the composition as a spray. 
     
     
         23 . A container according to  claim 22 , wherein the valve assembly contains at least one aperture with a diameter of 0.05-1 mm. 
     
     
         24 . A container according to  claim 22 , wherein the actuator is provided with an orifice with a diameter of 0.3-1.5 mm. 
     
     
         25 - 26 . (canceled)