Topically applicable anti-inflammatory o/w emulsions comprising pro-penetrating glycols

Abstract

Stable, topically applicable, non-greasy and non-tacky oil-in-water (O/W) anti-inflammatory emulsions, useful, e.g., for the treatment of psoriasis, contain: a. a therapeutically effective amount of at least one steroidal anti-inflammatory agent, notably clobetasol propionate; b. a pro-penetrating system which includes at least one pro-penetrating glycol and at least one other pro-penetrating agent; and c. at least one polymeric emulsifier not sensitive to electrolytes, for example not an acrylate/C 10 -C 30 alkyl acrylate copolymer, formulated into a topically applicable, pharmaceutically acceptable vehicle therefor.

1 . A stable, topically applicable, non-greasy and non-tacky oil-in-water (O/W) anti-inflammatory emulsion, comprising:
 a. a therapeutically effective amount of clobetasol propionate;   b. a pro-penetrating system which comprises at least one pro-penetrating glycol and at least one other pro-penetrating agent; and   c. at least one polymeric emulsifier not sensitive to electrolytes, formulated into a topically applicable, pharmaceutically acceptable vehicle therefor;   said emulsion excluding acrylate/C 10 -C 30  alkyl acrylate crosspolymers.   
   
   
       2 . The topically applicable O/W anti-inflammatory emulsion as defined by  claim 1 , said at least one pro-penetrating glycol comprising a C 1  to C 6  alkylene or polyalkylene glycol or a glycol ether and said at least one other pro-penetrating agent comprising a glycol, fatty ester, fatty acid, fatty alcohol or alcohol. 
   
   
       3 . The topically applicable O/W anti-inflammatory emulsion as defined by  claim 1 , said at least one pro-penetrating glycol being selected from the group consisting of ethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, butylene glycol, pentylene glycol, hexylene glycol, propylene glycol dipelargonate, diethylene glycol monoethyl ether, propylene glycol laurate, propylene glycol dicaprate dicaprylate and ethoxydiglycol, and said at least one other pro-penetrating agent being selected from the group consisting of ethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, butylene glycol, pentylene glycol, hexylene glycol, propylene glycol dipelargonate, diethylene glycol monoethyl ether, propylene glycol laurate, propylene glycol dicaprate dicaprylate, ethoxydiglycol, ethanol, dimethyl isosorbide, methylpyrrolidone, oleic acid, PEG-8 capric/caprylic glycerides and oleyl alcohol. 
   
   
       4 . The topically applicable O/W anti-inflammatory emulsion as defined by  claim 1 , said pro-penetrating system comprising a combination of pro-penetrating glycols/agents selected from the group consisting of:
 1. propylene glycol and dimethyl isosorbide,   2. propylene glycol and ethanol,   3. propylene glycol, diethylene glycol monoethyl ether and propylene glycol laurate,   4. propylene glycol and methylpyrrolidone,   5. propylene glycol, dimethyl isosorbide and ethanol, and   6. propylene glycol, methylpyrrolidone and oleyl alcohol.   
   
   
       5 . The topically applicable O/W anti-inflammatory emulsion as defined by  claim 1 , further comprising at least one co-emulsifier. 
   
   
       6 . The topically applicable O/W anti-inflammatory emulsion as defined by  claim 5 , said at least one co-emulsifier being selected from the group consisting of polyglycerol esters of isostearic acid, sorbitan isostearate, sorbitan sesquioleate, sorbitan laurate, glycol esters of isostearic acid, sorbitol esters of oleic acid, glycol esters of oleyl alcohol, oxyethylenated sorbitan monostearate, stearyl alcohol and cetyl alcohol. 
   
   
       7 . The topically applicable O/W anti-inflammatory emulsion as defined by  claim 1 , said at least one polymeric emulsifier not sensitive to electrolytes comprising (a) an acrylic polymer other than an acrylate/C 10 -C 30  alkyl acrylate crosspolymer, and/or comprising (b) a cyanoacrylic polymer. 
   
   
       8 . The topically applicable O/W anti-inflammatory emulsion as defined by  claim 1 , comprising:
 0.0025% to 0.5% of clobetasol propionate,   30% to 50% of a pro-penetrating glycol,   1% to 20% of at least one other pro-penetrating agent,   0.1% to 5% of at least one polymeric emulsifier,   0 to 5% of co-emulsifier.   
   
   
       9 . The topically applicable O/W anti-inflammatory emulsion as defined by  claim 8 , comprising:
 0.0025% to 0.5% of clobetasol propionate,   30% to 50% of at least one pro-penetrating glycol selected from the group consisting of propylene glycol, diethylene glycol monoethyl ether and propylene glycol laurate,   1% to 20% of at least one other pro-penetrating agent selected from the group consisting of diethylene glycol monoethyl ether, propylene glycol laurate, dimethyl isosorbide, ethanol and methylpyrrolidone,   0.1% to 5% of at least one polymeric emulsifier comprising (a) an acrylic polymer other than an acrylate/C 10 -C 30  alkyl acrylate crosspolymer, and/or comprising (b) a cyanoacrylic polymer,   up to 5% of a co-emulsifier selected from the group consisting of PEG-6 isostearate, sorbitan laurate and polyglyceryl-3 disostearate.   
   
   
       10 . The topically applicable O/W anti-inflammatory emulsion as defined by  claim 1 , said at least one polymeric emulsifier not sensitive to electrolytes comprising acrylamide/sodium acryloyldimethyltaurate in a mixture of polysorbate-80 and isohexadecane. 
   
   
       11 . The topically applicable O/W anti-inflammatory emulsion as defined by  claim 1 , comprising from 35% to 47% by weight of said at least one pro-penetrating glycol. 
   
   
       12 . The topically applicable O/W anti-inflammatory emulsion as defined by  claim 11 , comprising from 1% to 20% by weight of said at least one other pro-penetrating agent. 
   
   
       13 . The topically applicable O/W anti-inflammatory emulsion as defined by  claim 1 , having a pH ranging from 5 to 7.5. 
   
   
       14 . The topically applicable O/W anti-inflammatory emulsion as defined by  claim 13 , having a pH ranging from 5.5 to 6.5. 
   
   
       15 . The topically applicable O/W anti-inflammatory emulsion as defined by  claim 4 , further comprising at least one co-emulsifier selected from the group consisting of polyglycerol esters of isostearic acid, sorbitan isostearate, sorbitan sesquioleate, sorbitan laurate, glycol esters of isostearic acid, sorbitol esters of oleic acid, glycol esters of oleyl alcohol, oxyethylenated sorbitan monostearate, stearyl alcohol and cetyl alcohol. 
   
   
       16 . The topically applicable O/W anti-inflammatory emulsion as defined by  claim 15 , said at least one polymeric emulsifier not sensitive to electrolytes comprising (a) an acrylic polymer other than an acrylate/C 10 -C 30  alkyl acrylate crosspolymer and/or comprising (b) a cyanoacrylic polymer. 
   
   
       17 . The topically applicable O/W anti-inflammatory emulsion as defined by  claim 16 , wherein said at least one polymeric emulsifier not sensitive to electrolytes comprises acrylamide/sodium acryloyldimethyltaurate in a mixture of polysorbate-80 and isohexadecane. 
   
   
       18 . A regime or regimen for treating psoriasis, which comprises topically applying onto the affected skin area of an individual in need of such treatment, a thus effective amount of a stable, topically applicable, non-greasy and non-tacky oil-in-water (O/W) anti-inflammatory emulsion as defined by  claim 1 .