Compositions for topical application comprising a peroxide and retinoid

Abstract

The invention relates to a composition for topical application comprising as an active ingredient a peroxide and a retinoid wherein one of said peroxide and retinoid is in the form of first microparticles comprising a solid particulate matter of the active ingredient coated by a metal oxide layer and the other of said peroxide and retinoid is present in an uncoated free form or in a coated form of the active ingredient. The invention further relates to method for treating a surface condition in a subject using said composition, a method for preparing a composition exhibiting improved stability, and a kit comprising: (a) a first composition comprising a peroxide as a first active ingredient; and (b) a second composition comprising a retinoid as a second active ingredient; at least one of said first and said second active ingredient being coated by a metal oxide layer.

1 . A composition for topical application comprising as an active ingredient a peroxide and a retinoid wherein one of said peroxide and retinoid is in the form of first microparticles comprising a solid particulate matter of the active ingredient coated by a metal oxide layer and the other of said peroxide and retinoid is present in an uncoated free form or in a coated form of the active ingredient. 
   
   
       2 . The composition of  claim 1 , wherein said coated form of the active ingredient is second microparticles comprising a solid particulate matter of the active ingredient coated by a metal oxide layer. 
   
   
       3 . The composition of  claim 1 , wherein said first microparticles comprise a solid particulate matter of a peroxide coated by a metal oxide layer. 
   
   
       4 . The composition of  claim 1 , wherein said peroxide is in the form of first microparticles comprising solid particulate matter of peroxide coated by a metal oxide layer and said retinoid is in the form of second microparticles comprising a solid particulate matter of retinoid coated by a metal oxide layer. 
   
   
       5 . The composition of  claim 1 , wherein said peroxide is benzoyl peroxide. 
   
   
       6 . The composition of  claim 1 , wherein said retinoid is selected from all trans retinoic acid, iso-tretinoin, adapalene, tazarotene, and mixtures thereof. 
   
   
       7 . The composition of  claim 1  having an improved stability as compared to a reference composition the difference between said composition and the reference composition being in that in the reference composition the active ingredients are not coated. 
   
   
       8 . The composition according to  claim 1  further comprising an additional active agent. 
   
   
       9 . The composition of  claim 8  wherein said additional active agent is an antibiotic agent. 
   
   
       10 . The composition according to  claim 1 , wherein said metal oxide is selected from silica, titania, alumina, zirconia, ZnO, and mixtures thereof. 
   
   
       11 . The composition according to  claim 10 , wherein said metal oxide is silica. 
   
   
       12 . A composition for topical application comprising as an active ingredient benzoyl peroxide and all trans retinoic acid wherein one of said benzoyl peroxide and all trans retinoic acid is in the form of first microparticles comprising a solid particulate matter of the active ingredient coated by a metal oxide layer and the other of said benzoyl peroxide and all trans retinoic acid is present in an uncoated free form or in a coated form of the active ingredient. 
   
   
       13 . A composition for topical application comprising as an active ingredient benzoyl peroxide and tazarotene wherein one of said benzoyl peroxide and tazarotene is in the form of first microparticles comprising a solid particulate matter of the active ingredient coated by a metal oxide layer and the other of said benzoyl peroxide and tazarotene is present in an uncoated free form or in a coated form of the active ingredient. 
   
   
       14 . The composition of  claim 1 , wherein said first microparticles are prepared by deposition of metal oxide on the surface of the solid particulate matter. 
   
   
       15 . The composition of  claim 14  wherein said first microparticles are prepared by
 (a) contacting the solid, water-insoluble particulate matter, with an ionic additive and an aqueous medium to obtain a dispersion of said particulate matter having positive charges on its surface;   (b) coating the solid, water-insoluble particulate matter, by precipitation of a metal oxide salt onto the surface of the particulate matter, forming a metal oxide coating layer thereon; and   (c) aging said coating layer.   
   
   
       16 . A composition for topical application as defined in  claim 1 , said composition having reduced side effects as compared to a reference composition in which the active ingredients are uncoated. 
   
   
       17 . The composition of  claim 16 , wherein said side effects are selected from irritation, erythema, stinging, itching, scaling, dryness, and combinations thereof. 
   
   
       18 . A method for treating a surface condition in a subject comprising topically administering onto the surface a composition of  claim 1 . 
   
   
       19 . The method of  claim 18 , wherein said surface is skin or mucosal membrane. 
   
   
       20 . The method of  claim 18 , wherein said surface condition is selected from acne, rosacea, psoriasis, photoaging skin, hyperpigmented skin, mucosal infected areas, inflamed dermatitis, and combinations thereof. 
   
   
       21 . A method for preparing a composition comprising as active ingredients a peroxide and a retinoid which are chemically unstable when formulated together, wherein the composition exhibits improved stability of at least one of the active ingredients, the method comprising:
 (a) separating said peroxide and retinoid from each other in the composition by coating a solid particulate matter of one of said active ingredients by a metal oxide coating layer to form first microparticles, the other of said peroxide and retinoid is incorporated into the composition in an uncoated free form or in a coated form of the active ingredient; and   (b) adding excipients for the preparation of the composition.   
   
   
       22 . The method of  claim 21 , wherein said coated form of the active ingredient is prepared by coating a solid particulate matter of the active ingredient by a metal oxide coating layer to form second microparticles. 
   
   
       23 . A kit comprising:
 (a) a first composition comprising a peroxide as a first active ingredient; and   (b) a second composition comprising a retinoid as a second active ingredient; at least one of said first and said second active ingredient being coated by a metal oxide layer.   
   
   
       24 . The kit of  claim 23  wherein one of said first and said second active ingredient being coated by a metal oxide layer and the other is present in an uncoated free form or in a coated form of the active ingredient. 
   
   
       25 . The kit of  claim 23 , further comprising instructions for use in the treatment of a disease or disorder selected from one or more of acne, rosacea, psoriasis, photoaging skin, hyperpigmented skin, inflamed dermatitis, mucosal infected areas, the use comprising combining said first and said second composition for said treatment. 
   
   
       26 . A method of using the kit of  claim 23  wherein said first composition and said second composition are applied concomitantly or sequentially onto a surface of a subject's body.