Hydrogen sulfide releasing polymer compounds

Abstract

The invention provides a hydrogen sulfide releasing polymer compound having a polysaccharide backbone, wherein the compound has at least two substructures, and wherein said substructures are capable of releasing hydrogen sulfide by thiol activation as well as uses thereof. Additionally, a method of treatment and prevention of a skin condition, an ocular disease or osteoarthritis is provided.

1 . A method of treating or preventing a condition, the method comprising the steps of:
 i) providing a hydrogen sulfide releasing polymer compound, wherein the compound has a polysaccharide backbone and at least two substructures,
 wherein said polysaccharide backbone is selected from the group consisting of hyaluronic acid, cellulose derivatives, salts of alginic acid, chondroitin sulfate, dermatan sulfate, chitosan, chitosan derivatives, pectin, and salts of pectin, and 
 wherein said substructures are capable of releasing hydrogen sulfide by thiol activation, and 
   ii) administering the compound locally to an application site, wherein the condition occurs or is expected to occur at said application site.   
     
     
         2 . The method according to  claim 1 , wherein the condition is selected from the group consisting of a skin condition and a skin disease. 
     
     
         3 . The method according to  claim 2 , wherein the condition is a skin disease or skin condition and the step of administering the compound includes topically applying the compound to the skin and subcutaneous or intradermal injection. 
     
     
         4 . The method according to  claim 2 , wherein the condition is a skin disease selected from the group consisting of a wound, a scar, a skin disease being associated with an inflammatory condition, and a reaction following exposure to an allergen or chemical irritant. 
     
     
         5 . The method according to  claim 2 , wherein the condition is a cosmetic condition that is a sign of aging skin selected from the group consisting of skin wrinkles, fine lines, decreased elasticity, broken capillaries, and sun damage. 
     
     
         6 . The method according to  claim 1 , further comprising
 iii) administering a thiol-group containing reaction partner to said application site.   
     
     
         7 . The method according to  claim 6 , wherein the thiol-group containing reaction partner is administered simultaneously with or sequentially to the compound. 
     
     
         8 . The method according to  claim 6 , wherein the thiol-group containing reaction partner is an organic compound of low molecular weight of about 500 Da or below or is selected from the group consisting of cysteine, cysteamine, N-acylcysteine, homocysteine, and glutathione. 
     
     
         9 . The method according to  claim 6 , wherein the thiol-group containing reaction partner is a thiol-group containing polymer having a same polysaccharide backbone selected from the group consisting of hyaluronic acid, cellulose derivatives, salts of alginic acid, chondroitin sulfate, dermatan sulfate, chitosan, chitosan derivatives, pectin, and salts of pectin. 
     
     
         10 . The method according to  claim 1 , wherein said polysaccharide backbone is comprised of hyaluronic acid having a mean molecular weight in the range of about 90 kDa to about 3 MDa. 
     
     
         11 . The method according to  claim 1 , wherein each of the at least two substructures capable of releasing hydrogen sulfide by thiol activation is independently selected from the group consisting of acyl-protected perthiols, N-(acylthio)-benzamides, dithioperoxyanhydrides, arylthioamides, and diallyl disulfide or diallyl trisulfide structures derived from garlic. 
     
     
         12 . The method according to  claim 11 , wherein the at least two substructures are acyl-protected perthiol substructures according to formula I 
       
         
           
           
               
               
           
         
         wherein R 1  is an alkyl, an alkenyl, an alkinyl, an alkylaryl, an aralkyl, or an aryl group, and R 4  is an atom of a repetitive unit of the polysaccharide backbone to which the acyl-protected perthiol substructure is covalently bound. 
       
     
     
         13 . The method according to  claim 1 , wherein said substructures release essentially no hydrogen sulfide by hydrolysis. 
     
     
         14 . A composition comprising:
 i) a hydrogen sulfide releasing polymer compound, wherein the compound has a polysaccharide backbone and at least two substructures,   wherein said polysaccharide backbone is selected from the group consisting of hyaluronic acid, cellulose derivatives, salts of alginic acid, chondroitin sulfate, dermatan sulfate, chitosan, chitosan derivatives, pectin, and salts of pectin and,   wherein said substructures are capable of releasing hydrogen sulfide by thiol activation, and   ii) one or more suitable excipients.   
     
     
         15 . The composition according to  claim 14 , wherein the composition is a hydrogel or aqueous solution. 
     
     
         16 . The composition according to  claim 14 , wherein the composition is provided in the form of kit, the kit comprising a) said composition, b) a second composition comprising a thiol-group containing reaction partner, and c) an instruction for use. 
     
     
         17 . The composition according to  claim 16 , wherein the instruction indicates to administer the composition comprising the thiol-group containing reaction partner simultaneously or sequentially to the composition comprising the compound. 
     
     
         18 . The composition according to  claim 14 , wherein the composition is a stable composition in the sense that it does not release hydrogen sulfide without contact to a thiol-group containing reaction partner. 
     
     
         19 . A method of treating or preventing a skin condition, wherein the skin condition is a cosmetic or medical condition, the method comprising the steps of:
 i) providing a topical formulation comprising a hydrogen sulfide releasing polymer compound, wherein the compound has a polysaccharide backbone and at least two sub structures,
 wherein said polysaccharide backbone is selected from the group consisting of hyaluronic acid, cellulose derivatives, salts of alginic acid, chondroitin sulfate, dermatan sulfate, chitosan, chitosan derivatives, pectin, and salts of pectin, and 
 wherein said substructures are capable of releasing hydrogen sulfide by thiol activation, and 
   ii) administering the topical formulation locally onto or into a skin area, wherein the skin area shows the cosmetic or medical skin condition or wherein the skin area is suspected to develop the cosmetic or medical skin condition.   
     
     
         20 . The method according to  claim 19 , wherein the topical formulation is
 a wound dressing   a dermal patch, or   a liquid or semi-solid preparation, such as a suspension, emulsion, gel, ointment, or cream.