Hyaluronic acid derivatives containing groups able to release no

Abstract

Disclosed are hyaluronic acid derivatives functionalised with S-nitrosothiol groups of the general formula: wherein HA indicates hyaluronic acid and G indicates a suitable spacer.

1 . A hyaluronic acid derivative functionalised with S-nitrosothiol groups of the general formula: 
     
       
         
         
             
             
         
       
       wherein HA indicates hyaluronic acid and G indicates a suitable spacer. 
     
   
   
       2 . The hyaluronic acid derivative according to in  claim 1 , wherein spacer G is an N-acetylpenicillamine residue of formula: 
     
       
         
         
             
             
         
       
     
   
   
       3 . The hyaluronic acid derivative according to  claim 1 , wherein spacer G is a cysteine residue of formula: 
     
       
         
         
             
             
         
       
       wherein GrPr represents a protective group. 
     
   
   
       4 . The hyaluronic acid derivative according to any one of  claims 1  and  2 , wherein the functionalisation with S-nitroso-N-acetylpenicillamine groups may involve amine groups deriving from deacetylation of the N-acetylglucosamine residues of hyaluronic acid or amine groups introduced by esterifying the carboxyl groups of the glucuronic acid units with aminoalkyl residues. 
   
   
       5 . The hyaluronic acid derivative according to  claim 1 , wherein the functionalisation with cysteine, possibly protected as carboxyl ester, involves the carboxyl groups present in the glucuronic acid residues of hyaluronic acid. 
   
   
       6 . The hyaluronic acid derivative according to  claim 1 , wherein the functionalisation with S-nitroso-N-acetylpenicillamine or S-nitroso-cysteine groups relates to amine groups deriving from deacetylation of the N-acetylglucosamine residues of hyaluronic acid. 
   
   
       7 . The hyaluronic acid derivative according to  claim 1 , wherein the functionalisation with S-nitroso-N-acetylpenicillamine or S-nitroso-cysteine groups involves amine groups introduced by esterifying the carboxyl groups of the glucuronic acid units with residues of formula X-A-NH2, wherein X is a halogen atom, preferably bromine, and A is an aliphatic or arylaliphatic spacer residue having 2 to 16 carbon atoms, preferably a —(CH2) n — group where n is an integer between 2 and 16, and preferably between 2 and 7. 
   
   
       8 . The hyaluronic acid derivative according to  claim 1 , wherein the hyaluronic acid is of extractive, fermentative or biotechnological origin and has a molecular weight of between 400 and 3×10 6  Da, in particular between 1×10 5  Da and 1×10 6  Da, and even more particularly between 200,000 and 750,000 Da. 
   
   
       9 . The hyaluronic acid derivative according to  claim 1  for dermatological and cosmetic applications, in particular for the correction of skin lesions and defects, biorevitalisation of tissues, tissue healing after intradermal, subcutaneous or topical administration, for cardiovascular applications and controlled release of drugs, after systemic and/or locoregional administration. 
   
   
       10 . A cosmestic or pharmaceutical composition or medical device containing at least one hyaluronic acid derivative according to  claim 1 .