Hyaluronic Acid Derivatives

Abstract

The present invention relates to the modification of hyaluronic acid (HA) with aryl/alkyl succinic anhydrides (ASA) to produce aryl/alkyl succinic anhydride HA derivatives, to the derivatives as such, and to their applications and uses, particularly in the cosmetic and biomedical industries. The ASA-HA derivatives are expected to have interesting properties that can be used for advanced formulation (bind stronger to the skin compared to non-modified HA), possibly also in delivery systems for actives or drugs by encapsulation (nano/micro capsules) or formation of nano/micro spheres. Further, the low MW ASA-HA derivatives are expected to penetrate the skin more efficiently than non-modified HA of the same MW.

1 - 63 . (canceled) 
     
     
         64 . A hyaluronic acid derivative comprising n repeating units of formula (I): 
       
         
           
           
               
               
           
         
         wherein
 (a) in at least one repeating unit, one or more of the R1, R2, R3, and R4 groups is an alkyl-succinic acid of formula (II): 
 
       
       
         
           
           
               
               
           
         
         wherein at least one of the R5, R6, R7, and R8 groups is an alkyl-group and the other R5, R6, R7, and R8 groups are hydrogen, and the oxygen labelled “ester” forms an ester bond with structure (I); and 
         (b) in the other repeating units, the R1, R2, R3, and R4 groups are hydroxyl groups. 
       
     
     
         65 . The hyaluronic acid derivative of  claim 64 , wherein one of the R1, R2, R3, and R4 groups is an alkyl-succinic acid of formula (II). 
     
     
         66 . The hyaluronic acid derivative of  claim 64 , wherein two of the R1, R2, R3, and R4 groups are an alkyl-succinic acid of formula (II). 
     
     
         67 . The hyaluronic acid derivative of  claim 64 , wherein three of the R1, R2, R3, and R4 groups are an alkyl-succinic acid of formula (II). 
     
     
         68 . The hyaluronic acid derivative of  claim 64 , wherein the alkyl group is C1-C20 alkyl group. 
     
     
         69 . The hyaluronic acid derivative of  claim 64 , wherein the alkyl group is propyl, 2-octenyl, 2-dodecenyl, 2-hexadecenyl, or 2-octadecenyl. 
     
     
         70 . The hyaluronic acid derivative of  claim 64 , which has an average molecular weight of between 10,000 and 1,500,000 Da. 
     
     
         71 . The hyaluronic acid derivative of  claim 64 , which has an average molecular weight of between 10,000 and 50,000 Da. 
     
     
         72 . The hyaluronic acid derivative of  claim 64 , which has an average molecular weight of between 50,000 and 500,000 Da. 
     
     
         73 . A composition comprising a hyaluronic acid derivative of  claim 64  and a water-soluble excipient. 
     
     
         74 . The composition of  claim 73 , wherein the excipient is lactose. 
     
     
         75 . A pharmaceutical composition comprising an effective amount of a hyaluronic acid derivative of  claim 64  and a pharmaceutically acceptable carrier, excipient or diluent. 
     
     
         76 . A cosmetic article comprising a hyaluronic acid derivative of  claim 64 . 
     
     
         77 . A sanitary, medical or surgical article comprising a hyaluronic acid derivative of  claim 64 , which is a diaper, a sanitary towel, a surgical sponge, a wound healing sponge, or a part comprised in a band aid or other wound dressing material. 
     
     
         78 . A medicament capsule, microcapsule, nanocapsules, microsphere or nanosphere comprising a hyaluronic acid derivative of  claim 64 .