Aryl/Alkyl Succinic Anhydride Hyaluronan 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 . 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,. 
 
     
     
         2 . The hyaluronic acid derivative of  claim 1 , wherein one of the R1, R2, R3, and R4 groups is an alkyl-succinic acid of formula (II). 
     
     
         3 . The hyaluronic acid derivative of  claim 1 , wherein two of the R1, R2, R3, and R4 groups are an alkyl-succinic acid of formula (II). 
     
     
         4 . The hyaluronic acid derivative of  claim 1 , wherein three of the R1, R2, R3, and R4 groups are an alkyl-succinic acid of formula (II). 
     
     
         5 . The hyaluronic acid derivative of  claim 1 , wherein the alkyl group is C1-C20 alkyl group. 
     
     
         6 . The hyaluronic acid derivative of  claim 1 , wherein the alkyl group is propyl, 2-octenyl, 2-dodecenyl, 2-hexadecenyl, or 2-octadecenyl. 
     
     
         7 . The hyaluronic acid derivative of  claim 1 , which has an average molecular weight of between 10,000 and 1,500,000 Da. 
     
     
         8 . The hyaluronic acid derivative of  claim 1 , which has an average molecular weight of between 10,000 and 50,000 Da. 
     
     
         9 . The hyaluronic acid derivative of  claim 1 , which has an average molecular weight of between 50,000 and 500,000 Da. 
     
     
         10 . A composition comprising a hyaluronic acid derivative of  claim 1  and a water-soluble excipient. 
     
     
         11 . The composition of  claim 10 , wherein the excipient is lactose. 
     
     
         12 . A pharmaceutical composition comprising an effective amount of a hyaluronic acid derivative of  claim 1  and a pharmaceutically acceptable carrier, excipient or diluent. 
     
     
         13 . A cosmetic article comprising a hyaluronic acid derivative of  claim 1 . 
     
     
         14 . A sanitary, medical or surgical article comprising a hyaluronic acid derivative of  claim 1 , 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. 
     
     
         15 . A medicament capsule, microcapsule, nanocapsules, microsphere or nanosphere comprising a hyaluronic acid derivative of  claim 1 .