Carbohydrate crosslinker

Abstract

The invention relates to a hydrogel product comprising glycosaminoglycan molecules as the swellable polymer, wherein the glycosaminoglycan molecules are covalently crosslinked via crosslinks comprising a spacer group selected from the group consisting of di-, tri-, tetra-, and oligosaccharides.

What is claimed is: 
     
         1 . A hyaluronic acid (HA) hydrogel comprising HA molecules crosslinked by diaminotrehalose (DATH), wherein the hydrogel is prepared by a process comprising:
 hydrolyzing ester bonds in the crosslinked HA molecules via alkaline hydrolysis to obtain a hydrogel having less than 50% non-crosslinked HA molecules by weight of the hydrogel.   
     
     
         2 . The HA hydrogel according to  claim 2 , wherein the HA molecules are crosslinked by the DATH via activated carboxyl groups on the HA molecules. 
     
     
         3 . The HA hydrogel according to  claim 1 , wherein the DATH crosslinks the HA molecules via amide bonds. 
     
     
         4 . The HA hydrogel according to  claim 1 , wherein at least 90% of bonds between the HA molecules and the DATH are amide bonds. 
     
     
         5 . The HA hydrogel according to  claim 1 , wherein at least 95% of bonds between the HA molecules and the DATH are amide bonds. 
     
     
         6 . The HA hydrogel according to  claim 1 , wherein less than 5% of bonds between the HA molecules and DATH are ester bonds. 
     
     
         7 . The HA hydrogel according to  claim 1 , wherein less than 1% of bonds between the HA molecules and DATH are ester bonds. 
     
     
         8 . The HA hydrogel according to  claim 1 , wherein the crosslinked HA molecules are in the form of gel particles. 
     
     
         9 . The HA hydrogel according to  claim 8 , wherein the gel particles have an average size in the range of 0.01 mm to 5 mm. 
     
     
         10 . The HA hydrogel according to  claim 1 , wherein the hydrogel has a corrected swelling capacity (SwCC) of 101 ml/g or greater. 
     
     
         11 . The HA hydrogel according to  claim 1 , wherein the hydrogel has a corrected swelling capacity (SwCC) of 445 ml/g or greater. 
     
     
         12 . The HA hydrogel according to  claim 1 , wherein the hydrogel has an effective crosslinking ratio (CrR) of at least 0.43. 
     
     
         13 . The HA hydrogel according to  claim 1 , wherein the hydrogel has an effective crosslinking ratio (CrR) of at least 0.63. 
     
     
         14 . The HA hydrogel according to  claim 1 , wherein the molar ratio of DATH to HA in is 0.03 to 0.79 mol % per GAG disaccharide. 
     
     
         15 . The HA hydrogel according to  claim 1 , wherein less than 20% by weight of the hydrogel obtained after the hydrolyzing comprises HA molecules that are not crosslinked. 
     
     
         16 . The HA hydrogel according to  claim 1 , wherein the crosslinked HA molecules are free from synthetic non-carbohydrate structures and synthetic non-carbohydrate crosslinkers. 
     
     
         17 . The HA hydrogel according to  claim 1 , wherein the process further comprises, before the hydrolyzing, crosslinking activated carboxyl groups of the HA molecules using the diaminotrehalose (DATH) to obtain the crosslinked HA molecules. 
     
     
         18 . The HA hydrogel according to  claim 17 , wherein the process further comprises, before the crosslinking, activating carboxyl groups of the HA molecules with a coupling agent to produce the activated carboxyl groups. 
     
     
         19 . The HA hydrogel according to  claim 18 , wherein the hydrolyzing is performed using an alkaline solution comprising a hydroxide. 
     
     
         20 . A syringe containing a HA hydrogel according to  claim 1 .