Patent ID: 8481080

Claim:
A method of producing a hydrogel comprising hyaluronic acid or a salt thereof, cross-linked with divinylsulfone (DVS), said method comprising the steps of: (a) providing an alkaline solution of hyaluronic acid or salt thereof, wherein the alkaline solution comprises dissolved hyaluronic acid or salt thereof in a concentration of between 0.1-40% (w/v); (b) forming a gel of hyaluronic acid or salt thereof cross-linked with DVS by: (i) adding DVS to the solution of step (a) in a weight ratio of between 1:1 and 100:1 of hyaluronic acid or salt thereof/DVS (dry weight) and stirring the solution of hyaluronic acid or salt thereof/DVS while the temperature of the solution of hyaluronic acid or salt thereof/DVS is maintained in the range of 15-30° C., wherein the stirring is for a period of 1-180 minutes; and (ii) heating the hyaluronic acid or salt thereof/DVS solution of step (i) to a temperature in the range of 35-55° C., and maintaining the temperature in the range of 35-55° C. for at least 5 minutes; and (c) forming a hydrogel comprising the hyaluronic acid or salt thereof, cross-linked with DVS by treating the gel of produced from step (b) with a buffer to swell the gel and form a hydrogel.