Method for manufacturing a shaped crosslinked hyaluronic acid product

Abstract

A method for manufacturing a shaped cross-linked hyaluronic acid product including the step of subjecting a non-cross-linked precipitated hyaluronic acid substrate in a desired shape to a single cross-linking reaction in a liquid medium having a pH of 11.5 or higher and including one or more polyfunctional cross-linking agent(s) and an amount of one or more organic solvent(s) giving precipitating conditions for hyaluronic acid, under suitable conditions to obtain a precipitated, shaped cross-linked hyaluronic acid product having a degree of modification of 1-40 cross-linking agent units per 1000 disaccharide units.

1 . (canceled) 
     
     
         2 . A shaped cross-linked hyaluronic acid product having a degree of modification of 1-40 cross-linking agent units per 1000 disaccharide units, a swelling degree of 4-300 mL per g hyaluronic acid, and a modification efficiency of 10 or higher. 
     
     
         3 . The shaped cross-linked hyaluronic acid product according to  claim 2 , wherein the product has a shape selected from the group consisting of a particle, a fibre, a string, a strand, a net, a film, a disc and a bead. 
     
     
         4 . The shaped cross-linked hyaluronic acid product according to  claim 3 , wherein the product is a fibre and the ratio between its length and its width is 10:1 or higher. 
     
     
         5 . The shaped cross-linked hyaluronic acid product according to  claim 3 , wherein the product is a fibre, and wherein its longitudinal extension is more than 2 mm. 
     
     
         6 . The shaped cross-linked hyaluronic acid product according to  claim 2 , wherein said swelling degree is 15-180 mL per g hyaluronic acid. 
     
     
         7 . The shaped cross-linked hyaluronic acid product according to  claim 2 , wherein the modification efficiency is in the range of 20-190. 
     
     
         8 . The shaped cross-linked hyaluronic acid product according to  claim 2 , wherein the cross-linker ratio is 35% or higher. 
     
     
         9 . The shaped cross-linked hyaluronic acid product according to  claim 2 , which is cross-linked with one or more polyfunctional cross-linking agent(s) individually selected from the group consisting of divinyl sulfone, multiepoxides and diepoxides. 
     
     
         10 . The shaped cross-linked hyaluronic acid product according to  claim 9 , said polyfunctional cross-linking agent(s) being individually selected from the group consisting of 1,4-butanediol diglycidyl ether (BDDE), 1,2-ethanediol diglycidyl ether (EDDE) and diepoxyoctane. 
     
     
         11 . The shaped cross-linked hyaluronic acid product according to  claim 10 , wherein the polyfunctional cross-linking agent is 1,4-butanediol diglycidyl ether (BDDE). 
     
     
         12 . The shaped cross-linked hyaluronic acid product according to  claim 2 , wherein the product is sterilized. 
     
     
         13 . An aqueous composition comprising a shaped cross-linked hyaluronic acid product according to  claim 2 , and optionally a buffering agent. 
     
     
         14 . A method of treatment of a subject undergoing cosmetic or medical surgery, the method comprising administration of a shaped cross-linked hyaluronic acid product according to  claim 2  to a subject in need thereof. 
     
     
         15 . The method according to  claim 14 , wherein the shaped cross-linked hyaluronic acid product is administrated comprised in an aqueous composition. 
     
     
         16 . The method according to  claim 15 , wherein the aqueous composition is further comprising a buffering agent. 
     
     
         17 . The method according to  claim 14 , wherein the cosmetic surgery is selected from dermal filling and body contouring. 
     
     
         18 . The method according to  claim 14 , wherein the medical surgery is selected from dermal filling, body contouring, prevention of tissue adhesion, formation of channels, incontinence treatment, and orthopaedic applications. 
     
     
         19 . The method according to  claim 14 , wherein the shaped, cross-linked product achieves drug delivery to the subject.