	US 11,866,556 B2
	Process for efficient cross-linking of hyaluronic acid
Morgan Karlsson, Almunge (SE)
Assigned to Galderma Holding SA, Zug (CH)
Filed by Galderma Holding SA, La Tour-de-Peilz (CH)
Filed on Feb. 3, 2021, as Appl. No. 17/166,909.
Application 17/166,909 is a continuation of application No. 15/747,648, granted, now 11,021,580, previously published as PCT/EP2016/067072, filed on Jul. 18, 2016.
Claims priority of application No. 15178526 (EP), filed on Jul. 27, 2015.
Prior Publication US 2021/0155763 A1, May 27, 2021
Int. Cl. C08J 3/24 (2006.01); C08B 37/08 (2006.01); C08L 5/08 (2006.01); A61K 8/73 (2006.01); A61K 31/728 (2006.01); A61K 47/36 (2006.01); A61K 9/06 (2006.01); A61Q 19/08 (2006.01); A61L 27/20 (2006.01); C08J 3/075 (2006.01)

CPC C08J 3/24 (2013.01) [A61K 8/735 (2013.01); A61K 9/06 (2013.01); A61K 31/728 (2013.01); A61K 47/36 (2013.01); A61L 27/20 (2013.01); A61Q 19/08 (2013.01); C08B 37/0072 (2013.01); C08J 3/075 (2013.01); C08L 5/08 (2013.01); A61K 2800/91 (2013.01); A61L 2430/34 (2013.01); C08J 2305/08 (2013.01); C08L 2201/54 (2013.01); C08L 2203/02 (2013.01)]

21 Claims

1. A process for manufacturing a cross-linked hyaluronic acid (HA) gel product, the process comprising:

(a) obtaining an aqueous mixture of HA and a diepoxide cross-linking agent selected from the group consisting of 1,4-butanediol diglycidyl ether (BODE), 1,2-ethanediol diglycidyl ether (EDDE) and diepoxyoctane, wherein the HA is dissolved in an aqueous solution comprising 2.5-4% (w/w) inorganic hydroxide, and wherein the dissolved HA constitutes 33-35% (w/w) of the aqueous mixture; and

(b) cross-linking the aqueous mixture at 10-75° C. to obtain the cross-linked HA gel product, wherein the HA is cross-linked in a single step, and wherein the cross-linked HA gel product has a GelC of 90% or greater.