Cross-linked sodium hyaluronate gel for tissue filler for plastic surgery and preparation method thereof

1. A method for preparing a cross-linked sodium hyaluronate gel for tissue filler suitable for plastic surgery, consisting of:

{circle around (1)} dissolving a dry powder of sodium hyaluronate in a mixture of 0.2˜0.5M aqueous sodium hydroxide solution and dimethyl sulfoxide to produce an alkaline solution of sodium hyaluronate, and then adding a long-chain alkane containing a single epoxy group and a cross-linking agent containing an epoxy group, heating the alkaline solution of sodium hyaluronate to 35° C.˜50° C. with stirring for 2˜5 hours to produce a product solution, cooling the product solution down to room temperature; then adding acetone dropwise while stirring to form a solid-liquid mixture, adding hydrochloric acid to adjust the pH value of the solid-liquid mixture to 6.5˜7.4, filtering the solid-liquid mixture and collecting a solid material, which is washed 3˜5 times using isopropanol and acetone, respectively, and then drying the solid material under vacuum until a content of a volatile matter is lower than 2 ppm to produce a cross-linked sodium hyaluronate powder; wherein a weight ratio of sodium hyaluronate:the cross-linking agent containing an epoxy group:the long-chain alkane containing a single epoxy group is 10:4˜1:1˜4; a number of carbon atoms in the long-chain alkane containing the epoxy group is 6˜18; a volume ratio of 0.2-0.5M sodium hydroxide solution to dimethyl sulfoxide is 10:7˜1; a concentration of sodium hyaluronate is 4 wt % to 8 wt % in the sodium hyaluronate alkaline solution; a volume ratio of the sodium hydroxide solution to acetone added dropwise is 1:4˜2:3; an average molecular weight of sodium hyaluronate is 500,000˜2,000,000 Da; the cross-linking agent containing an epoxy group is one of the following: 1,4-butanediol diglycidyl ether, polyethylene glycol diglycidyl ether with a molecular weight of 500˜6,000, 1,2,7,8-diepoxyoctane, or 1,2,3,4-diepoxybutane;

{circle around (2)} adding water to the cross-linked sodium hyaluronate powder obtained in step {circle around (1)} to form a cross-linked sodium hyaluronate gel; collecting gel particles, which are washed with water while stirring for 2˜5 hours at 15° C.˜35° C., followed by filtration to collect the gel particles, and repeating water washing 4˜5 times, and then collecting the gel particles;

{circle around (3)} adding isotonic saline to the gel particles collected in step {circle around (2)}; after stirring for 2˜5 hours at 15° C.˜35° C. collecting the gel particles by filtration, followed by washing with isotonic saline, repeating isotonic saline washing 4˜5 times, and then collecting gel particles with an average particle size of 150 μm-350 μm by screen sieving; and

{circle around (4)} filling a pre-sterilized disposable syringe with the gel particles collected in step {circle around (3)}, and sterilizing the filled syringe by steam at 121° C.˜125° C. for 15˜25 min to produce the cross-linked sodium hyaluronate gel for tissue filler suitable for plastic surgery.

2. The method for preparing the cross-linked sodium hyaluronate gel according to claim 1 , wherein the cross-linked sodium hyaluronate gel contains chemically bonded hydrophobic groups having a self-adhesive self-aggregating property.