Preparation method for agranular crosslinking sodium hyaluronate with high-temperature-resistant and enzymatic-hydrolysis-resistant characteristics

Abstract

The invention relates to a novel preparation method for agranular crosslinking sodium hyaluronate. Crosslinking reaction is performed in the low-concentration linear molecule state, and accordingly excess exposure of enzymatic-hydrolysis sites caused by crushing or extrusion of mechanical external forces of crosslinking sodium hyaluronate in traditional processes can be avoided. Redundant crosslinker can be eliminated effectively by white-powdered crosslinking sodium hyaluronate particles obtained by physical precipitation by using organic solvent, and accordingly accurate distribution of different concentrations of products can be guaranteed. The crosslinking sodium hyaluronate has the characteristics of high-temperature resistance, enzymatic-hydrolysis resistance and agranulation, and excellent injectability can be improved evidently. Kinetic viscosity of the agranular crosslinking sodium hyaluronate is reduced by 3-10% after sterilizing at 121 DEG C for 30 minutes, enzymatic hydrolysis is performed to 1000 U of sodium hyaluronate for 48 hours, and releasing amount of uronic acid is smaller than 40%.

Description

technical field [0001] The invention relates to the technical field of medical biomaterials, and relates to a preparation method of a novel cross-linked hyaluronic acid, which is used for medical filling and cosmetology. Background technique [0002] Hyaluronic acid is an important component of human and animal skin, vitreous, joint lubricating fluid and cartilage tissue, which consists of (1-β-4) D-glucuronic acid and (1-β-3) N-acetyl-D -Glucosamine disaccharide units are repeatedly connected, and are widely used in repair surgery, eye surgery or as cosmetic products to fill wrinkles. Hyaluronic acid has good physical and chemical properties and biocompatibility. However, it is rapidly degraded by the enzymatic hydrolysis of hyaluronidase in the body, and its retention time is short, requiring repeated injections to achieve curative effect. Cross-linked hyaluronic acid is a polymer gel obtained by cross-linking and modifying hyaluronic acid with a cross-linking agent, whi...

AI Technical Summary

Problems solved by technology

[0005] The ultimate goal of the cross-linking reaction of sodium hyaluronate is to increase its residual time in the body as much as possible on the basis of ensuring its biocompatibility. Although the current patent uses various methods such as increasing the degree of cross-linking and improving the initial reaction Concentration, shorter reaction time, etc., but still cannot get rid of the use of traditional crushing and extrusion processes. ZL200480010239.1 uses high molecular weight fibrous sodium hyaluronate samples, but still obtains a longer degradation time through traditional extrusion processes The cross-linked sodium hyaluronate gel, whose high enzyme concentration (1000U) degrades the amount of uronic acid released after 48h is 75%. This patent examines the huge influence of physical mechanical force on cross-linked sodium hyaluronate, so How to effectively reduce the impact of physical extrusion or crushing on the product in the preparation process of cross-linked sodium hyaluronate is an effective means to improve the degradation time in vivo

So far, there is no patent related to the preparation method without extrusion or crushing process

Images