Method for preparing medical cross-linking sodium hyaluronate gel

Abstract

The invention discloses a method for preparing medical cross-linking sodium hyaluronate gel. The method comprises the following steps: mixing and reacting sodium hyaluronate with glycidyl ether under the alkali condition, namely, reacting for 1-4 hours at 40-60 DEG C firstly, further reacting for more than 48 hours at 15-30 DEG C to form the cross-linking sodium hyaluronate gel, washing, performing gelation and crushing the gel into grains of certain sizes, and subsequently sterilizing, thereby obtaining the medical cross-linking sodium hyaluronate gel. By adopting the method, the residual amount of a cross-linking agent can be reduced without a purification step by prolonging the cross-linking reaction time at low temperature, the difficulty that the residual cross-linking agent is hard to remove by using a conventional method is solved, and the prepared gel is uniform in grain and can be used in fields such as the cosmetic industry and the medicinal industry.

Description

technical field [0001] The invention relates to a medical cross-linked sodium hyaluronate gel and a preparation method thereof. The cross-linked sodium hyaluronate gel is used in the field of medicine or cosmetology. Background technique [0002] Hyaluronic acid (Hyalouronic Acid, hereinafter referred to as HA) or its sodium salt is a straight-chain polysaccharide composed of D-glucuronic acid and N-acetylglucosamine disaccharide units repeatedly linked. Important component of lubricating fluid and cartilage tissue. Because of its high viscoelasticity, plasticity and biocompatibility, it is widely used in medical and beauty industries. However, natural HA has strong water solubility, is easy to diffuse and degrade in tissues, and has a short retention time in the body, so its application is limited. In order to make up for these defects, modification and cross-linking methods are usually used to modify hyaluronic acid molecules, change some of its properties, and obtain in...

AI Technical Summary

Problems solved by technology

If the amount of cross-linking agent is high, the residence time in the body will be prolonged accordingly, but the hardness will increase and the injectability will decrease. At the same time, excess cross-linking agent will remain in the product, and it is difficult to purify and clean

Moreover, removing the cross-linking agent in the gel product is also a big problem at present. The most commonly used methods to remove or reduce the residual cross-linking agent include dialysis or washing with water or buffer solution, but these methods cannot effectively remove or reduce The content of cross-linking agent is low, and the cycle is long, so it is not easy to realize industrial production

Another kind, if it is to prepare cross-linked hyaluronic acid solids, the commonly used method to remove cross-linking agent is precipitation method, wash with organic solvent to precipitate cross-linked sodium hyaluronate gel, but this method still cannot completely remove residual free cross-linking agent

Many domestic patents (CN101759881, CN101502677, CN1590444, CN102558600, etc.) all use sodium hyaluronate and cross-linking agent 1,4-butanediol diglycidyl ether (hereinafter referred to as BDDE) to react in alkaline solution. Gel, wherein the patent CN101759881 discloses BDDE cross-linked HA to prepare medical cross-linked sodium hyaluronate gel derivative products. Although the prepared gel has a long retention time in the body and good biocompatibility, the cycle of removing the cross-linking agent is long and difficult. Completely remove or reduce the residual amount of crosslinker