Emulsified cross-linked sodium hyaluronate gel microspheres for injection and preparation method thereof

Abstract

The invention provides a preparation method of emulsified cross-linked sodium hyaluronate gel microspheres for injection. The preparation method comprises the following steps: firstly, preparing an emulsion of sodium hyaluronate microsphere particles; adding a cross-linking agent into the emulsion according to a certain mass ratio of the cross-linking agent to the sodium hyaluronate;, stirring anduniformly mixing the components in an ice bath, then stirring the mixture at room temperature to carry out primary reaction; and finally stirring the reactant in a water bath at 35-42 DEG C to reactto obtain a microsphere emulsion; cleaning the reaction product with n-hexane, ethyl acetate and absolute ethyl alcohol in sequence. According to the preparation method, uniform and ordered cross-linking reaction in a single sodium hyaluronate colloidal particle is ensured, so that proper viscous modulus, elastic modulus and pushing force are obtained, cross-linking reaction among the particles isavoided, and the yield of qualified gel microspheres is increased. The gel microsphere is suitable for injection and has a wide application prospect.

Description

technical field [0001] The invention relates to the technical field of medical materials, in particular to an emulsified cross-linked sodium hyaluronate gel microsphere for injection and a preparation method thereof. Background technique [0002] Sodium hyaluronate (SH) is an acidic mucopolysaccharide. As early as 1930-1940, Meyer extracted sodium hyaluronate from animal synovial fluid, skin, rooster comb, and human umbilical cord. Kendell et al. extracted SH from bacteria in 1937. Although SH obtained from different sources and different refining methods has different molecular weights, there is no species difference. Hyaluronic acid preparations have a long history of medical use, usually in ophthalmology and orthopedics. In 1962, sodium hyaluronate preparations (Healon Xilang) were approved by the FDA for use as substitutes for aqueous humor and vitreous in ophthalmic surgery and Substrates for ophthalmic topical drugs. Since then, it has also been used for joint cavit...

AI Technical Summary

Problems solved by technology

At present, there are many methods for preparing cross-linked hyaluronic acid at home and abroad. Usually, hyaluronic acid and cross-linking agent are stirred and mixed in an aqueous solution, and the cross-linking agent is added to form chemical bonds between hyaluronic acid polymer chains. Block gels are generally crushed mechanically or passed through a sieve under pressure to obtain different particle sizes, but the prepared cross-linked hyaluronic acid gels have uneven cross-linking degrees, irregular particle shapes, and uneven particle sizes. question

The patent with publication number EP2225281 describes a preparation method of crosslinked hyaluronic acid microspheres in emulsion. The microspheres obtained by this method are uniform in shape and the particle size distribution is between 1nm and 1μm, but the final crosslinked hyaluronic acid Acid microbeads have not taken effective oil phase residue and crosslinking agent residue control measures, and the biocompatibility and water retention performance are still not ideal, and there are problems such as product instability, which cannot well meet market demand