Hyaluronic acid and epsilon-polylysine cross-linking method, obtained composite cross-linked product and application

Abstract

The invention discloses a hyaluronic acid and epsilon-polylysine cross-linking method, an obtained composite cross-linked product and an application. The method includes subjecting hyaluronic acid orsalt thereof and epsilon-polylysine or salt thereof to a cross-linking reaction in condition of a coupling agent, an auxiliary coupling agent and a neutral or alkaline water environment to obtain thecomposite cross-linked product. According to the method, protonation of epsilon-polylysine or salt thereof is inhibited in a neutral or alkaline environment, so that carboxyl of hyaluronic acid or salt thereof and amino of epsilon-polylysine or salt thereof are subjected to amidation reaction, and flocculating settling is inhibited or avoided. The hyaluronic acid or the salt thereof is crosslinkedwith the epsilon-polylysine or the salt thereof, the epsilon-polylysine or the salt thereof is equivalent to a cross-linking agent, catabolism of the epsilon-polylysine or the salt thereof in vivo can be absorbed and utilized by a human body, the biocompatibility is good, and cytotoxicity easily caused by a traditional cross-linking agent can be avoided.

Description

technical field [0001] The invention relates to a method for cross-linking hyaluronic acid and ε-polylysine, in particular to a method for preparing a composite cross-linked product of hyaluronic acid and ε-polylysine, as well as the obtained product and its application. Background technique [0002] Hyaluronic acid is a naturally occurring polyanionic mucopolysaccharide, which is a linear polymer composed of repeating disaccharide units composed of D-glucuronic acid and D-N-acetylglucosamine. Hyaluronic acid widely exists in living organisms and has excellent biocompatibility, so it is an ideal natural polymer medical material. However, hyaluronic acid is easily degraded by enzymes in the human body, resulting in a short half-life in the body. In order to prolong the residence time of hyaluronic acid in the body, a lot of modification and cross-linking of hyaluronic acid have been carried out. [0003] ε-polylysine (ε-PL) is a lysine homopolymer produced by microbial ferm...

AI Technical Summary

Problems solved by technology

In this preparation method, hyaluronic acid first needs to be oxidized into aldehyde groups under the action of a strong oxidant, then a reaction terminator is added to terminate the oxidation reaction, and then the strong oxidant and reaction terminator are removed by dialysis, and finally the aldehyde group is decomposed in PBS with a pH of 7.4. Adding cationic polymers to purified oxidized polysaccharides under buffer conditions for cross-linking reaction, the preparation process is relatively complicated

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