Synthesis method of 6-O-carboxymethyl chitosan sulfuric sulfation product

Abstract

The invention discloses a synthesis method of a 6-O-carboxymethyl chitosan sulfation product. The method comprises the following steps: (1) chitin alkaline treatment of chitin; (2) carboxymethylation of C6-O site of chitin; (3) deacetylation reaction of 6-O-carboxymethyl chitin; and (4) sulfation of 6-O-carboxymethyl chitosan. The synthesis method disclosed by the invention is a bran-new method for selectively replacing and controlling the replacement rate by using chitin. The synthesis product of the method provides N-site -SO3H with main anticoagulant activity and introduces -COOH, so that a lot of -COOH and SO3H which have negative electricity in the molecular structure are regularly distributed, and an anticoagulant effect of heparinoid is generated by the synergistic effect. High molecular polysaccharide is a heparinoid drug which is selectively modified by chitin via a safe reagent, so that reagent pollution of bulk drugs is reduced, the virus contamination risk of heparin biological extraction is avoided, the safety performance of the drug in the clinical experiment is more excellent in theory as compared with heparin sodium, so the 6-O-carboxymethyl chitosan sulfation product provided by the invention is expected to serve as a cheap direct thrombin inhibitor to replace heparin sodium anti coagulation drugs.

Description

technical field [0001] The invention relates to the field of medical polymers, in particular to a synthesis method of a 6-O-carboxymethyl chitosan sulfated product. Background technique [0002] Since heparin, which is expensive and in short supply, has become an anticoagulant drug, researchers have been looking for ways to synthesize heparin substitutes with high anticoagulant activity and low side effects. There have been many reports on chemically synthesized heparin substitutes. The schematic diagram of the molecular chain structure of heparin is shown in the figure below. [0003] [0004] Most of the domestic and foreign studies focus on chitosan sulfonated derivatives as the target drug. Chitosan is a functional biopolymer obtained by deacetylation of chitin with relatively high chemical activity. G.Vikhoreva (G.Vikhoreva, G.Bannikova, et al.Preparation and anticoagulant activity of a low-molecular-weight sulfated chitosan[J].Carbohydrate Polymers, 2005, 62:327-33...

AI Technical Summary

Problems solved by technology

[0011] The above carboxymethylation and sulfation modifications all use chitosan as raw material, and chitosan is made from chitin through multiple deacetylation reactions. The high degree of deacetylation results in a large amount of highly active amino groups. Existence, leading to carboxymethyl selective substitution and control of degree of substitution is very difficult

In addition, synthetic methods such as selecting sulfur trioxide / N, N-dimethylformamide as sulfonating agent, and chelating protection of amino groups are not ideal

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