Sheep enoxaparin sodium compound preparation method, compound and application of compound

Abstract

The invention discloses a method for preparing sheep enoxaparin sodium from sheep intestinal mucosa heparin. The method comprises the following steps: 1, preprocessing sheep heparins; 2, preparing a sheep heparin quaternary ammonium salt; 3, preparing sheep heparin benzyl ester; and 4, carrying out alkali depolymerization on the sheep heparin benzyl ester, decoloring, neutralizing by using an acid, carrying out alcohol precipitation, refining, and drying to obtain finished sheep enoxaparin sodium. The simple and efficient method for preparing the sheep enoxaparin sodium from the sheep intestinal mucosa heparin is screened and established, and researches of the systemic physical and chemical properties, the biological activity and the molecule structure are carried out on the prepared sheep enoxaparin sodium. The sheep enoxaparin sodium prepared in the invention completely accords with USP37 and EP8.0 quality release criteria of sheep enoxaparin sodium, and has extremely high practical values and medical application prospect. The sheep enoxaparin sodium has the advantages of simple and easily available raw material, controllable quality, no existence of bovine spongiform encephalopathy virus risk, promotion of the effective utilization of sheep culture and slaughter wastes (intestinal mucosa), and great economy potential.

Description

technical field [0001] The invention relates to a preparation method of an enoxaparin sodium compound, in particular to a preparation method of a sheep enoxaparin sodium compound, and belongs to the field of medical biotechnology. Background technique [0002] Heparin is a sulfated acidic polysaccharide ester that is produced and secreted by mast cells of animal connective tissue. It is currently the most widely used anticoagulant and antithrombotic drug in clinical practice. Among them, enoxaparin sodium (Enoxaparin Sodium, ES) is a low-molecular-weight heparin sodium salt, and is one of the most clinically important heparin anticoagulants, with a global annual sales volume exceeding US$3 billion. Heparin was first found in the liver of dogs, so it is called heparin. But in fact, heparin is widely distributed in mammals, and exists in the heart, liver, lung, intestinal mucosa, duodenum and blood vessel wall. Heparin is first obtained from the liver, but it is most abundant...

AI Technical Summary

Problems solved by technology

[0014] The preparation, analysis and characterization of enoxaparin sodium are complicated, and the process and technical requirements are extremely high. At present, there is no literature to systematically study the preparation of enoxaparin sodium from different animal sources and organs, and there is no comparison of their physical, chemical and biological properties. There is no such product on the market, let alone qualified cattle and sheep enoxaparin sodium products

[0015] Chinese patent application number 201210064430.0 introduces a production and purification method of bovine lung heparin to produce halal enoxaparin sodium, but this article does not explain the difference in physical and chemical properties between bovine lung heparin and porcine intestinal mucosal heparin, let alone description and data comparison Such differences will lead to similarities and differences in products produced under the same process

The conditions of the core benzyl esterification and alkali depolymerization steps of the announced preparation process are the same as those listed in US Patent US005389618A and its sister patents, but qualified bovine lung enoxaparin sodium cannot be obtained by following the technology disclosed in this Chinese patent application

In addition, this Chinese patent application did not test the percentage content of 1,6-anhydride ring, the core index characteristic of enoxaparin sodium. According to the preparation and purification of its specific example 1, the obtained 1,6-anhydride ring percentage The component content is not between 15%-25% stipulated in USP37 and EP8.0, and does not have real practical value

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