Heparanase composition capable of complete specific enzymolysis of enoxaparin sodium and application of heparanase composition

Abstract

The invention provides a heparanase composition capable of complete specific enzymolysis of enoxaparin sodium. The heparanase composition is a mixture of heparanase II and heparanase III, wherein the enzyme activity ratio of heparanase II to heparanase III is 3: 1. According to the invention, the heparanase composition can realize the complete specific enzymolysis of enoxaparin sodium and is reduced to obtain 1, 6-anhydride derivatives, and the contents are in an acceptable range; the heparanase composition is free from heparanase I to reduce the introduction of enzyme impurities, so that the method is more reliable, is an important supplement for several pharmacopoeia methods, has high practical use value and significance.

Description

technical field [0001] The invention relates to a heparanase composition without heparanase I for detecting the content of 1,6 anhydride in enoxaparin sodium and its application and detection method, belonging to the technical field of medicine and biology. Background technique [0002] Enoxaparin Sodium (Enoxaparin Sodium, ES) is a low-molecular-weight heparin sodium salt obtained by alkaline depolymerization of pig intestinal mucosal heparin benzyl ester derivatives. US Patent US005389618A describes the preparation process of this enoxaparin sodium in detail . The United States Pharmacopoeia and European Pharmacopoeia have many requirements for the quality control of enoxaparin sodium. In addition to the detection of physical and chemical items such as potency, molecular weight distribution, heavy metal content and reagent residue content, the determination of 1,6-anhydride content is also required. Since the percentage of oligosaccharide chains with 1,6-anhydride ring st...

AI Technical Summary

Problems solved by technology

However, in practical applications, the results often fail to meet the standards when this method is used. The main reason is that the enzymatic hydrolysis process cannot be completed completely due to the special nature of heparinase, so that the performance of the sample cannot be judged.

In particular, heparanase I is unstable, high in price, and poor in selectivity. Different sources of heparanase have a great influence on the determination method of 1,6-anhydride content.

Therefore, the method has poor stability and poor repeatability. So far, this method is only a general detection method, and has not been used as a quality inspection and release method for enoxaparin.

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