Preparation process of enoxaparin sodium

Abstract

The invention discloses a preparation process of enoxaparin sodium, which comprises the steps of preparing heparin sodium solution, preparing heparin degradation solution, preparing reducing solution, preparing crude product, refining, freeze-drying and the like. The weight-average molecular weight of the obtained product is 5000-6000, the peak molecular weight is 3000-6000, the component with molecular weight less than 3000 is not more than 11%, the component with molecular weight greater than 8000 is not more than 13%, and the anti-Xa activity is ≥ 135IU / mg.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to a production process of enoxaparin sodium. Background technique [0002] Enoxaparin sodium is a low-molecular sodium salt, which is mainly used in the prevention of coagulation and deep vein thrombosis in hemodialysis, the treatment of unstable coronary artery disease and the prevention of thrombosis related to surgery. Heparin is a kind of glycosaminoglycan widely present in animal organs, small intestinal mucosa, lung and other tissues. [0003] In addition to having all the pharmacological effects of unfractionated heparin, low-molecular-weight heparin is used as an anticoagulant, usually for short-term use, and has a high therapeutic index. The US FDA has approved enoxaparin sodium as a prophylactic drug after low limb replacement. [0004] At present, the degradation methods of low molecular weight heparins produced in China mainly include sodium nitrite degradatio...

AI Technical Summary

Problems solved by technology

However, the degradation of hydrogen peroxide may introduce foreign matter, and the quality is not easy to control; the end of the enzymatic degradation product has unsaturated groups, which has poor stability and high cost; in terms of impurity removal and decolorization methods, at present, potassium permanganate under different pH conditions is mainly used in China. and hydrogen peroxide secondary oxidation method or hydrogen peroxide oxidation method

The disadvantage of the secondary oxidation method of potassium permanganate and hydrogen peroxide is that the manganese dioxide produced is difficult to filter out, and manganese dioxide has an adsorption effect on some products, which reduces the product recovery rate; in terms of product purification technology, there are mainly condensation Gel chromatography, ultrafiltration and other methods, although the quality of the product obtained by gel chromatography is high, it is difficult to produce on a large scale, and the cost is high