Preparation process of dalteparin sodium

Abstract

The invention discloses a preparation process of dalteparin sodium. The preparation process comprises the following steps: preparing a heparin sodium solution, a heparin degradation fluid, a reducing solution and a crude product, refining, freeze-drying and the like. The average molecular weight of the obtained product is 5,500 to 6,500, the peak molecular weight is 3,500 to 6,000, a component with the molecular weight of less than 3,000 is not greater than 13% , a component with the molecular weight of greater than 8,000 is not greater than 15%, anti-Xa activity is more than or equal to 130IU / mg. The invention has the advantages of rich source of raw materials, high yield, stable and reliable quality, high purity, low cost, simple process, easiness in operation and no waste discharge. The dalteparin sodium has the anticoagulant, antithrombotic, anti-tumor, anti-inflammatory, anti-allergy and blood lipid regulating effects, thereby having a significant curative effect. The dalteparin sodium can be used for preventing preoperative and postoperative thrombosis of general surgery, orthopedic surgery and neurosurgery, effectively preventing venous thromboembolism of ischemic stroke patients, greatly reducing the risk of stroke, effectively preventing the solidification caused by extracorporeal circulation of blood, effectively preventing the instable coronary heart disease, and having a wide usable range.

Description

technical field [0001] The invention relates to a production process of dalteparin sodium. Background technique [0002] Dalteparin sodium is a low-molecular sodium salt, which is mainly used for 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 dalteparin 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 degradation method, hydrogen peroxide degradation method, enzymati...

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

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