A kind of method of producing nadroparin calcium from heparin sodium crude product

Abstract

The invention discloses a method for producing nadroparin calcium from crude heparin sodium. The present invention uses crude heparin sodium as a raw material, after adding water to dissolve, and then precipitates and removes impurities in the crude heparin sodium by centrifugation and secondary salting out, then degrades and reduces with nitrous acid to obtain low-molecular-weight heparin containing free sulfate radicals, and then adds chlorinated Barium removes free sulfate radicals produced by degradation, then uses anion exchange resin, and adjusts appropriate parameters for calcium conversion and final impurity removal, and finally oxidative decolorization, filter sterilization, dehydration and drying to obtain nadroparin calcium raw material. The invention uses crude heparin sodium as a raw material, reduces the production cost, improves the yield of nadroparin calcium by simplifying the process steps, reduces the potency loss of the nadroparin calcium, can ensure the safety of the product, and is convenient for large-scale industrial production.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a method for producing nadroparin calcium from crude heparin sodium. Background technique [0002] Heparin sodium is a sodium salt of aminodextran sulfate proposed in pig intestinal mucosa. It is a natural anticoagulant substance. Heparin sodium has a history of more than 70 years and is widely used in the treatment of arteriosclerosis and venous thrombosis. and prevent blood clotting. However, unfractionated heparin has low bioavailability and severe side effects. Low molecular weight heparin is a component or fragment with a relatively low molecular weight in unfractionated heparin, and is a new generation of heparin antithrombotic drugs. Low-molecular-weight heparin is prepared by depolymerization of heparin, with an average molecular weight of 4000-6000 Daltons. Ordinary heparin products are in the sodium salt type. Compared with the calcium salt type, the latter has the advantag...

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Problems solved by technology

[0006] Patent CN1268650C provides a method for preparing low-molecular-weight heparin calcium with low nitrate content. The method uses heparin sodium fine-quality goods as raw materials, which not only increases the cost of preparing nadroparin calcium, but also undergoes a process from crude heparin sodium to high-quality heparin sodium. In the two-step independent process from the high-quality heparin sodium to low-molecular-weight heparin calcium, more preparation steps will not only cause the loss of potency, but also affect the yield of nadroparin calcium

[0007] Patent CN103214596A provides a kind of method directly producing low molecular weight heparin sodium by crude product heparin sodium, although this method is raw material with heparin sodium crude product, but before heparin sodium degrades, the processing process to heparin sodium crude product is comparatively loaded down with trivial details, and the impurity removal step is comparatively complicated. More, it will also affect the potency, quality and yield of the product

In the production process of nadroparin calcium, a new impurity, free sulfuric acid, needs to be strictly controlled during the cracking process. It can be seen that the processes of low-molecular-weight heparin calcium and low-molecular-weight heparin sodium are not consistent, so this method is not completely suitable for low-molecular-weight heparin. calcium preparation