Method for producing nadroparin calcium from heparin sodium crude product

Abstract

The invention discloses a method for producing nadroparin calcium from a heparin sodium crude product. The method comprises the following steps: dissolving the raw material crude product heparin sodium in water, precipitating by centrifugation and secondary salting-out to remove impurities in the heparin sodium crude product, carrying out nitrous degradation and reduction to obtain low-molecular heparin containing free sulfates, adding barium chloride to remove the free sulfates generated by degradation, and using an anion exchange resin and adjusting to appropriate parameters to carry out calcium conversion and final impurity removal; and finally, carrying out oxidation decolorization, sterile filtration and dehydration to obtain the nadroparin calcium raw material. By using the crude product heparin sodium as the raw material, the production cost is lowered; the technical steps are simplified to enhance the yield of the nadroparin calcium and reduce the titer loss of the nadroparin calcium; and the method can ensure the safety of the product, and is convenient for industrialized mass 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