Crude heparin sodium purification technology

Abstract

The invention relates to a heparin sodium purification technology. The crude heparin sodium purification technology sequentially comprises the following steps: 1, dissolving crude heparin sodium in a sodium chloride solution, and adding an alkaline protease for enzymatic hydrolysis; 2, inactivating, adding diatomite, carrying out high speed centrifugation, and removing insoluble impurities; 3, adding polysilicate, carrying out high speed centrifugation, and removing insoluble impurities; 4, adding alcohol for precipitating, and removing supernatant alcohol; 5, dissolving in the sodium chloride solution, adding hydrogen peroxide for oxidizing, carrying out high speed centrifugation after oxidation, and removing insoluble impurities; 6, adding alcohol for precipitating, and removing supernatant alcohol; and 7, filtering, and carrying out vacuum lyophilizing to obtain refined heparin sodium. The crude heparin sodium purification technology has the advantages of low content of proteins in the refined heparin sodium, and high yield of the refined heparin sodium.

Description

technical field [0001] The invention relates to a purification process of heparin sodium. Background technique [0002] As an anticoagulant, heparin was officially used in clinical treatment in 1935 and has a history of more than 70 years. So far, it is still the most effective and clinically used anticoagulant drug in the world, and it has been included in the Pharmacopoeia of major countries in the world. Heparin is an acidic mucopolysaccharide found in pig liver tissue by Mclean when he was studying the mechanism of coagulation, and it is a natural anticoagulant substance. Heparin is a natural active substance, and its activity cannot be determined by chemical or physical methods, but can only be determined by biological assays. Different countries and different periods adopt different methods and formulate different standards. Howell's definition of heparin activity unit is: the amount of heparin required to prevent 1 mL of fresh pigeon blood from clotting within 24 h...

AI Technical Summary

Problems solved by technology

The Chinese Pharmacopoeia (2010 edition) has improved the requirements for the impurity content on the basis of the Chinese Pharmacopoeia (2005 edition). ) light absorption value ≤0.20 has raised the requirements, so the high-quality heparin sodium produced by the traditional process can no longer meet the relevant requirements

The existing technology has the following disadvantages: (1) acid-base protein in the solution is not easy to separate during acid-base treatment, it is difficult to remove the protein, and the protein content of the final high-quality heparin sodium is on the high side, thereby affecting the quality of the high-quality heparin sodium; The process of adsorbing and removing protein has a long production cycle and produces a large amount of waste water, which increases the pressure on environmental protection, especially the resin is reused many times, the definition of each batch of products is not obvious, and there are many residual impurities in the resin, which is not easy Cleaning is easy to cause the previous batch of products to contaminate the next batch of products. Therefore, the method of producing high-quality heparin sodium by ion exchange resin method has been basically eliminated in foreign countries; adding alcohol to treat protein is to add alcohol as a precipitant for protein to speed up the sedimentation of protein , the effect is not good and the acidic protein cannot be completely removed, and the potency of the final high-quality heparin sodium does not exceed 150iu / mg

(2) During acid treatment, because acid has a degradative effect on heparin, the time of acid treatment in the existing process is too long, resulting in low yield of high-quality heparin sodium, and acid will destroy heparin molecules to produce many small molecules, affecting heparin molecules Structure, and then affect the quality of high-quality heparin sodium

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