Method for removing impurities in coarse heparin product by using ceramic membrane

Abstract

The invention discloses a method for removing impurities in a coarse heparin product by using a ceramic membrane. The method comprises the following steps: mixing intestinal mucosa with water and then adding NaCl and protease to carry out enzymolysis; filtering by a ceramic membrane after filtering enzymatic hydrolysate; eluting exchange resin after carrying out ion exchange on the clear liquor; and adding ethanol to eluent and then standing, participating, dewatering and drying, so as to obtain the coarse heparin product. By adopting a dynamic cross flow filtration mode, the enzymatic hydrolysate flows at a high speed on the surface of an inside membrane of a ceramic membrane tube at a certain flow rate; and enabling the enzymatic hydrolysate to penetrate a microporous membrane along the direction vertical to the ceramic membrane, intercepting macromolecular proteins by the membrane, so that the enzymatic hydrolysate and the impurities are separated and purified. The method is high in separation accuracy, and high in filtering efficiency, the yield of the product can be up to 99.5%, and the enzymatic hydrolysate has the advantages of being clear, lower in impurity content, free of heparin loss, convenient and fast for later adsorption and the like. The impurities in the extraction process of the coarse heparin product can be furthest removed under the condition that the heparin is not lost, the quality and the yield of the product are ensured, and the method is reasonable in production cost and applicable to large-scale industrial production.

Description

technical field [0001] The invention relates to a method for removing impurities in crude heparin sodium with a ceramic membrane. Background technique [0002] Heparin is a glycosaminoglycan widely present in animal organs, small intestinal mucosa, lung and other tissues. In the conventional extraction process, a large number of impurities such as proteins, polypeptides, amino acids, nucleic acids, etc. affect the purification process of heparin sodium, and the content of these impurities in crude heparin sodium directly affects the activity and quality of heparin sodium products. [0003] The traditional process removes impurities such as macromolecular proteins, polypeptides, amino acids, and nucleic acids in the enzymatic hydrolysis solution. At present, there are two methods used by most domestically: one is to use traditional filtration methods or separation equipment such as plate and frame filtration, drums, and centrifugal separation. , this kind of filtration metho...

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Problems solved by technology

[0003] The traditional process removes impurities such as macromolecular proteins, polypeptides, amino acids, and nucleic acids in the enzymatic hydrolysis solution. At present, there are two methods used by most domestically: one is to use traditional filtration methods or separation equipment such as plate and frame filtration, drums, and centrifugal separation. , this kind of filtration method can only filter out visible impurities and a small amount of large particle impurities, but there are still a large number of water-soluble protein impurities that are difficult to filter out in the enzymolysis solution; the other is to add complexing agent flocculation sedimentation (such as through Add complexing agent, alum, calcium carbonate, polyaluminum chloride, etc.) or the method of isoelectric point precipitation, this method can make the complexing agent and protein complex into larger particles, and then filter through the plate frame, centrifuge Filtration and other traditional filtration methods such as "dead end filtration" and "filter cake filtration" etc. The disadvantage of this method is that there are strict requirements on the amount of complexes added, the ratio of concentration, and the speed and cycle of adding complexing agents, and a certain amount of static time is required. At the same time, due to the complexation of this complexing agent with heparin sodium, it is easy to cause the loss of heparin activity, and this complexing method is generally no longer used.

The traditional techniques mentioned above have been used for a long time and are widely used. However, these traditional techniques can only roughly separate large suspended solids and other solids in the enzymolysis solution, and cannot separate soluble proteins, miscellaneous sugars, pigments, etc. that exist in large quantities in the enzymolysis solution. separate

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