New production process for refining crude heparin sodium

Abstract

The invention relates to a new production process for refining crude heparin sodium. The new process comprises the following steps of: firstly, preparing biological enzyme powder which is porcine trypsin hydrolase powder; then, mixing self-made content-known crude heparin sodium and a sodium chloride solution in a certain proportion to prepare a crude heparin sodium solution; removing protein by catalytically cracking, adjusting acid content and oxidizing; and carrying out the processes and biological technical methods of low-temperature centrifugal separation, ultrafiltration fraction, concentration, precipitation, dehydration, drying and the like to obtain a heparin sodium fine product. The invention has the advantages of short production period, low raw and auxiliary material energy consumption, high product recovery rate, good purity, high valence and good quality; when the recovery valence of the product is 150-160 u / mg, the recovery rate can be higher than 96 percent; and other indexes can reach the requirements of the national pharmacopeia standard.

Description

technical field [0001] The present invention relates to a refining production process of crude heparin sodium, in particular to a new process of refining heparin sodium by using biological enzyme catalyzed cracking to deproteinize and adjusting acid to remove protein, and then using low-temperature centrifugal separation technology combined with primary oxidation treatment and ultrafiltration classification to refine heparin sodium . Background technique [0002] Heparin is a natural bioactive mucopolysaccharide substance discovered from the liver of dogs by McLane in 1916 when he was studying blood coagulation. More than ten years later, developed countries in Europe and the United States discovered and extracted it from bovine lung, and later found that it was extremely rich in small intestinal mucosa of pigs and sheep, and began to conduct medical clinical research. Heparin was officially listed in the United States Pharmacopoeia in 1940, and it is widely used in anticoa...

AI Technical Summary

Problems solved by technology

However, there are deficiencies in the above-mentioned several processes; in the first two-step oxidation method of potassium permanganate and hydrogen peroxide, manganese dioxide absorbs heparin, which causes a large loss of heparin activity and a low recovery rate; it is difficult to filter, the production cycle is long, and the color is not good. Good, poor quality and other disadvantages; the second secondary oxidation process of adding hydrogen peroxide in stages is currently widely used because of the better color of the product

However, this process mainly has the disadvantage that the secondary hydrogen oxidation treatment will damage the heparin structure, and it is difficult to obtain high-quality heparin products with high titer; the third enzymatic hydrolysis combined with oxidation process has been reported but has not been widely used. Deficiencies in process design and optimization of solution conditions, oxidation conditions, and combined use of biological product extraction, separation, and purification technologies

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