Method for extracting and purifying pravastatin sodium from fermentation liquor

Abstract

The invention provides a method for extracting and purifying pravastatin sodium from a fermentation liquor, and belongs to the field of biological medicine preparation. According to the method for extracting and purifying pravastatin sodium from the fermentation liquor, a large amount of impurities and pigments are removed by alkalizing and acidifying the fermentation liquor, and the effective components in an acidizing liquid are enriched by an adsorbent, so that the purity of an extraction substrate is improved, the quantity of the extraction substrate is greatly reduced, and the quality ofan extraction liquid is further improved; in the whole production process, a single solvent system is adopted, the process is not complicated, the generated three wastes are low in amount, and the method is suitable for large-scale production. The content of pravastatin sodium produced by the method is more than 98.8 percent, the content of main impurity 6-epipravastatin is less than 0.15%, the content of total related substances is less than 0.4%, the product quality accords with the EP9.6 edition quality standard (the content of the pravastatin sodium is between 97.0% and 102.0%; a main impurity A, namely6-epipravastatin, is less than or equal to 0.3%; the content of the total related substances is less than or equal to 0.6%) of qualified pravastatin sodium, the total yield can reach more than 75%, and the large-scale production prospect is good.

Description

technical field [0001] The invention relates to the technical field of biofermentation pharmaceuticals, in particular to a method for extracting and purifying pravastatin sodium from fermentation broth. Background technique [0002] Pravastatin Sodium, chemical name: {1S-[1a(bs*, ds*), 2a, 6a, 8b(R*), 8aa]}-1, 2, 6, 7, 8, 8a-Hexahydro-b,d,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-1-naphthoheptanoic acid monosodium salt, molecular formula: C 23 h 35 NaO 7 , molecular weight: 446.52. Pravastatin sodium, as a high-efficiency hypolipidemic drug, can significantly slow down the process of atherosclerosis, and has excellent tolerance and high safety. For hyperlipidemia, familial hypercholesterolemia. [0003] The prior art methods of extracting and purifying pravastatin sodium from fermented liquid mainly contain: [0004] 1. Most reports use organic solvents to directly extract the fermentation broth, and then use other types of organic solvents for back extraction, an...

AI Technical Summary

Problems solved by technology

The problems that this method exists in the industrialized production are: at first, because there are a large amount of impurities in the pravastatin sodium fermented liquid, these impurities can not be removed well by the extraction process of organic solvent, thus generally in the ester phase The purity of pravastatin sodium is lower; secondly, because the concentration of pravastatin sodium in fermented liquid is generally very low, only 0.5-5g / L, need to use a large amount of solvent when purifying pravastatin sodium with organic solvent extraction method (generally 1-2.5 times of fermented liquid), moreover, because multiple solvents (usually more than three kinds of being seen in the report at present) are used in the production process, it is very easy to cause cross-contamination, and like this in industrialized large-scale production process It will bring more serious environmental pollution and three wastes problems, and endanger the health of production operators;

This method also has the problems brought about by the first method above, and at the same time, it has produced a relatively cumbersome inconvenience for supply and demand, and because the method of ion exchange has produced a large amount of waste water, the risk of environmental pollution has increased to a certain extent. In addition, waste water treatment It takes a lot of manpower and material resources, which virtually increases the production cost of pharmaceutical companies;

[0006] 3. CN1229326C has a report to adopt the method of macroporous adsorption resin purification, although this method has avoided the drawback that a large amount of organic solvents use, it has used the mixture of a large amount of water-soluble organic solvents and water in the production process, and during continuous scale production The application of the solvent is cumbersome and difficult, and the consumption is large, and through its purification and refinement, the content of pravastatin sodium is only 95.6%, which still cannot meet the industry's requirements for its purity, and can not reach the relevant quality standards

[0007] And the ideal method of purifying pravastatin sodium from fermented liquid is to meet the requirements of high purity, high yield and low pollution simultaneously, but the purification method in the prior art often cannot satisfy above-mentioned three requirements simultaneously