Purification method of liprestatin

Abstract

The invention provides a method for purifying lipstatin, which comprises the following steps: 1)providing an organic solvent extract of lipstatin; 2)concentrating the organic solvent extract of lipstatin; 3)mixing an concentrate obtained in the step 2) with C5-C20 alkane and a liquid state organic salt, filtering to obtain a filtrate; and 4)cooling the filtrate obtained in the step 3) and crystallizing to obtain the lipstatin. Compared with the prior art, the method has the following advantages and active effect that the simple processes of extraction, concentration and crystallization can realize extraction of lipstatin, the HPLC purity of lipstatin can reach as high as 86% (for instance); and absolute content can reach as high as 74% (for instance). According to the method, defects of high equipment cost, large energy consumption, complex operation and little one-time treatment capacity in prior art can be overcome, production cost is reduced, production efficiency is increased, and the method is suitable for industrial large-production.

Description

technical field [0001] The invention belongs to the field of pharmacy, and in particular relates to a method for purifying liprestatin. Background technique [0002] The English name of Lipstatin (also known as Nibostatin) is Lipstatin, CAS number: 96829-59-3, molecular formula: C 29 h 49 NO 5 , molecular weight: 491.708, structural formula as shown in formula I below: [0003] [0004] Liprestatin is a metabolite of Streptomyces toxytricini, which can selectively inhibit the activity of pancreatic lipase in the gastrointestinal tract and reduce the decomposition and absorption of fat. Its tetrahydro derivative orlistat (orlistat) has been successfully developed by Roche Inc. as a weight-loss drug Xenical. It is currently a new type of weight-loss and lipid-lowering drug recognized internationally. Orlistat is currently the only OTC weight-loss drug in the world. It is a potent and long-acting specific gastrointestinal lipase inhibitor. Once less than consumed, body ...

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Problems solved by technology

[0006] U.S. Patent No. 4,598,089 disclosed the technology of producing liprestatin through microbial fermentation in 1986. The extraction takes silica gel as a carrier, elution with chloroform, elution on silica gel, n-hexane and ethyl acetate, upper reverse-phase chromatographic column, methanol washing detachment, repeated chromatography, this method needs to adopt silica gel column, the cost is high, and it is not suitable for industrialization

[0007] Chinese Patent Publication No. 201010229409.2 uses a nozzle-type centrifuge to pre-concentrate the fermented liquid, centrifugally atomize and dry the bacteria residue, solvent extract, and concentrate to obtain liprestatin in the form of a paste, with a yield of more than 80%, but this method uses a spray Drying, high energy consumption, and low purity of the resulting product, so it is not suitable for industrialized large-scale production

[0008] Scientific literature: Hu Weimin et al., Fermentation and Extraction of Liplastatin Produced by Streptomyces Toxicina, Chinese Journal of Pharmaceutical Industry, Volume 38, No. 10, 2007, 705-708 discloses a method for extracting liplastatin, It includes: ultrasonic crushing of cells, acetone extraction, ethyl acetate extraction, normal phase column chromatography and semi-preparative column separation. The obtained riprestatin reaches 94%, but the yield and content are not mentioned. This method is still relatively cumbersome. Large investment and large consumption, so the cost is high, so it is not suitable for large-scale industrial production

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