Method for preparing polymyxin sodium methanesulfonate by crystallization process

Abstract

The invention belongs to the technical field of synthetic antibiotic extraction and purification, and particularly relates to a method for preparing polymyxin sodium methanesulfonate by a crystallization process, which comprises the following steps: (1) reacting colistin, formaldehyde and sodium hydrogen sulfite under certain conditions to obtain a polymyxin sodium methanesulfonate solution, and drying to obtain a polymyxin sodium methanesulfonate crude product; (2) stirring and dissolving the polymyxin sodium methanesulfonate crude product in a solvent A at 30-45 DEG C for 0.5-5 hours according to a mass volume ratio of the polymyxin sodium methanesulfonate crude product to the solvent A of 1: (3-10), preserving heat and filtering to obtain insoluble substance sodium salt, thereby obtaining filtrate; (3) slowly cooling the filtrate to 0-20 DEG C, then adding a poor solvent B with a volume of 20-50% of the filtrate volume, and carrying out stirring crystallization at the rotating speed of 20-60 r / min for 0.5-3 h; and (4) filtering, and drying a filter cake to obtain the polymyxin sodium methanesulfonate. The method has the advantages of short steps, simple operation and high yield, and is suitable for commercial popularization and production.

Description

technical field [0001] The invention belongs to the technical field of extraction and purification of synthetic antibiotics, and in particular relates to a method for preparing polymyxin sodium methanesulfonate through a crystallization process. Background technique [0002] Sodium polymyxin methanesulfonate is the prodrug of colistin sulfate, which is the product after colistin sulfate introduces methanesulfonic acid group, the purpose is to reduce the toxicity of colistin sulfate. Because colistin sulfate is too toxic, parenteral administration is not allowed in the United States. It is generally used orally for the treatment of intestinal infections. The toxicity of the chemically modified sulfomixin will be greatly reduced, and the LD50 will be reduced by 50 times. The above, therefore, can be administered intravenously and is the drug of choice for the treatment of Pseudomonas aeruginosa infection. [0003] The synthetic method about polymyxin sodium methanesulfonate b...

AI Technical Summary

Problems solved by technology

CN102161694B This patent provides a process of separation and purification using resin, the production operation is cumbersome, and it needs to use a large amount of acid and alkali to regenerate the resin, causing a certain burden on the environment

CN101525377B This patent provides a process for separation and purification using ultrafiltration membranes. This method has a long operating period and the yield is limited by the dead volume of the ultrafiltration membrane equipment. It is difficult to achieve a higher yield in actual production

Therefore, there is an obvious shortcoming in the preparation method of polymyxin sodium methanesulfonate mentioned in the above two patents: it is very easy to cause changes in the composition of polymyxin sodium methanesulfonate, which affects the quality of finished products

And above two kinds of preparations all are small-batch preparations, are not suitable for large-scale production, therefore, be necessary to invent a kind of simple to operate, stable process, and the obtained product meets the polymyxin sodium methanesulfonate required by Pharmacopoeia, and make Its production volume and quality meet the requirements of industrial production

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