The Improved Process Of Mezlocillin Sodium

Mezlocillin sodium is one of the national essential drugs, which belongs to the third generation semi-synthetic penicillin antibiotics and was listed first in 1977 in Germany, Then Japan, Europe and the United States Department of Drug Administration approved. The antibacterial effecttiveness of the product is similar to that of the Carbenicillin, but its using scope is more extensive, and the antibacterial spectrum is also wider than natural penicillin. The simple recipe is reduced gradually, and it always be combined with Sulbactam as compound preparation.This paper takes 2-imidazolizone as the starting material, the production process of mezlocillin sodium was improved:1) 2-imidazolidone and methanesulfonyl chloride are reacted directly,1-methyl sulfonyl-2-imidazolidinon is obtained, which is reacted with environmental and safety BTC, named as Chlorine formylation reaction. Through the optimization of the reaction conditions, the total yield of 3-Methanesulfonyl-2-oxo-imidazolidine-l-carbonyl chloride is increased to 50% from the original 45%2) By improving the synthetic process of mezlocillin in this paper, purity of mezlocillin was increased from 97.5% to 99%.3) Solvent crystallization process of mezlocillin sodium was improved, suitable solvent and Salting out agent were selected. The addition amount of solvent was studied., which improvements improve the solubility of mezlocillin sodium, redissolving time was changed from 30min to less than 3min.Base on trial and combined with the actual production equipment and conditions, We conducted a trial of Mezlocillin sodium in synthesis. A total of 5 trials were conducted, and the yield of each step was stable. The results were basically the same, the quality of the products met fully requirement of CP2010. The reaction conditions of the synthesis process of this product is mild, the operation steps are simple and can be used for industrial production.In May 2013, production equipment was transformed, synthesis process of 3-Methanesulfonyl-2-oxo-imidazolidine-l-carbonyl chloride was carried out successfully. After a month of trial production, it is entirely self-produced from the side chain of Mezlocillin to Mezlocillin sodium in one company. It breaks through the bottleneck of production and quality. Because produced the side chain of Mezlocillin by us, more than 4 million yuan was saved per year. This project was authorized the first prize of scientific and technological progress in Shandong Lukang Pharmaceutical Co. Ltd.