Separation And Preparation Process Of Isovaleryl Spiramycin Ⅲ

Kelimycin is one of the newest drugs and the only antibiotic which has the independent intellectual property rights in China. Clinical results show that the antibacterial activity and pharmacodynamic activity is significant higher than similar antibiotic drugs, so the development and application of Kelimycin would have a good prospect in the future. Kelimycin is a multi-component drug, mainly composed of Isoamyl acyl spiramycin Ⅰ, Isoamyl acyl spiramycin Ⅱ, Isoamyl acyl spiramycinⅢ and a variety of acylate spiramycin. Isovaleryl spiramycin Ⅲ is the highest pharmacodynamic activity and the best stability component in the body. This component is also the most important component for further research. Therefore, we need to establish an industrial method for preparing Isovaleryl spiramycin Ⅲ. In this paper, we built a technical process called "Double column chromatography separation-Extraction and purification-Recrystallization". In this process, the Isoamyl acyl spiramycinⅢ content can rise from34%to67%. The entire process is mainly consisted of the following aspects of study:1, The kinetics and thermodynamics adsorption. We studied a few factors that influenced the adsorptive process, like pH conditions, temperatures and ionic strength conditions. It is learned that the higher pH, higher temperature and higher ionic strength are better for the adsorption.2, On the study of the different flow rates, we get the breakthrough curve with all and separate components, from which we can have the adsorption capacity and adsorption flow rate optimized.3, Chromatographic separation. The Kelimycin was firstly adsorbed by the resin, and then washed through by solvent so that components in the resin will be redistributed. After that, two columns in series resolved by Petroleum ether and the production was then obtained. In the production, the content of isovaleryl spiramycin Ⅲ could reach67%.4, Impurities separation. There are varieties of unknown components that the polarity is less than Isoamyl acyl spiramycinⅢ, but their structure and nature have not been reported in any article. It turned out that after recrystallization, this kind of impurities could possibly be reduced by67.2%.