Multi-Stage Counter-Current Distribution-Two Steps Crystallization To Separate Spiramycin And Bitespiramycin

Bitespiramycin, having similar structure and property with spiramycin, is a kind of macrolide antibiotics comprising with various derivatives of spiramycin. Spiramycin is not only the material of bitespiramycin, but also the main impurity in the final product. Thus the downstream separation and purification process is important for obtaining qualified product. Based on the different polarity between bitespiramycin and spiramycin in phosphate solution and the change of solubility at different pH value, spiramycin can be separated from bitespiramycin by the process of multi-stage counter-current distribution-two steps crystallization. The larger drivingforce can be provided to separate the multi-components antibiotic with similar chemical structure and property by multi-stage counter-current operation. And two steps crystallization is favourable to the purification of spiramycin.The following results have been obtained:(1) The main factors affecting distribution coefficient of spiramycin and bitespiranycin in aqueous and ester phase was investigated. The optimal conditions in single stage washing had been obtained and a theoretical model of multi-stage counter-current washing was introduced. (2) The three-stage counter-current washing operation was developed, the removal rate of spiramycin and the retention rate of acylated spiramycin, isovaleryl spiramycin and isovalerylspiramycin III were as high as 79.14%,92.41%,92.56%and 92.12% respectively. (3) Two-steps crystallization was developed to separate isovaleryl spiramycin with weak polar and purify the final product of spiramycin. At 50℃, the best split pH was 7.6.This paper developed multi-stage counter-current washing technique and two-steps crystallization to separate spiramycin and purify the crude sample of bitespiramycin. This operation can not only make the recycle of spiramycin available, but also improve the effective components of bitespiramycin.