The Study On Producition Process Optimization Of Ep Spiramycin

EP Spiramycin is in line with the European Pharmacopoeia quality standards of spiramycin short,the product is currently only a domestic production line,the basic export of all products,production and profit margins are high,but in the actual production process,EP9.0 Spirulina The qualified rate of only about 70%,sales of products and even due to quality reasons for the return situation,the enterprise is a very serious problem,the product quality needs to be improvedThe aim of this study was to solve the problem that the quality of the finished product was unstable and the purity of the purified product was unbalanced.In the small test,the pilot to optimize the medium and change the feeding method to improve the fermentation broth price,reduce the fermentation liquid impurity content,70m3 fermentation production to verify its stability;while optimizing the extraction process,improve production efficiency and ensure that drugs Meet quality standards.Based on the purpose of improving product quality,we use the fermentation medium and feeding method for the production of spiramycin from S.slofaciens and the primary washing and stripping of the stripping process after extraction and purification.Phase pH was optimized,mainly to improve the fermentation of impurities and improve the product yield,the following conclusions:1、By analyzing the effect of the fermentation medium on the fermentation titer of the fermentation medium of Streptomyces aureus and found that the use of starch in the fermentation medium instead of 0.5% dextrin,cottonseed protein instead of soybean meal,corn oil instead of soybean oil,The pH of the fermentation process was more stable,especially in the middle and late stages of fermentation.The pH was basically above 5.80,and the fermentation titer increased by 4.3% in the 5.0m3 tank.2、 In the feeding strategy to change the automatic feeding method,re-use of batch of manual feeding,in the feeding cycle of continuous adjustment of Streptomyces avium fermentation metabolic pathway,at the end of fermentation makes the fermentation of three main Impurity content impurity B1,impurity F,impurity D situation has greatly improved,the maximum decline of 25%,for the downstream extraction and purification provides favorable conditions;3 、 In the production of European Spiramycin EP9.0 version of the extraction and purification process to improve the product yield and yield.In the extraction and purification of the extraction process,according to the fermentation liquid liquid chromatographic data accurate control of a washing and stripping phase pH,so that the next phase of the water from the previous range of 6.90 ~ 7.0 to adjust the two gradient of 6.90 ~ 7.0,7.0 ~ 7.15,increase the gradient value,the operation requires more fine,the pH increase is conducive to increase the yield;back extraction of the lower phase of the pH adjustment is adjusted to the optimal four gradient from the previous 6.20 ~ 6.30,Adjusted to 5.70 ~ 5.80,5.80 ~ 5.90,5.90 ~6.05,6.05 ~ 6.30,the production of no longer occurs in the fermentation liquid impurity content is low and adjust the high pH loss of production,high impurity content but low pH caused product failure mistakes,product qualification rate reached 100%.