大孔树脂法分离纯化那他霉素工艺研究.docVIP

大孔树脂法分离纯化那他霉素的工艺研究 王海燕 李晓露 王健 张丽 林旸 张金娟 张雪霞* （华北制药集团新药研究开发有限责任公司，微生物药物国家工程研究中心，石家庄 050015） 摘要 研究大孔吸附树脂分离纯化那他霉素发酵液的工艺，提高那他霉素成品质量，得到高纯度药用级那他霉素。 用HPLC检测方法以那他霉素的洗脱率为指标考察大孔树脂分离纯化那他霉素的吸附性能和洗脱参数。 那他霉素从发酵液中的最佳溶出pH值为11；分离纯化那他霉素的有效吸附剂为大孔吸附树脂HZ816，其动态吸附量为150mg/mL，解吸收率在90%以上，成品纯度大于98%。 该高纯度药用级那他霉素的规模化分离纯化方法为国内首次应用，工艺简单可靠，分离效果好，适于工业化生产。 关键词 那他霉素；大孔吸附树脂；分离纯化 中图分类号A Studies on Separation and Purification of Natamycin by Macroporons Resin Wang Hai-yan, Li Xiao-lu, Wang Jian, Zhang Li, Lin Yang, Zhang Jin-juan, Zhang Xue-xia (New Drug Research Development Company of NCPC, National Engineering Research Center of Microbial Medicine, Shijiazhuang 050015) Abstract Objective The method that separation and purification of high-purity Natamycin for pharmaceutical use from fermentation broth by macroporous resins was studied. Methods Based on adsorption capacity and elution efficiency of Natamycin, the conditions to separation and purification of Natamycin by macroporous resins were optimized. Results The optimum pH value for releasing Natamycin from the fermentation broth was 11. HZ816 was selected as the effective macroporous adsorbent for separation and purification of Natamycin from fermentation broth. The desorption rate of Natamycin was over 90% and the purity of the final product was over 98% under the optimal conditions. Conclusion This method about separation and purification of high-purity Natamycin for pharmaceutical use was discovered for the first time and was warranted for the commercial process. Key words Natamycin; Macroporous resin; Separation and purification 那他霉素是一种多烯大环内酯类抗真菌抗生素，是一种白色至乳白色几乎无臭无味的结晶粉末。分子式C33H47NO13，分子量为665.73。化学结构式如下： 图1 那他霉素的结构式 Fig. 1 The structure of natamycin 那他霉素是那塔尔链霉菌(Streptomyces natalenis)、恰塔努加链霉菌(Streptomyces chattanoogensis)或褐黄孢链霉菌(Streptomyces gilvosPoreus)等微生物的次代谢产物，从发酵液中提取纯化后获得。那他霉素是一种高效、低毒的具有广谱的抗霉菌、酵母菌、某些原生动物和藻类剂，可以用于医疗、食品、饲料、粮储防霉，特别是在食品原料保鲜、食品防腐等方面具有良好的使用[1, 2]。 那他霉素是两性物质，分子中含有一个碱性基团和一个酸性基团，其电离常数pKa值为8.35和4.6，相应的等