大孔弱酸树脂纯化庆大霉素单组分C1a  

Purification Process of Gentamicin C1a by Macroporous Weak Acidic Resin

作　　者：李亚军[1] 林惠敏[1] 陈代杰[2] 孟宪纬 李继安[1] LI Yajun;LIN Huimin;CHEN Daijie;MENG Xianwei;LI Ji'an(State Key Lab.of New Drug and Pharmaceutical Process,Shanghai Institute of Pharmaceutical Industry,China State Institute of Pharmaceutical Industry,Shanghai 201203;School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240)

机构地区：[1]中国医药工业研究总院上海医药工业研究院,创新药物与制药工艺国家重点实验室,上海201203 [2]上海交通大学药学院,上海200240

出　　处：《中国医药工业杂志》2020年第2期264-269,共6页Chinese Journal of Pharmaceuticals

摘　　要：为从庆大霉素发酵产物中分离得到高纯度的C1a单组分(1),本试验采用单因素法考察了不同类型大孔弱酸树脂(D 152、D 155、D 157、HD-2、XR 140B和XR 157型)对1的吸附和解吸附能力,以及粗提液的pH值、流速和解吸液氨水浓度对纯化产物中1的纯度及杂质西索米星含量的影响。静态吸附法筛选结果显示,D157大孔弱酸树脂的分离效果和效率较好。动态吸附法的优选条件如下:将粗提液调节至pH 8.0~9.0,流速0.8 BV/h,洗脱液为0.15 mol/L氨水溶液,解吸流速为0.2 BV/h,树脂柱高径比4∶1。按照上述优化结果,最终可获得HPLC纯度93%以上、主要杂质西索米星降低至2.0%以下的高纯度1,可作为中间体用于合成依替米星。To obtain the high-purity gentamicin individual component C1 a(1) from gentamicin fermentation products, a single factor method was adopted to optimize the adsorption and desorption capabilities of the different types of macroporous weak acidic resin(D 152, D 155, D 157, HD-2, XR 140 B and XR 157) for 1. The effects of the pH value and flow velocity of crude extraction liquid and ammonia concentration of eluent were also investigated. The results of the static adsorption method showed that D 157 resin had better separation and efficiency. The optimal parameters of dynamic adsorption method were as follows: the crude extraction liquid whose pH value was adjusted to 8.0-9.0 was sampled at flow rate of 0.8 BV/h, then 0.15 mol/L ammonia solution was used to elute the target product at flow rate of 0.2 BV/h from the column of D 157 resin with height-diameter ratio of 4∶1. Finally, high-purity 1(HPLC purity above 93%) with sisomicin below 2.0% was obtained, which was suitably used as the intermediate for the synthesis of etimicin.

关 键 词：庆大霉素C1a 依替米星 西索米星 分离纯化 大孔弱酸树脂 

分 类 号：R978.12[医药卫生—药品]