环孢素衍生物(γ-hydroxylmethylleucine^4)-cyclosporin A的分离纯化与鉴定  

Purification and identification of (γ-hydroxylmethylleucine^4)-cyclosporin A

作　　者：任风芝[1] 张雪霞[1] 陈书红[1] 李丽红[1] 段宝玲[1] 

机构地区：[1]微生物药物国家工程研究中心,河北省工业微生物代谢工程技术研究中心,华北制药集团新药研究开发有限责任公司,石家庄050015

出　　处：《中国抗生素杂志》2013年第7期512-515,共4页Chinese Journal of Antibiotics

基　　金：国家"重大新药创制"科技专项(项目编号2010ZX09401-403)

摘　　要：目的研究高纯度环孢素衍生物(γ-hydroxylmethylleucine4)-cyclosporin A的分离纯化工艺。方法采用HPLC检测方法,以大孔树脂、聚合物微球为载体进行分离纯化。利用质谱(MS)和核磁共振谱(NMR)解析化合物的结构。结果发酵液经过滤,吸附,结晶得到粗提物,粗提物再经聚合物微球,浓缩,萃取,结晶得到高纯度产品,光谱数据确定为(γ-hydroxylmethylleucine4)-cyclosporin A,所得产品纯度≥95%,收率大于70%。结论建立(γ-hydroxylmethylleucine4)-cyclosporin A的分离纯化工艺,流程简单、可行,为该产品产业化开发提供基础。Objective To study the separation and purification process of high-purity （γ-hydroxylmethylleucine4）-cyclosporinA. Methods （γ-hydroxylmethylleucine4）-cyclosporinA was separated and purified by macroporous resin and nanoscale polymer particles. The chemical structure was analyzed by the spectral analysis including MS and NMR. Results The crude （γ-hydroxylmethylleucine4）-cyclosporinA was obtained from the fermentation broth by methods of filtration, adsorption and crystallization. After a further purification by nanoscale polymer particles, concentration, solvent extraction and crystallization, the high purity （γ-hydroxylmethylleucine4）-cyclosporinA was isolated. The structure was identified by spectral data. The purity of the final product was more than 95% and the total yield was above 70%. Conclusion The established purification process was simple and feasible for further industrialization of this product.

关 键 词：(γ-hydroxylmethylleucine4)-cyclosporinA 大孔树脂 聚合物微球 分离纯化 结构鉴定 

分 类 号：R979.5[医药卫生—药品]