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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

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【作者】 任风芝张雪霞陈书红李丽红段宝玲

【Author】 Ren Feng-zhi;Zhang Xue-xia;Chen Shu-hong;Li Li-hong;Duan Bao-ling;National Engineering Research Center of Microbial Medicine,Hebei Industry Microbial Metabolic Engineering & Technology Research Center,New Drug Research & Development Company of NCPC;

【机构】 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

【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。

【Abstract】 Objective To study the separation and purification process of high-purity(γ-hydroxylmethylleucine4)-cyclosporin A.Methods(γ-hydroxylmethylleucine4)-cyclosporin A 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)-cyclosporin A 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)cyclosporin A 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.

【基金】 国家“重大新药创制”科技专项(项目编号2010ZX09401-403)
  • 【文献出处】 中国抗生素杂志 ,Chinese Journal of Antibiotics , 编辑部邮箱 ,2013年07期
  • 【分类号】TQ464
  • 【被引频次】3
  • 【下载频次】182
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