共晶分离技术在染料木素-葛根素-大豆苷元三元体系分离纯化中的应用  

Application of cocrystal separation technology in the separation and purification of genistein-puerarin-daidzein ternary system

作　　者：李雪铭 卢燕 钱帅[1] 庞遵霆 魏元锋[1] LI Xue-ming;LU Yan;QIAN Shuai;PANG Zun-ting;WEI Yuan-feng(School of Traditional Chinese Pharmacy,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学中药学院,江苏南京211198

出　　处：《药学学报》2023年第2期439-446,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81873012,82074029,82104401,82274217);中国药科大学“双一流”建设项目(CPU2018GY11,CPU2018GY27);江苏省青年基金项目(SBK2020042291);中国博士后面上项目(2020M671665);中央高校基金资助项目(2632021ZD15).

摘　　要：共晶分离技术是一种利用配体选择性与目标化合物形成共晶后从混合体系中分离的技术。葛根素、染料木素及大豆苷元是葛根中的主要成分,这3种结构相似的成分的分离精制多采用常规柱色谱、重结晶等技术,具有分离周期长、溶剂消耗量大、制备效率低等问题。本团队利用前期新发现的共晶分离现象设计并实现了染料木素-葛根素-大豆苷元三元混合物的分步提取分离实验,在混合体系中依次加入咖啡因和脯氨酸作为共晶配体,通过混悬液法形成了染料木素-咖啡因共晶和葛根素-脯氨酸共晶,并从溶液中分别分离析出,最终得到染料木素纯度为93%的染料木素-咖啡因共晶和葛根素纯度为99%的葛根素-脯氨酸共晶,且大豆苷元的纯度也提高了6.76倍。本研究提出了一种不同于传统分离方法、操作简单、成本低、适用范围广的分离方法,实现了中药中结构相近化学组分的分离,为共晶技术应用于中药的分离与精制奠定基础。Cocrystal separation technology is a technology that utilizes coformers to selectively form cocrystals with target compounds and separate them from mixed systems.Our study used puerarin(PUE),daidzein(DDZ),and genistein(GEN)as model drugs,which have similar structures and are the main isoflavones in Pueraria lobata root.The separation and purification processes in the modern traditional Chinese medicine(TCM)of these three components use conventional column chromatography,recrystallization,and other technologies,which have the issues of lengthy separation cycles,high solvent consumption,and inefficient preparation.Different with existing separation technology,our team used the early-found cocrystal separation method to design a step-bystep extraction and separation experiment of GEN-PUE-DDZ ternary mixture.Caffeine and L-proline were added to the mixed system in turn,GEN-caffeine cocrystal and PUE-proline cocrystal were prepared by suspension method.The cocrystals precipitated out of the solution.The purities of the GEN-caffeine cocrystal and the PUEproline cocrystal could achieve 93%(the purity of GEN)and 99%(the purity of PUE).Besides,the purity of DDZ could also be increased by 6.76 times.This study proposed a simple operating,low cost and wide application range separation method different from the traditional separation method and realized the separation of structurally similar chemical components in TCM,laying a foundation for the application of cocrystal technology in the separation and refining of TCM.

关 键 词：葛根素 染料木素 大豆苷元 共晶 分离方法 

分 类 号：R943[医药卫生—药剂学]