基于超分子“气析”理论构建中药制剂靶向性评价方法及实验验证  

Construction of Evaluating Method and Experimental Research for Targeting of Traditional Chinese Medicine Preparations Based on Supramolecular Qi Chromatography Theory

作　　者：王敏存 胡超 贺玉婷 周燕子 刘有志 樊启猛 陈定芳 李海英 潘雪 周逸群 贺福元 WANG Min-cun;HU Chao;HE Yu-ting;ZHOU Yan-zi;LIU You-zhi;FAN Qi-meng;CHEN Ding-fang;LI Hai-ying;PAN Xue;ZHOU Yi-qun;HE Fu-yuan(Laboratory of Supramolecular Mechanism and Mathematic-physics Chracterization for Traditional Chinese Medicine,Hunan Provincial Key Laboratory of Druggability and Preparation Modification for ChineseMateria Medica,School of Pharmacy,Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学药学院,中药成药性与制剂制备湖南省重点实验室,中医药超分子机理与数理特征化实验室,长沙410208

出　　处：《中国实验方剂学杂志》2021年第20期113-120,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81573691,81874507,81803729,81903759);湖南省自然科学基金项目(2019JJ50430);中药成药性与制剂制备湖南省重点实验室开放基金项目(201705);长沙市科技计划项目(kq1907137);长沙市科学技术局项目(kq2004059);湖南省教育厅优秀青年项目(20B438)。

摘　　要：目的:构建基于超分子"气析"理论的中药制剂的靶向性评价方法,并对柴胡影响片仔癀的肝靶向性进行研究。方法:采用分子连接性指数分析主要归肝经的药材、片仔癀中的各成分"印迹模板"特征及肝靶向趋势;利用中药多成分"印迹模板"自主作用特征,结合靶区动力学和总量统计矩原理建立中药制剂的靶向性评价方法,并对片仔癀组、柴胡组、片仔癀+柴胡组、空白组4组作用的肝癌大鼠进行实验验证。结果:扣除主要归肝经药材分子连接性指数平均值后,片仔癀组与柴胡组的分子连接性指数相似度0.376 8,片仔癀+柴胡组与柴胡组的分子连接性指数相似度0.988 2,预测柴胡可增强片仔癀的肝靶向性。建立中药复方靶向性的评价体系,包括相对总量摄取率(RUET),相对总量浓度(RCT),相对"印迹"趋势(RITT)及相对"印迹"方差(RIVT);各组织中肝脏的RUET和RCT均为最大(RUET=1.88>1,RCT=2.30>1),其他组织这2个参数则均<1,说明片仔癀结合柴胡后能增加其在肝脏的分布,肝靶向性增强;除血浆外,其他组织的RITT及RIVT均在1.0附近波动,说明靶向修饰不改变片仔癀的"印迹"作用趋势,对成分种类也无明显影响。结论:在超分子"气析"理论指导下,可建立以分子连接性指数和总量统计矩参数表征中药制剂多成分"印迹"作用的靶向性评价参数体系,实现对中药制剂靶向性的评价,柴胡的加入可增加片仔癀的肝靶向性。Objective: To construct the targeting evaluation method of traditional Chinese medicine(TCM)preparations based on supramolecular Qi chromatography theory,and to study the liver targeting effect of Bupleuri Radix on Pien Tze Huang. Method: The molecular connectivity index(MCI)was used to analyze the characteristics of imprinted template and liver targeting tendency of TCM mainly attributed to liver meridian and components of Pien Tze Huang,and combined with target dynamics and total statistical moment principle,aimed at the independent action characteristics of multi-component imprinted template of TCM,a method for evaluating the targeting of TCM preparations was established. Hepatoma rats in Pien Tze Huang group,Bupleuri Radix group,Pien Tze Huang+Bupleuri Radix group and blank group were tested and verified. Result: After the average value of MCI of TCM mainly attributed to liver meridian was deducted,the MCI similarity between Pien Tze Huang group and Bupleuri Radix group was 0.376 8,Pien Tze Huang+Bupleuri Radix group and Bupleuri Radix group was 0.988 2,so it was predicted that Bupleuri Radix could enhance the liver targeting of Pien Tze Huang. A system for evaluating the targeting of TCM compounds was established,including relative total uptake efficiency(RUET),relative total concentration(RCT),relative imprinted tendency(RITT)and relative imprinted variance(RIVT). The RUET and RCT of liver were the highest in all tissues(RUET=1.88>1,RCT=2.30>1),and the corresponding values of other tissues were all <1,indicating that Pien Tze Huang combined with Bupleuri Radix could increase its distribution in liver and enhance liver targeting. Except for plasma,the RITT and RIVT of other tissues fluctuated around 1.0,indicating that targeted modification did not change imprinted tendency of Pien Tze Huang and had no significant effect on the types of components.Conclusion: Under the guidance of supramolecular Qi chromatography theory,a targeting evaluation parameter system can be established to characterize the multi-comp

关 键 词：中医药 超分子“气析”理论 分子连接性指数 肝靶向性 片仔癀 柴胡 印迹模板 

分 类 号：R22[医药卫生—中医基础理论] R94[医药卫生—中医学]