摘要
针对多成分、多靶点的中药药动/药效(PK/PD)相关性研究进行研读与解析,通过示范性的研究方案,提出创新策略。中药PK/PD相关性研究要求在机体病理状态下,同一含药血清平行进行,内容主要包括多成分PK参数测定;血清/靶组织动态指纹图谱和多靶/生物标志物药效动力学模型的建立;研究PK/PD结合模型,选择分析程序,表征有效成分群浓度-时间-效应三者之间的内在关系;开展指纹谱-PD相关性分析,从化学指纹和代谢指纹追踪药效变化规律;构建能表征保留时间和效应相关的特征效应峰指纹谱和能表征峰面积消长和效应相关的量效指纹谱;将成分群指纹-药效指纹(特征效应峰指纹谱和量效指纹谱)-药代指纹谱图中的多维特征信息整合;加工与编辑,构建有效成分群的"活性整合指纹图谱"的多维图像。基于多成分、多靶点的中药PK/PD相关性研究为中药PK/PD结合模型研究及阐明真正起作用的物质基础,弄清有效成分群的体内相互作用等开拓新的研究思路。
To analyze the correlation of pharmacokinetic/pharmacodynamic（PK/PD） of Chinese materia medica（CMM） based on the multi-components and multi-targets,through the example of demonstrative research,we brought forward some innovative strategies.The research requires to use a medicated serum in parallel at a pathologic state.The experiments included the determination of multi-components PK parameters,the establishment of serum dynamic fingerprints and multi-targets PD models,the research on PK/PD binding model,the selection of the analytic program,the representation of internal relations among the concentration,time,and effect in the effective component group,the analyses on the correlation between fingerprint and PD,the tracing of the rule of PD from the chemical fingerprints and metabolic fingerprints,and the construction of a spectrum which could represent the characterization of the correlation between the retention time and the effect and the characterization of dose-effect fingerprint spectrum of the correlation between peak area growth and effects.The multi-dimensional characteristics of fingerprint-pharmacophore fingerprints（feature effect peak and dose-effect fingerprint spectrum）-fingerprint spectrum of PK are integrated,processed,and edited and a multi-dimensional image of ＂active integration fingerprint＂ in the active component group was built.A new research method on the combination of the PK/PD of CMM was explored.Only by this way,we will really understand the interaction in active component group in vivo and clearly explain the material base which truly works.
出处
《中草药》
CAS
CSCD
北大核心
2013年第12期1521-1528,共8页
Chinese Traditional and Herbal Drugs
基金
国家"重大新药创制"科技重大专项"十一五"计划资助项目(2009ZX09301-007)
上海市自然科学基金资助项目(06ZR14078)
上海市中药现代化专项资助项目(08DZ1971801
09DZ1975200)
关键词
中药
多成分多靶点
药动学
药效动力学结合模型
活性整合指纹图谱
解读与策略
Chinese materia medica
multi-components and multi-targets
pharmacokinetic/pharmacodynamic model
active integration fingerprint
analysis and strategy
作者简介
杨义芳Tel：（021）62473018E—mail：yangyf4912@163．com
