摘要
中药多来源于动植物,具有遗传多态性,成分具有动态性,反映到指纹图谱中以特征峰和指纹峰出现,其谱动学处于动态变化之中,不宜用确定成分的谱动学方法进行研究。该文在前期谱动学研究的基础上,运用总量统计矩原理,叠加减药物血样和空白血样指纹图谱的总量统计矩参数,创建动态中药多成分的谱动学数学模型及参数体系,并以补阳还五汤为模型进行验证,为中药谱动学研究提供新方法。实验采用HPLC测得补阳还五汤空白血样及各时间点血样指纹图谱总量统计矩参数,利用总量统计矩加合计算含药血样的整体总量统计矩参数及空白血样的总量统计矩参数,两者相减可得纯药物的初次总量统计矩参数,运用代谢平衡常数迭代计算,至吸收和代谢平衡常数达稳态,即得补阳还五汤在大鼠体内代谢的谱动学参数VUC_T 1.262×10~8 mAu·s,MRT_T 37.48 h,VRT_T 9.016×10~2 h~2,CL_T 25.79 mL·h~(-1)·kg~(-1),V_s 1.586×10~2 mL·kg~(-1),t_(T,0.5) 6.15 h,表明经0~96.33 h后整方95%的成分被排除体外。实验证明所建的中药谱动学数学模型及参数体系能表征补阳还五汤的量-时作用关系,能用于中药成分群的体内代谢动力学研究。
The Chinese medicine is mostly derived from plants or animals, highly polymorphic, with dynamic components which are reflected by the characteristic peaks and fingerprint peaks in chromatographic fingerprints. The chromatopharmacokinetics method for determined components is not applicable due to dynamic changes of chromatopharmacokinetics. Based on the preliminary study, dynamic pharmacokinetics mathematical model for multiple components in Chinese medicine was set up and verified by Buyang Huanwu Decoction as the model drug, applying the principle of the total quantum statistical moment(TQSM), superimposing or subtracting the relevant statistical parameters in blood samples and blank samples. This provided a new method for the chromatopharmacokinetic study of Chinese medicine. HPLC was used to determine the TQSM parameters in blood and blank sample fingerprints of Buyang Huanwu Decoction at each point, and the overall TQSM parameters of drug-containing blood sample and blank samples were obtained with addition calculation of TQSM; while the initial TQSM of the pure drug can be obtained with subtraction calculation. The metabolic and absorption equilibrium constants were calculated iteratively to a steady state using the estimated metabolic equilibrium constants, then the metabolic chromatopharmacokinetic parameters in rats were obtained: VUC_T 1.262×10~8 mAu·s, MRT_T 37.48 h, VRT_T 9.016×10~2 h~2, CL_T 25.79 mL·h~(-1)·kg~(-1), Vs 1.586×10~2 mL·kg~(-1), t_(T,0.5) 6.15 h, respectively. This suggested that 95% of the compounds in whole recipe were metabolized and secreted from the body after 0-96.33 h. The experiment verified that the established mathematical model and the total quantum moment statistics parameters can represent the dose-time relationship of Buyang Huanwu Decoction, which can be used to study on in vivo metabolism dynamics for Chinese medicine.
引文
[1] 贺福元,邓凯文,刘文龙,等.中药复方药物动力学总量统计矩法的实验验证研究[J]. 中国中药杂志,2013,38(2):253.
[2] 闫冬酶,闫小萍.近10年补阳还五汤实验研究概况[J].中国中医药信息杂志,1999,6(6):16.
[3] 刘志龙,邓常青,葛金文,等.补阳还五汤抗脑缺血再灌注损伤作用机理的研究[J].中国中医基础杂志,1998,4(8):32.
[4] 贺福元, 周宏灏, 邓凯文, 等.指纹图谱的一种定性定量研究新方法:总量统计矩分析法[J],药学学报,2008, 43(2): 195.
[5] 数学手册编写组.数学手册[M].北京:高等教育出版社,2010.
[6] 魏树礼,张强.生物药剂学与药物动力学[M]. 北京:北京大学医学出版社,2004.
[7] 邓俊林,邓凯文,刘文龙,等.中药多成分体系谱动学数学模型的研究[J].中华中医药杂志,2013,28(10):3058.
[8] 段晓鹏,贺福元,周晋,等.补阳还五汤指纹图谱总量统计矩加合性的研究[J].中国中药杂志,2011,36(23):29.
[9] 贺福元,周逸群,邓凯文, 等.超分子化学对中医药理论的特殊影响[J].中国中药杂志,2014,39(8):1534.
[10] 张翠英,任伟光.基于经典丹参药对“丹参-冰片”“丹参-红花”的药动学研究探讨中药配伍增效的药动学研究策略[J].中国中药杂志,2017,42(12):2413.