中药药代动力学与谱动学量-时表征方法的理论与分析

Theory and Analysis of Pharmacokinetic and Chromatokinetics Dose-time Characterization Methods in Traditional Chinese Medicine

目的:建立中药药代动力学与谱动学量-时表征理论体系。通过分析山银花、鱼腥草注射剂、金银花及补阳还五汤等制剂的药代动力学与谱动学行为,比较半衰期、统计矩和统计学3种方法表征量-时关系的异同,找到最适宜的表征方法。方法:从100只昆明种小鼠中随机选取10只作为空白组,其余小鼠耳廓涂抹二甲苯建立耳肿胀急性炎症模型。造模成功后的小鼠灌胃山银花水提液(30 g·kg^(-1)),空白组灌胃等体积的生理盐水。收集不同时间点的小鼠血浆,测定成分含量变化。同时,将前期的鱼腥草注射剂、金银花、补阳还五汤的药代动力学结果纳入,计算药代动力学、谱动学参数,比较使用半衰期法、统计矩法、统计学法计算代谢95%总成分时间的差异。结果:在半衰期法的基础上,建立了适宜中药多成分体系量-时关系表征的统计矩法和统计学法数学表达式。药动学结果显示,山银花中单个成分药代动力学参数各异,隐绿原酸、芦丁表现为二室模型,其余成分表现为一室模型;经谱动学相似度计算,鱼腥草注射剂、金银花、山银花及补阳还五汤中所含各成分间的体内代谢方式不一,差异较大。经半衰期法、统计矩法、统计学法计算4种中药或制剂在体内代谢95%总成分时间,发现与统计矩法比较,半衰期法计算结果差异较大,而统计学法则差异较小。结论:统计学法既可体现统计矩法的特点,表征各成分的离散程度,又可与指纹图谱关联构成谱动学,表征95%的药物成分的量-时关系,是较宜表征中药成分群量-时关系的方法。

Objective:To establish a theoretical system of pharmacokinetic and spectrokinetic dosetime characterization of traditional Chinese medicine(TCM).By analyzing the pharmacokinetic and spectrokinetic behaviors of Lonicerae Flos,Houttuyniae Herba injection,Lonicerae Japonicae Flosand Buyang Huanwutang,this paper compared the similarities and differences of the three methods for characterizing the dose-time relationship,namely half-life,statistical moment and statistics,in order to find the most suitable method for characterizing the relationship.Method:Ten mice were randomly selected from 100 Kunming mice as the blank group,and the remaining mice were coated with xylene in the auricle to establish the acute inflammation model of ear swelling.After successful modeling,the mice were gavaged with aqueous extract of Lonicerae Flos(30 g∙kg^(-1)),and the blank group was gavaged with an equal volume of normal saline.The plasma of mice was collected at different time points to determine the content changes of components.At the same time,the pharmacokinetic results of Houttuyniae Herba injection,Lonicerae Japonicae Flos and Buyang Huanwutang were included,and the pharmacokinetic and spectrokinetic parameters were calculated.Then the difference in the time of calculating 95%total component content of metabolism by half-life method,statistical moment method and statistical method was compared.Result:On the basis of the half-life method,the mathematical expressions of statistical moment method and statistical method suitable for the characterization of dose-time relationship of multi-component system of TCM were established.The results showed that the pharmacokinetic parameters of the individual components in Lonicerae Flos varied,with cryptochlorogenic acid and rutin showing a twocompartment model and the other components showing a one-compartment model.After calculation of spectrokinetic similarity,the metabolic patterns among the components contained in Houttuyniae Herba injection,Lonicerae Japonicae Flos,Lonicerae Flos and Buyang Huanwutang were different and varied greatly in vivo.The time to metabolize 95%of the total components of the four research subjects in vivo was calculated by the half-life method,statistical moment method and statistical method,and it was found that the difference between statistical moment method and half-life method was large,and the difference between statistical moment method and statistical method was small.Conclusion:Statistical method not only reflects the characteristics of statistical moment method,characterizes the dispersion degree of each component,but also can be associated with fingerprint to form spectrokinetics,characterizing the dose-time relationship of 95%of drug components,which is a more desirable method to characterize the dose-time relationship of the component groups in TCM.