补阳还五汤11种成分的药物动力学与谱动学关系研究

目的阐明中药复方药物动力学与谱动学总量统计矩的数学模型与参数关系,示范性地用补阳还五汤中11种成分进行药物动力学与谱动学研究,探讨其量-时关系,包括代谢时间和色谱保留时间关系。方法采用HPLC/MS法测定补阳还五汤中黄芪甲苷等11种成分的药物浓度,并根据已建立的中药药物动力学与谱动学的总量统计矩数学模型,计算药物动力学与谱动学参数。结果补阳还五汤中11种成分的药物动力学总量统计矩参数分别为AUCT为432.9 ng·h·m L^(-1),MRTT为2.185 h,VRTT为5.259 h2;CLT为82.95 m L·h^(-1);VT为139.9 m L;95%的代谢时间区间为[0,6.680]h。谱动学的VUCT为457.5 ng·h·min·m L^(-1);MCRTT为5.625 min;VCRTT为7.949 min2,95%的时间区间为[0.09898,11.15]min。各取样点的谱动学总量零、一、二阶矩的RSD分别为86.09%、2.299%、7.587%,相似度基本上都在0.875以上。结论中药药物动力学与谱动学总量统计矩法能表征多成分代谢的量-时关系,其中谱动学还能表征所测定代谢成分的构成比的变化和色谱学特征,可为临床合理用药奠定理论与实验研究基础。

A novel method for integrating chromatographic fingerprint analytical units of Chinese materia medica:the matching frequency statistical moment method

Objective To facilitate the quality evaluation suitable for the unique characteristics of Chinese materia medica(CMM)by developing and implementing a novel approach known as the matching frequency statistical moment(MFSM)method.Methods This study established the MFSM method.To demonstrate its effectiveness,we applied this novel approach to analyze Danxi Granules(丹膝颗粒,DXG)and its constituent herbal materials.To begin with,the ultra-performance liquid chromatography(UPLC)was applied to obtain the chromatographic fingerprints of DXG and its constituent herbal materi-als.Next,the MFSM was leveraged to compress and integrate them into a new fingerprint with fewer analytical units.Then,we characterized the properties and variability of both the original and integrated fingerprints by calculating total quantum statistical moment(TQSM)parameters,information entropy and information amount,along with their relative standard deviation(RSD).Finally,we compared the TQSM parameters,information entropy and infor-mation amount,and their RSD between the traditional and novel fingerprints to validate the new analytical method.Results The chromatographic peaks of DXG and its 12 raw herbal materials were divided and integrated into peak families by the MFSM method.Before integration,the ranges of the peak number,three TQSM parameters,information entropy and information amount for each peak or peak family of UPLC fingerprints of DXG and its 12 raw herbal materials were 95.07−209.73,9390−183064μv·s,5.928−21.33 min,22.62−106.69 min^(2),4.230−6.539,and 50530−974186μv·s,respectively.After integration,the ranges of these parameters were 10.00−88.00,9390−183064μv·s,5.951−22.02 min,22.27−104.73 min^(2),2.223−5.277,and 38159−807200μv·s,respectively.Correspondingly,the RSD of all the aforementioned pa-rameters before integration were 2.12%−9.15%,6.04%−49.78%,1.15%−23.10%,3.97%−25.79%,1.49%−19.86%,and 6.64%−51.20%,respectively.However,after integration,they changed to 0.00%,6.04%−49.87%,1.73%−23.02%,3.84%−26.85%,1.17%−16.54%,and 6.40%−48.59%,respectively.The results demonstrated that in the newly integrated fingerprint,the analytical units of constituent herbal materials,information entropy and information amount were significantly reduced(P<0.05),while the TQSM parameters remained unchanged(P>0.05).Additionally,the RSD of the TQSM parameters,information entropy,and information amount didn’t show significant difference before and after integration(P>0.05),but the RSD of the number and area of the integrated analytical units significantly decreased(P<0.05).Conclusion The MFSM method could reduce the analytical units of constituent herbal mate-rials while maintain the properties and variability from their original fingerprint.Thus,it could serve as a feasible and reliable tool to reduce difficulties in analyzing multi-compo-nents within CMMs and facilitating the evaluation of their quality.

回眸中医药超分子化学研究十载,构筑中医药超分子“气析”理论

回眸中医药超分子化学研究历程,梳理和阐明怎样由中医药理论现代化所面临的问题推论出中医药超分子化学的破解之策,由此建立中医药超分子“气析”理论,找准现代化研究方法学大门。置自然界生物演化的大背景中来考虑,中医药理论是古代医家对生命体微观物质运行规律的宏观总结,本质上是对人体与自然界“分子社会”信息交流管控规律的揭示,常采用人文社会科学语言来表述医学科学的运行规律,具人文自然交融特质,是最典型的交叉学科。若要破解,就必须从现代自然科学中去寻觅既具有人文社会自然交融属性,又能反映生命体本质演化规律的学科,这便是生物超分子化学。为此,本团队于2011年展开了中医药理论、经络、药性、药理、品种归属、炮制、药剂、质量等超分子化学研究,完整提出了中医药学科发展面临的3个重大科学前沿问题和3个重大工程技术难题的破解之策,继而总结形成了现代化的中医药超分子“气析”理论诠释体系。

桑源中药用药规律及超分子作用机制研究

本文以超分子“印迹模板”自主作用规律为基础,旨在阐明桑源中药“同源异效”用药规律的超分子作用机制:由于中药和人体均为由超分子自识别、自组装、自组织、自复制而成的巨复超分子体。在体内气析作用下,“印迹模板”与外邪侵扰状态下的超分子体产生印迹作用,纠正机体的病理状态。桑源中药在机体内“印迹模板”差异的程度及变化的程度就是造成“异效”的物质基础。该理论能为桑源中药及其他“同源异效”中药的用药规律及“同病异治”机制研究提供借鉴。