Department of Pharmaceutics, Pharmacy College, Hunan University of Chinese Medicine, Changsha, Hunan 410208, P.R. China; Hunan Key Laboratory of Druggability and Preparation Modification for Traditional Chinese Medicine, Changsha, Hunan 410208, P.R. China.
Department of Pharmaceutics, Pharmacy College, Hunan University of Chinese Medicine, Changsha, Hunan 410208, P.R. China; Hunan Key Laboratory of Druggability and Preparation Modification for Traditional Chinese Medicine, Changsha, Hunan 410208, P.R. China; Department of Supramolecular Mechanism and Mathematic-Physics Characterization for Chinese Materia Medicine, Changsha, Hunan 410208, P.R. China.
Phytomedicine. 2018 Jun 1;45:18-25. doi: 10.1016/j.phymed.2018.03.012. Epub 2018 Mar 7.
It is well-known that the public still have been facing on a severe issue about the inconsistency of quality and therapeutic efficacy of traditional medicines. Recently, Professor Chang-Xiao Liu has created a new promising concept for identifying relevant quality-markers (Q-marker) from herbs, their formulas and manufacturing products. Therefore, building up a new approach is necessary for us to bridge over quality to efficacy of pharmaceutical products.
In this paper, five candidate Q-markers, astragaloside IV, paeonflorin, amygdalin, tetramethylpyrazine, ferulic acid in Buyanghuanwu injection (BYHWI) had been designed to carry out in rat by using single and polypharmacokinetic models for total quanta to ascertain adequate Q-marker.
The Q-marker transitivity in vivo was studied with polypharmacokinetic model and its similarity approach, which were modeled with TQSM principle. The Q-marker was ascertained with transitive similarity and bioavailability in polypharmacokinetics. Their concentrations in plasma sample of white rat were determined by RP-HPLC. Data analyses were used by the DAS software for singles and myself-written-program with EXCEL for multiples.
In BYHWI, five candidate Q-marker pharmacokinetic profiles were singly fixed to two compartmental models in rat using classical compartmental analysis, but there were tremendous differences among which the candidate parameters were fluctuated from nearly 3552 folds to equivalency. The theoretical value of TQSM polypharmacokinetic parameters such as AUC, MRT, VRT, CL, V over the mixure of five drugs were 110.8 ± 51.91 mg min ml, 176.0 ± 36.5 min, 39,921 ± 4311 min, 0.3116 ± 0.02347 ml min kg, 54.83 ± 7.683 ml kg respectively. The TQSM polypharmacokinetic parameters in astragaloside Ⅳ ordered by AUC, MRT, VRT, CL, V were 110.8 ± 51.91 mg min ml, 176.0 ± 36.5 min, 39,921 ± 4311 min, 0.3116 ± 0.02347 ml min kg, 54.83 ± 7.683 ml kg, respectively, which were closed to the theoretical values. TQSM similarity versus astragaloside Ⅳ was 0.9661.
The results represented that the optimum Q-marker in BYHWI is astragaloside Ⅳ, whose transitivity in vivo similarity was close to the behavior of polypharmacokinetics with maximum bioavailability to the total quanta. It is feasible for Q-marker in CMMs to screen on the comparison of single pharmacokinetic behavior and bioavailability to the total quanta.
众所周知，公众仍然面临着传统药物质量和治疗效果不一致的严重问题。最近，刘昌孝教授提出了一种从草药、其配方和制造产品中识别相关质量标志物（Q-marker）的新的有前途的概念。因此，我们有必要建立一种新的方法来将质量与药物产品的疗效联系起来。
本文设计了 5 个候选 Q-marker（黄芪甲苷、芍药苷、苦杏仁苷、川芎嗪和阿魏酸），用于通过单和多药代动力学模型对补阳还五汤（BYHWI）中的总量子进行定量，以确定合适的 Q-marker。
使用 TQSM 原理的多药代动力学模型和相似性方法，研究 Q-marker 的体内传递性。用传递相似性和多药代动力学中的生物利用度来确定 Q-marker。用 RP-HPLC 测定大白鼠血浆样品中的浓度。数据分析采用 DAS 软件进行单分析，采用 EXCEL 编写程序进行多分析。
在 BYHWI 中，5 种候选 Q-marker 的药代动力学图谱分别采用经典房室分析固定在大鼠的 2 室模型中，但差异很大，候选参数波动范围从近 3552 倍到等价。5 种药物混合后的 TQSM 多药代动力学参数如 AUC、MRT、VRT、CL、V 的理论值分别为 110.8±51.91mg·min·ml、176.0±36.5min、39921±4311min、0.3116±0.02347ml·min·kg、54.83±7.683ml·kg。黄芪甲苷按 AUC、MRT、VRT、CL、V 顺序排列的 TQSM 多药代动力学参数分别为 110.8±51.91mg·min·ml、176.0±36.5min、39921±4311min、0.3116±0.02347ml·min·kg、54.83±7.683ml·kg，接近理论值。黄芪甲苷的 TQSM 相似度为 0.9661。
结果表明，BYHWI 中的最佳 Q-marker 是黄芪甲苷，其体内传递相似性接近多药代动力学的行为，具有最大的总量子生物利用度。在比较单药代动力学行为和总量子生物利用度的情况下，CMMs 中的 Q-marker 筛选是可行的。
