Xiao Mei-Feng, Duan Xiao-Peng, Deng Kai-Wen, Yang Yan-Tao, Liu Wen-Long, He Fu-Yuan
College of Pharmacy, Hunan University of Chinese Medicine Changsha 410208, China Hunan Provincial Key Laboratory of Drugability and Preparation Modification of Traditional Chinese Medicine Changsha 410208, China.
College of Pharmacy, Hunan University of Chinese Medicine Changsha 410208, China Supramolecular Mechanism and Mathematic-Physics Chracterization for Chinese Materia Medica, Hunan University of Chinese Medicine Changsha 410208, China.
Zhongguo Zhong Yao Za Zhi. 2019 Feb;44(3):574-581. doi: 10.19540/j.cnki.cjcmm.20180925.005.
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 1.262×108 mAu·s, MRT_T 37.48 h, VRT_T 9.016×102 h2, CL_T 25.79 mL·h(-1)·kg(-1), Vs 1.586×102 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.
中药大多来源于植物或动物，具有高度多态性，其成分动态变化，可通过色谱指纹图谱中的特征峰和指纹峰反映出来。由于色谱药代动力学的动态变化，用于测定成分的色谱药代动力学方法并不适用。基于前期研究，建立了中药多成分动态药代动力学数学模型，并以补阳还五汤为模型药物进行验证，应用总量统计矩原理，对血样和空白样品中的相关统计参数进行叠加或相减。这为中药色谱药代动力学研究提供了一种新方法。采用高效液相色谱法测定补阳还五汤血样和空白样品指纹图谱各点的总量统计矩参数，通过总量统计矩相加计算得到含药血样和空白样品的总体总量统计矩参数；而通过相减计算可得到纯药物的初始总量统计矩。利用估算的代谢平衡常数迭代计算至稳态，得到大鼠的代谢色谱药代动力学参数：VUC_T 1.262×108 mAu·s，MRT_T 37.48 h，VRT_T 9.016×102 h2，CL_T 25.79 mL·h(-1)·kg(-1)，Vs 1.586×102 mL·kg~(-1)，t_(T,0.5) 6.15 h。这表明在0 - 96.33 h后，全方95%的化合物在体内代谢并排出。实验验证了所建立的数学模型和总量矩统计参数能够表征补阳还五汤的剂量 - 时间关系，可用于研究中药的体内代谢动力学。
