Ding Xue, Sun Yuming, Wang Qing, Pu Tingting, Li Xiaohui, Pan Yaqing, Yang Yang
School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, China.
Chemical Analysis and Research Center, Dalian University of Technology, Dalian, China.
Phytomedicine. 2016 Jul 15;23(8):864-71. doi: 10.1016/j.phymed.2016.05.005. Epub 2016 May 17.
Glycyrrhetinic acid (GA) and paeoniflorin (PF) are the main active ingredients in Chinese peony- Liquorice Decoction, a widely used Traditional Chinese Medicine.
HYPOTHESIS/PURPOSE: The aim of this work was to investigate the combinatory analgesic effect of GA and PF after percutaneous administration and to define their pharmacokinetic/pharmacodynamic (PK/PD) characteristics.
GA and PF were produced to transdermal patches based on previous research, and the permeation parameters of GA and PF in the patches were investigated with in vitro experiments. Dysmenorrhea model mice were then produced to compare the analgesic effects of the patches with different proportions of GA-PF. In the in vivo assessment, the number of writhes exhibited by the dysmenorrhea mice was recorded at designated time points, and skin, muscle under skin and plasma samples were collected, for assessments of drug distribution, pharmacokinetics parameters and PK/PD characteristics.
In dysmenorrhea mice, GA-PF and meloxicam (the positive control drug) could relieve pain to equal degrees. Specifically, a single dose of the optimized patches (10%GA-10%PF, wt) exerted a steady analgesic effect for 48h in dysmenorrhea mice, but this effect lagged behind the changes in the plasma concentration. Evaluation with the Bliss Independence criterion revealed that the two ingredients displayed a synergistic effect. Then the PK/PD relationship of GA in this compound preparation was defined with this synergistic effect. The preparation might be suitable for topical spasmolysis and anti-inflammatory therapy.
甘草次酸（GA）和芍药苷（PF）是中药芍药甘草汤中主要的活性成分，芍药甘草汤是一种广泛应用的传统中药。
假设/目的：本研究旨在探讨GA和PF经皮给药后的联合镇痛效果，并确定其药代动力学/药效学（PK/PD）特征。
基于前期研究制备GA和PF的透皮贴剂，通过体外实验研究贴剂中GA和PF的渗透参数。随后制备痛经模型小鼠，比较不同GA-PF比例贴剂的镇痛效果。在体内评估中，记录痛经小鼠在指定时间点的扭体次数，并采集皮肤、皮下肌肉和血浆样本，用于评估药物分布、药代动力学参数和PK/PD特征。
在痛经小鼠中，GA-PF与美洛昔康（阳性对照药物）的镇痛效果相当。具体而言，单剂量的优化贴剂（10%GA-10%PF，重量比）在痛经小鼠中产生了48小时的稳定镇痛效果，但该效果滞后于血浆浓度的变化。采用 Bliss 独立性标准评估显示，两种成分具有协同作用。然后利用这种协同作用确定了该复方制剂中GA的PK/PD关系。该制剂可能适用于局部解痉和抗炎治疗。
