温里药配伍提高赤芍效应成分芍药苷生物利用度的研究

Study on Enhancing Bioavailability of Paeoniflorin by Combined Use with Chinese Herbs for Inner-Warming

目的研究温里药配伍对活血药赤芍效应成分芍药苷生物利用度的影响,探讨活血温里复方的药物配伍机理。方法将温里药胡椒、吴茱萸、肉桂、小茴香、花椒分别与活血药赤芍配伍后灌胃小鼠,采用反相高效液相色谱法(reversedphasehighperformanceliquidchromatography,RPHPLC)测定各复方在小鼠血浆中芍药苷血药浓度,以单用赤芍为对照,计算各配伍复方的相对生物利用度。结果芍药苷在小鼠体内的药动学过程符合一室模型,温里药胡椒、吴茱萸、肉桂、小茴香、花椒分别与活血药赤芍配伍后,芍药苷相对生物利用度分别为137.22%、123.62%、108.39%、226.02%和116.73%。各实验组与对照组峰浓度(Cmax)、血浆药物浓度-时间曲线下面积(AUC0∝)存在差异(P<0.05),而达峰时间(tmax)无差异(P>0.05)。结论温里药胡椒、肉桂、小茴香、吴茱萸、花椒分别与活血药赤芍配伍,能提高赤芍主要效应成分芍药苷的生物利用度,从复方效应成分药代动力学的角度揭示了活血温里复方配伍的科学内涵。

Objective To study the influence of Chinese herbs for inner-warming on the bioavailability of paeoniflorin （PF） and its mechanism. Methods Chinese herbs （pepper fruit, evodia fruit, cassia bark, fennel fruit and prickly-ash peel） were separately used in combination with PF for gastrogavage to mice. Reversed phase high-performance liquid chromatography was used to determine the plasma concentration of PF in mice after medication. The bioavailability of PF was calculated and compared, taking single use of red peony root for control. Results The pharmacokinetics of PF in mice was conformed to the one-compartment model, as combined use with Chinese herbs for inner-warming, the relative bioavailability of PF was 137.22% for pepper fruit, 123.62% for evodia fruit, 108.39% for cassia bark, 226.02% for fennel fruit and 116.73% for pricklyash peel, there were difference of Cmax and AUC0-∞： in comparison of these data with the control group （P 0.05）, but with no difference of tmax （P 〉 0.05）. Conclusion The Chinese herbs used in this experiment in combination with red peony root could enhance the bioavailability of PF, which illustrated the scientific meaning of the recipe combination of Chinese herbs for activating blood circulation and inner-warming viewing from pharmacodynamics.