在体皮肤微透析分析制川乌-白芍配伍对芍药苷局部药代动力学的影响

Effect of Compatibility of Paeoniae Radix Alba and Aconiti Radix Cocta on Partial Pharmacokinetics of Paeoniflorin by in vivo Skin Microdialysis

目的:考察制川乌对白芍中芍药苷经皮转运的影响,从经皮转运角度研究制川乌-白芍配伍协同增效作用机制。方法:以昆明种清洁级小鼠为实验对象,分别经皮给予白芍凝胶、制川乌-白芍凝胶和白芍-氮酮凝胶,采用皮肤微透析取样技术,建立HPLC测定透析液中芍药苷的浓度,流动相乙腈-0.1%磷酸水溶液(14∶86),检测波长230 nm;利用DAS 2.0软件计算局部药动学参数,采用扫描电镜考察药物对小鼠皮肤角质层的影响。结果:白芍凝胶组的药时曲线下面积(AUC_(0-t)),平均滞留时间(MRT_(0-t)),半衰期(t_(1/2)),达峰时间(T_(max))和药峰浓度(C_(max))分别为(3.28±1.01)mg·L^(-1)·h,(3.95±0.32)h,(0.92±0.44)h,(2.00±0)h和(0.72±0.24)mg·L^(-1);白芍-制川乌凝胶组MRT_(0-t),AUC_(0-t),t_(1/2),T_(max)和C_(max)分别为(3.35±0.08)h,(10.64±1.24)mg·L^(-1)·h,(1.32±0.67)h,(1.00±0)h和(3.06±0.38)mg·L^(-1),白芍-氮酮凝胶组AUC_(0-t),MRT_(0-t),t_(1/2),T_(max),C_(max)分别为(59.82±13.51)mg·L^(-1)·h,(3.67±0.08)h,(0.89±0.16)h,(2.67±0.29)h和(13.24±4.14)mg·L^(-1)。与白芍凝胶组比较,制川乌-白芍凝胶组AUC_(0-t)和C_(max)均显著增大,T_(max)明显缩短。扫描电镜观察结果表明制川乌作用皮肤后,角质层细胞间隙明显增加,且与氮酮对皮肤的作用类似。结论:制川乌-白芍配伍能显著提高芍药苷的透皮吸收,达到配伍"增效"的目的,这可能与制川乌降低角质层的屏障作用有关。

Objective： To investigate the influence of Aconiti Radix Cocta extract on percutaneous absorption of paeoniflorin and explore synergistic effect of Aconiti Radix Cocta and Paeoniae Radix Alba. Method：KM mice were randomly divided into the Paeoniae Radix Alba gel group,Paeoniae Radix Alba and Aconiti Radix Cocta gel group and Paeoniae Radix Alba-azone gel group. Microdialysis sampling was employed, the concentration of paeoniflorin in dialysate was determined by HPLC, DAS 2. 0 software was used to caculate pharmacokinetic parameters of paeoniflorin,scanning electron microscope was employed to investigate the changes of mouse skin stratum corneum. Result： AUC_（0-t）,MRT_（0-t）,t_（1 /2）,Tmaxand Cmaxof Paeoniae Radix Alba gel group were（ 3. 28 ± 1. 01） mg·L^（-1）·h,（ 3. 95 ± 0. 32） h,（ 0. 92 ± 0. 44） h,（ 2. 00 ± 0） h and（ 0. 72 ± 0. 24）mg·L^-1; these parameters of Paeoniae Radix Alba and Aconiti Radix Cocta gel group were（ 10. 64 ± 1. 24）mg·L-1·h,（ 3. 35 ± 0. 08） h,（ 1. 32 ± 0. 67） h,（ 1. 00 ± 0） h and（ 3. 06 ± 0. 38） mg·L^-1; these parameters of Paeoniae Radix Alba-azone gel group were（ 59. 82 ± 13. 51） mg·L^（-1）·h,（ 3. 67 ± 0. 08） h,（ 0. 89 ± 0. 16） h,（ 2. 67 ± 0. 29） h and（ 13. 24 ± 4. 14） mg·L^-1,respectively. Scanning electron microscope results indicated that Aconiti Radix Cocta extract had the same effect on the skin surface structure as azone in exerting its permeation enhancing effect. Conclusion： Aconiti Radix Cocta extract can significantly promote transdermal absorption of paeoniflorin in herb couple of Aconiti Radix Cocta and Paeoniae Radix Alba,which may be related to the decrease of barrier function of stratum corneum and the improvement of epidermal permeability by some ingredients in Aconiti Radix Cocta.