芍药甘草汤中自组装纳米粒形成对甘草主要成分体外释放和肠吸收的影响

Effects of self-assembled nanoparticles from Shaoyao gancao decoction on the in vitro release and intestinal absorption of the main components of Glycyrrhiza uralensis

目的研究芍药甘草汤中自组装纳米粒(SGD-SAN)形成对甘草主要成分体外释放和肠吸收的影响。方法制备甘草单煎液(GSD)、芍药单煎液(SSD)、芍药-甘草单煎混合液(MSSGD)和SGD(即芍药、甘草合煎液),并对其中的SAN进行表征。采用高效液相色谱法测定甘草中7种主要成分(芹糖甘草苷、甘草苷、芹糖异甘草苷、异甘草苷、甘草素、甘草酸、异甘草素)的含量。采用透析袋法,以pH1.2 HCl溶液和p H6.8磷酸盐缓冲液(PBS)为释放介质,考察SGD-SAN形成对甘草中7种主要成分体外释放的影响;采用在体单向肠灌流实验考察SGD-SAN形成对甘草中7种主要成分在大鼠肠段吸收的影响。结果 GSD、MSSGD和SGD中存在粒径为200~300 nm、多分散性指数为0.3~0.5的SAN;透射电镜观察结果显示,GSD-SAN、MSSGD-SAN呈棒状,SGD-SAN呈不规则球形。体外释放实验结果显示,在p H1.2 HCl溶液中,SGD-SAN形成能显著增加甘草素、异甘草素和甘草酸的体外释放,对其他成分的释放无明显影响;在p H6.8 PBS中,SGD-SAN形成对甘草中各成分的释放均没有明显影响。在体单向肠灌流实验结果显示,SGD-SAN形成能显著促进甘草中各成分在回肠的吸收。结论 SGD-SAN形成能显著改善甘草中难溶性成分的体外释放、促进甘草中主要成分的肠吸收,是芍药、甘草配伍增效的物理结构基础。

OBJECTIVE To study the effects of self-assembled nanoparticles from Shaoyao gancao decoction(SGD-SAN)on the in vitro release and intestinal absorption of the main components of Glycyrrhiza uralensis. METHODS Gancao single decoction(GSD),Shaoyao single decoction(SSD),mixed suspension of Shaoyao and Gancao single decoction(MSSGD)and SGD(i.e.Shaoyao-Gancao decoction)were prepared,and SAN was characterized. HPLC method was adopted to determine the contents of 7 main components(liquiritin apioside, liquiritin, isoliquiritin apioside, isoliquiritin, liquiritigenin, glycyrrhizic acid,isoliquiritigenin)in G. uralensis. The dialysis bag method was used to investigate the effects of the formation of SGD-SAN on in vitro release of 7 main components in G. uralensis with pH1.2 HCl solution and pH6.8 phosphate buffered solution(PBS) as release media. Single-pass intestinal perfusion study was performed to investigate the effects of the formation of SGD-SAN on the intestinal absorption of 7 main components from G. uralensis. RESULTS SAN with particle size of 200-300 nm and polydispersity index of 0.3-0.5 was found in GSD,MSSGD and SGD. GSD-SAN and MSSGD-SAN were in rod shape while SGD-SAN was irregularly spherical under transmission electron microscope. The results of in vitro release study showed that the formation of SGD-SAN could significantly increase in vitro release of liquiritigenin,isoliquiritigenin and glycyrrhizic acid,and had no effect on other components of G. uralensis in pH1.2 HCl solution. The formation of SGD-SAN also had no effect on the release of each component from G. uralensis in p H6.8 PBS. The results of intestinal perfusion experiments showed that the formation of SGD-SAN could significantly promote the absorption of each component from G. uralensis in the ileum. CONCLUSIONS The formation of SGD-SAN significantly improves the in vitro release of poorly soluble components from G. uralensis and promotes the intestinal absorption of main components from G. uralensis,which is the physical structure basis for the compatibility and synergy of Paeonia lactiflora and G. uralensis.