目的 研究黄芩Scutellariae Radix-炙甘草Glycyrrhizae Radix et Rhizoma Praeparata cum Melle配伍合煎液不同相态的成分分布、体外释放及药动学行为，揭示两者配伍缓性增效的物理结构基础。方法 采用离心结合透析法拆分黄芩-炙甘草配伍合煎液不同相态，并进行粒径和形态表征；采用HPLC法测定不同相态中主要有效成分黄芩苷、汉黄芩苷、芹糖甘草苷、甘草酸的含量，并考察其体外释放情况；采用LC-MS/MS法测定大鼠ig不同相态后黄芩苷的血药浓度，并计算药动学参数。结果 黄芩-炙甘草配伍合煎液不同相态的粒径和形态存在明显差异；各相态中芹糖甘草苷、黄芩苷、汉黄芩苷、甘草酸质量分数排序为纳米相态＞真溶液相态＞沉淀相态；4种成分在纳米相态中释放最好，其次是真溶液相态，沉淀相态最差；全浸膏及不同相态ig给药后，黄芩苷的最大血药浓度（C_max）和血药浓度-时间曲线下面积（AUC_0～t）顺序均为纳米相态＞全浸膏＞真溶液相态＞沉淀相态。结论 黄芩-炙甘草合煎液复杂相态体系的形成，显著影响有效成分的空间分布、体外释放及药动学行为，可能是其发挥配伍缓性增效作用的物理结构基础。

Objective To investigate the compositional distribution, in vitro release, and pharmacokinetic behavior of different phases in the Huangqin (Scutellariae Radix, SR)-Zhigancao (Glycyrrhizae Radix et Rhizoma Praeparata cum Melle, GRRPM) decoction, and to elucidate the physical structural basis for the delayed and enhanced efficacy mediated by herb compatibility. Methods The decoction was separated into nanoparticulate, true solution, and precipitate phases by centrifugation combined with dialysis. The particle size and morphology of these phases were characterized. The contents of major active components baicalin, wogonoside, liquiritin apioside, glycyrrhizic acid, and others were determined by HPLC, and their in vitro release profiles were evaluated. The plasma concentration of baicalin in rats after oral administration of different phases was measured using LC-MS/MS, and pharmacokinetic parameters were calculated. Results Significant differences in particle size and morphology were observed among the phases. The mass fractions of liquiritin apioside, baicalin, wogonoside, and glycyrrhizic acid in each phase decreased in the order: nanoparticulate phase > true solution phase > precipitate phase. All four components showed the highest release from the nanoparticulate phase, followed by the true solution phase, and the lowest release from the precipitate phase. After oral administration of the whole extract and the different phases, the C_max and AUC_0-t of baicalin ranked as follows: nanoparticulate phase > whole extract > true solution phase > precipitate phase. Conclusion The formation of a complex multiphase system in the SR-GRRPM decoction significantly affects the spatial distribution, in vitro release, and pharmacokinetic behavior of the active constituents. This may represent the physical structural basis underlying the delayed and enhanced efficacy resulting from the combination of the two herbs.

R283.6

国家自然科学基金资助项目（82460852）；江西省自然科学基金资助项目（20232BAB216139）；江西中医药大学校级科技创新团队发展计划项目（CXTD22006）