山楂消脂胶囊超微粉与细粉中大黄酸在大鼠体内的药代动力学差异研究

Pharmacokinetic study of rhein from the ultra-micro and fine powder of Shanzha Xiaozhi Capsules in rats

目的比较大鼠灌胃山楂消脂胶囊超微粉和细粉后大黄酸的药代动力学特征差异。方法大鼠分别灌胃给予超微粉混悬液或细粉混悬液,用高效液相色谱法测定大黄酸的血药浓度变化。色谱柱为Uranus C_(18)(250 mm×4.6 mm,5μm),流动相为甲醇-0.1%磷酸水溶液(85∶15),流速为1 m L/min,检测波长为254 nm,血药浓度-时间数据采用PKSolver2.0药代动力学软件进行分析。结果大黄酸血药浓度在0.16~40.00μg/m L线性关系良好。大鼠灌胃给予山楂消脂胶囊超微粉混悬液及细粉混悬液后大黄酸血浆-时间曲线均符合二房室模型,山楂消脂胶囊超微粉及山楂消脂胶囊细粉的主要药动学参数AUC分别为(4.08±4.96)μg/(m L·h)和(0.74±0.06)μg/(m L·h)(P<0.05),药峰浓度(C_(max))分别为(0.79±0.15)μg/m L和(0.17±0.02)μg/m L(P<0.05)。结论超微粉碎能使大黄酸在大鼠体内的吸收更完全,提高生物利用度。

Objective To compare the differences of pharmacokinetic characteristics of rhein after rats received ultra micro and fine powder of Shanzha Xiaozhi Capsules by gavage. Methods The experimental rats were given suspensions of the ultra-micro and fine powder of Shanzha Xiaozhi Capsules. The plasma concentration of rhein in rats was measured by high performance liquid chromatography. Uranus Cl8 （250 mm× 4.6 mm, 5 μm） was used as the analytical column. The mobile phase was methanol-water-0.1% phosphoric acid （85：15）, the wavelength of detection was set at 254 nm, and the flow rate was 1.0 mL/min. Serum concentration-time data was processed by pharmacokinetics software PKSolver 2.0. Results The linear range of rhein was from 0.16 to 40.00 μg/mL. The concentration-time curves of rhein in rats fitted well into two compartment model. The main pharmacokinetic parameters of the AUC of rhein from the uhra-micro and fine powder of Shanzha Xiaozhi Capsules were （4.08±4.96） μg/（mL·h） and （0.74±0.06） μg/（mL·h） （P 〈 0.05）, the maximum plasma concentration of rhein from the ultra-micro and fine powder ：of Shanzha Xiaozhi Capsules were （0.79±0.15）μg/mL and （0.17±0.02） μg/mL （P 〈 0.05）. Conclusion The uhra-micro porphyrization can make the absorption of rhein more complete in rats and improve bioavailability.