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本研究旨在对20(S)-原人参二醇(PPD)的生物药剂学性质进行多元化研究。首先测定PPD的平衡溶解度和表观油水分配系数,预测其在体内的吸收行为;其次结合Caco-2细胞模型与在体单向肠灌流模型,探讨PPD的膜渗透性和吸收窗;最后将生物利用度与体内代谢相结合,多元化研究分析PPD在体内的吸收和代谢特性,为PPD的剂型设计提供理论和实践基础。结果表明:PPD的水溶性较差,在水中的平衡溶解度仅为35.24mg.L 1,油水分配系数(P)为46.21(logP=1.66)。Caco-2细胞模型显示PPD吸收一般,有一定的外排现象。在体肠灌流模型结果表明,PPD在各肠段吸收良好,且各段的有效渗透系数按大小依次为十二指肠、空肠、回肠和结肠。PPD的口服生物利用度较低,为29.39%。代谢研究表明PPD在体内存在广泛的代谢。因此PPD的溶解性差和首过作用是影响其口服生物利用度的主要因素。
This study aimed to diversify the biopharmaceutical properties of 20 (S) -protopanaxadiol (PPD). Firstly, the equilibrium solubility and apparent oil-water partition coefficient of PPD were measured to predict its absorption behavior in vivo. Secondly, the membrane permeability and absorption window of PPD were studied by Caco-2 cell model and in vivo one-way intestinal perfusion model. Finally, Utilization and in vivo metabolism, PPD in vivo analysis of the absorption and metabolism characteristics, provide theoretical and practical basis for PPD dosage form design. The results showed that the water solubility of PPD was poor, the equilibrium solubility in water was only 35.24 mg.L 1, and the oil-water partition coefficient (P) was 46.21 (logP = 1.66). Caco-2 cell model shows PPD absorption in general, there is a certain efflux. The model of intestinal perfusion in vivo showed that PPD was well absorbed in all intestine segments and the effective permeability coefficients of each segment were duodenum, jejunum, ileum and colon in order of size. The oral bioavailability of PPD was low at 29.39%. Metabolic studies show that PPD has extensive metabolism in the body. Therefore, poor solubility and first pass PPD affect the oral bioavailability of the main factors.