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目的探讨丹参酮脂溶性成分自乳化释药系统(TC-SEDDS)的肠吸收特征。方法采用大鼠在体单向肠灌流实验,以隐丹参酮、丹参酮I和丹参酮IIA 3个成分的吸收[吸收速率常数(Ka)和表观吸收系数(Papp)]为指标,研究其在十二指肠、空肠、回肠和结肠不同肠段的吸收情况;并考察不同药物质量浓度、P-糖蛋白(P-gp)抑制剂盐酸维拉帕米、多药耐药蛋白(MRP2)抑制剂丙磺舒和能量抑制剂2,4-二硝基苯酚对3个成分肠吸收的影响。结果隐丹参酮、丹参酮I和丹参酮IIA在小肠全肠段均有吸收,且小肠上段(十二指肠)的吸收最佳;隐丹参酮和丹参酮I的吸收在实验质量浓度范围内(1.05~4.19 mg/L和1.22~5.56 mg/L)具有浓度依赖性,丹参酮IIA的吸收不受质量浓度(2.43~11.126 mg/L)影响;盐酸维拉帕米对隐丹参酮和丹参酮I的吸收无明显影响,却显著提高了丹参酮IIA的吸收;丙磺舒显著增加了隐丹参酮和丹参酮I的吸收,对丹参酮IIA的影响不显著;2,4-二硝基苯酚均能显著降低3个成分的吸收。结论隐丹参酮和丹参酮I可能是MRP2的底物,不是P-gp底物。丹参酮IIA可能是P-gp底物,不是MRP2底物。3个成分的吸收均有能量的参与。隐丹参酮、丹参酮I和丹参酮IIA的吸收可能均有主动吸收过程。
Objective To explore the intestinal absorption characteristics of self-emulsifying drug delivery system (TC-SEDDS) of tanshinone fat-soluble components. Methods The rats were subjected to unilateral intestinal perfusion in vivo. The absorption (Ka and Papp) of three components of Cryptotanshinone, Tanshinone I and Tanshinone IIA were studied. Jejunum, ileum and colon different intestine; and investigate the effects of different drug concentrations, verapamil, a P-glycoprotein inhibitor, and a multidrug resistance protein (MRP2) inhibitor, Effects of sulphate and energy inhibitor 2,4-dinitrophenol on intestinal absorption of three components. Results Cryptotanshinone, tanshinone I and tanshinone IIA were absorbed in the whole intestine of the small intestine, and absorbed in the upper intestine (duodenum). The absorption of cryptotanshinone and tanshinone I was in the range of 1.05 ~ 4.19 mg / L and 1.22 ~ 5.56 mg / L, respectively). The absorption of tanshinone IIA was not affected by the concentration of 2.43 ~ 11.126 mg / L. Verapamil hydrochloride had no significant effect on the absorption of cryptotanshinone and tanshinone I, But significantly increased the absorption of tanshinone IIA; probenecid significantly increased the absorption of cryptotanshinone and tanshinone I, and had no significant effect on tanshinone IIA; 2,4-dinitrophenol significantly reduced the absorption of three components. Conclusions Cryptotanshinone and tanshinone I may be substrates of MRP2, not P-gp substrate. Tanshinone IIA may be a P-gp substrate, not a MRP2 substrate. The absorption of 3 ingredients all have energy participation. The absorption of cryptotanshinone, tanshinone I and tanshinone IIA may all have the active absorption process.