丹参酮类组分自乳化释药系统的肠吸收特征研究

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。

Intestinal absorption characteristic of tanshinone components SEDDS using one-way intestinal perfusion in situ

Objective To explore the intestinal absorption characteristics of tanshinone components self emulsifying drug delivery system (SEDDS). Methods In situ single-pass perfusion method was used to investigate the absorption characteristics of cryptonshinone, tanshinone I, and tanshinone IIA in rats. The absorption parameters (K_a, P_app) of cryptotanshinone, tanshinone I, and tanshinone II_A were used as indicators to study their optimum absorption site among duodenum, jejunum, ileum, and colon. The effects of verapamil hydrochloride (P-glycoprotein inhibitor, P-gp inhibitor), probenecid (multi-drug resistant protein MRP2), and 2, 4-dinitrophenol (energy inhibitor) on the absorption of cryptonshinone, tanshinone I, and tanshinone II_A were also studied, as well as the effects of their different concentration. Results Cryptonshinone, tanshinone I, and tanshinone II_A could be absorbed at all four intestinal segments, and the optimum absorption site was the upper segment of small intestine. The absorption of cryptotanshinone and tanshinone I were concentration-dependent at experimental concentration levels (1.05-4.19 mg/L and 1.22-5.56 mg/L), while tanshinone II_A was not affected obviously by its concentrations (2.43-11.12 mg/L). Verapamil hydrochloride had no significant influence on the absorption of cryptotanshinone or tanshinone I, while the absorption of tanshinone II_A was improved remarkably. Probenecid increased the absorption of cryptonshinone and tanshinone I apparently, while had no obvious effect on that of tanshinone II_A. 2,4-Dinitrophenol could decrease the absorption of cryptonshinone, tanshinone I, and tanshinone II_A apparently. Conclusion Cryptonshinone and tanshinone I are supposed to be the substrate of MRP2 instead of P-gp. Tanshinone II_A is supposed to be the substrate of P-gp, instead of MRP2. The energy participated in the absorption of cryptonshinone, tanshinone I, and tanshinone II_A. Active absorption maybe also involved in the absorption of cryptonshinone, tanshinone I, and tanshinone II_A.