外翻肠囊法研究黄芩清肺汤肠吸收成分

目的: 建立发现黄芩清肺汤吸收成分群的外翻肠囊模型法,研究黄芩清肺汤主要化学成分的肠道吸收特性。 方法: 采用大鼠外翻肠囊模型,收集黄芩清肺汤3个浓度在肠道不同部位给药后不同时间的肠囊液样品,用UPLC检测分析,并计算各有效成分的累积吸收量(Q)及吸收速率常数(K_a)。采用Agilent Proshell 120 EC-C₁₈(4.6 mm×50 mm,2.7 μm)色谱柱,以乙腈(A)-0.2%乙酸水溶液(B)为流动相进行梯度洗脱(0~2 min,20%A→30%A;2~5 min,30%A→36%A;5~7 min,36%A→45%A;7~12 min,45%A→55%A),流速1 mL·min^-1,柱温25 ℃,紫外检测波长254 nm。 结果: 黄芩清肺汤中9个成分可进入肠囊,分别为黄芩苷、汉黄芩苷、汉黄芩素、野黄芩苷、栀子苷、京尼平、京尼平酸、西红花苷-Ⅰ、绿原酸,此9个成分在各肠段中的吸收速率常数(K_a)均随黄芩清肺汤浓度的增加而增加(P<0.05),符合被动吸收。 结论: 肠囊对药物成分吸收有选择性,选择外翻肠囊法可评价黄芩清肺汤多成分的肠吸收特性。

Objective: To establish an everted intestinal sac model method for determining absorbable ingredients of Huangqin Qingfei decoction and study the absorptive characteristics of major chemical constituents of Huangqin Qingfei decoction. Methods: The rat everted intestinal sac model was adopted.Intestinal sac fluid samples at different time points after administration of three different concentrations of Huangqin Qingfei decoction were collected and determined by UPLC.The accumulative absorption (Q) and the absorption rate constant (K_a) of active constituents were calculated.The separation was performed on an Agilent Proshell 120 EC-C₁₈ (4.6 mm×50 mm,2.7 μm) chromatographic column,the mobile phase consisted of acetonitrile (A) and 0.2% acetic acid water (B) with a gradient elution (0-2 min,20%A→30%A;2-5 min,30%A→36%A;5-7 min,36%A→45%A;7-12 min,45%A→55%A) at a flow rate of 1.0 mL·min^-1.The column temperature was 25 ℃ and the detection wavelength was 254 nm. Results: Nine ingredients of Huangqin Qingfei decoction were detected in the intestinal sac which were baicalin,wogonoside,wogonin,scutellarin,geniposide,genipin,geniposidic acid,crocin-Ⅰ and chlorogenic acid.The absorption rate constant (K_a) of nine constituents increased in jejunum and ileum with the increase of the concentration of Huangqin Qingfei decoction(P＜0.05),consistent with passive absorption. Conclusion: As the ingredients are selectively absorbed in intestinal sac,the everted intestinal sac method is selected to assess the intestinal absorption characteristics of the ingredients of Huangqin Qingfei decoction.