| Oral administration is the most commonly used way in drugs' clinical application.The absorption mechanism of drugs is the first step for their ADME process,which is also the premise for the accomplishment of their therapeutic effects. TanshinoneⅡA(TSⅡA) is one of the effective components of Danshen(Radix Salviae Miltiorrhiaze) which demonstrates wide pharmacological activities,but its oral bioavailability is extremely low.In order to reveal the reason for the low bioavailability of TSⅡA and provide references for the dosage form design of TSⅡA, the thesis studied the intestinal absorption state of TSⅡA and the influences of various active compositions existing in the alcohol extract of Radix Salviae Miltiorrhiaze on the absorption of TSⅡA.The studies on absorption of TSⅡA and alcohol extract of Radix Salviae Miltiorrhiaze were carried out to reveal the absorption mechanism of TSⅡA.Besides, the information of the factors that influence absorption,clarification of the roles and effect extent of the transporters such as P-glycoprotein(P-gp) was studied. Additionally,we investigated the contributions of various active ingredients existing in the alcohol extract of Radix Salviae Miltiorrhiaze on the absorption of TSⅡA.A method for the simultaneous determination of TSⅡA and CTS from the alcohol extract of Radix Salviae Miltiorrhiaze was establsihed to study their absorption.This method was simple,accurate and reliable.The intestinal absorption mechanism of TSⅡA was studied by the everted rat gut sacs and the affection of some factors such as different intestinal location and different drug concentration on their absorption was also investigated.Moreover,the comparison of TSⅡA absorption administrated with the simple substance of TSⅡA alone and the whole alcohol extract of Radix Salviae Miltiorrhiaze was observed.The results suggested that TSⅡA could be absorbed in all segments of intestine in rat and it might be a first-order process with the passive diffusion mechanism in the range of the tested concentration,and could be absorbed in all segment of intestine in rat.The percentage of absorption decreased in the order of duodenum,jejunum and colon,but there were no obvious differences among them.Other substances in the alcohol extract of Radix Salviae Miltiorrhiaze did not promote the absorption of TSⅡA.On the other hand,an intestine loop model was applied to investigate interactions of TSⅡA and the other ingredients coexisting in the alcohol extract of Radix Salviae Miltiorrhiaze.The role of verapamil which is an inhibitor of P-gp was also studied.It showed that after the alcohol extract administration,the peak concentration(Cmax) of TSⅡA was higher in comparison with that of TSⅡA alone administration.Besides,the absorption of TSⅡA administrated by the alcohol extract was slightly enhanced in the presence of verapamil.However,there's no significant differences(p＞0.05).It indicated that its bioavailability wasn't influenced by the excretion of drug at the experimental concentration.In addition,a HPLC method for simultaneous determination of four major alkaloids in Lindera aggregate was performed to evaluate the quality of the famous-region drug- Lindera aggregate in Zhejiang province.The detection was carried out by an Agilent ZORBAX SB-C18 column(4.6 mm×250 mm,5μm) with gradient elution.The mobile phase were:A:acetonitrile;B:water(containing 0.15% diethylamine,adjusted to pH=3.0 with acetic acid).Flow rate was 1.0 ml/min and the detection wavelength was 289 nm.The calibration curves were linear over the range of 0.428-8.560μg for Boldine,2.122-31.83μg for Norboldine,0.760-15.20μg for Reticuline and 0.0204-0.4008μg for Linderegatine,respectively.The average recoveries were 99.18%for Boldine,100.94%for Norboldine,100.31%for Reticuline and 99.17%for Linderegatine,respectively,and each RSD was less than 2.95%.The described method is reliable and convenient and could be used for the quality control of Lindera aggregate.
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