The Intestinal Absorption Of Bioactive Compounds In Traditional Chinese Medicine

Pharmaceutical analytical technology provides powerful tools for the pharmaceutical and related field. Now the research field expands further and the instrumentation is developed. The research in absorption, distribution, metabolism, excretion (ADME) of drugs has increasingly developed in the pharmaceutical domain. The research of drug absorption is the first step of ADME research. Now the intestinal absorption research of the bioactive compounds in Chinese Medicine become the focus gradually. However, the study route is familiar with that of chemical medicine and not considers the complex chemical system of Chinese Medicine, so the results maybe not reflect the real situation. The high performance liquid chromatography coupled with mass spectrum (HPLC/MS) technique is provided with higher sensitivity than the usual analytical technique in research of drug absorption, and become one of key tools step by step.This thesis studied the intestinal absorption of the bioactive compounds in Chinese Medicine with the model of everted sac of rats from the different point of views by HPLC/MS. The main contents and productions were as followed:(1) We studied the absorption mechanism of paeoniflorin in rats' small intestines;discussed the influence factors of absorption and the differences of absorption in different intestinal segments. The results showed that there wasn't significant difference in the permeability coefficient between the jejunum and ileum at low concentration, but the latter was higher than the former at middle and high concentration. The absorption mechanism was passive diffusion and was accorded with First-order kinetics. Verapamil and Tween-80 showed effect on increasing the absorption of paeoniflorin remarkably.(2) The rat everted gut sac was incubated with salvianolic acid B solution and decoction of Radix Salviae Miltiorrhizae respectively, and the absorption of salvianolic acid B between the two modes was compared.The result showed that the intestinal absorption of salvianolic acid B in monomer was better than that in water extract. It was demonstrated that the other constituents in decoction of Radix Salviae Miltiorrhizae inhibited the absorption of salvianolic acid B. Salvianolic acid B wasn't the substrate of /^-glycoprotein and its bioavailability wasn't influenced by the excretion of drug.(3) We investigated the absorption of notoginsenoside Ri, ginsenoside Rgi, ginsenoside Re, ginsenoside Rbi, ginsenoside Rd when the rat everted gut sac was incubated with decoction of panax notoginoside (PNS). The results indicated that the absorption of these triterpenoids from P. notoginseng changed with the concentration of PNS. The absorptions of notoginsenoside Ri and ginsenoside Rbi were better in monomer solution than that in decoction. The difference was significant (p<0.05). Maybe these constituents in the decoction of P. notoginseng inhibited the absorption of each other.This thesis began with the intestinal absorption of bioactive compounds, investigated the absorption mechanism and the influence factors of absorption, compared the difference of absorption of bioactive compounds between the monomer and decoction. We studied the absorption and mechanism of multi-constituents in complex extract for the first time. The production of this thesis can exploit an aspect of intestinal absorption of bioactive compounds in Chinese Medicine, and give reference for the development of the Chinese drugs pharmaceutics. It can also develop the HPLC/MS analytical technical in application for ADME of drugs.