Investigation Of Absorption Characteristics Of Anti-Inflammatory Effective Parts From Smilax China In Rat Intestinal Valgus Test And Pharmacokinetics In Rat

Smilax china L. is known as Jinggangteng and belongs to the Lillacaee family, Medication site is dry rhizomeit. It contains a variety of natural and organic components, Including flavonoids, saponins and aglycone, phytosterols, stilbene, terpenes, organic acids, amino acids, tannin and so on. It is used in the treatment of patients with gynecological appendagitis, annex inflammatory and other inflammation in the traditional Chinese medicine clinical,curative effect is remarkable. Active ingredients in smilax anti-inflammatory this paper as the research object, on the tube in vitro intestinal absorption characteristics research, pharmacokinetic study and plasma protein binding. For the study of the clinical drug dosage forms and provide a scientific basis for the clinical medication safety. The research content is as follows:(1)In vitro study of intestinal absorption characteristicsTo investigate absorption characteristics of six components from anti-inflammatory effective parts of Smilax china and guiding the studies on preparation and pharmacokinetics. Using rat everted gut sac model, the intestinal sac contents were collected at different time and the absorption concentration of polydatin, astilbin, oxide resveratrol, quercetin, Huang Qi glycosides and resveratrol was determined by HPLC, and the absorption kinetics parameters were calculated for describing their absorption characters in different intestinal segments(duodenum, jejunum and ileum). Absorption of Polydatin in duodenum, jejunum and ileum was no significant difference, while the other five kinds of components shows large differences. Absorption of six kinds of ingredients shows significant differences in the same intestinal site, and the absorptivity at duodenum, jejunum and ileum is 0.85~2.79%,0.70~2.73% and 0.90~1.77%,respectively. Quercetin shows the highest absorption rate in the duodenum and jejunum, polydatin shows the highest absorption rate in the ileum. The absorption rate of oxide resveratrol was significantly slower than the other five ingredients, it just shows obvious absorption after 90 min in the duodenum. The absorption of polydatin, astilbin,quercetin, Huang Qi glycosides and resveratrol conforms the first order kinetics, everted sac method can evaluate intestinal absorption characteristics of Smilax extracts.(2)Pharmacokinetic studyTo establish a method for the simultaneous determination of astilbin, resveratrol, Huang Qi glycosides and polydatin by UPLC-MS / MS for the first time, puerarin as internal standard, using ESI source in negative ion mode,multiple reaction monitoring(MRM) analysis. Analyte recoveries were greater than 65%, Specificity of the methods, matrix effects, precision, accuracy and stability are in line with the requirements of biological sample analysis. Using the established method measured determine plasma concentrations of four components in normal rats and pelvic inflammatory disease rats caused by E. Coli after oral Smilax china extract, access to its pharmacokinetics in normal rats and model rats parameters. Study the above four kinds of Antiinflammatory effective parts from Smilax under normal and pathological conditions process in vivo. The results showed that the four substances pharmacokinetic C-T process are in line with the two-compartment model in normal rats and model rats. Under pathological conditions, the organism's absorptive capacity was lessen with astilbin, elimination rate is decreased;the absorption of Huang Qi glycoside ability has reduced, elimination rate is faster;the absorption of resveratrol ability has increases, elimination rate is faster;the absorption of polydatin ability has increases, the elimination rate is slower. Prompt smilax anti-inflammatory active ingredients pharmacokinetic studies should be advisable to animal model.(3)The determination of plasma protein bindingTo establish a UPLC-MS/MS assay for seven kinds of anti- inflammatory effective parts from Smilax in rat plasma,determination of the six kinds of components protein binding rate in plasma of rat,and to and to provide the reference for security of drug usage in clinical practice. Ultrafiltratio-UPLC-MS/MS method is adopted to simultaneous determine taxifolin, resveratrol, Huang Qi glycosides, quercetin, quercitrin, resveratrol glucoside six kinds of Smilax china effective anti-inflammatory components plasma protein binding situations. The ultrafiltration membrane can adsorb each test object,which adsorbs Huang Qi glycosides strongest.The content detection in high, medium and low concentration of plasma protein combined rate was(72.27% ~ 98.77%),the concentration of plasma protein binding rate of no concentration dependent and from high to low: quercetin, quercitrin, taxifolin, resveratrol glucoside, resveratrol and Huang Qi glycosides. The combination of these 6 components with the rat plasma protein binding, The experiment for clinical safe medication to provide a reference.