Study On The Basic Biopharmaceutics Of Cynarin In Artichoke Extract

Cynarin is the main pharmacological active substance of artichoke extract.Its chemical name is 1,3-dicaffeoylquinic acid(C₂₅H₂₄O₁₂).It has various pharmacological effects,such as lowering cholesterol and promoting liver cell regeneration.Its chemical structure and pharmacological activity have been confirmed.At present,there is a lack of relevant research on the basis biopharmaceutics of cynarin.This paper takes cynarin as the research object,and uses a combination of in vivo and in vitro methods to investigate its biopharmaceutical basic data,which served as the basis for the development of artichoke related preparations.A method for the determination of cynarin in vitro was established by high performance liquid chromatography（HPLC）,and the methodology was investigated.This method is accurate,fast and easy-to-operate.The optimal extraction process of cynarin from artichoke leaves was determined by using an orthogonal experiment method.The concentration of ethanol was 70%,the ratio of material to liquid was 1:20,and the extraction time was 1.5 h at 50℃.The content of cynarin in the extract was0.02%.The stability of cynarin in rat plasma and gastrointestinal contents was investigated by in vitro incubation method.In the process of investigating the stability of cynarin in plasma,the results showed that the stability of high-concentration cynarin in plasma was greater than that of low-concentration,and there was a small amount of degradation in p H 7.4 solution,indicating that the stability of cynarin in plasma is affected by both p H and plasma metabolic enzymes,the latter effect is the main one,and it has a concentration-dependent effect on the metabolism of cynarin;In the process of investigating the stability of cynarin in gastrointestinal contents,It was found that the stability of cynarin in stomach and each segment of intestinal contents showed significant differences.It is relatively stable in the stomach and small intestine contents,with a degradation rate of about 10%in 12 hours,and unstable in the colon,with a degradation rate of about 96%in 24 hours.The results showed that the stability of cynarin in the gastrointestinal contents was mainly affected by the p H and the colonic flora,the latter and its related enzymes were the main factors affecting the degradation of cynarin in the gastrointestinal content.On this basis,in situ intestinal absorption model of rats was established and single pass perfusion method was performed to study the absorption parameters,absorption mechanism and pharmacokinetic characteristics of different drug concentrations and flow rates in different intestinal segments.The results showed that the absorption effect of different intestinal segments was significantly different,and the absorption gradually decreased with the increase of the concentration.It is speculated that there may be active transport in its absorption mode.The absorption in the small intestine is more,and the colon is less.The absorption rate constants of duodenum,jejunum,ileum and colon were 5.68×10^-2min^-1、2.56×10^-2min^-1、2.33×10^-2min^-1、2.06×10^-2min^-1,respectively.Because cynarin is a weakly acidic compound,the reason for its less absorption in the colon may be that the alkaline environment causes it to dissociate,or the intestinal mucosa has less absorption of cynarin,which is not conducive to absorption at this site,while the acidic environment of it in the small intestine is conducive to absorption.To investigate the pharmacokinetics of cynarin in rats,and an in vivo UPLC-QTof-MS analysis method was established,using puerarin as an internal standard.After methodological verification,it provided a method for the subsequent determination of plasma concentration in rats.Rats were administered intragastrically at a dose of 50mg/kg,and the peak plasma concentration was reached 0.5 h after administration,and the area under the curve AUC_0-t was 524.47±23.65 ng/ml·h,and the absorption peak appeared again after 6 hours of administration,and there was a phenomenon of enterohepatic circulation,which slowed down the decrease of plasma concentration,prolonged the action time,and improved bioavailability.By investigating the stability of cynarin in different environments and its absorption in different intestinal segments,the absorption mechanism of the drug in vivo was basically clarified.Combined with the analysis of the pharmacokinetics in vivo,drugs were absorbed from the gastrointestinal tract after oral administration,most of which were absorbed in the duodenum and jejunum,and less absorbed in the large intestine.The drug in the colon segment was degraded largely by the influence of intestinal flora,which affected the plasma concentration.After administration,the phenomenon of enterohepatic circulation appears,which increases the drug action time and improves the bioavailability.The basic data of biopharmaceutics obtained from the research plays an important role in the research and development of cynarin-related preparations.