Study On Gastrointestinal Absorption Of Extract Of Andrographis Paniculata(Burm.f.) Nees.

Objective:Gastrointestinal absorption kinetics characteristics of extract of Andrographis paniculata(Burm.f.)Nees.(SEA) was studied, gastrointestinal absorption mechanism andrographolide (A) anddehydrographolide (DDA) in extract of Andrographis paniculata (Burm.f.)Nees. were preliminary explored,and the gastrointestinal absorption method of Chinese medicine multicomponent was established.Method:Using rats gastric perfusion in situ studied stomach absorption situation of A and DDA inSEA.Setting up content determination method for determination of two active ingredients in the artificialgastric juice, to calculate the drug absorption in the stomach.Using rats intestine perfusion in situ modelstudied intestinal absorption situation of A and DDA in SEA.Setting up content determination method fordetermination of two active ingredients in the artificial intestinal juice, to explore different massconcentration, different pH’s influence on the absorption of A and DDA in SEA, at the same time studybest absorption parts through the intestine test on two kinds of active ingredients in the SEA. The intestinalabsorption mechanism of A and DDA in SEA was preliminary analyzed.Results:1. The study results using rats gastric perfusion in situ of the absorb of A and DDA in SEAshowed that A and DDA in SEA have good absorption in the stomach, the other components in the SEAalmost have no effect on stomach absorb of A and DDA.2. The results about SEA compared to monomer in the whole intestine absorption found that, forA and DDA, absorption rate and absorption of SEA are better than the monomer. For A, there was nosignificant difference for the absorption rate constant (ka) and absorption percentage (p)(p>0.05). ForDDA,there was significant difference for the absorption rate constant (ka) and absorption percentage (p)(p<0.05).3. The study results using intestinal perfusion in situ of the absorb of A in SEA found that:In110~330μg/mL dose range, ka and P are reduced with the increase of concentration.The concentration of110μg/mL has the best absorption. ka and p of low,medium and high concentrationsbetween the two had significant difference (P <0.05), and which suggests that the absorption existssaturation phenomenon.So the absorption mechanism of A in SEA in small intestine may not be a simplepassive diffusion, but mainly be the carrier medium of transport. Weather the specific active transport orfacilitated diffusion, further studies are needed to be conclusive evidence.With the pH rose to6.38from5.34, ka and P were increased slightly.With the pH from6.38to7.40, ka and P have a downward trend. Besides P under the condition of pH5.34and7.40，pH6.38and7.40have significant difference (P <0.05), other groups have no significant difference (P>0.05). So theintestinal absorption of A in SEA is affected by pH, pH7.40significantly below pH5.34and6.38.A in SEA have absorption in the absorption model established in duodenum, jejunum, ileum andcolon, P in various intestine absorption in the duodenum, jejunum, ileum, colon order down.ka and P ofduodenum between jejunum, ileum, colon had significant difference (P <0.05), and jejunum, ileum andcolon have similar absorption rate, there was no statistically significant difference between two group (P>0.05). So the best absorption parts of A in SEA is duodenum.4.The study results using intestinal perfusion in situ of the absorb of DDA in SEA found that:In110~220μg/mL dose range, ka and P are reduced with the increase of concentration.In220~330μg/mL dose range, ka and P have no change with the increase of concentration.The concentration of110μg/mL has the best absorption. There were extremely significant differences of ka and P between110to220, and110to330(P <0.01), while the ka and P of220to330had no significant difference (P>0.05).So the preliminary judgments is the absorption mechanism of DDA in small intestine mainly have carriermedium transport and passive diffusion absorption two ways. In the dose range110~220μg/mL ofSEA,was the carrier medium of transport, and with the increase of concentration, translated into passivetransport.Under the condition of PH5.34, the absorption is better.with the pH rose to7.40from5.34, ka andP showed a slight downward trend,a slight weakening in the permeability of the drug. Besides P under thecondition of pH5.34and pH7.40have significant difference (P <0.05), the other groups have no significantdifference (P>0.05). So the intestinal absorption of DDA in SEA is affected by pH,the greater theconcentration, absorbing the worse. DDA in SEA have absorption in the absorption model established in duodenum, jejunum, ileumand colon, P in various intestine absorption in the ileum, jejunum, colon, duodenum order down.ka ofileum and duodenum, jejunum, colon had very significant difference (P <0.01),duodenum, jejunum andcolon between any two have similar absorption rate,and had no significant difference (P>0.05). For P,ileum, duodenum, colon had very significant difference (P <0.01). So the best absorption parts of DDA inSEA is ileum.Conclusion:A in SEA had better absorbed in the stomach,the intestinal absorption mechanism was the carriermedium transport. The intestinal absorption of A in SEA is affected by pH, pH7.40significantly belowpH5.34and6.38. The best absorption parts of A in SEA is duodenal,other components in the SEA mayhave no significant influence to the intestinal absorption of A.DDA in SEA had better absorbed in the stomach,the intestinal absorption mechanism was thecarrier medium transport in low concentration of SEA, and with the increase of concentration, translatedinto passive transport.The intestinal absorption of DDA in SEA is affected by pH, the greater theconcentration, absorbing the worse. the best absorption parts of DDA in SEA is ileum,other components inthe SEA may promote the intestinal absorption of DDA.