Study On Biopharmaceutics And Pharmacokinetics Of Jinhao Anti-influenza Dropping Pills

Objective: Study on biopharmaceutics and pharmacokinetic of Jinhao anti-influenzadropping pills.(1) Establish the HPLC analysis method of JinHao dropping. Study onbasic physical and chemical properties of drug;(2) Examine the stability of JinHaodropping under different pH conditions and the gastrointestinal tract;(3) To study JinHaodropping pillsintestinal absorption mechanism through the Caco-2cells transport model,the body one-way perfusion model, and Evaginate bowel capsule method.investigateetabolize of Isorupestonic acid and hyperoside;(4) JinHao dropping effectivecomponent in the liver microsomal;(5) To sdudy pharmacokinetics of JinHao droppingin mice, to analysis pharmacokinetic parameter；Investigate whether it changes thePharmacokinetic body after oral administration of traditional Chinese medicine frominside and outside the results. Further discuss influence on Absorption, distribution,metabolism and excretion of medicine efficient composition expound Pharmacokineticprocess of herbal medicine. Method:(1) Research physical and chemical propertiesofJinHao dropping from ketone acid, hyperosidet through oil and water distribution efficientdetermination;(2) Study the stabilityof drug in gastrointestinal: determine effectivecomponents from a ketone acid, hyperoside in different pH medium, artificial gastric juiceand intestinal juice, artificial animals gastrointestinal contents，investigate drugs inanaerobic conditions and animal manure common after incubation of the stability, the drugin gastrointestinal tract degraded in the position and its influence factor, discusses themedicine to cooperate after use whether can influence the stability of effective ingredientsof the gastrointestinal tract;(3) Established Caco-2cells transport mode，investigateJinHao dropping pills in Caco-2cells transport transshipment model of the mechanism.Investgate absorbing state of JinHao effective component rupestonic acid and hyperosidein vivo intestinal absorption test；Investgate P-gp inhibitors and MRP1inhibitors effect on JinHao dropping pills intestinal absorption. Investigate absorbing properties.of JinHaodropping pills in the bowel mucosa using the method of bowel holds the capsule;(4) Ratswere given JinHao dropping from ketone acid, hyperosideta nucleoside by the twomethods of oral irrigation stomach and intravenous drug given way;(5) Established inJinHao dropping blood drug concentration analysis method, determine JinHao effectivecomponents from JinHao dropping pills Rupestonic acid, hyperoside pharmacokinetic data.Preliminary exploration from JinHao dropping pills pharmacokinetic body. Results:(1)LogP of JinHao effective components from rupestonic acid as medium pH risesignificantly lower; when hyperoside pH＜5, LogP no significant difference, while pH＞5,st. John’s wort oil and water distribution coefficient，LogP no significant difference, whenpH＞5, LogP reduce gradually.(2) In stability test,JinHao effective components fromrupestonic acid are stable with in8h. Hyperoside remains stable In different pH conditions,artificial gastric juice and the artificial intestinal juice, but are not stable Large intestinethe content, the intestinal mucosa, stability: the intestinal mucosa＞small intestinal content＞contents.Stability significant increase In the sterilized bowel content in the intestinalmucosain.(3)The body one-way perfusion experiment: a testosterone from the intestinalabsorption with bowel acid for specific absorption, because of the pH value of theintestine at the differences and active transport carrier distribution exist specificity, atestosterone from the intestinal absorption acid from P-gp protein discharge role, ATPinhibitors significant suppress a testosterone from acid in the absorption of the smallintestine, a testosterone from the Peff acid＞1.2x10-2cm/min, so im absorb good; St.John’s wort intestinal absorption with the intestinal absorption section with specificity, dueto the difference of the pH value of the bowel period, active transport carrier distributionexist specificity, P-gp discharge protein affect st. John’s wort in of the small intestine (atthe top of the absorption and ATP inhibitors inhibit st. John’s wort significantly in smallintestine (at the top of the absorption, st. John’s wort Peff＞1.2×10-2cm/min, so imabsorption is good.Caco-2(4)In vivo intestinal absorption test，Rupestonic acid in differentsection of the intestinal absorption dodecadactylon＞jejunum＞ileum＞colon, JoinVER,there is no significant differance Ka andPef.add sodium azide Small intestine havesignificant effects on top.Significantly reduced from a testosterone acid Ka andPefRupestonic acid In different section of the intestinal absorption dodecadactylon＞jejunum＞ileum＞colon.P-gp inhibitors and ATP inhibitors significantly reduce the st.(4)John’s wort Ka value In the small intestine. JinHao dropping in the accumulation ofintestinal can absorb a size order: the ileum＞colon jejunum＞duodenum＞in everted gut sac test, hyperoside cumulant：the jejunum＞duodenum＞ileum colon stabilty is good.(5)Establish (HPLC-ESI-MS/MS) JinHao was dropping blood inside body drugconcentration analysis method. rupestonic acid and hyperoside. Conclusion： StudyPhysical and chemical properties of intestinal absorption mechanism, stability, metabolismrupestonic acid and hyperoside of Jin Hao dropping pills.