| Objective: The Chinese medicine culture has a long history, rich in traditionalChinese medicine resources. The research and development of new traditional Chinesemedicine preparation expands a broad road for new drug development in China. Applyingthe new technology and new dosage forms of drug preparations in traditional Chinesemedicine preparation of secondary development not only can improve marketcompetitiveness and efficacy of the drug product, but also can be used as a kind of newdrugs to market and has a broad market space. Drug absorption mechanism andpharmacokinetics research laid the foundation for the development of new drugs.Traditional Chinese medicine preparation, especially the compound preparation oftraditional Chinese medicine composition is complicated, too much most effectivecomponent is unknown or disturbance factors, lack of analytic methods for tracequantitative in vivo. The mechanism of drug absorption and pharmacokinetic study laggingbehind become a bottleneck of new drug research and development to be solved. This topicwill firstly apply modern micro emulsion type release system to the secondary developmentof two great pill of traditional Chinese medicine preparation. It will be made of nanoemulsion preparation, in order to improve the bioavailability of drugs, increase the stabilityof drugs. The in vivo intestinal absorption mechanisms and pharmacokinetics were studied,and lay a foundation for its further development.Methods:(1)Using the small intestine of rats with similar characteristics, chooseunidirectional perfusion method in the small intestine of rats model, the content ofberberine hydrochloride in pale nano emulsion was assayed by HPLC method, and thecontent of the pale nano emulsion perfusion liquid index of berberine hydrochloride.Investigate pale nano emulsion and rhizoma atractylodis parker cortex phellodendriintestinal absorption of the extract solution; Pale under different drug concentrations ofnano emulsion parker intestinal absorption; P-glycoprotein inhibitor verapamil to paleimpact the intestinal absorption of nano emulsion parker, Investigate the absorption kinetics, biopharmaceutical studies providing basis for dosage form design.(2)Using the method ofblood drug concentration in vivo pharmacokinetics research of the pale microemulsionsparker. Choose healthy male SD rats, randomly divided into2groups, respectively bygastric pale nano emulsion preparation and rhizoma atractylodis parker cortex phellodendriextract mixed suspension, and at different time points after lavage tail take blood. UsingLC-MS/MS determination of drug concentration in rat plasma, analysis of statisticalmoments of non compartmental model by using DAS2.0software, then calculating thepharmacokinetic parameters, further discussing the characteristic of drug absorption, andthe correlation of evaluation model.Results: Using high performance liquid chromatography, tetrahydropalmatine as theinternal standard, set up internal standard method to determine pale cypress berberinehydrochloride content in nanometer emulsions, perfusion method. Pale microemulsions,parker in the absorption of berberine hydrochloride in rats duodenal parameters Ka, Pappvalues is significantly higher than its absorption in the jejunum, ileum, colon, withstatistical difference (P<0.05). Pale microemulsions group, parker and rhizoma atractylodiscortex phellodendri extract solution group comparison showed that the absorption of nanoemulsion group parameter Ka, Papp values were larger than the extract solution set of Ka,Papp values, but pairwise comparison has no significant difference (P>0.05). Differentconcentrations of pale nano emulsion absorption display comparing low, mediumconcentration group of microemulsions intestinal absorption parameters with highconcentration group (49.6μg/mL) of intestinal absorption parameters has significantdifference (P<0.05).The P-glycoprotein inhibitor on pale nano emulsion small intestinalabsorption results show that containing P-glycoprotein inhibitor groups and excludinginhibitors of pale nano emulsion absorption parameter parker Ka compare, and no obviousincrease, but slightly decrease, and the result has no significant difference (P>0.05). UsingLC-MS/MS method, dictamnine as internal standard substance, set up internal standardmethod to determine content of berberine hydrochloride in rat plasma samples. Intragastricadministration of pale nanoemulsion and Rhizoma Atractylodis Phellodendron extractsuspension, pharmacokinetics parameters are as follows:AUC0-24:(199.498±103.358)μg/L·h,(87.765±32.165)μg/L·h;AUC0-∞:(321.641±298.927)μg/L·h,(185.414±163.053)μg/L·h; Cmax（27.45±16.952）ng/L,(15.275±2.772）ng/L; t1/2z（8.307±4.453）h,（9.688±4.815）h.Conclusion: Pale nano emulsion best absorption intestinal segment of duodenum,jejunum, ileum, colon absorption is the worst, nano emulsion group of intestinal absorption was slightly better than the extract solution group. Berberine hydrochloride in palenanoemulsion has high saturation phenomenon in the process of absorption which canpreliminary judge the absorption of berberine hydrochloride as an active transport andberberine hydrochloride may not be a P-glycoprotein substrates, not affected byP-glycoprotein inhibitors or P-glycoprotein less expression in the duodenum result ininhibitor effect is not obvious. Preliminary pharmacokinetic study showed that rats’ oralbioavailability of pale nanoemulsion is about1.7times oforal suspension of rhizomaatractylodis cortex phellodendri extractive, explaining the pale of preparation ofnanoemulsion can significantly improve the absorption of drug in rats and itsbioavailability. |
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