戊己丸与超微戊己丸实验比较研究

【作者】 江星明；

【导师】 周日宝；

【作者基本信息】 湖南中医药大学 ， 中药学， 2011， 硕士

【摘要】 目前：戊己丸由黄连、白芍、吴茱萸三味中药组成。主治肝火犯胃、肝胃不和所致的胃脘灼热疼痛、呕吐吞酸、口苦嘈杂、腹痛泄泻。超微粉碎技术用于复方制剂可提高药物制剂的有效成分含量和生物利用度。本文采用HPLC法测定戊已丸中盐酸小檗碱的含量,方便、准确地反映戊已丸的有效成分,以大鼠做动物的药物代谢动力学、组织分布与排泄实验,分别用戊己丸和超微戊己丸灌胃,测定其血药浓度,计算动力学参数进行统计分析并进行比较研究,为进一步研究超微戊已丸的体内生物利用度和临床应用提供实验依据。方法：以大鼠为实验对象,分别用戊己丸和超微戊己丸灌胃,采用HPLC法测定指标成分盐酸小檗碱的含量,测定其血药浓度,计算戊已丸在大鼠体内的药物代谢动力学、组织分布与排泄参数,进行统计分析并进行对比研究,为进一步研究超微戊已丸的体内生物利用度和临床应用提供实验依据。1、药代动力学实验：用戊己丸和超微戊己丸给大鼠灌胃,HPLC法测定指标成分盐酸小檗碱的血药浓度,药动学软件计算相关参数,进行对比研究。2、组织分布实验：选用盐酸小檗碱为指标,HPLC法测定小檗碱在大鼠体内和小檗碱在大鼠各组织中的浓度随时间的变化。大鼠灌胃戊己丸和超微戊己丸后在组织中的浓度高低。再对比戊己丸组和超微戊己丸组的实验数据,超微戊己丸组较戊己丸组在组织中小檗浓度和曲线下面积AUC是否有一定程度的增大。3、排泄实验：给大鼠灌胃后,在一定的时间点段收集大鼠的胆汁,粪,尿。测定戊己丸在其中的排泄率,累积排泄率。比较戊己丸组和超微戊己丸组的异同。结果：1通过对戊己丸和超微戊己丸药动学实验比较研究,等剂量的超微戊己丸灌胃后在每一个时间点的血药浓度值均大于戊己丸超微戊己丸组的Cmax,AUC值均较常规组增大,超微组较常规组的Cmax和AUC值分别增加了15.7%和12.8%,而其指标成分出峰时间及其他化学成分均未显示有明显变化(见表4)。说明等剂量的药物,超微中药的有效血药浓度比常规制剂中药的血药浓度要高,相关化学成分浓度有所增大。2在胆汁排泄实验中则两者的排泄率均较低,说明戊己丸灌胃在胆汁中排泄少,两实验组无明显差异。3在粪和尿排泄物的实验对比研究中,发现戊己丸主要是经过粪排泄途径,而尿中排泄甚少。以上实验对比研究为进一步研究超微戊已丸的体内生物利用度和临床应用有着积极的意义结论：超微粉碎技术应用于戊己丸的制备后,提高了戊己丸有效成分的溶出度。通过含量测定比较戊己丸和超微戊己丸的实验组,超微戊己丸组在血药浓度、主要排泄物中均高于戊己丸更多还原

【Abstract】 Objective:Wujiwan composed of three herbs such as Coptis、Evodia rutaecarpa(Juss.)Benth、Paeonia lactiflora Pall. The major functions of Wujiwan are liver-fire attacking stomach, stomach-ache, acid requrqitation, bitter taste and diarrhea. Ultra-fine powder technology for compound preparation can enchance the effective component content thing preparation and bioavailability, this article were determined by HPLC method in already shot the content of berberine hydrochloride, conveniently, accurately reflect the shot of the effective components already to rat doing animal pharmacokinetic, organization distribution and discharge experiment, respectively for Wujiwan and superfine pill irrigation, determine its stomach blood medicine density, calculate dynamic parameters of statistical analysis and comparison and study for the further research and the body already ultrastructural Wujiwan bioavailability and clinical application provides experimental basis.Methods:For subjects in rats with conventional e respectively, has shot and superfine Wujiwan irrigation stomach, determined by HPLC method index component berberine hydrochloride content, determine its blood drug concentration, already shot in calculating rats in vivo pharmacoki-netic, organization distribution and discharge parameters, statistical ana-lysis and comparison for further research, already pill body ultra bioa-vailability and clinical application provides experimental basis.1, pharmacokinetic experiment:with conventional e yourself pills and sup-erfine e rats irrigation has shot stomach, by reveed-phase HPLC index component berberine hydrochloride, the blood drug concentration cal-culated pharmacokinetic software related parameters, a comparative study. 2, the organization distribution experiment:choose berberine hydrochlo-ride as index, berberine by reveed-phase HPLC in rats in vivo in rats and berberine, the concentration of each organization changes over time. Rat stomach conventional irrigation has e has shot blasting and superfine e after the concentration discretion in organizations. Then compare conve-ntional e f pill group and superfine e of the experimental data has bolus group, utrasmall e f pill group compared with conventional e in the org-anization has bolus group dissolubility concentration and curve area under the AUC whether a certain degree of increased.3 Excretion experiment:rats after filling in certain stomach, collect rats time period of bile, muck, urine. Determination of blasting in them has e excretion rates, and a cumulative excretion rate. The above experiments contrast research for further research on the body already Ultra-fine powder pill for bioa- vailability and clinical application has positive significance.Results:1 Through to ordinary e f pills and superfine e dynamic learning experimental comparison has the pills were pleasant, etc doses of superfine e after filling in stomach has shot at a point in time were greater than the conventional blood medicine density has pills, Ultra-fine powder Cmax, has shot groups are more routine group AUC value increases, utrasmall group compared with conventional group of Cmax and AUC value increased by 15.7% respectively, and the index and 12.8% a peak time and other ingredients are not shown chemical changes significantly. Specifications dose of the drug, utrasmall Chinese medicine’s effective blood drug concentration than conventional preparation medicine blood drug concentration, related to the high concentration of chemical composition is increased.2 In radicles draining experiments are both excretion rates were lower, explain e in bile irrigation has shot in the stomach and the two experimental excrete less without obvious difference. 3 In dung and urine excreta experimental study, found that e is primarily through dung has shot, while urinary excretion way in little. Drain The above experiments contrast research for further research on the body already pill ultrastructural e bioavailability and clinical application has positive significance. Conclusion:By using ultra-fine powder technology in the preparation of wujiwan, Superfine grinding technology used in the preparation of cyclopentanone himself after blasting, improving the effective components has shot dissloution degrees. Through comparing conventional pentosan content determination of blasting and superfine e has the group has shot blasting group, utrasmall e in blood has feces, mainly drug concentration is higher than conventional wujiwan.更多还原