【作者】 赵继华；

【导师】 张承忠； 贺殿；

【作者基本信息】 兰州大学 ， 药物化学， 2006， 硕士

【摘要】 赭朴九味润燥汤具养血、行淤、润下之功,经兰州大学第一医院近20年临床使用证明治疗老年顽固性便秘疗效确切,但新药及文献检索表明,目前尚未有与之相同或相近的配方申报国家新药或研究报道。依据临床和市场需求为开发安全、有效、稳定的中药新型复方制剂,本课题主要研究赭朴九味润燥颗粒的稳定性、药理作用和安全性。 首先,考察赭朴九味润燥颗粒混悬液对阿托品、肾上腺素、盐酸吗啡负荷小鼠以及正常小鼠小肠推进运动的影响,并用t检验分析,评价该药对小鼠小肠推进功能的影响。结果该药的3个剂量组与对照组相比较,P均小于0.01,表明该药对促进4种不同负荷的小鼠小肠推进功能作用显著,并具有明显的量效关系。 第二,观察该药混悬液对正常小鼠、燥结便秘模型以及复方地芬诺酯(DC)便秘模型小鼠排便作用的影响,并用t检验分析,评价该药对小鼠排便作用的影响。结果该药明显缩短正常小鼠、燥结便秘模型小鼠首次排出黑便时间(P<0.01),排便粒数增多(P<0.05),排便重量增加(P<0.01);并能使DC便秘模型小鼠干粪点数增加(P<0.05)及出现稀粪点数增多,不排便动物数也减少,表明该药有明显的促进小鼠排便效果,并呈一定程度的量效关系。 第三,考察该药对实热型便秘小鼠排便功能、小肠推进功能和肠道水分的影响及其急性毒性和长期毒性试验结果,探讨该药对实热型便秘小鼠的作用及其安全性。结果该药能明显促进实热模型小鼠的排更多还原

【Abstract】 Zhepujiuweirunzao Tang with the main effect enriching blood, eliminating blood stasis, relieving dryness and promoting purgation was used to treat pertinacious aged constipation, which had been proved by 20-year clinical test of the First Hospital of Lanzhou University. But its pharmaceutical basic research was still blank, and new drug and literature retrieval had indicated that there was no the same prescription or new-drug- researching report about it so far. In order to develop its granule without sugar according with clinic and market demand, the pharmacological effects, stability and security had been investigated.First of all, the effect of Zhepujiuweirunzao granule on intestinal propulsion and intestinal propulsion induced by adrenaline, atropine and morphine hydrochloride in mice and that in normal mice was analyzed via t test. Compared with the corresponding control groups, all P of 3 different dosages was less than 0.01, and the differences between them were significant. There was evidently increasing intestinal propulsion and intestinal propulsion of Zhepujiuweirunzao granule and remarkable dosage-effect relationship in mice.Secondary, the cathartic action in normal mice(Gl), mice with constipation induced by water-free diet(G2) and mice with diphenoxylati compositae-induced constipation(G3) was investigated and the data wasanalyzed via t test. It shortened the time of bowel movement in the first time (P<0.0l), increased the number of stool granules (P<0.05) and the weight of stool (P<0.01)in Gl and G2. It also increased the number of hard stool granule(P<0.05) and the soft stool dot in G3 and decreased the number of mice without bowel movement. There was evidently increasing cathartic action and certain dosage-effect relationship in mice.Thirdly, its effect on the defecation, small intestine propulsion and the water volume in intestinal cavities in sthenic heat mice and security was investigated individually. It had significant positive effect on the aspects above in sthenic heat mice. The acute and long term toxicity experiment showed that the drug was secure.Fourthly, to probe into the mechanism of cathartic action in mice of Zhepujiuweirunzao granule, the effect on the inhibition of small intestine propulsion and the water volume in intestinal cavities induced by adrenaline, atropine and morphine hydrochloride in mice was investigated individually. The experimental results showed that it had significant antagonistic effect on the inhibition of small intestine propulsion in experimental mice, increasing the water volume in intestinal cavities. It may be the main cathartic action mechanism for it to promote small intestine propulsion, to reduce intestine tension, and to increase intestinal volume.Finally, the accelerating test, the long-term test and the illuminationaccelerating test was separately used to inspect the character, the distribution of granule size, the dry weightlessness, the qualitative identification and the content determination. The indexes conformed to the stipulation of the quality standards in experimental period exception for Emodin content to change significantly in the illumination accelerating test. The experedimental result commended that Zhepujiuweirunzao granule should be stored dodging packing with good stability.更多还原