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中药胃肠安丸原料药材质量及作用物质基础研究
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摘要
本文首先对胃肠安丸中大黄、厚朴、川芎、大枣进行了原料药材质量控制的研究,从而在源头上保证了胃肠安丸的质量;在此基础上根据胃肠安丸组方配伍规律,研究了方中大黄与枳壳配伍前后化学成分的变化;此外,本论文还研究了胃肠安丸的抗炎及镇痛活性。
     对方中大黄进行质量控制研究时,建立了大黄药材中五种蒽醌类化合物含量测定的定量分析方法;比较了不同产地的大黄药材质量,甘肃产地的大黄药材中五种蒽醌类化合物的含量在2%以上,质量最佳。采用HPLC-UV的方法分析了不同产地厚朴药材中厚朴酚和和厚朴酚的含量,结果显示湖北产的厚朴药材含量最高,达到3.34%;河北、山东地带所产的大枣中大枣多糖的含量均在50%左右,综合考虑优选河北沧州的大枣;通过比较不同产地川芎药材中川芎嗪和阿魏酸的含量,得出道地产区都江堰所产的川芎药材中川芎嗪和阿魏酸含量最高,分别为0.38%和0.63%。
     方中泻下药大黄和枳壳作为药对,分析其成分变化对胃肠安丸的药效研究具有重要意义。根据指纹图谱分析,显示大黄枳壳配伍后大黄中五种蒽醌类成分及枳壳中四种黄酮苷类的含量发生了变化,大黄中蒽醌类化合物总量由2.39%增加到3.30%,枳壳中黄酮苷类成分总量由7.55%增加到9.38%,表明大黄枳壳配伍促进了其有效成分蒽醌类化合物及黄酮苷的溶出。
     采用了四种炎症模型来探索胃肠安丸的抗炎作用,结果显示其对急性、慢性炎症模型的抑制率均在30%以上,表明胃肠安丸具有较好的抗炎作用;镇痛实验显示胃肠安丸对醋酸扭体抑制率达到84.69%,对福尔马林镇痛模型的抑制率在40%以上,表明胃肠安丸具有镇痛活性。
     以酚红为标记物测定了胃肠安丸对小肠肠推进距离的定性和定量实验。结果显示胃肠安丸显著促进了正常小鼠的小肠推进速度,同时也抑制了新斯的明小鼠模型的胃肠亢进,这表明胃肠安丸对胃肠的作用并不是单纯的抑制或促进,其能够根据机体状态的不同进行双向调节,并且发挥这种双向调节作用的活性部位可能为胃肠安丸甲醇提取物的石油醚层。
     以上研究对提升胃肠安丸的质量及内在科技含量具有重要意义。
The purpose of this study is to control the quality of Wei-Chang-An-Wan throughthe quality control of the crude drugs, which was chosen according to the compositionof the formulation. On this basis, changes in the chemical compositions of Rheumpalmatum and Fructus Aurantii were studied. In order to explain the rational use ofWei-Chang-An-Wan, this study was also to evaluate the anti-inflammatory andanalgesic actitivites.
     We developed a new method to determine the content of five anthraquinones inthe Rheum palmatum. Further more, we used this method to evaluate the drugscollected from different areas and found that the quality of the herbals collected fromGansu province was the best and the contents was2%. For Magnolia officinalis, aHPLC-UV method was developed for the determination of magnolol and honokiol.With the highest contents3.34%of magnolol and honokiol, the herbal collected fromHubei province was the best. When compared the polysaccharides of Fructus Jujubae,the herbals collected from Hebei and Shandong provinces showed the same contents.However, herbals from Hebei province were the best choice from the whole point. ForRhizoma Chuanxiong, the contents of ligustrazine and ferulic were used as theevaluation criterion. The results showed that Doujiang Weir as the genuine RhizomaChuanxiong producing area produced the best herbs.
     We determined the contents changes of five anthraquinones from Rheumpalmatum and four flavonoid glycosides from Fructus Aurantii at the compatibility ofRheum palmatum and Fructus Aurantii. The anthraquinones from2.39%to3.30%while flavonoid glycosides could increase from7.55%to9.38%. The results showedthat all the contents of them were increased.
     Four inflammation models including three acute inflammation models of earedema induced by xylene in mice, paw edema induced by carrageenan in rat andincreased capillary permeability induced by acetic acid in mice and one chronicinflammation model of granulomatous tissue induced by cotton pellet implantation inrat were used to evaluated the anti-inflammatory activity of Wei-Chang-An-Wan. Theresults showed that it could inhibit all of these inflammation models with theinhibition over30%. We used acetic acid-induced abdominal writhings, formalin andhot plate test to research the analgesic activities of this formulation. Wei-Chang-An-Wan could reduce the number of writhings with the inhibition rate84.69%, and decreases the licking time in the formalin test with the inhibition rate40%, but not hot plate test.
     Phenol red was used as a marker to investigate the effects ofWei-Chang-An-Wan on motility of small intestine and gastric emptying in mice. Theresults suggested that Wei-Chang-An-Wan possessed spasmogenic and spasmolyticproperties, and the active parts might be P.E. extracts of the Methanol extracts ofWei-Chang-An-Wan.
     In conclusion, all these researches provide a theoretical support for the herbalsquality control, lay the foundation for the anti-inflammatory and analgesic activities,and supply the basis for the clinical application and further development ofWei-Chang-An-Wan.
引文
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