發(fā)布時間：2018-05-25 14:19

  本文選題：幽門螺桿菌 + NE-2001��； 參考：《中國科學院研究生院（上海生命科學研究院）》2006年碩士論文

【摘要】：幽門螺桿菌是一種生長于胃粘膜層的革蘭氏陰性細菌,據(jù)報道全世界約有一半人群感染了此病原菌。根除幽門螺桿菌對于治療胃炎、胃潰瘍以及減少胃癌發(fā)生的積極作用已經(jīng)得到了廣泛的共識。 NE-2001是由我國研究開發(fā)的一個具有自主知識產(chǎn)權(quán)的新化學實體。本論文的主要內(nèi)容包括:(1)系統(tǒng)考察NE-2001對幽門螺桿菌標準菌株以及不同來源的臨床菌株,特別是臨床常見耐藥菌株的抗菌活性。(2)針對NE-2001水溶性差的缺點,開發(fā)基于2-羥丙基-β-環(huán)糊精包合的制劑技術(shù),并通過動物實驗研究包合物的體內(nèi)抗幽門螺桿菌作用。(3)以幽門螺桿菌體特異性亮氨酸氨肽酶為靶點,建立相應的高通量篩選模型并完成對國家新藥篩選中心化合物庫的大規(guī)模篩選。 結(jié)論:(1)通過對江蘇省人民醫(yī)院及上海仁濟醫(yī)院隨機采集的24株幽門螺桿菌臨床菌株,以及從50株臨床菌株中篩選得到的13株對甲硝唑和克拉霉素耐藥菌株所進行的兩組獨立的體外藥敏實驗表明, NE-2001對臨床隨機樣本及耐藥菌株均有明顯的抑制作用,提示其良好的抗菌活性并具有深入研究開發(fā)的價值。(2)建立了一套基于2-羥丙基-β-環(huán)糊精包合技術(shù)的制劑工藝流程,顯著地改善了NE-2001的水溶性,包合效果通過X射線衍射和差示掃描量熱分析得以證實。引建了C57BL/6小鼠感染幽門螺桿菌SS1菌株的動物模型,初步實驗顯示感染小鼠單獨口服NE-2001即具有一定的幽門螺桿菌根除效果,NE-2001與其它兩種藥物聯(lián)用的藥效學實驗正在進行之中。(3)建立了基于亮氨酸氨肽酶的高通量篩選模型并完成了對國家新藥篩選中心化合物庫32000個樣品的大規(guī)模篩選,發(fā)現(xiàn)多個對該酶具有抑制活性的化合物,其中一個具有一定的抗幽門螺桿菌活性,相關(guān)的構(gòu)效關(guān)系研究已經(jīng)展開。
[Abstract]:Helicobacter pylori is a gram-negative bacterium that grows in the gastric mucosa and is reported to infect about half of the world's population. Eradication of Helicobacter pylori has been widely recognized as a positive role in the treatment of gastritis, gastric ulcers and the reduction of gastric cancer. NE-2001 is a new chemical entity with independent intellectual property rights developed by our country. The main contents of this thesis include: (1) to investigate the antibacterial activity of NE-2001 against standard strains of Helicobacter pylori and clinical strains from different sources, especially the common clinical resistant strains. To develop a preparation technology based on 2-hydroxypropyl- 尾 -cyclodextrin inclusion, and to study the anti-Helicobacter pylori effect of inclusion complex in vivo by animal experiments.) to target helicobacter pylori specific leucine aminopeptidase, A high-throughput screening model was established and a large-scale screening of the compound library of the National Center for New Drug screening was completed. Conclusion Twenty four clinical strains of Helicobacter pylori were randomly collected from Jiangsu Provincial people's Hospital and Shanghai Renji Hospital. Two independent in vitro drug sensitivity tests of 13 strains of metronidazole and clarithromycin resistant strains screened from 50 clinical strains showed that NE-2001 had obvious inhibitory effects on clinical random samples and drug-resistant strains. It was suggested that the preparation process based on 2-hydroxypropyl- 尾 -cyclodextrin inclusion technology was established, and the water solubility of NE-2001 was significantly improved, which indicated that it had good antibacterial activity and had the value of further research and development, and established a set of preparation process based on 2-hydroxypropyl- 尾 -cyclodextrin inclusion technology. The inclusion effect was confirmed by X-ray diffraction and differential scanning calorimetry. An animal model of C57BL/6 mice infected with Helicobacter pylori SS1 strain was established. Preliminary experiments showed that NE-2001 alone in infected mice had a certain eradication effect of Helicobacter pylori. The pharmacodynamics experiment of NE-2001 combined with two other drugs was under way.) High throughput screening based on leucine aminopeptidase was established. The model also completed the large-scale screening of 32000 samples from the compound library of the National Center for New Drug screening. A number of compounds with inhibitory activity to the enzyme were found, one of which had a certain activity against Helicobacter pylori, and the studies on the structure-activity relationship have been carried out.
【學位授予單位】：中國科學院研究生院（上海生命科學研究院）
【學位級別】：碩士
【學位授予年份】：2006
【分類號】：R378;R96

【參考文獻】

相關(guān)期刊論文 前5條

1 丁平田,吳雪梅;藥物制劑的新型輔料2-羥丙基-β-環(huán)糊精[J];國外醫(yī)藥.合成藥.生化藥.制劑分冊;1996年02期

2 劉青,王明偉;抗幽門螺桿菌藥物的研究進展[J];生命科學;2005年03期

3 姜典卓,王志宣,武鳳蘭;維甲酸羥丙-β-環(huán)糊精包合物制備條件的優(yōu)化及包合過程熱力學參數(shù)的測定[J];沈陽藥科大學學報;2004年01期

4 胡伏蓮;幽門螺桿菌感染治療方案的合理應用[J];中國醫(yī)院用藥評價與分析;2003年03期

5 史彤,劉文忠,蕭樹東,徐蔚文;幽門螺桿菌對克拉霉素耐藥的分子機制研究[J];中華消化雜志;2001年01期

，

本文編號：1933472