装载小檗碱的羧甲基β-环糊精修饰的蒙脱石超分子网络的抗菌活性

发布时间：2018-06-28 22:29

  本文选题：超分子网络材料 + 羧甲基环糊精　； 参考：《重庆医科大学》2017年硕士论文

【摘要】：本文采用廉价、简便、安全环保的合成方法,首次成功制备了羧甲基β-环糊精修饰的蒙脱石,然后通过分子间氢键自组装成超分子网络结构,并将其用于装载小檗碱,提高盐酸小檗碱的溶解度,改善其生物利用度,最终达到增强盐酸小檗碱抗菌性能的目的。本研究内容主要包括以下两个部分:第一部分:超分子网络载体材料的制备、表征及载药性能研究。采用β-环糊精在碱性条件下与一氯乙酸反应合成羧甲基环糊精;对蒙脱石进行硅烷化,得到三氨丙基三乙氧基硅烷修饰的蒙脱石;在室温条件下通过1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐和N-羟基琥珀酰亚胺催化,使羧甲基环糊精的羧基与三氨丙基三乙氧基硅烷硅烷化的蒙脱石上的伯胺基发生缩合反应,最终得到羧甲基环糊精修饰的蒙脱石超分子网络材料。通过红外光谱分析、热重分析、X射线粉末衍射分析以及场发射扫描电镜分析,对材料进行了表征。采用盐酸小檗碱作为模型药物考查超分子网络载体材料的体外载药和释放性能。结果:通过红外光谱分析可知,超分子网络材料在587,613和745cm-1出现了环糊精的特征峰,证明羧甲基环糊精对蒙脱石的成功嫁接;X射线粉末衍射分析显示蒙脱石经过修饰后特征峰左移,层空间扩大,说明羧甲基环糊精的嫁接反应不仅发生在蒙脱石表面也发生在蒙脱石层间;热重分析显示,环糊精基团在超分子网络材料中的质量占比为6.9%。应用场发射扫描电镜观察超分子载体材料的独特网络结构。体外载药试验表明超分子网络载体材料在50℃,p H7.0的条件下载药5小时可达最大载药量28.0%;体外释放试验表明,在p H=7.4条件下,载药超分子材料具有缓释特征,在12小时内释放度可达49.3%。第二部分:载药超分子网络体外抗菌性能研究。采用稀释平板法,比较载药超分子网络和游离药物的体外抗菌性能。采用荧光显微镜观察细菌对药物的吸收,以考察载药超分子材料抗菌能力的浓度依赖性。采用紫外分光光度计于600 nm处测定菌悬液的光密度,考查不同浓度的载药超分子载体材料的长期抗菌性能,应用场发射扫描电镜研究载药超分子材料与细菌相互作用的机制。结果:经过浓度分别为150、400μg/mL载药超分子材料处理的金黄色葡萄球菌和大肠杆菌菌悬液,菌落总数从107下降到102,载药超分子网络材料的体外抗菌性能明显优于游离的药物。平板稀释计数法和荧光显微镜观察,确证了载药超分子网络材料的抗菌性能随浓度的增加而升高。不同浓度载药超分子材料与细菌一起培育3天的光密度曲线显示,载药超分子材料具有长效抑菌功能,对金黄色葡萄球菌的抑制率可达到97.81%,对大肠杆菌的抑制率达98.45%。
[Abstract]:In this paper, carboxymethyl 尾 -cyclodextrin modified montmorillonite was successfully prepared by a cheap, simple, safe and environmentally friendly method, and then self-assembled into supramolecular network structure by intermolecular hydrogen bonding, and used for loading berberine. To improve the solubility and bioavailability of berberine hydrochloride, the antibacterial activity of berberine hydrochloride was enhanced. The main contents of this study are as follows: the first part: preparation, characterization and drug loading properties of supramolecular network carrier materials. Carboxymethyl cyclodextrin was synthesized by the reaction of 尾 -cyclodextrin with monochloroacetic acid in alkaline condition, and montmorillonite modified by triaminopropyltriethoxysilane was obtained by silanizing montmorillonite. At room temperature, the carboxyl group of carboxymethyl cyclodextrin reacted with the primary group of triaminopropyl triethoxysilane on montmorillonite catalyzed by 1- (3-dimethylaminopropyl) -3-ethyl carbodiimide hydrochloride and N-hydroxysuccinimide. Finally, carboxymethyl cyclodextrin modified montmorillonite supramolecular network material was obtained. The materials were characterized by infrared spectroscopy, thermogravimetric analysis, X-ray powder diffraction and field emission scanning electron microscopy. Berberine hydrochloride was used as a model drug to investigate the drug loading and release properties of supramolecular network carrier in vitro. Results: the characteristic peaks of cyclodextrin appeared in 587613 and 745cm-1 of supramolecular network materials. It is proved that the successful grafting of montmorillonite with carboxymethyl cyclodextrin by X-ray powder diffraction shows that the characteristic peak of montmorillonite is shifted to the left and the layer space is enlarged after modification. The results show that the grafting reaction of carboxymethyl cyclodextrin occurs not only on the surface of montmorillonite but also on the interlayer of montmorillonite, and the mass ratio of cyclodextrin group in supramolecular network material is 6.9% by thermogravimetric analysis. The unique network structure of supramolecular carrier material was observed by field emission scanning electron microscope. The drug loading test in vitro showed that the supramolecular network carrier material could download the drug at 50 鈩，

本文编号：2079608