【作者】 刘美华；

【导师】 郑敦胜；

【作者基本信息】 广东药学院 ， 药剂学， 2010， 硕士

【摘要】 淀粉是自然界中最为丰富的碳水化合物,具有良好的生物相容性,无毒,可降解。淀粉分子链上含有大量的醇羟基,可以与多种物质反应,得到多种不同性能的变性淀粉,是食品、医药、制革、废水处理、造纸、铸造、纺织、材料等众多工业的原辅料,尤其在药物研究方面具有广泛的应用前景。本文以淀粉(starch)、马来酸酐(MAH)、N-异丙基丙酰胺(NIPA)和甲基丙烯酸二甲胺基乙酯(DMAEMA)为原料,合成了高取代度的马来酸酐淀粉酯(starch-MAH),制备了具有温度和pH敏感的马来酸酐淀粉酯-N-异丙基丙酰胺( starch-MAH/NIPA )和马来酸酐淀粉酯-甲基丙烯酸二甲胺基乙酯(starch-MAH/DMAEMA)水凝胶,研究了淀粉酯和水凝胶的制备工艺,并进行结构表征和性能测试。采用模型计算和分析,结合体外实验的结果研究了水凝胶的释药行为,并探讨了水凝胶的释药机理。本论文的具体研究内容如下:1.高取代度马来酸酐淀粉酯的制备用溶剂法制备高取代度的starch-MAH,对取代度、结构等方面进行了研究,探讨淀粉用量、反应温度、时间等对产物性能的影响,通过正交设计实验得出了最优工艺。另外对原料和产物的结构进行红外、差热、13~C-NMR分析。实验结果表明该方法制备的淀粉酯取代度较高。2.starch-MAH/NIPA水凝胶的制备与性能研究以马来酸酐淀粉酯和N-异丙基丙烯酰胺为原料,合成具有温度和pH敏感的水凝胶,对其性能和结构进行了表征。研究了多种因素对水凝胶形态、膨胀度和载药量的影响。通过星点设计——效应面法,对评价指标和各影响因素之间的模型进行计算,得到优化工艺:当用8 mgBIS,5 ml含NIPA和starch-MAH的水溶液,25μlAPS和33μlTEMED,室温下反应24小时,可得到性能最好的水凝胶。对最佳条件下制备的水凝胶进行了结构表征和性能考察。结果表明,制备的水凝胶具有较好的膨胀性能以及温度和pH敏感性。3. starch-MAH/DMAEMA水凝胶的制备制备了starch-MAH/DMAEMA水凝胶,对其结构和性能进行研究,考察各种因素对产物的影响。通过星点设计——效应面法,得到优化工艺,并对制备的水凝胶进行结构和性能研究,发现starch-MAH/DMAEMA水凝胶的LCST在44℃左右,比starch-MAH/NIPA水凝胶的LCST高,且具有较好的pH/温度敏感性。4.探讨载药水凝胶的体外释放并进行模型计算研究载药水凝胶starch-MAH/NIPA和starch-MAH/DMAEMA在不同pH值的磷酸盐缓冲液中的释放行为,分析水凝胶的药物释放过程。药物释放的模型计算表明,制备的两种水凝胶均具有较好的缓释性能,释放机理属于一级动力学模型,且starch-MAH/NIPA水凝胶具有更好的pH/温度敏感性和缓释性能。这些结果为载药水凝胶的进一步研究提供实验和理论参考。更多还原

【Abstract】 Starch is the most abundant carbohydrate in nature, which posses good biocompatibility, non-toxic and biodegradable. In starch molecular chain, there are a large number of alcoholic hydroxyl, which can reacted with a variety of substances to got different properties of modified starch. It’s the raw materials of food, medicine, leather, wastewater treatment, paper making, casting, textiles, materials and other industrial, especially in drug research has broad application prospects.In this paper, high degree of substitution of starch, temperature and pH-sensitive starch-MAH/NIPA hydrogel and starch-MAH/DMAEMA hydrogel were prepared using starch, MAH, NIPA and DMAEMA as the raw material. Optimized processes, structure characterization and performance testing were studied. Drug release behavior was investigated through model calculations and analysis, combined with the results of experiments. The mechanisms were also explored. The specific studies were as follows:1. Preparation of high degree substitution of starchHigh degree substitution of starch was prepared by solvent, and the degree of substitution, structure were studied. Through discussion of factors (starch concentration, reaction temperature, time) on the impact of products. Through the orthogonal design, the optimum process was obtained. In addition, the final product was analysised via IR, DSC and 13~C-NMR. The results show that the product prepared by this method posses high degree substitution.2. Preparation and Characterization of starch-MAH/NIPA hydrogelThe temperature and pH sensitive starch-MAH/NIPA hydrogel was synthesized by starch-MAH and N-isopropylacrylamide. The structure characterization and performance testing were studied. In the preparing process, various factors were investigated according to their influences on the morphology, swelling, and drug loading of hydrogel. Through the central composite design– response surface method, the mathematical models of evaluation indicators and impact factors were established, the process were optimized. The hydrogel with optimal performance could obtained when using 8mgBIS, 5ml solution with NIPA and starch-MAH, 25μlAPS and 33μlTEMED, room temperature for 24 hours. The hydrogel which was prepared under the best conditions was characterized and tested. The results showed that the hydrogel posses good swelling properties, temperature and pH sensitivity. 3. Preparation and Characterization of starch-MAH/DMAEMA hydrogelStarch-MAH/DMAEMA hydrogel was prepared, and structure characterization and performance testing were studied. Various factors were investigated according to their influences on the product. Through the central composite design– response surface method, the mathematical models of evaluation indicators and impact factors were established, the process were optimized. The hydrogel which was prepared under the best conditions was also characterized and tested, which showed that the LCST of starch-MAH/DMAEMA hydrogel is around 44℃, higher than starch-MAH/NIPA hydrogel, and also has good pH and temperature sensitivity.4. Explore the in vitro release and doing model calculationsThe in vitro release of drug-loaded starch-MAH/NIPA and starch-MAH/ DMAEMA hydrogel were researched in different pH phosphate buffer. Drug release process was also investigated. Commonly used models in vitro release were fitted. It was found that first order kinetics model can be in line with the release characteristics better. And starch-MAH/NIPA hydrogel showed better pH/temperature sensitivity and sustained release performance. It will provide a theoretical basis and data reference for further research on hydrogel.更多还原