【作者】 程丽鸿；

【导师】 赵静；

【作者基本信息】 北京化工大学 ， 应用化学， 2005， 硕士

【摘要】 本论文采用了两步加碱的新方法制备羧甲基壳聚糖(CMCTS),并采用等电点沉降—钠盐化—有机溶剂沉降法对CMCTS进行分离精制,并从取代度、特性粘度、粘均分子量及FTIR谱图等对其进行了表征。 分别以工业虾壳和自制蟹壳CMCTS为载体材料,吡虫啉为模型药物,采用氯化钙—戊二醛双组分交联剂的悬浮交联新方法制备吡虫啉/羧甲基壳聚糖凝胶球,采用扫描电镜和红外光谱对凝胶球进行表征。利用体外释放实验测定凝胶球的释放特性,并测定其溶胀和溶蚀性能。系统地研究了凝胶球的制剂条件及制剂组成对凝胶球外观、载药量、包封率和释药性能的影响,得到了相应的影响规律。吡虫啉释放数据利用通用模型进行回归,并与溶胀和溶蚀结果相关联,确立控制吡虫啉从交联羧甲基壳聚糖凝胶球中释放的机理。 制剂条件对凝胶球外观的影响研究表明:CMCTS浓度是影响凝胶球粒径的关键因素,随其浓度的增加,凝胶球粒径显著增大,颜色也随之变深。粒径随交联时间和交联剂浓度的增加变化不显著。 制剂条件和制剂组成对凝胶球载药量和包封率的影响研究表明:载药量和包封率随戊二醛体积分数增加而下降,随CMCTS质量浓度及其分子量和羧甲基取代度的增加而加大,随交联时间和氯化钙浓度增加变化不显著。自制蟹壳CMCTS为载体材料,蒙脱土的添加和内外源制备法都可显著提高凝胶球的载药量和包封率。高分子量蟹壳更多还原

【Abstract】 Carboxymethyl chitosan (CMCTS) was prepared by a two-step alkalization and refined by isoelectric-point precipitation followed by conversion to water-soluble sodium carboxymethyl chitosan (CMCNa) with sodium hydroxide and then organic-solvent precipitation. The CMCNa products were characterized for the degree of substitution (DS), intrinsic viscosity, viscosity average molecular weight and IR spectroscopy, respectively.The commercial shrimp-shell and self-made crab-shell carboxymethyl chitosan were used respectively as a carrier to formulate gel beads with the model drug imidacloprid by using a mixture of calcium chloride and glutaraldehyde as a cross-linking agent. The gel beads were characterized using FTIR and SEM. The release profiles of imidacloprid from the beads were investigated in-vitro. Swelling and erosion experiments of the beads were performed. The factors influencing the formulation of beads, drug loading, encapsulation efficiency and the release rate of imidacloprid were investigated, including the viscosity-average molecular weight and the degree of substitution (DS) of CMCTS, the concentration of CMCTS solution, cross-linking methods, the amount of cross-linking agent, cross-linking time, drying conditions, and the addition of an inorganic filler as well. The release results were evaluated using the generalized model, and related to the results of swelling and erosion of beads to understand the transport mechanism.The size of beads remarkably increased with the concentration of carboxymethylchitosan solution used for formulation, and the color of the beads darkened accordingly, and was not significantly changed by increasing the exposure time and concentrations of the cross-linking agent.The loading of imidacloprid and the encapsulation efficiency considerably decreased by increasing the concentration of glutaraldehyde, and increased by increasing the concentration, the viscosity-average molecular weight and the DS of CMCTS, and was not significantly changed by increasing the exposure time and concentrations of the cross-linking agent. The use of high viscosity-average-molecular-weight crab-shell CMCTS and the addition of an inorganic filler in formulation considerably increased the loading of imidacloprid and the encapsulation efficiency, and has the benefits of lowing the cost of formulations .The release rate of imidacloprid reduced and followed an increase with increasing concentrations of glutaraldehyde and CaCl2, and decreased with increasing the concentration, the viscosity-average molecular weight and the DS of CMCTS, the use of high viscosity-average-molecular-weight crab-shell CMCTS, the addition of an inorganic filler and pre-crosslinking in formulation, but was not significantly affected by increasing cross-linking time. The release time was prolonged from 80h to 108h with the use of self-made crab-shell CMCTS (cone: 23g/L) instead of commercial shrimp-shell CMCTS (cone: 35g/L) as a carrier for the formulation under the optimized conditions, i.e.: the concentration of glutaraldehyde of 10%, the concentration of CaCl2 of 0.25mol/L, the cross-linking time of 1h.The percentage water uptake of imidacloprid-loaded beads indicated that the swelling ratio was lower for the gel beads based on the high viscosity-average-molecular-weight crab-shell CMCTS (5.17×10~5) than that based on the low one(4.22 × 10~5). The erosion rates of the gel beads based on the crab-shell CMCTS decreased with increasing the DS of CMCTS as a carrier. The results of swelling and erosion were in good agreement with the release results.The SEM data indicated that the imidacloprid-loaded beads had spherical shape with rough surface. The ionically-covalently cross-linked network of gel formed by chelating of Ca2+ and covalent bonding of glutaraldehyde with CMCTS and the absence更多还原