再生纤维素微球的可控制备及结构和性能关系研究

Regenerated microspheres have been widely used in chromatography packing, separation technologies, controlled drug delivery devices, biomedical drug and catalyst carrier, also in the fields of environment protection and food science due to their biocompatibility and biodegradability. However, almost all of these products have been prepared from toxic organic solvent or cellulose derivatives, leaving difficult to eliminate the residues of toxic contaminants and the residual groups or leading the microsphere difficult to wash, which will limit the use of these microsphere products in biological and medical fields. To solve the problems mentioned above, some new methods will be developed to prepare novel plain cellulose microspheres by using the cellulose solution, in which cellulose is directly dissolved in a new "green" cellulose solvent of NaOH/urea solution; cellulose microspheres with good morphology, nano-size or micro-size or millimeter-size, and narrow size distribution will be fabricated by various manufacturing process, and to analysis mechanism of forming microspheres; process of the particle formation and mechanism of pore formation will be analyzed to achieve controllable adjustment of particle size and pore size of the microspheres, and to establish the corresponding mathematical model to analyse the relationships between microsphere products performance and fabrication process of microspheres; the characterization of the systems of the cellulose microsphere products will be built to explore the relationships between structure and property of the microspheres, and we can get a series of microsphere samples with better integrative properties for both research and industrial applications. Therefore we will provide important scientific data for the novel cellulose microspheres preparation methods, study the relationships between the structure and property,and potential bioapplication of the cellulose microspheres products.

再生纤维素微球由于可生物降解和生物相容广泛应用于色谱、分离科学、可控制载体和贮藏体、生物医药和催化剂支撑体、环境和食品等领域。采用传统纤维素溶剂制备微球会造成环境污染，更限制了产品在生物及医学方面的应用；另外采用纤维素衍生物制备微球则难以避免带有残留基团而影响性能。针对这一情况，本项目以NaOH/尿素体系新溶剂直接溶解纤维素用于纤维素微球的制备，并发展新的制备方法；揭示微球的形成机理，制备形貌良好、窄粒径分布的纳米级、微米级和毫米级纯纤维素微球；系统研究纤维素微球的粒径调节和孔形成机理，达到对微球产品的粒径和孔径进行可控调节，并建立对应的数学模型，分析微球产品性能与制备工艺方法的关系；建立纤维素微球产品的表征体系,并揭示纤维素微球的结构与性能的关系，获得综合性能优异的实验室研究用和小规模实用微球样品。为新型纤维素微球的制备方法、结构和性能关系及潜在的生物应用建立提供重要科学数据。

本工作主要利用纤维素为原料，通过碱/尿素水体系新溶剂（NaOH/尿素，LiOH/尿素）直接溶解纤维素用于纤维素微球的制备。首先发展新的和改良了原有的制备工艺方法：针对纳米级的纤维素颗粒不易制备，受电纺法及电喷法的启发，通过工艺参数及设备改进制备了形貌良好，均一的纳米级的纤维素颗粒；尺寸均一窄粒径分布的纳米到微米级的纤维素在光电或生物医药领域有更好的应用，采用膜乳化法解决了此产品的制备问题；豪米级纤维素微球方面，本工作中改进了直接滴落固化法，改手动挤出为电动挤出，大大提高了生产效益；对于天然高分子微球传统制备方法溶胶凝胶转相法，本工作探索了同时溶解其它天然高分子如壳聚糖，制备了多种天然高分复合微米级微球，并采用共混改性或化学改性等方法提高制备复合微球产品的应用性能。.揭示各类制备工艺微球的水诱导相分离形成机理，通过工艺参数的调节使制备的微球有良好的圆形形貌、窄粒径分布和合适的微纳级多层次孔结构。.初步达到对微球产品的孔径进行可控调节。相对粒径的调节，纤维素微球的孔形成和调节机理更难达到和对应用的影响更直接，本工作并建立对应的数学模型，分析微球产品性能与制备工艺方法的关系。 .建立了纤维素微球产品的形貌结构及其它理化性质表征体系,并揭示纤维素微球的结构与应用性能的关系，获得综合性能优异的实验室研究用和小规模实用微球样品。另外在高值化纤维素膜和生物质如木质素基材料的制备及应用方面也进行了一些拓展。.探索了制备微球产品的不同领域应用并深入研究了其应用机理。用于吸附分离科学：用作水相中重金属如铅，镉，铜及锌等、富营养化离子如磷酸根和药物残留如阿莫西林等的高效吸附剂；用作药物可控释载体和贮藏体：用于抗癌药物阿霉素载体用作伤口敷料，及壳聚糖载体用于抗菌伤口敷料，复合材料用于X射线材料等；环境和食品：用于益生菌的载体用作食品营养强化剂等领域。拓展了其在催化剂支撑体领域的应用，用于水相中染料、抗生素等的吸附催化降解。