城镇固体废弃物在血吸虫尾蚴长效型药物制剂中的再利用研究

The Schistosoma japonicum cercaria is the only stage of the infection of human and animal. More than 98% of them are floating in the water in a static way. On this basis, the self-diffusion drugs have been invented with fast effectiveness on killing Schistosoma japonicum cercariae. However, it is still difficult to solve the problem of long-term pharmaceutical effect because of the influence of complex environmental factors in natural waters. This project will focus on urban solid waste as raw materials, such as sawdust, bamboo powder, organic silt. These raw materials will be treated by physical and chemical processes to prepare mesoporous materials. The independent invention of the Self-diffusion drug will be loaded into these mesoporous materials. One or several long-term agents with sustained release effect for Schistosoma japonicum cercariae will be invented. Firstly, the mesoporous materials aperture, diameter and morphology will be prepared through carbonization or burning process. Then these mesoporous materials will be modified by small organic molecules with multi-functional groups and loaded into self-diffusion drugs. Secondly, the adsorption or release dynamics will be investigated to establish the theoretical model. Thirdly, it is studied for the long-term effect evaluation and effectiveness of these new agents on killing cercaria. Finally, the production process will be established and optimized. The results of this project will not only implement recycling and utilization of urban solid wastes, but also provide scientific basis for designing and exploring pharmaceutical agents with environment friendly and long-acting.

血吸虫尾蚴是感染人和哺乳动物的唯一阶段，98%以上的日本血吸虫尾蚴生活在水面上，基于此课题组研发了具有快速杀灭血吸虫尾蚴的水面自扩散型药物。但由于受自然水域环境因素的影响，药物分子薄膜难以在水面上保持长期防治效果。本项目拟以城镇固体废弃物如锯末、竹粉、有机淤泥等为原料，分别对其进行物理和化学修饰形成介孔材料，然后负载自主创制的聚醚苯酰胺水面自扩散型药物，从而制备一种或几种具有缓释作用的长效型血吸虫尾蚴防治制剂。首先通过碳化或者焚烧等物理过程制备不同孔径、粒径和形貌的介孔材料；采用含多官能团的有机小分子对其内孔进行化学改性并嫁接自扩散药物；其次开展负载与缓释动力学研究，建立理论模型；然后开展此类新型制剂的长期效应评价和对尾蚴的防治效果研究；最后建立并优化制剂的生产工艺路线与流程。本项目不仅能实现城镇固体废弃物的回收与利用，而且为环境友好、长效型血吸虫尾蚴药物制剂的设计与开发提供了科学依据。

血吸虫尾蚴是血吸虫感染人类的唯一阶段。以水面漂浮的血吸虫尾蚴作为防治对象，可以有效地切断吸血病的传播途径。现有的灭血吸虫尾蚴药效时间短，需要制备灭血吸 虫尾蚴的长效型缓释制剂。详细开展了多孔生物质炭材料的制备及其结构表征研究，选用多种农林固体废弃物作为生物质原料，从表面形貌、官能团和比表面积等方面探索热解温度、热解时间和升温速率对生物质炭化的影响。同时，探索了化学活化法制备高比表面积和不同孔径类型的炭材料。针对血吸虫尾蚴的水面漂浮习性，研究了生物质炭材料的漂浮能力，利用石蜡疏水修饰的方法增加生物质炭材料的疏水性。生物质炭对灭尾蚴药物聚醚苯酰胺的吸附机理研究，通过吸附动力学研究表明生物质炭材料对药物的吸附符合准二级反应动力学。基于生物质炭的抗血吸虫尾蚴药物体系的缓释动力学研究，微孔数量多的炭材料缓释体系药物释放时间较长，但释放率低。介孔数量多的炭材料缓释体系药物缓释时间短，但缓释率高。基于生物质炭材料药物缓释体系用于尾蚴的杀灭效果测试，验结果表明载药缓释体系在水中缓释溶液即可有效杀灭血吸虫尾蚴。本项目研究结果为长效型抗血吸虫尾蚴药物制剂的制备提供了理论指导基础。