聚合物载药缓释微球药物释放动力学模拟

论文编号:HG211  论文字数:10465,页数:24

 摘 要：药物控制释放技术在医药领域有着广泛的应用。本文以聚合物载药微球为对象，建立了其药物释放的费克扩散模型。由模拟结果可见，扩散系数决定了药物在聚合物中的扩散速率，从而决定了药物的释放速率。释放模型有必要考虑微球群体的粒度分布对药物释放的综合贡献。只有粒径分布较窄时，才能将平均粒径作为模型的参数。另外，本文将载药微球药物扩散模型与药物在体内的药代动力学模型相结合，计算得到了载药微球型药剂产生的血药浓度随时间的变化曲线。相对于药物溶液形式的给药，微球中的药物通过载体的控制释放，血药浓度峰值有很大的降低，实现了药物的缓慢释放，抑制了首过突释效应。多剂量给药时，载药微球这一给药方式能大大减小体内血药浓度波动。
 关键词：控制释放；聚合物微球；费克扩散；药代动力学；模型
英文摘要

Abstract: The technology of controlled release is widely used in the field of medicine. In this work, a Fickian diffusion model of controlled release for the polymer-drug microspheres was established firstly. The simulation results show that the diffusion rate of drug in polymer carrier was determined by the diffusion coefficient greatly. Moreover, the particle size distribution of microspheres had a significant influence on the release performance. Therefore, the average particle size can be adopted as the model parameters only if the narrow particle size distribution exists. In addition, plasma concentration-time curves have been obtained on the basis of the integration model of Fickian diffusion and in vivo pharmaco-kinetic. Compared to the solution dosage, the polymer-drug microspheres dosage provided a reduced plasma concentration peak, a slower release of drug. The polymer-drug microspheres dosage can significantly reduce the blood concentration fluctuations between dosage intervals as well.
Keywords: Controlled release; Polymer microsphere; Fickian diffusion; Pharmoco-kinetics; Modeling

目  录
中文摘要 I
英文摘要 II
目  录 III
1 绪论 1
1.1 药物控制释放技术简介 1
1.2 聚合物微球载体系统 2
1.3 药物释放过程机理及模型 3
1.3.1 经验及半经验模型 5
1.3.2 机理模型 6
2 聚合物载药微球控释机理的模型化 8
2.1 微球的释放机理 8
2.2 药物释放的费克扩散模型 8
2.3 药物释放及药代动力学集成模型 10
3 结果与讨论 12
3.1 扩散系数对释放速率的影响 12
3.2 聚合物载药微球粒径及粒径分布对释放速率的影响 12
3.3 释放速率对血液药物浓度的影响 14
3.3.1 单剂量给药 14
3.3.2 多剂量给药 14
4 总结与展望 17
致  谢 18
参考文献 19