聚合物載藥緩釋微球藥物釋放動(dòng)力學(xué)模擬

化工論文編號(hào):HG211  論文字?jǐn)?shù):10465,頁(yè)數(shù):24

 目  錄
中文摘要 I
英文摘要 II
目  錄 III
1 緒論 1
1.1 藥物控制釋放技術(shù)簡(jiǎn)介 1
1.2 聚合物微球載體系統(tǒng) 2
1.3 藥物釋放過(guò)程機(jī)理及模型 3
1.3.1 經(jīng)驗(yàn)及半經(jīng)驗(yàn)?zāi)Ｐ?nbsp;5
1.3.2 機(jī)理模型 6
2 聚合物載藥微球控釋機(jī)理的模型化 8
2.1 微球的釋放機(jī)理 8
2.2 藥物釋放的費(fèi)克擴(kuò)散模型 8
2.3 藥物釋放及藥代動(dòng)力學(xué)集成模型 10
3 結(jié)果與討論 12
3.1 擴(kuò)散系數(shù)對(duì)釋放速率的影響 12
3.2 聚合物載藥微球粒徑及粒徑分布對(duì)釋放速率的影響 12
3.3 釋放速率對(duì)血液藥物濃度的影響 14
3.3.1 單劑量給藥 14
3.3.2 多劑量給藥 14
4 總結(jié)與展望 17
致  謝 18
參考文獻(xiàn) 19

摘 要：藥物控制釋放技術(shù)在醫(yī)藥領(lǐng)域有著廣泛的應(yīng)用。本文以聚合物載藥微球?yàn)閷?duì)象，建立了其藥物釋放的費(fèi)克擴(kuò)散模型。由模擬結(jié)果可見(jiàn)，擴(kuò)散系數(shù)決定了藥物在聚合物中的擴(kuò)散速率，從而決定了藥物的釋放速率。釋放模型有必要考慮微球群體的粒度分布對(duì)藥物釋放的綜合貢獻(xiàn)。只有粒徑分布較窄時(shí)，才能將平均粒徑作為模型的參數(shù)。另外，本文將載藥微球藥物擴(kuò)散模型與藥物在體內(nèi)的藥代動(dòng)力學(xué)模型相結(jié)合，計(jì)算得到了載藥微球型藥劑產(chǎn)生的血藥濃度隨時(shí)間的變化曲線。相對(duì)于藥物溶液形式的給藥，微球中的藥物通過(guò)載體的控制釋放，血藥濃度峰值有很大的降低，實(shí)現(xiàn)了藥物的緩慢釋放，抑制了首過(guò)突釋效應(yīng)。多劑量給藥時(shí)，載藥微球這一給藥方式能大大減小體內(nèi)血藥濃度波動(dòng)。
 關(guān)鍵詞：控制釋放；聚合物微球；費(fèi)克擴(kuò)散；藥代動(dòng)力學(xué)；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