考察聚乳酸微球體外長期釋放和加速釋放的相關

論文編號:HG252   論文字數:19685,頁數:32

 摘要
 目的：本實驗是考察聚乳酸微球體外長期釋放和加速釋放的相關性，建立異環磷酰聚乳酸微球的體外加速釋放方法。方法：用紫外分光光度法測定微球中異環磷酰胺的含量。本研究采用動態透析法分別在不同的溫度的介質中進行體外加速度釋放試驗和長期釋放試驗。及進行兩者相關性的考察。結果：本研究異環磷酰胺制備聚乳酸微球在37℃放置145小時內釋放達到94.90%，微球在42℃，47℃，55℃和58℃下的加速釋放均明顯加速，釋放動力學分別符合一級釋放方程及Higuchi方程。異環磷酰胺制備聚乳酸微球在55℃的條件的加速釋放與在37℃長期釋放有較良好的相關性。結論：異環磷酰胺制備聚乳酸微球具有很好的緩釋能力，采用體外加速試驗的方法可以快速考察異環磷酰胺聚乳酸微球的體外釋藥能力。
 
 
關鍵詞：異環磷酰胺  聚乳酸  加速釋放  紫外分光光度法  微球

【Abstract】
Objective: This experiment is the inspection gathers the relevance which lactic acid microballoons in vitro releases for a long time and accelerates to release, constructs takes ifosfamide to gather lactic acid microballoons in vitro to accelerate to release the method. Method: Determines in the microballoons with the ultraviolet spectrophotometric method Ifosfamide content. This research uses the dynamic dialysis law to carry on vitro acceleration release experiment and the long-term release separately in the different temperature medium experiments. And carries on both relevant inspection. Finally: This research  Ifosfamide preparation gathers the lactic acid microballoons, in 37℃ lays aside in 145 hours to release achieves 94.90%, the microballoons accelerate the release in 42℃,47℃,55℃ and 58℃ under obviously to accelerate, release dynamics conforms to as well as the release equation and the Higuchi equation separately. The Ifosfamide preparation gathers the lactic acid microballoons in 55℃ the condition accelerates the release with to have the good relevance at 37℃ the long-term release. Conclusion: The Ifosfamide preparation gathers the lactic acid microballoons to have the very good slow release ability, uses in vitro the acceleration test the method to be possible to inspect the Ifosfamide to gather fast lactic acid microballoons in vitro to release the medicine ability.
 
 
key word: Ifosfamide gathers the lactic acid to accelerate to release    ultraviolet spectrophotometric method microballoons
 
 
 
目錄
第一章  文獻綜述 5
1.1緩釋制劑概念及特點 5
1.2緩控釋制劑釋藥類型 6
1.3 緩釋制劑體外藥物釋放度試驗 6
1.3.1  儀器裝置 6
1.3.2  溫度控制 6
1.3.3  釋放介質 6
1.3.4  釋放度取樣時間點 6
1.3.5 釋藥模型的擬合 7
1.4 異環磷酰胺 7
1.4.1異環磷酰胺性質及檢測方法 7
1.4.2 藥理毒理 8
1.4.3 藥代動力學 9
1.4.4 適應癥 9
1.4.5 不良反應 9
1.5微球的制備技術及特點 10
1.5.1概述 10
1.5.2制備方法多樣 10
1.5.3試驗采用的方法 12
1.5.4 微球載體的應用 12
1.5.5 微球技術的發展前景 15
1.6聚乳酸概述 16
1.7 微球釋藥測定方法 16
1.7.1膜擴散法 16
1.7.2動態透析法（本實驗采用的方法） 17
1.7.3取樣分離法 17
1.8 本課題研究的目的和意義 17
第二章   異環磷酰胺聚乳酸微球制備及體外釋放實驗 18
2.1試藥及儀器 18
2.2實驗樣品的制備 18
2.3異環磷酰胺標準曲線測定 19
2.3.1 測定波長的選擇 19
2.3.2  標準曲線的建立 20
2.4微球載藥量及包封率的測定 20
2.5異環磷酰胺聚乳酸微球的體外釋放 21
2.5.1 透析袋及透析膜的前處理 21
2.5.2 異環磷酰胺聚乳酸微球體外長期釋放 22
2.5.3 異環磷酰胺聚乳酸微球的加速釋放 22
2.5.4  加速釋放與長期釋放的相關性 22
第三章  實驗結果及分析 23
3.1異環磷酰胺在釋放介質中標準曲線 23
3.2異環磷酰胺聚乳酸微球載藥量、包封率的測定 24
3.3體外長期釋放結果及討論 24
3.4 體外加速釋放實驗結果和討論 25
3.5微球加速釋放與長期釋放的相關性 26
3.6討 論 28
第四章 結 論 29
參考文獻 30
致    謝 32