Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/3151
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dc.contributor林松池zh_TW
dc.contributorSung-Chyr Linen_US
dc.contributor.author藍裕臻zh_TW
dc.contributor.authorLan, Yu-Chenen_US
dc.contributor.other化學工程學系所zh_TW
dc.date2013en_US
dc.date.accessioned2014-06-06T05:31:17Z-
dc.date.available2014-06-06T05:31:17Z-
dc.identifierU0005-2308201314052900en_US
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dc.identifier.urihttp://hdl.handle.net/11455/3151-
dc.description.abstract本研究利用具生物降解性高分子共聚乳酸-甘醇酸(poly(lactide-co-glycolide);PLGA)包覆新型抗精神疾病藥物奧氮平(olanzapine),並製備出達到14~30天長效型植入式的肌肉注射劑型微粒。研究中PLGA分別利用水溶性高分子聚乙二醇(mPEG)及蔗糖(sucrose)進行化學改質,賦予PLGA具有雙性性質,進而改善由PLGA所製備之藥物微粒的非連續性釋放藥物行為。PLGA的化學改質透過N-hydroxysuccinimide (NHS)以DCC作為coupling agent使PLGA末端的羧酸官能基與mPEG或蔗糖形成共價鍵結,其化學改質率約70~85%,產率為80%。成功利用一次乳化法製備出表面光滑且結構紮實之PLGA/olanzapine微粒,粒徑約30 μm、藥物包覆效率約為72%。結果顯示,30 wt% PLGA (50/50, Mw 10000)與70 wt% PLGA (85/15, Mw 73000)摻混所製備之PLGA/olanzapine微粒,體外釋放以每日3~4 %速率持續釋放olanzapine長達一個月。zh_TW
dc.description.abstractIn this study, to develop intramuscularly injectable microparticles from biodegradable poly(lactide-co-glycolide) (PLGA) and chemically modified PLGA-PEG and PLGA-sucrose for long-term sustained release of olanzapine. PLGA was respectively conjugated with PEG and sucrose in order to enhance the amphiphilic property of the copolymer and, therefore, improve the discontinuous drug release profile that was usually observed from PLGA matrices. The conjugation of mPEG and sucrose with PLGA was achieved in this project via the activation of the end carboxyl group of PLGA with N-hydroxysuccinimide using DCC as the coupling agent, followed by aminolysis with mPEG-NH2 and trans-esterification with sucrose. The PLGA/olanzapine microparticles prepared by employing the oil-in-water emulsion/solvent evaporation technique have shown an average size of ca. 30 μm, an encapsulation efficiency of ca. 72%, and smooth particle surface and compact interior sturacture. The PLGA/olanzapine microspheres consisting of 30 wt% PLGA (50/50) and 70 wt% PLGA (85/15), exhibit a long-term sustained release behavior of olanzapine for up to 1 month in vitro.en_US
dc.description.tableofcontents誌謝................................................II 中文摘要............................................III Abstract...........................................IV 目錄.................................................V 表目錄.............................................VIII 圖目錄................................................X 第一章 緒論............................................1 第二章 文獻回顧.........................................3 2.1 藥物模型-奧氮平olanzapine.............................3 2.2 生物降解性高分子......................................3 2.2.1聚酯類高分子........................................3 2.3. 生物相容性材料.......................................5 2.3.1 聚乙二醇poly(ethylene glycol) (PEG)................5 2.3.2. 蔗糖(sucrose)....................................6 2.3.3. Vitamin E TPGS..................................6 第三章 實驗部份.........................................8 3.1.實驗藥品.............................................8 3.2. 實驗儀器與設備.......................................10 3.3. 高分子合成..........................................11 3.3.1. DMF除水..........................................11 3.3.2. mPEG-NH2之合成....................................11 3.3.2.1. mPEG-Cl的合成...................................11 3.3.2.2. mPEG-N3的合成...................................11 3.3.2.3. mPEG-NH2的合成..................................12 3.3.2.4 mPEG-NH2轉化率之測定..............................12 3.3.3 PLGA末端COOH官能基之活化.............................13 3.3.4. PLGA-mPEG2000之合成...............................13 3.3.5. PLGA-mPEG350 及PLGA-mPEG750之合成.................14 3.3.6. PLGA-sucrose之合成 ................................14 3.4. PLGA改質高分子之鑑定分析...............................15 3.4.1. PLGA-mPEG之改質率分析...............................15 3.4.2. PLGA-sucrose之改質率分析............................15 3.4.3. PLGA改質高分子純度分析...............................16 3.5. PLGA/olanzapine 微粒配方製備..........................17 3.5.1. 純PLGA/olanzapine微粒製備..........................17 3.5.1.1. 機械攪拌乳化-磁石攪拌溶劑揮發法I.....................17 3.5.1.2. 機械攪拌乳化-溶劑揮發法II-低轉速....................17 3.5.1.3. 機械攪拌乳化-溶劑揮發法III-高轉速....................17 3.5.1.4. 均質機乳化-磁石攪拌溶劑揮發法IV......................18 3.5.2. PLGA/改質PLGA高分子/olanzapine微粒製備...............18 3.5.3. PLGA/TPGS/olanzapine微粒製備.......................18 3.6 PLGA/olanzapine微粒性質分析...........................19 3.6.1. PLGA/olanzapine微粒之尺寸大小量測...................19 3.6.2. PLGA/olanzapine微粒之表面型態分析...................19 3.6.3. PLGA/olanzapine 微粒中之藥物包覆量與包覆效率之測定.....19 3.7. PLGA/olanzapine 微粒體外藥物釋放實驗 (in vitro release) ........................................................20 第四章 結果與討論.........................................21 4.1.化學改質PLGA雙性高分子之性質鑑定..........................21 4.1.1. PLGA-mPEG系列改質高分子鑑定結果.......................21 4.1.2. PLGA-Sucrose系列改質高分子鑑定結果....................24 4.2. PLGA/olanzapine微粒製備參數探討........................26 4.3. PLGA/olanzapine微粒製備-方法一.........................26 4.3.1. PLGA (50/50)/olanzapine微粒-製備條件之探討............26 4.3.1.1. 不同油/水體積比....................................27 4.3.1.2. 外部水相的PVA濃度..................................27 4.3.1.3. 不同PLGA於DCM中的濃度..............................27 4.3.1.4. 不同olanzapine/PLGA重量比 (D/P值)..................28 4.3.2. PLGA(50/50)/PLGA-mPEG/olanzapine微粒製備............35 4.3.3. PLGA/PLGA-sucrose/olanzapine微粒製備................40 4.4. PLGA/olanzapine微粒製備-方法二.........................44 4.4.1. PLGA(50/50)/olanzapine微粒製備......................44 4.4.2. PLGA(50/50)/PLGA(50/50)–mPEG/olanzapine微粒........47 4.5. PLGA/olanzapine微粒製備-方法三.........................50 4.5.1. 機械攪拌乳化/溶劑揮發法(高轉速)-參數調整I................50 4.5.2. PLGA/olanzapine微粒-不同LA/GA比之PLGA................54 4.5.3. 機械攪拌乳化/溶劑揮發法(高轉速)-參數調整II...............58 4.6. PLGA/TPGS/olanzapine微粒製備 .........................61 4.6.1. PLGA(50/50)/TPGS/olanzapine微粒....................61 4.6.1.1. 微粒製備參數調整...................................61 4.6.1.2. TPGS添加量的影響..................................64 4.6.2. PLGA(75/25)/TPGS/olanzapine微粒製備................68 4.6.3. PLGA(85/15)/TPGS/olanzapine微粒....................71 4.7. PLGA(75/25)/PLGA(75/25)改質高分子/olanzapine微粒.......75 4.8. PLGA(85/15)/PLGA(50/50)/olanzapine微粒...............81 4.9. PLGA/olanzapine微粒-均質機乳化法.......................86 第五章 結論.............................................91 第六章 參考文獻..........................................92zh_TW
dc.language.isozh_TWen_US
dc.publisher化學工程學系所zh_TW
dc.relation.urihttp://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-2308201314052900en_US
dc.subject共聚乳酸-甘醇酸zh_TW
dc.subjectpoly(lactide-co-glycolide) (PLGA)en_US
dc.subject奧氮平zh_TW
dc.subject聚乙二醇zh_TW
dc.subject蔗糖zh_TW
dc.subject長效釋放zh_TW
dc.subjectmonomethoxy poly(ethylene glycol) (mPEG)en_US
dc.subjectsucroseen_US
dc.subjectolanzapineen_US
dc.subjectlong-term sustained releaseen_US
dc.titlePLGA的化學改質與包覆抗精神疾病藥物olanzapine之製備及功效評估zh_TW
dc.titleChemical Modification of Ploy(Lactic Acid-co-Glycolic Acid) and the Applications for Long-Term Drug Release of Olanzapine-Encapusulated Microspheresen_US
dc.typeThesis and Dissertationzh_TW
item.cerifentitytypePublications-
item.grantfulltextnone-
item.languageiso639-1zh_TW-
item.fulltextno fulltext-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypeThesis and Dissertation-
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