本文以改良式滴入法應用各種製備條件製備符合治療牙周病所需之幾丁聚醣-四環素微小球，並以二次乳化法將聚乳酸-甘醇酸共聚物（PLGA 50：50），及褐藻酸（Alginate）乳化具有幾丁聚醣-四環素溶液之微小球，並探討微小球的特性。
結果顯示以乾式法製備，經戊二醛（濃度2.5%）交聯六十分鐘的條件為最佳，其包覆效率為67.4%±5.6%（n=3），釋放時間可達11天，仍能達到抑菌的最低有效濃度（1~2μg/ml），且無突釋（initial burst）的現象。經細菌抑菌測定試驗，確定微小球所釋出的四環素仍保有抑菌活性。
以濕式法製備之微小球，四環素於製備過程中即大量損失，包覆效率幾乎不超過50%，釋放結果也不理想，經改變不同條件如：戊二醛交聯時間增加及濃度提昇，也無法達到要求。
以二次乳化製備之聚乳酸-甘醇酸共聚物-幾丁聚醣微小球發現，外部水相中加入0.05%褐藻酸可有效的提昇包覆效率達19.6%±4.3%，且釋放時間達至9天。

In this study, we fabricated tetracycline (Tc) loaded chitosan microspheres by using different preparing process, conditions and methods for therapy of periodontal disease. Modified orifice and double emulsion method have been applied to fabricate chitosan microspheres. The results showed that pre-dried microspheres prior to cross-linking by 2.5% glutaraldehyde at 60 minutes would be the best conditions for microspheres, fabricated by modified orifice method. The encapsulation efficiency were 67.4%±5.6% (n=3) and could maintain 11 days of in-vitro release characteristics test. The efficacy of encapsulated Tc has been confirmed by bacteriostatic tests.
Double emulsion (w/o/w) technique can also fabricate Tc loaded alginate / poly(d,l-lactide-co-glycolide) / chitosan multilayered microspheres. They could also release Tc (in vitro test ) up to 9 days although the encapsulation efficiency was only 19.6%±4.3% (n=3).
Through the study, we found the best conditions for fabricating Tc loaded microspheres, which can be applied for therapy of periodontal disease, by modified orifice and double emulsion method.

目 錄
中文摘要………………………………………………………...………..I
英文文摘要……………………..……………………………...………..II
謝誌……………………..………………………………………………III
目錄…………………………………………………………………..…IV
圖索引………………………………………………………...………VIII
表索引……………………………………………………….…………XI
第一章 緒論
§1-1 前言……………………………………………………………...1
§1-2 微膠囊…………………………………………………………...2
§1-2-1 微膠囊簡介…………………………………………….2
§1-2-2 微膠囊的應用特性…………………………………….4
§1-2-3 微膠囊的製備技術…………………………………….5
§1-2-4 微膠囊內藥物釋放模式…………………………….…8
§1-3 幾丁聚醣………………………………………….…………….11
§1-3-1 幾丁聚醣簡介…………………………………….…...11
§1-3-2 幾丁質之構造…………………………………….…...12
§1-3-3 幾丁聚醣之應用………………………………….…...15


§1-4 牙周病與四環素……………………………………………….19
§1-4-1 牙周病簡介…………………………………………...19
§1-4-2 四環素的介紹…………………………………….…...21
§1-5聚乳酸與聚甘醇酸共聚物…………………………….………..25
§1-6 研究目的…………………………………………………….….27
第二章 實驗材料與方法
§2-1 實驗設備………………………………………….…….……….28
§2-2 實驗藥品…………………………………………………..…….30
§2-3 實驗方法……………………………………………………..….31
§2-3-1 溶液配製……………………...…………………..……31
§2-3-2 以相分離法製備濕式幾丁聚醣-四環素微小球…..….33
§2-3-3 以相分離法製備乾式幾丁聚醣-四環素微小球…..….35
§2-3-4 四環素包覆效率之計算方式……………………..…...37
§2-3-5 幾丁聚醣-四環素微小球生物體外釋放實驗……..….37
§2-3-6 PLGA乳化幾丁聚醣—四環素溶液之微小球製備…....38
§2-3-7 幾丁聚醣—四環素之乳化微小球包覆效率測定……...39
§2-3-8 幾丁聚醣-四環素之乳化微小球生物體外釋放實驗...39
§2-3-9 微小球粒徑測量…………………………………….....39
§2-3-10 掃描式電子顯微鏡之觀察………………………..….40
§2-3-11 幾丁聚醣膨潤度的測定……………………….…….40
第三章 結果與討論………………………………………...………41
§3-1 幾丁聚醣-四環素微小球結構形態分析……….…….………...42
§3-1-1 戊二醛交聯時間及濃度對微小球結構形態之影響.…43
§3-1-2 戊二醛對乾式微小球交聯後的表面形態分析…….....48
§3-2幾丁聚醣-四環素微小球包覆效率之研究………………..…….53
§3-2-1交聯時間對包覆效率之影響………………………..…53
§3-2-2 交聯劑濃度對包覆效率之影響…………………..…...55
§3-2-3 微小球粒徑大小對包覆效率之影響……………….....58
§3-2-4 交聯程序對微小球包覆效率之影響………..………...60
§3-3 幾丁聚醣-四環素微小球生物體外釋放之研究………..……...63
§3-3-1 交聯劑反應時間對生物體外釋放之影響………….....64
§3-3-2 交聯劑濃度對生物體外釋放之影響…………..……...66
§3-3-3 微小球粒徑對生物體外釋放之影響…………..……...69
§3-3-4 交聯程序對生物體外釋放之影響…………..………...71
§3-3-5 預先乾燥程序中交聯時間與交聯劑濃度對生物體外釋放之影響……………………….…………….……..….74
§3-4 幾丁聚醣-四環素微小球釋放行為之分析………………..…...78
§3-4-1 以model解釋釋放行為………………..………………78
§3-4-2 每日釋出四環素含量計算……………………..……...80
§3-5 四環素抑菌活性測試……………..…………………………….83
§3-6 以PLGA乳化幾丁聚醣-四環素溶液之微小球表面形態分析..85
§3-7 PLGA乳化微小球粒徑分析…………………………..………...86
§3-8 PLGA乳化幾丁聚醣-四環素之微小球包覆效率的分析……...90
§3-9 PLGA乳化幾丁聚醣-四環素之微小球生物體外釋放分析…...92
§3-10表面官能基分析-FTIR………………………..………………..94
第四章 結論………………………………………………….………96
第五章 未來展望……………………….………………….………..98
參考文獻………………………………………………….…….……..99

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