製備與評估具藥物釋放功能之牙科組織調理材｜國立臺灣科技大學博碩士論文系統

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研究生：	羅濟生 Chi-sheng Lo
論文名稱：	製備與評估具藥物釋放功能之牙科組織調理材 Preparation and In Vitro Evaluation of Drug Loaded Tissue Conditioners
指導教授：	高震宇 Chen-yu Kao
口試委員:	石淦生 Kan-sheng Shih 洪伯達 Po-da Hong
學位類別：	碩士 Master
系所名稱：	應用科技學院 - 醫學工程研究所 Graduate Institute of Biomedical Engineering
論文出版年：	2012
畢業學年度：	100
語文別：	中文
論文頁數：	128
中文關鍵詞：	組織調理材、抗發炎藥物、抗真菌藥物、義齒性口腔炎、白色念珠菌
外文關鍵詞：	tissue conditioner, anti-inflammatory drug, anti-fungal drug, denture-related stomatitis, candida albicans
相關次數：	點閱：309 下載：6
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上一筆

本研究目的在發展一個具多功能之組織調理材(tissue conditioner, TC)，使其具備快速釋放抗發炎藥物與長效性釋放抗真菌藥物之特點，以其為日益漸增的義齒性口腔炎患者提供一個新的治療策略，同時亦可減少患者往返醫院之頻率及龐大的醫療花費。其中抗發炎藥物Flurbiprofen (FB)可較迅速釋放以減緩因配戴義齒術後產生的發炎反應，而抗真菌藥物Itraconazole (ITZ)則以緩慢釋放方式達到長效性抑制口腔黏膜上的白色念珠菌之效果。初步結果顯示，此多功能組織調理材具有兩階段式藥物釋放之特性，在一周時間內從組織調理材中足以釋放96% 之FB，而ITZ則呈現長效緩慢釋放，釋放時間可持續兩周之久，此外，未來將結合in vitro細胞實驗及抑菌實驗的結果來尋求藥物間之最佳比例。

In this study, a drug incorporated tissue conditioner is developed for the delivery of Flurbiprofen (FB),an anti-inflammatory drug, and itraconazole (ITZ), an anti-fungal drug in the oral environment. This drug incorporated tissue conditioner provides two unique properties for treating denture-related stomatitis: (1) the tissue conditioner is used to reduce the damage of unfit denture by cushioning the hard denture base against the healing extraction sites. (2) the tissue conditioner is used as a depot for both anti-inflammatory drugs and anti-fungal drugs. In our study, the drug incorporated tissue conditioner showed a dual-phase release kinetics. The hydrophilic anti-inflammatory drug was rapidly released (96% of FB was released in a 7 day period) and the hydrophobic anti-fungal drug was released at a relatively slow pattern (30% of ITZ was released within 7 days, and 33% released within 14 days). We expected this drug incorporated tissue conditioner will create a synergistic effect of physical/chemical therapy for treating denture related stomatitis.

中文摘要------------------------------------------------------------------------Ⅰ
英文摘要------------------------------------------------------------------------Ⅱ
誌 謝--------------------------------------------------------------------------Ⅲ
圖表索引-----------------------------------------------------------------------Ⅶ
第一章緒論 ......................................................................................................................... 1
第二章 文獻回顧................................................................................................................. 4
1 高齡化社會............................................................................................................ 4
1.1 人口老化..................................................................................................... 4
1.2 高齡人口之健康問題................................................................................. 4
1.3 高齡人口之口腔問題................................................................................. 5
2 義齒性相關之口腔疾病........................................................................................ 5
2.1 義齒性口腔炎............................................................................................. 5
2.2 白色念珠菌................................................................................................. 7
2.3 念珠菌相關義齒性口腔炎......................................................................... 8
3 常見之念珠菌相關義齒性口腔炎治療方法........................................................ 8
3.1 物理性治療................................................................................................. 8
3.1.1組織調理材....................................................................................... 9
3.1.2 凝膠化作用機制............................................................................ 10
3.2化學性治療................................................................................................ 11
3.3物理性與化學性治療之結合.................................................................... 12
4藥物傳輸系統....................................................................................................... 13
4.1 高分子材料載送系統............................................................................... 13
4.2 非生物可降解性高分子........................................................................... 14
4.3 生物可降解性高分子............................................................................... 14
4.4 聚乳酸聚甘醇酸(PLGA).......................................................................... 15
4.5 PLGA微米顆粒.......................................................................................... 16
5 伊曲康唑(Itraconazole, ITZ)................................................................................ 19
6 氟比洛芬(Flurbiprofen, FB) ................................................................................ 20
7 巨噬細胞(Marcophage) ....................................................................................... 21
第三章 研究設計與方法................................................................................................... 22
1 研究設計.............................................................................................................. 22
1.1 實驗理論................................................................................................... 22
1.2 實驗設計................................................................................................... 22
1.3 實驗架構與流程....................................................................................... 25
V
2 藥物、細胞培養試劑、試驗菌株與設備.......................................................... 26
2.1 藥劑藥物................................................................................................... 26
2.2 細胞培養試劑........................................................................................... 27
2.3試驗菌株培養試劑.................................................................................... 27
2.4 實驗儀器設備........................................................................................... 27
3 微米顆粒製備方法.............................................................................................. 30
3.1 製備FB-PLGA MPs .................................................................................. 30
3.2 製備ITZ-PLGA MPs與ITZ-PEMA MPs .................................................. 31
4 組織調理材製備方法.......................................................................................... 32
4.1 製備blank TC ............................................................................................ 32
4.2 製備FB/TC及FB-PLGA MPs/TC............................................................. 32
4.3 製備ITZ/TC及ITZ-PEMA TC .................................................................. 32
4.4 製備FB/ITZ-PEMA TC............................................................................. 33
5 藥物劑型量測與分析.......................................................................................... 34
5.1 粒徑大小分析........................................................................................... 34
5.2 界面電位測量........................................................................................... 34
5.3 形態觀察................................................................................................... 35
5.4 Flurbiprofen、Itraconazole UV光檢測標準曲線..................................... 36
5.5 包覆效率評估........................................................................................... 36
5.6懸浮特性評估............................................................................................ 38
5.7 釋放效率評估........................................................................................... 38
6 PLGA 微米顆粒分子量分析............................................................................... 41
7 組織調理材物理性質分析.................................................................................. 41
7.1 測量凝膠化時間....................................................................................... 41
7.2 機械性質測試(最大抗張強度)............................................................... 43
8 In vitro Candida albicans真菌平台...................................................................... 44
8.1 真菌培養................................................................................................... 44
8.2 抑菌能力測試........................................................................................... 47
第四章 結果 ....................................................................................................................... 49
1 微米顆粒特性評估.............................................................................................. 49
1.1 構形評估、粒徑大小分析及界面電位測定........................................... 49
1.2 微米顆粒藥物包覆效率評估................................................................... 56
1.3 ITZ、ITZ-PLGA MPs懸浮特性評估........................................................ 58
2 Drug-PLGA MPs及drug/TC藥物制放系統釋放效能評估................................. 59
2.1 Drug-PLGA MPs藥物釋放效能評估........................................................ 59
2.2 Drug/TC之藥物分佈均勻度評估.............................................................. 62
2.3 Drug/TC 藥物釋放效能評估.................................................................... 64
3 組織調理材物理性質分析.................................................................................. 71
VI
3.1 凝膠化時間測定....................................................................................... 71
3.2 最大抗張強度測定................................................................................... 80
4抑菌能力評估....................................................................................................... 81
第五章 討論 ....................................................................................................................... 85
1 微米顆粒特性探討.............................................................................................. 85
2 ITZ及ITZ-PLGA MPs懸浮特性探討................................................................... 89
3 In vitro藥物釋放效率探討................................................................................... 89
4 組織調理材物理性質分析探討.......................................................................... 96
5 抑菌能力探討...................................................................................................... 97
第六章 結論 ..................................................................................................................... 100
未 來 展 望 ..................................................................................................................... 101
參 考 文 獻 ..................................................................................................................... 103
附 錄 ........................................................................................................................... 109

                                

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