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研究生: 周啟君
Chi-chun Chou
論文名稱: 製備與評估適合作為抗菌組織調理材之聚甲基丙烯酸乙酯之微米顆粒
Preparation and Characterizations of Various poly (ethyl methacrylate) Microparticles Intended for a Novel Anti-fungal Tissue Conditioner
指導教授: 高震宇
Chen yu-Kao
口試委員: 蔡協致
none
李曉屏
none
朱兆秀
none
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: 2013
畢業學年度: 101
語文別: 中文
論文頁數: 70
中文關鍵詞: 組織調理材顆粒大小表面性質凝膠時間伊曲康唑抗菌性
外文關鍵詞: tissue conditioner, particle size, surface properties, gelation time, itraconazole, antibacterial
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臨床上組織調理材 (tissue conditioner) 常被用於治療義齒性口腔炎 (denture-related stomatitis) 之初期發炎反應。其中組織調理材粉劑 (powder)主要由聚甲基丙烯酸乙酯 poly(ethyl methacrylate) (PEMA) 及其共聚物之微粒 (microparticles) 所組成。然而粉劑微粒的顆粒大小、形態、表面性質及包裹藥物皆會影響組織調理材的機械性質與凝膠時間 (gelation time),進而影響其臨床應用性,並且能達到抑菌效果。
本研究目的為發展具有抑菌能力之組織調理材,藉由不同之製備條件與分析技術,製備所需之含抗真菌藥物伊曲康唑 itraconazole 之PEMA微粒。此微粒所製備的組織調理材則以高效能液相層析 (HPLC) 量測 itraconazole 之藥物釋放模式,及利用體外抑制白色念珠菌 (Candida albican) 抑菌實驗評估其抗菌效果。
初步研究顯示,粒徑介於23.98 - 19.10 μm 之 PEMA 含藥微粒(含3.5 %之 itraconazole) 之凝膠時間為 5.28 ± 1.68 min,與市售組織調理材最為接近。而此微粒所製備之含藥藥物之組織調理材可在 14 天內持續釋放 itraconazole,且白色念珠菌 (Candida albicans) (BCRC 21538) 之體外抑菌實驗也同時證實此含藥組織調理材可維持長效性抑菌能力達14 天。


Poly(ethyl methacrylate) (PEMA) and it’s copolymers are the main powder component of the tissue conditioner., a material used in the treatment of the denture-related stomatitis. Several things might affect the mechanical properties and gelation time of the tissue conditioners, including the particle size and surface properties of the PEMA particles, and adding of therapeutic agents to the tissue conditioners. In this study, various blank PEMA microparticles and intraconazole loaded PEMA microparticles were prepared by the emulsion technique. And the effect of particle size, surface morphology and properties of PEMA microparticles on its gelation time was investigated. In our study, the itraconazole-PEMA particles size range from 23.98 to 19.10 μm and are used to prepare the drug loaded tissue conditioners. And the gelation time of the drug loaded tissue conditioner is 5.28 ± 1.68 min which is the closest to the DENTSPLY Visco gel, a comericial tissue conditioner. More importantly, this drug loaded tissue conditioner could continuously release itraconazole and maintain its inhibitory effects of Candida albicans (BCRC 21538) for at least 14 days.

中文摘要 I Abstract II 致謝 III 圖目錄 VII 表目錄 X 第一章 緒論 1 第二章 文獻回顧 3 2.1 伊曲康唑 (Itraconazole, ITZ) 3 2.2 白色念珠菌 (Candida albicans) 3 2.3 組織調理材 (Tissue conditioner) 4 2.3.1組織調理材簡介 4 2.3.2 組織調理材之成分 4 2.4 流變原理與黏彈體性質 8 2.4.1 流變學 8 2.4.2 黏彈體 8 2.4.3 凝膠簡介 9 2.5 藥物傳輸系統 11 2.6 乳化法 (Emulsions) 12 2.6.1 界面活性劑 (surfactants) [25] 12 2.6.2 影響顆粒大小因素 15 第三章 實驗藥品、設備、原理及步驟 16 3.1 實驗藥品 16 3.2 實驗設備與器材 16 3.2.1 掃描式電子顯微鏡 (Scanning Electron Microscopy) 16 3.2.2 冷凍乾燥機 (Freeze Dry Systems) 16 3.2.3 迴轉式動態流變儀 (Modular compact rheometer) 17 3.2.4 傅立葉轉換紅外光譜儀 (Fourier transform infrared spectroscopy、FTIR) 鑑定 18 3.2.5 界達電位 (Zeta potential) 分析 19 3.2.6 高效能液相層析儀 (High performance liquid chromatography、HPLC) 19 3.2.7 實驗器材 20 3.3 微米顆粒製備 21 3.3.1 乳化法 (Emulsion) 21 3.3.2 製備PEMA (PVA) 微米顆粒 21 3.3.3 製備PEMA (SDS) 微米顆粒 22 3.3.4 製備PEMA-ITZ 微米顆粒 23 3.4 包覆效率評估 24 3.5 組織調理材製備 24 3.6 凝膠化時間測量 24 3.7 機械性質測試 (最大抗張強度) 25 3.8 組織調理材之釋放效率 26 3.9 In vitro Candida albicans 白色念珠菌測試 27 3.9.1 抑菌實驗儀器 27 3.9.2 白色念珠菌培養 27 3.9.3 抑菌能力測試 30 第四章 結果與討論 31 4.1 聚甲基丙烯酸乙酯 (PEMA) 之微米顆粒特性評估 31 4.1.1 PEMA 微米顆粒之表面形態及粒徑大小 31 4.1.2 PEMA 微米顆粒之表面性質 39 4.2伊曲康唑-聚甲基丙烯酸乙酯 (itraconazole-PEMA) 之微米顆粒特性評估 42 4.2.1 Itraconazole-PEMA 微米顆粒之表面形態及粒徑大小 42 4.2.2 Itraconazole-PEMA 微米顆粒之表面性質 44 4.2.3 Itraconazole-PEMA 微米顆粒之藥物包覆效率 45 4.3 組織調理材 (tissue conditioner) 物理性質分析 46 4.3.1 組織調理材之凝膠時間測定 46 4.3.2 組織調理材之機械性質分析 48 4.4 組織調理材 (tissue conditioner) 藥物釋放系統 52 4.4.1 DENTSPLY Visco gel mix itraconazole 組織調理材 55 4.4.2 PEMA Particle mix itraconazole 組織調理材 57 4.4.3 PEMA itraconazole particle (surfactant by PVA) 組織調理材 59 4.5 組織調理材 (tissue conditioner) 之抑菌能力測試 64 第五章 結論 66 未來展望 67 第六章 文獻參考 68

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