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研究生： 張芳瑜
Fang-Yu Chang
論文名稱： 製備與評估包覆氯己定微米顆粒應用於口腔藥物制放之可行性
Preparation and Evaluation of the Chlorhexidine Loaded Microparticles for Oral Drug Delivery
指導教授： 高震宇
Chen-Yu Kao
口試委員: 蔡協致
Hsieh-Chih Tsai
黃仁勇
Ren-Yeong Huang
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： 2014
畢業學年度： 102
語文別： 中文
論文頁數： 96
中文關鍵詞： 口腔藥物制放 、氯己定 、組織調理材 、白色念珠菌 、齒齦視紫單胞菌
外文關鍵詞： tissue conditioner, Chlorhexidine, oral drug delivery, Candida albicans, Porphyromonas gingivalis
相關次數： 點閱：197  下載：6 
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  •  上一筆

    • Chlorhexidine為牙科常見用於控制口腔衛生之抗菌藥物，目前已知Chlorhexidine可有效降低革蘭氏陽性菌和革蘭氏陰性菌的繁殖，但其對念珠菌的抑制效果仍不明確。本研究希望能結合藥物制放系統之概念，利用單一乳化法與多重乳化法，分別包覆Chlorhexidine及Chlorhexidine gluconate兩種不同親疏水性之藥物，製備與評估適合應用於組織調理材粉劑之高分子藥物微粒，發展一可長效釋放抗菌藥物之口腔藥物制放系統，了解藥物在藥物制放系統中的釋放特性，並探討Chlorhexidine及Chlorhexidine gluconate對白色念珠菌以及齒齦視紫單胞菌抑菌能力之效果，探討其同時治療義齒性口腔炎與抑制口腔常見厭氧菌之可行性。
    研究結果顯示，含Chlorhexidine之高分子微粒其粒徑為17.60 ± 1.59 μm，以此微粒所製備之含藥組織調理材呈現長效緩慢釋放，可持續釋放兩周之久，而由抑菌實驗得知，在未釋放前之含藥組織調理材可同時抑制白色念珠菌及齒齦視紫單胞菌的生長，但其經釋放後只對齒齦視紫單胞菌有抑菌效果，可維持長效抑菌能力達十四天。

    Chlorhexidine has been used in control the hygiene in oral cavity, however, the inhibitory effect of Chlorhexidine on Candida albicans is not clear. In this study, we developed a novel drug delivery system of Chlorhexidine, and evaluate its anti-fungal and anti-bacterial properties. The microparticles containing Chlorhexidine（CHX）or Chlorhexidine gluconate（CHG）were prepared and analyzed. We used both single emulsion method and double emulsion method to prepare CHX-loaded and CHG-loaded microparticles. These microparticles were used to prepare the drug loaded tissue conditioner. And the growth of Candida albicans and Porphyromonas gingivalis were used to evaluate the anti-fungal and anti-bacterial properties of drug loaded tissue conditioner. The preliminary data showed that the sizes of CHX-loaded microparticles were 17.60 ± 1.59 μm, and the encapsulation efficiency were 20.88 ± 1.76 %, respectively. The anti-bacterial drug loaded tissue conditioner was released in a relatively slow pattern（20% of CHX was released within 14 days）. Moreover, it could inhibit both the growth of Candida albicans and Porphyromonas gingivalis before drug release, but only maintain its effect for Porphyromonas gingivalis at least 14 days.

    中文摘要 I 英文摘要 II 誌謝 III 目錄 IV 縮寫表 VIII 圖表索引 X 第一章 緒論 1 第二章 文獻回顧 4 2.1. 口腔微生物叢（Oral microflora） 4 2.1.1. 微生物叢在人體的分布 4 2.1.2. 口腔微生物叢在各年齡的變化 6 2.1.3. 口腔微生物叢與疾病的關係 7 2.2. 高齡化社會 8 2.2.1. 人口老化 8 2.2.2. 老年人口之健康問題 9 2.2.3. 老年人口之口腔問題 9 2.3. 牙周疾病 10 2.3.1. 齒齦視紫單胞菌（Porphyromonas gingivalis） 10 2.3.2. 牙周病的發生 11 2.4. 念珠菌相關義齒性口腔炎 13 2.4.1. 白色念珠菌（Candida albicans） 13 2.4.2. 念珠菌相關義齒性口腔炎的發生 14 2.4.3. 念珠菌相關義齒性口腔炎之治療方法 15 2.5. 組織調理材 16 2.5.1. 組織調理材之成分 17 2.5.2. 凝膠化作用機制 17 2.5.3. 含藥之組織調理材 18 2.6. 藥物傳遞系統 18 2.6.1. 藥物傳遞原理 19 2.6.2. 口腔藥物傳遞系統 19 2.6.3. 高分子之藥物載體 21 2.7. 氯己定（Chlorhexidine） 23 第三章 實驗材料與方法 25 3.1. 研究設計 25 3.1.1. 實驗理論 25 3.1.2. 實驗設計 25 3.1.3. 實驗架構與流程 27 3.2. 藥物藥劑、試驗菌株與培養試劑及設備 28 3.2.1. 藥物藥劑 28 3.2.2. 試驗菌株與培養試劑 29 3.2.3. 實驗儀器設備 29 3.3. 微米顆粒製備 31 3.3.1. 製備CHX-PEMA MPs 31 3.3.2. 製備CHG-PEMA MPs 32 3.4. 組織調理材製備 32 3.4.1. 製備Blank TC 32 3.4.2. 製備Free CHX/TC 33 3.4.3. 製備Free CHG/TC 33 3.4.4. 製備CHX-PEMA TC 33 3.5. 藥物劑型量測與分析 34 3.5.1. 包覆效率評估 34 3.5.2. 表面形態觀察 35 3.5.3. 表面電位（zeta potential）測量 36 3.5.4. 釋放效率評估 36 3.6. 測量凝膠化時間 37 3.7. 組織調理材之抑菌能力評估 38 3.7.1. 菌株培養 38 3.7.2. 菌數計算（生菌數法, CFU/mL） 41 3.7.3. 有效抑菌之菌液濃度檢測 42 3.7.4. 抑菌環測試 43 3.8. 統計學分析（Statistical analysis） 43 第四章 結果 44 4.1. 微米顆粒特性評估 44 4.1.1. 微米顆粒之表面型態與粒徑大小分析 44 4.1.2. 藥物包覆效率評估 51 4.1.3. 表面電位（zeta potential）測定 55 4.2. 組織調理材之藥物制放系統效能評估 56 4.2.1. 藥物均勻度評估 56 4.2.2. 組織調理材藥物釋放效能評估 58 4.3. 組織調理材之抑菌能力評估 64 4.3.1. 有效抑菌之菌液濃度檢測 64 4.3.2. 抑菌環測試 66 4.4. 凝膠化時間測試 77 第五章 討論 80 5.1. 微米顆粒特性與包覆效率探討 80 5.2. 藥物釋放效率探討 82 5.3. 抑菌能力探討 83 5.3.1. C. albicans之抑菌能力探討 83 5.3.2. P. gingivalis之抑菌能力探討 83 5.4. 凝膠化時間探討 84 第六章 結論 87 未來展望 88 參考文獻 89 附錄 95

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