English  |  正體中文  |  简体中文  |  全文筆數/總筆數 : 45023/58199 (77%)
造訪人次 : 2077839      線上人數 : 191
RC Version 7.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜尋範圍 查詢小技巧：
  • 您可在西文檢索詞彙前後加上"雙引號"，以獲取較精準的檢索結果
  • 若欲以作者姓名搜尋，建議至進階搜尋限定作者欄位，可獲得較完整資料
    •  進階搜尋


    請使用永久網址來引用或連結此文件: http://libir.tmu.edu.tw/handle/987654321/54558


    題名: Adenosine analogue自發性微乳化給藥系統
    Self- microemulsifying drug delivery system for oral delivery of an adenosine analogue
    作者: 張齡云
    Chang, Ling-Yun
    關鍵詞: 腺苷;類似物;亨丁頓氏舞蹈症;自發性微乳化釋藥系統;Caco-2細胞;藥物動力學試驗;adenosine analogue;Huntington’s disease;SMEDDS;Caco-2 cells;pharmacokinetics
    日期: 2013-07-17
    上傳時間: 2018-11-22 11:56:03 (UTC+8)
    摘要: 目的：腺苷類似物來源中國藥材萃取出來，在動物模型已被證明能延緩亨丁頓氏舞蹈症的進展。然而，腺苷類似物之水溶解度差，且口服生體可用率低。為了提高腺苷類似物溶解度及口服生體可用率，進行SMEDDS（自發性微乳化釋藥系統）開發。

    方法：為了獲得合適的自發性微乳化釋藥系統，進行脂質、表面活性劑和輔助表面活性劑組成的三相圖構建。 在28天內利用粒徑儀 (N5 submicron particle size analyzer) 測量SMEDDS在水性介質中形成的液滴大小。利用高效能液相層析法（HPLC）測量溶液中腺苷類似物的溶液濃度之方法開發。此外，利用超高效液相色譜-串聯質譜(UPLC-MS/MS)測定在大鼠腺苷類似物血漿中的濃度也被開發和驗證。SMEDDS利用Caco-2細胞進行體外模擬測試腺苷類似物於小腸穿透率。最後口服給予腺苷類似物於雄性Sprague - Dawley大鼠，進行藥物動力學試驗。

    結果與結論：油相、界面活性劑、輔助介面活性劑所組成之自發性微乳化劑能顯著提高藥物的溶解度。在28天內在水介質中形成液滴的大小約200 nm左右。腺苷類似物自發性微乳化劑通過Caco-2細胞之穿透率較對照組溶液高。此外，自發性微乳化劑口服給予雄性Sprague - Dawley大鼠進行藥物動力學試驗，顯示出自發性微乳化劑對於水不溶性藥物腺苷類似物略提高其口服生體可用率。

    Purpose: An adenosine analogue isolated from a Chinese medicinal herb has been shown to delay the progression of Huntington’s disease in an animal model. However, the solubility of this adenosine analogue is poor with very low oral bioavailability. In order to improve the oral bioavailability of the adenosine analogue, a solubility enhancement system SMEDDS (Self Microemulsifying Drug Delivery System) was developed. SMEDDS is a strategy for the delivery of hydrophobic drugs that are insoluble in water in order to improve the oral bioavailability.

    Methods: In order to obtain a suitable SMEDDS, ternary phase diagrams composed of lipids, surfactants, and co-surfactants were constructed. SMEDDS in aqueous media formed droplet size from day 1 within 28 days by N5 submicron particle size analyzer. A simple and reproducible high performance liquid chromatography (HPLC) method for determining the concentration of the adenosine analogue in the solution was developed and validated. UPLC-MS/MS (Ultra Performance Liquid Chromatography-tandem mass spectrometry method for determination the concentration of the adenosine analogue in rat plasma was also developed and validated. The permeation of the adenosine analogue SMEDDS in vitro studies using Caco-2 cells was tested. Oral absorption of the adenosine analogue SMEDDS was evaluated the pharmacokinetics and bioavailability in male Sprague - Dawley rats.

    Results and conclusions: The SMEDDS composed of oil phase, surfactant phase and co-surfactant phase was able to significantly increase the drug solubility. The SMEDDS in aqueous media formed droplet size around 200 nm from day 1 within 28 days. The permeability of the adenosine analogue SMEDDS compound through Caco-2 cells was more than the permeability of the adenosine analogue solution. In male Sprague-Dawley rats, this study illustrated the potential use of SMEDDS to improve bioavailability of the water - insoluble drug by oral route.
    描述: 碩士
    指導教授-許明照
    共同指導教授-蔡翠敏
    委員-蔡義弘
    委員-林山陽
    委員-謝堅銘
    資料類型: thesis
    顯示於類別:[生技製藥產業碩士專班] 博碩士論文

    文件中的檔案:

    檔案 描述 大小格式瀏覽次數
    index.html0KbHTML275檢視/開啟


    檢視Licence

    在TMUIR中所有的資料項目都受到原著作權保護.

    TAIR相關文章

    著作權聲明 Copyright Notice

    • 本平台之數位內容為臺北醫學大學所收錄之機構典藏，包含體系內各式學術著作及學術產出。秉持開放取用的精神，提供使用者進行資料檢索、下載與取用，惟仍請適度、合理地於合法範圍內使用本平台之內容，以尊重著作權人之權益。商業上之利用，請先取得著作權人之授權。

      The digital content on this platform is part of the Taipei Medical University Institutional Repository, featuring various academic works and outputs from the institution. It offers free access to academic research and public education for non-commercial use. Please use the content appropriately and within legal boundaries to respect copyright owners' rights. For commercial use, please obtain prior authorization from the copyright owner.

    • 瀏覽或使用本平台，視同使用者已完全接受並瞭解聲明中所有規範、中華民國相關法規、一切國際網路規定及使用慣例，並不得為任何不法目的使用TMUIR。

      By utilising the platform, users are deemed to have fully accepted and understood all the regulations set out in the statement, relevant laws of the Republic of China, all international internet regulations, and usage conventions. Furthermore, users must not use TMUIR for any illegal purposes.

    • 本平台盡力防止侵害著作權人之權益。若發現本平台之數位內容有侵害著作權人權益情事者，煩請權利人通知本平台維護人員([email protected])，將立即採取移除該數位著作等補救措施。

      TMUIR is made to protect the interests of copyright owners. If you believe that any material on the website infringes copyright, please contact our staff([email protected]). We will remove the work from the repository.

    Back to Top
    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - 回饋