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    題名: 生物可分解PHA材料包覆四環素藥物之釋放研究
    其他題名: Studies on tetracycline drug release behavior of biodegradable poly(hydroxyalkanoate) material
    作者: 劉淑媛;Liu, Shu-yuan
    貢獻者: 淡江大學化學工程與材料工程學系碩士班
    董崇民;Don, Trong-ming
    關鍵詞: 聚羥基丁酯;聚羥基丁酯-羥基戊酯;四環素;藥物釋放;poly(hydroxybutyrate);poly(hydroxybutyrate-co-hydroxyvalerate);tetracycline;drug release
    日期: 2005
    上傳時間: 2010-01-11 05:45:03 (UTC+8)
    摘要: 以擠壓米糠/澱粉(1:8)作為碳源,從嗜鹽菌發酵生產出來的聚羥基烷酯經過FTIR及NMR分析後,確認為聚(羥基丁酯-羥基戊酯)共聚合體(Poly(3-hydroxybutyrate-co-3-hydroxyvalerate),PHBV),其中羥基戊酯(HV)單元佔了9.2%。利用刮膜的方式將嗜鹽菌生產的PHBV共聚合體(HmPHBV)及從化學藥品公司提供之聚羥基丁酯單聚合體(PHB)及聚(羥基丁酯-羥基戊酯)共聚合體(HV單元佔8%,PHBV8)製作不同四環素含藥量的薄膜,然後在磷酸鹽緩衝溶液(PBS)中進行藥物釋放實驗。藉由ATR-FTIR、EDS及SEM來觀察四環素在薄膜的分佈情形,結果發現薄膜上表面及截面具有比下表面多的四環素。TGA分析中包覆四環素的PHB及PHBV8薄膜的起始裂解溫度(Tonset)比純PHB及PHBV8的Tonset增加了約20oC,而嗜鹽菌生產的HmPHBV則約提高了10oC。包覆四環素藥物的PHB、PHBV8及HmPHBV薄膜在磷酸鹽緩衝溶液(PBS)進行釋放,所有的薄膜在20小時之內達到最大藥物累積釋放量。在藥物釋放部分中,包覆四環素的PHB、PHBV8及HmPHBV薄膜皆呈現二階段釋放模式。另外利用單乳化製作包覆四環素的PHB微粒,水相中分別使用了界面活性劑Tween80及水溶性高分子(WCS),其作用皆為幫助油相(氯仿)形成分散的油滴。使用Tween80製造PHB微粒的優點為微粒中四環素的包覆率及裝載量皆比使用WCS所製造的PHB微粒高,而使用WCS所製造的PHB微粒的優點為微粒的產率較高,若混合使用Tween80及WCS製造PHB微粒的四環素包覆率及裝載量與單獨使用WCS一樣低。原因在於四環素雖然溶於氯仿,卻大部分會擴散至水中,因此在單乳化的實驗中,PHB微粒包覆四環素的產率、包覆率及裝載量皆很低。
    In this study, poly(hydroxyalkanoate) was produced by Haloferax Mediterranei. The poly(hydroxyalkanoate) was analyized by FTIR and NMR. Poly(hydroxybutyrate-co-hydroxyvalerate), PHBV (HmPHBV), confirmed the structure of the poly(hydroxyalkanoate). The HV content of the HmPHBV was only 9.2 mol%. Poly(hydroxybutyrate), PHB, and poly(hydroxybutyrate-co-hydroxyvalerate), PHBV (PHBV8), were provided by Aldrich, and the HV content of PHBV8 was 8 mol%. PHB, PHBV8 and HmPHBV membranes which were contained tetracycline were made by scraping method. The distributions of tetracycline in the membranes were investigated by FTIR, SEM and EDS. Tetracycline existed on the top and in the cross-section of the membranes was more then it existed on the bottom of the membranes. In the TGA analysis, the maxium degradation temperature of PHB and PHBV8 membranes containg tetracycline were increased 20oC then pure membranes. And the temperature of HmPHBV containg tetracycline membranes was increased about 10oC then pure HmPHBV membrane. The drug release experiment was monitored in a buffer solution (PBS) at 37oC. Abount 20 hours, drug release amounts of all membranes were almost the largest. Releasing models of PHB and PHBV8 membranes were first-order release model, and HmPHBV membranes was t1/2 release model.Single emulsion (O/W) was used to made PHB microparticles containing tetracycline. Surfactant (Tween80) and carboxymethyl chitosan (WCS) were prevented from oil drops aggregating in water phase. Structures of PHB microparticles were observed using SEM. The adventage of using Tween80 as emulsifier was that the encapsulation efficiency and loading of PHB microparticles were higher then that of the PHB micropartilces being made by using WCS as emulsifier. But the yield of PHB microparticles using WCS as emulsifier was higher that using Tween80. If Tween80 and WCS were togegher using as emulsifier, problems of the lower encapsulation efficiency and loading of PHB microparticles still could not be solved.
    顯示於類別:[化學工程與材料工程學系暨研究所] 學位論文

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