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    標題: 以人造油體為新的藥物傳遞系統之研究
    Investigation of artificial oil-bodies as a novel drug delivery system
    作者: 廖婉岑
    貢獻者: 嘉南藥理科技大學:藥物科技研究所
    陳俊仁
    關鍵字: 培氏斑
    油體鈣蛋白
    人造油體
    雌激素
    Peye
    Artificial oil bodies
    Caleosin
    Estradiol
    日期: 2011
    上傳時間: 2011-10-27 11:23:51 (UTC+8)
    摘要: 疏水性藥物以結晶性固體的劑型使用時,常有生體可用率低的問題,脂質處方為提高生體可用率的常用方法之一。人造油體是以人為方式由三酸甘油酯、油體鈣蛋白及磷脂質所組成的一種人工脂蛋白,可作為一種新的脂質處方。
    人造油體攜帶疏水性藥物並提高生體可用率的種種優點,仍有待發掘,例如與不同親脂性溶劑是否可形成不同的人造油體及是否可保護藥物免於酵素破壞的能力,都值得進一步的探討。雌激素為疏水性藥物,口服後在胃腸道時易受酵素破壞,經由肝臟未達全身血液循環時,會產生廣泛的首渡效應,故雌激素被選為模式藥物,期望以人造油體攜帶雌激素來提高生體可用率。
      本研究利用三酸甘油酯、二酸甘油酯、礦物油、Span 80或複合溶劑配方(由油、助溶劑、界面活性劑及輔界面活性劑組成)製備成不同油水型的人造油體,並觀察其穩定性。之後選定穩定性佳的篦麻油與複合溶劑配方形成的油水型人造油體攜帶雌激素,以胃管餵給SD大鼠,再以酵素免疫分析法來偵測雌激素含量,以評估人造油體作為脂溶性藥物傳遞系統的可能性。
      結果證實,不同性質的親脂性溶劑及複合溶劑配方能成功地與油體鈣蛋白及磷脂質形成油水型人造油體。而由篦麻油與複合溶劑配方形成的油水型人造油體來攜帶雌激素,均有明顯提高雌激素的生體可用率。顯示人造油體有保護雌激素在磷脂質及油體鈣蛋白內,免於酵素的破壞作用。其中複合溶劑配方形成的人造油體具有最佳的生體可用率,這可能因其形成較小粒徑的液滴,可經由腸道培氏斑的吸收,除了減少腸道酵素的破壞外,也可避免肝臟的首渡代謝。
    The bioavailability of a poorly water-soluble drug in a crystalline solid dosage form is usually poor. The lipid formulation is one of the common methods used to increase the bioavailability and the artificial oil body can be a new lipid formulation. The artificial oil body, an artificial lipoprotein, is composed with triglyceride, cleocin and phospholipid.
    The full advantages of the artificial oil body to carry a poorly water-soluble drug and increase its bioavailability remain to be explored, for example, its ability to form the artificial oil body with various oils or lipid formulations and protect the drug from enzyme degradation. Therefore, estradiol, a poorly water-soluble drug with extensive enzyme degradation and first pass effect, was chosen as a model drug to be encapsulated into the artificial oil body to increase the bioavailability.
    Mineral oil, diglyceride, various triglycerides, or lipid formulations containing a surfactant, cosurfactant or solubilizer were used to prepare artificial oil bodies and their stability was observed.
    Male Sprague-Dawley rats were gavaged by various artificial oil bodies with estradiol, and the level of serum estradiol was determined by EIA to investigate the potential of the artificial oil body as a drug delivery system.
    The results show that cleocin and phospholipid have the ability to form the artificial oil body with every kind of oil and lipid formulations. The artificial oil body can protect the estradiol from degradation and increase the bioavailability. The artificial oil body containing the specific lipid formulation has the best bioavailability, indicating it might be absorbed through the peyer’s patches because of its smaller size and avoid the hepatic first-pass metabolism.
    關聯: 校內校外均不公開,學年度:99,124頁
    Appears in Collections:[藥學系(所)] 博碩士論文

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