Tiopronin之牛血清白蛋白微粒製備及其特性探討

Preparation and Characterization of Tiopronin Bovine Serum Albumin Microsphere

蔣筱凡(Hsiao-Fan Jiang)

指導教授 ： 詹道明

高雄醫學大學/藥學院/藥學研究所/碩士(2012年)

摘要

Tiopronin (N-(2-Mercaptopropionyl)-glycine) 為一具有保護肝臟、代謝系統的解毒作用之mercaptopropionic acid衍生物。除此之外，Tiopronin亦具有增加重金屬排泄、降低cystine的濃度以及預防白內障之作用。
本研究以牛血清白蛋白為基礎，運用乳化-熱穩定技術 (emulsification–heat stabilization technique) 形成包覆Tiopronin之白蛋白微球 (microsphere)，再以不同比例聚合物和藥物所製備之微球來探討其性質的相互關係。利用高效能液相層析儀檢測微球所包覆的藥物含量；使用光學顯微鏡觀察微球的粒徑分佈及表面性質，並測試其在不同條件下之溶出行為，以及體內試驗中肝臟修復程度之觀察。實驗結果顯示所製備的微球具有光滑的表面，而提高聚合物比例可提高藥物包覆率；同時，在體外釋出試驗發現，Tiopronin之初始釋出速率隨聚合物之比例之增加而下降，但改變聚合物比例與微球粒徑大小並無相對關係；此外，體內試驗結果顯示，Tiopronin白蛋白微球並未出現靶向 (drug target) 效果；另一方面，於試驗開始後第六週，出現明顯之藥理效果，其效果與Silymarin相似。

關鍵字

tiopronin ； 牛血清白蛋白 ； 微球

並列摘要

Tiopronin (N-(2-Mercaptopropionyl)-glycine) is a derivative of mercaptopropionic acid known to protect the liver, the detoxification of metabolic system. Also, it can enhance the excretion of heavy metals, lower cysteine concentrations and prevent cataract.
In this study, we utilized bovine serum albumin as base to incorporate Tiopronin by using emulsification–heat stabilization technique. The prepared albumin microsphere, with different proportions of the polymers and drugs, were used to explore the relationship between composition of microsphere and properties. Tiopronin loading in microsphere was measured by using high-performance liquid chromatography (HPLC) method. This study employed an optical microscope to observe the particle size distribution and surface properties of microsphere. Furthermore, this study tested the releasing behaviors in different conditions and the degree of liver repair observed in-vivo test. The result shown the formulated microsphere has smooth surface, and the drug loading efficiency is enhanced by increasing the ratio of polymer in formulation. Also, in-vitro test showing increases of the initial releasing rate of Tiopronin by reducing the ratio of polymer in the formulation, but the relative relationship between polymer ratio and particle size of microspheres was not observed. Additionally, the in-vivo test result of Tiopronin albumin microparticles showed no drug target effect. The sixth week after the treatment, it's shown apparent pharmacological effect, and the effect is similar to Silymarin.

並列關鍵字

tiopronin ； bovine serum albumin ； microsphere

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