pH－刺激應答低分子量醣凝膠因子的開發研究：具備不同樣式羧酸之β-(對-(N-組氨醯胺基)苯基) D-半乳糖苷的合成及其在體外藥物釋放的應用

Studies on the Development of the pH Responsive Low-Molecular-Weight Glycolipids-Based Gelators: Synthesis of β-(p-(N-histidylamino)phenyl) D-Galactopyranoside with various Carboxyl-Fragments and its Application of Drug Release in vitro

李昕遠(Shin-Yuan Lee)

指導教授 ： 蔡祐輔

中原大學/理學院/化學研究所/碩士(2013年)

https://doi.org/10.6840/cycu201300174

摘要

本論文旨在從事智慧型低分子量凝膠因子的開發研究，以應用在藥物傳遞系統。
在此，我們已開發出可逆型pH刺激應答低分子量醣凝膠因子GHL-1b，其組成分別為D-半乳糖、對-胺苯氧基、L-組氨酸以及十六烷酸。
凝膠測試中，凝膠因子GHL-1b可以在純水中形成穩定的凝膠型態；其最小凝膠濃度為 10 mg/mL，凝膠-溶液相轉變溫度(Tg)為67 oC。
pH刺激應答測試中，凝膠因子GHL-1b生成的水凝膠可以對酸鹼的改變產生應答，只在pH 6.0以及7.0時生成凝膠，並證實了其對pH刺激應答具備了可逆性。
體外藥物釋放測試中，以凝膠因子GHL-1b生成的水凝膠做為藥物的載體，外在環境為pH 7.4時，可以用18小時達到95 %的釋放率；而將外在環境pH值降低後(pH 4.0 or 5.0)，可以在測試16小時後將釋放率提高到99%以上。

關鍵字

低分子量醣凝膠因子 ； 體外藥物釋放

並列摘要

The primary concern of this study is to explore the research on the development of intelligent low-molecular-weight gelators and apply the research to drug delivery system.
Whereas a reversible pH-stimuli responsive low molecular weight gelators GHL-1b, which consists of D-glactose, p-aminophenoxy、L-histidine, and palmitic acid, has been thus developed.
In gelation test, the gelators GHL-1b developed a stable gel form in purified water, in which the minimal gelation concentration was 10 mg/mL and the gel-solution transition temperature (Tg) was at 67 oC.
In the pH-stimuli responsive test, the hydrogel generated from gelators GHL-1b was responsive to the change of pH value, which formed gel only at pH 6.0 and pH 7.0. This has hence identified the reversible feature when the gelator responds to the pH-stimuli.
In the test of drug delivery in vitro, the hydrogel generated from gelators GHL-1b was taken as the carrier, pH 7.4 as the external environment, it took 18 h to reach a release rate of 95 %. When the pH value in the external environment was lowered (pH 4.0 or 5.0), the release rate increased to more than 99% in 16 h of test.

並列關鍵字

Glycolipids-Based Gelators ； Drug Release in vitro

參考文獻

1.Weiss, R. G.; Terech, P. Chem. Rev. 1997, 97, 3133.

3.Blume, A. Angew. Chem. Int. Ed. 2004, 43, 245.

6.Sangeetha, N. M.; Maitra, U. Chem. Soc. Rev. 2005, 34, 821.

7.Molecular Gels: Materials with Self-Assembled Fibrillar Networks.; Weiss, R. G.; Terech, P.; Springer, Dordrecht, 2005.

8.Bhattacharya, S.; Ghanashyam Acharya, S. N. Chem. Mater. 1999, 11, 3504.