交聯硫酸化軟骨素在藥物釋放上的探討

Cross-Linking Reaction of Chondroitin Sulfate ：Potential for Drug Delivery

姜雅齡(Ya-Ling Chiang)

指導教授 ： 王麗芳

高雄醫學大學/生命科學院/化學系/碩士(2003年)

摘要

因多醣體能在大腸被酵素分解，因此能應用在口服持續釋放上。硫酸化軟骨素便為其中之一，本實驗室先前的計劃中多探討如何解決其易溶的缺點。本篇實驗中，我們利用EX-810來交聯CS（CS-EX），來降低它的水溶性質。在探討EX-810與CS交聯反應時，我們改變了以下幾個變數：加入Lysine參與交聯反應（CS-EX-Ly）；利用NaCl改變反應溶液之離子強度（CS-Na）；將CS與CaCl2形成離子錯化合物（CS-Ca or CS-Ca-EX）。更以Diclofenac sodium（DS）作為標準藥物，來探討修飾後的CS對藥物制放的行為。由GPC的觀察EX-810與CS反應後，其分子量分布有向較大分子量偏移的現象；而IR的觀察發現，Epoxide groups的吸收，1251cm-1位置的peak有變小的現象，可知Epoxide groups可能有產生反應而減少。在黏度方面以反應在0.05 M NaCl時黏度（hInh）為0.35；UV的觀察可知在0.1 M CaCl2時滴入之CS幾乎完全與鈣離子形成離子錯合物。溶離測試上可看到不管在PBS buffer或是模擬胃液中CS-Ca-EX-DS-Dy之藥物釋放最慢。在探討enzyme對修飾後CS切割的能力，發現CS-Ca與CS-Ca-EX似可被enzyme分解，而分解速率又以CS-Ca-EX較快。

關鍵字

硫酸化軟骨素 ； 藥物釋放 ； 交聯

並列摘要

Polysaccharides, Chondroitin Sulfate(CS) is one of them, can be used in oral administration, because they are degraded by enzymes in the colon. In previous studies, we have made a lot of efforts in our laboratory to reduce the high water solubility of CS. In this study, we used EX-810 to cross-link CS(CS-EX)and diclofenac sodium as a model drug to improve gastrointestinal side effects. The more parameters were used to study the crosslinking reaction including adding Lysine during cross-linking reactions(CS-EX-Ly); changing solvent ionic strength by NaCl(CS-Na); forming ionic complexes with CaCl2(CS-Ca or CS-Ca-EX). The chemical reactions between CS and EX-810 were observed by GPC, FT-IR, and Viscometer. The highest viscosity, 0.350 g / dl, was observed in 0.05M NaCl solution. One Ca2+ dications exchanged with two Na+ monocations in CS to produce precipitated ionic complexes. In dissolution tests, CS-Ca-EX-DS-Dy showed the better control-released property in PBS buffer as well as in the simulated gastric fluid. The modified CS-Ca and CS-Ca-EX were still cleaved by Chondroitinase ABC.

並列關鍵字

Chondroitin Sulfate ； Drug Delivery ； Cross-Linking

參考文獻

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