不同接枝率的硫酸化軟骨素-甲基丙烯酸酯與丙烯酸交聯聚合水膠之製備及其物性與形態分析

Synthesis, Physical Characterization and Morphology of Chondroitin Sulfate Graft Methacrylate Copolymerized with Acrylic Acid

蔡明峰(Ming-Fong Tsai)

指導教授 ： 王麗芳

高雄醫學大學/生命科學院/醫藥暨應用化學研究所/碩士(2005年)

摘要

Chondroitin sulfate（CS）為已知的一種天然多醣體，具有高度的生物相容性且無毒性，在近年來廣泛的被運用在生醫材料上，所以本實驗上我們選用CS作為水膠製備的基質。但由於水膠具有高度水溶性，所以我們將具有反應活性之雙鍵Methacrylate（MA）基團接枝到CS上，分別製備不同鍵結程度（Degree of substitution，DS）的CS-MA作為水膠合成的單體，由NMR分析鍵結程度分別為75%、45%、20%等三組單體，將與莫耳數比為 1：5 之Acrylic acid (AA)進行交聯聚合的方式製備水膠，並以這幾組水膠作為酵素的降解與藥物的釋放控制材料，分別以凝膠滲透層析儀（Gel Permeation Chromatography，GPC）、以及材料試驗機(Material Testing Machine)與掃描式電子顯微鏡（Scanning Electron Microscope）分析這三組單體與所製備的水膠，在酵素的降解與藥物釋放行為，以及機械性質與不同狀態下的表面形態。期望在本研究中的實驗所得到的結果，能進一歩探討以CS-MA-AA水膠為基質材料的物理性質、酵素的降解、及藥物的控制釋放等條件，以評估其在生醫材料上多元化使用之潛能。

關鍵字

藥物投遞 ； 膨潤 ； 甲基丙烯酸酯 ； 硫酸化軟骨素 ； 水膠 ； 丙烯酸 ； 酵素降解

並列摘要

Chondroitin sulfate（CS）is one of the polysaccharide in nature and has been used as a biomaterial widely because of biocompatibility, nontoxicity and highly enzymatic hydrolysis. Therefore to prepare CS hydrogel, which can be used to sustain drug release well is of great interest. Since the natural CS is highly water soluble, which may not maintain as a solid form in the human physiological condition, therefore the incorporation of methacrylate (MA) groups on CS side chain to introduce the double bonds, which can further polymerized with any vinyl monomers to form hydrogels. Three degrees of substitution (DS) determined by 1H-NMR were prepared in the order of 75%, 45%, and 20% respectively. These CS-MAs are further copolymerized with acrylic acid as a molar ratio of 1: 5 to form hydrogels. The enzymatic degradation by GPC and the drug-released behavior by HPLC will be traced. The compression modulus evaluated by material testing machine and hydrogel morphology observed by scanning electron microscope will be presented in this article. Finally, the potentially sustain-released efficiency of these hydrogels will be tested using the BSA as a protein model drug.

並列關鍵字

Chondroitin sulfate ； Methacrylate ； Acrylic Acid ； Swelling ； Hydrogels ； enzyme degradation ； Drug Deliver.

參考文獻

1. Sujata V. Bhat, Biomaterials, 2002.

2. Severian Dumitriu, Polysaccharides in Medicinal Applications, 1996.

3. 蘇莉婷, 軟骨硫素在生物醫學上的應用, 民91.

4. 蘇肇偉, 養殖漁業廢棄物之有效處理與應用之研究, 民90.

5. Sintov A., Capua N. D., Rubinstein A., Cross-linkedchondroitin sulphate:Characterization for drug delivery purposes, Biomaterials 1995, 16, 473-467.