硫酸化軟骨素-甲基丙烯酸酯與丙烯酸共聚物水凝膠之合成與分析

Synthesis and characterization of ChSMA-co-AA hydrogels

曾善章(Shan-Jhang Zeng)

指導教授 ： 王麗芳 博士

高雄醫學大學/藥學院/藥學研究所碩士在職專班/碩士(2003年)

摘要

在本實驗中我們先將硫酸化軟骨素（ChS）與甲基丙烯酸酐（MAA）在氫氧化鈉水溶液中反應，以得到固定鍵結程度的硫酸化軟骨素－甲基丙烯酸酯單體(ChSMA)，再由1莫爾ChSMA單體與5莫爾丙烯酸（AAc）於60 ℃下進行自由基聚合反應而形成水膠(ChSMA-AA)。水膠的膨潤程度會從610~2640％，隨著合成濃度的增加則平衡膨潤降低。由於AA的架橋作用在共聚合反應時會隨著濃度的增加則交聯密度上升。玻璃轉移溫度會隨著AA濃度的下降而降低。利用EA分析萃取後共聚物水膠內ChSMA的含量有560~670mg/g matrix。利用GPC觀察ChSMA單體受到酵素作用而產生的降解情形，使用Chondroitinase ABC時ChSMA無法受到酵素作用而產生明顯降解情形，可能結構改變太大而無法產生降解。若同時加入Chondroitinase ABC和Esterase時ChSMA則受到酵素作用而產生降解情形。最後模擬在腸液中其藥物釋放情形，在15分鐘時其藥物釋放量已達60﹪。各個不同交聯程度的水膠其藥物釋放並無多大變化。

關鍵字

硫酸化軟骨素 ； 甲基丙烯酸酐 ； 丙烯酸 ； 水膠

並列摘要

The degree of methacrylate (MA) substitution on chondroitin sulfate (ChS) was prepared by reacting chondroitin sulfate with methacrylic anhydride (MAA) in presence of sodium hydroxide (NaOH) as a base. Hydrogels were prepared by free radical polymerization of ChSMA precursors with acrylic acid (AA) as a mole ratio of 1 to 5 at 60℃. ChSMA-AA hydrogels remained completely and showed a range of swelling ratio from 610 to 2640﹪and exhibited an increase in swelling ratio with a decreasing concentration. Copolymerization of ChSMA with AA increased the crosslinking density of hydrogel by the bridging effect of AA. Glass transition temperature (Tg) of hydrogels was decreased with decreasing concentration. The ChSMA composition in copolymer was determined by elemental analysis in the ranges of 560~670mg/g matrix after 48h water extraction of hydrogels The ChSMA monomer were still cleaved by Chondroitinase ABC and Esterase but ChSMA-AA hydrogels were not cleavable. The drug release from ChSMA-AA hydrogels was simulated in the intestinal fluid. The drug-released amount exceeded 60% within 15 minute. The drug released profile was independent of AA concentration in preparation of hydrogels.

並列關鍵字

none

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