溫敏性生物可分解智慧型材料之製備與性質研究

STUDIES ON PREPARATION AND PROPERTIES OF THE BIODEGRADABLE THERMOSENSITIVE INTELLIGENT MATERIAL

王竣暉(Chun-Hui Wang)

指導教授 ： 李文福

大同大學/工程學院/化學工程學系所/碩士(2009年)

摘要

本論文包括兩部分，第一部分主要在合成具生物可分解性[Polyethylene Glycol (PEG) / Polycaprolactone (PCL)]- polyurethanes (PCEU)之形狀記憶聚氨酯材料。由於具有生物分解性的PCL較為疏水，將其作為軟鏈搭配由各種Diisocyanate及鏈延長劑合成的PU為硬鏈來組成具形狀記憶能力之聚氨酯也呈現疏水狀況，為使其適用於人體，因此，本實驗導入PEG來增加其親水性使其更具生物相容性，並比較由2,4-toluene diisocyanate (TDI), 4, 4’-diphenyl methane diisocyanate (MDI), Isophorone diisocyanate (IPDI)及延長劑1,4-butanediol所組成之聚氨酯之性質。本實驗採二步反應，由IR光譜追蹤分析可以發現第一步於40分鐘時可使Diisocyanate封端完全反應，而第二步加入1,4-butanediol則於2小時即可完成反應。另外，由XRD與DSC發現不同的軟硬段比例下，聚氨酯隨著導入硬段的比例上升，硬段在結構中所形成的物理交聯會使的PCL的結晶度下降，進而造成熔點下降。而因導入不同疏水性的硬段造成其生物分解與水接觸角則呈現相同趨勢。而PCE6TU176, PCE6MU154 and PCE6MU176 因為硬鏈的量可以有效形成足夠的物理交聯而使得材料有高形狀記憶回復率。
第二部分中，因為聚乙二醇(PEG)/聚乳酸-甘醇酸(PLGA)共聚物具有可生物分解性及不具毒性，近年來再作為藥物載體及組織工程方面十分受到重視，但是其共聚物因為分解速率快及分子量較低的關係而有藥物瞬放及凝膠範圍狹小等問題。本實驗以辛酸亞錫(Sn(oct)2)為催化劑，聚乙二醇、甲氧基聚乙二醇(mPEG)、為共催化劑進行聚乳酸-甘醇酸開環聚合，合成一系列無毒性、無溶劑性、可注射性之具溫度敏感性之聚乙二醇/聚乳酸-甘醇酸三團聯共聚物(PLGA-PEG-PLGA)及甲氧基聚乙二醇/聚乳酸-甘醇酸雙團聯共聚物(mPEG-PLGA)，探討末端以2, 2-bis(2-oxazoline)(BOX)聯結及封端之共聚物對其最低臨界轉移溫度(LCST)、相圖、臨界成膠濃度及降解性的影響。實驗結果顯示，無論三團聯共聚物或雙團聯共聚物，當以2, 2'-Bis(2-oxazoline) (BOX) 作聯結劑增加其分子量及分子鏈長度之後，其共聚物之最低臨界轉移溫度會提高，而在相圖之中可發現，以BOX聯結後凝膠態的臨界凝膠溶液溫度會上升使得凝膠的範圍增加且有效降低臨界成膠濃度、在降解實驗中未以BOX聯結之共聚物於1~2週時有一明顯降解，但以BOX聯結後則有速度減緩的現象。

關鍵字

智慧材料 ； 聚氨酯 ； 形狀記憶

並列摘要

The thesis includes two parts. In first part, a series of shape memory materials based on [poly(ethylene glycol ) (PEG) /poly(ε-caprolactone)(PCL) - polyurethanes ] (PCEU) block copolymer were prepared from PCL diol, poly(ethylene glycol) diacid, 2,4-toluene diisocyanate (TDI), 4, 4’-diphenyl methane diisocyanate (MDI), isophorone diisocyanate (IPDI) and 1,4-butanediol. Two molecular weights (Mn = 600 and 2000) of PEG and PCL were used to prepare PCE as the soft segment. The molar ratio of soft segment-to-hard segment was ranged from 1:2 to 1:6. In this research, three kinds of PCEU were synthesized in a two-step method and the reaction kinetics was investigated by IR spectroscopy. The results showed that the end-cap of diisocyanate in step 1 was completed at 40 mins and the reaction adding 1,4-butanediol in step 2 was completed at 2 h. The results from XRD and DSC showed that the melting temperature (Tm) and crystallinity (Xc) of the PCEU decreased with increasing of the ratio of soft segment-to-hard segment. The contact angles and biodegradability also showed the same tendency as Tm and Xc due to the introduction of hard segment that increasing the hydrophobicity of the block copolymer and consequently decreasing the wettability and biodegradability. The recovery ratio of shape memory effect of PCE6TU176, PCE6MU154 and PCE6MU176 could reach upper than 95% due to physical crosslinking when the hard segment ratio was raised to enough amount for each block copolymer. But for other samples the recovery ratio of shape memory effect was not completed as the temperature was higher than the melting point.
In the second part, Thermosensitive block copolymers composed of biodegradable polyesters, such as poly[(lactic acid)-co-(glycolic acid)] (PLGA) and hydrophilic polymers poly(ethylene glycol) (PEG) have been investigated extensively for medical applications in the past decades. The applications of PEG/PLGA block copolymer might be limited because the burst release of drug from PEG/PLGA block copolymer considerably faster and lower temperature range of gel phase comparing to human body temperature (37~42℃). In this study, the MPEG-PLGA diblock copolymer and PLGA-PEG-PLGA triblock copolymer were synthesized by ring-opening reaction of D, L-lactide, glycolide, poly(ethylene glycol) methyl ether and polyethylene glycol. 2, 2'-Bis(2-oxazoline) (BOX) was introduced as linker to control the sol-gel transition range and degradation of PEG/PLGA block copolymer. It was mentioned that introducing the BOX as linker to increase the molecular weight would result in the higher lower critical solution temperature. In the phase diagrams, introducing the BOX were increased the critical gel-to-sol line. That made the gel phase range be wider and critical gel concentration be lower. At biodegradability, the diblock and triblocl copolymer showed the fast rate in the 1~2 weeks. After introducing the BOX, both of two samples appeared lower degradation rate.

並列關鍵字

shape memory ； hydrogel

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