生物可分解智慧型凝膠材料之製備與性質研究

Studies on Preparation and Properties of The Biodegradable Intelligent Hydrogels

林昶廷(Chang-Ting Lin)

指導教授 ： 李文福

大同大學/工程學院/化學工程學系所/碩士(2010年)

摘要

partI
本研究是利用季戊四醇(Pentaerythritol，PTOL)為起始劑，辛酸亞錫Sn(Oct)2為觸媒，開環聚合glycolide (GA)，lactide (LA)使其成為結構(I)，隨後將(I)尾端的OH與acryloyl chloride反應，合成具雙鍵之單體(II)。利用此單體製備生物可分解性的多臂型凝膠材料。
由實驗結果顯示，成功合成出具雙鍵之多臂型單體，利用其當交聯劑和NIPAAm共聚合時，整塊膠體的強度、緊密度，皆優於由NMBA和NIPAAm共聚合之膠體，膠體的膨潤度隨著交聯劑添加量增加而下降，藥物釋放量隨交聯劑增加而減少，由不同濃度添加量也可看出其膨潤度及藥物釋放行為的規律性。在本實驗中也將探討含PLGA膠體其降解週期，並測試其分解前後的單體與膠體是否具有毒性，是否適合應用在人體內部。

partII
本研究是利用山梨醇(Sorbitol)為起始劑，辛酸亞錫Sn(Oct)2為觸媒，開環聚合glycolide (GA)，lactide (LA)使其成為結構(I)，隨後將(I)尾端的OH與acryloyl chloride反應，合成具雙鍵之單體(II)。利用此單體製備生物可分解性的多臂型凝膠材料。
由實驗結果顯示，成功合成出具雙鍵之多臂型單體，利用其當交聯劑和NIPAAm共聚合時，整塊膠體的強度、緊密度，皆優於由NMBA和NIPAAm或是六臂交聯劑 (Sorbitol-PLGAdA) 和NIPAAm共聚合之膠體，膠體的膨潤度隨著交聯劑添加量增加而下降，藥物釋放量隨交聯劑增加而減少，此外在實驗中就相同濃度或是相同C=C數目的交聯劑做比較，從中也可看中出其膨潤度及藥物釋放行為的規律性。另外實驗中也將探討含PLGA膠體其降解週期，並測試其分解前後的單體與膠體是否具有毒性，是否適合應用在人體內部。

partIII
本研究是以乳酸羥基乙酸[Poly(lactide-co-glycolide )，PLGA] 共聚物為基質，利用噴霧乾燥技術製備微小球(microspheres)。探討噴霧乾燥技術製程參數對微小球(microspheres)產率的影響，研究結果顯示噴霧乾燥技術能製備出粒徑為1~30 μm 的微小球(microspheres)。SEM 的分析顯示所製得的微小球(microspheres)內部為交錯式的孔洞結構，而表面則是緻密的薄層，聚集的方式為團聚。產率分析的結果顯示能藉由使用溶劑的比例不同與進出口端的溫度來提升微小球(microspheres)的產率，最高能獲得53% 的產率。

關鍵字

山梨醇 ； 丙交酯 ； 乙交酯 ； 凝膠 ； 生物可分解性 ； 季戊四醇 ； 微小球

並列摘要

partI
A novel four-arm biodegradable compound (I) was prepared from pentaerythritol (PTOL) as initiator, stannous octoate Sn(Oct)2 as catalyst, glycolide (GA), and lactide (LA) via ring-opening polymerization. The compound (I) containing terminal hydroxyl group was reacted with acryloyl chloride to obtain the monomer (II) containing terminal vinyl group. The monomer (II) as crosslinker was copolymerized with thermosensitive monomer, N-isopropyl acrylamide (NIPAAm) to prepare a series of biodegradable four-arm thermosensitive hydrogels. The results show that the swelling ratios decrease with an increase of the crosslinker content in the hydrogels. The gel strength and gel modulus of hydrogels are also increased with increasing of crosslinker content. But, the drug release decreases with an increase of the crosslinker content in the hydrogels. The effects of crosslinker content on the drug release and the degradation cycle of the hydrogels containing PLGA were investigated. In this study, toxicity of the monomer and the hydrogels are also tested before and after biodegradation in order to confirm whether they can apply in the body or not.

partII
A novel six-arm biodegradable compound (I) synthesized from sorbitol as initiator, stannous octoate Sn(Oct)2 as catalyst, and glycolide (GA), and lactide (LA) via ring-opening polymerization. The compound (I) containing terminal hydroxyl group was reacted with acryloyl chloride to obtain the monomer (II) containing terminal vinyl group. The monomer (II) as crosslinker was copolymerized with thermosensitive monomer, N-isopropyl acrylamide (NIPAAm) to prepare a series of biodegradable six-arm thermosensitive hydrogels. The results show that the swelling ratios decrease with an increase of the crosslinker content in the hydrogels. The gel strength and gel modulus of the hydrogels are also increased with an increase of the crosslinker content. But the drug release decreases with an increase of the crosslinker content in the hydrogels. The effect of crosslinker content on drug release of the hydrogels and the biodegradation cycle of the hydrogels containing PLGA were investigated. In addition, the gels crosslinked by the same concentration of crosslinker (four or six-arm) or the same number of vinyl groups of crosslinker were designed to compare swelling ratio and drug release behavior, the results show that swelling ratio of the hydrogels and drug release behavior follow the rule of crosslinking density. In this study, toxicity of the monomer and the hydrogels are also tested before and after biodegradation to confirm whether they can apply in the body or not.

partIII
In this study, poly(lactide-co-glycolide) (PLGA) as matrix was used to prepare microspheres by spray drying process. The effect of different spray drying process parameters on the yield of microspheres was investigated. The results showed that spray drying can prepare 1 ~ 30 μm diameter of the microspheres (microspheres).
SEM analysis shows that the pores of the microspheres prepared by spray drying process are the interconnected structure in the inside microspheres but their surface structures show dense layer; the way of gathering is flocculation. The yield analysis showed that the yield of microspheres can be improved by adjusting different ratios of solvents and temperatures of inlet and outlet. The maximum yield can be achieved about 53%.

並列關鍵字

PLGA ； hydrogel ； microsphere ； biodegradable ； sorbitol ； pentaerythritol (PTOL)

參考文獻

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