聚乙二醇二酸衍生之樹枝狀單體之合成及其智慧型凝膠材料之製備與性質研究

STUDIES ON THE SYNTHESIS OF DENDRITIC MONOMERS BASED ON POLY(ETHYLENE GLYCOL) DIACID AND PROPERTIES OF SMART HYDROGELS PREPARED FROM THEIRS

陳峻豪(Chun-Hao Chen)

指導教授 ： 李文褔

大同大學/工程學院/化學工程學系所/碩士(2009年)

摘要

本論文主要包含三部分，第一部分主要是使用PEG diacid為核心、以乙二胺 (ethylenediamine, EDA) 和丙烯酸甲酯 (methyl acrylate, MA) 反覆反應合成出三系列 (D, T, O) 的新穎樹枝狀單體(PEG/n-AAm)(n是樹枝狀單體端末acrylamido基的數量)。我們合成出在端末基帶有丙烯醯胺基的樹枝狀單體，並且使用FTIR、1H NMR和13C NMR進行結構分析。我們設計本身就具良好生物相容性的PEG當作樹枝狀單體的核心，以提升此樹枝狀單體的生物相容性。我們期待此樹枝狀單體將來在藥物釋放方面有所應用。
第二部分是利用第一部分所合成出來端末基帶有丙烯醯胺基的樹枝狀單體為交聯劑，然後再與NIPAAm共聚合合成出3個不同系列 (ND, NT及NO) 的熱感性膠體。探討不同樹枝狀單體含量及交聯結構對於水膠的膨潤行為及機械性質的影響。結果顯示，膠體的膨潤度會隨著當作交聯劑的樹枝狀單體量增加而減少。比較ND、NT、NO三系列膠體的膨潤度其大小為ND＞NT＞NO。此結果與樹枝狀單體雙鍵數目多寡有關。由膠體在不同溫度下的平衡膨潤度可以發現到膠體的CGTT在35℃。當樹枝狀單體含量添加越多時，交聯密度及膠體強度也就越大，膠體就越來越緊密。
第三部分係利用第一部分所合成之端末基帶有丙烯醯胺基的樹枝狀單體為交聯劑，再與NIPAAm和丙烯酸 (acrylic acid, AA) 共聚合製備三個不同系列具有熱感應性及pH感應性之NAD, NAT, 及NAO膠體。探討不同樹枝狀單體含量及交聯結構對於水膠的膨潤行為及機械性質的影響。結果顯示，膠體的膨潤度會隨著樹枝狀單體含量增加而減少。比較NAD、NAT、NAO三系列膠體的膨潤度其大小為NAD＞NAT＞NAO。膠體在不同溫度下的平衡膨潤度可以發現到膠體的CGTT在36℃。當樹枝狀單體含量添加越多時，交聯密度及膠體強度也就越大，膠體就越來越緊密。在鹼性溶液(pH=8)中，poly(NIPAAm-co-AA)膠體裡的COO-，電荷負負相斥造成膠體變大。

關鍵字

熱-pH感應性水膠 ； 樹枝狀單體 ； 異丙基丙烯醯胺

並列摘要

The thesis contains three parts. In first part, three series (D, T, O) of dendritic monomers, poly (ethylene glycol/n-acrylamide) (PEG/n-AAm, n is synthesized the number of acrylamido in the end group), were prepared from poly (ethylene glycol) 600 diacid(PEG6 diacid) as a internal core and iterately reacted with ethylenediamine (EDA) and methyl acrylate (MA), their end-cap reaction with acryloyl chloride (AC).The structures of the synthesized PEG/n-AAm were confirmed by FTIR spectroscopy, 1H NMR and 13C NMR. The results showed that dendritic monomers have acrylamido group in the end. PEG6 diacid was chosen as the core of dendritic monomers in order to enhance the biocompatibility. Modification of PEG core with vinyl groups could supply widely applications such as futher free radical polymerization. The chemical structure is biocompatible and therefore be considered for biomedical applications.
In second part, three series of thermosensitive hydrogels (ND, NT, and NO) were prepared from N-isopropylacrylamide (NIPAAm), and three different dendritic monomers as crosslinkers. The influence of dendritic monomer content and different dendritic structure on the swelling behavior and mechanical properties of the three series hydrogels was investigated. Results showed that the swelling ratios of the hydrogels decreased with an increase of dendritic monomer content in feed composition. Comparing these swelling ratios of the three hydrogels, the results showed that the swelling ratio is in the order ND＞NT＞NO due to the higher functionality of NO gel resulted in higher crosslinking density. Rusults from equilibrium swelling ratios at different temperatures showed that the gel had a critical gel transition temperature (CGTT) around 35°C. It was also observed that the more the dendritic monomer incorporated into gel, the higher the crosslinking density and shear modulus of the gel due to the formation of more condense structure. The increase in crosslinking density of the N series hydrogels would cause the gel network more compact and improve the gel strength.
In third part, the dendritic monomers (G0, G1, and G2) with acrylamido group in the end were first synthesized, and three series of thermo-pHsensitive hydrogels (NAD, NAT, and NAO) were prepared from N-isopropylacrylamide (NIPAAm), acrylic Acid (AA), and dendritic monomers as crosslinkers. The influence of dendritic monomer content and different structure on the swelling behavior and mechanical properties of the three series hydrogels was investigated. Results showed that the swelling ratios of the hydrogels decreased with an increase of the content of dendritic monomer as crosslinker in feed composition. Comparing these swelling ratios of the three hydrogels, the results showed that the swelling ratio is in the order NAD＞NAT＞NAO due to the higher functionality of NAO gel resulted in higher crosslinking density. Rusults from equilibrium swelling ratios at different temperatures showed that the gel had a critical gel transition temperature (CGTT) around 36°C. It was also observed that the more the dendritic monomer incorporated into gel, the higher the crosslinking density and shear modulus of the gel due to the formation of more condense structure. The increase in crosslinking density of the N series hydrogels would cause the gel network more compact, and improve the gel strength. In alkali solution, the deprotonation of carboxylic groups (-COOH) in the poly (NIPAAm-co-AA) gel develops an internal ion osmotic pressure and induces the gel to max swell at pH=8.

並列關鍵字

NIPAAm ； thermo-pHsensitive hydrogel ； dendrimer

參考文獻

1. Buhleier, E.; Wehener, E.; Vogtle, F. Synthesis 1978, 155-58.

2. Moors, R.; Vogtle, F. Chem Ber 1993, 126, 2133-2135.

4. Tomalia, D. A.; Baker, H.; Dewald, J. R.; Hall, M.; Kallos, G..; Martin, S.; Roeck, J.; Smith, P. Macromolecules 1986, 2466-2468.

8. Cloninger, M. J. Curr Opin Chem Biol 2002, 6, 742.

13. Namazi, H.; Adeli, M. Biomaterials 2005, 26, 1175-1183.