pH敏感性PMAA类水凝胶的合成及性能研究
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摘要
“智能”高分子水凝胶是一类对于外界环境微小的物理和化学刺激(如:温度、pH等),其自身性质会发生明显改变的聚合物,具有传感、处理和执行功能,以及在医药与生物工程中具有良好的应用和发展前景。聚丙烯酸类水凝胶属于pH敏感型水凝胶,改变环境pH值将引起聚丙烯酸类水凝胶发生体积相转变。
本文系统地对聚甲基丙烯酸水凝胶的制备及其性能进行了研究,首先合成了聚甲基丙烯酸水凝胶,并通过红外光谱对所合成的产物进行了结构确认,然后与海藻酸钠进行共混制备共混微球,通过扫描电子显微镜对共混微球的内部和外部结构进行了观察,并进行了共混微球的体外载药释放实验研究,主要结果如下:
1、以甲基丙烯酸为起始原料,通过自由基反应40℃时成功合成聚甲基丙烯酸(PMAA)水凝胶,并对其性能进行了研究,研究结果表明:PMAA类水凝胶显示明显的pH敏感性,其溶胀程度随pH值的增大而升高;PMM类水凝胶的溶胀度随交联剂含量的升高而下降。
2、以海藻酸钠为原料,对海藻酸钠微球的制备进行了研究,研究结果表明:海藻酸钠浓度大于2.5%、CaCl_2浓度大于2.0%时,所得的海藻酸钠凝胶微球在圆整性和强度方面均表现较好,并且微球在pH6.8、7.4处表现出较好的溶胀性能,其溶胀的实质是由于Na~+-Ca~(2+)交换所引起的溶胶—凝胶变化。
3、通过将聚甲基丙烯酸钠与海藻酸钠进行共混,制备了聚甲基丙烯酸钠与海藻酸钠共混微球,其溶胀变化在pH6.8—7.4之间,能够使药物只在结肠内释放,可以有效的预防药物在胃和小肠内分解损失。
4、对共混的载药微球进行了体外药物释放实验研究,结果发现:在24h内90%药物释放出来,2天内药物基本释放完全,6天后,载药微球完全破裂;在释药时间上,基本上能够跟微球在结肠内的停留时间相吻合。
"Intelligent"polymer hydrogels were those polymers which could respond with large property changes to small physical or chemical stimulations such as temperature and pH , and could perform sensing , processing and actuating functions. and "intelligent" polymer hydrogels have a good applications to medicines and biotechnology and their promising potentiality of development. The polyacrylic acid size hydrogels belongs to the pH-sensitive hydrogels, changing the pH of the environment would cause the phase changing of the polyacrylic acid size hydrogels.
The paper gives a system study on the preparation and the properties of the polymethacrylic acid hydrogels (PMAA),First, we synthesis the polymethacrylic acid hydrogels, and determined its structure by Infrared Spectrum.then we prepare the blend microspheres by blending the sodium of polymethacrylic acid with sodium alginate, and we observe the internal and external structures of the blend microspheres by scanning electron microscope,and give a study on the external-load-drug experiment. Main results were as follows:
1、We use methacrylic acid for initial raw materials by free radical reaction ynthesis the PMAA hydrogels at 40℃and give a research on his properties, The result showed that:PMAA hydrogels showed significantly pH-sensitive, and the pH increased , the swelling degree increased; However, the crosslinking agent content increased, the swelling degree decreased.
2、We give a study on the preparation of sodium alginate microspheres with the sodium alginate as material, The result showed that: When the concentration of sodium alginate is more than 2.5% and the concentration of CaC12 is more than 2.0%, the acquired sodium alginate microspheres have a better round resistance and strength, and sodium alginate microspheres shows better swelling properties in pH6.8 or pH7.4, its essence of the swelling is that the exchange of Na~+-Ca~(2+) caused sol-gel variation.
3、By blending the polymethacrylic acid sobium and sodium alginate. we prepare the blend microspheres and make the swelling variation between pH6.8-7.4 in order to make the drag only released in the colon. So that we can effectively prevent the drug released in stomach and small intestine.
4、We give the blending load-drug microspheres a study on its external- drug-releasing experiment, the result showed that:90% of the drug was released in 24 hours and the drug was completely released about 2 days, the load-drug microspheres completely reptured in 6 days;The realeased time can basically anastomosed with the microspheres' residence time at colon.
本文系统地对聚甲基丙烯酸水凝胶的制备及其性能进行了研究,首先合成了聚甲基丙烯酸水凝胶,并通过红外光谱对所合成的产物进行了结构确认,然后与海藻酸钠进行共混制备共混微球,通过扫描电子显微镜对共混微球的内部和外部结构进行了观察,并进行了共混微球的体外载药释放实验研究,主要结果如下:
1、以甲基丙烯酸为起始原料,通过自由基反应40℃时成功合成聚甲基丙烯酸(PMAA)水凝胶,并对其性能进行了研究,研究结果表明:PMAA类水凝胶显示明显的pH敏感性,其溶胀程度随pH值的增大而升高;PMM类水凝胶的溶胀度随交联剂含量的升高而下降。
2、以海藻酸钠为原料,对海藻酸钠微球的制备进行了研究,研究结果表明:海藻酸钠浓度大于2.5%、CaCl_2浓度大于2.0%时,所得的海藻酸钠凝胶微球在圆整性和强度方面均表现较好,并且微球在pH6.8、7.4处表现出较好的溶胀性能,其溶胀的实质是由于Na~+-Ca~(2+)交换所引起的溶胶—凝胶变化。
3、通过将聚甲基丙烯酸钠与海藻酸钠进行共混,制备了聚甲基丙烯酸钠与海藻酸钠共混微球,其溶胀变化在pH6.8—7.4之间,能够使药物只在结肠内释放,可以有效的预防药物在胃和小肠内分解损失。
4、对共混的载药微球进行了体外药物释放实验研究,结果发现:在24h内90%药物释放出来,2天内药物基本释放完全,6天后,载药微球完全破裂;在释药时间上,基本上能够跟微球在结肠内的停留时间相吻合。
"Intelligent"polymer hydrogels were those polymers which could respond with large property changes to small physical or chemical stimulations such as temperature and pH , and could perform sensing , processing and actuating functions. and "intelligent" polymer hydrogels have a good applications to medicines and biotechnology and their promising potentiality of development. The polyacrylic acid size hydrogels belongs to the pH-sensitive hydrogels, changing the pH of the environment would cause the phase changing of the polyacrylic acid size hydrogels.
The paper gives a system study on the preparation and the properties of the polymethacrylic acid hydrogels (PMAA),First, we synthesis the polymethacrylic acid hydrogels, and determined its structure by Infrared Spectrum.then we prepare the blend microspheres by blending the sodium of polymethacrylic acid with sodium alginate, and we observe the internal and external structures of the blend microspheres by scanning electron microscope,and give a study on the external-load-drug experiment. Main results were as follows:
1、We use methacrylic acid for initial raw materials by free radical reaction ynthesis the PMAA hydrogels at 40℃and give a research on his properties, The result showed that:PMAA hydrogels showed significantly pH-sensitive, and the pH increased , the swelling degree increased; However, the crosslinking agent content increased, the swelling degree decreased.
2、We give a study on the preparation of sodium alginate microspheres with the sodium alginate as material, The result showed that: When the concentration of sodium alginate is more than 2.5% and the concentration of CaC12 is more than 2.0%, the acquired sodium alginate microspheres have a better round resistance and strength, and sodium alginate microspheres shows better swelling properties in pH6.8 or pH7.4, its essence of the swelling is that the exchange of Na~+-Ca~(2+) caused sol-gel variation.
3、By blending the polymethacrylic acid sobium and sodium alginate. we prepare the blend microspheres and make the swelling variation between pH6.8-7.4 in order to make the drag only released in the colon. So that we can effectively prevent the drug released in stomach and small intestine.
4、We give the blending load-drug microspheres a study on its external- drug-releasing experiment, the result showed that:90% of the drug was released in 24 hours and the drug was completely released about 2 days, the load-drug microspheres completely reptured in 6 days;The realeased time can basically anastomosed with the microspheres' residence time at colon.
引文
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[14]殷以华.pH敏感的疏水型凝胶在直流电场中的刺激响应.高分子学报.2002,4:414.
[15]郑俊民,平其能,杨丽,等.药用高分子材料学.北京:中国医药科技出版社.2000,61-63
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[30]祁荣,何仲贵.“智能”水凝胶研究进展及其在医药与生物工程中的应用.沈阳药科大学学报.2001,18(11):447-451.
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[33]HeHongyan,Cao Xia,Lee,L.James.Design of a novel hydrogel-based intelligent system for controlled drug release J.Journal of Controlled Release.2004,95(3):391-402.
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