新型温敏凝胶及其在生物分离中的应用研究
|
摘要
本论文从合成N-异丙基丙烯酰胺(NIPA)与葡聚糖的共聚及互穿(IPN)水凝胶出发，研究环境刺激下凝胶的溶胀、吸附行为，并进一步探索其在生物分离中的应用。
本文采用甲基丙烯酸环氧丙酯(GMA)对葡聚糖(Dextran 40000)进行化学改性，合成出了具有反应活性的葡聚糖衍生物(GMA-Dex)；使用过硫酸铵和N，N，N'，N'-四甲基乙二胺作为氧化还原引发剂引发GMA-Dex与NIPA聚合，合成出了质量比r(r=GMA-Dex/(GMA-Dex+NIPA))分别为0.2、0.4、0.5、0.6和0.8的新型共聚水凝胶(P(NIPA-co-GMA-Dex))。利用红外光谱(IR)分析和核磁共振(~1H-NMR)等方法对GMA-Dex及P(NIPA-co-GMA-Dex)凝胶的结构和组成进行了表征，并分别考察了不同r值对凝胶的较低临界溶解温度(LCST)、溶胀性、退溶胀/再溶胀动力学等性能的影响。结果发现，P(NIPA-co-GMA-Dex)凝胶具有温度敏感性，pH值敏感性和离子强度敏感性。同时，P(NIPA-co-GMA-Dex)水凝胶对温度的响应还具有很好的可逆性。室温(20℃)时，P(NIPA-co-GMA-Dex)凝胶具有较高的溶胀率，而且r越大，凝胶的溶胀率越小。P(NIPA-co-GMA-Dex)凝胶的LCST均大于PNIPA凝胶的LCST(32℃)，并且随r的增大而增大。退溶胀动力学的研究结果表明在50℃时，凝胶剧烈收缩，并且其r越大，凝胶退溶胀越慢，水保留率越高。再溶胀过程中，凝胶的再溶胀速率随着r的增大而增大，但均低于PNIPA凝胶再溶胀速率。此外，通过变化氯化钠的浓度来改变溶液的离子强度，研究了离子强度对P(NIPA-co-GMA-Dex)凝胶溶胀率的影响。发现所有凝胶都具有相似的变化趋势，当离子强度低于0.5mol L~(-1)时，凝胶具有较高的溶胀率；而当离子强度逐渐增大至2mol L~(-1)时，凝胶溶胀率则显著变小，其中r=0.8凝胶的溶胀率仅为其在水中溶胀率的1/10。
本文成功合成了GMA-Dex与PNIPA的互穿/半互穿凝胶，并对凝胶的溶胀性能进行了研究，发现PNIPA/GMA-Dex半IPN和IPN凝胶同样具有对温度敏感的特性。改变NIPA和GMA-Dex的配比对凝胶的溶胀率、退溶胀率和再溶胀率都有很大的影响。一般的GMA-Dex的质量百分比c越大，凝胶的溶
胀率越小，LCST越高，退溶胀、再溶胀速率越慢。
通过凝胶的单轴压缩实验对P(N IPA一co一GMA一Dex)凝胶的力学性能进行
了研究。发现P(N IPA一co一GMA一Dex)凝胶具有较好的力学性能，其剪切模量和
有效交联密度均随着r的增加而增大。
本文对P困IPA一co一GMA一Dex)凝胶在生物分离中的应用进行了初步的研
究。结果表明P困IPA一co一GMA一Dex)凝胶与十二烷基硫酸钠(SDS)、芦丁和丙
氨酸之间的相互作用具有明显的对温度的依赖性，当温度高于凝胶的LCST
时，凝胶与SDS、芦丁和丙氨酸之间的相互作用显著增强，对它们的吸附量
也会相应增加，这种特性有望在生物大分子的纯化、分离等领域得到实际应
用。通过考察P伽IPA一co一GMA一Dex)凝胶对多糖和蛋白质的浓缩分离行为发
现，P伽IPA一co一GMA一Dex)凝胶对多糖和蛋白质的分离效率在LCsT附近发生
突跃，显示出较好的浓缩分离能力。
The synthesis and properties of poly (NIPA-co-GMA-Dex) hydrogels and PNIPA/GMA-Dex IPN/semi IPN hydrogels, including the swelling and absorbing behaviors in response to environmental stimuli were studied. The applications of poly (NIPA-co-GMA-Dex) hydrogels in bioseparation were also investigated.
Glycidyl methacrylate (GMA) derivatized dextran (GMA-Dex) was synthesized by coupling GMA to dextran in the presence of 4-(N,N-dimethylamino) pyridine using DMSO as an aprotic solvent. Through copolymerization of this active monomer with N-isopropylacrylamide (NIPA) in aqueous solution, a series of novel hydrogels (poly (NIPA-co-GMA-Dex)) with different weight ratio r(r=GMA-Dex/(GMA-Dex+NIPA)) were prepared using radical polymerization method. Both GMA-Dex monomer and poly (NIPA-co-GMA-Dex) gels were characterized using FTIR spectra and 1H-NMR, and the influence of r on the swelling ratio (SR), deswelling/reswelling kinetics has been studied. It is found that poly (NIPA-co-GMA-Dex) gels are temperature-, pH- and ionic strength-sensitive. Their SR(20℃C) decreased and the lower critical solution temperature(LCST) increased with increase of r, and the LCSTs of poly (NIPA-co-GMA-Dex) gels are all higher than that of PNIPA gel(32℃). The smaller the r is, the faster the gels deswell; but the reswelling speed incre
ased with increase of r. The results also indicated that the SR of poly (NIPA-co-GMA-Dex) gels was affected by ionic strength of solution. When ionic strength<0.5mol L-1, the SR remained high; when ionic strength was increased to 2mol L-1 gradually, the gels shrinked significantly.
PNIPA/GMA-Dex IPN/semi-IPN gels were also synthesized successfully. The influence of c (weight concentration of GMA) on SR, deswelling/reswelling kinetics has been studied. It has found that PNIPA/GMA-Dex IPN/semi-IPN gels are also temperature-sensitive. The SR and deswell/reswell speeds are affected greatly by the component of the hydrogel.
The mechanical properties of poly (NIPA-co-GMA-Dex) hydrogels were investigated using uni-axis compressive experiments in this study. We found that poly (NIPA-co-GMA-Dex) hydrogel show much better mechanical properties than PNIPA hydrogel, which is too soft to measure. The shear modulus and the effective cross-linking density increased with the increase of r.
The applications of poly (NIPA-co-GMA-Dex) hydrogels in bioseparation have been investigated. The results indicated that the interactions between poly (NIPA-co-GMA-Dex) hydrogels and sodium dodecylsulfate (SDS) or Rutin or DL-a -Alanine show obvious dependence on the temperature. At higher temperature(>LCST), poly (NIPA-co-GMA-Dex) hydrogels deswelled and were susceptible to absorb larger amount of SDS or Rutin or DL- a -Alanine, some of them could be desorbed at lower temperature( .
本文采用甲基丙烯酸环氧丙酯(GMA)对葡聚糖(Dextran 40000)进行化学改性，合成出了具有反应活性的葡聚糖衍生物(GMA-Dex)；使用过硫酸铵和N，N，N'，N'-四甲基乙二胺作为氧化还原引发剂引发GMA-Dex与NIPA聚合，合成出了质量比r(r=GMA-Dex/(GMA-Dex+NIPA))分别为0.2、0.4、0.5、0.6和0.8的新型共聚水凝胶(P(NIPA-co-GMA-Dex))。利用红外光谱(IR)分析和核磁共振(~1H-NMR)等方法对GMA-Dex及P(NIPA-co-GMA-Dex)凝胶的结构和组成进行了表征，并分别考察了不同r值对凝胶的较低临界溶解温度(LCST)、溶胀性、退溶胀/再溶胀动力学等性能的影响。结果发现，P(NIPA-co-GMA-Dex)凝胶具有温度敏感性，pH值敏感性和离子强度敏感性。同时，P(NIPA-co-GMA-Dex)水凝胶对温度的响应还具有很好的可逆性。室温(20℃)时，P(NIPA-co-GMA-Dex)凝胶具有较高的溶胀率，而且r越大，凝胶的溶胀率越小。P(NIPA-co-GMA-Dex)凝胶的LCST均大于PNIPA凝胶的LCST(32℃)，并且随r的增大而增大。退溶胀动力学的研究结果表明在50℃时，凝胶剧烈收缩，并且其r越大，凝胶退溶胀越慢，水保留率越高。再溶胀过程中，凝胶的再溶胀速率随着r的增大而增大，但均低于PNIPA凝胶再溶胀速率。此外，通过变化氯化钠的浓度来改变溶液的离子强度，研究了离子强度对P(NIPA-co-GMA-Dex)凝胶溶胀率的影响。发现所有凝胶都具有相似的变化趋势，当离子强度低于0.5mol L~(-1)时，凝胶具有较高的溶胀率；而当离子强度逐渐增大至2mol L~(-1)时，凝胶溶胀率则显著变小，其中r=0.8凝胶的溶胀率仅为其在水中溶胀率的1/10。
本文成功合成了GMA-Dex与PNIPA的互穿/半互穿凝胶，并对凝胶的溶胀性能进行了研究，发现PNIPA/GMA-Dex半IPN和IPN凝胶同样具有对温度敏感的特性。改变NIPA和GMA-Dex的配比对凝胶的溶胀率、退溶胀率和再溶胀率都有很大的影响。一般的GMA-Dex的质量百分比c越大，凝胶的溶
胀率越小，LCST越高，退溶胀、再溶胀速率越慢。
通过凝胶的单轴压缩实验对P(N IPA一co一GMA一Dex)凝胶的力学性能进行
了研究。发现P(N IPA一co一GMA一Dex)凝胶具有较好的力学性能，其剪切模量和
有效交联密度均随着r的增加而增大。
本文对P困IPA一co一GMA一Dex)凝胶在生物分离中的应用进行了初步的研
究。结果表明P困IPA一co一GMA一Dex)凝胶与十二烷基硫酸钠(SDS)、芦丁和丙
氨酸之间的相互作用具有明显的对温度的依赖性，当温度高于凝胶的LCST
时，凝胶与SDS、芦丁和丙氨酸之间的相互作用显著增强，对它们的吸附量
也会相应增加，这种特性有望在生物大分子的纯化、分离等领域得到实际应
用。通过考察P伽IPA一co一GMA一Dex)凝胶对多糖和蛋白质的浓缩分离行为发
现，P伽IPA一co一GMA一Dex)凝胶对多糖和蛋白质的分离效率在LCsT附近发生
突跃，显示出较好的浓缩分离能力。
The synthesis and properties of poly (NIPA-co-GMA-Dex) hydrogels and PNIPA/GMA-Dex IPN/semi IPN hydrogels, including the swelling and absorbing behaviors in response to environmental stimuli were studied. The applications of poly (NIPA-co-GMA-Dex) hydrogels in bioseparation were also investigated.
Glycidyl methacrylate (GMA) derivatized dextran (GMA-Dex) was synthesized by coupling GMA to dextran in the presence of 4-(N,N-dimethylamino) pyridine using DMSO as an aprotic solvent. Through copolymerization of this active monomer with N-isopropylacrylamide (NIPA) in aqueous solution, a series of novel hydrogels (poly (NIPA-co-GMA-Dex)) with different weight ratio r(r=GMA-Dex/(GMA-Dex+NIPA)) were prepared using radical polymerization method. Both GMA-Dex monomer and poly (NIPA-co-GMA-Dex) gels were characterized using FTIR spectra and 1H-NMR, and the influence of r on the swelling ratio (SR), deswelling/reswelling kinetics has been studied. It is found that poly (NIPA-co-GMA-Dex) gels are temperature-, pH- and ionic strength-sensitive. Their SR(20℃C) decreased and the lower critical solution temperature(LCST) increased with increase of r, and the LCSTs of poly (NIPA-co-GMA-Dex) gels are all higher than that of PNIPA gel(32℃). The smaller the r is, the faster the gels deswell; but the reswelling speed incre
ased with increase of r. The results also indicated that the SR of poly (NIPA-co-GMA-Dex) gels was affected by ionic strength of solution. When ionic strength<0.5mol L-1, the SR remained high; when ionic strength was increased to 2mol L-1 gradually, the gels shrinked significantly.
PNIPA/GMA-Dex IPN/semi-IPN gels were also synthesized successfully. The influence of c (weight concentration of GMA) on SR, deswelling/reswelling kinetics has been studied. It has found that PNIPA/GMA-Dex IPN/semi-IPN gels are also temperature-sensitive. The SR and deswell/reswell speeds are affected greatly by the component of the hydrogel.
The mechanical properties of poly (NIPA-co-GMA-Dex) hydrogels were investigated using uni-axis compressive experiments in this study. We found that poly (NIPA-co-GMA-Dex) hydrogel show much better mechanical properties than PNIPA hydrogel, which is too soft to measure. The shear modulus and the effective cross-linking density increased with the increase of r.
The applications of poly (NIPA-co-GMA-Dex) hydrogels in bioseparation have been investigated. The results indicated that the interactions between poly (NIPA-co-GMA-Dex) hydrogels and sodium dodecylsulfate (SDS) or Rutin or DL-a -Alanine show obvious dependence on the temperature. At higher temperature(>LCST), poly (NIPA-co-GMA-Dex) hydrogels deswelled and were susceptible to absorb larger amount of SDS or Rutin or DL- a -Alanine, some of them could be desorbed at lower temperature(
引文
[1] 姚康德，成国祥，等。智能材料，北京：化学工业出版社，2002．
[2] 何天白，胡汉杰．海外高分子科学的新进展．北京：化学工业出版社，1997．
[3] 沈峰，杨丽芳，等。智能水凝胶研究进展．材料研究学报，2000，14(1)：1-11．
[4] 刘晓华，王晓工，刘德山。智能型水凝胶结构及响应机理的研究进展，化学通报，2000，10：1-6．
[5] 余耀庭。生物医用材料，天津：天津大学出版社，2000．
[6] L Chen, Y Honma, T Mizutani, D- J Liaw, J P Gong, Y Osada. Effects of polyelectrolyte complexation on the UCST of zwitterionic polymer, Polymer, 2000, 41 : 141-147.
[7] 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，2001，6：1-5．_
[8] 王玉翠，陈莉。新型环境响应型高分子凝胶的研究，天津工业大学本科毕业论文，2003．
[9] 焦正，边立峰等。智能凝胶材料研究和发展现状，Sensor World，2006，6：1-7．
[10] Patience M, Genevena F. Macromolecules, 2000, 33(5): 1716.
[11] Hirokawa Y, Tanaka T. Volume phase-transition in a nonionic gel. J Chem Phys. 1984, 81(12): 6379-6380.
[12] 罗宣干，王坦。N-异丙基丙烯酰胺系温度敏感聚合物和水凝胶的研究进展，化学通报，1996，4：10-15．
[13] 王昌华，曹维孝。温敏水凝胶，化学通报，1996，1：33-35．
[14] Nagaoka N, Kubota H, Safrani A, et al. Synthesis of poly (N-isopropylacrylamide) hydrogels by radiation polymerization and crioss-linking. Macromolecules. 1993, 26(26): 7386-7391.
[15] 张先正，卓仁禧．快速温度敏感(N-异丙基丙烯酰胺-co-丙烯酰胺)水凝胶的制备及性能研究．高等学校化学学报．2000，21：1309-1311．
[16] 刘郁扬，范晓东，邵颖慧．N-异丙基丙烯酰胺／N-乙烯基吡咯烷酮水凝胶的研究．功能高分子学报．2000．13：380-385．
[17] Mingzhen W, Junchao Q, Yu E Preparation and propreties of chitosan-poly (N-isopropylacryamide) semi-IPN hydrogels. J Polym Chem. 2000, 38: 474-481.
[18] 耿奎士，方静，唐明义，等．热敏性互穿网络聚合物．化工新型材料。1996，(3)：16-21．
[19] 卓仁禧，张先正．温度及pH敏感聚(丙烯酸)／聚(N-异丙基丙烯酰胺)互穿聚合物网络水凝胶的合成及性能研究．高分子学报．1998．(1)：39-42．
[20] Wei Xue, Simon Champ, Malcolm B Huglin. New superabsorbent thermoreversible hydrogels. Polymer. 2001,42: 2247-2250.
[21] 杨大智．智能材料与智能系统．天津：天津大学出版社．2000，237-239．
[22] Wei Xue, Ian W Hamley. Thermoreversible swelling behavior of hydrogels based on N-isopropylacrylamide with a hydrophobic comonomer. Polymer. 2002, 43: 3069-3077.
[23] Dong L C, Hoffman A S. A novel-approach for preparation of PH-sensitive hydrogels for enteric drug delivery. J Controlled Release. 1991, 15(2): 141-152.
[24] Tatsuya Motonaga, Mitsuhiro Shibayama. Studies on PH and temperature dependence of the dynamics and heterogenities in poly (N-isopropylacrylamide-co-sodium acrylate) gels. Polymer. 2002, 42: 8925-8934.
[25] 王昌华，卢英先，曹维孝．阳离子型温敏水凝胶的合成和性质．高分子学报．1998，(2)：236-240．
[26] 陈莉，董晶，孟庆杰。阳离子型温敏水凝胶的溶胀性能及其对表面活性剂的吸附行为。应用化学，2003，4：328-331．
[27] Wei Xue, Simon Champ, Malcolm B Hugling. Thermoreversible swelling behavior of hydrogels based on N-isopropylacrylamide with zwitterionic comonomer. European Polymer Journal. 2001, 37: 869-875.
[28] Mingzhen W, Yu F, Daodao H. Preparation and properties of chitosan-poly (N-isopropylacrylamide) full-IPN hydrogels. Reactive & Functional Polymers. 2001, 48: 215-221.
[29] Wenfu Lee, Yingjou Chen. Studies on preparation and swelling properties of the N-isopropylacrylamide/chitosan semi-IPN and IPN hydrogels. Journal of Applied Polymer Science. 2001, 82: 2487-2469.
[30] Hee Kyung Ju, So Yeon Kim, Seon Jeong Kim. pH/temperature-responsive semi-IPN hydrogels composed of alginate and poly(N-isopropylacrylamide). Journal of Applied Polymer Science. 2002, 83:1128-1139.
[31] 张艳群，哈鸿飞．氯化钠相转变k-型卡拉胶/N-异丙基丙烯酰胺共混凝胶的辐射合成及性质研究．高分子学报．2001，4：485-488．
[32] 张先正，卓仁禧．温度敏感聚(N-异丙基丙烯酰胺)/聚(乙烯醇)水凝胶的制备及性能研究．高等学校化学学报．2000，21：1776-177
[33] 黄健，王晓琳，陈秀珍等。聚(N-异丙基丙烯酰胺)的体积相转变及在分离领域中的应用研究，高分子材料科学与工程，2001，17(6)：35-39．
[34] 周加祥，刘铮。生物分离技术与过程研究，化工进展，2000，6：38-41
[35] 金曼蓉，吴长发，张桂英等。聚N-异丙基丙烯酰胺类凝胶及其溫敏特性，高分子学报，1995，3：321-326．
[36] 詹劲，周蕊，刘铮．智能聚合物在生物分离工程中的应用现状与展望，精细化工，2001．18(9)：534-537
[37] I Y Galaev, B Mattiasson. 'Smart' polymers and what they could do in biotechnology and medicine, Tibtech, 1999, 17: 335-340.
[38] I Y Galaev, M N Gupta, B Mattiasson. Use smart polymer for separation, Chemtech, 1996, 12:19-24.
[39] Allan S Hoffman. 智能聚合物在医药与生物工程中的应用，高分通报，1995, 4:245-253.
[40] Simon Champ, Wei Xue, Malcolm B Hugling. A novel semi-automated apparatus to concentrate aqueous polymer solutions with a thermosensitive hydrogels, Polymer, 2001, 42: 6439-6445.
[41] B Yldz, B Isk, M.Ks. Synthesis of thermoresponsive N-isopropylacrylamide-Nhydroxymethl acrylamide hydrogels by redox polymerization. Polymer. 2001, 42: 2521-2529.
[42] Hee Kyung Ju, So Yeon Kim, Young Moo Lee. pH/temperature-responsive behaviors of semi-lPN and comb-type graft hydrogels composed of alginate and poly (N-isopropylacrylamide), Polymer, 2001, 42:6851-6857.
[43] Wensheng Cai, Ram B.Gupta. Fast-responding bulk hydrogels with Microstructure, Jouranl of Applier Polymer Science, 2002, 83: 169-178.
[44] Bronsted H, Hovgaard L, Simonsen L. Dextran hydrogels for colon-specific drug-delivery. 3. in-vitro and in-vivo degrandtion. STP Pharma Sci, 1995, 5: 60.
[45] 王芝祥，戴剑平，张培华等。无外相的葡聚糖凝胶的合成，离子交换与吸附，1992，8(1)：30-33．
[46] 王钒，宋国强，陈群等。交联烯丙基葡聚糖凝胶的合成及性能，高分子材料科学与工程，1997，13(1)：120-122．
[47] 王钒，宋国强，王忱等。悬浮聚合交联烯丙基葡聚糖微球的粒径分布，高校化学工程学报，1997，11(3)：327-330．
[48] W N E van Dijk-Wolthuis, J J Kettenes den Bosch, A van der Kerk-van Hoof. Synthesis, Characterization, and Polymerization of Glycidyl Methacrylate Derivatized Dextran, Macromolcules, 1995, 28:6317-6322.
[49] W N E van Dijk-Wolthuis, J J Kettenes den Bosch, A van der Kerk-van Hoof. Reaction of Dextran with Glycidyl Methacrylate: An Unexpected Transesterification, Macromolecules, 1997, 30:3411-3413.
[50] W N E van Dijk-Wolthuis, J J Kettenes den Bosch, A van der Kerk-van Hoof. A new class of polymerizable dextrans with hydrolysable groups: hydroxyethyl methacrylated dextran with and without oligolactate spacer, Polymer, 1997,38 (25): 6235-6241.
[51] H C Chiu, A T Wu, Y FLin. Synthesis and charaterization of acrylic acid-containing dextran hydrogels, Polymer, 2001, 42: 1471-1479.
[52] H C Chiu, Y F Lin, S H Hung. Equilibrium swelling of copolymerized acrylic acid-mathacrylated dextran networks: effects of pH and neutral salt, Macromolecules, 2002, 35: 5235-5242.
[53] H C Chiu, Y F Lin, Y H Hsu. Effects of acrylic acid on preparation and swelling properties of PH-sensitive dextran hydrogels, Biomaterials, 2002, 23:1103-1112.
[54] Kang Moo Huh, Yoshikazu Kumashiro,Yooru Ooya. New synthetic route for dextran graft copolymers containing thermoresponsive polymers, Polymer Jouranl, 2001, 33(1): 108-111.
[55] Motoichi Kurisawa, Nobuhiko Yui. Modulated degradation of dextran hydrogels grafted with poly(N-isopropylacrylamide-c0-N,N-dimethylacrylamide) in response to temperature, Macromol. Chem. Phys., 1998, 199:2613-2618.
[56] Moon Sik Shin, Hyung Seok Kang, Tae Gwan Park. Synthesis characterization of pH/temperature-sensitive hydrogels based on chitosan derivative, Polymer Bulletin, 2002, 47: 451-456.
[57] Yuyang Liu, Xiaodong Fan. Synthesis and characterization of pH- and temperature-sensitive hydrogel of N-isopropylacrylamide.cyclodextrin based copolymer, Polymer, 2002, 43: 4997-5003.
[2] 何天白，胡汉杰．海外高分子科学的新进展．北京：化学工业出版社，1997．
[3] 沈峰，杨丽芳，等。智能水凝胶研究进展．材料研究学报，2000，14(1)：1-11．
[4] 刘晓华，王晓工，刘德山。智能型水凝胶结构及响应机理的研究进展，化学通报，2000，10：1-6．
[5] 余耀庭。生物医用材料，天津：天津大学出版社，2000．
[6] L Chen, Y Honma, T Mizutani, D- J Liaw, J P Gong, Y Osada. Effects of polyelectrolyte complexation on the UCST of zwitterionic polymer, Polymer, 2000, 41 : 141-147.
[7] 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，2001，6：1-5．_
[8] 王玉翠，陈莉。新型环境响应型高分子凝胶的研究，天津工业大学本科毕业论文，2003．
[9] 焦正，边立峰等。智能凝胶材料研究和发展现状，Sensor World，2006，6：1-7．
[10] Patience M, Genevena F. Macromolecules, 2000, 33(5): 1716.
[11] Hirokawa Y, Tanaka T. Volume phase-transition in a nonionic gel. J Chem Phys. 1984, 81(12): 6379-6380.
[12] 罗宣干，王坦。N-异丙基丙烯酰胺系温度敏感聚合物和水凝胶的研究进展，化学通报，1996，4：10-15．
[13] 王昌华，曹维孝。温敏水凝胶，化学通报，1996，1：33-35．
[14] Nagaoka N, Kubota H, Safrani A, et al. Synthesis of poly (N-isopropylacrylamide) hydrogels by radiation polymerization and crioss-linking. Macromolecules. 1993, 26(26): 7386-7391.
[15] 张先正，卓仁禧．快速温度敏感(N-异丙基丙烯酰胺-co-丙烯酰胺)水凝胶的制备及性能研究．高等学校化学学报．2000，21：1309-1311．
[16] 刘郁扬，范晓东，邵颖慧．N-异丙基丙烯酰胺／N-乙烯基吡咯烷酮水凝胶的研究．功能高分子学报．2000．13：380-385．
[17] Mingzhen W, Junchao Q, Yu E Preparation and propreties of chitosan-poly (N-isopropylacryamide) semi-IPN hydrogels. J Polym Chem. 2000, 38: 474-481.
[18] 耿奎士，方静，唐明义，等．热敏性互穿网络聚合物．化工新型材料。1996，(3)：16-21．
[19] 卓仁禧，张先正．温度及pH敏感聚(丙烯酸)／聚(N-异丙基丙烯酰胺)互穿聚合物网络水凝胶的合成及性能研究．高分子学报．1998．(1)：39-42．
[20] Wei Xue, Simon Champ, Malcolm B Huglin. New superabsorbent thermoreversible hydrogels. Polymer. 2001,42: 2247-2250.
[21] 杨大智．智能材料与智能系统．天津：天津大学出版社．2000，237-239．
[22] Wei Xue, Ian W Hamley. Thermoreversible swelling behavior of hydrogels based on N-isopropylacrylamide with a hydrophobic comonomer. Polymer. 2002, 43: 3069-3077.
[23] Dong L C, Hoffman A S. A novel-approach for preparation of PH-sensitive hydrogels for enteric drug delivery. J Controlled Release. 1991, 15(2): 141-152.
[24] Tatsuya Motonaga, Mitsuhiro Shibayama. Studies on PH and temperature dependence of the dynamics and heterogenities in poly (N-isopropylacrylamide-co-sodium acrylate) gels. Polymer. 2002, 42: 8925-8934.
[25] 王昌华，卢英先，曹维孝．阳离子型温敏水凝胶的合成和性质．高分子学报．1998，(2)：236-240．
[26] 陈莉，董晶，孟庆杰。阳离子型温敏水凝胶的溶胀性能及其对表面活性剂的吸附行为。应用化学，2003，4：328-331．
[27] Wei Xue, Simon Champ, Malcolm B Hugling. Thermoreversible swelling behavior of hydrogels based on N-isopropylacrylamide with zwitterionic comonomer. European Polymer Journal. 2001, 37: 869-875.
[28] Mingzhen W, Yu F, Daodao H. Preparation and properties of chitosan-poly (N-isopropylacrylamide) full-IPN hydrogels. Reactive & Functional Polymers. 2001, 48: 215-221.
[29] Wenfu Lee, Yingjou Chen. Studies on preparation and swelling properties of the N-isopropylacrylamide/chitosan semi-IPN and IPN hydrogels. Journal of Applied Polymer Science. 2001, 82: 2487-2469.
[30] Hee Kyung Ju, So Yeon Kim, Seon Jeong Kim. pH/temperature-responsive semi-IPN hydrogels composed of alginate and poly(N-isopropylacrylamide). Journal of Applied Polymer Science. 2002, 83:1128-1139.
[31] 张艳群，哈鸿飞．氯化钠相转变k-型卡拉胶/N-异丙基丙烯酰胺共混凝胶的辐射合成及性质研究．高分子学报．2001，4：485-488．
[32] 张先正，卓仁禧．温度敏感聚(N-异丙基丙烯酰胺)/聚(乙烯醇)水凝胶的制备及性能研究．高等学校化学学报．2000，21：1776-177
[33] 黄健，王晓琳，陈秀珍等。聚(N-异丙基丙烯酰胺)的体积相转变及在分离领域中的应用研究，高分子材料科学与工程，2001，17(6)：35-39．
[34] 周加祥，刘铮。生物分离技术与过程研究，化工进展，2000，6：38-41
[35] 金曼蓉，吴长发，张桂英等。聚N-异丙基丙烯酰胺类凝胶及其溫敏特性，高分子学报，1995，3：321-326．
[36] 詹劲，周蕊，刘铮．智能聚合物在生物分离工程中的应用现状与展望，精细化工，2001．18(9)：534-537
[37] I Y Galaev, B Mattiasson. 'Smart' polymers and what they could do in biotechnology and medicine, Tibtech, 1999, 17: 335-340.
[38] I Y Galaev, M N Gupta, B Mattiasson. Use smart polymer for separation, Chemtech, 1996, 12:19-24.
[39] Allan S Hoffman. 智能聚合物在医药与生物工程中的应用，高分通报，1995, 4:245-253.
[40] Simon Champ, Wei Xue, Malcolm B Hugling. A novel semi-automated apparatus to concentrate aqueous polymer solutions with a thermosensitive hydrogels, Polymer, 2001, 42: 6439-6445.
[41] B Yldz, B Isk, M.Ks. Synthesis of thermoresponsive N-isopropylacrylamide-Nhydroxymethl acrylamide hydrogels by redox polymerization. Polymer. 2001, 42: 2521-2529.
[42] Hee Kyung Ju, So Yeon Kim, Young Moo Lee. pH/temperature-responsive behaviors of semi-lPN and comb-type graft hydrogels composed of alginate and poly (N-isopropylacrylamide), Polymer, 2001, 42:6851-6857.
[43] Wensheng Cai, Ram B.Gupta. Fast-responding bulk hydrogels with Microstructure, Jouranl of Applier Polymer Science, 2002, 83: 169-178.
[44] Bronsted H, Hovgaard L, Simonsen L. Dextran hydrogels for colon-specific drug-delivery. 3. in-vitro and in-vivo degrandtion. STP Pharma Sci, 1995, 5: 60.
[45] 王芝祥，戴剑平，张培华等。无外相的葡聚糖凝胶的合成，离子交换与吸附，1992，8(1)：30-33．
[46] 王钒，宋国强，陈群等。交联烯丙基葡聚糖凝胶的合成及性能，高分子材料科学与工程，1997，13(1)：120-122．
[47] 王钒，宋国强，王忱等。悬浮聚合交联烯丙基葡聚糖微球的粒径分布，高校化学工程学报，1997，11(3)：327-330．
[48] W N E van Dijk-Wolthuis, J J Kettenes den Bosch, A van der Kerk-van Hoof. Synthesis, Characterization, and Polymerization of Glycidyl Methacrylate Derivatized Dextran, Macromolcules, 1995, 28:6317-6322.
[49] W N E van Dijk-Wolthuis, J J Kettenes den Bosch, A van der Kerk-van Hoof. Reaction of Dextran with Glycidyl Methacrylate: An Unexpected Transesterification, Macromolecules, 1997, 30:3411-3413.
[50] W N E van Dijk-Wolthuis, J J Kettenes den Bosch, A van der Kerk-van Hoof. A new class of polymerizable dextrans with hydrolysable groups: hydroxyethyl methacrylated dextran with and without oligolactate spacer, Polymer, 1997,38 (25): 6235-6241.
[51] H C Chiu, A T Wu, Y FLin. Synthesis and charaterization of acrylic acid-containing dextran hydrogels, Polymer, 2001, 42: 1471-1479.
[52] H C Chiu, Y F Lin, S H Hung. Equilibrium swelling of copolymerized acrylic acid-mathacrylated dextran networks: effects of pH and neutral salt, Macromolecules, 2002, 35: 5235-5242.
[53] H C Chiu, Y F Lin, Y H Hsu. Effects of acrylic acid on preparation and swelling properties of PH-sensitive dextran hydrogels, Biomaterials, 2002, 23:1103-1112.
[54] Kang Moo Huh, Yoshikazu Kumashiro,Yooru Ooya. New synthetic route for dextran graft copolymers containing thermoresponsive polymers, Polymer Jouranl, 2001, 33(1): 108-111.
[55] Motoichi Kurisawa, Nobuhiko Yui. Modulated degradation of dextran hydrogels grafted with poly(N-isopropylacrylamide-c0-N,N-dimethylacrylamide) in response to temperature, Macromol. Chem. Phys., 1998, 199:2613-2618.
[56] Moon Sik Shin, Hyung Seok Kang, Tae Gwan Park. Synthesis characterization of pH/temperature-sensitive hydrogels based on chitosan derivative, Polymer Bulletin, 2002, 47: 451-456.
[57] Yuyang Liu, Xiaodong Fan. Synthesis and characterization of pH- and temperature-sensitive hydrogel of N-isopropylacrylamide.cyclodextrin based copolymer, Polymer, 2002, 43: 4997-5003.