摘要
壳聚糖(Chitosan)是虾、蟹和昆虫壳骨架中提取物甲壳素的脱乙酰产物,是自然界中唯一的碱性多糖。它来源丰富,是一种可再生的天然高分子材料。壳聚糖具有生物相容性好、易生物降解、无毒、环境友好等特性;壳聚糖及其衍生物有着广泛的用途,特别是在生物医学领域,可用作药物载体、人工软组织材料(如人工皮)等。壳聚糖富含羟基和氨基,通过改性可以得到特定的功能高分子材料。如引入羧基后可得到特殊的聚两性电解质的性能。本文通过三种改性方法,在壳聚糖中引入羧基,成功地制备了三种具有特殊pH和温度敏感性的智能水凝胶。
采用~(60)Co-γ射线和电子束对壳聚糖—丙烯酸混合水溶液辐照,制得了具有pH敏感性的壳聚糖(CS)/聚丙烯酸(PAAc)互穿网络水凝胶。该水凝胶在pH<4和pH>6的条件下溶胀较大,而在pH4至5之间的缓冲溶液中溶胀较小,具有明显的“酸”、“碱”双重敏感特性;采用反相乳液聚合法制备了CS/PAAC磁性水凝胶微球,通过溶胀吸附法将一种广谱抗癌药物—平阳霉素包埋于该磁性水凝胶微球,测定了其体外模拟药物释放的性能。动物实验结果表明,该磁微球在外磁场的作用下,能有效地进入肿瘤细胞的“靶区”,对肿瘤细胞的主动脉具有栓塞作用,同时具有药物缓释作用,对肿瘤细胞具有明显的疗效。
采用~(60)Co-γ射线对羧甲基壳聚糖(CMCS)和N-异丙基丙烯酰胺(NIPAAm)混合水溶液进行辐照,制得了具有温度和pH双重敏感性的聚N-异丙基丙烯酰胺(PNIPAAm)/CMCS半互穿网络水凝胶。该水凝胶将PNIPAAm温度敏感性的低临界溶解温度(LCST)由32℃提高到人体温度37℃以上,同时也大幅度提高了水凝胶的溶胀比;用考马斯亮蓝作为药物模型,研究了该共聚物水凝胶在不同温度下的药物释放性能。
采用丙酮酸对壳聚糖进行化学改性,通过丙酮酸的羰基基与壳聚糖的氨基反应生成Schiff碱化合物,再用NaBH_4进行还原,制备了聚两性电解质丙酮酸壳聚糖(PCS),然后采用聚乙二醇双缩水甘油醚为交联剂制得具有pH敏感性的丙酮酸壳聚糖(CPCS)水凝胶。该水凝胶显示出独特的酸碱两性响应性和良好的溶胀可逆性。
Chitosan is obtained by alkaline deacetylation of chitin from the shell of shrimp, crab and insects etc, is an alkaline polymer, one of the abundant and reproducible natural polymers in the world. Due to the biocompatibility, biodegradable, no toxicity and environmental friendship, chitosan and its ramifications are potentially be widely applied especially in biomedical applications such as in drug delivery system and artificial soft tissues and so on. Chitosan contains hydroxyl and ammoniac in its unit structure and a special kind of polar polymer could be obtained by the introduction of carbonyl group. Three kind techniques were used for introducing carbonyl group and three kind hydrogels with special pH sensitive were obtained in this paper.
~(60)Co γ-ray and electron beam was applied as irradiation source and the pH sensitive chitosan (CS)/poly acrylic acid (PAAc) was obtained by irradiating the solution mixture of chitosan (CS) and acrylic acid (AAc). The CS/PAAc hydrogel obtained in this experimental swelled in the conditions of pH<4 and pH>6, but de-swelled during the pH range of 4-5, which indicated that hydrogel is sensitive in both basic and acidic solution. The magnetic hydrogel microsphere (ferrogel) was synthesized by reversed emulsion polymerization. An anticancer drug, Bleomycin A5 Hydrochloride (BLM) is immobilized into the ferrogel by swollen adsorption and the experiments in vitro and in vivo were performed. The experiment result in vivo indicated that the ferrogel could be easily droved into the targeted area near the tumor by outside magnetic field. The function of embolism and slow release of drug were approved in vivo. An obvious effect of the BLM immobilized ferrogel was observed on the healing of explanted tumor.
Carboxyl methyl chitosan (CMCS)/poly-N-isopropylacrylamide (PNIPAAm) hydrogel was prepared by irradiating the aqueous solution mixture of Carboxyl methyl chitosan (CMCS) and N-isopropylacrylamide (NIPAAm) with ~(60)Co γ-ray. The swelling behavior was determined in the media of deionized water, different ionic strength solutions and different pH buffer solutions at different temperature, respectively. The results indicated that the low critical solution temperature (LCST) of the CMCS/PNIPAAm hydrogel could be increased above the 37℃ with the content of CMCS. On the other hand, the swelling ratio also much increased compared the homopolymer hydrogel of PNIPAAm. The drug delivery behavior of the CMCS/PNIPAAm hydrogel was studied by using Commas bright blue as the drug
引文
[1] 蒋挺大主编.甲壳素[M].北京:化学工业出版社,2003.
[2] 胡继飞.甲壳质及其衍生物的开发利用[J].生物技术,1994,(4):45-47.
[3] 俞继华,冯才旺,唐有根.甲壳素和壳聚糖的化学改性及其应用[J].广西化工,1997,26(3):28-32.
[4] 杨冬梅,缪进康,黄明智.天然生物材料——甲壳素和壳聚糖的开发及应用[J].化学工业与工程,1999,16(6):35-340.
[5] 董学畅,杨燕兵.甲壳素和壳聚糖应用研究新动向[J].云南民族学院学报(自然科学版),2002,11(1):566-571.
[6] Lili Shi, Liming Yang, Jie Chen, Yong Pei, Min Chen, Baojun Hui, Jian Li, Preparation and characterization of pH-sensitive hydrogei of chitosan/poly(acrylic acid) copolymer[J]. Journal of Biomaterials Science, Polymer Edition (JBSPE), 2004,15(4): 465-474.
[7] 施丽莉,杨黎明,陈捷,壳聚糖/聚丙烯酸共聚物微球的制备及性能[J].精细化工,2004年,21(11):47-50.
[8] 杨黎明,施丽莉,陈捷,电子束辐射法制备壳聚糖/聚丙烯酸水凝胶薄膜[J].化学世界,2004年,41(增刊):147-149.
[9] 蒋挺大.壳聚糖[M].北京:环境科学与工程出版社,2001.
[10] 施建军,丁明,高建峰,皇甫立霞,康玲,徐基安.壳聚糖羧甲基化改性的制备研究[J].安徽化工,1998,94:26-28.
[11] 肖振宇,原续波,盛京.甲壳素、壳聚糖的改性[J].广州化学,2002,27(2):60-64.
[12] Wan Ngah W.S., Endud C.S., Mayanar R., Removal ofcopper(Ⅱ) ions from aqueous solution onto chitosan and cross-linked chitosan beads[J]. Reactive & Functional Polymers, 2001, 50: 181-190.
[13] 傅民,陈妹,金鑫荣.壳聚糖对Fe~(2+)吸附作用的研究[J].化学世界,1998,(2):79-84.
[14] 许勇,洪华,钱颍,刘昌胜.医用壳聚糖膜的制备和性能研究[J].功能高分子学报,2004,17(1):55-60.
[15] 任静,哈鸿飞,聚两性电解质及其水凝胶的研究进展[J].高分子通报,2000,3:8-15.
[16] 冯梦凰,邓联东,张晓丽,董岸杰..聚乙二醇单甲醚接枝壳聚糖的合成与表征[J].化学工业与工程.2005,22(2):79-82.
[17] 许晨,卢灿辉,丁马太.壳聚糖季铵盐的合成及结构表征[J].功能高分子学报,1997,10(1):51-55.
[18] 张文清,柴平海,夏玮.NaOC1/H_2O_2协同氧化制备壳寡糖[J].华东理工大学学报.2000,26(4):425-428.
[19] 范国枝,水溶性壳聚糖的制备[J].应用化工,2004.33(5):29-30.
[20] 马宁,汪琴,孙胜玲,王爱勤.甲壳素和壳聚糖化学改性研究进展[J].化学进展,2004,16(4):643-651.
[21] 鲁从华.壳聚糖的改性及其应用[J].高分子通报,2001,6:46-50.
[22] 杨俊玲.甲壳索和壳聚糖的化学改性研究[J].天津工艺大学学报,2001,20(5):79-82.
[23] Tolaimate A., Desbrieres J., Rhazi M. et al., On the influence of deacetylation process on the physicochemical characteristics of chitosan from squid chitin[J]. Polym,2000, 41: 2463-2469.
[24] 蒋珍菊,王周玉,胡星琪.硫酸/氯磺酸混酸酯化壳聚糖的研究[J].化学研究与应用,2005,17(3):347-349.
[25] 许晶,周雪琴,姚康德,迟玮,刘东志.水溶性O-羟乙基壳聚糖的合成[J].化学研究与应用,2004,16(2):225-226.
[26] 黄增慰,黄道战.羧甲基壳聚糖防止硫酸钙水垢的性能研究[J].广西民族学院学报,自然科学版,2001,7(2):104~106.
[27] 余艺华,何炳林.甲壳素/壳聚糖的化学修饰[J].高分子通报,1997,4:232-237.
[28] 张永刚,左秀锦.甲壳素、壳聚糖及其衍生物的研究进展[J].大连大学学报,2000,21(4):52-60.
[29] 唐振兴,钱俊青,葛立军,何志平.甲壳素/壳聚糖的化学修饰及其研究进展[J].浙江化工,2003,34(7):4-6.
[30] 王爱勤,俞贤达,烷基化壳聚糖衍生物的制备与性能研究[J].功能高分子学报,1998,11(1):83-86.
[31] 叶筠,蔡伟民,沈雄飞.壳聚糖季铵盐的合成及其对炼油废水的絮凝和灭菌性能[J].福州大学学报(自然科学版)2000,28(4):18-22
[32] 董玉莲,肖锦.两性高分子水处理剂的研究现状与发展[J].化工进展,1999,(6):16-18.
[33] 臧庆达.两性高分子与小分子及大分子的相互作用(上)[J].高分子通报,1993,(3):151-154.
[34] 王周玉,蒋珍菊,李富生等.水溶性N-(2-羧基苯甲酰基)化壳聚糖的合成[J].化学研究与应用,2004,16(1):8-10.
[35] 单军,智能性高聚物水凝胶的种类及其合成方法[J].化工新型材料,1996,4:20-22.
[36] 夏彩芬,邢东阳,陈炳稔.交联壳聚糖的制备及其研究进展[J].化工时刊,2004,18(2): 25-27.
[37] 彭湘红,杜金平,王敏娟,甲基丙烯酸与壳聚糖接枝共聚物的制备及应用研究[J].精细化工.2000,17(3):137-139.
[38] 刘峥,蒋先民,壳聚糖与丙烯腈接枝共聚物的制备及固定化α—淀粉酶研究[J].离子交换与吸附,2001,17(3):262-265.
[39] 程建华,胡勇有,李泗清,壳聚糖接枝聚季铵盐的合成及调理性能[J].精细化工,2005,22(2):130-132.
[40] Sabina P.S., Kjell M.V., Interactions between chitosans and bacterial suspensions:adsorption and flocculation [J]. Colloids and Surfaces Biointerfaces, 2003, 27(3): 71-81.
[41] 陈捷,卢永畅,预辐射聚丙烯膜接枝甲基丙烯酸聚乙二醇酯及其性能研究[J].辐射研究与辐射工艺学报,1999,17(4):193-197.
[42] Chen J., Nho Y.C., and Park J.S., Grafting polymerization of acrylic Acid onto preirradiated polypropylene fabric[J]. Radiat. Phys. Chem., 1998, 52 (1): 201-206.
[43] Chen J., Wu W.B. et al., Grug carrying hydrogel base wound dressing[J]. Radiat. Phys. Chem., 1993, 42(4): 915-918.
[44] 陈捷,杨黎明,马瑞德.聚乙烯醇薄膜的辐射交联研究[J].上海科技大学学报,1994,17(3):267-271.
[45] Nho Y.C., Chen J. and Jin J.H., Grafting polymerization of styrene onto preirradiated polypropylene fabric[J]. Radiat. Phys. Chem. 1999, 54 (3): 317-322.
[46] 胡龙飞,杨伯伦,李福华,吴莹莹.改性壳聚糖渗透蒸发膜分离叔丁酵—水[J].应用化学,2005,22(1):5-8.
[47] 张高奇,查刘生,周美华,马敬红,梁伯润,海藻酸钠/聚(N异丙基丙烯酰胺)半互穿网络水凝胶的制备及性能研究[J].功能高分子学报,2004,17(1):40-45.
[48] 方军,黄继才,陈联楷等.壳聚糖.醋酸纤维素共混膜的制备及其渗透汽化性能[J].膜科学与技术,1997,17(5):60-65.
[49] Yuan Y., Zhang P.Y., Yang Y.M. et al., The interaction of Schwann cells with chitosan membranes and fibers in vivo [J]. Biomateriais, 2004, 25(18): 4273-4278.
[50] Li L.H., Zhou C.D., Preparation and application of the PLA/chitosan composite materials [J]. Journal of Applied Polymerscience, 2004, 91 (1): 274-277.
[51] Tolaimate A., Desbrieres J., Rhazi M. et al., Contribution to the preparation of chitins and chitosans with controlled physicochemical properties [J]. Polymer, 2003, 44(26): 7939-7952.
[52] Juang R.S., Wu F.C., Tsng R.L., Solute adsorption and enzyme immobilization on chitosan beads prepared from shrimp shell wastes[J]. Bioresour Technol, 2001, 80(3): 187-193.
[53] Erbeldinger M., Mesiano A.J., Russell A J. Enzymatic catalysis of formation of Z-aspartame in ionic liquid - an alternative to enzymatic catalysis in organic solvents[J]. Biotechnol Prog, 2000, 16: 1129-1131.
[54] Kim M.J., Choi M.Y., Lee J K. et al., Enzymatic selective acylation of glycosides in ionic liquids: significantly enhanced reactivity and regioselectivity [J]. J Mol Catal B:enzyme, 2003, 26 (3-6): 115- 118.
[55] SchO S. H., Kaftzik N., Wasserscheid P, et al. Enzyme catalysis in ionic liquids: lipase catalysed kinetic resolution of 1-phenylethanol with improved enantioselectivity [J].Chem Commun, 2001, 1: 425- 426.
[56] 张虎,杜昱光,壳聚糖酶的研究进展[J].化学通报,1999,(5):32-35.
[57] 陈天,张皓冰,叶秀莲,壳聚糖常温保鲜猕猴桃的研究[J].食品科学,1991,10:37-42.
[58] 乐培思,徐茂军,甲壳素膜对果蔬保鲜效果研究[J].食品科学,1991,12:57-60.
[59] 张声辉,壳聚糖衍生物果蔬保鲜剂的配制[P].中国,发明专利,94101978
[60] 魏涛,唐粉芳,高兆兰,壳聚糖降血脂、降血糖及增强免疫作用的研究[J].食品科学,2000,21(4):48-52.
[61] 张文清,柴平海,金鑫荣,应东飞,壳聚糖及其衍生物在化妆品中的应用[J].高分子通报,1999,2:73-76.
[62] 黄华芹,高洗,李文国,壳聚糖在纺织工业中的应用[J].针织工业,2003,2:126-127.
[63] 孙伟,夏春谷,王爱勤,壳聚糖希夫碱铜多相催化剂催化苯乙烯环丙烷化反应研究[J].化学学报,2002,60(1):162-165
[64] 刘蒲,王岚,刘一真,壳聚糖钯催化Heck 反应合成肉桂酸丁酯的研究[J].分子催化,2004,18(4):275-280
[65] 王昌文,壳聚糖开发应用及市场状况[J].江苏食品与发酵[J],2003,113:11-14
[66] 刘长岚,崔文新,李成彬,壳聚糖及其衍生物在化工方面应用的研究[J].山东师范大学学报(自然科学版),2003.18(13):98-102.
[67] 王春华,曲荣君,孙昌梅,纪春暖,周欣,成国祥,黄海兰,羧甲基壳聚糖/聚乙烯醇/甘油环氧树脂蛇笼型复合螯合膜的制备及对金属离子的吸附性能[J].离子交换与吸附,2004,20(6):494-500.
[68] 王岚,刘一真,刘蒲,王向宇.壳聚糖钯配位络合物的合成、表征及其催化性能研究[J].离子交换与吸附,2004,20(6):501-507.
[69] Ma Z.G., Gao J.G., Liu X.Y., Du B.A., Shan J.H., Shen S.G., Studies on the adsorption of Zn~(2+) for chitosan with high degree of deacetylation[J]. Chemical Journal on Internet, 2003, 5(11): 88-90.
[70] 莫健伟,姚兴东,张谷兰等,海藻去除水中双偶氮染料机理及重金属离子研究[J].中国环境科学,1997,17(3):241-243.
[71] 汪玉庭,程格,接枝羧基淀粉去除水体中有毒重金属离子的研究[J].环境污染与防治,1996,18(2):16-18.
[72] 祝巨,天然生物高分子絮凝剂的研究进展[J].浙江科技学院学报,2003,15(2):1-5.
[73] 徐鑫,王静,甲壳质和壳聚糖的开发及应用[J].哈尔滨工业大学学报,2002,34(1):95-101.
[74] Anseth K.S., Bownan C.X., Peppar D.B., (1996) Mechanical properties of hydrogels and their experimental determination. Biomaterials, 17:1647-1657.
[75] 张生大,陈梅莉,曹国建,壳聚糖在医学中的应用[J].医药导报,2002,5(21):53-57
[76] 曹健,陆锦芳.壳聚糖在生物大分子约物给药中的应用[J].中国医约工业杂志,2002,33(7):353-357.
[77] Wu M.H., B.R., Chen J., Xu Y.J., Zhou S.R., Ma Z.D., Preparation of thermosensitive hydrogel (PP-g-NIPAAm) with on-off switching for controlled release of drugs[J]. Radiation Physics and Chemistry, 1999, 56:341-346.
[78] Chen J., Yang L.M., Wu M.H., Xi Q., He S.M., Li Y.W., Nho Y.C., Preparation of interpenetrating polymer networks by two times grafting of monomers onto preirradiated polypropylene film[J]. Radiation Physics and Chemistry, 2000, 59: 313-316.
[79] RAJEEV A. Jain, The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide)(PLGA) devices[J]. Biomaterials, 2000, 21(23): 2475-2490.
[80] Feng Z, Yuji Y, William WL, et al. Preparation and histological evaluation of biomimetie three-dimensional hydroxyapatite/chitosan-gelatin network composite scaffolds [J]. Biomaterials, 2002, 23: 3227-3234.
[81] Chenite A, Chaput C, Wang D. et al., Novel injectable neutral solutions of chitosan form biodegradable gels in situ [J]. Biomaterials, 2000, 21: 2155-2161.
[82] Park Y.J., Lee Y.M., Lee J.Y. et al., Controlled release of platelet-derived growth factor-BB from chondroitin sulfate-chitosan sponge for guided bone regeneration[J]. J Control Release, 2000, 67: 385-394,
[82] 姚康德,成国祥,智能材料[M].北京:化学工业出版社,2002
[83] 何乃普,宋鹏飞,王荣民,张慧,王云普,甲壳素/壳聚糖及其衍生物抗菌、抗肿瘤活性研究进展[J].高分子通报,2004,3:14-18.
[84] 胡巧玲,钱秀珍,李宝强等.原位沉析法制备壳聚糖棒材的研究[J].高等学校化学学报,2003,24(3):528-531.
[85] 王中和,陆顺娟,胡海生等,低分子壳聚糖对癌症放疗患者免疫功能的影响[J].首都医科大学报,1997,18(1):80-82.
[86] 石明健,刘惟莞,王仁英,壳多糖免疫调节作用的实验观察[J].上海免疫学杂志,1999,(2):116-117.
[87] 魏涛,唐粉芳,高兆兰等,壳聚糖降血脂、降血糖及增强免疫作用的研究[J].食品科学,2000,(4):48-52.
[88] 丁明,施建军,皇甫立霞等,壳聚糖微球的制备研究[J].化学世界,1998,12:636-639.
[89] 王志国,张敏卿,邢爱华,杨林,壳聚糖在靶向制剂中的研究进展[J].化工进展,2004,23(4):374-379.
[90] 杨越冬,甲壳质/壳聚糖特性及其在农业中的应用[J].河北农业技术师范学院学报,1998,12(4):55-59.
[91] Freepons D., Enhancing food production with chitosan seed-coating technology In: Donald Freepsns(ed). Application of chitin and chitosan[M]. Lancaster: Teehnomie Publishing Company In, 1997: 129-139.
[92] 周天,胡永军,姜坤,郭继勋,壳聚糖对玉米种子萌发和幼苗生长的影响[J].吉林农业科学,2004,29(3):8-10.
[93] 王铁,张黎明.医用高分子水凝胶的设计与合成[J].功能高分子学报,2004,17(2):330-336.
[94] 翟茂林,哈鸿飞,水凝胶的合成、性质及应用[J].大学化学,2001,16(5):23-27.
[95] 任静,哈鸿飞,聚两性电解质及其水凝胶的研究进展[J].高分子通报.2000,3:8-15.
[96] 张侃等.环境敏感水凝胶的研究进展[J].广州化学,2001,26(4):46-54.
[97] Chen J., Nho Y.C., Kwon O.H., Hoffman A.S., Grafting copolymerization ofacrylamide onto preirradiated PP films[J]. Radiat. Phys. Chem. 1999, 55: 87-92.
[98] 毛津淑,王向辉,崔元璐,姚康德,透明质酸.壳聚糖-明胶复合体系对L929细胞凋亡和细胞周期的影响[J].科学通报,2003,48(9):917-920.
[99] 任广智,李振华,何炳林,磁性壳聚糖微球用于酶的同定化研究-Ⅲ.磁性壳聚糖微球的活人及其对脲酶的固定化研究[J].离子交换与吸附,2001,17(2):152-158.
[100] Nabi Saheb D, Jog J.P., Natural fiber polymer composites:A Review [J]. Advancesin Polymer Technology, 1999, 18(4) 351-357.
[101] Chen J., Nho Y.C., Kwon O.H., and Hoffman A.S., Grafting coplymerization of polyethylene glycol methacry-late (PEGMA) onto preirradi-ated PP films,[J] Journal of Radio Analytical and Nuclear Chemistry, 1999, 24 (3): 943-948.
[102] 黄荣华,杜予民,陈凌云,樊李红,孙立苹,pH值对壳聚糖/羧甲基壳聚糖水凝胶溶胀行为的影响[J].武汉大学学报(理学版)2003,49(4):465-469.
[103] Mi F.L., Shyu S.S., Chen C.T. et al., Porous Chitosan Microsphere for Controlling the Antigen Release of Newcastle Disease Vaccine: Preparation of Antigen-adsorbed Microsphere and in Vitro Release [J]. Biomaterials, 1999, 20(17): 1603- 1612.
[104] 肖慧.刘兆民,环境敏感性水凝胶的制备和应用[J].上海大学学报(自然科学版),2003,9(1):67-72.
[105] 刘锋,卓仁禧,温度及pH敏感水凝胶的合成及其在生物大分子控制释放中的应用[J].高分子材料科学与工程,1998,14(2):54-62.
[106] Sanjeeb Kumar Sahho,Tapas K. De, P K Ghosh. pH—and thermo—sensitive hydrogel nanoparticles[J]. J Colloidand Interfaces Science,1998, 206:361—368.
[107] Wu M.H., Bao B.R., Chen J., Study on antithrombosis dialytic membrane prepared by preirradiatiion grafting [J]. Journal of Applied Polymer Science, 2000, 78: 1321-1327.
[108] Chen J., Yang L.M., Wu M.H., Nho Y.C., Grafting copolymerization of styrene and acrylic acid onto pre-irradiated polypropylene fabric[J]. Journal of Shanghai University, 2000, 1.4: 173-177.
[109] 李亦文,陈捷,智能水凝胶膜的及体外细胞相容性研究[J].上海第二医科大学学报,1997,17(4):293-295
[110] Liu Y.M., Yang Y.Q., Chen J., Ma Z.T., Study on the Kinetics and Influence Factors of Radiation Synthesis Hydrogel Material[J]. Radiat. Phys. Chem., 1990, 35 (1): 122-125.
[111] Richardson S. C. W, Kolbe H. V. J, Duncan R., Potentialof Low Molecular Mass Chitosan as a DNA Delivery System: Biocompatibility, Body Distribution and Ability to Complex and Protect DNA [J]. Intern J Pharmaceutics, 1999,178 (2) :231-243.
[112] Peniche C., Waldo A. M., Natalia D. K, et al. SelfCuringMembranes of Chitosan/PAA IPNs Obtained by Radical Polymerization : Preparation, Characterization and Interpolymer Complexation [J]. Biomaterials, 1999, 20(20):1869-1878.
[113] Nho Y.C., Kwon O.H. and Chen J., Introduction of phosphoric acid group to polypropylene film by fadiation grafting and its blood compatibility, Radiation Physics and Chemistry[J]. 2002, 64: 67-75.
[114] Kwon O.H., Nho Y.C. and Chen J., Surface Modification of Polypropylene Film by Radiation-Induced Grafting and Its Blood Compatibility[J]. J. of Applied Polymer Science, 2003, 88: 1726-1736.
[115] Wu M.H., Chen J., Qian Q. and Bao B.R., Thermo-responsive interpenetrating polymer networks composed of AAc/AAm/NMA by radiation grafting[J]. Journal of Applied Polymer Science, 2002, 252(3): 531-535.
[116] Chen J., Yang L.M., Chen L.Q., Wu M.H., Nho Y.C., Kaetsu I., An interesting grafting reactivity of EB preirradiated polypropylene film[J]. Radiation Physics and Chemistry, 2004, 69 (2): 149-154.
[117] Chen J., Nho Y.C. and Hoffman A.S., Grafting copolymerization of 2-meth-acryloyloxyethyl phosphhorylcholine (MPC) onto pre-irradiated cellulose films[J]. Journal of Biomaterial Science, Polymer Edition (JBSPE), 2004, 15(7): 841-849.
[118] Hui B.J., Chen J., Yang L.M., Li J., Pei Y., and Shi L.L., Preparation of pH sensitive hydrogel by two times grafting of acrylamide and acrylic acid onto preirradiated polyethylene film[J]. Journal of Radio Analytical and Nuclear Chemistry, 2004, 260(3): 673-677.
[119] Pei Y., Chen J., Yang L.M., Shi L.L., Tao Q., Hui B.J., and Li J., The effect of pH on LCST of Poly(N-isopropylacrylamide) and Poly(N-isopropylacrylamide-co-acrylic acid) [J]. Journal of Biomaterial Science, Polymer Edition, 2004, 15(5): 585-594.
[120] Shi L.L., Yang L.M., Chen J., Pei Y., Chen M., Hui B.J. and Li J., Preparation and characterization of pH-sensitive hydrogel of chitosan/poly(acrylic acid) copolymer[J]. Journal of Biomaterial Science, Polymer Edition, 2004, 15(4): 465-474.
[121] Wang Hart-ling, Li Wen-jun, Lu Yin, et al. Studies on Chitosan and Poly(Acrylic Acid) Interpolymer Complex. Ⅰ. Preparation, Structure, pH-sensitivity and Salt Sensitivity of Complex Forming Poly (Acrylic Acid): Chi2tosan Semi2interpenetrating Polymer Network[J]. J A ppl. Polym. Sci., 1997,65 (8): 1445-1450.
[122] 张先正,卓仁禧,快速温度敏感聚(N-异丙基丙烯酰胺-co-丙烯酰胺)水凝胶的制备及性能研究[J].高等学校化学学报,2000,21(8):1309-1311.
[123] 高青雨,张玉娟,俞贤达,温度及pH敏感性N-乙烯基吡咯烷酮与丙烯酸B-羟基丙酯共聚物/聚(丙烯酸)互穿网络水凝胶的合成及其性能研究[J].高分子学报,2001,3:329-332.
[124] Mun G.A., Suleimenov I.E. and Nurkeeva Z.S. et al., Effect of the structural inhomogeneity of polyelectrolyte gels on their thermal sensitivity[J]. Polymer Science, 1998, 40(3): 253-259.
[125] Galaev I.Y. and Mattiasson B., Thermoreactive water-soluble polymers, nonionic surfactants, and hydrogels as reagents in biotechnology[J]. Enzyme Microb. Technol., 1993, 15: 354-366.
[126] Park T.G., Stabilization of Enzyme Immobilized in Temperature-Sensitive Hydrogels[J]. Biotechnology Letters, 1993, 15(1): 57-60.
[127] Mun G.A., Suleimenov I.E. and Nurkeeva Z.S. et al., Effect of the Structural Inhomogeneity of Polyelectrolyte Gels on Their Thermal Sensitivity[J]. Polymer Science, 1998, 40(3): 253-259.
[128] 萧聪明,何月英,吴宏.海藻酸钙水凝胶小球与丙烯腈的接枝共聚改性[J].应用化学,2004,21(5):535-537.
[129] 王胜林,王强斌,古宏晨,磁性微球的生物医学应用研究进展[J].化学世界,2001,7:384-386.
[130] 王云普,袁昆,李全莲,顾生玖.可生物降解的pH敏感水凝胶的合成及其溶胀性能研究[J].功能高分子学报,2004,17(4):586-590.
[131] Chung J. E., Yokoyama M. and Okano T., Inner core segment design for drug delivery control of thermo-responsive polymeric micelles[J]. J Control Release, 2000, 65:93 -103.
[132] 郭兴林,谢琼丹,赵宁,梁松苗,王笃金,徐坚,仿生高分子的研究进展[J].化学进展,2004,16(6):1023-1029.
[133] Musale D.A. and Kumar A., Effects of surface crosslinking on sieving characteristics of chitosan/poly(acrylonitrile) composite nanofiltration membranes[J]. Separation and Purification Technology, 2000, 21:27-38
[134] Risbud M.V, Hardikar A.A., Bhat S.V. and Bhonde R.R., pH-sensitive freeze-dried ehitosan-polyvinyl pyrrolidone hydrogels as controlled release system for antibiotic delivery[J]. Journal of Controlled Release, 2000, 68:23-30
[135] Genta I., Costantini M., Asti A. and Conti B., Luisa Montanari Influence of glutaraldehyde on drug release and mucoadhesive properties of chitosan mierospheres. Carbohydrate Polymers, 1998, 36: 81-88.
[136] Chiou M.S. and Li H.Y., Adsorption behavior of reactive dye in aqueous solution on chemical cross-linked chitosan beads. Chemosphere, 2003, 50:1095-1105.
[137] 胡博路,杭瑚,李永安,新型敏感性水凝胶的研究—Ⅰ.聚合条件对水凝胶溶胀性能的影响[J].青岛大学学报,1998,11(4):68-71.
[138] 刘晨光,刘成圣,孟祥红,陈西广,刘万顺,壳聚糖作为药物缓释材料的研究进展[J].高科技通讯,2003,3:98-102.
[139] 辛嘉英,张复升,沈思远,一种壳聚糖免疫缓释微球的制备方法[J].甘肃科学学报,1997,9(1):63-65.
[140] 唐明义,耿奎士,巩运兰,壳聚糖在缓释制剂中的应用[J].国外医药,2002,23(6):370-372.
[141] 徐蔚,曹毅,张纪,壳聚糖微球释药机制的研究[J].昆明医学院学报,2002,(1):7-10.
[142] 蒋新宁,周春山,邓晔,壳聚糖载药微球的研制[J].常德师范学院学报(自然科学版),2003,15(1):36-39.
[143] 曹健,陆锦芳,壳聚糖在生物大分子药物给药中的应用[J].中国医药工业杂志,2002,33(7):353-357.
[144] Ahn J.S., Choi H.K. and Cho C.S., A novel mucoadhesive polymer prepared by template polymerization of acrylic acid in the presence ofchitosan[J]. Biomaterials, 2001, 22: 923-928.
[145] Chena S.C., Wua Y.C., Mib F.L., Lina Y.H., Yua L.C. and Sunga H.W., A novel pH-sensitive hydrogel composed of N,O-carboxymethylchitosan and alginate cross-linked by genipin for proteindrug delivery[J]. Journal of Controlled Release, 2004, 96:285- 300
[146] 龚剑萍,智能型凝胶,见:海外高分子科学的新进展[M].何天白,胡汉杰编.北京:化学工业出版社,1997,174.
[147] 刘文辉,刘晓亚,陈明清,杨成,倪忠斌,壳聚糖基生物医用材料及其应用研究进展[J].功能高分子学报,2001,14(4):493-498
[148] 张胜,吴汉江,凌天牖,平阳霉素磁性微球的制备及特性检测[J].湖南医科大学学报,2003,28(2):191-193.
[149] 林赴田,李恭才,顾建章等,平阳霉素的抗肿瘤作用与临床前药理研究[J].中华肿瘤杂志,1997,19(3):161-161.
[150] 胡晓光,李德伦,平阳霉素磁性微球靶向治疗的实验研究[J].口腔颌面外科杂志,1997,7(2):105-108.
[1] Needleman I.G., Smales F.C., In vitro assessment of bioadhesion for periodontal and buccal drug delivery[J]. Biomaterials, 1995, 16: 617-624.
[2] Choi H.K., Kim O.J., Chung C.K., Cho C.S., A novel mucoadhesive polymer prepared by template polymerization of acrylic acid in the presence ofpoly(ethylene glycol)[J]. J. Appl. Polym. Sci., 1999, 73: 2749-2754.
[3] Ahn JS, Choi HK, Chun MK, Ryu JM, Jung JH, Kim YK, Cho CS. Release oftriamcinolone acetonide from mucoadhesive polymer composed of chitosan and poly(acrylic acid) in vitro[J]. Biomaterials, 2002, 23:1411-1416
[4] 李文俊,王汉夫,卢玉华,汪志亮,钟伟,壳聚糖·聚丙烯酸配合物半互穿聚合物网络膜及其对pH和离子的刺激响应[J].高分子学报,1997,1:109-113
[5] Paloma M., Torte D., Enobakhare Y., Torrado G., Torrado S.. Release of amoxicillin from polyionic complexes of chitosan and poly(acrylic acid). Study of polymer/polymer and polymer/drug interactions within the network structure[J]. Biomaterials, 2003, 24:1499-1506.
[6] Susana T., Pablo P., Paloma M. de la Torre, Santiago Torrado. Chitosan- poly(acrylie) acid polyionic complex: in vivo study to demonstrate prolonged gastric retention[J]. Biomateriais, 2004, 25: 917-923.
[7] Nam S. Y., Lee Y. M., Pervaporation and properties of chitosan-poly(acrylic acid) complex membrane[J]. Journal of Membrane Science, 1997, 135:161-171.
[8] 施艳荞,陈观文.壳聚糖/聚丙烯酸聚电解质复合物膜对水/有机液体系的渗透汽化性能[J].功能高分子学报,1998,11(3):385-391
[9] Peniche C. W., Davidenko A. M., Sastre R., Oallardo A. and Roman J.S., Self-curing membranes of chitosan/PAA IPNs obtained by radical polymerization: preparation, characterization and interpolymer complexation[J]. Biomaterials, 1999, 20:1869-1878.
[10] Sivakumar M., Manjubala I., Panduranga Rao K.. Preparation, characterization and in-vitro release of gentamicin from corailine hydroxyapatite-chitosan composite microspheres[J]. Carbohydrate Polymers, 2002, 49:281-288.
[11] Jameela S.R., Kumary T.V., Lal A.V., Jayakrishnan A., Progesterone-loaded chitosan microspheres:a long acting biodegradable controlled delivery system[J]. Journal of Controlled Release, 1998, 52:17-24.
[12] Abd E1-Hameed M.D., Kellaway I.W.. Preparation and in vitro characterization of mucoadhesive polymeric microspheres as intra-nasal delivery systems[J]. European Journal of Pharmaceutics and Biopharmaceutics, 1997, 44: 53-60.
[13] Antonio J. Ribeiro, Ronald J. Neufeld, Philippe Amaud, Jean C. Chaumeil.
[15] 刘利萍,李苹,吴泽志,蔡绍皙.肺靶向利福平壳聚糖磁微球的构建[J].化学世界,2003,4:200-203.
[16] Carreno-Gomez B., Duncan R.. Evaluation of the biological properties of soluble chitosan and chitosan microspheres[J]. International Journal of Pharmaceutics, 1997, 148: 231-240.
[17] Fwu-Long M, Chih-Yang K, Shin-Shing S, Sung-Tao L, Shon-Foun C. The study ofgelation kinetics and chain relaxation properties of glutaraldehyde-cross-linked chitosan gel and their effects on microspheres preparation and drug release[J]. Biomaterials, 2002, 41:389-396.
[18] Tokumitsu H, Ichikaw A. H, Fukumor I. Y. Chitosan-gadopentetie acid complex nanoparticles for gadolinium neutron-capture therapy of cancer: preparation by novel emulsion-droplet coalescence technique and characterization[J]. Pharm. Res., 1999, 16(12): 1830-1835.
[19] Mi F. L., Wang T. B., Shyu S. S., Chang S.F., Chitosan microspheres: modification of polymeric them-physical properties of spray-dried microspheres to control the release of antibiotic drug[J]. Journal of Applied Polymer Science, 1999, 71: 747-759.
[20] Hu Y., Jiang X., Ding Y., Ge H., Yuan Y., Yang C. Z., Synthesis and characterization of chitosan-poly(acrylic acid) nanoparticles[J]. Biomaterials, 2002, 23:3193-3201.
[21] 姚康德,成国祥 主编[M]智能材料.北京:化学工业出版社,2002.
[22] Sea M., Vzun C. A saftany changing of network characteristics of acrylamidel maleic acid hydrogels by alteration of irradiation dose rate. [J]. Radiation physics and chemistry, 2003, 67: 371-374.
[23] Shantha K. L., Bala U., and Panduranga K. RAO. Tailor-made chitosans for drug delivery[J]. Eur. Polym. J., 1995, 31(4):377-382
[24] Jin JJ, Chen GC, Huang MY, Jiang YY(1994) Catalytic hydrogenation behavious of palladium complexes of chitosan-polyacrylic acid and chitosan-polymethacrylic acid. Reactive Polymers, 23:95-100.
[25] 吴季兰,戚生初主编[M]辐射化学.北京:原子能出版社,1993
[26] Osada Y. and Khokhlov A. R., Polymer gels and networks [M]. New York: Marcel Dekker, 2002.
[27] Tanaka T,, Kinetics of phase transition in polymer gels [J]. Physica 1986, 140A: 261-268.
[28] Matsuo E. S. andTanaka T., Kinetics of discontinuous volume-phase transition of gels [J]. J. Chem. Phys. 1988, 89 (3): 1695-1703.
[29] Khokhlov A. R. and Kramarenko E. Y., Weakly charged polyelectrolytes: collapse induced by extra ionization [J]. Macromolecules 1996, 29: 681-685.
[30] Kaneko Y., Yoshida Ryo and Okano T., Temperature-responsive shrinking kinetics of poly(N-isopropylacrylamide) copolymer gels with hydrophilic and hydrophobic comonomers [J]. J. Membrane Sci., 1995, 101: 13-22.
[31] 郑根健,周嘉秀,李德伦等.平阳霉素磁控缓释微球的制备.华西口腔医学杂志,1996,14(3):220-222.
[32] Horak D., Rittich B., Safar J., et al. Properties of RNase A immobilized on magnetic Poly(2-hydroxyethyl methacrylate) micropheres. Biotechnol Prog 2001, 17(3): 447-452.
[1] 王海青,高忠良,羧甲基壳聚糖的制备及应用现状[J].中国食品添加剂,2002,6:68-71.
[2] 刘瑾,唐梓进,羧甲基壳聚糖对口腔变形链球菌和口腔乳酸杆菌的抑制作用[J].南京师大学报自然科学版,1999,22(4):73-76.
[3] 李治,刘晓非,管云林,O—羧甲基壳聚糖抗菌性的研究[J].日用化学工业,2000,30(3):10-11.
[4] 陈凌云,杜予民,刘义,羧甲基壳聚糖的结构与抗菌性能研究[J].武汉大学学报自然科学版,2000,46(2):191-194.
[5] 刘秉涛,姜安玺,羧甲基壳聚糖处理染料废水的正交试验研究[J].工业水处理,200525(2):23-25.
[6] 刘万顺,贺君,韩宝芹等,羧甲基壳聚糖在治疗胃炎、胃溃疡中的应用[P].国家发明专利,申请号01107718.2.
[7] Li Q., Dunn E. T., Grandmaison E.W. et al., Application and properties of chitosan [J]. Journal of Bioactive and Compatible Polymers, 1992, (7): 371~397.
[8] Muzzarelli R.A., Chitosan and its derivatives[J]. Carbohydrate Polymers, 1983, (3): 53~75.
[9] 师素云,薛启汉,壳聚糖对玉米的生长调节作用[J].大然产物研究与开发,1999,11,(2):32-36.
[10] 夏文水,吴炎楠,甲壳素酶研究现状[J].生物工程进展,2000,20,(5):12~15.
[11] 张秋华,唐小琪,羧甲基壳聚糖处理印染废水试验[J].环境污染与防治,1995,17,(5):7~9.
[12] 孙立苹,杜予民,陈凌云,黄荣华,陈效,羧甲基壳聚糖水凝胶制备及其在药物控释中的应用[J].高分子学报,2004,2:191-195.
[13] 马晓梅,赵喜安,唐小真,智能水凝胶[J].化学通报,2004,2:117-123.
[14] Mun G. A., Suleimenov I.E. and Nurkeeva Z.S. et al., Effect of the Structural Inhomogeneity of Polyelectrolyte Gels on Their Thermal Sensitivity [J]. Polymer Science, 1998, 40(3): 253-259.
[15] Lee W. F. and Chiu R.J., Thermoreversible hydrogel: ⅩⅤⅡ Investigation of the drug release behavior for [N-isopropylacrylamide-co-trimethyl acrylamidopropyl ammonium iodide-co-3-dimethyl (methacryloyloxyethyl) ammonium propane sulfonate] copolymeric hydrogels [J]. J Appl Polym Sci., 2002, 86: 1592-1598.
[16] Kono K., Yoshino K. and Takagishi T., Effect of poly (ethylene glycol) grafts on temperature-sensitivity of thermosensitive polymer-modified liposomes [J]. J Control Release, 2002, 80: 321-332.
[17] Xu S.Q, Zhang J.G. and Paquet C. et al. From hybrid microgels, to photonic crystals[J]. Adv Funct Mater, 2003, 13: 468-472.
[18] Kim D.J., Heo J.Y. and Kim K.S et al., Formation of themoresponsive poly (N-isopropylacrylamide)/dextran particles by atom tranafer radical polymerization [J]. Macromol Rapid Commun, 2003, 24:517-521.
[19] Zha L.S, Zhang Y., Yang W.L, et al. Monodisperse temperature-sensitive microcontainers[J]. Adv. Mater., 2002, 14: 1090-1093.
[20] Uguzdogan E., Kayi H., Denkbas E.B., et al., Stiuli-responsive properties of aminophenylboronic acid-carrying thermosensitive copolymers [J]. Polym Int, 2003, 52: 639-657.
[21] Zhu L.Y., Zhu G.L. and Li M.Z. et aI.Thermosensitive aggregates self-assembled by an asymmetric block copolymer of dendritic polyether and poly(N-isopropylacrylamide)[J]. Eur Polym J., 2002, 38: 2503-2506.
[22] Yoshida R., Uchida K., Kansko Y., Soksi K., Kikuohi A., Sakuhal Y. and Okano T., Comb-type gralled hydrogels with rapid de-swelling response to temperature changes[J]. Nature, 1995, 374(16): 240-242.
[23] Hirose H S,Hibayama M.Kinetics of Volume phase Transition in Poly(Nisopropylacrylamide-co-acrylic acid) Gels[J]. Macromolecules, 1998, 31: 5336-5342.
[24] Zhang X.Z. and Zhuo R.X., A novel method to prepare a fast responsive, thermosensitive poly(N-isopropylaerylamide) hydrogel[J].Macromol Rapid Commun, 1999, 20:229-231.
[1] 北京大学生命科学学院编写组,生命科学导论[M].北京,高等教育出版社,2000.
[2] 闫征,王昌禄,顾晓波,丙酮酸对细菌L-乳酸发酵的促进作用[J].氨基酸和生物资源,2003,25(2):21-23.
[3] 张方,迟伟,金成哲,王强,张其德,吴乃虎,高粱C4型磷酸烯醇式丙酮酸羧化酶基因的分子克隆及其转基因水稻的培育[J].科学通报,2003,48(14):1542-1546.
[4] 马全红,高永红,邹宗柏,丙酮酸壳聚糖衍生物的制备及其吸附性能的研究[J].东南大学学报(自然科学版)2000,30(6):127-131
[5] Dufes C., Schatzlein A.G., Tetley L. et al., Niosome and polymeric chitosan based vesicles bearing transferrin and glucose ligands for drug targeting [J]. Pharm Res, 2000, 17 (10): 1250-1258.
[6] 汪玉庭,刘玉红,张淑琴,甲壳素、壳聚糖的化学改性及其衍生物应用研究进展[J].功能高分子学报,2002,(1):107-114.
[7] 邵键,杨字民,香草醛改性壳聚糖的制备及其吸附性能[J].中国环境科学,2000,(1):61-64.
[8] 马宁,汪琴,孙胜玲,王爱勤,甲壳素和壳聚糖化学改性研究进展[J].化学进展,2004,16(4):643-653.
[9] 陶国良,陈震华,卓仁禧,磺化羟丙基壳聚糖凝胶的研制及其功效[J].功能高分子学报,1989,2(2):11-118.
[10] 郑立,陈西广,刘万顺,韩笑天,严小军,羧甲基壳聚糖膜对皮肤成纤维细胞相容性研究[J].生物化学与生物物理进展,2003,30(2):314-321.
[11] Wan Ngah W.S., Endud C.S., Mayanar R., Removal of copper(Ⅱ) ions from aqueous solution onto ehitosan and cross-linked ehitosan beads[J]. Reactive & Functional Polymers, 2002, 50: 181-190.
[12] Heras A., Rodriguez N.M., Ramos V.M., and E.Agullo,N-methylene phosphonic chitosan:a novel soluble derivative[J]. Carbohydrate Polymers, 2001, 44: 1-8.
[13] Holme K.R, Perlin A.S, Chitosan N-sulfate. A water-soluble polyelectrolyte[J]. Carbohydrate Research, 1997, 302:7-12.
[14] Heras A., Rodriguez N.M., Ramos V.M., Agullo E., N-methylene phosphonic chitosan: a novel soluble derivative[J], carbohydrate Polymers, 2001,44: 1-8.
[15] Majeti N.V. and Kumar R., A review of chitin and chitosan applications[J]. Reactive & Funetional Polymers, 2000, 46: 1-27.
[16] Chen X.G. and Park H. J., Chemical characteristics of O-carboxymethyl chitosans related to the preparation conditions[J]. Carbohydrate Polymers, 2003, 53: 355-359.
[17] 蒋珍菊,王周玉,冯冬,水溶性N-(2-羧基苯甲酰基)化壳聚糖等电点的测定[J].应用化工,2005,34(4):245-247.