乳液模板法多孔海藻酸钙凝胶微球的制备研究
摘要
乳液模板法是近年来发展起来的一种制备多孔材料的方法。用乳液模板法制孔可以精确控制孔的大小和分布。目前乳液模板法多用于无机多孔材料的制备，关于乳液模板法制备多孔天然聚合物材料的研究较少。
海藻酸钠是一种从海藻中提取的天然多糖聚合物，具有良好的生物相容性和可降解性，价格低廉，近年来在生物医学领域应用十分广泛。
本论文对反相悬浮交联法海藻酸钙凝胶微球的制备、乳液模板体系的确定、模板物在海藻酸钙凝胶中的存在状态以及模板物撤离后材料的形貌进行了较为详细的考察和总结。用表面张力仪和粒度测试仪对乳液进行了表征，用光学显微镜和扫描电镜观察了海藻酸钙凝胶的形貌。
结果表明，用反相悬浮交联法制备海藻酸钙微球，分散介质的用量、海藻酸钠水溶液的浓度、搅拌速度以及分散剂的种类和用量等都会影响微球的形貌。对于本体系，分散介质和分散相的体积比不能小于2:1；海藻酸钠的浓度应控制在2％－3.5%之间；要得到具有良好球形的海藻酸钙凝胶粒子，搅拌速度应控制在300r/min－450r/min之间；用Span85&Span80表面活性剂和PVP作为微球制备的悬浮分散剂，通过调节其用量，可以得到不同尺度、均一而规整的海藻酸钙微球。
对乳液表面张力的测试结果表明，制备均一稳定的石蜡/Span85&Tween60/海藻酸钠乳液，最佳的HLB值为12.3，乳化剂含量以70－110％为宜，乳化时间应控制在60min左右。观察由乳液制得的海藻酸钙凝胶膜中模板物的存在状态，认为甲苯和十二醇不适合作为本实验乳液模板体系的分散相，而液体石蜡适合作为制备多孔海藻酸钙凝胶的模板；调节乳化剂和液体石蜡的用量可以控制模板物石蜡在凝胶中的分布和液滴的大小。用扫描电镜观察脱除模板的干态凝胶，可以观察到凝胶膜的表面有尺寸均一的球形孔存在；在干态凝胶微球的表面和断面上也观察到很多微孔。
Emulsion templating technique is a newly developed method for producing highly monodispersed porous materials. Most of its applications focused on the fabrication of inorganic porous materials. Little study was directed to form porous materials based on natural polymers via emulsion templating technique.
Sodium alginate derived from brown sea algae is an anionic linear polysaccharide. It is biocompatible, biodegradable and relatively economical, and has been much used in biomedical field in recent years.
In this thesis, the preparation of calcium alginate microspheres through inverse suspension-crosslinking method, the parameter choosing of emulsion templating system, the state of templates in alginate gels and the morphology of the obtained materials were investigated in detail. The emulsion and calcium alginate gels were characterized by surface tension test, particle size and size distribution test, optical microscope and SEM, etc.
The results showed that the relative amount of dispersing medium, the concentration of sodium alginate solution, the stirring rate, the dispersant and its quantity were all the factors influencing the preparation of alginate microspheres by inverse suspension-crosslinking method. The volume ratio of dispersing medium to dispersed phase should not be less than 2:1. The concentration of sodium alginate solution should be controlled in the range of 2%－3.5%. Stirring rate between 300r/min and 450r/min was necessary for good spherical particles. Using suitable quantity of Span85&Span80 and PVP as dispersants could lead to microspheres with uniform size.
The emulsion surface tension tests showed that for a relatively stable emulsion based on liquid paraffin, Span85&Tween60 and sodium alginate solution, the optimal HLB, the content of surfactants were 12.3, 70－110% respectively, and the proper emulsification time was about 60min. The observation of templates in alginate gels indicated that toluene and 1-dodecanol were not the right candidates as dispersed phase of the emulsion templating system, while liquid paraffin was the selected template. Size and distribution of liquid paraffin droplets in the prepared gels could be controlled precisely by adjusting the amount of surfactants and template. The SEM
photographs of dried alginate gels showed that there were monosized pores in the final products.
海藻酸钠是一种从海藻中提取的天然多糖聚合物，具有良好的生物相容性和可降解性，价格低廉，近年来在生物医学领域应用十分广泛。
本论文对反相悬浮交联法海藻酸钙凝胶微球的制备、乳液模板体系的确定、模板物在海藻酸钙凝胶中的存在状态以及模板物撤离后材料的形貌进行了较为详细的考察和总结。用表面张力仪和粒度测试仪对乳液进行了表征，用光学显微镜和扫描电镜观察了海藻酸钙凝胶的形貌。
结果表明，用反相悬浮交联法制备海藻酸钙微球，分散介质的用量、海藻酸钠水溶液的浓度、搅拌速度以及分散剂的种类和用量等都会影响微球的形貌。对于本体系，分散介质和分散相的体积比不能小于2:1；海藻酸钠的浓度应控制在2％－3.5%之间；要得到具有良好球形的海藻酸钙凝胶粒子，搅拌速度应控制在300r/min－450r/min之间；用Span85&Span80表面活性剂和PVP作为微球制备的悬浮分散剂，通过调节其用量，可以得到不同尺度、均一而规整的海藻酸钙微球。
对乳液表面张力的测试结果表明，制备均一稳定的石蜡/Span85&Tween60/海藻酸钠乳液，最佳的HLB值为12.3，乳化剂含量以70－110％为宜，乳化时间应控制在60min左右。观察由乳液制得的海藻酸钙凝胶膜中模板物的存在状态，认为甲苯和十二醇不适合作为本实验乳液模板体系的分散相，而液体石蜡适合作为制备多孔海藻酸钙凝胶的模板；调节乳化剂和液体石蜡的用量可以控制模板物石蜡在凝胶中的分布和液滴的大小。用扫描电镜观察脱除模板的干态凝胶，可以观察到凝胶膜的表面有尺寸均一的球形孔存在；在干态凝胶微球的表面和断面上也观察到很多微孔。
Emulsion templating technique is a newly developed method for producing highly monodispersed porous materials. Most of its applications focused on the fabrication of inorganic porous materials. Little study was directed to form porous materials based on natural polymers via emulsion templating technique.
Sodium alginate derived from brown sea algae is an anionic linear polysaccharide. It is biocompatible, biodegradable and relatively economical, and has been much used in biomedical field in recent years.
In this thesis, the preparation of calcium alginate microspheres through inverse suspension-crosslinking method, the parameter choosing of emulsion templating system, the state of templates in alginate gels and the morphology of the obtained materials were investigated in detail. The emulsion and calcium alginate gels were characterized by surface tension test, particle size and size distribution test, optical microscope and SEM, etc.
The results showed that the relative amount of dispersing medium, the concentration of sodium alginate solution, the stirring rate, the dispersant and its quantity were all the factors influencing the preparation of alginate microspheres by inverse suspension-crosslinking method. The volume ratio of dispersing medium to dispersed phase should not be less than 2:1. The concentration of sodium alginate solution should be controlled in the range of 2%－3.5%. Stirring rate between 300r/min and 450r/min was necessary for good spherical particles. Using suitable quantity of Span85&Span80 and PVP as dispersants could lead to microspheres with uniform size.
The emulsion surface tension tests showed that for a relatively stable emulsion based on liquid paraffin, Span85&Tween60 and sodium alginate solution, the optimal HLB, the content of surfactants were 12.3, 70－110% respectively, and the proper emulsification time was about 60min. The observation of templates in alginate gels indicated that toluene and 1-dodecanol were not the right candidates as dispersed phase of the emulsion templating system, while liquid paraffin was the selected template. Size and distribution of liquid paraffin droplets in the prepared gels could be controlled precisely by adjusting the amount of surfactants and template. The SEM
photographs of dried alginate gels showed that there were monosized pores in the final products.
引文
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[2]Sellergren B. Imprinted polymers with memory for small molecules, proteins, or crystals. Angew Chem, Int Ed Engl, 2000, 39:6.
[3]Vallano PT, Remcho VT. Highly selective separations by capillary ectrochromatography: molecular imprint polymer sorbents. J Chromatogr A, 2000, 887(1-2):125–135.
[4]Yano K, Karube I. Molecularly imprinted polymers for biosensor applications. Trends Anal Chem 1999,18(3):199–204.
[5]D’Souza SM, Alexander C, Carr SW, et al. Directed nucleation of calcite at a crystal-imprinted polymer surface. Nature 1999, 398(6725):312–316.
[6]Xia YN, Gates B, Yin YD, Lu Y. Monodispersed colloidal spheres:old materials with new applications.Adv Mater 2000,12(10):693–713.
[7]Velev OD, Lenhoff AM. Colloidal crystals as templates for porous polymerized
materials. Curr Opin Colloid Interface Sci 2000,5(1–2):56–63.
[8]Gates B, Yin YD, Xia YN. Fabrication and characterization of porous membranes with highly ordered three-dimensional periodic structures. Chem Mater,1999, 11(10):2827–36.
[9]Menger FM, Tsuno T, Hammond GS. Cross-linked polystyrene incorporating water pools. J Am Chem Soc, 1990,112(3): 1263–1264.
[10]Zhu XX, Banana K, Yen R. Pore size control in cross-linked polymers resins by reverse micellar imprinting. Macromolecules, 1997, 30(10): 3031–3035.
[11]Zhu XX, Banana K, Liu HY, Krause M, Yang M. Cross-linked porous polymer resins with reverse micellar imprints: factors affecting the porosity of the polymers. Macromolecules, 1999, 32(2):277–281.
[12]M.Estermann， L.B.Mccusker，C.Baerlocher, et al. A synthetic gallophosphate molecular sieve with a 20-tetrahedral-atom pore opening. Nature, 1991, 352:320
[13]A.Imhof，D.J.Pine. Ordered macroporous materials by emulsion templating. Nature, 1997, 389:948
[14]熊博辉,沈丽,从润滋 等．单分效多孔交联聚苯乙烯色谱填料的合成.色谱，1998,(16):492—494．
[15]Frank Caruso，Rachel A.Caruso，Helmuth.M.Wald, et al. Nanoengineering of inorganic and hybrid hollow spheres by colloidal templating. Science, 1998,282:1111-1114
[16]Wijnhoven E G J, Vos W L. Preparation of photonic crystal made of air sphere in
titania. Science, 1998,281(5378): 802-804
[17]C.T.Kresge， M.E.Leonawize，W.J.Roth, et al. Ordered mesoporous molecular sieves synthesized by a liquid crystal template mechanism. Nature, 1992, 359:710-713
[18]A.Firouzi. Cooperative organization of inorganic-surfactant and biomimetic assemblies. Science, 1995, 267: 1138-1143
[19]S.H.Tolbert，A.Firouzi，G.D.Stucky, et al. Magnetic field alignment of ordered silicate-surfatant composites and mesoporous silica. Science, 1997, 278:264-266
[20]K.M.Mcgrath，D.M.Dabbs，N.Yao, et al. Formation of a silicates L3 phase with continuously adjustable pore sizes. Science, 1997, 277:552
[21]Haug, A., Larsen, B., and Smidsrod, O. Uronic Acid Sequence in Alginate from Different Sources. Carbohydrate Res., 1974, 32: 217–225.
[22]Draget KI, Skjak-Brak G, Christensen BE, et al. Swelling and partial solubilization of alginic acid gel beads in acidic buffer. Carbohydr Polym, 1996, 29:209
[23]Lewis, J.C., Stanley, N.F., and Guist, G.G., Commercial Production and Applications of Algal Hydrocolloids, Algae and Human Affairs, Lembi, C.A. and Waaland, J.R., Eds., Cambridge Univ. Press, 1988, pp. 205–236.
[24]张善明,刘强,张善磊.从海带中提取高粘度海藻酸钠.食品加工,2002, 23:86-87
[25]Ofstad R. and Larsen B. In Proceedings of the 10th International Seaweed Symposium,1980, p.485
[26]Kurt Ingar Draget, Gudmund Skjak-Brak and Olav Smidred. Alginate based new materials. International journal of Biological Macromolecules, 1997, 21:47-55
[27]宗会.海藻酸钠涂膜对苹果生理变化的影晌.果树科学,1999(16):263-266
[28]Doyle, J.M., Roth, T.P., Smith, R.M., et al., Effect of Calcium Alginate on Cellular Wound Healing Processes Modeled in vitro. J. Biomed. Mater. Res., 1996, 32: 561–568.
[29]Zee, S., Body Weight Loss with the Aid of Alginic Acid. Med. Arch., 1991, 45: 113–114.
[30]Torsdottir, I., Alpsten, M., Holm, G., et al., A Small Dose of Soluble Alginate-Fiber Affects Postprandial Glycemia and Gastric Emptying in Humans with Diabetes. J. Nutr., 1991, 121:795–799.
[31]Paul, T.M., Skoryna, S.C.and Waldron-Edward, D. Studies of Inhibition of Intestinal Absorption of Radioactive Strontium. V. Effect of Administration of Calcium Alginate. Can. Med. Ass. J., 1996, 95:553–557.
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