粒径均一的聚甲基丙烯酸羟乙酯微球的制备及应用研究
文献类型：学位论文
| 作者 | 瞿欢欢 |
| 学位类别 | 博士 |
| 答辩日期 | 2008-06-05 |
| 授予单位 | 中国科学院过程工程研究所 |
| 授予地点 | 过程工程研究所 |
| 导师 | 马光辉 |
| 关键词 | 多孔聚合物微球 膜乳化 粒径可控 层析介质 中药现代化 |
| 其他题名 | Strategy for the design of uniform PHEMA microspheres and their chromatographic application |
| 学位专业 | 生物化工 |
| 中文摘要 | 本论文研究了粒径均一可控、结构可控的多孔聚甲基丙烯酸羟乙酯（PHEMA）微球的制备过程，并考察其作为层析介质在中药有效成分（淫羊藿甙）分离纯化中的应用。 首先对悬浮聚合制备PHEMA微球的过程进行了研究，发现浓度为1%的PVA217作为分散剂时，既能保持良好的稳定液滴作用，又不覆盖微球表面的孔结构；乙酸乙酯、甲苯、正己醇三种致孔剂对相分离的影响程度依次减弱，经过对比发现甲苯最适合作为PHEMA聚合体系的致孔剂。 针对悬浮聚合难以制备粒径均一可控的PHEMA微球这一难题，探索了一种新型的膜乳化-液滴溶胀-聚合固化方法。该新方法先采用膜乳化制备粒径均一的疏水性液滴，再通过液滴溶胀过程吸收相对亲水的单体，然后对溶胀液滴进行聚合得到粒径均一的多孔PHEMA微球。经过对液滴溶胀过程的观测，发现含有亲水性单体的二次小液滴在1小时之内即完全消失，而种子液滴的粒径则随之增大，溶胀结束后经聚合反应，得到的微球粒径分布系数在20%左右，远远优于悬浮聚合的粒径分布（CV= 126%）。考察了阻聚剂（对苯二酚）的浓度对阻止二次成核的效果及PHEMA微球产率的影响，发现对苯二酚的浓度保持在0.06%时可以得到最优的结果。 在上述基础上，研究了不同粒径、不同结构的PHEMA微球的制备。通过调节种子乳液的油相组成、膜孔径及溶胀比，成功地制备了不同粒径的PHEMA微球，可控范围为3-100μm；通过对致孔剂组成的改变，使PHEMA微球的孔径在0-199nm之间变动，最高比表面积可以达到129m2/g；通过引入第三单体（苯乙烯、甲基丙烯酸甲酯、甲基丙烯酸），实现了微球表面极性的控制；通过引入疏水性单体--苯乙烯，制备了多孔/无孔或多孔/微孔的半月形复合微球。 将所制备的粒径均一PHEMA微球作为层析介质，对中药淫羊藿提取物中的淫羊藿甙进行了分离纯化，并同粒径均一的聚苯乙烯微球（PSt）进行了比较。结果发现，在同等条件下，PHEMA介质对极性分子具有更好的吸附选择性，而且所用流动相中有机溶剂的浓度更低。在PHEMA30（粒径为30μm的PHEMA微球）柱上采用30%的乙醇进行一步洗脱，可以得到纯度为91%的淫羊藿甙产品，回收率高达98%；而且还发现在乙醇-水体系中PHEMA介质与淫羊藿甙分子之间存在氢键作用。 |
| 英文摘要 | This thesis is focused on the preparation process of monodisperse porous poly(2-hydroxyethylmethacrylate) (PHEMA) microspheres with controllable size and structure, and their application in the chromatographic separation of bioactive compound (icariin) from the Traditional Chinese Medicine. Firstly, the preparation process of PHEMA microspheres by suspension polymerization method is investigated. It is observed that PVA217 (1% based on the water weight) is the most suitable stabilizer for porous PHEMA microspheres. The phase separation is affected by the type and concentration of porogenic agents, which obeys the order: hexanol < toluene < ethyl acetate. Moreover, toluene is the optimum porogenic agent, whose concentration is determined by the content of crosslinker (ethylene dimethacrylate, EDMA) in the monomer recipes. Secondly, in order to improve the size distribution that is broad in the above method, a novel method that combining membrane emulsification method, droplets swelling method and suspension polymerization is developed. After the monodisperse seed droplets composed of hydrophobic components are prepared by membrane emulsification method, the droplets swelling process is performed to absorb the relatively hydrophilic monomers including 2-hydroxyethylmethacrylate (HEMA) and EDMA. By monitoring the swollen course, it is found that the secondary droplets disappear as quickly as 1 h. However, the seed droplets become larger gradually. By polymerizing the swollen droplets, monodisperse porous PHEMA microspheres are obtained with a low CV value (about 20%), which is superior to the result of conventional suspension polymerization (CV value =126%). In addition, the effect of inhibitor on the prevention of secondary neucleatin and the yield of PHEMA microspheres is also investigated. An optimum result is obtained when hydroquinone (HQ) with the concentration of 0.06% is added to the aqueous solution. Subsequently, the factors that affect size and structure of PHEMA microspheres prepared by the new method are studied. By changing the total oil composition, membrane pore size and the swelling ratio, monodisperse PHEMA microspheres can be prepared with the size ranging from 3 to 100μm. By changing the composition of porogenic agents, the pore size of PHEMA microspheres is controlled ranging from 0 to 199nm. Moreover, the maximal specific surface area can attain to 129m2/g. By introducing a third monomer (such as styrene, methyl methacrylate or methacrylate acid), the surface polarity of the microspheres also can be controlled. In addition, it is interesting that half-moon microspheres with composite structures are obtained when styrene is added into the oil phase. The monodisperse PHEMA microspheres are applied as chromatographic packing materials for isolation of icariin from the extract of Epimedium Brevicomum Maxin. For comparison, monodispersed polystyrene (PSt) microspheres with hydrophobic structure are chosen as reference packing materials. It is observed that better separation selectivity and lower organic solvent (ethanol or actronitrile) consumption for polar molecules are achieved in the former case. High purity icariin (91%) with the recovery of 98% can be isolated from the crude extraction under low pressure on the column packed with PHEMA microspheres of 30μm. Moreover, it is found that hydrogen bond interaction between PHEMA and the solute exists in the ethanol-water system. |
| 语种 | 中文 |
| 公开日期 | 2013-09-13 |
| 页码 | 141 |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/1179]  |
| 专题 | 过程工程研究所_研究所（批量导入） |
| 推荐引用方式 GB/T 7714 | 瞿欢欢. 粒径均一的聚甲基丙烯酸羟乙酯微球的制备及应用研究[D]. 过程工程研究所. 中国科学院过程工程研究所. 2008. |
入库方式： OAI收割
来源：过程工程研究所
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