聚二乙烯基苯微球介质制备及其在奥曲肽层析分离中的应用

以二乙烯基苯为单体,采用微孔膜乳化法制备了尺寸均一的水包油乳液,在75℃下悬浮聚合20 h,制得均一的聚二乙烯基苯微球填料,粒径为14.2μm,粒径分布系数Rspan=0.71,孔径为65 nm,比表面积为160 m2/g.通过高压匀浆法将合成的微球介质高效装填不锈钢液相色谱柱(ψ4.6 mm×250 mm),使柱效达11000塔板数.利用装填的色谱柱进行多肽药物奥曲肽的分离纯化,奥曲肽从固相合成粗品中快速有效分离,纯度由42.89%提高到99.99%.     

快速膜乳化技术制备均一小粒径复合多糖微球及其色谱性能评价

采用快速膜乳化技术制备均一小粒径复合多糖微球,重点探究膜乳化工艺关键参数和微球固化冷却工艺等对微球形貌、粒径及其分布的影响,以及制备工艺对微球耐压性能的影响,在此基础上制备粒径均一、耐压性能良好的小粒径复合多糖微球。色谱研究表明,该均一小粒径复合多糖微球具有较高的色谱分离度,在高分辨率色谱领域具有良好的应用前景。     

微孔膜乳化与悬浮聚合结合法制备均一PST-DVB多孔微球

使用自制的微孔膜乳化装置,通过微孔膜乳化结合悬浮聚合方法,批量制备了微米级的聚(苯乙烯-二乙烯基苯)(PST-DVB)微球. 实验中采用孔径为5.2 mm的微孔膜,考察了膜线剪切力、管线速度和膜乳化压力对微球粒径及其分布的影响,以及膜乳化压力和膜线剪切力对分散相流速的影响. 研究结果表明,膜线剪切力在合适的范围内对微球粒径影响不大,而管线速度在14.38~26.49 m/min之间、膜乳化压力在0.008~0.012 MPa之间时,所制备微球的尺寸均一. 研究还发现膜乳化压力是影响分散相流速的最主要因素. 研究结果为装置的规模化放大奠定了理论基础.     

交联聚苯乙烯微球沉淀聚合法制备及其色谱性能

以二乙烯基苯(DVB)为交联剂、苯乙烯(ST)为共聚单体,采用沉淀聚合法合成了聚(苯乙烯-co-二乙烯基苯)微球[P(ST-co-DVB)]。扫描电子显微镜分析(SEM)显示微球表面无大孔结构,粒径统计分析表明粒径单分散微球的平均直径为3.2μm,FT-IR表明两种单体实现了共聚。BET分析可知比表面积为2.7m2.g-1,平均孔径为10.0nm。以碱性化合物为探针分子,采用反相液相色谱模式考察了P(ST-co-DVB)微球的色谱性能,色谱结果显示固定相具有较高的柱效和较好的色谱峰形,表明沉淀聚合法用作固定相具有较好前景。     

高分子微球的沉淀聚合法制备及色谱性能

以二乙烯基苯(DVB-55)和二缩三乙二醇二甲基丙烯酸酯(TGD)为共聚单体,以乙腈为溶剂,采用沉淀聚合法一步合成了聚(二乙烯基苯-co-二缩三乙二醇二甲基丙烯酸酯)[P(DVB-co-TGD)]微球。采用反相液相色谱模式考察了微球的色谱性能。结果表明,共聚微球表面无大孔,单分散微球数均粒径为3.5μm,比表面积为2.9 m2/g,用作固定相具有较高的柱效,碱性物质具有对称的色谱峰形。     

微球材料尺寸和结构控制的过程工程

微球材料的粒径均一性和结构可控性直接影响其应用效果,这对过程工程提出了挑战。在发展微孔膜乳化过程制备均一乳液和微球的基础上,对均一乳液的形成机理进行了研究,通过对液滴形成过程的控制,在油/水、水/油、水/油/水等体系成功制备出了均一微球。通过发展微球结构演变过程的定量研究方法,成功对微球结构进行了调控;针对生化工程对超大孔微球的重要需求,发展了超大孔微球制备方法,实现了孔径在100 nm到微米级的调控。研究了粒径均一性和结构对其应用效果的影响。微球应用于生物分离介质时,粒径均一性提高了蛋白质的分离度;超大孔微球可使超大生物分子快速进入介质内部,显著提高纯化回收率。微球应用于胰岛素口服药物载体时,粒径对其在消化道的分布有显著影响,中空-多孔微球显示了最佳的降血糖效果。     

微球材料尺寸和结构控制的过程工程

微球材料的粒径均一性和结构可控性直接影响其应用效果,这对过程工程提出了挑战。在发展微孔膜乳化过程制备均一乳液和微球的基础上,对均一乳液的形成机理进行了研究,通过对液滴形成过程的控制,在油/水、水/油、水/油/水等体系成功制备出了均一微球。通过发展微球结构演变过程的定量研究方法,成功对微球结构进行了调控;针对生化工程对超大孔微球的重要需求,发展了超大孔微球制备方法,实现了孔径在100 nm到微米级的调控。研究了粒径均一性和结构对其应用效果的影响。微球应用于生物分离介质时,粒径均一性提高了蛋白质的分离度;超大孔微球可使超大生物分子快速进入介质内部,显著提高纯化回收率。微球应用于胰岛素口服药物载体时,粒径对其在消化道的分布有显著影响,中空-多孔微球显示了最佳的降血糖效果。     

P(St-GMA-DVB)/Fe3O4高分子磁性微球的合成与表征

以FeCl3×6H2O和FeCl2×4H2O为原料,采用化学共沉淀法制备了Fe3O4油基磁流体,设计的合成工艺克服了合成磁流体过程中Fe3O4磁性粒子易团聚的缺点,合成了具有很好分散性和稳定性的磁流体,比饱和磁化强度达72.60 emu/g. 采用悬浮聚合方法合成了聚苯乙烯-甲基丙烯酸缩水甘油酯-二乙烯基苯[P(St-GMA-DVB)]高分子磁性微球,搅拌转速对磁性微球粒径影响大,磁性微球粒径在55~300 mm范围内,外形为具有单分散性的球形,表面环氧基团含量达17 mmol/g.     

单分散多孔聚合物微球的制备及其反相色谱应用

用分散聚合的方法制得单分散微米级聚苯乙烯微球(PS),以此聚苯乙烯微球作为种子,以邻苯二甲酸二丁酯为溶胀剂,苯乙烯为单体,二乙烯基苯为交联剂,甲苯为致孔剂,采用种子溶胀聚合的方法制得粒径分布较窄的多孔高交联的聚苯乙烯-二乙烯基苯微球(PS-DVB)。研究了交联剂与致孔剂的加入量对微球形貌、粒径及孔结构参数的影响。结果表明,所得多孔微球球形圆整,库尔特测得平均粒径为5.067~5.520μm,粒径分布窄,D90/D10为1.23~1.56,孔结构可控,并以此多孔微球作为反相色谱填料基质,理论塔板数每米可达6 000~15 000,可以用作高效液相色谱(HPLC)填料。     

PLGA微球粒径对HPV L1五聚体候选疫苗免疫效果的调控

以聚乳酸-羟基乙酸共聚物(PLGA)为疫苗递送和佐剂系统,采用快速膜乳化技术制备了粒径0.43和1.38 mm的均一PLGA微球,以其包埋HPV L1五聚体抗原,考察微球粒径对体内免疫应答强度和水平的影响. 结果表明,1.38 mm粒径载抗原PLGA微球组产生的IgG滴度(87771±24983.0)和中和抗体滴度(30720±15863.7)显著高于0.43 mm粒径组的IgG滴度(38400±14021.7) (P<0.05)和中和抗体滴度(2480±3892.6) (P<0.01),且1.38 mm载抗原PLGA微球能更显著提高Th2型细胞因子IL-6(0.43 mm微球的4.7倍)和IL-4(0.43 mm微球的1.5倍)的分泌水平;而0.43 mm载抗原PLGA微球能显著提升Th1型细胞因子IFN-γ(1.38 mm微球的2.1倍)的分泌水平,表明对于HPV疫苗佐剂与递送系统,小粒径微球有利于细胞免疫的提升,可用于治疗性疫苗的开发;而大粒径微球则有利于诱导高效体液免疫,可用于预防性疫苗的开发.     

Film formation of poly (methyl methacrylate) latex with pyrene functional poly (divinylbenzene) microspheres prepared by click chemistry

This work reports on the application of steady state fluorescence (SSF) technique for studying film formation from poly(methyl methacrylate) (PMMA) latex and poly(divinylbenzene) (PDVB) microsphere composites. Pyrene (P) functionalized PDVB cross‐linked spherical microspheres with diameters of 2.5 μm were synthesized by using precipitation polymerization technique followed by click coupling reaction. The diameter of the PMMA particles prepared by emulsion polymerization were in the range of 0.5–0.7 μm. PMMA/PDVB composite films were then prepared by physically blending of PMMA latex with PDVB microspheres at various composition (0, 1, 3, 5, 10, 20, 40, and 60 wt%). After drying, films were annealed at elevated temperatures above T_g of PMMA ranging from 100 to 270°C for 10 min time intervals. Evolution of transparency of the composite films was monitored by using photon transmission intensity, I_tr. Monomer (I_P) and excimer (I_E) fluorescence intensities from P were measured after each annealing step. The possibility of using the excimer‐to‐monomer intensity ratio (I_E/I_P) from PDVB microparticles as a measure of PMMA latex coalescence was demonstrated. Diffusion of the PMMA chains across the particle–particle interfaces dilutes the dyes, increasing their separation. The film formation stages of PMMA latexes were modeled by monitoring the I_E/I_P ratios and related activation energies were determined. There was no observable change in activation energies confirming that film formation behavior is not affected by varying the PDVB composition in the studied range. SEM images of PMMA/PDVB composites confirmed that the PMMA particles undergo complete coalescence forming a continuous phase in where PDVB microspheres are dispersed. POLYM. COMPOS., 2011. © 2011 Society of Plastics Engineers     

A facile route to poly(divinylbenzene) hollow microspheres with pyridyl group on the interior surface

Poly(divinylbenzene) (PDVB) hollow microspheres with pyridyl group located on their interior surface were prepared by a facile route with the aid of the vinyl groups on the surface of poly(methacrylic acid) (PMAA) microspheres, which were incorporated through the hydrogen-bonding interaction between the carboxylic acid group and pyridyl group of 4-vinylpyridine (VPy). Poly(methacrylic acid)@polydivinylbenzene (PMAA@PDVB) core-shell structure microspheres with PMAA as core and PDVB as shell were synthesized by a two-stage distillation-precipitation polymerization technique through the capture of the DVB monomer from solution of the reactive vinyl groups on pyridyl-functionalized PMAA microspheres based on a seeded-nucleation mechanism during the second-stage polymerization. The PDVB hollow microspheres with different shell thicknesses were developed after the PMAA core particles were removed by selective dissolution under basic condition in ethanol, during which the pyridyl group was left on the interior surface of the shell layer in PDVB hollow microspheres. The resultant core-shell and hollow microspheres were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier transform infrared spectra (FT-IR) and elemental analysis.     

快速膜乳化法制备载生长激素释放肽-6的PLGA微球

采用快速膜乳化法制备了聚(乳酸-羟基乙酸)(PLGA)微球,得到制备PLGA微球的优化条件为：过膜压力5 kPa,水相中PVA浓度19 g/L,油/水相体积比1:10,该条件下所制空白微球的平均粒径约为24 mm,粒径分布系数Span<0.7. 在此基础上制备载生长激素释放肽-6(GHRP-6)微球,油相乳化剂浓度2.5 g/L、外水相中NaCl浓度10 g/L条件下所制载GHRP-6微球包埋率最高可达85%,初乳制备方式对药物包埋率及体外释放行为均有较大影响,超声法制备的初乳所得微球内部结构紧密,药物包埋率较高(85%),但释药缓慢;而均质法制备的初乳所得微球内部结构疏松,药物包埋率较低(76.8%),但在体外释放更完全.     

SiO2@PDA微球结构色织物的制备

采用溶胶-凝胶法制备了二氧化硅(Si O2)微球,并利用聚多巴胺(PDA)作为黑色吸光物质制备了Si O2@PDA微球;利用重力沉积法将Si O2@PDA微球沉积到白色涤纶织物表面,通过添加自制结构色粘合剂聚(甲基丙烯酸缩水甘油酯-co-丙烯酸六氟丁酯)-g-聚乙二醇甲基丙烯酸酯〔P(GMA-co-FHBMA)-g-PEGMA〕以制备高牢度结构色织物。采用马尔文高灵敏纳米粒度分析仪、SEM、测色仪、测量显微镜对Si O2微球、Si O2@PDA微球和结构色织物进行了表征,探究了多巴胺用量与Si O2@PDA微球的粒径、形貌及织物结构色的关系;考察了粘合剂用量对结构色牢度和色彩的影响。结果表明,制备的SiO2微球粒径均匀、单分散性较好;随着多巴胺用量的增多,制备的SiO2@PDA微球粒径增大,织物结构色红移;但多巴胺用量过多会使微球形貌粗糙,降低微球的粒径均匀性、单分散性及结构色的亮度;P(GMA-co-FHBMA)-g-PEGMA的加入可以抑制结构色开裂,提升牢度。     

Facile synthesis of silica/polymer hybrid microspheres and hollow polymer microspheres

Monodisperse silica/polydivinylbenzene (SiO₂/PDVB) and silica/poly(ethyleneglycol dimethacrylate) (SiO₂/PEGDMA) core-shell hybrid microspheres were prepared by a two-stage reaction with silica particles' grafting of 3-(methacryloxy)propyltrimethoxysilane (MPS) as core and PDVB or PEGDMA as shell, in which the MPS-modified silica core with diameter of 238 nm was synthesized by Stöber method and subsequently grafted with MPS as the first-stage reaction. The PDVB or PEGDMA shell was then encapsulated over the MPS-modified silica core by distillation precipitation polymerization of divinylbenzene (DVB) or ethyleneglycol dimethacrylate (EGDMA) in neat acetonitrile with 2,2′-azobisisobutyronitrile (AIBN) initiator as the second-stage reaction. The encapsulation of PDVB and PEGDMA on modified silica core particles was driven by the capture of DVB or EGDMA oligomer radicals via the vinyl groups on the surface of the modified silica cores during the second-stage polymerization in the absence of any stabilizer or surfactant. The shell thickness of the core-shell hybrid particles was controlled by the feed of DVB or EGDMA monomer during the polymerization. Hollow PDVB or PEGDMA microspheres with various shell thickness were further developed after selective removal of the modified silica cores with hydrofluoric acid. The resultant core-shell hybrid materials and hollow microspheres were characterized by transmission electron microscopy (TEM), and Fourier transform infrared spectra (FT-IR).     

Preparation of monodispersed porous polyacrylamide microspheres via phase separation in microchannels

We report on the formation of polyacrylamide (PAM)/polyethylene glycol (PEG) core/shell droplets in a microchannel via the polymerization-induced phase separation of an acrylamide (AM)/PEG aqueous system. Monodispersed porous PAM microspheres were prepared from the PAM/PEG core/shell droplets, and we examined the effects of experimental parameters on the phase separation process and on the particle size and pore structure of the resulting PAM microspheres. PAM microspheres could be readily obtained with adjustable particle sizes and porosities by altering the PEG and crosslinker contents and by using PEG with different molecular weights. The relation between the swelling value and porosity is correlated.     

羧基磁性微球的制备及其用于CD4细胞分离应用

采用溶液聚合法制备具有良好悬浮性和磁响应性的羧基聚丙烯酰胺磁珠,对羧基磁性微球的形貌、结构、悬浮稳定性进行表征.研究结果显示,羧基聚丙烯酰胺磁性微球的平均粒径为20nm,粒径分布比较均匀,近似为球形的壳核结构,核为磁性基质,壳为羧基聚丙烯酰胺;将羧基聚丙烯酰胺磁珠用于CD4细胞分离研究表明,分选后的细胞纯度高达94％.     

双马来酰亚胺树脂微球的制备

合成了1种新型的聚醚酰亚胺(PEI-A)。将PEI-A与双马来酰亚胺树脂(BMI)和二烯丙基双酚A(DBA)体系共混,经反应诱导相分离,制备了3～5μmBMI树脂微球。     

Optical percolation and oxygen diffusion in poly(divinylbenzene) doped poly(methyl methacrylate) latex flms

A simple fluorescence technique is proposed for the measurement of the diffusion coefficient of oxygen into poly(methyl methacrylate) (PMMA) latex‐poly(divinylbenzene) (PDVB) composite films. Percolation model was used by using photon transmission (PT) technique to interpret the distribution of PDVB particles in PMMA lattice. Optical results were interpreted according to site percolation theory. The optical percolation threshold value and critical exponent were calculated as, R_c = 0.03 and, β = 0.34, respectively. PT measurements were performed for eight different PDVB content (0, 1.5, 3, 5, 10, 20, 40, and 60) wt%. Pyrene (P) functionalized PDVB cross‐linked spherical microspheres with diameters of 2.5 μm were synthesized by using precipitation polymerization technique followed by click coupling reaction. The diameter of the PMMA particles prepared by emulsion polymerization was in the range of 0.5–0.7 μm. PMMA/PDVB composite films were then prepared by physically blending of PMMA latex with PDVB microspheres at various compositions. The steady‐state fluorescence method was used to monitor oxygen diffusion into these (0, 5, 10, 20, and 40 wt%) latex films. Diffusion coefficients, D, of oxygen were determined by the fluorescence quenching method by assuming Fickian transport and were found to be increased from 1.8 × 10⁻¹¹ to 36.6 × 10⁻¹¹ cm² s⁻¹ with increasing PDVB content. This increase in D values was explained with formation of microvoids in the film by using PT technique. POLYM. COMPOS., 2013. © 2012 Society of Plastics Engineers