及酚醛树脂基炭球的研究
摘 要
微球因具有规整结构及功能可调性，常用于医疗、吸附、催化等领域。聚乙烯醇（PVA）微球是常用的载药栓塞剂，其载药量依赖微球的溶胀能力。目前商用的栓塞剂在粒径均匀及药物释放速度可调方面仍有很大的提升空间。炭球具有优异的稳定性而得到广泛的应用，在众多碳源中，苯酚酚醛树脂（PF）具有残炭率高及机械强度大等优点，但因PF活性差使得以其为原料制备粒径大于几十微米的炭球时间过长。微流体微球制备法不仅可以获得粒径可调且均一的微球，还可灵活调节微球性质与功能。为此，本文以此方法结合溶剂萃取手段制备上述两种微球。将高比表面积且不耐酸的ZIF-8掺杂到PVA中，制得ZIF-8/PVA微球，有望改善栓塞微球的载药及酸性环境下快速释放的能力；另外，通过在PF溶液中加入少量的硅溶胶促进PF溶液的固化来缩短PF基炭球的制备时间，并改变硅溶胶加入量来调变其孔结构。 以分散有ZIF-8纳米颗粒的PVA水溶液为分散相，脂肪酸甲酯（FAME）或正十六烷为连续相，
经简易同轴微流体装置制得ZIF-8/PVA液滴，液滴在萃取相中因失水导致PVA析出从而固化，得到ZIF-8/PVA微球。考察了连续相种类对微球球形度的影响，发现FAME为连续相时，微球球形度好。进一步研究发现了ZIF-8占固体总重最大为55.6%时（55.6%ZP），微球表面ZIF-8稳定不脱落；证明了减慢萃取速度、分散相中添加木质素磺酸或NaCl，均能改善微球球形度，并确定以乙酸乙酯/FAME=3:1（质量比）为萃取相。最后以四环素（TC）为例，探讨了微球的载药及释放性能，测得55.6%ZP载药量为111.4mg/g，是纯PVA微球的5倍；且吸附有TC的55.6%ZP在pH=4.5的PBS水溶液中2.0h脱附95.4%，而在pH=7.4时62.0h脱附63.3%，证明了ZIF-8/PVA微球载药量明显提升且具备靶向快速释药效果。 以加有少量硅溶胶的PF乙醇溶液为分散相，液体石蜡为连续相，经上述微流体装置制得液滴，液滴在萃取剂正己烷及催化剂二异丙胺的混合液中固化成型，制得硅凝胶/PF微球，经老化碳化得到SiO2/C微球，最后利用去除SiO2得到炭球。研究了硅溶胶引入量对微球的影响，发现m(C/Si)>15时，硅溶胶/PF液滴粘连成团状且长时间难以成型，而m(C/Si)≤15时，可30min内形成单分散硅凝胶/PF微球；以m(C/Si)=15为例，SiO2/C微球除去SiO2得到炭球，比表面积由230.3m2/g增至554.6m2/g（均远高于纯PF基炭颗粒），
黄鳝精平均孔径由2.4nm增大至9.2nm。探究了硅凝胶/PF微球的成型机理，确定是硅溶胶凝胶化与液滴整体收缩的共同作用，并据此制得具有核壳结构的SiOeva母2/C微球。此外，为拓展SiO2/C微球的应用，在分散相中引入Ni(NO3)2制得Ni-SiO2/C微球，其微球对4-硝基苯酚还原具有明显的催化效果。
关键词：溶剂萃取 微流体 PVA微球 PF基炭球
ABSTRACT
Microspheres have been often used in medical treatment, adsorption, catalysis and other fields because of their regular structure and functional tunability. Poly(vinyl alcohol) (PVA) microspheres are commonly used as drug-loaded embolic agents, and their drug loading depends on the swelling ability of microspheres. At present, however, commercial embolic agents still have great room for improvement in uniform particle size and adjustable drug release rate. Carbon spheres are widely utilized due to their excellent sta
bility. Among many carbon sources, phenolic resin (PF) has the advantages of high char yield and mechanical strength, but it takes too long to prepare carbon spheres with a particle size of more than several tens of microns owing to the poor PF activity. Not only can microfluidic microsphere preparation method obtain size-tunable microspheres, but also adjust the properties and functions of microspheres flexibly. In this thesis, the above two microspheres were prepared by this method combined with solvent extraction.ZIF-8/PVA microspheres were prepared by adding high specific surface area and acid nonresistant ZIF-8 into an aqueous PVA solution in order to increase the drug loading and improve rapid-release ability of embolic microspheres in acid environment. In addition, a small amount of silica sol was mixed with the PF solution to promote the curing of the PF solution, thereby shortening the preparation time of the PF-based carbon spheres, and the pore structure could be changed by varying the amount of silica sol.
ZIF-8/PVA microspheres were prepared by first generating ZIF-8/PVA droplets in a simple co-flow microfluidic device by using an aqueous PVA solution with ZIF-8 nanoparticles as the dispersed phase and while fatty acid methyl ester (FAME) or n-hexadecane as the co
ntinuous phase, followed by extracting water from these droplets to precipitate PVA in the extraction phase. The influence of continuous phase type on the sphericity of microspheres was investigated and it was found that when FAME was continuous phase, microspheres had good sphericity. Further studies showed that when ZIF-8 accounted for a maximum of 55.6% of the total solid weight (55.6%ZP), ZIF-8 on the surface of the microspheres was stable. Additionally, it was proved that decreasing extraction speed and adding lignosulfonic acid or NaCl in dispersed phase could both improve the sphericity, and the extraction phase was determined to be ethyl acetate/FAME=3:1(mass ratio). Finally, taking tetracycline (TC) as an example, the drug loading and release properties of the microspheres were examined. The measured drug loading of 55.6%ZP sample was 111.4 mg/g, which was 5 times that of pure PVA microspheres, and the 55.6%ZP sample adsorbed with TC was desorbed with 95.4% of TC in 2 hours in PBS solution with pH 4.5, nevertheless 62.3% in 62h when pH was 7.4. These indicate that the drug loading of ZIF-8/PVA microspheres has increased significantly and the microspheres have the ability to target rapid release乙氧酰胺苯甲酯.
Carbon microspheres were prepared by first obtaining droplets through the above microfluidic device by using PF ethanol solution with a small amount of silica sol as the dispersed phase and liquid paraffin as the continuous phase, followed by extracting ethanol in the droplets in a mixed solution of the hexane as extractant and the diisopropylamine as catalyst to obtain silica gel/PF microspheres, aging, carboning, and removing silica by hydrofluoric acid. The effect of the amount of silica sol on the microspheres was studied. It was found that the silica sol/PF droplets were agglomerated and difficult to form with C/Si>15, however, monodispersed silica gel/PF microspheres were prepared in 30 minutes with C/Si≤海绵真空吸盘15. And in the terms of C/Si=15, after SiO2/C microspheres were removed from SiO2 to obtain carbon microspheres, the specific surface area increased from 230.3m间戊二烯2/g to 554.7m2/g (much higher than pure PF-based carbon particles), and the average pore size enlarged from 2.4nm to 9.2nm. The formation mechanism of the silica gel/PF microspheres was further explored, and it was determined that the gelation of the silica sol and the overall contraction of the droplets. Based on this, SiO2/C microspheres with a core-shell structure was prepared. Besides, in
order to expand the application of SiO2/C microspheres, the SiO2/C microspheres were prepared by introducing Ni(NO3)2 医用拉链into the dispersed phase, and the microspheres had obvious catalytic effect on the reduction of 4-nitrophenol.
KEYWORDS: Solvent extraction；Microfluidics；PVA microsphere；PF-based carbon microsphere
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