【作者】 周超；

【导师】 戴红莲；

【作者基本信息】 武汉理工大学 ， 生物材料学， 2007， 硕士

【摘要】 本论文针对目前临床上无机栓塞材料密度大、悬浮稳定性差、易误栓；有机栓塞材料密度小、透X光、粘导管等问题，选择钡铁氧体微粒和聚氨酯高分子为研究对象，制备出了一种结合了BaFe₁₂O₁₉的X光显影性、高磁响应性和聚氨酯高分子的低密度、优良的生物相容性等优点的BaFe₁₂O₁₉／聚氨酯磁性复合微球，并对合成微球的影响因素进行了分析，对微球合成机理作了初步探讨，对微球的理化性能进行了表征，对微球的生物相容性作了评价。研究确定了BaFe₁₂O₁₉／聚氨酯磁性复合微球的制备工艺：自燃烧法合成BaFe₁₂O₁₉微粒，硅烷偶联剂改性BaFe₁₂O₁₉微粒，聚乙二醇（PEG1000）、甲苯-2，4-二异氰酸酯（TDI）以BaFe₁₂O₁₉为中心在二甲苯溶液中预聚合，预聚物的二甲苯溶液在分散剂聚乙烯吡咯烷酮（PVPK30）的水溶液中悬浮聚合，四步合成BaFe₁₂O₁₉／聚氨酯磁性复合微球。通过分析改性效果、预聚合前处理、预聚合反应温度和时间、悬浮聚合反应温度和时间、分散剂的用量等因素对微球形成的影响，确定了制备微球的最佳参数：使用经1.2％偶联剂HC-792改性的BaFe₁₂O₁₉，控制BaFe₁₂O₁₉与甲苯-2，4-二异氰酸酯预先反应时间为25min，甲苯-2，4-二异氰酸酯与聚乙二醇的预聚合时间为120min，水浴控制温度在40℃，悬浮聚合时使用1.0％PVP作分散剂，水浴控制温度在80℃，聚合4h。本研究结合扫描电子显微镜（SEM）观察了微球的表面和截面形貌，红外光谱仪（IR）表征了微球的化学结构，热重-差示扫描（TG-DSC）同步热分析仪分析了微球的热稳定性和磁性无机物的含量，振动样品磁强计（VSM）分析了微球的磁性能，比重瓶法测量微球的密度，并对微球进行了生物学相容性评价。结果表明：合成微球为多核心的核／壳型BaFe₁₂O₁₉／聚氨酯复合微球，复合微球的平均粒径约为400μm，核层均质致密、壳层疏松、表面多孔，BaFe₁₂O₁₉微粒被包裹于聚氨酯高分子的核层和壳层内；微球的热稳定性好，玻璃化温度Tg在290℃左右；微球的磁性物质含量为11.11％，饱和磁化强度为3.36emu／g，矫顽力为306Oe，有利于外磁场的导向；微球的密度为0.92g／cm³接近水的密度较容易在水或血液中悬浮分散；微球的生物相容性优良，是一种有潜在应用价值的新型血管内栓塞材料。对复合微球形成机理的初步探讨表明：通过改性在BaFe₁₂O₁₉表面接枝的功能基团-NH-、-NH₂使-NCO与聚多元醇-OH的逐步加成聚合反应以BaFe₁₂O₁₉为中心发生，悬浮聚合时，以BaFe₁₂O₁₉为中心的聚氨酯预聚物胶束在液滴内成核，逐步聚合将BaFe₁₂O₁₉包埋于聚合微球内部。更多还原

【Abstract】 At present, the inorganic embolism materials are easy to mistakenly embolize due to high density and poor suspension stability; the organic embolism materials also have a lot of disadvantage such as low density, X-rays radioparency and adhesiveness. In this study, barium ferrite particles and polyurethane were selected as embolism materials. Four-Step Method prepared BaFe12O19/polyurethane magnetic composite microspheres, which combined virtues of barium ferrite particles and polyurethane, such as X-rays developable, good magnetic responsiveness, low density and excellent biocompatibility. Furthermore, the influence factors in the synthesis of microspheres were investigated, the synthetic mechanism of microspheres was preliminarily discussed and biocompatibility of microspheres also was evaluated.In this study, an appropriate preparation technology was established. BaFe₁₂O₁₉/polyurethane magnetic composite microspheres were prepared by the following steps: Firstly, BaFe₁₂O₁₉ was synthesized by auto-combustion method Secondly, the surface of BaFe₁₂O₁₉ was modified with silane coupling agent; Thirdly, the polyethylene glycol （PEG1,000） and2,4-toluene diisocyanate （TDI） were prepolymerized in the xylene solution; Finally, the prepolymer was suspension-polymerized in aqueous solution with dispersant polyethylene pyrrolidone （PVP K30）. The optimum operation parameters were determined by studying on the influence factors in the synthesis of microspheres as modification effectivity, pre-treatment of prepolymerization, prepolymerization temperature and time, suspension-polymerization temperature and time, the concentration of dispersant, and so on. The optimum operation parameters are as follows: BaFe₁₂O₁₉ can be modified by using 1.2% silane coupling agent; the reaction time between BaFe₁₂O₁₉ and TDI should be controlled within 25min; prepolymerization of TDI and PEG should spend 120min at 40℃; suspension polymerization will last 4h at 80℃, and the concentration of dispersant is 1 .0%PVPThe surface morphology and the section of composite microspheres was observed with the scanning electron microscope （SEM）; the chemical structure of composite microspheres were analysed with Fourier transform infrared spectroscopy （FTIR）; the content of BaFe₁₂O₁₉ and the vitrification point （Tg） of composite micropheres were determined by differential thermal analysis dta-thermogravimetry （TG-DSC）; the magnetic properties of microspheres were measured with the vibration sample magnetometer; the density of microspheres was tested with pycnometer;and the biocompatibility of microspheres was evaluated by a series of experiments. The results showed that BaFe₁₂O₁₉ /polyurethane magnetic composite microspheres were about 400um and had a core-shell structure with multinuclear. The BaFe₁₂O₁₉ particles were encapsulated in cores and shells, the cores were homogeneous and compact, the shells were loose and the surfaces were porous. The Tg of microspheres was about 290°C ,has good heat stability. The content of BaFe₁₂O₁₉ was 11.11wt% in microspheres, the saturation magnetization of microspheres.was 3.36emu/g, and the coercivity Hc was 306Oe, which was in favor of magnetic guidance. The density of microspheres was 0.92g/cm3, which was easy to be dispersed in water or blood. The composite micropheres had a good biocompatibility, and could be a new type of intravascular embolization materials.In this paper, synthetic mechanism of microspheres was preliminarily discussed. The investigation indicated that the active groups-NH-and-NH₂ were connected to the surface of BaFe₁₂O₁₉ by modification, the step addition polymerization between -NCO and polymer polyols -OH occured on BaFe₁₂O₁₉ as center, The prepolymer micelles with BaFe₁₂O₁₉ as the center nucleated in liquid drops, and BaFe₁₂O₁₉ particles were embedded into the interior of the composite micropheres during suspension polymerization.更多还原