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改性聚醚砜微球在高胆红素血症中的应用研究

Application of Modified Polyether Sulfone Microspheres in Hyperbilirubinemia

    摘要
  • 摘要:
    目的 设计并制备一种具有良好机械性能和生物相容性的高效率胆红素吸附剂。
    方法 设计合成吡啶季铵盐，随后通过相转化法和静电喷雾技术制备改性聚醚砜微球PES/p(4-VP-co-N-VP)@6。通过核磁共振谱图、扫描电镜等测试手段研究聚合物组分及微球的形貌，测试微球的基本性能，以及胆红素的吸附效率，并深入探究其吸附机制。同时对微球的血细胞计数和凝血时间进行测试。
    结果 制备的改性聚醚砜微球直径约为700～800 μm。与原始PES微球相比，PES/p(4-VP-co-N-VP)@6的表面和内部结构并无明显变化，同样具备疏松多孔结构，除却不规则大孔外还散在分布一些微孔。与对照PES组相比，改性后的微球在胆红素PBS缓冲溶液中静态吸附180 min后胆红素清除效果为（94.91±0.73）%，差异有统计学意义（P<0.0001）。凝血时间检测中，空白血浆组、对照PES组及改性PES微球组的活化部分凝血活酶时间（activated partial thromboplastin time, APTT）分别为（27.57±1.25） s、（28.47±0.45） s及（30.4±0.872） s，实验组与其余两组差异均有统计学意义（P<0.01，P<0.05）。红细胞、白细胞计数无明显改变。
    结论 制备的微球具有高效胆红素吸附性能、优异力学性能和热稳定性，以及良好血液相容性，有望应用于肝衰竭患者的临床治疗。

     

    Abstract:
    Objective To design and prepare a high efficiency bilirubin adsorbent with good mechanical properties and biocompatibility.
    Methods In this study, quaternary ammonium pyridine was designed and synthesized, and then modified polyether sulfone microspheres, or PES/p(4-VP-co-N-VP)@6 microspheres, were prepared by phase conversion and electrostatic spraying. The morphology of the polymer components and the microspheres were studied by means of nuclear magnetic resonance (NMR) spectroscopy and scanning electron microscopy. The basic properties of the microspheres and their bilirubin adsorption efficiency were tested, and the adsorption mechanism was further explored. Blood cell counts and the clotting time of the microspheres were also measured.
    Results The diameter of the modified polyether sulfone microspheres prepared in the study was approximately 700-800 μm. Compared with the original PES microspheres, the surface and internal structure of PES/p(4-VP-co-N-VP)@6 microspheres did not change significantly, and they also had a loose porous structure, with some micropores scattered around in addition to irregular large pores. Compared with the control group, the bilirubin removal effect of the modified microspheres was (94.91±0.73)% after static adsorption in bilirubin PBS buffer solution for 180 min, with the difference being statistically significant (P<0.0001). According to the findings for the clotting time, the activated partial thromboplastin time (APTT) of the blank plasma group, the control PES group, and the modified PES microsphere group were (27.57±1.25) s, (28.47±0.45) s, and (30.4±0.872) s, respectively, and the difference between the experimental group and the other two groups was statistically significant (P<0.01, P<0.05). There was no significant change in red blood cell and white blood cell counts.
    Conclusion The microspheres prepared in the study have high efficiency in bilirubin adsorption, excellent mechanical properties and thermal stability, and good blood biocompatibility, and are expected to be used in the clinical treatment of patients with liver failure.

     

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