壳聚糖基多孔微球的制备及其止血性能的研究

发布时间：2018-07-03 19:01

本文选题：壳聚糖 + 多孔微球　；参考：《福建师范大学》2016年硕士论文

【摘要】：作为甲壳素的脱乙酰产物,壳聚糖(CS)是仅次于纤维素的自然界最丰富的可再生高分子,且具有无毒、无害、成本低、生物相容性、易于加工以及生物降解性等优点。同时,由于壳聚糖分子每个葡萄糖胺单元中含有1个氨基(.NH2),它可以与血液中细胞,血小板,蛋白质发生相互作用,从而对创伤止血产生影响。本研究致力于调控壳聚糖颗粒的微观结构以提高它的止血性能。采用乳液制球与热致相分离相结合,制备了高孔隙率,高吸水率,低密度的壳聚糖基多孔微球,并研究了它的体内外伤口止血性能。主要内容如下：(1)所制得微球表面和内部都呈现多孔结构。通过改变壳聚糖乳液的乳化条件包括乳化剂配比,乳化温度等成功调控了所制得微球的尺寸,当乳化剂配比Tween60/Span 80为0.2/4.8且乳化温度为40℃时可得到平均直径较小(167+38.5 μm),尺寸相对均一的多孔微球产品；通过调节淬火温度和使用共混聚合物原料可以实现对多孔微球表面孔径的调控。当淬火温度降低时,微球表面孔径随之减小,当将CS与PVA共混后乳化时,微球表面孔径也减小,并且当共混比例CS/PVA为6/4时孔径达到最小(0.49+0.07μm)。对CSMS和CS/PVA微球的密度,吸水率,孔隙率及体外降解能力进行了表征,结果表明多孔微球的密度很小:CSMS-7:0.0609g/cm3),孔隙率很大(CSMS-7:97.55%)吸水率很高(CSMS-7:1552%).当微球尺寸相近时,微球表面孔径减小时,微球密度增大,吸水率减小,孔隙率改变不明显；CSMS有着比CS/PVA更好的体外降解能力,四周后降解了自身质量的60%。对CS/PVA微球的红外和热性能测试结果表明,当CS/PVA的共混比例为6/4时,微球热失重速率较慢,两种聚合物的相容性较好。(2)微球的止血效果与微球表面孔径大小有着很大关联,当微球表面孔径较大时(大于红细胞和血小板的平均直径),微球的止血效果相对于商业化的Celox止血粉提升不明显；当微球孔径减小时(小于红细胞血小板的平均直径)微球的止血效果相对于Celox有了明显的提升。大鼠断尾法模型试验测得的止血时间(CSMS-7:189s),大鼠肝脏止血模型试验测得的止血时间(CSMS-7:80s)和促凝血时间(CSMS-7:105s)相对于Celox (299s,117s和115s)都有明显缩短,血栓形成速度明显变快。组织学检验表明壳聚糖微球对伤口的组织几乎没有任何刺激作用,不会引起伤口的不良反应。多孔结构的引入不会影响壳聚糖对红细胞和血小板的吸附能力,微球表面凹凸不平的结构有利于血小板的粘附和激活。当壳聚糖微球负载氨甲环酸时,氨甲环酸在血液中可快速释放,并与多孔壳聚糖微球发生良好的协同止血作用使载药壳聚糖多孔微球的止血性能进一步提升,大鼠肝脏止血模型试验测得的止血时间(CSMS-7TA:138s),大鼠肝脏止血模型试验测得的止血时间(CSMS-7TA:61s)和促凝血时间(CSMS-7TA:70s)明显缩短,血栓形成速度也有所加快。(3)本文所制备的壳聚糖多孔微球细胞相容性良好,没有毒性,肝细胞在其表面12h,24h,72h均能正常增殖。与市售细胞载体cytodex的细胞相容性相当,甚至优于cytodex。CSMS-5样品的大孔结构十分有利于细胞粘附与增殖,虽然其止血效果一般,但其有望作为一种新型高密度细胞培养的载体。
[Abstract]:A chitosan - based porous microsphere with high porosity , high water absorption and low density was prepared by changing the emulsifying conditions of chitosan emulsion .
The pore size of porous microspheres can be controlled by adjusting the quenching temperature and using the blended polymer raw materials . When the quenching temperature is reduced , the pore diameter of the microspheres decreases . When CS and PVA are blended , the pore diameter of the microspheres is reduced . The density , water absorption , porosity and in vitro degradation ability of CSMS and CS / PVA microspheres are characterized . The results show that the density of CSMS and CS / PVA microspheres is very small ( CSMS - 7 : 0.0609g / cm3 ) , and the porosity is very large ( CSMS - 7 : 97.55 % ) . The water absorption is very high ( CSMS - 7 : 1552 % ) . When the size of the microspheres is close , the density of the microspheres is increased , the water absorption is reduced , and the porosity change is not obvious .
The results of infrared and thermal properties of CS / PVA microspheres showed that when CS / PVA blending ratio was 6 / 4 , the thermal loss rate of microspheres was slow , and the compatibility of the two polymers was good . ( 2 ) The hemostatic effect of microspheres was correlated with the pore size of microspheres .
The hemostatic time ( CSMS - 7 : 80s ) and coagulation time ( CSMS - 7 : 105s ) measured in rat liver haemostasis model were significantly shorter than that of Celox ( 29 s , 117s and 115s ) . The hemostatic time ( CSMS - 7TA : 61s ) and coagulation time ( CSMS - 7 : 105s ) were significantly shorter than that of Celox ( 29s , 117s and 115s ) .
【学位授予单位】：福建师范大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：O636.1

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