栓塞用水凝胶微球的制备及其理化性质的评价

Preparation and physicochemical characterization of hydrogel microspheres for embolization

目的:研究栓塞用微球的制备方法、理化性质及影响因素。方法:采用反相悬浮聚合法制备出N-[三(羟甲基)甲基]丙烯酰胺-明胶微球。考查了明胶(10.0～100.0g/L)、N-[三(羟甲基)甲基]丙烯酰胺单体(33～200g/L)、交联剂N,N′-亚甲基双丙烯酰胺(3.3～10.0g/L)、表面活性剂Span80(0.5～1.8g/L)和引发剂过硫酸铵(1.0～5.0g/L)等各因素对微球粒径、吸水率和弹性的影响,采用光学显微镜观察了微球的表面形态,并对微球的红外光谱作了分析。结果:制备的微球圆整、表面光滑;平均粒径随着明胶、N-[三(羟甲基)甲基]丙烯酰胺单体、交联剂质量浓度的增加而变大,随着表面活性剂、引发剂浓度的增加而减少;吸水率随着明胶、交联剂质量浓度的增加而降低,表面活性剂的增加对吸水率的影响不大;弹性随明胶浓度的增加而降低,随单体、交联剂浓度的增加而增加,与表面活性剂、引发剂的关系不大。通过综合考虑粒径、吸水率、弹性各影响因素选择的最后反应条件为明胶10.0g/L、单体100.0g/L、交联剂6.7g/L、表面活性剂0.9g/L、引发剂3.0g/L,得到的微球平均粒径约为700.0μm,吸水率为12.4(g/g),弹性(通过微导管最大粒径)为1600.0μm;红外光谱结果证明单体发生了聚合反应,得到N-[三(羟甲基)甲基]丙烯酰胺-明胶微球。结论:研制出的微球外观圆整、亲水性强、弹性良好,具备用于栓塞治疗的特点。

Objective： To develop and characterize the hydrogel microspheres for embolization. Methods： N- [ tris （hydroxymethyl） methyl ] acrylamide-gelatin microspheres （ TGMs ） were prepared by an inverse suspension polymerization approach. Effects of materials on size, water absorption rate and elasticity of the microspheres were investigated. The materials which were included consisted of gelatin in the range of 10.0 - 100.0 g/L, N-[ tris（hydroxymethyl） methyl] acrylamide in the range of 33.3 - 200 g/L, cross-linking agent N, N＇-methylene-bis-acrylamide in the range of 3.3 - 10.0 g/L, surfactant Span 80 in the range of 0.5 - 1.8 g/L, and initiator ammonium persulfate in the range of 1.0 - 5.0 g/L. The appearance of TGMs was observed under microscope. TGMs were analyzed by infrared spectrum （IR）. Results ： The TGMs were round with smooth surface in view of photograph of microscope. The average diameter of TGMs was increased with the increase of gelatin, monomer or cross-linking agent concentrations but decreased with the increase of surfactant or initiator Concentration. The water adsorption rate of the microspheres was decreased with the increase of gelatin or cross-linking agent concentration but not affected by surfactant concentration. The elasticity of TGMs was increased with the increase of monomer or cross-linking agent concentration, decreased with the increase of gelatin concentration, but not affected by surfactant or initiator concentration. All factors above considered, the final prepared TGMs consisted of 10 g/L gelatin, 100.0 g/L monomer, 6.7 g/L cross-linking agent, 0.9 g/L surfactant, and 3.0 g/L initiator. The average diameter of TGMs obtained was about 700.0 μm. The water adsorption rate and the elasticity in accordance with the maximum diameter of the microspheres passed through a microcatheter of TGMs were 12.4 （ g/g）, and 1 600.0 μm, respectively. The results of IR spectra confirmed the polymerization of monomer, resulting in N-[ tris （hydroxymethyl） methyl ] acrylamide-gelatin microspheres. Conclusion： The developed TGMs seemed to be suitable for clinical embolization according to the surface, average diameter, elastic and hydrophilic property of TGMs.