新型内毒素特异吸附血液净化材料的制备与性能研究

Study on Preparation and Property of a New Adsorbent for Endotoxin Removal in Blood Purification

本研究目的是制备一种带有肝素(heparin)分子臂和多黏菌素B(PMB)配基的用于清除内毒素的血液净化吸附材料,探讨其在内毒素血症治疗方面的潜在应用价值。首先采用氯甲基树脂(PS)为载体,经乙二胺活化后引入肝素分子臂,戊二醛将PMB配基固定于吸附剂;荧光标记内毒素(FITC-LPS)体外静态吸附实验直接观察材料吸附性能,内毒素体外静态吸附实验测定其吸附量和吸附率,并对吸附剂血液相容性进行了评价。结果表明,吸附剂在2h左右能够达到吸附平衡,对脂多糖(LPS)的去除率能够达到70%以上,对血细胞和血浆蛋白的吸附率分别小于10%和20%。吸附剂对于LPS具有高选择性及高吸附量,并具有良好的生物相容性,在内毒素血症治疗方面具有一定的临床应用前景。

In order to remove the endotoxin from the blood of endotoxemia patients, we prepared a new adsorbent with heparin space arm and polymyxin B （PMB） ligand. The carrier of chloromethyl polystyrene resin was activated and heparin space arm was grafted, and then PMB ligand was immobilized onto adsorbent with glutaraldehyde. We employed in vitro FITC-lipopolysaccharide （FITC-LPS） static adsorption to characterize the adsorption properties on the adsorbent, and conducted in vitro lipopolysaccharide （LPS） static adsorption to measure quantitavely the adsorp- tion capacity and rate, and then evaluated the blood compatibility. The in vitro static adsorption indicated that the adsorbent had the removal rate of LPS above 70~ with the adsorption equilibrium time for 2 hours. Blood compati- bility experiment showed that the adsorbent had little negative effects on blood cells and plasma protein, and their ad- sorption rates were less than 10% for hemocytes and 20~ for plasma protein respectively. This adsorbent exhibited high selectivity, high adsorption capacity and good biocompatibility, and presented a promising clinical application in the treatment of endotoxemia.