| Endotoxemia is a common and complex problem for medicine,and drug therapeutic efficacy is not very well.Hemoperfusion can remove endotoxin,but the endotoxin adsorption materials which can be used in clinical are still at the exploratory stage.Objective To design and synthesise the expected endotoxin adsorption resin- HB-H-7.Tocompare and test its performance.To study the efficacy and safety of the adsorption of endotoxin and cytokines with HB-H-7 resin in vitro.Methods HB-H-7 resin synthesise:Styrene and DVB were polymerized suspensiblily to obtain copolymer beads body in the water phase.Then repeatedly introduce the ionization of the group to the copolymer.Adsorption materials performance comparative experiment:To compare HB-H-7 resin with other commonly used adsorbents.All of these commonly used adsorbents including,acidic cation exchange resin,sodium alginate fixed polymyxin B,macroporous adsorption resin,Japan carbonized resin,weak polar resin and alkaline anion exchange resin.Before and after the static adsorption experiment with 14 kinds of adsorption materials respectively,plasma endotoxin, protein and electrolytes were detected,and the rate of 2-hour adsorption was calculated.The experiment was repeated 10 times.Static adsorption experiment for endotoxin and cytokines.Adsorption material was added into endotoxin-positive patients plasma according to the volume ratio of 1:10.Then,they were put in a constant temperature water bath oscillator,and oscillated for 2 hours.Before and after the experiment,plasma endotoxin and cytokines were detected,and the rate of 2-hour adsorption was calculated.The experiment was repeated 10 times.Dynamic adsorption experiment for endotoxin.5ml resin was put into a self-made perfusion unit.Endotoxin-positive patients plasma(50ml) had been perfused for 2 hours.The flow rate of plasma was controlled at 4ml/min with the infusion pump,the plasma endotoxin were detected at 0,30,60 and 120 minutes after plasma hemoperfusion, and the adsorption rates were calculated.The results were compared with static adsorption's.The influence of temperature during adsorption experiment was determined as follows.Perfusion method was similar with dynamic adsorption experiments.The perfusion units were either placed in a 37℃water tanks or 25℃(room temperature).Then,the plasma endotoxin was measured after 2 hours' plasma perfusion,and the adsorption rates were calculated.HB-H-7 resin safety experiments. Before and after the static adsorption experiment with HB-H-7,plasma protein and electrolytes were detected,and the rate of 2-hour adsorption was calculated, L=(C0-C)/C0×100%.The experiment was repeated 10 times.The supernatent of resin extracts was screened by ultraviolet light sepetrophotometer.The pyrogen was detected by rising temperature technique in rabbits.Results After performance testing, HB-H-7 was anion exchange resin.Surface active group was -N+(CH3)2.Aperture was 80-100nm.Porosity was 45-52%.Volume was 0.75-0.84ml/g.Specific surface area was 850-1000m2/g.Adsorption materials performance comparison experiments:The plasma endotoxin were significantly lower after adsorption with HB-H-7,and the adsorption rate were 99.2%(P < 0.05).The plasma protein adsorption rates of HB-H-7 were lower than 15%respectively(P < 0.05).But the plasma electrolytes had not been significantly changed by HB-H-7.Adsorption endotoxin and cytokines experiments with HB-H-7 resin adsorption.The plasma endotoxin and proinflammatory cytokines were significantly lower with HB-H-7 resin static adsorption(all P<0.05).The adsorption rate of endotoxin,tumor necrosis factor-αand interleukin-1,6,8 were 99.2%,55.0%,57.0%,75.0%,42.0%,respectively.Dynamic Adsorption rate was higher than static's,but we didn't detect the significant changes (99.8%vs.99.1%,P>0.05).There was no statistically significant differnce in tempreture(37℃vs.25℃,99.9%vs.99.8%,P>0.05).HB-H-7 resin safety experiment.Changes in protein were small(P<0.05),and there was no statistically significant change in plasma electrolytes(all P>0.05).No dissolved matters of resins were found.The test of pyrogen was negative.Conclusion HB-H-7 resin was styrene series anion exchange resin and synthesised for the adsorption of endotoxins in specifically.Adsorption materials performance comparison experiments:HB-H-7 effectively adsorbed endotoxin,and it hadn't obvious effects on electrolytes adsorption.Though it had some effects on plasma protien,but all of their adsorption rates were lower than 15%.HB-H-7 resin could effectively adsorb endotoxin and proinflammatory cytokines in vitro.No dissolved matters of resins were found.The test of pyrogen was negative.So HB-H-7 resin was efficient and safe on endotoxin and cytokines adsorption.Further experiments in vivo could be carried out.
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