血红蛋白最佳聚合工艺匹配条件的研究

Study of optimal matching conditions for hemoglobin polymerization process

目的 探讨以戊二醛为交联剂的血红蛋白类氧载体（HBOCs）的聚合工艺匹配条件的优化研究,进一步降低终产品的平均分子质量和超大分子含量,提高聚合血红蛋白的有效转化率.方法 在前期对人胎盘血红蛋白与戊二醛交联的单因素影响水平的研究基础上,选取戊二醛的加样速度、血红蛋白的质量浓度和戊二醛与血红蛋白的摩尔比3个因素做正交试验以优化血红蛋白聚合工艺的匹配条件.结果 戊二醛与血红蛋白的摩尔比对聚合血红蛋白分子质量分布的影响最大,其次是血红蛋白的质量浓度,最后为戊二醛的加样速度.对平均分子质量的影响分析,不同的戊二醛与血红蛋白摩尔比条件下的平均分子质量间的差异均具有统计学意义（P＜0.05）,而不同的血红蛋白质量浓度和戊二醛的加样速度条件下的平均分子质量间的差异均无统计学意义（P＞0.05）;对有效转化率的影响分析,不同的戊二醛与血红蛋白摩尔比和不同的血红蛋白质量浓度条件下的有效转化率间的差异均具有统计学意义（P＜0.05）,不同的戊二醛加样速度条件下的有效转化率间的差异均无统计学意义（P＞0.05）;对超大分子含量的影响分析,不同的戊二醛与血红蛋白摩尔比条件下的超大分子含量间的差异均具有统计学意义（P＜0.05）,不同血红蛋白的质量浓度和戊二醛的加样速度条件下超大分子含量间的差异均无统计学意义（P＞0.05）.结论 通过以上实验分析,优化确定了血红蛋白聚合工艺的最佳匹配条件.

Objective To study the optimization process of matching conditions using glutaraldehyde （GDA） as crosslinking agent of hemoglobin based oxygen carriers （HBOCs）,to further reduce the average molecular weight and the content of super-weight molecular,and improve the conversion ratio of polymerization.Methods The orthogonal designs were done on the basis of the previous single influencing factor research of human placenta hemoglobin crosslinking GDA.Three factors were selected including molar ratio of GDA to hemoglobin,mass concentration of hemoglobin and the rate of the feeding GDA.Results The molar ratio of GDA to hemoglobin is the most important influencing factor on the molecular weight distribution of polymerized hemoglobin,followed by the mass concentration of hemoglobin and the rate of feeding GDA.When analyzing the impact on the mean molecular weight,there were significant differences between mean molecular weight corresponding to different molar ratios of GDA to hemoglobin （P〈0.05）,while there was no statistical significance between mean molecular weight corresponding to different mass concentrations of hemoglobin and the rates of feeding GDA （P〉0.05）.When analyzing the impact on the effective conversion ratio,there were significant differences between effective conversion ratios corresponding to different molar ratios of GDA to hemoglobin and different mass concentrations of hemoglobin （P〈0.05）,while there were no statistical significances between effective conversion ratios corresponding to different rates of feeding GDA （P〉0.05）.When analyzing the impact on the content of super-weight molecular,there were significant differences between content of super-weight molecular corresponding to different molar ratios of GDA to hemoglobin,while there were no statistical significances between content of super-weight molecular corresponding to different mass concentrations of hemoglobin and different rates of feeding GDA.Conclusions The optimal matching conditions of hemoglobin polymerization process were determined by orthogonal designs.