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目的研究聚乙二醇化重组人生长激素的免疫原性及药动学。方法用rhGH及其两种mPEG修饰物PGH1、PGH2免疫家兔,检测兔血清中的抗体滴度;对家兔单次背部皮下给药,定时取血清,建立rhGH及其修饰物的ELISA双抗夹心检测法,检测血清中的药物浓度,并计算药动学参数。结果经过mPEG修饰后,明显降低了rhGH的抗体滴度,缩短了抗体持续时间。在药动学研究中发现,其t1/2β从3.1h显著延长到PGH1的9.9h和PGH2的22.5h,其AUC也有很大的提高。结论mPEG修饰后可明显降低rhGH的免疫原性,延长药物在动物体内的半衰期,降低清除率,改善其药动学性质。且改善程度随mPEG相对分子质量的增大而增强。
Objective To study the immunogenicity and pharmacokinetics of pegylated recombinant human growth hormone. Methods Rabbit was immunized with rhGH and its two mPEG modified PGH1 and PGH2 to detect the antibody titers in rabbits. Subcutaneous administration was given to the back of rabbits once a day, serum was taken at regular intervals, and ELISA double antibody against rhGH and its modification Sandwich detection, detection of serum drug concentration, and calculation of pharmacokinetic parameters. Results After mPEG modification, the antibody titer of rhGH was significantly reduced and the antibody duration was shortened. In the study of pharmacokinetics, it was found that its t1 / 2β significantly prolonged from 3.1h to 9.9h for PGH1 and 22.5h for PGH2, and its AUC was also greatly improved. Conclusion mPEG modification can significantly reduce the immunogenicity of rhGH, extend the half-life of drugs in animals, reduce clearance and improve its pharmacokinetic properties. And the degree of improvement with the increase of relative molecular mass of mPEG.