聚乙二醇修饰干扰素α2b的稳定性研究

Study on stability of polyethylene glycol-IFN α 2b conjugates

目的研究聚乙二醇修饰干扰素α 2b的稳定性。方法以抗病毒活性为指标 ,考察单修饰干扰素α 2b、多修饰干扰素α 2b和干扰素α 2b的稳定性 (4℃、2 5℃、37℃ )、抗胰蛋白酶水解能力和 37℃人血清稳定性。结果在4℃、2 5℃和 37℃条件下 ,稳定性依次为多修饰干扰素α 2b >单修饰干扰素α 2b >干扰素α 2b。抗胰蛋白酶水解试验表明 :干扰素α 2b在 30min时抗病毒活性迅速降到原来的 7.1% ,单修饰干扰素α 2b剩余 5 0 % ,多修饰干扰素α 2b仍保留 71%。体外稳定性试验表明 ,在 37℃人血清放置 10h ,干扰素α 2b只保留 35 % ,单修饰干扰素α 2b保留 71% ,而多修饰干扰素α 2b仍保留 95 %的抗病毒活性。结论聚乙二醇修饰可以增加干扰素α 2b的稳定性 ,抗胰蛋白酶水解能力和 37℃人血清稳定性。除了抗胰蛋白酶水解能力 。

PurposeThe research was developed to evaluate the stability of polyethylene glycol IFN α 2b conjugates .MethodsAnti viral activity is used as an index to evaluate the thermal stability (at 4℃, 25℃ and 37℃), and the ability of avoiding the trypsin digestion and stability in vitro ( at 37℃ in human serum) of mono PEG IFN α 2b and poly PEG IFN α 2b, then it is compared with IFN α 2b. ResultsPoly PEG IFN α 2b is thermally more stable than mono PEG IFN α 2b, and mono PEG IFN α 2b more stable than IFN α 2b. The test of anti trypsin digestion suggests that poly PEG IFN α 2b retains 71 % of its anti viral activity 1, mono PEG IFN α 2b 50%, IFN α 2b only 7.1% 30 minutes after being reserved in trypsin solution. Stability in vitro indicates that the anti viral activity of poly PEG IFN α 2b is reduced to 95%, mono PEG IFN α 2b 71% and IFN α 2b 35% 10 hours after being preserved in human serum at 37 ℃.ConclusionPolyethylene glycol IFN α 2b conjugates have improved thermal stability, ability of protecting from trypsin digestion and stability in vitro . Moreover, the higher the degree of modification, the more stable the IFN α 2b conjugates except in the test of anti trypsin digestion.