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雾化给药对重组人干扰素-α2b生物活性和分子结构的影响 被引量:22

The Effects of Atomization Inhalation on Biological Activity and Molecular Structure of Human Recombinant Interferon Alpha 2b
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摘要 目的:评估雾化吸入给药对重组人干扰素-α2b(rhIFN-α2b)生物活性和分子结构的影响。方法:采用病毒抑制法检测rhIFN-α2b的生物活性,通过比较雾化前后rhIFN-α2b生物活性的变化分析空气射流对其生物活性的影响。采用高效液相色谱(HPLC)法和十二烷基磺酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)法分析干扰素分子结构的改变。结果:雾化给药不会造成rhIFN-α2b蛋白质肽键断裂,但是空气射流会造成二硫键断裂,断裂比例与雾化前rhIFN-α2b浓度有关,600万IU/m L、300万IU/m L和100万IU/m L rhIFN-α2b雾化后纯度分别为82.9%、90.1%和94.9%。600万IU/m L rhIFN-α2b溶液雾化后17.1%的rhIFN-α2b分子出现二硫键的断裂,其中0.5%的rhIFN-α2b分子出现双二硫键断裂,雾化后喷雾壶内未完全汽化的剩余液中rhIFN-α2b的生物活性保留率为98.2%,雾化后收集的凝集液中rhIFN-α2b的生物活性保留率为96.1%。结论:rhIFN-α2b能以雾化状态稳定传输给药,生物活性基本保留。雾化后绝大部分rhIFN-α2b分子结构保持完整,少数分子出现单个或双二硫键断裂,为了尽量减少rhIFN-α2b分子的损耗,临床上雾化吸入rhIFN-α2b的浓度不应超过100万IU/m L。 Objective: To evaluate the effects of atomization inhalation of administration with recombinant human interferon alpha 2b( rhIFN-α2b) on its biological activity and molecular structure. Methods: The rhIFN-α2b biological activity was detected by virus inhibition method. The influence of the air jet on IFN-α2b biological activity was studied by comparing its biological activity before and after atomization. The changes of IFN-α2b molecular structure were analyzed by high performance liquid chromatography( HPLC)method and sodium dodecyl sulfate-polyacrylamide gel electrophoresis( SDS-PAGE) method. Results: Atomization inhalation of administration didn't cause the peptide bond of IFN-α2b protein to break,but air jet could cause disulfide bond to break. The ratio of IFN-α2b molecular with disulfide bond breaking was related to its concentration before atomization. After atomization the purity of 6millions IU / m L,3 millions IU / m L and 1 million IU / m L IFN-α2b were 82.9%,90.1% and 94.9% respectively. For 6 millions IU / m L concentration rhIFN-α2b solution,after atomization would cause disulfide bond of 17.1% rhIFN-α2b molecular to break. Therein a pair of two disulfide bonds breaking occured in 0.5% of rhIFN-α2b molecules. And the retention rate of rhIFN-α2b biological activity after atomization in remainder fluid was about 98.2% and in condensed fluid was 96.1%. Conclusion: Recombinant human interferon α2b can be transmitted stably in spray pattern. Its biological activity can be retained basic completely. The molecular structure of most of IFN-α2b keeps perfectly after the atomization. Single or double disulfide bond breaking in a few molecules of rhIFN-α2b is caused by air jet. In order to minimize the loss of rhIFN-α2b molecules,it is suggested atomization rhIFN-α2b concentration should be controlled under 1million IU / m L in clinical treatment.
作者 王兵 程婷 卢晨 周乐春 倪晓燕 李增礼 王荣海 宋礼华 Wang Bing Cheng Ting Lu Chen Zhou Lechun Ni Xiaoyan Li Zengli Wang Ronghai Song Lihua(Anhui Anke Biotechnology (Group) Co., Ltd. Anhui Hefei 230088, China Anhui Biological Institute, Anhui Hefei 230032, China)
出处 《儿科药学杂志》 CAS 2017年第3期1-5,共5页 Journal of Pediatric Pharmacy
关键词 重组人干扰素-α2b 雾化给药 生物活性 分子结构 二硫键 recombinant human interferon alpha 2b atomization inhalation of administration biological activity molecular structure disulfide bond
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