注射用重组人干扰素α1b与常用药物的配伍研究

Study on compatibility of recombinant human interferon α1b for injection with common drugs YANG Ming-ming*,

目的分析重组人干扰素α1b(rh IFN-α1b)与临床常用的异丙托溴铵、硫酸特布他林、布地奈德联合配伍后用于雾化疗法的可行性。方法使用WISH/VSV微量细胞病变抑制法检测rh IFN-α1b与药物配伍0、1、4、12 h后的生物学活性,比较雾化前后rh IFN-α1b生物学活性的改变。使用高效液相色谱法(HPLC)和十二烷基磺酸钠—聚丙烯酰胺凝胶电泳(SDS-PAGE)法测定配伍试剂中rh IFN-α1b在雾化前后分子结构的改变;检测rh IFN-α1b与上述药物配伍后溶液的外观等物理性质。结果 rh IFN-α1b与3种药物进行配伍各时间点的生物学活性在93. 1%～100. 0%之间,配伍后其外观、含量、结构、纯度均未发生较大变化。配伍后雾化收集液中rh IFN-α1b生物学活性0～4 h是在74. 0%～82. 4%之间,12 h时保留率在56. 9%～78. 5%之间。结论 rh IFN-α1b与异丙托溴铵、硫酸特布他林、布地奈德配伍后在0～4 h内药物外观、含量、纯度与干扰素活性均无明显变化,且雾化后生物活性基本保留,绝大部分分子结构保持完整。

Objective To analyze the feasibility of fog chemotherapy with recombinant human interferon-α1 b( rh IFN-α1 b) combined with ipratropium bromide,terbutaline sulfate and budesonide.Methods The biological activity of rh IFN-α1 b was detected by WISH/VSV microcytopathy inhibition method after 0,1,4,12 hours of combination of rh IFN-α1 b and drugs,and the changes of rh IFN-α1 b biological activity before and after atomization were compared.The changes of molecular structure of rh IFN-α1 b in compatibility reagent before and after atomization were determined by high performance liquid chromatography( HPLC) and twelve alkyl sulfonate polyacrylamide gel electrophoresis( SDS-PAGE).The physical properties of rh IFN-α1 b solution were tested after it was compatible with the above drugs.Results The biological activity of rh IFN-α1 b was93.1%~ 100.0% at each time point when it was compatible with three drugs.After compatibility,the appearance,content,structure and purity of rh IFN-α1 b did not change significantly.The biological activity of rh IFN-α1 b in the collected solution was 74.0%~ 82.4% for 0 ~ 4 h,and the retention rate was 56.9%~ 78.5% for 12 h.Conclusion The appearance,content,purity and interferon activity of rh IFN-α1 b in combination with ipratropium bromide,terbutaline sulfate and budesonide did not change significantly within 0 ~ 4 hours.The biological activity of rh IFN-α1 b remained basically after atomization,and most of its molecular structure remained intact.