重组人骨形态发生蛋白-2膜片的研制及其稳定性实验

Preparation of the clinical form of recombinant human bone morphogenetic protein-2 and its stability research

目的研制重组人骨形态发生蛋白-2(rhBMP-2)膜片并对其稳定性进行研究,最终提供用于临床试验的合格样品。方法1.采用医用胶原蛋白海绵作为辅料,与rhBMP-2悬液复合,制作成膜片,钴60消毒后测活并送检各项指标。2.采用血清钙试剂盒的方法,通过检测不同条件处理后的rhBMP-2样品的活性变化来反映样品的生物稳定性。结果rhBMP-2膜片生物活性良好,经中国药品生物制品检定所检验各项指标符合要求;在4℃放置两年,活性依然保持良好;在室温放置6个月,活性略有降低;而在37℃条件下,放置1个月活性明显降低,但放置半年与放置1个月活性差别不大。结论所研制的rhBMP-2膜片,稳定性良好,符合临床试验的各项指标。

Purpose To prepare the befitting form of recombinant human bone morphogenetic protein-2 （rhBMP-2）for clinical trial and to observe the stability of the products. Methods 1. The composite film was prepared by dropping suspended liquid of rhBMP-2 samples onto the collagen sponge which is used for assistive supplement in clinic. After sterilization with cobalt 60, the products were tested for biological activity and oth- er medical indexes. 2. Using serum calcium test kit, the stability of rhBMP-2 products were investigated by measuring the biological activity of the samples treated under different conditions. Results The rbBMP-2 composite with collagen film showed a satisfying biological activity. And the quality of the composite patch con- formed to the clinical demands tested by National Institute for the Control of Pharmaceutical and Biological Products. The results showed that after 2 years storage at 4℃, the biological activity of rhBMP-2 was retained good. The biological activity showed a slight decrease when the sample was placed at room temperature for 6 months, compared to a marked decrease at 37℃ for 1 month. But the difference is inconspicuous between 1 month treatment and 6 month treatment under 37℃ condition. Conclusion The prepared composite film of rhBMP-2 and collagen sponge conforms to the clinical demands and is stable. It can be used in the clinical trial.