Ruiz Llamil, Aroche Kethia, Reyes Nuria
Center for Genetic Engineering and Biotechnology, PO Box 6162, Havana, Cuba.
AAPS PharmSciTech. 2006;7(4):99. doi: 10.1208/pt070499.
Sodium phosphate buffer increased the aggregation of rhIFN-α2b in the range of 1.55 to 1.810 day, as determined by SDS/PAGE under reduced and nonreduced conditions. In contrast, sodium citrate buffer decreased the aggregation rate of this cytokine, as compared with those samples in sodium phosphate buffer. Results from sodium citrate-phosphate buffer were very similar to those obtained with sodium citrate solutions. On the other hand, EDTA Na×2HO reduced the aggregation rate of rhIFN-α2b, showing an aggregation kinetic constant in the range of 0.52 to 0.75×10 day. Polysorbates 20 and 80 were less effective than the chelating agent in preventing this degradation pathway. Additionally, metal ions (Zn and Cu) increased the aggregation kinetic constant of rhIFN-α2b, probably through undetermined metal-catalyzing reactions. Taken together, these data can be useful for the development of new formulations containing rhIFN-α2b as an active ingredient.
在还原和非还原条件下通过SDS/PAGE测定，磷酸钠缓冲液在1.55至1.810天范围内增加了重组人干扰素α2b（rhIFN-α2b）的聚集。相比之下，与磷酸钠缓冲液中的样品相比，柠檬酸钠缓冲液降低了这种细胞因子的聚集速率。柠檬酸盐 - 磷酸盐缓冲液的结果与柠檬酸钠溶液的结果非常相似。另一方面，乙二胺四乙酸二钠（EDTA Na×2H₂O）降低了rhIFN-α2b的聚集速率，其聚集动力学常数在0.52至0.75×10⁻³天范围内。聚山梨酯20和80在防止这种降解途径方面比螯合剂效果差。此外，金属离子（锌和铜）可能通过未确定的金属催化反应增加了rhIFN-α2b的聚集动力学常数。综上所述，这些数据对于开发含有rhIFN-α2b作为活性成分的新制剂可能是有用的。
