High concentration formulations of recombinant human interleukin-1 receptor antagonist: II. Aggregation kinetics

High concentration formulations of recombinant human interleukin-1 receptor antagonist: II. Aggregation kinetics
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DOI:
10.1002/jps.21205
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发表时间:
2008-08-01
影响因子:
3.8
通讯作者:
Randolph, Theodore W.
Randolph, Theodore W.
中科院分区:
医学3区
文献类型:
--
作者:
Alford, John R.;Kendrick, Brent S.;Randolph, Theodore W.

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在高蛋白浓度(即50-100 mg/mL)和37℃时,低离子强度的溶液可加速重组人白介素1受体拮抗剂(rhIL-1ra)的聚集。我们使用了各种物理和光谱技术来解释这一观测结果。将颗粒平衡模型应用于稳态的连续混合悬浮混合产物去除(MSMPR)反应器,以确定聚集体的形核和生长速率。当离子强度较低时,成核速率增加,而生长速率不受影响。在低浓度的rhIL-1ra(即,
At high protein concentrations (i.e., 50-100 mg/mL) and 37 degrees C, low solution ionic strength accelerates aggregation of recombinant human interleukin-1 receptor antagonist (rhIL-1ra). We have used a variety of physical and spectroscopic techniques to explain this observation. A population balance model was applied to a continuous mixed suspension, mixed product removal (MSMPR) reactor at steady-state to determine aggregate nucleation and growth rates. Nucleation rates increase at low ionic strength, while growth rates are unaffected. At low rhIL-1ra concentrations (i.e.,