کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2487345 | 1114413 | 2008 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
High Concentration Formulations of Recombinant Human Interleukin-1 Receptor Antagonist: I. Physical Characterization
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
At relatively high protein concentrations (i.e., up to 100 mg/mL), recombinant human interleukin-1 receptor antagonist (rhIL-1ra) was found to exist in a monomer-dimer equilibrium controlled by solution ionic strength. Sedimentation equilibrium at 25°C was used to measure the increase in the dimer dissociation constant (Kd) as a function of ionic strength. Kd increased from 2.0 to 12.6 mM as the solution ionic strength was increased from 0.011 to 0.184 molal. These Kd values were used with both static light scattering and membrane osmometry data collected over a protein concentration range of 1-100 mg/mL to determine second osmotic virial coefficients. Expanding the second osmotic virial coefficient model to account for separate monomer-monomer (B22), monomer-dimer (B23), and dimer-dimer (B33) interactions reveals net monomer-dimer interactions are attractive, whereas the others are repulsive. Lastly, isothermal titration calorimetry dilution experiments showed that rhIL-1ra dimerization is enthalpically driven (ÎHdimerizationââªâ0), which is consistent with intermolecular cation-Ï interactions previously proposed as the monomer-monomer contact sites in dimers. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 3035-3050, 2008
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 8, August 2008, Pages 3035-3050
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 8, August 2008, Pages 3035-3050
نویسندگان
John R. Alford, Stanley C. Kwok, Jennifer N. Roberts, Deborah S. Wuttke, Brent S. Kendrick, John F. Carpenter, Theodore W. Randolph,