Bednarek Elżbieta, Sitkowski Jerzy, Bocian Wojciech, Borowicz Piotr, Płucienniczak Grażyna, Stadnik Dorota, Surmacz-Chwedoruk Weronika, Jaworska Beata, Kozerski Lech
National Medicines Institute, 00-725 Warsaw, Poland.
Institute of Biotechnology and Antibiotics, Warsaw, Poland.
J Pharm Biomed Anal. 2017 Feb 20;135:126-132. doi: 10.1016/j.jpba.2016.12.005. Epub 2016 Dec 15.
A monomer structure of a novel human insulin analog A22-B3-B31 (SK3R) has been characterized by NMR in water/acetonitrile solution and compared with the structure of human insulin (HIS) established in the same medium. The composition of the oligomer ensemble for neat insulins in water was qualitatively assessed by monitoring, derived from NMR experiment, translational diffusion coefficient Dix10ms, whose value is a population averaged of individual coefficients for species in oligomeric ensemble. Nanospray ESI/MS experiment was used to establish the masses of oligomers in pharmaceutical formulation of the SK3R insulin. The pharmacodynamic data were established and compared to insulin glargine characterized by the same profile of action in diabetics. The oligomerization process of insulin during development of pharmaceutical formulation with routinely used excipients has been studied using translation diffusion coefficient Dix10ms established in water solution. These properties were compared with those of human insulin (HIS) which is a standard reference for novel recombinant insulins.
一种新型人胰岛素类似物A22 - B3 - B31（SK3R）的单体结构已在水/乙腈溶液中通过核磁共振（NMR）进行了表征，并与在相同介质中确定的人胰岛素（HIS）结构进行了比较。通过监测源自NMR实验的平移扩散系数Dix10ms，对水中纯胰岛素的寡聚体集合组成进行了定性评估，该值是寡聚体集合中各物种个体系数的总体平均值。纳米喷雾电喷雾电离质谱（Nanospray ESI/MS）实验用于确定SK3R胰岛素药物制剂中寡聚体的质量。建立了药效学数据，并与在糖尿病患者中具有相同作用特征的甘精胰岛素进行了比较。利用在水溶液中建立的平移扩散系数Dix10ms，研究了胰岛素在使用常规辅料开发药物制剂过程中的寡聚化过程。将这些性质与作为新型重组胰岛素标准参考的人胰岛素（HIS）的性质进行了比较。
