School of Basic Medicine, Yunnan University of Traditional Chinese Medicine, 1076, Yuhua Rd., Kunming, 650500, China.
School of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, 1076, Yuhua Rd., Kunming, 650500, China.
BMC Pharmacol Toxicol. 2022 Jul 18;23(1):52. doi: 10.1186/s40360-022-00591-5.
Polysorbate 80 for injection (TW80) is a common excipient used for injection whose macromolecular impurities, including those that cause anaphylactoid reactions, are frequently ignored. The main aim of this study was to prove that the macromolecular impurities in the excipient are an important cause of anaphylactoid reactions. Component A (containing macromolecules > 100 kDa), Component B (containing macromolecules from 10 to 100 kDa), and Component C (containing substances < 10 kDa) were prepaired from the original TW80 using ultrafilters. The original TW80 contained numerous substances with molecular weights > 10kD. The original TW80 and Components A and B caused strong anaphylactoid reactions in both guinea pigs and rabbits by intravenous administration. Moreover, the original TW80 and Components A and B even caused strong passive cutaneous anaphylactoid (PCA) reactions and pulmonary capillary permeability. The PCA reaction and increased permeability were partly prevented by cromolyn sodium. Additionally, the original TW80 and Components A and B caused vasodilation and severe hemolysis in vitro. The anaphylactoid reactions were associated with histamine release but not with mast cell degranulation. Nevertheless, Component C almost caused no anaphylactoid reactions or hemolysis and was weaker in the few reactions that ocurred. Taken together, these results suggest that macromolecular substances are one of the main risk factors responsible for anaphylactoid reactions and hemolysis caused by TW80.
注射用聚山梨酯 80（TW80）是一种常用的注射用辅料，其高分子杂质，包括引起过敏样反应的杂质，常被忽视。本研究的主要目的是证明辅料中的高分子杂质是引起过敏样反应的重要原因。使用超滤法从原始 TW80 制备成分 A（含有分子量> 100 kDa 的高分子）、成分 B（含有 10 至 100 kDa 分子量的高分子）和成分 C（含有< 10 kDa 的物质）。原始 TW80 含有许多分子量> 10kD 的物质。原始 TW80 和成分 A 和 B 通过静脉给药在豚鼠和兔中均引起强烈的过敏样反应。此外，原始 TW80 和成分 A 和 B 甚至引起强烈的被动皮肤过敏样（PCA）反应和肺毛细血管通透性增加。原 TW80 和成分 A 和 B 引起的 PCA 反应和通透性增加部分被 cromolyn 钠预防。此外，原始 TW80 和成分 A 和 B 在体外引起血管扩张和严重溶血。过敏样反应与组胺释放有关，但与肥大细胞脱颗粒无关。然而，成分 C 几乎不会引起过敏样反应或溶血，并且在发生的少数反应中较弱。综上所述，这些结果表明，高分子物质是引起 TW80 引起过敏样反应和溶血的主要危险因素之一。
