Utsunomiya Hirotoshi, Ichinose Masao, Tsujimoto Kazuko, Katsuyama Yukiko, Yamasaki Hisashi, Koyama A Hajime, Ejima Daisuke, Arakawa Tsutomu
Department of Strategic Surveillance for Functional Food and Comprehensive Traditional Medicine, Wakayama Medical University Graduate School of Medicine, Wakayama 641-8509, Japan.
Int J Pharm. 2009 Jan 21;366(1-2):99-102. doi: 10.1016/j.ijpharm.2008.09.012. Epub 2008 Sep 18.
Elevated temperatures have been used to inactivate viruses for plasma-derived biopharmaceuticals. This paper describes the effects of arginine and NaCl in conjunction with elevated temperature for inactivation of two enveloped viruses, i.e., herpes simplex virus type 1 (HSV-1) and influenza virus type A at neutral pH. In phosphate-buffered saline, a significant inactivation of HSV-1 occurred above 40 degrees C, resulting in less than 10% surviving virus (over 90% virus inactivation) at 50 degrees C. Arginine concentration dependently decreased the temperature required for virus inactivation, leading to temperature shift by almost 17 degrees C at 1.2M. NaCl also decreased the inactivation temperature, but to a considerably lesser extent, indicating that virus inactivation effect of arginine is not simply due to ionic strength. Influenza virus was also inactivated by high temperature, but its responses to arginine and NaCl were different from those on HSV-1, suggesting that virus inactivation mechanism is different between these two viruses, i.e., the effects of these reagents are virus specific.
升高温度已被用于使血浆源性生物制药中的病毒失活。本文描述了精氨酸和氯化钠与升高温度共同作用对两种包膜病毒(即1型单纯疱疹病毒(HSV-1)和甲型流感病毒)在中性pH下的失活效果。在磷酸盐缓冲盐溶液中,HSV-1在40摄氏度以上发生显著失活,在50摄氏度时存活病毒少于10%(病毒失活超过90%)。精氨酸浓度依赖性地降低了病毒失活所需的温度,在1.2M时导致温度偏移近17摄氏度。氯化钠也降低了失活温度,但程度要小得多,这表明精氨酸的病毒失活作用并非仅仅归因于离子强度。甲型流感病毒也可被高温失活,但其对精氨酸和氯化钠的反应与对HSV-1的反应不同,这表明这两种病毒的病毒失活机制不同,即这些试剂的作用具有病毒特异性。