東京工科大学 研究報告等

藤沢 章雄
所属  応用生物学部 応用生物学科
職種  教授
言語種別
英語
発行・発表の年月
2017年11月
形態種別
学術論文
査読
査読あり
標題
Stabilizers of edaravone aqueous solution and their action mechanisms. 1. Sodium bisulfite.
執筆形態
共著
掲載誌名
Journal of Clinical Biochemistry and Nutrition
出版社・発行元
Society for Free Radical Research Japan
巻・号・頁
61(3),159-163
担当範囲
HPLC Analysis
著者・共著者
Tanaka M, Sugimura N, Fujisawa A, Yamamoto Y.
概要
Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has been used as a free radical scavenging drug for the treatment of acute ischemic stroke in Japan since 2001. Edaravone is given to patients intravenously; therefore, it is distributed in the form of an aqueous solution. However, aqueous solutions of edaravone are very unstable because it is present as edaravone anion, which is capable of transferring an electron to free radicals including oxygen, and becomes edaravone radical. We observed the formation of hydrogen peroxide and edaravone trimer when aqueous edaravone solution was kept at 60°C for 4 weeks. We proposed the mechanism of edaravone trimer formation from edaravone radicals. Lowering the pH and deoxygenation can effectively increase the stability of aqueous edaravone solution, since the former reduces edaravone anion concentration and the latter inhibits edaravone radical formation. Addition of sodium bisulfite partially stabilized aqueous edaravone solutions and partially inhibited the formation of edaravone trimer. Formation of bisulfite adduct was suggested by 13C NMR and HPLC studies. Therefore, the stabilizing effect of sodium bisulfite is ascribed to the formation of a bisulfite adduct of edaravone and, consequently, reduction in the concentration of edaravone anion.
論文(査読付)ファイル