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. 2. Glutathione.
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),164-168
担当範囲
HPLC Analysis
著者・共著者
Tanaka M, Motomiya S, Fujisawa A, Yamamoto Y.
概要
Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has garnered attention since its approval for amyotrophic lateral sclerosis in Japan (2015) and the United States (2017). Edaravone is administered intravenously, and as such, is distributed in the form of an aqueous solution. However, aqueous solutions of edaravone are very unstable because they present as edaravone anions, which become edaravone radicals when the anion donates an electron to free radicals including oxygen. In this study, glutathione (GSH) stabilized an aqueous edaravone solution during storage at 60°C for 4 weeks, and prevented the formation of potentially carcinogenic phenylhydrazine, while cysteine did not. One possible explanation is that GSH undergoes intermolecular hydrogen bonding with edaravone anions, while cysteine does not, as it favors intramolecular hydrogen boding. The combination of GSH and sodium bisulfite (NaHSO3) stabilized aqueous edaravone at room temperature for more than 1 year even under aerobic conditions. However, the U.S. Food and Drug Administration cautioned that NaHSO3 may cause allergic reactions. Therefore, we developed a stable edaravone aqueous solution without using NaHSO3, namely a combination of GSH with deoxygenation, which resulted in better stabilization of aqueous edaravone than the combination of GSH and NaHSO3.
論文(査読付)ファイル