Pharmacokinetics and pharmaceutics investigation on copper complex to development an oral therapeutic agent for Menkes disease.

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K06762
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Musashino University
• Principal Investigator: Kudo Toshiyuki 武蔵野大学, 薬学部, 講師 (10584815)
• Co-Investigator(Kenkyū-buntansha): 深水 啓朗 明治薬科大学, 薬学部, 教授 (20366628) ; 高橋 秀依 東京理科大学, 薬学部薬学科, 教授 (10266348) ; 児玉 浩子 帝京大学, 医学部, 講師 (00093386)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 銅錯体 / メンケス病 / ナノ粒子化

Outline of Final Research Achievements

Menkes disease is a rare hereditary disease in which systemic deficiency of copper due to mutation of ATP7A result in decreased copper absorption and tissue distribution, and most patients die in early childhood. In this study, we investigated the pharmacokinetics of the copper complex CuGTSM in macular mice, a murine model of Menkes disease, as part of development of a therapeutic agent for Menkes disease which can be orally administered. Absorption and dissociation of orally administered CuGTSM has been confirmed in macular mice, and absorption was improved by nanoparticulation. In addition, it was suggested that CuGTSM is easily dissociated into copper and ligand in macular mice.

Free Research Field

薬物動態学

Academic Significance and Societal Importance of the Research Achievements

本研究は、有機化学、製剤学、薬物動態学の専門家が連携して行ったことで市販されていない銅錯体について体内動態の評価および製剤的工夫ができた。メンケス病患者においては銅とリガンドへの解離が亢進している可能性が示唆されたこと、また、製剤的工夫により銅錯体の吸収性を高めることができたことを活用し、今後も有用なメンケス病治療薬創製を目指していきたい。