Pharmacokinetics and pharmaceutics investigation on copper complex to development an oral therapeutic agent for Menkes disease.
| Project/Area Number |
18K06762
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Musashino University |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 銅錯体 / メンケス病 / ナノ粒子化 / ATP7A / 銅 / Cu-GTSM |
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| 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.
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| 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。
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Report
(5 results)
Research Products
(24 results)
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[Journal Article] Early clinical signs and treatment of Menkes disease.2022
Author(s)
Fujisawa C, Kodama H, Sato Y, Mimaki M, Yagi M, Awano H, Matsuo M, Shintaku H, Yoshida S, Takayanagi M, Kubota M, Takahashi A, Akasaka Y.
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Journal Title
Mol Genet Metab Rep.
Volume: 31
Pages: 100849-100849
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pharmacokinetics of CuGTSM, a Novel Drug Candidate, in a Mouse Model of Menkes Disease.2021
Author(s)
Yamagishi Y, Kudo T, Oyumi M, Sakamoto Y, Takahashi K, Akashi T, Kobayashi S, Kawakami T, Goda H, Sato Y, Mimaki M, Kodama H, Munakata M, Makino K, Takahashi H, Fukami T, Ito K.
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Journal Title
Pharm Res.
Volume: 38
Issue: 8
Pages: 1335-1344
DOI
Related Report
Peer Reviewed
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