| Project/Area Number |
17K15522
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 非攪拌水層 / 膜結合型mucin / MUC1 / 腸管吸収 / 粘液層 / mucin / 薬物吸収 / 抗がん剤 / 相互作用 / 薬学 / 生体分子 / 蛋白質 |
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| Outline of Final Research Achievements |
The unstirred water layer (UWL) permeation is suggested to be a rate-limiting step in the intestinal absorption of hydrophobic drugs. The major glycoprotein components of the UWL are mucins, which classified into two structural types: secretory and membrane-bound mucins. Each membrane-bound mucin has a large extracellular domain, which is heavily glycosylated, their intestinal expression in gastrointestinal tract may affect intestinal drug absorption. However, there have been no reports that describe the contribution of mucins to intestinal drug absorption at the molecular level. In this research project, we focused on typical membrane-bound type mucins (MUC1 and MUC13) expressed in gastrointestinal tract, and demonstrated that MUC1 could be limit the permeation of hydrophobic drugs. Furthermore, we found that the effect of mucin on the membrane permeation process may be different from molecular types, based on the molecular size of extracellular domain.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、これまでの薬物吸収理論において粘液層全体への考察に留まっていた脂溶性薬物と粘液層との関係性について分子論的な評価・考察を可能にした。本研究で得られた成果は、医薬品開発における腸管吸収の適正な評価法を確立する上での有益な情報を与えるものと考えられ、ヒト腸管における薬物吸収の高精度予測を可能にするための基盤情報を提供し、医薬品開発の効率化・臨床開発の成功確率向上にも貢献するものと期待される。
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