| Project/Area Number |
16590029
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Nagasaki University |
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Principal Investigator |
NISHIDA Koyo Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (20237704)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Junzo Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (30115901)
FUMOTO Shintaro Nagasaki University, Graduate School of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (70380988)
NAKASHIMA Mikiro Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (00260737)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | liver / anticancer drug / drug interaction / liver disease / intraperitoneal administration / pharmacokinetics / 粘性 / 吸収速度 |
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| Research Abstract |
Development of drug delivery system (DDS) to achieve site-specific delivery or prolonged retention in the circulation has attracted attention, because new types of drugs are expected to be created with advance in life science and biotechnology such as human genome project. We have tried to develop a new administration route for drug targeting to the liver, since normal drug administration by intravenous and oral route have difficulty in achieving a local site of action in the liver. As a basic research of developing liver surface application formulation for anticancer drugs and genome, we studied the effect of viscosity of viscous additives on the absorption of 5-fluorouracil (5-FU) from the liver surface and the organ-specific inhibition of elimination process. In the fiscal year of 2004, we employed the diffusion cell for liver surface application and clarified that the absorption rate of 5-FU was decreased by addition of viscous additives (polyvinyl alcohol PVA, sodium carboxymethylcellulose). Moreover, we suggested that site specificity of 5-FU in the liver was improved by addition of PVA 15%. Furthermore, in 2005, we examined the organ-specific inhibition of elimination process of phenolsulfonphthalein (PSP) by probenecid organic anion transport inhibitor by liver or kidney surface application, aiming to develop the new DDS capable of inhibition of elimination process. In the case of i.v. probenecid administration, organ-specific inhibition was not seen. In the case of liver surface application, significant inhibition effect was not recognized in the liver and kidney. On the other hand, kidney surface application of probenecid resulted in 20% of renal clearance of PSP. Accordingly, significant inhibition of urinary secretion of PSP was implied, due to suppression of probenecid amount in the liver.
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