| Project/Area Number |
10672092
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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 |
医薬分子機能学
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| Research Institution | Showa Pharmaceutical University |
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Principal Investigator |
WATANABE Yoshiteru Showa Pharmaceutical University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (70175131)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Mitsuo Showa Pharmaceutical University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (10077513)
FUJII Makiko Showa Pharmaceutical University, Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 講師 (50199296)
UTOGUCHI Naoki Showa Pharmaceutical University, Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 講師 (80276633)
ENDO Kazutoyo Showa Pharmaceutical University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (50106598)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Physiological action of nitric oxide / Nitric oxide donor / Absorption-enhancing effect / Transmuscosal drug absorption / Protein drug / 一酸化窒素生理作用 / 経粘膜吸収 |
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| Research Abstract |
The objective of this investigation was to evaluate the potential of nitric oxide (NO) donors as a new class of absorption-enhancing agent which may act on epithelial cells of mucosal membrane (intestinal, rectal, nasal and so on) through epithelial actions of a chemical mediator, NO, released from each donor such as S-nitroso-N-acetyl-DL-penicillamine (SNAP). When model drug of poorly absorbed macromolecule such as inslulin and recombinant human granulocyte colony-stimulating factor was administered with SNAP into the rectum or the nasal cavity of rabbits, significant increase of absorption of these macromolecular drugs was observed. The absorption enhancement of macromolecular drug by SNAP was decreased when these two drugs were administered in combination with NO scavenger such as carboxy-PTIO. These results suggest that NO plays an essential role in enhancement of drug absorption. We found that SNAP had very low potential for cytotoxicity, as evaluated by the cell detachment assay, release of lactate dehydrogenase (LDH) from cultured cells and morphological observations of rectal and nasal tissue of rabbits that received SNAP. A NO donor such as SNAP is a promising absorption-enhancing agent for rectal and nasal delivery systems of poorly absorbed drug such as protein drug. However, several research subjects concerning the absorption-enhancing mechanism of NO in detail remain to he done. Further experiments including instrumental analysis should be studied.
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