| Project/Area Number |
11672265
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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 |
応用薬理学・医療系薬学
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| Research Institution | Kumamoto University |
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Principal Investigator |
UEKAMA Kaneto Faculty of Pharmaceutical Sciences, Pharmaceutics, Kumamoto University, Professor, 薬学部, 教授 (90040328)
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| Co-Investigator(Kenkyū-buntansha) |
HIRAYAMA Fumitoshi Faculty of Pharmaceutical Sciences, Pharmaceutics, Kumamoto University, Associate Professor, 薬学部, 助教授 (90094036)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | Cyclodextrin / Colon specific delivery / Biodegradable drug carrier / Ester-type prodrug / Colonic microflora / Prednisolone / Inflammatory bowel disease rats / Alleviation of side effect / n-酪酸 |
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| Research Abstract |
The biodegradable characteristics of cyclodextrins (CyDs) are found to be useful as a source of site-specific delivery of drugs to colon and as a pro-moiety for construction of glucocorticoid prodrug with low adverse effect. Prednisolone succinate (PDsuc), a typical glucocorticoid, was conjugated onto one of the secondary hydroxyl groups of CyDs through an ester bond. The hydrolysis of ester conjugates proceeded intramolecularly through both acyl migrations between the C_2 and C_3 hydroxyl groups of CyDs and between the C_<17> and C_<21> hydroxyl groups of PD.The ester conjugates were stable in rat blood and intestinal homogenates without contents, the hydrolysis rate being almost same as that in phosphate buffer. The anti-inflammatory effect after oral and intracolonic administrations of the PDsuc/α-CyD ester conjugate to inflammatory bowel disease model rats was comparable to those after a direct intracolonic administration of PD.However the adverse effect of PD monitored by change in thymus/body weight ratio, was significantly alleviated by the administrations of the PDsuc/α-CyD ester conjugate. These data indicated that the PDsuc/α-CyD ester conjugate is useful as a delayed release type prodrug for colon-specific delivery owing to alleviation of the systemic side effect, while maintaining the therapeutic effect. Therefore, the PDsuc (Steroid)/CyD ester conjugates may be particularly useful as novel IBD (Inflammatory Bowel Disease) therapeutic prodrugs.
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