| Project/Area Number |
12557206
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Physical pharmacy
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| Research Institution | Kumamoto University |
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Principal Investigator |
UEKAMA Kaneto Kumamoto University, Faculty of Pharmaceutical Sciences, Pharmaceutics, Professor, 薬学部, 教授 (90040328)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUOKA Toshikazu Kumamoto University, Faculty of Pharmaceutical Sciences, Pharmaceutics, Associate Professor, 薬学部, 助教授 (50150545)
HIRAYAMA Fumitoshi Kumamoto University, Faculty of Pharmaceutical Sciences, Pharmaceutics, Associate Professor, 薬学部, 助教授 (90094036)
有馬 英俊 熊本大学, 薬学部, 助手 (50260964)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Keywords | Cyclodextrins / Functional drug carrier / Peptide / protein drugs / Bioadaptability / Inhibition of aggregation / Absorption enhancement / Release-control / Targeting / 熱変性 / 安定化剤 / 可溶化剤 / 環状オリゴ糖 / 粘膜付着性 / 薬物放出制御 |
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| Research Abstract |
This study dealed with the investigation of the multi-funtional properties, biological properties, and inclusion properties of various β-cyclodextrin derivativess (β-CyDs), anticipating the novel drug carriers for peptide/protein drugs. Results obtained were as follows;
(1) Among various acylated β-CyDs with different chain lengths (C_1-C_<12>), per-O-butanoyl and per-O-valery-β-CyDs formed transparent, adhesive sheet-like films without any chemical cross-linkings. These films worked as a reservoir-type carrier with high bioadaptability in transdermal delivery system, thus prolonging the release of water-soluble drugs including peptide drugs, such as isosorbide dinitrate, molsidomine, buserelin acetate and insulin.
(2) Sulfobutyl ether β-CyD, a polyanionic highly water-soluble CyD derivative with a hydrophobic butyl spacer between CyD and the sulfonate, strongly interacted with a model peptide, insulin. This interaction significantly inhibited both aggregation and enzymatic degradation of insulin, leading the high bioavailability and hypoglycaemic effect of insulin after subcutaneous administration in rats.
(3) Effect of 6-O-(4-O-α-D-Glucuronyl)-D-glucosyl-β-CyD (GUG-β-CyD) on the aggregation of recombinant human growth hormon (rhGH) was studied and compared with hydrophilic CyDs. The results indicated that GUG-β-CyD interacts with the exposed hydrophobic surfaces of the molten globule-like intermediates of rhGH and reduces the protein-protein interaction, resulting in the inhibition of aggregations induced by various chemical and physical stimulus such as guanidine-, voltexing- and thermal-denaturations. Moreover, GUG-β-CyD interacted strongly with basic drugs, and may be useful as a safe solubilizer and/or stabilizer for basic drugs such as chlorpromazine and cinnarizine.
Since the CyD derivatives developed here have higher bioadaptability, they can be useful as drug carries for protein and peptide drugs in both parenteral and nonparenteral adminstrations.
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