1994 Fiscal Year Final Research Report Summary
Improvemrnt of Drug Absorption in Gastro intestinal Tract
| Project/Area Number |
05454573
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
AWAZU Shoji School of Pharmacy, Tokyo University of Pharmarcy and Life Science Professor, 薬学部, 教授 (60012621)
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| Co-Investigator(Kenkyū-buntansha) |
HORIE Toshiharu University of Chiba Professor, 薬学部, 教授 (90120154)
TOMITA Mikio School of Pharmacy Assistant, 薬学部, 助手 (60207610)
MIZUMA Takashi School of Pharmacy Lecturer, 薬学部, 講師 (80229715)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Absorption enhancement / Caco-2 / Tight iunction / Intracellular calcium / Peptide / Glucose transporter / VitaminA / Enkephalin |
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| Research Abstract |
Relation between the Modified Structure of Digestive Tract and Absorption Ability, and the Absorption Improvement by Peyer's Patch. Absorption enhancers, both of C10 and PC increased the intracellular Ca level. Following the increase, C10 opened the tight junction by the activation of actomyosin ring cascade, but it was shown clearly that PC opened the junction b the different mechanism. Glucose did not show the enhancing effect. The absorbability of BSA and concanavalin A was larger in the rabbit Peyer's patch than in jejunum. The possibility to use Peyer's patch to enhance the macromolecules was shown. Among peptidases, the exo peptidases exhibited the absorption enhancing effect, showing the possible new type enhancer. Inhibition Effect of Vitamin A on Membrane Damage induced by Anticancer Drug. IEC-6 was not used successfully to investigate the vitamin A mechanism, but it was shown clearly that vitamin A inhibits the decrease of absorbability of intestins as well as structural change induced by methotrexate.Improvement of Absorption by Glucose Transporter.Tripeptide Tyr-Gly-Gly (TGG) which is a part of enkephaline was with glucose and galactose by coupline method. Every sugar-coupling inhibited the degradation of TGG and increased the absorbability. Na^+-dependent transport worked partly at least for the absorption. Aminopeptidase was inhibited by the sugar-coupling, but enkephalinase was not. The enkephalinase inhibitor increased the stability and absorbability of the sugar-coupled enkephalin. These findings suggests the absorption improvement peptides by sugar coupling. Sugar conjugates with acetaminophen were synthesized, and their absorptions proceeded partly by glucose transporter. The order of absorbability was alpha-glucoside > beta-glucode > beta-galactoside. This order coincided with the former reported one.
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