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Improvemrnt of Drug Absorption in Gastro intestinal Tract

Research Project

Project/Area Number 05454573
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionTokyo University of Pharmacy and Life Science

Principal Investigator

AWAZU Shoji  School of Pharmacy, Tokyo University of Pharmarcy and Life Science Professor, 薬学部, 教授 (60012621)

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)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1993: ¥5,700,000 (Direct Cost: ¥5,700,000)
KeywordsAbsorption enhancement / Caco-2 / Tight iunction / Intracellular calcium / Peptide / Glucose transporter / VitaminA / Enkephalin / 吸収改善 / 吸収促進剤 / レクチン / パイエル板 / 糖付加
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.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] M.Tomita,M.Hayashi and S.Awazu: "Absorption-enhancing mechanism of sodium caprate and decanoyol-carnitine in Caco-2 cells" J.Pharmacol.Exp.Ther.272. 739-743 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Mizuma,N.Sakai and S.Awazu: "Na^+-dependent transport of aminopeptidase-resistant sugar-coupled tripeptides in rat intestine" Biochem.Biophys.Res.Commun.203. 1412-1416 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Mizuma,K.Ohta and S.Awazu: "The β-anomeric and glucose preferences of glucose transport carrier for intestinal active absorption of monosaccharide conjugates." Biochim.Biophys.Acta.1200. 117-122 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Horie and S.Awazu: "Retinoids:From Basic Science to Applications" M.A.Livrea&G.Vidali, 11 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mikio Tomita, Masahiro Hayashi and Shoji Awazu: "Absorption-enhancing mechanism of sodium caprate and decanoyol-carnitine in Caco-2 cells" J.Pharmacol.Exp.Ther. 272. 739-743 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takashi Mizuma, N.orio Sakai and Shoji Awazu: "Na^+-dependent transport of aminopeptidase-resistant sugar-coupled tripeptides in rat intestine" Biochem.Biophys.Res.Commun.203. 1412-1416 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takashi Mizuma, Kunihiro Ohta and Shoji Awazu: "The beta-anomeric and glucose preferences of glucose transport carrier for intestinal active absorption of monosaccharide conjugates." Biochem.Biophys.Acta.1200. 117-122 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Toshiharu Horie and Shoji Awazu: Protective effect of vitamin A against the small Eds., M.A.Livrea & G.Vidali, intestinal damage during methotrexate treatment Birkhauser Verlag Basel/Switzerland. In "Retinoids : From Basic Science to Applications", 281-291 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Tomita,M.Hayashi and S.Awazu: "Absorption-enhancing mechanism of sodium caprate and decanoyol- carnitine in Caco-2 cells" J.Pharmacol.Exp.Ther.272. 739-743 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Mizuma,N.Sakai and S.Awazu: "Na^+-dependent transport of aminopeptidase-resistant sugar-coupled tripeptides in rat intestine" Biochem.Biophys.Res.Commun.203. 1412-1416 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Mizuma,K.Ohta and S,Awazu: "The β-anomeric and glucose preferences of glucose transport carrier for intestinal active absorption of monosaccharide conjugates." Biochim.Biophys.Acta.1200. 117-122 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Horie and S.Awazu: "Retinoids:From Basic Science to Applications" M.A.Livrea & G.Vidali, 11 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] S.Haseto,H.Ouchi,T.Isoda,et al.: "Transport of low and high molecular peptides across rabbit peyer's patches." Pharmaceutical Research. 11. 361-364 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] J-I.Yamamoto,Y.Nagai,T.Horie and S.Awazu: "Effect of vitamin A on methotrexate cytotoxicity in L1210 murine leukemia cells in culture." Cancer Chemother.Pharmacol.32. 263-267 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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