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Elucidation of pemeable mechanism of new intestinal permeable peptide

Research Project

Project/Area Number 16K15162
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionKumamoto University

Principal Investigator

OHTSUKI Sumio  熊本大学, 大学院生命科学研究部(薬), 教授 (60323036)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords環状ペプチド / 小腸透過 / Caco-2細胞 / Caco2細胞 / 小腸 / 透過 / DDS / ペプチド
Outline of Final Research Achievements

In order to develop macromolecular drugs, it has been desired to realize carriers that allow macromolecule to permeate the small intestine. Using a newly identified cyclic peptide that promotes penetration of the small intestine, the purpose of this study was to elucidate the characteristics and mechanism of cyclic peptide permeation through the small intestine. Phage penetration was inhibited by synthetic peptides in both Caco-2 cells and mouse small intestine closed loop. In addition, it was suggested that the fluorescence labeled cyclic peptide was internalized into Caco-2 cells and its internalization was mediated by energy-dependent process, and macro-pinocytosis was involved. In addition, it was revealed that cyclic structure is necessary for promoting the penetration, and that small the cyclic peptides do not weaken tight junctions and have low toxicity to small intestinal epithelial cells.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (11 results)

All 2018 2017 2016 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Journal Article] Identification of cyclic peptides for facilitation of transcellular transport of phages across intestinal epithelium in vitro and in vivo2017

    • Author(s)
      Yamaguchi Shunsuke、Ito Shingo、Kurogi-Hirayama Mio、Ohtsuki Sumio
    • Journal Title

      Journal of Controlled Release

      Volume: 262 Pages: 232-238

    • DOI

      10.1016/j.jconrel.2017.07.037

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] 環状ペプチドによる小腸透過キャリアの開発2018

    • Author(s)
      大槻純男、増田豪、伊藤慎悟
    • Organizer
      立命館大学創剤研究コンソーシアム2017年度第2回研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 高分子医薬品の経口投与型DDS開発を目指した小腸透過性環状ペプチドの同定と評価2017

    • Author(s)
      伊藤慎悟
    • Organizer
      第10回若手ネットワーキングシンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 経口投与型高分子医薬品の開発を目指した小腸透過性環状ペプチドの同定と評価2017

    • Author(s)
      原田智徳、山口駿介、増田豪、伊藤慎悟、大槻純男
    • Organizer
      第41回蛋白質と酵素の構造と機能に関する九州シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 経口投与型バイオ医薬品の開発に資する小腸透過性環状ペプチドの同定2016

    • Author(s)
      山口駿介、伊藤慎悟、平山未央、大槻純男
    • Organizer
      第33回日本薬学会九州支部大会
    • Place of Presentation
      鹿児島
    • Year and Date
      2016-12-03
    • Related Report
      2016 Research-status Report
  • [Presentation] Identification of Novel Cyclic Peptides for Facilitating Intestinal Permeability of Macromolecule2016

    • Author(s)
      Shunsuke Yamaguchi, Shingo Ito, Mio Hirayama, Sumio Ohtsuki
    • Organizer
      2016 AAPS Annual Meeting and Exposition
    • Place of Presentation
      Debver, USA
    • Year and Date
      2016-11-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 経口投与型DDS開発を目指した小腸透過性環状ペプチドの同定とin vivo有効性評価2016

    • Author(s)
      伊藤慎悟、大槻純男
    • Organizer
      第39回薬物動態懇談会
    • Place of Presentation
      浜松
    • Year and Date
      2016-11-10
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 高分子医薬品の小腸透過を改善させる小腸透過性環状ペプチドの同定2016

    • Author(s)
      山口駿介、伊藤慎悟、平山未央、大槻純男
    • Organizer
      第32回DDS学会
    • Place of Presentation
      静岡
    • Year and Date
      2016-06-30
    • Related Report
      2016 Research-status Report
  • [Remarks] 熊本大学大学院生命科学研究部微生物薬学分野

    • URL

      http://ohtsuki-lab.jp/

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
  • [Patent(Industrial Property Rights)] 新規な細胞膜透過性ペプチド2017

    • Inventor(s)
      伊藤慎悟、大槻純男
    • Industrial Property Rights Holder
      伊藤慎悟、大槻純男
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 新規な細胞膜透過性ペプチド2016

    • Inventor(s)
      伊藤慎悟、大槻純男
    • Industrial Property Rights Holder
      熊本大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-05-18
    • Related Report
      2016 Research-status Report
    • Overseas

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Published: 2016-04-21   Modified: 2019-03-29  

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