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Establishment of innovative biomembrane permeation boosting technology aiming for early clinical development

Research Project

Project/Area Number 16K08211
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Physical pharmacy
Research InstitutionKobe Gakuin University

Principal Investigator

Takeda Mariko  神戸学院大学, 薬学部, 教授 (70257096)

Co-Investigator(Kenkyū-buntansha) 亀井 敬泰  神戸学院大学, 薬学部, 助教 (40637451)
Research Collaborator Khafagy El-Sayed  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords細胞膜透過ペプチド / バイオ薬物 / バイオアベイラビリティ / 生体膜透過 / 吸収促進 / インスリン / アルギニン / トリプトファン / バイオ医薬 / 難吸収性薬物 / 経口製剤 / ドラッグデリバリー / 吸収改善
Outline of Final Research Achievements

This study aimed to establish an effective biomembrane permeation delivery technology that can be utilized for preparing oral drug formulation of poorly absorbed substances (biopharmaceuticals and medium molecular drugs). As a result of the research, it was clearly demonstrated that cell-penetrating peptides (CPPs) can exert bioavailability (BA) boosting effects not only on biopharmaceuticals but also on low to medium molecular drugs (molecular weight 300 to 1000) belonging to BCS Class III. Furthermore, arginine and tryptophan, those are constituent amino acids of CPPs, showed powerful BA boosting effects for a number of biopharmaceuticals as well as high molecular weight materials. Since they have been clinically used, it could be considered the possibility of early use of this basic technology for oral formulation development of poorly absorbed drugs.

Academic Significance and Societal Importance of the Research Achievements

現在、創薬とそれに続く臨床開発分野では “難吸収性(低膜透過性)の克服”という困難な課題に直面している。本研究は、その課題に対し普遍的な解決法を提案することを究極の目標として、難吸収性物の経口創薬に有効活用できる生体膜透過デリバリー基盤技術を確立することを目的としている。CPPsおよび構成アミノ酸を非架橋型で用いる本BAブースティング技術は、本研究の成果が示すように、低分子、高分子およびナノ粒子などのDDSキャリアにも万能に適用可能な革新的な技術であり、今後、世界の経口製剤開発をリードし、創薬・創剤開発に多大な貢献ができるものと期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (35 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (3 results) Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (24 results) (of which Int'l Joint Research: 3 results,  Invited: 10 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] The University of Texas at Austin(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] The Suez Canal University(Egypt)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Suez Canal University(Egypt)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Combination Strategy with Complexation Hydrogels and Cell-Penetrating Peptides for Oral Delivery of Insulin2018

    • Author(s)
      Y. Fukuoka, E. S. Khafagy, T. Goto, N. Kamei, K. Takayama, N. A. Peppas, M. Takeda-Morishita
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Issue: 5 Pages: 811-814

    • DOI

      10.1248/bpb.b17-00951

    • NAID

      130006730708

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2018-05-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exploration of the Key Factors for Optimizing the <i>in Vivo</i> Oral Delivery of Insulin by Using a Noncovalent Strategy with Cell-Penetrating Peptides2018

    • Author(s)
      Kamei N, Shigei C, Hasegawa R, Takeda-Morishita M
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Issue: 2 Pages: 239-246

    • DOI

      10.1248/bpb.b17-00798

    • NAID

      130006329268

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hydrophobic Amino Acid Tryptophan Shows Promise as a Potential Absorption Enhancer for Oral Delivery of Biopharmaceuticals2018

    • Author(s)
      Kamei N, Tamiwa H, Miyata M, Haruna Y, Matsumura K, Ogino H, Hirano S, Higashiyama K, Takeda-Morishita M
    • Journal Title

      Pharmaceutics

      Volume: 10 Issue: 4 Pages: 182-202

    • DOI

      10.3390/pharmaceutics10040182

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential of Single Cationic Amino Acid Molecule “Arginine” for Stimulating Oral Absorption of Insulin2017

    • Author(s)
      Noriyasu Kamei, El-Sayed Khafagy, Jun Hirose, Mariko Takeda-Morishita
    • Journal Title

      International Journal of Pharmaceutics

      Volume: 521 Issue: 1-2 Pages: 176-183

    • DOI

      10.1016/j.ijpharm.2017.01.066

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 膜透過促進戦略に基づくバイオ薬物の経口吸収改善2019

    • Author(s)
      亀井敬泰, 武田真莉子
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] バイオ医薬の経口製剤化・脳標的化にチャレンジするDDS研究最前線2019

    • Author(s)
      武田真莉子
    • Organizer
      神戸ポートアイランド創薬フォーラム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Drug delivery and pharmaceutical technology: Recent advances in DDS research on the key molecule "cell- penetrating peptides" that controls the kinetics of the next- generation drug "biopharmaceuticals"2018

    • Author(s)
      Takeda-Morishita M, Kamei N
    • Organizer
      International Conference on Applied Pharmaceutical Sciences
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Potential of hydrophobic amino acid tryptophan as an absorption enhancer for the oral delivery of biopharmaceutics2018

    • Author(s)
      Kamei N, Tamiwa H, Miyata M, Takeda-Morishita M
    • Organizer
      The 45th Annual Meeting and Exposition, the Controlled Release Society
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] バイオ医薬の動態を制御するキー分子“細胞膜透過ペプチド”のDDSフロンティア研究2018

    • Author(s)
      武田真莉子
    • Organizer
      薬物動態懇話会4月例会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 細胞膜透過ペプチド併用経鼻投与によるレプチンの全身および脳送達と肥満治療効果2018

    • Author(s)
      加藤雅大, 有銘兼史, 野々村杏奈, 藤原由衣, 湯浅瑛代, 荻野秀侑, 平野聖怜奈, Khafagy El-S, 亀井敬泰, 武田真莉子
    • Organizer
      第24回創剤フォーラム若手研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] トリプトファン併用投与によるバイオ薬物の消化管吸収改善効果の評価2018

    • Author(s)
      春名裕太, 宮田真里, 松村康耀, 民輪英之, 亀井敬泰, 武田真莉子
    • Organizer
      第24回創剤フォーラム若手研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 膜透過促進機能を搭載したpH応答性ハイドロゲルによるインスリン経口送達システムの開発2018

    • Author(s)
      東山和広, 山本万由, 亀井敬泰, Peppas NA, 武田真莉子
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] レプチンの全身吸収および脳移行性を高める細胞膜透過ペプチド併用経鼻投与法の有用性評価2018

    • Author(s)
      藤原由衣, 奥村遥, 湯浅瑛代, 亀井敬泰, 武田真莉子
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] レプチンおよび細胞膜透過ペプチドの繰り返し経鼻投与による肥満抑制効果の検証2018

    • Author(s)
      加藤雅大, 有銘兼史, 野々村杏奈, 荻野秀侑, 平野聖怜奈, 藤原由衣, 湯浅瑛代, Khafagy El-S, 亀井敬泰, 武田真莉子
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 難吸収性低分子薬物の膜透過性改善における細胞膜透過ペプチド併用戦略の有用性評価2018

    • Author(s)
      金岡将平, 小出夢子, 亀井敬泰, 武田真莉子
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 糖尿病治療薬開発を推進するDDSの最新の話題2018

    • Author(s)
      武田真莉子
    • Organizer
      第79回大阪薬科大学公開教育講座
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 難吸収性薬物の経口bioavailabilityを 改善するDDS研究最前線2018

    • Author(s)
      武田真莉子
    • Organizer
      - 新適塾 -「未来創薬への誘い」第41回会合
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] トリプトファン併用投与によるバイオ薬物の消化管粘膜吸収促進作用の評価2018

    • Author(s)
      亀井敬泰、宮田真里、武田真莉子
    • Organizer
      日本薬学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 細胞膜透過ペプチドの生体膜透過ブースティング効果を基盤とするバイオ医薬の経粘膜デリバリーシステムの開発2017

    • Author(s)
      武田真莉子
    • Organizer
      日本薬学会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 細胞膜透過ペプチドを利用した難吸収性薬物の経口吸収促進基盤技術の確立2017

    • Author(s)
      亀井敬泰、武田真莉子
    • Organizer
      日本薬学会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] Recent advances in DDS research on the key molecule "cell-penetrating peptudes" that controls the kinetics of the next-generation drug "biopharmaceuticals".2017

    • Author(s)
      Takeda-Morishita M, Kamei N,
    • Organizer
      Pharmaceutical Sciences Seminar, Mahidon Univ., Thailand
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] インスリン経口製剤化 ~臨床開発動向と基礎研究の進展~2017

    • Author(s)
      武田真莉子
    • Organizer
      第27回 DM Club Meeting
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 疎水性アミノ酸併用によるインスリン経口吸収性の改善2017

    • Author(s)
      宮田真里、民輪英之、東山和広、平野聖怜奈、荻野秀侑、亀井敬泰、武田真莉子
    • Organizer
      第6回日本くすりと糖尿病学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 疎水性アミノ酸併用によるペプチド薬物の経口吸収性の改善2017

    • Author(s)
      民輪英之、宮田真里、東山和広、荻野秀侑、平野聖怜奈、亀井敬泰、武田真莉子
    • Organizer
      日本薬剤学会第32年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 細胞膜透過ペプチド併用による難吸収性薬物の消化管粘膜透過性の改善2017

    • Author(s)
      金岡将平、小出夢子、亀井敬泰、武田真莉子
    • Organizer
      日本薬学会近畿支部大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 塩基性アミノ酸によるインスリンの消化管粘膜透過促進作用の評価2016

    • Author(s)
      今西 晴紀、牛尾 吏佐、広瀬 淳、Khafagy El-Sayed、亀井 敬泰、武田 真莉子
    • Organizer
      第5回日本くすりと糖尿病学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2016-10-29
    • Related Report
      2016 Research-status Report
  • [Presentation] 非侵襲的投与ルートを介するインターフェロンβ送達法の開発2016

    • Author(s)
      小倉未咲, 民輪英之, 亀井敬泰, 武田真莉子
    • Organizer
      第66回日本薬学会近畿支部総会
    • Place of Presentation
      神戸
    • Year and Date
      2016-10-15
    • Related Report
      2016 Research-status Report
  • [Presentation] Usefulness of Cell-Penetrating Peptides in Noninvasive Nasal Delivery of PEGylated Interferon Beta2016

    • Author(s)
      N. Kamei, Y. Iwase, El-S. Khafagy, M. MIyamoto and M. Takeda-Morishita
    • Organizer
      43rd Annual Meeting of the Controlled Release Society
    • Place of Presentation
      Seattle, Washington, USA
    • Year and Date
      2016-07-17
    • Related Report
      2016 Research-status Report
  • [Book] 医療・診断をささえるペプチド科学2017

    • Author(s)
      武田真莉子
    • Total Pages
      315
    • Publisher
      シーエムシー出版
    • Related Report
      2017 Research-status Report
  • [Remarks] 神戸学院大学薬学部 薬物送達システム学研究室

    • URL

      http://www.pharm.kobegakuin.ac.jp/~dds/index.html

    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 抗がん剤を含む難吸収性薬物の消化管吸収促進剤2017

    • Inventor(s)
      武田真莉子、亀井敬泰
    • Industrial Property Rights Holder
      学校法人神戸学院
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017-02-10
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] インスリンを含むバイオ薬物の消化管吸収促進剤2016

    • Inventor(s)
      武田真莉子、亀井敬泰
    • Industrial Property Rights Holder
      学校法人神戸学院
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-04-16
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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