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Molecular crystal imprinting for rapid formation of cocrystal

Research Project

Project/Area Number 20K21105
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 27:Chemical engineering and related fields
Research InstitutionTokyo Institute of Technology

Principal Investigator

Shimoyama Yusuke  東京工業大学, 物質理工学院, 教授 (30403984)

Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywords共結晶 / 高圧二酸化炭素 / 分子結晶
Outline of Research at the Start

本研究課題では,高圧二酸化炭素を媒体とした「分子結晶インプリンティング技術」を創生し,医薬物質と共有体から成る「共結晶の形成を超高速化」する技術の確立を目的とする.共結晶を形成する上で,高圧二酸化炭素を「固体物質や液体物質の構造・物性変化」に利用し,医薬物質の分子結晶構造内へ共有体を輸送し,分子結晶内へ取り込ませ,共結晶を形成する「分子結晶インプリンティング」技術を創生する.

Outline of Final Research Achievements

High-pressure CO2 can be used as medium for dissolution and transport of coformer on process development of pharmaceutical cocrystal formation with a beads-milling and fused lipid phase. This cocrystal formation process achieves a solvent separation by only depressurization. Knowledge of pharmaceutical cocrystal formation process in high-pressure CO2 is accumulated in this work.

Academic Significance and Societal Importance of the Research Achievements

本研究で得られた成果により,高圧二酸化炭素を媒体とする医薬品共結晶の形成において,人体に無害な二酸化炭素を媒体として利用することで,有機溶媒の残留にかんする問題が回避されることが期待でき,体内における医薬物質の溶解度向上が期待できる共結晶の実用化が期待される.高圧二酸化炭素中における粉砕法,ならびに脂質融液を共結晶形成場として利用することで,分子インプリンティングによる共結晶形成の高速化が期待される.このように,新たな医薬品結晶形成に関する知見が蓄積されることで,共結晶を利用した医薬品投与への展開が促進されると考えられる.

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (18 results)

All 2022 2021 2020

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (17 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results)

  • [Journal Article] Theophylline polymorph control by high-pressure pure CO2 via its monohydrate2022

    • Author(s)
      Yingquan Hao, Crystal Gong, Kinari Kobayashi, Seika Akiyama, Yusuke Shimoyama
    • Journal Title

      Crystal Growth and Design

      Volume: 22 Issue: 1 Pages: 159-166

    • DOI

      10.1021/acs.cgd.1c00718

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 超臨界二酸化炭素中におけるメカノケミカル効果を利用したテオフィリン結晶多形の形成2022

    • Author(s)
      小林生成, Hao Yingquan, 織田耕彦, 下山裕介
    • Organizer
      化学工学会第87年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] CO2分子結晶の粉末との混合による医薬剤溶解性の促進2022

    • Author(s)
      谷越陽, 秋山星佳, Hao Yingquan, 織田耕彦, 下山裕介
    • Organizer
      化学工学会第87年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 高圧CO2中における脂質メディアを活用した共結晶の形成機構2022

    • Author(s)
      巽由奈, 織田耕彦, 下山裕介
    • Organizer
      化学工学会第87年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Estimation of melting point depression driven by CO2 from molecular informatic apporoach2021

    • Author(s)
      Yuna Tatsumi, Yasuhiko Orita, Hung Ying Chieh, Yusuke Shimoyama
    • Organizer
      18th European Meeting on Supercritical Fluids
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脂質メディアによるテオフィリン共結晶の形成促進2021

    • Author(s)
      巽由奈, Hao Yingquan, 下山裕介
    • Organizer
      化学工学会秋田大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] High-pressure CO2 for lipid-mediated cocrystallization of theophylline and nicotinamide2021

    • Author(s)
      Yuna Tatsumi, Hao Yingquan, Yusuke Shimoyama
    • Organizer
      25th Congress of the International Union of Crystallography
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Itraconazole cocrystallization in fatty acid under high-pressure CO22021

    • Author(s)
      Yuna Tatsumi, Hao Yingquan, Yasuhiko Orita, Yusuke Shimoyama
    • Organizer
      9th International Symposium on Molecular Thermodynamics and Molecular Simulation
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 分子情報の入力による学習とデータ処理を活用した高圧CO2融液システムの設計2021

    • Author(s)
      巽由奈, Hao Yingquan, 下山裕介
    • Organizer
      化学工学会第52回秋季大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] CO2分子を封入したDrug-Drug共結晶の形成2021

    • Author(s)
      谷越陽, 秋山星佳, Hao Yingquan, 織田耕彦, 下山裕介
    • Organizer
      化学工学会第52回秋季大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 分子情報と熱力学モデルに基づく共結晶探索設計システムの構築2021

    • Author(s)
      秋山星佳, Hao Yingquan, 織田耕彦, 下山裕介
    • Organizer
      化学工学会第52回秋季大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Screening of pharmaceutical cocrystal formation with machine learning by molecular informatics2021

    • Author(s)
      Hao Yingquan, Hung Ying Chieh, Yusuke Shimoyama
    • Organizer
      化学工学会第52回秋季大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Lipid-mediated cocrystallization for formation of theophylline-nicotinamide cocrystal2021

    • Author(s)
      Yuna Tatsumi, Yusuke Shimoyama
    • Organizer
      8th Asian Particle Technology Symposium APT2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 超臨界CO2ビーズ粉砕法による共結晶の形成2021

    • Author(s)
      小林生成, 織田耕彦, 下山裕介
    • Organizer
      分離技術会年会2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] CO2分子の封入によるDrug-Drug共結晶の溶解特性の促進2021

    • Author(s)
      谷越陽, 秋山星佳, Hao Yingquan, 織田耕彦, 下山裕介
    • Organizer
      分離技術会年会2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] Pharmaceutical cocrystal screening by machine learning with molecular surface charge distribution2021

    • Author(s)
      Hao Yingquan, 片岡大志,村上広樹,Hung Ying Chieh,織田耕彦,下山裕介
    • Organizer
      International Chemical Engineering Symposia
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 超臨界二酸化炭素相と界面を利用した材料プロセス2020

    • Author(s)
      下山裕介
    • Organizer
      化学工学会第51回秋季大会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 高圧CO2を媒体としたメカノケミカル効果による共結晶形成の促進2020

    • Author(s)
      小林生成,織田耕彦,下山裕介
    • Organizer
      第23回化学工学会学生発表会
    • Related Report
      2020 Research-status Report

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Published: 2020-08-03   Modified: 2023-01-30  

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