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Realization of precision medicine by constructing platform of dry powder inhaler formulation

Research Project

Project/Area Number 20K07212
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionOsaka Medical and Pharmaceutical University (2021-2022)
Osaka University of Pharmaceutical Sciences (2020)

Principal Investigator

KADOTA Kazunori  大阪医科薬科大学, 薬学部, 准教授 (50709516)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords数値シミュレーション / 機能性素材 / 吸入粉末剤 / 粒子設計 / 噴霧乾燥法 / 水溶性多糖類 / 金属有機構造体 / シクロデキストリン / in silico / 有機構造体 / 疎水性薬物 / 実験計画法 / 凍結噴霧乾燥法 / ナノ粒子 / 肺疾患患者 / COPD / 凍結乾燥法 / 粒子形態制御 / 肺胞 / フィトグリコーゲン / プレシジョンメディシン
Outline of Research at the Start

本研究は、限られた添加剤や薬物だけで粒子物性を制御した粒子設計の実現方法を確立し個別の肺構造や吸入パターンを数理モデルにより精度よく予想する技術の確立を追求することになる。その結果、患者に対する薬剤を減らし、副作用を軽減し、プレシジョン・メディシンの実現に向けた加速化を実現できる。

Outline of Final Research Achievements

In this study, the composite particles between drugs and biocompatible excipients were prepared by spray-drying to have better advantages to carrier techniques. Specifically, sugars have advantages like cheap in cost and have low probability to trigger toxicity in the human body. Their building blocks are usually monosaccharides which have excellent biocompatibility. We succeeded in preparing composite particles with low density and large surface areas. Also, we succeeded in preparing particles of polysaccharides with desired aerodynamic diameters via spray-freeze drying. In addition, the differences in pulmonary morphology and particle behavior among patients were compared using in silico simulations.

Academic Significance and Societal Importance of the Research Achievements

本研究で、生体適合性が高い多糖類により様々な空気力学的粒子径を有する粒子を設計することに成功した。この技術は、低分子医薬品の吸入粉末剤だけでなく、中分子や抗体医薬といった様々なモダリティへの応用も期待できる点で非常に重要である。また、in silico技術によって確認した患者毎の肺の違いやその中での粒子挙動については、これまでin vitroでの評価しかなかった吸入粉末剤について、新たな適正評価に関する可能性が期待できる。また、AI技術の発達に伴い、肺モデルの作製をより潤滑にして、肺内部での粒子挙動について把握できれば、患者の特性に応じた粒子設計情報を得ることも可能となる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (25 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results) Presentation (15 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Warsaw University of Technology(ポーランド)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Modulating Pore Space Architecture of Ice-Templated Dextran Microparticles Using Molecular Weight and Concentration2022

    • Author(s)
      T. Kamarainen, K. Kadota, J. Y. Tse, H. Uchiyama, S. Yamanaka, Y. Tozuka
    • Journal Title

      Langmuir

      Volume: 38 Issue: 21 Pages: 6741-6751

    • DOI

      10.1021/acs.langmuir.2c00721

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In silico evaluation of particle transport and deposition in the airways of individual patients with chronic obstructive pulmonary disease2022

    • Author(s)
      Kadota Kazunori、Matsumoto Koichi、Uchiyama Hiromasa、Tobita Satoshi、Maeda Munehiro、Maki Daisuke、Kinehara Yuhei、Tachibana Isao、Sosnowski Tomasz R.、Tozuka Yuichi
    • Journal Title

      European Journal of Pharmaceutics and Biopharmaceutics

      Volume: 174 Pages: 10-19

    • DOI

      10.1016/j.ejpb.2022.03.010

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Porous particles and novel carrier particles with enhanced penetration for efficient pulmonary delivery of antitubercular drugs2021

    • Author(s)
      Tse Jun Yee、Koike Atsushi、Kadota Kazunori、Uchiyama Hiromasa、Fujimori Ko、Tozuka Yuichi
    • Journal Title

      European Journal of Pharmaceutics and Biopharmaceutics

      Volume: 167 Pages: 116-126

    • DOI

      10.1016/j.ejpb.2021.07.017

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Crystalline Rearranged CD-MOF Particles Obtained via Spray-Drying Synthesis Applied to Inhalable Formulations with High Drug Loading2021

    • Author(s)
      Tse Jun Yee、Kadota Kazunori、Nakajima Toshiki、Uchiyama Hiromasa、Tanaka Shunsuke、Tozuka Yuichi
    • Journal Title

      Crystal Growth & Design

      Volume: 22 Issue: 2 Pages: 1143-1154

    • DOI

      10.1021/acs.cgd.1c01091

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Enhancement of the extra-fine particle fraction of levofloxacin embedded in excipient matrix formulations for dry powder inhaler using response surface methodology2021

    • Author(s)
      Tse Jun Yee、Kadota Kazunori、Imakubo Tetsuya、Uchiyama Hiromasa、Tozuka Yuichi
    • Journal Title

      European Journal of Pharmaceutical Sciences

      Volume: 156 Pages: 105600-105600

    • DOI

      10.1016/j.ejps.2020.105600

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] An effective approach to modify the inhalable betamethasone powders based on morphology and surface control using a biosurfactant2020

    • Author(s)
      Kadota Kazunori、Tanaka Moe、Nishiyama Hikaru、Tse Jun Yee、Uchiyama Hiromasa、Shirakawa Yoshiyuki、Tozuka Yuichi
    • Journal Title

      Powder Technology

      Volume: 376 Pages: 517-526

    • DOI

      10.1016/j.powtec.2020.08.063

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 噴霧乾燥法によるアミロイドナノフィブリルをバインダーとした超微粒子集合体の設計2023

    • Author(s)
      中山結月、Tero O. Kamarainen、内山博雅、門田和紀、戸塚裕一
    • Organizer
      日本海水学会若手会第14回
    • Related Report
      2022 Annual Research Report
  • [Presentation] Ice templated dextran microparticles by spray freeze drying: Influence of molecular weight and concentration.2022

    • Author(s)
      T. O. Kamarainen, J.Y. Tse, H. Uchiyama, K. Kadota, Y. Tozuka
    • Organizer
      粉体工学会2022年度春期研究発表会シンポジウム
    • Related Report
      2022 Annual Research Report
  • [Presentation] 噴霧乾燥法による新規キャリア粒子による吸入粉末製剤の設計.2022

    • Author(s)
      門田和紀、謝 晉頤、T. O. Kamarainen、内山博雅、戸塚裕一
    • Organizer
      粉体工学会第 56 回技術討論会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Image analysis routines toward pore characterization of spray freeze dried dextran microparticles.2022

    • Author(s)
      T. O. Kamarainen, H. Uchiyama, K. Kadota, Y. Tozuka
    • Organizer
      粉体工学会第 56 回技術討論会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 数値流体力学による慢性閉塞性肺疾患患者の肺気管支モデル内での粒子沈着評価.2021

    • Author(s)
      松本功一、内山博雅、門田和紀、飛田哲志、立花功、戸塚裕一
    • Organizer
      日本薬学会第141年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 新規キャリア粒子による肺深部への高効率な到達性を実現した抗結核薬吸入粉末剤の設計2021

    • Author(s)
      入船三奈子、謝晉頤、小池敦資、内山博雅、門田和紀、藤森功、戸塚裕一
    • Organizer
      日本薬剤学会第36年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 噴霧乾燥法による薬物含有シクロデキストリン金属有機構造体の創製及び経肺製剤への応用2021

    • Author(s)
      謝晉頤、内山博雅、門田和紀、戸塚裕一、中島稔生、田中 俊輔
    • Organizer
      粉体工学会2021年度春期研究発表会
    • Related Report
      2021 Research-status Report
  • [Presentation] In silico 技術による慢性閉塞性肺疾患患者の肺内粒子沈着解析 ―COPD 患者毎の肺内粒子挙動評価―2021

    • Author(s)
      松本功一、内山博雅、門田和紀、飛田哲志、立花 功、戸塚裕一
    • Organizer
      第71回日本薬学会関西支部会
    • Related Report
      2021 Research-status Report
  • [Presentation] Application of spray-dried particles of drug-containing cyclodextrin metal-organic framework to pulmonary drug delivery2021

    • Author(s)
      Kazunori Kadota, Jun Yee Tse, Toshiki Nakajima, Shunsuke Tanaka, Hiromasa Uchiyama, Yuichi Tozuka
    • Organizer
      8th Asian Particle Technology Symposium APT 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Difference in particle morphology of betamethasone by the addition of bio-surfactant between spray-drying and freeze-drying2021

    • Author(s)
      Kazunori Kadota, Hiromasa Uchiyama, Yuichi Tozuka
    • Organizer
      21st International Symposium on Industrial Crystallization
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] in silico技術を利用した吸入粉末製剤の気管支内での粒子沈着挙動の解析と予測2021

    • Author(s)
      門田和紀
    • Organizer
      日本薬剤学会第36年会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] in silico 技術を利用した個別化医療を目指した吸入粉末剤の開発2021

    • Author(s)
      門田和紀
    • Organizer
      第 1 2 回 粉末吸入剤研究会シンポジウム
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] デキストランを基剤とした二成分の医薬品を含む吸入粉末剤の設計.2020

    • Author(s)
      門田和紀、斎藤香菜子、内山博雅、戸塚裕一
    • Organizer
      粉体工学会 2020年度 春期研究発表会
    • Related Report
      2020 Research-status Report
  • [Presentation] 吸入速度および吸入パターン変化が与える気管支内での粒子挙動への影響.2020

    • Author(s)
      松永佳宏、内山博雅、門田和紀、戸塚裕一
    • Organizer
      日本薬剤学会第35年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Evaluation of dry powder inhaler formulations with enhanced extra-fine particle fraction using phytoglycogen as an excipient for adhesive mixtures.2020

    • Author(s)
      謝晉頤、内山博雅、門田和紀、戸塚裕一
    • Organizer
      日本薬剤学会第35年会
    • Related Report
      2020 Research-status Report
  • [Book] 医薬品におけるDDS技術開発と製剤への応用2021

    • Author(s)
      戸塚裕一、門田和紀 他多数
    • Total Pages
      401
    • Publisher
      情報機構
    • ISBN
      9784865022278
    • Related Report
      2021 Research-status Report
  • [Remarks] 製剤設計学研究室

    • URL

      https://www.ompu.ac.jp/class/pharm/fd.html

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
  • [Patent(Industrial Property Rights)] 呼吸器系医薬品粉末及びその製造方法2020

    • Inventor(s)
      戸塚裕一、門田和紀、内山博雅
    • Industrial Property Rights Holder
      キユーピー株式会社
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-075983
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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