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In-situ evaluation of frozen protein solutions to maintain the stability of biopharmaceuticals

Research Project

Project/Area Number 26630066
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Thermal engineering
Research InstitutionKyushu University

Principal Investigator

TAKAMATSU Hiroshi  九州大学, 工学(系)研究科(研究院), 教授 (20179550)

Co-Investigator(Kenkyū-buntansha) KURATA Kosaku  九州大学, 大学院工学研究院, 准教授 (00368870)
FUKUNAGA Takanobu  九州大学, 大学院工学研究院, 技術職員 (60591196)
Wang Haidong (WANG Haidong)  九州大学, 工学(系)研究科(研究院), 助教 (30729405)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords凍結保存 / バイオ医薬品 / ラマンイメージング / タンパク質変性
Outline of Final Research Achievements

Freezing of protein solutions is an important process for production, transportation, and storage of biopharmaceuticals. The aim of this study was to minimize the denaturation of an organic matter due to the freezing process. A lysozyme aqueous solution was used as a model protein with trehalose as a cryoprotective agent. The binary solution or each component solution was frozen in a microchannel on a directional solidification stage combined with a laser Raman microscope, and observed to obtain spatial distribution of water, ice, and each solute. Protein denaturation was also evaluated from the Raman spectra. These experimental results revealed that optimization of lysozyme/trehalose concentration and the freezing speed led to colocalization of both solutes, which is helpful in enhancing the stability of lysozyme because of the cryoprotective effect of trehalose.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (4 results)

All 2015 2014

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results) Presentation (2 results)

  • [Journal Article] Microheterogeneity in frozen protein solutions2015

    • Author(s)
      Alan Twomey, Kosaku Kurata, Hiroshi Takamatsu, Alptekin Aksan
    • Journal Title

      International Journal of Pharmaceutics

      Volume: 487 Pages: 91-100

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Observation of ice-solute interaction in freezing of trehalose and albumin solutions by using confocal Raman microscope equipped with directional solidification stage2014

    • Author(s)
      Hideto Hirahara, Yutaka Nagare, Alan Twomey, Kosaku Kurata, Takanobu Fukunaga, Alptekin Aksan, Hiroshi Takamatsu
    • Journal Title

      Proceedings of the 15th International Heat Transfer Conference

      Volume: IHTC15-8933 Pages: 14-14

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] 凍結トレハロース-リゾチーム混合水溶液のラマンイメージング計測2014

    • Author(s)
      岡晋司,平原豪人,藏田耕作,福永鷹信,高松洋
    • Organizer
      熱工学コンファレンス2014
    • Place of Presentation
      東京都江東区
    • Year and Date
      2014-11-08 – 2014-11-09
    • Related Report
      2014 Research-status Report
  • [Presentation] Raman microscopic observation of ice-solute distribution after directional solidification of sugar and protein solutions2014

    • Author(s)
      Hideto Hirahara, Yutaka Nagare, Alan Twomey, Kosaku Kurata, Takanobu Fukunaga, Alptekin Aksan, Hiroshi Takamatsu
    • Organizer
      The 7th Kyushu University-KAIST Joint Workshop on Frontiers in Mechanical Engineering
    • Place of Presentation
      福岡県福岡市
    • Year and Date
      2014-09-26
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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