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Establishment of production process of cellular- type oxygen carriers

Research Project

Project/Area Number 12558112
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Biomedical engineering/Biological material science
Research InstitutionWaseda University

Principal Investigator

TAKEOKA Shinji  Waseda University, School of Science and Engineering, Associate Professor, 理工学部, 助教授 (20222094)

Co-Investigator(Kenkyū-buntansha) SAKAI Kiyotaka  Waseda University, School of Science and Engineering, Professor, 理工学部, 教授 (00063727)
NISHIDA Hiroyuki  Waseda University, School of Science and Engineering, Professor, 理工学部, 教授 (90120930)
TSUCHIDA Eishun  Waseda University, Emeritus Professor, 理工学部, 名誉教授 (90063461)
SAKAI Hiromi  Waseda University, Advanced Research Institute for Science and Engineering, Lecturer, 理工学総合研究センター, 講師 (70318830)
UMEZU Mitsuo  Waseda University, School of Science and Engineering, Professor, 理工学部, 教授 (90132927)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 2001: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2000: ¥7,800,000 (Direct Cost: ¥7,800,000)
Keywordshemoglobin / hemoglobin vesicles / production procass / artificial lung / freeze-thawing / freeze-drying / multistage-combined type extruder / polyoxyethylene-conjugated lipids / aminolipid / 一酸化炭素化ヘモグロビン / 多段・凍結式高圧押出装置 / 細胞型酸素輸液 / 多段式高圧押出機
Research Abstract

In order to establish the large-scale production process of cellular-type oxygen carriers (hemoglobin (Hb)-vesicles), the following subjects were finished.
1. Carbonylation and deoxygenation process of the Hb solutions : The carbonylation (CO) and deoxygenation of a hemoglobin (Hb) solution were performed with an artificial lung.
2. Electrochemical deoxygenation of the HbO_2 solution : The dissolved oxygen (pO_2<1O Torr) was electrochemically reduced to water under the diluted hydrogen/ nitrogen mixture gas condition.
3. Ligand-exchange process of HbCO to HbO_2 : The Ligand-exchange process was carried out by visible-light irradiation to the HbCO solution using a liquid thin film or a silicon hollow fiber module.
4. Synthesis of new aminolipids and the use : The polyoxyethylen-conjugated or negatively-charged aminolipids were newly synthesized and the Hb-vesicles were prepared with these lipids.
5. Scaling up of an extrusion process : To improve the efficiency of the extrusion process, the mixced lipid dispersion was previously freeze-mawed and -dried. The necessary time during the extrusion process of the dispersion of the powder to the Hb solution was largely reduced, and the efficiency of the extrusion was also dramatically increased with the multistage-combined type extruder.
6. Evaluation of the 10L-scale production of the Hb vesicles : The apparatus in an each process was lined, and me 10L-scale production of the Hb vesicles are being evaluated. The pilot plants on the scale of 300 L will be planned.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] Takeoka, et al.: "Synthesis and Assembly of Poly(ethylene glycol)-Lipids with Mono-, Di-, and Tetraacyl Chains and a Poly(ethylene glycol) Chain of Various Molecular Weights"J.Am.Chem.Soc.. 122. 7927-7935 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeoka, et al.: "Synthesis of Multiacyl Poly(ethylene glycol) for the Conjugation of Cytochrome c to Phospholipid Vesicle"Bioconjugate Chem.. 11. 815-821 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeoka, et al.: "Poly(ethylene glycol)-Conjugation and Deoxygenation Enable Long-Term Preservation of Hemoglobin-Vesicles as Oxygen Carriers in a Liquid State"Bioconjugate Chem.. 11. 425-432 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeoka, et al.: "Poly(oxyethylene)-Modification of the Phospholipid Vesicles by Using the Spontaneous Incorporation of Poly(oxyethylene)-Lipid into the Vesicles"Bioconjugate Chem.. 11. 372-379 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeoka, et al.: "Molecular dimensions of Hb-based O_2 carriers determine constriction of resistance arteries and hypertension in conscious hamster model"Am.J.Physiol.Heart Circ.Physiol.. 279. 908-915 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeoka, et al.: "Photoreduction of Methemoglobin by Irradiation in the Near-Ultraviolet Region"Biochemistry. 39. 14595-14602 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 武岡真司 他: "人工血液の開発動向"バイオサイエンスとインダストリー. 58. 252-255 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeoka, et al.: "Hemoglobin-Vesicles as Oxygen Carriers : Influence on Phagocytic Activity and Histopathological Changes in Reticuloendothelial System"Am.J.Pathol.. 159. 1079-1088 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeoka, et al.: "Carbonylation of oxyhemoglobin solution using a membrane oxygenator"J.Artif.Organs. 5. 102-107 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeoka, et al.: "Study of virus removal from hemoglobin solution using PLANOVA^<TM>-15N"J.Artif.Organs. 39. 141-145 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeoka, et al.: "Characteristics of Bovine Hemoglobin as a Potential Source of Hemoglobin-Vesicles for an Artificial Oxygen Carrier"J.Biochem.. 131. 611-617 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeoka, et al.: "Complete deoxygenation from a hemoglobin solution by an electrochemical method and heat treatment for virus inactivation"Biotechnol.Progress. 18. 101-107 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeoka, et al.: "Effect of Hb-Encapsulation with Vesicles on H_2O_2 Reaction and Lipid Peroxidation"Bioconjugate Chem.. 13. 1302-1308 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeoka, et al.: "Systemic and microvascular responses to hemorrhagic shock and resuscitation with Hb-vesicles"Am.J.Physiol.Heart Circ.Physiol.. 283. H1191-H1199 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeoka, et al.: "Pretreatment of serum containing Hb-vesicles (oxygen carriers) to avoid their interference in laboratory tests"Clin.Chem.Lab.Med.. 41. 222-231 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeoka, et al.: "Efficient up-scale production of hemoglobin-vesicles (HbV) using the freeze-thawing and rapid extrusion"Biotechnol.Prog. 19(印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 武岡真司他: "バイオミメティックスハンドブック"酸素輸液としての人工赤血球. 5 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Takeoka, K. Mori, H. Ohkawa, K. Sou, E. Tsuchida.: "Synthesis and assembly of poly(ethylene glycol)-lipids with mono-, di-, and tetraacyl chains and a polyethylene glycol) chain of various molecular weights"J. Am. Chem. Soc.. 122. 7927-7935 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Ohkawa, Y. Teramura, S. Takeoka, E. Tsuchida.: "Synthesis of multiacyl poly (etiiylene glycol) for the conjugation of cytochrome c to phospholipid vesicle"Bioconjugate Chem.. 11. 815-821 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Sakai, K. Tomiyama, K. Sou, S. Takeoka, and E. Tsuchida.: "Poly(ethyleneglycol)-conjugation and deoxygenation enable long term preservation of hemoglobin vesicles as oxygen carriers"Bioconjugate Chem.. 11. 425-432 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Sou, T. Endo, S. Takeoka, E.Tsuchida.: "Poiyoxyethylene-modification of the phospholipid vesicles by using the spontaneous incorporation of polyoxyethylene-lipid into the vesicles"Bioconjugate Chem.. 11. 372-379 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Sakai, EL Kara, M. Yuasa, A.G. Tsai, S. Takeoka, E. Tsuchida, and M. Intaglietta.: "Molecular Dimensions of Hb-based O_2 Carriers Determine Constriction of Resistance Arteries and Hypertension in Conscious Hamster Model"Am. J. Physiol Heart Circ. Physiol. 279. 908-911 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Sakai, H. Onuma, M. Umeyama, S. Takeoka, and E, Tsuchida.: "Photoreduction of Methemoglobin by Itradiation in Near-ultraviolet Region"Biochemistry. 39. 14595-14602 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Sakai, H. Horinouchi, K. Tomiyama, E. Dceda, S. Takeoka, K. Kobayashi, and E. Tsuchida: "Hemoglobin-vesicles as oxygen carriers : Influence on phagocytic activity and histopathological changes in reticuloendothelial system"Am, J. Pathol. 159. 1079-1088 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] I. Fukutomi, H. Sakai, S. Takeoka, H. Nishide, E. Tsuchida, K. Sakai: "Carbonylation of oxyhemoglobin solution using a membrane oxygenator"J. Artif Organs. 5. 102-107 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Naito, I. Fukutomi, Y. Masada, H. Sakai, S. Takeoka, E. Tsuchida, H. Abe, J. Hirayama, K. Ikebuchi, H. Dteda: "Study of virus removal from hemoglobin solution using PLANOVA^<th> -15N"J. Artif Organs. 5. 141-145 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Sakai, Y. Masada, S. Takeoka, E. Tsuchida: "Characteristics of bovine hemoglobin for the potential source of hemoglobin-vesicles as an artificial oxygen carrier"J. Biochem.. 131. 611-617 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y Huang, S. Takeoka, H. Sakai, H. Abe,J. Hirayama, K. Ikebuchi, H. Dceda, E. Tsuchida.: "Complete deoxygenation from a hemoglobin solution by an electrochemical method and heat treatment for virus inactivation"Biotechnol Progress. 18. 101-107 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Takeoka, Y. Teramura, T. Atoji, E. Tsuchida,: "Effect of Hb-encapsulation with vesicles on H_2O_2 reaction and lipid peroxidation"Bioconjugate Chem.. 13. 1302-1308 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H.Sakai, S. Takeoka,R.Wettstein,A.G.Tsai, M. Intaglietta, E. isucmoa: "Systemic and microvascular responses to the hemorrhagic shock and resuscitation with Hb-vesicles"Am. J. Physiol. Heart Ciro. Physiol.. 283. H1191-H1199 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Sakai, K. Tomiyama, Y. Masada , S. Takeoka , H. Horinouchi, K. Kobayashi, E. Tsuchida: "Pretreatment of serum containing Hb-vesicles (oxygen cairiers) to avoid their interference in laboratory tests"Clin. Chem. Lab. Med.. 41. 222-231 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Sou, Y. Naito, T. Endo, S. Takeoka, E. Tsuchida: "Efficient up-scale production of hemoglobin-vesicles (HbV) using the freeze-thawing and rapid extrusion"Biotechnol. Prog.. 19 (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yubin Huang, shinji, Tokaoka, Hiromi Sakai, Eishun Tsuchida 他: "Coamplete Deoxygenation from a Hemoglobin Solution by an Electrochemical Method and Heart Treatment for Virus Imactivation"Biotechnology Progress. 18・1. 101-107 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ippei Fukutomi, Hiromi Sakai, Shinji Takeoka, Eishun Tsuchida, Kiyotaka Sakai: "Carbonylation of Oxyhemoglobin Solution (HbO_2-HbCO)Using a Membrane Oxygenator"Journal of Artificial Organs. 5・2(in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshiyasu Naito, Hiromi Sakai, Shinji Takeoka, Eishun Tsuchida 他: "Study of Virus Removol from Hemoglobin Solution Using PLANOVA^<TM>-15N"Journal of Artificial Organs. 5・2(in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hiromi Sakai, Yuhei Masada, Shinji Takeoka, Eishun Tsuchida: "Characteristics of Bovine Hemoglobin for the Potential Source of Hemoglobin-vesicles as an Artificial Oxygen Carrier"Journal of Biochemistry. 131(in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Ohkawa,Y.Teramura,S.Takeoka,E.Tsuchida: "Synthesis of Multiacyl Poly(ethylene glycol) for the conjugation of Cytochrome o to Phospholipid resicle"Bioconjugate Chemistry. 11・6. 815-821 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Sakai,H.Onuma,M.Umeyama,S.Takeoka,E.Tsuchida: "Photoreduction of Methemoglobin by Irradiation in the Near-Ultraviolet Region"Biochemistry. 39・47. 14595-14602 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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