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2001 Fiscal Year Final Research Report Summary

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
Keywordshemoglobin / hemoglobin vesicles / production procass / artificial lung / freeze-thawing / freeze-drying / multistage-combined type extruder / polyoxyethylene-conjugated lipids / aminolipid
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.

  • Research Products

    (32 results)

All Other

All Publications (32 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 2004-04-14  

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