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A RESERACH ON DEVELOPMENT AND APPLICATION OF THE CLINICALLY APPRICABLE NEW ARTIFICIALRED BLOOD CELLAND ARTIFICIAL OXYGEN CARRIER

Research Project

Project/Area Number 14370479
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

SAKUMA Ichiro  Hokkaido University Hospital, Lec., 病院, 講師 (40260393)

Co-Investigator(Kenkyū-buntansha) FUJII Satoshi  Hokkaido University Hospital, Lect., 病院・講師 (90291228)
YOSHIOKA Mitsuhiro  Hokkaido Univ., Grad.School of Med., Prof., 大学院・医学研究科, 教授 (40182729)
TOGASHI Hiroko  Hokkaido Univ., Grad.School of Med., Asso.Prof., 大学院・医学研究科, 助教授 (20113590)
NAKAI Kunihiko  Tohoku Univ., Grad.School of Med., Asso.Prof., 大学院・医学系研究科, 助教授 (00291336)
FUKUSHIMA Shoji  Kobe Gakuin Univ., Fac.of Pharmaceut.Sci., Asso.Prof., 薬学部, 助教授 (80248103)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 2004: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥4,500,000 (Direct Cost: ¥4,500,000)
KeywordsARTIFICIAL RED BLOOD CELL / MODIFIED HEMOGLOBIN / NITRIC OXIDE / PLATELET AGGRIGABILITY / PLATELET ADHESIBILITY / POLYETHYLENE GLYCOL / S-NITROSOHEMOGLOBIN / PERFLUOROCARBON / ヘモクロビン修飾体
Research Abstract

Hemoglobin (Hb)-modified artificial red blood cell has clinically problematic adverse reactions such as blood elevation or activation of platelets and coagulation due to its nitric oxide (NO) quenching. This is derived from absorption of NO released from endothelial cells or nerve endings by heme of Hb molecule. In the present study we developed a new clinically applicable Hb modified molecule in which its SH moiety is s-nitrosylated, thus, can release NO. Also we developed a new perfluorocarbon (PFC) by using a new milking machine, which is melting in a equal sized, stable and with better bioavailability. We checked its bioavailability, clinical availability as an artificial oxygen carrier and artificial organ preserver.
1.We planned the clinical application of NO-PEG-Hb to brain ischemia, and recognized its utility in rat 2VO model. Its mechanism seemed to quench large amount of NO synthesized by iNOS and also NO release from NO-PEG-Hb.
2.To utilized the new PFC as a plasma expander for artificial cardiopulmonary bypass in children, we conduced a simulated experiment using dog and recognized its clinical utility from various cardiac functions, arrhythmias and biochemical parameters.
3.We recognized that the utility of prophylactic application of the new PFC for cardiac ischemia reperfusion injury by measuring cardiac functions, arrhythmias and biochemical parameters.
4.To evaluate effects of various artificial red blood cells on brain ischemia preservation we established a new evaluation method for cognition using the rat.
5.We recognized that the utility of prophylactic application of a liposome-encapsulated hemoglobin, Neo Red Cell (NRC), for cardiac ischemia reperfusion injury by measuring cardiac functions, arrhythmias and biochemical parameters.
6.We recognized the preserving effect of NRC on brain ischemia. by an evaluation method for cognitive function in the rat.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (22 results)

All 2004 2003 2002 2000 Other

All Journal Article (12 results) Book (2 results) Patent(Industrial Property Rights) (2 results) Publications (6 results)

  • [Journal Article] An S-nitrosylated hemoglobin derivative protects the rat hippocampus from ischemia-induced long-term potentiation impairment with a time window.2004

    • Author(s)
      Otani H, et al.
    • Journal Title

      J Pharmacol Sci. 96(2)

      Pages: 188-198

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 虚血-再開通モデルラットにおける脳機能不全の多角的評価と人工酸素運搬体の有効性について2004

    • Author(s)
      富樫広子ほか
    • Journal Title

      人工血液 12(4)

      Pages: 121-126

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Beneficial effects of an artificial oxygen-carrier, liposome-encapsulated hemoglobin, on post-ischemic cerebral dysfunction in Rats.2004

    • Author(s)
      Togashi H, et al.
    • Journal Title

      Artificial Blood 12(4)

      Pages: 121-126

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hemoglobin-based artificial blood and perfluorochemical.2004

    • Author(s)
      Sakuma I
    • Journal Title

      In Frontier of perioperative fluid infusion

      Pages: 169-176

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] As S-nitrosylated hemoglobin derivative protects the rat hippocampus from is chemia-induced long-term potentiation impairment with a time window.2004

    • Author(s)
      Otani H, et al.
    • Journal Title

      J Pharmacol Sci. 96(2)

      Pages: 188-198

    • Related Report
      2004 Annual Research Report
  • [Journal Article] NOと病態.人工赤血球2003

    • Author(s)
      佐久間一郎, 北畠 顕
    • Journal Title

      医学のあゆみ 204(9)

      Pages: 631-635

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] S-nitrosylated polyethylene glycol-conjugated hemoglobin derivative as a candidate material for oxygen therapeutics.2003

    • Author(s)
      Nakai K, et al.
    • Journal Title

      Adv Exp Med Biol. 519

      Pages: 207-216

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] NO and pathogenesis. Artificial red blood Cell.2003

    • Author(s)
      Sakuma I, Kitabatake A
    • Journal Title

      Igaku no Ayumi 204(9)

      Pages: 631-635

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ヘモグロビン系人工酸素運搬体:体外循環、人工血管コーティング、心筋保護等臨床応用にむけての基礎的検討2002

    • Author(s)
      藤井 聡ほか
    • Journal Title

      Cardiovascular Anesthesia 6(1)

      Pages: 67-72

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ヘモグロビン系人工酸素運搬体を用いた抗血栓性材料の開発2002

    • Author(s)
      藤井 聡ほか
    • Journal Title

      循環制御 23(1)

      Pages: 31-34

    • NAID

      10012614316

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Application of hemoglobin based oxygen carrier : Implications for extracorporeal circuit, vascular grafts and myocardial Protection.2002

    • Author(s)
      Fujii S, et al.
    • Journal Title

      Cardiovascular Anesthesia 6(1)

      Pages: 67-72

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Development of antithrombotic material utilizing hemoglobin Based oxygen carrier.2002

    • Author(s)
      Fujii S, et al.
    • Journal Title

      Circulatory Regulation 23(1)

      Pages: 31-34

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] ヘモグロビン修飾型人工血液とパーフルオロケミカル.周術期輸液の最前線2004

    • Author(s)
      佐久間一郎
    • Total Pages
      307
    • Publisher
      真興交易(株)医書出版部
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] ヘモグロビン修飾型人工血液とパーフルオロケミカル. 周術期輸液の最前線2004

    • Author(s)
      佐久間一郎
    • Total Pages
      307
    • Publisher
      真興交易(株)医書出版部
    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 一酸化窒素代謝物-ポリオキシアルキレン-ヘモグロビン結合体2000

    • Inventor(s)
      北畠 顕, 佐久間 一郎, 安河内 徹, 仲井 邦彦
    • Industrial Property Rights Holder
      北海道大学, 日本油脂
    • Filing Date
      2000-02-06
    • Acquisition Date
      2003-12-23
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 一酸化窒素代謝物-ポリオキシアルキレン-ヘモグロビン結合体2000

    • Inventor(s)
      北畠 顕, 佐久間 一郎, 安河内 徹, 仲井 邦彦
    • Industrial Property Rights Holder
      北海道大学, 日本油脂
    • Filing Date
      2000-02-08
    • Acquisition Date
      2004-09-01
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Nakai K, Sakuma I, Togashi H, Yoshioka M, Sugawara T, Satoh H, Kitabatake A: "S-nitrosylated poly- ethylene glycol-conjugated hemo- globin derivative as a candidate material_for_oxygen_therapeutics"Adv_Exp Med Biol. 519. 207-216 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 佐久間一郎: "Hb修飾型人工血液とPFC.周術期輸液の最前線"真興交易(in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 藤井 聡, 藤井ひとみ, 富樫廣子, 吉岡充宏, 仲井邦彦, 佐藤 洋, 佐久間一郎, 劔物 修, 北畠 顕: "ヘモグロビン系人工酸素運搬体の血小板に及ぼす影響と人工材料としての臨床応用の可能性"人工血液10(1). 10(1). 17-20 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 佐久間一郎, 北畠 顕: "人工赤血球.NOと病態"医学のあゆみ. 204(9). 631-635 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 藤井 聡, 藤井ひとみ, 富樫廣子, 吉岡充宏, 佐久間一郎, 仲井邦彦, 佐藤 洋, 北畠 顕, 劔物 修: "ヘモグロビン系人工酸素運搬体を用いた抗血栓性材料の開発"循環制御. 23(1). 31-34 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kunihiko Nakai, Ichiro Sakuma, Hiroko Togashi, Mitsuhiro Yoshioka, Hiroshi Satoh, Akira Kitabatake: "S-nitrosylated polyethylene glycol-conjugated hemoglobin derivertive as a candidate meaterial for oxygen therapeutics. In : Polymer drugs in the clinical stage : Advantages and prospects"Kluwer Academic/Plenum Publishers (in press). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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