A RESERACH ON DEVELOPMENT AND APPLICATION OF THE CLINICALLY APPRICABLE NEW ARTIFICIALRED BLOOD CELLAND ARTIFICIAL OXYGEN CARRIER
A RESERACH ON DEVELOPMENT AND APPLICATION OF THE CLINICALLY APPRICABLE NEW ARTIFICIALRED BLOOD CELLAND ARTIFICIAL OXYGEN CARRIER
批准号:
14370479
负责人:
SAKUMA Ichiro
金额:
$7.17万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
2002
资助国家:
日本
项目状态:
已结题
起止时间:
2002 至 2004
中文摘要
血红蛋白(Hb)修饰的人造红细胞由于其一氧化氮(NO)猝灭,存在血液升高或血小板活化、凝血等临床问题不良反应。这是由于血红素分子吸收内皮细胞或神经末梢释放的NO所致。在本研究中,我们开发了一种新的临床应用的Hb修饰分子,其SH部分被s-亚硝基化,因此可以释放NO。此外,我们还开发了一种新的全氟碳(PFC),通过使用一种新的挤奶机,它是在一个相同的大小,稳定和更好的生物利用度融化。我们考察了其作为人工氧载体和人工器官保存剂的生物利用度、临床应用价值。我们计划了NO-PEG-Hb在脑缺血中的临床应用,并确认了其在大鼠2VO模型中的实用性。其机制似乎是抑制iNOS合成的大量NO和NO- peg - hb .2释放的NO。为了将新型PFC作为儿童人工体外循环的血浆扩张器,我们在狗身上进行了模拟实验,并从各种心功能、心律失常和生化参数中认识到它的临床应用价值。我们认识到,通过测量心功能、心律失常和生化参数,新型PFC对心脏缺血再灌注损伤的预防性应用的实用性。为了评价各种人工红细胞对脑缺血保存的作用,我们建立了一种新的大鼠认知评价方法。我们认识到,通过测量心功能、心律失常和生化参数,脂质体包裹的血红蛋白(NRC)对心脏缺血再灌注损伤的预防性应用的实用性。我们认识到NRC对脑缺血的保护作用。用一种大鼠认知功能评价方法。
英文摘要
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.
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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
Kunihiko Nakai、Ichiro Sakuma、Hiroko Togashi、Mitsuhiro Yoshioka、Hiroshi Satoh、Akira Kitabatake:“S-亚硝基化聚乙二醇结合血红蛋白衍生物作为氧治疗的候选材料。在:临床中的聚合物药物
DOI:
--
发表时间:
期刊:
影响因子:
--
作者:
[]
通讯作者:
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
血红蛋白基人工氧载体:体外循环、人工血管涂层、心肌保护等临床应用的基础研究。
DOI:
--
发表时间:
2002
期刊:
Cardiovascular Anesthesia 6(1)
影响因子:
--
作者:
[Hirota K, Kushikata T, Kudo M, Kudo T, Smart D, Matsuki A., 藤井 聡ほか]
通讯作者:
藤井 聡ほか
DOI:
10.1254/jphs.fp0040385
发表时间:
2004
期刊:
Journal of pharmacological sciences
影响因子:
3.5
作者:
[H. Otani;S. Jesmin;H. Togashi;I. Sakuma;K. Nakai;H. Satoh;M. Yoshioka;A. Kitabatake]
通讯作者:
H. Otani;S. Jesmin;H. Togashi;I. Sakuma;K. Nakai;H. Satoh;M. Yoshioka;A. Kitabatake
NOと病態.人工赤血球
NO 与病理状况。人工红细胞
DOI:
--
发表时间:
2003
期刊:
医学のあゆみ 204(9)
影响因子:
--
作者:
[佐久間一郎, 北畠 顕]
通讯作者:
北畠 顕
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)
佐久间一郎:“Hb 改良人工血液和 PFC。围手术期输注的前沿”Shinko Trading(出版中)。
DOI:
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发表时间:
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作者:
[]
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共 20 条
Reconstruction of three dimensional excitation propagation waveform in heart wall from two dimensional optical mapping data
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Cardiac action potential and Ca2+ ion simultaneous dual measurement and temporal and spatial high resolution optical mapping system
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OPTICAL MAPPING SYSTEM WITH DUAL HIGH SPEED VIDEO CAMERAS FOR OBSERVATION OF THREE DIMENSIONAL CARDIAC EXCITATION PROPAGATION DURING ARRHYTHMIA
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High spatial-temporal resolution optical mapping of cardiac membrane action potentials using high intensity light emitting diodes and high spee3 digital video cameras
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A study forthe effects of estrogen on actions ofendothelium-derived hyperpolarizing factor
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A study on the development and application of clinically available new artificial bloods and artificial oxygen carriers
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DEVELOPMENT OF EFFICIENT PRODUCTION SYSTEM OF TRANSGENIC MINIPIG
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REDUCTION OF DIABETIC CARDIOVASCULAROPATHY BY AMINOGUANIDINE
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海外基金