Virus removal from hemoglobin solution using Planova Membrane

Naito, Yoshiyasu; Fukutomi, Ippei; Masada, Youhei; Sakai, Hiromi; Takeoka, Shinji; Tsuchida, Eishun; Abe, Hideki; Hirayama, Junji; Ikebuchi, Kenji; Ikeda, Hisami

doi:10.1007/s100470200025

Cited by 17 publications

(11 citation statements)

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“…Human Hb is purified completely via pasteurization at 60 °C and ultrafiltration; no viruses exist [19–21];…”

Section: Physiological Significance Of Cellular Structurementioning

confidence: 99%

“…1 Human Hb is purified completely via pasteurization at 60°C and ultrafiltration; no viruses exist [19][20][21]; 2 A concentrated Hb solution, nearly 35 g dL )1 , is encapsulated with a thin bilayer membrane [16][17][18]; 3 A new synthetic lipid is used to prevent platelet (PLT) activation [22,23]; 4 PEG-modification guarantees long-term storage over 2 years at room temperature, blood compatibility and extended circulation half-life [24][25][26][27][28][29][30];…”

Section: Physiological Significance Of Cellular Structurementioning

confidence: 99%

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Haemoglobin‐vesicles as artificial oxygen carriers: present situation and future visions

Sakai

Sou

Horinouchi

et al. 2007

Journal of Internal Medicine

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During the long history of development of haemoglobin (Hb)-based O2 carriers (HBOCs), many side effects of Hb molecules have become apparent. They imply the physiological importance of the cellular structure of red blood cells. Hb-vesicles (HbV) are artificial O2 carriers that encapsulate concentrated Hb solution with a thin lipid membrane. We have overcome the intrinsic issues of the suspension of HbV as a molecular assembly, such as stability for storage and in blood circulation, blood compatibility and prompt degradation in the reticuloendothelial system. Animal tests clarified the efficacy of HbV as a transfusion alternative and the possibility for other clinical applications. The results of ongoing HbV research make us confident in advancing further development of HbV, with the expectation of its eventual realization.

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“…Human Hb is purified completely via pasteurization at 60 °C and ultrafiltration; no viruses exist [19–21];…”

Section: Physiological Significance Of Cellular Structurementioning

confidence: 99%

Section: Physiological Significance Of Cellular Structurementioning

confidence: 99%

Haemoglobin‐vesicles as artificial oxygen carriers: present situation and future visions

Sakai

Sou

Horinouchi

et al. 2007

Journal of Internal Medicine

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“…Human Hb is purified completely via pasteurization at 60°C and ultrafiltration; no viruses are included in it (Sakai et al, 1993;Abe et al, 2001;Naito et al, 2002). ii.…”

Section: Development Of Hb-vesicles As a Transfusion Alternativementioning

confidence: 99%

Hemoglobin-vesicles for a Transfusion Alternative and Targeted Oxygen Delivery

Sakai

Tsuchida

2007

Journal of Liposome Research

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Hb-vesicles (HbV) are artificial oxygen carriers that encapsulate purified Hb solution (35 g/dl) in unilamellar phospholipid vesicles (liposomes). The dispersion stability of HbV is attained using surface-modification with polyethylene glycol (PEG), so that the deoxygenated HbV can be stored at room temperature for years. Moreover, the intravenously injected HbV does not induce aggregation when contacted with blood components. Animal experiments have verified the safety and efficacy of HbV as a transfusion alternative. One advantage of HbV is that the O(2) affinity (P(50)) of HbV can be regulated easily to that of RBC (28 torr) and to other values by manipulating the amount of the allosteric effectors, such as pyridoxal 5'-phosphate, coencapsulated in HbV. It is possible that HbV with a lower P(50) (higher O(2) affinity) would retain O(2) in the normal tissue while unloading O(2) to a targeted hypoxic tissue. Small HbV (250-280 nm diameter) is distributed homogeneously in the plasma phase, and HbV would transport oxygen through collateral arteries in the ischemic tissues. Results of in vitro and in vivo experiments of the domestic and international collaborations have confirmed the possibility of targeted O(2) delivery by HbV.

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“…Furthermore, ROS are eliminated by SOD, catalase, or peroxidase to suppress metHb formation [16,17]. In contrast, metHb molecules generated in the Hb vesicle are not reduced to the ferrous state due to the absence of the reduction systems, because the constitutive enzymes and reductants necessary for metHb reduction in the human erythrocyte are removed during Hb purification process [18]. Furthermore, ROS elimination enzymes are also completely removed in the process.…”

Section: Introductionmentioning

confidence: 99%

Enzymatic Elimination of Hydrogen Peroxide by a Methemoglobin/L-Tyrosine System

Atoji

Yatami

Aihara

et al. 2007

Artificial Cells, Blood Substitutes, and Biotechnology

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We studied the peroxidase activity of ferrylhemoglobin radical (Hb(Fe(4+) = O*)) generated by the reaction of metHb (Hb(Fe(3+))) with hydrogen peroxide (H(2)O(2)). To clarify the behaviors of ferrylHb radical, it was isolated from the reaction mixture of metHb and H(2)O(2) by GPC at 4 degrees C. The radical species underwent rapid autoreduction to metHb at 37 degrees C accompanied with denaturation; however, it was stable for several minutes at 4 degrees C. In ESR measurements, the signal of the ferrylHb radical immediately disappeared in the presence of L-Tyrosine (L-Tyr), and simultaneously, the signal of the ferric heme increased. This suggested that the ferrylHb radical immediately converted to metHb by L-Tyr even at 4 degrees C. Furthermore, dimerized L-Tyr was detected in the reaction mixture. This showed that the ferrylHb radical was reduced to metHb by electron donation from L-Tyr. The enzymatic reaction using L-Tyr as the substrate resulted in the elimination of H(2)O(2) in this system.

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Virus removal from hemoglobin solution using Planova Membrane

Cited by 17 publications

References 0 publications

Haemoglobin‐vesicles as artificial oxygen carriers: present situation and future visions

Haemoglobin‐vesicles as artificial oxygen carriers: present situation and future visions

Hemoglobin-vesicles for a Transfusion Alternative and Targeted Oxygen Delivery

Enzymatic Elimination of Hydrogen Peroxide by a Methemoglobin/L-Tyrosine System

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