Establishment of production process of cellular- type oxygen carriers

细胞型氧载体生产工艺的建立

• 批准号: 12558112
• 负责人: TAKEOKA Shinji
• 金额: $ 7.94万
• 依托单位: Waseda University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12558112/
• 关键词: hemoglobin; 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

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.

为了建立细胞型氧载体（血红蛋白（HB） - 速囊）的大规模生产过程，以下受试者完成了。1。 HB溶液的羰基化和脱氧过程：用人工肺进行了血红蛋白（HB）溶液的羰基（CO）和脱氧溶液。2。 HBO_2溶液的电化学去氧：在稀释的氢/氮混合物气体条件下，将溶解的氧（PO_2 <1O TORR）电化学降低至水。3。 HBCO至HBO_2的配体交换过程：使用液体薄膜或硅基空心纤维模块可见光辐射到HBCO溶液中，进行了配体交换过程。4。新氨基脂质的合成和用途：新合成的聚氧乙烯偶联或负含量的氨基脂质，并用这些脂质制备HB-sepicles.5。扩展挤出过程：为了提高挤出过程的效率，以前冻结并干燥的混合脂质分散体。粉末挤出过程中挤出过程中的必要时间大大降低了，并且随着多抗兼式型挤出仪的形式，挤出的效率也大大提高。6。评估HB囊泡的10L尺度产生：每个过程中的设备都排列了，并且正在评估HB囊泡的10L尺度产生。计划在300升的规模上进行飞行员。

项目成果

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)

Ippei Fukutomi、Hiromi Sakai、Shinji Takeoka、Eishun Tsuchida、Kiyotaka Sakai：“使用膜氧合器进行氧合血红蛋白溶液 (HbO_2-HbCO) 的羰基化”人工器官杂志 5・2（出版中）。

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)

Takeoka 等人：“预处理含有 Hb 囊泡（氧载体）的血清以避免其对实验室测试的干扰”Clin.Chem.Lab.Med.. 41. 222-231 (2003)

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)

H. Sakai、H. Onuma、M. Umeyama、S. Takeoka 和 E, Tsuchida.：“近紫外区辐射对高铁血红蛋白的光还原”生物化学。

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)

Takeoka 等人：“利用冷冻解冻和快速挤出进行血红蛋白囊泡 (HbV) 的高效大规模生产”Biotechnol.Prog 19（出版中）。

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)

Hiromi Sakai、Yuhei Masada、Shinji Takeoka、Eishun Tsuchida：“牛血红蛋白的特征作为人工氧载体的血红蛋白囊泡的潜在来源”生物化学杂志。