Establishment of production process of cellular- type oxygen carriers

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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.