Establishment of production process of cellular- type oxygen carriers

为了建立细胞型氧载体(血红蛋白-囊泡)的规模化生产工艺，完成了以下课题的研究工作。研究结果：1.血红蛋白溶液的羰化和脱氧过程：利用人工肺进行血红蛋白溶液的羰化和脱氧反应。HBO_2溶液的电化学除氧：在稀氢/氮气混合气体条件下，将溶解氧(PO_2&lt；1OTorr)电化学还原为水。HbCO向HBO_2的配体交换过程：利用液体薄膜或硅中空纤维模块对HbCO溶液进行可见光照射的配体交换过程。新型氨基脂的合成及用途：新合成了聚氧乙烯偶联或带负电荷的氨基脂，并以此为原料制备了HB-囊泡。挤压过程的放大：为了提高挤压过程的效率，混合的脂类分散体先前被冷冻切割和干燥。采用多级组合式挤出机，大大缩短了粉末在HB溶液中分散所需的挤出时间，大大提高了挤出效率。评价10L规模的Hb囊泡生产：每个过程中的仪器都是内衬的，正在评估10L规模的Hb囊泡的生产。将规划300个L规模的试点工厂。

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.