Hemoglobin-based oxygen carriers have been developed to compensate the needs of blood for transfusions. Most of them were based on intracellular hemoglobin extracted from bovine or human blood, but unfortunately, this type of hemoglobin did not pass through the last steps of clinical trials. In this context, HEMARINA discovered a natural extracellular hemoglobin, possessing several advantages avoiding intracellular hemoglobin-related side effects. Many preclinical studies assessed the safety of M101 used in intravenous (IV) injection in rodents. To explore the safety of IV injections of M101 in large mammals, six dogs received each a single injection of liquid M101 according to a dose escalation with a 48 h follow-up. Then, two monkeys received multiple IV injections of the same dose of M101 every hour for seven hours. This study showed that single and multiple IV injections in dogs and monkeys did not cause clinical or histological lesions, nor did they induce immunological reactions. This makes M101 the best candidate to date for human use in emergency situations requiring blood and, in several diseases, causing hypoxia problems.
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