Relationship Between Chemical Properties and Biological Properties of Pyridoxalated Hemoglobin-Polyoxyethylene

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Abstract
Pyridoxalated hemoglobin-polyoxyethylene (PHP) is a conjugate of human hemoglobin with alpha-carboxymethyl, omega-carboxymethoxypolyoxyethylene(POE). This conjugate is selected as an oxygen carrier for blood substitute because it can survive for a long time in the circulation and also it can transport the same amount of oxygen as red cell. Optimization of PHP has been done by changing the degree of the modification and reaction procedures in order to adjust viscosity and colloid osmotic pressure to physiological values. The oxygen carrying capacity was physically evaluated by oxygen equilibrium curves and biologically by an ATP content in perfused isolated liver. Structural relationship of PHP to the binding properties to haptoglobin was studied and the effect of the POE modification on the binding properties was observed when the number of POE per one hemoglobin molecule is over six. Based on the comparative study of solubility of met-PHP and met-SFH, the POE modification was suggested to reduce the toxicity of hemoglobin against organs. Finally physical properties of PHP at low temperature was discussed in relation to organ preservation.