Abstract
In order to design an injectable formulation of E5531, a novel synthetic disaccharide analog of lipid A, for the treatment of septic shock, a 'pH-jump method' was developed. In this method, E5531 was dispersed in 0.003 mol/L NaOH (pH 11.0, above pKa2) at 50°C (above phase transition temperature) and then mixed with buffer to neutralize the pH 7.3. E5531 was dispersed as the particles and the size was approximately 20 nm. The membrane fluidity of the particles was correlated with the pharmacokinetics in rats and effective dose (ED50) in BCG/LPS treatment mice.
