Hitoshi Matsumoto

Synthesis and biological activities of novel antiallergic agents with 5-lipoxygenase inhibiting action

Novel benzimidazole derivatives were synthesized and their pharmacological activities were examined. These compounds showed a good suppressive action on histamine release from rat peritoneal mast cells produced by antigen-antibody reaction, an antagonistic action on guinea pig ileum contraction caused by histamine, an inhibitory action on 5-lipoxygenase in rat basophilic leukemia-1 (RBL-1) cells, and a preventive action on NADPH dependent lipid peroxidation induced by Fe3+-ADP in rat liver microsomes. In addition, 1-[2-[2-(4-Hydroxy-2,3,5-trimethylphenoxy)ethoxy]-ethyl]-2-(4-meth yl-1-homopiperazino)-1H-benzimidazole difumarate (BOM1006) exhibited a dose dependent suppressive action on 48 h homologous passive cutaneous anaphylaxis (PCA) reaction in rats orally administered the drug.

Mutual effect of egg albumin and fatty acids on bioavailability of dl-α-tocopherol

Abstract We studied the dissolution behavior and oral absorption of dl-α-tocopherol (VE) from solid dispersions of egg albumin in the presence or absence of a series of saturated fatty acids. The solubility diagram of VE–egg albumin was of the Bs-type. The solubility of VE was increased by 300-fold in the presence of egg albumin. The egg albumin complex of the drug was obtained in a molar ratio of 20:1 (VE:egg albumin) from the aqueous solubility diagram. The apparent dissolution rate of VE from solid dispersion with egg albumin was markedly enhanced in comparison with VE alone. Addition of various fatty acids to VE–egg albumin solid dispersions had different effects on the dissolution of VE due to mutual effect of fatty acid and egg albumin. Myristic acid was found to improve the dissolution of VE maximally, while capric acid decreased the solubility of VE obtained from egg albumin solid dispersion. The mean serum levels of VE following oral administration of egg albumin solid dispersions, especially egg albumin solid dispersion containing myristic acid, were significantly higher than those of the drug alone. No significant differences were found between the mean residence times of drug and its solid dispersions. In addition, degradation of VE was inhibited by dispersion in egg albumin.