Preparation And Pharmacodynamic Study Of EST Suspensions For Injection

Abstract:OBJECTIVE To prepare EST suspensions for injection and to evaluate the effects of its therapeutic effect on the acute radiation sickness (ARS). METHODS EST suspensions were prepared using the precipitation method and then the suspension was freeze-dried to obtain a powder. The quality control and stability method of EST suspensions for injection were built. Mice were irradiated with60Co y-rays to make the ARS models to evaluate the effect of EST suspensions for injection. The safety of the EST injection was evaluated by hypersensitivity of guinea pig, rabbit s muscle stimulation and haemolytic test. RESULTS The stability of EST suspensions was the best when the water/alcohol ratio was1:1(v/v), drug concentration was1667mg.mI-1, and EST/soybean phospholipid ratio was1:2(w/w) in the formulation. The properties of the freeze-dried samples were the best with mannitol as the lyophilization protector. Three batches of samples were quality-confirmed according to the quality standard. When mice were irradiated with6.5Gy60Co y-ray, the EST injection promoted the restoration of hematopoietic function in the ARS mice. When mice were irradiated with8.0Gy60Co y-ray, the EST injection significantly prolonged the survival days of the ARS mice and raised the survival rate. The EST injection had no allergic reaction on the guinea pigs, no stimulation on the rabbits’muscles, and no hemolytic or aggregation reaction. CONCLUSION The EST suspensions for injection developed in this study were rationally designed, quality-controllable, highly stable. The EST injection has obvious therapeutic effect on the acute radiation injury of mice exposed to60Co y-rays. It may become a novel formulation to cure ARS in the future.