Methodology for preclinical assay of pseudoallergy of injectable drugs(I)——mouse model for assay of pseudoallergy induced by injections

Objective: To develop animal models and methodologies for assay of pseudoallergy induced by injectable drugs.Method: Mouse anaphylactoid reaction model was developed by intravenous injection of test substance solutions containing Evans blue(EB).Scores of ear blue staining and quantitation of ear EB exudation were the parameters for the pseudoallergy reaction.Result: Mouse anaphylactoid reaction was characterized as vascular hyperpermeability which was detectable in ears by quantitation of blue staining score and EB exudation.Compound 48/80 and histamine caused severe ear bluing and EB exudation by inducing obvious vascular hyperpermeability which indicated that they can induce mouse pseudoallergy.Intravenous injection of either normal saline or 5% glucose injection showed no ear bluing.The mouse pseudoallergy model was validated by intravenous injections of western drugs and Chinese medicine.Conclusion: Mice could be developed into pseudoallergy model for preclinical safety evaluation of injectable drugs.The pseudoallergy reaction in this model is of high clinic consistency,sensitivity,reproducibility,and maneuverability.The model is suitable for the evaluation for pseudoallergy induced by injectable products prepared from Chinese materia medica.This model can also be used for safety assay and quality control in manufacturing process,spot checking of marketed products,screening of allergen as well as studying of pseudoallergy mechanism.