ABSTRACT
OBJECTIVE To compare the difference of methods for active systemic anaphylactic reaction induced by breviscapine injection between ″Pharmacopoeia″ 2010 edition, an Attached ⅫG in Traditional Chinese Medicine lnjection Safety Test Application Guidelines ″ Anaphylactic Reaction Test″(thereafter referred to as the method of ″Pharmacopoeia″) and the Traditional Chinese Medicine, Natural Medicine lmmune Toxicity (Anaphylaxis, Anaphylactic Reaction of Light) Technology Guiding Principles in the 2005 Version (thereafter referred to as the method of ″Guiding Principle″) and provide reference for non-clinical safety evaluation of drugs. METHODS According to the methods of ″Pharmacopoeia″and ″Guiding Principle″, respectively, the effect of breviscapine injection on active systemic anaphylactic reaction of guinea pigs was investigated. The guinea pigs were divided into four groups, negative control group, positive control group, breviscapine injection 5 and 50 mg.kg-1 groups. ln the sensitization phase, the guinea pigs were ip administrered with breviscapine injection 0.5 mL each every other day for 3 times. The dose was 5 and 50 mg.kg-1 , respectively. For the method of ″Pharmacopoeia″, on the 14th and 21st days after the first sensitization, the guinea pigs were iv administrered with breviscapine injec-tion 1 mL. For the method of ″Guiding Principle″, the guinea pigs were provocated on the 12th day after the first sensitization. Each group was studied by observing the symptom of anaphylactic reaction and immune time. RESULTS For the method of ″Pharmacopoeia″, on the 14th day after the first sensitization, there was 1 guinea pig with sneezing and (or) the nose-scratching at different time in the 5 mg.kg-1 group. ln the 50 mg.kg-1 group, there was one or two cases of sneezing and (or) 1 case of nose-scratc-hing. The 5 and 50 mg.kg-1 dose groups conformed to the regulations. On the 21st day after the first sensitization, trembling occurred in the 5 mg.kg-1 group, with 1 or 2 guinea pigs sneezing and ( or) scratching the nose. There were 4 guinea pigs (4/ 4) with sneezing 1 and 3 times, cough once or twice, 1 scratching nose and urination at different time, and 1 guinea pigs (1/ 4) appeared 3 times consecutive sneezing and shivering in 50 mg.kg-1 group. The 5 mg.kg-1 group conformed to the regulations, while the 50 mg.kg-1 group did not. For the method of ″Guiding Principle″, the 5 mg.kg-1 group was weak positive or positive, with different degrees of symptoms of an anaphylactic reaction, including 3 guinea pigs scratched nasal symptoms. And the 50 mg.kg-1 group of anaphylactic symptoms including scratc-hing nose, sneezing, coughing and (or) urination, showed positive. CONCLUSION During the active systemic anaphylactic reaction of drugs non-clinical safety evaluation of drugs the advantage of either method should be brought into play. The method of ″ Pharmacopoeia″ may be used for preliminary screening of test samples. ln case pf suspected reactions, the method of ″Guiding Principle″ should be used for more detailed observations.