Non-Clinical Safety Evaluation of Self-Made Acetylcysteine Solution for Inhalation
Objective To provide a basis for the clinical safe use of self-made Acetylcysteine Solution for Inhalation.Methods Eighteen Japanese male white rabbits were selected and divided into the negative control group(equal volume of 0.9%Sodium Chloride Injection),the marketed drug control group(original-patented drug,0.1 mg/mL),the treatment group(self-made drug,0.1 mg/mL)by the stratified randomization method based on body mass,with six rabbits in each group.The drugs were given by atomizing inhalation at a dosage of 35 mg/kg and a volume of 0.35 mL/kg.Each group was given the corresponding drug once a day in the morning and afternoon for 14 d.The occurrence and recovery time of respiratory irritation symptoms was recorded.After 24 h and 14 d of the last administration,three rabbits in each group were selected for dissection respectively,and the irritation reaction was observed by naked eyes.The hematoxylin-eosin staining was used to observe pathological morphology.Thirty Hartley guinea pigs were selected and divided into the negative control group(0.9%Sodium Chloride Injection,0.8 mL/d),the positive control group(0.9%Sodium Chloride Injection,0.8 mL/d),the marketed drug control group[original-patented drug,80 mg/d(0.8 mL/d)],the low-dose group[self-made drug,40 mg/d(0.4 mL/d)],and the high-dose group[self-made drug,80 mg/d(0.8 mL/d)]by the stratified randomization method based on body mass,with six guinea pigs in each group.Guinea pigs in each group were given drugs(10%ovalbumin solution,0.6 mL/d)once every other day for three times.After 14 d and 21 d of the last administration,three guinea pigs in each group were selected and stimulated at the twice dose of the above administration.The active systemic allergic reaction was comprehensively evaluated based on the incidence and severity of the allergic reactions.Results The appearance,behavior and feces in each group of rabbits were normal,and there was no relevant symptoms such as cough;after gross anatomy,no obvious abnormality was observed;and there was no drug delay or accumulation effect in the treatment group compared with the negative control group and the marketed drug control group.No drug-related abnormal symptom was observed in each group of guinea pigs,and all allergic reactions were negative.Conclusion Self-made Acetylcysteine Solution for Inhalation dose not induce the obvious respiratory irritation in Japanese white rabbits or obvious systemic sensitization in guinea pigs.
Acetylcysteine Solution for Inhalationself-made drugsafety evaluationrespiratory irritation testactive systemic allergic test
万方数据
维普
