Study On Toxicity And Safety Pharmacology Of The "Ku Lian Ma Yang" Compound Injection

The"Ku Lian Ma Yang"compound injection is composed of Ephedra sinica,Forsythia suspensa,Datura metel L.,and Semen Armeniacae Amarum.It is included in the 2015edition of Chinese Pharmacopoeia.This study aimed at the harm of animal respiratory diseases,put forward that the traditional Chinese medicine compound"Ku Lian Ma Yang"injection with cough and asthma effect is used in the prevention and control of animal respiratory diseases.According to the Compendium of Technical Guiding Principles of Veterinary Medicine Research,this study carried out three aspects:acute toxicity test,subchronic toxicity test for 30 day and safety pharmacology test,evaluated its safety and provided the basis for its clinical application.The main findings are as follows:1.Acute toxicity test of"Ku Lian Ma Yang"compound injectionIn the pre-test,healthy Kunming mice were randomly divided into 5 groups,4 in each group,30 g/kg,25 g/kg,12.3 g/kg,6.2 g/kg and 3.1 g/kg were injected intraperitoneally according to the dosage of crude drug.LDn（minimum lethal dose）=3.1 g/kg and LDm（maximum lethal dose）=25 g/kg.Based on the pre-test,50 mice were randomly divided into 5 dose groups:25 g/kg,14.81 g/kg,8.84 g/kg,5.25 g/kg and 3.12 g/kg,were administered intraperitoneal injection.The LD₅₀ and 95%confidence interval of compound injection were calculated by modified Kirschner method.The LD₅₀ was 8.375 g/kg,and the95%confidence interval was 6.592 g/kg～10.641 g/kg,and the LD₅₀ of rats was 5.863 g/kg according to the equivalent metrological relationship.According to the classification standard of acute toxicity of exogenous chemical drugs in WHO,the"Ku Lian Ma Yang"compound injection belongs to micro toxicity drug.2.Subchronic toxicity test of"Ku Lian Ma Yang"compound injectionThe subchronic toxicity test selected 80 healthy sexually mature SD rats,designed high dose group（1.173 g/kg）,medium dose group（0.586 g/kg）,low dose group（0.293 g/kg）and blank control group.The trial rats were randomly grouped,20 in each group,with male and female distributed equally.Intramuscular injection once a day for a continuous injection of30 days,during which free intake of drinking water.The results showed that compared with the blank control group,food intake of female rats in high dose group of"Ku Lian Ma Yang"compound injection decreased significantly（P<0.05）,and weight gain of male rats in low dose group decreased significantly（P<0.05）.There was no effect on blood routine indices of rats in each dose group（P>0.05）.The triglycerides in the blood biochemical indices of rats in the high-dose group were significantly increased（P<0.05）.According to the indices of organ coefficient,the heart coefficient of female rats in low dose group and middle dose group increased significantly（P<0.05）.The results of histopathology showed that the high-dose group could cause granular degeneration and vesicular degeneration in rat hepatocytes and no lesions in other organs.The results showed that the"Ku Lian Ma Yang"compound injection had no long-term toxicity,and had no effect on the clinical status and weight gain of the rats basically.There was no significant effect on blood routine and blood biochemical indices in rats.And it may cause granular degeneration and vesicular degeneration in hepatocytes.3.Safety pharmacological test of"Ku Lian Ma Yang"compound injectionThe high dose group（1.173 g/kg）,the medium dose group（0.586 g/kg）,the low dose group（0.293 g/kg）and blank control group were designed in safety pharmacological test.Intramuscular injection once every morning for 5 consecutive days.The results showed that compared with the blank control group,there was no obvious abnormality in the clinical manifestations of the rats in each dose group of the"Ku Lian Ma Yang"compound injection,and there was no downward trend in autonomous activity,and the evaluation of pole-jump test was grade 0.There was no significant difference（P>0.05）in heart rate before,the day after and one week after dosing,and there was no significant difference（P>0.05）between different time points in the group.And there was no significant difference（P>0.05）in breathing rate before,the day after and one week after dosing,and there was no significant difference（P>0.05）between different time points in the group.The results showed that the"Ku Lian Ma Yang"compound injection had no effect on the central nervous system,cardiovascular system and respiratory system of rats.