Pharmacodynamic And Safety Evaluation Of Wupi Oral Liquid

Chicken gout is a nutritional metabolic disease with high morbidity and mortality,which often causes great breeding industry losses.The prescription o f Wupi oral liquid is derived from Wupisan powder.It is made of Poriae Cutiis,Citri Reticulatae Pericarpium,Mori Cortex,Arecae Pericarpium and Zingiberis Cortex.Its efficacy is promoting qi,removing dampness and alleviating water retention,and can be used to treat edema.Previous studies have found that Wupi oral liquid can prevent and treat chicken gout effectively.On the basis of the previous studies,according to the new veterinary drug declaration requirements,the diuretic effect,acute toxicity,sub-chronic toxicity and target animal safety experiments were carried out with Wupi oral liquid,and the following results were obtained:（1）Diuretic effect of Wupi oral liquidA total of 50 male Kunming mice were randomly divided into 5 groups with 10 mice in each group.Mice in high,medium and low dose group were administrated with Wupi oral liquid in 13.5,6.75,3.375g/kg,respectively.Mice in drug control group were administrated with Wupi San decoction.Mice in negative control group were administrated with same volume of normal saline.The mouse water loading model was prepared by intraperitoneal injection of 1mL of normal saline before oral administration.Urinary output was recorded continuously up to 4 hours.The results indicated:during 4 hours after administration,urine output of Wupi oral liquid high and medium dose group were1.78±0.42g and 1.73±0.60g,respectively,which were extremely significantly higher than that in negative control group（the urine output was 1.18±0.42g,P<0.01）.The urine output of the low dose group was 1.34±0.91g,which was significantly increased（P<0.05）.The above results demonstrated Wupi oral liquid has significant diuretic effect.（2）Acute toxicity of Wupi oral liquidA.Determination of the median lethal dose(LD₅₀):A total of 28 Kunming mice with half males and half females were oral administered with a dose of 27000mg/kg for the determination of LD₅₀.The usual manifestations and deaths were observed.The results showed that the LD₅₀ of Wupi oral liquid was greater than 5000mg/kg.Consequently,Wupi oral liquid belongs to non-toxic substance.B.Determination of the maximum dose:A total of 40 Kunming mice with half males and half females were randomly divided into 2 groups with 20 mice in each group.The experimental group was orally administered Wupi oral liquid with a volume of 0.2 mL/10 g body weight,once every 3 hours,three times,with a total dose of 81 g/kg,continued observe for 7 days.The results showed that the mice in the Wupi oral liquid test group did not show any abnormal manifestations or death.The maximum dosage of Wupi oral liquid was 81 g/kg,and the maximum dosage multiple was 600 times of the recommended dosage of chicken.（3）Sub-chronic toxicity of Wupi oral liquidA total of 80 SD rats with half males and half females were randomly divided into 4groups with 20 rats in each group.The doses of the high,medium and low Wupi oral liquid dose group were 40.5,11.46,3.24g/kg,respectively,with the volume of 1mL/100g,once a day for 28d.The results showed that there were no abnormal changes in the general signs,body weight gain and hematological parameters of the rats in each dose group during the administration period.Compared with the control group,the levels of a lanine aminotransferase,aspartate aminotransferase and urea nitrogen in the high and middle dose group increased significantly or extremely significantly（P<0.05,or P<0.01）,separately,and the blood biochemical parameters of the low dose group were not significantly different（P>0.05）.No obvious abnormalities were found in histopathological examination.The above results indicated that Wupi oral liquid is safe to use at a dose of 3.24g/kg body weight for a long time.（4）Target animal safety of Wupi oral liquidA total of 80 healthy Isa brown chicken,35-day-old,were randomly divided into 4groups with 20 chicken in each group.1,3,5 times and 0 times of the recommended dose of Wupi oral liquid was added to 1L of drinking water,respectively,continue for 7 days.The results showed that 1,3,5 times of the clinical recommended dose of Wupi oral liquid had no abnormal effects on the clinical signs of the test chickens,and no obvious abnormal changes were found in hematological parameters,blood biochemical indexes and histopathological changes.It is safe to use Wupi oral liquid in clinical recommended dose.