Studies On The Toxicity,Pharmacodynamics And Quality Control Method Of DANQIRONG Granules

Objective:To observe acute toxicity of DANQIRONG Granules in mice and chronic toxicity of DANQIRONG Granules in rats.To inquire into the effect of DANQIRONG Granules on the kidney function,blood and urine index of the rat kidney acute-injury caused by Gentamicin(GM).Determine the content of Betaine in DANQIRONG Granules by spectrophotometry in order to establish the method of quality control.Methods:Acute toxicity test was to preparate the original powder of DANQIRONG Granules into suspension solution.Crude drug equivalent dose 0.5g/mL administered to mice three times a day,observe for a week.After treatment,the mice were gross anatomy,organs found there when the volume,color,texture change,then changing the supply of organs for histopathological examination.Long-term toxicity tests was to preparate the original powder of DANQIRONG Granules into suspension solution,respectively,in low doses[0.6g/(kg·d)]and high dose[3g/(kg·d)]administered to rats,7 days a week straight three months to observe the rats hematologic indicators(including the clotting time,RBC,WBC,platelet count,WBC and hemoglobin content),urine routine,blood biochemical parameters(AST,ALT,Urea,Cr,CT)and the various organs(heart,liver,spleen,lung,kidney,adrenal gland,thyroid,testes or ovaries)and to carry out histopathological examination.The kidney acute-injury model was induced by injected GM in large doses.The rats were administered DANQIRONG Granules higher or lower doses.After 28 days' curing,it has been determined that blood creatinine(Cr),BUN,total protein(TP),albumin(ALB),urine protein,glucose,ketone bodies and the pathological changes of renal tissue in each group.Use the U3310 UV visible spectrophotometer to determine the content of Betaine in DANQIRONG GranulesRESULTS:Acute toxicity test results in mice showed that the appearance of action,reflex activity,water intake,feces and urinary conditions were all normal.Compared with the blank control group,long-term toxicity tests in rats showed that participants spent two dose granules against weight gain and general behavior of rats had no significant effect;No significant changes of blood,urine routine,blood biochemistry index in the two groups of rats.The major organs indexes of rats in treated group have no significant difference between the control animals.The histopathological examination showed the major organs in each group were non-toxic venereal reason to change.The indexes of hematological,biochemical and uric in DANQIRONG Granules administered rats are significant different from the model group rats and no different from the blank group.It was showed that the Betaine had a good linearity within the range of 0.1-1.2 mg/mL.The amount of 80%,100%,120%of betaine sample recovery rate was 100.09%,101.16%and 99.87 respectively;RSD was 1.15%,1.28%and 0.92%respectively.Conclusions:Intragastric administration can not measured the median lethal dose(LD50)of the DANQIRONG Granules,which suggested that the drug was safe to use.DANQIRONG Granules equivalent to 50 times of the clinical dose in rats given oral gavage doses of 3 months,no obvious toxicity.The DANQIRONG Granules had marked curative effect on rats in kidney acute-injury caused by GM.This method is simple and accurate for determination of betaine in DANQIRONG Granules.