Studies On TheToxicity, Pharmacodynamics And Quality Control Method Of QIQISHEN Granules

Objective:To observe acute toxicity of QIQISHEN Granules in mice and chronic toxicity of QIQISHEN Granules in rats.Observe the influence of qiqishen granules upon the phagocytic function of the macrophages in the mice abdominal cavity?the mice NK cell activity and the organ?body weight ratio,to study the influence of qiqishen granules upon the immune function model mice.Determine the content of Ginsenoside Rb1 in QIQISHEN Granules by HPLC in order to establish the method of quality control.Methods:Acute toxicity test will participate in the original powder dubbed spend granules suspension,Crude drug equivalent dose 0.5g/mL administered to mice for a week.During this period,the observation of mice weight,feeding,drinking and defecation situation.Long-term toxicity tests in rats spent Granules will participate in the original powder paired suspension,respectively,in low doses[0.5g/(kg · d)],medium dose[1.32g/(kg · d)]and high dose[2.36g/(kg · d)]administered to rats,7 days a week straight a month 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.To study the influence of qiqishen granules upon the immune function model mice,that is Injecting the suspension of chicken red blood cell into the mice abdominal cavity.Then the influence of qiqishen granules upon the phagocytic function of the macrophages in the mice abdominal cavity was observed;the SRBC was prepared.the degree of the blood corpuscle coagulation was observed,then determination of the serum hemolysin was did;the mice NK cell activity were detected by the interaction between the target cell(YAC-1)and spleen cell(the response cell);the observation of the influence of qiqishen granules upon the cellutarimmunity was made by the lymphocyte transforming assay;then the influence upon the organ/body weight ratio was measured by calculating the thymus/body and spleen/body ratio.Use the Kromasil C18(250mm×4.6,5?m)column,its mobile phase was Acetonitrile and water(30:70).The flow velocity was 1.0mL-min-1 and the detective wavelength of Ginsenoside Rbl was 203nm,and the temperature of the column was 40?,the sensitivity was 0.01AUFS,the injection volume was 20?L.RESULTS:Acute toxicity test results in mice showed that the appearance of action in mice,reflex activity,water intake,large urinary conditions were normal.Compared with the control group,long-term toxicity tests in rats showed that participants spent three dose granuless against weight gain and general behavior of rats had no effect cn activity;three hematology,urine and blood chemistry were measured no significant change.The major organs in rats treated group index and the control animals no significant difference.The histopathological examination showed the major organs in each group were non-toxic venereal reason to change.Compared with the control,qiqishen granules could significantly improve phagocytic function of the macrophages in the mice abdominal cavity(P<0.05);it could also improve the humoral imnmne function in the mice;It could increase NK cell activity(P<0.05);it could enhance the lymphocyte transforming,inducing by the ConA(P<0.01):and it had no effect upon the organ/body weight ratio.It was showed that the Ginsenoside Rbl had a good linearity within the range of 2.5-25 mg/L,The amount of 80%,100%,120%of Ginsenoside Rbl sample recovery rate was 100.41%,100.33%and 99.59 respectively;RSD was 0.32%,0.20%and 0.18%respectively.Conclusions:Iavage can not spend Granules measured parameters of the LD50,the drug use of safety tips.QIQISHEN Granuless equivalent to 50 times the clinical dose in rats given oral gavage doses of 1 month,no obvious toxicity.QIQISHEN Granules could increase the immunomodulating effect,indicating it would have a good using prospect.This method is simple and accurate for determination of Ginsenoside Rbl in QIQISHEN Granules.