Study On The Preparation And Pharmacodynamics Of Oxyclozanide Suspension

Oxyclozanide is a new antiparasitic drugs which has a good effect on anti fluke.This text describes acute toxicity test of active pharmaceutical ingredient,the prescription selection and optimization of oxyclozanide suspension,content measurement,pharmacodynamic of oxyclozanide suspension,etc.,to evaluate the pharmacological,toxicological and pharmacodynamic of oxyclozanide suspension.The sedimentation volume ratio and redispersibility were used as variable factors,the quadratic regression orthogonal combination design were carried out to optimize the prescription and prepare the suspension.The suspension?100 mL?was consisted of 3.2g oxyclozanide,0.2g carbomer 974p,0.3g sodium dodecyl sulfate sodium salt,0.02g methyl 4-hydroxybenzoate and 0.4g sodium pyrosulfite.With good redispersibility,the sedimentation volume ratio of oxyclozanide suspension was 0.999.The distribution of particle size is uniform,the size is about 1000 nm,and the distribution is normal.The method to detect the content of oxyclozanide suspension was established.The column:Hypersil ODS?150 mm×4.6 mm,5?m?;the mobile phase consisted of methanol?100%?:0.1%phosphoric acid water=80:20;the flow rate was 1.0 mL/min;the detection wavelength was 300 nm;the column temperature was?25±5??and the injection volume was 20?L.The method had high accuracy and precision,the linear relationship between the concentration of oxyclozanide and the corresponding peak area in the concentration range of 18¹00?g/mL was good,determination of the content of oxyclozanide suspension in the marked range of 95%to 105%,in line with Pharmacopoeia.The method is sensitive,rapid and simple.Use the incremental method in pre-test to determine the dose range and group distance in the formal test.Mice were orally administered for 7 days,the LD₅₀ value and its 95%confidence interval were calculated by the simplified Kirschner method and the observation of the change of the signs,the mortality rate and the time of death of mice were counted.The results showed that the acute toxicity LD₅₀ of rats oxyclozanide was 3.707 g/kg in rats,95%confidence interval ranged from 3.148 g/kg to4.365 g/kg;the LD₅₀ of mice oral administration of oxyclozanide was 1.130 g/kg,and the 95%confidence interval was 0.940 g/kg to 1.359 g/kg;the acute toxicity LD₅₀ of oxyclozanide suspension in rats was 5.563 g/kg and the confidence interval was 5.149 g/kg to 6.010 g/kg;the oral LD₅₀ value of the oral suspension in mice was 2.794 g/kg,95%confidence interval was 2.402 g/kg to 3.251 g/kg.Positive buffalo were detected by fecal egg detection and ELISA test.EPG was recorded before or after the experiment.105 positive buffalo were divided into several groups,including test groups:the recommended dose group?45 positive buffalo,10mg/kg?,double recommended dose group?15 positive buffalo,20 mg/kg?,halved recommended dose group?15 positive buffalo,5 mg/kg?;the positive drug group?15 positive buffalo,10 mg/kg?;the negative group?15 positive buffalo,no drug?.EPG values in the feces were examined at 3d,7d,14d,21d,28d and 56d after treatment.The results showed that 80%of the positive buffalo turned negative on the 7th day after the administration,and the negative conversion rate reached 98.87%after 14 days,and the infection was not relapse after treatment until 56days,treatment effect of the recommended dose group is remarkable.