| Animal parasitic disease was an important animal disease,which was often neglected because it had no obvious pathogenic characteristics.It had caused huge economic losses,including many zoonotic parasites,which have an important impact on human health and economic development.The combination of ivermectin and levamisole hydrochloride was used in this study.Ivermectin(IVM)was currently recognized as a 16-membered macrolide antibiotic with broad spectrum,high efficiency,low toxicity and low residue.It had been found to be effective against gastrointestinal nematodes and ectoparasites in livestock.Special curative effect.Levamisole hydrochloride(LMS)was a broad-spectrum,highly effective,low toxic and safe nematode repellent commonly used in animal production,and had the function of immune regulation.The combination of the two drugs can improve the efficacy of drugs,and can also enhance the immune function of animals while repelling insects.Compared with the traditional oral and intramuscular administration,the transdermal dosage form had the advantages of reducing adverse reactions,reducing stress,avoiding the first-pass effect of liver,improving the bioavailability of drugs,and simplifying the operation,so the transdermal dosage form was increasing.In this study,chemical penetration enhancers were used to increase skin absorption of drugs,and compound ivermectin pouring agent was prepared.The stability and quality standard of the compound ivermectin pouring agent were studied,and the effect of the compound ivermectin pouring agent on Trichinella spiralis was tested.A high performance liquid chromatography method for the determination of ivermectin in vitro was established.Acetonitrile-methanol-water(53:35:12)was selected as the mobile phase and the detection wavelength was 254 nm.The results showed that the linearity of ivermectin was good in the range of 10-150 ug/m L.The equation was y=23569x+1464.6 and 2=0.99783.The specificity,precision and recovery of ivermectin were all up to the method standard.A non-aqueous potentiometric titration method for the determination of levamisole hydrochloride in vitro was established.It was proved that the linear relationship of levamisole hydrochloride was good in the range of 0.34 mg/m L-1.67 mg/m L.The equation was y=41.9x+11.2 and 2=0.9999.The method has good specificity,high precision and simple operation,and meets the standard of content determination.In this study,Azone,dimethyl sulfoxide and propylene glycol were used as chemical penetration enhancers,sodium benzoate as antioxidants and anhydrous ethanol as solvents.Five concentrations of each chemical penetration enhancer were set up.The contents of ivermectin and levamisole hydrochloride were determined by HPLC and potentiometric titration through in vitro percutaneous diffusion experiments.Three optimized concentrations were screened out.Four factors and three corresponding levels were selected to carry out orthogonal experiments according to the25(34)experimental schedule.The best prescription was screened out by the same experimental method.The final prescription was 0.5% ivermectin,10% levamisole hydrochloride,0.5% sodium benzoate,A3 Azone,B3 dimethyl sulfoxide,C5 propylene glycol and 100% anhydrous ethanol.In this study,the quality standard of compound ivermectin pouring agent was studied,and the appearance of the product was determined as a colourless clarifying liquid diagram.A method for identifying ivermectin and levamisole hydrochloride was established.The established method for the determination of ivermectin and levamisole in pouring agent was universal to in vitro analysis.In this study,the stability of compound ivermectin pouring agent was investigated.It was proved that the stability of compound ivermectin pouring agent was good under 4500 lx±500 xl strong light irradiation,90%±5% high humidity and 60? high temperature.The content and appearance of compound ivermectin pouring agent were changed in six months' temperature 40 ? ±2?,relative humidity 75%±5% accelerated experiment.It meets the quality standard.The results showed that the stability of compound ivermectin pouring agent was excellent under all conditions.In order to test the efficacy of compound ivermectin spray in the treatment of Trichinella spiralis,mice infected with Trichinella spiralis were divided into three stages: adult,transitional and cystic stages.Each treatment group was given ivermectin orally,levamisole hydrochloride orally,ivermectin pouring agent,levamisole hydrochloride pouring agent and compound ivermectin pouring respectively.A comparative experiment was conducted in 15 treatment groups.The results showed that 71.1% of adult Trichinella spiralis and 92.9% and 91.7% of transitional and cystic larvae were treated with compound ivermectin spray.The rate of insecticidal treatment by Ivermectin gavage and pouring agent was 23.4% and 20.7% in adults,62.1% and 65.4% in transitional period,59.7 % and 61.3 % in cystic period.The rate of insecticidal treatment with Limidazole hydrochloride by gavage and pouring agent was 64.9% and 66.7% in adults,70.2% and 74.1% in transitional period,67.5% and 72.5% in cystic period.During the treatment,the mice were in good condition,and there was no skin irritation in the spray group.It is proved that the compound prescription can obviously improve the rate of insecticide repellency,prove its high efficacy and safety and convenience in use,and the combination of drug prescriptions is reasonable and effective,and the advantages of transdermal preparation are considerable.In conclusion,the compound pouring agent of ivermectin and levamisole prepared in this study has the advantages of high transdermal efficiency,convenient and safe use,scientific and reasonable quality standard detection,good drug stability,high medicinal effect,wide range of insect repellents,and was a new and feasible broad-spectrum insecticide repellent. |
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