Study On The Toxicity And Acaricid Pharmacodynamics Of Hymecromone Microemulsion

Hymecromone is a kind of compounds with high acaricidal activity which isolated from the leave and stem of Artemisia scoparia Waldst. et Kit., Hymecromone microemulsion can improve drug solubility, stability and bioavailability significantly, and it have the targeting activity and slow-release action, and which can reduce the drug dose and toxicity, and ease off drug residues in animal products, and improve animal product quality and security. In order to further reveal the hymecromone microemulsion clinical application reliability, stability and security, according to the submission requirements of the first class of veterinary drugs, through the experiment of acute toxicity, subchronic toxicity, spermatozoa teratogenic assay and other bone marrow micronucleus test, we had evaluated the effect of hymecromone microemulsion in the treatment of acariasis. The results are as follows:1.Study on killing Psoroptes cuniculi with hymecromone microemulsion.The acaricidal activity of hymecromone microemulsion was determined through the titration method and the filter paper method in vitro. The results showed that in the titration test, undiluted hymecromone began to kill P. cuniculi in 15 min, and killed all the Psoroptes cuniculi in 45.00min. and 4.50g/L, 2.25g/L, 1.125g/L and 0.563g/L hymecromone began to kill P. cuniculi in 85.00min, 90.00min, 110.00 min, 130.00min, respectively. The acaricidal time of 4.50g/L and 2.25g/L hymecromone microemulsion was significantly lower than that of Abamectin (P<0.05), and The acaricidal time of 1.125g/L, 0.563g/L hymecromone microemulsion was close to that of Abamectin (P>0.05), The acaricidal activity of hymecromone microemulsion was significantly higher than the negative control group (P<0.05). In the filter paper test, undiluted hymecromone microemulsion began to kill P. cuniculi in 30min, and killed all the P.cuniculi in 70.00min. The acaricidal time of filter paper method was longer than that of immersion method (P<0.05).The half lethal concentration (LC₅₀) of hymecromone microemulsion for P.cuniculi was 0.70g/L, 95% confidence limit of LC₅₀ was between 0.61g/L to 0.78g/L, Toxicity regression curve: y = 141.93x + 72.71(R²= 0.9661,P<0.01). The concentration of hymecromone microemulsion had the strong correlation with mite mortality (P<0.05), and hymecromone microemulsion has obvious therapeutic effect in vivo acaricidal test. The clinical treatment effect of hymecromone microemulsion was close to that of abamectin (P>0.05).2. Study on curative effect of hymecromone microemulsion in the treatment of Demodiosiseanis.The acaricidal tests were conduct with hymecromone microemulsion and sensitive- antibiotic in the treatment of Demodiosiseanis in vitro and in vivo. The results showed that hymecromone microemulsion have a very strong role in the killing Demodex, and the time of killing all the Demodex were in 3.00h, 3.33h, 4.00h with 9.00g/L, 4.50g/L, 2.25g/L hymecromone microemulsion, and with 1.125g/L and 0.563g/L hymecromone microemulsion was in 5.33h, 5.67h, The acaricidal activity of hymecromone microemulsion was close to that of abamectin (P>0.05). The major bacterial noxae of dog demodex had Staphylococcus intermedius, Streptococcus pyogenes, wound Escherich's bacillus and Pseudomonas aeruginosa, but the isolation rate of Staphylococcus was the highest one. These 4 strains were sensitive to Ceftriaxone Sodium, Cefalotin, Erythromycin and Sarafloxacin hymecromone microemulsion can decline mites number and rapidly improve skin inflammation, the cure rate was 59.09% and effective rate was 81.82% in the treatmen of dander type of mite disease, and which had an significant advantage to the treatment of avermectin (P<0.05). Pyodermia caused by mites could be significant cured with hymecromone microemulsion and sensitive-antibiotics, its cure rate was 58.33% and effective rate was 83.33%. Hymecromone microemulsion had a slight irritation on the damaged skin, and no anaphylaxis and lick poisoning in this experiment.3. Acute toxicity test on hymecromone microemulsion in ratsThe acute toxicity test on hymecromone microemulsion was conduct by means of oral and skin coating in rats. The results showed that: (1) the LD₅₀ of hymecromone microemulsion was 26.30g/kg by means of oral, its 95% confidence interval was between 22.01g/kg to 31.43g/kg and toxicity regression equation was y=0.04x-0.44 (R²= 0.9776). (2) the LD₅₀ of hymecromone microemulsion was 67.76g/kg by means of skin coating, its 95% confidence interval was between 59.37g/kg to 77.33g/kg and toxicity regression equation was y=0.01x-0.43(R²= 0.8815). In a word,hymecromone microemulsion are nontoxic drugs.4. Sub-chronic toxicity test on hymecromone microemulsion in rats.The sub-chronic toxicity test on hymecromone microemulsion was conduct by means of fixed dose skin coating in rats. The results showed that hymecromone microemulsion had no effect on clinical manifestations, blood physiological parameters and organ index of rats. Howeve, prolonged high doses of hymecromone microemulsion could reduce body weight of rats, and the low dose had no effect.In the early trial stage, hymecromone microemulsion had a certain of impact on serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin and urea nitrogen, but at post-test, all indicators consistent with the control group (P>0.05). Hymecromone microemulsion had no significant effects on total protein, albumin, glucose, creatinine and total cholesterol (P>0.05). High-dose hymecromone microemulsion induced certain damages on the structure of rat liver, lung and kidney, but hymecromone microemulsion had no toxic reaction on the rat heart, spleen, ovary, testis, and skin.5. Mutagenic test on hymecromone microemulsion in rats.The mutagenic test on hymecromone microemulsion was conduct by mice micronucleus test and sperm abnormality test. The results showed that hymecromone microemulsion had no significant effects on mouse bone marrow micronucleus rate and sperm abnormality rate. Hymecromone microemulsion had no mutagenic effect on mice.