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Development Of Antifungal Preparation-Yipikang Injection For Dog

Posted on:2011-11-17Degree:MasterType:Thesis
Country:ChinaCandidate:L ChenFull Text:PDF
GTID:2143360308481840Subject:Clinical Veterinary Medicine
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In recent years, with the development of the pet profession, the incidence of fungous skin disease in dogs and cats was rising as well. The fungous skin disease of dogs and cats was at the head of pet′s disease, incidence of which was the highest. People were close with pets, so infection phenomenon with each other was serious between human and animals. It not only brought negative impact on the pet profession, but also seriously affected human's life. Therefore, it was important for the protection of human and animal's health and food safety to research animals'fungous skin disease and develop effective antifungal drugs as well as new related forms.Through the research of solvent, concentrated hydrochloric acid amount, addition time, inclusion temperature and inclusion time, Yipikang injection was prepared based on the best condition by HP-β-CD inclusion technique in the experiment; the concentration of injection was determined by the UV Spectrophotometry, according to the NCCLS M38-A program, the MIC value was determined by the drug sensitivity tests of Microsporum Canis, fungi inhibition tests of Microsporum Canis with the ketocanazde powder and the Yipikang injection for dog; after subcutaneous injection to six dogs by 4mg·kg-1, the blood was carried out respectively after 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72h and the blood samples were purified by anticoagulation with heparin, protein precipitated with acetonitrile and highspeed centrifugal; the blood drug concentration was determined by high performance liquid chromatogram-violet detect method, and then incorporated it into the plasma processing software 3p97 pharmacokinetic analysis; mice were used in the acute toxicity test, accumulation toxicity test, tolerance test, irritation test and sub-chronic toxicity test, meanwhile rabbits of New Zealander were used in the partial stimulation test; three different proposals were given to twelve dogs with fungous skin disease, and during the treatment the smear microscopy was conducted every one week. After two treatmental crouses, the effect of drug was evaluated.Experiment result: Yipikang injection was prepared successfully, the concentration of itraconazole was 18.33mg·mL-1, fungi inhibition test indicated that MIC value of ketocanazde powder and the Yipikang injection was 2.6094μg·mL-1 and 1.0891μg·mL-1; the pharmacokinetics indicated the limit of detection for itraconazole was 10ng·mL-1, and a good linearity was obtained in the range of 10~1000ng·mL-1, recovery rate and precision were permitted within the scope of the method, and the method was suitable for clinical application; the pharmacokinetic parameters of Yipikang injection were as follow: an excretion rate constant 0.0209h-1, the absorption rate constant was 1.2928h-1, drug half-life was 33.1033h, the time to get the highest concentration was 3.2415h, maximum drug concentration was 239.4724ng·mL-1, the area under the plasma concentration-time curve was 8614.3587 mg·L-1·h-1, plasma clearance rate was 0.0019 L·kg-1·h-1, the apparent volume of distribution was 0.0161L·kg-1, the results showed that the pharmacokinetics of injection in dogs conformed with one compartmentopen model; the acute toxicity test showed LD50 was 129.57mg·kg-1, the 95% confidence limit was 106.66~157.40mg·kg-1; for the accumulation toxicity, the accumulation coefficient K was 5.3; the result showed accumlations were slight for mice by Yipikang injection; the result of tolerance test showed good tolerance; irritation test showed injection had slight irritation for rabbits; for the sub-chronic toxicity test, the average weight of the mice of the the high dose group was the lightest at the 28d, compared to the other three groups, the difference was significant(P<0.05)and the GPT appeared higher, some mice'livers had degeneration, even necrosis and no abnormal changes in other groups; clinical efficacy showed that the efficacy of injection was good, and it can be used for dog with fungal skin disease.
Keywords/Search Tags:canine fungous disease, Yipikang injection, itraconazole, pharmacokinetics, toxicity test
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