Study On The Preparation And Pharmacokinetics Of Long-Acting Oxytetracycline Injection

In this study, we selected the best formula of long-acting Oxytetracycline injection by orthogonal test, as the standard was the change value of the Oxytetracycline,s content. Flowing the best formula, we can prepare a kind of long-acting Oxytetracycline injection. Then the stability, safety, pharmacokinetics, pharmacy of long-acting Oxytetracycline injection were studied to provide a theoretical basis for it in the veterinary clinical application.Part I: Establish the analytical methord of long-acting Oxytetracycline injection. The content determination of long-acting Oxytetracycline injection analytical methods were established by ultraviolet-visible spectrophotometer. The results showed that the good linearity of Oxytetracycline were obtained in the range of 5～30μg·mL^-1, and the average recovery, relative standard deviation RSD, RSD of the with-in-day precision, RSD of the day-to-day precision of Oxytetracycline were respectively(97.86±1.27)%, 1.15%, 0.42%, 1.07%. The analytical method of ultraviolet spectrophotometry UV which established had high recovery rate, good repetitiveness and precision in this research. It could offer a good specificity method of content determination of long-acting Oxytetracycline injection.Part II: The preparation and the quality evaluation of long-acting Oxytetracycline injection. We studied the factors such as controlled-release formulation,antioxygen, Compound organic solvent and complexant which can effect the stability and the long-acting of Oxytetracycline injection in three levers by orthogonal test, then made a decision to select the best formula of long-acting Oxytetracycline injection.Following the best formula,we completed the preparation of long-acting Oxytetracycline injection.We investigated the stability of long-acting Oxytetracycline injection by light accelerating test,long term stability test,humid joint acceleration test.The best precentage of long-acting of Oxytetracycline injection is W/V(Oxytetracycline)=30%, ( W/V ) (magnesium chloride)= 6%, ( W/V ) (sodium formaldehyde sulphoxylate)=0.6%,(W/V)(Compound organic solvent)=60%,(W/V)(polyvinylpyrrolidone K17)= 7.5%,(W/V)(ethanolamine)= 5.4%,(W/V)(water for injection)= 0.9%.The long-acting Oxytetracycline injection is stable in light accelerating test,long term stability test,humid joint acceleration test.The investigation can fullfill the requirement of the veterinary drug. Part III: The safty evaluation of long-acting Oxytetracycline Injection. We investigate the safty of long-acting Oxytetracycline injection by acute toxicity test, Local irritation test, pyrogen test, Hemolytic test for providing safty evidence of clinical veterinary medicine. The median lethal dose(LD₅₀) of long-acting Oxytetracycline injection was 609.50mg/kg, so it belong to Low toxicity drug. Serious irritation didn't appear when long-acting Oxytetracycline injection was used on complete and damaged skin of rabbits respectively. The results showed that long-acting Oxytetracycline injection was safe by intramuscular injection, pyrogen test and Hemolytic test.Part IV: Pharmacokinetic Study of long-acting Oxytetracycline injection. Study, before this chapter, is basic of the establishment of plasma long-acting Oxytetracycline injection HPLC method, the standard curve equation is Y=1345.2X+3951.8(R²=0.9995).This methord can fulfill the requirement of experiment in many respects such as recovery rate, stability, repeatability and accuracy. At the same time, it can provide the pharmacokinetic evidence of long-acting Oxytetracycline injection. The results showed that long-acting Oxytetracycline injection can release formulation medicine when the data are consistent with first order absorption two-compartment model, sustained-release agent pharmacokinetic equation is C=3944.95e-0.0754t+293.72e-0.00751t+4238.67e-2.0483t. Comparing with the long-acting Oxytetracycline injection investigated by Jinhua Cai(Tmax=2h, T_1/2α=11.053 h,T_1/2β=69.315 h), the new kind of long-acting Oxytetracycline injection investigated by this study(Tmax=1.72 h,T_1/2α=9.19 h,T_1/2β=92.98 h) has better effect on the respect of long-term effect. For example, It's sustained-release agent plasma concentration reached the maximum time is about 14% ahead; It's absorption half-life is Shortened about 16.83%; the elimination half-life is extended about 33.12%.Part VI: long-acting Oxytetracycline injection release agent to combat the Chicken poison mycoplasma disease. The chicken, which were infected by Mycoplasma gallisepticum with the symptom of respiratory disease, was injected long-acting Oxytetracycline injection in high, medium and low concentration. The last three groups were compared with the experimental group, tylosin injection as a positive control group and blank control group of patients treated chicken. Treatment effect showed that For the long-acting Oxytetracycline injection groaps in high, medium and low concentration and tylosin injection groap,weigt gain rate is 91.1%,94.3%,86.1%,93.0% repectively; The balloon relative damage rate is 87.8%,89.4%,83.3%,90.9%; It means high medium and low long-acting oxytetracycline injection groups and tylosin tartrate group could significantly reduce the incidence of mortality in chicken; weight gain of high, medium and low-dose long-acting oxytetracycline injection groups and drug control group were higher than the positive control group; long-acting oxytetracycline hydrochloride injection can effectively reduce the balloon injury, And the treatment effect of medium-dose group is better than the treatment effect of low dose group and high dose group, The medium-dose long-acting oxytetracycline injection group had no significant differences with tylosin tartrate group in treatmemnt effect. long-acting oxytetracycline injection and tylosin tartrate can reduce antibody levels in chickens. long-acting oxytetracycline injection group with the role of efficient respiratory disease has a good application prospects in the veterinary clinic.