| Mycoplasma pneumonia of swine have causing serious economic losses in breeding industry, it can cause pig growth retardation, reduce productivity and feed efficiency. The high incidence of it and low mortality are the main features of the disease, but the disease secondary to other diseases easily. The disease mainly in the comprehensive measures of vaccine and antibiotics to prevent and control, using of antibiotics long-term can become resistant pathogens and drug side effects, a high amount of drug residues and affecting human health.Nifedipine was used treatment of cardiovascular diseases such as arrhythmia, hypertension, angina in clinical, in recent years,literature reported that NF have good effect of the treatment of asthma and the side effect is small, the price is low. The commercially available formulations which have sustained-release tablets, controlled-release tablets, capsules, creams and so on, but there has not been listed injections, injections are commonly used formulations in veterinary clinic, this paper developed nifedipine injection for the treatment of swine enzootic pneumonia, this paper prescription the formula and preparation technique, quality standards, stability and anti-asthmatic effects of injection which were evaluated before clinically according to 《Chinese Pharmacopoeia》2010edition, the purpose is to provide a reference for the next clinical trials and register new animal drug.The preparation technique and quality evaluation of nifedipine injection:by filtering ethanol,1,2-propanediol and water for injection dosage,100mL nifedipine injection composition of prescription drug nifedipine raw0.110g, sodium metabisulfite0.001g, nicotinamide right amount,1,2-propanediol45mL, ethanol lOmL, water for injection was added to100mL and the trait of nifedipine injection is pale yellow clear liquid. Nifedipin injectione was prepared to identify,inspect,determine and do other researches. As a result,identification of responsive; the pH, content difference, clarity which are in line with the relevant requirements of injection; determination of the nifedipine in injection with RP-HPLC, chromatographic conditions:Column:Sepax HP-C18(4.6mm×150mm,5μm); mobile phase:methanol-water (60:40), adjust the pH to4.8; flow rate1.OmL/min-1; detection wavelength of235nm; column temperature was30℃; as a result, the injection concentration of nifedipine in10-100μg/mL-1has good linear, regression equation:y=69699x-876.89, r=0.9999; quantification limit is0.05μg/mL-1; ntra-day and inter-day precision(RSD)values were less than10%; average recovery was98.5%, RSD=0.41%; measured under the conditions of the average content of nifedipine injection1.08±0.06mg/mL-1.The stability research of nifedipine injection:illumination test conditions:light intensity4500Lx±500Lx; high temperature test conditions temperature60℃±2℃; repeated freezing and thawing test conditions:-20℃for2days;40℃under heating conditions placed2days, three cycles;accelerated test conditions:temperature40℃±2℃. The results after10days of light test that nifedipine injection was significantly decreased, the appearance of color change from pale yellow to slightly yellow, but pH and clarity has little changes; through10days of high temperature test, nifedipine injection content has dropped, the injection conforms with the regulations, pH, traits and clarity have changed little;12days after repeated freezing and thawing three trials, nifedipine injection was decreased by3.84%, the injection conforms with the regulations, pH values, character and clarity changes minimal; accelerated test six months, nifedipine injections content, pH value, character and clarity have changed little.Pharmacokinetic study of nifedipine injection:six healthy SD rats, intramuscular injection with a single dose of nifedipine(8mg/kg-1), and after the administration0.12,0.25,0.5,1,2,3,4,6,8,12h collect blood through venous sinus of eye-orbit in rat, put into anticoagulant heparin of0.5ml tubes placed, and-20℃cryopreserved.200μL whole blood is added with deionized water in a centrifuge tube, with absolute eiethyl ether extraction, and the supernatant was evaporated to dryness at40℃, the residue was dissolved in mobile phase with a1mL and filtered. RP-HPLC analysis of drug concentration in the blood sample, and count the pharmacokinetic parameters by DAS3.0. As a result, the blood concentration of nifedipine in0.05-2μg/mL-1has good linear, egression equation:y=54.369x-1172.100, the correlation coefficient r=0.9995, lower limit of quantification is0.05μg/mL-1; nifedipine in vivo of rats to meet absorption with a two-compartment model by intramuscular administration, the main pharmacokinetic parameters:Cmax=851.83±43.52μg/L-1,Tmax=2.00±0.00h,tl/2a=0.66±0.15h,t1/2β=4.32±1.96h,AUC0-t=148.17±8.10μg-h-L-1,AUC0-∞=296.33±16.19μg·h·L-1. Relieving asthma test of nifedipine injection:rats was screened for acetylcholine and phosphate groups by sensitive, which were divided into control group, low-dose group, middle dose group and high-dose group, the control group received normal saline. The results show low, medium and high dose groups of rats could significantly prolong the incubation period of asthma,and increased with the increases of the dose. The rat tracheal spiral strip made to observe the effect of drugs on airway smooth muscle resting tension and CaCl2on Ach-induced bronchoconstriction and a diastolic. The results showed that resting tension of tracheal smooth muscle inhibition rates were12.34%,24.56%,33.87%and41.36%; maximum effect on the dose-response curve of Ach and CaCl2decreased in a dose-dependent manner; Ach raised on tracheal smooth muscle contraction inhibition rates were26.82%,38.24%and47.51%, CaCl2raised on tracheal smooth muscle contraction inhibition rates were39.68%,52.35%and64.06%respectively. |
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