土霉素辅助新宫得康混悬剂治疗产后急性子宫内膜炎的效果分析

为有效的治疗奶牛的产后急性子宫内膜炎,选用土霉素辅助新宫得康混悬剂对患急性子宫内膜炎的奶牛进行治疗.结果表明,从治疗效果和治疗成本综合考虑,用土霉素辅助新宫得康混悬剂的治疗方法优于单用土霉素或新宫得康混悬剂的治疗方法.     

氟苯尼考混悬注射液的研制及含量测定

以氟苯尼考为主药,采用正交试验筛选配方,分散法制备氟苯尼考混悬注射液,HPLCUV法测定氟苯尼考的含量。质量评价试验表明,该混悬注射液符合药剂学中规定的混悬剂的要求,具有通针性好、不结块、易重分散、刺激性小的特点,易于注射给药。     

恩诺沙星注射混悬剂的研制及药物含量测定

以恩诺沙星和林可霉素为主药，以多因素正交设计优选配方，采用分散法制备了复方恩诺沙星注射混悬剂，并用紫外-可见分光光度计测定了恩诺沙星含量。结果显示，按照优选条件制备的混悬剂样品具有通针性好、不结块、易重分散的特点，可方便注射给药。所制备的恩诺沙星浓度分别为40mg/mL和80mg/mL的混悬剂样品，经180d室温下储存，药物含量无明显改变。     

穿心莲内酯纳米混悬剂的制备与评价

为优选穿心莲内酯纳米混悬剂的制备工艺并进行初步评价,试验以二甲基亚砜为溶剂、水为反溶剂,采用反溶剂法制备穿心莲内酯纳米混悬剂(ANDRO-NS),以得率为指标,通过单因素试验和正交试验优化了ANDRO-NS的制备工艺,并进行验证试验,采用透射电镜、激光粒径仪对所制备的纳米混悬剂进行表征。结果显示:1%吐温-80混和0.05%泊洛沙姆为稳定剂,药物浓度为40 mg/mL,反溶剂和溶剂的体积比为20,搅拌速率为1400 r/min,搅拌时间为80 min,制得的ANDRO-NS平均粒径为568.51±13.74 nm,粒径合适,稳定性良好。试验表明,采用反溶剂沉淀法制备的ANDRO-NS工艺简单,值得进一步研究。     

替米考星长效混悬剂的研制与质量评价

[目的]利用现代缓释技术,以替米考星为原料药,研制出溶解度较高、疗效强、可减少给药次数的替米考星长效混悬剂,并对其进行质量评价,为该药的批量生产提供可靠依据。[方法]通过正交优化法选择最优处方,并对最优处方进行含量测定试验、稳定性试验和药动学试验。[结果]替米考星长效混悬剂最佳处方为:替米考星原料药2.5g/100 mL,有机溶媒(1,2-丙二醇:乙醇=9:1)占比65%,润湿剂(吐温-80)0.3%,助悬剂(羟丙甲纤维素)5%,抗氧剂(无水亚硫酸钠)0.03%;含量测定结果为合格;影响因素试验发现替米考星长效混悬剂对高温和强光照敏感,对湿度不敏感;加速试验和长期试验发现替米考星长效混悬剂稳定性良好;药动学试验发现替米考星长效混悬剂和实验室自制替米考星溶液的AUC分别为43.164 9μg·h·mL~(-1)和26.206 5μg·h·mL~(-1),替米考星长效混悬剂的相对生物利用度为164.71%。[结论]本试验制得的替米考星长效混悬剂含量合格、稳定性良好、相对生物利用度高,可以批量生产,用于大型养殖场的大规模给药。     

硫酸头孢喹肟混悬剂的质量检验及体外抑菌实验

对自制的硫酸头孢喹肟混悬剂进行质量检验和体外抑菌实验.按照筛选出的配方,应用分散法制备硫酸头孢喹肟混悬型制剂,检验混悬剂的质量并针对临床分离的奶牛乳房炎混合菌株进行体外抑菌实验.结果表明:制得的硫酸头孢喹肟混悬剂符合国家质量标准要求,体外抑菌实验效果明显.     

我国对纳米混悬剂优势和应用的研究进展

纳米混悬剂（Nanosuspensions）是以表面活性剂为助悬剂将药物颗粒分散在水中，通过粉碎或者控制析晶技术形成的稳定的纳米胶态分散体，与传统意义上的基质骨架型纳米体系不同，纳米混悬剂无需载体材料，它可通过表面活性剂的稳定作用，将纳米尺度的药物粒子分散在水中形成稳定的体系。由于纳米混悬剂的特性，其在各种给药途径中都体现出了独特的优势。国外从20世纪末开始就已经展开了对纳米混悬剂的研究，国内有关研究近几年也相继增多，现将国内对纳米混悬剂优势和应用的研究情况介绍如下。     

恩诺沙星注射混悬剂在猪体内的药物动力学用生物利用度

本试验是探讨恩诺沙星注射混悬剂肌注给药的药物动力学特征,同时进行恩诺沙星普通注射剂静注和肌注给药的药物动力学试验,目的在于比较注射混悬剂和普通注射剂的药动学特征,并考察混悬剂的生物利用度,对恩诺沙星注射混悬剂作出药物动力学评价,以了解混悬剂能否达到长效的作用,为临床应用制剂提供理论依据.     

癸氧喹酯固体分散体制备及鉴定

本研究旨在通过研制癸氧喹酯固体分散体制剂,来提高其溶解度,为进一步研制水溶性制剂奠定基础.以熔融-溶剂法制备癸氧喹酯-PEG固体分散体,经差示扫描量热法和红外光谱法对固体分散体中药物的分散状态进行了鉴定,同时进行了溶出试验和含量测定试验.本研究成功制备出癸氧喹酯固体分散体,药物在固体分散体中以低共熔物状态存在；固体分散体中癸氧喹酯药物含量为10.97％,癸氧喹酯在水中的溶解度为152.28 μg/mL,癸氧喹酯溶液剂(3％)的推荐使用量15～ 30 mg/L,本试验制备的癸氧喹酯固体分散体满足临床饮永给药要隶.     

三氯苯咪唑混悬剂对牦牛肝片吸虫的驱虫试验

应用三氯苯咪唑混悬剂,选择自然感染肝片吸虫的牦牛60头进行了驱虫试验。结果表明:①三氯苯咪唑混悬剂5mg/kg体重剂量对肝片吸虫的虫卵转阴率、减少率分别为83.3%、90.0%,对成虫的驱净率和驱虫率分别为91.7%、93.8%,对童虫的驱净率和驱虫率分别为83.3%、90.1%;10、15mg/kg剂量对肝片吸虫虫卵转阴率、减少率及成虫、童虫的驱净率和驱虫率均达100%;②三氯苯咪唑混悬剂10mg/kg剂量与同剂量三氯苯咪唑片剂的驱虫效果无明显差异;③三氯苯咪唑混悬剂3个剂量组试验牛未见异常反应。试验证明三氯苯咪唑混悬剂10、15mg/kg剂量驱除牦牛肝片吸虫高效安全,临床使用以10mg/kg剂量为宜。     

A Study of Drug Residues in Milk Following Intrauterine Infusion of Antibacterial Drugs in Lactating Cows

Intrauterine infusion of nine antibacterial compounds caused detectable drug residues in 17 out of 165 cows or in 25 out of 1110 posttreatment milkings. Four cows treated with pyrolidinomethyl tetracycline suspension had drug residues at the first milking. One cow had residues after oxytetracycline treatment, two after procaine penicillin G, three after acriflavin and after chloramphenicol-dapsone and four after hibitane. Nitrofurazone, nitrofurathiazide and Hibitane Compound® did not cause detectable inhibitory residues in any milk sample.     

Efficacy of parvaquone and long-acting oxytetracycline in Theileria annulata infection

Therapeutic and prophylactic efficacies of parvaquone and long-acting oxytetracycline were tested against Theileria annulata infection, induced by injecting a suspension of infected ground tick tissues (GUTS) into groups of 4 or 5 calves. This infection killed two of four control calves, while all the animals given a single intramuscular dose of 20 mg kg-1 parvaquone or long-acting oxytetracycline on the day of infection underwent mild reactions and recovered. Two separate doses of parvaquone of 10 mg kg-1 administered on the first and second days of fever protected four out of five calves. All the recovered animals from both treated and control groups resisted a homologous challenge with GUTS on Day 45 post-infection which killed three out of four susceptible unimmunized control calves.     

Bioavailability of oxytetracycline dihydrate tablets in dogs

Plasma oxytetracycline concentrations were studied in four healthy beagles after oral administration of four different commercial preparations of oxytetracycline dihydrate tablets. Although no statistically significant differences were found in the biological availability between the four tablets, assessed by the peak plasma level and the area under the plasma concentration—time curve, there was great variation in the plasma concentrations of oxytetracycline achieved in the sixteen experiments. This variation was not related to the in vitro dissolution properties of the tablets. As the amount of oxytetracycline dihydrate administered in die experiments was almost the maximum recommended dose and the mean peak plasma concentrations were either below or at the lower end of the therapeutic concentration range, it is suggested that higher oral doses than those officially recommended are required to attain effective plasma levels.     

牛奶中土霉素残留检测方法改进及临床消除规律探究

试验对牛奶中的土霉素残留检测方法进行了改进,并采用改进后的方法对牛奶中土霉素的临床消除情况进行了探究。样品前处理过程中,选取0.1mol/LNa₂EDTA-Mcllvaine缓冲溶液提取牛奶中的土霉素,正己烷除脂及HLB固相萃取柱净化浓缩。釆用Symmetry Shield RPC18(250mm×4.6mm,5μm)反相色谱柱,以乙腈和0.048%的磷酸溶液(pH2.5)为流动相,采用梯度洗脱的方式对样品进行分析。方法改进后,土霉素的出峰时间为6.5min,峰形尖锐,与样品中的杂质峰分离良好。土霉素标准溶液在5~2000μg/kg范围内线性关系良好,标准曲线R²=0.9999;牛奶中土霉素在10、20、100μg/kg3组浓度的加标回收率分别为87.9%、90.5%和87.8%,批内变异系数范围为2.2%~5.8%,批间变异系数范围为4.0%~5.1%。土霉素在牛奶中的检出限为5μg/kg,定量限为10μg/kg,适用于研究土霉素在牛奶中的残留消除规律。选取了29头产后患有子宫内膜炎的奶牛,分成4个不同剂量组(2、3、4和5g),通过子宫内灌注土霉素的方式进行治疗,然后采用优化后的方法检测牛奶中残留的土霉素。结果发现,4g及以下剂量组给药72h后,牛奶中的土霉素可以消除至残留限量以下;而当给药剂量达到5g时,72h后牛奶中的土霉素未消除至残留限量以下,因此不建议采用5g及以上剂量灌注病牛子宫。     

Study on Optimizations of Oxytetracycline Residues Detection Method in Milk and its Clinical Elimination

Here an improved HPLC-PAD method was developed and demonstrated suitable for studying the clinical residue elimination of oxytetracycline in milk from postpartum cows with uterine diseases after intrauterine treatment with oxytetracycline.In this study, 0.1 mol/L Na₂EDTA-Mcllvaine buffer solution was used to extract oxytetracycline from milk, n-hexane for degreasing, and a 3 CC Oasis HLB solid-phase extraction column for purification and concentration.A reversed phase chromatographic column Symmetry Shield RP C18 (250 mm×4.6 mm, 5 μm) with acetonitrile and 0.048% phosphoric acid solution (pH 2.5) as mobile phase by gradient eluting was applied to as the chromatographic separation condition.The results showed that the retention time of oxytetracycline was 6.5 min with a symmetrical and sharp peak, which was well separated from the impurity in the milk sample.Oxytetracycline standard solutions within the concentrations ranging from 5 to 2 000 μg/kg, had a good linearity between peak areas and the concentrations, R²=0.9999.The recoveries of oxytetracycline at three levels of 10, 20, 100 μg/kg were 87.9%, 90.5% and 87.8%, respectively, with the coefficient of variation ranged from 2.2% to 5.8% in intra-day and 4.0% to 5.1% in inter-day.The LOD was 5 μg/kg and the LOQ was 10 μg/kg.All of those parameters suggested that the optimized method was suitable for the study on the clinical residue elimination of oxytetracycline.29 postpartum cows with uterus disease were randomly divided into four different groups in terms of dosage, 2, 3, 4 and 5 g, and treated with oxytetracycline by intrauterine infusion administration, and the residues of oxytetracycline in milk were detected to study its clinical residue elimination.The results showed the oxytetracycline in milk fell to the MRL during 72 h after treatment at 4 g and below dose group.However, in 5 g dose group, residue levels of oxytetracycline in milk were above the MRL at 72 h after treatment.Therefore, 5 g and the higher were not recommended for intrauterine infusion administration.     

Inhibition of Babesia divergens in cattle by oxytetracycline

The effects of continuous oxytetracycline administration on the development of parasitaemia of Babesia divergens during both natural and artificial infections were studied. During natural exposure on grazing heavily infested with Ixodes ricinus, seven out of 42 cattle with no previous exposure to tick-borne diseases were injected every four days with a long acting preparation of oxytetracycline at a dose rate of 20 mg/kg. During the six week grazing period 21 untreated cattle developed a patent parasitaemia of B divergens and all became seropositive by the fluorescent antibody test. In contrast, no parasites were observed in treated cattle and antibody titres remained low. Artificial infections were studied with different dose levels of oxytetracycline and their effects on antibody stimulation noted. First, four groups of cows were infected with 10(8) erythrocytes infected with B divergens, three groups being injected every four days with the long acting oxytetracycline formulation at dose levels of 20, 10 and 5 mg/kg, respectively. The highest level completely inhibited parasite replication and antibody formation; the same was observed in one animal dosed at 10 mg/kg but the remainder, plus those treated at 5 mg/kg, developed both low parasitaemia and high antibody titres. The untreated cows developed severe babesiosis. A further untreated control group was added and three weeks after cessation of oxytetracycline treatment all were infected with 10(9) erythrocytes infected with a homologous isolate of B divergens. The controls, plus those in which the previous infection had been completely inhibited, developed severe clinical babesiosis but the remainder were refractory to parasite development.     

Influence of induced hypermagnesemia and hypocalcemia on neuromuscular blocking property of oxytetracycline in the horse.

The neurally evoked contractile response of the upper lip muscles of horses anesthetized with halothane was used to evaluate the neuromuscular blocking property of oxytetracycline which was administered intravenously at total dose rate of 21 to 28 mg/kg. This dose rate did not alter the contractile response which had a mean control value (and standard error; SE) of 1.76 plus or minus 0.22 kg. Arterial blood pressure was not affected by these dose rates. Neuromuscular blocking effect of the antibiotic occurred when it was administered during partial neuromuscular blockade which had been induced by infusion of magnesium sulfate (0.12 or 0.16 g/kg). Moderate hypocalcemia induced by infusion of sodium oxalate did not enhance the neuromuscular blocking property of this antibiotic. Since the dose rates of the oxytetracycline preparation used had a small effect on calcium concentration of equine serum (smaller than 0.3 mg/dl), calcium binding does not seem to play a major role in the neuromuscular blocking effect of this antibiotic. It was concluded that the weak neuromuscular blocking effect of oxytetracycline is not a significant etiologic factor in the acute type of adverse reaction to this antibiotic that is occasionally encountered in horses.     

Persistence of transferable drug resistance in the lactose-fermenting enteric flora of swine following antimicrobial feeding.

Six groups of swine (85 animals) were fed a combination of antimicrobial drugs (sulfamethazine 100 g/ton, chlortetracycline 100 g/ton and penicillin 50 g/ton). After two weeks the antimicronial drugs were removed from the diet of two groups (28 animals). These swine were compared to four groups fed the medicated diet to determine the effect of duration of treatment and degree of animal isolation on the persistence of resistance in lactose-fermenting enteric organisms. The degree of resistance to penicillin, oxytetracycline, dihydrostreptomycin and neomycin as determined by minimum inhibitory concentrations and the incidence of resistant organisms were examined during and after antibiotic feedings. Ninety-two percent or greater of all isolates tested during and after treatment had minimum inhibitory concentrations for oxytetracycline of greater than 100 mug/ml. Thirty-two weeks after cessation of dietary antibiotic, resistance to oxytetracycline and dihydrostreptomycin remained at 100% and 89% respectively. Variation in degree of contact between swine receiving medicated feed and those receiving nonmedicated feed was not sufficient to reduce the incidence of resistance to oxytetracycline or dihydrostreptomycin in all animals. Factors influencing persistence of resistant enteric organisms are discussed. Addition of the antimicrobials to the ration resulted in significantly greater weight gains for treated animals than for the controls but did not alter feed conversion.     

三种有机溶媒制备土霉素注射液的稳定性试验

采用甘油甲缩醛、二甲基乙酰胺、聚乙烯吡咯烷酮K30三种有机溶媒为主,经特殊制备工艺制成长效土霉素注射液样品,在前期获得满意的刺激性试验与临床治疗效果基础上,进行了为期两年的常温条件下制剂含量、外观色泽、澄明度、pH值、鉴别反应等质量指标试验观察,为药品的生产制造提供理论依据。结果表明:不同有机溶媒配比样品的稳定性均好,符合进口兽药质量标准要求,但以甘油甲缩醛、二甲基乙酰胺和注射用水溶媒联合使用,制剂成本最低。     

Efficacy of various treatment regimens, using liposomal streptomycin in cows with brucellosis

Thirty cows naturally infected with Brucella abortus were treated by various routes, using free or liposomal streptomycin or a combination of liposomal streptomycin and a long-acting oxytetracycline preparation. Of 21 cows treated with liposomal streptomycin alone, 3 (14%) were culture negative and 3 had 10 or fewer bacterial colonies isolated from tissues obtained at necropsy. Thirteen (62%) cows continued to shed organisms in udder secretions and were considered treatment failures. Of 9 cows that were given a combination of liposomal streptomycin and long-acting oxytetracycline, 5 (56%) were cured, 3 had 10 or fewer colonies on culture plates of tissue after necropsy and only 1 continued to shed B abortus in udder secretions after treatment. Eleven cows were given streptomycin liposomes by intramammary infusion with or without IM administration of long-acting oxytetracycline. The most effective regimen consisted of 2 intramammary infusions of streptomycin liposomes and 2 doses of oxytetracycline administered IM. Of 5 cows treated thusly, 2 were cured and all others had fewer than 10 B abortus colonies isolated from tissues obtained at necropsy.