复方长效土霉素注射液的工艺研究及疗效试验

改变原长效土霉素注射液的处方和溶解条件，加入适量的增效剂、抗原虫药、解热镇痛药和核心料，并调整了常规的生产工艺。结果表明，改进后的复方长效土霉素注射液，其稳定性能与进口长效土霉素注射液相近，疗效上则好于进口长效土霉素注射液。本产品经100℃、30min流通蒸汽灭菌，未见颜色变化，经微生物效价测得其相对含量与灭菌前差异不显著（P〉0．05）。最终结果表明，本产品的小试工艺稳定，但进行规模化生产还必须进一步对工艺进行研究。     

长效土霉素注射液的研究进展

综述了土霉素注射液在处方、局部刺激和局部残留、药代动力学、生物药剂学和在动物体内残留等方面的研究进展。     

影响长效土霉素注射液稳定性的几个因素

本试验适当改变长效土霉素注射液的处方和溶解条件,加入适当稳定剂,调整常规的生产工艺.结果表明,改进后的长效土霉素注射液的稳定性大大提高,颜色在标准范围之内,经105℃流通蒸气灭菌60 min,未见颜色变化,经微生物效价测定,含量为100.5%,可信限6.3%.说明采用该生产工艺能提高长效土霉素注射液的稳定性.     

分光光度法测定长效土霉素注射液含量

采用分光光度法测定长效土霉素注射液含量，结果表明在550～2000u／ml的浓度范围内，吸收度与浓度呈良好线性关系，其平均回收率100.33％，RSD=0．97％，并与生物效价法进行对照，结果基本一致。本法具有简便、快速、准确、重复性好等优点，可用于土霉素注射液制剂含量的快速测定。     

长效土霉素注射液治疗猪喘气病的效果观察

目的：探讨长效土霉素注射液对于猪喘气病的治疗效果;方法：选取60头50日龄的断奶幼猪作为研究对象,将其随机分成3组,给予不同的治疗方法,对比其治疗的效果;结果：土霉素注射液在治疗猪喘气疾病上的效果优于恩诺沙星注射液的效果;结论：给予30％长效土霉素注射液,剂量控制在0.1mL/kg进行肌注,一般只需肌注一次即可,重症病猪3d后再注射一次,能取得更好的治疗效果.     

长效土霉素注射液在猪体内的生物等效性研究

研究自制长效土霉素注射液与进口长效土霉素注射液(得米先注射液)在猪体内单剂量注射的药代动力学和生物等效性,为临床应用提供参考和依据.采用双处理、双周期随即交叉试验设计.12头健康猪分为两组,分别先后单剂量肌肉注射自制长效土霉素注射液与得米先注射液,用高效液相色谱法测定血浆中土霉素的浓度,3P97软件计算药代动力学参数.自制长效土霉素注射液与参比制剂的主要药动学参数如下:AUC分别为(145.41 ±3.59)、(159.28 ±4.47) μg·mL-1·h,T1/2β分别为(84.776±2.21)、(72.740±1.95)h,Cmax分别为(3.519±1.66)、(3.924±1.34)μg/mL,Tmax分别为(1.848±0.54)、(1.760±0.41)h.采用3P97药代动力学软件分析比较AUC和Cmx90％置信区间,自制长效土霉素注射液的AUC、Cmax的90％置信区间分别为94.7％～105.2％、85.0％ ～114.6％,分别落在参比制剂的80％～125％、70％ ～143％范围内,两组参数差异不显著(P＞0.05),结果表明二者具有生物等效性.     

长效土霉素注射液对猪喘气病临床治疗试验

[目的]验证长效土霉素注射液对猪喘气病的治疗效果。[方法]用30%长效土霉素注射液(0.1mL/kg)注射治疗猪喘气病,并设恩诺沙星注射液组(0.1mL/kg)、阳性感染组及阴性健康组为对照组,从临床症状、猪肺病变程度以及平均增重来进行对比试验。[结果]30%长效土霉素注射液组和恩诺沙星注射液组对猪喘气病均有效,同阳性对照组比较差异显著,且30%长效土霉素注射液组治疗效果优于恩诺沙星注射液组。[结论]综合增重、肺病变程度等指标,认为长效土霉素注射液组对猪喘气病较适合,并有较好的治疗效果。推荐剂量:每千克体重0.1mL,只注射1次即可,病情严重者3d后再注射1针。     

两种长效土霉素注射液在猪体内的生物等效性分析

研究分析长效土霉素注射液作用于猪体内的生物等效性,为临床的进一步研究提供参考依据。方法:选取24头猪,将其随机分为两组,对照组1和对照组2,对照组1注射30%长效土霉素注射液;对照组2则注射20%长效土霉素注射液。采用高效液相色谱法对猪体内的血浆土霉素浓度进行测定,分析其生物等效性。结果:对照组1和对照组2的药动学参数为:药物吸收半衰期为(0.088±0.014)h和(0.140±0.076)h;消除半衰期为(52.489±21.885)h和(36.481±21.568)h;峰浓度为(4.986±1.786)μg/ml和(5.016±0.948)μg/ml;达峰时间为(0.609±0.110)h和(0.823±0.372)h;药时曲线下面积为(112.482±18.564)mg/L.h和(109.877±19.946)mg/L.h;以20%长效土霉素注射液作为对照,30%长效土霉素注射液相对生物利用度为(105.465±26.103)%。结论:研究结果表明,两种不同浓度的长效土霉素注射液的药动学参数不具有显著差异,由此看来两种药物具有生物等效性。     

长效土霉素注射液对猪喘气病临床治疗分析

目的分析探讨长效土霉素注射液对猪喘气病临床治疗效果。方法选择某养猪场经诊断被确诊为猪喘气病的68头猪,选择时间为2018年7月-2019年7月,根据治疗方法将其分为常规组和研究组,常规组行恩诺沙星注射液治疗,研究组行长效土霉素注射液治疗,比较两组体重增长情况及治疗效果。结果研究组猪的最终体重(26.95±2.41)、平均体重(11.83±2.07)较常规组更重,治疗有效率(94.12%)较常规组(76.47%)更高,差异性显著(P<0.05)。结论将长效土霉素注射液应用于猪喘气病的治疗中,能显著提升猪的重量及治疗有效率,有效阻断传染源头,让疗效更加持久,从而避免疫情的出现,促进养猪场秩序的恢复。     

注射用盐酸土霉素的细菌内毒素检查

参照<中国兽药典>二○○○年版一部附录细菌内毒素检查法,研究了注射用盐酸土霉素对细菌内毒素检测的干扰情况,确定0.312 5 mg/mL浓度的供试品溶液对检测无干扰作用,建立了注射用盐酸土霉素的细菌内毒素限量检查方法.     

Comparison of the serum pharmacokinetics of a long acting and a conventional oxytetracycline injection

A crossover study was carried out in cattle to determine the serum pharmacokinetics of a standard dose (20 mg/kg bodyweight) of oxytetracycline given either as a conventional injectable formulation or as a long acting formulation. For reference purposes, an intravenous treatment (also given at 20 mg/kg) was included in the trial protocol. A comparison of the two treatment regimes showed that the long acting formulation gave a significantly lower peak oxytetracycline serum concentration, with a significant extension of drug serum concentration. The long acting formulation also showed a longer serum half life and a significantly greater area under the curve value, calculated from 36 hours onwards, together with serum oxytetracycline concentrations which exceeded 0.5 microgram/ml for 86.8 as opposed to 51.5 hours for the conventional formulation. It is concluded that the use of the long acting formulation in cattle leads to a more sustained serum oxytetracycline concentration than does the same dose of conventional formulation.     

Residues from long-acting antimicrobial preparations in injection sites in cattle

Objective To investigate tissue residues of two longacting oxytetracycline (OTC) preparations in cattle.
Design A randomised drug residue trial.  

Animals

Two hundred and forty beef cattle in 24 groups of ten.
Procedure Two blind-coded 200 mg/mL OTC preparations were used in five treatment regimens of various combinations of injection sites (from one to five) and administrations (one or two). Five cattle from each group were slaughtered at 21, 30 and 60 days after injection and the injection site, urine, kidney and diaphragm muscle analysed for residues.
Results The OTC concentration exceeded the maximum residue limit in kidney in animals slaughtered 21 days after treatment, which is the prescribed withholding period. Concentration at the injection site was much greater than the maximum residue limit 30 days post-treatment, but not 45 days post-treatment. The residue was smaller when OTC had been injected in multiple sites. There was no difference between the two OTC preparations.
Conclusion A review of the maximum injection volume, site of injection and the withholding period is needed for long-acting OTC formulations.     

乳酸恩诺沙星对小鼠的急性毒性试

采用新药乳酸恩诺沙星测定了其对实验小鼠的半数致死量（LD50）, 为其可溶性粉开展药效试验提供依据。按照农业部关于一般毒性试验及临床试验规范进行试验。结果表明, 乳酸恩诺沙星对小白鼠灌胃染毒及腹腔注射染毒的 LD50分别为3579 mg/kg,和571.3 mg/kg,其95％可信限分别为3011~4255 mg/kg和498.3~655.1 mg/kg。研究提示, 乳酸恩诺沙星属低毒物质,其可溶性粉能用于开展药效试验。     

金丝桃素浸膏的急性毒性试验

用小白鼠和5日龄雏鸡进行急性毒性试验,小白鼠口服金丝桃素浸膏23.6 g/kg体重时,仅死亡1只,其他各组小鼠全部存活;雏鸡口服金丝桃素浸膏的LD50为(32.42±0.031 2)g/kg体重,表明金丝桃素浸膏的毒性非常低.     

草甘膦与氰氟草酯对隆线溞的急性毒性研究

在水生食物链中,水溞是连结植物、微生物和动物的关键成员。草甘膦与氰氟草酯被广泛用于防除水生和稻田杂草,研究它们对水溞的毒性,有益于人们关注使用除草剂对水体生态系统的影响。试验以标准水体监测生物——隆线溞(Daphnia carinata)单克隆为材料,研究草甘膦和氰氟草酯对其泳动能力、存活率和趋光性的影响。结果表明,两种除草剂对隆线溞均有明显毒性,草甘膦对隆线溞24, 48和96 h的半致死浓度(LC₅₀)分别为66.58, 29.60和12.33 mg/L,为田间常规用药量的0.15%~0.81%;氰氟草酯对隆线溞24, 48和96 h的LC₅₀依次是63.15, 51.91和34.41 mg/L,为田间常规用药量的17.21%~31.58%。两种除草剂显著影响隆线溞的泳动能力和趋光指数。隆线溞接触草甘膦和氰氟草酯3 h后,导致其趋光指数显著改变的浓度分别是4.59和14.20 mg/L,分别为常规用药量的0.06%和7.10%。因此,草甘膦和氰氟草酯对水溞的毒性大,对水生食物链的影响不可忽视。利用水溞趋光性可快速、灵敏地监测除草剂使用后的水体生物毒性。     

硫酸头孢喹肟脂质体的毒理学试验及安全性评价

采用急性毒性试验、局部刺激性试验和亚慢性毒性试验对硫酸头孢喹肟脂质体安全性进行评价,以期为临床用药提供参考。小鼠腹腔注射硫酸头孢喹肟脂质体半数致死量（LD₅₀）为639.73 mg/kg,95%可信限为573.06~714.17 mg/kg;该制剂对家兔股四头肌未见明显刺激作用;各给药剂量组家兔的体重、血液学指标、生化指标与对照组比较均无显著差异（P>0.05）;对肝脏和肾脏病理学观察表明,正常治疗剂量和中剂量组肝脏和肾脏组织结构清晰,但高剂量组出现肝细胞排列紊乱,肝血窦间出血,肾小球、肾间质有散在出血。以上结果表明硫酸头孢喹肟脂质体安全可靠,可应用于兽医临床。     

Toxicology Test and Safety Evaluation of Cefquinome Sulfate Liposomes

The purpose of this study was to evaluate the safety of the cefquinome sulfate liposomes by using the acute toxicity test, local irritation test and chronic toxicity test. The results showed that the LD₅₀ of cefquinome sulfate liposomes was 639.73 mg/kg after intramuscular injection of its suspension and 95% confidence interval was 573.06 to 714.17 mg/kg. There was no significant stimulation to muscle. Subchronic toxicity test showed that the weight, haematological indexes and biochemical criterion of rabbits in variety dose had no significant difference compared with normal group (P>0.05). There was no visible pathological changes on the liver,kidney histology. According to pathological observation, the structure of liver and kidney were clear in treated and middle dose groups,but there existed disorganized hepatic cell cord in the liver and hemorrhag between glomerulopathy,tubulointerstitial and hepatic sinusoids in high dose group. All results proved that the cefquinome sulfate liposomes was safe and reliable based on the animal experiments.