Disposition kinetics of tylosin administered intravenously and intramuscularly in desert sheep and Nubian goats

The pharmacokinetic behaviour of tylosin was compared in five Desert sheep and five Nubian goats. The animals were given a single dose of 20% tylosin (15 mg/kg), either intravenously (i.v.) or intramuscularly (i.m.). Following i.v. administration, the volumes of distribution and the elimination half-life times were similar in both species, whereas in goats a greater volume of the central compartment and faster clearance were observed. For the i.m. route, similar pharmacokinetics were observed in both species. The bioavailability (f) of the drug in goats (0.84 +/- 0.11) was not significantly higher than that in sheep (0.73 +/- 0.08). The present study has shown that, despite the significant differences in some of the drug pharmacokinetic parameters between sheep and goats for the i.v. route, identical intravenous and intramuscular dosage regimens of tylosin may be recommended for the two species.     

乙酰异戊酰泰乐菌素的合成

以泰乐菌素为原料,经过乙酰化、异戊酰化、醇解反应,合成乙酰异戊酰泰乐菌素(Acetylisovaleryltylosin),反应总收率为21%,含量为98%(HPLC,面积归一法).     

磷酸泰乐菌素脂质体的制备及体外释放动力学研究

为延长磷酸泰乐菌素在体内的作用时间,通过比较采用硫酸铵梯度法制备其脂质体制剂。以包封率为指标,分别考察磷脂与胆固醇之比、药脂比、硫酸铵浓度、孵化温度和孵化时间对包封率的影响,并在此基础上进行正交试验筛选最优处方。同时,对所得脂质体的形态、粒径及分布、包封率及体外释放动力学进行研究。结果显示,正交试验优化得到的最佳处方工艺如下,磷脂与胆固醇质量比为4∶1,药脂比为1∶10,硫酸铵浓度为300 mmol/L,体系pH值为7.0,孵化温度为50℃,孵化时间为20 m in。电镜下观察脂质体呈球形或类球形,分布均匀,平均粒径为6.526μm,且大部分在1μm~12μm之间,包封率为58.32%,体外释药符合W eibull方程(r=0.976 4)。研究证实硫酸铵梯度法制备磷酸泰乐菌素脂质体方法可行,包封率高,稳定性好,体外释药具有一定的缓释效应。     

一例泰乐菌素生产中配料错误的补救

在泰乐菌素生产中,配料人员误将氢氧化钙当作轻质碳酸钙投入培养基中,致使培养基pH值升至9.23、散发恶臭、异味,营养成份也有所破坏,通过消毒前用强酸调节pH、移种后加强工艺控制,使该罐批基本达到正常发酵,取得了较高的生物效价和A组份相对含量。     

HPLC法在监控替米考星合成中的应用

采用高效液相色谱法对替米考星合成生产过程进行监控,对泰乐菌素原料A、B两种组分在合成替米考星反应过程中的变化进行了探讨,该项研究成功解决了替米考星合成过程中收率降低的问题。     

Increased bioavailability of tylosin phosphate as in-feed medication formulated for long-action pellets in broiler chickens

Circadian variation of serum concentrations of tylosin in broiler chickens after in-feed medication prompted a comparison study of the serum profiles of this drug after in-feed medication with standard tylosin phosphate (Tprf reference formulation group), and after in-feed medication with a sustained-release pellet formulation (Tpsr group), based on Patent No.MX/a/2012/013222 and PCT/MX2013/000137, in broiler chickens. Six hundred 4-week-old Ross broiler chickens were in-feed medicated with tylosin phosphate at an approximate dose of 25.2 mg/kg/d, based on daily feed consumption values and a final concentration of tylosin in feed of 200 mg/kg of feed. Approximately 2 to 3 mL of blood were obtained per 5 chickens every 2 h, avoiding the sampling of a bird more than once and during 72 h after making medicated feed available for the first time. Serum concentrations of tylosin were determined by HPLC. Gaussian multi-peak regressions were then fitted to serum concentration vs. time profiles. Day by d areas under the serum concentration vs. time profiles (AUC_0–24), as well as overall AUC_0–72, were statistically higher for the Tpsr group (P < 0.001). Also, maximum serum concentrations obtained and relative bioavailability for the Tpsr formulation were statistically higher (382.8%) as compared to the Tprf group (P < 0.01). Considering the referred improved values of AUC observed in the Tpsr formulation, as well as the fact that tylosin is a time-dependent antibacterial drug, better clinical responses are postulated with this pharmaceutical preparation intended for chickens. Tissue deposition studies for this new formulation of tylosin are required.     

利用响应面法优化泰乐菌素发酵培养基

采用响应面法对弗氏链霉菌发酵产泰乐菌素的培养基进行优化。首先用Plackett-Burman法对11个培养基因素进行筛选,结果发现,三个对泰乐菌素效价影响较大的重要因素分别为鱼粉、黄豆饼粉、油,然后进行最陡爬坡实验逼近最佳响应面区域,最后通过Box-Behnken设计,利用Design-Expert V8．0．5软件进行回归分析,得到各因素的最佳浓度,并验证响应面预测值与实测值的一致性。结果表明,在鱼粉10．64 g/L、黄豆饼粉14．69 g/L、油58 g/L的最优培养基下,泰乐菌素的产量可达14915 U/mL,实测值与响应面预测值拟合良好,说明通过响应面实验设计对泰乐菌素发酵培养基的优化是有效的,比优化前提高了15％。     

抗生素对组培条件下植物技原体作用的初探

采用3种国产医用抗生素（盐酸－四环素、交沙霉素、枝原清）以不同浓度处理组培条件下的泡桐丛核病组培苗和甘薯丛枝病组培苗。结果表明：15μg／ml盐酸－四环素对泡桐丛枝病组培苗连续作用60d，病株外观基本恢复正常，再连续作用60d，症状无复发，经电镜观察未发现植物枝原体的存在。2．5μg／ml盐酸－四环素对甘薯丛枝病效果最好，对处理60d的甘薯组培前做电镜观察，未发现植物枝原体的存在。交沙霉素和技原清均对泡桐丛枝病有一定效果，但交沙霉素对泡桐丛枝病组培苗，枝原清对泡桐丛技病组培苗和甘薯丛枝病组培苗均有毒害作用。     

桔梗石油醚提取物对酒石酸泰乐菌素在小鼠体内的药代动力学及组织分布的影响

以酒石酸泰乐菌素为靶标药物,探究药物中加入桔梗石油醚提取物对小鼠血浆中的药代动力学特征及组织分布的影响。采用高效液相色谱法测定不同时间点小鼠血浆及心脏、肝、肺、肾中酒石酸泰乐菌素的浓度,运用PKsolver程序及SPSS19.0统计软件处理数据,用非房室模型分析药代动力学参数。结果表明:酒石酸泰乐菌素的血–药时曲线呈现多峰;与对照组(药物未加桔梗石油醚提取物)相比,桔梗石油醚提取物组(桔梗组)消除半衰期和达峰时间均变短,达峰浓度降低;药时曲线下面积减少,而表观分布容积增加;平均滞留时间缩短,而药物清除率增大;组织分布图显示,与对照组相比,桔梗石油醚组小鼠心脏中的药物浓度明显比肺、肝、肾中药物浓度高,说明桔梗石油醚提取物改变了酒石酸泰乐菌素在小鼠体内的组织分布。综合分析,桔梗石油醚提取物对酒石酸泰乐菌素在小鼠体内的药代动力学特征有较大影响,表现为加快了药物的吸收速度,但减轻了吸收程度;使药物在体内分布更广泛,却加快了其在体内的消除速度。     

泰乐菌素的超声波降解效果及机制

为研究超声波对水体中大环内酯类抗生素的去除效果,以典型的专用兽药抗生素泰乐菌素(TYL)为研究对象,考察初始浓度、溶液pH值、超声波功率、超声波处理时间对超声波降解效果的影响。在此基础上进一步考察H_2O_2和蒙脱石分别与超声波联合降解TYL的效果,并对TYL的超声波降解机制进行了探讨。结果表明:超声波对TYL有一定的降解效果,在初始浓度10 mg·L~(-1)、pH值11、超声波功率280 W、超声波处理时间90 min的条件下,TYL的降解率为72%。自由基清除剂正丁醇的添加显著抑制了TYL的降解,而且不同超声波功率、超声波处理时间和不同初始浓度及pH值条件下羟基自由基的浓度变化与TYL降解率呈正相关,表明TYL超声波的降解机制可能主要是羟基自由基的氧化。溶液中添加H_2O_2或蒙脱石均对TYL超声波降解产生协同作用,TYL的去除率可分别提高至80.9%和93.9%。H_2O_2可直接氧化TYL、促进·OH生成;蒙脱石的吸附性能及其中少量的铁均可影响溶液中·OH含量。H_2O_2或蒙脱石联合超声波降解TYL的降解效果和降解机制与添加物质的性质密切相关,不能简单归因于羟基自由基的氧化。研究表明,合适的超声波处理方法对大环内酯类抗生素有很好的去除效果,可以考虑将超声波法用于含抗生素废水处理的工艺中。