Reverse micelle-based microencapsulation of oxytetracycline hydrochloride into poly-d,l-lactide-co-glycolide microspheres

The objectives of this study were to solubilize oxytetracycline hydrochloride (HCl) in reverse micelles to prepare poly-d,l-lactide-co-glycolide (PLGA) microspheres and to explore parameters affecting its encapsulation efficiency. Oxytetracycline HCl was dissolved in the reverse micelles consisting of cetyltrimethylammonium bromide, water, and ethyl formate. A PLGA polymer was then dissolved in the reverse micellar solution, and a modified solvent quenching procedure was carried out to prepare PLGA microspheres. Encapsulation efficiencies of oxytetracycline HCl ranged from 2.3 ± 0.2 to 24.9 ± 4.6%, depending on experimental conditions. Important parameters affecting its encapsulation efficiency included the amounts of water used to prepare the reverse micelles and PLGA polymer. With regard to microsphere morphology, the reverse micellar process produced the microspheres with smooth and pore-free surfaces. In particular, their internal matrices did not possess hollow cavities that were frequently observed when a typical double emulsion technique was used to make microspheres. In summary, it was possible to encapsulate oxytetracycline HCl into PLGA microspheres via the ethyl formate-based reverse micellar technique. We also anticipate that the use of ethyl formate could avoid environmental and human toxicity issues associated with methylene chloride.     

The Effects of pH and Mixed Solvent Systems on the Solubility of Oxytetracycline

The solubility of oxytetracycline (OTC) in aqueous and mixed solvent systems was studied. The effects of pH and cosolvent composition on the solubility and apparent dissociation constants (pK′_a) of OTC were determined by a solubility method. The pK′_a values of OTC in each mixed solvent system were estimated and used to generate expressions for predicting drug solubility in each cosolvent as a function of pH. Cosolvent systems of PEG 400, propylene glycol, glycerin, and 2-pyrrolidone were studied in the pH range of 2.5–9. Solubility results showed increased solubility with increased cosolvent concentration, especially in 2-pyrrolidone solvent systems. These results also showed that cosolvents enhanced drug solubility through either their effects on polarity of the solvent medium or complex formation with OTC. Aqueous and mixed solvent systems at lower pH values resulted in higher OTC solubilization because the drug existed primarily in its cationic form. A mass balance equation including all ionic species of OTC allowed for estimation of the intrinsic solubilities and pK′_a values in each solvent system. pK′_a values and intrinsic solubility of the OTC zwitterion increased with increasing cosolvent content. These parameters allowed prediction of drug solubility within the pH range and cosolvent concentrations used in this study.     

土霉素产生菌株相对湿度的考察

本文提出以相对湿度为考察指标，对斜面孢子进行质量考察，同时对实验结果进行讨论，选出最适宜菌种生长的最佳相对湿度，提高菌种质量。     

The oxidative stress response of oxytetracycline in the ciliate Pseudocohnilembus persalinus

Oxytetracycline (OTC) is commonly employed in fish farms to prevent bacterial infections in China, and because of their widely and intensive use, the potential harmful effects on organisms in aquatic environment are of great concern. Ciliates play an important role in aquatic food webs as secondary producers, and Pseudocohnilembus persalinus, is one kind of them which are easily found in fish farms, surviving in polluted water. Therefore, using P. persalinus as experimental models, this study investigated the effects of oxytetracycline (OTC) on the growth, antioxidant system and morphological damage in pollution-resistant ciliates species. Our results showed that the 96-h EC₅₀ values for OTC of P. persalinus was 21.38 mg L⁻¹. The increased level of SOD and GSH during 96 h OTC stress was related to an adaptive response under oxidative stress induced in ciliates. Additionally, sod1, sod2 and sod3 exhibited a significant increased expression level compared to control group at 24 h treatment, indicating a promoting of dense system in ciliates at this exposure time. However, only sod1 and sod2 showed raised expression level at 48 h stress, showing the different sensitive of gene isoforms to some extent. With OTC treatment, damage of regular wrinkles, shrunk, twisted on the cell surface, even forming cyst of scuticociliatid ciliate cells were firstly observed by SEM (scanning electron microscope) in this study. Overall, physiological, molecular and morphological information on the toxicological studies of ciliates and more information on possibility of ciliates as indicators of contamination were provided in this study.     

Immunomodulating Effects of Black Seed and Oxytetracycline in Pigeons

Chronic administration of oxytetracycline (OXT) (incorporated at a level of 0.05 g per kg of feed for 50 days) to pigeons, significantly decreased total leukocyte and lymphocyte counts, increased heterophil:lymphocyte ratio and lysosomal enzyme activity, and decreased reticuloendothelial system function compared with controls. Coadministration of black seed (BS) at a level of 2.5% with OXT completely blocked the effects elicited by OXT and produced immunostimulant effects in pigeons. The addition of BS to feed of pigeons could act as an immunoprotective agent when chronic administration of antibiotics are considered.     

Construction and characterization of potentiometric sensor for the determination of oxytetracycline hydrochloride

The construction and performance of plastic membrane (PME) oxytetracycline hydrochloride (OTC)-selective electrodes, based on three types of ion-pairs, OTC-tetraphenylborate (TPB), OTC-phosphotungstate (PT) and OTC-silicotungstate (SiT), as the electroactive substance in a plasticized PVC membrane with dibutylphthalate (DBP), were described. Furthermore, internal solid contact sensors (ISCS) OTC-selective sensors, based on a conducting polypyrrole (PPy) film immobilized on a platinum or glassy carbon electrode surface casted by a plasticized PVC membrane were constructed and evaluated. A novel optimization methodology in a numerical expression, comprehensive quality index (CQI) for a sensor, was used to optimize the composition of the membrane in the preparation of PME and screen the parameter of electropolymerization in the preparation of ISCS. Several PMEs and ISCSs were fully characterized and evaluated. An ISCS (Pt/PPy/PVC (OTC-TPB)) showed an excellent Nernstian response over the linear concentration range of 4.0 x 10(-7)-5.0 x 10(-2) M with the slope of 60.6 mV per decade (at 25 degrees C). The limit of detection was 1.0 x 10(-7) M of OTC (0.03 ppm). The response time was <25 s. The sensor was successfully used for the analysis of OTC in pharmaceutical formulation by using direct potentiometry.     

固相萃取-高效液相色谱法同时测定牛奶中3种四环素类抗生素残留量

目的:为快速、简便、灵敏地检测牛奶中土霉素、四环素、金霉素残留量,建立固相萃取(SPE)-高效液相色谱(HPLC)分析法。方法:样品用M c llvaine缓冲液提取,硫酸锌-亚铁氰化钾体系沉淀蛋白质后,再经超声波提取,固相萃取,高效液相色谱法同时测定3种抗生素。固相萃取小柱为W aters Sep-Pak C18Cart,洗脱液为甲醇柠檬酸溶液;色谱柱为Krom asil C18柱(5μm,150 mm×4.6 mm),流动相为乙腈:0.01 mol/L柠檬酸溶液=25:75(v/v,pH=2.5),流速0.4~0.8 m l/m in,检测波长为355 nm。结果:本方法的最低检出浓度分别为:土霉素(0.009μg/m l)、四环素(0.007μg/m l)、金霉素(0.034μg/m l),标准曲线线性良好,其回归方程及相关系数r分别为:土霉素:Y=490379X-13947,r=0.9998;四环素:Y=454806X-17029,r=0.9995;金霉素:Y=156256X-20479,r=0.9996,回收率在86.5%~95.0%之间,相对标准偏差(n=6)小于3%。结论:该方法简单、快速、灵敏度高,适用于牛奶中四环素类抗生素残留量检测。     

LC/MS/MS法测定猪肝中四环素类抗生素及盐酸克伦特罗药物残留

目的:建立高效液相色谱-串联质谱法同时检测猪肝样品中四环素类及克伦特罗药物残留。方法:样品经乙酸铵缓冲液提取,Oasis HLB固相萃取小柱净化后,用Atlantis C18柱分离,以乙腈水(含0.4%甲酸)作为流动相,采用电喷雾离子源(ESI),阳离子模式,多反应监测(MRM)方式检测,内标法定量。结果:在本实验条件下,几种药物在0~5.0 mg/L范围内线性良好,最低检出限0.02~0.56μg/kg,变异系数2.34%~7.63%,样品平均加标回收率在84.4%~101.7%之间。结论:该方法能同时对样品中四环素类及盐酸克伦特罗药物残留进行定性及定量分析,方法精密度较好、准确度较高,结果较满意。     

HPLC测定盐酸土霉素的含量和有关物质

目的 :建立HPLC测定盐酸土霉素有关物质和含量。方法 :采用ODS柱 ( 10 μm ,4 6mm× 2 5 0mm) ,以 0 1mo1·L-1草酸铵溶液 二甲基甲酰胺 0 2mo1·L-1磷酸氢二铵溶液 ( 6 0∶30∶10 ) (用氨试液调pH8 3)为流动相 ,检测波长 2 70nm。结果 :盐酸土霉素在 0 1～ 1 0mg·ml-1浓度范围内 ,呈良好的线性关系 (r =0 9999) ,精密度RSD为1 2 % ,平均回收率为 99 6 % ,RSD为 0 8% (n =4)。结论 :该法简便、准确 ,适用于盐酸土霉素杂质的检测和含量的测定。     

盐酸土霉素细菌内毒素检查方法的确立

目的：考察盐酸盐霉素进行细菌内毒检查的可行性,以便控制质量使其达到出口要求。方法：抑制／增强试验及细菌内毒发值检查,结果：0．156mg.ml^-1的盐酸土霉素溶液对细菌内毒素检查无干扰,其内毒素限值符合规定,结论：盐酸土霉素可采用细菌内毒素检查法来控制其质量。