达氟沙星对试验性感染仔猪副伤寒和霉形体肺炎的药效学研究

研究了国产新兽药达氟沙星对人工感染仔猪伤寒和霉形体肺炎的疗效。每个疗效试验用仔猪105只，随机分为达氟沙星3个不同剂量组，恩诺沙星对照组，强力霉素对照组，阳性对照组和阴性对照组，每组动物15只。当感染猪出现典型症状时，达氟沙星3个剂量组分别按每千克体重2．5ml,1.25mg,0.625mg，0.625mg及恩诺沙星组按2．5mg肌肉注射，每日2次，强力霉素按每千克体重3mg肌肉注射，每日2次。结果表明：达氟沙星3个不同剂量组、恩诺沙星组、强力霉素组连续用药4d，对仔猪副伤寒的治愈率分别是100％、80％、33．3％、80％、53．3％、而感染（阳性）对照组的死亡率为66．7％；达氟沙星3个不同剂量组、恩诺沙星组、强力霉素组连续用药5d,对霉形体肺炎的治愈率分别是100％、80％、93．3％，肺部病变率分别是20％、40％、60％、20％、60％，而感染（阳性）对照组的死亡率为40％，肺部病变率为1005。     

三种兽用氟喹诺酮类药物对人工诱发鸡霍乱的疗效比较

采用试管肉汤两部类法,测得恩诺沙星、单诺沙星脑二氟沙星对鸡多杀性巴氏杆菌的最小抑菌质量浓度分别是０．０５、０．２及０．４ｍｇ／Ｌ,按５ｍｇ／ｋｇ的剂量,分别给人工诱发霍乱病鸡内服恩诺沙星、单诺沙星脏一氟沙星,每１２ｈ给药１次,连续３ｄ,这些药物对鸡霍乱的治愈率分别为９６．７％、８３．３％及８３．３％。而感染对照鸡的死亡率为１００％。     

鲫血浆中甲磺酸达氟沙星的RP-HPLC法测定

建立了测定鲫血浆中甲磺酸达氟沙星浓度的反相高效液相色谱法(RP-HPLC).采用ZORBAX SB-C18色谱柱和SB-C18的保护柱;流动相:乙腈与磷酸盐缓冲液(含10 mmol.L-1磷酸二氢钠和15 mmol.L-1四丁基溴化铵,磷酸调节pH4.0)的体积比为8∶92;流速:1.0 mL.min-1;进样量:10μL;柱温:30℃;检测波长282 nm.内标物为盐酸氧氟沙星.本研究建立的甲磺酸达氟沙星标准曲线在0.05~5.00 mg.L-1范围内呈良好的线性关系(R=0.999 9),最低检测限为0.01 mg.L-1,提取回收率均大于80%,日内及日间相对标准偏差小于11%.     

猪肉组织中氟喹诺酮类药物残留检测

随机选取本实验室内的8名化验员,分别测定猪肉组织中氟喹诺酮类药物残留量,通过对结果数据的分析,得出本实验室测定结果的准确程度。通过磷酸盐缓冲溶液提取猪肉组织中的氟喹诺酮类药物残留,经C18柱净化后,用高效液相色谱法测定含量。环丙沙星、达氟沙星、恩诺沙星和沙拉沙星的平均回收率（%）分别为：95.6、86.9、89.3和95.6,批内变异系数均≤14%,批间变异系数均≤6%。结果数据满足标准要求,证明本实验室能准确开展此项检测活动。     

Preparation and Characterization of Danofloxacin Mmesylate Liposomes

Five different methods were tested and compared to prepare danofloxacin mesylate liposomes, the ammonium sulfate gradient method with freeze-thawing steps was validated as the best one; the optimal preparation condition confirmed by orthogonal experiment was as follows： EPC-CH ratio was 3 ： 2 and 2.6% SA was added to gain the positive electricity; drug-lipoid was 2 ： 5, the concentration of ammonium sulfate was 250 mmol·L-1, water-oil ratio was 1：5, and they were incubated at 35℃ for 15 min. The prepared liposome products were ivory white semitransparent suspension, the electron microscope appearance was intact and globular or globular-like vesicles with uniformed distribution; the particle size was centralized from 3 to 7 gm, zeta-electric potential valued＋ （15.92＋1.49） mV, pH valued 6.02~0.09; HPLC method was established in quantitative analyses of danofloxacin and reverse dialysis with RP-HPLC method was validated for determination of entrapment efficiency. The entrapment efficiency results were all above 90%. They were stored at 4℃ with satisfied stability. Six months later, the appearance, characters and entrapment efficiency were almost with no change     

甲磺酸单诺沙星脂质体包封率的测定

利用反透析-反相高效液相色谱法测定甲磺酸单诺沙星脂质体包封率。结果表明,该法能使甲磺酸单诺沙星与辅料及溶剂得到良好分离,甲磺酸单诺沙星在0.01～10μg.mL-1浓度范围内线性关系良好(r=0.9997,n=3),该法准确简单,重复性好,可用于甲磺酸单诺沙星脂质体包封率的测定。     

达氟沙星在健康和鳗弧菌感染牙鲆体内的药物代谢动力学比较

牙鲆随机分为3组，单剂量静注（健康）和口灌（健康对照和鳗弧菌感染）达氟沙星，进行健康和鳗弧菌感染牙鲆比较药动学和生物利用度的研究。药物浓度用高效液相色谱法测定，数据采用MCP-KP自动化药动学分析程序进行分析。结果表明，健康牙鲆静脉注射达氟沙星(5 mg·kg^-1)后，血药经时过程符合无吸收一室开放模型。口灌给药(10 mg·kg^-1)健康及感染牙鲆的血药浓度与时间关系均符合一级吸收一室开放模型；肝脏和肾脏中药物浓度与时间关系均符合一级吸收二室开放模型。与健康牙鲆药动学参数相比较，达氟沙星在鳗弧菌感染牙鲆中的药时曲线下面积由256.07 mg·h^{-1·L-1降为209.18 mg·h-1·L-1，最大血药浓度由5.699 μg·mL-1降低为2.932 μg·mL-1，消除半衰期由27.758 h延长为46.195 h，生物利用度由71.21%降低为58.17%。}     

Toxic effects of methylmercury,arsanilic acid and danofloxacin on the differentiation of mouse embryonic stem cells into neural cells

This study was performed to assess the neurotoxic effects of methylmercury, arsanilic acid and danofloxacin by quantification of neural-specific proteins in vitro. Quantitation of the protein markers during 14 days of differentiation indicated that the mouse ESCs were completely differentiated into neural cells by Day 8. The cells were treated with non-cytotoxic concentrations of three chemicals during differentiation. Low levels of exposure to methylmercury decreased the expression of GABA_A-R and Nestin during the differentiating stage, and Nestin during the differentiated stage. In contrast, GFAP, Tuj1, and MAP2 expression was affected only by relatively high doses during both stages. Arsanilic acid affected the levels of GABA_A-R and GFAP during the differentiated stage while the changes of Nestin and Tuj1 were greater during the differentiating stage. For the neural markers (except Nestin) expressed during both stages, danofloxacin affected protein levels at lower concentrations in the differentiated stage than the differentiating stage. Acetylcholinesterase activity was inhibited by relatively low concentrations of methylmercury and arsanilic acid during the differentiating stage while this activity was inhibited only by more than 40 µM of danofloxacin in the differentiated stage. Our results provide useful information about the different toxicities of chemicals and the impact on neural development.     

单诺沙星对昆明种小白鼠的急性毒性研究

对昆明种小白鼠口服、腹腔注射、静脉注射单诺沙星的急性毒性进行了研究。按简化机率单位法测行单诺沙星对小白鼠的品服LD50为2251.84mg/kg,LD50的95％可信限为1829．28－2674．32mg/kg，LD90为4207．11mg/kg，LD10为1025．26mg/kg。腹腔注射单诺沙星的LD50为300．95mg/kg，LD50的95％可信限为267．74－325．12mg/kg，LD90为388．31mg/kg，LD10为223．26mg/kg。静脉注射单诺沙星的LD50为52．02mg/kg，LD50的95％可信限为50．43－53．57mg/kg，LD90为57．29mg/kg，LD10为47．26mg/kg。表明单诺沙星的毒性较低。     

旋光法测定甲磺酸达氟沙星的含量

采用旋光法测定甲磺酸达氟沙星的含量,结果表明,在6～14 mg/mL浓度范围内,甲磺酸达氟沙星的旋光度与浓度呈良好的线性关系(r=0.999 8).与电位滴定法相比,本法具有简单、快速、易操作等优点.