兽药中间体氟尼辛的高效液相色谱分析

为了监控兽药的质量,建立测定兽药中间体氟尼辛的高效液相色谱分析方法。适宜的分析条件为:色谱柱为250×4.6mm不锈钢柱,内装C18键合硅胶填料;流动相:v(甲醇)∶v(水,pH调至为4.0)=82∶18;流速:1.0mL/min;紫外检测器,检测波长为254nm。测定方法的标准偏差、变异系数分别为0.217、0.0022,平均回收率为100.1%。     

利用三聚氰胺尾气生产尿素的工艺技术

论述了利用三聚氰胺尾气与现有尿素生产装置的碳铵液混合,形成的甲铵液作为尿素生产的原料,实现三聚氰胺装置与尿素装置联产的工艺技术。介绍了尿素合成、中压分解吸收、低压分解吸收的工艺流程,从氨碳比、水碳比、CO2转化率以及尿素合成塔和中压冷凝器等方面论述了生产工艺的改变对尿素生产操作控制的要求。结果表明,在氨碳比、水碳比均为4.5,操作温度为190℃时,尿素合成塔CO2转化率可达到55%。     

The binding of orally dosed hydrophobic active pharmaceutical ingredients to casein micelles in milk

Casein proteins (α_S1-, α_S2-, β- and κ-casein) account for 80% of the total protein content in bovine milk and form casein micelles (average diameter = 130 nm, approximately 10¹⁵ micelles/mL). The affinity of native casein micelles with the 3 hydrophobic active pharmaceutical ingredients (API), meloxicam [351.4 g/mol; log P = 3.43; acid dissociation constant (pK_a) = 4.08], flunixin (296.2 g/mol; log P = 4.1; pK_a = 5.82), and thiabendazole (201.2 g/mol; log P = 2.92; pK_a = 4.64), was evaluated in bovine milk collected from dosed Holstein cows. Native casein micelles were separated from raw bovine milk by mild techniques such as ultracentrifugation, diafiltration, isoelectric point precipitation (pH 4.6), and size exclusion chromatography. Acetonitrile extraction of hydrophobic API was then done, followed by quantification using HPLC-UV. For the API or metabolites meloxicam, 5-hyroxy flunixin and 5-hydroxy thiabendazole, 31 ± 3.90, 31 ± 1.3, and 28 ± 0.5% of the content in milk was associated with casein micelles, respectively. Less than ～5.0% of the recovered hydrophobic API were found in the milk fat fraction, and the remaining ～65% were associated with the whey/serum fraction. A separate in vitro study showed that 66 ± 6.4% of meloxicam, 29 ± 0.58% of flunixin, 34 ± 0.21% of the metabolite 5-hyroxy flunixin, 50 ± 4.5% of thiabendazole, and 33 ± 3.8% of metabolite 5-hydroxy thiabendazole was found partitioned into casein micelles. Our study supports the hypothesis that casein micelles are native carriers for hydrophobic compounds in bovine milk.     

Assessment of veterinary drugs present in pork kidney from a Midwest US retail market

A total of 1040 pork kidneys were purchased from 4 retail stores located in a Midwestern US town and screened for antibiotics with the Charm-KIS? screening test. Six samples (0.6%) tested positive with the Charm-KIS?. Sixty-five samples from each retail location and the 18 Charm-KIS? positive or ‘caution’ samples were also subjected to ELISA to determine the presence of commonly used veterinary drugs including flunixin, ractopamine, sulfamethazine, and/or tetracycline of the 278 samples assessed by ELISA, flunixin, ractopamine, sulfamethazine, and tetracycline residues were found to be 0%, 22%, 4%, and 10% ELISA positive respectively, and had greater than limit of quantitation concentrations as measured by LC-MS/MS. All residue levels determined by LC-MS/MS were well below US tolerances, regardless of analyte. These findings suggest that veterinary drugs are being used in accordance with US regulations and that veterinary drug residues in pork do not pose a health concern to US consumers.     

In vivo absorption comparison of nanotechnology-based silybin tablets with its water-soluble derivative

In this study, the in vivo oral absorption of a nanocrystal tablet formulation of a BCS II poorly water-soluble drug was compared with that of its water-soluble salt form. Silybin is used as the model drug, and its nanosuspension was prepared by high-pressure homogenization. Effect of process and formulation parameters on properties of the nansuspensions was investigated. Dried powder of the nanosuspension was prepared by spray drying and used for preparing tablets. A pharmacokinetic study was performed in Beagle dogs to compare the absorption for tablets of silybin nanocrystals and silybin meglumine. In vivo absorption of nanocrystal silybin tablet in Beagle dogs was determined. X-ray powder diffraction results indicated that silybin existed in a crystalline state after homogenization. In vivo absorption study in rats showed that the peroral absorption of silybin was enhanced remarkably by decreasing particle size. In vivo absorption of nanocrystal silybin tablet in Beagle dogs was comparable with that of the commercially available tablet of the water-soluble salt form of silybin. In conclusion, it is possible to increase the bioavailability of poorly soluble drugs by preparing its water-soluble derivative.     

Multicomponent Reactions of β‐Ketosulfones and Formaldehyde in a Bio‐Based Binary Mixture Solvent System Composed of Meglumine and Gluconic Acid Aqueous Solution

A mixture of two bio‐based chemicals, meglumine and gluconic acid aqueous solution (GAAS, 50 wt%), was demonstrated to be a task‐specific bio‐based solvent for performing the hydroxymethylation of β‐ketosulfones with formaldehyde. The formed hydroxymethylation product could further react with a nucleophile, which allowed us to develop some one‐pot, stepwise, three‐component reactions of β‐ketosulfones and formaldehyde in this binary mixture. Particularly, a one‐pot, two‐step, sequential four‐component reaction of α‐bromo ketone, sodium benzenesulfinate, thiophenol and formaldehyde was also developed. These results not only demonstrate that it is possible to develop a new bio‐based system by mixing two or more bio‐based chemicals together, but also confer us a convenient means for controlling the selectivity of some multicomponent reactions of formaldehyde. Because GAAS and meglumine are both highly hydrophilic, the mixed solvent system could thus be recovered after extraction of organic products. In a three‐component reaction of β‐ketosulfone, paraformaldehyde and α‐methylstyrene, the GAAS/meglumine system could be reused at least four times without significant loss of activity.     

液质联用测定肉制品中氟尼辛葡甲胺前处理方法的优化

以液相色谱-四级杆串联质谱法(LC-MS/MS为检测手段,通过考察回收率大小测定肉制品中氟尼辛葡甲胺的残留量,并对其的前处理条件进行了优化,最终确定了肉制品中氟尼辛葡甲胺前处理方法:采用乙腈-乙酸乙酯(11V/V提取,PCX固相萃取小柱净化,用正己烷-乙酸乙酯(91V/V淋洗,甲醇和氨化甲醇(595V/V洗脱,再用体积浓度0.1%甲酸(含0.5 mmol/L乙酸铵)定容,待测。方法回收率为85.0%110.0%相对标准偏差(RSD6.0%。     

环磷腺苷葡胺后处理对大鼠心肌缺血再灌注损伤的保护作用

目的观察环磷腺苷葡胺（MCA）对大鼠心肌缺血再灌注损伤的保护作用。方法40只大鼠按随机数字表法分为空白对照组、缺血再灌注损伤组（I／R组）、缺血后处理组（IPO组）和MCA后处理组（MCA组）,每组10只。空白对照组仅行左冠状动脉左前降支套线而不阻断150min,I／R组阻断30min、再灌注120min,IPO组在再灌注初短暂缺血10S,再灌注10S、反复6次、处理后同I／R组,MCA组在再灌注前10min经静脉给予环磷腺苷葡胺注射液5mg·kg-1,其他处理同I／R组。再灌注120min后,测各组血清SOD活性及血清MDA含量、心肌ATP酶活性和心肌细胞凋亡指数（AI）,电镜下观察细胞超微结构变化。结果与I／R组比,IPO组和MCA组血清SOD活性增高,血清MDA含量降低,ATP酶活性增高,AI减少显著,细胞结构损伤减轻。结论MCA对心肌缺血再灌注损伤具有保护作用,其机制可能与改善能量代谢障碍有关。     

Treatment of acute puerperal metritis with flunixin meglumine in addition to antibiotic treatment

The objective of this field trial was to evaluate effects of a single administration of 2.2 mg/kg of body weight (BW) of flunixin meglumine (FM) in addition to a systemic antibiotic treatment in cows with acute puerperal metritis (APM). Outcome variables tested were proportion of cows with a fever, prevalence of chronic endometritis 18 to 22 and 32 to 35 d in milk (DIM), and reproductive performance measures in the current lactation. In addition, serum concentrations of haptoglobin and fibrinogen were analyzed. Daily milk yield within 6 d after the first treatment was recorded. Cows were examined 4 to 5 DIM by rectal palpation and vaginoscopy, and rectal temperature was measured. Fetid vulvar discharge and a body temperature ≥39.5°C were signs of APM. Cows with APM were treated in the reference group with 1.0 mg/kg of BW of ceftiofur on 3 to 5 consecutive days (CEF, n = 119). In the study group, cows received the same antibiotic treatment as in CEF and 2.2 mg/kg of BW of FM on treatment d 1 (CEF + FM, n = 119). Blood samples were collected 4, 6, and 10 DIM and analyzed for concentrations of haptoglobin and fibrinogen. A group of cows without APM remained untreated and served as controls (n = 9). There were no significant differences between CEF and CEF + FM in the proportion of cows with fever 1 d after the first treatment (33.6 vs. 46.2%), milk yield per milking 10 DIM (7.5 ± 0.3 vs. 7.6 ± 0.3 kg in primiparous, 9.6 ± 0.4 vs. 10.6 ± 0.4 kg in multiparous cows), prevalence of chronic endometritis 32 to 35 DIM (64.3 vs. 52.2%), and in reproductive performance (31.5 vs. 34.3% conception to first AI, 58.0 vs. 54.6% pregnancy rate, 107.8 ± 36.9 vs. 101.6 ± 41.4 d open). Compared with the control, CEF and CEF + FM had significantly greater concentrations of haptoglobin (1.1 ± 0.28 vs. 1.9 ± 0.06 and 1.8 ± 0.07 mg/mL at 4 DIM; 0.3 ± 0.15 vs. 1.1 ± 0.06 and 1.2 ± 0.07 mg/mL at 10 DIM) and fibrinogen (2.2 ± 0.17 vs. 3.9 ± 0.14 and 3.7 ± 0.13 g/L at 4 DIM; 1.9 ± 0.1 vs. 2.6 ± 0.1 and 3.0 ± 0.13 g/L, respectively, at 10 DIM) on all test days. The additional treatment with FM had no effect on these acute phase proteins. In conclusion, the single administration of 2.2 mg/kg of BW of FM in addition to a systemic antibiotic treatment of cows having APM did not result in beneficial effects on clinical cure, milk yield within 6 d after the first treatment, or reproductive performance.     

Effects of a single transdermal administration of flunixin meglumine in early postpartum Holstein Friesian dairy cows: Part 1. Inflammatory and metabolic markers,uterine health,and indicators of pain

The objectives of this study were to assess the effects of a single transdermal administration of flunixin meglumine (FM) in early postpartum Holstein Friesian dairy cows on serum concentrations of inflammatory and metabolic markers, uterine health, and indicators of pain. The hypothesis was that the anti-inflammatory, antipyretic, and analgetic effects of the pharmaceutic agent would reduce systemic inflammation, resulting in improved metabolic and inflammatory profile, diminished incidence of metritis, and reduced expression of pain. A total of 500 cows (153 primiparous, 347 multiparous) from 3 different commercial dairy farms in the northeast of Germany were included in a randomized controlled clinical trial. Farms were preselected based on high haptoglobin concentrations in their fresh lactating cows. Cows were excluded if they had experienced dystocia, stillbirth, or twin birth, or if they showed any signs of milk fever, retained fetal membranes, or fever (>40°C). The cows were treated once with either FM (3.33 mg/kg) or a placebo as control (CON) through transdermal administration between 24 to 36 h postpartum (d 2). General health examinations were performed (daily from d 2–8 and additionally on d 15 postpartum), vaginal discharge was assessed using the Metricheck device (d 8 and 15 postpartum) and serum samples were analyzed for inflammatory and metabolic markers (d 2, 4, and 6 postpartum). Effects of treatment, parity, sampling day, and their interactions were evaluated using mixed effects models. Primiparous cows treated with FM showed lower serum haptoglobin concentrations (0.90 ± 0.08 vs. 1.17 ± 0.07 g/L; ± standard error of the mean) and higher serum albumin concentrations (35.5 ± 0.31 vs. 34.8 ± 0.31 g/L) on d 6 postpartum. They also had a lower risk for purulent vaginal discharge with or without a fever compared with CON cows on d 15 postpartum (odds ratio for CON vs. FM: 1.63, 95% CI: 1.26–2.00), and body temperature was lower throughout the first 15 d in milk (39.1 ± 0.11 vs. 39.2 ± 0.11°C). Multiparous cows treated with FM had lower serum β-hydroxybutyrate concentrations on d 4 postpartum (0.71 ± 0.05 vs. 0.78 ± 0.05 mmol/L) and d 6 postpartum (0.74 ± 0.05 vs. 0.80 ± 0.05 mmol/L). Regardless of parity, FM-treated cows were significantly less likely to abduct their tail from their body (14.3 vs. 23.6%) and show an arched back (27.9 vs. 39.7%) on the day after treatment compared with CON cows. It can be concluded that FM treatment slightly reduced inflammation and diminished the risk for metritis in primiparous cows, improved metabolic profile in multiparous cows, and reduced expressions of pain in all cows.