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。     

长效土霉素注射液的急性毒性及肌肉刺激性研究

为考察新型长效土霉素注射液的安全性,分别对小白鼠和家兔进行急性毒性和局部刺激性试验。随机将60只小白鼠分为6组,每组10只,其中雌雄各半,进行急性毒性试验考察;随机将9只家兔分为3组,每组3只,进行局部刺激性试验。结果表明,该新型长效土霉素注射液小鼠肌肉注射LD 50为600.32 mg/kg,LD 50的95%的可信区间为(600.32±2.44)mg/kg;随着时间延长和给药剂量增加,刺激性增强,注射长效土霉素7 d后,家兔股四头肌出现红肿、发紫、坏死、光泽消失现象,15 d后肌肉组织的坏死范围扩大。该产品对小白鼠表现为低毒,对家兔的股四头肌有局部刺激性。     

喹烯酮在猪组织中的残留研究

目的 :建立起定量测定猪肝脏、肾脏、肌肉、脂肪食用组织中喹烯酮的高效液相色谱检测方法 ,依据测定的结果制定最高残留限量 ,定出其休药期。方法 :猪 45头 ,公母各半 ,按正常饲料添加喹烯酮 50 mg/ kg饲喂 2 .5月后 ,分别于4h、1 d、2 d、3 d、4d、6d、8d、1 2 d、1 5d采样。检测采用 Prodigy5μ Phenyl-3色谱分析柱 (4.6mm× 2 50 mm5μm icron) ,Waters TM486可变波长紫外检测器 ,甲醇 -水 (70∶ 3 0 )为流动相。组织样品用乙酸乙酯、乙腈、正已烷、氯仿等试剂提取处理纯化后进样 ,在 3 1 2 nm波长处检测 ,流速为 1 .0 m L·min- 1。结果 :标准曲线的线性范围为 :脂肪、肝脏 ,0 .0 0 5～ 0 .80 0μg· g- 1;肾脏、肌肉 ,0 .0 0 8～ 0 .0 80μg· g- 1。它们的复相关系数均大于 0 .99。精密度考察喹烯酮的日内各组织各浓度的 RSD(相对标准差 )均小于1 2 % ,日间测得各组织各浓度的 RSD均小于1 8.5%。喹烯酮在肌肉、脂肪、肾脏中均无残留 ,而在肝脏中的残留量也很小 ,4d以后再无残留。结论 :本试验测定方法灵敏度高 ,重复性好。停药后 4h所有可食用猪组织中喹烯酮浓度均低于计算所得的安全组织浓度 ,故该药在猪使用上无休药期 ,即休药期为零天。     

氟苯尼考长效制剂对鸡大肠杆菌病的疗效试验

用试管二倍稀释法测定了氟苯尼考与丁胺卡那霉素对大肠杆菌质控菌株ATCC25922,菌株K88、HD1047和临床分离的36株大肠杆菌的体外抗菌活性,进行了鸡大肠杆菌病的临床疗效试验.结果质控菌株和K88、HD1047株对氟苯尼考均敏感,36株临床分离菌株对氟苯尼考的敏感率为96.2%.在临床疗效试验中,氟苯尼考长效口服液和注射剂组的死亡率低于感染对照组和丁胺卡那霉素对照组(P《0.01),治愈率及有效率高于感染对照组和丁胺卡那霉素对照组(P《0.01),表明氟苯尼考长效制剂对鸡大肠杆菌病的治疗有很好的疗效并有较好的应用前景.     

欧盟食品动物注射部位兽药残留指南概述

2022年3月25日,欧盟药品管理局(EMA)兽医药品委员会(CVMP)发布了食品动物注射部位兽药残留指南,并于2022年8月1日正式生效。该指南代替旧版的注射部位兽药残留指南(EMA/CVMP/542/03-FINAL)。本文就新发布指南的背景、适用范围、法律依据、评价方法、残留研究及相关定义等内容进行介绍。     

Epidural anesthesia in dogs undergoing hindlimb orthopedic surgery: effects of two injection sites

This prospective clinical trial evaluated the effects of epidural anesthesia (EA) placed at the lumbosacral compared to the L5–L6 junction in dogs undergoing hindlimb orthopedic surgery. In all, 98 dogs were randomly assigned to receive injection at either L7–S1 (LS group) or L5–L6 (LL group) at the same local anesthetic regimen (1 mg/kg bupivacaine 0.5% and 0.1 mg/kg morphine 1%). Fentanyl (1 µg/kg) was the intraoperative rescue analgesia (iRA) administered if mean arterial pressure increased by 30% above pre-stimulation value. Procedural failure, iRA, hypotension, motor block resolution, and postoperative side effects were recorded. There were 7/47 (15%) epidural procedural failures in the LS group and 8/51 (16%) (P=1.00) in the LL group; iRA was administered in 21/40 (52%) LS group dogs and in 13/43 (30%) LL group dogs, respectively (P=0.047). The incidence of hypotension was 10/40 (25%) and 16/43 (37%) in the LS group and the LL group, respectively (P=0.25). Proprioceptive residual deficit at 8 hr after EA was recorded in 3/26 (12%) in group LS dogs and in 13/26 (50%) group LL dogs, respectively (P=0.01). The proprioceptive residual deficit at 24 hr in one dog (LL group) resolved within 36 hr. No episodes of postoperative urinary retention, pruritus or neurological damage were recorded. The L5–L6 EA decreased significantly iRA but delays the proprioceptive recovery time. Further studies are needed to determine whether a lower bupivacaine dose reduces the duration of the residual block retaining the same incidence of iRA.     

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.     

长效盐酸多西环素注射液在猪体内残留的消除规律

在常规饲养条件下,对35头健康成年猪按10 mg/kg体质量的剂量肌肉注射10%长效盐酸多西环素注射液,给药2次,给药间隔时间为48 h。第2次给药后12 h及2、5、9、14、192、5 d分别屠宰5头猪,分别采取每头猪的肌肉、肝脏、肾脏、皮肤+脂肪和注射位点肌肉等5种组织,用高效液相色谱法进行残留量测定。结果表明:在第2次给药后19 d,多西环素在各组织均能检测到,且残留均低于残留限量。多西环素残留浓度大小顺序:注射部位(肾脏(肝脏(皮脂(肌肉。采用WT1.4软件制定的统计方法来处理猪组织中药物浓度-时间数据,以制定休药期。     

Urine retention in cattle putatively associated with injection of an ivermectin and closantel anthelmintic formulation into the ischiorectal fossa

Case History: A group of 39, 19–22-month-old Friesian bulls were administered an ivermectin/closantel anthelmintic via intended S/C injection in the ischiorectal fossa on 15 June 2017 (Day 0). Over the next 50 days, 22 affected bulls presented various degrees of anorexia, abdominal pain and urine dribbling. Seventeen bulls were examined by transrectal ultrasonography which revealed urinary bladder distension in all 17, and peritoneal fluid accumulation in some. Overall, eight bulls died or were subjected to euthanasia. On-farm postmortem examination of three bulls revealed urinary bladder rupture.

Clinical Findings: On Day 50 one affected live bull was admitted to Massey University for further investigation. This bull continuously dribbled urine and had an overtly distended urinary bladder as determined by rectal palpation and ultrasonography.

Pathological Findings: Postmortem examination of this bull revealed a markedly distended urinary bladder, massive subcapsular and pericapsular renal oedema with retroperitoneal fluid accumulation, minimal hydronephrosis and no evidence of mechanical urinary outflow obstruction. The right ischiorectal fossa contained multifocal areas of tissue fibrosis that extended into areas innervated by the distal cutaneous branch of the pudendal nerve and the pelvic nerve. Histopathological changes consisted of extensive fibrosis, myonecrosis and neurodegeneration, and evidence of granulation tissue and inflammation at the putative injection site and in surrounding tissues.

Diagnosis: A local inflammatory reaction at the presumed injection site together with localised peripheral neurodegeneration and myelopathy may have led to detrusor-sphincter dyssynergia causing urine retention.

Clinical Relevance: These cases of urine retention and bladder rupture in cattle were of putative iatrogenic origin. Veterinarians should be aware of this rare complication after S/C injections in the ischiorectal fossa.     

An eprinomectin extended-release injection formulation providing nematode control in cattle for up to 150 days

A series of 10 dose confirmation studies was conducted to evaluate the persistent activity of an extended-release injectable (ERI) formulation of eprinomectin against single point challenge infections of gastrointestinal and pulmonary nematodes of cattle. The formulation, selected based on the optimal combination of high nematode efficacy, appropriate plasma profile, and satisfactory tissue residue levels, includes 5% poly(d,l-lactide-co-glycolic)acid (PLGA) and is designed to deliver eprinomectin at a dose of 1.0 mg/kg bodyweight. Individual studies, included 16–30 cattle blocked based on pre-treatment bodyweight and randomly allocated to treatment with either ERI vehicle or saline (control), or the selected Eprinomectin ERI formulation. Treatments were administered once at a dose volume of 1 mL/50 kg bodyweight by subcutaneous injection in front of the shoulder. In each study, cattle were challenged with a combination of infective stages of gastrointestinal and/or pulmonary nematodes 100, 120 or 150 days after treatment and were processed for parasite recovery according to standard techniques 25–30 days after challenge. Based on parasite counts, Eprinomectin ERI (1 mg eprinomectin/kg bodyweight) provided >90% efficacy (p < 0.05) against challenge with Cooperia oncophora and Cooperia surnabada at 100 days after treatment; against challenge with Ostertagia ostertagi, Ostertagia lyrata, Ostertagia leptospicularis, Ostertagia circumcincta, Ostertagia trifurcata, Trichostrongylus axei, and Cooperia punctata at 120 days after treatment; and against challenge with Haemonchus contortus, Bunostomum phlebotomum, Oesophagostomum radiatum and Dictyocaulus viviparus at 150 days after treatment. Results of a study to evaluate eprinomectin plasma levels in cattle treated with the Eprinomectin ERI formulation reveal a characteristic second plasma concentration peak and a profile commensurate with the duration of efficacy. These results confirm that the Eprinomectin ERI formulation can provide high levels of parasite control against a range of nematodes of cattle for up to 5 months following a single treatment.     

Assessment of Antimicrobial Usage and Residues in Commercial Chicken Eggs from Smallholder Poultry Keepers in Morogoro Municipality,Tanzania

Occurrence of antimicrobial residues in commercial chicken eggs was determined in Morogoro municipality between January and February 2007. Twenty smallholder farmers were interviewed on the types of antimicrobials, reasons of use and their awareness on antimicrobial withdrawal period. Seventy egg samples were collected for qualitative antimicrobial drug residues analysis by use of agar well diffusion and Delvotest SP^® assays. It was found that farmers use antimicrobial drugs as prophylaxis and treatment of common chicken diseases namely fowl typhoid (85%), infectious bursa disease (Gumboro) (65%) infectious coryza (65%), collibacilosis (55%), coccidiosis (54%), Newcastle disease (50%), helminthosis (20%) and fowl pox (15%). Antimicrobials accounted for 85% of the drugs commonly used. It was also found that 65% of the farmers treat their chicken themselves. The common drugs were oxytetracycline (75%), egg booster (50%), amprolium (35%), sulphamethoxypyridazine (35%), sulphanilamide (25%), chlortetracyclines (10%), chloramphenicol (10%), sulphadiazine–trimethoprim (20%), duoxycycline (20%), sulphadiazine (25%) and flumequine (10%). Eighty per cent of the farmers had knowledge on antimicrobial withdrawal period sold eggs before withdrawal period and almost 85% were unaware of possible effects of antimicrobial residues in humans. All 70 eggs were positive to antimicrobial residues by Delvotest kit, but 21.4% positive with agar well diffusion test. It was concluded that the presence of antimicrobial residues in table eggs could be of public health significance to the egg consumers in Morogoro municipality.     

LongRange™ (eprinomectin 5%) extended-release injection parasiticide and the utility of extended-activity antiparasitics in cattle

An extended-release injection, which is administered at a rate of 1 mg eprinomectin/kg body weight, has been developed to provide up to 150 days control of parasites of cattle. The product can facilitate the achievement of two of the fundamental aims of parasite control. The first is protection of the host against the negative impact of susceptible parasites in order to ensure control of disease and to enhance performance. The second is to reduce parasite transmission and hence the challenge to animals when grazing. In addition, farmers and veterinarians can benefit from high levels of convenience and hence compliance from a single administration, which also limits handling stress in the cattle. This introductory paper provides some perspective on the practical applications for this extended-release product under various husbandry systems and in different classes of cattle and discusses its role in sustainable parasite control.     

中药复方宫炎净注射液对奶牛子宫内膜炎部分血液学指标影响及毒性试验研究

选择新疆第八师某团已确诊为患子宫内膜炎的奶牛20头,观察宫炎净注射液治疗前后的部分血液学指标变化,并与健康对照组和未治疗组进行比较,考察宫炎净注射液的抗炎作用;通过小鼠口服和腹腔注射宫炎净注射液进行急性毒性试验,观察给药后小鼠的临床症状和病理变化,考察宫炎净注射液的临床毒性.试验结果显示,使用宫炎净注射液治疗后,奶牛血液中的红细胞总数、血红蛋白含量和淋巴细胞数量均有所上升,白细胞总数和粒细胞数有所下降;2个疗程后,中药治疗组奶牛的部分血液学指标均接近正常水平,与正常对照组无显著性差异;毒性试验显示,用药后小白鼠临床表现和剖检均无异常情况。结果表明,中药复方宫炙净注射液安全无毒。     

利福平在脓肿病灶内的残效期及其耐受菌株的分离鉴定

将伪结核棒状杆菌人工接种５０只实验小鼠,４周后用利福平对其中存活的２７只进行治疗试验,疗程为１周。然后每周解剖３只实验小鼠,检测药物在其脓肿病灶内有效杀菌作用的持续时间即残效期;同时对耐受该药物的菌株进行分离鉴定。结果发现：停药后第８周病灶内不仅仍有药物残存,而且仍然具有强大的杀菌作用;同时由４只小鼠的脓肿病灶分离到接种菌,经鉴定确认均为利福平耐受菌。表明伪结核棒状杆菌对利福平极易产生耐受性。     

The efficacy of eprinomectin extended-release injection against Hypoderma spp. (Diptera: Oestridae) in cattle

The efficacy of eprinomectin in an extended-release injection (ERI) formulation was determined in cattle harboring naturally acquired infestations of first- or second- and third-stage larvae of Hypoderma spp. in three studies conducted according to the same protocol in the USA (two studies) and Germany (one study). Thirty cattle sourced from herds with a history of Hypoderma infestation were included in each study. Cattle were formed into replicates of three animals each on the basis of pre-treatment anti-Hypoderma antibody titers. Within replicates each animal was randomly allocated to one of the following treatments: ERI vehicle (control) at 1 mL/50 kg bodyweight, administered once on Day 0; Eprinomectin 5% ERI at 1 mL/50 kg bodyweight (1.0 mg eprinomectin/kg), administered once on Day 0 (when larvae were expected to be first instars); or Eprinomectin 5% ERI at 1 mL/50 kg bodyweight (1.0 mg eprinomectin/kg), administered once when larvae were second or third instars (study dependent, Day 73, 119, or 140). Treatments were administered by subcutaneous injection in front of the shoulder. In all studies, emerging and/or expressed Hypoderma larvae were recovered, speciated, and counted and viability was determined. Eprinomectin LAI treatment was 100% (p < 0.05) efficacious against first- and second- or third-stage larvae of Hypoderma bovis (two studies) and Hypoderma lineatum (one study). All animals accepted the treatment well. No adverse reaction to treatments was observed in any animal in any study.     

地胆头注射液的制备及其体外抑菌效果研究

分别用3种不同浓度的乙醇水溶液进行热回流浸提,制备地胆头原液.然后用醇溶液调pH值法除去鞣质以及乙醚脱脂、活性炭脱色等方法进行除杂脱色,制备地胆头有效部位注射液.对地胆头注射液进行了质量和安全性检查及体外药效试验.结果表明,制备的地胆头注射液对金黄色葡萄球菌、肺炎双球菌、大肠埃希氏杆菌和肠炎沙门氏菌均有明显的抑制作用,其中用65%乙醇提取制备的地胆头注射液效果最好,3种注射液都具有很好的澄明度和安全性.     

湟源县黄牛血钾浓度的测定

采用火焰光度计法测定了湟源县日月乡黄牛４０份血样的血钾浓度。测定结果为：全血钾浓度９．１６ｍｍｏｌ／Ｌ；红细胞钾浓度１９．７９ｍｍｏｌ／Ｌ；血清钾浓度４．３５ｍｍｏｌ／Ｌ。全血钾浓度和红细胞钾浓度呈显著的正相关关系（ｒ＝０．９４４１Ｐ＜０．００１）     

阿维菌素长效注射液(油悬剂)对绵羊痒螨的疗效试验

为了研究阿维菌素长效注射液(油悬剂)对绵羊痒螨疗效,将60只自然感染痒螨绵羊随机分为3组,每组20只。第1组每千克体重颈部皮下注射1 mg的阿维菌素油悬剂,第2组注射0.2 mg的阿维菌素普通注射液,第3组为不给药对照组。在给药后第7、14、21、28、35、42、49、56、63、70天对所有绵羊进行螨虫检查和计数,每天观察病变。结果表明:给自然感染痒螨的绵羊皮下注射1 mg/kg的阿维菌素长效注射液(油悬剂)可在给药后7 d内将痒螨完全杀灭,在给药后63 d内防止绵羊被痒螨再感染,其持效期远长于阿维菌素普通注射液(约为14 d)。     

高寒矿区采样位置和生长期及坡向对草本植物根系力学特性影响

以种植于青海刚察木里煤田江仓矿区排土场不同坡向(半阴半阳、阳坡和阴坡)、生长期为1～5 a的垂穗披碱草为研究对象,对该植物根系开展单根拉伸试验,测定其根径、单根抗拉力、抗拉强度、极限拉伸应变率和拉伸模量等力学指标。分别以采样位置、生长期和坡向为自变量,以上述力学指标为响应变量,通过单因素方差分析,探讨各自变量对上述指标的影响。结果表明：在半阴半阳坡和阴坡,各指标在不同取样点未表现出显著性差异,在阳坡,除根径外,其余指标均表现出显著性差异;随生长期增加,各坡向的植物抗拉力、抗拉强度等指标呈增加的变化特征;阳坡植物根径、单根抗拉力大于半阴半阳坡,而其余各指标则表现出相反的变化特征,在半阴半阳边坡,植物根系力学指标大于阴坡。     

Observations on the effects of long-term withdrawal on carcass composition and residue concentrations in clenbuterol-medicated cattle

The detection of the illegal use of clenbuterol (CBL) as a growth promoter has relied on detecting residual concentrations of the drug in body fluids or tissues. Analysis of retinal extracts has recently been shown to considerably extend the detection period following withdrawal. The withdrawal periods required to eliminate residues from the liver and retina were investigated by medicating 20 cattle with CBL for 30 days; 6 control animals remained unmedicated. Residual concentrations were monitored throughout this period and for the subsequent 140 days. Concurrent changes in muscle areas and backfat thicknesses were recorded by ultrasound.CBL was detectable in liver up to the 56th day of withdrawal (0.35 ng/g, SD=0.5), but retinal concentrations remained well above detectable concentrations throughout the withdrawal period (22.5 ng/g, SD=6.5). There were small gains (3–4%) in the muscle areas of treated cattle during medication as compared to controls (p>0.05). These comparative gains remained during withdrawal. Backfat thicknesses in treated animals were 40% lower than in controls at the end of medication (p<0.01). However, by 70 days after withdrawal this difference had disappeared (p>0.05) owing to accelerated fat deposition in the treated group. The retina has been shown to be a highly effective target matrix for detecting CBL administration after long withdrawal periods.Abbreviations CBL clenbuterol - CIM cimaterol - EC European Community - EIA enzyme immunoassay - GC-MS gas chromatography-mass spectrometry - HRPo horseradish peroxidase - L. dorsi, Longissimus dorsi - MRL maximum residue level - SD standard deviation - SED standard error of the difference