4''-methylaminoavermectin | 119791-41-2

• 物质功能分类: 化学农药原药 - 杀虫剂 - 其他杀虫剂
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4''-methylaminoavermectin
• 英文别名: emamectin B1a；emamectin；4''-deoxy-4''-epi-methylaminoavermectin B1a；(1'R,2R,3S,4'S,6S,8'R,10'E,12'S,13'S,14'E,16'E,20'R,21'R,24'S)-2-[(2S)-butan-2-yl]-21',24'-dihydroxy-12'-[(2R,4S,5S,6S)-4-methoxy-5-[(2S,4S,5R,6S)-4-methoxy-6-methyl-5-(methylamino)oxan-2-yl]oxy-6-methyloxan-2-yl]oxy-3,11',13',22'-tetramethylspiro[2,3-dihydropyran-6,6'-3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene]-2'-one
• CAS: 119791-41-2
• 化学式: C₄₉H₇₅NO₁₃
• mdl: MFCD07637273
• 分子量: 886.133
• InChiKey: CXEGAUYXQAKHKJ-COFQVFHOSA-N

物化性质

• 溶解度：
  可溶于二氯甲烷（少许）、氯仿（少许）、甲醇（少许）
• 颜色/状态：
  White to off-white powder
• 熔点：
  141-146 °C /Emamectin benzoate/
• 密度：
  1.20 at 23 °C /Emamectin benzoate/
• 蒸汽压力：
  3.8X10-8 mm Hg at 21 °C /Emamectin benzoate/
• 旋光度：
  Specific optical rotation: -6.9 deg (c = 0.5% in methanol)
• 分解：
  When heated to decomposition it emits toxic vapors of /Nitrogen oxide/.
• 解离常数：
  pKa: 4.18 (acidic, attributed to benzoate counter ion), 8.71 (basic, attributed to emamectin moiety)
• 碰撞截面：
  300.62 Ų [M+H]+

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  63
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  162
• 氢给体数：
  3
• 氢受体数：
  14

ADMET

代谢

大西洋鲑鱼（约1.3公斤）在5±1摄氏度的海水罐中饲养，通过饲料以50微克/公斤/天的名义剂量连续7天给予[(3)H]依玛菌素B1苯甲酸盐。在最终剂量后的3小时和12小时以及1、3、7、15、30、45、60和90天，从每组10条鱼中收集组织、血液和胆汁。从最终剂量前开始，每天从罐中收集粪便，直至最终剂量后90天。在给药期间，每日粪便样本的总放射性残留物（TRR）最大为0.25 ppm，且在覆盖给药期的合并粪便中，大于97%的TRR是依玛菌素B1a。粪便TRR随后迅速下降，最终剂量后1天大约降至0.05 ppm。在给药后90天内，组织的平均TRR范围如下：肾脏，1.4-3 ppm；肝脏，1.0-2.3 ppm；皮肤，0.04-0.09 ppm；肌肉，0.02-0.06 ppm；骨骼，小于0.01 ppm。按给药后时间间隔合并的肝脏、肾脏、肌肉和皮肤样本的残留物组分为依玛菌素B1a（81-100% TRR）和去甲基依玛菌素B1a（0-17% TRR），在一些肌肉样本中可以看到N-甲酰依玛菌素B1a的微量（小于2%）。选作依玛菌素残留监管监测的标志残留物是依玛菌素B1a。使用高效液相色谱-荧光法量化个体皮肤和肌肉样本中的依玛菌素B1a水平，在所有分析的样本中（给药后3小时至30天），该水平低于85 ppb。

Atlantic salmon (approximately 1.3 kg) maintained in tanks of seawater at 5 +/- 1 degrees C were dosed with [(3)H]emamectin B1 benzoate in feed at a nominal rate of 50 ug of emamectin benzoate/kg/day for 7 consecutive days. Tissues, blood, and bile were collected from 10 fish each at 3 and 12 hr and at 1, 3, 7, 15, 30, 45, 60, and 90 days post final dose. Feces were collected daily from the tanks beginning just prior to dosing to 90 days post final dose. The total radioactive residues (TRR) of the daily feces samples during dosing were 0.25 ppm maximal, and >97% of the TRR in pooled feces covering the dosing period was emamectin B1a. Feces TRR then rapidly declined to approximately 0.05 ppm by 1 day post final dose. The ranges of mean TRR for tissues over the 90 days post dose period were as follows: kidney, 1.4-3 ppm; liver, 1.0-2.3 ppm; skin, 0.04-0.09 ppm; muscle, 0.02-0.06 ppm; and bone, <0.01 ppm. The residue components of liver, kidney, muscle, and skin samples pooled by post dose interval were emamectin B1a (81-100% TRR) and desmethylemamectin B1a (0-17% TRR) with N-formylemamectin B1a seen in trace amounts (<2%) in some muscle samples. The marker residue selected for regulatory surveillance of emamectin residues was emamectin B1a. The emamectin B1a level was quantified in individual samples of skin and muscle using HPLC-fluorometry and was below 85 ppb in all samples analyzed (3 hr to 30 days post dose).

来源:Hazardous Substances Data Bank (HSDB)

代谢

...已鉴定出一个哺乳动物代谢物。这种代谢物被特征化为乙螨唑的N-去甲基化副产物。

...a single mammalian metabolite has been identified. This metabolite is characterized as an N-demethylation byproduct of emamectin.

来源:Hazardous Substances Data Bank (HSDB)

代谢

(3)H/(14)C-标记的4"-脱氧-4"-表甲基氨基阿维菌素B1a（MAB1a）苯甲酸盐的代谢被研究，这是阿维菌素类杀虫剂艾玛菌素苯甲酸盐的主要同系物（大于或等于90%）。十只莱杭鸡（Gallus domesticus）每天口服一次，连续7天（1毫克/千克体重/天）。每天收集鸡蛋和排泄物，然后将鸡蛋分离成蛋白和蛋黄。最后一次给药后20小时内，鸡被安乐死，收集肝脏、肾脏、心脏、肌肉、脂肪、卵巢、肌胃、胃肠道及其内容物和尸体。大约70%和6%的总给药剂量分别在排泄物加胃肠道及其内容物和组织加鸡蛋中回收。确定了两种新的代谢物，即原化合物的24-羟甲基衍生物（24-羟甲基-4"-脱氧-4"-表甲基氨基阿维菌素B1a）和24-羟甲基-4"-脱氧-4"-表甲基氨基阿维菌素B1a的N-去甲基衍生物（24-羟甲基-4"-脱氧-4"-表氨基阿维菌素B1a）。此外，还分离和鉴定了这两种代谢物的八个脂肪酸共轭物，这些共轭物在组织和鸡蛋中的总放射性残留物中占8-75%。尽管这在迄今为止报道的外源化学物质中代表了一些最广泛的体内脂肪酸结合，但由于本研究的剂量水平大约是作物中MAB1a残留水平的1000倍，且大部分应用的剂量在排泄物中回收，因此人类通过食用鸡肉对MAB1a残留的潜在暴露会非常低。根据这些发现，MAB1a的鸟类生物转化与哺乳动物生物转化有显著差异。

The metabolism of (3)H/(14)C-labeled 4"-deoxy-4"-epimethylaminoavermectin B1a (MAB1a) benzoate, the major homologue (>/=90%) of the avermectin insecticide emamectin benzoate, was studied in laying chickens. Ten Leghorn hens (Gallus domesticus) were orally dosed once daily for 7 days (1 mg/kg of body weight/day). Eggs and excreta were collected daily, and eggs were subsequently separated into whites and yolks. Chickens were euthanized within 20 hr after the last dose, and liver, kidney, heart, muscle, fat, ovaries, gizzard, gastrointestinal tract and contents, and carcass were collected. Approximately 70 and 6% of the total administered dose were recovered in the excreta plus gastrointestinal tract and contents and in the tissues plus eggs, respectively. Two novel metabolites, i.e. the 24-hydroxymethyl derivative of the parent compound (24-hydroxymethyl-4"-deoxy-4"-epimethylaminoavermectin B1a) and the N-demethylated derivative of 24-hydroxymethyl-4"-deoxy-4"-epimethylaminoavermectin B1a (24-hydroxymethyl-4"-deoxy-4"-epiaminoavermectin B1a), were identified. In addition, eight fatty acid conjugates of each of these two metabolites, comprising 8-75% of total radioactive residues in tissues and eggs, were isolated and identified. Although this represents some of the most extensive in vivo fatty acid conjugation to a xenobiotic reported to date, potential human exposure to MAB1a residues from consumption of chicken would be extremely low, because the dosage level in this study was approximately 1000-fold greater than the MAB1a residue levels seen in crops and because the majority of the applied dose was recovered in the excreta. Based on these findings, the avian biotransformation of MAB1a differs substantially from the mammalian biotransformation.

来源:Hazardous Substances Data Bank (HSDB)

代谢

苄氨基阿维菌素苯甲酸盐在哺乳动物体内并未广泛代谢，有限的代谢物信息表明代谢过程并未使苄氨基阿维菌素苯甲酸盐解毒。苄氨基阿维菌素苯甲酸盐的一个植物代谢物比其本身更具毒性。

While emamectin benzoate is not extensively metabolized in mammals, the limited information on the metabolites of emamectin benzoate suggests that metabolism does not result in the detoxification of emamectin benzoate. One plant metabolite of emamectin benzoate is somewhat more toxic than emamectin benzoate itself.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

家蝇（Musca domestica L.）是全球乳品作业的重要害虫，能够适应广泛的环境条件。目前有多种杀虫剂用于它们的防治，但抗药性的发展是一个严重的问题。杀虫剂混合使用可以提高杀虫剂对具有抗性的害虫的毒性，因此可能成为一种潜在的害虫抗药性管理工具。本研究评估了单独使用以及混合使用时， bifenthrin（联苯菊酯）、cypermethrin（氯氰菊酯）、deltamethrin（溴氰菊酯）、chlorpyrifos（毒死蜱）、profenofos（丙氟磷）、emamectin benzoate（甲氨基阿维菌素苯甲酸盐）和fipronil（氟虫腈）对家蝇的毒性。与实验室敏感品系相比，现场收集的家蝇群体对所有调查的杀虫剂均表现出显著抗性。大多数杀虫剂混合物，如将一种拟除虫菊酯与其他化合物混合，在两种条件下（1:1-"A"和LC50:LC50-"B"）显著提高了现场群体中拟除虫菊酯的毒性。在这两种条件下，拟除虫菊酯与其他化合物的组合指数在大多数情况下显著低于1，表明存在协同作用。当酶抑制剂PBO和DEF与杀虫剂联合用于抗性群体时，bifenthrin（联苯菊酯）、cypermethrin（氯氰菊酯）、deltamethrin（溴氰菊酯）和emamectin（甲氨基阿维菌素）的毒性显著提高，这表明存在酯酶和单加氧酶基础的抗性机制。在抗性家蝇群体中，bifenthrin（联苯菊酯）、cypermethrin（氯氰菊酯）和deltamethrin（溴氰菊酯）的毒性可以通过与chlorpyrifos（毒死蜱）、profenofos（丙氟磷）、emamectin（甲氨基阿维菌素）和fipronil（氟虫腈）的混合使用得到增强。目前的研究结果对于家蝇抗药性管理可能具有实际意义。

House flies, Musca domestica L., are important pests of dairy operations worldwide, with the ability to adapt wide range of environmental conditions. There are a number of insecticides used for their management, but development of resistance is a serious problem. Insecticide mixtures could enhance the toxicity of insecticides in resistant insect pests, thus resulting as a potential resistance management tool. The toxicity of bifenthrin, cypermethrin, deltamethrin, chlorpyrifos, profenofos, emamectin benzoate and fipronil were assessed separately, and in mixtures against house flies. A field-collected population was significantly resistant to all the insecticides under investigation when compared with a laboratory susceptible strain. Most of the insecticide mixtures like one pyrethroid with other compounds evaluated under two conditions (1?1-"A" and LC50: LC50-"B") significantly increased the toxicity of pyrethroids in the field population. Under both conditions, the combination indices of pyrethroids with other compounds, in most of the cases, were significantly below 1, suggesting synergism. The enzyme inhibitors, PBO and DEF, when used in combination with insecticides against the resistant population, toxicities of bifenthrin, cypermethrin, deltamethrin and emamectin were significantly increased, suggesting esterase and monooxygenase based resistance mechanism. The toxicities of bifenthrin, cypermethrin and deltamethrin in the resistant population of house flies could be enhanced by the combination with chlorpyrifos, profenofos, emamectin and fipronil. The findings of the present study might have practical significance for resistance management in house flies.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

早期中毒迹象包括瞳孔扩张、肌肉失调和肌肉震颤。在接触后半小时内呕吐可以减少误食该产品后的毒性；接触后迅速（<15分钟）反复给予大量水中的医疗活性炭……。如果接触中毒已经进展到引起严重呕吐，应评估由此引起的液体和电解质失衡的程度。应根据临床迹象、症状和测量给予适当的支持性静脉补液替代疗法，以及其他必要的支持性措施（例如维持血压水平和适当的呼吸功能）。在严重病例中，应继续观察至少数天，直到临床状况稳定和正常。由于认为乙螨唑苯甲酸盐在动物中增强GABA活性，因此避免给可能接触有毒乙螨唑苯甲酸盐的患者使用增强GABA活性的药物（巴比妥类药物、苯二氮卓类药物、丙戊酸）可能是明智的。

Early signs of intoxication include dilation of pupils, muscular incoordination, and muscular tremors. Vomiting within one-half hour of exposure can minimize toxicity following accidental ingestion of the product; rapidly after exposure (<15 minutes) administer repeatedly medical charcoal in a large quantity of water ... . If toxicity from exposure has progressed to cause severe vomiting, the extent of resultant fluid and electrolyte imbalance should be gauged. Appropriate supportive parenteral fluid replacement therapy should be given, along with other required supportive measures (such as maintenance of blood pressure levels and proper respiratory functionality) as indicated by clinical signs, symptoms, and measurements. In severe cases, observations should continue for at least several days until clinical condition is stable and normal. Since emamectin benzoate is believed to enhance GABA activity in animals, it is probably wise to avoid drugs that enhance GABA activity (barbiturates, benzodiazepines, valproic acid) in patients with potentially toxic emamectin benzoate exposure.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者向前倾或将其置于左侧（如果可能的话，头部向下），以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预防癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

有两个给药组，每组有2只雄性比格犬。第1组在第1天接受0.5 mg/kg的(3)H-MK-0243苯甲酸盐（1 mL/kg在5%乙醇中……0.239 mCi/mg；98.8%放射化学纯度），在第15天接受0.5 mg/kg的(3)H-MK-0243 HCl（1 mL/kg在去离子水中……0.229 mCi/mg；98.7%放射化学纯度）。第2组的给药顺序相反。每次给药前测定体重。在每次给药后的0.5、1、2、4、6、8、24、48、96和168小时，各取2 mL血液用于药物水平测定。在0至24小时和72至96小时收集尿液和粪便用于药物水平分析。没有发现药物效果的证据。苯甲酸盐和HCl盐的平均血浆半衰期分别为35.7 +/- 3.4小时和35.5 +/- 4.4小时。苯甲酸盐和HCl盐的平均血浆近似曲线下面积（AUC）分别为4479 +/- 1476和4574 +/- 1514 ng/g血浆/7天。两种盐的平均血浆MAB1a（MK-0243的主要成分，占90至95%）水平约为100 ng当量/g血浆，在大约6小时达到峰值。在第1天和第4天，粪便和尿液中回收的总和约为剂量的40%和0.01%。结论是，两种盐在雄性比格犬中是生物等效的。

There were 2 dosing groups, each consisting of 2 male beagles. Group 1 received 0.5 mg/kg of (3)H-MK-0243 benzoate (1 mL/kg in 5% ethanol ... 0.239 mCi/mg; 98.8% radiochemically pure) on day 1 and 0.5 mg/kg of (3)H-MK-0243 HCl (1 mL/kg in deionized water ... 0.229 mCi/mg; 98.7% radiochemically pure) on day 15. Dosing was reversed for Group 2. Body weights were determined before each dose. 2 mL of blood was withdrawn for drug level determinations following each dose at 0.5, 1, 2, 4, 6, 8, 24, 48, 96 and 168 hr. Urine and feces were collected for drug level analysis at 0 to 24 and 72 to 96 hr. There was no evidence of drug effects. The mean plasma half lives for the benzoate and HCl salts were 35.7 +/- 3.4 hr and 35.5 +/- 4.4 hr, respectively. The mean plasma approximate area under the curve (AUC) for the benzoate and HCl salts was 4479 +/- 1476 and 4574 +/- 1514 ng/g plasma/7days. The mean peak plasma MAB1a (the major component of MK-0243 at 90 to 95%) levels were ~100 ng equivalents/g plasma, occurring at ~6 hr for either salt. Combined fecal and urine recoveries during the 1st and 4th days were ~40% and 0.01% of the dose, respectively. It is concluded that the 2 salts are bioequivalent in male beagle dogs.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

实验性杀虫剂阿维菌素本贝酸盐的皮肤吸收在猕猴身上进行了研究。通过比较皮肤应用化合物的排泄物中放射性水平与等效静脉注射剂量后的放射性水平来计算皮肤吸收。给三只猴子静脉注射300微克(3)H-MAB1a(以丙二醇：盐水1:1溶液制备)后，血浆水平呈双相下降，放射性在最初的15分钟内迅速下降，随后较慢下降至背景水平。在给药后7天，大约90%和5%的给药放射性分别从粪便和尿液中回收。经过一段清洗期后，将300微克[(3)H]MAB1a(溶解在可乳化浓缩物中)涂在前臂剃毛的同一只猴子身上。经过10小时的暴露期后，大约90%的放射性通过肥皂和水清洗暴露的前臂回收。尽管血浆放射性水平通常保持在背景水平以下，但大约1.5%的给药剂量在排泄物中回收。阿维菌素本贝酸盐的皮肤吸收计算为1.6%。阿维菌素本贝酸盐的低皮肤渗透性表明，农业工作者实际接触该化合物的可能性极小。

The dermal absorption of the experimental avermectin insecticide emamectin benzoate was studied in the Rhesus monkey. Dermal absorption was calculated by comparing radioactivity levels in excreta following dermal application of the compound with those following administration of an equivalent intravenous dose. After iv administration of 300 ug (3)H-MAB1a (prepared as a 1:1 solution of propylene glycol:saline) to three monkeys, plasma levels decreased biphasically with a rapid decline in radioactivity during the first 15 min followed by a slower decline to background. By 7 days post-dose, approximately 90% and 5% of the administered radioactivity was recovered in the feces and urine, respectively. After a washout period, 300 micrograms [(3)H]MAB1a (dissolved in emulsifiable concentrate) was applied topically to the shaved forearm of the same monkeys. Following a 10-hr exposure period, approximately 90% of the radioactivity was recovered in a soap and water wash of the exposed forearms. Although plasma radioactivity levels generally remained below background levels, approximately 1.5% of the applied dose was recovered in the excreta. Dermal absorption of [()3H]emamectin benzoate was calculated as 1.6%. The low dermal penetration of emamectin benzoate indicates that minimal actual exposure of agricultural workers to this compound will occur.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

本研究的目标是调查在推荐剂量给药后血液、粘液和肌肉中的埃马霉素含量，以及与同一条鱼上的海虱感染的相关性（消除研究）。通过全身自动射线摄影和闪烁计数法，还研究了单次口服剂量后大西洋鲑鱼体内三标埃马霉素苄酯的分布情况（分布研究）。在消除研究中，埃马霉素苄酯的浓度在第7天（给药的最后一天）达到最高，分别为血液128、粘液105和肌肉68纳克/克（p.p.b.）。从第7天开始，血液中的浓度下降，直到第77天浓度低于检测限。除了第7天和第21天，粘液中的浓度高于血浆（P < 0.05）。埃马霉素苄酯的浓度从治疗结束（第7天）到第70天逐渐下降，肌肉、血浆和粘液的半衰期分别为9.2、10.0和11.3天。分布研究表明，在整个观察期（56天）内，粘膜（胃肠道、鳃）中的放射性活性很高。在整个研究期间，松果体、垂体和嗅球的活性很高。胆汁中的活性最高，表明这是排泄的重要途径。分布研究确认了消除研究中关于血液、皮肤粘液和肌肉浓度的结果。

The aims of this study were to investigate the content of emamectin in blood, mucus and muscle following field administration of the recommended dose, and correlation with sea lice infection on the same fish (elimination study). The tissue distribution of tritiated emamectin benzoate after a single oral dose in Atlantic salmon was also investigated by means of whole-body autoradiography and scintillation counting (distribution study). In the elimination study, concentrations of emamectin benzoate reached maximum levels of 128, 105 and 68 ng/g (p.p.b.) for blood, mucus and muscle respectively, on day 7, the last day of administration. From day 7, the concentration in the blood declined until concentration was less than the limit of detection on day 77. The concentration was higher in mucus compared with plasma (P < 0.05) except on days 7 and 21. The concentration of emamectin benzoate decreased gradually from the end of treatment (day 7) to day 70 with half-lives of 9.2, 10.0 and 11.3 days in muscle, plasma and mucus respectively. The distribution study demonstrated a high quantity of radioactivity in mucous membranes (gastrointestinal tract, gills) throughout the observation period (56 days). Activity was high in the epiphysis, hypophysis and olfactory rosette throughout the study. The highest activity was observed in the bile, indicating this to be an important route for excretion. The distribution study confirmed the results from the elimination study with respect to concentrations in blood, skin mucous and muscle.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

大西洋鲑鱼（约1.3公斤）在5±1摄氏度的海水罐中饲养，通过饲料以名义上的50微克/公斤/天的剂量给予3H-依马美汀B1苄酯，连续7天。在最后一次给药后3小时和12小时以及1、3、7、15、30、45、60和90天，从每组10条鱼中收集组织、血液和胆汁。从给药前开始到最后一次给药后90天，每天从罐中收集粪便。在给药期间，每日粪便样本的总放射性残留物（TRR）最大为0.25 ppm，且在覆盖给药期的合并粪便中>97%的TRR是依马美汀B1a。粪便TRR随后迅速下降，到最后一次给药后1天大约为0.05 ppm。在给药后90天内，组织的平均TRR范围如下：肾脏，1.4-3 ppm；肝脏，1.0-2.3 ppm；皮肤，0.04-0.09 ppm；肌肉，0.02-0.06 ppm；骨骼，<0.01 ppm。根据给药后间隔合并的肝脏、肾脏、肌肉和皮肤样本的残留物组成为依马美汀B1a（81-100% TRR）和去甲基依马美汀B1a（0-17% TRR），在一些肌肉样本中可见到N-甲酰依马美汀B1a的微量（<2%）。选作依马美汀残留监管监测的标志残留物是依马美汀B1a。使用高效液相色谱-荧光法在个体皮肤和肌肉样本中定量依马美汀B1a水平，在所有分析的样本中（给药后3小时至30天）均低于85 ppb。

Atlantic salmon (approximately 1.3 kg) maintained in tanks of seawater at 5 +/- 1 degrees C were dosed with 3H-emamectin B1 benzoate in feed at a nominal rate of 50 ug of emamectin benzoate/kg/day for 7 consecutive days. Tissues, blood, and bile were collected from 10 fish each at 3 and 12 hr and at 1, 3, 7, 15, 30, 45, 60, and 90 days post final dose. Feces were collected daily from the tanks beginning just prior to dosing to 90 days post final dose. The total radioactive residues (TRR) of the daily feces samples during dosing were 0.25 ppm maximal, and >97% of the TRR in pooled feces covering the dosing period was emamectin B1a. Feces TRR then rapidly declined to approximately 0.05 ppm by 1 day post final dose. The ranges of mean TRR for tissues over the 90 days post dose period were as follows: kidney, 1.4-3 ppm; liver, 1.0-2.3 ppm; skin, 0.04-0.09 ppm; muscle, 0.02-0.06 ppm; and bone, <0.01 ppm. The residue components of liver, kidney, muscle, and skin samples pooled by post dose interval were emamectin B1a (81-100% TRR) and desmethylemamectin B1a (0-17% TRR) with N-formylemamectin B1a seen in trace amounts (<2%) in some muscle samples. The marker residue selected for regulatory surveillance of emamectin residues was emamectin B1a. The emamectin B1a level was quantified in individual samples of skin and muscle using HPLC-fluorometry and was below 85 ppb in all samples analyzed (3 hr to 30 days post dose).

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

阿维菌素衍生品

埃玛菌素（emamectin，又称甲氨基阿维菌素）是以阿维菌素为母体通过半合成进行结构改造而开发出的一系列活性更高、选择性更强、安全性更优的衍生新品种。最初，阿维菌素主要用作驱寄生虫药剂，尽管它是一种优秀的兽用驱虫剂，但由于其经皮毒性很低但人畜口服毒性较高，做成口服剂时存在一个矛盾：用量太低效果不好，而用量太高则安全性不足。为了改善这一不足，默克公司对其化学结构进行了改造，从中筛选出了两个新的化合物即伊维菌素和埃玛菌素。

作用机理

伊维菌素明显地改善了人畜的急性口服毒性，因此兽用阿维菌素驱虫剂现在通常使用的是伊维菌素成分。埃玛菌素则扩大了阿维菌素的杀虫谱并克服了阿维菌素对鳞翅目害虫效果不佳的问题。埃玛菌素的制剂苯甲酸盐即为甲维盐，因此伊维菌素和甲维盐可视为原来阿维菌素的升级改良产品。伊维菌素毒性较低，主要用于动物（且其结构更稳定，也是全球销量最大的阿维菌素系列之一）。相比之下，甲维盐活性比阿维菌素高很多（胃毒毒性是阿维菌素的2146倍），尤其对鳞翅目、双翅目和蓟马类害虫表现出极高的活性。例如，对于斜纹夜蛾等鳞翅目害虫，阿维菌素效果不佳，但甲维盐却是特效药。

适用作物

埃玛菌素适用于蔬菜、果树、烟草、茶树、花卉及大田作物（如水稻、棉花、玉米、小麦和大豆等）。

防治对象

甲维盐对多种害虫具有其他农药无法比拟的活性，尤其对鳞翅目、双翅目和蓟马类害虫效果超群。具体防治对象包括红带卷叶蛾、烟蚜夜蛾、棉铃虫、烟草天蛾、小菜蛾黏虫、甜菜夜蛾、旱地贪夜蛾、纷纹夜蛾、甘蓝银纹夜蛾、菜粉蝶、菜心螟、甘蓝横条螟、番茄天蛾、马铃薯甲虫、墨西哥瓢虫、红蜘蛛和食心虫等。

合成方法

甲氨基阿维菌素可从一种天然的土壤放射菌——链霉菌的发酵分离得到。

反应信息

• 作为反应物：
  描述：

  苯甲酸 、 4''-methylaminoavermectin 反应 2.0h， 以74.1%的产率得到emamectin benzoate
  参考文献：
  名称：

  一种改善其可加工性的甲维盐的合成方法

  摘要：

  本发明公开了一种改善其可加工性的甲维盐的合成方法，是以阿维菌素B1a为起始原料，依次经过氧化、氨化、还原和成盐四步反应过程获得甲维盐。本发明采用的技术方案合成操作便捷，较比传统路线简化了工艺步骤，降低了生产成本，并且获得了收率在70％以上、纯度达到95％以上的甲维盐纯品。

  公开号：

  CN112920233A
• 作为产物：
  描述：

  七甲基二硅氮烷 、 阿维菌素 在 盐酸 、 silver carbonate 、 二叔丁基过氧化物 、 氨 、 sodium t-butanolate 、 sodium tetrahydroborate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 1.5h， 生成 4''-methylaminoavermectin
  参考文献：
  名称：

  一种改善其可加工性的甲维盐的合成方法

  摘要：

  本发明公开了一种改善其可加工性的甲维盐的合成方法，是以阿维菌素B1a为起始原料，依次经过氧化、氨化、还原和成盐四步反应过程获得甲维盐。本发明采用的技术方案合成操作便捷，较比传统路线简化了工艺步骤，降低了生产成本，并且获得了收率在70％以上、纯度达到95％以上的甲维盐纯品。

  公开号：

  CN112920233A

文献信息

• PROCESS FOR PREPARING A NOVEL CRYSTALLINE FORM OF EMAMECTIN BENZOATE AND USE THE SAME
  申请人：ROTAM AGROCHEM INTERNATIONAL CO., LTD.

  公开号：US20160355538A1

  公开（公告）日：2016-12-08

  A crystalline modification V of emamectin benzoate, exhibiting at least 3 of the following reflexes in an X-ray powder diffractogram recorded using Cu—Kα radiation at 25° C.: 2θ=4.34±0.2   (1) 2θ=10.58±0.2   (2) 2θ=12.32±0.2   (3) 2θ=15.19±0.2   (4) 2θ=18.57±0.2   (5) 2θ=20.41±0.2   (6) A process for the preparation of emamectin benzoate in the aforementioned form comprises i) preparing a solution of a solid form of emamectin benzoate in a solvent comprising ethyl acetate and n-hexane; ii) effecting crystallization of emamectin benzoate from the solution; and iii) isolating the emamectin benzoate formed. The crystalline modification V can be formulated to any suitable pesticidal formulations.
• US9549554B2
  申请人：——

  公开号：US9549554B2

  公开（公告）日：2017-01-24
• US9643991B2
  申请人：——

  公开号：US9643991B2

  公开（公告）日：2017-05-09
• 一种改善其可加工性的甲维盐的合成方法
  申请人：吴霜

  公开号：CN112920233A

  公开（公告）日：2021-06-08

  本发明公开了一种改善其可加工性的甲维盐的合成方法，是以阿维菌素B1a为起始原料，依次经过氧化、氨化、还原和成盐四步反应过程获得甲维盐。本发明采用的技术方案合成操作便捷，较比传统路线简化了工艺步骤，降低了生产成本，并且获得了收率在70％以上、纯度达到95％以上的甲维盐纯品。