Gentamicin | 1403-66-3

• 物质功能分类: 原料药 - 抗生素类药物 - 氨基糖苷类药
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Gentamicin
• 英文别名: 2-[4,6-diamino-3-[3-amino-6-[1-(methylamino)ethyl]oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol
• CAS: 1403-66-3
• 化学式: C₂₁H₄₃N₅O₇
• 分子量: 477.6
• InChiKey: CEAZRRDELHUEMR-UHFFFAOYSA-N

物化性质

• 熔点：
  102-108°
• 比旋光度：
  D25 +146°
• 物理描述：
  Solid
• 颜色/状态：
  White amorphous powder
• 溶解度：
  100 mg/mL
• 蒸汽压力：
  1.75X10-13 mm Hg at 25 °C (est)
• 稳定性/保质期：
  Stable in light, air, and heat /Gentamycin sulfate/
• 旋光度：
  Specific optical rotation: +146 deg at 25 °C/D
• 分解：
  Melts with decomposition between 220 °C and 240 °C. /Gentamycin sulfate/
• 解离常数：
  pKb = 9.0 (amine moieties) (est)

计算性质

• 辛醇/水分配系数(LogP)：
  -4.1
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  200
• 氢给体数：
  8
• 氢受体数：
  12

ADMET

代谢

庆大霉素几乎不代谢。

Gentamicin undergoes little to no metabolism.

来源:DrugBank

代谢

庆大霉素不被代谢。它以活性、未改变的形式通过肾小球滤过被排出。

Gentamicin is not metabolized. It is excreted by glomerular filtration in an active, unchanged form.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

硫酸庆大霉素是一种氨基糖苷类抗生素。庆大霉素广泛用于治疗严重感染。它对许多革兰氏阴性细菌和金黄色葡萄球菌具有活性。它对厌氧菌无效，对溶血性链球菌和肺炎球菌的作用较差。人类暴露和毒性：主要风险和靶器官：主要的有毒效果包括前庭损伤、耳聋和肾功能不全。前庭部分的第八对脑神经损伤似乎大于耳蜗部分。主要的靶器官是第八对脑神经和肾脏。第八对脑神经（两个部分）损伤导致耳鸣、耳聋、恶心、呕吐、眩晕、头晕和眼球震颤，以及肾毒性导致的急性管状坏死进而导致肾衰竭。在接受庆大霉素治疗的病人中出现听力丧失、头晕、眩晕、共济失调、恶心、呕吐和肾功能损害提示庆大霉素中毒的诊断。其他有毒特征包括肌肉麻痹和呼吸抑制。由于庆大霉素在肾皮质中积累，当肾脏的浓缩能力受损时，就会达到临界浓度。肾毒性似乎与谷底血清浓度超过2微克/毫升的时间有关。确切的毒性机制尚不清楚。耳毒性和前庭毒性似乎与庆大霉素峰值浓度升高（大于10微克/毫升）的相关性最高。庆大霉素在内淋巴和周围淋巴中积累，导致室管膜和耳蜗细胞的逐渐破坏。重复使用庆大霉素可能会导致细胞逐渐破坏，导致耳聋。庆大霉素似乎对前庭部分的损伤大于耳蜗部分。神经肌肉阻滞伴急性肌肉麻痹和呼吸暂停可能会很少发生。大多数事件与麻醉或其他神经肌肉阻滞剂的给药有关，但在大剂量庆大霉素或其他氨基糖苷类药物腹膜内或胸膜内给药后也可能发生。这种现象可能在静脉或肌内给药后发生。动物研究：啮齿类动物的中毒症状包括惊厥、衰竭、活动减少、多饮、呼吸困难和不稳定。狗出现肌肉震颤、流涎和厌食。对在给药后13天内死亡的狗的肾脏进行组织病理学检查，发现近端曲小管坏死。每组3只雌性恒河猴肌肉注射0、6或30毫克/千克体重/天的庆大霉素，用水作溶剂，持续3周。不良临床体征仅限于30毫克/千克体重/天组，包括明显的面色苍白和眼睑下垂，从第20天起明显平衡失调，从第2周开始食欲减退和体重增加下降。电子显微镜检查30毫克/千克体重/天组的肾小管，发现管状细胞和管腔内存在骨髓小体，吞噬体增多，刷状缘消失，基底膜上的上皮细胞脱落。每组4只/性别/组的比格犬口服0、2、10或60毫克/千克体重/天的庆大霉素胶囊，持续14周。治疗犬偶尔观察到呕吐和腹泻。唯一的大体变化是在高剂量组2只动物中观察到间质性肾炎。庆大霉素对大鼠的精子参数和睾丸凋亡有负面影响。在2代大鼠研究中，未报告与治疗相关的妊娠率、窝大小和重量、胎前死亡或胎儿异常。庆大霉素在体外用中国仓鼠卵巢细胞以128-5000微克/毫升的浓度诱导正向基因突变的能力进行了测试，以800-5000微克/毫升的浓度诱导这些细胞的染色体畸变，无论是否进行代谢激活。它还在体内测试了以静脉内剂量20-80毫克/千克体重诱导小鼠骨髓细胞核异常的能力，最高剂量为最大耐受剂量。没有发现致突变活性。

IDENTIFICATION AND USE: Gentamicin sulfate is an aminoglycoside antibiotic. Gentamicin is widely used in the treatment of severe infections. It is active against many strains of Gram-negative bacteria and Streptococus aureus. It is inactive against anaerobes and poorly active against Streptococus hemolyticus and Pneumococcus. HUMAN EXPOSURE AND TOXICITY: Main risks and target organs: The main toxic effects are vestibular damage, deafness and renal dysfunction. The damage on the vestibular portion of the eighth cranial nerve appears to be greater than that on the cochlear portion. The main target organs are the eighth cranial nerves and the kidneys. Damage to eighth cranial nerve (both divisions) resulting in tinnitus, deafness, nausea, vomiting, vertigo, dizziness and nystagmus, and nephrotoxicity causing acute tubular necrosis resulting in renal failure. Loss of hearing, dizziness, vertigo, ataxia, nausea, vomiting and renal impairment developing in a patient on gentamicin therapy suggests a diagnosis of gentamicin toxicity. Other toxic features are muscular paralysis and respiratory depression. As gentamicin accumulates in the renal cortex, a critical concentration is reached when the concentrating ability of the kidney becomes impaired. Nephrotoxicity appears to be related to the duration for which the trough serum concentration exceeds 2 ug/ml. The exact mechanism of toxicity is unknown. Ototoxicity and vestibular toxicity seem most highly correlated with elevated peak concentrations (greater than 10 ug/mL) of gentamicin. Gentamicin accumulates in endolymph and perilymph and progressive destruction of ventricular and cochlear cells occurs. Repeated courses of gentamicin may produce progressive destruction of cells leading to deafness. Gentamicin appears to damage the vestibular portion more than the cochlear portion. Neuromuscular blockade with acute muscular paralysis and apnea may occur rarely. Most episodes have occurred in association with anesthesia or administration of other neuromuscular blockers but may also occur after intrapleural or intraperitoneal instillation of large doses of gentamicin or other aminoglycosides. This phenomenon may occur after intravenous or intramuscular administration. ANIMAL STUDIES: Clinical signs of intoxication in rodents included convulsions, prostration, hypoactivity, polydipsia, dyspnoea and ataxia. Dogs exhibited muscle tremors, salivation, and anorexia. Histopathological examination of kidneys from dogs that died up to 13 days after dosing revealed necrosis of the proximal convoluted tubule. Groups of 3 female Rhesus monkeys were injected i.m. with doses of 0, 6 or 30 mg/kg bw/day gentamicin in an aqueous vehicle for 3 weeks. Adverse clinical signs were limited to the 30 mg/kg bw/day group, which included pronounced facial paling and ptosis, markedly disturbed equilibrium from day 20, and depressed food intake and body- weight gain from week 2 onwards. Electron microscopy of renal tubules from the 30 mg/kg bw/day monkeys revealed myeloid bodies present in both tubular cells and lumen, increased phagosomes, disappearance of brush borders and sloughing of epithelial cells from the basement membrane. Groups of beagle dogs (4/sex/group) were administered oral doses of 0, 2, 10, or 60 mg/kg bw/day gentamicin in capsules for 14 weeks. Emesis and diarrhoea were observed occasionally in treated dogs. The only postmortem change was interstitial nephritis observed in 2 animals in the high-dose group. Gentamicin had negative effects on sperm parameters and testis apoptosis in rats. No treatment-related changes in pregnancy rate, litter size and weight, prenatal mortality or fetal abnormalities were reported in 2 generation study in rats. Gentamicin was tested in vitro for its ability to induce forward gene mutation in Chinese hamster ovary cells at concentrations of 128-5000 ug/mL and chromosomal aberrations in these cells at concentrations of 800-5000 ug/mL, both with and without metabolic activation. It was also tested in vivo for its ability to induce nuclear anomalies in mouse bone-marrow cells at intravenous doses of 20-80 mg/kg bw, the highest dose being the maximum tolerated dose. There was no indication of mutagenic activity.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 肝毒性

静脉和肌肉内给药庆大霉素已与血清碱性磷酸酶水平轻度和无症状升高有关联，但很少影响转氨酶水平或胆红素，且一旦停用庆大霉素，变化就会迅速解决。只有急性肝损伤伴黄疸的孤立病例报告与包括庆大霉素在内的氨基糖苷类治疗有关，其中大多数并不十分令人信服。这些报告中描述的肝脏损伤通常是混合型的，但可以演变为胆汁淤积性肝炎。发病的潜伏期很短，发生在1到3周内，通常伴有皮疹、发热，有时还伴有嗜酸性粒细胞增多。恢复通常发生在1到2个月内，没有描述慢性损伤。氨基糖苷类药物在大规模药物诱导的肝病和急性肝衰竭的病例系列中并未列出或提及；因此，如果发生，庆大霉素引起的肝损伤是罕见的。

Intravenous and intramuscular therapy with gentamicin has been linked to mild and asymptomatic elevations in serum alkaline phosphatase levels, but rarely affects aminotransferase levels or bilirubin, and changes resolve rapidly once gentamicin is stopped. Only isolated case reports of acute liver injury with jaundice have been associated with aminoglycoside therapy including gentamicin, most of which are not very convincing. The hepatic injury described in these reports is typically mixed but can evolve into a cholestatic hepatitis. The latency to onset is rapid, occurring within 1 to 3 weeks and is typically associated with skin rash, fever and sometimes eosinophilia. Recovery typically occurs within 1 to 2 months and chronic injury has not been described. Aminoglycosides are not listed or mentioned in large case series of drug induced liver disease and acute liver failure; thus, hepatic injury due to gentamicin is rare if it occurs at all.

来源:LiverTox

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：庆大霉素不易排入母乳中。新生儿显然会吸收少量庆大霉素，但每日三次剂量的血清水平远低于治疗新生儿感染时达到的水平，因此庆大霉素的系统效应不太可能发生。较大婴儿预计会吸收更少的庆大霉素。由于在多次每日剂量方案中，母乳中庆大霉素水平的变化很小，因此相对于剂量安排哺乳时间对减少婴儿暴露几乎没有或没有好处。对于单次每日剂量方案的数据尚未获得。监测婴儿可能出现对胃肠道菌群的影响，如腹泻、念珠菌病（例如，鹅口疮、尿布疹）或罕见的情况下，粪便中的血液表明可能存在抗生素相关性结肠炎。 母亲使用含有庆大霉素的耳滴或眼滴对哺乳婴儿几乎没有或没有风险。 ◉ 对哺乳婴儿的影响：一名5天大的婴儿出现血便，可能是由于同时母亲使用克林霉素和庆大霉素引起的。 一名从出生起就接受母乳喂养的2个月大婴儿。他的母亲在怀孕期间服用过许多药物，但她不记得它们的身份。她患有乳腺炎，并接受阿莫西林-克拉维酸1克口服，每12小时一次和庆大霉素160毫克肌肉注射，每日一次的治疗。婴儿在两种药物首次给药后15分钟开始哺乳，持续10分钟。大约20分钟后，婴儿出现了全身性荨麻疹，30分钟后消失。几个小时后，婴儿再次哺乳，15分钟后荨麻疹再次出现，1小时后消失。在改用配方奶喂养，并且婴儿不再接触青霉素后，反应没有再次出现，随访至16个月大。不良反应很可能是由于母乳中的抗生素引起的。导致反应的药物无法确定，但很可能是阿莫西林-克拉维酸。 ◉ 对泌乳和母乳的影响：截至修订日期，未找到相关已发布信息。

◉ Summary of Use during Lactation:Gentamicin is poorly excreted into breastmilk. Newborn infants apparently absorb small amounts of gentamicin, but their serum levels with three times daily dosages are far below those attained when treating newborn infections and systemic effects of gentamicin are unlikely. Older infants would be expected to absorb even less gentamicin. Because there is little variability in the milk gentamicin levels during multiple daily dose regimens, timing breastfeeding with respect to the dose is of little or no benefit in reducing infant exposure. Data are not available with single daily dose regimens. Monitor the infant for possible effects on the gastrointestinal flora, such as diarrhea, candidiasis (e.g., thrush, diaper rash) or rarely, blood in the stool indicating possible antibiotic-associated colitis. Maternal use of an ear drop or eye drop that contains gentamicin presents little or no risk for the nursing infant. ◉ Effects in Breastfed Infants:Bloody stools in one 5-day-old infant were possibly caused by concurrent maternal administration of clindamycin and gentamicin. A 2-month-old infant breastfed since birth. His mother had taken many medications during pregnancy, but she did not recall their identity. She developed mastitis and was treated with amoxicillin-clavulanic acid 1 gram orally every 12 hours and gentamicin 160 mg intramuscularly once daily. The infant was breastfed for 10 minutes starting 15 minutes after the first dose of both drugs. About 20 minutes later, the infant developed a generalized urticaria which disappeared after 30 minutes. A few hours later, the infant breastfed again and the urticaria reappeared after 15 minutes and disappeared after an hour. After switching to formula feeding and no further infant exposure to penicillins, the reaction did not reappear with follow-up to 16 months of age. The adverse reaction was probably caused by the antibiotics in breastmilk. The drug that caused the reaction cannot be determined, but it was most likely the amoxicillin-clavulanic acid. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 副作用

皮肤致敏剂 - 一种可以诱导皮肤产生过敏反应的制剂。

Skin Sensitizer - An agent that can induce an allergic reaction in the skin.

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 相互作用

一项体外研究显示，阿糖胞苷可能拮抗庆大霉素对肺炎克雷伯菌的活性。

One in vitro study indicates that cytarabine may antagonize the activity of gentamicin against Klebsiella pneumoniae.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 消除途径

庆大霉素主要通过肾脏排泄。在肾功能正常的患者中，初次给予的庆大霉素剂量的70%或更多可以在24小时内通过尿液回收。在肾功能损害的患者中，庆大霉素的排泄显著减少。

Gentamicin is excreted primarily by the kidneys. In patients with normal renal function, 70% or more of an initial gentamicin dose can be recovered in the urine within 24 hours. Excretion of gentamicin is significantly reduced in patients with renal impairment.

来源:DrugBank

吸收、分配和排泄

• 清除

庆大霉素的肾清除率与个体肌酐清除率相当。

The renal clearance of gentamicin is comparable to individual creatinine clearance.

来源:DrugBank

吸收、分配和排泄

静脉注射后，庆大霉素会分布到乳汁中。

/MILK/ Gentamicin is distributed into milk following IM administration.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

庆大霉素在肌肉注射或静脉注射后以低浓度分布到脑脊液（CSF）中。鞘内注射庆大霉素后脑脊液中的浓度取决于给药剂量、注射部位、稀释剂量的大小以及脑脊液流动是否受阻。患者之间的浓度可能会有很大差异。在一项研究中，鞘内注射4毫克庆大霉素导致脑脊液中药物浓度在8小时内为19-46微克/毫升，在20小时时小于3微克/毫升。庆大霉素可穿过胎盘。

Gentamicin is distributed into cerebrospinal fluid (CSF) in low concentrations following IM or IV administration. CSF concentrations of gentamicin following intrathecal administration depend on the dose administered, the site of injection, the volume in which the dose is diluted, and the presence or absence of obstruction to CSF flow. There may be considerable interpatient variation in concentrations achieved. In one study, intrathecal administration of 4 mg of gentamicin resulted in CSF concentrations of the drug of 19-46 ug/mL for 8 hours and less than 3 ug/mL at 20 hours. Gentamicin crosses the placenta.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

静脉注射常规剂量的庆大霉素后，该药物可以在淋巴、皮下组织、肺、痰、支气管、胸膜、心包、滑膜、腹水和腹膜液中检测到。胆汁中的浓度可能较低，提示胆汁排泄量最小。在接受静脉注射庆大霉素（240毫克，每日一次）的呼吸机相关肺炎患者中，肺泡衬液中的药物浓度是血清浓度的32%，在给药后2小时平均为4.24微克/毫升。静脉或肌肉注射庆大霉素后，眼部组织中仅达到极低浓度。

Following parenteral administration of usual dosages of gentamicin, the drug can be detected in lymph, subcutaneous tissue, lung, sputum, and bronchial, pleural, pericardial, synovial, ascitic, and peritoneal fluids. Concentrations in bile may be low, suggesting minimal biliary excretion. In patients with ventilator-associated pneumonia receiving IV gentamicin (240 mg once daily), drug concentrations in alveolar lining fluid were 32% of serum concentrations and averaged 4.24 ug/mL 2 hours after a dose. Only minimal concentrations of gentamicin are attained in ocular tissue following IM or IV administration.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  3004909090

制备方法与用途

氨基苷类抗生素：庆大霉素 庆大霉素简介

庆大霉素（Gentamicin）是中国独立自主研制成功的广谱抗生素，是新中国成立以来的伟大科技成果之一。它开始于1967年的研发，并在1969年底成功鉴定并命名“庆大霉素”，意指庆祝“九大”以及庆祝工人阶级的伟大。庆大霉素系从放线菌科单孢子属发酵培养液中提取的碱性化合物，是常用的氨基糖苷类抗生素。

庆大霉素主要用于治疗细菌感染，特别是革兰氏阴性菌引起的感染，并且因其热稳定性而广泛应用于培养基配置。

庆大霉素与β内酰胺类抗生素联合使用

庆大霉素常与其他β内酰胺类抗生素（如青霉素或头孢菌素）联合使用。在兽医临床中，它通常用来治疗败血症、尿路感染和心内膜炎等疾病，并且适用于葡萄球菌感染及其他类型细菌引起的局部或系统性感染。

联合用药与相互作用 与其他抗生素的协同效应

• 庆大霉素与足量羧苄西林联合使用对铜绿假单胞菌某些敏感菌株具有协同抗菌作用。
• 与青霉素联用可能对粪球菌及其变种如屎球菌、坚忍球菌具有协同抗菌作用。

毒性相互影响

• 庆大霉素与其他氨基糖苷类抗生素合用或先后连续应用，可能会增加耳毒性、肾毒性和神经肌肉阻滞的作用。
• 与卷曲霉素、顺铂、依他尼酸、呋塞米等药物合用时也可能增强毒性。

其他相互作用

• 与两性霉素B、头孢噻吩、头孢唑林、右旋糖酐同用或先后使用可能加重肾毒性。
• 与多粘菌素类注射剂合用可增加肾毒性和神经肌肉阻滞作用。
• 与其他具有神经肌肉阻滞作用的药物如地西泮联用，可能会加重此副作用。

不良反应

庆大霉素的不良反应包括耳毒性、肾毒性及神经肌肉阻滞等。当血药峰浓度超过12μg/ml时，谷浓度超过2μg/ml以上的情况下可能发生毒性反应。因此对于肾功能不全或长期用药者应进行药物监测。

治疗用途

庆大霉素主要用于治疗由大肠埃希菌、产气杆菌等革兰氏阴性菌引起的系统或局部感染（对中枢感染无效）。此外，它也适用于败血症、尿路感染和葡萄球菌感染等情况。在特定情况下，庆大霉素还可能用于其他类型的细菌感染。

药物相互作用

• 庆大霉素与青霉素联用可能会增强粪球菌及其变种的抗菌效果。
• 与足量羧苄西林合用可以增强对铜绿假单胞菌某些敏感菌株的抗菌效果。

反应信息

• 作为反应物：
  描述：

  rifampicin 、 卡那霉素碱 、 Gentamicin 、 羧苄西林 在 Mg SO4 、 ( ii ) 、 甘油 、 2-吗啉乙磺酸 、 葡萄糖 、 头孢噻肟 作用下， 反应 124.25h， 以The number of Leu+ transformed RSY12 colonies obtained in this way的产率得到L-亮氨酸
  参考文献：
  名称：

  Transformation of eukaryotic cells by mobilizable plasmids

  摘要：

  通过一种类似于共轭的过程向真核细胞转移遗传物质，特别是一种部分基于农杆菌样转移系统的系统。使用可移动但非共轭质粒通过农杆菌毒力系统将遗传物质转移到植物细胞的方法。将遗传物质转移到真核宿主细胞的方法，不是来自农杆菌T边界包围的典型T-DNA，而是通过可移动质粒提供遗传物质，该质粒能够形成松弛体，将可移动质粒带入具有至少与可移动质粒上不存在的农杆菌转移基因活性的农杆菌中，在其中也存在提供与功能性VirB操纵子相同或相似活性的必要基因产物，并将农杆菌与真核宿主细胞共培养。

  公开号：

  US20030087439A1
• 作为产物：
  描述：

  Chloroform methanol water 、 反式-2-十二碳烯二酸 、 氯仿 、 水合茚三酮 、 Gentamicin, sulfate (salt) 以 甲醇 为溶剂， 生成 Gentamicin
  参考文献：
  名称：

  Trans and cis traumatic acid salts having cicatrizant activity

  摘要：

  创伤酸盐，其中B是从以下选择的阳离子：a）季铵盐，b）线性或支链C.sub.1-C.sub.20单，二或三烷基醇胺的阳离子，c）生物活性的一级、二级或三级胺的阳离子，d）银或锌阳离子，并且具有局部或静脉途径可给药的相关药物组合物，用于治疗皮肤病变，其中重要的是将抗菌，抗生素，抗真菌或抗病毒活性与创伤酸的愈合效果相结合。

  公开号：

  US05567716A1

文献信息

• [EN] ISOTHIAZOLOQUINOLONES AND RELATED COMPOUNDS AS ANTI-INFECTIVE AGENTS<br/>[FR] ANTI-INFECTIEUX A BASE D'ISOTHIAZOLOQUINOLONES ET DE SELS CORRESPONDANTS
  申请人：ACHILLION PHARMACEUTICALS INC

  公开号：WO2005019228A1

  公开（公告）日：2005-03-03

  The invention provides compounds and salts of Formula (I) and Formula (II): which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula (I) and Formula (II). The variables A1, R2, R3, R5, R6, R7, A8 and R9 are defined herein. Certain compounds of Formula (I) and Formula (II) disclosed herein are potent and selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula (I) or Formula (II) and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula (I) or Formula (II) as the only active agent or may contain a combination of a compound of Formula (I) or Formula (II) and one or more other active agents. The invention also provides methods for treating microbial infections in animals.

  本发明提供了具有抗菌活性的公式(I)和公式(II)的化合物及盐类：本发明还提供了用于制造公式(I)和公式(II)化合物的新的合成中间体。变量A1、R2、R3、R5、R6、R7、A8和R9在此文中定义。本文披露的某些公式(I)和公式(II)化合物是细菌DNA合成和细菌复制的强效和选择性抑制剂。本发明还提供了含有一种或多种公式(I)或公式(II)化合物以及一种或多种载体、辅料或稀释剂的抗菌组合物，包括药物组合物。这样的组合物可以只含有公式(I)或公式(II)的化合物作为唯一的活性成分，也可以含有公式(I)或公式(II)的化合物与一种或多种其他活性成分的组合。本发明还提供了用于治疗动物微生物感染的方法。
• Non-Polymeric Compositions for Controlled Drug Delivery
  申请人：Li Yuhua

  公开号：US20100034801A1

  公开（公告）日：2010-02-11

  The present invention provides a novel liquid composition suitable for in-situ formation of a depot system to deliver a bioactive substance in a controlled manner. The composition of the present invention comprises: (a) a hydrophobic non-polymeric carrier material; (b) a water miscible biocompatible organic solvent that dissolves the hydrophobic non-polymeric material; (c) an ionic complex that is formed between an amphiphilic molecule and a bioactive substance having a net charge at neutral pH in water. The present invention also provides a method of manufacturing and use of the composition thereof.

  本发明提供了一种新型液体组合物，适用于原位形成沉积系统，以控制方式释放生物活性物质。本发明的组合物包括：（a）疏水性非聚合载体材料；（b）可溶解疏水性非聚合材料的水亲和性生物相容性有机溶剂；（c）在中性pH下在水中具有净电荷的两性分子和生物活性物质之间形成的离子复合物。本发明还提供了该组合物的制造方法和使用方法。
• 8-N-substituted-2H-isothiazolo[5,4-b]quinolizine-3,4-diones and related compounds as antiinfective agents
  申请人：Bradbury J. Barton

  公开号：US20060173026A1

  公开（公告）日：2006-08-03

  The invention provides compounds and salts of Formula I and Formula II: which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula I and Formula II. The variables A 1 , A 8 , R 2 , R 3 , R 5 , R 6 , R 7 , and R 9 are defined herein. Certain compounds of Formula I and Formula II disclosed herein are potent and selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula I or Formula II and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula I or Formula II as the only active agent or may contain a combination of compounds of Formula I and/or Formula II and one or more other active agents. The invention also provides methods for treating microbial and protozoal infections in animals.

  该发明提供了具有抗微生物活性的化合物和盐，其化学结构分别为公式I和公式II。该发明还提供了在制备公式I和公式II化合物中有用的新型合成中间体。变量A1，A8，R2，R3，R5，R6，R7和R9在此处有定义。本文披露的公式I和公式II的某些化合物是细菌DNA合成和细菌复制的有效和选择性抑制剂。该发明还提供了包含公式I或公式II化合物以及一个或多个载体、赋形剂或稀释剂的抗微生物组合物，包括制药组合物。这些组合物可以含有公式I或公式II化合物作为唯一活性剂，也可以含有公式I和/或公式II化合物以及一个或多个其他活性剂的组合。该发明还提供了治疗动物微生物和原虫感染的方法。
• [EN] MODULATION OF IMMUNE RESPONSES BY ADMINISTRATION OF ROXITHROMYCIN OR ITS DERIVATIVE<br/>[FR] MODULATION DES RÉPONSES IMMUNES PAR ADMINISTRATION DE ROXITHROMYCINE OU DE SES DÉRIVÉS
  申请人：Y S THERAPEUTICS CO LTD

  公开号：WO2009023196A1

  公开（公告）日：2009-02-19

  Provided are compounds of formula (III) useful for modulation of immune responses, compositions comprising the compounds, and methods of use of such compositions for treating diseases or disorders involving an immune response. In certain embodiments, the compounds are useful for the treatment of diseases or disorders associated with transendothelial migration of T cells and activated T cells, and proinflammatory cytokine production from T cells and macrophages. Diseases or disorders that can be treated include arthritic and rheumatic disorders, such as rheumatoid arthritis.

  提供的是化合物的公式（III），用于调节免疫反应，包含这些化合物的组合物，以及使用这些组合物治疗涉及免疫反应的疾病或紊乱的方法。在某些实施例中，这些化合物可用于治疗与T细胞和活化T细胞的经内皮迁移以及T细胞和巨噬细胞的促炎细胞因子产生相关的疾病或紊乱。可以治疗的疾病或紊乱包括关节炎和风湿性疾病，如类风湿性关节炎。
• 8A,9-dihydro-4aH-isothiazolo[5,4-b]quinoline-3,4-diones and related compounds as anti-infective agents
  申请人：Bradbury J. Barton

  公开号：US20060100215A1

  公开（公告）日：2006-05-11

  The invention provides compounds and salts of Formula I and Formula II: which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula I and Formula II. The variables n, m, p, R A , R B , A 1 , R 2 , R 3 , R 5 , R 6 , R 7 , A 8 and R 9 are defined herein. Certain compounds of Formula I and Formula II disclosed herein are potent and/or selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula I or Formula II and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula I or Formula II as the only active agent or may contain a combination of a compound of Formula I or Formula II and one or more other active agents. The invention also provides methods for treating microbial infections in eukaryotes.

  该发明提供了化合物和盐的公式I和公式II：具有抗微生物活性。该发明还提供了在制备公式I和公式II化合物中有用的新型合成中间体。这里定义了变量n、m、p、RA、RB、A1、R2、R3、R5、R6、R7、A8和R9。本文披露的公式I和公式II的某些化合物是细菌DNA合成和细菌复制的有效和/或选择性抑制剂。该发明还提供了抗微生物组合物，包括含有一个或多个公式I或公式II化合物和一个或多个载体、赋形剂或稀释剂的制药组合物。这些组合物可能仅含有公式I或公式II化合物作为唯一活性剂，也可能含有公式I或公式II化合物与一个或多个其他活性剂的组合。该发明还提供了治疗真核生物微生物感染的方法。