Framycetin sulphate | 1405-10-3

• 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: Framycetin sulphate
• 英文别名: (2R,3S,4R,5R,6R)-5-amino-2-(aminomethyl)-6-[(1R,2R,3S,4R,6S)-4,6-diamino-2-[(2S,3R,4S,5R)-4-[(2R,3R,4R,5S,6S)-3-amino-6-(aminomethyl)-4,5-dihydroxyoxan-2-yl]oxy-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-3-hydroxycyclohexyl]oxyoxane-3,4-diol;sulfuric acid
• CAS: 1405-10-3
• 化学式: C23H52N6O25S3
• 分子量: 908.9
• InChiKey: KWBUARAINLGYMG-JGMIRXPNSA-N

物化性质

• 熔点：
  >187°C (dec.)
• 比旋光度：
  D20 +54° (c = 2 in H2O)
• 闪点：
  56℃
• 溶解度：
  H2O: 50 mg/mL 作为储备液。储备液应过滤灭菌并储存在 2-8°C。在 37°C 下稳定 5 天。
• LogP：
  -3.655 (est)
• 蒸汽压力：
  1.60X10-28 mm Hg at 25 °C (est)
• 稳定性/保质期：
  Hygroscopic. /Neomycin sulfate/
• 分解：
  When heated to decomposition it emits acrid smoke and irritating fumes.
• 解离常数：
  pKa = 12.9; pKb = 9.52 (25 °C)

计算性质

• 辛醇/水分配系数(LogP)：
  -10.85
• 重原子数：
  57
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  602
• 氢给体数：
  19
• 氢受体数：
  31

ADMET

代谢

氨基糖苷类药物不被代谢，主要通过肾小球滤过并以原形在尿液中排出。/氨基糖苷类/

Aminoglycosides are not metabolized and are excreted unchanged in the urine primarily by glomerular filtration. /Aminoglycosides/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 肝毒性

口服和局部使用新霉素尚未与血清碱性磷酸酶或转氨酶升高有关联，并且尚未有令人信服的因口服新霉素导致的有症状或黄疸性肝毒性的案例发表。新霉素吸收不良使得达到可能引起肝损伤的药物系统水平不太可能。此外，在肝毒性发生之前，吸收的新霉素的耳毒性可能会先出现。 关于新霉素的安全性和潜在肝毒性的参考资料，请参见氨基糖苷类药物概述部分。 药物类别：氨基糖苷类 同类其他药物：阿米卡星、庆大霉素、普拉佐米星、链霉素、妥布霉素

Oral and topical therapy with neomycin has not been linked serum alkaline phosphatase or aminotransferase elevations, and no convincing cases of symptomatic or icteric hepatotoxicity due to oral neomycin have been published. The poor absorption of neomycin makes it unlikely that systemic levels of the drug that might cause liver injury could be achieved. Furthermore, the ototoxicity of absorbed neomycin is likely to supervene before liver toxicity would occur. References to the safety and potential hepatotoxicity of neomycin are provided in the Overview section on the Aminoglycosides. Drug Class: Aminoglycosides Other Drugs in the Class: Amikacin, Gentamicin, Plazomicin, Streptomycin, Tobramycin

来源:LiverTox

毒理性

• 相互作用

六价阳离子糖苷类抗生素新霉素对血小板生理反应的影响，如聚集和分泌，以及磷脂酰肌醇代谢的变化进行了研究。新霉素强烈抑制了凝血酶诱导的聚集和分泌，而该抗生素对离子霉素或TPA诱导的血小板功能没有影响。凝血酶诱导的肌醇磷脂代谢增强被新霉素的存在强烈抑制，而TPA或离子霉素诱导的肌醇(32)P-聚磷脂增加未受影响。比较了其他一些糖苷类抗生素的抑制作用与新霉素的抑制作用，数据显示，对血小板分泌和磷脂酸生成的抑制取决于抗生素的阳离子电荷。

The effect of the hexacationic aminoglycoside antibiotic, neomycin, on platelet physiological responses, such as aggregation and secretion, as well as changes in phosphoinositide metabolism was studied. Neomycin strongly inhibited thrombin-induced aggregation and secretion whereas the antibiotic had no effect on ionomycin- or TPA-induced platelet functions. The thrombin-induced enhancement of inositol phospholipid metabolism was strongly inhibited by the presence of neomycin whereas the TPA- or ionomycin-induced increase in inositol (32)P-polyphospholipids remained unaffected. The inhibitory effect of some other aminoglycoside antibiotics was compared to that of neomycin and the data demonstrate that the inhibition of platelet secretion and phosphatidic acid production was dependent on the cationic charge of the antibiotic.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

口服新霉素可能会增强口服抗凝剂的效果，可能是通过干扰胃肠道对维生素K的吸收或合成。在接受口服氨基糖苷类和口服抗凝剂联合治疗的患者中，应监测凝血酶原时间，并根据需要调整抗凝剂的剂量。

Oral neomycin may potentiate the effects of oral anticoagulants, possibly by interfering with GI absorption or synthesis of vitamin K. Prothrombin times should be monitored in patients receiving concomitant oral aminoglycoside and oral anticoagulant therapy, and dosage of the anticoagulant should be adjusted as required.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

新霉素（I）和红霉素（II）的系统水平在8名接受结肠手术的患者中进行研究，这些患者在手术前19、18和9小时分别口服了硫酸新霉素（Mycifradin）和红霉素碱（E-Mycin），每种一片，每片一克。在初次给药后的26小时内，从每位患者的血清中采集了12个样本，伤口肌肉中采集了1个样本，肠壁中采集了1个样本。观察到水平之间存在较大差异。计算出的平均值如下：血清峰值水平分别为3.4和0.59微克/毫升，肌肉水平分别为1.68和0.23微克/克，肠壁水平分别为6.4和12.9微克/克，分别对应II和I。观察到达到峰值水平的时间分别为初次给药后19小时和12小时，分别对应II和I。当这些药物口服用于结肠手术前的肠道准备时，产生的可检测系统浓度可能有助于药物的疗效。

Systemic levels of neomycin (I) and erythromycin (II) were studied in 8 patients undergoing colon surgery who received oral neomycin sulfate (Mycifradin) and erythromycin base (E-Mycin), one g tablet each, 19, 18 and 9 hr preoperatively. Twelve samples from serum, one from wound muscle and one from the intestinal wall were obtained from each patient in the 26 hr after the initial dose. Considerable variation was observed among levels. The following means were calculated: peak serum levels were 3.4 and 0.59 ug/mL, muscle levels were 1.68 and 0.23 ucg/g and intestinal wall levels were 6.4 and 12.9 ug/g for II and I respectively. Observed times to peak levels were 19 and 12 hr after the initial dose for II and I respectively. The detectable systemic concentrations that result when these agents are given orally for bowel preparation before colon surgery may contribute to the drugs' efficacy.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

尽管临床重要性尚不清楚，但据报道口服新霉素会减少地高辛的胃肠道吸收，但显然不影响地高辛的终末血浆半衰期。在接受口服新霉素的患者中，应监测血清地高辛浓度。

Although the clinical importance is unclear, oral neomycin has been reported to decrease GI absorption of digoxin, but apparently does not affect the terminal plasma half-life of digoxin. Serum digoxin concentrations should be monitored in patients receiving oral neomycin.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

硫酸新霉素从正常的胃肠道的吸收较差。被吸收的小部分会迅速分布到组织中，并通过肾脏排出，排出的量与肾脏功能程度相一致。药物未被吸收的部分（大约97%）以原形在粪便中排出。

Neomycin sulfate is poorly absorbed from the normal gastrointestinal tract. The small absorbed fraction is rapidly distributed in the tissues and is excreted by the kidney in keeping with the degree of kidney function. The unabsorbed portion of the drug (approximately 97%) is eliminated unchanged in the feces.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

与其他氨基糖苷类药物一样，系统性吸收的链霉素转移到组织中的量随着每次重复剂量的增加而累积增加，直到达到稳态。肾脏作为主要的排泄途径和组织结合位点，在肾皮质中浓度最高。随着重复给药，内耳中也会逐渐积累。停止给药后，组织结合的链霉素会缓慢地在几周内释放。

As with other aminoglycosides, the amount of systemically absorbed neomycin transferred to the tissues increases cumulatively with each repeated dose administered until a steady state is achieved. The kidney functions as the primary excretory path as well as the tissue binding site, with the highest concentration found in the renal cortex. With repeated dosings, progressive accumulation also occurs in the inner ear. Release of tissue-bound neomycin occurs slowly over a period of several weeks after dosing has been discontinued.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在一项针对肾功能正常的成年人的研究中，单次口服硫酸新霉素4克后，大多数患者在1-4小时内达到2.5-6.1微克/毫升的血浆新霉素峰值浓度；在8小时时可以检测到较低的血药浓度，但在24小时时药物已检测不到。

In one study in adults with normal renal function, a single 4-g oral dose of neomycin sulfate produced peak plasma neomycin concentrations of 2.5-6.1 ug/mL 1-4 hours after the dose in most patients; low plasma concentrations of the drug were detectable at 8 hours but the drug was undetectable at 24 hours.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在接受1克口服硫酸新霉素和1克口服红霉素的成人中，分别于结肠直肠手术前19、18和9小时给药，硫酸新霉素的平均峰值血清浓度为0.59微克/毫升，在第一次给药后12小时达到（即第三次给药后2小时）。

In adults who received 1-g doses of oral neomycin sulfate and 1-g doses of oral erythromycin at 19, 18, and 9 hours before colorectal surgery, mean peak serum concentrations of neomycin were 0.59 ug/mL and were attained 12 hours after the first dose (i.e., 2 hours after the third dose).

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 危险品标志：
  Xn
• 安全说明：
  S22,S23,S24/25,S36,S36/37,S45
• 危险类别码：
  R42/43
• WGK Germany：
  3
• 海关编码：
  2941909000
• 危险品运输编号：
  NONH for all modes of transport
• RTECS号：
  QP4375000
• 危险标志：
  GHS08
• 危险性描述：
  H317,H334
• 危险性防范说明：
  P261,P280,P342 + P311

制备方法与用途

简介

硫酸新霉素是一种氨基糖苷类抗生素。它对葡萄球菌属（甲氧西林敏感株）、棒状杆菌属、大肠埃希菌、克雷伯菌属和变形杆菌属等肠杆菌科细菌具有良好的抗菌作用，但对链球菌组、肺炎链球菌、肠球菌属等细菌的活性较差。铜绿假单胞菌和厌氧菌对该品耐药。细菌对链霉素、新霉素以及卡那霉素、庆大霉素之间存在部分或完全交叉耐药性。

生物活性

Neomycin硫酸盐属于氨基糖苷类抗生素。

体外研究

Neomycin优先与核酶-底物复合物相互作用，这种相互作用导致切割率降低，通过稳定复合物的基态并使裂解步骤的过渡状态变得不稳定来实现。Neomycin引起反式激活区（TAR）结构构象的变化，可以通过圆二色光谱检测到。Neomycin作为非竞争性抑制剂结合到Tat-TAR复合物中，并增加RNA和肽的解离速率常数（Koff）。Neomycin是效果最显著的氨基糖苷类（沟结合物），用于稳定DNA的三股螺旋。与已知的小沟结合剂相比，它能更好地稳定TAT三螺旋，同时也能稳定CGC（+）三螺旋。在电压和浓度依赖性下，Neomycin诱导胞质和管腔面的部分通道抑制作用。在管腔内，其亲和力大于胞质：零电压下的离解常数(Kb(0))分别是210.2 nM和589.7 nM。在电位大于60 mV时，Neomycin表现出电压依赖性缓解抑制作用。

用途

硫酸新霉素是一种广谱抗生素，对金黄色葡萄球菌、白喉杆菌和炭疽杆菌具有良好的抗菌效果。

它还被用作一种氨基糖苷类抗生素，在不干扰神经元Na+/Ca2+反向转运蛋白（antiporter）的情况下阻断电压敏感的钙通道。结合到核糖体30S 和 50S 亚单位引起蛋白质错误编码；在蛋白质合成过程中抑制起始和延长。其抗菌谱包括革兰氏阴性和阳性细菌。

此外，它用于防治猪、鸡、牛等畜禽因大肠杆菌、沙门氏菌导致的痢疾、腹泻和发育不良等疾病，并可用于鱼虾肠炎的治疗。