左布比卡因 | 27262-47-1

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 左布比卡因
• 中文别名: 1-丁基-N-(2,6-二甲基苯基)-哌啶-2-甲酰胺；左旋布比卡因；LEVOBUPIVACAINE左布比卡因
• 英文名称: levobupivacaine
• 英文别名: (S)-bupivacaine；(-)-Bupivacaine；L-bupivacaine；(S)-1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide；(2S)-1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide
• CAS: 27262-47-1
• 化学式: C₁₈H₂₈N₂O
• 分子量: 288.433
• InChiKey: LEBVLXFERQHONN-INIZCTEOSA-N

物化性质

• 熔点：
  136-137°C
• 比旋光度：
  D25 -80.9° (c = 5 in methanol)
• 沸点：
  430.65°C (rough estimate)
• 密度：
  1.0238 (rough estimate)
• 溶解度：
  DMSO:58.0(最大浓度 mg/mL);201.09(最大浓度 mM)乙醇:58.0(最大浓度 mg/mL);201.09(最大浓度 mM)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

左布比卡因被广泛代谢，尿液中或粪便中没有检测到未改变的左布比卡因。使用[14 C]左布比卡因的体外研究表明，CYP3A4同种型和CYP1A2同种型分别介导左布比卡因代谢为脱丁基左布比卡因和3-羟基左布比卡因。在体内，3-羟基左布比卡因似乎会进一步转化为葡萄糖醛酸苷和硫酸盐结合物。左布比卡因到R(+)-布比卡因的代谢反转在体外和体内均不明显。

Levobupivacaine is extensively metabolized with no unchanged levobupivacaine detected in urine or feces. In vitro studies using [14 C] levobupivacaine showed that CYP3A4 isoform and CYP1A2 isoform mediate the metabolism of levobupivacaine to desbutyl levobupivacaine and 3-hydroxy levobupivacaine, respectively. In vivo, the 3-hydroxy levobupivacaine appears to undergo further transformation to glucuronide and sulfate conjugates. Metabolic inversion of levobupivacaine to R(+)-bupivacaine was not evident both in vitro and in vivo.

来源:DrugBank

代谢

左布比卡因已知的人类代谢物包括N-(2,6-二甲基苯基)哌啶-2-甲酰胺。

Levobupivacaine has known human metabolites that include N-(2,6-Dimethylphenyl)piperidine-2-carboxamide.

来源:NORMAN Suspect List Exchange

代谢

左布比卡因被广泛代谢，尿液中或粪便中没有检测到未改变的左布比卡因。使用[14C]左布比卡因的体外研究表明，CYP3A4同种型和CYP1A2同种型分别介导左布比卡因代谢为去丁基左布比卡因和3-羟基左布比卡因。在体内，3-羟基左布比卡因似乎会进一步转化为葡萄糖醛酸和硫酸结合物。左布比卡因到R(+)-布比卡因的代谢反转在体外和体内均不明显。 消除途径：静脉给药后，放射性标记剂量的左布比卡因的回收基本上是定量的，大约95%的平均总量在48小时内通过尿液和粪便回收。在这95%中，大约71%在尿液中，而24%在粪便中。 半衰期：3.3小时

Levobupivacaine is extensively metabolized with no unchanged levobupivacaine detected in urine or feces. In vitro studies using [14 C] levobupivacaine showed that CYP3A4 isoform and CYP1A2 isoform mediate the metabolism of levobupivacaine to desbutyl levobupivacaine and 3-hydroxy levobupivacaine, respectively. In vivo, the 3-hydroxy levobupivacaine appears to undergo further transformation to glucuronide and sulfate conjugates. Metabolic inversion of levobupivacaine to R(+)-bupivacaine was not evident both in vitro and in vivo. Route of Elimination: Following intravenous administration, recovery of the radiolabelled dose of levobupivacaine was essentially quantitative with a mean total of about 95% being recovered in urine and feces in 48 hours. Of this 95%, about 71% was in urine while 24% was in feces. Half Life: 3.3 hours

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

左布比卡因是一种胆碱酯酶或乙酰胆碱酯酶（AChE）抑制剂。胆碱酯酶抑制剂（或“抗胆碱酯酶”）抑制乙酰胆碱酯酶的作用。由于其基本功能，干扰乙酰胆碱酯酶作用的化学物质是强大的神经毒素，在低剂量时导致过度流涎和流泪，随后是肌肉痉挛，最终导致死亡。神经气体和许多用于杀虫剂的物质已被证明通过结合乙酰胆碱酯酶活性位点的丝氨酸，完全抑制该酶。乙酰胆碱酯酶分解神经递质乙酰胆碱，后者在神经和肌肉接头处释放，以允许肌肉或器官放松。乙酰胆碱酯酶抑制的结果是乙酰胆碱积聚并继续发挥作用，使得任何神经冲动不断传递，肌肉收缩不会停止。最常见的乙酰胆碱酯酶抑制剂之一是基于磷的化合物，它们被设计用来结合到酶的活性位点上。结构要求是一个带有两个亲脂性基团的磷原子，一个离去基团（如卤素或硫氰酸盐），以及一个末端的氧。

Levobupivacaine is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

急性接触胆碱酯酶抑制剂可能会导致胆碱能危象，表现为严重的恶心/呕吐、流涎、出汗、心动过缓、低血压、崩溃和抽搐。肌肉无力可能性增加，如果呼吸肌受到影响，可能会导致死亡。在运动神经积累的乙酰胆碱会导致神经肌肉接头处尼古丁受体的过度刺激。当这种情况发生时，可以看到肌肉无力、疲劳、肌肉痉挛、肌束震颤和麻痹的症状。当自主神经节积累乙酰胆碱时，这会导致交感系统中尼古丁受体的过度刺激。与此相关的症状包括高血压和低血糖。由于乙酰胆碱积累，中枢神经系统中尼古丁乙酰胆碱受体的过度刺激会导致焦虑、头痛、抽搐、共济失调、呼吸和循环抑制、震颤、全身无力，甚至可能昏迷。当由于乙酰胆碱过量在毒蕈碱乙酰胆碱受体上出现毒蕈碱过度刺激时，可能会出现视力障碍、胸部紧绷、由于支气管收缩引起的喘息、支气管分泌物增加、唾液分泌增加、流泪、出汗、肠蠕动和排尿的症状。对于男性和女性的生育、生长和发育，某些生殖效应与有机磷农药暴露有特定联系。关于生殖效应的大多数研究都是在农村地区使用农药和杀虫剂的农民中进行的。在女性中，月经周期紊乱、怀孕时间延长、自然流产、死产以及后代的一些发育效应与有机磷农药暴露有关。产前暴露与胎儿生长和发育受损有关。神经毒性效应也与有机磷农药中毒有关，在人类中引起四种神经毒性效应：胆碱能综合症、中间综合症、有机磷诱导的迟发性多发性神经病（OPIDP）和慢性有机磷诱导的神经精神障碍（COPIND）。这些综合症在急性 and 慢性暴露于有机磷农药后出现。

Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 在妊娠和哺乳期间的影响

哺乳期使用概要：左旋布比卡因在美国已不再销售。在母乳中的水平较低，且婴儿口服吸收不良。布比卡因是右旋和左旋布比卡因的消旋混合物，在哺乳的婴儿中没有引起任何不良反应。 一些报告称，在分娩和接生时使用局部麻醉药与其他麻醉药和镇痛药可能会干扰哺乳。然而，这种评估是有争议和复杂的，因为研究了多种不同的药物组合、剂量和患者群体，以及使用的各种技术。相比之下，脐带结扎后开始的硬脊膜外麻醉药似乎提高了哺乳成功率，因为疼痛控制得到改善。总的来说，在有良好的哺乳支持下，硬脊膜外左旋布比卡因（或不加芬太尼或其衍生物）对哺乳成功率几乎没有或没有不良影响。分娩 劳动疼痛药物可能会延迟哺乳的开始。在一项研究中，剖宫产后将左旋布比卡因伤口浸润加入到多模式镇痛中改善了哺乳的舒适度。 对哺乳婴儿的影响：截至修订日期，没有找到关于左旋布比卡因的相关已发布信息。然而，通过胸膜内或硬脊膜外途径给母亲注射布比卡因对13名哺乳婴儿没有影响。 对哺乳和母乳的影响：对209名接受分娩硬脊膜外镇痛和157名未接受分娩硬脊膜外镇痛的便利样本非随机妇女进行分析，以确定硬脊膜外麻醉是否影响哺乳的开始。虽然未标准化，但典型的程序使用舒芬太尼10至15毫克，同时使用罗哌卡因0.1%或左旋布比卡因0.0625%硬脊膜外给药，每2小时补充硬脊膜外注射罗哌卡因0.1%或左旋布比卡因0.0625%。两组之间哺乳开始的时间没有发现差异。尽管两组妇女在分娩前都表示希望哺乳，但在接受硬脊膜外麻醉的妇女中，产后20天纯哺乳的比例（43%）低于未接受硬脊膜外麻醉的妇女（57%）。 在一项对中国接受剖宫产的妇女进行的随机、非盲研究中，接受术后伤口浸润左旋布比卡因的妇女。在伤口切口侧方5厘米处皮下注入50毫克，随后以6.25毫克/小时的速度持续48小时。额外的镇痛包括对乙酰氨基酚、塞来昔布、奈福泮、吗啡和氟哌利多。在产后第二天，接受左旋布比卡因输注的妇女报告哺乳时感到更舒适。在第二天，接受左旋布比卡因的妇女中有更多人在哺乳，但差异无统计学意义。 在中国进行的一项回顾性病历研究中，比较了接受分娩患者控制硬脊膜外镇痛的妇女（n = 527）和未接受的妇女（n = 395）。硬脊膜外镇痛包括0.1%左旋布比卡因和10毫升生理盐水中5毫克的舒芬太尼。所有妇女在产后6个月完成了关于她们哺乳经历的问卷调查。两组在产后1小时内开始哺乳的比例或纯母乳或部分母乳喂养婴儿的比例在1、3或6个月时没有统计学上的显著差异。

◉ Summary of Use during Lactation:Levobupivacaine is no longer marketed in the US. Levels in breastmilk are low, and it is poorly absorbed orally by the infant. Bupivacaine, the racemic mixture of dextro- and levobupivacaine, has not caused any adverse effects in breastfed infants. Local anesthetics during labor and delivery with other anesthetics and analgesics has been reported by some to interfere with breastfeeding. However, this assessment is controversial and complex because of the many different combinations of drugs, dosages and patient populations studied as well as the variety of techniques used. In contrast, epidural local anesthetics begun after clamping of the umbilical cord appears to enhance breastfeeding success because of improved pain control. Overall, it appears that with good breastfeeding support epidural levobupivacaine with or without fentanyl or one of its derivatives has little or no adverse effect on breastfeeding success. Labor Labor pain medication may delay the onset of lactation. In one study, adding levobupivacaine wound infiltration to multimodal analgesia after cesarean section improved breastfeeding comfort. ◉ Effects in Breastfed Infants:Relevant published information on levobupivacaine was not found as of the revision date. However, bupivacaine administered to the mother by intrapleural or epidural routes had no effect on 13 breastfed infants. ◉ Effects on Lactation and Breastmilk:A nonrandomized convenience sample of women who did (n = 209) or did not (n = 157) receive epidural analgesia during labor was analyzed to determine whether epidurals affected the onset of lactation. Although not standardized, the typical procedure used sufentanil 10 to 15 mg together with either ropivacaine 0.1% or levobupivacaine 0.0625% epidurally, supplemented by epidural boluses of ropivacaine 0.1% or levobupivacaine 0.0625% about every 2 hours. No difference was found in the time of lactation onset between the two groups. Although women in both groups stated they wished to breastfeed prior to delivery, exclusive breastfeeding at 20 days postpartum was less frequent in the women who received an epidural (43%) than in women who did not (57%). A randomized, unblinded study of women undergoing cesarean section found that women who received postoperative wound infiltration with levobupivacaine. A bolus of 50 mg was infused subfascially 5 cm lateral to the wound incision, followed by 6.25 mg/hour for 48 hours. Additional analgesia included acetaminophen, celecoxib, nefopam, morphine and droperidol. On day 2 postpartum, women who received the levobupivacaine infusion reported more comfort with breastfeeding. More women who received the levobupivacaine were breastfeeding on day 2, but the difference was not statistically significant. A retrospective medical record study in China compared women who received patient-controlled epidural analgesia during labor (n = 527) to those who did not (n = 395). Epidural analgesia included 0.1% levobupivacaine and 5 mg of sufentanil in 10 mL of saline. All women completed a questionnaire regarding their breastfeeding experience at 6 months postpartum. There were no statistically significant differences between the groups in the proportion who initiated breastfeeding within 1 hour after birth or who exclusively or partially breastfed their infants at 1, 3, or 6 months postpartum.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 暴露途径

治疗给药后，左布比卡因的血浆浓度取决于剂量以及给药途径，因为药物从给药部位的吸收受组织血管分布的影响。硬脊膜外给药后，血液中的峰值浓度大约在30分钟左右达到，剂量达到150毫克时，平均Cmax（最高血药浓度）可达1.2微克/毫升。

The plasma concentration of levobupivacaine following therapeutic administration depends on dose and also on route of administration, because absorption from the site of administration is affected by the vascularity of the tissue. Peak levels in blood were reached approximately 30 minutes after epidural administration, and doses up to 150 mg resulted in mean C_max levels of up to 1.2 ug/mL.

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

• 吸收

治疗给药后，左布比卡因的血浆浓度取决于剂量以及给药途径，因为药物从给药部位的吸收受到组织血管分布的影响。硬脊膜外给药后大约30分钟达到血浆峰值，剂量达到150毫克时，平均Cmax水平可达1.2微克/毫升。

The plasma concentration of levobupivacaine following therapeutic administration depends on dose and also on route of administration, because absorption from the site of administration is affected by the vascularity of the tissue. Peak levels in blood were reached approximately 30 minutes after epidural administration, and doses up to 150 mg resulted in mean Cmax levels of up to 1.2 µg/mL.

来源:DrugBank

吸收、分配和排泄

• 消除途径

静脉给药后，左布比卡因放射性标记剂量的回收几乎是定量的，大约有95%的总剂量在48小时内通过尿液和粪便回收。在这95%中，约71%通过尿液回收，而24%通过粪便回收。

Following intravenous administration, recovery of the radiolabelled dose of levobupivacaine was essentially quantitative with a mean total of about 95% being recovered in urine and feces in 48 hours. Of this 95%, about 71% was in urine while 24% was in feces.

来源:DrugBank

吸收、分配和排泄

• 分布容积

在健康志愿者中静脉给药40毫克后，66.91 ±18.23升。

66.91 ±18.23 L [after intravenous administration of 40 mg in healthy volunteers]

来源:DrugBank

吸收、分配和排泄

• 清除

静脉给药40毫克于健康志愿者后，平均药物清除率为39.06 ± 13.29升/小时。

39.06 ±13.29 L/h [after intravenous administration of 40 mg in healthy volunteers]

来源:DrugBank

安全信息

• 危险品标志：
  Xn,T+
• 危险品运输编号：
  UN 2811 6
• 海关编码：
  2933399090
• 储存条件：
  库房应保持通风、低温和干燥，并与食品原料类分开存放。

制备方法与用途

类别：有毒物质
毒性分级：高毒
急性毒性：静脉-大鼠 LD50: 7.2 毫克/公斤；静脉-小鼠 LD50: 9.6 毫克/公斤
可燃性危险特性：热分解排出有毒氮氧化物烟雾
储运特性：库房通风低温干燥，与食品原料类分开存放
灭火剂：水、干粉、干砂、二氧化碳、泡沫、1211灭火剂

反应信息

• 作为反应物：
  描述：

  左布比卡因 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 7.0h， 以25.7%的产率得到(S)-N-(2,6-dimethylphenyl)-1-butylpiperidine-2-carbothioamide
  参考文献：
  名称：

  取代哌啶类酰胺衍生物及其制备方法和在药 学上的应用

  摘要：

  本发明涉及一种通式(I)所述的取代哌啶类酰胺衍生物或其立体异构体、药学上可接受的盐，及其制备方法、药物组合以及在局部麻醉或镇痛等方面的用途，通式(I)各基团定义与说明书一致；

  公开号：

  CN106928127B
• 作为产物：
  描述：

  bupivacaine N-oxide 在 盐酸 、 titanium(III) chloride 作用下， 以 甲醇 、 水 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 2.0h， 以62%的产率得到左布比卡因
  参考文献：
  名称：

  [EN] SELECTIVE MODIFICATION OF ORGANIC COMPOUNDS IN THE PRESENCE OF AMINES AND/OR SULFIDES
  [FR] MODIFICATION SÉLECTIVE DE COMPOSÉS ORGANIQUES EN PRÉSENCE D'AMINES ET/OU DE SULFURES

  摘要：

  本文揭示了一种用于选择性地修改含有胺、硫醚或胺和硫醚的有机化合物中可替代碳原子的方法。该方法利用了胺和硫醚的反应性，可以选择性地氧化形成在许多改性反应条件下是惰性的氧化物，并通过保护有机化合物中的胺、硫醚或胺和硫醚作为氧化物；将含氧化物的有机化合物置于适合进行改性反应的反应条件下；并使用还原剂去保护已修改的氧化物中的胺、硫醚或胺和硫醚，从而选择性地修改含有胺、硫醚或胺和硫醚的有机化合物中的可替代碳原子。

  公开号：

  WO2014152737A1
• 作为试剂：
  描述：

  盐酸左布比卡因 、 、 、 碳酸根离子 在 左布比卡因 作用下， 反应 216.0h， 生成 左布比卡因
  参考文献：
  名称：

  Biocompatible crosslinked hydrogels, drug-loaded hydrogels and methods of using the same

  摘要：

  本发明涉及一种由四甲基甲烷与一种或多种聚乙二醇混合形成的水凝胶组合物，其中每个聚乙二醇取代基独立地进一步取代有一种或多种亲电基团，以及由一种或多种聚乙二醇取代基独立地进一步取代有一种或多种亲核基团的四甲基甲烷与一种或多种聚乙二醇混合形成的水凝胶组合物。还公开了制备上述水凝胶的方法。水凝胶组合物还可以包含药物，例如镇痛剂或局部麻醉剂。还公开了使用所述水凝胶密封伤口、预防术后粘连和减少术后疼痛的方法。

  公开号：

  US09125814B2

文献信息

• MULTIFUNCTIONAL SMALL MOLECULES
  申请人：Baker, JR. James R.

  公开号：US20120259114A1

  公开（公告）日：2012-10-11

  The present invention relates to dendrimer synthesis. Specifically, the present invention relates to triazine scaffolds capable of click chemistry for one-step synthesis of functionalized dendrimers, and methods of making and using the same.

  本发明涉及树枝状大分子的合成。具体而言，本发明涉及能够进行点击化学的 三嗪支架，用于一步法合成功能化树枝状大分子，以及制造和使用该支架的方法。
• [EN] PHARMACEUTICAL COMPOSITIONS OF POLYANIONIC AND NON-IONIC CYCLODEXTRIN-BASED DENDRIMERS AND USES THEREOF<br/>[FR] COMPOSITIONS PHARMACEUTIQUES DE DENDRIMÈRES À BASE DE CYCLODEXTRINE POLYANIONIQUE ET NON-IONIQUE ET UTILISATIONS ASSOCIÉES
  申请人：LING CHANG-CHUN

  公开号：WO2016161501A1

  公开（公告）日：2016-10-13

  The present application provides pharmaceutical compositions comprising polyanionic and polynon-ionic cyclodextrin-based dendrimers. The compositions can be used as excipients, or to bind to compounds such as in the use as a rescue medicine to remove undesired drugs and metabolites from a subject. Methods of use in treating a subject are also provided.

  当前申请提供了包含多阴离子和多非离子环糊精基树枝状聚合物的药物组合物。这些组合物可以用作辅料，或者用于结合化合物，例如用作救援药物以从主体中去除不需要的药物和代谢物。还提供了用于治疗主体的方法。
• PHOSPHONIUM ION CHANNEL BLOCKERS AND METHODS FOR USE
  申请人：Nocion Therapeutics, Inc.

  公开号：US20210128589A1

  公开（公告）日：2021-05-06

  The invention provides compounds of Formula (I), or pharmaceutically acceptable salts thereof: The compounds, compositions, methods and kits of the invention are useful for the treatment of pain, itch, and neurogenic inflammation.

  本发明提供了式(I)的化合物，或其药用可接受的盐： 本发明的化合物、组合物、方法和试剂盒可用于治疗疼痛、瘙痒和神经性炎症。
• Methods for delivery of nucleic acids
  申请人：Satishchandran C.

  公开号：US20060084617A1

  公开（公告）日：2006-04-20

  This invention features methods and compositions for delivery of nucleic acids (e.g., DNA, RNA, PNA, and hybrids thereof) to cells. The nucleic acid delivery complexes of the invention permit biologically active nucleic acids to be delivered to cells and organisms in vitro and in vivo in a manner and form that allows the nucleic acids to carry out their desired biological function.

  这项发明涉及用于将核酸（例如，DNA、RNA、PNA及其杂合体）递送到细胞中的方法和组合物。本发明的核酸递送复合物使得生物活性的核酸能够以某种方式和形式递送到体外和体内的细胞和生物体中，从而允许核酸执行其所需的生物学功能。
• [EN] DEUTERATED MORPHINE DERIVATIVES<br/>[FR] DÉRIVÉS DE MORPHINE DEUTÉRÉS
  申请人：SZEGEDI TUDOMÁNYEGYETEM

  公开号：WO2014170704A1

  公开（公告）日：2014-10-23

  The invention relates to new morphine derivatives deuterated at the 7,8-position of the morphine ring, furthermore to a process for the preparation thereof, and to pharmaceutical compositions comprising them. The new deuterated morphine derivatives show high and selective μ-opioid receptor binding activity leading to the benefit of higher analgesic activity at lower dosages inducing thereby reduced adverse effects compared to the hydrogenated derivatives. The compounds of the invention are useful for example in the treatment of pain or can be used as antitussive agents with a reduced risk of the possibility of drug abuse.

  这项发明涉及新的吗啡衍生物，其在吗啡环的7,8-位置被氘代取，此外还涉及其制备方法以及包含它们的药物组合物。这些新的氘代吗啡衍生物显示出高度和选择性的μ-阿片受体结合活性，从而在较低剂量下产生更高的镇痛活性，因此与氢化衍生物相比，减少了不良反应。该发明的化合物可用于例如治疗疼痛，或可用作镇咳剂，具有较低的药物滥用可能性。