酒石酸氢胆碱 | 87-67-2

• 物质功能分类: 原料药 - 神经系统用药 - 拟胆碱药
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 酒石酸氢胆碱
• 中文别名: 胆碱酒石酸氢盐；DL-酒石酸氢胆碱；L(+)-重酒石酸胆碱；酒石酸(2-羟基乙基)三甲基铵；重酒石酸胆碱
• 英文名称: choline (R,R)-hydrogentartrate
• 英文别名: L-choline bitartrate；choline bitartrate；2-hydroxyethyl(trimethyl)azanium;(2R,3R)-2,3,4-trihydroxy-4-oxobutanoate
• CAS: 87-67-2
• 化学式: C₄H₅O₆*C₅H₁₄NO
• 分子量: 253.252
• InChiKey: QWJSAWXRUVVRLH-LREBCSMRSA-M

物化性质

• 熔点：
  151-153°C
• 比旋光度：
  [α]D20 +15～+18° (c=4, H2O)
• 溶解度：
  DMSO（轻微）、甲醇（轻微、加热）、水（轻微）
• LogP：
  -1.426 (est)
• 颜色/状态：
  White crystalline powder
• 气味：
  Odorless or faint trimethylamine-like odor
• 味道：
  Acid taste

计算性质

• 辛醇/水分配系数(LogP)：
  -4.99
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  138
• 氢给体数：
  4
• 氢受体数：
  7

ADMET

代谢

游离胆碱不完全被吸收，尤其是在服用大剂量之后，肠道细菌会将胆碱代谢成三甲胺。

Free choline is not fully absorbed, especially after large doses, and intestinal bacteria metabolize choline to trimethylamine. /Choline/

来源:Hazardous Substances Data Bank (HSDB)

代谢

通过使用S-adenosylmethionine作为甲基供体，主要通过肝脏对磷脂酰乙醇胺进行甲基化来从头合成胆碱的能力，意味着部分对胆碱的需求可以通过来自1碳代谢的甲基组来满足（通过甲基叶酸和甲硫氨酸）。几种维生素（叶酸、维生素B12、维生素B6和核黄素）和氨基酸甲硫氨酸在1碳代谢中与胆碱相互作用...甲硫氨酸、甲基四氢叶酸（THF）和胆碱可以是甲基组的可替代来源。/胆碱/

/The/ ability to form choline /de novo via the methylation of phosphatidylethanolamine using S-adenosylmethionine as the methyl donor, mostly in the liver,/ means that some of the demand for choline can ... be met using methyl groups derived from 1-carbon metabolism (via methyl-folate and methionine). Several vitamins (folate, vitamin B12, vitamin B6, and riboflavin) and the amino acid methionine interact with choline in 1-carbon metabolism ... Methionine, methyl-tetrahydrofolate (THF), and choline can be fungible sources of methyl groups. /Choline/

来源:Hazardous Substances Data Bank (HSDB)

代谢

在胆碱能够在肠道被吸收之前，一部分会被细菌代谢成甜菜碱和甲基胺（这些不是甲基供体）... 尽管有一些自由的胆碱会随着尿液排出，但大部分会在肾脏中被氧化成甜菜碱... /胆碱/

Before choline can be absorbed in the gut, some is metabolized by bacteria to form betaine and methylamines (which are not methyl donors) ... Although some free choline is excreted with urine, most is oxidized in the kidney to form betaine ... /Choline/

来源:Hazardous Substances Data Bank (HSDB)

代谢

乙酰胆碱是大脑记忆中心（海马和隔膜）神经元使用的一种最重要的神经递质。胆碱加速神经细胞中乙酰胆碱的合成和释放。大脑神经元使用的胆碱主要来源于膜磷脂（磷脂酰胆碱）或来自饮食中胆碱和磷脂的摄入... 当细胞外胆碱供应不足时，来自磷脂的胆碱可能尤为重要，这在预期中可能会在高级年龄由于大脑胆碱摄取减少而出现... /胆碱/

Acetylcholine is one of the most important neurotransmitters used by neurons in the memory centers of the brain (hippocampus and septum). Choline accelerates the synth and release of acetylcholine in nerve cells. Choline used by brain neurons is largely derived from membrane lecithin /(phosphatidylcholine)/, or from dietary intake of choline and lecithin ... Choline derived from lecithin may be especially important when extracellular choline is in short supply, as might be expected to occur in advanced age because of decr brain choline uptake ... /Choline/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

甲氨蝶呤可能会减少所有胆碱代谢物的含量。胆碱补充剂可以逆转大鼠因甲氨蝶呤给药引起的脂肪肝。/胆碱/

Methotrexate may diminish pools of all choline metabolites. Choline supplementation reverses fatty liver caused by methotrexate admin in rats. /Choline/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

重复给雌性大鼠施用氯化胆碱会增加由四氯化碳引起的肝脏坏死。

Repeated admin of choline chloride to female rats incr liver necrosis caused by carbon tetrachloride.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

这项研究旨在检查过量维生素A和甲基化途径成分（即叶酸和胆碱的缺乏以及蛋氨酸的减少）的生物化学和胚胎毒性相互作用。Simonsen白化大鼠在36天内维持正常（每克饮食4 IU）或过量棕榈酸视黄酯（RP）（每克饮食100或1000 IU）的饮食，以及正常（每克饮食2微克叶酸、5毫克蛋氨酸和4.2毫克酒石酸胆碱）或缺少这三种饮食因素。CD-1小鼠胚胎从妊娠第0天到第8天暴露于饮食中，从第8天到第10天在大鼠血清中进行全胚胎培养。当饮食中包含甲基化途径成分时，高剂量的RP诱导了55.4%的前神经孔开放，但當这些成分被省略时，同样的视黄酸水平仅产生了12.5%具有这种缺陷的胚胎。血清中的酸性视黄酸水平通过高效液相色谱法测量是低的（小于5 ng/mL）。对选定的甲基化和转硫途径组分的测量没有在这些生物化学中间体中产生差异。因此，饮食中的叶酸、胆碱和蛋氨酸促进了视黄酸诱导的神经管缺陷的发生。

This study was designed to examine the biochemical and embryotoxic interaction of excessive dietary vitamin A and deficiency of methylation pathway constituents, namely absence of folate and choline and a reduction of methionine. Simonsen albino rats were maintained for 36 days on a diet with either normal (4 IU per gram of diet) or excessive retinyl palmitate (RP) (100 or 1000 IU per gram of diet), and normal (2 ug folic acid, 5 mg methionine and 4.2 mg choline bitartrate per gram of diet) or absence of the three dietary factors. CD-1 mouse embryos were exposed to the diet from gestational day 0 to 8, and rat serum from day 8 to 10 during whole embryo culture. The high dose of RP induced 55.4% open anterior neuropores when methylation pathway constituents were included in the diet, but this same retinoid level produced only 12.5% embryos with this defect when these constituents were omitted. Acidic retinoid levels were low in serum (less than 5 ng/mL) via HPLC. Measurements of selected methylation and transsulfuration pathway components did not yield differences in these biochemical intermediates. Thus, dietary folate, choline and methionine facilitate the induction of retinoid-induced neural tube defects.

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。寻求医疗救助。 /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)

吸收、分配和排泄

胆碱以游离形式或作为卵磷脂从饮食中被吸收。后者被肠粘膜水解为甘油磷酰胆碱，它要么进入肝脏释放胆碱，要么通过肠道淋巴管进入外周组织。/胆碱/

Choline is absorbed from diet as such or as lecithin. Latter is hydrolyzed by intestinal mucosa to glycerophosphoryl choline, which either passes to liver to liberate choline or to peripheral tissues via intestinal lymphatics. /Choline/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

胆碱通过门脉循环被吸收...肝脏吸收了大部分胆碱，并以磷脂酰胆碱和鞘磷脂的形式储存。肾脏和大脑也积累胆碱...一些游离胆碱随尿液排出...游离胆碱穿过血脑屏障的运输需要一个特定的载体，尤其是在新生儿中，这种能力特别强。/胆碱/

Choline are absorbed via the portal circulation ... The liver takes up the majority of choline and stores it in the form of phosphatidylcholine and sphingomyelin. Kidney and brain also accumulate choline ... Some free choline is excreted with urine ... A specific carrier is needed for the transport of free choline across the blood-brain barrier, and the capacity is especially high in neonates. /Choline/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

游离胆碱以与血清胆碱水平成正比的速度穿过血脑屏障...在晚年...大脑胆碱摄取量减少...胆碱

Free choline is transported across the blood-brain barrier at a rate that is proportional to serum choline level ... In advanced age ... brain choline uptake /is decr/ ... /Choline/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在怀孕期间，大量的胆碱通过胎盘传递给胎儿，这会耗尽母体的储存。羊水中的胆碱浓度是母血的10倍。在出生时，人类和其他哺乳动物的血浆胆碱浓度远高于成年期...在大鼠中，晚期妊娠的肝脏胆碱浓度降至非妊娠雌性的三分之一以下.../胆碱/

During pregnancy, large amt of choline are delivered to the fetus across the placenta and this depletes maternal stores. Choline concn in amniotic fluid is 10-fold greater than that in maternal blood. At birth, humans and other mammals have plasma choline concn that are much higher than those in adults ... In rats, the liver choline concn in late pregnancy decr to less than one-third that of nonpregnant females ... /Choline/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  2923100000
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

制备方法与用途

胆碱简介

胆碱（HOCH₂CH₂N(CH₃)₃OH）是一种强有机碱，是卵磷脂的组成成分，并存在于神经鞘磷脂之中。它作为机体可变甲基的一个来源参与合成甲基产物的过程，同时也是乙酰胆碱的前体。胆碱耐热，在加工和烹调过程中损失较少。在干燥环境中，即使长时间储存，食物中的胆碱含量变化也很小。它是卵磷脂（磷脂酰胆碱）的重要组成部分，广泛存在于动植物中。

作用原理

胆碱的主要作用包括：

1. 促进脑发育和提高记忆能力；
2. 确保信息传递的准确性；
3. 调控细胞凋亡过程；
4. 构成生物膜的重要组成成分；
5. 促进脂肪代谢；
6. 促进体内甲基代谢；
7. 降低血清胆固醇水平。

胆碱广泛存在于各种食物中，尤其是肝脏、花生和蔬菜中的含量较高。维生素B族中的一种，是亲脂性维生素（可乳化脂肪）。胆碱的天敌包括水、磺胺药物、雌激素、食品加工过程以及酒精等。

制备

酒石酸氢胆碱可通过高浓度环氧乙烷水溶液与三甲胺在常温下反应获得胆碱，然后将其溶于甲醇中。按摩尔比例加入酒石酸进行中和，之后通过浓缩、干燥及丙酮重结晶等精制步骤制成。

含量分析

精确称取500毫克试样放入250毫升锥形烧瓶中，加入50毫升冰醋酸，并在蒸汽浴上加热至完全溶解。冷却后加入2滴龙胆紫试剂，使用0.1摩尔/升高氯酸的冰醋酸溶液滴定，直至达到绿色终点。同时进行空白试验并作必要校正。每毫升0.1摩尔/升高氯酸相当于本品(C₉H₁₉NO₇) 25.36毫克。

毒性

胆碱被美国食品药品监督管理局（FDA）列为GRAS物质，ADI值无限制（FAO/WHO, 2001）。

用途

• 维生素B类药物，用于治疗肝炎、早期肝硬化和恶性贫血等。
• 乙酰基团受体，是胆碱乙酰转移酶的底物。

反应信息

• 作为反应物：
  描述：

  正硅酸甲酯 、 酒石酸氢胆碱 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以83%的产率得到
  参考文献：
  名称：

  具有桥联（R，R）-Tratrato（4-）配体和SiO5骨架的两性离子和阴离子多核五配位硅（IV）配合物：水溶液中的合成和反应性

  摘要：

  两种营养成分在一个分子：两性离子λ 5的Si，λ 5 Si'-焦硅酸盐（1）的合成和表征。它包含专门来自天然产物（（R，R）-酒石酸，胆碱）的配体。1的水解产生2，在水中显示出显着的动力学稳定性。将1和2溶解在水中后，营养物质胆碱和原硅酸通过水解形成

  DOI：

  10.1002/chem.201102815

文献信息

• [EN] HETEROCYCLIC COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES ET LEURS UTILISATIONS
  申请人：INFINITY PHARMACEUTICALS INC

  公开号：WO2015051241A1

  公开（公告）日：2015-04-09

  Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

  本发明描述了调节激酶活性的化合物和药物组合物，包括PI3激酶活性，以及用于治疗与激酶活性相关的疾病和状况的化合物、药物组合物和方法，包括PI3激酶活性。
• [EN] COMPOSITIONS COMPRISING SELENIUM AND USE OF SAME FOR THE TREATMENT AND PREVENTION OF DISEASE OR CONDITIONS ASSOCIATED WITH MITOCHONDRIAL DYSFUNCTION<br/>[FR] COMPOSITIONS COMPRENANT DU SÉLÉNIUM ET UTILISATION DE CELLES-CI POUR LE TRAITEMENT ET LA PRÉVENTION DE MALADIE OU D'ÉTATS ASSOCIÉS AVEC UN DYSFONCTIONNEMENT MITOCHONDRIAL
  申请人：ALLTECH INC

  公开号：WO2014144776A1

  公开（公告）日：2014-09-18

  The present application relates to compositions comprising selenium (e.g., selenium enriched yeast and selenium containing compounds obtained or derived therefrom) and methods of using the same to treat and inhibit obesity, diabetes and related conditions. In particular, the present application provides compositions comprising selenium enriched yeast (e.g., selenium enriched yeast comprising 2% or less inorganic selenium), selenium containing compounds present therein and/or derived therefrom, and methods of using the same to enhance mitochondrial activity and function (e.g., in skeletal muscle and liver) in a subject (e.g., as a therapeutic and/or prophylactic treatment for diabetes, obesity and related conditions).

  本申请涉及含硒的组合物（例如，富硒酵母和从中获得或衍生的含硒化合物）及其用于治疗和抑制肥胖、糖尿病和相关疾病的方法。具体而言，本申请提供了含硒富集酵母的组合物（例如，含有2％或更少无机硒的富硒酵母），其中含有或从中衍生的含硒化合物，并使用它们的方法来增强线粒体活性和功能（例如，在骨骼肌和肝脏中）以治疗和/或预防糖尿病、肥胖和相关疾病。
• [EN] HETEROCYCLIC COMPOUNDS FOR USE IN THE TREATMENT OF PI3K-GAMMA MEDIATED DISORDERS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE TROUBLES MÉDIÉS PAR PI3K-GAMMA
  申请人：INFINITY PHARMACEUTICALS INC

  公开号：WO2015143012A1

  公开（公告）日：2015-09-24

  Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

  本文描述了调节激酶活性的化合物和药物组合物，包括PI3激酶活性，以及与激酶活性相关的疾病和状况的治疗方法，包括PI3激酶活性的化合物、药物组合物和治疗方法。
• Multivalent indole compounds and use thereof as phospholipase-A2 inhibitors
  申请人：Chang Han-Ting

  公开号：US20070135385A1

  公开（公告）日：2007-06-14

  Indole and indole-related compounds, compositions and methods are disclosed. The compounds of the invention are useful as phospholipase inhibitors. The compounds and compositions of the invention are useful for treatment of phospholipase-related conditions, such as insulin-related, weight-related and/or cholesterol-related conditions in an animal subject.

  吲哚和与吲哚相关的化合物、组合物以及方法被披露。发明中的这些化合物作为磷脂酶抑制剂非常有用。发明中的这些化合物和组合物用于治疗动物受试者中的磷脂酶相关状况，例如胰岛素相关、体重相关和/或胆固醇相关状况。
• HETEROCYCLIC COMPOUNDS AND USES THEREOF
  申请人：INFINITY PHARMACEUTICALS, INC.

  公开号：US20130267521A1

  公开（公告）日：2013-10-10

  Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

  本发明描述了调节激酶活性的化合物和药物组合物，包括PI3激酶活性，以及用于治疗与激酶活性相关的疾病和状况的化合物、药物组合物和方法，包括PI3激酶活性。