cobalt(3+);[(2R,3R,5S)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] 1-[3-[(2S,5Z,10Z,12R,15Z,18R)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2,7,12,17-tetrahydro-1H-corrin-24-id-3-yl]propanoylamino]propan-2-yl phosphate;cyanide | 68-19-9

• 物质功能分类: 原料药 - 维生素类与矿物质类药 - 维生素B类药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四吡咯及其衍生物
• 英文名称: cobalt(3+);[(2R,3R,5S)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] 1-[3-[(2S,5Z,10Z,12R,15Z,18R)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2,7,12,17-tetrahydro-1H-corrin-24-id-3-yl]propanoylamino]propan-2-yl phosphate;cyanide
• CAS: 68-19-9
• 化学式: C63H88CoN14O14P
• 分子量: 1355.4
• InChiKey: FDJOLVPMNUYSCM-RKLHWWGLSA-L

物化性质

• 熔点：
  >300°C
• 比旋光度：
  23656 -59 ± 9° (dil aq soln)
• 沸点：
  >300 °C
• 闪点：
  9℃
• 溶解度：
  微溶于水和乙醇（96%），几乎不溶于丙酮。无水物质极易吸湿。
• 暴露限值：
  NIOSH: IDLH 25 mg/m3
• LogP：
  3.570 (est)
• 颜色/状态：
  Dark red crystals or an amorphous or crystalline red powder
• 气味：
  Odorless
• 味道：
  Tasteless
• 稳定性/保质期：

  Solutions of cyanocobalamin in water or 0.9% sodium chloride are stable and can be autoclaved for short periods of time (15-20 minutes) at 121 °C.

• 旋光度：
  SPECIFIC OPTICAL ROTATION: -59 + or - 9 DEG @ 23 °C 656 NM (DILUTE AQ SOLN)

计算性质

• 辛醇/水分配系数(LogP)：
  3.41
• 重原子数：
  93
• 可旋转键数：
  16
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  476
• 氢给体数：
  9
• 氢受体数：
  21

ADMET

代谢

维生素B12被认为是转化成辅酶形式储存在肝脏中，并可能以这种形式储存在组织中。

Vitamin B12 is believed to be converted to coenzyme form in the liver and is probably stored in tissues in this form.

来源:Hazardous Substances Data Bank (HSDB)

代谢

细胞内维生素B12以两种活性辅酶形式存在，分别是甲钴胺和脱氧腺苷钴胺。

Intracellular vitamin B12 is maintained as two active coenzymes methylcobalamin and deoxyadenasylcobalamin.

来源:Hazardous Substances Data Bank (HSDB)

代谢

维生素B12被认为是转化成辅酶形式储存在肝脏中的，并且很可能会以这种形式储存在组织中。

Vitamin B12 is believed to be converted to coenzyme form in the liver and is probably stored in tissues in this form.

来源:Hazardous Substances Data Bank (HSDB)

代谢

细胞内的维生素B12以两种活性辅酶形式存在，分别是甲钴胺和脱氧腺苷钴胺。

Intracellular vitamin B12 is maintained as two active coenzymes methylcobalamin and deoxyadenasylcobalamin.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：维生素B12是人类母乳的正常组成部分。哺乳期妇女的推荐每日摄入量为2.8微克，对于6个月或以下的婴儿推荐摄入量为0.4微克。一些权威机构建议在哺乳期间每日摄入5.5微克。为了达到这些推荐的每日摄入量或纠正已知的缺乏，可能需要补充。低剂量（1到10微克）的维生素B12，在B族复合维生素或孕期维生素中，只能略微提高乳汁水平。在母亲缺乏的情况下，需要更高每日剂量，50到250微克。在这种情况下，母乳喂养的婴儿不会接触到过量的维生素B12，如果之前维生素B12不足，他们的维生素B12状况应该会改善。 维生素B12缺乏的婴儿健康状况不佳，包括贫血、皮肤和头发发育异常、惊厥、肌张力弱、生长迟缓、智力发育迟缓，以及可能的异常运动。一个公认的高风险群体是母亲由于极少的动物产品摄入或因母亲对维生素B12吸收不良引起的恶性贫血而缺乏维生素B12的，仅以母乳喂养的婴儿。通过在孕期和哺乳期补充维生素B12，可以改善婴儿的维生素B12状况。错过孕期补充机会的缺乏维生素B12的母亲，在早期哺乳期仍应鼓励补充，因为婴儿维生素B12状况与母乳喂养婴儿在6个月大之前的乳汁维生素B12水平相关。虽然有报道称，仅以母乳喂养的维生素B12缺乏婴儿通过充足的母体补充而有所生化改善和临床改善，但在有此类治疗的情况下，建议直接补充婴儿。 母乳的闪蒸巴氏杀菌不会降低乳汁维生素B12的浓度。 ◉ 对母乳喂养婴儿的影响：12名仅以母乳喂养，年龄在4到11个月之间的婴儿，出现了与维生素B12缺乏一致的生化、血液和临床发现。他们的母亲接受了50微克肌注维生素B12的单次剂量。在剂量后的5到8天内，婴儿的血红蛋白和网织红细胞计数显著增加，正常红细胞生成，精神状态改善，异常皮肤色素沉着消退，震颤减少。 在印度，366名孕妇从怀孕的第一月开始每天接受50微克口服维生素B12或安慰剂胶囊，持续到产后6周。在218名30个月大时接受神经发育测试的婴儿中，那些出生时母亲随机分配到维生素B12组的婴儿，在调整基线母亲维生素B12缺乏后，表达性语言评分高于安慰剂组。认知、接受性语言和运动评分在两组之间没有差异。在6岁时进行神经生理学评估，两组之间测量的脑活动没有差异。 ◉ 对哺乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:Vitamin B12 is a normal component of human milk. The recommended daily intake in lactating women is 2.8 mcg and for infants aged 6 months or less is 0.4 mcg. Some authorities recommend 5.5 mcg per day during lactation. Supplementation may be necessary to achieve these recommended daily intakes or to correct a known deficiency. Low doses (1 to 10 mcg) of vitamin B12 found in B complex or prenatal vitamins increase milk levels only slightly. Higher daily doses of 50 to 250 mcg are needed in cases of maternal deficiency. The breastfed infant is not exposed to excessive vitamin B12 in such cases, and their vitamin B12 status should improve if it was previously inadequate. Poor health outcomes in infants with vitamin B12 deficiency include anemia, abnormal skin and hair development, convulsions, weak muscle tone, failure to thrive, mental developmental delay, and possibly abnormal movements. One well-recognized at risk group are exclusively breastfed infants of mothers with B12 deficiency due to minimal or no dietary intake of animal products or pernicious anemia caused by a maternal malabsorption of B12. Infant vitamin B12 status can be improved through maternal B12 supplementation during pregnancy and lactation. Deficient mothers who miss the opportunity to supplement during pregnancy should still be encouraged to supplement during early lactation since infant vitamin B12 status correlates with milk vitamin B12 levels in breastfed infants up to 6 months of age. Although there are cases reported of exclusively breastfed infants with vitamin B12 deficiency having biochemical and clinical improvement through adequate maternal supplementation alone, direct supplementation of the infant is recommended when such treatments are available. Flash heat pasteurization of breastmilk does not reduce milk vitamin B12 concentration. ◉ Effects in Breastfed Infants:Twelve exclusively breastfed infants between 4 and 11 months of age had biochemical, hematological and clinical findings consistent with vitamin B12 deficiency. Their mothers received a 50 mcg single dose of intramuscular vitamin B12. Within 5 to 8 days after the dose, the infants experienced significantly increased hemoglobin and reticulocyte counts, normoblastic erythropoiesis, improved mental status, regression of abnormal skin pigmentation, and reduction in tremors. Three hundred sixty-six pregnant women in India received 50 mcg of oral vitamin B12 or placebo capsules once daily beginning during their first trimester of pregnancy and continuing until 6 weeks postpartum. Among 218 infants that underwent neurodevelopment testing at 30 months of age, those born to mothers randomized to vitamin B12 had higher expressive language scores than the placebo group when adjusted for baseline maternal vitamin B12 deficiency. Cognitive, receptive language and motor scores were not different between the two groups. Neurophysiological assessments were then conducted at 6 years of age and there were no differences in the measured brain activity between the two groups. ◉ 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

• 相互作用

维生素B12从胃肠道吸收可能会被氨基糖苷类抗生素、秋水仙碱、缓释钾制剂、氨水杨酸及其盐类、抗惊厥药（例如，苯妥英、苯巴比妥、普里马多）以及小肠钴照射和超过两周的过量饮酒所降低。

ABSORPTION OF VITAMINE B12 FROM THE GI TRACT MAY BE DECR BY AMINOGLYCOSIDE ANTIBIOTICS, COLCHICINE, EXTENTED-RELEASE POTASSIUM PREPN, AMINOSALICYLIC ACID & ITS SALTS, ANTICONVULSANTS (EG, PHENYTOIN, PHENOBARBITAL, PRIMADONE), COBALT IRRADIATION OF THE SMALL BOWEL, & BY EXCESSIVE ALCOHOL INTAKE LASTING LONGER THAN 2 WK.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

口服新霉素会显著降低维生素B12的胃肠道吸收。使用秋水仙碱似乎会增加新霉素引起的维生素B12吸收不良。

The gastrointestinal absorption of vitamin B12 can be considerably decreased by oral neomycin. Colchicine administration appears to increase neomycin-induced malabsorption of vitamin B12.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

氨水杨酸引起的维生素B12吸收减少可能是由于一些接受氨水杨酸（PAS）治疗的患者出现的轻度吸收不良综合征。

The decreased vitamin B12 absorption induced by aminosalicylic acid may be due to the mild malabsorption syndrome that occurs in some patients treated with aminosalicylic acid (PAS).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

患有恶性贫血的病人如果同时使用氯霉素，对维生素B12治疗的反应会很差。

Patients with pernicious anemia ... respond poorly to vitamin B12 therapy if chloroamphenicol is given concomitantly.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在给小鼠静脉注射维生素B12的实验中，维生素B12迅速积累在胎盘并且缓慢转移到胎儿。胎儿中的维生素B12浓度在给药后24小时达到峰值，而且胎儿的积累量与剂量有关。

IN MICE INJECTED IV WITH VITAMIN B12, THE VITAMIN ACCUMULATED RAPIDLY IN THE PLACENTA & WAS TRANSFERRED SLOWLY TO THE FETUSES. PEAK CONCN IN THE FETUSES WAS REACHED 24 HR AFTER DOSING, & FETAL ACCUMULATION WAS DOSE-DEPENDENT.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在/小鼠/中，维生素B12展现了不寻常的胎盘传递模式，即使是0.20微克母体剂量，胎儿平均浓度也是母体的130倍。这强烈表明存在特定的维生素B12运输机制，可能类似于它在胃肠道的吸收方式...

IN /MICE/ VITAMIN B12 PRESENTS UNUSUAL PATTERN OF PLACENTAL TRANSFER, FOR EVEN WITH 0.20 UG MATERNAL DOSE AVG FETAL CONCN IS 130 TIMES HIGHER THAN MATERNAL ONE. THIS INDICATES STRONGLY OPERATION OF SPECIFIC TRANSPORT MECHANISM FOR VITAMIN B12, POSSIBLY SIMILAR TO ITS GI ABSORPTION ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠中，已经证明在妊娠期间维生素B12的胎盘传递会增加。尽管每天传输的量与胎儿体重成比例，但从第10天到第19天，每克胎盘传输的量增加了十倍。

IN RATS, PLACENTAL TRANSFER OF VITAMIN B12 WAS SHOWN TO INCR DURING GESTATION. ALTHOUGH QUANTITY TRANSPORTED EACH DAY WAS PROPORTIONAL TO FETAL WT, THE AMT TRANSPORTED PER G OF PLACENTA INCR TEN-FOLD FROM DAY 10 TO DAY 19.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

维生素B12在口服给药后，从远端小肠不规则吸收。饮食中的维生素B12与蛋白质结合，这种结合必须通过蛋白水解和胃酸分解才能被吸收。在胃中，游离的维生素B12与内因子结合；内因子是一种由胃粘膜分泌的糖蛋白，对于从胃肠道主动吸收维生素是必要的。维生素B12-内因子复合物进入肠道，在维生素B12部分被吸收进入系统循环之前，大部分复合物在回肠下段的特定受体位点暂时保留。

Vitamin B12 is irregularly absorbed from the distal small intestine following oral administration. Dietary vitamin B12 is protein bound and this bond must be split by proteolysis and gastric acid before absorption. In the stomach, free vitamin B12 is attached to intrinsic factor; intrinsic factor a glycoprotein secreted by the gastric mucosa, is necessary for active absorption of the vitamin from the GI tract. The vitamin B12-intrinsic factor complex passes into the intestine, where much of the complex is transiently retained at specific receptor sites in the wall of the lower ileum before the vitamin B12 portion is absorbed into systemic circulation.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在给小鼠静脉注射维生素B12的实验中，维生素B12迅速积累在胎盘并且缓慢转移到胎儿。给药后24小时，胎儿中的维生素B12浓度达到峰值，且胎儿中的积累量与剂量有关。

IN MICE INJECTED IV WITH VITAMIN B12, THE VITAMIN ACCUMULATED RAPIDLY IN THE PLACENTA & WAS TRANSFERRED SLOWLY TO THE FETUSES. PEAK CONCN IN THE FETUSES WAS REACHED 24 HR AFTER DOSING, & FETAL ACCUMULATION WAS DOSE-DEPENDENT.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• WGK Germany：
  1
• RTECS号：
  GG3750000
• 海关编码：
  2936260000
• 安全说明：
  S24/25

制备方法与用途

维生素B12（Cobalamin）是一种水溶性维生素，在人体代谢中扮演着重要角色。下面是一些关于维生素B12的关键信息：

用途

1. 治疗贫血：特别是恶性贫血和巨幼红细胞贫血。
2. 神经系统支持：对于预防神经病变，如多发性神经炎有重要作用。
3. 营养强化剂：用于婴幼儿食品、强化饮料等。

化学性质

• 物理特性：深红色结晶或无定形粉末，无味无臭。
• 溶解性：1g维生素B12可溶于约80mL水中，易吸湿。
• 稳定性：在中性和微酸性溶液中较稳定；但在强碱、强酸和还原剂中不稳定。

用途与应用

• 食品强化：用于婴幼儿配方奶粉（剂量为0.001~0.003mg/100g）。
• 营养补充：在运动营养食品中添加，最大允许使用量为0.4至10μg/kg。

生产方法

目前主要通过以下两种方式生产：

1. 发酵法：

   • 利用灰色链霉菌（Streptomyces griseus）进行发酵。
   • 发酵液酸化后，利用弱酸性丙烯酸系阳离子交换树脂吸附、洗脱和净化。
   • 经氰化物转化、溶剂萃取、氧化铅层析等步骤最终得到成品。

2. 合成法：

   • 以葡萄糖和玉米浆为原料，接种薛氏丙酸杆菌发酵。
   • 向发酵液中加入氯化钴及5,6-二甲基苯并咪唑进行后续处理，提取干燥获得产品。

注意事项

尽管维生素B12是人体必需的营养素之一，但过多摄入也可能带来副作用。因此，在实际应用时应遵循相关安全标准与指导原则。

以上信息总结了关于维生素B12的基本特性、用途以及生产方法等关键内容，希望能帮助您更好地理解和使用这种重要的营养补充剂。