cobalt;[(2R,3S,4R,5S)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2R)-1-[3-[(1R,2R,3R,7S,12S,13S,17S,18S,19R)-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-21-id-3-yl]propanoylamino]propan-2-yl] phosphate

• 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;[(2R,3S,4R,5S)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2R)-1-[3-[(1R,2R,3R,7S,12S,13S,17S,18S,19R)-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-21-id-3-yl]propanoylamino]propan-2-yl] phosphate
• 化学式: C62H88CoN13O14P-2
• 分子量: 1329.3
• InChiKey: FEZWOUWWJOYMLT-DSRCUDDDSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  3.31
• 重原子数：
  91
• 可旋转键数：
  16
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  452
• 氢给体数：
  9
• 氢受体数：
  19

ADMET

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个月或以下的婴儿为0.4微克。一些权威机构建议在哺乳期间每日摄入量为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。在B族复合维生素或孕期维生素中发现的低剂量（1到10微克）的维生素B12只能略微提高乳汁水平。在母亲缺乏的情况下，需要更高每日剂量的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缺乏的婴儿健康结果不良，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饮食摄入动物产品或由于母亲对维生素B12的吸收不良导致的恶性贫血而缺乏维生素B12的仅母乳喂养的婴儿。通过在怀孕和哺乳期间补充母亲的维生素B12，可以改善婴儿的维生素B12状况。在怀孕期间错过补充机会的缺乏母亲仍应鼓励在早期哺乳期间进行补充，因为婴儿的维生素B12状况与母乳喂养婴儿的乳汁维生素B12水平相关，直到婴儿6个月大。尽管有报道称仅通过充足的母体补充，维生素B12缺乏的仅母乳喂养婴儿的生化和临床状况有所改善，但当有此类治疗时，建议直接补充婴儿。 母乳的闪蒸巴氏杀菌不会降低乳汁中的维生素B12浓度。 ◉ 对母乳喂养婴儿的影响：十二名4到11个月大的仅母乳喂养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微克肌肉注射维生素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，三百六十六名孕妇从怀孕的第一 trimester 开始每天服用一次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的婴儿，在调整基线母亲维生素B12缺乏后，比安慰剂组的表达性语言评分更高。认知、接受性语言和运动评分在两组之间没有差异。在6岁时进行的神经生理学评估中，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，未找到相关已发布信息。

◉ 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)