D-生物素 | 58-85-5

• 物质功能分类: 原料药 - 维生素类与矿物质类药 - 维生素C类药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• 中文名称: D-生物素
• 中文别名: D-促进素；生物素；维生素B7；D生物素；D-(+)-生物素；辅酶R；维生素H
• 英文名称: biotin
• 英文别名: D-biotin；vitamin B7；5-[(3AS,4S,6AR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoic acid；vitamin H；L-biotin；5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazolidin-4-yl]pentanoic acid；5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazole-4-yl)-pentanoic acid；5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoic acid
• CAS: 58-85-5
• 化学式: C₁₀H₁₆N₂O₃S
• mdl: MFCD00005541
• 分子量: 244.315
• InChiKey: YBJHBAHKTGYVGT-ZKWXMUAHSA-N

物化性质

• 熔点：
  231-233 °C(lit.)
• 比旋光度：
  89 º (c=1, 0.1N NaOH)
• 沸点：
  573.6±35.0 °C(Predicted)
• 密度：
  1.2693 (rough estimate)
• 溶解度：
  H2O:0.2 mg/mL添加1 NNaOH后溶解度增加。
• LogP：
  0.861 (est)
• 物理描述：
  Solid
• 颜色/状态：
  Long, thin needles from water
• 蒸汽压力：
  1.07X10-8 mm Hg at 25 °C (est)
• 稳定性/保质期：

  Water soln are stable at 100 °C; the dry substance is thermo- and photostable; unstable in strong acids and alkaline soln and in oxidizing agents.

• 旋光度：
  Specific optical rotation: +92 deg at 22 °C (c=1 at 0.4% NaOH)
• 分解：
  Emits toxic fumes of NOx and SOx when heated to decomp.
• 碰撞截面：
  150.4 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  4

ADMET

代谢

生物素以生物素、双降生物素、生物素亚砜、生物素砜、双降生物素甲酮和四降生物素-1-亚砜的形式在尿液中排出。

Biotin is excreted in the urine as biotin, bisnorbiotin, biotin sulfoxide, biotin sulfone, bisnorbiotin methyl ketone and tetranobiotin-1-sulfoxide.

来源:Hazardous Substances Data Bank (HSDB)

代谢

生物素被分解成多种不同的代谢物，包括双生物素、生物素亚砜、生物素砜、双生物素甲基酮和四生物素-1-亚砜。

Biotin is catabolized to a number of different metabolites, including bisnorbiotin, biotin sulfoxide, biotin sulfone, bisonorbiotin methylketone and tetranorbiotin-1-sulfoxide.

来源:Hazardous Substances Data Bank (HSDB)

代谢

95%以上的生物素在人类脱脂乳部分是自由的。在某些妇女中，生物素的浓度差异很大，比血清中的浓度高出一个到两个数量级，这表明有一种传输系统将生物素输送到乳汁中。生物素的代谢物双生物素醇约占50%。在早期和过渡期的人类乳汁中，生物素的代谢物生物素亚砜约占总生物素和代谢物的10%。随着产后成熟，生物素的浓度增加，但在产后5周时，双生物素醇和生物素亚砜的浓度仍分别占25%和8%。目前的研究没有提供证据表明存在一种可溶的生物素结合蛋白或任何其他机制在人类乳汁中捕获生物素。

More than 95% of the biotin is free in the skim fraction of human milk. The concentration of biotin varies substantially in some women and exceeds that in serum by one to two order of magnitude, suggesting that there is a transport system into milk. The biotin metabolite bisnorbiotin accounts for approximately 50%. In early and transitional human milk, the biotin metabolite biotin sulfoxide accounts for about 10% of the total biotin plus metabolites. With postpartum maturation, the biotin concentration increases, but the bisnorbiotin and biotin sulfoxide concentrations still account for 25% and 8% at 5 weeks postpartum. Current studies provide no evidence for a soluble biotin-binding protein or any other mechanism that traps biotin in human milk.

来源:Hazardous Substances Data Bank (HSDB)

代谢

以摩尔计算，生物素大约占人体血清和尿液中总亲和素结合物质的一半。生物素酪氨酸、双去甲生物素、双去甲生物素甲基酮、生物素亚砜和生物素砜构成了大部分剩余部分。在一些个体中，抗惊厥药物和怀孕期间会加速生物素的代谢，从而增加了尿液中生物素代谢物与生物素的比例。

On a molar basis, biotin accounts for approximately half of the total avidin-binding substances in human serum and urine. Biocytin, bisnorbiotin, bisnorbiotin methylketone, biotin sulfoxide, and biotin sulfone form most of the balance. Biotin metabolism is accelerated in some individuals by anticonvulsants and during pregnancy, thereby increasing the ratio of biotin metabolites to biotin excreted in urine.

来源:Hazardous Substances Data Bank (HSDB)

代谢

生物素在排泄前会被代谢成无活性的代谢物。大约一半的生物素在排泄前会经历代谢。哺乳动物中已经确定了两种主要的生物素分解途径。在第一种途径中，生物素的戊酸侧链通过β氧化被降解。这导致双非生物素、四非生物素和相关中间体的形成，这些中间体已知是由脂肪酸的β氧化产生的。生物素这种β氧化的细胞位置尚不确定。不稳定的β-酮生物素和β-酮-双非生物素的非酶促脱羧作用导致双非生物素甲基酮和四非生物素甲基酮的形成，这些物质出现在尿液中。在第二种途径中，生物素噻吩环中的硫被氧化，导致生物素L-亚砜、生物素D-亚砜和生物素砜的形成。环硫的氧化和侧链的β-氧化导致形成双非生物素砜等代谢物。在哺乳动物中，生物素环的降解释放二氧化碳和尿素的过程在数量上是微不足道的。

An alternate fate to being incorporated into carboxylases or unchanged excretion is catabolism to an inactive metabolite before excretion in urine. About half of biotin undergoes metabolism before excretion. Two principal pathways of biotin catabolism have been identified in mammals. In the first pathway, the valeric acid side chain of biotin is degraded by beta oxidation. This leads to the formation of bisnorbiotin, tetranorbiotin, and related intermediates that are known to result from beta-oxidation of fatty acids. The cellular site of this beta-oxidation of biotin is uncertain. Nonenzymatic decarboxylation of the unstable beta-ketobiotin and beta-keto-bisnorbiotin leads to formation of bisnorbiotin methylketone and tetranorbiotin methylketone, which appear in urine. In the second pathway, the sulfur in the thiophane ring of biotin is oxidized, leading to the formation of biotin L-sulfoxide, biotin D-sulfoxide, and biotin sulfone. Combined oxidation of the ring sulfur and beta-oxidation of the side chain lead to metabolites such as bisnorbiotin sulfone. In mammals, degradation of the biotin ring to release carbon dioxide and urea is quantitatively minor.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

生物素对于运输羧基单元和固定二氧化碳的酶的正常功能是必需的，它对于包括糖异生、脂肪生成、脂肪酸生物合成、丙酸代谢以及支链氨基酸的分解代谢在内的各种代谢功能也是必需的。

Biotin is necessary for the proper functioning of enzymes that transport carboxyl units and fix carbon dioxide, and is required for various metabolic functions, including gluconeogenesis, lipogenesis, fatty acid biosynthesis, propionate metabolism, and catabolism of branched-chain amino acids.

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

• 暴露途径

口腔。 系统性 - 大约 50%

Oral. Systemic - approximately 50%

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

长时间皮肤接触可能会引起刺激。

Prolonged skin contact may cause irritation.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 相互作用

卡马西平、苯妥英和苯巴比妥可以加速生物素的代谢，可能导致生物素状态降低。长期使用卡马西平、苯妥英、苯巴比妥和普里米酮与生物素血浆浓度降低有关。

Carbamazepine, phenytoin, and phenobarbital can accelerate biotin metabolism and may cause reduced biotin status. Long-term use of carbamazepine, phenytoin, phenobarbital and primidone has been associated with reduced plasma concentrations of biotin.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

系统性的 - 大约50%

Systemic - approximately 50%

来源:DrugBank

吸收、分配和排泄

肠道从几个来源接触到生物素：饮食、生物素补充剂和在大肠中由细菌合成的生物素。饮食中的生物素以自由形式和蛋白质结合形式存在。蛋白质结合的生物素被蛋白酶和肽酶消化成含有生物素的寡肽和生物细胞素（epsilon-N-生物素基-L-赖氨酸）。生物细胞素和含有生物素的寡肽通过生物素酶转化为生物素。生物素 - 包括饮食来源的生物素和补充生物素 - 从小肠有效地被吸收。在食物来源的生物素剂量下，生物素似乎是通过一种钠依赖性载体进入肠细胞的。在较高剂量的生物素下，吸收似乎是通过被动扩散发生的。由结肠微生物群产生的生物素的吸收，似乎是通过近端大肠的载体介导过程发生的。

The intestine is exposed to biotin from a few sources: the diet, biotin supplements and biotin synthesized by bacteria in the large intestine. Dietary biotin exists in free and protein-bound forms. Protein-bound biotin is digested by proteases and peptidases to biotin-containing oligopeptides and biocytin (epsilon-N-biotinyl-L-lysine). Biocytin and the biotin-containing oligopeptides are converted to biotin via the enzyme biotinidase. Biotin - both dietary-derived biotin and supplementary biotin - is efficiently absorbed from the small intestine. At doses of biotin derived from food, biotin appears to be transported into enterocytes by a sodium -dependent carrier. At higher doses of biotin,absorption appears to occur by passive diffusion. Absorption of the biotin produced by the colonic microflora, appears to occur by a carrier mediated process in the proximal large intestine.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

消除：主要在尿液中。

Elimination: Primarily in urine.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

蛋白质结合：主要与血浆蛋白结合。

Protein binding: Primarily to plasma proteins.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

吸收率：大约50%。

Absorption: approximately 50%.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 危险品标志：
  Xn
• 安全说明：
  S24/25
• 危险类别码：
  R20/21/22,R36/37/38
• WGK Germany：
  1
• 海关编码：
  29362930
• 危险品运输编号：
  OTH
• RTECS号：
  XJ9088200
• 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

根据所提供的信息，我们可以得出以下几点关于生物素在孕妇中的使用情况:

1. 大约50%的孕妇可能存在生物素缺乏问题。这主要是因为她们体内缺少一种用于正确使用生物素的酶。

2. 有研究表明,大剂量使用生物素可能会增加流产风险和导致胎儿畸形的风险。因此大多数医生不建议怀孕妇女采用生物素营养品作为治疗措施。

3. 虽然生物素本身毒性较低,但过量摄入仍需谨慎。研究发现最大安全摄入量为每日5000微克左右(具体数值可能因人而异)。

4. 孕妇最好通过均衡饮食来获取足够的生物素,而不是单独补充。富含生物素的食物包括全谷物、坚果种子、蛋类等。

5. 如果确实需要额外补充,建议在医生指导下进行,并密切关注任何不良反应。

总之,对于孕妇来说,谨慎使用生物素营养品是明智的选择。如有需求,应在专业医疗人员的评估下适量摄入。