2-Hydroxyethyl (2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydro-2H-chromen-6-yl butanedioate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 2-Hydroxyethyl (2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydro-2H-chromen-6-yl butanedioate
• 英文别名: 1-O-(2-hydroxyethyl) 4-O-[(2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-yl] butanedioate
• 化学式: C₃₅H₅₈O₆
• 分子量: 574.8
• InChiKey: AOBORMOPSGHCAX-AZAGJHQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.9
• 重原子数：
  41
• 可旋转键数：
  20
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

ADMET

代谢

tocofersolan的水解发生在肠道腔内。Tocofersolan被细胞吸收，α-生育酚部分以与从饮食来源吸收的维生素E相同的方式出现在淋巴系统中的乳糜微粒中。细胞摄取不需要受体、结合蛋白或代谢过程，也不是通过胞吞作用进行的。脱氘标记的tocofersolan的吸收在脂蛋白中显示出正常模式：α-生育酚首先在乳糜微粒中达到峰值，然后在极低密度脂蛋白（VLDL）中达到峰值，最后在低密度脂蛋白（LDL）和高密度脂蛋白（HDL）中达到峰值。

The hydrolysis of tocofersolan occurs in the gut lumen. Tocofersolan is absorbed by cells, and the alpha-tocopherol moiety appears in chylomicrons in the lymph system in a manner that is identical to vitamin E absorbed from dietary sources. Cellular uptake does not require receptors, binding proteins or metabolic processes and does not occur by pinocytosis. Absorption of deuterated tocofersolan demonstrated a normal pattern in lipoproteins: alpha-tocopherol peaked first in chylomicrons, then peaked in very low- density lipoproteins (VLDL) and finally in low-density lipoproteins (LDL) and high-density lipoproteins (HDL).

来源:DrugBank

毒理性

• 蛋白质结合

高度与脂蛋白结合。

Highly bound to lipoproteins.

来源:DrugBank

吸收、分配和排泄

• 吸收

维生素E的生物利用度在生育酚琥珀酸酯中是独特的，与其他药品不同。由于其两亲性特性，能够形成自己的胶束，生育酚琥珀酸酯即使在无胆盐的情况下也能被肠细胞轻易吸收；经水解后释放出水溶性的_d-α-生育酚_。这种配方增强了d-α-生育酚的吸收，与直接给药的自由形式d-α-生育酚相比。此外，生育酚琥珀酸酯可能还会增强水不溶性药物和其他脂溶性维生素的吸收。生育酚琥珀酸酯是一种前药；其活性代谢物是_d-α-生育酚_。在低浓度下，生育酚琥珀酸酯形成胶束，改善了对非极性脂质（如其他脂溶性维生素）的吸收。其所需的胶束浓度较低（0.04至0.06毫摩尔/升）。对12名健康受试者进行了一项药代动力学研究，比较了生育酚琥珀酸酯与一种水溶性参考维生素E在一次单次口服负荷剂量1200 IU（国际单位）后的情况。生育酚琥珀酸酯的相对生物利用度被发现为（Frel为1.01 ± 1.74），AUC0-t为0.383 ± 0.203μM·h/mg，Cmax为0.013 ± 0.006，Tmax为6.0小时（6.0 – 24.0）。有关维生素E代谢的更多信息，请访问药品条目[DB11251]。

The bioavailability of vitamin E from tocofersolan is unique from than that of other medicinal products. Due to its amphipathic property in which it forms its own micelles, tocofersolan is readily taken up into enterocytes, even in the absence of bile salts; fat-soluble _d-alpha-tocopherol_ is then released after hydrolysis. This formulation enhances the absorption of d-alpha-tocopherol compared to the administration of free d-alpha-tocopherol. Additionally, tocophersolan may enhance the absorption of water-insoluble agents and other fat-soluble vitamins. Tocofersolan is a pro-drug; the active metabolite is the _d-alpha-tocopherol_. At low concentrations, tocofersolan forms micelles which improve the absorption of non-polar lipids such as other fat-soluble vitamins. Its required micellar concentration is low (0.04 to 0.06 mmol/l). A pharmacokinetic study of 12 healthy subjects compared tocofersolan with a water-miscible reference vitamin E after one single oral loading dose of 1200 IU (international units). The relative bioavailability of tocofersolan was found to be (Frel of 1.01 ± 1.74) with AUC0-t of 0.383 ± 0.203μM.h/mg, Cmax of 0.013 ± 0.006, Tmax of 6.0 h (6.0 – 24.0). For more information about Vitamin E metabolism, please visit the drug entry [DB11251].

来源:DrugBank

吸收、分配和排泄

• 消除途径

维生素E主要通过胆汁（75%）和粪便排出，可能是自由的生育酚或氧化形式。尿液是维生素E的次要排泄途径（作为葡萄糖醛酸苷）。

Vitamin E is primarily eliminated in the bile (75%) and feces, either as free tocopherol or in oxidized forms. Urine is a minor elimination route of vitamin E (as glucuronic-conjugate).

来源:DrugBank

吸收、分配和排泄

• 分布容积

主要位于细胞膜、线粒体和微粒体上，维生素E在全身广泛分布（红细胞、大脑、肌肉、肝脏、血小板），脂肪组织是其主要的储存库。

Located principally on cell membranes, within mitochondria and microsomes, vitamin E is widely distributed throughout the body (red blood cells, brain, muscle, liver, platelets) and fat tissues are its primary reservoir.

来源:DrugBank

文献信息

• Pre-spray emulsions and powders containing non-polar compounds
  申请人：VIRUN, INC.

  公开号：US10016363B2

  公开（公告）日：2018-07-10

  Provided are compositions and methods for producing water-soluble powders that contain additives such as essential fatty acids, including omega-3 fatty acids, omega-6 fatty acids, conjugated fatty acids, and other fatty acids; phytochemicals, including phytosterols; other oils; and coenzymes, including coenzyme Q10, and other oil-based additives.

  本发明提供了生产水溶性粉末的组合物和方法，这些粉末含有添加剂，如必需脂肪酸，包括ω-3 脂肪酸、ω-6 脂肪酸、共轭脂肪酸和其他脂肪酸；植物化学物质，包括植物甾醇；其他油；以及辅酶，包括辅酶 Q10 和其他油基添加剂。
• PRE-SPRAY EMULSIONS AND POWDERS CONTAINING NON-POLAR COMPOUNDS
  申请人：VIRUN, INC.

  公开号：EP3193834B1

  公开（公告）日：2020-04-01
• Bioavailability Enhancement Delivery Composition
  申请人：Patel Bhiku G.

  公开号：US20120252906A1

  公开（公告）日：2012-10-04

  A composition for increasing the bioavailability of an active pharmaceutical ingredient (“API”) in humans and animals, comprising a first water soluble surfactant having a cloud point greater than about 37° C., a second water soluble surfactant having a cloud point greater than about 37° C., wherein a mixture of the first surfactant and the second surfactant comprises a cloud point less than about 37° C.
• Statin Bioavailability Enhancement Delivery Composition
  申请人：Prugen IP Holdings, Inc.

  公开号：US20130150393A1

  公开（公告）日：2013-06-13

  A composition for increasing the bioavailability of a statin active pharmaceutical ingredient (“API”) in humans and animals, wherein that composition includes a statin API selected from the group consisting of atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin, a first water soluble surfactant having a cloud point greater than about 37° C., a second water soluble surfactant having a cloud point greater than about 37° C., wherein a mixture of the first surfactant and the second surfactant comprises a cloud point less than about 37° C.
• Solubilization and Bioavailability of Acetaminophen
  申请人：Patel Bhiku G.

  公开号：US20130150396A1

  公开（公告）日：2013-06-13

  A composition for increasing the bioavailability of Acetaminophen in humans and animals, comprising Acetaminophen, a first water soluble surfactant having a cloud point greater than about 37° C., a second water soluble surfactant having a cloud point greater than about 37° C., wherein a mixture of the first surfactant and the second surfactant comprises a cloud point less than about 37° C.