去氧胆酸 | 83-44-3

• 物质功能分类: 生物化工 - 中草药成分
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 中文名称: 去氧胆酸
• 中文别名: 络胆酸；去氧膽酸；脱氧胆酸；3α,12α-二羟-5β-胆烷酸；3α,12α-二羟基-5β-胆烷酸
• 英文名称: Deoxycholic acid
• 英文别名: deoxycholate；DCA；DOCA；(4R)-4-[(3R,5R,8R,9S,10S,12S,13R,14S,17R)-3,12-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid
• CAS: 83-44-3
• 化学式: C₂₄H₄₀O₄
• mdl: MFCD00003673
• 分子量: 392.579
• InChiKey: KXGVEGMKQFWNSR-LLQZFEROSA-N

物化性质

• 熔点：
  171-174 °C(lit.)
• 比旋光度：
  55 º (c=1, EtOH)
• 沸点：
  437.26°C (rough estimate)
• 密度：
  0.9985 (rough estimate)
• 闪点：
  9℃
• 溶解度：
  0.24g/l(15°C)
• LogP：
  5.34 at 22℃ and pH5.7
• 表面张力：
  54mN/m at 51.3mg/L and 20℃
• 物理描述：
  Solid
• 颜色/状态：
  CRYSTALS FROM ALC
• 水溶性：
  -3.95
• 旋光度：
  SPECIFIC OPTICAL ROTATION: +55 DEG (ALCOHOL) @ 20 °C/D
• 分解：
  When heated to decomposition it emits acrid smoke and irritating fumes.
• 解离常数：
  pK= 6.58
• 碰撞截面：
  200.7 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)：
  4.9
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.958
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

ADMET

代谢

在正常条件下，脱氧胆酸不会显著代谢。

Deoxycholic acid is not metabolized to any significant extent under normal conditions.

来源:DrugBank

毒理性

• 致癌物分类

未列在IARC目录中。

Not listed by IARC.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

长期高水平的脱氧胆酸与包括结肠癌在内的几种癌症有关。

Chronically high levels of deoxycholic acid are associated with several forms of cancer including colon cancer.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 相互作用

非血管结合位点上的竞争可能会解释在胆酸存在下，脱氧胆酸减少了溴磺酚酞的分布体积。

...COMPETITION FOR EXTRAVASCULAR BINDING SITES BY DEOXYCHOLIC ACID MAY EXPLAIN REDUCED VOL OF DISTRIBUTION OF BROMSULFOPHTHALEIN IN PRESENCE OF BILE ACID.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

去氧胆酸增强庆大霉素、单霉素、卡那霉素和新霉素对葡萄球菌的抗菌活性。

COMPD INCL DEOXYCHOLATE POTENTIATED ANTISTAPHYLOCOCCI ACTIVITY OF GENTAMYCIN, MONOMYCIN, KANAMYCIN, & NEOMYCIN.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

去氧胆酸（DCA）单独使用以及作为N-亚硝基双（2-羟基丙基）胺诱导的大鼠致癌作用的促进剂进行了测试。使用了三组5到6周大的雄性叙利亚仓鼠（SYR）/NI，每组10只动物，每周一次皮下注射0.9% NaCl，共5周。第1组不接受进一步治疗；第2和第3组分别在饲料中添加0.1%和0.5% DCA，持续30周。动物在第35周进行尸检。第1组和第2组之间的体重没有显著差异，而第3组的体重显著下降（P<0.005）。这三组中没有肝肿瘤、胆管增生、胆囊病变或息肉、胰腺病变或胰腺导管增生。在促进剂研究中，三组5到6周大的仓鼠（数量未说明）每周皮下注射500 mg/kg体重的N-亚硝基双（2-羟基丙基）胺，共5周。第4组不接受进一步治疗，N-亚硝基双（2-羟基丙基）胺治疗后，第5组在饲料中添加0.1% DCA，第6组添加0.5% DCA，持续30周。与第4组相比，第5组和第6组的体重显著下降（P<0.005）。DCA显著增加了胆管癌的诱导，第5组有10/19（P<0.006），第6组有9/25（P<0.05），而第4组只有1/15。胰腺癌在第5组显著增加（14/19，P<0.03）。因此，在本实验条件下，DCA单独使用时并不具有致癌性，但却是N-亚硝基双（2-羟基丙基）胺诱导的大鼠肝和胰腺致癌的有效促进剂。

Deoxycholic acid was tested alone and as a promoter of N-nitrosobis(2-hydroxypropyl)amine induced carcinogenesis in the hamster. Three groups of 5 to 6-wk-old male Syrian hamsters (SYR)/NI were used and 10 animals per group were given subcutaneous injections of 0.9% NaCl, once per week for 5 weeks. Group 1 received no further treatment; groups 2 and 3 received 0.1% and 0.5% DCA in their feed for 30 weeks, respectively. Animals were autopsied at week 35. There was no significant difference in body wt. between groups 1 and 2, whereas there was a significant decrease in body weight for group 3 (P<0.005). There were no liver tumors, bile duct proliferation, gallbladder lesions or polyps, pancreatic lesions, or pancreatic duct hyperplasia in these 3 groups. In the promoter study, three groups of 5 to 6-wk-old hamsters (number not stated) were given a subcutaneous injection of 500 mg/kg body wt. N-nitrosobis(2-hydroxypropyl)amine per week for 5 weeks. Group 4 received no further treatment and the N-nitrosobis(2-hydroxypropyl)amine treatment was followed by 0.1% DCA (group 5) , or 0.5% DCA (group 6) in the feed for 30 weeks. There was a significant body weight loss (P<0.005) for groups 5 and 6 compared to group 4. DCA significantly increased the induction of cholangiocarcinomas 10/19 in group 5 (P<0.006); 9/25 in group 6 (P<0.05) compared to group 4 which had 1/15. Pancreatic carcinomas were significantly increased in group 5 (14/19, P<0.03). Therefore, under the conditions of this experiment, DCA was not carcinogenic when given alone but was an effective promoter of N-nitrosobis(2-hydroxypropyl)amine-induced hepatic and pancreatic carcinogenesis in hamsters.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

脱氧胆酸在皮下给药后迅速吸收。在推荐的最大单次治疗剂量100mg后，治疗后的血浆水平在24小时内恢复到内源性水平。根据提出的治疗指南，预计不会发生累积。

Deoxycholic acid is rapidly absorbed after subcutaneous administration. After maximum recommended single treatment dose, 100mg, the post-treatment plasma levels returned to endogenous levels within 24 hours. With the proposed treatment guideline, no accumulation is expected.

来源:DrugBank

吸收、分配和排泄

• 消除途径

外源性脱氧胆酸与内源性胆酸池在肠肝循环中结合，并以不变的形式与内源性脱氧胆酸一起随粪便排出。

The exogenous deoxycholic acid joins the endogenous bile acid pool in the enterohepatic circulation and is excreted unchanged in feces along with endogenous deoxycholic acid.

来源:DrugBank

吸收、分配和排泄

肝脏通常在24小时内分泌大约24克的胆盐到700到1000毫升的胆汁中。大部分胆盐在小肠下段被重新吸收，并再次可用于分泌。...胆盐的总量大约是2到5克。/胆盐/

LIVER NORMALLY SECRETES APPROX 24 G OF BILE SALTS IN 700 TO 1000 ML OF BILE IN 24 HR. MOST OF BILE SALTS ARE REABSORBED IN LOWER SMALL INTESTINE & AGAIN BECOME AVAILABLE FOR SECRETION. ... POOL OF BILE SALTS IS APPROX 2 TO 5 G. /BILE SALTS/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 危险品标志：
  Xn
• 安全说明：
  S26,S36,S37/39
• 危险类别码：
  R22,R36/37/38
• WGK Germany：
  3
• 海关编码：
  29181990
• 危险品运输编号：
  NONH for all modes of transport
• RTECS号：
  FZ2100000

制备方法与用途

脱氧胆酸由Kythera Biopharmaceuticals公司研发，于2015年4月获美国食品药品监督管理局(FDA)批准上市，成为全球首个局部溶脂药。这种药物存在于胆汁中，是一种游离胆汁酸，具有较强的表面活性，能够破坏和溶解细胞膜，使小范围局部皮下脂肪减少。临床试验表明，与安慰剂相比，脱氧胆酸能有效消除颏下脂肪并改善整体外观。

去氧胆酸适用于治疗和改善成人中度至重度颏下脂肪的凸起或丰满（双下巴）。

含量分析

方法同“胆酸(10005)”，但试样量改为约500mg。计算时，每毫升0.1mol/L氢氧化钠相当于脱氧胆酸(C₂₄H₄₀O₄)39.26毫克。

毒性

ADI值为0～1.25毫克/千克（FAO/WHO, 2001）。

化学性质

微溶于水，易溶于乙醇、醚、三氯甲烷、丙酮及冰醋酸。氢氧化钠和碳酸碱溶液中溶解良好。它来源于从猪胆汁中提取的胆烷酸。

用途

用作利胆药；用于细菌学和酶学研究；以及β-肾上腺素受体的增溶作用。