14605-22-2
基本信息
?;撬嵝苊撗跄懰?BR>?;切苋パ跄懰?BR>牛磺熊脫氧膽酸鈉鹽
TAUROURSODEOXYCHOLIC ACID
TAUROURSODESOXYCHOLIC ACID
2-(((3-alpha,5-beta,7-beta)-3,7-dihydroxy-24-oxocholan-24-ethanesulfonicaci
2-(((3-alpha,5-beta,7-beta)-3,7-dihydroxy-24-oxocholan-24-yl)amino)ethanesul
fonicacid
n-(3-alpha,7-beta-dihydroxy-5-beta-cholan-24-oyl)-taurin
ur906
ursodeoxycholyltaurine
yl)amino)-
tauroursodeoxycholic acid sodium
3a,7b-Dihydroxy-5b-cholan-24-oic Acid N-(2-Sulfoethyl)amide
Ursodeoxycholyltaurin
3α,7β-dihydroxy-5β-cholan-24-oic acid n-(2-sulfoethyl)amide
TUDCA Soduim Salt
TAUROURSODEOXYCHOLIC ACID DIHYDRATE: 90%
2-[[(3a,5,7)-3,7-Dihydroxy-24-oxocholan-24-yl]amino]ethanesulfonic Acid Sodium Salt
3a,7-Dihydroxy-5-cholan-24-oic Acid N-(2-Sulfoethyl)amide
Tauroursodeoxycholic acid sodium salt, 3α,7β-Dihydroxy-5β-cholan-24-oic acid N-(2-sulfoethyl)amide
2-[(3α,7β-Dihydroxy-24-oxo-5β-cholan-24-yl)amino]ethanesulfonic acid
物理化學性質
安全數據
常見問題列表
?;切苋パ跄懰?tauroursodeoxycholicacid)是熊膽汁的主要有效成分,也是人工合成熊膽的主要成分,廣泛存在于人和多種動物膽汁中的一種結合型膽汁酸,有著多種生理藥理作用,該藥及其制劑在國外已有二十年的上市臨床經驗,主要用于固醇性膽囊結石、膽汁郁積性肝病(如:原發(fā)性膽汁性肝硬化)、膽汁反流性胃炎、自身免疫性肝炎(AIH)、原發(fā)性膽汁性肝硬化(PBC)、原發(fā)性硬化性膽管炎(PSC)、慢性肝炎(乙肝、丙肝等)、酒精性脂肪肝、非酒精性脂肪肝、藥物性肝損害、肝移植術前后預防及治療并發(fā)癥等。
現代合成藥物牛磺熊去氧膽酸,是由熊去氧膽酸的梭基與?;撬岬陌被g縮水而成的結合型膽汁酸。國外?;切苋パ跄懰崮z囊已經上市,2007年作為進口藥品獲準在中國銷售,臨床主要用于治療膽囊膽固醇結石、原發(fā)硬化性膽管炎、原發(fā)膽汁性肝硬化和慢性丙型病毒性肝炎等。目前?;切苋パ跄懰嵩纤幖捌渲苿┰谥袊€沒有藥品注冊。
牛熊去氧膽酸鈉是從熊膽汁中分離出來一種天然膽汁酸,屬化學制劑,在體內與?;撬峤Y合存在于膽汁中,是一種親水性膽酸,為一種膽固醇結石溶解劑。能減少肝臟對膽固醇的分泌,降低膽汁中膽固醇的飽和度,促進膽汁酸的分泌,增加膽固醇在膽汁中的溶解度,使膽固醇結石溶解或防止結石的形成。可增加膽汁分泌量,松弛膽管口括約肌產生利膽作用,有利于結石的排出。本品不能溶解其他類型的膽結石。適用于治療膽固醇性結石、高脂血癥、膽汁分泌障礙性疾病、原發(fā)性膽汁性肝硬化、慢性肝炎、膽汁反流性胃炎和預防肝移植急性排斥及反應。本品的溶石作用略弱于鵝去氧膽酸。
以上信息由Chemicalbook的Andy編輯整理。
1)牛磺熊去氧膽酸粗品的制備,按以下步驟進行:
在反應釜中,加入4.0KG熊去氧膽酸,加入19KG丙酮,攪拌下加入三乙胺1650ml,開啟夾套制冷,將混合液的溫度降至-10℃。流加氯甲酸乙酯1120ml,控制氯甲酸乙酯的加入速度,使得反應液溫度維持在-5-0℃之間,30分鐘時加完,繼續(xù)維持溫度攪拌反應40分鐘,制得熊去氧膽酸與氯甲酸乙酯的混合酸酐,將上述混合酸酐反應液通過過濾器用氮氣壓濾至裝有4.2KG純化水,1.4KG?;撬?,0.4KG氫氧化鈉的50升反應釜中,充分攪拌反應3小時,進一步制得?;切苋パ跄懰岽制?.0KG。
2)?;切苋パ跄懰岽制返木疲匆韵虏襟E進行:
(1)將4.0KG?;切苋パ跄懰嵬度?0L反應釜中,加入4KG水和580ml丙酮,,加熱攪拌至全部溶解;
(2)攪拌下冷卻至-5-0℃,析晶30小時;
(3)放料至過濾器中抽濾,抽干后用冰水(-3-0℃)淋洗濾餅,再次抽干,得?;切苋パ跄懰?.3KG(純度99.6%,HPLC),其中?;蛆Z去氧膽酸的含量為0.3%,其他最大單雜含量0.05%(液相色譜測定)。
ERK
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Caspase-3
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Caspase-12
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Human Endogenous Metabolite
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Tauroursodeoxycholate (TUDCA) suppresses both viability and migration of vascular smooth muscle cells (VSMCs) through inhibition of ERK phosphorylation, by induction of mitogen-activated protein kinase phosphatase-1 (MKP-1) via PKCα. Tauroursodeoxycholate inhibits both the proliferation and migration of VSMCs via inhibition of ERK, through Ca 2+ -dependent PKCα translocation. Tauroursodeoxycholate prevents platelet-derived growth factor (PDGF) and vascular injury-induced MMP-9 expression. The knock-down of MKP-1 using specific si-RNA restores the reduced VSMC viability by Tauroursodeoxycholate (200 μM), which suggests that anti-proliferative effect of Tauroursodeoxycholate depended on the MKP-1 expression.
The effects of Tauroursodeoxycholate (TUDCA) on proliferation and apoptosis of VSMCs in vivo are examined using immunohistochemistry for proliferating cell nuclear antigen (PCNA) and the transferase dUTP nick-end labelling (TUNEL) assay. Tauroursodeoxycholate (10, 50, and 100 mg/kg) increases the caspase 3 activity of injured tissues in a dose-dependent manner, indicating that Tauroursodeoxycholate induces apoptosis of VSMCs in the neointima. Using the injured tissues, further examination and comparison of the phosphorylation level of ERK and MMP-9 expression is performed at 1 week after injury, compared with normal controls. Balloon injury increased both the phosphorylation of ERK and expression of MMP-9 in the tissues. Tauroursodeoxycholate (10, 50, and 100 mg/kg) inhibits phosphorylation of ERK and MMP-9 expression in a dose-dependent manner. Tauroursodeoxycholate (TUDCA) is a hydrophilic bile acid. Tauroursodeoxycholate as a cytoprotective agent improves liver function and can prevent hepatocellular carcinoma by reducing ER stress and apoptosis. Tauroursodeoxycholate significantly reduces expression of apoptosis molecules, such as caspase-3, caspase-12, C/EBP homologous protein, c-Jun N-terminal kinase (JNK), activating transcription factor 4 (ATF4), X-box binding protein (XBP), and eukaryotic initiation factor 2α (eIF2α) in Ang II induced ApoE -/- mice (p<0.05). Tauroursodeoxycholate reduces Angiotensin (Ang) II induced abdominal aortic aneurysm (AAA) formation in ApoE -/- mice. Tauroursodeoxycholate is used at a dose of 0.5 g/kg/day in treating Ang II induced ApoE -/- mice (ER stress inhibitor group). Systolic blood pressure (141.3±5.6 mmHg vs 145.9±8.9 mmHg; p>0.05) and total cholesterol levels (663.6±88.7 mg/dL vs 655.7±65.4 mg/dL; p>0 .05) do not differ between the AAA model group and Tauroursodeoxycholate group. In addition, maximum aortic diameter is significantly smaller in those in Tauroursodeoxycholate group compared with those in the AAA model group (0.95±0.03 mm vs 1.79±0.04 mm; p<0.05). AAA lesion areas are also smaller in those in Tauroursodeoxycholate group than in those in the AAA model group (0.37±0.03 mm 2 vs 1.51±0.06 mm 2 ; p<0.05).