熊去氧膽酸

Ursodeoxycholic acid
臨床資料
商品名（英語：Drug nomenclature）	Actigall
其他名稱	ursodeoxycholic acid, Actigall, Ursosan, Urso, Urso Forte
AHFS/Drugs.com	Monograph
MedlinePlus	a699047
核准狀況	美 DailyMed: 19396;
懷孕分級	澳: B3 ; ;
給藥途徑	oral
ATC碼	A05AA02 (WHO) ;
法律規範狀態
法律規範	澳：限醫生處方（S4）; 加：處方藥（℞-only）; 英：處方藥（℞-only） (POM); 美：處方藥（℞-only）;
識別資訊
	IUPAC命名法 3α,7β-dihydroxy-5β-cholan-24-oic acid; OR; (R)-4-((3R,5S,7S,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-; 10,13-dimethylhexadecahydro-; 1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid; ;
CAS號	128-13-2
PubChem CID	31401;
IUPHAR/BPS	7104;
DrugBank	DB01586 ;
ChemSpider	29131 ;
UNII	724L30Y2QR;
KEGG	D00734 ;
ChEBI	CHEBI:9907 ;
ChEMBL	ChEMBL1551 ;
PDB配體ID	IU5 (PDBe, RCSB PDB);
CompTox Dashboard（英語：CompTox Chemicals Dashboard） (EPA)	DTXSID6023731 ;
ECHA InfoCard	100.004.437
化學資訊
化學式	C24H40O4
摩爾質量	392.56 g/mol
3D模型（JSmol（英語：JSmol））	交互式圖像;
熔點	203 °C（397 °F）
	SMILES O=C(O)CC[C@H]([C@H]1CC[C@@H]2[C@]1(C)CC[C@H]4[C@H]2[C@@H](O)C[C@@H]3C[C@H](O)CC[C@@]34C)C;
	InChI InChI=1S/C24H40O4/c1-14(4-7-21(27)28)17-5-6-18-22-19(9-11-24(17,18)3)23(2)10-8-16(25)12-15(23)13-20(22)26/h14-20,22,25-26H,4-13H2,1-3H3,(H,27,28)/t14-,15+,16-,17-,18+,19+,20+,22+,23+,24-/m1/s1 ; Key:RUDATBOHQWOJDD-UZVSRGJWSA-N ;

熊去氧膽酸（英語：Ursodeoxycholic acid，也被稱為3α,7β-二羥基-5β-膽烷-24-羧酸，3α,7β-dihydroxy-5β-cholan-24-oic acid，縮寫 UDCA），是一種來自熊膽的膽汁酸^[1]，為次級膽汁酸，在大部分動物體內由初級膽汁酸經由細菌代謝生成。熊科動物可以直接合成這種膽汁酸。^[2]

提純的熊去氧膽酸在醫學上用來溶解膽結石、膽泥（英語：biliary sludge），作用機理是增加膽汁內膽固醇的溶解度。^[3]^[4]對於原發性膽汁性膽管炎、^[5]原發性硬化性膽管炎（英語：Primary sclerosing cholangitis）、^[6]妊娠期肝內膽汁淤積症（英語：intrahepatic cholestasis of pregnancy）^[7]以及其他膽汁淤積^[8]會造成化驗數據上的療效，但對移植率、生存率並沒有正面效果。

它可以降低細胞表面血管緊張素轉化酶2受體的表達量。^[9]

歷史

熊膽是熊去氧膽酸的天然來源。1955年，日本科學家成功化學合成了熊去氧膽酸^[10]。1987年12月，艾爾建申請的熊去氧膽酸獲准在美國上市。^[11]

合成

工業上是通過半合成製造。牛肉工業的副產物之一是牛膽汁，其中富含膽酸。膽酸經過化學修飾即可變成熊去氧膽酸，合成產率約30%。^[12]

參考文獻

^ 放過熊吧！可治療膽結石的熊膽早就能用化學合成. 食力 foodNEXT. [2021-12-08]. （原始內容存檔於2021-12-08）（中文（臺灣））.
^ Hagey LR, Crombie DL, Espinosa E, Carey MC, Igimi H, Hofmann AF. Ursodeoxycholic acid in the Ursidae: biliary bile acids of bears, pandas, and related carnivores. Journal of Lipid Research. November 1993, 34 (11): 1911–1917. PMID 8263415. doi:10.1016/S0022-2275(20)35109-9 .
^ Hofmann AF. Medical dissolution of gallstones by oral bile acid therapy. American Journal of Surgery. September 1989, 158 (3): 198–204. PMID 2672842. doi:10.1016/0002-9610(89)90252-3.
^ Jüngst C, Kullak-Ublick GA, Jüngst D. Gallstone disease: Microlithiasis and sludge. Best Practice & Research. Clinical Gastroenterology. 2006, 20 (6): 1053–1062. PMID 17127187. doi:10.1016/j.bpg.2006.03.007.
^ Shi J, Wu C, Lin Y, Chen YX, Zhu L, Xie WF. Long-term effects of mid-dose ursodeoxycholic acid in primary biliary cirrhosis: a meta-analysis of randomized controlled trials. The American Journal of Gastroenterology. July 2006, 101 (7): 1529–1538. PMID 16863557. S2CID 32076958. doi:10.1111/j.1572-0241.2006.00634.x.
^ Lindor KD, Kowdley KV, Luketic VA, Harrison ME, McCashland T, Befeler AS, Harnois D, Jorgensen R, Petz J, Keach J, Mooney J, Sargeant C, Braaten J, Bernard T, King D, Miceli E, Schmoll J, Hoskin T, Thapa P, Enders F. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. September 2009, 50 (3): 808–814. PMC 2758780 . PMID 19585548. doi:10.1002/hep.23082.
^ Walker KF, Chappell LC, Hague WM, Middleton P, Thornton JG. Pharmacological interventions for treating intrahepatic cholestasis of pregnancy. The Cochrane Database of Systematic Reviews. July 2020, 2020 (7): CD000493. PMC 7389072 . PMID 32716060. doi:10.1002/14651858.CD000493.pub3.
^ Kotb MA. Review of historical cohort: ursodeoxycholic acid in extrahepatic biliary atresia. Journal of Pediatric Surgery. July 2008, 43 (7): 1321–1327. PMID 18639689. doi:10.1016/j.jpedsurg.2007.11.043.
^ Teresa Brevini, Mailis Maes, Gwilym J. Webb, Binu V. John, Claudia D. Fuchs, Gustav Buescher, Lu Wang, Chelsea Griffiths, Marnie L. Brown, William E. Scott, Pehuén Pereyra-Gerber, William T. H. Gelson, Stephanie Brown, Scott Dillon, Daniele Muraro, Jo Sharp, Megan Neary, Helen Box, Lee Tatham, James Stewart, Paul Curley, Henry Pertinez, Sally Forrest, Petra Mlcochova, Sagar S. Varankar, Mahnaz Darvish-Damavandi, Victoria L. Mulcahy, Rhoda E. Kuc, Thomas L. Williams, James A. Heslop, Davide Rossetti, Olivia C. Tysoe, Vasileios Galanakis, Marta Vila-Gonzalez, Thomas W. M. Crozier, Johannes Bargehr, Sanjay Sinha, Sara S. Upponi, Corrina Fear, Lisa Swift, Kourosh Saeb-Parsy, Susan E. Davies, Axel Wester, Hannes Hagström, Espen Melum, Darran Clements, Peter Humphreys, Jo Herriott, Edyta Kijak, Helen Cox, Chloe Bramwell, Anthony Valentijn, Christopher J. R. Illingworth, UK-PBC research consortium, Bassam Dahman, Dustin R. Bastaich, Raphaella D. Ferreira, Thomas Marjot, Eleanor Barnes, Andrew M. Moon, Alfred S. Barritt, Ravindra K. Gupta, Stephen Baker, Anthony P. Davenport, Gareth Corbett, Vassilis G. Gorgoulis, Simon J. A. Buczacki, Joo-Hyeon Lee, Nicholas J. Matheson, Michael Trauner, Andrew J. Fisher, Paul Gibbs, Andrew J. Butler, Christopher J. E. Watson, George F. Mells, Gordon Dougan, Andrew Owen, Ansgar W. Lohse, Ludovic Vallier, Fotios Sampaziotis. FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2. Nature. 2022-12-05 [2022-12-07]. ISSN 0028-0836. doi:10.1038/s41586-022-05594-0. （原始內容存檔於2023-06-26）（英語）.
^ Feng Y, Siu K, Wang N, Ng KM, Tsao SW, Nagamatsu T, Tong Y. Bear bile: dilemma of traditional medicinal use and animal protection. Journal of Ethnobiology and Ethnomedicine. 2009, 5 (1): 2. PMC 2630947 . PMID 19138420. doi:10.1186/1746-4269-5-2.
^ Actigall: FDA-Approved Drugs. U.S. [[美國食品藥品監督管理局|]] (FDA). [29 April 2020]. （原始內容存檔於2020-10-19）.
^ Tonin F, Arends IW. Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review. Beilstein Journal of Organic Chemistry. 2018, 14: 470–483. PMC 5827811 . PMID 29520309. doi:10.3762/bjoc.14.33 .

外部連結

Ursodeoxycholic acid information （頁面存檔備份，存於互聯網檔案館） at MedlinePlus

[1] 放過熊吧！可治療膽結石的熊膽早就能用化學合成. 食力 foodNEXT. [2021-12-08]. （原始內容存檔於2021-12-08）（中文（臺灣））.

[pmid8263415-2] Hagey LR, Crombie DL, Espinosa E, Carey MC, Igimi H, Hofmann AF. Ursodeoxycholic acid in the Ursidae: biliary bile acids of bears, pandas, and related carnivores. Journal of Lipid Research. November 1993, 34 (11): 1911–1917. PMID 8263415. doi:10.1016/S0022-2275(20)35109-9 .

[PMID2672842-3] Hofmann AF. Medical dissolution of gallstones by oral bile acid therapy. American Journal of Surgery. September 1989, 158 (3): 198–204. PMID 2672842. doi:10.1016/0002-9610(89)90252-3.

[4] Jüngst C, Kullak-Ublick GA, Jüngst D. Gallstone disease: Microlithiasis and sludge. Best Practice & Research. Clinical Gastroenterology. 2006, 20 (6): 1053–1062. PMID 17127187. doi:10.1016/j.bpg.2006.03.007.

[5] Shi J, Wu C, Lin Y, Chen YX, Zhu L, Xie WF. Long-term effects of mid-dose ursodeoxycholic acid in primary biliary cirrhosis: a meta-analysis of randomized controlled trials. The American Journal of Gastroenterology. July 2006, 101 (7): 1529–1538. PMID 16863557. S2CID 32076958. doi:10.1111/j.1572-0241.2006.00634.x.

[6] Lindor KD, Kowdley KV, Luketic VA, Harrison ME, McCashland T, Befeler AS, Harnois D, Jorgensen R, Petz J, Keach J, Mooney J, Sargeant C, Braaten J, Bernard T, King D, Miceli E, Schmoll J, Hoskin T, Thapa P, Enders F. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. September 2009, 50 (3): 808–814. PMC 2758780 . PMID 19585548. doi:10.1002/hep.23082.

[7] Walker KF, Chappell LC, Hague WM, Middleton P, Thornton JG. Pharmacological interventions for treating intrahepatic cholestasis of pregnancy. The Cochrane Database of Systematic Reviews. July 2020, 2020 (7): CD000493. PMC 7389072 . PMID 32716060. doi:10.1002/14651858.CD000493.pub3.

[8] Kotb MA. Review of historical cohort: ursodeoxycholic acid in extrahepatic biliary atresia. Journal of Pediatric Surgery. July 2008, 43 (7): 1321–1327. PMID 18639689. doi:10.1016/j.jpedsurg.2007.11.043.

[9] Teresa Brevini, Mailis Maes, Gwilym J. Webb, Binu V. John, Claudia D. Fuchs, Gustav Buescher, Lu Wang, Chelsea Griffiths, Marnie L. Brown, William E. Scott, Pehuén Pereyra-Gerber, William T. H. Gelson, Stephanie Brown, Scott Dillon, Daniele Muraro, Jo Sharp, Megan Neary, Helen Box, Lee Tatham, James Stewart, Paul Curley, Henry Pertinez, Sally Forrest, Petra Mlcochova, Sagar S. Varankar, Mahnaz Darvish-Damavandi, Victoria L. Mulcahy, Rhoda E. Kuc, Thomas L. Williams, James A. Heslop, Davide Rossetti, Olivia C. Tysoe, Vasileios Galanakis, Marta Vila-Gonzalez, Thomas W. M. Crozier, Johannes Bargehr, Sanjay Sinha, Sara S. Upponi, Corrina Fear, Lisa Swift, Kourosh Saeb-Parsy, Susan E. Davies, Axel Wester, Hannes Hagström, Espen Melum, Darran Clements, Peter Humphreys, Jo Herriott, Edyta Kijak, Helen Cox, Chloe Bramwell, Anthony Valentijn, Christopher J. R. Illingworth, UK-PBC research consortium, Bassam Dahman, Dustin R. Bastaich, Raphaella D. Ferreira, Thomas Marjot, Eleanor Barnes, Andrew M. Moon, Alfred S. Barritt, Ravindra K. Gupta, Stephen Baker, Anthony P. Davenport, Gareth Corbett, Vassilis G. Gorgoulis, Simon J. A. Buczacki, Joo-Hyeon Lee, Nicholas J. Matheson, Michael Trauner, Andrew J. Fisher, Paul Gibbs, Andrew J. Butler, Christopher J. E. Watson, George F. Mells, Gordon Dougan, Andrew Owen, Ansgar W. Lohse, Ludovic Vallier, Fotios Sampaziotis. FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2. Nature. 2022-12-05 [2022-12-07]. ISSN 0028-0836. doi:10.1038/s41586-022-05594-0. （原始內容存檔於2023-06-26）（英語）.

[Feng-10] Feng Y, Siu K, Wang N, Ng KM, Tsao SW, Nagamatsu T, Tong Y. Bear bile: dilemma of traditional medicinal use and animal protection. Journal of Ethnobiology and Ethnomedicine. 2009, 5 (1): 2. PMC 2630947 . PMID 19138420. doi:10.1186/1746-4269-5-2.

[11] Actigall: FDA-Approved Drugs. U.S. [[美國食品藥品監督管理局|]] (FDA). [29 April 2020]. （原始內容存檔於2020-10-19）.

[12] Tonin F, Arends IW. Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review. Beilstein Journal of Organic Chemistry. 2018, 14: 470–483. PMC 5827811 . PMID 29520309. doi:10.3762/bjoc.14.33 .

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