| 词条 | Ursodeoxycholic acid |
| 释义 |
| verifiedrevid = 470620651 | IUPAC_name = 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 | image = Ursodeoxycholic acid acsv.svg | width = 300 | image2 = Ursodeoxycholic acid ball-and-stick.png | width2 = 300 | tradename = Actigall, Udcasid, others | Drugs.com = {{drugs.com|monograph|ursodiol}} | licence_EU = | licence_US = Ursodiol | pregnancy_AU = B3 | pregnancy_US = B | pregnancy_category = | legal_AU = S4 | legal_CA = Rx-only | legal_UK = POM | legal_US = Rx-only | legal_status = | dependency_liability = | routes_of_administration = oral | MedlinePlus = a699047 | DailyMedID = 19396 | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | IUPHAR_ligand = 7104 | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 128-13-2 | ATC_prefix = A05 | ATC_suffix = AA02 | ATC_supplemental = | PubChem = 31401 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01586 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 29131 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 724L30Y2QR | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00734 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 9907 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 1551 | PDB_ligand = IU5 | C=24 | H=40 | O=4 | molecular_weight = 392.56 g/mol | 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 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 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 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = RUDATBOHQWOJDD-UZVSRGJWSA-N | synonyms = ursodeoxycholic acid, Actigall, Ursosan, Urso, Urso Forte | density = | melting_point = 203 | boiling_point = | solubility = | specific_rotation = }} Ursodeoxycholic acid (INN, BAN and AAN), also known as ursodiol (USAN) and the abbreviation UDCA, from the Latin noun ursus meaning bear, as bear bile contains the substance, is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria. Endogenous effectsPrimary bile acids are produced by the liver and stored in the gall bladder. When secreted into the intestine, primary bile acids can be metabolized into secondary bile acids by intestinal bacteria. Primary and secondary bile acids help the body digest fats. Ursodeoxycholic acid helps regulate cholesterol by reducing the rate at which the intestine absorbs cholesterol molecules while breaking up micelles containing cholesterol. Because of this property, ursodeoxycholic acid is used to treat (cholesterol) gallstones non-surgically. It is also used to relieve itching in pregnancy for some women who suffer obstetric cholestasis. While some bile acids are known to be colon tumor promoters (e.g. deoxycholic acid), others such as ursodeoxycholic acid are thought to be chemopreventive, perhaps by inducing cellular differentiation and/or cellular senescence in colon epithelial cells.[1] It is believed to inhibit apoptosis.[2] Ursodeoxycholic acid has also been shown experimentally to suppress immune response such as immune cell phagocytosis. Prolonged exposure and/or increased quantities of systemic (throughout the body, not just in the digestive system) ursodeoxycholic acid can be toxic.[3] Medical usesAn incomplete list of the current uses is as follows:
Meta-analyses have borne out conflicting results on the mortality benefit of UDCA in PBC, however analyses that exclude trials of short duration (i.e. < 2 years) have demonstrated a survival benefit and are generally considered more clinically relevant.[8][9] A Cochrane systematic review in 2012 found no significant benefit in reducing mortality, the rate of liver transplantation, pruritus or fatigue.[10] Ursodiol is the only FDA approved drug to treat PBC but many patients do not respond; other treatments are under study.[11] Ursodiol may be used to treat intrahepatic cholestasis of pregnancy, to relieve the symptoms of itching, to decrease infant mortality rate, and to decrease bile absorption.[12] Ursodiol is not believed to reduce maternal mortality from hemorrhage in such cases. In children, ursodeoxycholic acid use is not licensed, as its safety and effectiveness have not been established. Evidence is accumulating that ursodeoxycholic acid is ineffective and unsafe in neonatal hepatitis and neonatal cholestasis.[13][14][15] There is insufficient evidence to justify routine use of ursodeoxycholic acid in cystic fibrosis, especially that available data for analysis of long-term outcomes such as death or need for liver transplantation is lacking.[16]{{Update inline|reason=Updated version https://www.ncbi.nlm.nih.gov/pubmed/28891588|date = October 2018}} In double the recommended daily dose, ursodeoxycholic acid reduces elevated liver enzyme levels in those with primary sclerosing cholangitis, but its use was associated with an increased risk of serious adverse events (the development of cirrhosis, varices, death or liver transplantation) in patients who received ursodeoxycholic acid compared with those who received placebo. Serious adverse events were more common in the ursodeoxycholic acid group than the placebo group. The risk was 2.1 times greater for death, transplantation, or minimal listing criteria in patients on ursodeoxycholic acid than for those on placebo.[17] It is concluded that ursodeoxycholic acid use is associated with improved serum liver tests that do not always correlate with improved liver disease status. WHO Drug Information advises against its use in primary sclerosing cholangitis in unapproved doses beyond 13–15 mg/kg/day.[18] Recent research at the University of Sheffield indicates that Ursodeoxycholic Acid shows promise in the treatment of Alzheimer's Disease.[19][20] Mechanism of actionThe drug reduces cholesterol absorption and is used to dissolve (cholesterol) gallstones in patients who want an alternative to surgery. If the patient stops taking the drug, the gallstones tend to recur if the condition that gave rise to their formation does not change.[21][22] For this reason, it has not supplanted surgical treatment by cholecystectomy. Ursodeoxycholic acid has been shown to exert anti-inflammatory and protective effects in human epithelial cells of the gastrointestinal tract. It has been linked to regulation of immunoregulatory responses via regulation of cytokines,[23] antimicrobial peptides defensins,[24] and take an active part in increased restitution of wound in the colon.[25] Moreover, UDCA's effects has been shown to have exert actions outside the epithelial cells.[26] Trade namesUrsodeoxycholic acid can be chemically synthesized and is marketed under multiple trade names, including Ursetor, Actibile, Actigall, Biliver, Deursil, Egyurso, Udcasid, Udiliv, Udoxyl, Urso, Urso Forte, Ursocol, Ursoliv, Ursofalk, Ursosan, Ursoserinox, Udimarin, Ursonova, and Stener. See also
References1. ^{{cite journal | vauthors = Akare S, Jean-Louis S, Chen W, Wood DJ, Powell AA, Martinez JD | title = Ursodeoxycholic acid modulates histone acetylation and induces differentiation and senescence | journal = International Journal of Cancer | volume = 119 | issue = 12 | pages = 2958–69 | date = December 2006 | pmid = 17019713 | doi = 10.1002/ijc.22231 }} 2. ^{{cite journal | vauthors = Amaral JD, Viana RJ, Ramalho RM, Steer CJ, Rodrigues CM | title = Bile acids: regulation of apoptosis by ursodeoxycholic acid | journal = Journal of Lipid Research | volume = 50 | issue = 9 | pages = 1721–34 | date = September 2009 | pmid = 19417220 | pmc = 2724780 | doi = 10.1194/jlr.R900011-JLR200 }} 3. ^Material Safety Data Sheet on Ursodiol MSDS. https://fscimage.fishersci.com/msds/70916.htm 4. ^1 {{cite web|url=https://www.uptodate.com/contents/ursodeoxycholic-acid-ursodiol-drug-information?source=preview&search=ursodeoxycholic+acid&anchor=F232620#F232620|title=Ursodeoxycholic acid ursodiol drug information|website=www.uptodate.com}} 5. ^{{cite web|url=https://www.uptodate.com/contents/cystic-fibrosis-hepatobiliary-disease?source=search_result&search=cystic+fibrosis&selectedTitle=2~150#H106943356|title=Cystic fibrosis: Hepatobiliary disease|website=www.uptodate.com}} 6. ^{{cite web|url=https://www.uptodate.com/contents/treatment-of-unconjugated-hyperbilirubinemia-in-term-and-late-preterm-infants?source=see_link#H30|title=Treatment of unconjugated hyperbilirubinemia in term and late preterm infants|website=www.uptodate.com}} 7. ^{{cite journal | vauthors = Uy MC, Talingdan-Te MC, Espinosa WZ, Daez ML, Ong JP | title = Ursodeoxycholic acid in the prevention of gallstone formation after bariatric surgery: a meta-analysis | journal = Obesity Surgery | volume = 18 | issue = 12 | pages = 1532–8 | date = December 2008 | pmid = 18574646 | doi = 10.1007/s11695-008-9587-7 | url = https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0025733/ }} 8. ^{{cite journal | vauthors = Shi J, Wu C, Lin Y, Chen YX, Zhu L, Xie WF | title = Long-term effects of mid-dose ursodeoxycholic acid in primary biliary cirrhosis: a meta-analysis of randomized controlled trials | journal = The American Journal of Gastroenterology | volume = 101 | issue = 7 | pages = 1529–38 | date = July 2006 | pmid = 16863557 | doi = 10.1111/j.1572-0241.2006.00634.x }} 9. ^{{Cite web|url=https://www.uptodate.com/contents/trials-of-ursodeoxycholic-acid-for-the-treatment-of-primary-biliary-cholangitis-primary-biliary-cirrhosis?source=see_link#H6|title=Trials of ursodeoxycholic acid for the treatment of primary biliary cholangitis (primary biliary cirrhosis)|website=www.uptodate.com|access-date=2016-12-27}} 10. ^{{cite journal | vauthors = Rudic JS, Poropat G, Krstic MN, Bjelakovic G, Gluud C | title = Ursodeoxycholic acid for primary biliary cirrhosis | journal = The Cochrane Database of Systematic Reviews | volume = 12 | pages = CD000551 | date = December 2012 | pmid = 23235576 | doi = 10.1002/14651858.CD000551.pub3 }} 11. ^{{cite journal | vauthors = Bowlus CL, Kenney JT, Rice G, Navarro R | title = Primary Biliary Cholangitis: Medical and Specialty Pharmacy Management Update | journal = Journal of Managed Care & Specialty Pharmacy | volume = 22 | issue = 10–a–s Suppl | pages = S3–S15 | date = October 2016 | pmid = 27700211 | doi = 10.18553/jmcp.2016.22.10-a-s.s3 }} 12. ^{{cite web|last=Mayo Clinic Staff|title=Cholestasis of pregnancy: Treatment and Drugs|url=http://www.mayoclinic.com/health/cholestasis-of-pregnancy/DS01033/DSECTION=treatments-and-drugs|publisher=Mayo Clinic}} 13. ^{{cite journal | vauthors = Kotb MA | title = Review of historical cohort: ursodeoxycholic acid in extrahepatic biliary atresia | journal = Journal of Pediatric Surgery | volume = 43 | issue = 7 | pages = 1321–7 | date = July 2008 | pmid = 18639689 | doi = 10.1016/j.jpedsurg.2007.11.043 }} 14. ^{{cite book |author=Paediatric Formulary Committee |title=British National Formulary for Children 2008 |publisher=Pharmaceutical Press |location=London |year=2008 |page=91 |isbn=978-0-85369-780-0}} 15. ^{{cite web | title = Urso package insert. | location = Birmingham, AL | publisher = Axcan Pharma U.S. | date = January 2000 | url = http://www.axcan.com/pdf/urso_patient_brochure.pdf }} 16. ^{{cite journal | vauthors = Cheng K, Ashby D, Smyth RL | title = Ursodeoxycholic acid for cystic fibrosis-related liver disease | journal = The Cochrane Database of Systematic Reviews | issue = 12 | pages = CD000222 | date = December 2014 | pmid = 25501301 | doi = 10.1002/14651858.CD000222.pub3 }} 17. ^{{cite journal | vauthors = 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 | title = High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis | journal = Hepatology | volume = 50 | issue = 3 | pages = 808–14 | date = September 2009 | pmid = 19585548 | pmc = 2758780 | doi = 10.1002/hep.23082 }} 18. ^{{cite journal | journal = WHO Drug Information | volume = 26 | issue = 1 | date = 2012 | title = Ursodeoxycholic acid: serious hepatic events | url = http://www.who.int/medicines/publications/druginformation/issues/26-1.pdf }} 19. ^{{cite web | first = Maria | last = Cohut | name-list-format = vanc | title = Existing liver drug can help treat Alzheimer's | work = Medical News Today | url = https://www.medicalnewstoday.com/articles/322964.php }} 20. ^{{cite journal | vauthors = Bell SM, Barnes K, Clemmens H, Al-Rafiah AR, Al-Ofi EA, Leech V, Bandmann O, Shaw PJ, Blackburn DJ, Ferraiuolo L, Mortiboys H | display-authors = 6 | title = Ursodeoxycholic Acid Improves Mitochondrial Function and Redistributes Drp1 in Fibroblasts from Patients with either Sporadic or Familial Alzheimer's Disease | journal = Journal of Molecular Biology | volume = 430 | issue = 21 | pages = 3942–3953 | date = August 2018 | pmid = 30171839 | pmc = 6193139 | doi = 10.1016/j.jmb.2018.08.019 }} 21. ^{{cite web | title = URSODEOXYCHOLIC ACID | work = Public Assessment Report for paediatric studies submitted in accordance with Article 45 of Regulation (EC) No1901/2006, as amended | url = http://www.db.cbg-meb.nl/veegactie/nlvert/Alprazolam_January2012.pdf }} 22. ^{{cite web | title = PUBLIC ASSESSMENT REPORT | publisher = Medicines Evaluation Board in the Netherlands | url = http://mri.medagencies.org/download/NL_H_2516_001_PAR.pdf }} 23. ^{{cite journal | vauthors = Ward JB, Lajczak NK, Kelly OB, O'Dwyer AM, Giddam AK, Ní Gabhann J, Franco P, Tambuwala MM, Jefferies CA, Keely S, Roda A, Keely SJ | title = Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon | journal = American Journal of Physiology. Gastrointestinal and Liver Physiology | volume = 312 | issue = 6 | pages = G550–G558 | date = June 2017 | pmid = 28360029 | doi = 10.1152/ajpgi.00256.2016 }} 24. ^{{cite journal | vauthors = Lajczak NK, Saint-Criq V, O'Dwyer AM, Perino A, Adorini L, Schoonjans K, Keely SJ | title = Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β-defensin-1 and -2 secretion by colonic epithelial cells | journal = FASEB Journal | volume = 31 | issue = 9 | pages = 3848–3857 | date = September 2017 | pmid = 28487283 | doi = 10.1096/fj.201601365R }} 25. ^{{cite journal | vauthors = Mroz MS, Lajczak NK, Goggins BJ, Keely S, Keely SJ | title = The bile acids, deoxycholic acid and ursodeoxycholic acid, regulate colonic epithelial wound healing | journal = American Journal of Physiology. Gastrointestinal and Liver Physiology | volume = 314 | issue = 3 | pages = G378–G387 | date = March 2018 | pmid = 29351391 | doi = 10.1152/ajpgi.00435.2016 }} 26. ^{{cite journal | vauthors = O'Dwyer AM, Lajczak NK, Keyes JA, Ward JB, Greene CM, Keely SJ | title = Ursodeoxycholic acid inhibits TNFα-induced IL-8 release from monocytes | journal = American Journal of Physiology. Gastrointestinal and Liver Physiology | volume = 311 | issue = 2 | pages = G334–41 | date = August 2016 | pmid = 27340129 | doi = 10.1152/ajpgi.00406.2015 }} External links
3 : Bile acids|Cholanes|Drugs acting on the gastrointestinal system and metabolism |
| 随便看 |
|
开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。