Ursodeoxycholic acid

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Ursodeoxycholic acid
Ursodeoxycholic acid acsv.svg
Ursodeoxycholic acid ball-and-stick.png
Clinical data
Trade names Actigall, Urso, others
Other namesUrsodiol
AHFS/Drugs.com Monograph
MedlinePlus a699047
License data
Pregnancy
category
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Identifiers
  • 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 Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.004.437 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C24H40O4
Molar mass 392.580 g·mol−1
3D model (JSmol)
Melting point 203 °C (397 °F)
  • 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=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 Yes check.svgY
  • Key:RUDATBOHQWOJDD-UZVSRGJWSA-N Yes check.svgY
   (verify)

Ursodeoxycholic acid (UDCA), also known as ursodiol, is a secondary bile acid, produced in humans and most other species from metabolism by intestinal bacteria. It is synthesized in the liver in some species, and was first identified in bile of bears of genus Ursus , from which its name derived. [8] In purified form, it has been used to treat or prevent several diseases of the liver or bile ducts.

Contents

It is available as a generic medication. [9] [10]

Medical uses

UDCA has been used as medical therapy in gallstone disease (cholelithiasis) and for biliary sludge. [11] [12] UDCA helps reduce the cholesterol saturation of bile and leads to gradual dissolution of cholesterol-rich gallstones. [11]

UDCA may be given after bariatric surgery to prevent cholelithiasis, which commonly occurs due to the rapid weight loss producing biliary cholesterol oversaturation and also biliary dyskinesia secondary to hormonal changes. [13]

Primary biliary cholangitis

UDCA is used as therapy in primary biliary cholangitis (PBC; previously known as primary biliary cirrhosis) where it can produce an improvement in biomarkers. [14] Meta-analyses have borne out conflicting results on the mortality benefit. [15] However analyses that exclude trials of short duration (i.e. < 2 years) have demonstrated a survival benefit and are generally considered more clinically relevant. [16] A Cochrane systematic review in 2012 found no significant benefit in reducing mortality, the rate of liver transplantation, pruritus or fatigue. [17] Ursodiol and obeticholic acid are FDA-approved for the treatment of primary biliary cholangitis. [18]

Primary sclerosing cholangitis

UDCA use is associated with improved serum liver tests that do not always correlate with improved liver disease status. [19] WHO Drug Information advises against its use in primary sclerosing cholangitis in unapproved doses beyond 13–15 mg/kg/day. [20]

UDCA in a dose of 28–30 mg/kg/day increases risk of death and need for liver transplant by 2.3-fold among those with primary sclerosing cholangitis, despite decrease in liver enzymes. [21]

Intrahepatic cholestasis of pregnancy

UDCA has been used for intrahepatic cholestasis of pregnancy. UDCA lessens itching in the mother and may reduce the number of preterm births. Effects on fetal distress and other adverse outcomes are unlikely to be great. [22] [23]

Cholestasis

UDCA use is not licensed in children, as its safety and effectiveness have not been established. Evidence is accumulating that ursodeoxycholic acid is ineffective, unsafe and its use is associated with significant risk of morbidity and mortality in neonatal hepatitis and neonatal cholestasis. [24] [25] [26] [27]

Other conditions

UDCA has been suggested to be an adequate treatment of bile reflux gastritis. [28]

In cystic fibrosis there is insufficient evidence to justify routine use of UDCA, especially as there is a lack of available data for long-term outcomes such as death or need for liver transplantation. [29]

UDCA has also been in effective in non-alcoholic fatty liver disease, in liver bile duct-paucity syndromes. It has been used as adjunct therapy in conditions with biliary tract obstruction such as biliary atresia; however liver transplant is often still required as definitive treatment for atresia. It is not effective in liver allograft rejection, and in Graft-versus-host disease involving the liver.[ medical citation needed ]

Adverse effects

Diarrhea was the most frequent adverse event seen in trial of UDCA in gallstone dissolution, occurring in 2 to 9%, which is less frequent than with chenodeoxycholic acid therapy. Bacterial conversion of UDCA to chenodeoxycholic acid may be the mechanism for this side effect. Right upper quadrant abdominal pain and exacerbation of pruritus was occasionally reported in trials in patients with PBC. [30] Additional symptoms may include bloating, weight gain, and occasionally, thinning of hair. [31]

Mechanisms of action

Choleretic effects

Primary 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. The drug reduces cholesterol absorption and is used to dissolve (cholesterol) gallstones in patients who want an alternative to surgery. [32] There are multiple mechanisms involved in cholestatic liver diseases. [33]

Immunomodulating effects

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. [34]

Anti-inflammatory effects

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 by regulation of cytokines, [35] antimicrobial peptides defensins, [36] and take an active part in increased restitution of wound in the colon. [37] Moreover, UDCA's effects has been shown to have exert actions outside the epithelial cells. [38]

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. [39]

Chemistry

Ursodeoxycholic acid is an epimer of chenodeoxycholic acid, which has similar choleretic effects and a wider species distribution. However, CDCA is not as well-tolerated in humans and it does not show immunomodulating or chemoprotective effects. Both are 7-hydroxyl derivatives of deoxycholic acid, but UDCA has the group in the beta instead of the alpha orientation. [40]

Biosynthesis

Among mammals, only bears (Ursidae; excluding giant pandas) produce UDCA at useful amounts [40] (>30%). It is produced in the bear liver, but the pathway remains unknown. [8]

Other vertebrates produce UDCA in much smaller amounts by gut bacteria. CDCA is oxidized into 7-oxo-CDCA then reduced into UDCA. [41]

Industrial production

UDCA is most commonly produced from cholic acid (CA) derived from bovine bile, a by-product of the beef industry. The current yield of this semisynthesis is about 30%. [42]

Society and culture

Names

The term is from the Latin noun ursus meaning bear, as bear bile contains the substance. [43]

Ursodeoxycholic acid can be chemically synthesized and is marketed under multiple trade names, including Ursetor, Udikast, Actibile, Actigall, Biliver, Deursil, Egyurso, Heptiza 300/150, Stener, Udcasid, Udiliv, Udinorm, Udoxyl, Urso, Urso Forte, Ursocol, Ursoliv, Ursofalk, [44] Ursosan, Ursoserinox, Udimarin, and Ursonova.[ citation needed ]

History

Bear bile, a natural source of UDCA, is used in traditional Chinese medicine since the seventh century. Japanese scientists successfully synthesized UDCA chemically in 1955. [40] The earliest reference to UDCA in PubMed dates to 1957 under an alternative spelling "ursodesoxycholic acid", in a small-scale clinical trial. [45]

Ursodeoxycholic acid (application filed by Allergan) was approved for use in the United States in December 1987, [46] and was designated an orphan drug. [47]

Related Research Articles

<span class="mw-page-title-main">Bile</span> Dark greenish-brown fluid aiding in the digestion of fats

Bile, or gall, is a yellow-green/misty green fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is primarily composed of water, is produced continuously by the liver, and is stored and concentrated in the gallbladder. After a human eats, this stored bile is discharged into the first section of the small intestine.

<span class="mw-page-title-main">Gallstone</span> Disease where stones form in the gallbladder

A gallstone is a stone formed within the gallbladder from precipitated bile components. The term cholelithiasis may refer to the presence of gallstones or to any disease caused by gallstones, and choledocholithiasis refers to the presence of migrated gallstones within bile ducts.

<span class="mw-page-title-main">Primary biliary cholangitis</span> Autoimmune disease of the liver

Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to build up in the liver, a condition called cholestasis. Further slow damage to the liver tissue can lead to scarring, fibrosis, and eventually cirrhosis.

<span class="mw-page-title-main">Primary sclerosing cholangitis</span> Hardening of the bile ducts due to scarring and inflammation

Primary sclerosing cholangitis (PSC) is a long-term progressive disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts, which normally allow bile to drain from the gallbladder. Affected individuals may have no symptoms or may experience signs and symptoms of liver disease, such as yellow discoloration of the skin and eyes, itching, and abdominal pain.

<span class="mw-page-title-main">Liver disease</span> Medical condition

Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.

<span class="mw-page-title-main">Cholangiocarcinoma</span> Cancer of the bile ducts

Cholangiocarcinoma, also known as bile duct cancer, is a type of cancer that forms in the bile ducts. Symptoms of cholangiocarcinoma may include abdominal pain, yellowish skin, weight loss, generalized itching, and fever. Light colored stool or dark urine may also occur. Other biliary tract cancers include gallbladder cancer and cancer of the ampulla of Vater.

<span class="mw-page-title-main">Alagille syndrome</span> Medical condition

Alagille syndrome (ALGS) is a genetic disorder that affects primarily the liver and the heart. Problems associated with the disorder generally become evident in infancy or early childhood. The disorder is inherited in an autosomal dominant pattern, and the estimated prevalence of Alagille syndrome is 1 in every 30,000 to 1 in every 40,000 live births. It is named after the French pediatrician Daniel Alagille, who first described the condition in 1969. Children with Alagille syndrome live to the age of 18 in about 90% of the cases.

<span class="mw-page-title-main">Cholestasis</span> Medical condition

Cholestasis is a condition where the flow of bile from the liver to the duodenum is impaired. The two basic distinctions are:

<span class="mw-page-title-main">Chenodeoxycholic acid</span> One of the main bile acids

Chenodeoxycholic acid is a bile acid. Salts of this carboxylic acid are called chenodeoxycholates. Chenodeoxycholic acid is one of the main bile acids. It was first isolated from the bile of the domestic goose, which gives it the "cheno" portion of its name.

<span class="mw-page-title-main">Bile acid</span> Steroid acid found predominantly in the bile of mammals and other vertebrates

Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts.

Progressive familial intrahepatic cholestasis (PFIC) is a group of familial cholestatic conditions caused by defects in biliary epithelial transporters. The clinical presentation usually occurs first in childhood with progressive cholestasis. This usually leads to failure to thrive, cirrhosis, and the need for liver transplantation.

<span class="mw-page-title-main">Biliary tract</span> Organ system which creates, stores, and transports bile

The biliary tract refers to the liver, gallbladder and bile ducts, and how they work together to make, store and secrete bile. Bile consists of water, electrolytes, bile acids, cholesterol, phospholipids and conjugated bilirubin. Some components are synthesized by hepatocytes ; the rest are extracted from the blood by the liver.

<span class="mw-page-title-main">Gallbladder disease</span> Medical condition

Gallbladder diseases are diseases involving the gallbladder and is closely linked to biliary disease, with the most common cause being gallstones (cholelithiasis).

<span class="mw-page-title-main">Hyodeoxycholic acid</span> Chemical compound

Hyodeoxycholic acid, also known as 3α,6α-Dihydroxy-5β-cholan-24-oic acid or HDCA, is a secondary bile acid, one of the metabolic byproducts of intestinal bacteria. It differs from deoxycholic acid in that the 6α-hydroxyl is in the 12 position in the former. The 6α-hydroxyl group makes HDCA a hydrophilic acid, a property it shares with hyocholic acid. HDCA is present in mammalian species in different proportions. It is the main acid constituent of hog bile, and for this reason it was used industrially as precursor for steroid synthesis before total synthesis became practical.

Secondary sclerosing cholangitis (SSC) is a chronic cholestatic liver disease. SSC is a sclerosing cholangitis with a known cause. Alternatively, if no cause can be identified, then primary sclerosing cholangitis is diagnosed. SSC is an aggressive and rare disease with complex and multiple causes. It is characterized by inflammation, fibrosis, destruction of the biliary tree and biliary cirrhosis. It can be treated with minor interventions such as continued antibiotic use and monitoring, or in more serious cases, laparoscopic surgery intervention, and possibly a liver transplant.

Vanishing bile duct syndrome is a loose collection of diseases leading to hepatic bile duct injury and eventual ductopenia.

<span class="mw-page-title-main">Ursodoxicoltaurine</span> Chemical compound

Ursodoxicoltaurine is the international nonproprietary name (INN) for the pharmaceutical form of tauroursodeoxycholic acid (TUDCA). It is also known as taurursodiol. Tauroursodeoxycholic acid is a naturally occurring hydrophilic bile acid which is the taurine conjugated form of ursodeoxycholic acid (UDCA). Humans have only trace amounts of tauroursodeoxycholic acid but bears have large amounts of tauroursodeoxycholic acid and ursodeoxycholic acid in their bile.

<span class="mw-page-title-main">Elafibranor</span> Chemical compound

Elafibranor (INN), sold under the brand name Iqirvo, is a medication used for the treatment of primary biliary cholangitis.

<span class="mw-page-title-main">Obeticholic acid</span> Chemical compound

Obeticholic acid (OCA), sold under the brand name Ocaliva, is a semi-synthetic bile acid analogue which has the chemical structure 6α-ethyl-chenodeoxycholic acid. It is used as a medication used to treat primary biliary cholangitis. Intercept Pharmaceuticals Inc. hold the worldwide rights to develop OCA outside Japan and China, where it is licensed to Dainippon Sumitomo Pharma.

References

  1. ↑ "Ursodiol, Heptiza 300/150 Use During Pregnancy". Drugs.com. 4 November 2019. Retrieved 20 February 2020.
  2. ↑ "Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 30 March 2024.
  3. ↑ "Product information". Health Canada . 3 August 2000. Retrieved 3 March 2024.
  4. ↑ "Details for: Ursodiol C". Health Canada . 25 October 2021. Retrieved 3 March 2024.
  5. ↑ "Ursodeoxycholic acid 300mg Tablets - Summary of Product Characteristics (SmPC)". (emc). 10 July 2019. Retrieved 29 April 2020.
  6. ↑ "Actigall- ursodiol capsule". DailyMed. Retrieved 25 September 2021.
  7. ↑ "Urso 250- ursodiol tablet, film coated Urso Forte- ursodiol tablet, film coated". DailyMed. Retrieved 25 September 2021.
  8. 1 2 Hagey LR, Crombie DL, Espinosa E, Carey MC, Igimi H, Hofmann AF (November 1993). "Ursodeoxycholic acid in the Ursidae: biliary bile acids of bears, pandas, and related carnivores". Journal of Lipid Research. 34 (11): 1911–1917. doi: 10.1016/S0022-2275(20)35109-9 . PMID   8263415.
  9. ↑ "2020 First Generic Drug Approvals". U.S. Food and Drug Administration (FDA). 23 February 2021. Retrieved 25 September 2021.
  10. ↑ "Ursodiol: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 25 September 2021.
  11. 1 2 Hofmann AF (September 1989). "Medical dissolution of gallstones by oral bile acid therapy". American Journal of Surgery. 158 (3): 198–204. doi:10.1016/0002-9610(89)90252-3. PMID   2672842.
  12. ↑ Jüngst C, Kullak-Ublick GA, Jüngst D (2006). "Gallstone disease: Microlithiasis and sludge". Best Practice & Research. Clinical Gastroenterology. 20 (6): 1053–1062. doi:10.1016/j.bpg.2006.03.007. PMID   17127187.
  13. ↑ Magouliotis DE, Tasiopoulou VS, Svokos AA, Svokos KA, Chatedaki C, Sioka E, et al. (November 2017). "Ursodeoxycholic Acid in the Prevention of Gallstone Formation After Bariatric Surgery: an Updated Systematic Review and Meta-analysis". Obesity Surgery. 27 (11): 3021–3030. doi:10.1007/s11695-017-2924-y. PMID   28889240. S2CID   4622165.
  14. ↑ Poupon RE, Balkau B, Eschwège E, Poupon R (May 1991). "A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group". The New England Journal of Medicine. 324 (22): 1548–1554. doi: 10.1056/NEJM199105303242204 . PMID   1674105.
  15. ↑ Goulis J, Leandro G, Burroughs AK (September 1999). "Randomised controlled trials of ursodeoxycholic-acid therapy for primary biliary cirrhosis: a meta-analysis". Lancet. 354 (9184): 1053–1060. doi:10.1016/S0140-6736(98)11293-X. PMID   10509495. S2CID   25562983.
  16. ↑ Shi J, Wu C, Lin Y, Chen YX, Zhu L, Xie WF (July 2006). "Long-term effects of mid-dose ursodeoxycholic acid in primary biliary cirrhosis: a meta-analysis of randomized controlled trials". The American Journal of Gastroenterology. 101 (7): 1529–1538. doi:10.1111/j.1572-0241.2006.00634.x. PMID   16863557. S2CID   32076958.
  17. ↑ Rudic JS, Poropat G, Krstic MN, Bjelakovic G, Gluud C (December 2012). "Ursodeoxycholic acid for primary biliary cirrhosis". The Cochrane Database of Systematic Reviews. 12 (12): CD000551. doi:10.1002/14651858.CD000551.pub3. PMC   7045744 . PMID   23235576.
  18. ↑ Bowlus CL, Kenney JT, Rice G, Navarro R (October 2016). "Primary Biliary Cholangitis: Medical and Specialty Pharmacy Management Update". Journal of Managed Care & Specialty Pharmacy. 22 (10-a-s Suppl): S3 –S15. doi: 10.18553/jmcp.2016.22.10-a-s.s3 . PMC   10408407 . PMID   27700211.
  19. ↑ Poropat G, Giljaca V, Stimac D, Gluud C (January 2011). "Bile acids for primary sclerosing cholangitis". The Cochrane Database of Systematic Reviews. 2011 (1): CD003626. doi:10.1002/14651858.CD003626.pub2. PMC   7163275 . PMID   21249655.
  20. ↑ "Ursodeoxycholic acid: serious hepatic events" (PDF). WHO Drug Information. 26 (1). 2012.
  21. ↑ Lindor KD, Kowdley KV, Luketic VA, Harrison ME, McCashland T, Befeler AS, et al. (September 2009). "High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis". Hepatology. 50 (3): 808–814. doi:10.1002/hep.23082. PMC   2758780 . PMID   19585548.
  22. ↑ Walker KF, Chappell LC, Hague WM, Middleton P, Thornton JG (July 2020). "Pharmacological interventions for treating intrahepatic cholestasis of pregnancy". The Cochrane Database of Systematic Reviews. 2020 (7): CD000493. doi:10.1002/14651858.CD000493.pub3. PMC   7389072 . PMID   32716060.
  23. ↑ Chappell LC, Bell JL, Smith A, Linsell L, Juszczak E, Dixon PH, et al. (September 2019). "Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial". Lancet. 394 (10201): 849–860. doi:10.1016/S0140-6736(19)31270-X. PMC   6739598 . PMID   31378395.
  24. ↑ Kotb MA (July 2008). "Review of historical cohort: ursodeoxycholic acid in extrahepatic biliary atresia". Journal of Pediatric Surgery. 43 (7): 1321–1327. doi:10.1016/j.jpedsurg.2007.11.043. PMID   18639689.
  25. ↑ Paediatric Formulary Committee (2008). British National Formulary for Children 2008. London: Pharmaceutical Press. p. 91. ISBN   978-0-85369-780-0.
  26. ↑ "Urso package insert" (PDF). Birmingham, AL: Axcan Pharma U.S. January 2000. Archived from the original (PDF) on 17 October 2006. Retrieved 25 April 2009.
  27. ↑ Kotb MA, Mosallam D, Basanti CW, El Sorogy ST, Badr AM, Abd El Baky HE, et al. (February 2020). "Ursodeoxycholic acid use is associated with significant risk of morbidity and mortality in infants with cholestasis: A strobe compliant study". Medicine. 99 (7): e18730. doi:10.1097/MD.0000000000018730. PMC   7035015 . PMID   32049781.
  28. ↑ McCabe ME, Dilly CK (September 2018). "New Causes for the Old Problem of Bile Reflux Gastritis". Clinical Gastroenterology and Hepatology. 16 (9): 1389–1392. doi:10.1016/j.cgh.2018.02.034. hdl: 1805/15771 . PMID   29505908. S2CID   3748071.
  29. ↑ Cheng K, Ashby D, Smyth RL, et al. (Cochrane Cystic Fibrosis and Genetic Disorders Group) (September 2017). "Ursodeoxycholic acid for cystic fibrosis-related liver disease". The Cochrane Database of Systematic Reviews. 9 (9): CD000222. doi:10.1002/14651858.CD000222.pub4. PMC   6483662 . PMID   28891588.
  30. ↑ Hempfling W, Dilger K, Beuers U (November 2003). "Systematic review: ursodeoxycholic acid--adverse effects and drug interactions". Alimentary Pharmacology & Therapeutics. 18 (10): 963–972. doi: 10.1046/j.1365-2036.2003.01792.x . PMID   14616161. S2CID   25738560.
  31. ↑ Lleo A, Wang GQ, Gershwin ME, Hirschfield GM (December 2020). "Primary biliary cholangitis". Lancet. 396 (10266): 1915–1926. doi:10.1016/S0140-6736(20)31607-X. PMID   33308474. S2CID   228086916.
  32. ↑ Tint GS, Salen G, Shefer S (October 1986). "Effect of ursodeoxycholic acid and chenodeoxycholic acid on cholesterol and bile acid metabolism". Gastroenterology. 91 (4): 1007–1018. doi: 10.1016/0016-5085(86)90708-0 . PMID   3527851.
  33. ↑ Paumgartner G, Beuers U (September 2002). "Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited". Hepatology. 36 (3): 525–531. doi: 10.1053/jhep.2002.36088 . PMID   12198643. S2CID   28282761.
  34. ↑ Material Safety Data Sheet on Ursodiol MSDS. https://fscimage.fishersci.com/msds/70916.htm
  35. ↑ Ward JB, Lajczak NK, Kelly OB, O'Dwyer AM, Giddam AK, Ní Gabhann J, et al. (June 2017). "Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon". American Journal of Physiology. Gastrointestinal and Liver Physiology. 312 (6): G550 –G558. doi: 10.1152/ajpgi.00256.2016 . PMID   28360029.
  36. ↑ Lajczak NK, Saint-Criq V, O'Dwyer AM, Perino A, Adorini L, Schoonjans K, et al. (September 2017). "Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β-defensin-1 and -2 secretion by colonic epithelial cells". FASEB Journal. 31 (9): 3848–3857. doi: 10.1096/fj.201601365R . PMID   28487283. S2CID   46877147.
  37. ↑ Mroz MS, Lajczak NK, Goggins BJ, Keely S, Keely SJ (March 2018). "The bile acids, deoxycholic acid and ursodeoxycholic acid, regulate colonic epithelial wound healing". American Journal of Physiology. Gastrointestinal and Liver Physiology. 314 (3): G378 –G387. doi:10.1152/ajpgi.00435.2016. PMID   29351391. S2CID   3767047.
  38. ↑ O'Dwyer AM, Lajczak NK, Keyes JA, Ward JB, Greene CM, Keely SJ (August 2016). "Ursodeoxycholic acid inhibits TNFα-induced IL-8 release from monocytes". American Journal of Physiology. Gastrointestinal and Liver Physiology. 311 (2): G334 –G341. doi: 10.1152/ajpgi.00406.2015 . PMID   27340129.
  39. ↑ Akare S, Jean-Louis S, Chen W, Wood DJ, Powell AA, Martinez JD (December 2006). "Ursodeoxycholic acid modulates histone acetylation and induces differentiation and senescence". International Journal of Cancer. 119 (12): 2958–2969. doi:10.1002/ijc.22231. PMID   17019713. S2CID   21187798.
  40. 1 2 3 Feng Y, Siu K, Wang N, Ng KM, Tsao SW, Nagamatsu T, et al. (January 2009). "Bear bile: dilemma of traditional medicinal use and animal protection". Journal of Ethnobiology and Ethnomedicine. 5 (1): 2. doi: 10.1186/1746-4269-5-2 . PMC   2630947 . PMID   19138420.
  41. ↑ Devlin AS, Fischbach MA (September 2015). "A biosynthetic pathway for a prominent class of microbiota-derived bile acids". Nature Chemical Biology. 11 (9): 685–690. doi:10.1038/nchembio.1864. PMC   4543561 . PMID   26192599.
  42. ↑ Tonin F, Arends IW (2018). "Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review". Beilstein Journal of Organic Chemistry. 14: 470–483. doi: 10.3762/bjoc.14.33 . PMC   5827811 . PMID   29520309.
  43. ↑ https://pubchem.ncbi.nlm.nih.gov/compound/Ursodiol
  44. ↑ https://prehledy.sukl.cz/prehled_leciv.html#/detail-reg/0148926
  45. ↑ Arakawa T, Kagaya A, Inaba Y (September 1957). "Ursodesoxycholic acid as in accelerator for riboflavin phosphorylation in children with nutritional dystrophy". The Journal of Vitaminology. 3 (3): 165–167. doi: 10.5925/jnsv1954.3.165 . PMID   13476545.
  46. ↑ "Actigall: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 29 April 2020.
  47. ↑ "Actigall Orphan Drug Designation and Approval". U.S. Food and Drug Administration (FDA). Retrieved 29 April 2020.
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