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Chenodeoxycholic acid was isolated in 1924 from goose gall by Adolf Windaus and human gall by Heinrich Wieland.Its complete structural configuation was elucidated by Hans Lettre at the University of Gottingen.   In 1968, William Admirand and Donald Small at Boston University Medical School established that in patients with gallstones their bile was saturated with cholesterol, sometimes even exhibiting microcrystals, whereas this was not the case in normal people.It was then found that biliary levels of cholic acid and chenodeoxycholic acid were lower in patients with cholesterol gallstones than in normal people. Leslie Thistle and John Schoenfield at the Mayo Clinic in Rochester, Minnesota, then administered individual bile salts by mouth for four months and found that chenodeoxycholic acid reduced the amount of cholesterol in the bile.This led to a national collaborative study in the United States, which confirmed the effectiveness of chenodeoxycholic acid in bringing about dissolution of gallstones in selected patients. However, recent developments such as laparoscopic cholecystectomy and endoscopic biliary techniques have curtailed the role of chenodeoxycholic acid and ursodeoxycholic acid in the treatment of cholelithiasis.     Chenodeoxycholic acid is a bile acid synthesized in the liver from cholesterol. henodeoxycholic acid has been used in a study to assess its effects as a long-term replacement therapy for cerebrotendinous xanthomatosis (CTX). It has also been used in a study to investigate its effects on the small-intestinal absorption of bile acids in patients with ileostomies. Chenodeoxycholic acid is the first agent to be introduced into the US market for the treatment of radiolucent gallstones. Large scale clinical trials have demonstrated the safety and efficacy of this agent.     Chenodeoxycholic acid reduces the biliary concentration of cholesterol relative to that of bile acids and phospholipid, reducing the saturation and thus the lithogenicity of the bile. Success rates in dissolving gallstones are in the range of 50-70% within 4-24 months of treatment. Continuation of the drug after stone dissolution may be required to prevent reoccurrence. Chenodeoxycholic acid is the 7α-isomer of ursodeoxycholic acid which was introduced into the European market in 1978.     Chenodeoxycholic acid is a bile acid that induces apoptosis through protein kinase C signaling pathways.It is a major bile acid in many vertebrates, occurring as the N-glycine and/or N-taurine conjugate. With other bile acids, forms mixed micelles with lecithin in bile which solubilize cholesterol and thus facilitates its excretion.Bile acids are essential for solubilization and transport of dietary lipids, are the major products of cholesterol catabolism, and are physiological ligands for farnesoid X receptor (FXR), a nuclear receptor that regulates genes involved in lipid metabolism.They are also inherently cytotoxic, as physiological imbalance contributes to increased oxidative stress. Bile acid-controlled signaling pathways are promising novel targets to treat such metabolic diseases as obesity, type II diabetes, hyperlipidemia, and atherosclerosis.     Chenodeoxycholic acid is widely utilized in therapeutic applications. It is applied in medical therapy to dissolve gallstones. It is employed in the treatment of cerebrotendineous xanthomatosis. It is used to treat constipation and cerebrotendineous xanthomatosis. It acts as a urea receptor in supramolecular chemistry which can contain anions. It is a staining additive commonly used with ruthenium or organic photo-sensitizers in the preparation of staining solutions for dye solar cells.   Chenodeoxycholic Acid is a staining additive commonly used with ruthenium or organic photo-sensitizers in the preparation of staining solutions for Dye Solar Cells. This co-adsorbent will prevent dye aggregation on the semiconductor surface, reducing losses in the solar cell's operation.   Chenodeoxycholic Acid is a white solid added with the dye powder to the solvent while preparing staining solutions. The concentration of co-adsorbent is typically 10 fold the dye concentration.   Chenodeoxycholic acid has been used in a study to assess its effects as a long-term replacement therapy for cerebrotendinous xanthomatosis (CTX).   It has also been used in a study to investigate its effects on the small-intestinal absorption of bile acids in patients with ileostomies. Chenodeoxycholic acid (CDCA) is a hydrophobic primary bile acid that activates nuclear receptors involved in cholesterol metabolism.EC50 concentrations for activation of FXR range from 13-34 μM.In cells, CDCA also binds to bile acid binding proteins (BABP) with a reported stoichiometry of 1:2.CDCA toxicity is linked to increased cellular glutathione levels and increased oxidative stress. Exposure of cells to excess CDCA contributes to liver and intestinal cancers.  

Bile promoting drugs can generally be divided into two types: bile promoting agents and liquid enhancing bile promoting agents. The former refers to drugs that can promote bile secretion, while the latter refers to drugs that only increase bile volume but do not increase bile components. The commonly used cholestatic drugs are mainly bile acids. There are sodium cholic acid, dehydrocholic acid, chenodeoxycholic acid, and ursodeoxycholic acid.   Ursodeoxycholic acid is a chemical preparation that separates natural bile acids from bear bile. It is a stereoisomer of chenodeoxycholic acid, and its litholytic effect and therapeutic effect are similar to those of chenodeoxycholic acid, but the treatment course is short and the dosage is small. It combines with taurine in the body and exists in bile as a hydrophilic bile acid, serving as a cholesterol stone solubilizer. It can reduce the secretion of cholesterol by the liver, lower the saturation of cholesterol in bile, promote the secretion of bile acids, increase the solubility of cholesterol in bile, dissolve cholesterol stones, or prevent the formation of stones. It can increase the secretion of bile, relax the sphincter of the bile duct, and have a diuretic effect, which is conducive to the discharge of stones. This product cannot dissolve other types of gallstones. Ursodeoxycholic acid is suitable for treating cholesterol stones, hyperlipidemia, bile secretion disorders, primary biliary cirrhosis, chronic hepatitis, bile reflux gastritis, and preventing acute rejection and reactions of liver transplantation. The stone dissolving effect of this product is slightly weaker than that of chenodeoxycholic acid.     Production method Method 1: Use chenodeoxycholic acid as raw materials Preparation of 3α, 7α-diacetyl cholic acid methyl ester; Take 36ml of anhydrous methanol, and pass through 1g dried hydrogen chloride gas, add bile acid 12g, stir, heat and reflux for 20-30min. After standing for several hours at room temperature when crystals are separated out, freeze, filter, wash with ether, and dry to obtain methyl cholate. Take 2g methyl cholate, add 9.6 mL of benzene, 2.4mL pyridine, 2.4 mL of acetic anhydride, shake for 10-15min, stand for 20h at room temperature, then pour the reaction mixture into 100ml of water, remove the benzene layer, repeatedly wash with distilled water before recycling the solvents. Wash the solid residue with petroleum ether once, and re-crystallize with methanol-aqueous solution to obtain 3α, 7α-diacetyl bile acid methyl ester. Bile acid methyl → → 3α, 7α-diacetyl bile acid methyl ester Preparation of Chenodeoxycholic acid: Take the 1.5 g diacetyl bile acid methyl ester, add 24 mL acetic acid, add potassium chromate solution (Take 0.76g potassium chromate to dissolve it in 1.8ml take in water), heated to 40 °C, perform reaction for 8h, add water 120ml, shaking for some moment, placed 12h, filter, wash with distilled water till neutralization, dry to give 3α, 7α-diacetoxy-12-keto bile acid methyl ester, referred briefly as the 12-ketone. Take 12-15 g 12-ketone, add 150 mL 2-glycol ether, 15 mL 80% hydrazine hydrate solution, and 15 g potassium hydroxide. Heat to 30 °C and reflux for 15h, heat to 195-200 °C, refluxed for 2.5h, heat to 217 °C for some moment of reaction cool to 190 °C, add 0.7ml hydrazine hydrate solution, heat from within 215 °C to 220 °C within 3h, cool, add 600mL distilled water, adjust to pH 3 with 10% sulfuric acid, separate out the crystals, filter, wash with water until neutralization. Add ethyl acetate, dump the aqueous layer, use water to wash the organic layer was washed for 1-2 times, vacuum distillation and obtain 3α, 7α-dihydroxy cholanic acid, namely Chenodeoxycholic acid. 3α, 7α-diacetyl methyl cholate → 3α, 7α-diacetoxy-12-Keto ursodeoxycholic acid methyl ester → 3α, 7α-dihydroxy ursodeoxycholic acid (Chenodeoxycholic acid) Preparation of refined ursodeoxycholic acid; Taken 2 g chenodeoxycholic acid, add 100ml of acetic acid and 20g potassium acetate, shake to dissolve. Add potassium chromate 1.5g (dissolved in 10 mL of water), at room temperature overnight, add water 200ml, separate out the crystals, filter, wash, and dry to obtain 3α-hydroxy-7-keto-ursodeoxycholic acid. Take 4g 3α-hydroxy-7-keto-ursodeoxycholic acid, add 100 mL n-butanol, heat to about 115 °C, gradually add 8 g metal sodium after which, white slurry gradually comes out, keep reaction for 30min, add 120ml water, stir and heat to transparently dissolve. Evaporate the organic layer under reduced pressure; add 500 mL water to the residue, dissolve, and filter. Adjust the pH the filtrate to pH 3 with 10% sulfuric acid which will yield white precipitate, filter, wash till neutralization with water, dry, wash with ethyl acetate, crystallize with diluted ethanol and obtain 3α, 7β-dihydroxycholanic acid, that’s refined ursodeoxycholic acid. Chenodeoxycholic acid [potassium chromate] → 3α-hydroxy-7-keto acid [sodium metal, 115 °C] → 3α, 7β-Keto ursodeoxycholic acid methyl ester (Ursodeoxycholic acid) Method 2: Use pig bile or bile salts as raw material; Use thin layer chromatography to isolate ursodeoxycholic acid from pigs bile or bile salt. Pig bile salt contains free and bound type of UDCA whose content is about 30%; pig bile contains bound UDCA whose content is about 0.6%.