Lactulose
[CAS# 4618-18-2]

Identification

• Classification: API >> Water, electrolyte and acid-base balance regulator >> Glucose drug
• Name: Lactulose
• Synonyms: 4-O-beta-D-Galactopyranosyl-alpha-D-fructose
• Molecular Formula: C₁₂H₂₂O₁₁
• Molecular Weight: 342.30
• CAS Registry Number: 4618-18-2
• EC Number: 225-027-7
• SMILES: C([C@@H]1[C@@H]([C@@H]([C@H]([C@@H](O1)O[C@@H]2[C@H](O[C@@]([C@H]2O)(CO)O)CO)O)O)O)O

Properties

• Melting point: 173-178 °C
• alpha: -47 ° (c=5, H2O, 12hr)
• Water solubility: 76.4 g/100 mL (30 °C)

Safety Data

• Safety Statements: S24/25

Discovery and Applications

Lactulose is a synthetic sugar derived from lactose that is used primarily as a laxative and to treat hepatic encephalopathy. Lactulose was first synthesized in the 1920s by chemists who wanted to create a compound with similar properties to lactose but with enhanced therapeutic effects. Its synthesis involves the isomerization of lactose, a natural disaccharide found in milk, to form a mixture of lactulose and lactose. Isolation and purification of lactulose from this mixture yields the pure compound for medical applications.

Lactulose is a synthetic, non-digestible disaccharide composed of galactose and fructose linked by beta bonds instead of the alpha bonds found in lactose. This alteration makes it resistant to human digestive enzymes and is able to reach the colon intact. In the colon, lactulose is fermented by bacteria, producing short-chain fatty acids and lowering the pH of the colonic contents. These actions promote water retention in the colon, soften stools, and stimulate peristalsis, thereby relieving constipation.

Lactulose is widely used to treat constipation, especially when dietary changes and other laxatives have been ineffective. It is effective for both acute and chronic constipation due to its ability to draw water into the colon and promote bowel movements. Another important application of lactulose is in the treatment of hepatic encephalopathy, a neuropsychiatric complication of liver disease. In this condition, bacterial fermentation of lactulose in the colon produces acidic metabolites that acidify the colonic contents. This reduces intestinal absorption of ammonia, which in turn reduces ammonia levels in the blood and improves symptoms of hepatic encephalopathy, such as confusion and altered mental status. Lactulose is also a prebiotic, promoting the growth of beneficial gut bacteria such as Bifidobacterium. This prebiotic effect contributes to overall gut health, providing additional benefits beyond its primary therapeutic use.

References

1984. Refractive index and dry-substance content. Journal of Pharmaceutical Sciences, 73(10).
DOI: 10.1002/jps.2600731039

2024. Ammonia metabolism in liver disease. npj Gut and Liver.
DOI: 10.1038/s44355-024-00011-x