History Pharmacological action Mechanism of action Synthesis in Chemical Method Synthesis in Biological method Pharmacokinetics Indication Adverse reaction Drug interaction Precaution
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History Pharmacological action Mechanism of action Synthesis in Chemical Method Synthesis in Biological method Pharmacokinetics Indication Adverse reaction Drug interaction Precaution
Lactulose Structure
  • CAS No.4618-18-2
  • Chemical Name:Lactulose
  • CBNumber:CB2779607
  • Molecular Formula:C12H22O11
  • Formula Weight:342.3
  • MOL File:4618-18-2.mol
Lactulose Property
  • Melting point: :~169 °C (dec.)
  • alpha  :-47 º (C=5, H2O, 12HR)
  • Boiling point: :397.76°C (rough estimate)
  • Density  :1,32g/cm
  • refractive index  :1,45-1,47
  • storage temp.  :Refrigerator
  • solubility  :Freely soluble in water, sparingly soluble in methanol, practically insoluble in toluene.
  • form  :Powder
  • pka :11.67±0.20(Predicted)
  • color  :White to almost white
  • optical activity :[α]20/D 48±2°, 24 hr, c = 1% in H2O
  • Water Solubility  :76.4 G/100 ML (30 ºC)
  • Merck  :5346
  • BRN  :93773
  • CAS DataBase Reference :4618-18-2(CAS DataBase Reference)
  • EWG's Food Scores :1
  • EPA Substance Registry System :D-Fructose, 4-O-.beta.-D-galactopyranosyl- (4618-18-2)
  • Safety Statements  :24/25
  • WGK Germany  :2
  • RTECS  :LS6965000
  • TSCA  :Yes
  • HS Code  :29400090
  • NFPA 704:
    1 0
Hazard and Precautionary Statements (GHS)
  • Symbol(GHS)
  • Signal word
  • Hazard statements
  • Precautionary statements
Lactulose Price More Price(14)
  • Brand: Sigma-Aldrich
  • Product number: 61360
  • Product name : Lactulose
  • Purity: ≥98.0% (HPLC)
  • Packaging: 5g
  • Price: $108
  • Updated: 2021/03/22
  • Buy: Buy
  • Brand: Sigma-Aldrich
  • Product number: Y0001510
  • Product name : Lactulose for peak identification
  • Purity: European Pharmacopoeia (EP) Reference Standard
  • Packaging: 
  • Price: $190
  • Updated: 2021/03/22
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  • Brand: Sigma-Aldrich
  • Product number: L0130000
  • Product name : Lactulose
  • Purity: European Pharmacopoeia (EP) Reference Standard
  • Packaging: 
  • Price: $190
  • Updated: 2021/03/22
  • Buy: Buy
  • Brand: Sigma-Aldrich
  • Product number: 61360
  • Product name : Lactulose
  • Purity: ≥98.0% (HPLC)
  • Packaging: 25g
  • Price: $335
  • Updated: 2021/03/22
  • Buy: Buy
  • Brand: Sigma-Aldrich
  • Product number: 1356803
  • Product name : Lactulose
  • Purity: United States Pharmacopeia (USP) Reference Standard
  • Packaging: 1 g
  • Price: $414
  • Updated: 2021/03/22
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Lactulose Chemical Properties,Usage,Production

  • History In 1957 Peitele found lactulose is a bifidobacterium proliferation factor.In 1964, Hoffman found that only bifidobacteria, Lactobacillus, LD Streptococcus could make lactulose produce lactic acid and acetic acid.
    The metabolic process of lactulose bacteria was clarified for the first time. In 1966 Baicier found that use of lactulose can promote the growth of basophilic gram-positive bacteria lacking urease (escherichia coli etc..) and reduce ammonia production. It has been proved that lactulose has the effect of reducing blood ammonia and has been successfully used in the treatment of hepatic encephalopathy.1979 Nianmoleyou treated the viral hepatitis with lactulose and he found that lactulose has the effect of reducing plasma endotoxin. From 1980 to 1981, Leicier found limulus test agglutination reaction of lactulose inhibiting endotoxin in vitro, alleviating the liver injury of rats induced by D - amino galactose. He believed that lactulose has the effect of anti endotoxin activity and can be used in the treatment of liver and kidney syndrome.
  • Pharmacological action
    1. Lactulose is synthesized nonabsorbable disaccharide. It is not absorbed in the intestinal tract, and can be decomposed into lactic acid and acetic acid by colonic bacteria, and the pH value of intestinal tract is reduced to less than 6. It can block the absorption of ammonia, reduce the accumulation and absorption of endotoxin, restore the patient's blood ammonia to normal, making the patient turn from coma to sober.
    2. Lactulose also has the osmotic activity of disaccharide, making water and electrolytes retained in the intestinal cavity to produce hypertonic effects. Therefore, it's also a kind of osmotic laxative. Without intestinal irritation, it can also be used to treat chronic functional constipation.
    3. It has the effect of anti endotoxin.
  • Mechanism of action Lactulose is transformed into a low molecular weight organic acid by the digestive tract bacteria in the colon, which leads to a decrease in the pH value in the intestinal tract.The volume of the feces was increased by retaining the water. The above effects stimulate the peristalsis of the colon, keep the bowel smooth, relieve constipation, and restore the physiological rhythm of the colon. In hepatic encephalopathy (PSE), hepatic coma and pre coma, these effects promote the growth of intestinal acidophilic bacteria (such as lactobacillus), inhibit protein decomposing bacteria, and turn ammonia into ionic state. By reducing the contact pH value, play osmotic effect, and improve bacterial ammonia metabolism, it plays a laxative effect.
  • Synthesis in Chemical Method Alkali single catalysis:The system mainly uses sodium hydroxide, potassium hydroxide, potassium carbonate and tertiary amine as the catalyst, and the conversion rate of lactulose is about 20%. This kind of alkaline reagent acts on lactose, making lactose isomerization of lactulose. But at the same time, a considerable amount of degradation products such as galactose and fructose are produced. The product is not only difficult to separate, but also the color is often deeper. The production of by-products and pigments not only reduces the yield of lactulose, but also brings difficulties to the further purification and crystallization of the syrup.

    Synergistic catalysis of acid and alkali: In this system, boric acid is added to the reaction system. In alkaline condition, boric acid can make lactulose to form lactulose borate complex.The balance of the reaction moves towards the direction of the production of lactulose. The formation of the complex and the movement of the reaction equilibrium reduce the production of the degradation products to the maximum extent. Only a small part of the lactulose in the whole process will be converted into by-products. The conversion rate of lactulose is about 70% and up to 75%. After the conversion is completed, the pH of the reaction system is converted to acidity, and the complex will be decomposed to produce lactulose and borate. After the borate is removed, pure lactoacetone can be obtained. Because borate is a weak acid, the general anion exchange resin can hardly remove it to the safety standard. It is necessary to use the ion exchange resin that specifically removes boric acid, which is more expensive. The preparation of lactulose by the co - catalysis of acid and alkali reduces the production of byproducts and improves the yield of lactulose. It is beneficial to the purification and extraction of lactulose. This is also the main method of the industrial production of lactulose at present.

    Sodium aluminate catalysis: The mechanism of the system is similar to that of boric acid. Sodium aluminate can react with the lactose sugar produced by isomerization. The conversion rate of lactulose is about 60%. But in general, the ratio of the by-products in the aluminate system is higher than that of the borate system, and the removal of aluminum ions is difficult. In recent years, some non-homogeneous catalysts, including zeolite, sepiolite, eggshell powder and oyster shell powder, have been used to prepare lactulose. It was found that the conversion rate of lactulose is 20% with the addition of 15g/L and with degree of 90℃. If the egg shell powder is used as the catalyst, the conversion of lactulose is 18%-21% in 120min with the addition of 12g/L and degree of 96 ℃. Although zeolite, sepiolite, eggshell powder and oyster shell powder are used as catalyst, the conversion rate of lactulose is not high. But they remain in solid state and are easily removed by filtration. Therefore, the preparation of lactulose with non-homogeneous catalyst has a strong potential for development.
    Reaction process of lactulose production by chemical isomerization
  • Synthesis in Biological method Enzyme method is the biological production of lactulose main method. The main enzyme used is beta galactosidase. Its principle is to hydrolyze lactose to galactose and glucose through the hydrolysis activity of beta galactosidase, and transfer galactose to fructose receptor to form lactulose through the transglycation activity of beta galactosidase. The full name of beta galactosidase is beta -D- galactoside galactohydrolysase. In addition to the high hydrolytic lactose activity, the enzyme also has a higher activity of transferring Glucoside from the lactose to the fructose receptor. Early studies showed that there are two functional groups on the active sites of the galactosidase: the sulfhydryl group of Cys and the imidazole group of His, which play an important role in the hydrolysis of lactose by beta galactosidase. It is assumed that the sulfur base can be used as a generalized acid to protonate the oxygen atoms of the galactoside. The imidazole base can be used as a nucleophilic to attack nucleophilic center on first carbon atoms of galactose molecule, forming 1 C-H bonds covalent intermediate. After the imidazolyl is cut, the sulfhydryl anion extracts 1 protons from the water molecules and forms the -OH to attack C. Beta galactosidase is mainly derived from animal, plant and microorganism, such as the bacteria including lactic acid bacteria, bacillus cereus, escherichia coli, streptococcus thermophilus, gas producing bacteria; the mucedine including aspergillus oryzae, aspergillus niger, aspergillus Ryukyu, yellow penicillium, aspergillus charcoal etc.; yeast inclduing kluyveromyces fragilis, kluyveromyces lactis, candida tropicalis etc.;actinomyces including streptomyces coelicolor etc.. They all produce beta galactoenzyme. Due to the rapid growth of microbes and the biological characteristics of efficient metabolism, beta galactosidase derived from microorganisms only has industrial application value. The commercial enzyme source generally believes that the yeast is the most safe, followed by aspergillus niger. At present, due to the low activity of glucoside of beta galactosidase and low conversion rate of lactulose, the application of biological method to the preparation of lactulose is limited. Some scholars at home and abroad have done some research on this, and the aim is to screen out microbial strains with high activity of glucoside of beta galactosidase as much as possible. 50mg/ml lactulose can be produced by modifying the heat resistant lactase with lactose and fructose as substrates with reaction period of 6h at 80 ℃. The preparation of lactulose by enzymatic method can overcome the difficulty in separating a large amount of coloured by-products produced by chemical method. It is of great theoretical and practical significance to isolate these byproducts with high cost and to degrade lactulose during the separation process.This is an important development direction for the preparation of lactulose in the future.
  • Pharmacokinetics Lactulose is almost not absorbed after oral administration, reaching the colon in prototype, and then catabolized by intestinal flora. At a dose of 25-50 grams (40-75 milliliters), it can be completely metabolized; when exceeding this dose, it is partially discharged in the form of the prototype.
  • Indication This product is not digested and decomposed in the stomach and small intestine, and is almost not absorbed in the small intestine. There are a variety of bacteria in the large intestine. Some of the beneficial bacteria (such as lactobacillus bifidobacterium) use lactulose as nutrients. This product in the colon is decomposed into low molecular weight organic acids such as lactic acid and acetic acid, so that intestinal pH decreases below 6, which is conducive to the growth of beneficial bacteria and has therapeutic action. First is can cure constipation: the decomposition of this product can stimulate the peristalsis of the large intestine, while keeping more water in the large intestine, softening the feces and relieving constipation. Second, its can lower the blood ammonia: a larger dose of this product can promote the reproduction of sugar decomposing bacteria, thus inhibiting the growth of proteolytic bacteria, reducing the production of ammonia and other endotoxins and the pH in the colon. In this state, most of the ammonia is converted into an ammonium ion that is difficult to absorb, reducing the absorption of ammonia and reducing the blood ammonia. This product is not digested and absorbed in the stomach and small intestine, and has little absorption. It can play a role in the large intestine. Therefore, the effect will be seen 24~48 hours after taking this product. Metabolism takes place in the colon, less than 3% of the original medicine is excreted with urine, and a small amount is excreted with feces through bile. It can be used in the adjuvant treatment of hepatic coma and pre coma in hepatic encephalopathy. It is also used for the treatment of acute and chronic constipation and the adjuvant medication used as endotoxemia.
  • Adverse reaction There is rare serious adverse reaction. In the first few days of the beginning of the treatment, there may appear abdominal discomfort, such as flatulence and spasm. Large dose of medication can result in nausea, vomiting as well as abnormal taste. Excessive doses can lead to diarrhoea with dehydration and electrolyte loss. Hyponatremia is also reported.
  • Drug interaction
    • The combination of neomycin and neomycin can improve the curative effect of liver disease.
    • It is not suitable to take the anti acid agent in the same way so as not to reduce the curative effect.
  • Precaution It cannot be used by the patients with gastrointestinal obstruction, lactic acidemia, uremia, diabetic acidosis, and low galactose diet and lactose intolerance. Patients with diabetes should be careful in use of large doses. It is not suitable for the women to be used with 3 months of pregnancy. The drug safety for women in lactation period has not been established.
  • Chemical Properties White Powder
  • Originator Duphalac,Philips-Duphar,UK,1969
  • Uses Lactulose is is a synthetic, non-digestible sugar used in the treatment of chronic constipation; laxative.
  • Uses pharmaceutical excipient
  • Uses A keto analogue of lactose.
  • Definition ChEBI: A synthetic galactosylfructose disaccharide used in the treatment of constipation and hepatic encephalopathy.
  • Indications Osmotic laxatives (e.g., lactulose, sorbitol) are poorly absorbed or nonabsorbable compounds that draw additional fluid into the GI tract. Lumen osmolality increases, and fluid movement occurs secondary to osmotic pressure. Lactulose is a synthetic disaccharide that is poorly absorbed from the GI tract, since no mammalian enzyme is capable of hydrolyzing it to its monosaccharide components. It therefore reaches the colon unchanged and is metabolized by colonic bacteria to lactic acid and to small quantities of formic and acetic acids.
  • Manufacturing Process 105 g of lactose monohydrate were dissolved in 500 ml of water. 48 g of NaAlO2 was dissolved in 100 ml of water and was then added to the lactose solution. The mixture was then diluted to one liter to provide a pH of 11.5. The reactant concentrations of 48 g of sodium aluminate and 105 g of lactose are equivalent to a mol ratio of two mols of aluminate to one mol of lactose. The mixture was then heated to 50°C and 100 ml aliquots were removed at periodic intervals to determine the level of conversion. The reaction was terminated after three hours by adding sufficient 30% HCl to lower the pH to 4.2. The pH was then raised to neutrality, i.e., 6.5 to 7.0, with ammonium hydroxide so as to completely precipitate insoluble aluminum hydroxide. The precipitate was then removed by vacuum filtration and the filtrate was analyzed for the presence of ketose sugar by chromatographic analysis. The chromatographic analysis of the filtrate confirmed that the main component of the filtrate was lactulose and not the monosaccharide ketose sugar, fructose.
  • brand name Cephulac (Sanofi Aventis); Chronulac (Sanofi Aventis); Constulose (Acta- vis); Duphalac (Solvay Pharmaceuticals); Enulose (Actavis); Evalose (Teva); Generlac (Morton Grove); Heptalac (Teva); Laxilose (Technilab); Portalac (Solvay Pharma- ceuticals).
  • Therapeutic Function Laxative
  • Clinical Use Lactulose is used in the treatment of hepatic encephalopathy.
  • Side effects Since lactulose does contain galactose, it is contraindicated in patients who require a galactose-free diet. Metabolism of lactulose by intestinal bacteria may result in increased formation of intraluminal gas and abdominal distention.
  • Veterinary Drugs and Treatments The primary use of lactulose in veterinary medicine is to reduce ammonia blood levels in the prevention and treatment of hepatic encephalopathy (portal-systemic encephalopathy; PSE) in small animals and pet birds. It is also used as a laxative in small animals.
  • Purification Methods Crystallise lactulose from MeOH or 50% MeOH. It mutarotates from [] D 20 -11.9o to –50.7o (c 1, H2O). [Montgomery & Hudson J Am Chem Soc 32 2101, 2104 1930, Beilstein 17 III/IV 3094, 17/7 V 214.] NMR in Me2SO at 24o shows 0% -pyranose, 27% -pyranose, 20% -furanose and 52% -furanose fforms [Angyal Adv Carbohydr Chem 42 15 1984].
Lactulose Preparation Products And Raw materials
Raw materials
Preparation Products
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4618-18-2, LactuloseRelated Search:
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  • 4-o-beta-d-galactopyranosyl-d-fructos
  • 4-o-beta-d-galattopiranosil-d-fruttofuranosio
  • 4-O-D-Galactopyranosyl-D-fructose
  • 4-O-β-D-Galactopyranosyl-D-fructose, 4-O-β-D-Galactopyranosyl-D-fructofuranose
  • lactutose syrup
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  • Lactulose,4-O-β-D-Galactopyranosyl-D-fructofuranose, 4-O-β-D-Galactopyranosyl-D-fructose
  • Lactulose (1 g)
  • 4-O-β-D-Glactosyl-D-fructose
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  • Isomerized lactose syrup
  • (3S,4R,5R)-1,3,5,6-tetrahydroxy-4-(((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxyMethyl)tetrahydro-2H-pyran-2-yl)oxy)hexan-2-one
  • [UL-13C12]lactulose
  • D-Fructose, 4-O-b-D-galactopyranosyl-
  • Lactulose for peak identification
  • 4-O-hexopyranosylhex-2-ulofuranose
  • ruguotang
  • D-Fructose, 4-O-β-D-galactopyranosyl-
  • bifiteral
  • cephulac
  • chronulac
  • d-fructofuranos
  • d-lactulose
  • isolactose
  • lactulosa
  • Lactuloseliquid
  • lactulosum(latin)
  • laevolac
  • lattulosio
  • LACTULOSE, >95%
  • Lactulose, 50 wt.% solution in water
  • Lactulose, 99+%
  • 4-O-D-Galactopyranosyl-D-fructofuranose Cephulac
  • Cholac
  • Constilac
  • Constulose
  • Duphalac
  • Enulose
  • Lactulos
  • D-Fructose, 4-O-.beta.-D-galactopyranosyl-
  • 4-O-b-D-galactopyranosyl-D-fructofuranose
  • 4-O-β-D-Galactopyranosyl-D-fructofuranose