Lactitol (NSC-231323; Lactosit Miruhen; Lactit; trade name: pizensy) is a naturally occuring sweetener used as a gastrointestinal agent as well as an osmotic laxative for the treatment of chronic idiopathic constipation (CIC) in adults. It was approved in 2020 for medical uses as an oral solution to help produce bowel movements. In addition, it is also a reduced calorie sweetener derived from natural milk sugar, and has been used in a various sweetening applications.
Physicochemical Properties
| Molecular Formula | C12H24O11 |
| Molecular Weight | 344.31 |
| Exact Mass | 344.131 |
| Elemental Analysis | C, 41.86; H, 7.03; O, 51.11 |
| CAS # | 585-86-4 |
| Related CAS # | Lactitol monohydrate;81025-04-9 |
| PubChem CID | 157355 |
| Appearance | Crystals from absolute ethanol |
| Density | 1.7±0.1 g/cm3 |
| Boiling Point | 788.5±60.0 °C at 760 mmHg |
| Melting Point | 98-102ºC |
| Flash Point | 430.7±32.9 °C |
| Vapour Pressure | 0.0±6.2 mmHg at 25°C |
| Index of Refraction | 1.634 |
| LogP | -5.14 |
| Hydrogen Bond Donor Count | 9 |
| Hydrogen Bond Acceptor Count | 11 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 23 |
| Complexity | 343 |
| Defined Atom Stereocenter Count | 9 |
| SMILES | OC[C@@H]([C@H]([C@H](O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)[C@@H](CO)O)O)O |
| InChi Key | VQHSOMBJVWLPSR-JVCRWLNRSA-N |
| InChi Code | InChI=1S/C12H24O11/c13-1-4(16)7(18)11(5(17)2-14)23-12-10(21)9(20)8(19)6(3-15)22-12/h4-21H,1-3H2/t4-,5+,6+,7+,8-,9-,10+,11+,12-/m0/s1 |
| Chemical Name | (2S,3R,4R,5R)-4-(((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)hexane-1,2,3,5,6-pentaol |
| Synonyms | Lactitol; Lactit; Lactosit Miruhen; NSC 231323; NSC-231323; NSC231323; |
| HS Tariff Code | 2934.99.03.00 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion In healthy subjects under fed conditions, oral administration of 20 grams of lactitol resulted in a mean Tmax of 3.6 ± 1.2 hours, Cmax of 776 ± 253 ng/mL, and a mean AUC of 6,019 ± 1,771 ng*hr/mL. Lactitol is not absorbed in the gastrointestinal tract to any significant extent. The vast majority of an ingested dose is likely degraded into organic acids in the colon and eliminated in the feces. Data regarding the volume of distribution of lactitol are unavailable. Data regarding the clearance of lactitol are unavailable. Three male rats (150-200 g; six to eight weeks of age; one not pretreated and two habituated to a diet containing 7% lactitol) were orally intubated with about 2 mg D-(sorbitol-1-(14)C) lactitol. In the studies with the rats habituated to lactitol, 9-15% of the radioactivity was recovered from the air exhaled in the period 0-5 hours and 48% from the air exhaled in the period 0-24 hours. The urine and the feces contained a minor proportion of the administered radioactivity (urine, 2.3% after five hours and 6.8% after 24 hours; feces, 11.7% after 24 hours). The gastrointestinal tract contained 33% of the radioactivity after five hours and 5% after 24 hours; the remainder of the body contained 20% after five hours and 9% after 24 hours. It was concluded that lactitol is extensively degraded in the rat after oral administration presumably mainly by the intestinal microflora and that habituation of the rats to unlabelled lactitol did not essentially affect the rate and extent of degradation. In studies designed to investigate the metabolism of erythritol in vivo in healthy volunteers and to compare the fermentation of erythritol by human fecal flora in vitro with that of glucose and lactitol, four male and two female volunteers aged 21-25 undertook an overnight fast and were then chosen at random to receive a single dose of 25 g (13)C-erythritol, (13)C-glucose, and (13)C-lactitol in 250 mL of water with at least three days between each treatment. Breath samples were taken for analysis of (13)C-carbon dioxide and hydrogen gas before treatment and at 30 min intervals up to 6 hr after treatment. The ratio of (13)C: (12)C-carbon dioxide was measured by isotope-ratio mass spectrometry. Urine samples were collected over 0-6 and 6-24 hr after treatment, and the erythritol and lactitol concentrations in urine were measured by HPLC. ... During the first 6 and 24 hr after dosing, 52 and 84%, respectively, of the administered erythritol was recovered in the urine. No increase in expired (13)C-carbon dioxide or hydrogen gas was observed, indicating that no fermentation had occurred in the gut. In contrast, there was a rapid increase in expired (13)C-carbon dioxide after consumption of glucose and a more gradual rise after ingestion of lactitol. Excretion of hydrogen gas in expired air was also increased after treatment with lactitol. Neither lactitol nor glucose was detected in significant amounts in the urine. ... The gastrointestinal absorption of lactitol has been studied in 6 healthy volunteers and 8 patients with cirrhosis. Following administration of lactitol 0.5 g/kg, no lactitol was found in serum. The urinary excretion of lactitol over 24 hr ranged from 0.1 to 1.4% of the administered dose (0.46% in cirrhotics and 0.35% in healthy volunteers). Blood D- and L-lactate and plasma glucose did not increase following lactitol. The data indicate that lactitol was poorly absorbed from the gastrointestinal tract in healthy volunteers and patients with cirrhosis, and that the disaccharide did not disturb glucose or lactate homeostasis. The fate of orally ingested lactitol, a non-absorbed sugar, was measured in six healthy human subjects by following the three routes of disposal of universally (14)C-labelled sugar. Lactitol was given as a 20 g daily dose to six healthy volunteers for 14 days and on the seventh day, 10 muCi of L-[U-(14)C]-lactitol was given with the unlabelled sugar and excretion of the (14)C in breath, urine and faeces was followed. The peak of (14)CO2 excretion occurred at six hours and total (14)CO2 accounted for 62.9 (5.0)% of isotope given, whilst 6.5 (3.6)% and 2.0 (0.3)% of the label were recovered from faeces and urine respectively. These data suggest that lactitol is extensively metabolised in the human colon and that a significant proportion of the bacterial metabolites are available for colonic absorption. Calculation revealed that 54.5% of the theoretical energy content of this compound was utilised by the subjects. ... Metabolism / Metabolites As it undergoes little-to-no systemic absorption, lactitol is unlikely to undergo any significant degree of metabolism. In studies designed to investigate the metabolism of erythritol in vivo in healthy volunteers and to compare the fermentation of erythritol by human fecal flora in vitro with that of glucose and lactitol, four male and two female volunteers aged 21-25 undertook an overnight fast and were then chosen at random to receive a single dose of 25 g (13)C-erythritol, (13)C-glucose, and (13)C-lactitol in 250 mL of water with at least three days between each treatment. Breath samples were taken for analysis of (13)C-carbon dioxide and hydrogen gas before treatment and at 30 min intervals up to 6 hrs after treatment. The ratio of (13)C: (12)C-carbon dioxide was measured by isotope-ratio mass spectrometry. ... In order to maintain a constant metabolic rate, the subjects remained at rest during the study. For the assay of fermentation in vitro, fecal samples were collected from six healthy volunteers (sex and age not specified) who ate a normal western diet. None of the subjects complained of gastrointestinal symptomsand none had used antibiotics in the past six months. The samples were incubated under anaerobic conditions for 6 hr, and then the hydrogen gas concentration was measured in the head-space of the incubation vials. ... After a 6 hr incubation with erythritol, the amount of hydrogen gas formed by the fecal flora was comparable to that in control vials, but significantly (p < 0.001) more hydrogen gas was produced in the glucose and lactitol vials than in either control or erythritol. Biological Half-Life The average half-life of orally administered lactitol is 2.4 hours. |
| Toxicity/Toxicokinetics |
Protein Binding As it undergoes little-to-no systemic absorption, lactitol is unlikely to be subject to protein binding. Non-Human Toxicity Values LD50 Rat dermal >4,500 mg/kg bw LD50 Rat oral > 10,000 mg/kg bw LD50 Rat oral 30 g/kg LD50 Mouse oral >23 g/kg |
| References | Lactitol or lactulose in the treatment of chronic constipation: result of a systematic. J Indian Med Assoc. 2010 Nov;108(11):789-92. |
| Additional Infomation |
Therapeutic Uses Sugar Alcohols; Cathartics; Sweetening Agents Lactitol (beta-galactosido-sorbitol) has been recently compared with lactulose for the treatment of chronic hepatic encephalopathy in a few studies, each comprising a small number of patients. The results are controversial. We studied the efficiency and tolerance of both compounds by using a meta-analysis on the basis of published controlled trials. /This/ study only included controlled or randomized trials comprising cirrhotic patients with chronic hepatic encephalopathy. Analyzed parameters were the portosystemic encephalopathy index of Conn after treatment, the percentage of improved patients and the percentage of patients who had ill effects related to the treatment (flatulence, diarrhea). Bibliographical screening revealed five studies comparing the effects of lactitol and lactulose in chronic hepatic encephalopathy. Four crossover studies were done that included 48 patients and one parallel study that included 29 patients. The duration of the treatment ranged from 3 to 6 mo. All studies found a similar efficiency with both drugs. However, they exhibited some discrepancies in the relative frequency of adverse reactions (flatulence). Meta-analysis showed no statistical differences in the portosystemic encephalopathy index after lactitol or lactulose treatment. The percentage of improved patients after lactitol or lactulose was similar. In contrast, the analysis revealed a higher frequency (p less than 0.01) of flatulence in patients treated with lactulose compared with those treated with lactitol. In conclusion, this meta-analysis shows no statistical difference between therapeutic effects of lactitol and lactulose, but it does show a higher frequency of flatulence with lactulose. This suggests that lactitol should be preferred to lactulose for the treatment of chronic hepatic encephalopathy. Preliminary data suggest that lactitol (beta-galactoside-sorbitol), a new synthetic non-absorbable disaccharide, has beneficial effects on chronic portal systemic encephalopathy. To compare the efficacy of lactitol vs. lactulose in the treatment of acute portal systemic encephalopathy (PSE), 40 cirrhotic patients with an acute episode of PSE were randomly allocated to one of two groups: group A (20 patients) received lactulose (30 mL/6 hr) and group B (20 patients) lactitol (12 g/6 hr). These doses were adjusted daily to obtain two bowel movements per day. The duration of treatment was 5 days. Age, sex, hepatic and renal function, precipitating factors and level of PSE measured by clinical examination, EEG and number connection test were similar in the two groups. A complete clinical resolution of PSE occurred in 11 patients in each group. In 5 patients of the lactulose group and in 6 of the lactitol group there was a moderate improvement of PSE during the study. Finally, 4 patients in the lactulose group and 3 in the lactitol group did not respond to treatment. No side effects attributable to therapy were observed in either group. These results indicate that lactitol is as effective as lactulose in the management of patients with cirrhosis and acute PSE. Pharmacodynamics Lactitol helps to facilitate bowel movements by drawing water into the gastrointestinal tract. The oral administration of lactitol may reduce the absorption of concomitant medications - other oral medications should be administered at least 2 hours before or 2 hours after lactitol. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~68 mg/mL ( ~197.49 mM) |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9044 mL | 14.5218 mL | 29.0436 mL | |
| 5 mM | 0.5809 mL | 2.9044 mL | 5.8087 mL | |
| 10 mM | 0.2904 mL | 1.4522 mL | 2.9044 mL |