Docusate is the common chemical and pharmaceutical name of the anion bis(2-ethylhexyl) sulfosuccinate, also commonly called dioctyl sulfosuccinate ( DOSS).[
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Salts of this anion, especially docusate sodium, are widely used in medicine as an emollient laxative and as stool softeners, by mouth or rectally.[ Docusate salts are also used as , , dispersants, and , among other uses.]
It is on the World Health Organization's List of Essential Medicines.
History
Sodium docusate was patented in 1937 by Coleman R. Caryl and Alphons O. Jaeger for American Cyanamid,
Its use for the treatment of constipation was first proposed in 1955 by James L. Wilson and David G. Dickinson,
Medical use
Constipation
The main medical use of docusate sodium is to treat constipation, acting as a laxative and stool softener. In painful anorectal conditions such as hemorrhoid and , it can help avoid pain caused by straining during bowel movements.
When administered by mouth, a bowel movement often occurs in 1 to 3 days,[ while rectal use may be effective within 20 minutes.]
Sodium docusate is sometimes used as a stool softener for children.[
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However, its effectiveness for constipation is poorly supported by evidence.
The medication may be given to people who are receiving opioid medication, although prolonged use may cause irritation of the gastrointestinal tract and there is no high-quality evidence supporting its use.
Other medical uses
Docusate sodium, when used with ear syringing, may help with cerumen removal, particularly in the case of impaction.
Sodium docusate is also used as a lubricant in the production of tablets and as an emulsifier in topical preparations and other suspensions.
Precautions and contraindications
Docusate sodium is approved and recommended as safe during pregnancy and breastfeeding.
Docusate is not recommended in people with appendicitis, acute abdomen, or ileus.
When taken by mouth it should be ingested with plenty of water.
Side effects
Side effects are uncommon and typically mild,[ and may include stomach pain, or diarrhea,][ Efficacy decreases with long-term use, and may cause poor bowel function.]
Serious allergic reactions may occur with the drug. The most severe side effect of docusate, although very rare, is rectal bleeding.[drugs.com: Docusate ]
Interactions
Docusate might increase the resorption of other drugs, for example, dantron (1,8-dihydroxyanthraquinone).
Mechanism of action
Docusate is an anionic surfactant, which works by reducing the surface tension of the Feces, allowing more intestinal water and fat to combine with the stool.
It does not stay in the gastrointestinal tract but is absorbed into the bloodstream and excreted via the gallbladder
Pharmaceutical brand names
In the U.S., docusate sodium for pharmaceutical use is available under multiple brand names: Aqualax, Calube, Colace, Colace Micro-Enema, Correctol Softgel Extra Gentle, DC-240, Dialose, Diocto, Dioctocal, Dioctosoftez, Dioctyn, Dionex, Doc-Q-Lace, Docu Soft, Docucal, Doculax, Docusoft S, DOK, DOS, Doss-Relief, DSS, Dulcolax - Stool Softener (not to be confused with another drug marketed under the Dulcolax brand, bisacodyl, which is a stimulant laxative), Ex-Lax Stool Softener, Fleet Sof-Lax, Genasoft, Kasof, Laxa-basic, Modane Soft, Octycine-100, Pedia-Lax, Preferred Plus Pharmacy Stool Softener, Regulax SS, Sulfalax Calcium, Sur-Q-Lax, Surfak Stool Softener, and Therevac-SB. Generic preparations are also available.
In the UK, dioctyl sodium sulfosuccinate is sold under the brand names Docusol (Typharm Ltd) and DulcoEase (Boehringer Ingelheim).
In Australia, dioctyl sodium sulfosuccinate is sold as Coloxyl and Coloxyl with Senna glycoside.
In India, preparations include Laxatin by Alembic, Doslax by Raptakos Laboratories, Cellubril by AstraZeneca, and Laxicon by Stadmed.
Other uses
Dioctyl sodium sulfosuccinate is used as a surfactant in a wide range of applications, often under the name Aerosol-OT.
Food additive
Dioctyl sodium sulfosuccinate has been approved by the US FDA as a "generally recognized as safe" (GRAS) additive.[ It is used in a variety of food products, as a surface active agent, stabilizer, thickener, wetting agent, processing aid, solubilizer, emulsifier, and dispersant. The highest amount found in food products is 0.5% by weight, which include pasteurized cheese spreads, cream cheeses and salad dressings.]
Microencapsulation
Sodium docusate is the most widely used surfactant in reverse micelle encapsulation studies.
Non-medical brand names
As a surfactant, docusate sodium is or has been commercialized under many brand names, including DSS, Aerosol OT, Alphasol OT, Colace, Complemix, Coprol, Dioctylal, Dioctyl-Medo Forte, Diotilan, Diovac, Disonate, Doxinate, Doxol, Dulsivac, Molatoc, Molofac, Nevax, Norval, Regutol, Softili, Solusol, Sulfimel DOS, Vatsol OT, Velmol, and Waxsol
Chemistry
Structure and properties
The structural formula of the docusate anion is , where R is the 2-ethylhexyl group . The conjugate acid can be described as the twofold ester of sulfosuccinic acid with 2-ethylhexanol.
The compound is a white, wax-like, plastic solid, with an odor suggestive of octyl alcohol. It starts to decompose at about 220 °C.[
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The solubility of dioctyl sodium sulfosuccinate in water is 14 g/L at 25 °C, increasing to 55 g/L at 70 °C.[ Solubility is better in less polar solvents: 1:30 in ethanol, 1:1 in chloroform and diethylether, and practically unlimited in petroleum ether (25 °C). It also is highly soluble in glycerol, although this is a rather polar solvent. It is also highly soluble in xylene, oleic acid, acetone, diacetone alcohol, methanol, isopropanol, 2-butanol, methyl acetate, ethyl acetate, furfurol, and .][
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The ester groups are easily cleaved under basic conditions, but are stable against .
Synthesis
Sodium dioctyl sulfosuccinate can be obtained by treating dioctyl maleate with sodium bisulfite. The bisulfite anion adds to the double bond:
- +
Toxicity
Ingestion may cause the side effects described above, such as diarrhea, intestinal bloating, and occasionally cramping pains. Dioctyl sodium sulfosuccinate is not known to be , , or .[ScienceLab.com: Docusate sodium Material Safety Data Sheet ]
Marine species
Dioctyl sodium sulfosuccinate is of low toxicity for such as the hermit crab Clibanarius erythropus and the shrimp Crangon crangon. Toxicity for varies widely, with 48-hour found between 5 mg/L for the common limpet and 100 mg/L for the common periwinkle. Various species of phytoplankton have an LD50 around 8 mg/L.
In a 2010 study, dioctyl sodium sulfosuccinate exhibited higher toxicity against bacteria ( Vibrio fischeri, Anabaena sp.) and algae ( Pseudokirchneriella subcapitata) than did a number of fluorinated surfactants (PFOS, PFOA, or PFBS). Measuring bioluminescence inhibition of the bacteria and growth inhibition of the algae, the LD50 were in the range of 43–75 mg/L. Combinations of the fluorinated compounds with dioctyl sodium sulfosuccinate showed mid to highly synergistic effects in most settings, meaning that such combinations are significantly more toxic than the individual substances.
Freshwater species
The substance is highly toxic for rainbow trout with a median lethal concentration (LC50) of 0.56 mg/L after 48 hours for the pure substance. It is only slightly to moderately toxic for rainbow trout fingerlings, and slightly toxic for harlequin rasboras (LC50 27 mg/L of a 60% formulation after 48 hours).
