Dioctyl sodium sulfosuccinate

Dioctyl sodium sulfosuccinate[1][2]
IUPAC name Sodium 1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate
Other names Aerosol OT; AOT; sodium bis(2-ethylhexyl) sulfosuccinate; docusate sodium
Identifiers
CAS number	577-11-7 Y
PubChem	23673837
ChemSpider	10861 Y
UNII	F05Q2T2JA0 Y
ATC code	A06AA02
Jmol-3D images	Image 1
SMILES [Na+].[O-]S(=O)(=O)C(C(=O)OCC(CC)CCCC)CC(=O)OCC(CC)CCCC
InChI InChI=1S/C20H38O7S.Na/c1-5-9-11-16(7-3)14-26-19(21)13-18(28(23,24)25)20(22)27-15-17(8-4)12-10-6-2;/h16-18H,5-15H2,1-4H3,(H,23,24,25);/q;+1/p-1 Y Key: APSBXTVYXVQYAB-UHFFFAOYSA-M Y InChI=1/C20H38O7S.Na/c1-5-9-11-16(7-3)14-26-19(21)13-18(28(23,24)25)20(22)27-15-17(8-4)12-10-6-2;/h16-18H,5-15H2,1-4H3,(H,23,24,25);/q;+1/p-1 Key: APSBXTVYXVQYAB-REWHXWOFAT
Properties
Molecular formula	C20H37NaO7S
Molar mass	444.56 g/mol
Appearance	White to off-white, wax-like solid, bitter, smells of octanol
Density	1.1 g/cm³
Melting point	153–157 °C
Solubility in water	1:70
Solubility in petroleum ether	Highly soluble
Hazards
NFPA 704	1 2 0
LD50	1900 mg/kg (rat, oral)
Y sodium sulfosuccinate (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Dioctyl sodium sulfosuccinate or docusate sodium (INN,  /ˈdɒkjuːseɪt/) – often referred to as DSS, Aerosol OT or AOT – is a common ingredient in consumer products, especially laxatives of the stool softener type. It is also used as an emulsifying, wetting, and dispersing agent, as a pesticide,^[3] as well as a component of the oil dispersant Corexit which was used in the Deepwater Horizon oil spill of 2010.^[4] It is an anionic surfactant, a substance that lowers the surface tension of water.

Docusate calcium and docusate potassium, as well as other dioctyl sulfosuccinate salts^{[citation needed]}, are also widely used in the same areas.

Uses

Clinical use

Docusate is given to make stools softer and easier to pass. It is used to treat constipation due to hard stools, in painful anorectal conditions such as hemorrhoids, and for people who should avoid straining during bowel movements. Patients should take plenty of water to help the movement of feces, therefore speeding up the initial bowel movement. Given orally, the effect on stools is usually seen 1 to 3 days after the first dose.^[5] Given rectally as an enema or mini-enema, a bowel movement usually occurs within 5 to 20 minutes.^[6]

The drug may be used in a daily regimen in persons who are undergoing narcotic pain medication therapy, are opioid dependent, or are on opioid replacement therapy such as with methadone or buprenorphine to treat a previous opioid dependency, to reduce the effects of chronic constipation or hardened stools which can cause severe straining, impaction, and torn rectal tissues. However, both polyethylene glycol (3350 Da) and lactulose have been proven vastly more effective^{[citation needed]}, more well-tolerated with less incidence of adverse reaction^{[citation needed]}, and much safer in the long term^{[citation needed]}, as they do not cause a physical dependency on the laxative to form, as it does with docusate and stimulant laxatives, nor do they cause an imbalance of electrolytes unless used to the point where the patient is having constant diarrhea.

Despite its popularity, data supporting its efficacy in treating chronic constipation is lacking.^[7] It is frequently used to prevent constipation, and is routinely used concomittantly with opioids to prevent opioid-induced constipation.

Available forms

Docusate sodium is administered orally or rectally; as a tablet disintegrant or as an emulsifier and dispersant in topical preparations. Docusate calcium and docusate potassium are used as stool softeners administered orally.

Other uses

• Dioctyl sodium sulfosuccinate is a pesticide^[3] used popularly for crops of olives, almonds, wine grapes, corn and oranges.
• It is used as an excipient in the production of tablets (as a lubricant) and suspensions (as an emulsifier).^[8]
• It is the most widely used surfactant in reverse micelle encapsulation studies.^[9]
• Docusate sodium, when used in conjunction with irrigation, is also an effective means of earwax removal.^[10]

Contraindications

Docusate is contraindicated in patients with appendicitis, acute abdomen or ileus. It is not suitable for the treatment of chronic obstipation.^[7]

Side effects

Possible side effects are typically mild and include stomach pain, diarrhea, or cramping. Serious allergic reactions can occur with the drug. The most severe side effect of docusate, although very rare, is rectal bleeding.^[5]

Physical and chemical properties

Solubility of dioctyl sodium sulfosuccinate in water is 1:70 (14 g/l) at 25 °C, increasing to 1:20 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 is also highly soluble in glycerol, although this is a rather polar solvent.

The ester groups are easily cleaved under basic conditions, but are stable against acids.^[7]

Pharmacokinetics and mechanism of action

Docusate does not stay in the gastrointestinal tract, but is absorbed into the bloodstream and excreted via the gallbladder^[7] after undergoing extensive metabolism.

The effect of docusate may not necessarily be all due to its surfactant properties. Perfusion studies suggest that docusate inhibits fluid absorption or stimulates secretion in the portion of the small intestine known as the jejunum.

Interactions

Docusate should not be used in addition to mineral oil as the emulsifier will result in mineral oil being absorbed rather than functioning as a lubricant for the bowel walls, possibly resulting in foreign body granulomas. The substance might also increase resorption of other drugs, for example dantron (1,8-dihydroxyanthraquinone).^[7]

Toxicity

Toxicity for different species varies in a wide range, but dioctyl sulfosuccinate biodegrades quickly in soil and water, a typical finding being >90% in 12 to 17 days. In the atmosphere, it is destroyed by a photochemical reaction with an estimated half-life of 18 hours.^[11]

In humans

Dioctyl sodium sulfosuccinate is a strong irritant for eyes and lungs, and also a skin irritant. Ingestion can cause the side effects described above, such as diarrhea, intestinal bloating and occasionally cramping pains. DSS is not known to be carcinogenic, mutagenic or teratogenic.^[12]

In marine species

Dioctyl sodium sulfosuccinate has been determined to be of low toxicity for crustaceans like the hermit crab Clibanarius erythropus and the shrimp Crangon crangon. The median lethal dose (LD₅₀) for these species is about 100 mg/l of a docusate containing formulation after 48 hours of exposition, although the concentration of the formulation is not specified in the study.

Toxicity for molluscs varies widely, with 48-hour LD₅₀ found between 5 mg/l for the common limpet and 100 mg/l for the common periwinkle. Various species of phytoplankton have an LD₅₀ of around 8 mg/l. All of these doses refer to the mentioned formulation, not the pure chemical.^[13]

In a 2010 study, dioctyl sodium sulfosuccinate exhibited higher toxicity against bacteria (Vibrio fischeri, Anabaena sp.) and algae (Pseudokirchneriella subcapitata) than a number of fluorinated surfactants (PFOS, PFOA, PFBS). Measuring bioluminescence inhibition of the bacteria and growth inhibition of the algae, the ED₅₀ were in the range of 43–75 mg/l. Combinations of the fluorinated compounds with DSS showed mid to highly synergistic effects in most settings, meaning that such combinations are significantly more toxic than the individual substances.^[14]

In 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).^[13]

Trade marks

In the U.S. it 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, Ex-Lax Stool Softener, Fleet Sof-Lax, Genasoft, Kasof, Laxa-basic, Modane Soft, Octycine-100, 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 it sold under the brand name Docusol (Typharm Ltd) and DulcoEase (Boehringer Ingelheim).

In Australia it is sold as Coloxyl, or Coloxyl with senna.

References

1. ^ Merck Index, 14th Edition, 3401.
2. ^ Dioctyl Sulfosuccinic Acid at PubChem
3. ^ ^{a b} PAN Pesticides Database: Dioctyl sodium sulfosuccinate
4. ^ Schor, Elana (2010-06-09). "Ingredients of Controversial Dispersants Used on Gulf Spill Are Secrets No More". The New York Times. http://www.nytimes.com/gwire/2010/06/09/09greenwire-ingredients-of-controversial-dispersants-used-42891.html. 
5. ^ ^{a b} drugs.com: Docusate
6. ^ nursingTimes.com: Docusate sodium
7. ^ ^{a b c d e} Dinnendahl, V, Fricke, U, ed (2010) (in German). Arzneistoff-Profile. 2 (23 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-98-46-3. 
8. ^ Jasek, W, ed (2008) (in German). Austria-Codex Stoffliste (41 ed.). Vienna: Österreichischer Apothekerverlag. p. 316. ISBN 3-85200-190-6. 
9. ^ Flynn, P.F. (2004). "Multidimensional multinuclear solution NMR studies of encapsulated macromolecules". Prog. Nucl. Magn. Reson. Spectrosc. 45: 31–51. doi:10.1016/j.pnmrs.2004.04.003. 
10. ^ GlobalRPH.com: How effective is docusate as a cerumenolytic agent?
11. ^ Hazardous Substances Data Bank: Bis(2-Ethylhexyl) Sodium Sulfosuccinate
12. ^ ScienceLab.com: Docusate sodium Material Safety Data Sheet
13. ^ ^{a b} PAN Pesticides Database – Chemical Toxicity Studies on Aquatic Organisms: Dioctyl sodium sulfosuccinate
14. ^ Rosal, R; Rodea-Palomares, I; Boltes, K; Fernández-Piñas, F; Leganés, F; Petre, A (2010). "Ecotoxicological assessment of surfactants in the aquatic environment: combined toxicity of docusate sodium with chlorinated pollutants.". Chemosphere 81 (2): 288–93. doi:10.1016/j.chemosphere.2010.05.050. PMID 20579683. 

External links

• Stool Softeners at the N.I.H. PubMed Health resource.