Polyethylene glycol

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Polyethylene glycol
Polyethylene glycol.png
Identifiers
CAS number 25322-68-3 YesY
ChEMBL CHEMBL1201478 N
ATC code A06AD15
Properties
Molecular formula C2nH4n+2On+1
Molar mass variable
Hazards
Flash point 182 to 287 °C; 360 to 549 °F; 455 to 560 K
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
Infobox references

Polyethylene glycol (PEG) is a polyether compound with many applications from industrial manufacturing to medicine. The structure of PEG is (note the repeated element in parentheses):

H-(O-CH2-CH2)n-OH

PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular weight.

Available forms and nomenclature[edit]

PEG, PEO, or POE refers to an oligomer or polymer of ethylene oxide. The three names are chemically synonymous, but historically PEG has tended to refer to oligomers and polymers with a molecular mass below 20,000 g/mol, PEO to polymers with a molecular mass above 20,000 g/mol, and POE to a polymer of any molecular mass.[2] PEG and PEO are liquids or low-melting solids, depending on their molecular weights. PEGs are prepared by polymerization of ethylene oxide and are commercially available over a wide range of molecular weights from 300 g/mol to 10,000,000 g/mol. While PEG and PEO with different molecular weights find use in different applications, and have different physical properties (e.g. viscosity) due to chain length effects, their chemical properties are nearly identical. Different forms of PEG are also available, depending on the initiator used for the polymerization process – the most common initiator is a monofunctional methyl ether PEG, or methoxypoly(ethylene glycol), abbreviated mPEG. Lower-molecular-weight PEGs are also available as purer oligomers, referred to as monodisperse, uniform, or discrete. Very high purity PEG has recently been shown to be crystalline, allowing determination of a crystal structure by x-ray diffraction.[3] Since purification and separation of pure oligomers is difficult, the price for this type of quality is often 10-1000 fold that of polydisperse PEG.

PEGs are also available with different geometries.

  • Branched PEGs have three to ten PEG chains emanating from a central core group.
  • Star PEGs have 10 to 100 PEG chains emanating from a central core group.
  • Comb PEGs have multiple PEG chains normally grafted onto a polymer backbone.

The numbers that are often included in the names of PEGs indicate their average molecular weights (e.g. a PEG with n = 9 would have an average molecular weight of approximately 400 daltons, and would be labeled PEG 400. Most PEGs include molecules with a distribution of molecular weights (i.e. they are polydisperse). The size distribution can be characterized statistically by its weight average molecular weight (Mw) and its number average molecular weight (Mn), the ratio of which is called the polydispersity index (Mw/Mn). MW and Mn can be measured by mass spectrometry.

PEGylation is the act of covalently coupling a PEG structure to another larger molecule, for example, a therapeutic protein, which is then referred to as a PEGylated protein. PEGylated interferon alfa-2a or −2b are commonly used injectable treatments for Hepatitis C infection.

PEG is soluble in water, methanol, ethanol, acetonitrile, benzene, and dichloromethane, and is insoluble in diethyl ether and hexane. It is coupled to hydrophobic molecules to produce non-ionic surfactants.

PEGs contain potential toxic impurities, such as ethylene oxide and 1,4-dioxane. Ethylene Glycol and its ethers are nephrotoxic if applied to damaged skin.[4]

Polyethylene oxide (PEO, Mw 4 kDa) nanometric crystallites (4 nm)

PEGs and methoxypolyethylene glycols are manufactured by Dow Chemical under the tradename Carbowax for industrial use, and Carbowax Sentry for food and pharmaceutical use. They vary in consistency from liquid to solid, depending on the molecular weight, as indicated by a number following the name. They are used commercially in numerous applications, including as surfactants, in foods, in cosmetics, in pharmaceutics, in biomedicine, as dispersing agents, as solvents, in ointments, in suppository bases, as tablet excipients, and as laxatives. Some specific groups are lauromacrogols, nonoxynols, octoxynols, and poloxamers.

Macrogol, used as a laxative, is a form of polyethylene glycol. The name may be followed by a number which represents the average molecular weight (e.g. macrogol 4000, macrogol 3350 or macrogol 6000).

Production[edit]

Polyethylene glycol is produced by the interaction of ethylene oxide with water, ethylene glycol, or ethylene glycol oligomers.[5] The reaction is catalyzed by acidic or basic catalysts. Ethylene glycol and its oligomers are preferable as a starting material instead of water, because they allow the creation of polymers with a low polydispersity (narrow molecular weight distribution). Polymer chain length depends on the ratio of reactants.

HOCH2CH2OH + n(CH2CH2O) → HO(CH2CH2O)n+1H

Depending on the catalyst type, the mechanism of polymerization can be cationic or anionic. The anionic mechanism is preferable because it allows one to obtain PEG with a low polydispersity. Polymerization of ethylene oxide is an exothermic process. Overheating or contaminating ethylene oxide with catalysts such as alkalis or metal oxides can lead to runaway polymerization, which can end in an explosion after a few hours.

Polyethylene oxide, or high-molecular weight polyethylene glycol, is synthesized by suspension polymerization. It is necessary to hold the growing polymer chain in solution in the course of the polycondensation process. The reaction is catalyzed by magnesium-, aluminium-, or calcium-organoelement compounds. To prevent coagulation of polymer chains from solution, chelating additives such as dimethylglyoxime are used.

Alkali catalysts such as sodium hydroxide (NaOH), potassium hydroxide (KOH), or sodium carbonate (Na2CO3) are used to prepare low-molecular-weight polyethylene glycol.

Medical uses[edit]

PEG is the basis of a number of laxatives (e.g., macrogol-containing products, such as Movicol and polyethylene glycol 3350, or SoftLax, MiraLAX,ClearLAX, or GlycoLax). Whole bowel irrigation with polyethylene glycol and added electrolytes is used for bowel preparation before surgery or colonoscopy. The preparation is sold under the brand names GoLYTELY, GaviLyte C, NuLytely, GlycoLax, Fortrans, TriLyte, Colyte, Halflytely, Softlax, Lax-a-Day, ClearLax and MoviPrep. In the United States, MiraLAX and Dulcolax Balance are sold without prescription for short-term relief of chronic constipation. Miralax is currently FDA approved for adults for a period of seven days, and is not approved for children.[6] A 2007 comparison showed that patients suffering from constipation had a better response to PEG medications than to tegaserod.[7] These medications soften the fecal mass by osmotically drawing water into the GI tract. It is generally well tolerated, however, side effects are possible bloating, nausea, gas, and diarrhea (with excessive use).

When attached to various protein medications, polyethylene glycol allows a slowed clearance of the carried protein from the blood. This makes for a longer-acting medicinal effect and reduces toxicity, and allows longer dosing intervals. Examples include PEG-interferon alpha, which is used to treat hepatitis C, and PEGfilgrastim (Neulasta), which is used to treat neutropenia. It has been shown that polyethylene glycol can improve healing of spinal injuries in dogs.[8] One of the earlier findings, that polyethylene glycol can aid in nerve repair, came from the University of Texas (Krause and Bittner).[9] Polyethylene glycol is also commonly used to fuse B-cells with myeloma cells in monoclonal antibody production.

PEG is used as an excipient in many pharmaceutical products. Lower-molecular-weight variants are used as solvents in oral liquids and soft capsules, whereas solid variants are used as ointment bases, tablet binders, film coatings, and lubricants.[10]

PEG is also used in lubricating eye drops.

Research for new clinical uses[edit]

  • PEG, when labeled with a near-infrared fluorophore, has been used in preclinical work as a vascular agent, lymphatic agent, and general tumor-imaging agent by exploiting the Enhanced permeability and retention effect (EPR) of tumors.[11]
  • High-molecular-weight PEG (e.g. PEG 8000) has been shown to be a dietary preventive agent against colorectal cancer in animal models.[12]
  • The Chemoprevention Database shows PEG is the most effective known agent for the suppression of chemical carcinogenesis in rats. Cancer prevention applications in humans, however, have not yet been tested in clinical trials.[13]
  • The injection of PEG 2000 into the bloodstream of guinea pigs after spinal cord injury leads to rapid recovery through molecular repair of nerve membranes.[14] The effectiveness of this treatment to prevent paraplegia in humans after an accident is not known yet.
  • PEG is being used in the repair of motor neurons damaged in crush or laceration incidents in vivo and in vitro. When coupled with melatonin, 75% of damaged sciatic nerves were rendered viable.[15]

Other uses[edit]

Chemical uses[edit]

  • Polyethylene glycol has a low toxicity and is used in a variety of products.[16] The polymer is used as a lubricating coating for various surfaces in aqueous and non-aqueous environments.[17]
  • Since PEG is a flexible, water-soluble polymer, it can be used to create very high osmotic pressures (on the order of tens of atmospheres). It also is unlikely to have specific interactions with biological chemicals. These properties make PEG one of the most useful molecules for applying osmotic pressure in biochemistry and biomembranes experiments, in particular when using the osmotic stress technique.
  • PEG has also been used to preserve objects that have been salvaged from underwater, as was the case with the warship Vasa in Stockholm,[18] the Mary Rose in England and the Ma'agan Michael Ship in Israel.[19] It replaces water in wooden objects, making the wood dimensionally stable and preventing warping or shrinking of the wood when it dries. In addition, PEG is used when working with green wood as a stabilizer, and to prevent shrinkage.[20]
  • PEG is often used (as an internal calibration compound) in mass spectrometry experiments, with its characteristic fragmentation pattern allowing accurate and reproducible tuning.

Biological uses[edit]

  • In microbiology, PEG precipitation is used to concentrate viruses. PEG is also used to induce complete fusion (mixing of both inner and outer leaflets) in liposomes reconstituted in vitro.
  • Gene therapy vectors (such as viruses) can be PEG-coated to shield them from inactivation by the immune system and to de-target them from organs where they may build up and have a toxic effect.[22] The size of the PEG polymer has been shown to be important, with larger polymers achieving the best immune protection.
  • When working with phenol in a laboratory situation, PEG 300 can be used on phenol skin burns to deactivate any residual phenol.

Commercial uses[edit]

  • PEG is used in a number of toothpastes as a dispersant. In this application, it binds water and helps keep xanthan gum uniformly distributed throughout the toothpaste.
  • PEG is also one of the main ingredients in paintball fills, due to its thickness and flexibility. However, as early as 2006, some Paintball manufacturers began substituting cheaper oil-based alternatives for PEG.[citation needed]
  • PEG is also used as an anti-foaming agent in food[28] – its INS number is 1521[29] or E1521 in the EU.[30]

Industrial uses[edit]

  • PEG has been used as the gate insulator in an electric double-layer transistor to induce superconductivity in an insulator.[32]
  • PEG is also used as a polymer host for solid polymer electrolytes. Although not yet in commercial production, many groups around the globe are engaged in research on solid polymer electrolytes involving PEG, with the aim of improving their properties, and in permitting their use in batteries, electro-chromic display systems, and other products in the future.

See also[edit]

References[edit]

  1. ^ J. Kahovec, R. B. Fox and K. Hatada (2002). "Nomenclature of regular single-strand organic polymers". Pure and Applied Chemistry 74 (10): 1921–1956. doi:10.1351/pac200274101921. 
  2. ^ For example, in the online catalog of Scientific Polymer Products, Inc., poly(ethylene glycol) molecular weights run up to about 20,000, while those of poly(ethylene oxide) have six or seven digits.
  3. ^ French, Alister C.; Thompson, Amber L.; Davis, Benjamin G. (2009). "High Purity Discrete PEG Oligomer Crystals Allow Structural Insight". Angewandte Chemie International Edition 48 (7): 1248–1252. doi:10.1002/anie.200804623. PMID 19142918. 
  4. ^ Andersen, F. A. (1999). "Special Report: Reproductive and Developmental Toxicity of Ethylene Glycol and Its Ethers". International Journal of Toxicology 18 (3): 53–10. doi:10.1177/109158189901800208.  edit
  5. ^ Polyethylene glycol, Chemindustry.ru
  6. ^ Louis, Catherine Saint (May 25, 2012). "Drug for Adults Is Popular as Children’s Remedy". The New York Times. Retrieved 29 August 2012. 
  7. ^ Di Palma, Jack A.; Cleveland, Mark vB.; McGowan, John; Herrera, Jorge L. (2007). "A Randomized, Multicenter Comparison of Polyethylene Glycol Laxative and Tegaserod in Treatment of Patients With Chronic Constipation". The American Journal of Gastroenterology 102 (9): 1964–71. doi:10.1111/j.1572-0241.2007.01365.x. PMID 17573794. 
  8. ^ Lee Bowman (4 December 2004). "Study on dogs yields hope in human paralysis treatment". seattlepi.com. 
  9. ^ T. L. Krause and G. D. Bittner (1990). "Rapid morphological fusion of severed myelinated axons by polyethylene glycol". PNAS 87 (4): 1471–1475. Bibcode:1990PNAS...87.1471K. doi:10.1073/pnas.87.4.1471. PMC 53497. PMID 2304913. 
  10. ^ Smolinske, Susan C. (1992). Handbook of Food, Drug, and Cosmetic Excipients. Boca Raton: CRC Press. p. 287. ISBN 0-8493-3585-X. 
  11. ^ Kovar, J., Wang, Y., Simpson, M.A., and Olive, D.M., "Imaging Lymphatics With A Variety of Near-Infrared-Labeled Optical Agents", World Molecular Imaging, (2009)
  12. ^ D. E. Corpet, G. Parnaud, M. Delverdier, G. Peiffer and S. Tache (2000). "Consistent and Fast Inhibition of Colon Carcinogenesis by Polyethylene Glycol in Mice and Rats Given Various Carcinogens". Cancer Research 60 (12): 3160–3164. PMID 10866305. 
  13. ^ Chemoprevention Database. Inra.fr. Retrieved on 2012-11-30.
  14. ^ R. B. Borgens and D. Bohnert (2001). "Rapid recovery from spinal cord injury after subcutaneously administered polyethylene glycol". Journal of Neuroscience Research 66 (6): 1179–1186. doi:10.1002/jnr.1254. PMID 11746451. 
  15. ^ G. Bittner el. al. (2005). "Melatonin enhances the in vitro and in vivo repair of severed rat sciatic axons". Neouroscience Letters 376 (2): 98–101. doi:10.1016/j.neulet.2004.11.033. PMID 15698928. 
  16. ^ Victor O. Sheftel (2000). Indirect Food Additives and Polymers: Migration and Toxicology. CRC. pp. 1114–1116. 
  17. ^ Nalam, Prathima C.; Clasohm, Jarred N.; Mashaghi, Alireza; Spencer, Nicholas D. (2009). "Macrotribological Studies of Poly(L-lysine)-graft-Poly(ethylene glycol) in Aqueous Glycerol Mixtures". Tribology Letters 37 (3): 541. doi:10.1007/s11249-009-9549-9. 
  18. ^ Lars-Åke Kvarning, Bengt Ohrelius (1998), The Vasa – The Royal Ship, ISBN 91-7486-581-1, pp. 133–141
  19. ^ Linder, Elisha (1992). "Excavating an Ancient Merchantman". Biblical Archaeology Review (Biblical Archaeology Society) 18 (6): 24–35. 
  20. ^ Anti-Freeze is Not a Green Wood Stabilizer – Buzz Saw, The Rockler Blog. Rockler.com (2006-05-02). Retrieved on 2012-11-30.
  21. ^ Rameez, Shahid; Alosta, Houssam; Palmer, Andre F. (2008). "Biocompatible and Biodegradable Polymersome Encapsulated Hemoglobin: A Potential Oxygen Carrier". Bioconjugate Chemistry 19 (5): 1025–32. doi:10.1021/bc700465v. PMID 18442283. 
  22. ^ Kreppel, Florian; Kochanek, Stefan (2007). "Modification of Adenovirus Gene Transfer Vectors With Synthetic Polymers: A Scientific Review and Technical Guide". Molecular Therapy 16 (1): 16–29. doi:10.1038/sj.mt.6300321. PMID 17912234. 
  23. ^ J.J. Rossi (2006). "RNAi therapeutics: SNALPing siRNAs in vivo". Gene Therapy 13 (7): 583–584. doi:10.1038/sj.gt.3302661. PMID 17526070. 
  24. ^ Thomas W. Geisbert; Lee, Amy CH; Robbins, Marjorie; Geisbert, Joan B; Honko, Anna N; Sood, Vandana; Johnson, Joshua C; De Jong, Susan et al. (2010-05-29). "Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study". The Lancet 375 (9729): 1896–905. doi:10.1016/S0140-6736(10)60357-1. PMID 20511019.  (free with registration)
  25. ^ Harmening, Denise M. (2005). Modern Blood Banking & Transfusion Practices. F. A. Davis Company. ISBN 0-8036-1248-6. 
  26. ^ Tonya Johnson (21 April 2004). "Army Scientists, Engineers develop Liquid Body Armor". 
  27. ^ "Tattoo to monitor diabetes". BBC News. 1 September 2002. 
  28. ^ US Government – Food and Drug Agency "Listing of Food Additive Status Part II". Retrieved 2011-10-21. 
  29. ^ "Codex Alimentarius". 
  30. ^ UK Government – Food Standards Agency "Current EU approved additives and their E Numbers". Retrieved 2010-10-21. 
  31. ^ Spinardi, Graham (1994). From Polaris to Trident : the development of US fleet ballistic missile technology. Cambridge: Cambridge Univ. Press. p. 159. ISBN 0-521-41357-5. 
  32. ^ Ueno, K.; Nakamura, S.; Shimotani, H.; Ohtomo, A.; Kimura, N.; Nojima, T.; Aoki, H.; Iwasa, Y.; Kawasaki, M. (2008). "Electric-field-induced superconductivity in an insulator". Nature Materials 7 (11): 855–858. Bibcode:2008NatMa...7..855U. doi:10.1038/nmat2298. PMID 18849974.  edit
  33. ^ Volume 4, Engineered Materials Handbook: Ceramics and Glasses, ASM International, 1991, ISBN 0-87170-282-7, p 49.

External links[edit]