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|Related compounds||D-glucosamine and N-Acetylglucosamine (monomers)|
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Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Chitosan // is a linear polysaccharide composed of randomly distributed β-(1-4)-linked D-glucosamine (deacetylated unit) and N-acetyl-D-glucosamine (acetylated unit). It is made by treating shrimp and other crustacean shells with the alkali sodium hydroxide.
Chitosan has a number of commercial and possible biomedical uses. It can be used in agriculture as a seed treatment and biopesticide, helping plants to fight off fungal infections. In winemaking it can be used as a fining agent, also helping to prevent spoilage. In industry, it can be used in a self-healing polyurethane paint coating. In medicine, it may be useful in bandages to reduce bleeding and as an antibacterial agent; it can also be used to help deliver drugs through the skin.
More controversially, chitosan has been asserted to have use in limiting fat absorption, which would make it useful for dieting, but there is evidence against this.
Other uses of chitosan that have been researched include use as a soluble dietary fiber.
- 1 Manufacture and properties
- 2 Usage
- 3 See also
- 4 References
- 5 External links
Chitosan is produced commercially by deacetylation of chitin, which is the structural element in the exoskeleton of crustaceans (such as crabs and shrimp) and cell walls of fungi. The degree of deacetylation (%DD) can be determined by NMR spectroscopy, and the %DD in commercial chitosans ranges from 60 to 100%. On average, the molecular weight of commercially produced chitosan is between 3800 and 20,000 Daltons. A common method for the synthesis of chitosan is the deacetylation of chitin using sodium hydroxide in excess as a reagent and water as a solvent. This reaction pathway, when allowed to go to completion (complete deacetylation) yields up to 98% product.2
The amino group in chitosan has a pKa value of ~6.5, which leads to a protonation in acidic to neutral solution with a charge density dependent on pH and the %DA-value. This makes chitosan water soluble and a bioadhesive which readily binds to negatively charged surfaces such as mucosal membranes. Chitosan enhances the transport of polar drugs across epithelial surfaces, and is biocompatible and biodegradable. It is not approved by FDA for drug delivery though. Purified quantities of chitosans are available for biomedical applications.
Chitosan and its derivatives, such as trimethylchitosan (where the amino group has been trimethylated), have been used in nonviral gene delivery. Trimethylchitosan, or quaternised chitosan, has been shown to transfect breast cancer cells, with increased degree of trimethylation increasing the cytotoxicity; at approximately 50% trimethylation, the derivative is the most efficient at gene delivery. Oligomeric derivatives (3-6 kDa) are relatively nontoxic and have good gene delivery properties.3
The agricultural and horticultural uses for chitosan, primarily for plant defense and yield increase, are based on how this glucosamine polymer influences the biochemistry and molecular biology of the plant cell. The cellular targets are the plasma membrane and nuclear chromatin. Subsequent changes occur in cell membranes, chromatin, DNA, calcium, MAP Kinase, oxidative burst, reactive oxygen species, callose pathogenesis-related (PR) genes and phytoalexins.4
In agriculture, chitosan is used primarily as a natural seed treatment and plant growth enhancer, and as an ecologically friendly biopesticide substance that boosts the innate ability of plants to defend themselves against fungal infections.5 The natural biocontrol active ingredients, chitin/chitosan, are found in the shells of crustaceans, such as lobsters, crabs, and shrimp, and many other organisms, including insects and fungi. It is one of the most abundant biodegradable materials in the world.
Degraded molecules of chitin/chitosan exist in soil and water. Chitosan applications for plants and crops are regulated by the EPA, and the USDA National Organic Program regulates its use on organic certified farms and crops.6 EPA-approved, biodegradable chitosan products are allowed for use outdoors and indoors on plants and crops grown commercially and by consumers.7
The natural biocontrol ability of chitosan should not be confused with the effects of fertilizers or pesticides upon plants or the environment. Chitosan active biopesticides represent a new tier of cost-effective biological control of crops for agriculture and horticulture.8 The biocontrol mode of action of chitosan elicits natural innate defense responses within plant to resist insects, pathogens, and soil-borne diseases when applied to foliage or the soil.9 Chitosan increases photosynthesis, promotes and enhances plant growth, stimulates nutrient uptake, increases germination and sprouting, and boosts plant vigor. When used as seed treatment or seed coating on cotton, corn, seed potatoes, soybeans, sugar beets, tomatoes, wheat and many other seeds, it elicits an innate immunity response in developing roots which destroys parasitic cyst nematodes without harming beneficial nematodes and organisms.1011
Agricultural applications of chitosan can reduce environmental stress due to drought and soil deficiencies, strengthen seed vitality, improve stand quality, increase yields, and reduce fruit decay of vegetables, fruits and citrus crops (see photo right).12 Horticultural application of chitosan increases blooms and extends the life of cut flowers and Christmas trees.13 The US Forest Service has conducted research on chitosan to control pathogens in pine trees1415 and increase resin pitch outflow which resists pine beetle infestation.16
Chitosan has a rich history of being researched for applications in agriculture and horticulture dating back to the 1980s.17 By 1989, chitosan salt solutions were applied to crops for improved freeze protection or to crop seed for seed priming.18 Shortly thereafter, chitosan salt received the first ever biopesticide label from the EPA, then followed by other intellectual property applications.
Chitosan has been used to protect plants in space, as well, exemplified by NASA's experiment to protect adzuki beans grown aboard the space shuttle and Mir space station in 1997 (see photo left).19 NASA results revealed chitosan induces increased growth (biomass) and pathogen resistance due to elevated levels of beta 1-3 glucanase enzymes within plant cells. NASA confirmed chitosan elicits the same effect in plants on earth.20
Nontoxic, low molecular weight chitosan polymer solutions appear to be safe enough for broad-spectrum agricultural and horticultural uses.2122 In 2008, the EPA approved natural broad-spectrum elicitor status for an ultralow molecular active ingredient of 0.25% chitosan.23
A natural chitosan elicitor solution for agriculture and horticultural uses was granted an amended label for foliar and irrigation applications by the EPA in 2009.12 Given its low potential for toxicity and abundance in the natural environment, chitosan does not harm people, pets, wildlife, or the environment when used according to label directions.242526 The US Forest Service tested chitosan as an ecofriendly biopesticide to prearm pine trees to defend themselves against mountain pine beetles.
Chitosan can also be used in water processing engineering as a part of a filtration process. Chitosan causes the fine sediment particles to bind together, and is subsequently removed with the sediment during sand filtration. It also removes phosphorus, heavy minerals, and oils from the water. Chitosan is an important additive in the filtration process. Sand filtration apparently can remove up to 50% of the turbidity alone, while the chitosan with sand filtration removes up to 99% turbidity.27 Chitosan has been used to precipitate caseins from bovine milk and cheese making.2829
Chitosan is also useful in other filtration situations, where one may need to remove suspended particles from a liquid. In combination with bentonite, gelatin, silica gel, isinglass, or other fining agents, it is used to clarify wine, mead, and beer. Added late in the brewing process, chitosan improves flocculation, and removes yeast cells, fruit particles, and other detritus that cause hazy wine. Chitosan combined with colloidal silica is becoming a popular fining agent for white wines, because chitosan does not require acidic tannins (found primarily in red wines) with which to flocculate.30
Chitosan has a long history for use as a fining agent in winemaking. Fungal source Chitosan has shown an increase in settling activity, reduction of oxidized polyphenolics in juice and wine as well as the chelation and removal of copper (post-racking). Fungal-source Chitosan can also be used in winemaking for the control of the spoilage yeast Brettanomyces. These products and uses are approved for European use by the EU and OIV standards.3132
Scientists have recently developed a polyurethane coating that heals its own scratches when exposed to sunlight, offering the promise of scratch-free cars and other products. The self-healing coating uses chitosan incorporated into traditional polymer materials, such as those used in coatings on cars, to protect paint. When a scratch damages the chemical structure, the chitosan responds to ultraviolet light by forming chemical chains that begin bonding with other materials in the substance, eventually smoothing the scratch. The process can take less than an hour.33
Marek W. Urban, a scientist working on this project, said the polymer can only repair itself in the same spot once, and would not work after repeated scratches.34 Whether this technology can be applied to industrial materials, however, depends on a number of factors (long-term persistence of "healability", stiffness and heat resistance of coating, knowledge of the exact mechanism of healing, etc.) not present initial studies; further investigation into these factors can potentially take decades to rectify.
Chitosan's properties allow it to rapidly clot blood, and has recently gained approval in the United States and Europe for use in bandages and other hemostatic agents. Chitosan hemostatic products have been shown in testing by the U.S. Marine Corps to quickly stop bleeding and to reduce blood loss, and result in 100% survival of otherwise lethal arterial wounds in swine.35 Chitosan hemostatic products reduce blood loss in comparison to gauze dressings and increase patient survival.36 Chitosan hemostatic products have been sold to the U.S. Army and are currently used by the UK military. Both the US and UK have already used the bandages on the battlefields of Iraq and Afghanistan.37 Chitosan is hypoallergenic and has natural antibacterial properties, which further support its use in field bandages.38
Chitosan hemostatic agents are often chitosan salts made from mixing chitosan with an organic acid (such as succinic or lactic acid).39 The hemostatic agent works by an interaction between the cell membrane of erythrocytes (negative charge) and the protonated chitosan (positive charge) leading to involvement of platelets and rapid thrombus formation.40 The chitosan salts can be mixed with other materials to make them more absorbent (such as mixing with alginate),41 or to vary the rate of solubility and bioabsorbability of the chitosan salt.39 The chitosan salts are biocompatible and biodegradable making them useful as absorbable haemostats. The protonated chitosan is broken down by lysozyme in the body to glucosamine 40 and the conjugate base of the acid (such as lactate or succinate) are substances naturally found in the body. The chitosan salt may be placed on an absorbable backing.42 The absorbable backing may be synthetic (for instance made from existing absorbable suture materials e.g. Tephaflex polymer) or natural (e.g. cellulose or gelled/solidified honey).
Chitosan's properties also allow it to be used in transdermal drug delivery; it is mucoadhesive in nature, reactive (so it can be produced in many different forms), and most importantly, has a positive charge under acidic conditions. This positive charge comes from protonation of its free amino groups. Lack of a positive charge means chitosan is insoluble in neutral and basic environments. However, in acidic environments, protonation of the amino groups leads to an increase in solubility. The implications of this are very important to biomedical applications. This molecule will maintain its structure in a neutral environment, but will solubilize and degrade in an acidic environment. This means chitosan can be used to transport a drug to an acidic environment, where the chitosan packaging will then degrade, releasing the drug to the desired environment. One example of this drug delivery has been the transport of insulin.43
Supposed to limit fat absorption in the body, chitosan may be sold in tablet form as a "fat binder". In one preliminary study, a 1% decrease in body mass index was seen with supplementation of chitosan over 8 weeks.44
However, in a Cochrane meta-analysis,45 which evaluated clinical trials performed with dietary chitosan over a minimum of four weeks, body weight, blood pressure and parameters related to cholesterol were changed only in some low-quality trials, indicating a minor effect on body weight. Other higher quality trials indicated no significant effect of chitosan and no clinical justification for advising overweight patients to take chitosan supplements.45
In an experimental model of the digestive tract, chitosan was shown to interact with oil, which inhibited duodenal absorption and enhanced lipid excretion.46 However, the mechanism of interaction between chitosan and fat is not well understood and has not been proved clinically.47 In mice, dietary ingestion of chitosan did not depress the level of iron, zinc or copper.48
Chitosan is under research for several potential clinical applications:50
- As a soluble dietary fiber, it increases gastrointestinal lumen viscosity and slows down the emptying of the stomach.
- It alters bile acid composition, increasing the excretion of sterols and reducing the digestibility of ileal fats.515253 It is unclear how chitosan does this, but the currently favored hypotheses involve the increase of intestinal viscosity or bile acid-binding capacity.54
- Chitosan is relatively insoluble in water, but can be dissolved by dilute acids, which would make it a highly-viscous dietary fiber.54 Such fibers might inhibit the uptake of dietary lipids by increasing the thickness of the boundary layer of the intestinal lumen, which has been observed in animal experiments.55
- Having very few acetyl groups, chitosan contains cationic groups. This may cause chitosan to have bile acid-binding capacity, which causes mixed micelles to be entrapped or disintegrated in the duodenum and ileum.54 This would interrupt bile acid circulation, causing reduced lipid absorption and increased sterol excretion, which has also been observed in animal experiments.535455
- Shahidi, Fereidoon; Synowiecki, Jozef (1991). "Isolation and characterization of nutrients and value-added products from snow crab (Chionoecetes opilio) and shrimp (Pandalus borealis) processing discards". Journal of Agricultural and Food Chemistry 39 (8): 1527–32. doi:10.1021/jf00008a032.
- , "Process for the manufacture of chitosan"
- Kean, Thomas; Roth, Susanne; Thanou, Maya (2005). "Trimethylated chitosans as non-viral gene delivery vectors: Cytotoxicity and transfection efficiency". Journal of Controlled Release 103 (3): 643–53. doi:10.1016/j.jconrel.2005.01.001. PMID 15820411.
- Hadwiger, Lee A. (2013). "Multiple effects of chitosan on plant systems: Solid science or hype". Plant Science 208: 42–9. doi:10.1016/j.plantsci.2013.03.007. PMID 23683928.
- Linden, James C.; Stoner, Richard J.; Knutson, Kenneth W.; Gardner-Hughes, Cecilie A. (2000). "Organic disease control elicitors". Agro Food Industry Hi-Tech 11 (5): 32–4.
- "USDA NOP and EPA Rule on Chitosan, Federal Register/Vol. 72, No. 236/Monday, December 10, 2007/Rules and Regulation".
- "Chitin and Chitosan Final Registration Review Decision, Document ID: EPA-HQ-OPP-2007-0566-0019, Dec 11, 2008, pp 10–15, Regulations.gov".
- Goosen, Mattheus F. A (1996). Applications of Chitin and Chitosan. CRC. pp. 132–9. ISBN 978-1-56676-449-0.
- Linden, J.C.; Stoner, R.J. (2005). "Proprietary Elicitor Affects Seed Germination and Delays Fruit Senescence". Journal of Food, Agriculture & Environment.
- "Smiley R., Cook R.J., Pauliz T., Seed Treatment for Sample Cereal Grains Oregon State University, 2002, EM 8797".dead link
- "Stoner R., Linden J., Micronutrient elicitor for treating nematodes in field crops, 2006, Patent Pending, Pub. no.: US 2008/0072494 A1".
- Linden, J. C.; Stoner, R. J. (2007). "Pre-harvest application of proprietary elicitor delays fruit senescence". Advances in Plant Ethylene Research. pp. 301–2. doi:10.1007/978-1-4020-6014-4_65. ISBN 978-1-4020-6013-7.
- "YouTube video / Chitosan Extends the Life of Plants and Trees".
- Mason, Mary E.; Davis, John M. (1997). "Defense Response in Slash Pine: Chitosan Treatment Alters the Abundance of Specific mRNAs". Molecular Plant-Microbe Interactions 10 (1): 135–7. doi:10.1094/MPMI.19126.96.36.199. PMID 9002276.
- Klepzig, Kier D.; Walkinshaw, Charles H. (2003). "Cellular response of loblolly pine to wound inoculation with bark beetle-associated fungi and chitosan".
- O'Toole, Erin (2009-09-10). "Solution for Pine Bark Beetles May Help Front Range Trees". NPR Morning Edition - KUNC 91.5 FM Greeley, CO.
- Croteau, R.; Gurkewitz, S.; Johnson, M. A.; Fisk, H. J. (1987). "Biochemistry of Oleoresinosis : Monoterpene and Diterpene Biosynthesis in Lodgepole Pine Saplings Infected with Ceratocystis clavigera or Treated with Carbohydrate Elicitors". Plant Physiology 85 (4): 1123–8. doi:10.1104/pp.85.4.1123. PMC 1054405. PMID 16665815.
- "Treatment of Plants with Chitosan Salts, 1989, Patent WO/1989/007395".
- "Stoner, R., Progressive Plant Growing Has Business Blooming, Environmental and Agricultural Resources NASA Spinoff 2006, pp. 68–71"..
- Linden, James C.; Stoner, Richard J. (October 21, 2008). "YEA! Elicitor Response Comparison to Chitin / Chitosan in Mung Bean and Adzuki Bean Germination Experiments".
- "BIOPOLYMERS Making Materials Nature's Way".
- "SeedQuest Press Release: AgriHouse Acquires DCV Chitosan IP and Patents".
- "Chitin/Chitosan, Farnesol/Nerolidol and Nosema locustae Final Registration Review Decision; Federal Register Notice of Availability December 24, 2008 (Volume 73, Number 248) EPA".
- "Chitosan Exemption from the Requirement of a Tolerance".
- "Control Strategies to reduce postharvest decay of fresh fruits and vegetables".
- "Chitosan; Poly-D-glucosamine (128930) Fact Sheet". US Environmental Protection Agency. May 2nd 2006. Retrieved 2006-07-10.
- Alan Woodmansey (Highway Engineer) (March 19 2002). "Chitosan Treatment of Sediment Laden Water - Washington State I-90 Issaquah Project". Federal Highway Administration. U.S. Department of Transportation. Retrieved 2006-07-10.
- Ausar, Salvador F; Passalacqua, Nancy; Castagna, Leonardo F; Bianco, Ismael D; Beltramo, Dante M (2002). "Growth of milk fermentative bacteria in the presence of chitosan for potential use in cheese making". International Dairy Journal 12 (11): 899–906. doi:10.1016/S0958-6946(02)00114-0.
- http://jds.fass.org/cgi/content/abstract/84/2/361full citation neededdead link
- Rayner, Terry. "Fining and Clarifying Agents". Archived from the original on June 16, 2006. Retrieved 2006-07-18.
- Escudero-Abarca, Blanca I.; Escudero-Abarca, M. Guadalupe; Aguilar-Uscanga, Patricia M.; Hayward-Jones, Patricia; Mendoza, Mario; Ramírez, Leticia (2004). "Selective antimicrobial action of chitosan against spoilage yeasts in mixed culture fermentations". Journal of Industrial Microbiology and Biotechnology 31 (1): 16–22. doi:10.1007/s10295-004-0112-2. PMID 14747932.
- http://wineindustryinsight.com/?p=41707full citation needed
- Ghosh, B.; Urban, M. W. (2009). "Self-Repairing Oxetane-Substituted Chitosan Polyurethane Networks". Science 323 (5920): 1458–60. doi:10.1126/science.1167391. PMID 19286550.
- Coating makes scratches on cars disappear
- Brown, Mark A.; Daya, Mohamud R.; Worley, Joseph A. (2009). "Experience with Chitosan Dressings in a Civilian EMS System". The Journal of Emergency Medicine 37 (1): 1–7. doi:10.1016/j.jemermed.2007.05.043. PMID 18024069.
- Pusateri, Anthony E.; McCarthy, Simon J.; Gregory, Kenton W.; Harris, Richard A.; Cardenas, Luis; McManus, Albert T.; Goodwin, Cleon W. (2003). "Effect of a Chitosan-Based Hemostatic Dressing on Blood Loss and Survival in a Model of Severe Venous Hemorrhage and Hepatic Injury in Swine". The Journal of Trauma: Injury, Infection, and Critical Care 54 (1): 177–82. doi:10.1097/00005373-200301000-00023. PMID 12544915.
- Karen Lurie. "War Bandages".dead link
- Kevin McCue (March 3 2003). "New Bandage Uses Biopolymer" (- Scholar search). Chemistry.org (American Chemical Society). Archived from the original on November 28, 2005. Retrieved 2006-07-10.dead link
- US patent 8106030, Craig Hardy, Lee Johnson & Paul Luksch, "Hemostatic Material", issued 2012-01-31
- Baldrick, Paul (2010). "The safety of chitosan as a pharmaceutical excipient". Regulatory Toxicology and Pharmacology 56 (3): 290–9. doi:10.1016/j.yrtph.2009.09.015. PMID 19788905.
- US patent 5836970, Abhay S. Pandit, "Hemostatic Wound Dressing", issued 1998-11-17
- US application 2011052665, Craig Hardy, Andrew Darby & Guy Eason, "Hemostatic Material"
- Agnihotri, Sunil A.; Mallikarjuna, Nadagouda N.; Aminabhavi, Tejraj M. (2004). "Recent advances on chitosan-based micro- and nanoparticles in drug delivery". Journal of Controlled Release 100 (1): 5–28. doi:10.1016/j.jconrel.2004.08.010. PMID 15491807.
- Schiller RN, Barrager E, Schauss AG, Nichols EJ. (2001). "A Randomized, Double-Blind, Placebo-Controlled Study Examining the Effects of a Rapidly Soluble Chitosan Dietary Supplement on Weight Loss and Body Composition in Overweight and Mildly Obese Individuals". J Am Nutraceutical Assoc 4 (1): 42–9.dead link
- Jull, Andrew B; Ni Mhurchu, Cliona; Bennett, Derrick A; Dunshea-Mooij, Christel AE; Rodgers, Anthony (2008). "Chitosan for overweight or obesity". In Jull, Andrew B. Cochrane Database of Systematic Reviews (3): CD003892. doi:10.1002/14651858.CD003892.pub3. PMID 18646097.
- Rodríguez, María Susana; Albertengo, Liliana Elena (2005). "Interaction between Chitosan and Oil under Stomach and Duodenal Digestive Chemical Conditions". Bioscience, Biotechnology, and Biochemistry 69 (11): 2057–62. doi:10.1271/bbb.69.2057. PMID 16306685.
- Gades, Matthew D.; Stern, Judith S. (2003). "Chitosan Supplementation and Fecal Fat Excretion in Men". Obesity 11 (5): 683–8. doi:10.1038/oby.2003.97. PMID 12740459.
- Zeng, Lintao; Qin, Caiqin; He, Guanghui; Wang, Wei; Li, Wei; Xu, Dongsheng (2008). "Effect of dietary chitosans on trace iron, copper and zinc in mice". Carbohydrate Polymers 74 (2): 279–82. doi:10.1016/j.carbpol.2008.02.022.
- "FDA Warning Letter for Chitosan Weight Loss Products".
- Knorr, D. (January 1991). "Recovery and utilization of chitin and chitosan in food processing waste management". Food Technology 45 (1): 114–22.
- Fukada, Yasuhiko; Kimura, Koji; Ayaki, Yoshikazu (1991). "Effect of chitosan feeding on intestinal bile acid metabolism in rats". Lipids 26 (5): 395–9. doi:10.1007/BF02537206. PMID 1895888.
- Maezaki, Yuji; Tsuji, Keisuke; Nakagawa, Yasue; Kawai, Yoshiyuki; Akimoto, Makoto; Tsugita, Takashi; Takekawa, Wataru; Terada, Atsushi; Hara, Hiroyoshi; Mitsuoka, Tomotari (1993). "Hypocholesterolemic Effect of Chitosan in Adult Males". Bioscience, Biotechnology, and Biochemistry 57 (9): 1439–44. doi:10.1271/bbb.57.1439.
- Razdan, A.; Pettersson, D. (2007). "Effect of chitin and chitosan on nutrient digestibility and plasma lipid concentrations in broiler chickens". British Journal of Nutrition 72 (2): 277–88. doi:10.1079/BJN19940029. PMID 7947645.
- Furda, Ivan (1990). "Interaction of Dietary Fiber with Lipids — Mechanistic Theories and their Limitations". New Developments in Dietary Fiber. Advances in Experimental Medicine and Biology 270. pp. 67–82. doi:10.1007/978-1-4684-5784-1_7. ISBN 978-1-4684-5786-5. PMID 1964019.
- Ikeda, Ikuo.; Sugano, Michihiro.; Yoshida, Katsuko.; Sasaki, Eiji.; Iwamoto, Yasushi.; Hatano, Kouta. (1993). "Effects of chitosan hydrolyzates on lipid absorption and on serum and liver lipid concentration in rats". Journal of Agricultural and Food Chemistry 41 (3): 431–5. doi:10.1021/jf00027a016.
- Battlefield Band-Aidsdead link — "But now, scientists have created a bandage that is actually able to clot a bullet wound in less than a minute. The bandages are laced with a mixture of ground shrimp shells and vinegar, a concoction that has been found to clot blood. The key ingredient in the shrimp shells is called chitosan."
- Is Chitosan a "Fat Magnet"? — Quackwatch: A critical look on the claims how chitosan can be used for weight management