Mannitol

Last updated

Mannitol
D-Mannitol structure.svg
Mannitol-3D-balls.png
Clinical data
Trade names Osmitrol, Bronchitol, others
Other namesd-Mannitol, mannite, manna sugar
AHFS/Drugs.com Monograph
License data
Pregnancy
category
  • AU:B2
Routes of
administration 		Intravenous, By mouth, inhalation
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability ~7%
Metabolism Liver, negligible
Elimination half-life 100 minutes
Excretion Kidney: 90%
Identifiers
  • D-Mannitol
    (2R,3R,4R,5R)-Hexane-1,2,3,4,5,6-hexol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
E number E421 (thickeners, ...) OOjs UI icon edit-ltr-progressive.svg
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.647 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C6H14O6
Molar mass 182.172 g·mol−1
3D model (JSmol)
  • O[C@H]([C@H](O)CO)[C@H](O)[C@H](O)CO
  • InChI=1S/C6H14O6/c7-1-3(9)5(11)6(12)4(10)2-8/h3-12H,1-2H2/t3-,4-,5-,6-/m1/s1 Yes check.svgY
  • Key:FBPFZTCFMRRESA-KVTDHHQDSA-N Yes check.svgY
   (verify)

Mannitol is a type of sugar alcohol used as a sweetener and medication. [5] [6] It is used as a low calorie sweetener as it is poorly absorbed by the intestines. [5] As a medication, it is used to decrease pressure in the eyes, as in glaucoma, and to lower increased intracranial pressure. [7] [8] [6] Medically, it is given by injection or inhalation. [9] [10] Effects typically begin within 15 minutes and last up to 8 hours. [9]

Contents

Common side effects from medical use include electrolyte problems and dehydration. [9] Other serious side effects may include worsening heart failure and kidney problems. [9] [6] It is unclear if use is safe in pregnancy. [9] Mannitol is in the osmotic diuretic family of medications and works by pulling fluid from the brain and eyes. [9]

The discovery of mannitol is attributed to Joseph Louis Proust in 1806. [11] It is on the World Health Organization's List of Essential Medicines. [12] It was originally made from the flowering ash and called manna due to its supposed resemblance to the Biblical food. [13] [14] Mannitol is on the World Anti-Doping Agency's banned substances list due to concerns that it may mask prohibited drugs. [15]

Uses

Mannitol 15% solution for intravenous use Mannitol 15%25 yellow background 2.jpg
Mannitol 15% solution for intravenous use

Medical uses

In the United States, mannitol is indicated for the reduction of intracranial pressure and treatment of cerebral edema and elevated intraocular pressure. [3]

In the European Union, mannitol is indicated for the treatment of cystic fibrosis (CF) in adults aged 18 years and above as an add-on therapy to best standard of care. [4]

Mannitol is used intravenously to reduce acutely raised intracranial pressure until more definitive treatment can be applied, [16] e.g., after head trauma. While mannitol injection is the mainstay for treating high pressure in the skull after a bad brain injury, it is no better than hypertonic saline as a first-line treatment. In treatment-resistant cases, hypertonic saline works better. [17] Intra-arterial infusions of mannitol can transiently open the blood–brain barrier by disrupting tight junctions. [18] [19]

It may also be used for certain cases of kidney failure with low urine output, decreasing pressure in the eye, to increase the elimination of certain toxins, and to treat fluid build up. [9]

Intraoperative mannitol prior to vessel clamp release during renal transplant has been shown to reduce post-transplant kidney injury, but has not been shown to reduce graft rejection.[ medical citation needed ]

Mannitol acts as an osmotic laxative [3] [20] in oral doses larger than 20 g, [21] and is sometimes sold as a laxative for children.[ citation needed ]

The use of mannitol, when inhaled, as a bronchial irritant as an alternative method of diagnosis of exercise-induced asthma has been proposed. A 2013 systematic review concluded evidence to support its use for this purpose at this time is insufficient. [22]

Mannitol is commonly used in the circuit prime of a heart lung machine during cardiopulmonary bypass. The presence of mannitol preserves renal function during the times of low blood flow and pressure, while the patient is on bypass. The solution prevents the swelling of endothelial cells in the kidney, which may have otherwise reduced blood flow to this area and resulted in cell damage.

Mannitol can also be used to temporarily encapsulate a sharp object (such as a helix on a lead for an artificial pacemaker) while it passes through the venous system. Because the mannitol dissolves readily in blood, the sharp point becomes exposed at its destination.

Mannitol is also the first drug of choice to treat acute glaucoma in veterinary medicine. It is administered as a 20% solution intravenously. It dehydrates the vitreous humor and, therefore, lowers the intraocular pressure. However, it requires an intact blood-ocular barrier to work. [23]

Food

Mannitol increases blood glucose to a lesser extent than sucrose (thus having a relatively low glycemic index [24] ) so is used as a sweetener for people with diabetes, and in chewing gums. Although mannitol has a higher heat of solution than most sugar alcohols, its comparatively low solubility reduces the cooling effect usually found in mint candies and gums. However, when mannitol is completely dissolved in a product, it induces a strong cooling effect. [25] Also, it has a very low hygroscopicity – it does not pick up water from the air until the humidity level is 98%. This makes mannitol very useful as a coating for hard candies, dried fruits, and chewing gums, and it is often included as an ingredient in candies and chewing gum. [26] The pleasant taste and mouthfeel of mannitol also makes it a popular excipient for chewable tablets. [27]

Analytical chemistry

Mannitol can be used to form a complex with boric acid. This increases the acid strength of the boric acid, permitting better precision in volumetric analysis of this acid. [28]

Other

Mannitol is the primary ingredient of mannitol salt agar, a bacterial growth medium, and is used in others.

Mannitol is used as a cutting agent [29] [30] in various drugs that are used intranasally (snorted), such as heroin and cocaine. A mixture of mannitol and fentanyl (or fentanyl analogs) in ratio 1:10 is labeled and sold as "China white", a popular heroin substitute.[ citation needed ]

Mannitol is a sugar alcohol with "50-70 percent of the relative sweetness of sugar, which means more must be used to equal the sweetness of sugar. Mannitol lingers in the intestines for a long time and therefore often causes bloating and diarrhea." [31]

Contraindications

Mannitol is contraindicated in people with anuria, severe hypovolemia, pre-existing severe pulmonary vascular congestion or pulmonary edema, irritable bowel syndrome (IBS), and active intracranial bleeding except during craniotomy. [3]

Adverse effects include hyponatremia and volume depletion leading to metabolic acidosis. [11]

Chemistry

Mannitol is an isomer of sorbitol, another sugar alcohol; the two differ only in the orientation of the hydroxyl group on carbon 2. [25] While similar, the two sugar alcohols have very different sources in nature, melting points, and uses.

Production

Mannitol is classified as a sugar alcohol; that is, it can be derived from a sugar (mannose) by reduction. Other sugar alcohols include xylitol and sorbitol.

Industrial synthesis

Mannitol is commonly produced via the hydrogenation of fructose, which is formed from either starch or sucrose (common table sugar). Although starch is a cheaper source than sucrose, the transformation of starch is much more complicated. Eventually, it yields a syrup containing about 42% fructose, 52% glucose, and 6% maltose. Sucrose is simply hydrolyzed into an invert sugar syrup, which contains about 50% fructose. In both cases, the syrups are chromatographically purified to contain 90–95% fructose. The fructose is then hydrogenated over a nickel catalyst into a mixture of isomers sorbitol and mannitol. Yield is typically 50%:50%, although slightly alkaline reaction conditions can slightly increase mannitol yields. [25]

Biosyntheses

Mannitol is one of the most abundant energy and carbon storage molecules in nature, produced by a plethora of organisms, including bacteria, yeasts, fungi, algae, lichens, and many plants. [32] Fermentation by microorganisms is an alternative to the traditional industrial synthesis. A fructose to mannitol metabolic pathway, known as the mannitol cycle in fungi, has been discovered in a type of red algae (Caloglossa leprieurii), and it is highly possible that other microorganisms employ similar such pathways. [33] A class of lactic acid bacteria, labeled heterofermentive because of their multiple fermentation pathways, convert either three fructose molecules or two fructose and one glucose molecule into two mannitol molecules, and one molecule each of lactic acid, acetic acid, and carbon dioxide. Feedstock syrups containing medium to large concentrations of fructose (for example, cashew apple juice, containing 55% fructose: 45% glucose) can produce yields 200 g (7.1 oz) mannitol per liter of feedstock. Further research is being conducted, studying ways to engineer even more efficient mannitol pathways in lactic acid bacteria, as well as the use of other microorganisms such as yeast [32] and E. coli in mannitol production. When food-grade strains of any of the aforementioned microorganisms are used, the mannitol and the organism itself are directly applicable to food products, avoiding the need for careful separation of microorganism and mannitol crystals. Although this is a promising method, steps are needed to scale it up to industrially needed quantities. [33]

Natural extraction

Since mannitol is found in a wide variety of natural products, including almost all plants, it can be directly extracted from natural products, rather than chemical or biological syntheses. In fact, in China, isolation from seaweed is the most common form of mannitol production. [26] Mannitol concentrations of plant exudates can range from 20% in seaweeds to 90% in the plane tree. It is a constituent of saw palmetto ( Serenoa ). [34]

Traditionally, mannitol is extracted by the Soxhlet extraction, using ethanol, water, and methanol to steam and then hydrolysis of the crude material. The mannitol is then recrystallized from the extract, generally resulting in yields of about 18% of the original natural product. Another method of extraction is using supercritical and subcritical fluids. These fluids are at such a stage that no difference exists between the liquid and gas stages, so are more diffusive than normal fluids. This is considered to make them much more effective mass transfer agents than normal liquids. The super- or subcritical fluid is pumped through the natural product, and the mostly mannitol product is easily separated from the solvent and minute amount of byproduct.

Supercritical carbon dioxide extraction of olive leaves has been shown to require less solvent per measure of leaf than a traditional extraction – 141.7 g (5.00 oz) CO2 versus 194.4 g (6.86 oz) ethanol per 1 g (0.035 oz) olive leaf. Heated, pressurized, subcritical water is even cheaper, and is shown to have dramatically greater results than traditional extraction. It requires only 4.01 g (0.141 oz) water per 1 g (0.035 oz) of olive leaf, and gives a yield of 76.75% mannitol. Both super- and subcritical extractions are cheaper, faster, purer, and more environmentally friendly than the traditional extraction. However, the required high operating temperatures and pressures are causes for hesitancy in the industrial use of this technique. [33]

History

In the early 1880s, Julije Domac elucidated the structure of hexene and mannitol obtained from Caspian manna. He determined the place of the double bond in hexene obtained from mannitol and proved that it is a derivative of a normal hexene. This also solved the structure of mannitol, which was unknown until then. [35] [36] [37] [38]

Controversy

The three studies [39] [40] [41] that originally found high-dose mannitol effective in treating severe head injury were the subject of an investigation. Published in 2007 after the lead author Dr Julio Cruz's death, the investigation questioned whether the studies had actually taken place. [42] The co-authors of the paper were not able to confirm the existence of the study patients, and the Federal University of São Paulo, which Cruz gave as his affiliation, had never employed him. As a result of doubt surrounding Cruz's work, an updated version of the Cochrane review excludes all studies by Julio Cruz, leaving only four studies. [7] Due to differences in selection of control groups, a conclusion about the clinical use of mannitol has not been reached.

Compendial status

See also

Related Research Articles

<span class="mw-page-title-main">Glucose</span> Naturally produced monosaccharide

Glucose is a sugar with the molecular formula C6H12O6. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using energy from sunlight. It is used by plants to make cellulose—the most abundant carbohydrate in the world—for use in cell walls, and by all living organisms to make adenosine triphosphate (ATP), which is used by the cell as energy.

<span class="mw-page-title-main">Fructose</span> Simple ketonic monosaccharide found in many plants

Fructose, or fruit sugar, is a ketonic simple sugar found in many plants, where it is often bonded to glucose to form the disaccharide sucrose. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed by the gut directly into the blood of the portal vein during digestion. The liver then converts most fructose and galactose into glucose for distribution in the bloodstream or deposition into glycogen.

<span class="mw-page-title-main">Sorbitol</span> Chemical compound

Sorbitol, less commonly known as glucitol, is a sugar alcohol with a sweet taste which the human body metabolizes slowly. It can be obtained by reduction of glucose, which changes the converted aldehyde group (−CHO) to a primary alcohol group (−CH2OH). Most sorbitol is made from potato starch, but it is also found in nature, for example in apples, pears, peaches, and prunes. It is converted to fructose by sorbitol-6-phosphate 2-dehydrogenase. Sorbitol is an isomer of mannitol, another sugar alcohol; the two differ only in the orientation of the hydroxyl group on carbon 2. While similar, the two sugar alcohols have very different sources in nature, melting points, and uses.

<span class="mw-page-title-main">Sugar substitute</span> Sugarless food additive intended to provide a sweet taste

A sugar substitute is a food additive that provides a sweetness like that of sugar while containing significantly less food energy than sugar-based sweeteners, making it a zero-calorie or low-calorie sweetener. Artificial sweeteners may be derived through manufacturing of plant extracts or processed by chemical synthesis. Sugar substitute products are commercially available in various forms, such as small pills, powders, and packets.

<span class="mw-page-title-main">Xylitol</span> Synthetic sweetener

Xylitol is a chemical compound with the formula C
5H
12O
5, or HO(CH2)(CHOH)3(CH2)OH; specifically, one particular stereoisomer with that structural formula. It is a colorless or white crystalline solid. It is classified as a polyalcohol and a sugar alcohol, specifically an alditol. Of the common sugar alcohols, only sorbitol is more soluble in water.

<span class="mw-page-title-main">Cerebral edema</span> Excess accumulation of fluid (edema) in the intracellular or extracellular spaces of the brain

Cerebral edema is excess accumulation of fluid (edema) in the intracellular or extracellular spaces of the brain. This typically causes impaired nerve function, increased pressure within the skull, and can eventually lead to direct compression of brain tissue and blood vessels. Symptoms vary based on the location and extent of edema and generally include headaches, nausea, vomiting, seizures, drowsiness, visual disturbances, dizziness, and in severe cases, death.

<span class="mw-page-title-main">Intracranial pressure</span> Pressure exerted by fluids inside the skull and on the brain

Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 mmHg for a supine adult. This equals to 9–20 cmH2O, which is a common scale used in lumbar punctures. The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF.

<span class="mw-page-title-main">Sugar alcohol</span> Organic compounds

Sugar alcohols are organic compounds, typically derived from sugars, containing one hydroxyl group (−OH) attached to each carbon atom. They are white, water-soluble solids that can occur naturally or be produced industrially by hydrogenating sugars. Since they contain multiple (−OH) groups, they are classified as polyols.

<span class="mw-page-title-main">Fructose malabsorption</span> Medical condition

Fructose malabsorption, formerly named dietary fructose intolerance (DFI), is a digestive disorder in which absorption of fructose is impaired by deficient fructose carriers in the small intestine's enterocytes. This results in an increased concentration of fructose. Intolerance to fructose was first identified and reported in 1956.

An osmotic diuretic is a type of diuretic that inhibits reabsorption of water and sodium (Na). They are pharmacologically inert substances that are given intravenously. They increase the osmolarity of blood and renal filtrate. This fluid eventually becomes urine.

<span class="mw-page-title-main">Isomalt</span> Chemical compound

Isomalt is a sugar substitute, a mixture of the two disaccharide alcohols 1,6-GPS and 1,1-GPM. It is used primarily for its sugar-like physical properties. It has little to no impact on blood sugar levels, and does not stimulate the release of insulin. It also does not promote tooth decay and is considered to be tooth-friendly. Its energy value is 2 kcal per gram, half that of sugars. It is less sweet than sugar, but can be blended with high-intensity sweeteners such as sucralose to create a mixture with the same sweetness as sucrose (‘sugar’).

<span class="mw-page-title-main">Psicose</span> Chemical compound

D-Psicose (C6H12O6), also known as D-allulose or simply allulose, is an epimer of fructose that is used by some commercial food and beverage manufacturers as a low-calorie sweetener. Allulose occurs naturally in small quantities in a variety of foods. It was first identified in the 1940s, although the enzymes needed to produce it on an industrial scale were not discovered until the 1990s.

<span class="mw-page-title-main">Isomaltulose</span> Chemical compound

Isomaltulose is a disaccharide carbohydrate composed of glucose and fructose. It is naturally present in honey and sugarcane extracts and is also produced industrially from table sugar (sucrose) and used as a sugar alternative.

<span class="mw-page-title-main">Osmotherapy</span> Medical treatment for cerebral edema

Osmotherapy is the use of osmotically active substances to reduce the volume of intracranial contents. Osmotherapy serves as the primary medical treatment for cerebral edema. The primary purpose of osmotherapy is to improve elasticity and decrease intracranial volume by removing free water, accumulated as a result of cerebral edema, from brain's extracellular and intracellular space into vascular compartment by creating an osmotic gradient between the blood and brain. Normal serum osmolality ranges from 280 to 290 mOsm/kg and serum osmolality to cause water removal from brain without much side effects ranges from 300 to 320 mOsm/kg. Usually, 90 mL of space is created in the intracranial vault by 1.6% reduction in brain water content. Osmotherapy has cerebral dehydrating effects. The main goal of osmotherapy is to decrease intracranial pressure (ICP) by shifting excess fluid from brain. This is accomplished by intravenous administration of osmotic agents which increase serum osmolality in order to shift excess fluid from intracellular or extracellular space of the brain to intravascular compartment. The resulting brain shrinkage effectively reduces intracranial volume and decreases ICP.

<span class="mw-page-title-main">Aldose reductase</span> Enzyme

In enzymology, aldose reductase is an enzyme in humans encoded by the gene AKR1B1. It is an cytosolic NADPH-dependent oxidoreductase that catalyzes the reduction of a variety of aldehydes and carbonyls, including monosaccharides, and primarily known for catalyzing the reduction of glucose to sorbitol, the first step in polyol pathway of glucose metabolism.

<span class="mw-page-title-main">Sorbitol dehydrogenase</span> Enzyme

Sorbitol dehydrogenase is a cytosolic enzyme. In humans this protein is encoded by the SORD gene.

<span class="mw-page-title-main">Fructokinase</span> Class of enzymes

Fructokinase, also known as D-fructokinase or D-fructose (D-mannose) kinase, is an enzyme of the liver, intestine, and kidney cortex. Fructokinase is in a family of enzymes called transferases, meaning that this enzyme transfers functional groups; it is also considered a phosphotransferase since it specifically transfers a phosphate group. Fructokinase specifically catalyzes the transfer of a phosphate group from adenosine triphosphate to fructose as the initial step in its utilization. The main role of fructokinase is in carbohydrate metabolism, more specifically, sucrose and fructose metabolism. The reaction equation is as follows:

In enzymology, a sorbitol-6-phosphate dehydrogenase (EC 1.1.1.140) is an enzyme that catalyzes the chemical reaction

Single cell oil, also known as Microbial oil consists of the intracellular storage lipids, triacyglycerols. It is similar to vegetable oil, another biologically produced oil. They are produced by oleaginous microorganisms, which is the term for those bacteria, molds, algae and yeast, which can accumulate 20% to 80% lipids of their biomass. The accumulation of lipids take place by the end of logarithmic phase and continues during station phase until carbon source begins to reduce with nutrition limitation.

Pseudohypoxia refers to a condition that mimics hypoxia, by having sufficient oxygen yet impaired mitochondrial respiration due to a deficiency of necessary co-enzymes, such as NAD+ and TPP. The increased cytosolic ratio of free NADH/NAD+ in cells (more NADH than NAD+) can be caused by diabetic hyperglycemia and by excessive alcohol consumption. Low levels of TPP results from thiamine deficiency.

References

  1. ↑ "Regulatory Decision Summary - Aridol". Health Canada. 23 October 2014. Retrieved 7 June 2022.
  2. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 October 2023.
  3. 1 2 3 4 "Osmitrol- mannitol injection, solution". DailyMed. 15 November 2018. Retrieved 28 October 2020.
  4. 1 2 "Bronchitol EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 28 October 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  5. 1 2 Varzakas T, Labropoulos A, Anestis S (2012). Sweeteners: Nutritional Aspects, Applications, and Production Technology. CRC Press. pp. 59–60. ISBN   9781439876732. Archived from the original on 10 September 2017.
  6. 1 2 3 World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. p. 332. hdl: 10665/44053 . ISBN   9789241547659.
  7. 1 2 Wakai A, McCabe A, Roberts I, Schierhout G (August 2013). "Mannitol for acute traumatic brain injury". The Cochrane Database of Systematic Reviews. 2013 (8): CD001049. doi:10.1002/14651858.CD001049.pub5. PMC   7050611 . PMID   23918314.
  8. ↑ World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. p. 332. hdl: 10665/44053 . ISBN   9789241547659.
  9. 1 2 3 4 5 6 7 "Mannitol". The American Society of Health-System Pharmacists. Archived from the original on 26 May 2015. Retrieved 8 January 2015.
  10. ↑ "BRONCHITOL® (mannitol) inhalation powder Patient Site". bronchitol.com.
  11. 1 2 Kremers E, Sonnedecker G (1986). Kremers and Urdang's History of Pharmacy. Amer. Inst. History of Pharmacy. p. 360. ISBN   9780931292170. Archived from the original on 10 September 2017.
  12. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  13. ↑ Cottrell JE, Patel P (2016). Cottrell and Patel's Neuroanesthesia. Elsevier Health Sciences. p. 160. ISBN   9780323461122.
  14. ↑ Bardal S, Waechter J, Martin D (2010). Applied Pharmacology. Elsevier Health Sciences. p. 411. ISBN   978-1437735789.
  15. ↑ "THE 2017 PROHIBITED LIST INTERNATIONAL STANDARD" (PDF). January 2017. p. 5. Retrieved 7 July 2018.
  16. ↑ "Mannitol (Intravenous Route)". Mayo Clinic.
  17. ↑ Gu J, Huang H, Huang Y, Sun H, Xu H (June 2019). "Hypertonic saline or mannitol for treating elevated intracranial pressure in traumatic brain injury: a meta-analysis of randomized controlled trials". Neurosurgical Review. 42 (2): 499–509. doi:10.1007/s10143-018-0991-8. PMID   29905883.
  18. ↑ Rapoport SI (April 2000). "Osmotic opening of the blood-brain barrier: principles, mechanism, and therapeutic applications". Cellular and Molecular Neurobiology. 20 (2): 217–230. doi:10.1023/a:1007049806660. PMID   10696511. S2CID   20258642.
  19. ↑ Linville RM, DeStefano JG, Sklar MB, Chu C, Walczak P, Searson PC (July 2020). "Modeling hyperosmotic blood-brain barrier opening within human tissue-engineered in vitro brain microvessels". Journal of Cerebral Blood Flow and Metabolism. 40 (7): 1517–1532. doi:10.1177/0271678X19867980. PMC   7308510 . PMID   31394959. S2CID   199507024.
  20. ↑ "Select Committee on GRAS Substances (SCOGS) Opinion: Mannitol". FDA.gov. April 2013. Archived from the original on 22 October 2014.
  21. ↑ Ellis FW, Krantz JC (1941). "Sugar alcohols: XXII. Metabolism and toxicity studies with mannitol and sorbitol in man and animals". J. Biol. Chem. 141: 147–154. doi: 10.1016/S0021-9258(18)72829-9 . Archived from the original on 10 September 2017.
  22. ↑ Stickland MK, Rowe BH, Spooner CH, Vandermeer B, Dryden DM (September 2011). "Accuracy of eucapnic hyperpnea or mannitol to diagnose exercise-induced bronchoconstriction: a systematic review". Annals of Allergy, Asthma & Immunology. 107 (3): 229–34.e8. doi:10.1016/j.anai.2011.06.013. PMID   21875541.
  23. ↑ Veterinary Class Notes, Ophthalmology, The Ohio State University, provided by David Wilkie, DVM, DACVO
  24. ↑ Grenby TH (2011). Advances in Sweeteners. Springer. p. 66. ISBN   978-1461285229.
  25. 1 2 3 Kearsley MW, Deis RC (2006). "Sorbitol and Mannitol". Sweeteners and Sugar Alternatives in Food Technology. Wiley-Blackwell. pp. 249–261. ISBN   0470659688.
  26. 1 2 Lawson P (2007). Mannitol. Blackwell Publishing Ltd. pp. 219–225.
  27. ↑ Weiner ML, Kotkoskie LA (1999). Excipient Toxicity and Safety . Taylor & Francis. pp.  370. ISBN   9780824782108.
  28. ↑ Belcher R, Nutten AJ (1960). Quantitative Inorganic Analysis (2nd ed.). London, UK: Butterworths. p. 194.
  29. ↑ "Cut the Shit". December 2005. Archived from the original on 27 September 2016. Retrieved 4 September 2017.
  30. ↑ El-Haj BM, Al-Amri AM, Ali HS (October 2004). "Heroin profiling: mannitol hexaacetate as an unusual ingredient of some illicit drug seizures". Forensic Science International. 145 (1): 41–46. doi:10.1016/j.forsciint.2004.03.012. PMID   15374593.
  31. ↑ "Eat Any Sugar Alcohol Lately?". Archived from the original on 4 July 2024.
  32. 1 2 Song SH, Vieille C (August 2009). "Recent advances in the biological production of mannitol". Applied Microbiology and Biotechnology. 84 (1): 55–62. doi:10.1007/s00253-009-2086-5. PMID   19578847. S2CID   42103028.
  33. 1 2 3 Ghoreishi SM, Shahrestani RG (2009). "Innovative strategies for engineering mannitol production". Trends in Food Science & Technology. 20 (6–7): 263–270. doi:10.1016/j.tifs.2009.03.006.
  34. ↑ Wagner H, Flachsbarth H, Vogel G (March 1981). "[A New Antiphlogistic Principle from Sabal serrulata, II]". Planta Medica. 41 (3): 252–258. doi:10.1055/s-2007-971711. PMID   17401849. S2CID   260249165.
  35. ↑ Inić S, Kujundzić N (September 2011). "The first independent pharmacognosy institute in the world and its founder Julije Domac (1853-1928)". Die Pharmazie (in German). 66 (9): 720–726. PMID   22026131.
  36. ↑ Domac J (1881). "Über das Hexylen aus Mannit". Sitzungsberichte der Kaiserlichen Akademie der Wissenschaften, Mathematisch-Naturwissenschaftliche Classe (in German). 23: 1038–1051.
  37. ↑ Domac J (1881). "Über das Hexylen aus Mannit". Monatshefte für Chemie (in German). 2: 309–322. doi:10.1007/BF01516516. S2CID   94940823.
  38. ↑ Domac J (1882). "II. Ueber die Einwirkung der Unterchlorsäure auf Hexylen". Justus Liebig's Annalen der Chemie (in German). 213: 124–132. doi:10.1002/jlac.18822130107.
  39. ↑ Cruz J, Minoja G, Okuchi K (October 2001). "Improving clinical outcomes from acute subdural hematomas with the emergency preoperative administration of high doses of mannitol: a randomized trial". Neurosurgery. 49 (4): 864–871. doi:10.1097/00006123-200110000-00016. PMID   11564247. S2CID   43880412.
  40. ↑ Cruz J, Minoja G, Okuchi K (September 2002). "Major clinical and physiological benefits of early high doses of mannitol for intraparenchymal temporal lobe hemorrhages with abnormal pupillary widening: a randomized trial". Neurosurgery. 51 (3): 628–37, discussion 637–8. doi:10.1097/00006123-200209000-00006. PMID   12188940. S2CID   20678448.
  41. ↑ Cruz J, Minoja G, Okuchi K, Facco E (March 2004). "Successful use of the new high-dose mannitol treatment in patients with Glasgow Coma Scale scores of 3 and bilateral abnormal pupillary widening: a randomized trial". Journal of Neurosurgery. 100 (3): 376–383. doi:10.3171/jns.2004.100.3.0376. PMID   15035271.
  42. ↑ Roberts I, Smith R, Evans S (February 2007). "Doubts over head injury studies". BMJ. 334 (7590): 392–394. doi:10.1136/bmj.39118.480023.BE. PMC   1804156 . PMID   17322250.
  43. ↑ British Pharmacopoeia Commission Secretariat (2009). "Index, BP 2009" (PDF). Archived from the original (PDF) on 11 April 2009. Retrieved 31 January 2010.
  44. ↑ "Japanese Pharmacopoeia" (PDF) (Fifteenth ed.). 2006. Archived from the original (PDF) on 22 July 2011. Retrieved 31 January 2010.
  45. ↑ "Mannitol Injection" (PDF). USP 32. 2008. Archived from the original (PDF) on 6 July 2010. Retrieved 31 January 2010.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.