E421 (Mannitol)

E421 (Mannitol) = Mannite

CAS Number: 69-65-8
PubChem Client ID: 6251
DrugBank Number: DB00742
ChemSpider Number : 6015
KEGG Number: D00062
E number: E421 (thickeners, ...)

E421 (Mannitol) is a type of sugar alcohol used as a sweetener and medicine.
Mannite is used as a low-calorie sweetener, as it is poorly absorbed by the intestines.
E421 (Mannitol) is used as a medicine to reduce the pressure in the eyes and to lower the increased intracranial pressure, as in glaucoma.
E421 (Mannitol) is given medically by injection.
Effects usually begin within 15 minutes and last up to 8 hours.

Common side effects from medical use include electrolyte problems and dehydration.
Other serious side effects include worsening heart failure and kidney problems.
E421 (Mannitol) is unclear whether the use of mannite is safe in pregnancy.
E421 (Mannitol) is in the osmotic diuretic family of drugs and works by drawing fluid from the brain and eyes.
The discovery of E421 (Mannitol) is attributed to Joseph Louis Proust in 1806.
Mannit is on the World Health Organization's List of Essential Medicines.

Mannite was originally made from flowering ash and was named manna because of its supposed resemblance to biblical food.
E421 (Mannitol) is on the World Anti-Doping Agency's banned drug list for fear it might mask other drugs.
E421 (Mannitol) is a diuretic used to reduce swelling and pressure inside the eye or around the brain.
E421 (Mannitol) is also used to help your body produce more urine.
This drug is used in people with kidney failure to remove excess water and toxins from the body.
E421 (Mannitol) is sometimes given to make your body produce enough urine to be collected and tested.
This helps your doctor determine if your kidneys are working properly.
E421 (Mannitol) may also be used for purposes not listed in this medication guide.

What is E421 (Mannitol)?
E421 (Mannitol) is a diuretic used to reduce swelling and pressure inside the eye or around the brain.
E421 (Mannitol) is also used to help your body produce more urine. This drug is used in people with kidney failure to remove excess water and toxins from the body.
E421 (Mannitol) is sometimes given to make your body produce enough urine to be collected and tested.
This helps your doctor determine if your kidneys are working properly.

E421 (Mannitol) may also be used for purposes not listed in this medication guide.
E421 (Mannitol) is the reduced form of the 6-carbon sugar mannose.
Mannite is an ancient osmotic diuretic for research purposes.
Urea and other clinically popular osmotic diuretics consist of small particles that are freely filtered from the glomerulus into the lumen of the renal tubule.

Urinary excretion of particles with obligate water produces osmotic diuresis.
E421 (Mannitol) is widely used in the management of high intracranial pressure (ICP), kidney protection in cardiovascular and kidney transplant surgery, and management of rhabdomyolysis.
Mannite has also been used previously for bowel preparation prior to colorectal surgery.

Description
E421 (Mannitol) is a sterile, non-pyrogenic solution in water for injection available at concentrations of 5%, 10%, 15%, 20% in flexible plastic containers and 25% in a Fliptop vial.
Concentrations up to 20% may include sodium bicarbonate for pH adjustment.
The 25% concentration may contain sodium bicarbonate and/or hydrochloric acid for pH adjustment.
The solutions do not contain bacteriostats, antimicrobial agents, or added buffers (except for pH adjustment), and each is designed as a single-dose injection only.

When smaller doses are required, the unused portion should be discarded.
The uptake and phosphorylation of D-E421 (Mannitol) is catalyzed by E421 (Mannitol)-specific phosphoenolpyruvate-dependent phosphotransferase systems.
E421 (Mannitol) may interact with neutrophils and monocytes. Experiments have shown that it can reduce neutrophil apoptosis in vitro.
The compound has been used in studies as a stimulator of cecal microbial growth and cellulolytic activity in rabbits.
E421 (Mannitol) has been observed to reduce fat digestibility and body fat accumulation in both normal and cesectomized rats, as well as upregulate monocyte HLA-DR, monocyte and neutrophil CD11b.

Usage areas
E421 (Mannitol) 15% solution for intravenous use

Medical uses:
In the United States, E421 (Mannitol) is indicated for the reduction of intracranial pressure and for the treatment of cerebral edema and elevated intraocular pressure.
In the European Union, E421 (Mannitol) is indicated as an adjunct to best standard of care for the treatment of cystic fibrosis (CF) in adults 18 years of age and older.
E421 (Mannitol) is used intravenously, for example, to reduce acutely elevated intracranial pressure after head injury until more definitive treatment can be administered.

Intra-arterial infusions of E421 (Mannitol) may temporarily open the blood-brain barrier by disrupting tight junctions.
It can also be used in certain cases of kidney failure with low urine output, reducing pressure in the eye, increasing the excretion of certain toxins, and treating fluid buildup.
Intraoperative E421 (Mannitol) prior to release of the vessel clamp during renal transplantation has not been shown to reduce post-transplant kidney injury but reduce graft rejection.

E421 (Mannitol) acts as an osmotic laxative in oral doses greater than 20 g and is sometimes sold as a laxative for children.
The use of E421 (Mannitol) as an inhaled bronchial irritant has been proposed as an alternative diagnostic method for exercise-induced asthma.
E421 (Mannitol) is commonly used to prime a heart-lung machine during cardiopulmonary bypass.
The presence of E421 (Mannitol) preserves kidney function during times of low blood flow and pressure while the patient is in bypass.
The solution prevents swelling of the endothelial cells in the kidney, which could otherwise reduce blood flow to this area and cause cell damage.

E421 (Mannitol) can also be used to temporarily encapsulate a sharp object (such as a tip coil for an artificial pacemaker) as it passes through the venous system.
Since E421 (Mannitol) dissolves easily in blood, it is exposed on the sharp point target.
E421 (Mannitol) is also the first-choice drug for the treatment of acute glaucoma in veterinary medicine.
Mannite is administered intravenously as a 20% solution.
Mannite dries out the vitreous humor and therefore lowers intraocular pressure.
However, it requires a solid blood-ocular barrier to function.

Food:
E421 (Mannitol) raises blood sugar less than sucrose, so it is used as a sweetener for diabetics and in chewing gums.
Although E421 (Mannitol) has a higher temperature of solution than most sugar alcohols, its relatively low solubility reduces the cooling effect often found in mints and chewing gums.
However, when E421 (Mannitol) is completely dissolved in a product, it creates a strong cooling effect.
Also, Mannit has a very low hygroscopicity - it does not absorb water from the air until the humidity level is 98%.
This makes E421 (Mannitol) very useful as a coating for hard candies, dried fruits and chewing gums, and is often found as an ingredient in candies and chewing gums.
The pleasant taste and mouthfeel of E421 (Mannitol) make it a popular excipient for chewable tablets.

Analytical chemistry:
E421 (Mannitol) can be used to form a complex with boric acid.
This increases the acid strength of boric acid and provides better precision in the volumetric analysis of this acid.

Other:
E421 (Mannitol) is the primary component of E421 (Mannitol) salt agar, a bacterial growth medium, and is used in others.
A 1:10 mixture of E421 (Mannitol) and fentanyl (or fentanyl analogues) is labeled and sold as "Chinese white," a popular heroin substitute.

Chemical:
E421 (Mannitol) is an isomer of another sugar alcohol, sorbitol; the two differ only in the orientation of the hydroxyl group on carbon 2.
While similar, the nature, melting points, and uses of the two sugar alcohols have very different origins.

Production:
E421 (Mannitol) is classified as a sugar alcohol; that is, it can be obtained from a sugar (mannose) by reduction.
Other sugar alcohols include xylitol and sorbitol.
E421 (Mannitol) and sorbitol are isomers, the only difference being the orientation of the hydroxyl group on carbon 2.

Industrial synthesis:
E421 (Mannitol) is commonly produced through the hydrogenation of fructose, which consists of starch or sucrose (common table sugar).
Although starch is a cheaper source than sucrose, the conversion of starch is much more complicated.
Eventually, it yields a syrup containing about 42% fructose, 52% glucose, and 6% maltose.
The sucrose is simply hydrolyzed to an invert sugar syrup containing about 50% fructose.
In both cases the syrups are chromatographically purified to contain 90-95% fructose.
Fructose is then hydrogenated over a nickel catalyst to a mixture of sorbitol and E421 (Mannitol) isomers.
Yields are typically 50:50%, although slightly alkaline reaction conditions can slightly increase E421 (Mannitol) yield.

WHAT IS E421 (Mannitol) AND HOW DOES IT WORK?
E421 (Mannitol) is a diuretic used to force urine production in people with acute (sudden) kidney failure.
E421 (Mannitol) injection is also used to reduce swelling and pressure inside the eye or around the brain.

Background:
E421 (Mannitol) is an osmotic diuretic that is metabolically inert in humans and occurs naturally as a sugar or sugar alcohol in fruits and vegetables.
E421 (Mannitol) raises blood plasma osmolality, resulting in increased water flow from tissues, including the brain and cerebrospinal fluid, into the interstitial fluid and plasma.
As a result, cerebral edema, increased intracranial pressure, and cerebrospinal fluid volume and pressure may decrease.
E421 (Mannitol) can also be used to induce diuresis before irreversible renal failure occurs; promotion of urinary excretion of toxic substances; as an Antiglaucoma agent; and as a kidney function diagnostic aid.

Indicator:
It is used to promote diuresis, lower intracranial pressure, treat cerebral edema, and increase urinary excretion of toxic substances before irreversible renal failure occurs.
E421 (Mannitol) is also indicated as adjunctive maintenance therapy to improve pulmonary function in cystic fibrosis patients aged 18 years and older who pass the BRONCHITOL tolerance test.
It is recommended that patients take a short-acting bronchodilator 5-15 minutes before each dose of E421 (Mannitol).

Pharmacodynamics:
Chemically, E421 (Mannitol) is an alcohol and a sugar or a polyol; similar to xylitol or sorbitol.
However, E421 (Mannitol) has a tendency to lose a hydrogen ion in aqueous solutions, causing the solution to become acidic.
Therefore, it is not unusual to add a substance such as sodium bicarbonate to adjust its pH.
E421 (Mannitol) is commonly used to increase urine production (diuretic).
Mannite is also used to treat or prevent medical conditions caused by an increase in body fluids/water.
E421 (Mannitol) is often given with other diuretics and/or IV fluid replacement.
Inhaled E421 (Mannitol) is likely to cause bronchospasm and hemoptysis; occurrence of any should result in discontinuation of inhaled E421 (Mannitol).

Movement mechanism:
E421 (Mannitol) is an osmotic diuretic that is metabolically inert in humans and occurs naturally as a sugar or sugar alcohol in fruits and vegetables.
E421 (Mannitol) raises blood plasma osmolality, resulting in increased water flow from tissues, including the brain and cerebrospinal fluid, into the interstitial fluid and plasma.
As a result, cerebral edema, increased intracranial pressure, and cerebrospinal fluid volume and pressure may decrease.
As a diuretic, E421 (Mannitol) induces diuresis as it is not reabsorbed in the renal tubule, thereby increasing the osmolality of the glomerular filtrate, facilitating water excretion, and inhibiting renal tubular reabsorption of sodium, chloride and other solutes.
E421 (Mannitol) promotes urinary excretion of toxic substances and protects against nephrotoxicity by preventing the concentration of toxic substances in tubular fluid.

As an Antiglaucoma agent, E421 (Mannitol) raises the blood plasma osmolarity, resulting in an increased flow of water from the eye to the plasma, resulting in a reduction in intraocular pressure.
As a renal function diagnostic aid, E421 (Mannitol) is freely filtered by the glomeruli with less than 10% tubular reabsorption.
Thus, the urinary excretion rate can serve as a measure of the glomerular filtration rate.
The precise mechanism of action of inhaled E421 (Mannitol) in the symptomatic maintenance treatment of cystic fibrosis remains unclear.
It is hypothesized that E421 (Mannitol) produces an osmotic gradient across the airway epithelium that draws fluid into the extracellular space and alters the properties of the airway surface mucus layer, allowing for easier mucociliary clearance.

Calculated Properties    
Molecular Weight: 182.17    
XLogP3 : -3.1
Number of Hydrogen Bond Donors: 6    
Number of Hydrogen Bond Acceptors: 6    
Number of Rotatable Ties: 5    
Full Mass: 182.07903816    
Mass : 182.07903816    
Topological Polar Surface Area: 121 Å ²    
Heavy Atom Count: 12    
Isotope Atomic Number: 0    
Defined Atomic Stereocenter Number: 4    
Number of Undefined Atom Stereocenters: 0    
Defined Bond Stereocenter Number : 0    
Undefined Bond Stereocenter Number : 0    
Number of Covalently Bonded Units: 1    

Physicochemical Information
Boiling point: 290 - 295 °C
Density: 1.52 g/cm3 (20 °C)
Ignition temperature: 410 °C
Melting Point: 164 - 169 °C
pH value: 5.0 - 6.5
Bulk density: 400 - 500 kg/m3
Resolution: 213 g/l

Chemical Information
Molecular Weight: 182.17
Formula     : C6H14O6
CAS No.: 69-65-8
Storage: 3 years     -20°Cdust
2 years     -80°C

Fundamentals of E421 (Mannitol)
E421 (Mannitol) is a type of carbohydrate called a sugar alcohol or polyol, which are water-soluble compounds found naturally in many fruits and vegetables.
E421 (Mannitol) is also produced commercially to provide body, sweetness, refreshing taste and texture in chocolate coatings, candies, chewing gums, powders and tablets.
Mannite is also useful as an anti-caking agent due to its minimal water absorption.
E421 (Mannitol) safety has been studied and approved by health authorities around the world, including the World Health Organization, the European Union, and the countries of Australia, Canada, and Japan.
The US Food and Drug Administration (FDA) also recognizes that E421 (Mannitol) is safe.
While the safety of E421 (Mannitol) (and other sugar alcohols) is well documented, some sugar alcohols can cause gastrointestinal upset such as gas, bloating and diarrhea when eaten in excessive amounts.
As a result, packaged foods containing E421 (Mannitol) or sorbitol should include a warning on their labels about their potential laxative effects.

E421 (Mannitol) and health
Like most sugar alcohols, E421 (Mannitol) is neither as sweet as sugar nor as calorie dense as sugar.
E421 (Mannitol) is half as sweet as sugar and has about 60 percent fewer calories per gram (1.6 calories for E421 (Mannitol) compared to 4 calories for sugar).
But E421 (Mannitol) health benefits go beyond calories.
Two areas known for the positive effects of sugar alcohols are oral health and their effect on blood sugar.

oral health
Sugar alcohols, including E421 (Mannitol), have been shown to benefit oral health in several ways.
They are primarily considered “tooth-friendly” because they are non-cariogenic, meaning they do not contribute to cavity formation.
The chewing action also promotes the flow of saliva, protecting the teeth from decay-causing bacteria.
Increased saliva and non-carcinogenic properties (along with sweetness and cool taste) are the reason sugar alcohols such as maltitol, E421 (Mannitol), sorbitol, and xylitol are used in sugar-free gums.
Because of these properties, the FDA considers E421 (Mannitol) and other sugar alcohols beneficial for oral health.

Blood sugar
Like other sugar alcohols (except erythritol), E421 (Mannitol) contains calories in the form of carbohydrates.
E421 (Mannitol) is slowly and incompletely absorbed from our small intestine.
The remaining E421 (Mannitol) continues into the large intestine, where its metabolism delivers fewer calories.
Therefore, consumption of E421 (Mannitol) (compared to an equal amount of sugar) reduces insulin secretion, which ultimately helps keep blood sugar levels lower.

Interaction with other medicinal products and other forms of interaction

Impact Potentiation
Concomitant use of other diuretics may increase the effects of E421 (Mannitol) and dose adjustment may be required.

Effect Inhibition
E421 (Mannitol) promotes urinary flow, which will primarily affect drugs that are largely renally reabsorbed, thereby increasing their clearance and reducing their exposure.
E421 (Mannitol) increases the urinary excretion of lithium and therefore the use of E421 (Mannitol) may impair the response to lithium.

Nephrotoxicity of drugs due to E421 (Mannitol)-induced fluid imbalance
Although an interaction in humans is unlikely, patients receiving concomitant cyclosporine and aminoglycoside should be closely monitored for signs of nephrotoxicity.

neurotoxic agents
Concomitant use of neurotoxic agents (eg aminoglycoside) and E421 (Mannitol) may potentiate the toxicity of neurotoxic agents.

Agents affected by electrolyte imbalances
The development of electrolyte imbalances associated with E421 (Mannitol) administration may alter the effects of agents sensitive to such imbalances.
Other potential interactions are tubocurarine and depolarizing neuromuscular blocking drugs, oral anticoagulants (E421 (Mannitol) may decrease their effects by increasing the concentration of coagulation factors secondary to dehydration), and digoxin.

Pharmacology
E421 (Mannitol), chemically 1,2,3,4,5,6-hexanehexol (C6H8(OH)6), is a polyol (sugar alcohol) widely used in the food and pharmaceutical industries due to its unique functional properties.
In particular, it is half as sweet as sucrose and has a desirable cooling effect in masking bitter tastes when taken orally.
Mannite is a naturally occurring substance found in seaweeds, fresh mushrooms, and the secretions of trees. It is an isomer of sorbitol, usually synthesized by the hydrogenation of special glucose syrups.
E421 (Mannitol) is commercially available in various forms of white crystalline powder and granules, all of which are water-soluble.

Generic Drug Information
Indications and Dosage
intravenous
Cerebral edema, Decrease in elevated intracranial pressure, Decrease in elevated intraocular pressure
Adult: as a 10%, 15% or 20% solution: 1.5-2 g/kg by infusion over 30-60 minutes.

What is E421 (Mannitol)?
E421 (Mannitol) is a plant-based ingredient used in foods, derived from grains (corn and wheat) in the EU.
Mannit belongs to the Carbohydrates family. E421 (Mannitol) is a polyol, also known as sugar alcohols.
E421 (Mannitol) is less sweet than sucrose (about 60% of sweetness). E421 (Mannitol) has fewer calories than sugar, can help control the blood sugar response, and is tooth-friendly (non-cariogenic - it doesn't cause tooth decay).
E421 (Mannitol) occurs naturally in some fruits such as apples, pears, peaches, and prunes.
E421 (Mannitol) is an approved food additive in the EU carrying the identifier E-number E421.
It is obtained from E421 (Mannitol), dextrose and glucose syrups.

Where and Why Is It Used?
E421 (Mannitol) is used for its sweetening power in a wide variety of food products.
Mannite is a preferred ingredient in sugar-free confectionery and energy-reduced products due to its tooth-friendliness (non-cariogenic) and low caloric value.
The relatively low solubility of E421 (Mannitol) reduces the cooling effect often found in mints and chewing gums.
However, when E421 (Mannitol) is completely dissolved in a product, it creates a strong cooling effect.
Mannite is often used in chewing gums, candies, frozen desserts, cookies, cakes, creams and fillings.
E421 (Mannitol) does not absorb water from the air until the humidity is 98%.
This makes E421 (Mannitol) very useful as a coating for hard candies, dried fruits and chewing gums, and is often found as an ingredient in candies and chewing gums.
E421 (Mannitol) pleasant taste and mouthfeel make it a popular ingredient for chewable tablets.
When E421 (Mannitol) is used in food, it must be labeled with the name or E-number (E421) in the E421 (Mannitol) ingredient list.

Features
Appearance: White powder to crystalline
Purity(Iodometric Titration): min. 99.0%
Melting point: 166.0 to 170.0 °C
Specific rotation: +22.0 to +24.0 degrees (C=10, sodium tetraborate solution)
Water Solubility: almost completely

Features
Melting Point: 168 °C
Specific Rotation: 23° (C=10, Sodium tetraborate solution)
Solubility in water: Soluble
Solubility (insoluble): Ether

FEATURES
Class: Rx
Medical License Required: Yes
Container: Bottle
Form: SDV
Generic Name: E421 (Mannitol)
Size: 50mL
Storage Temperature: 15º - 30ºC (59º - 86ºF)
Strength: 12.5 gm/Bottle
Therapeutic Class: Diuretic/Cardiovascular

The easiest way to grow E421 (Mannitol) sticks is from a slightly supersaturated solution:
Prepare a saturated solution of E421 (Mannitol) at room temperature. Its resolution at room temperature is 21.6g/100ml.
Warm the solution and dissolve a few more grams of E421 (Mannitol) per 100 ml of solution.
Allow the solution to cool to room temperature. The supersaturated solution is ready.
Now put a seed inside, cover the growing container and let it grow. When growth has stopped, repeat the previous steps, keeping the crystal in a small container with the solution.

Synonyms    
D-E421 (Mannitol)
E421 (Mannitol)
69-65-8
mannite
Osmitrol
manna sugar
87-78-5
osmofundin
cordycepic acid
mannite
osmosis
mannazucker
mannidex
mannigen
mannistol
resectisol
diosmol
Invenex
isotol
sea crystal
Maniton-S
D-(-)-E421 (Mannitol)
(2R,3R,4R,5R)-hexane-1,2,3,4,5,6-hexol
Mannogem 2080
(2R,3R,4R,5R)-Hexane-1,2,3,4,5,6-hexaol
E421 (Mannitol), D-
E421 (Mannitol) (VAN)
bronchitol
Aridol
SDM No.35
hexahydroxyhexane
NCI-C50362
UNII-3OWL53L36A
E421 (Mannitol) (USP)
E421 (Mannitol) [USP]
BRN 1721898
CHEBI:16899
MFCD00064287
3OWL53L36A
E421 (Mannitol)-d
E421 (Mannitol) 5%
133-43-7
E421 (Mannitol) [USA]
1,2,3,4,5,6-Hexanehexol
E421 (Mannitol) 10%
E421 (Mannitol) 15%
E421 (Mannitol) 20%
C6H14O6
NCGC00164246-01
E421
Mannidex 16700
E-421