Cromoglicic acid Chemical Properties

Melting point:

241-242°C

Boiling point:

752.3±60.0 °C(Predicted)

Density 

1.623

storage temp. 

2-8°C

pka

pKa 2.0 (Uncertain)

CAS DataBase Reference

16110-51-3(CAS DataBase Reference)

EPA Substance Registry System

Cromolyn (16110-51-3)

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36

WGK Germany 

2

RTECS 

DJ2380000

Hazardous Substances Data

16110-51-3(Hazardous Substances Data)

Toxicity

rat,LD50,oral,> 2150mg/kg (2150mg/kg),United States Patent Document. Vol. #4407810,

MSDS

• Language:English Provider:1,3-Bis(2-carboxychromon-5-yloxy)-2-hydroxypropane
• Language:English Provider:SigmaAldrich

Cromoglicic acid Usage And Synthesis

Description

Cromolyn is a synthetic analog of the plant extract khellin that was first developed in the late 1960s and introduced into clinical practice the following decade. It is continued to be used widely in the treatment of allergic rhinitis, asthma, mastocytosis, and conjunctivitis. It has an outstanding safety profile and can be readily obtained without prescription in many countries.

Originator

Intal,Fisons,UK,1969

Uses

Cromolyn is used primarily for the prophylaxis of various types of asthma and in the treatment of allergic rhinitis, mastocytosis, and vernal conjunctivitis.

Uses

It is used for bronchial asthma, as well as prevention of seasonal, constant, and physically caused asthma attacks and allergic rhinitis.

Uses

Anti Asthamatic

Definition

ChEBI: A dicarboxylic acid that is the bis-chromone derivative of glycerol. It is effective as a mast cell stabilizer.

Manufacturing Process

To a solution of 970 parts of 2,6-dihydroxyacetophenone and 325 parts of epichlorohydrin in 1,500 parts of hot isopropanol was added, with stirring under reflux, a solution of 233 parts of 85% KOH in 2,500 parts of isopropanol and sufficient water (ca 100 parts) to dissolve the solid. The mixture was heated, with stirring, under reflux for 48 hours. Half the solvent was then distilled off and 5,000 parts of water were added. The mixture was cooled and the solid filtered off and washed with isopropanol and ether. It was then recrystallized from 12,500 parts of isopropanol to obtain a first crop of 380 parts and a second crop, after concentration, of 300 parts of 1,3-bis(2- acetyl-3-hydroxyphenoxy)-2hydroxypropane.
4.6 parts of 1,3-bis(2-acetyl-3-hydroxyphenoxy)-2-hydroxypropane were reacted with diethyl oxalate and the product cyclized to obtain 4.4 parts of pure diethyl ester of 1,3-bis(2-carboxychromon-5-yloxy)-2-hydroxypropane as pale yellow crystals melting between 180° and 182°C from a mixture of benzene and petrol, 4 parts of the diethyl ester of 1,3-bis(2-carboxychromon5-yloxy)-2-hydroxypropane were saponified with sodium hydroxide to obtain 3.2 parts of the disodium salt tetrahydrate as colorless crystals from aqueous alcohol.

Therapeutic Function

Bronchodilator

General Description

Solid.

Air & Water Reactions

Water soluble.

Reactivity Profile

Carboxylic acids donate hydrogen ions if a base is present to accept them. They react in this way with all bases, both organic (for example, the amines) and inorganic. Their reactions with bases, called "neutralizations", are accompanied by the evolution of substantial amounts of heat. Neutralization between an acid and a base produces water plus a salt. Carboxylic acids in aqueous solution and liquid or molten carboxylic acids can react with active metals to form gaseous hydrogen and a metal salt. Such reactions occur in principle for solid carboxylic acids as well, but are slow if the solid acid remains dry. Even "insoluble" carboxylic acids may absorb enough water from the air and dissolve sufficiently in Cromoglicic acid to corrode or dissolve iron, steel, and aluminum parts and containers. Carboxylic acids, especially in aqueous solution, also react with sulfites, nitrites, thiosulfates (to give H2S and SO3), dithionites (SO2), to generate flammable and/or toxic gases and heat.

Fire Hazard

Flash point data for Cromoglicic acid are not available. Cromoglicic acid is probably combustible.

Mechanism of action

Cromolyn stabilizes the membranes of mast cells, stopping the release of allergy mediators and suppressing activation of eosinophiles, neutrophilis, thrombocytes, and macrophages, which take part in the formation of bronchospasms. Cromylyn differs from the majority of medications taken for obstructive diseases of the respiratory tract in that it is used only as a preventative agent.

Clinical Use

Cromolyn generally is used prophylactically for bronchial asthma (as an inhaled powder), for prevention of exercise-induced bronchospasm, and for seasonal and perennial allergic rhinitis (nasal solution). Topically, it also is used as eye drops for allergic conjunctivitis and keratitis. In the management of asthmatic conditions, it is administered using a power-operated nebulizer. The bioavailability is very low with oral administration because of poor absorption. By inhalation, the powder is irritating to some patients. After inhalation, much less than 10% of the dose reaches the systemic circulation. An oral dosage form is used for mastocytosis.

Synthesis

Cromolyn, 5,5[(2-hydroxytrimethylen)dioxy] bis 4-oxo-4H-1-benzopiran-2- carboxylic acid (23.3.9), are synthesized by reacting 2,6-dihydroxyacetophenone with epichlorohydrine, during which the chlorine atom in epichlorohydrine is replaced and an opening of the epoxide ring takes place, resulting in a bis-product 23.3.7. Cyclization of this product into a bis-derivative 23.3.8 is accomplished using diethyloxalate, subsequent alkaline hydrolysis of the ester groups of which gives the desired cromolyn (23.3.9).

Environmental Fate

The major prophylactic effect of cromolyn is centered on inhibition of the degranulation of pulmonary mast cells causing a reduction in histamine release, reduced leukotriene production, and inhibition of release of inflammatory mediators from several cell types.

Toxicity evaluation

Cromolyn is a mast cell stabilizer and typically marketed as the sodium salt in the United States. It is typically found in solution as a clear and colorless liquid. Cromolyn is soluble in water and the solution is completely soluble in water.

Cromoglicic acid(16110-51-3)Related Product Information

• Glyceryl monostearate
• EPA
• Citric acid
• Fmoc-D-Trp(Boc)-OH
• Folic acid
• Ethyl 2-(Chlorosulfonyl)acetate
• Stearic acid
• Ascoric Acid
• Cromolyn Disodium Salt
• 1,3-Bis(2-hydroxyethoxy)benzene
• Diethyl cromoglycate
• 2',6'-Dihydroxyacetophenone
• 1,3-Diphenoxy-2-propanol
• 2,2’-(1,3-Propanediyldioxy)bisbenzaldehyde
• 5-HYDROXY-4-OXO-4H-CHROMENE-2-CARBOXYLIC ACID
• N 556
• Cromoglicic acid
• CARBOXYLIC ACID