| Description | Cromolyn is a synthetic analog of the plant extract khellin thatwas first developed in the late 1960s and introduced intoclinical practice the following decade. It is continued to be usedwidely in the treatment of allergic rhinitis, asthma, mastocytosis,and conjunctivitis. It has an outstanding safety profileand can be readily obtained without prescription in manycountries. |
| Originator | Intal,Fisons,UK,1969 |
| Uses | It is used for bronchial asthma, as well as prevention of seasonal, constant, and physicallycaused asthma attacks and allergic rhinitis. |
| Uses | Cromolyn is used primarily for the prophylaxis of various typesof asthma and in the treatment of allergic rhinitis, mastocytosis,and vernal conjunctivitis. |
| 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 ofepichlorohydrin 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 ofisopropanol and sufficient water (ca 100 parts) to dissolve the solid. Themixture was heated, with stirring, under reflux for 48 hours. Half the solventwas then distilled off and 5,000 parts of water were added. The mixture wascooled and the solid filtered off and washed with isopropanol and ether. It wasthen recrystallized from 12,500 parts of isopropanol to obtain a first crop of380 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 werereacted with diethyl oxalate and the product cyclized to obtain 4.4 parts ofpure diethyl ester of 1,3-bis(2-carboxychromon-5-yloxy)-2-hydroxypropane aspale yellow crystals melting between 180° and 182°C from a mixture ofbenzene and petrol, 4 parts of the diethyl ester of 1,3-bis(2-carboxychromon5-yloxy)-2-hydroxypropane were saponified with sodium hydroxide to obtain3.2 parts of the disodium salt tetrahydrate as colorless crystals from aqueousalcohol. |
| 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 mediatorsand suppressing activation of eosinophiles, neutrophilis, thrombocytes, andmacrophages, which take part in the formation of bronchospasms.Cromylyn differs from the majority of medications taken for obstructive diseases of therespiratory 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), forprevention 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.Inthe management of asthmatic conditions, it is administered using a power-operated nebulizer.The bioavailability is very low with oral administration because of poor absorption. Byinhalation, the powder is irritating to some patients. After inhalation, much less than 10% ofthe 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 withepichlorohydrine, during which the chlorine atom in epichlorohydrine is replaced and anopening of the epoxide ring takes place, resulting in a bis-product 23.3.7. Cyclization ofthis product into a bis-derivative 23.3.8 is accomplished using diethyloxalate, subsequentalkaline hydrolysis of the ester groups of which gives the desired cromolyn (23.3.9). |
| Environmental Fate | The major prophylactic effect of cromolyn is centered oninhibition of the degranulation of pulmonary mast cellscausing a reduction in histamine release, reduced leukotrieneproduction, and inhibition of release of inflammatory mediatorsfrom several cell types. |
| Toxicity evaluation | Cromolyn is a mast cell stabilizer and typically marketed as thesodium salt in the United States. It is typically found in solutionas a clear and colorless liquid. Cromolyn is soluble inwater and the solution is completely soluble in water. |
