15826-37-6 Usage
References
https://www.drugbank.ca/drugs/DB01003
https://en.wikipedia.org/wiki/Cromoglicic_acid
Chemical Properties
White Crystalline Powder
Originator
Intal,Fisons,UK,1969
Uses
Different sources of media describe the Uses of 15826-37-6 differently. You can refer to the following data:
1. antiasthmatic, antiallergy
2. Anti Asthamatic
3. Chromone complex which blocks mast cell degranulation
Indications
Cromolyn sodium (Intal) is chemically related drugs called chromones that is used for the prophylaxis of mild or moderate
asthma. It is administered by inhalation and has very good safety profiles, making them particularly useful
in treating children.
Definition
ChEBI: An organic sodium salt that is the disodium salt of cromoglycic acid.
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
Cromolyn sodium, disodium 1,3-bis(2-carboxychromon-5-yloxy)-2-hydroxypropane (Intal), isa hygroscopic, white, hydrated crystalline powder that is solublein water (1:10). It is tasteless at first but leaves a veryslightly bitter aftertaste. The pK of cromolyn is 2. It is availableas a solution for a nebulizer, an aerosol spray, a nasal solution,an ophthalmic solution, and an oral concentrate.Nebulized and aerosol cromolyn has been used for prophylacticmanagement of bronchial asthma and prevention ofexercise-induced bronchospasm. Cromolyn nasal solution isused for the prevention and treatment of allergic rhinitis, andoral concentrate is used to treat the histaminic symptomsof mastocytosis (diarrhea, flushing, headaches, vomiting, urticaria,abdominal pain, nausea, and itching). Topical cromolyn(eye drops) is used to treat allergic conjunctivitis andkeratitis. In the treatment of asthma, cromolyn efficacy is manifestedby decreased severity of clinical symptoms, or need for concomitant therapy, or both. Long-term use is justified if thedrug significantly reduces the severity of asthma symptoms;permits a significant reduction in, or elimination of, steroiddosage; or improves management of those who have intolerableside effects to sympathomimetic agents or methylxanthines.For cromolyn to be effective, it must be administered atleast 30 minutes prior to antigen challenge and administered atregular intervals (see dosing information that follows). Wheninhaled, the powder does produce irritation in some patients.Also, overuse of cromolyn can result in tolerance.
Biochem/physiol Actions
Cromolyn blocks the release of histamine and other pro-inflammatory mediators from mast cells.
Mechanism of action
The precise mechanism or mechanisms whereby cromolyn
sodium and nedocromil sodium exert their antiasthmatic
activities is unknown. Early work suggested
that these agents act by “stabilizing” mast cells, preventing
mediator release. However, several other compounds
exhibit greater potency for stabilization of mast
cells yet possess no clinical efficacy in asthma.This suggests
that the therapeutic activity of cromolyn sodium
and nedocromil sodium in asthma is related to one or
more other pharmacological mechanisms. Postulates include
inhibitory effects on irritant receptors, nerves,
plasma exudation, and inflammatory cells in general.
Pharmacokinetics
Cromolyn sodium is a bischromone that contains the fundamental benzopyrone moiety of khellin. The two chromone rings are necessary for activity and must be coplanar, with a linking chain of no longer than six carbons. If one changes the linking chain to positions 8 and 8′, coplanarity cannot be maintained, and the compound loses all activity. Cromolyn sodium is poorly absorbed from the lungs (~8%), insignificantly from the eye (~0.07%), and by approximately 1% from the GI tract. What little that finds its way into systemic circulation is eliminated intact in the urine and the bile. For the treatment of asthma, cromolyn sodium is available as a solution for both intranasal and inhalation administration. There also is an oral concentrate (100 mg/5 mL), which is administered as a 200-mg dose given four times a day.
Clinical Use
Cromolyn sodium is used almost
exclusively for the prophylactic treatment of mild
to moderate asthma and should not be used for the control
of acute bronchospasm. This agent is effective
in about 60 to 70% of children and adolescents with
asthma. Unfortunately, there is no reliable means to
predict which patients will respond.It is less effective
in older patients and in patients with severe
asthma. It may take up to 4 to 6 weeks of treatment for
cromolyn sodium to be effective in chronic asthma, but
it is effective after a single dose in exercise-induced
asthma. With respect to clinical efficacy, cromolyn
sodium and nedocromil sodium do not differ in a substantial
way.
Side effects
Cromolyn sodium is the least
toxic of available therapies for asthma. Adverse reactions
are rare and generally minor. Those occurring in
fewer than 1 in 10,000 patients include transient bronchospasm,
cough or wheezing, dryness of throat, laryngeal
edema, swollen parotid gland, angioedema, joint
swelling and pain, dizziness, dysuria, nausea, headache,
nasal congestion, rash, and urticaria.
Check Digit Verification of cas no
The CAS Registry Mumber 15826-37-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,5,8,2 and 6 respectively; the second part has 2 digits, 3 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 15826-37:
(7*1)+(6*5)+(5*8)+(4*2)+(3*6)+(2*3)+(1*7)=116
116 % 10 = 6
So 15826-37-6 is a valid CAS Registry Number.
InChI:InChI=1/C23H16O11.2Na/c24-11(9-31-12-1-3-18-14(5-12)16(25)7-20(33-18)22(27)28)10-32-13-2-4-19-15(6-13)17(26)8-21(34-19)23(29)30;;/h1-8,11,24H,9-10H2,(H,27,28)(H,29,30);;/q;2*+1/p-2
15826-37-6Relevant articles and documents
Preparation method of diethyl cromoglycate and sodium cromoglycate
-
Paragraph 0072; 0080-0085; 0087-0088; 0090-0091; 0093-0094, (2021/02/20)
The invention relates to the technical field of medicines, in particular to a preparation method of diethyl cromoglycate and sodium cromoglycate. The preparation method comprises the following steps:reacting 2, 6-dihydroxy acetophenone with diethyl oxalate to obtain 7-hydroxy-4-oxo-4H-benzopyran-2-carboxylic acid ethyl ester, and then reacting with 1, 3-dibromo-2-propanol(or epoxy chloropropane)to prepare diethyl cromoglycinate, because one phenolic hydroxyl group in the 7-hydroxy-4-oxo-4H-benzopyran-2-carboxylic acid ethyl ester molecule is protected, cutting off the source of polymolecularpolycondensation reaction, wherein two reaction sites of 1, 3-dibromo-2-propanol(or epoxy chloropropane) need to participate in the reaction, and obtaining the unique product diethyl cromoglycate through the reaction. Therefore, the yield of the diethyl cromoglycate is very high.
Synthesis of nitric acid esters from alcohols in a dinitrogen pentoxide/carbon dioxide liquid system
Kuchurov, Ilya V.,Fomenkov, Igor V.,Zlotin, Sergei G.,Tartakovsky, Vladimir A.
experimental part, p. 67 - 69 (2012/07/02)
Organic nitric acid esters have been prepared in 89-98% yield by the nitration of the corresponding alcohols and polyols with N2O5 in liquid CO2.
HYDROGEL CONTACT LENS FOR SUSTAINED DRUG RELEASE AND DRUG RELEASE METHOD USING HYDROGEL CONTACT LENS FOR SUSTAINED DRUG RELEASE
-
, (2012/01/03)
Disclosed is a sustainedly drug-releasing hydrogel contact lens which can sustainedly release an anionic medicament such as an allergy-treating agent in a mildly irritating and effective manner while achieving vision correction. Specifically disclosed is a hydrogel comprising ionic monomers composed of at least a cationic monomer and an anionic monomer, wherein the component ratio of the ionic monomers is 5 to 20 mol % inclusive relative to the total amount of monomers that constitute the gel, and the content of the anionic monomer is 15 to 25 mol % inclusive relative to the content of the cationic monomer.
Clear, stable cromolyn formulation
-
, (2008/06/13)
A substantially clear, sterile, aqueous tonicity adjusted composition of 1,3-bis(2-carboxychromon-5-yloxy)propan-2--ol, other bis-cromolyn derivatives, or pharmaceutically acceptable salts thereof, is provided which contains over 20 ppm transition metal ions or ions of Group IIA, IB, IIB or IV B. The composition is useful as an anti-inflammatory agent in the treatment of bronchial asthmatics and allergic or immune reactions in the eye and nose.
Method of treating atopic eczema
-
, (2008/06/13)
The present invention relates to methods of treating chronic skin disorders by externally applying to the skin compounds by the following formula STR1 and therapeutically acceptable salts, esters and amides thereof, wherein R1 through R6 and X are as hereinafter defined.
Pharmaceutical composition and process of treatment
-
, (2008/06/13)
A process for alleviating proliferative skin diseases such as psoriasis, atopic dermatitis, etc. comprising administering to humans, or domesticated animals, topically and/or systemically a composition comprising a pharmaceutical carrier and at least one active compound selected from the groups, substituted alkyl zanthines, tricyclic antidepressants, organic nitrates, antihypertensives, anti-asthma agents and central nervous system depressants and combinations of certain compounds from specifically named groups of compounds.
