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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/07 18:13:59」(JST)

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Cromoglicic acid (INN) (also referred to as cromolyn (USAN), cromoglycate (former BAN), or cromoglicate) is traditionally described as a mast cell stabilizer, and is commonly marketed as the sodium salt sodium cromoglicate or cromolyn sodium. This drug prevents the release of inflammatory chemicals such as histamine from mast cells.

Because of their convenience (and perceived safety), leukotriene receptor antagonists have largely replaced it as the non-corticosteroid treatment of choice in the treatment of asthma. Cromoglicic acid requires administration four times daily, and does not provide additive benefit in combination with inhaled corticosteroids.^[1]

History

Cromolyn sodium was discovered by Roger Altounyan who was himself a lifelong asthma sufferer. It is considered a breakthrough drug in management of asthma, as the patients can be freed from steroids in many cases; however, it is mainly effective as a prophylaxis for allergic and exercise induced asthma, not as a treatment for acute attacks. Altounyan was investigating certain plants and herbs which have bronchodilating properties. One such plant was Khella (Ammi visnaga) which had been used as a muscle relaxant since ancient times in Egypt. Altounyan deliberately inhaled derivatives of the active ingredient khellin to determine if they could block his asthma attacks. After several years of trial he isolated an effective and safe asthma-preventing compound called cromolyn sodium.

Preparations

Cromoglicic acid is available in multiple forms:

as a nasal spray (Rynacrom(UK), Lomusol(France), Nasalcrom(US) ) to treat allergic rhinitis.

in a nebulizer solution for aerosol administration to treat asthma.

as an inhaler (Intal) for preventive management of asthma.^[2] The maker of Intal, King Pharmaceuticals, has discontinued manufacturing the inhaled form, cromolyn sodium inhalation aerosol, due to issues involving CFC-free propellant.^[3] As stocks are depleted, this inhaler preparation will no longer be available to patients.^[4] In the EU it is manufactured without CFCs by Sanofi, although it must be imported from Canada for USA residents.

as eye drops (Opticrom and Optrex Allergy (UK), Crolom, Cromolyn (Canada)) for allergic conjunctivitis

in an oral form (Gastrocrom) to treat mastocytosis,^[5] dermatographic urticaria and ulcerative colitis. Another oral product, Intercron (sodium cromoglicate in distilled water, from Zambon France), is used for food allergies.

Mechanism of action

"Cromolyn works because it prevents the release of mediators that would normally attract inflammatory cells and because it stabilizes the inflammatory cells. MCT mast cells found in the mucosa are stabilised."^[6] Nedocromil is another mast cell stabilizer that also works in controlling asthma. The underlying mechanism of action is not fully understood; for while cromoglicate stabilizes mast cells, this mechanism is probably not why it works in asthma.^[7] Pharmaceutical companies have produced 20 related compounds that are equally or more potent at stabilising mast cells and none of them have shown any anti-asthmatic effect.^[7] It is more likely that these work by inhibiting the response of sensory C fibers to the irritant capsaicin, inhibiting local axon reflexes involved in asthma, and may inhibit the release of preformed T cell cytokines and mediators involved in asthma. (see review by Garland, 1991)

It is known to somewhat inhibit chloride channels (37% ± 7%)^[8] and thus may inhibit the:

exaggerated neuronal reflexes triggered by stimulation of irritant receptors on sensory nerve endings (e.g. exercise-induced asthma)
release of preformed cytokines from several type of inflammatory cells (T cells, eosinophils) in allergen-induced asthma

Note: Another chemical (NPPB: 5-nitro-2(3-phenyl) propylamino-benzoic acid) was shown, in the same study, to be a more effective chloride channel blocker.

Finally it may act by inhibiting calcium influx.

Cromoglicate is classified as a chromone.

Cromolyn is also being tested as a drug to treat insulin-induced lipoatrophy.^[9]^[10]

References

^ Fanta CH (March 2009). "Asthma". New England Journal of Medicine 360 (10): 1002–14. doi:10.1056/NEJMra0804579. PMID 19264689. Review.
^ Schwartz HJ, Blumenthal M, Brady R et al. (April 1996). "A comparative study of the clinical efficacy of nedocromil sodium and placebo. How does cromolyn sodium compare as an active control treatment?". Chest 109 (4): 945–52. doi:10.1378/chest.109.4.945. PMID 8635375.
^ Eric Carter (July 31, 2009). "King Pharmaceuticals: Dear Healthcare Professionals" (PDF). Food and Drug Administration. King Pharmaceuticals. Retrieved May 28, 2012.
^ "Intal Inhaler discontinued - MPR". Empr.com. Retrieved 2012-05-28.
^ Horan RF, Sheffer AL, Austen KF (May 1990). "Cromolyn sodium in the management of systemic mastocytosis". J. Allergy Clin. Immunol. 85 (5): 852–5. doi:10.1016/0091-6749(90)90067-E. PMID 2110198.
^ Werner's Pathophysiology page 224
^ ^a ^b H. P. Rang et al., Pharmacology, Fifth Edition. (2003) ISBN 0-443-07145-4
^ Heinke, S; Szucs G; Norris A; Droogmans G; Nilius B (August 1995). "Inhibition of volume-activated chloride currents in endothelial cells by chromones". Br J Pharmacol. 115 (8): 1393–8. doi:10.1111/j.1476-5381.1995.tb16629.x. PMC 1908889. PMID 8564197.
^ Phua, EJ; Lopez, X; Ramus, J; Goldfine, AB (December 2013). "Cromolyn sodium for insulin-induced lipoatrophy: old drug, new use.". Diabetes care 36 (12): e204–5. doi:10.2337/dc13-1123. PMID 24265375.
^ http://www.empr.com/a-surprising-option-for-managing-insulin-induced-lipoatrophy/article/325863/

English Journal

A comparative study of validated spectrophotometric and TLC- spectrodensitometric methods for the determination of sodium cromoglicate and fluorometholone in ophthalmic solution.

Saleh SS, Lotfy HM, Hassan NY, Elgizawy SM.Author information Analytical Chemistry Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), 11787 6[th] October City, Egypt.AbstractThe determination of sodium cromoglicate (SCG) and fluorometholone (FLU) in ophthalmic solution was developed by simple, sensitive and precise methods. Three spectrophotometric methods were applied: absorptivity factor (a-Factor method), absorption factor (AFM) and mean centering of ratio spectra (MCR). The linearity ranges of SCG were found to be (2.5-35 μg/mL) for (a-Factor method) and (MCR); while for (AFM), it was found to be (7.5-50 μg/mL). The linearity ranges of FLU were found to be (4-16 μg/mL) for (a-Factor method) and (AFM); while for (MCR), it was found to be (2-16 μg/mL). The mean percentage recoveries/RSD for SCG were found to be 100.31/0.90, 100.23/0.57 and 100.43/1.21; while for FLU, they were found to be 100.11/0.56, 99.97/0.35 and 99.94/0.88 using (a-Factor method), (AFM) and (MCR), respectively. A TLC-spectrodensitometric method was developed by separation of SCG and FLU on silica gel 60 F254 using chloroform:methanol:toluene:triethylamine in the ratio of (5:2:4:1 v/v/v/v) as developing system, followed by spectrodensitometric measurement of the bands at 241 nm. The linearity ranges and the mean percentage recoveries/RSD were found to be (0.4-4.4 μg/band), 100.24/1.44 and (0.2-1.6 μg/band), 99.95/1.50 for SCG and FLU, respectively. A comparative study was conducted between the proposed methods to discuss the advantage of each method. The suggested methods were validated in compliance with the ICH guidelines and were successfully applied for the determination of SCG and FLU in their laboratory prepared mixtures and commercial ophthalmic solution in the presence of benzalkonium chloride as a preservative. These methods could be an alternative to different HPLC techniques in quality control laboratories lacking the required facilities for those expensive techniques.
Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society.Saudi Pharm J.2013 Oct;21(4):411-21. doi: 10.1016/j.jsps.2012.11.001.
The determination of sodium cromoglicate (SCG) and fluorometholone (FLU) in ophthalmic solution was developed by simple, sensitive and precise methods. Three spectrophotometric methods were applied: absorptivity factor (a-Factor method), absorption factor (AFM) and mean centering of ratio spectra (M
PMID 24227962

Topical use of sodium cromoglicate (cromolyn sodium) to treat atopic dermatitis and other skin allergies.

Zur E.Author information Super-Pharm, Petach-Tikvah, Israel. eyalz@super-pharm.co.ilAbstractSodium cromoglicate (cromolyn sodium) is a very well-known medicine that has been used for many years for various allergic conditions. The topical use of this medicine is less known, and there are no commercial medicines of cream, gel, or lotion in most of the world. This article summarizes the clinical data accumulated from seventeen trials that checked the topical efficacy and safety of sodium cromoglicate and analyzes the clinical implementations of this medicine in the topical treatment of atopic dermatitis and other skin allergies. In addition, this article analyzes the various formulations that have been used in the clinical trials in an attempt to find the optimal formulation. The topical use of sodium cromoglicate seemed to have a promising potential, and implementing the data of this article can allow the compounding pharmacist a very interesting professional activity in very common and widespread allergic pathologies.
International journal of pharmaceutical compounding.Int J Pharm Compd.2012 Sep-Oct;16(5):386-93.
Sodium cromoglicate (cromolyn sodium) is a very well-known medicine that has been used for many years for various allergic conditions. The topical use of this medicine is less known, and there are no commercial medicines of cream, gel, or lotion in most of the world. This article summarizes the clin
PMID 23072198

In vivo hydroquinone exposure causes tracheal hyperresponsiveness due to TNF secretion by epithelial cells.

Shimada AL, Lino-Dos-Santos-Franco A, Bolonheis SM, Nakasato A, Damazo AS, Tavares-de-Lima W, Farsky SH.Author information Laboratory of Experimental Toxicology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, Brazil.AbstractHydroquinone (HQ) is the main oxidative substance in cigarette smoke and a toxic product of benzene biotransformation. Although the respiratory tract is an inlet pathway of HQ exposure, its effect on airway muscle responsiveness has not been assessed. We thus investigated the effects of low dose in vivo HQ-exposure on tracheal responsiveness to a muscarinic receptor agonist. Male Swiss mice were exposed to aerosolised 5% ethanol/saline solution (HQ vehicle; control) or 0.04 ppm HQ (1h/day for 5 days) and tracheal rings were collected 1h after the last exposure. HQ exposure caused tracheal hyperresponsiveness to methacholine (MCh), which was abolished by mechanical removal of the epithelium. This hyperresponsiveness was not dependent on neutrophil infiltration, but on tumour necrosis factor (TNF) secretion by epithelial cells. This conclusion was based on the following data: (1) trachea from HQ-exposed mice presented a higher amount of TNF, which was abrogated following removal of the epithelium; (2) the trachea hyperresponsiveness and TNF levels were attenuated by in vivo chlorpromazine (CPZ) treatment, an inhibitor of TNF synthesis. The involvement of HQ-induced TNF secretion in trachea mast cell degranulation was also demonstrated by the partial reversion of tracheal hyperresponsiveness in sodium cromoglicate-treated animals, and the in vivo HQ-exposure-induced degranulation of trachea connective tissue and mucosal mast cells, which was reversed by CPZ treatment. Our data show that in vivo HQ exposure indirectly exacerbates the parasympathetic-induced contraction of airway smooth muscle cells, mediated by TNF secreted by tracheal epithelial cells, clearly showing the link between environmental HQ exposure and the reactivity of airways.
Toxicology letters.Toxicol Lett.2012 May 20;211(1):10-7. doi: 10.1016/j.toxlet.2012.02.016. Epub 2012 Mar 5.
Hydroquinone (HQ) is the main oxidative substance in cigarette smoke and a toxic product of benzene biotransformation. Although the respiratory tract is an inlet pathway of HQ exposure, its effect on airway muscle responsiveness has not been assessed. We thus investigated the effects of low dose in
PMID 22414385

Japanese Journal

クロモグリク酸ナトリウム点眼液の角膜細胞への影響

福田正道,村野秀和,山本佳代,山代陽子,高橋信夫,萩原健太,北川和子,佐々木洋
眼薬理 = Japanese journal of ocular pharmacology 20(1), 41-44, 2006-09-08
NAID 10018257013

クロモグリク酸ナトリウム点眼液の角膜細胞への影響

福田正道,村野秀和,山本佳代 [他],山代陽子,高橋信夫,萩原健太,北川和子,佐々木洋
あたらしい眼科 = Journal of the eye 22(12), 1675-1678, 2005-12-30
NAID 10020399982

A RANDOMIZED, GROUP-PARALLEL COMPARATIVE TRIAL OF THE SUPPRESSIVE EFFECT OF CHINESE TRADITIONAL MEDICINE, SHEN-MI-TANG (SHIN-PI-TO), COMPARED TO SODIUM ORAMOYLYCATE INHALATION IN IMPROVING SUBJECTIVE AND OBJECTIVE SYMPTOMS IN BRONCHIAL ASTHMATICS

西澤芳男,西澤恭子,後藤グレイシイ・広恵,吉岡二三,野坂修一,雨森保憲,谷垣由美子,永野富美代,山田まゆみ,平田弥生,安田理絵,川田陽子,天方義邦,伏木信次
耳鼻咽喉科展望 47, 20-27, 2004
… Patients in group B inhaled sodium cromoglicate (CSCG) (20 mg/1 capsule) in the same administraton using DSCG-spinhela. …
NAID 130003975310

Related Pictures

Sodium Cromoglicate Hayfever Eye Drops 2% /sodium-cromoglicate-eye-drops-2-10ml.jpg - Sodium Cromoglicate Eyedrops 10ml cromoglicate aerosol sodium cromoglicate Alairgix Cromoglicate de sodium 2% Sodium Cromoglicate Eye Drops Nacromin Sodium Cromoglicate BP 15 ml 2% Sodium Cromoglicate Aerosol (Inhalation)

★リンクテーブル★

リンク元	「クロモグリク酸」
拡張検索	「cromoglicate lisetil hydrochloride」「sodium cromoglicate」

「クロモグリク酸」

Cromoglicic acid
Systematic (IUPAC) name
	5,5′-(2-hydroxypropane-1,3-diyl)bis(oxy)bis(4-oxo-4H-chromene-2-carboxylic acid)
Clinical data
AHFS/Drugs.com	International Drug Names
Licence data	US FDA:link
Pregnancy; category	AU: B1; US: B (No risk in non-human studies);
Legal status	AU: Pharmacy Only (S2); inhaler POM, eye OTC(UK) nasal OTC, eye, inhaler Rx(US);
Routes of; administration	topical: oral, nasal spray, inhaled, eye drops
Pharmacokinetic data
Bioavailability	1%
Biological half-life	1.3 hours
Identifiers
CAS Registry Number	16110-51-3
ATC code	A07EB01 D11AH03 R01AC01 R03BC01 S01GX01
PubChem	CID: 2882
IUPHAR/BPS	7608
DrugBank	DB01003
ChemSpider	2779
UNII	Y0TK0FS77W
KEGG	D07753
ChEBI	CHEBI:59773
ChEMBL	CHEMBL74
Chemical data
Formula	C23H16O11
Molecular mass	468.367 g/mol
	SMILES O=C(O)C=4Oc3cccc(OCC(O)COc2cccc1O/C(=C\C(=O)c12)C(=O)O)c3C(=O)C=4 ;
	InChI InChI=1S/C23H16O11/c24-11(9-31-14-3-1-5-16-20(14)12(25)7-18(33-16)22(27)28)10-32-15-4-2-6-17-21(15)13(26)8-19(34-17)23(29)30/h1-8,11,24H,9-10H2,(H,27,28)(H,29,30) ; Key:IMZMKUWMOSJXDT-UHFFFAOYSA-N ;
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