GSK-3β (IC50 = 2.0 μM)

Cromoglycate sodium (Cromolyn disodium; FPL-670) is a chromone compound that operates by blocking the release of chemical mediators from sensitized mast cells. It is used for the preventive treatment of allergy and exercise-induced asthma but does not affect established asthma episodes.

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Cromolyn sodium was originally characterised as a mast cell stabiliser (Hoag 1991). However, it also inhibits neutrophil activation (Kay 1987), neutrophil chemotaxis (Bruijnzeel 1989), macrophage activation, tachykinin action, eicosanoid and cytokine release, and adhesion molecule expression (Yazid 2009). A more recent in vitro study (Yazid 2009) showed that Cromolyn sodium stimulates the anti‐inflammatory intracellular protein annexin‐A1 trafficking and release. Cromolyn sodium inhibits eicosanoid release due to inhibition of a phosphatase PP2A (phosphoprotein phosphatase; EC 3.1.3.16), which probably forms part of a control loop to limit annexin‐A1 release [3].

There were no alterations in ET-1 levels, damage scores, or inflammation in IIR mice treated with cromoglycate sodium (cromoglycate disodium; FPL-670) prior to ischemia (P>0.05, PreCr group vs. M group). In conclusion, by downregulating ET-1 and preventing persistent MC activation, the injection of Cromolyn (sodium) after reperfusion, but not before ischemia, attenuates IIRI [1]. The action of Cromolyn (sodium) is to prevent chronic lung disease (CLD). It is not advised to use cromolyn (sodium) to protect premature newborns from developing chronic lung illness [2].

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Stabilizing mast cells (MCs) can either inhibit or augment inflammation; however, how improved therapeutic benefits against small intestinal ischemia-reperfusion injury (IIRI) can be achieved by stabilizing MCs remains to be elucidated. The present study was designed to evaluate different treatments with Cromolyn sodium (CS, an MC stabilizer), which was administrated either prior to ischemia or after reperfusion. Kunming mice were randomized into a sham-operated group (SH), a sole IIR group (M), in which mice were subjected to 30 min superior mesenteric artery occlusion followed by 3 day or 3 h reperfusion, or IIR, treated with CS 15 min prior to ischemia or 15 min after reperfusion in the PreCr and PostCr groups. The survival rate and Chiu's scores were evaluated. The levels of ET-1, histamine, TNF-α and IL-6, and expression of MC protease 7 (MCP7), MC counts and myeloperoxidase (MPO) activity were quantified. IIR resulted in severe injury as demonstrated by significant increases in mortality and injury score. IIR also led to substantial elevations in the levels of ET-1, histamine, TNF-α and IL-6, expression of MCP7, MC counts and MPO activities (P<0.05, M vs. SH groups). All biochemical changes were markedly reduced in the PostCr group (P<0.05, PostCr vs. M groups), whereas pretreatment of IIR mice with CS prior to ischemia exhibited no changes of ET-1 levels, injury score and inflammation (P>0.05, PreCr vs. M groups). In conclusion, administration of CS after reperfusion, but not prior to ischemia, attenuates IIRI by downregulating ET-1 and suppressing sustained MC activation. [1]

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Cromolyn, tranilast and cetirizine ameliorate SIN-triggered local HRARs [2]
As SIN-triggered HRARs are mainly mediated by histamine release, we examined whether clinically available mast cell stabilizers and histamine receptor blockers could prevent SIN-induced HRARs. Hence, cromolyn, tranilast and cetirizine were employed in the experiments. The results demonstrated that cromolyn, tranilast and cetirizine significantly decreased the amount of Evans blue dye in the skin of SIN-treated animals (Fig. 4A and B) alongside with reduction of SIN-induced increase of mast cell numbers (Fig. 4C and D). Considering the critical role of IL-33 in SIN-triggered HRARs, we determined whether inhibition of IL-33 production contributed to the ameliorative effect of these three agents in the PCA model. Immunohistochemistry analysis revealed that cromolyn, tranilast and cetirizine inhibited SIN-induced IL-33 production in the skin of PCA rats (Fig. 4E), which is consistent with previous reports

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Cromolyn, tranilast and cetirizine block SIN-triggered systemic HRARs [2]
We further validated the effect of these mast cell stabilizers on the prevention of SIN-triggered systemic HRARs in rats, and the results demonstrated that cromolyn, tranilast and cetirizine could effectively reverse SIN-induced body temperature reductions, and animals treated with 200 mg/kg SIN exhibited an increase in body temperature from 35.0 °C to 35.9 °C, 36.0 °C and 36.2 °C, respectively (Fig. 5A). Additionally, cromolyn, tranilast, and cetirizine significantly reduced histamine concentrations in the plasma of animals treated with 200 mg/kg SIN from 5.5 μg/ml to 3.1, 1.0 and 0.9 μg/ml, respectively (Fig. 5B). Significant amelioration of lung injury was observed in animals treated with these mast cell stabilizers, exhibiting reduced immune cell infiltration in the lung tissues (Fig. 5C). Given that IL-33 is a critical cytokine in the initiation and exacerbation of inflammatory responses and histamine release in mouse mast cells, we further examined whether the inhibitory effect of three mast cell stabilizers on histamine release resulted from reduction of IL-33 secretion. As shown in Fig. 5D and E, the levels of IL-33 in plasma and lung tissues were significantly increased in animals treated with SIN intravenously, whereas co-treatment with SIN and cromolyn, tranilast, or cetirizine induced reductions in IL-33 levels in plasma or lung tissues of rats. Collectively, mast cell stabilizers are effective in preventing SIN-triggered systemic HRARs.

Experimental model of IIR and animal groups [1]
Four sets of healthy male Kunming mice weighing 20–22 g were anesthetized by intraperitoneal injection of 10% chloral hydrate (3.0 ml/kg) after they were fasted for 16 h prior to surgery. Animals had free access to water prior to surgery. After ensuring an adequate depth of anesthesia, the mice were fixed in the supine position. In the IIR group (M group), the abdomen was opened and the superior mesenteric artery (SMA) was identified and clamped for 30 min. The clamp was then released and reperfusion of the splanchnic region was maintained for 3 days to observe survival rates or maintained for 3 h to define early small intestinal injury. In the sham-operated group (SH group), the abdomen was opened and the SMA was isolated but not clamped. In the other two treatment groups, mice subjected to IIR in the PreCr group and PostCr group were injected intravenously with Cromolyn sodium/CS (25 mg/kg in 0.1 ml) through the caudal vein at 15 min prior to ischemia and 15 min after releasing of the clamp, respectively. Mice in the SH and M groups received the same volumes of normal saline at 15 min prior to ischemia. In addition, pre-warmed normal saline (0.033 ml/g body weight) was administered subcutaneously to avoid fluid loss following surgery. The dose of CS/Cromolyn sodium was selected in accordance with previous publications.

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Induction and measurement of local HRARs in rat skins [2]
SIN induced local HRARs in rats was performed according to the methods described previously with modifications. SD rats were randomly divided into different groups. As positive control, rats were intradermally injected in the dorsal skin with anti-DNP-IgE (500 ng in 100 μl PBS). After 24 h, rats were challenged intravenously with or without 1 μg DNP-HSA containing 1% Evans blue dye. SIN (10 mg in 100 μl PBS) or PBS (100 μl) was intradermally injected in the dorsal skin of rats challenged with 1% Evans blue dye after 2 h. Cromolyn and cetirizine were dissolved in PBS. Tranilast was dissolved in CMC-Na (sodium carboxylmethyl cellulose). Cromolyn (30 mg/kg) was administered intravenously once before the challenge with DNP-HSA or injection of SIN or PBS. Cetirizine (15 mg/kg) and tranilast (400 mg/kg) were administered orally 1 h or 30 min before the challenge with DNP-HSA or injection of SIN or PBS. Vascular permeability was visualized 2 h later based on blue staining of the injection sites on the reverse side of the skin. Skin samples were harvested, and Evans blue dye was extracted from the tissues upon incubation at 55 °C for 48 h with 2 ml of formamide and quantified by OD at 610 nm.

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Induction and measurement of systemic HRARs in rats [2]
The experiment protocol was modified according to the previous description. Briefly, rats were intravenously injected with PBS or SIN at doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg. Cromolyn, cetirizine and tranilast were prepared as described above. Cromolyn (30 mg/kg) was administered intravenously once before injection of SIN or PBS. Cetirizine (15 mg/kg) and tranilast (400 mg/kg) were administered orally 1 h or 30 min before the injection of SIN or PBS. Changes in body temperature were monitored though rectal temperature every 30 min until recovery of normal body temperature. Plasma was collected in each experiment at different time intervals for different purposes. Rats were sacrificed 2 h later, and their lung tissues were collected for histological analysis or stored at −80 °C until later use. IL-4, IL-18, IL-33, and LTB4 production levels in the plasma were determined by ELISA according to the manufacturer’s instructions.

Absorption, Distribution and Excretion
1%
MOST OF ABSORBED DRUG IS EXCRETED UNCHANGED BY LIVER & KIDNEYS WITHIN A FEW DAYS & NONE APPEARS TO UNDERGO METABOLIC DEGRADATION. THE UNABSORBED PORTION (APPROX 80%) IS RECOVERABLE FROM FECES. FOLLOWING INHALATION, MAX PLASMA LEVEL...REACHED WITHIN SEVERAL MIN, & PLASMA T1/2 IS ONE TO ONE-HALF HOURS. /CROMOLYN DISODIUM/
THE AMT OF CROMOLYN...ABSORBED INTO BLOODSTREAM FOLLOWING INHALATION OF A DOSE OF 20 MG DOES NOT APPEAR TO EXERT ANY GENERALIZED PHARMACOLOGIC EFFECTS. /CROMOLYN DISODIUM/
THE SMALL AMT OF CROMOLYN THAT IS ABSORBED IS EXCRETED UNCHANGED BY LIVER & KIDNEYS... APPROX 10% OF A 20% MG DOSE...MAY REMAIN IN INHALER AFTER PATIENTS /USE/ &...APPROX 8% OF DOSE IS ABSORBED INTO BLOODSTREAM (PRIMARILY BY LUNG BUT ALSO BY GI TRACT). /CROMOLYN DISODIUM/
FATE OF CROMOLYN WAS EXAMINED IN 12 ASTHMATIC PATIENTS. MAX PLASMA CONCN (MEAN 9.2 NG/ML OBTAINED WITHIN 15 MIN OF INHALING 20 MG). ABSORPTION FROM LUNG IS RAPID, MOST OF INHALED DOSE IS SWALLOWED.
For more Absorption, Distribution and Excretion (Complete) data for CROMOLYN (10 total), please visit the HSDB record page.

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Metabolism / Metabolites
NO METABOLITES WERE DETECTED IN MAN & IN NINE MAMMALIAN SPECIES AFTER ORAL & IV ADMIN. /CROMOLYN DISODIUM/

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Biological Half-Life
1.3 hours
FATE OF CROMOLYN WAS EXAMINED IN 12 ASTHMATIC PATIENTS. AVG PLASMA T/2 WAS 81 MIN.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Although no published data exist on the use of cromolyn during lactation, maternal milk levels are likely to be very low and it is expected to be poorly absorbed from the infant's gastrointestinal tract. An expert panel considers use of cromolyn to be acceptable during breastfeeding.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Interactions
Studies demonstrating a lack of ion pair formation between sodium cromoglycate (cromolyn sodium) and alkylbenzdimethylamonium ions in rat intestine are briefly discussed. /Cromolyn sodium/
An analysis of the absorption and desorption isotherms for sodium cromoglycate (cromolyn sodium) and cromolyn sodium lactose moisture uptake is presented. Up to 15% moisture content had no effect on the tensile and shear properties of cromolyn sodium, due to adsorption into the interior of cromolyn sodium, leaving little absorbed moisture on the surface of the particles.
The mechanism of action of the mast cell stabilizers sodium cromoglycate and FPL-52694 as protective agents against ethanol induced gastric mucosal damage was investigated in the rat. Using an ex vivo gastric chamber model, various concn (l0-80 mg/ml) of the two agents were applied to the gastric mucosa prior to exposure to 40% ethanol. Both agents significantly reduced ethanol induced damage in a dose dependent manner. When given orally (80 mg/kg) both agents significantly reduced gastric damage induced by subsequent oral administration of absolute ethanol. Pretreatment with indomethacin did not significantly affect the protection afforded by FPL-52694, but did cause a partial reversal of the protective effect of sodium cromoglycate. Changes in gastric leukotriene C4 synthesis did not correlate with the protective effects of the two agents. Both mucosal and connective tissue mast cell numbers were significantly reduced following oral ethanol administration. In the groups pretreated with FPL-52694 or sodium cromoglycate, mucosal mast cell numbers were not significantly different from those in rats not treated with ethanol. Furthermore, the connective tissue mast cell numbers were significantly lower than in ethanol treated control rats, despite a greater than 95% reduction of ethanol induced hemorrhagic damage. These results therefore suggest that stimulation of gastric prostaglandin synthesis is not important in the mechanism of action of FPL-52694, and neither agent appears to reduce damage through a mechanism related to effects on gastric leukotriene C4 synthesis. The present studies further suggest that the protection afforded by pretreatment with sodium cromoglycate or FPL-52694 may be unrelated to effects of these agents on the connective tissue mast cell population in the stomach. /Sodium cromoglycate/
The effect of histamine on the absorption and clearance of inhaled cromolyn sodium (sodium cromoglycate) was examined in 7 mildly asthmatic patients with hyperresponsive airways and 8 normal subjects who inhaled either placebo or histamine followed by cromolyn. In the asthmatic group histamine inhalation led to a mean 24% reduction in the forced expiratory volume in 1 second but had no effect on the normal subjects. When compared with the inhaled placebo, histamine incr the initial pulmonary absorption of cromolyn without influencing the total amount of drug absorbed in both asthmatics and normals. These observations suggest that the pharmacokinetics of the inhaled drug may be altered significantly by inflammatory mediators present at the site of drug absorption from the airways. /Cromolyn sodium/
For more Interactions (Complete) data for CROMOLYN (9 total), please visit the HSDB record page.

[1]. Treatment of mice with cromolyn sodium after reperfusion, but not prior to ischemia, attenuates small intestinal ischemia-reperfusion injury. Mol Med Rep, 2013. 8(3): p. 928-34.

[2]. Sinomenine-induced histamine release-like anaphylactoid reactions are blocked by tranilast via inhibiting NF-κB signaling. Pharmacol Res. 2017 Aug 31. pii: S1043-6618(17)30796-X.

[3]. Ng, G. and A. Ohlsson, Cromolyn sodium for the prevention of chronic lung disease in preterm infants. Cochrane Database Syst Rev, 2012. 6: p. CD003059.

Chromoglicic acid is a solid. (NTP, 1992)
Cromoglycic acid is a dicarboxylic acid that is the bis-chromone derivative of glycerol. It is effective as a mast cell stabilizer. It has a role as a calcium channel blocker and an anti-asthmatic drug. It is a dicarboxylic acid and a member of chromones. It is a conjugate acid of a cromoglycate(1-).
A chromone complex that acts by inhibiting the release of chemical mediators from sensitized mast cells. It is used in the prophylactic treatment of both allergic and exercise-induced asthma, but does not affect an established asthmatic attack.
Cromolyn is a Mast Cell Stabilizer. The physiologic effect of cromolyn is by means of Decreased Histamine Release.
Cromolyn is a synthetic mast cell stabilizer with anti-inflammatory activity. Cromolyn probably interferes with the antigen-mediated calcium ion influx into mast cells. This prevents mast cell degranulation, resulting in mast cell stabilization and inhibition of the release of inflammatory mediators, such as histamine and leukotrienes, which are involved in type I allergic reactions. Cromolyn also prevents inflammatory mediator release from eosinophils.
A chromone complex that acts by inhibiting the release of chemical mediators from sensitized mast cells. It is used in the prophylactic treatment of both allergic and exercise-induced asthma, but does not affect an established asthmatic attack.
See also: Cromolyn Sodium (has salt form).

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Drug Indication
For the management of patients with bronchial asthma. Also used in the treatment of vernal keratoconjunctivitis, vernal conjunctivitis, and vernal keratitis.

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Mechanism of Action
Cromoglicate inhibits degranulation of mast cells, subsequently preventing the release of histamine and slow-reacting substance of anaphylaxis (SRS-A), mediators of type I allergic reactions. Cromoglicate also may reduce the release of inflammatory leukotrienes. Cromoglicate may act by inhibiting calcium influx.
One important action of cromolyn is believed to be the inhibition of pulmonary mast cell degranulation in response to a variety of stimuli, including the interaction between cell-bound IgE and specific antigen. ... The release of histamine and other granular contents, as well as the production of leukotrienes, can be shown to be markedly reduced in vitro by cromolyn. However, its efficacy and potency are highly dependent on the source of the mast cells.
... Attention has been focused on the ability of cromolyn to reverse various functional changes in leukocytes obtained from the blood of asthmatic subjects undergoing allergen challenge, such as increased expression of membrane-bound receptors.
... Low concentrations (100 nM) of cromolyn can suppress completely the activation effects of chemoattractant peptides of human neutrophils, eosinophils, or monocytes.
The mechanisms of action of cromolyn remain relatively poorly defined. Most attention has been focused on the ability of cromolyn to reduce the accumulation of intracellular Ca +2 induced by antigen in sensitized mast cells. One biochemical correlate of the reduction of histamine release from mast cells by cromolyn is the enhanced phosphorylation of a 78,000-dalton protein. Unfortunately, these observations have been made using rather high concn of cromolyn (50 to 200 uM), and their relationship to therapeutic response has yet to be established.
For more Mechanism of Action (Complete) data for CROMOLYN (6 total), please visit the HSDB record page.

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Therapeutic Uses
Anti-Asthmatic Agents
A LARGE PROPORTION OF CHILDREN WITH CHRONIC, INTRACTABLE ASTHMA (MILD OR SEVERE) EXPERIENCE EITHER PARTIAL OR COMPLETE PROTECTION AFTER ORAL INHALATION OF CROMOLYN. /CROMOLYN DISODIUM/
...EVIDENCE APPEARS TO INDICATE THAT PATIENTS WITH EXTRINSIC ASTHMA /KNOWN HYPERSENSITIVITY TO AN EXTRINSIC ALLERGEN/ ARE MORE LIKELY TO RESPOND TO CROMOLYN THAN PATIENTS WITH INTRINSIC ASTHMA /NO SUCH HYPERSENSITIVITY KNOWN/. HOWEVER, IT IS NOT CURRENTLY POSSIBLE TO PREDICT WHICH PATIENTS WILL RESPOND SATISFACTORILY TO CROMOLYN. /CROMOLYN DISODIUM/
THE INHALATION OF CROMOLYN SHORTLY BEFORE EXERCISE LESSENS BRONCHOCONSTRICTION THAT SOME ASTHMATIC PATIENTS THEN DEVELOP. THIS EFFECT MAY BE ENHANCED IF PATIENT IS RECEIVING CONTINUOUS THERAPY. /CROMOLYN DISODIUM/
For more Therapeutic Uses (Complete) data for CROMOLYN (20 total), please visit the HSDB record page.

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Drug Warnings
ANAPHYLAXIS, VASCULITIS, OR OTHER SERIOUS ADVERSE EFFECTS HAVE NOT BEEN REPORTED IN MAN. URTICARIA & MACULOPAPULAR RASHES HAVE OCCURRED RARELY BUT HAVE CLEARED WHEN DRUG WAS WITHDRAWN. EOSINOPHILIC PNEUMONIA HAS BEEN ASSOCIATED WITH /INHALATION/ ADMIN OF CROMOLYN IN TWO PATIENTS. /DISODIUM/
DESCRIBED IS A 42 YR OLD MALE PATIENTS WHO DEVELOPED SEVERE BRONCHOCONSTRICTION AFTER INHALING SODIUM CROMOGLYCATE (CROMOLYN).
A STUDY OF THE FREQUENCY OF ADVERSE REACTIONS (DERMATITIS, MYOSITIS, GASTROENTERITIS) TO CROMOLYN SODIUM, 0.5%, IN 375 ASTHMATIC PATIENTS, IS PRESENTED. THE FREQUENCY RATES WERE FOUND TO BE 2%; REACTIONS WERE NONLIFE THREATENING & COMPLETELY REVERSIBLE.
SEVERE NASAL CONGESTION DEVELOPED IN 13 YR OLD ASTHMATIC PATIENTS AFTER 4 WK OF THERAPY WITH CROMOLYN & DISAPPEARED WITHIN 24 HR OF DISCONTINUANCE OF THERAPY. REACTION OCCURRED AGAIN WHEN REINITIATION OF CROMOLYN WAS ATTEMPTED 3 DAYS & 3 WEEKS AFTER FIRST ATTACK.
For more Drug Warnings (Complete) data for CROMOLYN (25 total), please visit the HSDB record page.

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Pharmacodynamics
Cromoglicate or cromolyn (USAN), a synthetic compound, inhibits antigen-induced bronchospasms and, hence, is used to treat asthma and allergic rhinitis. Cromoglicate is used as an ophthalmic solution to treat conjunctivitis and is taken orally to treat systemic mastocytosis and ulcerative colitis.

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Disodium cromoglycate is an organic sodium salt that is the disodium salt of cromoglycic acid. It has a role as an anti-asthmatic drug and a drug allergen. It contains a cromoglycate(2-).
Cromolyn Sodium is the sodium salt form of cromolyn, a mast cell stabilizer with anti-inflammatory activity. Cromolyn sodium probably interferes with the antigen-stimulated calcium transport across the mast cell membrane, thereby inhibiting mast cell release of histamine, leukotrienes, and other substances that cause hypersensitivity reactions. Cromolyn sodium also inhibits eosinophil chemotaxis.
A chromone complex that acts by inhibiting the release of chemical mediators from sensitized mast cells. It is used in the prophylactic treatment of both allergic and exercise-induced asthma, but does not affect an established asthmatic attack.
See also: Cromolyn (has active moiety).

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In conclusion, treatment of mice with CS at early reperfusion, but not prior to ischemia, displays promising therapeutic benefits against IIRI. Appropriate MC activation can suppress inflammation by degrading ET-1; however, sustained MC activation may exacerbate inflammation by releasing tryptase, histamine and pro-inflammatory cytokines.[1]

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Zhengqing Fengtongning (ZQFTN), the pharmaceutical preparation of sinomenine (SIN) derived from the medicinal plant Sinmenium acutum, is well-known in China as an effective treatment for rheumatoid arthritis (RA). However, its histamine-release anaphylactoid reactions (HRARs) occur often in some patients. Therefore, it is desirable to establish effective clinical protocols to manage such HRARs. In the study, rat models with systemic HRARs and local HRARs of the skin were established. The level of vascular permeability and mast cell numbers was determined by quantitative analysis using Evans blue dye and histological assays. The levels of histamine, leukotriene B4 (LTB4) and IL-33 in plasma were detected by UHPLC-SPE-MS, ELISA and immunohistochemistry assays, respectively. The results demonstrated that SIN significantly induced both systemic and local HRARs in rats, showing significant decrease of body temperature, increases in vascular permeability in skin, injury of lung tissues and mast cell infiltration and IL-33 expression in skin and lung tissues. Mechanistic study showed that tranilast could prevent SIN-triggered HRARs via inhibition of H1 receptor gene expression and NF-κB signaling. Our findings provide evidence that mast cell membrane stabilizers and H1 receptor blockers effectively prevent SIN-induced HRARs, and Cromolyn, cetirizine and tranilast can be used in the clinic for the management of HRARs induced by ZQFTN. [2]

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Background: Chronic lung disease (CLD) frequently occurs in preterm infants and has a multifactorial aetiology including inflammation. Cromolyn sodium is a mast cell stabiliser that inhibits neutrophil activation and neutrophil chemotaxis and may, therefore, have a role in the prevention of CLD.

Objectives: To determine the effect of prophylactic administration of Cromolyn sodium on the incidence of CLD, mortality or the combined outcome of mortality or CLD at 28 days of life in preterm infants at risk of CLD.

Search methods: The search strategy of the Cochrane Neonatal Review Group was used to identify studies. Searches were made of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2009), MEDLINE, EMBASE, CINAHL up to and including July 2009, personal files and reference lists of identified trials. For this update the same data bases were searched on 12 April 2012. In addition, on the same date, abstracts from the Pediatric Academic Societies' Annual Meetings (2000 to 2012) were searched on the website PAS2View(TM) as was the Web of Science website using the two previously identified trials as starting points.

Selection criteria: Randomised or quasi-randomised controlled clinical trials involving preterm infants. Initiation of cromolyn sodium administration during the first two weeks of life. The intervention had to include administration of cromolyn sodium by nebuliser or metered dose inhaler with or without spacer device versus placebo or no intervention. Eligible studies had to include at least one of the following outcomes: overall mortality, CLD at 28 days, CLD at 36 weeks' postmenstrual age (PMA), or the combined outcome mortality or CLD at 28 days.

Data collection and analysis: The standard method for The Cochrane Collaboration as described in the Cochrane Handbook for Systematic Reviews of Interventions was used. Risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) are reported for dichotomous outcomes and weighted mean difference (WMD) for continuous data. A fixed-effect model was used for meta-analysis. Heterogeneity was examined using the I(2) statistic.

Main results: Two eligible studies were identified with small numbers of infants enrolled. Prophylaxis with Cromolyn sodium did not result in a statistically significant effect on the combined outcome of mortality or CLD at 28 days; CLD at 28 days or at 36 weeks' PMA; or CLD in survivors at 28 days or at 36 weeks' PMA. Prophylaxis with cromolyn sodium did not show a statistically significant difference in overall neonatal mortality, incidence of air leaks, necrotising enterocolitis, intraventricular haemorrhage, sepsis, and days of mechanical ventilation. No side effects were noted. Further research does not seem to be justified. Authors' conclusions: There is currently no evidence from randomised trials that cromolyn sodium has a role in the prevention of CLD. Cromolyn sodium cannot be recommended for the prevention of CLD in preterm infants. [3]

C23H16O11

468.36654

468.069

16110-51-3

Cromolyn sodium;15826-37-6;Cromoglicic acid-d5;2140317-08-2

2882

Colorless crystals from ethanol + ether

1.623

752.3ºC at 760 mmHg

241-242ºC

263.9ºC

1.08E-23mmHg at 25°C

1.681

2.114

3

11

8

34

835

0

OC(COC1=CC=CC2=C1C(C=C(C(O)=O)O2)=O)COC3=CC=CC4=C3C(C=C(C(O)=O)O4)=O

IMZMKUWMOSJXDT-UHFFFAOYSA-N

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)

5-[3-(2-carboxy-4-oxochromen-5-yl)oxy-2-hydroxypropoxy]-4-oxochromene-2-carboxylic acid

cromolyn; Cromoglicic acid; 16110-51-3; Cromoglycic acid; Cromoglicate; Acido cromoglicico; Acide cromoglicique; Acidum cromoglicicum;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)