Bis-chromonyl compounds of the formula: ##SPC1## And therapeutically acceptable salts, esters and amides thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are the same or different and each is H or halogen, lower alkyl, hydroxy, lower alkoxy, substituted lower alkyl or substituted lower alkoxy, and X is a saturated or unsaturated, substituted or unsubstituted, straight or branched polymethylene chain which may be interrupted by one or more carbocyclic rings or oxygen-containing heterocyclic rings, oxygen atoms or carbonyl groups are particularly useful for the relief and prophylaxis of asthma when mixed with bronchodilators. 14 Claims, No Drawings
This application is a continuation of application Ser. No. 650,663, filed July 3, 1967, which in turn is a continuation of application Ser. No. 536,285, filed Mar. 22, 1966, both earlier applications being now abandoned.
There are described compounds of formula I, ##STR1## and pharmaceutically acceptable derivatives thereof, in which R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are the same or are different and each is a hydrogen or halogen atom or an alkyl, hydroxy, alkoxy, or substituted alkyl or alkoxy group, (for example a hydroxy-alkoxy, alkoxyalkoxy or carboxyalkoxy group), and X is a saturated or unsaturated, substituted or unsubstituted, straight or branched hydrocarbon chain which may be interrupted by a carbocyclic or heterocyclic ring, or by one or more oxygen atoms or carbonyl groups. There are also described processes for making the compounds and pharmaceutical compositions, for the treatment of asthma, containing the compounds.
The use of quaternary salts of promethazine by the inhalation route is described. The thus administered compositions provide new, non-toxic, potent means for relieving bronchial spasm and bronchoconstriction in warm-blooded animals.
There are provided compounds of formula I, ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.7 may be the same or different, and are hydrogen, hydroxy, alkoxy, alkoxy substituted by phenyl, acyl, amino, acylamino, alkenyl, halogen, or alkyl, provided that at least one of R.sup.1, R.sup.2, R.sup.3 and R.sup.7 are other than hydrogen and hydroxy, Or an adjacent pair of R.sup.1, R.sup.2, R.sup.3 and R.sup.7 represent a chain --COCH=CH--O--, X is a hydrocarbon chain containing from 2 to 10 carbon atoms and optionally substituted by a hydroxy group, and E is a carboxy group or a tetrazole group, And pharmaceutically acceptable derivatives thereof. The compounds are indicated for use as antagonists of SRS-A.
There is described a composition comprising a substantially clear, sterile aqueous solution containing as active ingredient a therapeutically useful proportion of 1,3-bis(2-carboxy-chromon-5-yloxy)-propan-2-ol, or a pharmaceutically acceptable (e.g. the di-sodium) salt thereof, or of 5,5'-[[5,5'-(2-hydroxytrimethylene)dioxy]bis[4-oxo-4H-1-benzopyran-2-yl]]t etrazole, or a pharmaceutically acceptable (e.g. the di-sodium) salt thereof. The composition is indicated for the treatment of conditions of the eye and the nose.
A powder composition comprising a mixture of the di-sodium salt of 1,3-bis(2-carboxychromon-5-yloxy) propan-2-ol having a mass median diameter in the range of 2 to 4, preferably 2.5 to 3.5 microns and a solid carrier acceptable in the lungs and having a particle size in the range of from 30 to 150 microns.