MEDICAMENT COMPOSITIONS CONTAINING ANTICHOLINERGICALLY-EFFECTIVE COMPOUNDS AND BETAMIMETICS
A pharmaceutical composition comprising: (a) an anticholinergic selected from glycopyrronium bromide or an ester of a bi- or tricyclic amino alcohol of formula (I) wherein: Q, R, R′, and Z are defined in the claims and an equivalent of an anion X counters the positive charge of the N atom; and (b) a betamimetic selected from the group consisting of: formoterol; salmeterol; 4-hydroxy-7-[2-{[2-{[3-(2-phenylethoxy)propyl]sulfonyl}ethyl]amino}ethyl]-2(3H)-benzothiazolone; 1-(2-fluoro-4-hydroxyphenyl)-2-[4-(1-benzimidazolyl)-2-methyl-2-butylamino]ethanol; 1-[3-(4-methoxybenzylamino)-4-hydroxyphenyl]-2-[4-(1-benzimidazolyl)-2-methyl-2-butylamino]ethanol; 1-[2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl]-2-[3-(4-N,N-dimethylaminophenyl)-2-methyl-2-propylamino]ethanol; 1-[2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl]-2-[3-(4-methoxyphenyl)-2-methyl-2-propylamino]ethanol; 1-[2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl]-2-[3-(4-n-butyloxyphenyl)-2-methyl-2-propylamino]ethanol; and 1-[2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl]-2-{4-[3-(4-methoxyphenyl)-1,2,4-triazol-3-yl]-2-methyl-2-butylamino}ethanol, and a pharmacologically compatible acid addition salt thereof, and its use in the therapy of respiratory ailments.
1 . A pharmaceutical composition comprising:
(a) an anticholinergic selected from glycopyrronium bromide or an ester of a bi- or tricyclic amino alcohol of formula (I)
wherein:
Q is one of the groups —CH 2 —CH 2 —, —CH═CH—, or
R is methyl, ethyl, or propyl optionally substituted by fluorine or hydroxy,
R′ is methyl, ethyl, or propyl, and
an equivalent of an anion X counters the positive charge of the N atom; and
Z is one of the groups
wherein:
Y is a single bond or an O atom,
R 1 is hydrogen, hydroxy, methoxy, ethoxy, propoxy, methyl, ethyl, propyl, hydroxymethyl, hydroxyethyl, or hydroxypropyl,
R 2 is a thienyl, phenyl, or cyclohexyl group, wherein these groups are optionally substituted by methyl, and thienyl and phenyl are optionally substituted by fluorine or chlorine, and
R 3 is hydrogen, or a thienyl or phenyl group which is optionally substituted by fluorine, chlorine, or methyl; and
(b) a betamimetic selected from the group consisting of: formoterol; salmeterol; 4-hydroxy-7-[2-{[2-{[3-(2-phenylethoxy)propyl]sulfonyl}ethyl]amino}ethyl]-2(3H)-benzothiazolone; 1-(2-fluoro-4-hydroxyphenyl)-2-[4-(1-benzimidazolyl)-2-methyl-2-butylamino]ethanol; 1-[3-(4-methoxybenzylamino)-4-hydroxyphenyl]-2-[4-(1-benzimidazolyl)-2-methyl-2-butylamino]ethanol; 1-[2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl]-2-[3-(4-N,N-dimethylaminophenyl)-2-methyl-2-propylamino]ethanol; 1-[2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl]-2-[3-(4-methoxyphenyl)-2-methyl-2-propylamino]ethanol; 1-[2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl]-2-[3-(4-n-butyloxyphenyl)-2-methyl-2-propylamino]ethanol; and 1-[2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl]-2-{4-[3-(4-methoxyphenyl)-1,2,4-triazol-3-yl]-2-methyl-2-butylamino}ethanol, and a pharmacologically compatible acid addition salt thereof.
2 . The pharmaceutical composition according to claim 1 , wherein the anticholinergic is an ester of a bi- and tricyclic amino alcohol of formula (I)
wherein:
Q is one of the groups —CH 2 —CH 2 —, —CH═CH—, or
R is methyl or ethyl,
R′ is methyl, and
anion X is bromide; and
Z is one of the groups
wherein:
R 1 is hydrogen, hydroxy, or hydroxymethyl,
R 2 is a thienyl, phenyl, or cyclohexyl group, and
R 3 is hydrogen, or a thienyl or phenyl group.
3 . The pharmaceutical composition according to claim 1 , wherein the anticholinergic is a salt of tiotropium.
4 . The pharmaceutical composition according to claim 1 , wherein the anticholinergic is tiotropium bromide.
5 . The pharmaceutical composition according to claim 1 , wherein the betamimetic is formoterol or salmeterol, or a pharmacologically compatible acid addition salt thereof.
6 . The pharmaceutical composition according to claim 1 , wherein the anticholinergic is tiotropium bromide and the betamimetic is formoterol, or a pharmacologically compatible acid addition salt thereof.
7 . The pharmaceutical composition according to claim 1 , wherein the anticholinergic is tiotropium bromide and the betamimetic is salmeterol, or a pharmacologically compatible acid addition salt thereof.
8 . The pharmaceutical composition according to claim 1 , wherein the anion X is selected from the group consisting of: chloride, bromide, and methanesulfonate,
9 . The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is an inhaled pharmaceutical composition.
10 . A process for the production of a pharmaceutical composition according to claim 1 , comprising:
(a) mixing the anticholinergic and the betamimetic; and optionally
(b) adding an adjuvant and/or carrier materials.
11 . A method of treating respiratory ailments by administering to a host in need of such treatment a pharmaceutical composition according to claim 1 .
12 . The method according to claim 11 , wherein the respiratory ailment is asthma or COPD.
13 . A method of treating respiratory ailments by administering to a host in need of such treatment a pharmaceutical composition according to claim 9 .
14 . The method according to claim 13 , wherein the respiratory ailment is asthma or COPD.