Patent EA-004657-B1 (EA)
Title: A pharmaceutical composition based on anticholinergically effective compounds, method of production and use thereof
Inventor: PAIRET MICHEL
IPC: A61P11/08
Filed: 2000-05-03
Abstract: 1. Pharmaceutical composition comprising anticholinergic, which is selected from glycopyrronium bromide or esters bi- and tricyclic alkamines of the formula (I) where A is a radical of the formula (II) where Q is one of bivalent group -CH2-CH2-, -CH=CH- or R is methyl, ethyl or propyl optionally substituted with fluorine or hydroxy, R' is methyl, ethyl or propyl, preferably methyl, and N-atom positive charge is opposed to X anion equivalent selected from the group comprising chloride, bromide and metasulfonat, preferably bromide, Z is one of the group, wherein Y is a single bond or O-, R<1> is hydrogen, OH, methoxy, ethoxy, propoxy, methyl, ethyl, propyl, hydroxymethyl, hydroxyethyl and hydroxypropyl, R<2> is thienyl, phenyl or cyclohexyl radical, and said radicals can be also substituted with methyl, thienyl and phenyl in addition can be substituted with fluorine or chlorine, R<3> is hydrogen or thienyl or phenyl radical, which can be optionally substituted with fluorine, chlorine or methyl, optionally substituted in the form of racemates thereof, enantiomers thereof, diastereomers and mixtures thereof, and beta-mimetic selected from the group comprising formoterol, salmeterol, 4-hydroxy-7-[2-{[2-{[3-(2-phenylethoxy)propyl]sulphonyl}ethyl]-amino}ethyl]-2(3H)-benzothiazolone, 1-(2-fluoro-4-hydroxyphenyl)-2-[4-(1-benzimidazolyl)-2-methyl-2-butylamino]ethanol, 1-[3-(4-methoxybenzyl-amino)-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-methyl2-propylamino]ethanol, 1-[2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl]-2-[3-(4-n-butyloxyphenyl)-2methyl-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, optionally in the form of racemates thereof, enantiometers thereof, diastereometers and mixtures thereof, and also optionally in the form of pharmacologically acceptable acid-additive salts thereof. 2. Pharmaceutical composition of claim 1 characterized in that anticholinergic is selected from the group of esters bi- and tricyclic alkamines of the formula (I) where A is a radical of the formula (II) wherein Q is one of bivalent group -CH2-CH2-, -CH=CH- or R is methyl, or ethyl, R' is methyl and N-atom positive charge is opposed to X anion equivalent selected from the group comprising chloride, bromide and metasulfonat, preferably bromide, Z is one of the group wherein Y is O-atom, R<1> is hydrogen, OH or hydroxymethyl, R<2> is thienyl, phenyl or cyclohexyl radical, R<3> is hydrogen or thienyl or phenyl radical, which can be optionally in the form of racemates thereof, enantiomers thereof, diastereomers and mixtures thereof. 3. Pharmaceutical composition of claim 1 or 2 characterized in that anticholinergic is selected from tiotropium salts. 4. Pharmaceutical composition of claim 1, 2 or 3 characterized in that anticholinergic, which has prolonged action, is tiotropium salts. 5. Pharmaceutical composition according to any of claims 1-4 characterized in that beta-mimetic, which has prolonged action, is selected from formoterol and salmeterol, optionally in the form of racemates thereof, enentiometer thereof, diastereometers and mixtures thereof, and also optionally in the form of pharmacologically acceptable acid-additive salts. 6. Pharmaceutical composition according to any of claims 1-5 characterized in that anticholinergic is tiotropium bromide, and beta-mimetic is formoterol fumarat. 7. Pharmaceutical composition according to any of claims 1-5 characterized in that anticholinergic is tiotropium bromide, and beta-mimetic is salmeterol. 8. Pharmaceutical composition according to any of claims 1-7 characterized as a composition, which is administered by inhalation. 9. Pharmaceutical composition according to any of claims 1-8 characterized in that anticholinergic and beta-mimetic, and also, if necessary, other adjuvants and/or carriers are mixed according to as a composition, which is administered by inhalation. 10. Use of a composition according to any of claims 1-8 for preparing a medicament for treating diseases of the respiratory tract. 11. Use of a composition according to claim 10 for preparing a medicament for treating asthma or chronic obstructive lung diseases. 12. Use of a composition according to claim 11 for preparing a medicament for treating asthma or chronic obstructive lung diseases with minimal heart side reaction.