Quinuclidine derivatives and medicinal compositions containing the same
View Patent ↗The invention provides 3-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane in salt form, pharmaceutical compositions comprising it, and methods of using it for treatment of respiratory disorders, in association with β 2 agonist.
1. A pharmaceutical composition comprising:
(i) 3-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane, wherein an anion X − is associated with the positive charge of the nitrogen atom and wherein X − is a pharmaceutically acceptable anion of a mono- or polyvalent acid; and
(ii) a β 2 agonist.
2. The composition of claim 1 comprising 3-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide.
3. The composition of claim 1 in admixture with a pharmaceutically acceptable carrier or diluent.
4. The composition of claim 3 comprising 3(S)-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane, wherein an anion X − is associated with the positive charge of the nitrogen atom and wherein X − is a pharmaceutically acceptable anion of a mono- or polyvalent acid.
5. The composition of claim 4 comprising 3(R)-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane, wherein an anion X − is associated with the positive charge of the nitrogen atom and wherein X − is a pharmaceutically acceptable anion of a mono- or polyvalent acid.
6. The composition of claim 1 wherein the pharmaceutical composition is suitable for inhalation.
7. The pharmaceutical composition according to claim 1 further comprising a steroid or phosphodiesterase IV inhibitor.
8. A method for treating chronic obstructive pulmonary disease, chronic bronchitis, bronchial hyperreactivity, asthma, or rhinitis which method comprises administering to a human or animal patient in need of such treatment an effective amount of:
(i) 3-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane, wherein an anion X − is associated with the positive charge of the nitrogen atom and wherein X − is a pharmaceutically acceptable anion of a mono- or polyvalent acid; and
(ii) a β 2 agonist.
9. The method according to claim 8 , wherein the anion X − is Br − .
10. The method of claim 8 comprising administering an effective amount of 3(S)-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane, wherein an anion X − is associated with the positive charge of the nitrogen atom and wherein X − is a pharmaceutically acceptable anion of a mono- or polyvalent acid.
11. The method of claim 10 comprising administering an effective amount of 3(R)-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane, wherein an anion X − is associated with the positive charge of the nitrogen atom and wherein X − is a pharmaceutically acceptable anion of a mono- or polyvalent acid.
12. The method of claim 8 wherein administration is by inhalation.
13. The method of claim 8 comprising administering an effective amount of a steroid or phosphodiesterase IV inhibitor.