Quinuclidine derivatives and medicinal compositions containing the same

• US 8,513,279 B2
• Filed: 01/20/2012
• Issued: 08/20/2013
• Est. Priority Date: 07/14/1999
• Status: Expired due to Fees

• Current Assignee: Almirall, S.A. (Grupo Corporativo Landon SL)
• Original Assignee: Almirall, S.A. (Grupo Corporativo Landon SL)
• Inventors: Fernandez Forner, Maria Dolors, Prat Quinones, Maria, Buil Albero, Maria Antonia
• Primary Examiner(s): Aulakh, Charanjit
• Application Number:
  US13/354,873
• Publication Number:
  US 20120122826A1
• Time in Patent Office: 578 Days
• Field of Search: 514/305, 514/826
• US Class Current: 514/305
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/06 Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 11/14 Antitussive agents
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/06 Anti-spasmodics
• CPC Class Codes: A61P 13/10 : of the bladder
• CPC Class Codes: A61P 27/16 : Otologicals
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 453/02 : containing not further condensed quinuclidine ring systems

Abstract

The invention provides 3-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide in combination with a steroid, and methods of using it for treatment of respiratory disorders.

Claims

1. A pharmaceutical composition comprising:

(i) 3-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane or an enantiomer, mixture of enantiomers, or a racemate thereof, wherein an anion X⁻

with a single negative charge is associated with the positive charge of the nitrogen atom; and

(ii) a steroid.

2. The composition of claim 1 further comprising a pharmaceutically acceptable carrier or diluent.

3. The composition of claim 1 wherein the anion X⁻

is chloride, bromide, iodide, sulfate, nitrate, phosphate, acetate, maleate, fumarate, citrate, oxalate, succinate, tartrate, malate, mandelate, methanesulfonate, p-toluenesulfonate, or trifluoroacetate.

4. The composition of claim 1 which is suitable for inhalation.

5. The composition of claim 1 wherein the composition is a liquid inhalant, powder inhalant, or inhalation aerosol.

6. The composition of claim 1 further comprising a phosphodiesterase IV inhibitor.

7. The composition of claim 6 further comprising a β

₂ agonist.

8. The composition of claim 1 further comprising a β

2 agonist.

9. The composition of claim 2 wherein the pharmaceutically acceptable carrier or diluent is lactose.

10. 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 the composition of claim 1.

11. The method of claim 10 further comprising administering an effective amount of a phosphodiesterase IV inhibitor.

12. The method of claim 11 further comprising administering an effective amount of β

2 agonist.