Combinations of muscarinic receptor antagonist and a beta-2 adrenoreceptor agonist

Patent metadata

Field	Value
Publication number	US-2025339413-A1
Application number	US-202519270808-A
Country	US
Kind code	A1
Filing date	Jul 16, 2025
Priority date	Dec 1, 2009
Publication date	Nov 6, 2025
Grant date	—

Abstract

Combinations of a muscarinic acetylcholine receptor antagonist and a beta 2 agonist for inhaled administration via the nose or mouth, compositions thereof, and methods of using them are provided.

First claim

1 . A pharmaceutical combination product comprising
a) a compound of the formula

wherein
X − is a pharmaceutically acceptable anion; and
b) a compound of the formula:

or a pharmaceutically acceptable salt thereof.

2 . A product according to claim 1 wherein for Compound (I) the pharmaceutically acceptable anion is selected from the group consisting of chloride, bromide, iodide, hydroxide, sulfate, nitrate, phosphate, acetate, trifluoroacetate, fumarate, citrate, tartrate, oxalate, succinate, mandelate, methanesulfonate or p-toluenesulfonate.

3 . A product according to claim 1 or claim 2 wherein Compound (I) is 4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide.

4 . A product according to any of claims 1 to 3 wherein Compound (II) is 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol α-phenylcinnamate.

5 . A product according to any of claims 1 to 3 wherein Compound (II) is 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol triphenylacetate.

6 . A product according to any of claims 1 to 5 wherein Compound (I) and Compound (II) are presented in a form adapted for separate administration.

7 . A product according to any of claims 1 to 5 wherein Compound (I) and Compound (II) are presented in a form adapted for sequential administration.

8 . A product according to any of claims 1 to 5 wherein Compound (I) and Compound (II) are presented in a form adapted for simultaneous administration.

9 . A product according to claim 8 wherein Compound (I) and Compound (II) are in admixture with each other.

10 . A product according to any of claims 1 to 9 wherein at least one of Compound (I) and Compound (II) is formulated with a pharmaceutically acceptable carrier or excipient.

11 . A product according to any of claims 1 to 9 in a form suitable for administration by oral or nasal inhalation.

12 . A product according to claim 11 wherein the form is suitable for administration by inhalation via a medicament dispenser selected from a reservoir dry powder inhaler, a unit-dose dry powder inhaler, a pre-metered multi-dose dry powder inhaler, a nasal inhaler or a pressurized metered dose inhaler.

13 . A product as claimed in claim 12 wherein each of Compound (I) and Compound (II) is presented in the form of a dry powder composition.

14 . A product as claimed in claim 13 wherein Compound (I) and Compound (II) are presented as separate compositions.

15 . A product as claimed in claim 13 wherein Compound (I) and Compound (II) are presented as admixed compositions.

16 . A product as claimed in claim 14 or 15 wherein at least one of said compositions of Compound (I) or Compound (II) contains a carrier.

17 . A product as claimed in claim 14 or 15 wherein both compositions of Compound (I) and Compound (II) contain a carrier.

18 . A product as claimed in claim 16 or 17 wherein the carrier is lactose.

19 . A product as claimed in any of claims 13 to 18 wherein at least one of said compositions contains a temary agent.

20 . A product as claimed in any of claims 13 to 18 wherein both compositions contain a ternary agent.

21 . A product as claimed in claim 19 wherein the ternary agent is magnesium stearate.

22 . A product as claimed in claim 20 , wherein the ternary agent in both compositions is magnesium stearate.

23 . A product as claimed in claim 22 , wherein magnesium stearate is present in an amount of about 0.6% w/w in a composition of Compound (I), and/or an amount of about 1.0% w/w in a composition of Compound (II).

24 . A product as claimed in any one of claims 13 to 23 wherein said separate or admixed compositions are in unit dose form.

25 . A product as claimed in claim 24 wherein the unit dose form is in a capsule, cartridge or blister pack.

26 . A product as claimed in any of claims 13 to 25 wherein the composition is administered via a dry powder inhaler.

27 . A product as claimed in claim 26 wherein said inhaler permits separate containment of the active ingredients.

28 . A product as claimed in any one of claims 1 to 27 wherein Compound (I) is present in an amount of about 1 to 1000 meg/dose.

29 . A product as claimed in any one of claims 1 to 27 wherein Compound (I) is present in an amount of 125 mcg/dose.

30 . A product as claimed in any one of claims 1 to 27 wherein Compound (I) is present in an amount of 62.5 mcg/dose.

31 . A product according to any one of claims 1 to 30 wherein Compound (II) is present in an amount of 1 to 100 meg/dose.

32 . A product according to any one of claims 1 to 30 wherein Compound (II) is present in an amount of 25 mcg/dose.

33 . A dry powder inhaler containing a product as defined in any of claims 1 to 32 .

34 . A product according to claim 1 1 wherein each of Compound (I) and Compound (II) is presented in the form of a spray composition for inhalation.

35 . A product according to claim 34 wherein Compound (I) and Compound (II) are presented as separate or admixed compositions.

36 . A product according to claim 34 or claim 35 wherein the spray composition is an aqueous solution or suspension.

37 . A product according to claim 34 or 35 wherein the spray composition is an aerosol composition.

38 . A product according to claim 37 comprising as propellant a fluorocarbon or hydrogen-containing chlorofluorocarbon.

39 . A product according to claim 38 wherein the propellant is a hydrofluoroalkane.

40 . A product according to claim 39 wherein the propellant is 1, 1, 1,2-tetrafluoroethane, 1,1, 1,2,3,3,3-heptafluoro-n-propane or a mixture thereof.

41 . A product according to any of claims 34 to 40 further comprising a co-solvent.

42 . A product according to any of claims 34 to 41 further comprising a surface-active agent.

43 . A product according to any of claims 1 to 42 further comprising an inhaled corticosteroid selected from the group consisting of fluticasone propionate, mometasone furoate, budesonide and 6α,9α-difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester (fluticasone furoate).

44 . A product according to claim 43 wherein the inhaled corticosteroid is 6α,9α-difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester (fluticasone furoate).

45 . A product according to claim 44 , wherein 6α,9α-difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester (fluticasone furoate) is present in an amount of 100 mcg/dose.

46 . A pressurised metered dose inhaler containing a product as defined

Assignees

• Glaxo Group Ltd

Inventors

• Baker Darrell
• Bruce Mark
• Crater Glenn
• Noga Brian
• Thomas Marian
• Wire Patrick

Classifications

• B65D75/36

  one sheet or blank being recessed and the other formed of relatively stiff flat sheet material, e.g. blister packages {, the recess or recesses being preformed (B65D73/0057, B65D73/0092 take precedence)} · CPC title

• A61K9/0075

  for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles · CPC title

• C07H15/26

  Acyclic or carbocyclic radicals, substituted by hetero rings · CPC title

• C07H15/203

  Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems · CPC title

• A61K31/7052

  having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides · CPC title