# US 9,750,726 B2 · Combinations of a muscarinic receptor antagonist and a beta-2 adrenoreceptor agonist > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,750,726 B2 - Document ID: US9750726B2 - Status: Granted - Kind: B2 - Application number: 14/970,945 - Filed: 2015-12-16 - Published: 2016-04-07 - Granted: 2017-09-05 - Earliest claimed: 2009-12-01 - Assignees: Glaxo Group Limited - Applicants: Glaxo Group Limited - Inventors: Darrell Baker; Mark Bruce; Glenn Crater; Brian Noga; Marian Thomas; Patrick Wire - Web page: https://patentgrep.com/patent/US9750726B2 ## CPC - A61K 31/439: the ring forming part of a bridged ring system, e.g. quinuclidine (8-azabicyclo [3.2.1] octanes A61K31/46) - A61K 9/0075: {for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles} - A61K 31/138: Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine (atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377) - A61K 31/7052: having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 11/00: Drugs for disorders of the respiratory system - A61P 11/02: Nasal agents, e.g. decongestants - A61P 11/06: Antiasthmatics - A61P 11/08: Bronchodilators - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 31/04: Antibacterial agents - A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - B65D 75/36: 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)} - C07H 15/203: Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems - C07H 15/26: Acyclic or carbocyclic radicals, substituted by hetero rings - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - B65D: CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES - C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13) - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract Combinations of a muscarinic acetylcholine receptor antagonist and a beta 2 agonist for inhaled administration via the nose or mouth, and methods of using them are provided. ## Claims ### Claim 1 A pharmaceutical combination product comprising: a) 4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide in an amount of about 62.5 mcg/dose, in the form of a dry powder; and b) 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol triphenylacetate, in an amount of about 25 mcg/dose, in the form of a dry powder, wherein said pharmaceutical combination product is suitable for once-daily administration, and compounds a) and b) are presented in a form adapted for simultaneous administration. ### Claim 2 (depends on 1) The product according to claim 1, in a dry powder composition form suitable for administration by inhalation via a medicament dispenser, selected from the group consisting of a reservoir dry powder inhaler, a unit-dose dry powder inhaler, and a pre-metered multi-dose dry powder inhaler. ### Claim 3 (depends on 2) The product according to claim 2, wherein 4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide and 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol triphenylacetate are separate dry powder compositions or admixed as a single dry powder composition. ### Claim 4 (depends on 3) The product according to claim 3, further comprising a carrier which comprises lactose. ### Claim 5 (depends on 3) The product according to claim 3, further comprising a ternary agent. ### Claim 6 (depends on 5) The product according to claim 5, further comprising a carrier; and wherein the ternary agent comprises magnesium stearate, wherein said magnesium stearate is present in an amount of about 0.6% w/w in the composition of 4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide, and/or an amount of about 1.0% w/w in a composition of 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol triphenylacetate. ### Claim 7 (depends on 3) The product according to claim 3, wherein said separate compositions are in unit dose form selected from the group consisting of a capsule, a cartridge or a blister. ### Claim 8 (depends on 1) The product according to claim 1, further comprising 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). ### Claim 9 (depends on 8) The product according to claim 8, wherein 6α,9αdifluoro-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 about 100 mcg/dose. ### Claim 10 A pharmaceutical combination product comprising: a) a first dry powder composition comprising 4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide, in an amount of about 62.5 mcg/dose; lactose; and magnesium stearate in an amount of about 0.6% w/w of said first dry powder composition; and b) a second dry powder composition comprising 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol triphenylacetate, in an amount of about 25 mcg/dose; lactose, and; magnesium stearate in an amount of about 1.0% w/w of said second dry powder composition; wherein said pharmaceutical combination product is suitable for once-daily administration, and wherein the first and second dry powder compositions are configured for simultaneous administration. ### Claim 11 (depends on 10) The product according to claim 10, wherein the first and second dry powder compositions are presented in a form suitable for administration by inhalation via a medicament dispenser, said medicament dispenser being selected from the group consisting of a reservoir dry powder inhaler, a unit-dose dry powder inhaler, and a pre-metered multi-dose dry powder inhaler. ### Claim 12 A pharmaceutical combination product comprising: a) 4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide in an amount of 62.5 mcg/dose, in the form of a dry powder; b) 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol triphenylacetate, in an amount of 25 mcg/dose, in the form of a dry powder, c) 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), in an amount of 100 mcg/dose, in the form of a dry powder, d) carrier excipient, and e) ternary agent, wherein said pharmaceutical combination product is suitable for once-daily administration, and compounds a), b) and c) are presented in a form adapted for simultaneous administration. ### Claim 13 (depends on 12) The pharmaceutical combination product of claim 12, wherein: a first dry powder composition comprises an admixture of compound a), compound b), carrier excipient d), and ternary agent e); and a second dry powder compositions comprises an admixture of compound c) and carrier excipient d). ### Claim 14 (depends on 12) The pharmaceutical combination product of claim 12, wherein the carrier excipient in said first and second dry powder compositions is lactose monohydrate, and the ternary agent in said first dry powder composition is magnesium stearate. ### Claim 15 (depends on 13) The pharmaceutical combination product of claim 13, wherein said first and second dry powder compositions are in unit dose form and in the form of a capsule, a cartridge or a blister. ### Claim 16 (depends on 12) The pharmaceutical combination product according to claim 12, in a dry powder composition form suitable for administration by inhalation via a medicament dispenser selected from a reservoir dry powder inhaler, a unit-dose dry powder inhaler, or a pre-metered multi-dose dry powder inhaler. ### Claim 17 (depends on 15) The pharmaceutical combination product according to claim 15, in a dry powder composition form suitable for administration by inhalation via a medicament dispenser selected from a unit-dose dry powder inhaler, or a pre-metered multi-dose dry powder inhaler.