Granted Patent B2

US 8,486,923 · App. 12/973,414 · Granted Jul 16, 2013

Abstract

Claims (20)

1. A method for the treatment of allergic rhinitis and/or allergic conjunctivitis in a patient, comprising administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition comprising, as sole active ingredients, a combination of

at least one antihistamine, a stereoisomer, a pharmaceutically acceptable salt, thereof, and

ciclesonide, pharmaceutically acceptable salts of ciclesonide, or epimers of ciclesonide optionally in any mixing ratio with ciclesonide

and a pharmaceutically acceptable carrier and/or one or more excipients, wherein the pharmaceutical composition is administered as one to four sprays per nostril once or twice a day, and wherein the dose of ciclesonide per actuation is 10μg to 400μg and the dose of antihistamine per actuation is 10μg to 500μg.

2. The method of claim 1 , wherein said patient is a human.

3. The method according to claim 1 , wherein the pharmaceutical composition is an aqueous pharmaceutical composition comprising the active ingredients together with one or more water-insoluble and/or water-low soluble substances, and wherein said pharmaceutical composition has an osmotic pressure of less than 290 mOsm.

4. The method according to claim 2 , wherein said pharmaceutical composition has an osmotic pressure of 150 mOsm or less.

5. The method according to claim 2 , wherein said pharmaceutical composition has an osmotic pressure of 60 mOsm or less.

6. The method according to claim 2 , wherein said pharmaceutical composition has an osmotic pressure of 40 mOsm or less.

7. The method according to claim 2 , wherein said pharmaceutical composition has an osmotic pressure of 20 mOsm or less.

8. The method according to claim 2 , wherein said pharmaceutical composition further comprises an osmotic pressure-controlling agent.

9. The method according to claim 2 , wherein said water-insoluble and/or water-low soluble substance is a cellulose.

10. The method according to claim 9 , wherein said cellulose is microcrystalline cellulose.

11. The method according to claim 2 , wherein said one or more water-insoluble and/or water-low soluble substances is/are present as solid particles in an aqueous medium.

12. The method according to claim 2 , wherein said pharmaceutical composition further comprises a water-soluble polymer substance.

13. The method according to claim 12 , wherein a combination of said water-insoluble substance and water-soluble polymer is present which is microcrystalline cellulose and carboxymethyl cellulose sodium.

14. The method according to claim 2 , wherein said pharmaceutical composition further comprises a surfactant and/or a wetting agent.

15. The method according to claim 1 , wherein the antihistamine is selected from the group consisting of (E)-6-[(E)-3-(1-pyrrolidinyl)-1-p-tolylpropenyl]-2-pyridineacrylic acid (ACRIVASTINE), 6,11-Dihydro-11-(1-methyl-4-piperidyliden)-5H-benzo[5,6]cyclohepta-[1,2-b]pyridine (AZATADINE), 4-[(4-chlorophenyl)methyl]-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1(2H)phthalazinone (AZELASTINE), (+)-(S)-4-[4-[1-(4-chlorophenyl)-1-(2-pyridyl)methoxy]piperidin-1-yl]-butanoic acid (BEPOTASTINE), (+/+)-[2-[4-(p-chloro-alpha-phenylbenzyl)-1-piperazinyl]ethoxy]-acetic acid (CETIRIZINE), (+)-2-{2-[(p-Chlor-alpha-methyl-alpha phenylbenzyl)oxy]-ethyl}-1-methylpyrrolidin (CLEMASTINE), 8-chloro-6,11-dihydro-11-(4-piperidylidene-5H-benzo[5,6]-cyclohepta-[1,2-b]pyridine (DESLORATADINE), [3-(4-Chlorophenyl)-3-pyridin-2-yl-propyl]-dimethylamine (DEXCHLORPHENIRAMINE), 4′-tert-butyl-4-[4-(diphenylmethoxy)-piperidino]butyrophenone (EBASTINE), [2-[4-[bis(p-fluorophenyl)methyl]-1-piperazinyl]ethoxy]-acetic acid (EFLETIRIZINE), 1-(2-ethoxyethyl)-2-hexahydro-4-methyl-1H-1,4-diazepin-1-ylybenzimidazole (EMEDASTINE), 3-amino-9,13b-dihydro-1H-dibenz[c,f]imidazo[1,5-a]azepine (EPINASTINE), (+/−)-p-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)piperidino]-butyl]-alpha-methylhydratropic acid (FEXOFENADINE), 3-[4-(8-fluoro-5,11-dihydrobenz[b]oxepino[4,3-b]pyridin-11-ylidene)-piperidin-1-yl]propionic acid (Research Code HSR-609), (−)-(3S,4R)-1-[cis-4-cyano-4-(p-fluorophenyl)cyclohexyl]-3-methyl-4-phenylisonipecotic acid (LEVOCABASTINE), [2-[4-[(R)-p-chloro-alpha-phenylbenzyl)-1-piperazinyl]ethoxy]-acetic acid (LEVOCETIRIZINE), ethyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinecarboxylate (LORATADINE), 2-[N-[1-(4-fluorobenzyl)-1H-benzimidazol-2-yl]-4-piperidinyl]-N-methyl-amino]pyrimidin-4(3H)-one (MIZOLASTINE), 1-(4-fluorobenzyl)-2-(piperidin-4-ylamino)-1H-benzimidazole (NORASTMIZOLE), 3-(10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5-ylidene)-N-methyl-1-propanamine (NORTRIPTYLINE), 9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (PEMIROLAST), 8-chloro-11-[1-(5-methylpyridin-3-ylmethyl)-piperidin-4-ylidene]-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (RUPATADINE), 1-[2-[(p-chloro-alpha-methyl-alpha-phenylbenzyl)-oxy]ethyl]hexahydro-1H-azepine (SETASTINE), S-(7-carboxy-4-hexyl-9-oxoxanthen-2-yl)-S-methylsulfoximine (SUDEXANOX), 1-(p-tert-butyl-phenyl)-4-[4′-(alpha-hydroxydiphenylmethyl)-t-piperidyl]-butanol (TERFENADINE), N-benzyl-N,N′-dimethyl-N-(2-pyridyl)-ethylenediamine (TRIPELENAMINE), 1-(4-fluorobenzyl)-2-(piperidin-4-ylamino)-1H-benzimidazole (TECASTEMIZOLE), stereoisomers thereof, pharmaceutically acceptable salts thereof, and mixtures thereof.

16. The method according to claim 1 , wherein the antihistamine is selected from the group consisting of azelastine, levocabastine, and pharmaceutically acceptable salts thereof.

17. The method according to claim 1 , wherein said epimer of ciclesonide is [11β,16α(S)]-16,17-[(cyclohexylmethylen)bis(oxy)]-11-hydroxy-21-(2-methyl-1-oxopropoxy)-pregna-1,4-dien-3,20-dion and is present in any mixing ratio with ciclesonide, [11β,16α(R)]-16,17-[(cyclohexylmethylen)bis(oxy)]-11-hydroxy-21-(2-methyl-1-oxopropoxy)-pregna-1,4-dien-3,20-dion.

Assignments (17)