Use of an H+, K+-atpase inhibitor in the treatment of nasal polyps

• US 6,380,222 B2
• Filed: 04/13/2001
• Issued: 04/30/2002
• Est. Priority Date: 10/11/1996
• Status: Expired due to Fees

• Current Assignee: Astrazeneca AB (Astrazeneca PLC)
• Original Assignee: Astrazeneca AB (Astrazeneca PLC)
• Inventors: Trofast, Jan, Lindberg, Per, Serra-Carreras, Jordi, Piñas-Massó, Joan
• Primary Examiner(s): FAY, ZOHREH A
• Application Number:
  US09/833,699
• Publication Number:
  US 20010020014A1
• Time in Patent Office: 382 Days
• Field of Search: 514/339, 514/395
• US Class Current: 514/339
• 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 31/4184 condensed with carbocyclic rings, e.g. benzimidazoles
• CPC Class Codes: A61K 31/435 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00

Abstract

The invention provides a method for the treatment of polyposis which comprises treating a subject suffering from polyposis with an H⁺,K⁺-ATPase inhibitor and, optionally, a glucocorticoid. The invention also relates to a pharmaceutical formulation for simultaneous, separate or sequential administration in the treatment of Widal'"'"'s Syndrome and in the treatment of asthma.

Claims

1. A method for the treatment of nasal polyps which comprises administering a pharmaceutical formulation comprising an H⁺, K⁺-ATPase inhibitor to a subject in need of such treatment.

4. The method according to any one of claims 1, 2 and 3, wherein the H³⁰, K⁺-ATPase inhibitor is a compound of the formula

wherein Het₁ is

Het₂ is

and X=

wherein N in the benzimidazole moiety of Het₂ means that one of the ring carbon atoms substituted by R₆-R₉ optionally may be exchanged for a nitrogen atom without any substituents;

R₁ and R₃ each independently represent hydrogen, alkyl or alkoxy on the condition that R₁ and R₃ do not simultaneously represent alkoxy; and

R₂ represents alkyl, alkoxy, fluoro-substituted alkoxy, alkylthio or alkyoxyalkoxy;

or one of R₁ and R₃ is halogen and the other is hydrogen and R₂ is 1-morpholino, 1-piperidino or dialkylamino;

R₄ and R₅ are the same or different and selected from the group consisting of hydrogen and alkyl;

R₆-R₉ are the same or different and selected from the gorup consisting of hydrogen, halogen, alkyl, alkoxy, haloalkoxy, alkylcarbonyl and alkoxycarbonyl;

R₁₀ is hydrogen or R10 and R3 together complete a ring containing 6 to 8 carbon atoms; and

R₁₁ represents hydrogen, halogen or alkyl;

wherein each alkyl or alkylenyl moiety has a branched or straight chain and has 1 to 6 carbon atoms.

6. The method according to claim 4, wherein the compound of formula (I) is in its neutral form or in the form of a pharmaceutically acceptable salt, a single enantiomer or a racemic mixture.

7. The method according to claim 4, wherein the compound of formula (I) is a compound of formula

8. The method according to claim 7, wherein the compound of the formula (Ia) is in the form of an alkaline salt, the (−

)-enantiomer or an alkaline salt of the (−

)-enantiomer.

2. A method for the treatment of nasal polyps which comprises administering simultaneously, separately or sequentially a pharmaceutical formulation comprising an H⁺,K⁺-ATPase inhibitor and a glucocorticoid to a subject in need of such treatment.

3. The method according to claim 2, wherein the glucocorticoid is a topically active anti-inflammatory steroid.

5. The method according to claim 3, wherein the glucocorticoid is budesonide, beclomethasone diproprionate or fluticasone propionate.