Combination of anticholinergics and inhibitors of phosphodiesterase type 4 for the treatment of respiratory diseases

Abstract

The present invention relates to a combination of an inhaled/oral PDE 4 inhibitor in combination with inhaled anticholinergic bronchodilators (muscarinic receptor antagonists), preferentially Roflumilast or AWD-12-281 and R,R-glycopyrrolate, for symptomatic or prophylactic treatment of respiratory diseases, especially those accompanied by obstruction or inflammation such as chronic obstructive pulmonary disease (COPD) or asthma. It further comprises the presentation of this combination in a locally applied (inhaled) formulation and application in an inhalation device for instance in the Novolizer®.

1 - 20 . (canceled)  
     
     
         21 . A combination of topical R,R-glycopyrrolate or a physiologically acceptable salt thereof with at least one phosphodiesterase (PDE) 4 inhibitor or physiologically acceptable salt thereof for the treatment of respiratory diseases, including bronchial asthma and chronic obstructive pulmonary disease (COPD).  
     
     
         22 . The combination according to claim  1  wherein the PDE 4 inhibitor is selected from the group consisting of Roflumilast and AWD12-281 and physiologically acceptable salts thereof.  
     
     
         23 . The combination according to  claim 22  wherein the PDE 4 inhibitor is Roflumilast or a physiologically acceptable salt thereof.  
     
     
         24 . The combination according to  claim 22  wherein the PDE 4 inhibitor is AWD12-281 or a physiologically acceptable salt thereof.  
     
     
         25 . The combination according to  claim 21  wherein the daily dose of R,R-glycopyrrolate is from 5 to 500 μg and the daily dose of the PDE 4 inhibitor is between 200 and 5,000 μg/day.  
     
     
         26 . The combination according to  claim 21  wherein the daily dose of R,R-glycopyrrolate is from 5 to 100 μg and the daily dose of the PDE 4 inhibitor is between 200 and 5,000 μg/day.  
     
     
         27 . A pharmaceutical for the treatment of asthma or respiratory diseases containing a topical R,R-glycopyrrolate or a physiologically acceptable salt thereof and at least a PDE 4 inhibitor or a physiologically acceptable salt thereof.  
     
     
         28 . The pharmaceutical according to  claim 27 , wherein the PDE 4 inhibitor and/or physiologically acceptable salt thereof are available in an appropriate particle size dispersion when inhaled.  
     
     
         29 . The pharmaceutical according to  claim 27 , that is an inhalable aerosol with or without propellant.  
     
     
         30 . The pharmaceutical according to  claim 27 , that is an inhalable dry powder.  
     
     
         31 . The pharmaceutical according to  claim 27 , that is an inhalable suspension or solution.  
     
     
         32 . The pharmaceutical according to  claim 27 , presented in an inhaler.  
     
     
         33 . The pharmaceutical according to  claim 32 , containing R,R-glycopyrrolate and AWD12-281 or their physiologically acceptable salts.  
     
     
         34 . The pharmaceutical according to  claim 32 , containing R,R-glycopyrrolate and Rofumilast or their physiologically acceptable salts.  
     
     
         35 . The pharmaceutical according to  claim 27 , wherein the R,R-glycopyrrolate, PDE 4 inhibitor and/or physiologically acceptable salts thereof are presented in fixed or free combination for simultaneous, sequential or separate administration together with the usual excipients, adjuncts, and additives in a pharmaceutical form suitable for inhalative application.  
     
     
         36 . The combination according to  claim 25  wherein the daily dose of R,R-glycopyrrolate is from 15 to 300 μg.  
     
     
         37 . The combination according to  claim 25  wherein the daily dose of the PDE 4 inhibitor is 500 to 2.000 μg/day.  
     
     
         38 . A method of treating asthma/allergies and/or respiratory diseases in a mammal comprising administering an effective amount of a combination of topical R,R-glycopyrrolate or a physiologically acceptable salt thereof and at least a PDE 4 inhibitor or a physiologically acceptable salt thereof to said mammal.  
     
     
         39 . The method according to  claim 38  wherein the mammal is a human or a horse.