Method for preventing influenza virus infection by administering a dry powder pharmaceutical composition

Abstract

A method for preventing an influenza virus infection by administering by inhalation to a patient a pharmaceutically effective amount of a dry powder composition containing a first lactose hydrate and a second lactose hydrate.

1 . A method for preventing an influenza virus infection which comprises administering by inhalation to a patient a pharmaceutically effective amount of a dry powder pharmaceutical composition comprising a mixture of (a) a medicinal component which is a mixture of (i) a compound represented by the following formula (I): 
       
         
           
           
               
               
           
         
       
       a pharmaceutically acceptable salt thereof, or a hydrate thereof, and (ii) a compound of the following formula (II): 
       
         
           
           
               
               
           
         
       
       a pharmacologically acceptable salt thereof, or a hydrate thereof, and (b) a diluting agent comprising a mixture of a first lactose hydrate and a second lactose hydrate which have different particle size distributions, wherein the medicinal component has a 50% by weight particle size of 3.2 μm or less and a 90% by weight particle size of 8.0 μm or less as measured by a particle size analysis-laser diffraction method, and having 15% to 25% by weight on an anhydrous basis of the medicinal component,
 wherein the first lactose hydrate has a particle size distribution satisfying the following condition: the particle size distribution of the first lactose hydrate measured by a particle size analysis-laser diffraction method has 
 a 10% by weight particle size of 19 μm to 43 μm, 
 a 50% by weight particle size of 53 μm to 66 μm, and 
 a 90% by weight particle size of 75 μm to 106 μm, 
 and the second lactose hydrate satisfying the following condition: the particle size distribution of the second lactose hydrate measured by a particle size analysis-laser diffraction method has 
 a 10% by weight particle size of 1 μm to 3 μm, 
 a 50% by weight particle size of 11 μm to 20 μm, and 
 a 90% by weight particle size of 37 μm to 54 μm. 
 
     
     
         2 . The method according to  claim 1 , wherein the composition is administered in a single inhaled dose containing 20 mg of the medicinal component on an anhydrous basis. 
     
     
         3 . The method according to  claim 1 , wherein the composition is administered in two inhaled doses containing 20 mg each of the medicinal component on an anhydrous basis. 
     
     
         4 . The method according to  claim 1 , wherein the composition is administered in a single inhaled dose containing 40 mg of the medicinal component on an anhydrous basis. 
     
     
         5 . The method according to  claim 1 , wherein the composition is administered in a single inhaled dose containing 80 mg of the medicinal component on an anhydrous basis. 
     
     
         6 . The method according to  claim 1 , wherein the patient is a human. 
     
     
         7 . The method according to  claim 6 , wherein the dry powder composition is administered as a single dose or two divided doses. 
     
     
         8 . The method according to  claim 1 , wherein the medicinal component is contained in an amount of 5 to 120 mg on an anhydrous basis. 
     
     
         9 . The method according to  claim 1 , wherein the dry powder pharmaceutical composition for inhalation comprises 20% by weight, on an anhydrous basis, of the medicinal component. 
     
     
         10 . The method according to  claim 1 , wherein the compound of formula (I) is in a form of a crystalline hydrate, and the compound of formula (II) is in a form of a crystalline hydrate. 
     
     
         11 . The method according to  claim 1 , wherein the compound of formula (I) is in a form of a crystalline monohydrate, and the compound of formula (II) is in a form of a crystalline monohydrate. 
     
     
         12 . A method for avoiding an onset of an influenza virus infection which comprises administering by inhalation to a patient a pharmaceutically effective amount of a dry powder pharmaceutical composition comprising a mixture of (a) a medicinal component which is a mixture of (i) a compound represented by the following formula (I): 
       
         
           
           
               
               
           
         
       
       a pharmaceutically acceptable salt thereof, or a hydrate thereof, and (ii) a compound of the following formula (II): 
       
         
           
           
               
               
           
         
       
       a pharmacologically acceptable salt thereof, or a hydrate thereof, and (b) a diluting agent comprising a mixture of a first lactose hydrate and a second lactose hydrate which have different particle size distributions, wherein the medicinal component has a 50% by weight particle size of 3.2 μm or less and a 90% by weight particle size of 8.0 μm or less as measured by a particle size analysis-laser diffraction method, and having 15% to 25% by weight on an anhydrous basis of the medicinal component,
 wherein the first lactose hydrate has a particle size distribution satisfying the following condition: the particle size distribution of the first lactose hydrate measured by a particle size analysis-laser diffraction method has 
 a 10% by weight particle size of 19 μm to 43 μm, 
 a 50% by weight particle size of 53 μm to 66 μm, and 
 a 90% by weight particle size of 75 μm to 106 μm, 
 and the second lactose hydrate satisfying the following condition: the particle size distribution of the second lactose hydrate measured by a particle size analysis-laser diffraction method has 
 a 10% by weight particle size of 1 μm to 3 μm, 
 a 50% by weight particle size of 11 μm to 20 μm, and 
 a 90% by weight particle size of 37 μm to 54 μm.