Pharmaceutical composition

Abstract

To provide pharmaceutical preparation exhibiting satisfactory dissolution property in a wide pH range. The pharmaceutical composition is characterized by containing (A) N 1 -(5-chloropyridin-2-yl)-N 2 -((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide, represented by the following formula (1), a pharmacologically acceptable salt thereof, or a hydrate of any of these, and (B) one or more species selected from the group consisting of a sugar alcohol and a water-swelling additive.

1 . A pharmaceutical composition comprising (A) N 1 -(5-chloropyridin-2-yl)—N 2 -((1S,2R,4S)-4-[(dimethylamino)carbonyl]-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide, represented by formula (1): 
     
       
         
         
             
             
         
       
     
     a pharmacologically acceptable salt thereof, or a hydrate of any of these, and (B) one or more species selected from the group consisting of a sugar alcohol and a water-swelling additive. 
   
   
       2 . A pharmaceutical composition according to  claim 1 , wherein the sugar alcohol is mannitol, xylitol, or erythritol. 
   
   
       3 . A pharmaceutical composition according to  claim 1 , wherein the sugar alcohol is mannitol. 
   
   
       4 . A pharmaceutical composition according to  claim 1 , wherein the water-swelling additive is pregelatinized starch or crystalline cellulose. 
   
   
       5 . A pharmaceutical composition according to  claim 1 , wherein the water-swelling additive is pregelatinized starch. 
   
   
       6 . A pharmaceutical composition comprising, as an active ingredient, N 1 -(5-chloropyridin-2-yl)-N 2 -((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide, represented by formula (1): 
     
       
         
         
             
             
         
       
     
     a pharmacologically acceptable salt thereof, or a hydrate of any of these, which composition is coated with at least one coating agent selected from among a cellulose derivative, a polyvinyl compound, an acrylate derivative, and a saccharide. 
   
   
       7 . A pharmaceutical composition according to  claim 6 , wherein the coating agent is one or more species selected from among hypromellose, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol, povidone, Polyvinyl acetate, polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylate copolymer RS, ethyl acrylate-methyl methacrylate copolymer dispersion, sucrose, and mannitol. 
   
   
       8 . A pharmaceutical composition according to  claim 6 , wherein the coating agent is one or more species selected from among a cellulose derivative and a polyvinyl compound. 
   
   
       9 . A pharmaceutical composition according to  claim 6 , wherein the coating agent is one or more species selected from among hypromellose, ethyl cellulose, and polyvinyl alcohol. 
   
   
       10 . A pharmaceutical composition according to  claim 6 , wherein the coating agent is hypromellose. 
   
   
       11 . A pharmaceutical composition according to  claim 1 , which is coated with at least one coating agent selected from among a cellulose derivative, a polyvinyl compound, a acrylate derivative, and saccharide. 
   
   
       12 . A pharmaceutical composition according to  claim 11 , wherein the coating agent is one or more species selected from among hypromellose, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol, povidone, Polyvinyl acetate, polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylate copolymer RS, ethyl acrylate-methyl methacrylate copolymer dispersion, sucrose, and mannitol. 
   
   
       13 . A pharmaceutical composition according to  claim 11 , wherein the coating agent is one or more species selected from among a cellulose derivative and a polyvinyl compound. 
   
   
       14 . A pharmaceutical composition according to  claim 11 , wherein the coating agent is one or more species selected from among hypromellose, ethyl cellulose, and polyvinyl alcohol. 
   
   
       15 . A pharmaceutical composition according to  claim 11 , wherein the coating agent is hypromellose. 
   
   
       16 . A pharmaceutical composition according to  claim 6 , wherein the coating agent is contained in an amount of 0.5 to 20 wt. % with respect to the total weight of the pharmaceutical composition. 
   
   
       17 . A pharmaceutical composition according to  claim 1 , wherein the compound represented by formula (1) is N 1 -(5-chloropyridin-2-yl)-N 2 -((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide hydrochloride. 
   
   
       18 . A pharmaceutical composition according to  claim 1 , wherein the compound represented by formula (1) is N 1 -(5-chloropyridin-2-yl)-N 2 -((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide p-toluenesulfonate monohydrate. 
   
   
       19 . A pharmaceutical composition according to  claim 1 , which has a dosage form of oral preparation. 
   
   
       20 . A pharmaceutical composition according to  claim 1 , which has a dosage form of solid preparation. 
   
   
       21 . A pharmaceutical composition according to  claim 1 , which has a dosage form of tablet, capsule, granule, or powder. 
   
   
       22 . A pharmaceutical composition according to  claim 1 , which has a dosage form of tablet. 
   
   
       23 . A pharmaceutical composition according to  claim 1 , wherein, when the composition is subjected to a dissolution test by the paddle method at a rotation rate of 50 rpm, the composition exhibits an average percent dissolution of the compound represented by formula (1), in a dissolution test medium having a pH of 6.8, of 60% or higher in 30 minutes after the start of the dissolution test and 70% or higher in 60 minutes after the start. 
   
   
       24 . A pharmaceutical composition according to  claim 1 , wherein, when the composition is subjected to a dissolution test by the paddle method at a rotation rate of 50 rpm, the composition exhibits an average percent dissolution of the compound represented by formula (1), in a dissolution test medium having a pH of 6.8, of 70% or higher in 30 minutes after the start of the dissolution test and 80% or higher in 60 minutes after the start. 
   
   
       25 . A pharmaceutical composition according to  claim 1 , wherein, when the composition is subjected to a dissolution test by the paddle method at a rotation rate of 50 rpm, the composition exhibits an average percent dissolution of the compound represented by formula (1), in a dissolution test medium having a pH of 4.5, of 85% or higher in 30 minutes after the start of the dissolution test. 
   
   
       26 . A method for promoting dissolution of a compound represented by formula (1), the method employing a pharmaceutical composition as recited in  claim 1 . 
   
   
       27 . A pharmaceutical composition according to  claim 1 , wherein dissolution of the compound represented by formula (1) serving as an active ingredient is promoted. 
   
   
       28 . A pharmaceutical composition according to  claim 6 , wherein the compound represented by formula (1) is N 1 -(5-chloropyridin-2-yl)-N 2 -((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide hydrochloride. 
   
   
       29 . A pharmaceutical composition according to  claim 6 , wherein the compound represented by formula (1) is N 1 -(5-chloropyridin-2-yl)-N 2 -((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide p-toluenesulfonate monohydrate. 
   
   
       30 . A pharmaceutical composition according to  claim 6 , which has a dosage form of oral preparation. 
   
   
       31 . A pharmaceutical composition according to  claim 6 , which has a dosage form of solid preparation. 
   
   
       32 . A pharmaceutical composition according to  claim 6 , which has a dosage form of tablet, capsule, granule, or powder. 
   
   
       33 . A pharmaceutical composition according to  claim 6 , which has a dosage form of tablet. 
   
   
       34 . A pharmaceutical composition according to  claim 6 , wherein, when the composition is subjected to a dissolution test by the paddle method at a rotation rate of 50 rpm, the composition exhibits an average percent dissolution of the compound represented by formula (1), in a dissolution test medium having a pH of 6.8, of 60% or higher in 30 minutes after the start of the dissolution test and 70% or higher in 60 minutes after the start. 
   
   
       35 . A pharmaceutical composition according to  claim 6 , wherein, when the composition is subjected to a dissolution test by the paddle method at a rotation rate of 50 rpm, the composition exhibits an average percent dissolution of the compound represented by formula (1), in a dissolution test medium having a pH of 6.8, of 70% or higher in 30 minutes after the start of the dissolution test and 80% or higher in 60 minutes after the start. 
   
   
       36 . A pharmaceutical composition according to  claim 6 , wherein, when the composition is subjected to a dissolution test by the paddle method at a rotation rate of 50 rpm, the composition exhibits an average percent dissolution of the compound represented by formula (1), in a dissolution test medium having a pH of 4.5, of 85% or higher in 30 minutes after the start of the dissolution test. 
   
   
       37 . A method for promoting dissolution of a compound represented by formula (1), the method employing a pharmaceutical composition as recited in  claim 6 . 
   
   
       38 . A pharmaceutical composition according to  claim 6 , wherein dissolution of the compound represented by formula (1) serving as an active ingredient is promoted.