Pharmaceutical composition for modified release

Abstract

A pharmaceutical composition for modified release comprising (R)-2-(2-aminothiazol-4-yl)-4′-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide or a pharmaceutically acceptable salt thereof, and a carrier for a sustained release pharmaceutical composition, wherein a maximum blood drug concentration (Cmax) when administered in a fasted state is 400 ng/mL or less, is disclosed.

1 . A pharmaceutical composition for modified release comprising (R)-2-(2-aminothiazol-4-yl)-4′-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide or a pharmaceutically acceptable salt thereof, and a carrier for a sustained release pharmaceutical composition, wherein a maximum blood drug concentration (Cmax) when administered in a fasted state is 400 ng/mL or less. 
     
     
         2 . The pharmaceutical composition for modified release according to  claim 1 , wherein the maximum blood drug concentration (Cmax) when administered in a fasted state is 300 ng/mL or less. 
     
     
         3 . The pharmaceutical composition for modified release according to  claim 1 , comprising (R)-2-(2-aminothiazol-4-yl)-4′-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide or a pharmaceutically acceptable salt thereof, and a carrier for a sustained release pharmaceutical composition, wherein a rate of decrease of a maximum blood drug concentration (Cmax) thereof in comparison with a Cmax of a conventional formulation is 10% or more. 
     
     
         4 . The pharmaceutical composition for modified release according to  claim 1 , comprising (R)-2-(2-aminothiazol-4-yl)-4′-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide or a pharmaceutically acceptable salt thereof, and a carrier for a sustained release pharmaceutical composition, wherein a rate of decrease of a maximum blood drug concentration (Cmax) when administered after eating a meal, in comparison with a Cmax when administered in a fasted state, is 10% or more. 
     
     
         5 . The pharmaceutical composition for modified release according to  claim 1 , comprising (R)-2-(2-aminothiazol-4-yl)-4′-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide or a pharmaceutically acceptable salt thereof, and a carrier for a sustained release pharmaceutical composition, wherein a rate of decrease of an area under a blood drug concentration versus time curve (AUC) when administered after eating a meal, in comparison with an AUC when administered in a fasted state, is 10% or more. 
     
     
         6 . The pharmaceutical composition for modified release according to  claim 1 , which is selected from the group consisting of a sustained release hydrogel-forming formulation, a multi-layered formulation consisting of a drug core and a release-controlling layer which are geometrically arranged, a gel formulation in which a plurality of gums is combined, an osmotic pump type formulation, a formulation utilizing a swelling polymer, a matrix formulation utilizing a water-soluble polymer, a modified release formulation with a coating membrane, and a matrix formulation utilizing an insoluble polymer. 
     
     
         7 . A method of reducing an effect of food intake, comprising the step of administering a pharmaceutical composition comprising (R)-2-(2-aminothiazol-4-yl)-4′-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide or a pharmaceutically acceptable salt thereof, and a carrier for a sustained release pharmaceutical composition, wherein a maximum blood drug concentration (Cmax) when administered in a fasted state is 400 ng/mL or less. 
     
     
         8 . The method of reducing an effect of food intake according to  claim 7 , wherein the maximum blood drug concentration (Cmax) when administered in a fasted state is 300 ng/mL or less. 
     
     
         9 . The method of reducing an effect of food intake according to  claim 7 , comprising the step of administering a pharmaceutical composition comprising (R)-2-(2-aminothiazol-4-yl)-4′-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide or a pharmaceutically acceptable salt thereof, and a carrier for a sustained release pharmaceutical composition, wherein a rate of decrease of a maximum blood drug concentration (Cmax) thereof in comparison with a Cmax of a conventional formulation is 10% or more. 
     
     
         10 . The method of reducing an effect of food intake according to  claim 7 , comprising the step of administering a pharmaceutical composition comprising (R)-2-(2-aminothiazol-4-yl)-4′-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide or a pharmaceutically acceptable salt thereof, and a carrier for a sustained release pharmaceutical composition, wherein a rate of decrease of a maximum blood drug concentration (Cmax) when administered after eating a meal, in comparison with a Cmax when administered in a fasted state, is 10% or more. 
     
     
         11 . The method of reducing an effect of food intake according to  claim 7 , comprising the step of administering a pharmaceutical composition comprising (R)-2-(2-aminothiazol-4-yl)-4′-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide or a pharmaceutically acceptable salt thereof, and a carrier for a sustained release pharmaceutical composition, wherein a rate of decrease of an area under a blood drug concentration versus time curve (AUC) when administered after eating a meal, in comparison with an AUC when administered in a fasted state, is 10% or more. 
     
     
         12 . The method of reducing an effect of food intake according to  claim 7 , wherein the pharmaceutical composition is selected from the group consisting of a sustained release hydrogel-forming formulation, a multi-layered formulation consisting of a drug core and a release-controlling layer which are geometrically arranged, a gel formulation in which a plurality of gums is combined, an osmotic pump type formulation, a formulation utilizing a swelling polymer, a matrix formulation utilizing a water-soluble polymer, a modified release formulation with a coating membrane, and a matrix formulation utilizing an insoluble polymer. 
     
     
         13 . A method of inhibiting an increase in heart rate, comprising the step of administering a pharmaceutical composition comprising (R)-2-(2-aminothiazol-4-yl)-4′-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide or a pharmaceutically acceptable salt thereof, and a carrier for a sustained release pharmaceutical composition, wherein a maximum blood drug concentration (Cmax) when administered in a fasted state is 400 ng/mL or less. 
     
     
         14 . The method of inhibiting an increase in heart rate according to  claim 13 , wherein the maximum blood drug concentration (Cmax) when administered in a fasted state is 300 ng/mL or less. 
     
     
         15 . The method of inhibiting an increase in heart rate according to  claim 13 , comprising the step of administering a pharmaceutical composition comprising (R)-2-(2-aminothiazol-4-yl)-4′-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide or a pharmaceutically acceptable salt thereof, and a carrier for a sustained release pharmaceutical composition, wherein a rate of decrease of a maximum blood drug concentration (Cmax) thereof in comparison with a Cmax of a conventional formulation is 10% or more. 
     
     
         16 . The method of inhibiting an increase in heart rate according to  claim 13 , comprising the step of administering a pharmaceutical composition comprising (R)-2-(2-aminothiazol-4-yl)-4′-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide or a pharmaceutically acceptable salt thereof, and a carrier for a sustained release pharmaceutical composition, wherein a rate of decrease of a maximum blood drug concentration (Cmax) when administered after eating a meal, in comparison with a Cmax when administered in a fasted state, is 10% or more. 
     
     
         17 . The method of inhibiting an increase in heart rate according to  claim 13 , comprising the step of administering a pharmaceutical composition comprising (R)-2-(2-aminothiazol-4-yl)-4′-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide or a pharmaceutically acceptable salt thereof, and a carrier for a sustained release pharmaceutical composition, wherein a rate of decrease of an area under a blood drug concentration versus time curve (AUC) when administered after eating a meal, in comparison with an AUC when administered in a fasted state, is 10% or more. 
     
     
         18 . A method of inhibiting an increase in heart rate, comprising the step of administering a pharmaceutical composition comprising (R)-2-(2-aminothiazol-4-yl)-4′-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide or a pharmaceutically acceptable salt thereof, and a carrier for a sustained release pharmaceutical composition, wherein a dissolution rate of the drug from the composition is less than 85% after 30 minutes from the beginning of a dissolution test. 
     
     
         19 . The method of inhibiting an increase in heart rate according to  claim 18 , a dissolution rate is 75% or less after 1.5 hours from the beginning of the dissolution test. 
     
     
         20 . The method of inhibiting an increase in heart rate according to  claim 18 , wherein the dissolution rate is 75% or less after 1.5 hours from the beginning the dissolution test, and a dissolution rate is 75% to 100% after 7 hours from the beginning of the dissolution test. 
     
     
         21 . The method of inhibiting an increase in heart rate according to  claim 13 , wherein the pharmaceutical composition is selected from the group consisting of a sustained release hydrogel-forming formulation, a multi-layered formulation consisting of a drug core and a release-controlling layer which are geometrically arranged, a gel formulation in which a plurality of gums is combined, an osmotic pump type formulation, a formulation utilizing a swelling polymer, a matrix formulation utilizing a water-soluble polymer, a modified release formulation with a coating membrane, and a matrix formulation utilizing an insoluble polymer. 
     
     
         22 . The method of inhibiting an increase in heart rate according to  claim 18 , wherein the pharmaceutical composition is selected from the group consisting of a sustained release hydrogel-forming formulation, a multi-layered formulation consisting of a drug core and a release-controlling layer which are geometrically arranged, a gel formulation in which a plurality of gums is combined, an osmotic pump type formulation, a formulation utilizing a swelling polymer, a matrix formulation utilizing a water-soluble polymer, a modified release formulation with a coating membrane, and a matrix formulation utilizing an insoluble polymer.