Method for Suppressing Bitterness of Quinoline Derivative

Abstract

The present invention provides a method for suppressing bitterness of a quinoline derivative.

1 . A method for suppressing bitterness of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxyamide, comprising mixing 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxyamide or a pharmaceutically acceptable salt thereof and a basic substance. 
     
     
         2 . The method according to  claim 1 , wherein 0.01 to 50 parts by weight of the basic substance is mixed per 1 part by weight of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxyamide or the pharmaceutically acceptable salt thereof. 
     
     
         3 . The method according to  claim 1 , wherein 0.16 to 80 mol of the basic substance is mixed per 1 mol of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxyamide or the pharmaceutically acceptable salt thereof. 
     
     
         4 . The method according to  claim 1 , wherein the basic substance is a basic oxide, a basic carbonate or a basic hydroxide. 
     
     
         5 . The method according to  claim 1 , wherein the basic substance is calcium carbonate or magnesium oxide. 
     
     
         6 . The method according to  claim 1 , wherein the basic substance is calcium carbonate. 
     
     
         7 . The method according to  claim 1 , wherein the pharmaceutically acceptable salt is a mesylate. 
     
     
         8 . A pharmaceutical composition, comprising 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxyamide or a pharmaceutically acceptable salt thereof, and a basic substance in an amount effective for suppressing bitterness. 
     
     
         9 . A pharmaceutical composition, comprising 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxyamide or a pharmaceutically acceptable salt thereof, the pharmaceutical composition comprising means for mixing a basic substance for suppressing bitterness. 
     
     
         10 . A pharmaceutical composition, comprising 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxyamide or a pharmaceutically acceptable salt thereof and a basic substance, the pharmaceutical composition having bitterness suppressed. 
     
     
         11 . The pharmaceutical composition according to  claim 8 , comprising 0.01 to 50 parts by weight of the basic substance per 1 part by weight of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxyamide or the pharmaceutically acceptable salt thereof. 
     
     
         12 . The pharmaceutical composition according to  claim 8 , wherein 0.16 to 80 mol of the basic substance is mixed per 1 mol of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxyamide or the pharmaceutically acceptable salt thereof. 
     
     
         13 . The pharmaceutical composition according to  claim 8 , wherein the basic substance is a basic oxide, a basic carbonate or a basic hydroxide. 
     
     
         14 . The pharmaceutical composition according to  claim 8 , wherein the basic substance is calcium carbonate or magnesium oxide. 
     
     
         15 . The pharmaceutical composition according to  claim 8 , wherein the basic substance is calcium carbonate. 
     
     
         16 . The pharmaceutical composition according to  claim 8 , wherein the pharmaceutically acceptable salt is a mesylate. 
     
     
         17 . The pharmaceutical composition according to  claim 8 , in a dosage form of an orally disintegrating tablet, a chewable preparation, an effervescent tablet, a dispersible tablet, a soluble tablet, a syrup, a preparation for a syrup, a troche, or an oral liquid preparation. 
     
     
         18 . The pharmaceutical composition according to  claim 8 , being a preparation that can be suspended in an aqueous solvent upon an administration to prepare a suspension. 
     
     
         19 . A bitterness suppressing agent, comprising a basic substance, for 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxyamide or a pharmaceutically acceptable salt thereof. 
     
     
         20 . The bitterness suppressing agent according to  claim 19 , wherein the basic substance added is in an amount of 0.01 to 50 parts by weight per 1 part by weight of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxyamide or the pharmaceutically acceptable salt thereof. 
     
     
         21 . The bitterness suppressing agent according to  claim 19 , wherein the basic substance added is in an amount of 0.16 to 80 mol per 1 mol of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxyamide or the pharmaceutically acceptable salt thereof. 
     
     
         22 . The bitterness suppressing agent according to  claim 19 , wherein the basic substance is a basic oxide, a basic carbonate or a basic hydroxide. 
     
     
         23 . The bitterness suppressing agent according to  claim 19 , wherein the basic substance is calcium carbonate or magnesium oxide. 
     
     
         24 . The bitterness suppressing agent according to  claim 19 , wherein the basic substance is calcium carbonate. 
     
     
         25 . The bitterness suppressing agent according to  claim 19 , wherein the pharmaceutically acceptable salt is a mesylate. 
     
     
         26 . A method for administering a suspension comprising 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxyamide or a pharmaceutically acceptable salt thereof, and a basic substance, the method comprising:
 1) suspending a pharmaceutical composition comprising 1 to 24 mg of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxyamide or the pharmaceutically acceptable salt thereof, and the basic substance in an aqueous solvent in a vessel;   2) administering a suspension obtained in 1) to a patient from the vessel;   3) rinsing the vessel with an aqueous solvent; and   4) administering a rinsing solution obtained in 3) to the patient.   
     
     
         27 . The method according to  claim 26 , wherein 1) comprises: i) pouring the aqueous solvent in the vessel, ii) allowing the vessel to stand; and iii) shaking the vessel. 
     
     
         28 . The method according to  claim 26 , wherein the pharmaceutical composition is suspended in 1 to 10 mL of the aqueous solvent in 1). 
     
     
         29 . The method according to  claim 28 , wherein the pharmaceutical composition is suspended in about 3 mL of the aqueous solvent in 1). 
     
     
         30 . The method according to  claim 26 , wherein the vessel is rinsed with 1 to 10 mL of the aqueous solvent in 3). 
     
     
         31 . The method according to  claim 30 , wherein the vessel is rinsed with about 2 mL of the aqueous solvent in 3). 
     
     
         32 . A method for treating a cancer, comprising administering a suspension comprising 1 to 24 mg of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxyamide or a pharmaceutically acceptable salt thereof, and a basic substance. 
     
     
         33 . A method for treating a cancer, comprising administering a suspension comprising 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxyamide or a pharmaceutically acceptable salt thereof, and a basic substance, the method comprising:
 1) suspending, in an aqueous solvent in a vessel, a pharmaceutical composition comprising 1 to 24 mg of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxyamide or the pharmaceutically acceptable salt thereof, and the basic sub stance;   2) administering a suspension obtained in 1) to a patient from the vessel;   3) rinsing the vessel with an aqueous solvent; and   4) administering a rinsing solution obtained in 3) to the patient.