Stable pharmaceutical composition containing non-steroidal anti-inflammatory drug derivative

Abstract

A stable pharmaceutical composition containing a non-steroidal anti-inflammatory drug derivative, at least comprising a separated solid part and liquid part, the solid part comprising a therapeutically effective dose of non-steroidal anti-inflammatory drug derivative and the liquid part being a pharmaceutically acceptable solvent.

1 . A stable pharmaceutical composition containing a non-steroidal anti-inflammatory drug derivative, including at least a separated solid portion and a separated liquid portion, where the solid portion includes a therapeutically effective amount of a pharmaceutically acceptable salt of a compound represented by general Formula 1, and where the liquid portion includes a pharmaceutically acceptable solvent, 
       
         
           
           
               
               
           
         
         where, 
         Ar— represents 
       
       
         
           
           
               
               
           
         
         R 1  represents H, C1 alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl or C6 alkyl, preferably methyl or ethyl, 
         R 2  represents H, C1 alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl or C6 alkyl, preferably methyl or ethyl, and 
         n represents 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably 1 or 2. 
       
       
         
           
           
               
               
           
         
       
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutically acceptable solvent is selected from the group consisting of sterile water, decarbonated water, ethanol, sorbitol aqueous solution, and physiological saline. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the solid portion is in a dosage form selected from the group consisting of powders, granules, pills, tablets and capsules. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the solid portion further includes a pharmaceutically acceptable binder;
 preferably, the pharmaceutically acceptable binder is selected from the group consisting of hypromellose, carbomer, ethyl cellulose, hydroxypropyl cellulose, vinyl cellulose, starch, pregelatinized starch, and polyvinylpyrrolidone; more preferably, the pharmaceutically acceptable binder is hypromellose.   
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein the pharmaceutically acceptable salt of the compound represented by general Formula 1 forms particles with the pharmaceutically acceptable binder; preferably, the mass ratio of the pharmaceutically acceptable salt of the compound represented by general Formula 1 to the pharmaceutically acceptable binder is from 100:0.05 to 100:10, more preferably from 100:1 to 100:5, most preferably from 100:1 to 100:2. 
     
     
         6 . The pharmaceutical composition of  claim 3 , wherein the powders or granules have a repose angle of no more than 40°, preferably no more than 35°, more preferably no more than 30°. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the solid portion is stored in a hermetic, pharmaceutically acceptable packaging material; preferably, the pharmaceutically acceptable packaging material is selected from the group consisting of a low density polyethylene film, a low density polyethylene bag, a high density polyethylene film, a low density polyethylene bottle, a high density polyethylene bottle, a polypropylene bottle, a poly(ethylene terephthalate) bottle, a polyester/aluminum/polyethylene composite bag, a glass bottle, or a combination thereof; more preferably, the pharmaceutically acceptable packaging material is a combination of a high density polyethylene bottle and a polyester/aluminum/polyethylene composite bag. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition further includes a pharmaceutical spray device, a medicinal dropper, a medicinal soft brush, or a combination thereof. 
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein, when the pharmaceutical composition is used, the solid portion is mixed with the liquid portion to form a spray, a drop, or an inunction. 
     
     
         10 . The stable pharmaceutical composition of  claim 1 , wherein the compound represented by general Formula 1 is selected from the group consisting of the following compounds: 
       
         
           
           
               
               
           
         
       
     
     
         11 . The stable pharmaceutical composition of  claim 1 , wherein the pharmaceutically acceptable salt of the compound represented by general Formula 1 is a salt formed from the compound represented by general Formula 1 with an inorganic acid or an organic acid, preferably a salt formed from the compound represented by general Formula 1 with hydrochloric acid, hydrobromic acid, hydrofluoric acid, hydroiodic acid, phosphoric acid, acetic acid, oxalic acid, citric acid or thiocyanic acid. 
     
     
         12 . The stable pharmaceutical composition of  claim 1 , wherein the pharmaceutically acceptable salt of the compound represented by general Formula 1 comprises:
 2-(diethylamino)-ethyl-2-acetoxybenzoate hydrochloride;   salicylic acid-(2-diethylaminoethyl ester) hydrochloride; or   2-(diethylamino)-ethyl-2-(4-isobutylphenyl) propionate hydrochloride.   
     
     
         13 . The stable pharmaceutical composition of  claim 1 , wherein the mass ratio of the solid portion to the liquid portion is from 0.1:100 to 40:100, more preferably from 0.5:100 to 20:100, most preferably from 1:100 to 10:100
 preferably, the mass ratio of the pharmaceutically acceptable salt of the compound represented by general Formula 1 to the pharmaceutically acceptable solvent is from 0.1:100 to 40:100, more preferably from 0.5:100 to 20:100, most preferably from 1:100 to 10:100.