Sustained-release formulation for injection

Abstract

The present invention relates to a composition comprising N-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]-(2R,3R)-2,3-tetramethylene-butyl]-(1′R,2′S,3′R,4′S)-2,3-bicyclo[2,2,1]heptanedicarboximide or a pharmaceutically acceptable acid addition salt thereof. In detail, the composition relates to a sustained release formulation for injection which maintains an effective blood level of the above-mentioned compound.

1 . (canceled) 
     
     
         2 : A sustained release formulation, comprising:
 a composition including
 N-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]-(2R,3R)-2,3-tetra-methylene-butyl]-(1′R,2′S,3′R,4′S)-2,3-bicyclo[2,2,1]heptanedicarboximide as an active ingredient, which is in a form of a crystal having a mean particle size range within from 4 μm to 26 μm, and 
 a surfactant comprising at least one ingredient selected from the group consisting of polysorbate 80, polysorbate 20, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, poloxamer 188 and polyoxyethylene castor oil. 
   
     
     
         3 : The sustained release formulation of  claim 2 , wherein the mean particle size range is 4 μm-20 μm, 4 μm-18 μm, 4 μm-16 μm, 5 μm-26 μm, 5 μm-20 μm, 5 μm-18 μm, 5 μm-16 μm, 8 μm-20 μm, 10 μm-26 μm, 10 μm-20 μm, 10 μm-18 μm, or 10 μm-16 μm. 
     
     
         4 : The sustained release formulation of  claim 2 , wherein the crystal is a cubic crystal. 
     
     
         5 : The sustained release formulation of  claim 4 , wherein the cubic crystal has a length to width ratio of 1:1, and a length to height ratio of 1:0.8 to 1:1.2. 
     
     
         6 : The sustained release formulation of  claim 2 , wherein the active ingredient in the form of the crystal is included in 5% (w/v) to 60% (w/v) with respect to a total amount of the composition. 
     
     
         7 : The sustained release formulation of  claim 2 , wherein the surfactant is polysorbate 80. 
     
     
         8 : The sustained release formulation of  claim 2 , wherein the surfactant is included in a concentration of 0.05 mg/ml to 20 mg/ml. 
     
     
         9 : The sustained release formulation of  claim 2 , wherein the composition further comprises a buffer. 
     
     
         10 : The sustained release formulation of  claim 9 , wherein the buffer is at least one ingredient selected from the group consisting of sodium phosphate, disodium hydrogenphosphate, sodium dihydrogenphosphate, potassium phosphate, dipotassium hydrogenphosphate, potassium dihydrogenphosphate, trometamol, sodium carbonate, sodium bicarbonate, meglumine, arginine, triethanolamine and citric acid. 
     
     
         11 : The sustained release formulation of  claim 9 , wherein the buffer is included in 0.01% (w/v) to 2% (w/v) with respect to a total amount of the composition. 
     
     
         12 : The sustained release formulation of  claim 2 , wherein the composition further comprises an isotonic agent. 
     
     
         13 : The sustained release formulation of  claim 12 , wherein the isotonic agent is at least one ingredient selected from the group consisting of sodium chloride and D-mannitol. 
     
     
         14 : The sustained release formulation of  claim 12 , wherein the isotonic agent is included in 0.1% (w/v) to 10% (w/v) with respect to a total amount of the composition. 
     
     
         15 : The sustained release formulation of  claim 2 , wherein the composition further comprises water. 
     
     
         16 : The sustained release formulation of  claim 2 , wherein the active ingredient is included in a concentration of 50 mg/mL to 600 mg/mL. 
     
     
         17 : The sustained release formulation of  claim 9 , wherein the buffer is included in a concentration of 0.1 mg/mL to 20 mg/mL. 
     
     
         18 : The sustained release formulation of  claim 12 , wherein the isotonic agent is included in a concentration of 1 mg/mL to 100 mg/mL. 
     
     
         19 : The sustained release formulation of  claim 2 , which comprises 50 mg to 1200 mg of the active ingredient per a container. 
     
     
         20 : The sustained release formulation of  claim 2 , which passes through a needle of 18 to 23 gauges. 
     
     
         21 : The sustained release formulation of  claim 2 , which is a depot formulation. 
     
     
         22 : A method for treating psychiatric disease, comprising:
 administering the sustained release formulation of  claim 2 .   
     
     
         23 : The method of  claim 22 , wherein the psychiatric disease is schizophrenia. 
     
     
         24 : The method of  claim 22 , wherein the psychiatric disease is bipolar disorder. 
     
     
         25 : The method of  claim 22 , wherein the psychiatric disease is depression.