Injectable pharmaceutical compositions of an anthracenedione derivative with anti-tumoral activity

Abstract

Injectable pharmaceutical compositions containing 6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione dimaleate as active ingredient in the form of a lyophilised powder with a carrier selected from lactose and dextran, mixed with sodium chloride.

1 . A pharmaceutical composition comprising 6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione dimaleate and: i) a lactose carrier mixed with sodium chloride; or ii) a dextran carrier mixed with sodium chloride,
 wherein the composition is in the form of a lyophilized powder.   
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the carrier is lactose. 
     
     
         3 . The pharmaceutical composition of  claim 1 , further comprising an antioxidant. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the weight ratio of the carrier to the sodium chloride is between 1:1 and 3:1. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the weight ratio of the 6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione dimaleate to the carrier is between 1:2 and 1:6. 
     
     
         6 . An aqueous composition comprising 6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione dimaleate and: i) a lactose carrier mixed with sodium chloride; or ii) a dextran carrier mixed with sodium chloride,
 wherein the concentration of the 6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione dimaleate in the composition ranges from 7-15 mg/ml.   
     
     
         7 . The aqueous composition of  claim 6 , comprising from 10 to 40 mg/ml sodium choloride and from 20 to 60 mg/ml lactose. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition comprises a unit dose of between 25 and 200 mg of 6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione dimaleate. 
     
     
         9 . The pharmaceutical compositions of  claim 8 , wherein the unit dose comprises 50 mg of 6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione dimaleate. 
     
     
         10 . A kit comprising the pharmaceutical composition of  claim 1 , and an ampoule containing a sterile solvent suitable to reconstitute the lyophilized powder, such that the lyophilized powder is suitable for parenteral administration. 
     
     
         11 . A process for preparing the pharmaceutical composition of  claim 1 , the process comprising:
 lyophilizing an aqueous solution of 6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione dimaleate in the presence of: i) lactose and sodium chloride; or ii) dextran and sodium chloride, wherein the step of lyophilizing comprises:   freezing the solution at a temperature below at least −45° C. for at least 3 hours;   drying the frozen solution to form a product, by increasing the temperature of the frozen solution to −35° C.±5° C. in approximately 3 hours and maintaining said temperature for at least 40 hours; and   then drying the product by increasing the temperature of the product to +30° C.±5° C. in 10 hours and maintaining said temperature for at least 8 hours.