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 dimalcate as active ingredient in the form of a lyophilised powder with a carrier selected from lactose and dextran, mixed with sodium chloride.

1 . 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.  
   
   
       2 . Compositions as claimed in  claim 1 , wherein the carrier is lactose.  
   
   
       3 . Compositions as claimed in  claim 1  or  2 , further containing an antioxidant.  
   
   
       4 . Compositions as claimed in any one of  claims 1  to  3 , wherein the weight ratio between carrier and sodium chloride is between 1:1 and 3:1.  
   
   
       5 . Compositions as claimed in any one of  claims 1  to  4 , wherein the weight ratio between 6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione dimaleate and the carrier is between 1:2 and 1:6.  
   
   
       6 . Compositions as claimed in any one of  claims 1  to  5 , wherein 6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione dimaleate is present in the quantity of 7-15 mg/ml in the solution to be lyophilised.  
   
   
       7 . Compositions as claimed in  claim 6  containing 10 to 40 mg/ml of sodium chloride and 20 to 60 mg/ml of lactose in the solution to be lyophilised.  
   
   
       8 . Compositions as claimed in any one of  claims 1  to  7 , wherein the unit dose of 6,9-bis [(2-aminoethyl)amino]benzo [g]isoquinoline-5,10-dione dimaleate is between 25 and 200 mg.  
   
   
       9 . Compositions according to  claim 8 , wherein the unit dose of 6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione dimaleate is 50 mg.  
   
   
       10 . Compositions as claimed in any one of  claims 1  to  9 , associated with an ampoule containing a sterile solvent suitable to reconstitute the lyophilisate and suitable for parenteral administration.  
   
   
       11 . A process for preparation of the compositions claimed in claims  1 - 10  which involves lyophilisation of an aqueous solution of 6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione dimaleate, lactose or dextran and sodium chloride by means of: 
 a freezing stage at a temperature below at least −45° C. for at least 3 hours;    a primary drying stage consisting of increasing the temperature of the product to −35° C.±5° C. in approx. 3 hours and maintaining said temperature for at least 40 hours;    a secondary drying stage consisting of increasing the temperature of the Product to +30° C.±5° C. in 10 hours and maintaining said temperature for at least 8 hours.