Lyophilized formulation

Abstract

For clinical application of cis[((1R,2R)-1,2-cyclohexanediamine-N,N′)bis(R 1 )]platinum(II) (R 1 is an alkanoyloxy group having 6 to 20 carbon atoms), the present invention aims at providing a formulation which prevents layer separation and changes in viscosity, shows fine suspendability, and which is easy to handle during administration. The formulation of the present invention is a lyophilized a formulation for injection obtained by dissolving a cis[((1R,2R)-1,2-cyclohexanediamine-N,N′)bis(R 1 )]platinum(II) in 2-methyl-2-propanol and lyophilizing this solution, which has a central particle size distribution of around 3-25 μm and a D90% value of not more than 40 μm.

1 . A lyophilized formulation comprising a cis[((1R,2R)-1,2-cyclohexanediamine-N,N′)bis(R 1 )]platinum(II), wherein R 1  is a tetradecanoyloxy group, as a main ingredient, which has a central particle size distribution of around 3-25 μm and a D90% value of not more than 33 μm. 
     
     
         2 . The lyophilized formulation of  claim 1 , wherein the central particle size distribution is around 5-20 μm. 
     
     
         3 . (canceled) 
     
     
         4 . The lyophilized formulation of  claim 1  to  claim 2 , wherein the D90% value is not more than 30 μm. 
     
     
         5 . A lyophilized formulation comprising cis[((1R,2R)-1,2-cyclohexanediamine-N,N′)bis(R 1 )]platinum(II), wherein R 1  is an tetradecanoyloxy group, as a main ingredient, which is produced by a method comprising the following steps:
 (1) a step of dissolving cis[((1R,2R)-1,2-cyclohexanediamine-N,N′)bis(R 1 )]platinum(II) in 2-methyl-2-propanol,   (2) a step of adjusting a water content of said solution to 1.0-6.0 mg/mL,   (3) a step of quickly freezing said solution, and   (4) a step of lyophilizing said frozen solution.   
     
     
         6 . The lyophilized formulation of  claim 5 , wherein the freezing is done within 15 minutes. 
     
     
         7 . The lyophilized formulation of  claim 5  or  claim 6 , wherein, in the above-mentioned (2), the water content of the solution is adjusted to 1.5-5.0 mg/mL. 
     
     
         8 . The lyophilized formulation of  claim 5  or  claim 6 , wherein, in the above-mentioned (2), the water content of the solution is adjusted to 1.5-4.0 mg/mL. 
     
     
         9 . A lyophilized formulation comprising, as a main ingredient, a cis[((1R,2R)-1,2-cyclohexanediamine-N,N′)bis(tetradecanoyloxy)]platinum(II) having a central particle size distribution of around 3-25 μm and a D90% value of not more than 33 μm, which is produced by a method comprising the following steps:
 (1) a step of dissolving a cis[((1R,2R)-1,2-cyclohexanediamine-N,N′)bis(tetradecanoyloxy)]platinum(II) in 2-methyl-2-propanol,   (2) a step of adjusting a water content of said solution to 1.0-6.0 mg/mL,   (3) a step of quickly freezing said solution, and   (4) a step of lyophilizing said frozen solution.