Lyophilized preparation of cytotoxic dipeptides
The present invention is directed to novel lyophilized pharmaceutical preparations comprising a cytotoxic dipeptides such as melphalan flufenamide and one or more excipient(s) selected from the group comprising a polysorbate; a polyethylene glycol; β-cyclodextrin; ocyclodextrin; hydroxypropyl-β-cyclodextrin; sulfobutylether-β-cyclodextrin; lactose; benzyl alcohol; disodium succinate; propylene glycol; Cremophor EL; Dimethyl sulfoxide; D-mannitol; Trehalose; Sucrose and an amino acid. This preparation may be further formulated and is useful in cancer therapy.
1. A lyophilized pharmaceutical preparation which is directly soluble in a physiologically acceptable aqueous solution, comprising melphalan flufenamide hydrochloride (J1) and sucrose.
2. The lyophilized pharmaceutical preparation according to claim 1 , wherein the amount of sucrose is 10-100% by weight of said melphalan flufenamide hydrochloride (J1).
3. The lyophilized pharmaceutical preparation according to claim 1 , which is free, or substantially free from organic solvents.
4. The lyophilized pharmaceutical preparation according to claim 2 , which is free, or substantially free from organic solvents.
5. A pharmaceutical composition consisting of the lyophilized pharmaceutical preparation of claim 1 and a physiologically acceptable solution, wherein said physiologically acceptable solution is a glucose solution.
6. A pharmaceutical composition consisting of the lyophilized pharmaceutical preparation of claim 2 and a physiologically acceptable solution, wherein said physiologically acceptable solution is a glucose solution.
7. A pharmaceutical composition consisting of the lyophilized pharmaceutical preparation of claim 3 and a physiologically acceptable solution, wherein said physiologically acceptable solution is a glucose solution.
8. A pharmaceutical composition consisting of the lyophilized pharmaceutical preparation of claim 4 and a physiologically acceptable solution, wherein said physiologically acceptable solution is a glucose solution.
9. The lyophilized pharmaceutical preparation according to claim 1 , in which sucrose is the sole excipient.
10. The lyophilized pharmaceutical preparation according to claim 9 , which contains trace amounts of an organic solvent.
11. The lyophilized pharmaceutical preparation according to claim 1 , which consists essentially of J1 and sucrose.
12. The lyophilized pharmaceutical preparation according to claim 11 , which contains trace amounts of an organic solvent.
13. The lyophilized pharmaceutical preparation according to claim 9 , which consists essentially of J1 and sucrose.
14. The lyophilized pharmaceutical preparation according to claim 13 , which contains trace amounts of an organic solvent.
15. The lyophilized pharmaceutical preparation according to any one of claims 1 to 4 , which is obtained by lyophilizing a solution comprising J1, sucrose, an organic solvent and water.
16. The lyophilized pharmaceutical preparation according to any one of claims 9 to 14 , which is obtained by lyophilizing a solution of J1, sucrose, an organic solvent and water.