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-cycledextrin; ocyclodextrin; hydroxypropyl-β-cyclodextrin; sulfobutylether-β-cyclodextrin; lactose; benzyl alcohol; disodium succinate; propylene glycol; Cremsophor EL; Dimethyl sulfoxide; D-mannitol; Trebalose; Sucrose and an amino acid. This preparation may be further formulated and is useful in cancer therapy.
1 - 40 . (canceled)
41 . A lyophilized pharmaceutical preparation which is directly soluble in a physiologically acceptable aqueous solution, comprising (i) melphalan flufenamide or a pharmaceutically acceptable salt thereof and (ii) trehalose.
42 . The lyophilized pharmaceutical preparation according to claim 41 , wherein said melphalan flufenamide is melphalan flufenamide hydrochloride (J1).
43 . The lyophilized pharmaceutical preparation according to claim 41 , wherein the amount of trehalose is 10-100% by weight of said melphalan flufenamide.
44 . The lyophilized pharmaceutical preparation according to claim 41 , which contains less than 0.5% by weight organic solvents.
45 . The lyophilized pharmaceutical preparation according to claim 42 , which contains less than 0.5% by weight organic solvents.
46 . The lyophilized pharmaceutical preparation according to claim 43 , which contains less than 0.5% by weight organic solvents.
47 . The lyophilized pharmaceutical preparation according to claim 41 , which comprises trehalose as the sole excipient.
48 . The lyophilized pharmaceutical preparation according to claim 47 , which contains trace amounts of an organic solvent.
49 . The lyophilized pharmaceutical preparation according to claim 41 , which consists essentially of (i) melphalan flufenamide or a pharmaceutically acceptable salt thereof and (ii) trehalose.
50 . The lyophilized pharmaceutical preparation according to claim 49 , which contains trace amounts of an organic solvent.
51 . The lyophilized pharmaceutical preparation according to claim 47 , which consists essentially of (i) melphalan flufenamide or a pharmaceutically acceptable salt thereof and (ii) trehalose.
52 . The lyophilized pharmaceutical preparation according to claim 51 , which contains trace amounts of an organic solvent.
53 . The lyophilized pharmaceutical preparation according to claim 51 , wherein said melphalan flufenamide is melphalan flufenamide hydrochloride (J1).
54 . A pharmaceutical composition consisting of the lyophilized pharmaceutical preparation of claim 41 and a physiologically acceptable solution, wherein said physiologically acceptable solution is a glucose solution.
55 . A pharmaceutical composition consisting of the lyophilized pharmaceutical preparation of claim 42 and a physiologically acceptable solution, wherein said physiologically acceptable solution is a glucose solution.
56 . A pharmaceutical composition consisting of the lyophilized pharmaceutical preparation of claim 43 and a physiologically acceptable solution, wherein said physiologically acceptable solution is a glucose solution.
57 . A pharmaceutical composition consisting of the lyophilized pharmaceutical preparation of claim 44 and a physiologically acceptable solution, wherein said physiologically acceptable solution is a glucose solution.