Pharmaceutical compositions of fibrinolytic agent
AssigneeAmgen Inc.
InventorsBrent S. Kendrick, Brian A. Peterson
Life of this patent
Estimating the term…
Abstract
Frozen and lyophilized compositions for a metalloproteinase fibrinolytic agent (fibrolase or NAT), a method for preparing the lyophilized composition, and a kit and method for reconstituting the lyophilized composition are described herein.
Claims16
A pharmaceutical composition comprising a metalloproteinase fibrinolytic agent, a zinc stabilizer and, optionally, a bulking agent, in a pharmaceutically-acceptable buffer, wherein the metalloproteinase fibrinolytic agent comprises the amino acid sequence SEQ.ID NO:
- 1.
An aqueous pharmaceutical composition comprising about 0.1 to about 50 mg/ml of a metalloproteinase fibrinolytic agent comprising the amino acid sequence of SEQ. ID NO:
- 1, about 0.08 to about 0.12 mM of zinc sulfate, about 0.008 mM to about 0.012 mM of calcium acetate, and about 95 to 110 mM of citric acid or sodium citrate, with the pH of said composition being about 7.4.
An aqueous pharmaceutical composition comprising about 0.1 to about 50 mg/ml of a metalloproteinase fibrinolytic agent comprising the amino acid sequence of SEQ. ID NO:
- 1;
- about 0.08 to about 0.12 mM of zinc acetate, about 18 to about 22 mM of citric acid or sodium citrate, about 0.02 to about 0.06 mM of Tris, about 3 to about 6 percent (w/v) of mannitol, and about 0.008 to about 0.012 percent (w/v) of a surfactant, with the pH of said composition being about 8.0.
An aqueous pharmaceutical composition suitable for lyophilization, comprising about 0.1 to about 50 mg/ml of a metalloproteinase fibrinolytic agent comprising the amino acid sequence of SEQ. ID NO:
- 1;
- about 0.08 to about 0.12 mM of zinc sulfate, about 18 to about 22 mM of citric acid or sodium citrate, about 3 to about 6 mM of Tris, about 3 to about 6 percent (w/v) of mannitol, and about 0.008 to about 0.012 percent (w/v) of a surfactant, and optional about 0.1 to about 0.5 percent (w/v) of sucrose, with the pH of said composition being about 8.0.
A lyophilized pharmaceutical composition prepared by a method comprising the steps of:
- (a) preparing a solution of a zinc salt, a bulking agent and a stabilizing disaccharide,
- (b) adjusting the pH of the solution to a pH between 7.6 and 8.2,
- (c) preparing a solution containing a metalloproteinase fibrinolytic agent comprising the amino acid sequence of SEQ. ID NO:
- 1,
- (d) buffer exchanging the solution of step (c) into the solution of step (b),
- (e) adding an effective amount of a surfactant, and
- (f) lyophilizing the mixture from step (e).
A kit for preparing an aqueous pharmaceutical composition comprising a first container having a lyophilized composition of a metalloproteinase fibrinolytic agent comprising the amino acid sequence of SEQ. ID NO:
- 1 and a second container having a physiologically acceptable solvent for the lyophilized composition.
Dependencies are inferred from the claim text.