Stabilized preparations of serine endopeptidases, their preparation and use
View Patent ↗The invention relates to stabilized preparations of serine endopeptidases which are suitable for use as a test reagent in a diagnostic procedure or for a therapeutic use. As a result of the addition of various additives, the preparations have improved stability and shelf life.
1. A preparation for stabilizing serine endopeptidases, comprising at least one serine endopeptidase and an effective amount of glycerol together with at least one amino acid selected from the group consisting of aspartic acid and its salts, glutamic acid and its salts, histidine, and glycine.
2. The preparation of claim 1 , wherein glycerol is present in a final concentration of 0.5 to 50 percent by volume.
3. The preparation of claim 1 , wherein the amino acid is selected from the group consisting of histidine, and glycine, and wherein the amino acid is present in a final concentration of 10 to 250 mM.
4. The preparation of claim 1 , wherein the amino acid is selected from the group consisting of aspartic acid and its salts, and glutamic acid and its salts, and wherein the amino acid is present in a final concentration of 10 to 1000 mM.
5. The preparation of claim 1 further comprising at least one nonreducing sugar.
6. The preparation of claim 1 , wherein the serine endopeptidase is an animal or human blood clotting factor selected from the group consisting of F II, F VII, F IX, F X, F XI, F XII, F IIa, F VIIa, F IXa, F Xa, F XIa, and F XIIa.
7. The preparation of claim 1 , wherein the serine endopeptidase is an animal or human complement factor selected from the group consisting of C1r, C1s, complement factor D, and complement factor I.
8. The preparation of claim 1 , wherein the serine endopeptidase is selected from the group consisting of chymotrypsin, trypsin, plasmin, acrosin, cathepsin G, plasma kallikrein, tissue kallikrein, pancreatic elastase, leucocyte elastase, C3/C5 convertase (classical), C3/C5 convertase (alternative), subtilisin, proteinase K, activated protein C, tissue plasminogen activator, urokinase plasminogen activator, furin, limulus clotting factor C, limulus clotting factor B, limulus clotting enzyme, and snake venom factor V activator.
9. The preparation of claim 1 , wherein the preparation is liquid.
10. The preparation of claim 1 , wherein no lysine is added to the preparation.
11. The preparation of claim 1 , wherein glycerol is present in a final concentration of 10 to 50 percent by volume.
12. The preparation of claim 1 , wherein glycerol is present in a final concentration of 30 to 50 percent by volume.
13. The preparation of claim 1 , wherein the amino acid is selected from the group consisting of aspartic acid and its salts and glutamic acid and its salts, and wherein the amino acid is present in a final concentration of 400 to 1000 mM.
14. The preparation of claim 1 , wherein the amino acid is selected from the group consisting of aspartic acid and its salts and glutamic acid and its salts, and wherein the amino acid is present in a final concentration of 500 to 800 mM.
15. A preparation for stabilizing serine endopeptidases, comprising at least one serine endopeptidase and an effective amount of glycerol together with at least one of sodium aspartate and sodium glutamate.
16. A preparation for stabilizing serine endopeptidases, comprising at least one serine endopeptidase and an effective amount of ammonium acetate and glycerol together with at least one of sodium aspartate and sodium glutamate.
17. A preparation for stabilizing serine endopeptidases, comprising at least one serine endopeptidase and an effective amount of ammonium acetate.
18. The preparation of claim 17 , wherein ammonium acetate is present in a final concentration of 25 to 1000 mM.
19. The preparation of claim 17 further comprising at least one nonreducing sugar.
20. The preparation of claim 17 , wherein the serine endopeptidase is an animal or human blood clotting factor selected from the group consisting of F II, F VII, F IX, F X, F XI, F XII, F IIa, F VIIa, F IXa, F Xa, F XIa, and F XIIa.
21. The preparation of claim 17 , wherein the preparation is liquid.
22. The preparation of claim 17 , wherein ammonium acetate is present in a final concentration of 400 to 1000 mM.
23. The preparation of claim 17 , wherein ammonium acetate is present in a final concentration of 700 to 1000 mM.
24. A preparation for stabilizing serine endopeptidases, comprising at least one serine endopeptidase and an effective amount of at least one polyamino acid.
25. The preparation of claim 24 , wherein at least one polyamino acid is selected from the group consisting of poly-L-glutamate and poly-L-aspartate.
26. The preparation of claim 25 , wherein the polyamino acid is present in a final concentration of 1 to 10 mM.
27. The preparation of claim 24 further comprising at least one nonreducing sugar.
28. The preparation of claim 24 , wherein the serine endopeptidase is an animal or human blood clotting factor selected from the group consisting of F II, F VII, F IX, F X, F XI, F XII, F IIa, F VIIa, F IXa, F Xa, F XIa, and F XIIa.
29. The preparation of claim 24 , wherein the preparation is liquid.
30. The preparation of claim 24 , wherein the polyamino acid is present in a final concentration of 2 to 10 mM.
31. The preparation of claim 24 , wherein the polyamino acid is present in a final concentration of 2 to 5 mM.