Stable compositions containing thrombin and methods for preparation and use thereof
View Patent ↗Compositions comprising thrombin and collagen and methods of preparation thereof are disclosed herein. In one embodiment, a composition comprises thrombin and collagen in an aqueous buffer solution, wherein the buffer solution includes at least one of a first compound represented by Formula I: R 1 —C(O)—O − M + , wherein R 1 is —CH 3 , —CH 2 CH 2 C(O)OH, or —CH 2 CH 2 C(O)O − M + , and wherein M + is a monovalent ion; or a second compound represented by Formula II: R 2 —C(O)—O − M 2+− O—C(O)—R 2 , wherein R 2 is —CH 3 or —CH 2 CH 3 , and wherein M 2+ is a divalent ion. In one embodiment, the buffer solution includes sodium acetate, calcium propionate, and sorbitol.
1. An aqueous buffer solution, comprising:
sorbitol;
a first compound; and
a second compound,
wherein the first compound is represented by the following Formula I:
wherein R 1 is —CH 3 and wherein M + is a sodium ion (Na + );
wherein the second compound is represented by the following Formula II:
wherein R 2 is CH 2 CH 3 and wherein M 2+ is a calcium ion (Ca 2+ ), and
wherein the buffer solution does not include a chloride-containing salt.
2. The buffer solution of claim 1 , wherein the pH of the composition ranges from about 5.0 to about 8.5.
3. An aqueous buffer solution, comprising:
sodium succinate,
calcium propionate, and
sorbitol
wherein the buffer solution does not include a chloride-containing salt.
4. The buffer solution of claim 3 , wherein the sodium succinate is dibasic.
5. The buffer solution of claim 1 , wherein an amount of the first compound ranges from about 1 mg/ml to about 50 mg/ml.
6. The buffer solution of claim 1 , wherein an amount of the second compound ranges from about 1 mg/ml to about 50 mg/ml.
7. The buffer solution of claim 1 , wherein an amount of the sorbitol ranges from about 2.5 wt % to about 20 wt % of the buffer solution.
8. A composition including pepsinized microfibrillar collagen and thrombin in the aqueous buffer solution of claim 1 , wherein an initial thrombin activity ranges from about 400 to about 500 units of enzyme activity per milliliter of buffer solution.
9. The composition of claim 8 , where the thrombin is bovine thrombin or recombinant thrombin.
10. The composition of claim 8 , wherein an amount of the sorbitol ranges from about 0.1 to about 10 wt % of the composition.
11. The composition of claim 8 , wherein an amount of the first compound ranges from about 0.1 wt % to about 5 wt % of the composition, and wherein an amount of the second compound ranges from about 0.1 wt % to about 5 wt % of the composition.
12. The buffer solution of claim 3 , wherein an amount of the sodium succinate ranges from about 1 mg/ml to about 50 mg/ml.
13. The buffer solution of claim 3 , wherein an amount of the calcium propionate ranges from about 1 mg/ml to about 50 mg/ml.
14. The buffer solution of claim 3 , wherein an amount of the sorbitol ranges from about 2.5 wt % to about 20 wt % of the buffer solution.
15. A composition including pepsinized microfibrillar collagen and thrombin in the aqueous buffer solution of claim 3 , wherein an initial thrombin activity ranges from about 400 to about 500 units of enzyme activity per milliliter of buffer solution.
16. The composition of claim 15 , where the thrombin is bovine thrombin or recombinant thrombin.
17. The composition of claim 15 , wherein an amount of the sorbitol ranges from about 0.1 to about 10 wt % of the composition.
18. The composition of claim 15 , wherein an amount of the sodium succinate ranges from about 0.1 wt % to about 5 wt % of the composition, and wherein an amount of the calcium propionate ranges from about 0.1 wt % to about 5 wt % of the composition.