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. A composition comprising thrombin and pepsinized microfibrillar collagen in an aqueous buffer solution, wherein the buffer solution includes:
at least one sugar selected from the group consisting of mannitol, sorbitol, sucrose, raffinose, and trehalose; and at least one of a first compound or a second compound,
wherein the first compound is represented by the following Formula I:
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, and
wherein the second compound is represented by the following Formula II:
wherein R 2 is —CH 3 or —CH 2 CH 3 , and wherein M 2+ is a divalent ion, and
wherein the buffer solution does not include a chloride-containing salt.
2. The composition of claim 1 , where the thrombin is bovine thrombin.
3. The composition of claim 1 , wherein the thrombin is recombinant thrombin.
4. The composition of claim 1 , wherein M + is a sodium ion (Na + ).
5. The composition of claim 4 , wherein R 1 is —CH 3 .
6. The composition of claim 4 , wherein R 1 is —CH 2 CH 2 C(O)O − M + .
7. The composition of claim 1 , wherein M 2+ is a calcium ion (Ca 2+ ).
8. The composition of claim 7 , wherein R 2 is —CH 3 .
9. The composition of claim 7 , wherein R 2 is —CH 2 CH 3 .
10. The composition of claim 1 , wherein the pH of the composition ranges from about 5.5 to about 6.5.
11. The composition of claim 1 , wherein an initial thrombin activity ranges from about 400 to about 500 units of enzyme activity per milliliter of buffer solution.
12. The composition of claim 11 , wherein M+ is a sodium ion (Na + ), R 1 is —CH 3 , M 2+ is a calcium ion (Ca 2+ ) and R 2 is —CH 2 CH 3 , and wherein the buffer solution further comprises sorbitol.
13. The composition of claim 1 , wherein the buffer solution includes the second compound, and further comprises sorbitol.
14. The composition of claim 1 , wherein the buffer solution includes sodium acetate, calcium propionate, and sorbitol.
15. The composition of claim 1 , wherein the buffer solution includes sodium succinate, calcium propionate, and sorbitol.
16. The composition of claim 15 , wherein the sodium succinate is dibasic.
17. The composition of claim 1 , wherein the buffer solution include calcium acetate and sorbitol.
18. The composition of claim 1 , wherein the buffer solution includes calcium acetate and mannitol.