Tissue glue with improved antiadhesive properties
View Patent ↗The use of a tissue glue comprising a stabilized fibrinogen preparation, which can be stored in the liquid or frozen state and comprises a chaotropic substance, and a thrombin preparation, for reducing or preventing tissue adhesions, is described.
1. A method for reducing or preventing tissue adhesions comprising the application to a tissue of a tissue glue, wherein the tissue glue comprises:
a fibrinogen preparation, and
a thrombin preparation,
wherein the fibrinogen preparation can be stored in the liquid or frozen state, wherein the fibrinogen preparation further comprises a chaotropic substance in the range of more than about 0.04 M to less than about 0.28 M, wherein the total concentration of water-soluble inorganic salts in the fibrinogen preparation is equal to or less than about 100 mmol/liter; and
wherein the tissue glue reduces or prevents tissue adhesions.
2. The method according to claim 1 , wherein the tissue glue further comprises coagulation Factor XIII.
3. The method according to one of claims 1 or 2 , wherein the tissue glue further comprises an antifibrinolytic agent.
4. The method according to claim 3 , wherein the antifibrinolytic agent is ε-aminocaproic acid.
5. The method according to claim 3 , wherein the antifibrinolytic agent is p-aminomethylbenzoic acid.
6. The method according to claim 3 , wherein the antifibrinolytic agent is aprotinin.
7. The method according to one of claims 1 or 2 , wherein the preparation of the fibrinogen preparation comprises, purification steps.
8. The method according to claim 7 , wherein the fibrinogen preparation has a reduced plasminogen content.
9. The method according to claim 8 , wherein the ratio of plasminogen to fibrinogen is less than 1.8×10 -4 (w/w).
10. The method according to claim 2 , wherein the Factor XIII preparation further comprises one or more substances selected from stabilizers or buffer substances.
11. The method according to claim 10 , wherein the one or more stabilizers are selected from physiologically tolerated salts of an organic di-, tri- and tetracarboxylic acid.
12. The method according to claim 11 , wherein the carboxylic acid is citric acid.
13. The method according to claim 10 , wherein the Factor XIII preparation further comprises one or more stabilizers selected from:
a mono- or disaccharide or a sugar alcohol,
at least one amino acid selected from glycine, glycylglycine, alanine, cysteine, histidine, glutamine or a physiologically tolerated salt of glutamic or aspartic acid,
a reducing or oxidation-preventing agent, and
a surface-active substance.
14. The method according to one of claims 1 or 2 , wherein the one or more chaotropic substances is selected from arginine, guanidine, citrulline, urea, nicotine amide, and their derivatives.
15. The method according to one of claims 1 or 2 , wherein the fibrinogen preparation further comprises one or more stabilizers selected from:
an inorganic salt,
one or more physiologically tolerated salts of organic carboxylic acids,
one or more amino acids,
a mono- or disaccharide, and
a sugar alcohol.
16. The method according to claim 15 , wherein the carboxylic acid is selected from citric acid and lactic acid.
17. The method according to one of claims 1 or 2 , wherein the thrombin preparation further comprises one or more stabilizers.
18. The method according to claim 17 , wherein the one or more stabilizers are selected from: a soluble calcium salt,
sodium chloride,
a buffer substance,
a sugar,
a sugar alcohol,
an amino acid,
a salt of a mono- or polycarboxylic acid, and
a salt of a mono- or polyhydroxy carboxylic acid.
19. The method according to claim 17 , wherein the stabilizer is a non-covalently binding inhibitor.
20. The method according to one of claims 1 or 2 , wherein the preparation of the thrombin preparation comprises purification by hydrophobic interaction chromatography.
21. The method according to claim 20 , wherein the purification of the thrombin preparation further comprises purification by cation exchange chromatography.
22. The method according to one of claims 1 or 2 , wherein the tissue glue or the constituents of the tissue glue have been subjected to one or more methods for inactivating or removing viruses.
23. The method according to claim 3 , wherein the tissue glue or the constituents of the tissue glue have been subjected to one or more methods for inactivating or removing viruses.
24. A method for reducing or preventing tissue adhesions comprising the application to a tissue of a tissue glue, wherein the tissue glue comprises:
a fibrinogen preparation,
a thrombin preparation, wherein the fibrinogen preparation can be stored in liquid or frozen state,
wherein the fibrinogen preparation has a reduced plasminogen content, wherein the total concentration of water-soluble inorganic salts in the fibrinogen preparation is egual to or less than about 100 mmol/liter; and wherein the tissue glue reduces or prevents tissue adhesions.
25. The method according to claim 1 , wherein the tissue has optionally been treated with a conventional tissue glue prior to the application of the tissue glue of claim 1 .
26. The method according to claim 24 , wherein the tissue has optionally been treated with a conventional tissue glue prior to the application of the tissue glue of claim 24 .
27. The method according to claim 2 , wherein the total concentration of water-soluble inorganic salts in the fibrinogen preparation is equal to or less than about 50 mmol/liter.
28. The method according to claim 27 , wherein the total concentration of water-soluble inorganic salts in the fibrinogen preparation is equal to or less than about 20 mmol/liter.
29. The method according to claim 28 , wherein no water-soluble inorganic salts are added to the fibrinogen preparation.
30. The method according to claim 2 , wherein the fibrinogen preparation remains stable after 2 weeks of storage in the liquid state.