Composition consisting of a polymer containing amino groups and an aldehyde containing at least three aldehyde groups

• US 20050002893A1
• Filed: 10/24/2002
• Published: 01/06/2005
• Est. Priority Date: 10/24/2001
• Status: Abandoned Application

• Current Assignee: Aesculap AG (B. Braun Holding GmbH & Co. KG)
• Original Assignee: Aesculap AG (B. Braun Holding GmbH & Co. KG)
• Inventors: Goldmann, Helmut
• Application Number:
  US10/493,422
• Publication Number:
  US 20050002893A1
• Time in Patent Office: Days
• US Class Current: 424/70.270
• CPC Class Codes: A61L 24/043 Mixtures of macromolecular materials
• CPC Class Codes: A61L 24/08 Polysaccharides A61L24/043 takes precedence
• CPC Class Codes: C08B 37/003 Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
• CPC Class Codes: C08L 29/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: C08L 5/02 Dextran; Derivatives thereof
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

The invention relates to a composition of at least two, in particular two, biocompatible components which can be chemically crosslinked together, in particular for gluing biological tissue, comprising at least the following components: a) aqueous solution of at least one polymer having amino groups b) aqueous solution of at least one aldehyde having at least three aldehyde groups, where the composition is free of protein. The invention further relates to a provision of the composition for use as surgical tissue glue, and to a kit consisting of two substantially separate containers which contain components of the composition.

Claims

1. A composition of at least two, in particular two, biocompatible components which can be chemically crosslinked together, in particular for gluing biological tissue, comprising at least the following components:

a) aqueous solution of at least one polymer having amino groups

b) aqueous solution of at least one aldehyde having at least three aldehyde groups,

where the stoichiometric amount of aldehyde groups in component b) is at least three times the stoichiometric amount of amino groups in the polymer having amino groups, and the composition is free of protein.

2. The composition as claimed in claim 1, characterized in that the aldehyde and the polymer having amino groups can be crosslinked together at body temperature.

3. The composition as claimed in either of claims 1 or 2, characterized in that the polymer having amino groups is derived from a biodegradable natural material.

4. The composition as claimed in any of the preceding claims, characterized in that the polymer having amino groups is a polysaccharide, in particular a modified polysaccharide, in which the amino groups are liberated by deacetylation.

5. The composition as claimed in any of the preceding claims, characterized in that the polymer having amino groups is chitosan.

6. The composition as claimed in any of the preceding claims, characterized in that the polymer having amino groups is an at least partially deacetylated chitin having a degree of deacetylation of from 50 to 100%, preferably 60 to 90%, in particular 70 to 80%.

7. The composition as claimed in any of the preceding claims, in particular as claimed in claim 1 or 2, characterized in that the polymer having amino groups is a synthetic polymer, in particular a polymer which undergoes renal elimination.

8. The composition as claimed in claim 7, characterized in that the synthetic polymer is a modified polyvinyl alcohol having amino groups, preferably having a molecular weight of ≦

50 000, in particular ≦

20 000.

9. The composition as claimed in any of the preceding claims, characterized in that the aldehyde is a polyaldehyde.

10. The composition as claimed in any of the preceding claims, characterized in that the aldehyde is an oxidized polysaccharide.

11. The composition as claimed in claim 10, characterized in that the polysaccharide is at least one from the group of dextran, chitin, starch, agar, cellulose, alginic acid, glycosaminoglycans, hyaluronic acid, chondroitin sulfate and derivatives thereof.

12. The composition as claimed in any of the preceding claims, characterized in that the aldehyde, in particular dextranaldehyde, has a molecular weight of about 60 000 to 600 000, in particular about 200 000.

13. The composition as claimed in any of the preceding claims, characterized in that the aldehyde is partially or completely masked.

14. The composition as claimed in claim 13, characterized in that the aldehyde is masked with an S, O or N nucleophile.

15. The composition as claimed in either of claims 13 or 14, characterized in that the partially or completely masked aldehyde is a polysaccharide-alkali metal bisulfite adduct.

16. The composition as claimed in either of claims 13 or 14, characterized in that the aldehyde is partially or completely masked with ethanol or glycerol.

17. The composition as claimed in any of the preceding claims, characterized in that the content of aldehyde of component b) is from 5 to 20% by weight, in particular from 10 to 15% by weight.

18. The composition as claimed in any of the preceding claims, characterized in that the content of polymer having amino groups of component a) is from 1 to 25% by weight, in particular from 2 to 20% by weight.

19. The composition as claimed in any of the preceding claims, characterized in that the ph values of the components are adjusted so that the ph of a mixture of the components is between 3 and 8, in particular between 5 and 7.5.

20. The composition as claimed in any of the preceding claims, characterized in that the components are adjusted with respect to one another so that they crosslink together in a short time, in particular a time of from 15 to 200 sec, after they are combined.

21. The composition as claimed in any of the preceding claims, characterized in that the viscosities of the components are adjusted in relation to one another so that a layer of the composition with a thickness of from 0.1 to 1 mm can be applied.

22. The composition as claimed in any of claims 1 to 6 and 9 to 18, characterized in that component a) is a solution of chitosan in acetic acid, and component b) is an aqueous solution of dextranaldehyde.

23. The provision of the composition as claimed in any of the preceding claims for use as surgical tissue adhesive, in particular for sealing or closing surfaces or orifices.

24. The use as set forth in claim 23, characterized in that the components are mixed together shortly before application.

25. The use as set forth in claim 23, characterized in that the components are mixed on an application site.

26. A kit consisting of two substantially separate containers, where the containers each contain one component of the composition as claimed in any of claims 1 to 22.

27. The kit as claimed in claim 26, characterized in that the two containers function as syringe barrels of a double syringe.

28. The kit as claimed in either of claims 26 to 27, characterized in that it has a device for mixing the components.

29. The kit as claimed in any of claims 26 to 28, characterized in that it has a static mixer which can be fitted in particular onto a double syringe.