Crosslinked Polyalkyleneimine Hydrogels with Tunable Degradation Rates

• US 20090215923A1
• Filed: 02/13/2009
• Published: 08/27/2009
• Est. Priority Date: 02/13/2008
• Status: Active Grant

• Current Assignee: HyperBranch Medical Technology, Inc. (Stryker Corporation)
• Original Assignee: HyperBranch Medical Technology, Inc. (Stryker Corporation)
• Inventors: Carnahan, Michael A., Butlin, Jared D. G.
• Granted Patent: US 8,410,189 B2
• Time in Patent Office: Days
• US Class Current: 523/118
• CPC Class Codes: A61L 24/046 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043 takes precedence
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: C08G 65/326 containing sulfur
• CPC Class Codes: C08G 65/33337 cyclic
• CPC Class Codes: C08G 65/337 containing other elements organic compounds containing halogens only as halides of a carboxyl group C08G65/332
• CPC Class Codes: C08K 5/0025 Crosslinking or vulcanising agents; including accelerators
• CPC Class Codes: C08K 5/3415 Five-membered rings
• CPC Class Codes: C08L 101/02 characterised by the presence of specified groups , e.g. terminal or pendant functional groups
• CPC Class Codes: C08L 2203/02 for biomedical use
• CPC Class Codes: C08L 2666/20 Macromolecular compounds having nitrogen in the main chain according to C08L75/00 - C08L79/00; Derivatives thereof
• CPC Class Codes: C08L 71/02 Polyalkylene oxides
• CPC Class Codes: C08L 77/04 Polyamides derived from alpha-amino carboxylic acids C08L77/10 takes precedence
• CPC Class Codes: C08L 79/02 Polyamines

Abstract

One aspect of the present invention relates to methods of sealing a wound or tissue plane or filling a void space, or securing meshes, films or other devices within the body. In certain embodiments, the wound is an ophthalmic, pleural or dural wound, or a hernia repair mesh. Remarkably, disclosed herein is the discovery that the use of certain crosslinkers in combination with polyalkyleneimines at specific concentrations can result in hydrogels with tunable degradation properties.

Claims

1. A polymeric composition in contact with tissue, comprising an activated polyalkylene glycol diacid derivative and a crosslinking agent;

wherein the activated polyalkylene glycol diacid derivative is represented by formula I;

2. The polymeric composition of claim 1, wherein the crosslinking agent is a polyalkyleneimine or trilysine.

3. The polymeric composition of claim 1, wherein the crosslinking agent is PEI₂₀₀₀.

4. The polymeric composition of claim 1, wherein the crosslinking agent is trilysine.

5. The polymeric composition of claim 1, wherein m is 2-10 inclusive.

6. The polymeric composition of claim 1, wherein m is 2.

7. The polymeric composition of claim 1, wherein m is 3.

8. The polymeric composition of claim 1, wherein m is 4.

9. The polymeric composition of claim 1, wherein m is 6.

10. The polymeric composition of claim 1, wherein m is 8.

11. The polymeric composition of claim 1, wherein w is 20 to 120 inclusive.

12. The polymeric composition of claim 1, wherein w is 120 to 250 inclusive.

13. The polymeric composition of claim 1, wherein the activated polyalkylene glycol diacid derivative is R-PEG_n-R;

wherein n represents the number average molecular weight of the PEG and is about 2000 to about 12,000 inclusive; and

R is SS, SG, SA, SSub, or SSeb.

14. The polymeric composition of claim 13, wherein the activated polyalkylene glycol diacid derivative is PEG₃₃₅₀-(SS)₂.

15. The polymeric composition of claim 13, wherein the activated polyalkylene glycol diacid derivative is PEG₃₃₅₀-(SG)₂.

16. The polymeric composition of claim 13, wherein the activated polyalkylene glycol diacid derivative is PEG₃₃₅₀-(SA)₂.

17. The polymeric composition of claim 13, wherein the activated polyalkylene glycol diacid derivative is PEG₃₃₅₀-(SSeb)₂.

18. The polymeric composition of claim 13, wherein the activated polyalkylene glycol diacid derivative is PEG₃₃₅₀-(SSub)₂.

19. The polymeric composition of claim 1, wherein the weight percent crosslinker is between about 5% and about 50%.

20. The polymeric composition of claim 1, wherein the weight percent crosslinker is about 15%.

21. The polymeric composition of claim 1, wherein the ratio of activated esters on the polyalkylene glycol diacid derivatives to primary amines on the crosslinking agent is in the range from about 0.10:

1 to about 10;

1.

22. The polymeric composition of claim 1, wherein the ratio of activated esters on the polyalkylene glycol diacid derivatives to primary amines on the crosslinking agent is in the range from about 0.75:

1 to about 1.3;

1.

23. The polymeric composition of claim 1, wherein R is methyl or H.

24. The polymeric composition of claim 1, wherein R is H.

25. A method of sealing a wound of a patient, comprising the steps of:

combining effective amounts of an activated polyalkylene glycol diacid derivative and a crosslinking agent to form a composition, and applying said composition to a wound of a patient;

wherein the activated polyalkylene glycol diacid derivative is represented by formula I;

26. A method of augmenting soft tissue or filling a void of a patient, comprising the steps of:

combining effective amounts of an activated polyalkylene glycol diacid derivative and a crosslinking agent to form a composition, and applying said composition to soft tissue or a void of a patient;

wherein the activated polyalkylene glycol diacid derivative is represented by formula I;

27. A method of adhering tissues of a patient, comprising the steps of:

combining effective amounts of an activated polyalkylene glycol diacid derivative and a crosslinking agent to form a composition, applying said composition to a first tissue of a patient to form a modified tissue, and contacting said modified tissue with a second tissue of a patient;

wherein the activated polyalkylene glycol diacid derivative is represented by formula I;

28. A method of securing a prosthetic material to a tissue of a patient, comprising the steps of:

combining effective amounts of an activated polyalkylene glycol diacid derivative and a crosslinking agent to form a composition;

applying said composition to the prosthetic material, thereby forming a modified prosthetic material;

contacting the modified prosthetic material to the tissue of the patient, thereby securing the modified prosthetic material to the tissue of the patient;

wherein the activated polyalkylene glycol diacid derivative is represented by formula I;