IP Library Granted Patent US 8,025,901
Granted Patent B2
US 8,025,901 · App. 12/615,859 · Granted Sep 27, 2011

Bifunctional-modified hydrogels

Assignee: Wisconsin Alumni Research Foundation
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Quick Facts
Patent No.
US 8,025,901
App. No.
12/615,859
Granted
Sep 27, 2011
Kind
B2
Abstract

Disclosed are hydrogels wherein a polymer matrix is modified to contain a bifunctional poly(alkylene glycol) molecule covalently bonded to the polymer matrix. The hydrogels can be cross-linked using, for example, glutaraldehyde. The hydrogels may also be crosslinked via an interpenetrating network of a photopolymerizable acrylates. The hydrogels may also be modified to have pharmacologically-active agents covalently bonded to the poly(alkylene glycol) molecules or entrained within the hydrogel. Living cells may also be entrained within the hydrogels.

Claims (23)

1. A method of administering pharmacologically-active agents or cells to a patient in need thereof, the method comprising administering a hydrogel to a patient in need of the pharmacologically-active agent or cells, wherein the pharmacologically-active agent or living cells are entrained within the hydrogel, and the hydrogel comprises:

a first polymer matrix containing reactive amino acid moieties;

a second polymer matrix that interpenetrates with the first polymer matrix;

a bifunctional modifier comprising a compound of formula:

wherein at least one of the “A” or “Z” moieties is covalently bonded to the reactive amino moieties of the polymer matrix; and wherein “A” and “Z” are independently selected from the group consisting of hydrogen, halo, hydroxy, C 1 -C 24 -alkyl, C 1 -C 24 -alkenyl, C 1 C 24 -alkynyl, C 1 -C 24 -alkoxy, C 1 -C 24 -heteroalkyl, C 1 -C 24 -hetero alkenyl, C 1 -C 24 -heteroalkynyl, cyano-C 1 -C 24 -alkyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cyclo alkenyl, C 3 -C 10 -cycloalkynyl, C 3 -C 10 cycloheteroalkyl, C 3 -C 10 -cycloheteroalkenyl, C 3 -C 10 -cycloheteroalkynyl, acyl, acyl-C 1 -C 24 -alkyl, acyl-C 1 -C 24 -alkenyl, acyl-C 1 -C 24 -alkenyl, carboxy, C 1 -C 24 -alkylcarboxy, C 1 -C 24 -alkenylcarboxy, C 1 -C 24 -alkynylcarboxy, carboxy-C 1 -C 24 -alkyl, carboxy-C 1 -C 24 -alkenyl, carboxy-C 1 -C 24 -alkynyl, aryl, aryl-C 1 -C 24 -alkyl, aryl-C 1 -C 24 -alkenyl, aryl-C 1 -C 24 -alkynyl, heteroaryl, heteroaryl-C 1 -C 24 -alkyl, heteroaryl-C 1 -C 24 -alkenyl, heteroaryl-C 1 -C 24 -alkynyl, sulfonate, arylsulfonate, and heteroarylsulfonate;

“m” is an integer of from 2 to 8; and

“n” is an integer equal to or greater than 100.

2. The method of claim 1 , further comprising a pharmacologically-active agent covalently bonded to one of the “A” or “Z” moieties that is not bonded to the first polymer matrix.

3. The method of claim 1 , where the first polymer matrix is proteinaceous.

4. The method of claim 1 , wherein the first polymer matrix is selected from the group consisting of gelatin, calcium alginate, calcium/sodium alginate, collagen, oxidized regenerated cellulose, carboxymethylcellulose, amino-modified cellulose, and whey protein.

5. The method of claim 1 , wherein the first polymer matrix is selected from the group consisting of gelatin and collagen.

6. The method of claim 1 , wherein the first polymer matrix is cross-linked with a cross-linking reagent.

7. The method of claim 1 , wherein the first polymer matrix is cross-linked with glutaraldehyde.

8. The method of claim 1 , wherein the first polymer matrix further comprises EDTAD moieties bonded to it.

9. The method of claim 1 , wherein “n” is equal to or greater than 200.

10. The method of claim 1 wherein “n” is equal to or greater than 2,000.

11. The method of claim 1 , wherein “n” is equal to or greater than 20,000.

12. The method of claim 1 , wherein the pharmacologically active agent is selected from the group consisting of vulnerary agents, hemostatic agents, antibiotics, antithelmintics, antifungal agents, hormones, anti-inflammatory agents, proteins, polypeptides, oligonucleotides, cytokines, and enzymes.

13. The method of claim 12 , wherein the pharmacologically active agent is a vulnerary agent.

14. The method of claim 1 , wherein the pharmacologically active agent is selected from the group consisting of vulnerary agents, hemostatic agents, antibiotics, antithelmintics antifungal agents, hormones, anti-inflammatory agents, proteins, polypeptides, oligonucleotides, cytokines, and enzymes.

15. The method of claim 14 , wherein the pharmacologically active agent is a vulnerary agent.

16. The method of claim 1 , wherein the second polymer matrix comprises a photopolymerized poly(acrylate).

17. The method of claim 1 , wherein the second polymer matrix comprises one or more monomers selected from the group consisting of α-acrylate-ω-acrylate-poly(alkylene glycol), trimethylolpropane triacrylate, and acrylic acid.

Assignments (2)
CONFIRMATORY LICENSE Recorded Nov 7, 2019
From: WISCONSIN ALUMNI RESEARCH FOUNDATION
To: NATIONAL INSTITUTES OF HEALTH - DIRECTOR DEITR
Reel/Frame 050948/0575 →
CONFIRMATORY LICENSE Recorded Mar 17, 2010
From: UNIVERSITY OF WISCONSIN MADISON
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 024093/0798 →
Continuity (3)
Continuation 10128198 · Apr 23, 2002
Provisional Application 60285782 · Apr 23, 2001
Related Publication 20100209509A1 · Aug 19, 2010