Bifunctional-modified hydrogels

• US 8,025,901 B2
• Filed: 11/10/2009
• Issued: 09/27/2011
• Est. Priority Date: 04/23/2001
• Status: Expired due to Fees

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Li, Jing, Kao, Weiyuan John, Gundloori, Rathna, Lok, David
• Primary Examiner(s): Nutter; Nathan M
• Application Number:
  US12/615,859
• Publication Number:
  US 20100209509A1
• Time in Patent Office: 686 Days
• Field of Search: 424/484, 424/486, 514/772.1, 514/774, 435/177, 523/113, 530/815, 530/817
• US Class Current: 424/484
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/6903 the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel
• CPC Class Codes: A61L 15/225 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 15/32 Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin A61L15/225 takes precedence
• CPC Class Codes: A61L 15/325 Collagen
• CPC Class Codes: A61L 15/60 Liquid-swellable gel-forming materials, e.g. super-absorbents
• CPC Class Codes: C08G 81/00 Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers involving only carbon-to-carbon unsaturated bond reactions C08F299/00 ; polyester-amides C08G69/44; polyester-imides C08G73/16; polyamides-imides C08G73/14; block- or graft polymers containing polysiloxane sequences C08G77/42
• CPC Class Codes: C08L 101/14 the macromolecular compounds being water soluble or water swellable, e.g. aqueous gels
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin
• CPC Class Codes: Y10S 530/815 Carrier is a synthetic polymer
• CPC Class Codes: Y10S 530/817 Entrapped within the carrier, e.g. gel, hollow fibre

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

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;

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.