Macromonomer for preparation of a degradable hydrogel

• US 7,754,241 B1
• Filed: 11/10/2005
• Issued: 07/13/2010
• Est. Priority Date: 11/12/2004
• Status: Expired due to Fees

• Current Assignee: Clemson University
• Original Assignee: Clemson University
• Inventors: Webb, Charles K., Vyavahare, Naren R.
• Primary Examiner(s): Naff; David M
• Application Number:
  US11/271,405
• Time in Patent Office: 1,706 Days
• Field of Search: None
• US Class Current: 424/486
• 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: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: C08L 71/02 Polyalkylene oxides
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• 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

A degradable hydrogel and a method of making a degradable hydrogel is disclosed herein. The method comprises obtaining a hydrophilic polymer having at least two hydroxyl groups, reacting the hydrophilic polymer with a di-functional monomer comprised of an acid halide group and an alkyl halide group to form an intermediate having an ester bond and a terminal alkyl halide group, reacting the terminal alkyl halide group of the intermediate with a metallic salt of a vinyl acid monomer to form a macromonomer comprised of an ester, an alkyl group spacer, and a terminal vinyl group, and polymerizing the macromonomer to form a degradable hydrogel. A method is also disclosed for varying the degradation rate of the hydrogel as a function of the chemical composition of the alkyl group spacer in the terminal linkage of the macromonomer.

Claims

1. A macromonomer for preparation of a degradable hydrogel, the macromonomer formed by the process of reacting:

a) a hydrophilic polymer including at least two hydroxyl groups with;

b) a difunctional monomer to form an intermediate, the difunctional monomer comprising an acid halide group, an alkyl halide group, and a spacer that is a straight or branched alkyl group, wherein the acid halide group of the difunctional monomer reacts with one of the hydroxyl groups of the hydrophilic polymer such that the intermediate has a first ester bond on a backbone of the intermediate, the oxygen of the first ester bond being along the backbone of the intermediate and being between the hydrophilic polymer residue and the carbonyl group of the first ester bond, the intermediate including the alkyl halide group as a terminal group; and

reacting the intermediate with

c) a metallic salt of a vinyl acid monomer to form the macromonomer, wherein the terminal alkyl halide group of the intermediate reacts with the acid group of the vinyl acid monomer such that the macromonomer has a second ester bond on the backbone of the macromonomer, the oxygen of the second ester bond being along the backbone of the macromonomer and being between the alkyl group of the alkyl halide group and the carbonyl group of the second ester bond, the macromonomer having a terminal vinyl group;

the macromonomer comprising the structure

2. The macromonomer according to claim 1, wherein the macromonomer has a number average molecular weight between about 400 and about 100,000.

3. The macromonomer according to claim 1, wherein the hydrophilic polymer is selected from the group consisting of polyethylene glycol, polyvinyl alcohol, di- and tri-block copolymers of polyethylene glycol and polypropylene glycol, and a combination thereof.

4. The macromonomer according to claim 1, wherein R2 comprises 1 to 10 carbons.

5. The macromonomer according to claim 1, wherein R2 is a branched alkyl group.

6. The macromonomer according to claim 1, wherein R2 is a straight chain alkyl group.

7. The macromonomer according to claim 1, wherein the metallic salt of a vinyl acid monomer is sodium acrylate.

8. The macromonomer according to claim 1, wherein the metallic salt of a vinyl acid monomer is sodium methacrylate.

9. A macromonomer for preparation of a degradable hydrogel, the macromonomer formed by the process of reacting:

a) a hydrophilic polymer including at least two hydroxyl groups, the hydrophilic polymer being selected from the group consisting of polyethylene glycol, di- and tri-block copolymers of polyethylene glycol and polypropylene glycol, and a combination thereof with;

b) a difunctional monomer to form an intermediate, the difunctional monomer comprising an acid halide group, an alkyl halide group, and a spacer that is a straight or branched alkyl group, wherein the acid halide group of the difunctional monomer reacts with one of the hydroxyl groups of the hydrophilic polymer such that the intermediate has a first ester bond on a backbone of the intermediate, the oxygen of the first ester bond being along the backbone of the intermediate and being between the hydrophilic polymer residue and the carbonyl group of the first ester bond, the intermediate including the alkyl halide group as a terminal group; and

reacting the intermediate with

c) a metallic salt of a vinyl acid monomer to form the macromonomer, wherein the terminal alkyl halide group of the intermediate reacts with the acid group of the vinyl acid monomer such that the macromonomer has a second ester bond on the backbone of the macromonomer, the oxygen of the second ester bond being along the backbone of the macromonomer and being between the alkyl group of the alkyl halide group and the carbonyl group of the second ester bond, the macromonomer having a terminal vinyl group;

the macromonomer comprising the structure

10. The macromonomer according to claim 9, wherein the macromonomer has a number average molecular weight between about 400 and about 100,000.

11. The macromonomer according to claim 9, wherein R2 comprises 1 to 10 carbons.

12. The macromonomer according to claim 9, wherein R2 is a branched alkyl group.

13. The macromonomer according to claim 9, wherein R2 is a straight chain alkyl group.

14. The macromonomer according to claim 9, wherein the metallic salt of a vinyl acid monomer is sodium acrylate.

15. The macromonomer according to claim 9, wherein the metallic salt of a vinyl acid monomer is sodium methacrylate.