초록

The invention features polymeric biomaterials formed by nucleophilic addition reactions to conjugated unsaturated groups. These biomaterials may be used for medical treatments.

대표청구항 ▼

What is claimed is: 1. A method of forming a biomaterial, said method comprising the steps of: (a) attaching a pharmaceutically active compound or binding compound to a linker molecule comprising at least one thiol or amine group or incorporating a nucleophilic amine or thiol into a pharmaceuticall

What is claimed is: 1. A method of forming a biomaterial, said method comprising the steps of: (a) attaching a pharmaceutically active compound or binding compound to a linker molecule comprising at least one thiol or amine group or incorporating a nucleophilic amine or thiol into a pharmaceutically active compound or binding compound; b) coupling the thiol or amine in said linker or incorporated into said pharmaceutically active compound or binding compound to at least a first polymer comprising two or more conjugated unsaturated groups by a conjugate addition reaction to form a first precursor component; (c) providing at least a second precursor component comprising nucleophilic groups; and (d) cross-linking the conjugated unsaturated groups of the first precursor component to the nucleophilic groups of the second precursor component by a conjugated addition reaction. 2. The method of claim 1, wherein said cross-linking occurs at or near a site within the body of a mammal. 3. The method of claim 2, wherein said mammal is a human. 4. The method of claim 1, wherein said pharmaceutically active compound is selected from the group consisting of synthetic organic molecules, naturally occurring organic molecules, nucleic acid molecules, biosynthetic proteins or peptides, naturally occurring peptides or proteins, and modified naturally occurring peptides or proteins. 5. The method of claim 4, wherein said pharmaceutically active compound is paclitaxel, doxorubicin, 5-fluorodeoxyuridine, or estradiol, 2-methoxyestradiol. 6. The method of claim 4, wherein said pharmaceutically active compound is a growth factor or a hormone. 7. The method of claim 1, wherein said binding moiety is selected from the group consisting of a heparin, a heparin-binding moiety, a metal ion binding moiety, a carbohydrate moiety, a carbohydrate binding moiety, or a moiety that binds hydrophobic groups. 8. The method of claim 1, wherein said first polymer is a water-soluble or water-swellable polymer. 9. The method of claim 8, wherein said water-soluble or water-swellable polymer comprises poly(ethylene glycol), poly(ethylene oxide), poly(vinyl alcohol), poly(acrylic acid), poly(ethylene-co-vinyl alcohol), poly(hydroxypropyl methacrylamide), poly(N-isopropylacrylamide), poly(dimethyl acrylamide), poly(vinyl pyrrolidone), poly(acrylic acid), poly(ethyloxazoline), poly(ethylene oxide)-co-poly(propylene oxide) block copolymers, or a copolymer thereof. 10. The method of claim 1, wherein said unsaturated groups are not activated as to undergo nucleophilic substitution reactions. 11. The method of claim 1, wherein said conjugated unsaturated groups are selected from the group consisting of acrylates, methacrylates, acrylamides, methacrylamides, acrylonitriles, vinylsulfones, and quinones. 12. The method of claim 1, wherein said second precursor component comprises poly(ethylene glycol), poly(ethylene oxide), poly(vinyl alcohol), poly(acrylic acid), poly(ethylene-co-vinyl alcohol), poly(hydroxypropyl methacrylamide), poly(N-isopropylacrylamide), poly(dimethyl acrylamide), poly(vinyl pyrrolidone), poly(acrylic acid), poly(ethyloxazoline), or poly(ethylene oxide)-co-poly(propylene oxide) block copolymers. 13. The method of claim 1, wherein said nucleophilic groups of said second precursor component are selected from the group consisting of thiols and amines. 14. The method of claim 7, wherein said metal ion binding moiety is a Cu+2 binding moiety, a Co+2 binding moiety, or a Zn2+ binding moiety. 15. The method of claim 7, wherein said carbohydrate binding moiety is a phenylboronic acid. 16. The method of claim 15, wherein said phenylboronic acid is linked to said biomaterial through a secondary amine on the phenyl ring of said phenylboronic acid. 17. The method of claim 7, wherein said moiety that binds hydrophobic groups is a cyclodextrin. 18. The method of claim 1, wherein step (a) comprises incorporating a nucleophilic amine or thiol into a pharmaceutically active compound or binding compound. 19. The method of claim 18, wherein step (a) comprises incorporating a nucleophilic thiol into a pharmaceutically active compound. 20. The method of claim 18, wherein the first polymer is a poly(ethylene glycol). 21. The method of claim 20, wherein the conjugated unsaturated groups of the first polymer are selected from acrylate groups or vinylsulfones. 22. The method of claim 21, wherein the conjugated group of the first polymer is an acrylate. 23. The method of claim 22, wherein the first polymer is a poly(ethylene glycol) tetraacrylate. 24. The method of claim 20, wherein the second precursor component is a poly(ethylene glycol). 25. The method of claim 24, wherein the nucleophilic groups of the second precursor component are thiols or amines. 26. The method of claim 25 wherein the nucleophilic groups of the second precursor component are thiols. 27. The method of claim 26, wherein the second precursor component is a poly(ethylene glycol) dithiol. 28. The method of claim 18, wherein the pharmaceutically active compound is a hormone. 29. The method of claim 18, wherein the pharmaceutically active compound is a growth factor. 30. The method of claim 18, wherein the first polymer is a poly(ethylene glycol) comprising two or more acrylate groups, wherein the second precursor component is a poly(ethylene glycol) comprising two or more thiol groups, and wherein the pharmaceutically active molecule is a hormone having an incorporated thiol group. 31. The method of claim 18, wherein the first polymer is a poly(ethylene glycol) comprising two or more acrylate groups, wherein the second precursor component is a poly(ethylene glycol) comprising two or more thiol groups, and wherein the pharmaceutically active molecule is a growth factor having an incorporated thiol group. 32. The method of claim 1, wherein the pharmaceutical active compound is selected from the group having the formula D-OH, D-NH2, or D-NH, where D is a pharmaceutically active moiety. 33. The method of claim 1, wherein said pharmaceutically active compound is a peptide. 34. The method of claim 1, wherein said linker is able to react with a--OH,--NH2, or--NH group of said pharmaceutically active compound. 35. The method of claim 1, wherein the linker is R1-COOH, where R1 is an organic moiety comprising a protected thiol or amine moiety or CH2═CH--. 36. The method of claim 35, wherein the linker comprising CH2--CH--reacts with a second linker comprising a thiol or amino group and a protected thiol or amine moiety.