Conjugate addition reactions for the controlled delivery of pharmaceutically active compounds
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-038/54
A61K-038/43
A61K-039/40
A61K-039/00
C12Q-001/68
C07H-021/00
C12N-009/96
출원번호
US-0257818
(2005-10-25)
등록번호
US-7413739
(2008-08-19)
발명자
/ 주소
Hubbell,Jeffrey A.
Elbert,Donald
Schoenmakers,Ronald
출원인 / 주소
Eidgenossische Technische Hochschule Zurich
Universitat Zurich
대리인 / 주소
Clark & Elbing, LLP
인용정보
피인용 횟수 :
16인용 특허 :
30
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 biomaterial formed by combining two or more precursor components under conditions that allow polymerization of the two components, wherein said polymerization occurs through self selective reaction between a strong nucleophile and a conjugated unsaturated bond or a conjugat
What is claimed is: 1. A biomaterial formed by combining two or more precursor components under conditions that allow polymerization of the two components, wherein said polymerization occurs through self selective reaction between a strong nucleophile and a conjugated unsaturated bond or a conjugated unsaturated group, by nucleophilic addition, wherein each of said precursor components comprises at least two strong nucleophiles or at least two conjugated unsaturated bonds or conjugated unsaturated groups, said biomaterial does not comprise unprocessed albumin, and said unsaturated bond or group is not a maleimide or a vinyl sulfone. 2. The biomaterial of claim 1, wherein said components are selected from the group consisting of oligomers, polymers, biosynthetic proteins or peptides, naturally occurring peptides or proteins, processed naturally occurring peptides or proteins, and polysaccharides. 3. The biomaterial of claim 2, wherein said components are functionalized to comprise a strong nucleophile or a conjugated unsaturated bond or a conjugated unsaturated group. 4. The biomaterial of claim 1, wherein said strong nucleophile is selected from the group consisting of a thiol, or a group containing a thiol. 5. A biomaterial formed by combining two or more precursor components under conditions that allow polymerization of the two components, wherein said polymerization occurs through self selective reaction between an amine and a conjugated unsaturated bond or a conjugated unsaturated group, by nucleophulic addition, wherein each of said precursor components comprises at least two amines or at least two conjugated unsaturated bonds or conjugated unsaturated groups, said biomaterial does not comprise unprocessed albumin, and said unsaturated bond or group is not a maleimide or a vinyl sulfone. 6. The biomaterial of claim 1, wherein said unsaturated group is an acrylate, an acrylamide, a quinone, or a vinylpyridinium. 7. The biomaterial of claim 2, wherein said polymer is selected from the group consisting of poly(ethylene glycol), poly(ethylene oxide), poly(vinyl alcohol), poly(ethylene-co-vinyl alcohol), poly(acrylic acid), poly(ethylene-co-acrylic acid), poly(ethyloxazoline), poly(vinyl pyrrolidone), poly(ethylene-co-vinyl pyrrolidone), poly(maleic acid), poly(ethylene-co-maleic acid), poly(acrylamide), and poly(ethylene oxide)-co-poly(propylene oxide) block copolymers. 8. The biomaterial of claim 1, wherein one of said component comprises at least three strong nucleophiles or three conjugated unsaturated bonds or conjugated unsaturated groups. 9. The biomaterial of claim 1, further comprising a biologically active molecule. 10. The biomaterial of claim 1, further comprising a molecule that comprises an adhesion site, a growth factor binding site, or a heparin binding site and also comprises either a strong nucleophile or a conjugated unsaturated bond or a conjugated unsaturated group. 11. The biomaterial of claim 10, wherein said strong nucleophile is a thiol or said conjugated unsaturated bond or conjugated unsaturated group is an acrylate, a quinone, or a vinyl pyridinium. 12. The biomaterial of claim 1, wherein said biomaterial is a hydrogel. 13. The biomaterial of claim 1, wherein said biomaterial is degradable. 14. The biomaterial of claim 1, wherein said biomaterial is made in the presence of cells or tissues. 15. The biomaterial of claim 1, wherein said biomaterial is made within or upon the body of an animal. 16. The biomaterial of claim 1, further comprising an accelerator. 17. The biomaterial of claim 1, further comprising a component that comprises at least one conjugated unsaturated bond or conjugated unsaturated group and a least one amine reactive group. 18. The biomaterial of claim 14, further comprising an additional component coupled to the cell or tissue surface, the additional component comprising at least one conjugated unsaturated bond or conjugated unsaturated group and being coupled to the cell or tissue surface via by reaction of at least one amine reactive group. 19. The biomaterial of claim 1, further comprising a cell. 20. A kit comprising: (i) a precursor component comprising at least two strong nucleophiles; and (ii) a precursor component comprising at least two conjugated unsaturated bonds or conjugated unsaturated groups, wherein said precursor components are capable of polymerizing to form a biomaterial through self selective reaction between a strong nucleophile and a conjugated unsaturated bond or a conjugated unsaturated group, by nucleophilic addition, wherein said precursor components do not comprise unprocessed albumin, and said unsaturated bond or group is not a maleimide or a vinyl sulfone. 21. The kit of claim 20, wherein said components are selected from the group consisting of oligomers, polymers, biosynthetic proteins or peptides, naturally occurring peptides or proteins, processed naturally occurring peptides or proteins, and polysaccharides. 22. The kit of claim 20, wherein said strong nucleophile is selected from the group consisting of a thiol, or a group containing a thiol. 23. The kit of claim 20, wherein said unsaturated group is an acrylate, an acrylamide, a quinone, or a vinylpyridinium. 24. The kit of claim 21, wherein said polymer is selected from the group consisting of poly(ethylene glycol), poly(ethylene oxide), poly(vinyl alcohol), poly(ethylene-co-vinyl alcohol), poly(acrylic acid), poly(ethylene-co-acrylic acid), poly(ethyloxazoline), poly(vinyl pyrrolidone), poly(ethylene-co-vinyl pyrrolidone), poly(maleic acid), poly(ethylene-co-maleic acid), poly(acrylamide), and poly(ethylene oxide) block copolymers. 25. The kit of claim 20, wherein component (i) comprises at least three strong nucleophiles or component (ii) comprises at least three conjugated unsaturated bonds or conjugated unsaturated groups. 26. The kit of claim 20, further comprising a biologically active molecule. 27. The kit of claim 20, further comprising a molecule that comprises an adhesion site, a growth factor binding site, or a heparin binding site and also comprises either a strong nucleophile or a conjugated unsaturated bond or a conjugated unsaturated group. 28. The kit of claim 27, wherein said strong nucleophile is a thiol or said conjugated unsaturated bond or conjugated unsaturated group is an acrylate, a quinone, or a vinyl pyridinium. 29. The kit of claim 20, wherein said biomaterial is a hydrogel. 30. The kit of claim 20, wherein said biomaterial is degradable. 31. The kit of claim 20, wherein said biomaterial is capable of being made in the presence of cells or tissues. 32. The kit of claim 20, wherein said biomaterial is capable of being made within or upon the body of an animal. 33. The kit of claim 20, further comprising an accelerator. 34. The kit of claim 20, further comprising a component that comprises at least one conjugated unsaturated bond or conjugated unsaturated group and a least one amine reactive group. 35. The kit of claim 20, further comprising a cell. 36. The kit of claim 20, wherein said strong nucleophile of (i) is a thiol and said conjugated unsaturated group of (ii) is an acrylate. 37. The kit of claim 20, wherein said components of (i) and (ii) each comprise poly(ethylene glycol). 38. The kit of claim 20, wherein one of said components of (i) and (ii) comprises poly(ethylene glycol) and one of said components of (i) and (ii) does not comprise poly(ethylene glycol). 39. The kit of claim 20, wherein said component of (i) is poly(ethylene glycol) dithiol and said component of (ii) is poly(ethylene glycol) tetraacrylate. 40. The kit of claim 20, wherein one of said components of (i) and (ii) comprises pentaerythritol. 41. The kit of claim 20, wherein one of said components of (i) and (ii) is poly(ethylene glycol) dithiol with a molecular weight of 3400 Da. 42. The kit of claim 20, wherein one of said components of (i) and (ii) comprises a poly(ethylene oxide)-co-poly(propylene oxide) block copolymer.
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