초록 ▼

This invention relates generally to compositions and systems for forming biomaterials containing a transient colorant for visualizing tissue or surgical materials coated with such biomaterials, to methods of using such compositions as bioadhesives, for tissue augmentation, in the prevention of surgi

This invention relates generally to compositions and systems for forming biomaterials containing a transient colorant for visualizing tissue or surgical materials coated with such biomaterials, to methods of using such compositions as bioadhesives, for tissue augmentation, in the prevention of surgical adhesions, for coating surfaces of synthetic implants, as drug delivery matrices, for ophthalmic applications, and in other applications.

대표청구항 ▼

What is claimed is: 1. A composition comprising: (a) at least two polyethylene glycol (PEG) molecules each having a molecular weight in the range of about 7500 to about 20,000, wherein the PEG molecules include polymerizable groups; and (b) an excitation agent that initiates polymerization of the a

What is claimed is: 1. A composition comprising: (a) at least two polyethylene glycol (PEG) molecules each having a molecular weight in the range of about 7500 to about 20,000, wherein the PEG molecules include polymerizable groups; and (b) an excitation agent that initiates polymerization of the at least two PEG molecules; and (c) a colorant, wherein the colorant is non-reactive in the presence of the excitation agent and is visible or fluorescent in the presence of an excitation source and colorless in the absence of the excitation source. 2. The composition of claim 1, wherein the PEG has a molecular weight of approximately 10,000. 3. The composition of claim 1, wherein the PEG is activated PEG. 4. The composition of claim 3, wherein at least one of the at least two PEG molecules has a reactive electrophilic group. 5. The composition of claim 4, wherein the activated PEG has electrophilic groups selected from the group consisting of acid chloride groups, anhydrides, ketones, aldehydes, isocyanate, isothiocyanate, epoxides, and olefins. 6. The composition of claim 3, wherein the activated PEG is tetrafunctionally activated PEG. 7. The composition of claim 1, wherein the excitation agent is selected from the group consisting of moisture, a photopolymerization initiator, a catalyst, an agent that changes the pH of the composition, a basic reagent, a base, and a base-containing buffer. 8. The composition of claim 1, wherein the colorant is selected from the group consisting of a dye, a pigment, a luminescent agent, and mixtures thereof. 9. The composition of claim 8, wherein the colorant is a dye that includes a chromophore or a luminescent agent. 10. The composition of claim 8, wherein the colorant is a pigment that includes a chromophore or a luminescent agent. 11. The composition of claim 8, wherein the colorant is a fluorescent dye. 12. The composition of claim 11, wherein the fluorescent dye has an excitation wavelength from 300 nm to 700 nm. 13. The composition of claim 12, wherein the fluorescent dye is selected from the group consisting of fluorescein, carboxyfluorescein, eosin, erythrosine, a TEXAS RED짰 dye, rhodamine, coumarin, BODIPY짰 dye, or a combination thereof. 14. The composition of claim 1, further comprising at least one additional active component such as a small molecule therapeutic agent, a biopolymer, and a biological material. 15. The composition of claim 14, wherein the biopolymer is collagen or modified collagen. 16. The composition of claim 14, wherein the biological material is selected from the group consisting of tissue, cells, and mixtures thereof. 17. A composition comprising: (a) a polyethylene glycol (PEG) with polymerizable groups; (b) a poly(lysine); (c) an excitation agent that initiates polymerization of the PEG and the poly(lysine); and (d) a colorant, wherein the colorant is non-reactive in the presence of the excitation agent and is visible or fluorescent in the presence of an excitation source and colorless in the absence of the excitation source. 18. The composition of claim 17, wherein the PEG has a molecular weight in the range of approximately 7500 to 20,000. 19. The composition of claim 18, wherein the PEG has a molecular weight of about 10,000. 20. The composition of claim 17, wherein the poly(lysine) has a molecular weight in the range of about 8000 to about 15,000. 21. The composition of claim 17, wherein the excitation agent is selected from the group consisting of moisture, a photopolymerization initiator, a catalyst, an agent that changes the pH of the composition, a basic reagent, a base, and a base-containing buffer. 22. The composition of claim 17, wherein the colorant is selected from a dye, a pigment, a luminescent agent, and mixtures thereof. 23. The composition of claim 17, wherein the colorant is a dye that includes a chromophore or a luminescent agent. 24. The composition of claim 23, wherein the colorant is a pigment that includes a chromophore or a luminescent agent. 25. The composition of claim 22, wherein the colorant is a fluorescent dye. 26. The composition of claim 25, wherein the fluorescent dye has an excitation wavelength from 300 nm to 700 nm. 27. The composition of claim 26, wherein the fluorescent dye is selected from the group consisting of fluorescein, carboxyfluorescein, eosin, erythrosine, a TEXAS RED짰 dye, rhodamine, coumarin, BODIPY짰 dye, or a combination thereof. 28. The composition of claim 17, further comprising at least one additional active component such as a small molecule therapeutic agent, a biopolymer, and a biological material. 29. The composition of claim 28, wherein the biopolymer is collagen or modified collagen. 30. The composition of claim 28, wherein the biological material is selected from the group consisting of tissue, cells, and mixtures thereof. 31. The composition of claim 1, wherein at least one of the at least two PEG molecules has a nucleophilic group. 32. The composition of claim 1, wherein the excitation source is selected from the group consisting of visible light, ultraviolet light, electrical current, and laser stimulation. 33. The composition of claim 7, wherein the basic reagent is non-nucleophilic. 34. The composition of claim 7, wherein the excitation agent initiates polymerization of the at least two PEG molecules in the presence of the excitation source. 35. The composition of claim 15, wherein the modified collagen is methylated collagen. 36. The composition of claim 17, wherein the excitation source is selected from the group consisting of visible light, ultraviolet light, electrical current, and laser stimulation. 37. The composition of claim 17, wherein the poly(lysine) comprises 6 to about 4000 primary amino groups. 38. The composition of claim 21, wherein the basic reagent is non-nucleophilic. 39. The composition of claim 21, wherein the excitation agent initiates polymerization of the PEG and poly(lysine) in the presence of the excitation source. 40. The composition of claim 29, wherein the modified collagen is methylated collagen. 41. A method for visualizing, marking, or labeling a tissue surface comprising: (a) applying to a tissue surface a biocompatible composition comprising a colorant and at least two polyethylene glycol (PEG) molecules each having a molecular weight in the range of about 7500 to about 20,000, wherein the PEG molecules include polymerizable groups; and (b) applying to the tissue surface an excitation agent that initiates polymerization of the at least two PEG molecules, wherein the colorant is non-reactive in the presence of the excitation agent and is visible or fluorescent in the presence of irradiation and colorless in the absence of irradiation. 42. The method of claim 41, wherein the PEG is activated PEG. 43. The method of claim 41, wherein the activated PEG is tetrafunctionally activated PEG. 44. The method of claim 41, wherein the excitation agent is selected from the group consisting of moisture, a photopolymerization initiator, a catalyst, an agent that changes the pH of the composition, a basic reagent, a base, and a base-containing buffer. 45. The method of claim 41, wherein the excitation agent initiates polymerization of the PEG and poly(lysine) in the presence of the excitation source. 46. The method of claim 41, wherein the colorant is selected from the group consisting of a dye, a pigment, a luminescent agent, and mixtures thereof. 47. The method of claim 41, wherein the excitation source is selected from the group consisting of visible light, ultraviolet light, electrical current, and laser stimulation. 48. The method of claim 41, further comprising at least one additional active component such as a small molecule therapeutic agent, a biopolymer, and a biological material. 49. The method of claim 48, wherein the biopolymer is collagen or modified collagen. 50. The method of claim 48, wherein the biological material is selected from the group consisting of tissue, cells, and mixtures thereof. 51. A method for visualizing, marking, or labeling a tissue surface comprising the steps of: (a) applying to a tissue surface a biocompatible composition comprising a colorant, a polyethylene glycol (PEG) with polymerizable groups, and a poly(lysine) with polymerizable groups; and (b) applying to the tissue surface an excitation agent that initiates polymerization of the at least two PEG molecules, wherein the colorant is non-reactive in the presence of the excitation agent and is visible or fluorescent in the presence of irradiation and colorless in the absence of irradiation. 52. The method of claim 51, wherein the PEG has a molecular weight in the range of approximately 7500 to 20,000. 53. The method of claim 51, wherein the poly(lysine) has a molecular weight in the range of about 8000 to about 15,000. 54. The method of claim 51, wherein the poly(lysine) comprises 6 to about 4000 primary amino groups. 55. The method of claim 51, wherein the excitation agent is selected from the group consisting of moisture, a photopolymerization initiator, a catalyst, an agent that changes the pH of the composition, a basic reagent, a base, and a base-containing buffer. 56. The method of claim 51, wherein the excitation agent initiates polymerization of the PEG and the poly(lysine) in the presence of the excitation source. 57. The method of claim 51, wherein the colorant is selected from a dye, a pigment, a luminescent agent, and mixtures thereof. 58. The method of claim 51, wherein the excitation source is selected from the group consisting of visible light, ultraviolet light, electrical current, and laser stimulation. 59. The method of claim 51, further comprising at least one additional active component such as a small molecule therapeutic agent, a biopolymer, and a biological material. 60. The method of claim 59, wherein the biopolymer is collagen or modified collagen. 61. The method of claim 59, wherein the biological material is selected from the group consisting of tissue, cells, and mixtures thereof.