초록 ▼

Biocompatible crosslinked polymers, and methods for their preparation and use, are disclosed in which the biocompatible crosslinked polymers are formed from water soluble precursors having electrophilic and nucleophilic functional groups capable of reacting and crosslinking in situ. Methods for mak

Biocompatible crosslinked polymers, and methods for their preparation and use, are disclosed in which the biocompatible crosslinked polymers are formed from water soluble precursors having electrophilic and nucleophilic functional groups capable of reacting and crosslinking in situ. Methods for making the resulting biocompatible crosslinked polymers biodegradable or not are provided, as are methods for controlling the rate of degradation. The crosslinking reactions may be carried out in situ on organs or tissues or outside the body. Applications for such biocompatible crosslinked polymers and their precursors include controlled delivery of drugs, prevention of post-operative adhesions, coating of medical devices such as vascular grafts, wound dressings and surgical sealants. Visualization agents may be included with the crosslinked polymers.

대표청구항 ▼

What is claimed is: 1. A method of preparing a composition suitable to coat a tissue of a patient, the method comprising: mixing reactive precursor species comprising nucleophilic functional groups, reactive precursor species comprising electrophilic functional groups, and a visualization agent suc

What is claimed is: 1. A method of preparing a composition suitable to coat a tissue of a patient, the method comprising: mixing reactive precursor species comprising nucleophilic functional groups, reactive precursor species comprising electrophilic functional groups, and a visualization agent such that the nucleophilic functional groups and electrophilic functional groups crosslink after contact with the tissue to form a hydrogel having an interior and an exterior, with the exterior having at least one substrate coating surface and the visualization agent being at least partially disposed within the interior and reflecting or emitting light at a wavelength detectable to a human eye to thereby provide a means for visualization of the coating by a human eye. 2. The method of claim 1, wherein the hydrogel comprises crosslinked polymers that are selected from the group consisting of collagen, fibrinogen, albumin, and fibrin. 3. The method of claim 1, wherein the hydrogel is made of synthetic materials. 4. The method of claim 1, wherein the hydrogel is hydrolytically biodegradable. 5. The method of claim 1, wherein the hydrogel comprises covalently crosslinked hydrophilic polymers. 6. The polymeric coating method of claim 1, wherein the visualization agent is chosen from the group consisting of FD&C Blue #1, FD&C Blue #2, methylene blue, indocyanine green, visualization agents that provide a blue color, and visualization agents that provide a green color. 7. The method of claim 1, wherein the visualization agent is covalently linked to the hydrogel. 8. The method of claim 1, wherein the hydrogel comprises a biologically active agent. 9. The method of claim 1, wherein the hydrogel forms within 60 seconds after contact with the substrate. 10. The method of claim 1, wherein the hydrogel forms within 5 seconds after contact with the substrate. 11. The method of claim 1, wherein the biodegradable hydrogel is adherent to the tissue. 12. A hydrogel composition adapted for use with a tissue of a patient, the composition being made by the process of claim 11. 13. The method of claim 1, further comprising: applying the hydrogel onto the tissue until an average thickness is reached in which the color of the hydrogel indicates that a predetermined thickness of hydrogel has been deposited on the tissue. 14. The method of claim 13, comprising choosing the predetermined thickness to be about 0.5 to about 4.0 mm. 15. The method of claim 13, comprising choosing at least one of the reactive precursor species to have a hydrolytically biodegradable portion such that the hydrogel is biodegradable. 16. A method for formulating a polymer composition that crosslinks to form a hydrogel, the method comprising selecting a concentration of visualization agent for the polymer composition such that the visualization agent causes a visually observable change that indicates that a crosslinked hydrogel having a predetermined thickness has been formed on the tissue of a patient wherein the polymer composition comprises electrophilic functional groups and nucleophilic functional groups that crosslink to each other. 17. The method of claim 16, wherein the predetermined thickness is from about 0.1 mm to about 10.0 mm. 18. The method of claim 16, wherein the observable change is not being able to see a substrate through the polymer composition. 19. The method of claim 16, wherein the observable change is not being able to see patterns in a substrate surface through the polymer composition. 20. The method of claim 16, wherein the polymer composition crosslinks to form a hydrogel within about 60 seconds after being applied to a substrate. 21. The method of claim 16, further comprising mixing the visualization agent at a selected concentration with reactive precursor species. 22. The method of claim 16, further comprising a biologically active agent.