Water activated hydrogel-based medical patches, and methods of making and using such patches
A medical patch can comprise a biocompatible substrate and a dry hydrogel precursor layer on the substrate, the dry hydrogel precursor layer comprising an electrophilic-hydrogel precursor having a plurality of electrophilic functional groups and a nucleophilic-hydrogel precursor having a plurality of protonated amine groups and no more than about 2 weight percent water. Both the electrophilic-hydrogel precursor and the nucleophilic-hydrogel precursor are substantially uncrosslinked, and are blended or in direct contact with each other. The medical patches can be formed by coating a melt blend of hydrogel precursors in a dry environment or based on solution coating from a dry, non-aqueous solvent, onto a porous, hydrophilic substrate. The medical patches can be used for placement over a bleeding wound or the like and may function as a hemostatic patch. Shredded patches and compositions mimicking a shredded patch can be placed into a wound defect.
1. A medical patch comprising a biocompatible substrate and a dry hydrogel precursor layer on the substrate, the dry hydrogel precursor layer comprising an electrophilic-hydrogel precursor having a plurality of electrophilic functional groups and a nucleophilic-hydrogel precursor having a plurality of protonated amine groups and no more than about 2 weight percent water and wherein both the electrophilic-hydrogel precursor and the nucleophilic-hydrogel precursor are substantially uncrosslinked, and are blended or in direct contact with each other.
2. The medical patch of claim 1 wherein the dry hydrogel precursor layer comprises a blend of the electrophilic-hydrogel precursor and the nucleophilic-hydrogel precursor.
3. The medical patch of claim 1 wherein the substrate persists for less than 30 days in an in vitro physiological solution maintained at 37° C.
4. The medical patch of claim 1 wherein the substrate persists for less than 2 weeks in an in vitro physiological solution maintained at 37° C.
5. The medical patch of claim 1 wherein the substrate is capable of absorbing from 300 wt % to 3000 wt % water.
6. The medical patch of claim 1 wherein the substrate comprises gelatin.
7. The medical patch of claim 6 wherein the substrate is partially thermally crosslinked and wherein the substrate is a foam, a non-woven tufted material, or a non-woven felted material.
8. The medical patch of claim 1 wherein the dry hydrogel precursor layer comprises multiple layers of a blend of the electrophilic-hydrogel precursor and the nucleophilic-hydrogel precursor.
9. The medical patch of claim 8 wherein the dry hydrogel precursor layer is formed from a neat melt blend of the electrophilic-hydrogel precursor and the nucleophilic-hydrogel precursor.
10. The medical patch of claim 1 wherein the dry hydrogel precursor layer comprises a stack of one or more sublayers of the electrophilic-hydrogel precursor with one or more sublayers of the nucleophilic-hydrogel precursor, wherein adjacent sublayers are directly contacting each other.
11. The medical patch of claim 1 wherein the substrate consists essentially of gelatin and the dry hydrogel precursor layer consists of a single solid layer consisting essentially of the electrophilic-hydrogel precursor, the nucleophilic-hydrogel precursor, and an optional visualization agent, wherein the visualization agent is biocompatible.
12. The medical patch of claim 1 wherein the electrophilic-hydrogel precursor has a first hydrophilic core comprising a polymer having a molecular weight of at least about 5000 Da and wherein the nucleophilic-hydrogel precursor has a second hydrophilic core comprising a polymer having a molecular weight of at least about 2500 Da.
13. The medical patch of claim 12 wherein the first hydrophilic core and the second hydrophilic core independently have a molecular weight from about 10K Da to about 25K Da and from 4 to 8 arms.
14. The medical patch of claim 12 wherein the first hydrophilic core and/or the second hydrophilic core comprise polyethylene glycol, polyvinyl alcohol, polyoxazoline, copolymers thereof, or mixtures thereof or other water soluble medically acceptable polymers with functional groups that can be modified, wherein the first hydrophilic core and the second hydrophilic core comprise the same polymer.
15. The medical patch of claim 1 wherein the plurality of arms for the electrophilic-hydrogel precursor and for the nucleophilic-hydrogel precursor are independently from 3 to 8 and wherein the first hydrophilic core and the second hydrophilic core comprise polyethylene glycol.
16. The medical patch of claim 1 wherein the electrophilic-hydrogel precursor has electrophilic functional groups comprising an ester.
17. The medical patch of claim 16 wherein the ester is a succinimidyl ester.
18. The medical patch of claim 1 wherein the ratio of electrophilic functional groups to protonated amine groups is no more than about 1.
19. The medical patch of claim 1 wherein the ratio of electrophilic functional groups to protonated amine groups is approximately 1.
20. The medical patch of claim 1 wherein the ratio of electrophilic functional groups to protonated amine groups is about 0.95 to about 1.05.
21. The medical patch of claim 1 wherein the electrophilic-hydrogel precursor and the nucleophilic-hydrogel precursor are each water soluble.
22. The medical patch of claim 1 wherein the medical patch further comprises a therapeutic agent.
23. The medical patch of claim 1 wherein the therapeutic agent comprises an analgesic, an anesthetic, a steroid, an antibiotic, a steroid, an anti-infective, an anti-inflammatory drug, a non-steroidal anti-inflammatory drug, an anti-proliferative, or combinations thereof.
24. The medical patch of claim 1 wherein the dry hydrogel precursor layer further comprises a visualization agent.
25. The medical patch of claim 24 wherein the visualization agent is biocompatible and comprises a coloring agent, a fluorescent molecule, a contrast agent, or a combination thereof.
26. The medical patch of claim 24 wherein the medical patch has a first side comprising the substrate and a second side comprising the dry hydrogel precursor layer and the visualization agent, wherein the first side is essentially free of the visualization agent.
27. The medical patch of claim 1 wherein the medical patch is flexible and conformable when dry.
28. The medical patch of claim 27 wherein the patch can be rolled for laparoscopic delivery through a trocar.
29. The medical patch of claim 1 wherein the medical patch has a thickness from about 0.5 mm to about 5 mm and a width and length that are independently from about 1 cm to about 15 cm.
30. The medical patch of claim 1 wherein the medical patch is free of blood components and human components.
31. The medical patch according to claim 1 wherein contact with physiological fluids associated results in the dry hydrogel precursor layer forming a hydrogel.
32. The medical patch of claim 1 wherein the substrate when dry or wet is non-adhesive to surgical gloves or gauze wetted with a non-buffered solution.
33. The medical patch of claim 1 wherein the medical patch has a storage stability against significant gelation of a least about 1 year at refrigerated conditions.
34. The medical patch of claim 1 wherein contact with physiological fluids results in full absorption of the medical patch in no more than about 28 days.
35. The medical patch of claim 1 wherein contact with physiological fluids results in full absorption of the medical patch in no more than about 9 days.
36. The medical patch of claim 1 wherein the medical patch has a three dimensional contoured shape.
37. The medical patch of claim 36 wherein the three dimensional shape is a standard cone or a truncated cone.
38. A wound filing composition comprising a quantity of a shredded material from a patch of claim 1 .
39. The medical patch of claim 1 wherein the dry hydrogel precursor layer has no added buffer.