Apparatus and methods for sealing a vascular puncture
View Patent ↗A sealant for sealing a puncture through tissue includes a first section, e.g., formed from freeze-dried hydrogel, and a second section extending from the distal end. The second section may be formed from PEG-precursors including PEG-ester and PEG-amine, e.g., in an equivalent ratio of active group sites of PEG-ester/PEG-amine greater than one-to-one, e.g., such that excess esters may provide faster activation upon contact with physiological fluids and enhance adhesion of the sealant within a puncture. At least some of the precursors remain in an unreactive state until exposed to an aqueous physiological environment, e.g., within a puncture, whereupon the precursors undergo in-situ cross-linking to provide adhesion to tissue adjacent the puncture. For example, the PEG-amine precursors may include the free amine form and the salt form. The free amine form at least partially cross-links with the PEG-ester and the salt form remains in the unreactive state in the sealant before introduction into the puncture.
1. A sealant for sealing a puncture through tissue, comprising:
a mass of PEG precursors comprising PEG-ester precursors and PEG-amine precursors, the PEG-amine precursors including a free-amine form of PEG-amine precursors and a salt form of PEG-amine precursors;
wherein the sealant is provided such that the free-amine form of PEG-amine precursors are at least partially cross-linked with the PEG-ester precursors, and the salt form of PEG-amine precursors remain in an unreactive state until exposed to an aqueous physiological environment, whereupon the salt form of PEG-amine precursors undergo in-situ cross-linking with the PEG-ester precursors to provide adhesion to tissue adjacent the puncture.
2. The sealant of claim 1 , wherein a ratio of active group sites of PEG-ester precursors/salt form of PEG-amine precursors/free-amine form of PEG-amine precursors is between about 50/42/8 and 50/48/2.
3. The sealant of claim 1 , wherein a ratio of active group sites of PEG-ester precursors/salt form of PEG-amine precursors/free-amine form of PEG-amine precursors is between about 60/32/8 and 60/38/2.
4. The sealant of claim 1 , wherein a ratio of active group sites of PEG-ester precursors/salt form of PEG-amine precursors/free-amine form of PEG-amine precursors is between about 50/45/5 and 70/25/5.
5. The sealant of claim 1 , wherein a ratio of active group sites of PEG-ester precursors/salt form of PEG-amine precursors/free-amine form of PEG-amine precursors is about 60/35/5.
6. The sealant of claim 1 , wherein a ratio of active group sites of the PEG-ester precursors to the PEG-amine precursors is at least about one-to-one (1:1).
7. The sealant of claim 1 , wherein the sealant is able to withstand higher pressures as compared to a comparison sealant, wherein the mass of PEG precursors in the comparison sealant comprises PEG-ester precursors and a salt form of PEG-amine precursors, but does not include a free-amine form of PEG-amine precursors.
8. The sealant of claim 1 , wherein the sealant has a substantially uniform outer cross-section between about one and eight millimeters (1-8 mm).
9. The sealant of claim 1 , wherein the mass of PEG precursors comprises a substantially uniform plug of PEG precursors.
10. The sealant of 1 , wherein the sealant comprises a first section and a second section, the first section comprising a freeze-dried hydrogel that expands when exposed to physiological fluid within the puncture and the second section comprising the mass of PEG precursors fused to the freeze-dried hydrogel.
11. The sealant of claim 10 , wherein the first section comprises a sheet rolled into a tubular shape, thereby defining a lumen extending along a length of the freeze-dried hydrogel, and wherein the second section comprises a passage therethrough aligned with the lumen.
12. The sealant of claim 10 , wherein the first section has a length between about one and twenty millimeters (1-20 mm), and the second section has a length that is substantially shorter than the length of the first section.
13. The sealant of claim 10 , further comprising a transition zone between the first section and the second section, wherein PEG-precursors of the second section permeate into an end of the first section to form the transition zone.
14. The sealant of claim 10 , wherein the first section forms a proximal section of the sealant and wherein the second section forms a distal section of the sealant.
15. The sealant of claim 10 , wherein the sealant is provided in an apparatus for sealing a puncture extending through tissue, the apparatus comprising:
a tubular member comprising a proximal end, a distal end sized for insertion into the puncture, a lumen extending between the proximal end and the distal end, and a distal opening in communication with the lumen; and
wherein the sealant is disposed within the lumen of the tubular member such that the second section of the sealant is disposed closer to the distal opening of the tubular member than the first section.
16. A method for sealing a puncture extending through tissue, comprising:
introducing a sealant into a puncture, the sealant comprising a mass of PEG precursors comprising PEG-ester precursors, a free-amine form of PEG-amine precursors, and a salt form of PEG-amine precursors, wherein the free-amine form of PEG-amine precursors are at least partially cross-linked with the PEG-ester precursors, and the salt form of PEG-amine precursors remain in an unreactive state;
exposing the sealant to fluid within the puncture, whereupon the salt form of PEG-amine precursors undergo in-situ cross-linking with the PEG-ester precursors to provide adhesion to tissue adjacent the puncture.
17. The method of claim 16 , wherein the sealant is able to withstand higher pressures as compared to a comparison sealant, wherein the mass of PEG precursors in the comparison sealant comprises PEG-ester precursors and a salt form of PEG-amine precursors, but does not include a free-amine form of PEG-amine precursors.
18. The method of claim 16 , wherein the sealant further comprises a freeze-dried hydrogel, wherein the mass of PEG precursors is fused to the freeze-dried hydrogel, and wherein the mass of PEG precursors enters the puncture before the freeze-dried hydrogel when introducing the sealant into the puncture.
19. A method for making a sealant, comprising:
forming an elongate first section having a cross-section sized for delivery into a puncture through tissue;
melting a mixture of PEG precursors comprising PEG-ester precursors, a free-amine form of PEG-amine precursors, and a salt form of PEG-amine precursors; and
fusing the mixture of PEG precursors onto an end of the first section, wherein the free-amine form of PEG-amine precursors at least partially cross-links with the PEG-ester precursors, and the salt form of PEG-amine precursors remain in an unreactive state until exposed to an aqueous physiological environment.
20. The method of claim 19 , wherein fusing the mixture of PEG precursors onto the end of the first section comprises:
using a vacuum to apply the mixture of PEG precursors onto the end of the first section, and
allowing the mixture of PEG precursors to cool and solidify into a solid mass fused to the end of the first section.