APPARATUS AND METHODS FOR SEALING A VASCULAR PUNCTURE
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 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, PEG-amine precursors may include free amine form and 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 . (canceled)
2 . A sealant for adhering to tissue adjacent to an arterial opening of an artery in which there is provided an arterial pressure, the sealant comprising:
a mixture of PEG-precursors comprising PEG-ester precursors and PEG-amine precursors, the PEG-ester precursors and the PEG-amine precursors comprising a PEG-ester/PEG-amine ratio, wherein the mixture of PEG-precursors undergo in-situ cross-linking when exposed to an aqueous physiological environment for adhering to tissue adjacent the arterial opening; and
wherein when there is an excess of PEG-ester precursors in the PEG-ester/PEG-amine ratio the sealant remains adhered to tissue adjacent to the arterial opening at an arterial pressure that is higher than when there is not the excess of PEG-ester precursors in the PEG-ester/PEG-amine ratio.
3 . The sealant of claim 2 , wherein the mixture of PEG-precursors comprises an excess of PEG-ester active group sites in the PEG-ester/PEG-amine ratio.
4 . The sealant of claim 3 , wherein the sealant remains adhered to the tissue adjacent to the arterial opening at an arterial pressure of up to 8 pounds per square inch.
5 . The sealant of claim 2 , wherein the sealant remains adhered to the tissue adjacent to the arterial opening at an arterial pressure of up to 12 pounds per square inch.
6 . The sealant of claim 2 , wherein the mixture of PEG-precursors comprises the excess of PEG-ester precursors in a PEG-ester/PEG-amine ratio of up to 59.5/40.5.
7 . The sealant of claim 2 , wherein the PEG-amine precursors remain in an unreactive state until exposed to the aqueous physiological environment.
8 . The sealant of claim 2 , wherein the PEG-amine precursors are in both a free amine form and a salt form.
9 . The sealant of claim 8 , wherein the PEG-amine precursors are at least partially cross-linked.
10 . The sealant of claim 9 , wherein the sealant remains adhered to the tissue adjacent to the arterial opening at an arterial pressure of up to 8 pounds per square inch.
11 . The sealant of claim 8 , wherein a ratio of ester/salt form amine/amine free form ratio is up to 60.8/33.4/5.8.
12 . The sealant of claim 8 , wherein the salt form of PEG-amine precursors remains in an unreactive state until exposed to the aqueous physiological environment.
13 . The sealant of claim 2 , wherein the PEG-amine precursors are at least partially cross-linked.
14 . The sealant of claim 2 , wherein the sealant is in a shape of a tubular roll.
15 . The sealant of claim 2 , wherein the mixture of PEG-precursors comprises melted PEG-precursors.
16 . The sealant of claim 2 , wherein the mixture of PEG-precursors comprises one or more diluents which increase the mechanical strength of the sealant.
17 . The sealant of claim 16 , wherein one of the one or more diluents is a low molecular PEG.
18 . The sealant of claim 16 , wherein one of the one or more diluents is a glycerol.
19 . The sealant of claim 2 , wherein the sealant comprises two or more sections.
20 . The sealant of claim 19 , wherein one section of the two or more sections comprises one or more pH adjusting agents.
21 . The sealant of claim 20 , wherein the one or more pH adjusting agents increases cross-linking of the mixture of PEG-precursors when exposed to the aqueous physiological environment.