Apparatus and methods for sealing a vascular puncture
Inventors
Mylonakis, Andreas • Au-Yeung, Jacky • Lim, Florencia
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12268378-B2
Publication Date
2025-04-08
Expiration Date
Abstract
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.
Core Innovation
The invention relates to a sealant for sealing a puncture through tissue, including an elongate first section extending from a proximal end to a distal end and having a cross-section sized for delivery into a puncture through tissue. The sealant further includes a second section fused to and extending from the distal end of the first section, where the second section comprises PEG-precursors including PEG-ester and PEG-amine precursors. The PEG-precursors remain in an unreactive state until exposed to an aqueous physiological environment, whereupon the precursors undergo in-situ cross-linking with one another to provide adhesion to tissue adjacent the puncture.
In particular embodiments, the first section is formed from a freeze-dried hydrogel that expands when exposed to physiological fluid within a puncture. The second section includes PEG-precursors in an equivalent ratio of active group sites of PEG-ester/PEG-amine of at least about one-to-one (1:1). Some of the PEG precursors remain unreactive until exposed to an aqueous physiological environment, thereby providing adhesion to tissue adjacent the puncture upon exposure and in-situ cross-linking.
The invention also includes sealants in which the PEG-amine precursors include both a free amine form and a salt form. The free amine form is at least partially cross-linked with the PEG-ester precursors, while the salt form remains unreactive until exposed to an aqueous physiological environment, whereupon the salt form undergoes in-situ cross-linking with the PEG-ester precursors to provide adhesion to tissue adjacent the puncture.
The disclosure further describes sealing using a tubular member apparatus in which the second section is disposed closer to a distal opening than the first section, and the second section enters the puncture before the first section, followed by exposing the sealant to the aqueous physiological environment within the puncture.
Claims Coverage
The partial set includes four independent claims covering a fused two-section sealant architecture, PEG-ester/PEG-amine precursor chemistry that remains unreactive until aqueous physiological exposure, expansion of a freeze-dried hydrogel first section, and method/device arrangements for delivering the second section before the first section. Across these claims, the coverage centers on adhesion to tissue adjacent the puncture generated by in-situ cross-linking after exposure to an aqueous physiological environment.
Fused elongate first and second sections with PEG-precursors activated by aqueous physiological environment
A sealant for sealing a puncture through tissue comprising an elongate first section sized for delivery into a puncture and a second section fused to and extending from the distal end of the first section, the second section comprising PEG-precursors comprising PEG-ester and PEG-amine precursors in an equivalent ratio of active group sites of PEG-ester/PEG-amine of at least about one-to-one (1:1), at least some of the precursors remaining in an unreactive state until exposed to an aqueous physiological environment, whereupon the precursors undergo in-situ cross-linking with one another to provide adhesion to tissue adjacent the puncture.
Freeze-dried hydrogel first section that expands with aqueous physiological fluid and differential PEG-amine free/salt reactivity
A sealant for sealing a puncture through tissue comprising an elongate first section formed from a freeze-dried hydrogel that expands when exposed to physiological fluid within a puncture, and a second section fused to and extending from the distal end of the first section, the second section comprising PEG-precursors comprising PEG-ester and PEG-amine precursors, the PEG-amine precursors including both a free amine form of PEG-amine precursors that are at least partially cross-linked with the PEG-ester precursors and a salt form of PEG-amine precursors that 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.
Freeze-dried hydrogel first section and a fused solid PEG-precursor mass activated by aqueous physiological exposure
A sealant for sealing a puncture through tissue comprising an elongate first section consisting essentially of a freeze-dried hydrogel that expands when exposed to physiological fluid within a puncture, and a second section fused to and extending from the distal end of the first section, the second section formed from a solid mass of PEG-precursors consisting essentially of PEG-ester and PEG-amine precursors in an equivalent ratio of active group sites of PEG-ester/PEG-amine of at least about one-to-one (1:1), at least some of the precursors remaining in an unreactive state until exposed to an aqueous physiological environment, whereupon the precursors undergo in-situ cross-linking with one another to provide adhesion to tissue adjacent the puncture.
Method of sealing by delivering the second section into the puncture before the first and triggering in-situ cross-linking
A method for sealing a puncture extending through tissue of a patient, comprising providing sealant disposed within a lumen such that the second section is disposed closer to the distal opening than the first section, introducing the sealant into a puncture through tissue with the second section entering the puncture before the first section, and exposing the sealant to the aqueous physiological environment within the puncture, whereupon the at least some of the PEG precursors of the second section undergo in-situ cross-linking with one another to provide adhesion to tissue adjacent the puncture.
Apparatus with tubular member and lumen-deployed fused sealant sections
An apparatus for sealing a puncture extending through tissue, comprising a tubular member comprising a proximal end, a distal end sized for insertion into a puncture, a lumen extending between the proximal and distal ends, and a distal opening in communication with the lumen, and sealant disposed within the lumen and comprising an elongate first section and a second section fused to and extending from the distal end of the first section, the sealant disposed within the lumen such that the second section is disposed closer to the distal opening than the first section, the second section comprising PEG-precursors comprising PEG-ester and PEG-amine precursors in an equivalent ratio of active group sites of PEG-ester/PEG-amine of at least about one-to-one (1:1), at least some of the precursors remaining in an unreactive state until exposed to an aqueous physiological environment, whereupon the precursors undergo in-situ cross-linking with one another to provide adhesion to tissue adjacent the puncture.
Making sealant by melting PEG-amine and PEG-ester powders into non-cross-linked PEG precursors and fusing a solid PEG-precursor mass
A method for making a sealant for sealing a puncture through tissue, comprising forming an elongate first section extending from a proximal end to a distal end and a cross-section sized for delivery into a puncture through tissue, melting PEG-amine and PEG-ester powders into a liquid mixture comprising non-cross-linked PEG precursors, wherein an equivalent ratio of active group sites of the PEG-ester precursors to the PEG-amine precursors is at least about one-to-one (1:1), and fusing a solid mass of the mixed PEG precursors onto the distal end, at least some of the PEG precursors remaining in an unreactive state until exposed to an aqueous physiological, whereupon the precursors undergo in-situ cross-linking with one another to provide an adhesive layer bonded to the first section.
Across the independent claims, the inventive subject matter is the use of a fused two-section sealant architecture where an elongate first section, optionally a freeze-dried hydrogel that expands with physiological fluid, supports a distal PEG-precursor second section that remains unreactive until exposed to an aqueous physiological environment. After aqueous exposure, PEG-ester/PEG-amine precursors cross-link in situ to provide adhesion to tissue adjacent the puncture, including embodiments with differential PEG-amine free amine and salt forms and delivery arrangements where the second section enters the puncture before the first section.
Stated Advantages
Provides adhesion to tissue adjacent the puncture upon exposure to an aqueous physiological environment via in-situ cross-linking of PEG-precursors.
The first section is formed from a freeze-dried hydrogel that expands when exposed to physiological fluid within a puncture.
Enables adhesion using PEG-amine precursors in both a free amine form and a salt form that remains unreactive until aqueous physiological exposure.
Documented Applications
Sealing a puncture through tissue of a patient by introducing a sealant such that a second section enters the puncture before a first section, followed by exposure to an aqueous physiological environment to trigger in-situ cross-linking for adhesion to tissue adjacent the puncture.
Sealing a puncture through tissue using an apparatus including a tubular member with a lumen and distal opening, with sealant disposed in the lumen such that the second section is closer to the distal opening than the first section.
Interested in licensing this patent?