Apparatus for sealing a vascular puncture

0001The present invention relates to an instrument for occluding a puncture of a body, more specifically an instrument for occluding a vascular puncture that passes through a tissue and extends into a lumen, and a blood vessel or other body tube from a patient's skin. It relates to an instrument for delivering a plug into a percutaneous puncture extending into a lumen to occlude the puncture.

0002Background technology Instruments and methods are known for percutaneously accessing a patient's vascular structure, eg, for performing work within the vessel, and for occluding the puncture that occurs after the work is completed. For example, a hollow needle can be inserted into a blood vessel through the patient's skin and its covering tissue. The guide wire can be passed through the needle lumen into the blood vessel and then the needle can be removed. The induction sheath can then be advanced along the guide wire, eg, together or in succession, through one or more dilators into the vessel. Catheter or other device can also be advanced to a certain position in the induction sheath and on the guide wire to perform a medical procedure. In this way, the induction sheath facilitates access and / or introduction of the vascular device into the vessel, while minimizing trauma to the vessel wall and / or minimizing blood loss. After the procedure is complete, the device and induction sheath may be removed, leaving an extending puncture between the skin and the vessel wall.

0003Hemostasis may be applied to the covering tissue by applying external pressure, for example, by hand and / or using a punching bag to occlude the puncture. However, this method is time consuming and costly and requires as much as an hour of medical professional time. This is also unpleasant for the patient and requires the patient to remain immobile in the treatment room, catheter room, or waiting room. In addition, there is a risk of hematoma from bleeding before hemostasis.

0004Fowler's US Pat. No. 5,108,421 discloses a plug that can be delivered into the puncture through tissue. The stopper is a cylindrical member made of a porous, bioabsorbable, expandable hemostatic collagen sponge or polymerized polylactic acid or polyglycolic acid. In one embodiment, a catheter is inserted into the blood vessel through a puncture. The balloon on the catheter is inflated and pulled back until it is placed in close proximity to the puncture of the vessel wall. The stopper can advance through the puncture until the stopper touches the balloon. Once the plug is placed in the puncture, the balloon can be deflated and pulled out, leaving the plug in the puncture to occlude the puncture with the dilation and / or promote hemostasis.

0005Alternatively, US Pat. Nos. 5,192,302 and 5,222,974, given to Kensey et al., Describe bioabsorbable collagen plugs that can be delivered to the puncture site through an induction sheath. However, the disclosed plugs are difficult to place properly with respect to blood vessels, and when collagen material is exposed in the bloodstream, it flows downstream and causes embolism, which is generally undesirable. There is a problem with this method.

0006U.S. Pat. No. 6,605,295 is introduced into the lumen or void of the patient's body and is substantially dehydrated, capable of obstructing or plugging biopsy needle marks, reinforcing soft tissue, or delivering therapeutic compounds. Describes hydrogel rods, stoppers, crushed, or irregularly shaped pieces. In one embodiment, the dehydrated hydrogel plug is placed within the arteriotomy site and can hydrate in the presence of tissue fluid and blood to fill the catheter sheath scar and prevent further bleeding. By swelling to equilibrium hydration, the plug can be firmly anchored in its place, thereby reducing the risk of large hematomas forming at the puncture site.

0007U.S. Pat. No. 6,703,047 discloses a tissue-adhesive composition based on dehydrated hydrogel precursors. The hydrogel can be used, for example, as an adhesive drug delivery depot for blocking fluid leakage from tissue and as a means for growing and / or supporting tissue. Hydrogels can be administered directly to the open wound site or administered using, for example, non-adhesive backing materials, absorbent backing materials, syringe applicators, powder atomizers, or aerosolization systems, or needleless injectors. can do.

0008Disclosure of invention The invention is an instrument for occluding a puncture in the body, more specifically an instrument for providing temporary or permanent hemostasis within a vascular puncture extending into a blood vessel, and / or a blood vessel or other device from the patient's skin. It is intended as an instrument for delivering an occlusion plug into a percutaneous puncture that extends into a body lumen.

0009According to one embodiment, a device is provided for blocking a puncture extending through a tissue containing a carrier having a predetermined shape, such as a disk, cylinder, or other stopper. The first hydrogel precursor is placed on the carrier. The second hydrogel precursor is also placed on the carrier. The first and second hydrogel precursors are placed on the carrier in an unreacted state until exposed to an aqueous physiological environment.

0010In another aspect, a device comprising a tubular member and a plug carried by the tubular member is provided to occlude a puncture extending through the tissue. The stopper may include first and second hydrogel precursors placed on it, the first and second hydrogel precursors not prior to exposure to the aqueous physiological environment within the tissue. It is in a reactive state. The device may include a pusher for deploying the plug from the tubular member.

0011In one embodiment, the plug may comprise a lumen extending through it. The device may also include pusher and positioning members adapted to slide and / or pass through the tubing member. The positioning member may include an elongated member and an expansion member at one end, for example, an expandable mesh, a balloon, an expandable frame, or the like on a guide wire. In another aspect, the positioning member may be provided at one end with a bioabsorbable foot plate or other element to provide tactile feedback to the user, for example during occlusion work and / or puncture occlusion.

0012According to yet another aspect, an apparatus comprising a lyophilized hydrogel, such as polyethylene glycol (PEG), or other polymeric carrier for blocking a puncture extending through a tissue is provided.

0013In one embodiment, the lyophilized PEG carrier is preformed to the desired shape or geometric dimensions prior to the lyophilization step. In another aspect, the lyophilized PEG carrier is molded into the desired shape or geometric dimensions after the lyophilization step. For example, a "raw" dry-frozen PEG carrier material can be molded or otherwise deformed by steps such as cutting, rolling, rolling, compression molding.

0014According to another aspect, any of the above devices may comprise an adhesive "sticky" coating or layer disposed on the exposed surface of the polymer carrier. The adhesive coating can be formed from a mixture of a non-crosslinked PEG polymer and a pH regulator such as sodium borate crystals. In an exemplary step, the adhesive coating mixture can be heated to dissolve the polymer components and then applied to the lyophilized PEG carrier.

0015According to another aspect, an instrument is provided with a cartridge and plug device formed from a lyophilized PEG carrier for occluding a puncture extending through the tissue. The stopper can comprise a first and second PEG polymer placed on it, said first and second PEG polymer being unreacted prior to exposure to the aqueous physiological environment within the tissue. is there. The instrument may include a pusher member, a positioning member, and / or a closing member for deploying the plug from the cartridge.

0016Detailed description of the illustrated embodiment Turning to the drawing, FIGS. 1A-1D depict a device 2 for occluding a puncture extending through a tissue (not shown). Generally, the device 2 comprises a carrier or core 4, for example, in the shape of a stopper, on which the first hydrogel precursor 6 and the second hydrogel precursor 7 are arranged. The first and second hydrogel precursors 6 and 7 are placed on the carrier 4 in an unreacted state. The first and second hydrogel precursors 6 and 7 can remain unreacted, for example, before or until exposure to an aqueous physiological environment. The aqueous physiological environment will be, for example, inside a puncture mark that extends through the tissue.

0017Blood or other body fluids that come into contact with the precursor addition carrier 4 undergo a hydrogel formation reaction between the two precursors 6 and 7. The reaction of the hydrogel precursor can form a cross-linked adhesive or sticky coating that assists in retaining the plug device 2 within the puncture and / or promoting hemostasis within the puncture after deployment. As described below, an activator, such as a pH regulator 8, can optionally be placed on the carrier 4 to initiate, accelerate, or enhance the reaction of precursors 6, 7.

0018FIG. 1A depicts carrier 4 in the shape of a cylindrical plug. It will be recognized that carrier 4 can take other cross sections or shapes such as ellipses, triangles, quadrangles, cones, disks, polygons and the like. The carrier 4 can be formed from a biocompatible and / or bioabsorbable material, such as a porous bioabsorbable foam or other solid material. In one embodiment, the carrier 4 is formed from a biocompatible and / or bioabsorbable hydrogel, such as polyethylene glycol (PEG), or other synthetic material. In addition to, or in lieu of, carrier 4 may include, for example, collagen, fibrin, carboxymethyl cellulose, oxidized cellulose, alginate, gelatin, or other protein-based material, and / or polyglycolic acid (PGA), polyactidic acid. It can contain a parental thrombotic material containing one or more synthetic substances such as (PLA), polyvinyl alcohol. The material of carrier 4 is absorbed by the body at least in part over a long period of time, for example, days, weeks, or months. Carrier 4 may optionally contain therapeutic agents and / or pharmaceutical agents to promote healing, eg, to prevent infections and / or other adverse medical events. Such agents may be embedded in the carrier material and / or applied as one or more coatings or layers. In addition to this, the material of carrier 4 may have a substantially uniform composition, or the composition may vary, for example, along its entire length and / or within the lower layers within carrier 4.

0019In an exemplary embodiment, the carrier 4 comprises a lumen 10 extending between the proximal end and the distal ends 14, 16, which defines the major axis 18. The lumen 10 can be made at the time of making the carrier 4, for example, if the carrier 4 is formed by rolling one or more material sheets or layers, or by molding. Alternatively, the lumen 10 is formed by drilling a hole in the already formed solid support 4 or otherwise removing the material. The lumen 10 allows other elongated members, such as a guide wire or part of a positioning member 40 (described in detail below), to slide or pass through the carrier 4 while feeding the plug device 2. Has dimensions.

0020FIG. 1B depicts carrier 4 with primary and secondary hydrogel precursors 6 and 7 on top of it. In one embodiment, the first and second hydrogel precursors 6, 7 are added by sucking a mixture of liquid hydrogel precursors 6, 7 onto carrier 4. Depending on the material used, the hydrogel precursors 6 and 7 may initially be a solid dehydrating material, such as a powder, which may be heated above its melting point to a liquid suitable for absorption. For example, the first and second hydrogel precursors 6, 7 can be mixed well prior to addition on carrier 4.

0021Alternatively, the first and second precursor materials 6, 7 can be provided in liquid form, in which the carrier 4 is immersed, poured onto the carrier, and / or simultaneously or continuously in the carrier 4. It may be applied. For example, the first and second precursors can be dissolved in a solvent that can then be applied to carrier 4. In either case, the first and second hydrogel precursors 6 and 7 may be in a solid or semi-solid state after the first and second hydrogel precursors 6 and 7 have been added onto the carrier 4.

0022The first hydrogel precursor 6 includes US Pat. Nos. 6,152,943, 6,165,201, 6,179,862, 6,514,534, 6,379,373, 6,703,047, and US Patent Application Publications 2003-0012734, 2002-0114775. Many hydrogel precursor materials can be mentioned as disclosed in No. and No. 2004-0249342. For example, in one embodiment, the first hydrogel precursor 6 includes 10k dalton PEG with four arms or 20k dalton PEG amine with eight arms. .. Alternatively, the first hydrogel precursor 6 may include, for example, an amino acid having a reactive end group, for example, a bioabsorbable star-shaped high fraction having complementary crosslinked species such as lysine, dilysine, trilysine and the like.

0023Second hydrogel precursors 7 include a number of hydrogel precursors, first precursors 6 once exposed to a water or aqueous environment, for example substances that react with first precursors such as those mentioned above. .. For example, the second precursor 7 may be another 8-armed 20k Dalton PEG amine or a 4-armed 10k Dalton PEG ester. Alternatively, the second precursor 7 may be a complementary crosslinked species of a bioabsorbable star polymer such as an amino acid having a reactive end group, such as lysine, dilysine, trilysine.

0024Referring to FIG. 1C, the pH activator 8 is also added to the carrier 4. The pH activator 8 can cause local changes after exposure to a water or aqueous environment, eg, can initiate or accelerate a hydrogel formation reaction. In an exemplary embodiment, the pH activator 8 includes solid borate crystals such as Na2B4O7 / 10H2O, but other salt-based or other substances that alter local pH knowledge are also used. be able to. Alternatively, another pH changing agent such as sodium borate or sodium bicarbonate may be used. In one embodiment, the pH activator 8 physically attaches solid boric acid crystals, powder, or other particles to the carrier 4 to which the precursor has been added (first and second hydrogel precursors 6, 7). It is added onto the carrier 4 by contact. For example, the carrier 4 may simply be rolled over the pH activator 8, provided that the pH activator 8 is sufficiently pressed so that it is embedded in the outer surface 12 of the carrier 4. Alternatively, the pH activator 8 can be used, for example, by pushing particles of the pH activator 8 into the outer surface 12, or an adhesive (eg, substantially inert, or a first or second precursor. It can be attached to the outer surface 12 of the carrier 4 by using an adhesive) that is non-reactive to the bodies 6 and 7.

0025FIG. 1D depicts an enlarged cross-sectional view of the outer surface 12 of the precursor addition carrier 4 of FIG. 1D. As shown, the mixed layers of primary and secondary hydrogel precursors 6 and 7 substantially cover the outer surface 12 of carrier 4 as a relatively thin film or coating. Since the first and second hydrogel precursors 6 and 7 are preferably in the form of a liquid during the absorption process, the first and second hydrogel precursors 6 and 7 are outside the porous carrier 4. It can penetrate into the surface 12, for example holes that substantially cover all or most of the carrier 4, or other recesses.

0026FIG. 1D also shows the pH activator 8 added on the carrier 4 . In Figure 1D, the pH activator 8 is in the form of an independent particle solid (eg, boric acid crystal) that is aggregated at the top of the layers of the first and second hydrogel precursors 6 and 7. doing. However, the pH activator 8 is such that the pH activator 8 can take the form of a film, coating, or layer similar to that shown in the first and second hydrogel precursors 6 and 7 of FIG. 1D. It is understood that it can be added on the carrier 4 in a dissolved or other liquid form.

0027With reference to FIG. 2, the flowchart shows an exemplary method for making a blocking device such as the plug device 2. First, carrier 4 is provided, for example by forming a plug or other body from a porous, thrombotic, and / or biocompatible material (step A). As described above, the carrier 4 can be formed by machining, grinding, etc. by winding the material into a desired shape, molding and cutting out individual devices from a larger mass of material, and the like. it can. Mixtures of the first and second hydrogel precursors 6 and 7 are then provided in a predetermined ratio, eg, equimolar ratio (step B). Next, the first and second precursors 6 and 7 are added to the carrier 4 (step C), and the precursor may be a hydrogel precursor in the form of a liquid as described above. As shown in FIG. 2, one or more additional layers of hydrogel precursor material can optionally be added to carrier 4 (step D). Depending on the hydrogel used in the stopper device, multiple hydrogels (eg, 2 or more) may be required to initiate the hydrogel reaction. In addition, one or more therapeutic agents and / or pharmaceutical agents can optionally be applied to the carrier 4, eg, before or after coating the carrier 4 with the first and second precursors 6, 7. ..

0028Finally, an optional pH activator 8 can be added to the carrier 4 (step E). In one embodiment, the pH activator 8 is in the form of crystals or other particles that can be physically attached to the carrier 4, eg, on top of the first and second precursors 6, 7.

0029Turning to FIG. 3, an instrument 1 for occluding a puncture penetrating tissue is depicted. In general, the device 1 may include a delivery sheath or other tubular member 20, and a plug device 2 as described elsewhere herein. In addition, the instrument 1 may include a plunger or other pusher member 30, and / or a positioning member 40.

0030The delivery sheath 20 comprises a proximal end 22, a tip 24 having a size and shape suitable for insertion into the puncture 90, and a lumen 26 extending between them, substantially rigid, semi-rigid, and / Or a tubular body that is flexible. The tip 24 may be tapered to facilitate advancement within the puncture and / or may include a tip 28 that is substantially non-traumatic. The delivery sheath 20 may include a handle (not shown) at the proximal end 22 and / or one or more seals, such as a hemostatic seal (not shown). The plug device 2 can be arranged in the lumen 26 adjacent to the tip 24. The lumen 26 can be sized to allow passage through the delivery sheath 20 in the apical direction while the plug device 2 slides through it, eg, feeds as detailed below.

0031The pusher member 30 may be an elongated member having a proximal end (not shown) and a tip 34 having a size that allows it to be slidably inserted into the lumen 26 of the delivery sheath 20, such as a plunger, catheter or the like. The tip 34 of the pusher member 30 is substantially provided to facilitate contact, compression, and / or "tightening" of the plug device 2 within the delivery sheath 20 and / or puncture, as described in detail below. The smooth end may be used. The pusher member 30 may be substantially rigid, semi-rigid, and / or substantially flexible, sufficient column to allow the delivery sheath 20 to move relative to the plug device 2 without buckling the pusher member 30. Has a length. The pusher member 30 may also include, for example, a lumen 36 extending between the proximal end and the distal end 34 for accommodating the positioning member 40 and / or the guide wire (not shown).

0032In the embodiment shown in FIG. 3, the positioning member 40, eg, a guide wire, and / or other solid or hollow elongated body, may include a positioning element 46 on a proximal end 42, an distal end 44, and an distal end 44. .. The positioning element 46 may be an expandable element such as a wire mesh structure as shown in FIG. 3, an expandable frame 46'as shown in FIGS. 4A-4C, and / or a balloon (not shown). The positioning element 46 or 46'can optionally be provided with an exodermis or other cover (not shown) at least at its proximal end, which makes the positioning element 46 or 46'substantially non-perforated.

0033The positioning element 46 or 46'may be biased towards the expanded state, as shown in FIGS. 3 and 4A-4C, but is compressed into the contracted state, for example by covering it with a sleeve or other restraint (not shown). You can also do it. The restraint can be removed to expose the expandable element and automatically expand the expandable element into the expanded state. Alternatively, the expandable element may be, for example, a pull wire, an expansion medium source (eg, coupled to a lumen (not shown) that passes through the positioning member 40 and extends to an invisible inflatable positioning element), or positioning. Other actuators (also not shown) that can be operated from the base end of the member may be used for selective expansion. Further information on expandable structures that can be incorporated into the positioning member 40 is available in U.S. Pat. Nos. 6,238,412 and 6,635,068, U.S. Patent Application Publication No. US2003 / 0078616, and U.S. Patent Application Serial No. 10 / Found in 975,205.

0034Turning to FIGS. 4A-4F, an exemplary procedure is shown in which instrument 1 is used to occlude the puncture 90. The puncture 90 usually extends from the patient's skin 92 through the intermediate tissue 96, for example to the body lumen 94. In an exemplary embodiment, the puncture 90 is a percutaneous puncture that is in contact with a blood vessel 94, such as the femoral artery, carotid artery, and the like.

0035In an exemplary procedure, the puncture 90 can be made using known procedures, such as with a needle, guide wire, one or more dilators (not shown), and the like. The induction sheath (also not shown) can be advanced through the puncture 90 into the blood vessel 94 and, as is known in the art, can provide, for example, one or more instruments in the blood vessel, and / Or allow one or more diagnostic and / or interventional procedures to be performed from vessel 90. Once the procedure via vessel 94 is complete, the instrument and / or induction sheath (not shown) may be removed from puncture 90.

0036Turning to FIG. 4A with the positioning element 46 folded, the positioning member 40 can advance through the puncture 90 until the positioning element 46 is placed in the blood vessel 94, where the positioning element 46 is moved. , Can be expanded to the expanded state shown in Figure 4B. In one embodiment, the positioning member 40 can advance through a pre-arranged induction sheath (not shown), eg, before removing the induction sheath from the puncture 90. Alternatively, the positioning member 40 can advance directly through the puncture 90 after removing the induction sheath.

0037The positioning member 46 can be kept in a contracted state (shown in FIG. 4A) as it advances through the puncture 90, for example by a coated sheath or other restraint (not shown). Once the positioning element 46 is placed within the vessel 94, the restraint can be removed and the positioning element 46 can be automatically expanded into the expanded state (shown in FIG. 4B). Alternatively, the positioning element 46 can be expanded into an extended state using an actuator (not shown) at the proximal end 42 of the positioning element 40.

0038Once the positioning element 46 is expanded, as shown in FIG. 4B, the positioning member 40 can be partially withdrawn from the puncture 90 until the positioning member 46 contacts the wall of the blood vessel 94 as shown in FIG. 4B. If the positioning element 46 is substantially non-porous, the positioning element 46 substantially occludes the puncture 90 from the vessel 94.

0039Turning to FIG. 4C, instrument 1 can be introduced into the puncture 90, for example, before or after contacting the positioning element 46 with the wall of the vessel 94. For example, the proximal end 42 of the positioning member 40 passes through, for example, the lumens 26, 10, 36 of the delivery sheath 20, the plug device 2, and the pusher member 30, and is pulled into the tip 24 of the delivery sheath 20. be able to. The delivery sheath 20 can then advance beyond the positioning member 40 until, for example, the tip 24 is placed adjacent to the vessel 94.

0040If the positioning element 46 has not yet been pulled back, the base end 42 of the positioning member 40 may be pulled to push the positioning element 46 against the tip 24 of the delivery sheath 20 (providing tactile feedback). ). The positioning member 40 may then be pulled further (providing another tactile feedback) until the positioning element 46 contacts the wall of the vessel, thereby partially pulling the delivery sheath 20 back into the puncture 90.

0041Alternatively, if the positioning element 46 is already pressed against the vessel wall 94, the delivery sheath 20 is brought into contact with the positioning element 46 by the tip 24, whereby the tip 24 and, as a result, the plug device 2 is near the vessel 94. You may move forward until you get the tactile sensation of being placed in. If the positioning element 46 substantially occludes the puncture 90 from the vessel 94, this can suppress or minimize blood in the vessel 94 entering the puncture 90 and into the lumen 26 of the delivery sheath 20. Penetrates and contacts plug device 2. This would be desirable to reduce the premature reaction of the first and second precursors of puncture device 2.

0042Alternatively, the positioning member 40 can be brought into the delivery sheath 20 first. For example, as shown in FIGS. 5A and 5B, the positioning member 40 "can be provided with a foot plate 46" housed in the delivery sheath 20 lumen on the tip side of the plug device 2 at its tip 44 ". As shown in, the delivery sheath 20 can be advanced into the puncture 90, for example, directly or through an induction sheath (before removal), with the foot plate 46 enclosed therein. Once the tip 24 of the delivery sheath 20 is placed in the blood vessel 94, the positioning member 40 "can be advanced to expose the foot plate 46" in the blood vessel 94. The foot plate 46 "can change its orientation when exposed and / or can expand radially. Then, the positioning member 40" is partially pulled back so that the foot plate 46 "is brought into contact with the blood vessel 94 wall to bring the positioning member 46" into contact with the blood vessel 94 wall. 40 can be prevented from being pulled out any further. If the foot plate 46 "is wide enough, it can substantially occlude the puncture 90 from the vessel 94.

0043In yet another option, the delivery sheath 20 is placed in the induction sheath (before removal) along a guide wire (not shown) that can be left before introducing the positioning member 40, eg, after removal of the induction sheath. , Or you can go directly through the puncture 90. After removing the guide wire, the positioning member 40 can be advanced into the proximal end 22 of the delivery sheath 20 and into the lumen 10 of the plug device 2 together with, for example, the contracted positioning element 46. The tip 24 of the positioning member 40 can be advanced in the tip direction until the positioning element 46 is placed in the blood vessel 94. Once inside the blood vessel 94, the positioning element 46 can be expanded and brought into contact with the wall of the blood vessel 94 in the same manner as described above.

0044Now turning to FIG. 4D, the plug device 2 can then be deployed from the delivery sheath 20. For example, as described above in connection with FIG. 3, the delivery sheath 20 comprises a pusher member 30 in its lumen 26 and can be located at the base of the plug device 2. By arranging the tip 24 of the delivery sheath 20 and, as a result, the tip 16 of the plug device 2 adjacent to the blood vessel 94, the delivery sheath 20 is pulled back toward the base while keeping the pusher member 30 substantially stationary. Can be done. By doing so, the pusher member 30 can pull the delivery sheath 20 back from the periphery of the plug device 2 while keeping the plug device 2 in a predetermined position in the puncture 90.

0045In one embodiment, the plug device 2 may be ubiquitous from the tip 24 of the delivery sheath 20 at a predetermined distance, eg, about 2 mm (2 mm) to 10 mm (10 mm), towards the base, in an exemplary embodiment. , Approximately 5 mm (5 mm) may be unevenly distributed, so that the plug device 2 is delivered into the puncture 90 with an uneven distribution from the blood vessel 94 toward the base. Alternatively, the plug device 2 may be located in the immediate vicinity of the tip 24 of the delivery sheath 20.

0046Alternatively or additionally, the pusher member 30 may be advanced forward with respect to the delivery sheath 20 to feed the plug device 2 into the puncture 90. For example, the pusher member 30 is advanced until the plug device 2 is joined to the positioning element 46 of the positioning member 40. This ensures that the plug device 2 is fed to a position adjacent to the blood vessel 94 and tactile feedback can be obtained when the plug device is joined to the positioning element 46. Alternatively, as shown in FIG. 5B, if the plug device 2 is placed in the delivery sheath 20 together with the positioning element 46 , the pusher member 30 is used to continuously connect the positioning element 46 and the plug device 2. Can be deployed.

0047As shown in FIG. 4E, the pusher member 30 can be used to squeeze, jam, or tighten the plug device 2 into the puncture 90, if desired. For example, after exposing the plug device 2 into the puncture 90 (eg, using one of the steps above), the pusher member 30 is advanced to push the plug device 2 toward the tip and press it against the positioning element 46'. be able to. Thereby, the tip 16 of the plug device 2 can be placed close to or pressed against the wall of the blood vessel 94 to enhance hemostasis at the arteriotomy between the blood vessel 94 and the puncture 90. The pusher member 30 is optionally further advanced by pushing the plug device 2 axially, further expanding the plug device 2 radially to fill the puncture 90 and / or outward towards the surrounding tissue. Or it can be spread in it.

0048After deploying the plug device 2 within the puncture 90, an additional occlusion compound is optionally delivered into the puncture 90 to fill all or part of the puncture 90, eg, directly above and / or around the plug device 2. You may. For example, using the delivery sheath 20 or pusher member 30, a liquid occlusion compound, such as hydrogel (not shown), can be passed through, for example, lumen 26 (of delivery sheath 20) or the lumen of pusher member 30 (or either). It can be delivered into the puncture 90 (through another lumen of the device (not shown)).

0049In one embodiment, the delivery sheath 20 has one or more sides that can be attached to the proximal end of the delivery sheath 20 to an obstructive compound source, such as a syringe assembly (not shown) containing a hydrogel precursor. It can be equipped with a port (not shown). If the delivery sheath 20 has not yet been completely removed from the puncture 90, the delivery sheath 20 is advanced within the puncture 90 until its tip 24 is placed adjacent to the plug device 2, and then the obstructive compound is placed within the puncture 90. Can be sent to.

0050Alternatively, the delivery sheath 20 may deliver the occlusive compound and pull it back, for example when it partially fills the puncture 90. Alternatively, for example, if the delivery sheath 20 has been removed, the pusher member 30 can be used to deliver the occlusive compound in a manner similar to that described above. In yet another option, another sheath or other delivery device (not shown) may be introduced into the puncture 90 to deliver the liquid occlusion compound directly above and / or around the plug device 2. Illustrative instruments for delivering such obstructive compounds into Puncture 90 are disclosed in US Patent Application Publication Nos. 2004-0249342 and 2004-0267308.

0051Turning to FIG. 4F, the positioning member 40, pusher member 30, and delivery sheath 20 (if its tip 24 still extends into the puncture 90) are then removed, leaving the plug device 2 in the puncture 90. be able to. The components of instrument 1 can be removed in any, desired order. For example, in one procedure, the positioning member 40 can be pulled out through the lumen 36 of the plug device 2 and the pusher member 30. The pusher member 30 can hold the plug device 2 so that it does not move toward the base when the positioning member 40 is removed. Once the positioning member 30 has been removed, the pusher member 30 (and delivery sheath 20 if not yet removed) can then be removed.

0052Alternatively, the delivery sheath 20 and the pusher member 30 may be pulled out first, followed by the positioning member 40. In yet another option, a positioning element such as the foot plate 46 "may remain in the vessel 94 after feeding the plug device 2. In this option, the foot plate 46" (or other positioning element) may remain. At least in part can be made from bioabsorbable materials, such as those disclosed in US Patent Application Reference No. 10 / 928,744, which are absorbed relatively quickly.

0053When the positioning member 40 is removed, the positioning element 46 can be folded and the positioning member 40 can be removed through the lumen 10 of the plug device 2 without substantially moving or destroying the plug device. For example, a sleeve or other restraint (not shown) advances over a positioning member 40 when the positioning element 46 enters the sleeve until it contacts the positioning element 46 and forces the positioning element 46 to fold. Can be done. Alternatively, if the positioning element 46 is controlled by an actuator (not shown), the actuator can be operated to fold the positioning element 46 before removing the positioning member 40. In another option, the positioning member 40 simply pulls when the positioning element 46 enters the lumen 10 of the plug device 2 until it contacts the plug device 2 and forcibly folds the positioning element 46.

0054When the positioning element 46 is folded, blood and / or other fluid in the vessel 94 can enter the puncture 90, thereby exposing the plug device 2 to an aqueous physiological environment. An aqueous physiological environment that may contain blood or other body fluids from blood vessels 94 (or other body lumens) can moisten the plug device 2, thereby causing first and second precursors on the device. The reaction between the bodies begins. For example, the liquid can dissolve the activator 8 and change the pH of the liquid to initiate the interaction of the first and second hydrogel precursors 6, 8. The reactions of the first and second hydrogels 6, 7 form an adhesive or "sticky" hydrogel coating 38 that can bind or adhere to the tissue surrounding the puncture 90, which is predetermined within the puncture 90 of the stopper device 2. Facilitates holding in place. In addition, the hydrogel coating 38 can swell or swell to further aid the retention of the plug device 2 within the puncture 90 and / or enhance the sealing of the puncture 90. Although hydrogel precursors are described herein, another multi-component adhesive and / or reactive component is applied to the carrier 4 and the stopper device 2 is exposed to the liquid in the patient's body when the carrier 4 is exposed. Adhesive or other coatings can be made around it.

0055For the reactions of the first and second hydrogel precursors 6, 7, the porous carrier 4 is optionally placed in an aqueous physiological environment, eg, when the first and second precursors 6, 8 are dissolved and / or reacted. For example, the blood in the puncture 90 may be exposed. Thus, if the carrier 4 contains a thrombotic substance, the substance can coagulate and / or accelerate the blood in the puncture 90, thereby promoting hemostasis. When the carrier 4 comes into contact with the blood, the carrier 4 may optionally expand to substantially close the lumen, but another option is to make the lumen 10 sufficiently small to allow the blood to expand. It can also be blocked by natural hemostasis. In addition to this, if the carrier 4 contains a therapeutic agent and / or a pharmaceutical agent, the blood and / or surrounding tissues will be exposed to the drug, thereby stopping bleeding, patient comfort, healing, etc. Can also be increased.

0056Turning to FIGS. 6A-6C, another aspect of the plug device 102 that occludes a puncture that extends through a tissue (not shown) is shown. Generally, for example, a device 102 having a predetermined shape comprises a carrier or a core 104. The carrier 104 is formed from a lyophilized (ie, lyophilized) PEG polymer containing hydrolyzable chemical groups. FIGS. 6A and 6B depict a carrier 104 in the shape of a cylindrical stopper having a proximal end and tips 114, 116, but the carrier 104 has a different cross section or shape, such as an ellipse, a triangle, It will be understood that it may be a quadrangle, a cone, a disk, a polygon, etc. (not shown).

0057In one embodiment, the carrier 104 is formed from a lyophilized PEG polymer without a surface adhesive layer or adhesive coating. In this aspect, the carrier 104 or plug device 102 may be anchored within the puncture simply by extending the carrier 104 into the puncture and exposing it to, for example, blood or other bodily fluids. Lyophilized PEG polymers, such as PEG polymers containing a porous polymer network, can take up and expand liquids when exposed to an aqueous environment. The magnitude of swelling or swelling (ratio before and after hydration) is significant, for example 2 to 10 times (2X to 10X) the size of lyophilization based on its volume. In addition to or instead of this, the lyophilized hydrogel can absorb about 2-10 times its weight of liquid, substantially expanding the carrier 104. The hydrogel can absorb the liquid in a range, for example within a few minutes, for example not more than about 2 minutes, until it is substantially saturated.

0058Further referring to FIGS. 6B and 6C, all or part of the carrier 104 can optionally be optionally coated with a surface adhesive layer or coating 106. For example, the adhesive layer 106 is a mixture of uncrosslinked PEG polymers containing the initially unreacted first and second PEG polymers 107 and mixed with a pH regulator 108, similar to the previous embodiment. In an exemplary embodiment, the first PEG polymer can be formed from an amine-terminated PEG polymer, while the second PEG polymer can be formed from an ester-terminated hydrolyzable PEG polymer.

0059The first and second PEG polymers 107 are US Pat. Nos. 6,152,943, 6,165,201, 6,179,862, 6,514,534, 6,379,373, 6,703,047, and US Patent Application Publications 2003-0012734, 2002- It may contain multiple PEG polymer precursors as disclosed in 0114775 and 2004-0249342. The pH regulator 108 can change the local pH on or around the carrier 104, eg, sodium borate, sodium bicarbonate, or other salt such as crystalline or powdered Na2B4O7 / 10H2O, as in the preceding embodiment. Examples include substances based on.

0060The first and second PEG polymers 107 and the pH adjuster 108 can be applied to all or part of the carrier 104, for example by dispersing it on the outer surface or inside of the carrier 104. Specifically, the first and second PEG polymers 107 are in a non-reactive state, eg, before or until exposure to an aqueous physiological environment present in a passage through a puncture or other tissue. Can stay.

0061Blood or other body fluid that comes into contact with the PEG polymer addition carrier 104 causes a crosslink formation reaction with the two types of PEG polymer 107 brought into the adhesive layer 106. The reaction of the PEG polymer 107 creates a cross-linked adhesive or adhesive hydrogel, which aids in retention of the plug device 102 after deployment within the puncture and / or promotion of hemostasis within the puncture. The cross-linking reaction will occur, for example, when the plug device 104 is in close contact with the tissue surrounding the puncture, such as fascia or other tissue such as adipocytes within the panniculus.

0062This cross-linking reaction mechanically fixes or secures the plug device 102 in the puncture and maintains its position, for example, after deployment. This securing function is particularly advantageous when the patient moves immediately after the procedure is completed, in which case the plug may move without this function, resulting in bleeding complications. By substantially locating the plug device 102 locally within the puncture, the target deployment position can be maintained within the patient while the puncture site heals.

0063In addition to this, the lyophilized PEG polymer forming the carrier 104 can be immediately hydrated upon contact with blood or other body fluids. As a result, blood or other body fluid leaking from the puncture site and / or surrounding tissue can immediately resume the hydration reaction of the carrier 104 substance before the carrier 104 is sufficiently disintegrated, thereby enhancing the puncture closure. ..

0064The material of the plug device 102, i.e. the carrier 104 and / or the adhesive layer 106, is at least partially absorbed by the body over time, for example over days, weeks, or months. The carrier 104 and / or the adhesive layer 106 may optionally contain therapeutic agents and / or pharmaceutical agents, eg, promote healing and prevent infections and / or other harmful medical events. Such agents can be embedded within the carrier material and / or the adhesive layer 106 and / or applied as one or more coatings or layers. In addition to this, the material of the carrier 104 may have a substantially uniform composition, or the composition may vary, for example, along its entire length and / or within the lower layers within the carrier 104.

0065Turning to FIGS. 6A and 6B, in the illustrated embodiment, the carrier 104 comprises a proximal end and a distal end 114, 116, and a lumen 110 extending between the proximal end and the apical part 114, 116. , It defines the major axis 118. The lumen 110 can be made at the time of carrier 104 formation, for example if the carrier 104 is formed by winding one or more material sheets or layers, or by molding. Alternatively, the lumen 110 can be formed by boring the already formed solid support 104 or by removing the material. Lumen 110 can have dimensions and / or sizes that can accommodate and pass through catheters, guide wires, or other elongated members. For example, as further described below, a portion of the positioning member 140 can slide or pass through the lumen 110 of the carrier 104, eg, feeding the plug device 102.

0066The shape of the lyophilized PEG polymer forming the carrier 104 may be determined during lyophilization. Alternatively, the lyophilized PEG polymer can be formed into various preformed shapes, such as sheets and / or blocks, which are then dehydrated and then molded to the desired dimensions, eg, the instrument 101 described below. Can be facilitated installation within a delivery system such as. The lyophilized PEG polymer can be made into the desired size and / or shape using various molding / sizing steps such as die cutting, rolling, flattening and compression molding.

0067FIG. 6B depicts a carrier 104 with a mixture of primary and secondary PEG polymers 107 and a pH regulator 108 added. In one embodiment, as in the previous embodiment, the powder-shaped amine-terminated polymer can be used as the first PEG polymer, and the powder-shaped ester-terminated hydrolyzable PEG polymer can be used as the second PEG polymer. Unlike the previous embodiment, the two types of powder can be mixed in the powder form in the mixing container. Sodium borate powder crystals may be added to the primary and secondary PEG polymer 107 mixture, for example, by grinding into fine powders to reduce graininess and increase miscibility.

0068The resulting mixture (first and second PEG polymers 107 and pH regulator 108) is then heated to about 40 ° C to dissolve the first and second PEG polymers 107 and / or pH regulator 108. The dissolved mixture is preferably completely mixed to ensure, for example, substantially uniform distribution or distribution of other desired components.

0069The dissolved mixture (first and second PEG polymers 107 and / or pH regulator 108) can then be applied to all or part of the exposed surface of the carrier 104. The mixture can be obtained by applying the heated liquid mixture onto the carrier 104 using a number of known methods, such as a brush or other applicator, by spraying the aerosol of the heated liquid mixture onto the carrier 104, or. It can be applied by immersing or sucking the heated liquid mixture on the carrier 104 using a bathtub or the like containing the heated liquid mixture. Once the heated liquid mixture has been sufficiently applied to the carrier 104, the mixture is allowed to cool, eg, solidify, and / or form an adhesive layer 106. After cooling, a solid or semi-solid adhesive layer 106 surrounds the lyophilized carrier 102.

0070In one embodiment, as shown in FIG. 6B, the base end 114 and the tip end 116 of the carrier 104 are not covered by the adhesive layer 106. In this case, the lyophilized PEG polymers at the proximal and distal ends 114, 116 of the carrier 104 remain exposed, facilitating, for example, subsequent hydration. This special aspect has excellent swelling / swelling properties while substantially maintaining the plug device 102 in the desired target position.

0071FIG. 6C is an enlarged cross-sectional view of the outer surface of the adhesive layer 106 arranged on the exposed surface of the freeze-dried carrier 104. As shown, the first and second PEG polymers 107 and the pH regulator 108 are well mixed throughout the adhesive layer 106. Alternatively, the relative concentration of the components of the adhesive layer 106 may vary along the carrier 104.

0072Turning to FIG. 7, an exemplary method for making a block device such as the plug device 102 described above is shown. First, in step A, the lyophilized polymer carrier 104 is provided, for example, by forming a stopper or other body from a PEG polymer containing a hydrolyzable chemical group. As described above, the carrier 104 is machined, ground, etc. by rolling one or more material sheets into a desired shape, forming them, and cutting out individual devices from larger chunks of material, etc. Can be formed by.

0073Next, in step B, a mixture (non-crosslinked) of the first and second PEG polymers 107 is provided in a predetermined ratio, eg, an equimolar ratio. Then in step C, a solid pH activator 108 such as sodium borate is added to the mixture created in step B. In one embodiment, the pH activator 108 is ground into a fine powder before being added to the mixture of primary and secondary PEG polymers 107. In step D, the mixture formed and produced in step C is heated to a predetermined temperature to dissolve the first and second PEG polymers 107. In one embodiment, the mixture is heated to a temperature of about 40 degrees Celsius (40 ° C). Once the primary and secondary PEG polymers 107 are dissolved (while the boric acid crystals remain solid), the entire mixture can be completely mixed.

0074In step E, the then heated liquid mixture is applied to the carrier 104, eg, one or more exposed surfaces of the carrier 104, using one of the above methods to form an adhesive layer 106. In another embodiment, the first and second precursors can allow the precursors to be mixed and / or coated on the carrier 104 and at the same time remain non-reactive with each other, such as methylene chloride, dimethyl sulfoxide, warm acetone and the like. It is dissolved in one or more of the solvents of. The carrier 104 and / or the adhesive layer 106 can optionally be coated with one or more therapeutic agents and / or pharmaceutical agents. Alternatively, the adhesive layer 106 is applied to or dispersed in the carrier 104 by immersing or sucking up the carrier 104, which together after being coated to form the final carrier, or by forming multiple layers. Can be made to.

0075In another aspect, the plug device 102 is provided with another laminated structure. For example, a sheet containing multiple layers of different components, such as the one or more components described above, can be formed and the sheet can be wrapped around a tube or solid cylindrical structure. Illustrative embodiments of such sheets include, for example, three layers: a first layer of lyophilized hydrogel, a second layer of binary hydrogel adhesive, and a third layer of lyophilized hydrogel. Thus, in this embodiment, the adhesive layer, eg, the adhesive layer containing the two hydrogel precursors that are initially unreacted, will be sandwiched between layers of lyophilized hydrogel.

0076In another aspect, a lyophilized hydrogel layer is provided and an adhesive layer, eg, an adhesive layer containing two initially unreacted hydrogel precursors, is applied to one side of the lyophilized hydrogel layer. .. A pH regulator, such as boric acid crystals, is embedded or otherwise applied to the opposite side of the lyophilized hydrogel. Thus, in this embodiment, the pH regulator will be substantially separated from the adhesive layer. This is desirable to prevent the pH regulator adhesive layer material from initiating the reaction prematurely, otherwise such a reaction may occur to some extent in the absence of an aqueous environment. .. The composite material thus obtained can then be folded or rolled into the desired plug form.

0077Turning to FIGS. 8 and 9A-9D, a delivery device 101 similar to the previous embodiment is shown for occluding a puncture 90 that penetrates tissue 96 and reaches, for example, a blood vessel 94 or other body lumen. Generally, the instrument 101 comprises an induction sheath or delivery sheath, or other tubing member 20, and a positioning member 140, such as those similar to the prior embodiments. The delivery device 101 also comprises a plug device 102, such as one of those described above, and a cartridge 120 carrying a plunger, sinker, or other pusher member 130.

0078The cartridge 120 is generally elongated with a lumen 126 extending between the proximal end 122, the distal end 124, and the proximal end and the distal ends 122, 124 into which the plug device 102 can be brought. Includes tubular body. The pusher member 130 may also be an elongated tubular body comprising a proximal end 132, a distal end 134, and a lumen 136 extending between the proximal end and the distal ends 132, 134. The positioning member 140 is expandable, such as an extendable mesh (as shown in FIG. 8), a mechanically expandable structure, or a balloon (not shown) to the base 142, the tip 144, and the tip 144. The positioning element 146 can be provided.

0079The delivery device 101 can be used to place and deliver the plug device 102 into the puncture 90, eg, from outside the vessel, directly above the arteriotomy in the vessel 94 communicating with the puncture 90, or otherwise to it. Can be placed and fed in close proximity. In one embodiment, the cartridge 120 can be inserted or slid into the lumen 26 of the delivery sheath 20, and the pusher member 130 can glide through the lumen 126 of the cartridge 120. The plug device 102 may be compressed or otherwise placed in the lumen 126 of the cartridge 120, at the tip of the pusher member 130. The positioning member 140 can be inserted through the cartridge 120, for example, through the pusher member 130 and the plug device 102.

0080In this way, the plug device 102 can be arranged between the inner wall of the cartridge 120 and the outer surface of the positioning member 140. As described below, the cartridge 120 can be used to carry the plug device 102 to the unfolded position, i.e., through the delivery sheath 20. The pusher member 130 can be placed near the plug device 102 to place and / or maintain the plug device 102 in place during deployment.

0081With reference to FIGS. 9A-9D and 10A-10B, the delivery device 101 can be used to feed the plug device 102 into the puncture 90 penetrating the tissue 94 and / or promote hemostasis. First, the delivery sheath 20 can be placed within the puncture 90 to provide access to the blood vessel 94, eg, as in the preceding embodiment. With reference to FIG. 9A, the positioning member 140 can be introduced and / or passed into the lumen 26 of the delivery sheath 20 together with, for example, a folded expandable frame or other positioning member 146 above it. ..

0082The cartridge 120 (along with the plug device 102 and the pusher member 130) can first be provided at the proximal end 142 of the positioning member 140, as shown in FIG. 10A. Thus, when advancing the positioning member 130 into the puncture 90, the cartridge 120 can initially be located outside the puncture 90. Alternatively, the cartridge 120 can be brought to the tip 144 of the positioning member 140 and, for example, the cartridge 120 (along with the plug device 102 and the pusher member 130) can be introduced with the positioning member 140. A further option is to provide the cartridge 120 separately from the positioning device 140. When advancing the positioning member 140 into the puncture 90, the shaft of the positioning member 140 can be extended from the base end 22 of the delivery sheath 20 toward the base, and then into the cartridge 120, for example the lumen 136 of the pusher 130 and / Alternatively, it can be pulled back through the lumen 110 of the plug device 102.

0083Further referring to FIG. 9A, the tip 144 of the positioning member 140 can be inserted into the blood vessel 94 through the puncture 90 and the arteriotomy. The positioning element 146 at the tip 144 of the positioning member 140 can be expanded or deployed in the same manner as in the preceding embodiment. As shown in FIG. 9A, the expandable positioning element 146 of the positioning member 140 can be mechanically expanded or expanded to the expanded state.

0084After expanding the expansion element 146, the positioning member 140 can be pulled back at least partially until the positioning member 146 contacts the wall of the vessel 94, for example, from the puncture 90 to substantially occlude the vessel 94. This involves two steps, in a tactile step similar to the preceding embodiment, the positioning member 140 with the positioning element 146 in the expanded state is pulled back until it contacts the tip 24 of the delivery sheath 20, and further positioning. Pull back until element 146 contacts the wall of vessel 94. Base-wise tension can be applied to and / or maintained on the positioning member 140 to pull in the positioning element 146 and, for example, puncture 90. Tension in the base direction can be maintained manually or using a tensioning device (not shown), temporarily between, for example, subsequent steps, as disclosed in U.S. Patent Application Publication No. 2004-0267308. Can provide hemostasis.

0085Turning to FIG. 9B, the cartridge 120 carrying the plug device 102 can be advanced forward beyond the positioning member 140 into the puncture 90. In one embodiment, the cartridge 120 (and plug device 102) can advance in the delivery sheath 20 until the hub 123 of the cartridge 120 joins the hub 23 of the delivery sheath 20 (shown in FIG. 9C). The positioning member 140 and / or the pusher member 130 fits when the cartridge 120 reaches a predetermined position on the positioning member 140, for example, to prevent the pusher member 130 from moving further with respect to the positioning member 140. A detent can be optionally provided.

0086For example, as shown in FIGS. 10A and 10B, the positioning member 140 may include a ring, tab, or other raised element 145, and the pusher member 130 may include an integral hinge, tab, or other latching element 135, eg, base end 132. Can be provided. For example, the latch element 135 may simply be an annular notch at the proximal end 132 of the pusher member 130 for inwardly biasing the proximal end. If the cartridge 120 (and as a result the pusher member 130) advances, the latch element 135 is free to pass over the raised element 145. The latch element 135 then joins the blunt end of the latch element 135 to the ring 145 of the positioning member 140 to prevent the pusher member 130 from being pulled back again.

0087Alternatively, the cartridge 120 and the pusher member 130 may initially reside on the positioning member 140 as shown in FIG. 10B. In this option, the pusher member 130 and the positioning member 140 may include cooperating detents 133, 145 to prevent the pusher member 133 from moving in the base direction with respect to the positioning member 140. Alternatively, the pusher member 130 may be fixed to the positioning member 140 instead, for example, fixing the tip 134 of the pusher member 130 to the base of the positioning element 146 at a certain distance, for example, as shown in FIG. 10B. As such, the plug device 102 may be placed in the immediate vicinity of the positioning element 146. While advancing in the delivery sheath 20 or in the puncture 90, the plug device 102 does not come into direct or indirect contact with blood or other body fluids along the blood pathway.

0088Referring here to FIG. 9C, if the pusher member 130 is not previously provided in the cartridge 120, the pusher member 130 will be in the lumen 126 of the cartridge 120, for example, the marker 137 on the pusher member 130 will be the hub 123 of the cartridge 120. You can move forward until you come close to. As shown in FIG. 9C, the position of this marker allows the tip 134 of the pusher member 130 to be placed adjacent to the proximal end 114 of the plug device 102. Alternatively, the pusher member 130 and the plug device 102 are initially placed in the cartridge 120 as shown in FIG. 9C, i.e. the plug device 102 is placed adjacent to the tip 124 and the cartridge 120 so that the pusher member 130 You can eliminate the need to move forward.

0089The pusher member 130 is then held and the delivery sheath 20 and cartridge 120 are pulled back toward the base while the vessel 94 is occluded from the puncture 90 using the base tension on the positioning member 140, as shown in FIG. 9D. The plug device 102 is exposed or deployed in the puncture 90. The pusher member 130 acts as a stop device, and the delivery sheath 20 and the cartridge 120 are pulled out while the stopper device 102 is prevented from moving toward the base.

0090In one embodiment, the user of the delivery device 101 pulls back the delivery sheath 20 and the cartridge 120, using, for example, the index and middle fingers, while placing the thumb on the hub 133 of the pusher member 130 and maintaining its position. Can be done. For example, as shown in FIG. 9D, when the hub 123 of the cartridge 120 is joined to the hub 23 of the delivery sheath 20, the cartridge 120 can be pulled out at the same time by pulling out while fixing the delivery sheath 20. Alternatively, the cartridge 120 may be removed first and then the delivery sheath 20 may be removed. The cartridge 120 and the delivery sheath 20 can be removed entirely from the puncture 90, or only the plug device 102 can be exposed.

0091The plug device 102 optionally advances the pusher member 130 toward the tip and presses the plug device 102 against the wall and / or positioning element 146 of the blood vessel 94 in the same manner as in the previous embodiment. It can be pressed inside or otherwise compressed. This allows the plug device 102 to be firmly secured, the plug device 102 to be radially extended outward and / or the plug device 102 to be pressed against the arteriotomy, eg, the seal of the puncture 90 from the vessel 94. Can be enhanced.

0092When the plug device 102 is delivered, the tension on the base of the positioning member 140 can be released and / or the positioning element 146 can be folded into a folded state. For example, the positioning element 146 can be mechanically folded or retracted. When the positioning element 146 is folded, the positioning member 140 (and as a result, the positioning element 146) can be slowly pulled out through the lumen 110 of the plug 102.

0093In an exemplary embodiment, the positioning element 146 has dimensions of about 0.875 millimeters (035 inches) or less, and the positioning member 140 can be easily removed without substantially disturbing the deployed plug device 100. While pulling out the positioning member 140, the pusher member 130 functions as a stop device and can keep the plug device 102 from moving in the puncture 90 toward the base. In addition to this, in embodiments where the plug device 102 includes an adhesive layer (not shown in FIG. 9D), a "sticky" adhesive layer also helps to secure the plug device 102 to the surrounding tissue. ..

0094After removing the positioning member 140, the pusher member 130 may be pulled out to leave the plug device 102 in place. If desired, for example, if bleeding occurs in the base direction through the lumen 136 of the pusher member 130, in the same manner as in the preceding embodiment, the liquid hydrogel or other obstructive compound is punctured, directly above the plug device 102. And / or can be delivered to the surroundings to help achieve permanent hemostasis. For example, the source of the occluded compound (not shown) may be connected to the proximal end 132 of the pusher member 130, and the occluded compound may be fed into the puncture 90, directly above and / or around the plug device 102. it can. The pusher member 130 may optionally pull back towards the base when the occluded compound is fed and at least partially fills the puncture 90 with the occluded compound.

0095<figref num="1A">FIG. 1A is a perspective view of a porous carrier in the shape of a plug.</figref><figref num="1B">FIG. 1B is a perspective view of the porous carrier of FIG. 1A on which the first and second hydrogel precursors are placed.</figref><figref num="1C">FIG. 1C is a perspective view of the porous carrier of FIG. 1B on which a pH activator is arranged.</figref><figref num="1D">FIG. 1D is an enlarged cross-sectional view of the porous carrier shown in FIG. 1C, comprising first and second hydrogel precursors, as well as a pH activator.</figref><figref num="2">FIG. 2 is a flowchart showing a method of adding one or more hydrogel precursors on a porous carrier.</figref><figref num="3">FIG. 3 is a deployed side view of an instrument for delivering a plug device into a puncture penetrating tissue.</figref><figref num="4A-B">4A-B are cross-sectional views of the patient's body showing procedures for using a device according to an aspect of the invention to occlude a puncture extending from the patient's skin through intermediate tissue into the body lumen. is there.</figref><figref num="4C-D">FIG. 4C-D is a cross-sectional view of the patient's body showing the procedure for using a device according to an aspect of the invention to occlude a puncture extending from the patient's skin through intermediate tissue into the body lumen. is there.</figref><figref num="4E-F">FIG. 4E-F is a cross-sectional view of the patient's body showing the procedure for using a device according to an aspect of the invention to occlude a puncture extending from the patient's skin through intermediate tissue into the body lumen. is there.</figref><figref num="5A-B">5A and 5B are cross-sectional views of the patient's body showing another device for occluding a puncture extending from the patient's skin through intermediate tissue into the body lumen.</figref><figref num="6A">FIG. 6A is a perspective view of the lyophilized carrier in the shape of a stopper.</figref><figref num="6B">FIG. 6B is a perspective view of the lyophilized carrier of FIG. 6A, which provides a plug device for occluding a puncture penetrating tissue with an adhesive layer on top of it.</figref><figref num="6C">FIG. 6C is an enlarged cross-sectional view of the plug device of FIG. 6B showing the first and second polymers carried on the plug device and the pH activator.</figref><figref num="7">FIG. 7 is a flow chart showing the procedure for adding an adhesive adhesive layer on a lyophilized carrier.</figref><figref num="8">FIG. 8 is a deployed side view of an instrument for feeding a plug device into a puncture penetrating tissue.</figref><figref num="9A-B">9A-B are cross-sectional views of the patient's body showing the procedure of occluding the puncture extending from the patient's skin to the blood vessels using the instrument of FIG.</figref><figref num="9C">FIG. 9C is a cross-sectional view of the patient's body showing a procedure for occluding a puncture extending from the patient's skin to a blood vessel using the instrument of FIG.</figref><figref num="9D">FIG. 9D is a cross-sectional view of the patient's body showing a procedure for occluding a puncture extending from the patient's skin to a blood vessel using the instrument of FIG.</figref><figref num="10A-B">10A-10B is a cross-sectional view showing the deformation of the instrument of FIG.</figref>