WO1995008951A1

WO1995008951A1 - Vascular patch applicator

Info

Publication number: WO1995008951A1
Application number: PCT/US1994/010993
Authority: WO
Inventors: Julius G. Hammerslag
Original assignee: Hemodynamics
Priority date: 1993-09-28
Filing date: 1994-09-28
Publication date: 1995-04-06
Also published as: US5383899A; US5665106A; US5529577A; AU7921494A

Abstract

Disclosed is a device which can be used in the disclosed method for delivering tissue adhesives and/or sealant patches to a surface which covers or surrounds a lumen, cavity or organ, or potential lumen or cavity, within a human or other animal. The method is particularly suited to sealing perforations in vascular walls, such as after arterial access for Percutaneous Transluminal Coronary Angioplasty (PTCA). The device (8) includes a reservoir (16) for holding adhesive. A control (19) is used to actuate the slidable piston (32) thus forcing the adhesive from the reservoir, through valve (42), lumen (56), and to the distal applicator tip (18).

Description

VASCULAR PATCH APPLICATOR

Background of the Invention

1. Field of the Invention

This invention relates to a method and an associated device for sealing a puncture in a vessel within mammals. In particular, the invention relates to a method and an associated device for delivering a sealant patch and/or tissue adhesive to seal a puncture in a vessel.

2. Description of Related Art

Percutaneously accessing major vascular structures is a key step in a variety of diagnostic and therapeutic procedures, including Percutaneous Transluminal Coronary

Angioplasty (PTCA), Percutaneous Coronary Angiography and Percutaneous Coronary Atherectomy. After the procedure is completed, the instruments used to perform the procedure are withdrawn from the vessel leaving a potential source of bleeding.

The most common method used to prevent post-procedure bleeding at the access site involves the application of direct pressure to the perforation site until normal physiologic pathways have sealed the access site. There are several problems with this method. First, the pressure application technique may fail to prevent hemorrhage. Such a hemorrhage may be life-threatening hemorrhage or lead to a large hematoma. A large hematoma in the groin, for instance, may compromise the major nerve supply to the anterior lower extremity.

Secondly, the pressure application technique extends the length of the in-hospital stay. For example, a PTCA may be completed in 2 to 3 hours, but the patient will typically be hospitalized for several additional hours or overnight, simply to allow the access site to seal physiologically. During this extended hospital stay the patient is required to stay immobile, often with a sand bag taped to his thigh (in the case of femoral artery access).

These complication are exacerbated where PTCA procedures are performed in elderly patients which commonly have arteries with reduced natural elasticity. The access perforation in a relatively inelastic artery does not contract or shrink upon itself to the same extent that would occur with an artery of normal elasticity. The resulting undeflected perforation in a relatively inelastic artery typically is two to three times larger than an access perforation in a normal artery, further complicating the initiation of hemostasis and the normal physiologic sealing of the access site.

More than 500,000 PTC As were performed worldwide in 1992 (Cowen Report, March 1993), as well as several times that number of other procedures requiring accessing major vascular structures percutaneously. Thus, the increased length of in- hospital stay necessitated by the pressure application technique considerably increases the expense of procedures requiring such vascular access. A technique that would allow faster and safer sealing of a vascular access site would save a significant amount of health care resources. There remains a need for such a technique.

Summary of the Invention

There is provided in accordance with one aspect of the present invention, a method of closing a vascular perforation of the type produced during a percutaneous transluminal catheterization procedure. The method comprises the steps of providing an adhesive patch applicator kit of the type having a housing, an adhesive applicator therein, a patch applicator therein, and an adhesive patch. A first portion of the housing is manipulated with respect to the second portion of the housing to express a quantity of adhesive from the reservoir onto the patch. Thereafter, the applicator having the patch thereon is removed from the housing and advanced percutaneously to position the patch against the vascular perforation. The applicator is thereafter removed while leaving the patch adhered to the vascular perforation.

In accordance with another aspect of the present invention, there is provided an adhesive patch applicator kit. The kit comprises a housing having a rotatable cap and a chamber therein, said cap rotatable about a longitudinal axis.

A patch applicator within the chamber is removably connected to one of the housing or the rotatable cap. A reservoir is also provided in the chamber, said reservoir connected to the other of the housing and the cap. A tip on the reservoir is provided for expressing adhesive, and an adhesive patch is removably attached to the applicator such that rotation of the cap about the longitudinal axis relative to the housing expresses adhesive from the reservoir through the tip and onto the patch.

In accordance with a further aspect of the present invention, there is provided a method for patching a vascular puncture. The method comprises providing a patch applicator of the type having a proximal handle portion, an intermediate extender portion, and a distal patch contact surface.

A vascular patch is releasably secured to the contact surface, and a quantity of tissue adhesive is applied to the distal surface of the patch. The applicator is thereafter percutaneously advanced to contact the patch to the vascular perforation site. The applicator is thereafter removed, leaving the patch secured to the vessel wall at the perforation site.

Further features and advantages of the present invention will become apparent to those of ordinary skill in the art in view of the following disclosure when considered together with the attached drawings and claims.

Brief Description of the Drawings Figure 1 is a side elevational cross-sectional view of an adhesive applicator in accordance with one aspect of the present invention.

Figure 2 is a cross-sectional view taken along the line 2-2 of Figure 1. Figure 3 is a cross-sectional view taken along the line 3-3 of Figure 1. Figure 4 is a cross-sectional elevational view of an applicator kit in accordance with the present invention. Figure 5 is a cross-sectional view taken along the line 5-5 in Figure 4.

Figure 6 is a cross-sectional view taken along the line 6-6 in Figure 4. Figure 7 is a schematic representation of a catheter introduction sheath having expander and introducer cannulas thereon, in position within a vessel.

Figure 8 is a schematic representation as in Figure 7, with the catheter introduction sheath withdrawn from the artery.

Figure 9 is a schematic representation as in Figure 8, with the introducer and expander positioned against the artery wall, and the catheter introduction sheath removed.

Figure 10 is a schematic representation as in Figure 9, with the expander cannula removed. Figure 11 is a schematic representation as in Figure 10, with an adhesive patch applicator having a patch thereon advancing down the introducer cannula.

Figure 12 is a side elevational view of a vascular patch applicator in accordance with the present invention.

Figure 13 is a left end view of the patch applicator of Figure 12. Figure 14 is a bottom plan view of the patch applicator of Figure 12.

Figure 15 is a side elevational view of an expander cannula in accordance with the present invention.

Figure 16 is a left end view of the expander of Figure 15.

Figure 17 is a side elevational view of an introducer cannula in accordance with

" the present invention.

Figure 18 is a bottom plan view of the introducer of Figure 17. Figure 19 is a sectional side view of an applicator in accordance with an embodiment of the present invention. Figure 20 is a sectional side view of an applicator in accordance with another embodiment of the present invention.

Figure 21 is a cross sectional view of the applicator of Figure 20 taken along the lines 21-21.

Figures 22 and 23 schematically illustrate a series of method steps involved with a preferred treatment method of the present invention.

Figure 24 is a sectional side view of an applicator in accordance with an additional embodiment of the present invention.

Figure 25 is a sectional side view of an applicator in accordance with another embodiment of the present invention. Figure 25a is a front elevational view of the applicator of Figure 25 as seen in the direction of lines 25a-25a.

Figure 25b is a cross sectional view of the applicator of Figure 25 taken along the line 25b-25b.

Figure 26 is a sectional side view of an applicator in accordance with a further embodiment of the present invention.

Detailed Description of Preferred Embodiments As discussed above, there is a need for a technique which will seal a vascular perforation created during a variety of commonly performed diagnostic and therapeutic procedures, including for example, Percutaneous Transluminal Coronary Angioplasty (PTCA), Percutaneous Coronary Angiography and Percutaneous Coronary Atherectomy.

In addition, the device and method may have applications in the emergency treatment of trauma, wound closure following surgical procedures and the like. For convenience, the present disclosure will consider primarily the vascular perforation application.

An ideal technique would seal the perforation rapidly, cost effectively and permanently. If used to close a femoral or brachial artery, the technique should result in a seal that can withstand the uppermost potential limits of systolic blood pressure (around 300 mmHg) found in those vessels and the seal should be put in place with an absence of or no more than minimal enlargement of the original percutaneous entrance. One aspect of the present invention addresses the problems inherent in closing a perforation of a vessel, such as, for example, in a femoral or brachial artery following coronary artery or other vessel catheterization by providing a device, and a method that can be used to create a rapid and permanent seal.

The Adhesive Applicator Referring to Figure 1, there is illustrated one embodiment of the adhesive applicator for delivering a tissue adhesive to the surface of a vascular patch. For convenience, tissue adhesive will be discussed herein, although any of a wide variety of other fluids or fluid-like media can be delivered utilizing the reservoir of the present invention. The apparatus of the present invention can also be utilized to deliver materials to any of a wide variety of structures, as will be apparent to one of skill in the art. The present disclosure will discuss embodiments primarily intended for delivery to patches or to tissue of the type which covers or surrounds a lumen, cavity or organ, or potential lumen or cavity, within a human or other animal.

The illustrated embodiment comprises an applicator 8 having a generally tubular housing 10 with a proximal control end 12, a distal delivery end 14 and a reservoir 16.

The distal delivery and 14 is preferably provided with a delivery tip 18 for guiding the adhesive expressed from reservoir 16, as will become apparent in view of the disclosure below.

A control 19 is provided near proximal end 12 for controllably expressing adhesive from the reservoir 16, as will be discussed. Any of a variety of control structures can be used, such as push buttons, levers, plungers, movable walls and the like. Preferably, a control in the form of a rotating knob is provided, such that rotation of the knob causes a measured amount of adhesive to be expressed from the tip 18 as will be discussed. Other types of controls will be apparent to one of skill in the art in view of the disclosure herein.

In the illustrated embodiment, the control 19 comprises a threaded surface 20 for engaging a corresponding threaded surface 22 on the tubular housing 10. Threaded surface 20 is conveniently provided on the radially interior surface of a tubular end cap 24. End cap 24 is linked to movable wall 30 such as by way of a rod 26. In the foregoing embodiment, the cap 24 can be rotated with respect to tubular body 10 to produce an axial distal travel of the cap 24 with respect to the tubular body 10. Rod 26 causes the movable wall 30 to advance distally a corresponding distance, thereby expressing adhesive from the reservoir 16.

Preferably, either the proximal or distal ends of rod 26 are rotatably secured to the movable wall 30 or cap 24 so that the cap 24 can be freely rotated without causing a rotation of annular seal 31 with respect to the interior wall of tubular body 10. In the illustrated embodiment, the proximal end of rod 26 is rotatably received within an aperture 28 in the cap 24. A stop 29 is provided to limit proximal axial travel of rod 26 with respect to cap 24. Any of a wide variety of equivalent structures for accomplishing the objectives of the control 19 can be readily envisioned by one of ordinary skill in the art in view of the disclosure herein.

Manipulation of the control 19 advances the moveable wall 30 in a manner that reduces the volume of the reservoir 16, thereby expressing contents from the reservoir by way of distal tip 18 as discussed below. The moveable wall 30 may comprise a moveable diaphragm, other flexible wall, slidable piston, or other structure for expressing contents from reservoir 16 in response to manipulation of control 19. For instance, as illustrated in Figure 1, the moveable wall 30 is the distal face of a slidable piston 32 or plunger with a plurality of annular seals 31 which prevent undesired proximal flow of adhesive from the reservoir 16.

The reservoir 16 contains any of a variety of tissue adhesives. Suitable adhesives for in vivo use include adhesives within the cyanoacrylate family. In one embodiment, the tissue adhesive comprises one or more of methyl cyanoacrylate, ethyl cyanoacrylate, n-propyl cyanoacrylate, isopropyl cyanoacrylate, n-butyl cyanoacrylate, isobutyl cyanoacrylate, n-amyl cyanoacrylate, isoamyl cyanoacrylate, 3-acetoxypropyl cyanoacrylate, 2-methoxypropyl cyanoacrylate, 3-chloropropyl cyanoacrylate, benzyl cyanoacrylate, phenyl cyanoacrylate, alkenyl cyanoacrylate, butyl-2-cyanoacrylate, alkoxyalkyl 2-cyanoacrylates or fluorinated 2-cyanoacrylates or combinations, thereof. Biocompatibility for particular applications can be determined from the literature or through routine experimentation.

Preferably, the tissue adhesive comprises ethyl cyanoacrylate or butyl-2- cyanoacrylate. These latter two compounds, available from Loctite Corporation (Hartford, CT), are normally in a liquid state with water-like viscosity. They harden almost instantaneously upon exposure to atmospheric humidity. Therefore, the reservoir 16 is provided with moisture-tight proximal and distal ends formed by the moveable wall

30 and the valve 42 to maintain the tissue adhesive in liquid state prior to expression. Preferably, the device is also produced under low humidity conditions and stored in a desiccated package. A removable distal cap (not illustrated) may also be used.

Cyanoacrylate adhesives have been found to harden relatively rapidly when stored below a critical volume of adhesive. Hence, if cyanoacrylate is used, it will be preferable for the reservoir 16 to contain more adhesive than is necessary to seal a typical vascular access site. Preferably, a reservoir volume of at least about 1 to 2 gm is provided to maintain the cyanoacrylate in liquid form in the applicator prior to use. The total volume of adhesive, the desiccation measures and sealing structures on the reservoir 16 can be optimized to produce a desired shelf life by one of skill in the art in view of the disclosure herein.

When used to seal an in vivo tissue surface, cyanoacrylates have several particular advantages. First, they harden almost instantaneously on contact, because of the moisture content of most tissues. For example, they will harden when placed on living vascular walls, and endothelial and mesothelial surfaces. Second, experiments by the inventor indicate that cyanoacrylate sealed vascular punctures can withstand several times the maximum potential systolic pressure, and hence, would not be expected to fail when used to seal a perforation on a vascular wall. Also, cyanoacrylates are naturally thrombogenic. This is an advantage in sealing vascular walls as it promotes the first step in healing the wall. Further, because it seals so rapidly, the risk of embolization or migration can be minimized through the use of the applicators disclosed herein.

Various compounds may be added to the cyanoacrylates to alter the properties of the adhesive. For example, polyacrylic acid having a molecular weight of 200,000 to 600,000 may be cross-linked to the cyanoacrylate to form a suitable biocompatible material. These combination compounds allow the absorbability and resorption rate to be coordinated with the tissue regeneration rate and feature higher elasticity than cyanoacrylates alone. Other additives, such as stabilizers, viscosity modifiers and medications can also be included as desired. In a preferred embodiment of the present invention, the cyanoacrylate is mixed with a thickening agent to optimize the viscosity. In one embodiment, cyanoacrylate liquid is mixed with Cabosil™ (available from Cabot Manufacturing) to produce a relatively viscous cyanoacrylate gel. When the gel is expressed from the applicator 8 onto the vascular patch, it generally maintains its form as an annular bead without soaking into the patch.

Upon immersion of the patch in a body fluid such as blood, the inventor has determined that only an outer layer of the cyanoacrylate gel hardens to form a protective skin. As the vascular patch is thereafter pressed against the vessel wall, the pressure ruptures the cyanoacrylate gel skin, to release fresh cyanoacrylate and bond the patch to the vascular wall. The ability to transport uncured cyanoacrylate, within an outer cured skin, through an aqueous environment enables use of the present invention without the need to rigorously dry the access pathway for application of the vascular patch.

The distal delivery end 14 of the applicator 8 is provided with an annular valve seat 40 which cooperates with a valve 42. The valve seat 40 includes a proximal wall

44 which defines an aperture 35 that opens into the reservoir 16. The aperture 35 has a diameter smaller than that of the reservoir 16 as defined by the tubular housing 10. The valve seat 40 comprises a sealing surface which preferably tapers radially outwardly in the distal direction, from the aperture 35 towards the wall of the tubular housing 10. The sealing surface thus defines generally a frusto-conical shape which mates with a correspondingly shaped surface of the valve 42, as discussed below.

The valve 42 desirably is normally closed. That is, the valve 42 is preferably biased against the valve seat 40. Any of a variety of biasing structures can be used, such as, for example, springs, diaphragms, magnets, resilient polymeric materials, and the like. In the illustrated embodiment, a helical spring 46 biases the valve 42 in the proximal direction against the valve seat 40.

In one embodiment, a distal end of the spring 46 passes through a transverse aperture of the valve proximal end. The spring 46, however, may be attached to the valve 42 by any of a variety of other means known in the art as well. The tubular housing 10 includes structure which supports a proximal end of the spring 46. In the illustrated embodiment, the tubular housing 10 includes a spider structure 50 which extends within the tubular housing 10. As best illustrated in Figure 3, the spider structure 50 includes a plurality of legs 52, preferably three legs, which extend from the wall of the housing 10 to the center of the reservoir 16. The proximal end of the spring 46 is attached to the spider structure 50 in a conventional manner.

Alternatively, proximal end of spring 46 is secured directly to the inner surface of the housing 10 such as by a rivet, penetration through the wall, or spot weld, depending upon the construction material of the housing 10.

Activation of the control 19 advances the plunger 30 in the distal direction to increase the adhesive pressure within the reservoir 16. Once the produced pressure within the reservoir 16 exceeds the biasing force exerted by spring 46 on the valve 35, the valve 35 opens to express adhesive past the valve 42 and the valve seat 44.

In the illustrated embodiment, a space 48 is provided in the distal tip 18 to permit axial distal displacement of valve 42. Adhesive expressed past the valve 42 escapes around the radially outermost extent 54 of the valve 42 and into the space 48. Adhesive is thereafter conducted from the space 48 by way of a lumen 56 out of the distal end of delivery tip 18.

Referring to Figures 1 and 2, the housing 10 is further provided with an annular gear 58 to cooperate with annular gear 70 discussed infra. Gear 58 facilitates rotation of the housing 10 with respect to the end cap 24 to permit expression of adhesive by way of lumen 56.

Applicator Housing

Referring to Figures 4-6, there is disclosed an applicator housing 60 in accordance with the present invention. The housing 60 together with an adhesive reservoir and an adhesive patch applicator form a kit for preparing and applying a patch to a vascular wall. The kit illustrated in Figure 4 is automated to deliver a predetermined volume of adhesive to a preselected pattern or path along the vascular patch. In an alternative embodiment, the kit may simply include the basic components of an adhesive reservoir, a patch and a patch applicator, so that the adhesive can be manually applied to the patch by medical personnel.

The housing 60 generally comprises a relatively rotatably component 62 and a relatively nonrotatable component 64. The rotatable component can be generally in the form of a cap 63, and the nonrotatable component can be generally in the form of a tubular body 65. A releasable connection 66 is further provided, to enable opening the housing 60 to remove the contents thereof.

The main components of housing 60 may be produced in accordance with any of a variety of techniques known in the art, such as machining metal components or using any of a variety of known forming techniques for plastic components. Preferably, the housing 60 comprises injection molded or extruded and fabricated plastic components. The plastic is preferably any of a variety of medical grade, sterilizable plastics, such as high density polyethylene, and others well known in the art.

In general, the housing 60 provides a vehicle for applying a predetermined amount of tissue adhesive to the surface of a vascular patch which has been previously releasably connected to a patch applicator, so that the vascular patch is ready for application to the wall of a perforated vessel.

The housing 60 generally is provided with a tissue adhesive applicator of the type containing a reservoir of tissue adhesive. In the illustrated embodiment, the tissue adhesive applicator 8 is the same as that illustrated in Figure 1. Thus, the applicator 8 is provided with a generally tubular body 10, which is rotatable relative to an end cap 24. Rotation of tubular body 10 with respect to end cap 24 causes relative axial motion of tubular body 10 with respect to end cap 24, thereby advancing a movable wall 30 into adhesive reservoir 16 as has been discussed. The cap 63 is rotatable about a longitudinal axis 68, which, in a preferred embodiment, coincides with the longitudinal axis of the tubular body 65. End cap 24 is secured to the interior end wall of rotatable cap 63, such that the longitudinal axis of rotation of tubular body 10 is offset radially from longitudinal axis 68. In this manner, rotation of cap 63 about its longitudinal axis 68 causes the distal tip 18 of housing 10 to travel in a circle about longitudinal axis 68.

End cap 24 can be secured to the interior end wall of cap 63 in any of a variety of ways known in the art, such as by adhesives, thermal or solvent bonding, and the like. In the illustrated embodiment, end cap 24 is positioned within an axially extending annular flange 67 which was integrally molded with cap 63. The interior wall of housing 64 is provided with a radially inwardly directed annular ring of axially extending gear teeth 70 adapted for engaging the gear 58 on the housing 10. Tissue adhesive expression is accomplished by rotating the cap 63 with respect to the tubular body 65 such that gear 58 engages gear 70 and the tubular body 10 is thereby rotated with respect to end cap 24. The cap 63 is further provided with a radially inwardly extending tab 72 which engages an annular slot 74 on the outer wall of tubular body 65. Annular slot 74 lies in a plane which is inclined with respect to a perpendicular through longitudinal axis 68, so that rotation of cap 63 causes a reciprocal axial travel of cap 63 with respect to the housing 65. For this purpose, the gear teeth 70 on the interior wall of housing 64 are provided with a sufficient axial length that the gear 58 remains engaged with gear teeth

70 throughout the range of axial travel produced as tab 72 rides in annular recess 74.

Patch Applicator The apparatus 60 is further provided with a patch applicator 80 for transporting a vascular patch having adhesive thereon to a treatment site in a patient. In general, applicator 80 comprises a proximal handle portion 82, and an extender portion 84. The extender portion 84 terminates at its distal end at an inclined patch contact surface 86. In the illustrated embodiment, a patch 88 is shown on the patch surface 86. The patch applicator is shown in greater detail in Figures 10-12.

In the illustrated embodiment, the patch applicator 80 has an overall length within -l i¬ the range of from about 5 cm to about 15 cm and preferably and length of about 10 cm. The length and other dimensions of the patch applicator 80 can be varied widely to suit the intended use application, and the particular dimensions disclosed herein relate to an embodiment of the patch applicator intended for use in connection with the puncture of a femoral artery in a normal size and weight adult human.

The patch applicator 80 generally comprises a handle portion 82. Handle portion 82 is preferably provided with a slightly larger exterior diameter than the extender portion 84, and may also be provided with friction enhancing structures such as a knurled surface, or other structures known in the art to facilitate gripping by the medical personnel. In the illustrated embodiment, the handle portion 82 has a length of about 3 cm, and a diameter of about 1 cm.

The extender portion 84 is generally in the form of an elongate cylindrical shaft, for advancing through a tissue expanding cannula as will be discussed. The extender portion 84 in the illustrated embodiment has a length of about 7 cm, and a diameter of about 1/4". Typically, the diameter of the extender portion 84 and the interior diameter of the tissue expander 270 are compatible so that the extender portion 84 substantially fills the interior of tissue expander 270, but is axially slidably received therein. One or more axially extending channels 85 is preferably provided in the extender portion 84 to provide an axial flow path for body fluids such as blood, so that introduction of the patch applicator into the tissue expander will not operate to pump fluids back through a perforation and into the artery.

Preferably, the patch applicator 80 is additionally provided with a guidewire lumen 87 extending axially therethrough. In the preferred method of the present invention, the patch applicator 80 is advanced towards the vascular perforation along a guidewire, to ensure that the patch will be centered over the vascular perforation. The present inventor has determined that, although the patch applicator system of the present invention can be utilized in the absence of a guidewire, the risk of missing or only partially covering the perforation is increased due to the possibility of migration of the distal end of the tissue expander 270 with respect to the vascular perforation in the absence of a guidewire.

Referring to Figure 4, the patch surface 86 and distal tip 18 of the adhesive applicator are oriented within the housing 60 such that rotation of the cap 63 simultaneously expresses adhesive onto the patch 88 and travels in a circular path to produce an annular bead of adhesive on the patch 88. Due to the typical entrance angle -12- of the percutaneous puncture frequently utilized in catheterization procedures, as will be discussed, the patch surface 86 is preferably inclined at an angle with respect to a perpendicular to the longitudinal axis 68. Preferably, the patch surface 86 is inclined with the range of from about 20° to about 50° with respect to that perpendicular. Most preferably, the angle is about 30°. The angle of incline of the surface 86 corresponds to the angle of incline of the plane which contains annular recess 74, as illustrated. In this manner, the adhesive applicator tip 18 will travel at a preset distance from the patch 88 throughout the rotational travel of the cap 63.

In a typical embodiment, as illustrated in Figure 4, a gap is provided between the distal end of delivery tip 18 and the patch 88. This facilitates the flow of a bead of adhesive gel 19 into an annular path around patch 88. However, the gap may create some difficulty and/or irregularities in the size of the bead at the point of initiating adhesive flow. For this purpose, a threaded plug 90 is provided at the proximal end of the applicator 80, for threaded engagement with the wall 92 of tubular body 65. A knurled knob 94 or other gripping structure may be provided, to facilitate rotation of the plug 90 with respect to the wall 92. Plug 90 is further provided with a recess 96 for removably receiving the handle 82 of patch applicator 80.

In use, the cap 63 is initially rotated through a fraction of a rotation to develop a bead of adhesive 19 at delivery tip 18. The knob 94 is thereafter rotated to axially advance the patch 88 into contact with the bead of adhesive 19. Once contact has been established, the knob 94 can be rotated in a reverse direction, to stretch out the bead of adhesive 19. Thereafter, the cap 63 is rotated through one full revolution, to produce an annular bead of adhesive gel on the patch 88.

The patch 88 desirably has a size larger than the perforation of the vessel (e.g., an artery) and may have any of a variety of shapes depending upon the application of the patch 88. The patch 88 generally has a circular or oval shape of sufficient dimensions to completely cover the perforation. It is understood, however, that the size of the patch 88 may only cover a portion of the perforation, yet extend across the perforation such as in the form of a strip so as to attach to the surfaces of the vessel on either side of the perforation. The patch 88 preferably has a diameter of at least about

2 mm and preferably at least about 4 mm for applications with a PTCA arterial perforation formed in an inelastic artery.

The patch 88 in one embodiment is porous so tissue adhesive can flow through the pores of the patch 88 to attach the patch 88 to the surface adjacent the perforation -13- and to seal the portion of the patch 88 extending across the perforation. In an exemplary embodiment, the pores have a size of about 300 microns, although it is understood that the pores could have a size ranging between lOOμ to 500μ, and more preferably ranging between 200μ to 400μ. The foregoing embodiment of patch 88 is preferably formed of a mesh, weave or knitted material which is biocompatible, and preferably is biodegradable (i.e., is absorbable within the body). The patch 88 can be formed of any of a wide variety of suitable materials, such as, for example, polytetrafluoroethylene (PTFE), oxidized regenerated cellulose, GELFILM™ available from the Upjohn Co., and collagen. A suitable material from which to form the patch 88 is a sterile absorbable mesh material

(either knitted or woven) available commercially as VICRYL™ from Ethicon (a Johnson and Johnson company) of Somerville, New Jersey.

In a particularly preferred embodiment, the patch comprises a layer of a biocompatible material such as GELFILM™ available from the UpJohn Company. GELFILM patches cut or stamped from sheet stock having a thickness in the area of from about 0.003 to about 0.004 inches have been found to be particularly suited for the purpose of the present invention. However, other thicknesses can be readily used. Thickness and other patch dimensions can be optimized through routine experimentation by one of ordinary skill in the art, in view of the particular material selected for use as the patch.

In another embodiment of the patch, a GELFILM first layer is provided with a second layer comprising collagen. The collagen layer is disposed adjacent the patch surface 86 on applicator 80, and the cyanoacrylate gel or other adhesive is applied to the GELFILM layer. As discussed below in connection with the method of the present invention, the patch preferably has a guidewire aperture therein. In embodiments having a guidewire aperture in the form of a cylindrical puncture extending straight through the center of the patch, the upper collagen layer has been found to facilitate closure of the guidewire hole in the patch due to the tendency of collagen to swell in an aqueous environment. In an alternate embodiment of the patch of the present invention, the guidewire hole is replaced by a slit in the material of the patch. The slit may be a single linear slit, or two perpendicular slits oriented such as a plus symbol. The slit embodiment permits guidewire installation but tends to be self-closing following removal of the guidewire.

In use, the medical personnel will be required to thread the patch 88 and applicator 80 over the proximal end of a guidewire in position in the patient. To facilitate location of the guidewire opening in the patch, the present inventor has found it convenient to elevate one side of the slit above the plane of the patch while reducing the other side of the slit below the plane of the patch. This can be accomplished by extending a guidewire or mandrel through the slit in the patch, and then laying the guidewire against the patch so that it is generally parallel to the patch but perpendicular to the slit. If this is accomplished while the patch is somewhat moistened, and the guidewire is left in place while the patch dries, the dried patch will tend to retain its modified configuration. The ability to conform a GELFILM™ patch while it is moist and retain the memory in the dried patch is also desirable in connection with another embodiment of the applicator 80 of the present invention (not illustrated). In this embodiment, the surface 86 for applying the patch to the vessel wall is not planar in a manner that permits it to conform generally to the surface of the vessel. Thus, the surface 86 is provided with a configuration that allows it to generally conform to a portion of the wall of a cylinder which has a radius generally corresponding to the likely radius of the artery to which a patch is to be applied. In an embodiment having a curved surface 86, it has been determined to be preferable to preform the patch 88 so that it maintains a complementary curvature to the surface 86 and the vessel wall. The patch 88 can be used to seal a puncture site in a viscera or vascular structure by applying the patch 88 and adhesive to the surface of the walls surrounding the perforation to seal the viscera or vascular structure. In order to apply the patch 88 and adhesive over the puncture site, it is desirable to use an applicator which has planar or curved atraumatic delivery surface to deliver the adhesive and the patch 88 to the perforation site.

The patch 88 may be held in place on surface 86 in any of a variety of ways. In one embodiment, the patch 88 includes on its proximal side a light coating of a releasable adhesive, which removably holds the patch 88 on the distal surface 86 of the applicator 80 before application. The net release force required to pull the patch 88 from the patch surface 86 should be low enough to permit the patch 88 to adhere to the vascular wall while permitting the applicator 80 to be separated from the patch 88. This can be accomplished in a variety of ways which will be readily apparent to one of skill in the art, including, for example, appropriate adhesive selection, and optimizing the surface area coverage of the adhesive. -15-

In general, the angle of inclination of patch contact surface 86 conveniently facilitates the use of an oval patch 88. Thus, as illustrated in Figure 5, an end view of the patch 88 appears circular due to the angle of incline of the patch with respect to the longitudinal axis 68. In a representative PTCA procedure, the position and axial orientation of a vascular structure, for example, the femoral artery, is determined tactily using three adjacent finger tips. An introduction needle is inserted at about 30° into the artery using finger pressure against the artery upstream of the puncture to stop blood flow.

A short introduction guidewire is passed through the introduction needle and into the artery and the needle is withdrawn leaving the guidewire in position. Next, first and second sheaths, usually an introducer sheath and a dilator sheath, are passed over the guidewire and inserted into the vascular structure as is well known. The dilator sheath is removed leaving the introducer sheath in place to provide arterial access. A guidewire is threaded through the sheath and transluminally to the desired treatment location. Then the balloon catheter or other instrumentation is inserted through the introducer sheath and threaded over the guidewire to a desired location, such as an atherosclerotic plaque.

Once the intravascular procedure has been completed, the catheter is removed. The usual method of hemostasis involves also removing the introducer sheath and guidewire, and applying pressure to the perforation site through the skin until hemostasis has occurred. Alternatively, an obturator may be inserted into the introducer sheath and both obturator and introducer sheath left in place for a period of time, prior to their removal. This additional step depends on the type of procedure and the patient's state of coagulation among other variables.

Figures 7-11 schematically illustrate a series of method steps modified with a preferred method of the present invention for inhibiting arterial bleeding at the arterial access site following removal of a diagnostic or treatment catheter. For illustrative purposes, this method will be described as involving the use of the applicator illustrated in Figure 14; however, it is understood that other types of patch or adhesive applicators can be used as well. As discussed above, arterial catheterization commonly involves perforating a wall

260 of the vessel 262 such as, for example, the femoral artery, by introducing a needle percutaneously into the vascular structure. Various sheaths, catheters or other instrumentation are introduced through that puncture, as desired, to accomplish the medical procedure. Following the procedure, the guidewire and/or a tubular introduction sheath can be left in the artery to permit the puncture closure method of the present invention.

With reference to Figure 7, an introducer sheath 250 having a guidewire 252 extending there through is in position within the vascular structure 262. The introducer 250 may have been left in place following the vascular catheterization procedure, or may have been introduced subsequently for the purpose of the present vascular patching procedure.

During catheterization procedures, blood pressure is commonly measured at the arterial access site. As seen in Figure 7, a pressure sensor display 268 is connected to a side port 266 on the introducer 250.

As illustrated in Figure 7, the tubular sheath 250 is in one embodiment of the present invention modified by carrying an expander cannula 264 having a introducer cannula 270 slidably mounted thereon. The expander cannula 264 and introducer cannula 270 in this embodiment are mounted on the sheath 250 prior to commencement of the catherization procedure. In this embodiment, the catherization (e.g. balloon dilatation, drug delivery etc.) is conducted through the sheath 250 having the expander cannula 264 and introducer cannula 270 thereon throughout.

In an alternate embodiment of the invention, the expander cannula 264 is provided in two halves, and adapted to be mounted upon the sheath 250 at the clinical site. If the physician prefers the maneuverability of the sheath 250 without the expander cannula 264 and introducer cannula 270 thereon, he can use a standard cannula 250 for the catherization procedure. At the completion of that procedure, a two or more part expander cannula 264 is reassembled around the introducer sheath 250, and advanced distally along the sheath 250 in accordance with the procedure discussed below. Once the expander cannula 264 is in position against the outer wall of the artery as discussed below, the sheath 250 may be removed, and the distal end of the introducer cannula 270 is advanced over the proximal end of the expander cannula 264 and distally until it is appropriately positioned against the wall of the artery. At that time, the expander cannula 264 can be removed proximally leaving the introducer cannula 270 in place, and ready for the adhesive or adhesive patch application as discussed below.

The split expander cannula of the present invention can be manufactured in a variety of ways, as will be apparent to one of skill in the art. For example, the expander cannula described above and illustrated in Figures 15 and 16 can be cut in two halves along an axially extending plane. Preferably, releasable interlocking structures are -17- provided for retaining the two halves in an assembled configuration. For example, pins can be provided on one half of the expander cannula for engaging corresponding recesses on the other half of the cannula. Any of a variety of "snap fit" interlocking structures can be utilized, to accomplish the advantages of the present invention. Preferably, unlike the embodiment illustrated in Figures 15 and 16, the split expander cannula is provided with a substantially uniform outside diameter throughout its entire length. This facilitates mounting the distal end of the introducer cannula over the proximal end of the expander cannula, so that the introducer cannula can be advanced distally along the expander cannula into the appropriate position such as that illustrated in Figure 10.

Although the split expander cannula described above is described in terms of two opposing halves, the expander may be constructed from any of a variety of pieces which are reassembleable over the sheath into a generally tubular structure. Thus, three or more axially extending segments can be provided for reassembly into a unitary tubular structure. In the preferred embodiment, two halves are provided, which may be snapped fit together at both contact points. Alternatively, the two halves may be joined by an axially extending hinge such as a section of flexible material, so that the hinged expander halves can be positioned around the sheath 250 and then closed thereon to form a tubular expander. With reference to the embodiment illustrated in Figure 7, the introducer 250 is withdrawn from the vascular structure 262 to a location where its distal end is adjacent to the ablumenal surface of the vessel wall 260. See Fig. 8. The blood pressure display 268 aids in the proper positioning of the introducer 250 at this location. A surgeon, or like operator, slowly withdraws the introducer 250 from the vessel while monitoring the blood pressure displayed by the blood pressure display 268. The blood pressure significantly drops once the distal end of the introducer 250 is completely withdrawn from the vessel and the perforation shrinks to its nondilated size. In this manner, the operator knows when he or she has withdrawn the distal end of the introducer 250 to a position adjacent to the ablumenal surface of the vessel 262 as illustrated in Figure 8. With reference to Figures 8-10, the assembly of the expander cannula 264 and introducer cannula 270 is advanced distally along the catherization sheath 250, until the distal end 265 of the expander cannula 264 contacts the vessel wall. Contact with the vessel wall can be determine by tactile feedback to the operator. Alternatively, indium such as a line or other marking drawn around the outer circumference of the sheath 250 -18- can be positioned such that it becomes visible to the operator when the expander cannula 264 has been advanced sufficiently distally that the distal end 265 of expander cannula 264 is at the surface of the vessel.

Once the distal end 265 of expander cannula 264 is in position against the exterior wall of the vessel 262, the sheath 264 can be removed to produce the assembly schematically illustrated in Figure 9. Preferably, the guidewire 265 remains in place.

In the illustrated embodiment, once the introducer cannula 270 is seated against the vessel wall, the expander cannula 264 may be proximally withdrawn, to produce the assembly illustrated schematically in Figure 10. In an alternate embodiment, the function of the expander cannula 264 and introducer cannula 270 can be combined into a single device. A variety of specific structural modifications can be made, in view of the disclosure herein, by one of ordinary skill in the art in view of the objective to properly positioning the introducer cannula 270 against the vessel wall.

One embodiment of an introducer cannula 270 and dilator cannula 264 is shown in Figures 15-18. The cannula 270 has a proximal end 272, a distal end 274, and a minimum inner diameter, which is greater than the maximum diameter of the perforation 276 in the vessel wall 260. The cannula 270 also desirably has a minimum inner diameter, which is greater than the maximum external diameter of the patch applicator 80. This feature allows the applicator 80 to axially, movably fit within the cannula 270.

Preferably, the distal end 274 of cannula 270 is provided with an atraumatic tip 278 to minimize damage to the vessel or surrounding tissue. Distal end 274 is preferably also provided with an angled cut 280 which facilitates placement against the vessel wall at an introduction angle of about 30°. Preferably, the distal end 274 of the cannula 270 has a sufficient diameter to expose both the perforation 254 and a sufficient area of adjacent vessel wall surrounding the perforation 254 so that a sufficient overlap by the patch can be achieved. For a typical PTCA arterial perforation 254, having a diameter of about 1 mm, an introduction cannula 270 having an inside diameter of about 3 mm and an outside diameter of about 4 mm at its distal end 265 may conveniently be used.

Alternatively, the function of introducer cannula 270 can be readily accomplished by a structure integrally formed or secured to the applicator 80. For example, the delivery surface 86 can be retractably disposed within an outer tubular housing, as will be readily appreciated by one of skill in the art in view of the disclosure herein. -19-

At the point in the procedure illustrated at Figure 10, the site is prepared for the application of an adhesive patch 88. Patch 88 is preferably secured to a patch applicator 80, as has been previously discussed. Attachment of the patch 88 to the applicator 80 can be accomplished such as through the use of a relatively weak adhesive bond or mechanical interfitting. In one embodiment, the patch 88 is preassembled onto the applicator 80, such as at the point of manufacture, by placing a relatively short shipping guidewire through the patch and into the guidewire lumen of applicator 80. This shipping guidewire may be provided with a distal anchor, such as a T or other configuration, to prevent the patch 88 from advancing off the end of the shipping guidewire. The proximal end of the shipping guidewire extends into the guidewire lumen and possibly out the proximal end of the applicator 80. When ready for use, the shipping guidewire can be removed by gripping the anchor portion or other structure and pulling it from the guidewire lumen. The proximal end of the procedure guidewire 252 is then threaded into the patch 88 and distal end of applicator 80 as illustrated in Figure 11.

Once a patch 88 is positioned on a patch surface 86 of a patch applicator 80, adhesive can be applied to the patch in any of a variety of ways. In accordance with one aspect of the present invention, the adhesive is applied using an adhesive delivery kit of the type illustrated in Figure 4. Alternatively, adhesive can be manually applied to the tissue contacting surface of the patch 88 such as by the use of a squeeze tube, dropper, or other structure by the medical personnel at the time of the procedure.

In a typical procedure, the proximal end of a guidewire 252 extends through the perforation and out of the cannula 270. This may be a guidewire inserted for the purpose of the vascular patch procedure, or, more likely is the guidewire which was utilized in the original catherization. The patch applicator 80 having the patch 88 thereon is advanced over the proximal end of the guidewire, and advanced down the guidewire towards the patient. If the adhesive was applied to the patch by way of the automated kit disclosed herein, the patch will contain adhesive at the time it is threaded onto the guidewire. Alternatively, if the adhesive is manually applied to the patch, that application may be accomplished following threading the patch 88 applicator 80 onto the guidewire.

The operator then advances the applicator 80 along the guidewire and through the cannula 270 until the patch 88 contacts the vascular wall 260 without penetrating the perforation 254. See Figure 17. The operator tactily feels and recognizes when the -20- patch 88 contacts the ablumenal surface of the vessel wall 260.

As an alternative to tactile feedback once the introducer 270 has been properly positioned, the applicator 80 can be provided with visual or mechanical indicia which indicate that the appropriate depth has been reached. For example, applicator 80 can be provided with a mark or line around its circumference indicating the axial depth to which it should be advanced in a distal direction, before the mark disappears within introducer 270. Similarly, the applicator 80 can be advanced distally into the cannula 270 until a physical stop on the applicator 80 reaches the proximal end of the introducer 270.

The operator thereafter withdraws the applicator 80 from the cannula 270 after applying the patch 88 and tissue adhesive. The tissue compresses around the deposited patch 88 and percutaneous perforation. The tissue may be taped or bandaged subsequently to facilitate the physiological healing of the muscular and cutaneous tissue at the access site.

Referring to Figure 19, there is illustrated an embodiment of the invention for delivering a tissue adhesive to a bodily surface without the use of a vascular patch.

The illustrated embodiment comprises an applicator 108 having a generally tubular housing 110 with a proximal control end 112, a distal delivery end 114 and a reservoir 116. Located near the proximal control end 112 are gripping structures, such as a pair of rings 118 to improve the ease of grasping the applicator 108. A control 119 is provided near proximal end 112 for controllably expressing adhesive from the reservoir 116, as will be discussed. Any of a variety of control structures can be used, such as push buttons, levers, plungers and the like. In addition, a control in the form of a rotating knob may be provided, that functions such that rotation of the knob causes a measured amount of adhesive to be released onto the delivery surface by opening a valve, or consecutively opening and closing a valve, leading from the reservoir. Tactile, auditory or visual feedback or a combination of feedback may be provided as part of the knob control to alert the operator when the measured amount of adhesive has been expressed. Other types of controls will be apparent to one of skill in the art in view of the disclosure herein. The illustrated control 119 comprises a spring loaded proximal end 122, a distal end 124 and a shaft 126. The proximal end 122 comprises a movable button 120 having a stop 128 of such dimensions or structures that its axial distal travel is limited by the proximal end 112 of the tubular housing 110.

The permissible axial travel of moveable button 120 is determined by the desired -21- volume of adhesive to be expressed upon depression of the button 120. Preferably, the applicator 108 of the present invention is provided in a single unit dose delivery form, so that a single depression of button 120 or a singe activation of another control to its limit causes a single unit volume of adhesive, which has been predetermined at the point of manufacture for an intended application, to be expressed from the distal end 114 of the applicator 108.

For example, in an embodiment of the applicator 108 for use following PTCA arterial perforations, a volume of generally no more than about 1.0 mm³, and preferably no more than about 0.5 mm³ of adhesive will desirably be delivered. . Other structures for limiting the delivered volume can be readily incorporated into the applicator 8 by one of skill in the art.

The control 119 is preferably linked to a moveable wall 130 in the reservoir 116. Manipulation of the control 119 advances the moveable wall 130 in a manner that reduces the volume of the reservoir 116, thereby expressing the contents of the reservoir by way of an applicator 132, as discussed below. The moveable wall 130 may comprise a moveable diaphragm, other flexible wall, slidable piston, or other structure for expressing contents from reservoir 116 in response to manipulation of control 119. For instance, as illustrated in Figure 19, the flexible wall 130 is a slidable piston or plunger with a plurality of annular seals 131 which prevent undesired proximal flow of adhesive from the reservoir 116.

In the illustrated embodiment, adhesive is expressed from the reservoir 116 by way of a valved opening 135 for providing valved fluid communication between the reservoir and the delivery surface 133. Conveniently, the same axial distal motion produced by depression of button 120 both displaces the moveable wall 130 and opens the valve 135 to permit expression of adhesive therethrough.

In this embodiment, the applicator 132 comprises a generally radially symmetrical structure, such as a sphere. The proximal portion of this sphere seats within or against the distal end 114 of tubular body 110, to enclose the reservoir 116 therein. Preferably, a biasing means, such as a spring 140, is provided for biasing the valve 135 in the closed position. Alternative biasing means can also be used, such as polymeric springs and structures which utilize the elastic deformation properties of a plastic material.

Depression of button 120 unseats the applicator 132 from the distal end 114 of housing 110, to provide an annular flow path around applicator 132. Adhesive expressed -22- through valve 135 travels around the applicator 132 to coat a delivery surface 133 generally on the distal portion thereof.

The delivery surface 133 on the applicator 108 can take any of a variety of forms. Optimally, the delivery surface 133 facilitates the application of a substantially uniform coat or layer of adhesive over an area that is larger than the arterial perforation site. In general, forms of delivery surface 133 which reduce the risk of any traumatic injury to the tissue are preferred, such as spherical, or other rounded, blunt tips. A relatively flat distal delivery surface 133 can also be utilized, as will be apparent to one of skill in the art and as discussed below. Alternatively, delivery surface 133 comprises an absoφtive blotter material, a permeable membrane or other microporous structure for permitting expression of adhesive directly therethrough.

In general, it is desired that the delivery surface 133 be sufficiently sized relative to the perforation of the vessel wall that the delivery surface 133 will not be penetrable through the perforation unless excessive distal force is applied. In a typical PTCA procedure, the natural elasticity of a major artery wall will normally cause the perforation

160 (Figure 22) to shrink to about 30% of its original area, upon removal of the procedure instrumentation. This natural shrinkage leaves a vessel wall perforation approximately 1 mm in diameter for relatively elastic, healthy tissue. For the puφoses of the present invention, therefore, an applicator 108 having a delivery surface 133 with an effective delivery diameter of at least about 2 mm and preferably a delivery surface of about 3 mm will be utilized.

With this structure, the operator can readily determine through tactile feedback when the delivery surface 133 is securely placed in contact with the vessel wall, yet the risk of perforation through the vessel wall is minimized. This reduces the likelihood that the delivery surface 133 will be introduced into the vessel, which could undesirably introduce adhesive into the bloodstream.

In addition to or as an alternative to reliance upon the size of the delivery surface 133 for limiting distal travel of the applicator 108, other structures, such as distally extending locating pins, radio opaque markers, and the like, can be incoφorated into the applicator 108 of the present invention.

The distal end 114 of the applicator 108 is preferably configured in a manner that minimizes or prevents any contact between the delivery surface 133 and the tissue through which the delivery surface 133 must travel en route to the perforation 160 on the vessel wall. In one embodiment, this is accomplished by introducing the applicator 108 -23- through a tubular introduction cannula 150, as is illustrated in Figure 23 and will be described infra. In general, the cannula 150 has a sufficient interior diameter to accept the applicator 108, yet a sufficiently small exterior diameter to permit convenient penetration up to the perforated vessel wall. Preferably, the distal end 154 of the cannula 150 exposes both the perforation

160 and a sufficient area of adjacent vessel wall surrounding the perforation 160 so that a sufficient volume of adhesive can be delivered from delivery surface 133 to the vessel wall. For a typical PTCA arterial perforation 160, having a diameter of about 1 mm, an introduction cannula 150 having an inside diameter of about 3 mm and an outside diameter of about 4 mm at its distal end 154 may conveniently be used.

Alternatively, the function of introduction cannula 150 can be readily accomplished by a structure integrally formed or secured to the applicator 108. For example, the delivery surface 133 can be retractably disposed within an outer tubular housing, as will be readily appreciated by one of skill in the art in view of the disclosure herein. As is illustrated in Figure 22, the distal end of the cannula 150 or other introduction structure is preferably inclined in a manner that permits uniform contact to the vessel wall while the longitudinal axis of the applicator 108 is inclined at an angle to the vessel wall, which approximates the typical entry angle for the percutaneous perforation. The reservoir 116 contains any of a variety of tissue adhesives. Suitable adhesives for in vivo use include adhesives within the cyanoacrylate family. In one preferred embodiment, the tissue adhesive comprises one or more of methyl cyanoacrylate, ethyl cyanoacrylate, n-propyl cyanoacrylate, isopropyl cyanoacrylate, n- butyl cyanoacrylate, isobutyl cyanoacrylate, n-amyl cyanoacrylate, isoamyl cyanoacrylate, 3-acetoxypropyl cyanoacrylate, 2-methoxypropyl cyanoacrylate, 3-chloropropyl cyanoacrylate, benzyl cyanoacrylate, phenyl cyanoacrylate, alkenyl cyanoacrylate, butyl- 2-cyanoacrylate, alkoxyalkyl 2-cyanoacrylates or fluorinated 2-cyanoacrylates or combinations, thereof. More preferably, the tissue adhesive comprises ethyl cyanoacrylate or butyl-2-cyanoacrylate. These latter two compounds, available from Loctite Coφoration (Hartford, CT), are normally in a liquid state with water-like viscosity. They harden almost instantaneously upon exposure to atmospheric humidity. Therefore, the reservoir 116 is provided with moisture-tight proximal and distal ends formed by the moveable wall 130 and the proximal end of the applicator 132, to maintain the tissue adhesive in liquid state prior to expression. Preferably, the device is -24- also produced under low humidity conditions and stored in a desiccated package. A removable distal cap (not illustrated) may also be used.

Cyanoacrylate adhesives have been found to harden relatively rapidly when stored below a critical volume of adhesive. Hence, if cyanoacrylate is used, it will be preferable for the reservoir 116 to contain more adhesive than is necessary to seal a typical vascular access site. Preferably, a reservoir volume of at least about 1 to 2 gm is provided to maintain the cyanoacrylate in liquid form in the applicator prior to use. The total volume of adhesive, the desiccation measures and sealing structures on the reservoir 16 can be optimized to produce a desired shelf life by one of skill in the art in view of the disclosure herein.

Various compounds may be added to the cyanoacrylates to alter the properties of the adhesive. For example, polyacrylic acid having a molecular weight of 200,000 to 600,000 may be cross-linked to the cyanoacrylate to form a suitable biocompatible material. These combination compounds allow the absorbability and resoφtion rate to be coordinated with the tissue regeneration rate and feature higher elasticity than cyanoacrylates alone. Other additives, such as stabilizers, viscosity modifiers and medications can also be included as desired.

Figure 20 illustrates another embodiment of the invention for delivering a tissue adhesive to a body surface. The applicator 108a has a generally tubular housing 110a with a proximal control end 112a, a distal delivery end 114a and a reservoir 116a. The reservoir 116a desirably contains a tissue adhesive, and preferably contains any of the variety of tissue adhesives described above. As noted above, the reservoir 116a desirably contains more tissue adhesive than is necessary to seal a typical vascular access site in order to maintain the tissue adhesive in a liquid form. It is also contemplated, as noted -25- above, that the reservoir 116a could contain any of a wide variety of other fluids or fluid¬ like media as well.

The applicator 108a may include grasping structure to ease handling and manipulating the applicator 108a. For this puφose, in the illustrated embodiment, the applicator 108a includes a pair of rings 118a located near the proximal control end 112a of the applicator 108a.

The distal delivery end 114a of the applicator 108a defines an annular valve seat 100 which cooperates with a valve 135a. The valve seat 100 includes a proximal wall 102 which defines an aperture 104 that opens into the reservoir 116a. The aperture 104 has a diameter smaller than that of the reservoir 116a as defined by the tubular housing

110a. The valve seat 100 also includes a sealing surface 106 which preferably tapers, radially outwardly in the distal direction, from the aperture 104 towards the wall of the tubular housing 110a. The surface 106 thus defines generally a frusto-conical shape which mates with a correspondingly shaped surface of the valve 135a, as discussed below. The valve seat 100 also is configured to receive the valve 135a to a sufficient extent that an applicator surface 133a of the valve 135a lies generally flush with or slightly proximally of the distal delivery end 114a of the applicator 108a when the valve 135a is closed (i.e., is seated against the valve seat 100).

As seen in Figure 20, the applicator 108a also includes a control 119a which controls the expression of adhesive from the reservoir 116a. The control 119a is positioned at the proximal end 112a of the applicator 108a. As with the above-described embodiment, any of a variety of control structures can be used, such as, for example, push buttons, levers, plungers, rotatable knobs, and the like. In the illustrated embodiment, the control 119a includes a plunger 130a disposed within the reservoir 116a. A movable button 120a, attached to the plunger 130a by a stem 109, is provided for actuating movement of the plunger 130a within the reservoir 116a.

A distance X between the proximal end 112a of the tubular housing 110a and a distal surface 128a of the button 120a determines the permissible amount of axial travel of the button 120a and plunger 130a, and hence defines the desired volume of adhesive to be expressed upon depression of the button 120a.

Like the above-described applicator 108 of Figure 19, the present applicator 108a desirable delivers a single dose of tissue adhesive. The delivered volume of tissue adhesive desirably is predetermined at the point of manufacture for an intended application. It is contemplated that those skilled in the art will really appreciate that any -26- of a variety of volumes of adhesive may be expressed depending upon the particular surgical application.

The valve 135a, disposed at the distal delivery end 114a of the applicator 108a, generally has a conical configuration. The distal end of the valve 135a includes an atraumatic application surface 133a which transitions into a valve surface 110 of the valve 135a by a rounded shoulder region 112. The valve surface 110 of the valve 135a has a generally frusto-conical shape which is sized and configured to mate with the valve seat 100 at the distal end 114a of the tubular housing 110a so as to seal closed the reservoir 116a. The valve 135a desirably is normally closed. That is, the valve 135a desirably is biased against the valve seat 100. Any of a variety of biasing structures can be used, such as, for example, springs, diaphragms, magnets, and the like. In the illustrated embodiment, a helical spring 116 biases the valve 135a in the proximal direction against the valve seat 100. In one embodiment, a distal end 118 of the spring 116 passes through a transverse aperture of the valve proximal end 114. The spring 116, however, may be attached to the valve 135a by any of a variety of other means known in the art as well.

The tubular housing 110a includes structure which supports a proximal end 120 of the spring 116. In the illustrated embodiment, the tubular housing 110a includes a spider structure 122 which extends within the tubular housing 10a. As best illustrated in Figure 21, the spider structure 122 includes a plurality of legs 124, preferably three legs, which extend from the wall of the housing 110a to the center of the reservoir 116a. The proximal end 120 of the spring 116 is attached to the spider structure 122 in a conventional manner. Alternatively, proximal end 120 of spring 116 is secured directly to the inner surface of the housing 10a.

Activation of the control 119a advances the plunger 130a in the distal direction to compress the adhesive within the reservoir 116a. Once the produced pressure within the reservoir exceeds the biasing force acting on the valve 135a, the valve 135a opens to express adhesive onto the delivery surface 133a. The delivery surface 133a desirably extends near or beyond the distal delivery end 114a of the housing 110a with the valve 135a opened. In this manner, the delivery surface 133a is positioned to contact the vascular wall surrounding the arterial perforation site. Additionally, the generally blunt configuration of the delivery surface 133a with rounded edges 112 reduces the risk of any traumatic injury to the tissue as well as -27- prevents unintentional penetration or advancement into the vessel, as discussed above.

With reference to Figure 20, the applicator 108a may also include a release layer 126 which covers the distal delivery end 114a of the tubular housing 110a and the distal delivery surface 133a of the valve 135a. The release layer 126 desirably adheres to the annular distal end surface 128 of the tubular housing 110a and not to the delivery surface

133a. The release layer preferably includes a tab 130 to facilitate removal of the release layer 126 from the applicator 108a. In one embodiment, a small space is provided between the delivery surface 133a and the release layer 126 to permit coating the delivery surface 133a with adhesive prior to removal of the release layer 126. Preferably, the release layer is a transparent polymeric film such as teflon or polyethylene.

Referring now to Figures 22 and 23, one application of the present invention is illustrated. A cannula 150, of the present invention, has a proximal end 152, a distal end 154 and a minimum inner dimension 156 greater than the maximum dimension of the perforation 160. Further, the cannula 150 has a minimum inner dimension 156, at the proximal end 154 at least, that is greater than the maximum external dimension 138 of the tubular housing 110. This feature allows the applicator to axially movably fit within the cannula 150.

The cannula 150 may have a smaller inner dimension (not shown) at the distal end 154 than at the proximal end 152 to facilitate placement of the catheter through the skin tract. In this latter embodiment, the inner dimension of the distal end is still large enough to allow the delivery surface 133 of the applicator 108 to contact the portion of the vascular wall 170 surrounding the perforation. The cannula 150 alternatively is provided with a larger internal dimension at its distal end to expose a relatively larger area of vascular surface surrounding the perforation site.

After completing the intravascular surgical procedure, the catheter (not shown) is withdrawn. A guidewire, 180 is placed through the second sheath (not shown) and the second sheath is withdrawn. External pressure is applied proximal (upstream) to the perforation as needed to control bleeding. The cannula 150 is inserted over the guidewire 180 until the operator obtains tactile feedback that the cannula 150 has contracted the vascular wall 170. Figure 22 illustrates the placement of the cannula 150 over the guidewire at the point where the cannula contacts the portion of the vascular wall 170 surrounding the perforation.

The guidewire 180 is removed leaving the cannula 150 in position over the -28- perforation 160. Next, the applicator 108 is inserted through the cannula 150 and advanced distally until the delivery surface 133 contacts the vascular wall 170, without penetrating the perforation 60 into the vessel lumen 172. Again the operator will receive tactile feedback indicating that the delivery surface 133 has contacted the vascular wall 70. This step is shown in Figure 23. Finally, an aliquot of tissue adhesive is expressed from the distal end 133 of the applicator 108, sealing the perforation 160. Both cannula 150 and applicator 108 are withdrawn from the body and a suitable dressing applied. Alternately, the cannula 150 can be withdrawn prior to discharging an aliquot of tissue adhesive. Cyanoacrylate tissue adhesives will harden virtually on contact, and create a permanent seal. The operator may prefer to express tissue adhesive while the delivery surface 133 is spaced slightly apart from the tissue to be sealed. This permits the adhesive to flow over the delivery surface 133 and produce a relatively uniform coating for application to the target tissue. Referring to Figure 24, there has been provided in accordance with another aspect of the present invention an adhesive patch 150 used to seal a perforation in a vessel wall, and, more preferably, to seal a vascular perforation created during any of a variety of commonly performed diagnostic or therapeutic procedures.

The patch 150 desirably has a size larger than the perforation of the vessel (e.g., an artery) and may have any of a variety of shapes depending upon the application of the patch 150. In an illustrated embodiment, the patch 150 generally has a circular shape of a sufficient diameter to completely cover the perforation. It is understood, however, that the size of the patch 150 may only cover a portion of the perforation, yet extend across the perforation so as to attach to the surfaces of the vessel on either side of the perforation. The patch 150 preferably has a diameter of at last about 2 mm and preferably at least about 4 mm for application with a PTCA arterial perforation formed in an inelastic artery.

The patch 150 advantageously is porous so tissue adhesive can flow through the pores of the patch 150 to attach the patch 150 to the ablumenal surface adjacent the perforation and to seal the portion of the patch 150 extending across the perforation. In an exemplary embodiment, the pores have a size of about 300 microns, although it is understood that the pores could have a size ranging between lOOμ to 500μ, and more preferably ranging between 200μ to 400μ.

The patch 150 is preferably formed of a mesh, weave or knitted material which -29- is biocompatible, and preferably is biodegradable (i.e., is absorbable within the body). The patch 150 can be formed of any of a wide variety of suitable materials, such as, for example, polytetrafluoroethylene (PTFE), oxidized regenerated cellulose, Gelfilm™ available from the Upjohn Co. and collagen. A suitable material from which to form the patch 150 is a sterile absorbable mesh material (either knitted or woven) available commercially as VICRYL™ from Ethicon (a Johnson and Johnson company) of Somerville, New Jersey.

The patch 150 may be impregnated, coated, or otherwise pretreated at the point of manufacture with a tissue adhesive, such as, for example, any of the tissue adhesive types described above. In this manner, the adhesive coated surface of the patch 150 will adhere to the surface of the vessel surrounding the perforation upon application of the patch 150. Alternatively, the patch 150 and the tissue adhesive can be provided separately, and the patch 150 is saturated or coated with tissue adhesive at the time of application or just before application, as discussed below. The patch 150 can be used to seal a puncture site in a viscera or vascular structure by applying the patch 150 and adhesive to the surface of the walls surrounding the perforation to seal the viscera or vascular structure. In order to apply the patch 150 and adhesive over the puncture site, it is desirable to use an applicator which has an atraumatic delivery surface to deliver the adhesive and the patch 150 to the perforation site.

Thus, in accordance with another aspect of the present invention, there is provided an applicator 152 to both deliver adhesive and apply the patch 150 to the perforation site. Figure 24 illustrates an embodiment of applicator 152 in accordance with a preferred embodiment of the present invention. The applicator depicted by Figure 24 is substantially identical to that illustrated in Figures 20 and 21 and described above.

With reference to Figure 24, the distal delivery end 114b of the tubular housing 110b desirably extends slightly beyond the delivery surface 133b of the valve 135b. The distal delivery end 114b of the tubular housing 110b supports a patch 150. The patch 150 is constructed in accordance with the above description.

The patch 150 also includes on its proximal side around its peripheral edge a light coating of a releasable adhesive, which removably holds the patch 150 on the distal end 114b of the applicator 152 before application. The net release force required to pull the patch 150 from the adhesive should be low enough to permit the patch 150 to adhere -30- to the vascular wall while permitting the applicator 152 to be separated from the patch 150. This can be accomplished in a variety of ways which will be readily apparent to one of skill in the art, including, for example, appropriate adhesive selection, and optimizing the surface area coverage of the adhesive. The housing 110b defines a space between the patch 150 and the delivery surface

133b of the valve 135b. The space 154 has a sufficient size to allow adhesive expressed through the valve 135b to uniformly coat the patch 150 before application at the perforation site. In an exemplary embodiment, the space 154 has an axial depth ranging between 0.02 and 0.5 mm, and more preferably equal to about 0.1 mm. A cap (not shown) can cover the distal end of the applicator 152 to protect the patch 150 and to maintain its sterility before application.

Distal movement of the control button 119b causes the valve 135b to open and express adhesive between the distal delivery surface 133b of the valve 135b and the patch 150. Adhesive permeates through the patch 150 to a point of saturation and expresses onto the distal side (i.e., the ablumenal surface) of the patch 150. As discussed more fully below, the patch 150 is thereafter applied over the perforation site. The tissue adhesive will harden virtually on contact to secure the patch 150 over the perforation and to seal the patch 150. The applicator 152 may thereafter be retracted proximally, breaking the connection between the applicator 152 and the patch 150. Figure 25 illustrates another preferred embodiment of an applicator 160 for applying the sealant patch 150, which includes an atraumatic delivery surface 162, a reservoir 164 and a control 166 for expressing media from the reservoir 164 to the delivery surface 162 and the patch 150.

Like the above-described applicators, the present applicator 160 has a generally tubular housing 168 with a proximal end 170 and a distal end 172. The tubular housing

168 defines the reservoir 164. The reservoir 164 desirably contains a tissue adhesive, and preferably contains any of the variety of tissue adhesives described above. It is also contemplated, as noted above, that the reservoir 164 could contain any of a wide variety of other fluids or fluid-like media as well. Like the above-described applicators, the present applicator 160 desirable delivers a single dose of tissue adhesive. The delivered volume of tissue adhesive desirably is predetermined at the point of manufacture for an intended application. It is contemplated that those skilled in the art will really appreciate that a variety of volumetric sizes of adhesive may be expressed depending upon the particular surgical application. In -31- addition, as noted above, the reservoir 164 desirably contains more tissue adhesive than is necessary to seal a typical vascular access site in order to maintain the tissue adhesive in a liquid form for a suitable product shelf life.

The applicator 160 can also include grasping structures to ease handling and manipulating the applicator 160. For this puφose, in the illustrated embodiment, the applicator 160 includes a pair of rings 174 located near the proximal end 170 of the applicator 160.

The distal end 172 of the applicator 160 defines an annular valve seat 176 which cooperates with a valve 178. As with prior embodiments, the valve seat is conveniently formed by a radially inwardly extending annular ridge. The illustrated valve seat 176 includes a proximal wall 180 which defines an aperture 182 that opens into the reservoir 164. The aperture 182 has a diameter smaller than that of the reservoir 164 as defined by the inner surface of the tubular housing 168.

The valve seat 180 also includes a generally smooth sealing surface 184 which tapers radially outwardly in the distal direction, from the aperture 182 toward the wall of the tubular housing 168. The surface 184 defines generally a frusto-conical shape which mates with a corresponding surface of the valve 178, as discussed below. The valve seat 176 also is configured to receive the valve 178 such that the delivery surface 162 of the valve 178 lies within the tubular housing 168 when the valve 178 is closed (i.e., is seated against the valve seat 176).

The valve 178, disposed at the distal end 172 of the applicator 160, generally has a conical configuration. The distal end of the valve 178 includes the flat or slightly convex delivery surface 162. The valve 178 also includes a generally smooth valve surface 186 which is sized and configured to mate with the corresponding surface of the valve seat 176 so as to seal closed the reservoir. The valve 178 also includes a proximal tip 188 which is provided with a transverse aperture (not shown) for attachment to the spring.

As with the above embodiments, the valve desirably is normally closed, biased against the valve seat 176. Again, any of a variety of biasing structures can be used, such as, for example, springs, diaphragms, magnets and the like. In the illustrated embodiment, a helical tension spring 190 biases the valve 178 in the proximal direction against the valve seat 176.

A distal end 192 of the spring 190 passes through the transverse aperture of the valve proximal end 188 to attach the spring 190 to the valve 178. A spider structure -32-

194, similar to that described above in connection with the embodiment illustrated in Figure 20, supports a proximal end of the spring within the reservoir 164.

Figure 25 illustrates an alternate control 166 in the form of a screw knob to control the expression of adhesive from the distal delivery end 172 of the applicator 160. As noted above, however, the control 166 can have a variety of forms, including, but not limited to, a button, plunger, piston, and the like.

In the illustrated embodiment, the control 166 includes a plunger 194 disposed within the reservoir. The plunger 194 includes a plurality of annular seals 196. The diameter of each seal 196 is slightly larger than the inner diameter of the housing 168 such that the seal 196 compresses against the inner wall of the tubular housing 168 when the plunger 194 is inserted into the housing 168. The annular seals 196 are disposed upon the length of the plunger 194 so as to provide a generally labyrinth construction to substantially prevent expression of the adhesive from the reservoir 164 in the proximal direction. The control 166 also includes a cap 198 which defines a hollow interior cavity

200. The interior cavity 200 carries a series of internal threads 202. The internal threads 202 are sized and configured to engage a series of external threads 204 disposed on the proximal end 170 of the tubular housing 168. The pitch of the threads 202, 204 is chosen to control the volume of adhesive expressed at the distal end 172 of the applicator 160, as discussed below.

A rod 206 connects the screw cap 198 to the plunger 194. In the illustrated embodiment, the rod 206 connects the plunger 194 to the screw cap 198 in a manner which permits the screw cap 198 to rotate with respect to the tubular body 168 without rotating the plunger 194. For this puφose, the screw cap 198 includes a center aperture 208 with a portion of the rod 206 piloted into the aperture 208 to permit rotation of the screw cap 198 about the rod 206. The rod 206 also includes a collar 20 which abuts the proximal surface 212 of the interior cavity 200 to prevent the rod 206 from passing through the aperture 208. It is contemplated, however, that the screw cap 198 and plunger 194 can be directly connected so that the plunger 194 rotates with the screw cap 198.

The distance between the proximal surface 212 of the screw cap interior cavity 200 and the proximal end 170 of the tubular housing 168 limits the amount of adhesive which can be expressed through the valve 178. The screw cap 198 preferably also includes an indexing system, which indicates the extent of travel of the screw cap 178, -33- and thus the volume of adhesive expressed. For instance, the screw cap may be rotated such that at specific intervals of rotation the screw cap snaps or clicks into an index position.

For this puφose, as illustrated in Figure 25b, the cap 198 may carry one or more tangs 214, which extend radially inward from the threaded inner surface of the interior cavity 200. The tubular body 168 may also include at least one longitudinal groove 216, which releasably receives the tang of the cap 198. In the illustrated embodiment, as the cap 198 is rotated, the tang 214 snaps into the corresponding groove 216 on the tubular housing 168 for each quarter turn of rotation (i.e., 90° rotation) of the screw cap 198. It is understood that the tubular housing 168 may include more or less longitudinal grooves spaced about the circumference of the housing 168 to indicate specific incremental degrees of rotation. For instance, the housing 168 may include three grooves equally distanced from one another so as to define 120° rotation of the screw cap 198. By selecting an appropriate thread pitch and indexing the degree of rotation, the control 166 can indicate the volume of adhesive expressed at the distal end 172 of the applicator 160.

The volume of adhesive expressed will be equal to the axial displacement of the plunger 194 multiplied by the cross-sectional area of the reservoir 164. The axial displacement of the plunger 194, in turn, is directly proportional to the pitch of the threads multiplied by the number of revolutions of the screw cap 198. Thus, for example, where the thread pitch is 0.5 mm, the number of revolutions of the screw cap 198 is 2, and the cross-sectional area of the reservoir 164 is 28 mm², the expressed volume of adhesive will be about 28 mm³.

The distal end 172 of the housing 168 defines a cavity 220 in which the patch 150 is received. The patch 150 has a diameter substantially equal to the inside diameter of the cavity 220, and preferably slightly larger than that of the cavity 220 so as to form a slight interference fit with the wall of the cavity 220. The longitudinal length of the cavity 220 is preferably greater than the thickness of the patch 150 such that a small space exists between the patch 150 and the distal end 172 of the tubular housing 168. It is preferred that the patch 150, before application, is positioned within the cavity 220 against the application surface 162 of the valve 178.

At the time of application, the patch 150 desirably is presaturated with tissue adhesive before applying the patch 150 to the perforation site. For this puφose, the cavity 220 has a sufficient size such that a small volume of adhesive can be expressed through the valve 178 and into the distal cavity 220. In an exemplary embodiment, the cavity 220 has a volume of about 1 mm³ with a patch 150 having a thickness of 0.1 mm. The volume of expressed adhesive is sufficient to substantially saturate the sealant patch 150. A release layer 222 prevents the expressed adhesive from escaping from the distal end 172 of the applicator 168 before application. The release layer 222 desirably adheres to the annular distal end surface of the tubular housing 168 and not to the sealant patch 150. The release layer 222 also includes a tab 224 to facilitate removal of the release layer 222 from the applicator 168. Preferably, the release layer comprises teflon or polyethylene. The release layer 222 is later removed before application of the patch

150 to the puncture site.

To express adhesive into the cavity 220 initially, and onto the applicator surface 186 at the time of application, the controller knob 196 is rotated in a direction which causes the plunger 194 to move distally. Distal movement of the plunger 194 forces the adhesive within the reservoir 164 through the valve seat aperture 182, causing the valve

178 to open. Adhesive expresses through the valve 178 and into the cavity 220. Adhesive fills the cavity 220 and saturates the protective patch 150 contained therein.

Figure 26 illustrates an additional embodiment of an applicator 230 for use with a sealant patch 150 pretreated with a tissue adhesive. The applicator 230 includes a tubular body 232, having a proximal end 234 and a distal end 236, and an actuator mechanism 238 formed by a distal plunger 240, a linkage rod 242, and a proximal push button 244. Springs or other biasing mechanisms 246 bias the push button 244 to a position spaced from the proximal end 234 of the housing 232. The applicator 230 also can include gripping structure to ease handling and manipulating the applicator 230. For this puφose, in the illustrated embodiment, the applicator 230 includes a pair of rings 248 located near the proximal end 234 of the applicator 230. It is understood that other types of conventional gripping structures could be used as well. A sealant patch 150, of the type described above, is disposed at the distal end

236 of the applicator 230. The sealant patch 150 has a diameter substantially equal to the diameter of the tubular housing 232, and more preferably slightly larger so as to form a slight interference fit within the interior wall 250 of the applicator housing 232. Alternatively, radially inwardly directed ridges or other surface structures can removably -35- retain the patch 150 as will be appreciated by one of skill in the art.

The sealant patch 150, as noted above, may be precoated with an adhesive which hardens virtually on contact with tissue to permanently bind the sealant patch 150 to the tissue over the puncture site. Any of the variety of tissue adhesive discussed above can be used. It also is contemplated that an adhesive coating may be applied to the ablumenal side of the patch 150 just before application. Preferably, with most cyanoacrylate adhesives, adhesive will be applied to the patch just prior to the implantation of the patch.

The application of the adhesive coating can occur by direct application of the adhesive to the patch 150, by dipping the distal end of the applicator 230 into a reservoir of adhesive, or by contacting the patch 150 with fluid permeable membrane or absoφtive blotter material saturated with adhesive.

Other embodiments will be readily apparent to those with skill in the art. In all cases, bleeding from the perforation site is preferably controlled by applying external pressure proximal (upstream) to the perforation while applying the adhesive and/or closure device (patch). As described above, the natural elasticity of the vessel wall will normally cause the perforation to shrink, assisting in hemostasis.

As noted above, this method can be used to close any exposed surface which can be reached by any of the above-described applicators. For instance, the above-described applicators may be used in open laparotomy for closing the peritoneal surfaces of various hollow viscera, diaphragm and omentum. The patch 88 applied by the applicator also has the potential of sealing the surface of the liver or spleen, or used to seal perforated lungs, hearts, or pleura. It may also be used to seal a perforation of a vascular lumen, such as an artery or vessel. In this latter application, the present invention also includes a preferred method for inhibiting arterial bleeding at the arterial access site after percutaneous transluminal procedures, such as, for example, angioplasty, angiography, coronary angiography, atherectomy, or similar procedures.

Although the present invention has been described in terms of certain preferred embodiments, other embodiments can be readily devised by one with skill in the art in view of the foregoing, which will also use the basic concepts of the present invention.

Accordingly, the scope of the present invention is to be defined by reference to the following claims.

Claims

-36-WHAT IS CLAIMED IS:

1. An adhesive patch applicator kit, comprising: a housing having a rotatable cap, and a chamber therein, said cap rotatable about a longitudinal axis; an applicator within the chamber and removably connected to one of the housing or the rotatable cap; a reservoir in the chamber, said reservoir connected to the other of the housing and the cap; a tip on the reservoir for expressing adhesive; and an adhesive patch removably attached to the applicator in between the applicator and the tip; wherein rotation of the cap relative to the housing about the longitudinal axis expresses adhesive from the reservoir through the tip and on to the patch.

2. An adhesive patch applicator kit as in Claim 1, wherein the patch is positioned substantially symmetrically about the longitudinal axis and the tip is offset from the longitudinal axis so that rotation of the cap expresses an annular bead of adhesive on the patch.

3. An adhesive patch applicator kit as in Claim 1, wherein the adhesive patch is disposed in a plane which is inclined with respect to the longitudinal axis.

4. An adhesive patch applicator kit as in Claim 1, further comprising a generally tubular housing having a proximal end and a distal end and defining said reservoir therein, a movable wall on the housing for controllably reducing the volume of the reservoir to express adhesive therefrom, and a valve disposed in the fluid flow path between the reservoir and the tip.

5. An adhesive patch applicator kit as in Claim 4, further comprising a spring in the tubular housing for biasing the valve in the closed position.

6. An adhesive patch applicator kit as in Claim 4, wherein said movable wall comprises a slidable plunger.

7. An adhesive patch applicator kit as in Claim 4, further comprising a threaded drive mechanism for converting rotational movement of the cap relative to the housing into axial motion for advancing the movable wall into the reservoir to express adhesive.

8. An adhesive patch applicator kit as in Claim 1, wherein said applicator comprises a proximal handle portion and a distal extender portion, wherein the adhesive -37- patch is releasably secured to the distal end of the extender portion.

9. An adhesive patch applicator kit as in claim 8, wherein the distal end of the extender portion comprises an adhesive patch contact surface, and said surface lies generally in a plane which is inclined from a peφendicular to the longitudinal axis.

10. A fluid applicator for applying an annular bead of fluid to a surface, comprising: a housing having a first portion which is rotatable with respect to a second portion; a reservoir in the housing for containing a fluid, said reservoir having an applicator tip thereon for expressing fluid from the reservoir and onto said surface; and a drive mechanism for expressing fluid from the reservoir in response to rotation of the first portion of the housing with respect to the second portion of the housing; wherein the first portion of the housing is rotatable about a longitudinal axis and the reservoir is connected to the first portion of the housing such that the tip is radially offset from the longitudinal axis.

11. An applicator for percutaneously delivering a sealant patch to a surface of a perforated vascular wall, comprising: a tubular housing having a proximal end and a distal delivery end, said housing defining a reservoir for containing a volume of tissue adhesive and a recess for receiving a patch, said reservoir being positioned proximal of said recess; a valve positioned in said housing between said reservoir and said recess to selectively place said reservoir in fluidic communication with said recess; and a control at the proximal end of the housing, for controlling the expression of adhesive from said reservoir and through said valve.

12. The applicator of Claim 11, wherein said control comprises a moveable plunger positioned at a proximal end of said reservoir.

13. The applicator of Claim 11, further comprising a biasing mechanism which biases said valve to be normally closed.

14. An applicator for percutaneously delivering a tissue adhesive to the surface of a perforated vascular wall, comprising: a tubular housing having a proximal control end and a distal delivery -38- end; a reservoir in the housing for containing a volume of tissue adhesive; an applicator on the distal delivery end of the housing; and a control for expressing adhesive from the reservoir to the applicator; wherein said applicator comprises at lease one atraumatic delivery surface in fluid communication with the reservoir for applying tissue adhesive to the surface of a perforated vascular wall.

15. An applicator as in Claim 14, further comprising a piston in the reservoir for expressing tissue adhesive from the reservoir to the delivery surface.

16. An applicator as in Claim 15, further comprising a stop for limiting the travel of the piston, to set a predetermined maximum delivered volume of tissue adhesive.

17. An applicator as in Claim 14, further comprising a valve disposed in the flow patch between the reservoir and the delivery surface, for sealingly retaining the tissue adhesive within the reservoir.

18. An applicator as in Claim 17, further comprising an actuator for simultaneously opening the valve and expressing tissue adhesive from the reservoir to the delivery surface.