WO2007121747A1

WO2007121747A1 - A vascular access closure device

Info

Publication number: WO2007121747A1
Application number: PCT/DK2007/000187
Authority: WO
Inventors: Erik Christian Andersen
Original assignee: Cardio Capacity A/S
Priority date: 2006-04-20
Filing date: 2007-04-20
Publication date: 2007-11-01

Abstract

The present invention relates to a vascular access closure device for closing a puncture in a blood vessel formed during a diagnostic or therapeutic procedure. Furthermore, the present invention relates to a deployment instrument and a method of closing a vascular opening. A vascular closure device for closing a vascular opening is provided, having a proximal end and a distal end and which is made of a flexible material allowing the closure device to assume a plurality of shapes including a substantially cylindrical shape and a shape with a distal bulge near the distal end of the closure device.

Description

AVASCULARACCESS CLOSURE DEVICE

The present invention relates to a vascular access closure device for closing a puncture in a blood vessel formed during a diagnostic or therapeutic procedure.

BACKGROUND OF THE INVENTION Catheterization and interventional procedures, such as angioplasty or stenting, generally are performed by inserting a hollow needle through a patient's skin and muscle tissue into the vascular system. A guide wire may then be passed through the needle lumen into the patient's blood vessel accessed by the needle. The needle may be removed, and an introducer sheath may be advanced over the guide wire into the vessel, e.g. in conjunction with or subsequent to a dilator. A catheter or other device may then be advanced through a lumen of the introducer sheath and over the guide wire into a position for performing a medical procedure. Thus, the introducer sheath may facilitate introduction of various devices into the vessel, while minimizing trauma to the vessel wall and/or minimizing blood loss during a procedure. Upon completion of the procedure, the devices and introducer sheath may be removed, leaving a puncture site in the vessel wall. External pressure may be applied to compress the puncture site until clotting and wound sealing occur. This procedure, however, may be time consuming and expensive, requiring as much as an hour of a physician's or nurse's time. It is also uncomfortable for the patient, and requires that the patient remains immobilized in the operating room, catheter lab, or holding area. In addition, a risk of haematoma exists from bleeding before haemostasis occurs.

Various apparatus have been suggested for percutaneously sealing a vascular puncture by occluding the puncture site.

For example, US 2001/0003158 discloses a system, a closure, and a method of use for sealing a percutaneous puncture in a blood vessel. The puncture includes an opening in the vessel wall and a tract leading to the opening. The system includes an introducer sheath and associated positioning device, a haemostatic puncture closure, and a deployment instrument. The positioning device enables the introducer sheath to be positioned at a desired position within the vessel. The deployment instrument includes a tubular carrier storing the closure. The closure comprises a rigid, e.g., radio-opaque, anchor, a compressed collagen plug, and a thin filament connecting the two in a pulley- like arrangement. The instrument and introducer are used to introduce the closure into the puncture, with the anchor located within the artery and with the collagen plug within the puncture tract. A locking member is provided to hold the closure in place at its

CONFIRMATION COPV / operative position, whereupon haemostasis occurs rapidly, thereby sealing the puncture.

The disclosed closure system appears quite complex in construction and an improved sealing of various types of openings, e.g., small incisions or punctures in vessel walls, such as arteries and/or veins, is still desirable.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide an instrument, a closure device, and a method of use for quickly, easily, and effectively sealing a puncture or incision in vascular tissue of the body of a living being. It is another object of the present invention to provide a closure device for sealing an opening in the vascular tissue in the body of a living being, which is simple in construction, low in cost, and which will leave a biodegradable plug in place, sealing the puncture site.

It is a further object of the present invention to provide a deployment instrument and a method for easy positioning and securing the closure device.

According to a first aspect of the present invention, the above-mentioned and other objects are fulfilled by provision of a vascular closure device for closing a vascular opening, having a proximal end and a distal end and which is made of a flexible material allowing the closure device to assume a plurality of shapes including a substantially cylindrical shape and a shape with a distal bulge near the distal end of the closure device.

One or more of the plurality of shapes may be predetermined.

According to a second aspect of the invention, the above-mentioned and other objects are fulfilled by provision of a deployment instrument for closing a vascular opening with a vascular closure device as described above, comprising an inner tube having a distal end and a proximal end and being enclosed by the vascular closure device at its distal end and by an outer tube extending from a distal end at the proximal end of the closure device to a proximal end, and wherein the closure device has a first filament that is attached to the closure device at its distal end and extending inside the closure device. Preferably, the first filament extends between the inner tube and the outer tube through an opening at the proximal end of the outer tube for expansion of the periphery of the distal bulge. In another embodiment, the first filament extends inside the inner tube from its distal end towards the proximal end. In a first embodiment of the present invention, the first filament may extend on the outside of the outer tube.

The deployment instrument may comprise one or more locking members, preferably of a biodegradable material. The locking member may be a one way locking member. The locking member may be adapted for securing one or more filaments, e.g. a first filament and/or a second filament.

The filaments may be secured e.g. by tying one or more knots, by twisting the filaments and/or by employment of a ratchet locking member. Surgical glue may be employed to secure the filaments. Further, the vascular closure device may have a proximal bulge and an intermediate part between the distal bulge and the proximal bulge. Further, the closure device may have a second filament. Preferably, the second filament is attached to the closure device at the intermediate part. In a preferred embodiment the second filament extends outside the outer tube to the proximal end of the outer tube for expansion of the periphery of the proximal bulge.

According to a third aspect of the invention, the above-mentioned and other objects are fulfilled by provision of a method of closing a vascular opening in a vessel wall with a deployment instrument as described above, comprising the steps of

- inserting the distal end of the closure device into an introducer sheath inserted in the opening,

- pushing the closure device through the introducer sheath until the part of the closure device to form the distal bulge has passed the opening,

- moving the inner tube to allow expansion of the distal bulge,

- pulling the first filament to expand the periphery of the distal bulge thereby closing the opening from inside of the vessel wall, and

- securing the first filament.

The introducer sheath may be removed prior to securing the first filament.

For a closure device with one or more second filaments, the method may further comprise the step of securing one or more of the second filament(s). For a vascular closure device with a proximal bulge, the method may further comprise one or more of the following steps of - pulling the introducer sheath such that the part to form the proximal bulge is able to expand peripherally,

- retaining the second filament while moving the outer tube towards the opening to expand the periphery of the proximal bulge thereby locking the closure device to the opening, and

- removing the outer tube.

A step of securing second filaments may be performed prior to or after removing the outer tube.

Expansion of the distal bulge and/or the proximal bulge may be assisted by injecting a fluid, such as contrast medium, through the inner tube.

Preferably, the part to form the proximal bulge remains in the introducer sheath when the closure device is pushed through the introducer sheath until the part of the closure device to form the distal bulge has passed the opening.

The filaments may be secured in any suitable way, e.g. by tying the filaments, fixing the filaments extracorporal^, by gluing or using one or more locking members.

Thus, according to the present invention, a deployment instrument and a closure device is provided, which is simple in construction and can be readily inserted into a vascular opening, such as the vascular puncture site, to position the closure device therein for haemostatically sealing the vascular opening. It is an important advantage of the present invention that the inventive closure device can be inserted in the vascular opening through the vascular introducer sheath that has already been used for the procedure, e.g. catheterization, diagnostic procedures and/or interventional procedures, such as angioplasty or stenting.

It is another advantage of the present invention that upon closing of the vascular opening, the distal bulge seals the opening substantially along the entire periphery of the opening.

Further, it is an important advantage of the present invention that the closure device seals the vessel wall from the inside of the vessel.

The distal bulge may be positioned near or at the distal end of the closure device, e.g. less than 8 mm from the distal end of the closure device, preferably less than 3 mm , such as less than about 1.5 mm, preferably about 1 mm from the distal end of the closure device. Preferably, the closure device is hollow with a wall enclosing a cavity.

The distal end of the closure device may be an open end or a closed end. An open ended closure device enables venting and/or injection of fluid, e.g. contrast medium, before closure. During deployment, the distal end of the closure device is drawn towards the distal bulge, preferably into the cavity of the closure device, and provides further structural integrity to the distal bulge. Hereby, a substantially flat circumferential compliable patch is provided on the inner wall of the vessel.

Advantageously, contrast medium may be injected into the cavity of the closure device, e.g. after closure of the distal end of the closure device, whereby the position of the closure device can be accurately determined.

Further, for a closure device with a proximal bulge, the distal bulge and the proximal bulge are positioned inside and outside the vessel wall, respectively. Thereby, the closure device is locked in its closing position within the vascular opening located between the bulges.

Preferably, the distal bulge has a substantially circular periphery. However, other shapes, such as rectangular, oval, etc., enabling the distal bulge to substantially cover the opening may be employed.

Preferably, the proximal bulge has a substantially circular periphery. However, other shapes, such as rectangular, oval, etc., enabling the proximal bulge to lock the closure device in the opening may be employed.

Preferably, the distal bulge of the closure device forms a sealing cover complying with the inside of the vessel wall when deployed. It is an important advantage of the present invention that the bulges of the closure device due to their flexibility are able to adapt to irregular surfaces of a vessel wall.

Advantageously, the closure device is made of biodegradable material.

Advantageously, the closure device is made of electro-spun fibres, such as microfibres, nanofibres, etc. In a preferred embodiment, the electro-spun fibres are substantially orientated. The fibres may be orientated in one or more directions, e.g. in one or more layers. Preferably, the fibres are orientated in a direction substantially perpendicular to the longitudinal axis of the closure device.

The fibre material allows the closure device to change into a plurality of shapes and at the same time obtaining a suitable structural integrity of the device. Preferably, the fibres are incompressible fibres and the plurality of shapes may be obtained by moving the fibres in relation to each other.

Preferably, the closure device is made of a biodegradable material, such as biodegradable polymers, such as Resomer® polymers, such as poly lactic acid (PLA), poly (lactide co glycolide) acid (PLGA), Tempamine®, such as poly(ester amide)

(PEA), and the like, Isomer, e.g. Synplug® polymers 70PEGT30PBT, Tyrosine-derived polymers, such as Tyrosine-derived polyarylates or polycarbonate polymers and the like, etc., or mixtures thereof.

Further, a coagulation enhancing substance or a combination of such substances may be added to the material, such as oxidized regenerated cellulose, collagen, thrombin, fibrinogen, and the like.

In an embodiment of the present invention, at least a part of the closure device is loaded with fibrinogen and/or thrombin to enhance formation of fibrin fibres when wetted by body fluid, thereby enabling fast haemostasis and fixation of the closure device.

Also a healing enhancing substance or a combination of such substances may advantageously be added to the material. Examples, which are not limiting, of such healing enhancing substances are Nitride Oxide (NO), anti-proliferative drugs, such as taclolimus (FK506), Sirolimus or Rapamycin, and analogs thereof, such as SDZ-RAD, CCI-779, 7-epi-rapamycin, 7-thiomethyl-rapamycin, 7-epi-trimethoxyphenyl-rapamycin, 7-epi-thiomethyl-rapamycin, 7-demethoxy-rapamycin, 32-demethoxy-rapamycin, 2- desmethyl-rapamycin, proline-rapamycin, and the like.

Antibiotics, antibacterial and/or antiviral substances may be added to the closure device to kill or reduce undesirable micro organisms in the patient, and this may also reduce or avoid inflammation.

The content of additives may vary throughout the closure device.

The vascular closure device may further comprise a first filament, preferably a set of first filaments comprising two, three, four or more filaments. The first filament(s) may be attached to the closure device, e.g. by stitching, gluing, etc. In an embodiment of the present invention, the first filament(s) extend from the distal end towards the proximal end for expansion of the periphery of the distal bulge. A part of one or more of the first filament(s) may extend on the outside of the closure device.

Preferably, the vascular closure device further comprises a second filament, preferably a set of second filaments comprising two, three, four or more filaments. The second filament(s) may be attached to the closure device, e.g. by stitching, gluing, etc. Preferably, the second filament(s) are attached to the closure device between the distal bulge and the proximal end of the closure device. In an embodiment comprising a proximal bulge, one or more of the second filament(s) are advantageously attached to the intermediate part of the closure device between the distal bulge and the proximal bulge. In an embodiment of the present invention, one or more of the second filament(s) extend from the side of the proximal bulge closest to the distal end of the device and towards the proximal end for expansion of the periphery of the proximal bulge. Preferably, the filaments are sutures, e.g. biodegradable sutures.

Preferably, the pore diameters of the fibre matrix of the electro-spun fibres are less than 10 μm, more preferred less than 7 μm, to seal against platelets when the fibre matrix has been sucked and the bulges compressed.

However, if a coagulation enhancing substance has been added to the matrix, pore diameters of less than 50 μm are sufficient to seal the vascular opening.

The deployment instrument may further comprise a loading member. The loading member may be a slit tubular member, which can support and protect the closure device during insertion into the introducer sheath, e.g. through a haemostatic valve.

The inner tube and/or the outer tube of the deployment instrument may have one or more longitudinal recesses on the inner and/or the outer surface to accommodate one or more filaments.

BRIEF DESCRIPTION OF DRAWINGS

The above and other features and advantages of the present invention will become more apparent to those of ordinary skill in the art by describing in detail exemplary embodiments thereof with reference to the attached drawings in which:

Fig. 1 is a side view of a deployment instrument with a vascular closure device according to the invention,

Fig. 2 shows the vascular closure device of Fig. 1 in more detail,

Fig. 2A and 2B and 2C show an embodiment of the closure device according to the invention,

Fig. 3 shows the vascular closure device of Fig. 1 in various cross-sections and in perspective, Fig. 4 shows another vascular closure device according to the invention in various cross-sections and in perspective,

Fig. 5 is a side view of a deployment instrument with a vascular closure device in its substantially cylindrical shape, Fig. 6 shows the vascular closure device of Fig. 5 in more detail,

Fig. 7 is a longitudinal cross-section of an outer tube of a deployment instrument, Fig. 8 is a longitudinal cross-section of an introducer sheath, Fig. 9 is a longitudinal cross-section of an inner tube of a deployment instrument, Fig. 10 is a longitudinal cross-section of an artery, Fig. 11 illustrates a preferred embodiment of a method according to the present invention,

Fig. 12 illustrates a loading member of a deployment instrument according to the invention,

Fig. 13 illustrates different embodiments of a locking member of the deployment instrument according to the invention, and

Fig. 14 is a schematical flow chart of another preferred embodiment of the method according to the invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The present invention will now be described more fully hereinafter with reference to the accompanying drawings, in which exemplary embodiments of the invention are shown. The invention may, however, be embodied in different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Like reference numerals refer to like elements throughout.

Fig. 1 shows a deployment instrument 10 for closing a vascular opening 2 in an artery 4 with a vascular closure device 12. An introducer sheath 6 is inserted in the vascular opening 2 for use during the procedure, e.g. catheterization or stenting.

The introducer sheath 6 is illustrated in more details in Fig. 8, and a human artery is illustrated in more detail in Fig. 10. As illustrated in Fig. 1 , the deployment instrument 10 comprises an inner tube 14 having a distal end 16 and a proximal end 18. The instrument 10 is enclosed by the vascular closure device 12 at its distal end 16 and by an outer tube 20 extending from a distal end 22 at a proximal end 24 of the closure device 12 to a proximal end 26 of the outer tube.

The inner tube 14 is illustrated in more details in Fig. 9, and the outer tube 20 is illustrated in more detail in Fig. 7.

The vascular closure device 12 is illustrated in more detail in Figs. 2 and 3. The illustrated vascular closure device 12 has a proximal end 24 and a distal end 30 and the closure device 12 is made of a flexible material allowing the closure device to assume a plurality of shapes including a substantially cylindrical shape and a shape with a distal bulge 32 at the distal end 30, a proximal bulge 34, and an intermediate part 25 between the distal bulge 32 and the proximal bulge 34 as shown in Fig. 2. Fig. 3 C shows the vascular closure device 12 in its substantially cylindrical shape ready for insertion into the introducer sheath 6. Preferably, the outer diameter of the distal bulge 32 is about three times the internal diameter of the introducer sheath, e.g. in the range from about 2 mm to about 18 mm, preferably about 6 mm for a 6 French sheath. The outer diameter of the proximal bulge 34 may be about two times the internal diameter of the introducer sheath. However in the illustrated embodiment, the outer diameter of the proximal bulge 34 is about 6 mm. The distance between the bulges 32, 34, i.e. the length of the intermediate part 25 is adapted to the thickness of the vessel wall at the puncture site, e.g. about 2 mm.

Further, first filaments 36, 38 in Fig. 2 are attached to the closure device 12 by stitching at the distal end 30. The first filaments 36, 38 extend inside the closure device 12 on the outside of the inner tube 14. In another embodiment at least one of the first filaments 36, 38 may partly extend on the outside of the closure device 12. In the illustrated embodiment, the first filaments 36, 38 extend between the inner tube 14 and the outer tube 20 and out through an opening at the proximal end 26 of the outer tube 20. However, one or more of the first filaments 36, 38 may in another embodiment extend on the outside of the outer tube 14.

Pulling the first filaments 36, 38 cause an expansion of the periphery of the distal bulge 32.

Optionally, the deployment instrument 10 may comprise one or more locking members 45 as illustrated in Fig. 2. Different embodiments of the one or more locking members are illustrated in Fig. 13. The closure device 12 further has second filaments 40 and 42 (not visible) that are attached to the closure device 12 by stitching. In the illustrated embodiment, the second filaments 40, 42 are attached at the distal end 30. However, attachment of the second filaments 40, 42 at the intermediate part 25 or at the distal side 27 of the proximal bulge 34 may be advantageous for expansion of the periphery of the proximal bulge 34. The second filaments 40, 42 extend outside the outer tube 20 towards the proximal end of the outer tube 20. Figs. 3A and 3D shows the vascular closure device 12 in its expanded shape with two bulges 32, 34, i.e. a proximal bulge 34 and a distal bulge 32, the distal bulge 32 being adapted for closing and sealing the vascular opening 2 substantially around the entire periphery of the opening 2 and the proximal bulge 34 being adapted for locking the closure device 12 in its closing and sealing position.

Thus, an embodiment of a deployment instrument 10 and a closure device 12 is illustrated, which is simple in construction and can be readily inserted into a vascular opening 2 to position the closure device 12 therein for haemostatic sealing the vascular opening 2.

It is an important advantage of the present invention that the inventive closure device 12 can be inserted in the vascular opening 2 through the vascular introducer sheath 6 that has already been used for the procedure, e.g. catheterization or stenting. The illustrated closure device is hollow with a wall 43 enclosing a cavity 44 within the distal bulge 32. Advantageously, contrast media may be injected in the cavity 44 of the closure device 12, whereby the position of the closure device 12 can be accurately determined.

Preferably, the distal end of the closure device is drawn into the cavity 44 during deployment causing an expansion of the periphery of the distal bulge and resulting in a substantially flat cover sealing the puncture of the vessel.

Advantageously, the vascular closure device 12 is made of biodegradable material.

Advantageously, the vascular closure device 12 is made of electro-spun fibres, such as microfibres, nanofibres, etc, preferably of a biodegradable material, such as biodegradable polymers, such as Resomer®, such as poly lactic acid (PLA), poly

(lactide co glycolide) acid (PLGA), Tempamine®, such as poly(ester amide) (PEA), and the like, Isomer, e.g. Synplug® polymers 70PEGT30PBT, Tyrosine-derived polymers, such as Tyrosine-derived polycarbonate or polyarylates,, and the like, etc., or mixtures thereof. Further, a coagulation enhancing substance or a combination of such substances may be added to the material, such as oxidized regenerated cellulose, collagen, thrombin, fibrinogen, and the like.

At least a part of the closure device 12 is loaded with fibrinogen and/or thrombin to enhance formation of fibrin fibres, thereby enabling fast haemostasis and fixation of the closure device.

Also a healing enhancing substance or a combination of such substances may advantageously be added to the material. Examples, which are not limiting, of such healing enhancing substances are Nitride Oxide (NO), antiproliferative drugs, such as taclolimus (FK506), Sirolimus or Rapamycin, and analogs thereof, such as SDZ-RAD, CCI-779, 7-epi-rapamycin, 7-thiomethyl-rapamycin, 7-epi-trimethoxyphenyl-rapamycin, 7-epi-thiomethyl-rapamycin, 7-demethoxy-rapamycin, 32-demethoxy-rapamycin, 2- desmethyl-rapamycin, proline-rapamycin, and the like.

In an embodiment of the invention, contrast medium, such as iodid ions, is added to the material of the closure device.

The pore diameters of the fibre matrix of the electro-spun fibres are preferably less than 10 μm, more preferred less than 7 μm. This allows platelets to soak into the matrix. In a preferred embodiment, the matrix is subsequently compressed during deployment of the closure device. This reduces the matrix pore size, thereby sealing the puncture site.

Figs. 2A, 2B and 2C shows an embodiment of a closure device 112 according to the present invention. Fig. 2B shows the closure device upon closure of the vascular opening 2, which is performed by pulling the first filaments 36, 38 that are stitched through the sidewall 43 of the closure device112. The open distal end 30 of the closure device 112 is drawn into the cavity 44 when the first filaments are pulled and thereby the distal end 30 assists in providing further structural integrity to the distal bulge 32. Fig. 2C shows the closure device 112 with compressed proximal bulge.

Fig. 4 shows another embodiment of a vascular closure device 212 according to the present invention that has a single bulge 32 corresponding to the distal bulge of the closure device illustrated in Figs. 2 and 3. The vascular closure device 212 shown in Fig. 4 may be deployed with the deployment instrument 10 shown in Fig. 1.

A method of closing a vascular opening with a deployment instrument as described above is illustrated in Fig. 11, wherein puncturing of an artery 4 and insertion of an introducer sheath 6 in an opening 2 is illustrated in A and B.

C illustrates positioning of the deployment instrument 10 with the vascular closure device 12 at the opening of the introducer sheath 6 ready for insertion of the closure device 12 into the introducer sheath whereby the bulges 32, 34 collapse and the closure device 12 is forced into its substantially cylindrical shape. A loading member (not shown) may be employed to support and protect the closure device 12 during insertion into the introducer sheath. The closure device 12 is pushed manually through the introducer sheath 6 holding the inner tube 14 by the handle 28, and further through the opening 2 in the artery 4 until the part of the closure device 12 to be expanded into the distal bulge 32 enters the interior of the artery 4 while the part of the closure device 12 to be expanded into the proximal bulge 34 remains outside the artery 4, i.e. in the introducer sheath, as illustrated at D and E.

At E, the first filaments 36, 38 have been pulled to expand the periphery of the distal bulge 32 thereby closing the opening 2 from the inside of the artery 4. The inner tube may be moved by pulling the first filaments 36, 38 or by pulling the inner tube at the handle 28.

At F, the inner tube 14 has been removed, and the first filaments 36, 38 have been secured by tying. The introducer sheath 6 has been pulled such that the part to form the proximal bulge 34 is able to expand peripherally. Further, the second filaments 40, 42 have been retained while the outer tube 20 has been moved towards the opening 2 to expand the periphery of the part to form the proximal bulge 34 thereby locking the closure device 12 in its sealing position in the opening 2 of the artery 4. Subsequently, the second filaments have been secured, e.g. by tying and/or by employment of a locking member.

As already mentioned, the vascular closure device 12 may be made of electro-spun fibres, such as microfibres, nanofibres, etc., preferably by spinning a polymer material, such as biodegradable polymers, such as Resomer®, such as poly lactic acid (PLA), poly (lactide co glycolide) acid (PLGA), Tempamine®, such as poly(ester amide) (PEA), and the like, Isomer, e.g. Synplug® polymers 70PEGT30PBT, Tyrosine-derived polymers, such as Tyrosine-derived polycarbonate or polyarylate, and the like, etc., or mixtures thereof Processes for electro-spinning polymer fibres are well-known in the art.

In the process of electro-spinning, a polymer fibre is formed from an electrically chargeable solution of the thread-forming polymer in an electrostatic field created between an extrusion die and a collection means. The die orifice is oriented towards the collection means. Between the die and the collection means, the fibres are formed in an electrical field and deposited on the collection means. This facilitates a linear orientation in the solidifying polymer filament.

A solid polymer is converted to a fluid state so that it will pass under pressure through a fine extrusion die orifice. A continuous liquid phase filament is extruded and drawn though a zone in which solvent evaporation and cooling takes place, causing the filament to solidify and form a continuous, solid filament. The solid filament is collected by a rotating pre-form having the intended shape of the vascular closure device, preferably the shape with two bulges 32, 34, which will be the shape that the vascular closure device assumes when no external forces are applied to it. The extrusion die and the filament collection means are each electrically conductive, and the electric voltage difference between them is in the range of 5,000 to 30,000 volts, often about 20,000 volts. Preferably, the electro-spinning apparatus has a positively biased die and a negatively biased collection means. Alternatively, the electro-spinning apparatus has a negatively biased die and a positively biased collection means.

Fig. 12 schematically illustrates an embodiment of a loading member 50 of a deployment instrument according to the present invention. Fig. 12A is a perspective view of a loading member 50, Fig. 12B is a perspective view of a loading member accommodating a closure device 12, and Fig. 12C shows a cross section of the loading member 50. The loading member 50 is made from a tubular member having a longitudinal slit 52. Preferably, the loading member is made of a flexible material to enable circumferential compression of the closure device 12 and removal of the loading member 50 from the deployment instrument. The loading member facilitates smooth insertion of the closure device 12 into the introducer sheath 6, e.g. through a haemostatic valve, without damaging the closure device 12. Thus, the loading member 50 forces the vascular closure device 12 into its substantially cylindrical position making the vascular closure device 12 suitable for insertion into the insertion sheath 6.

Fig. 13 schematically illustrates embodiments of a locking member 45 of a deployment instrument according to the invention. The locking member may comprise one or more openings for accommodation of one or more filaments. Preferably, the locking member 45 is adapted to lock the closure device in a final position in the opening 2 of the vessel wall. The locking device may have any suitable shape such as circular, oval, rectangular, or other suitable shapes having a largest measure larger than the diameter of the opening 2 or a largest measure larger than the inner diameter of the closure device. The locking device may be a circular plate with a diameter around 2 mm or more and comprising one or more openings. The locking member may be a one way locking member, i.e. a filament can only pass through an opening in one direction.

Fig. 14 illustrates a schematic flow chart of a preferred embodiment of the method of closing a vascular opening in a vessel wall with a deployment instrument as described above. Step A comprises the steps of inserting the distal end of the closure device into an introducer sheath inserted in the opening and pushing the closure device through the introducer sheath until the part of the closure device to form the distal bulge has passed the opening. Step B includes the steps of moving the inner tube to allow expansion of the distal bulge and pulling the first filament to expand the periphery of the distal bulge thereby closing the opening from inside of the vessel wall. Step B may comprise the step of injecting a fluid, such as contrast medium, through the inner tube into a cavity of the closure device. Step C, which is optional as indicated by the dashed arrow, includes the step of removing the introducer sheath from the opening, and step D comprises the step of securing the first filament. Step E comprises the steps of securing one or more of the second filament(s) of a closure device. Step F is optional and includes the steps of pulling the introducer sheath such that the part of the closure device to form the proximal bulge is able to expand peripherally, retaining the second filament while moving the outer tube towards the opening to expand the periphery of the proximal bulge thereby locking the closure device to the opening, and removing the outer tube.

Claims

1. A vascular closure device for closing a vascular opening, having a proximal end and a distal end and which is made of a flexible material allowing the closure device to assume a plurality of shapes including a substantially cylindrical shape and a shape with a distal bulge near the distal end of the closure device.

2. A vascular closure device according to claim 1 , wherein the distal bulge has a substantially circular periphery.

3. A vascular closure device according to any of claims 1 or 2, wherein the distal bulge is adapted to substantially cover the vascular opening.

4. A vascular closure device according to any of the preceding claims, wherein the closure device can assume a shape with a distal bulge at the distal end and a proximal bulge spaced a distance from the distal bulge towards the proximal end.

5. A vascular closure device according to claim 4, wherein the proximal bulge has a substantially circular periphery.

6. A vascular closure device according to any of claims 4 or 5, wherein the proximal bulge is adapted to lock the vascular closure device in its intended position.

7. A vascular closure device according to any of claims 4-6, wherein the proximal bulge is adapted to substantially cover the vascular opening.

8. A vascular closure device according to any of the preceding claims, wherein the closure device is hollow with a wall enclosing a cavity.

9. A vascular closure device according to claim 8, wherein the cavity is adapted to accommodate contrast medium for allowing detection of the position of the closure device.

10. A vascular closure device according to any of the preceding claims, wherein the material comprises electro-spun fibres, such as microfibres, nanofibres, etc.

11. A vascular closure device according to any of the preceding claims, wherein the material is biodegradable.

12. A vascular closure device according to any of the preceding claims, wherein the material comprises biodegradable polymers, such as Resomer®, such as poly lactic acid (PLA), poly lactide co glycolide acid (PLGA), Tempamine®, such as

Poly(EsterAmine) (PEA), etc, Isomer, e.g. Synplug® polymers 70PEGT30PBT, etc, Tyrosine-derives polymers, such as Tyrosine-derived polycarbonate or polyarylates, and the like, etc. or mixtures thereof.

13. A vascular closure device according to any of the preceding claims, wherein the material comprises a coagulation enhancing substance, such as collagen, thrombin, fibrin, etc.

14. A vascular closure device according to any of the preceding claims, wherein the material comprises a healing enhancing substance, such as Nitride Oxide (NO), Sirolimus, and the like.

15. A vascular closure device according to any of the preceding claims, wherein the material comprises an inflammation inhibitor, such as antibiotics, antiviral substances, and the like.

16. A vascular closure device according to any of the preceding claims, further comprising a first filament attached to the closure device.

17. A vascular closure device according to claim 16, wherein the first filament comprises a set of first filaments comprising two, three, four, or more first filaments attached to the closure device.

18. A vascular closure device according to any of the claims16-17, wherein the first filament(s) are attached to the distal end of the closure device and extending at least partly inside the closure device.

19. A vascular closure device according to any of the preceding claims, further comprising a second filament attached to the closure device.

20. A vascular closure device according to claim 19, wherein the second filament comprises a set of second filaments comprising two, three, four, or more second filaments attached to the closure device.

21. A vascular closure device according to any of the claims 19-20, wherein the second filament(s) are attached to the closure device between the distal bulge and the proximal end of the closure device.

22. A vascular closure device according to any of the claims19-21 , wherein a second filament extends at least partly outside the closure device.

23. A vascular closure device according to any of the claimsi 9-22, wherein the second filament(s) extends towards the proximal end of the closure device.

24. A deployment instrument for closing a vascular opening with a vascular closure device according to any of the preceding claims, comprising an inner tube having a distal end and a proximal end and being enclosed by a vascular closure device according to any of the claims 1-23 at its distal end and by an outer tube extending from a distal end at the proximal end of the closure device to a proximal end, and a first filament that is attached to the closure device at its distal end and extending inside the closure device.

25. A deployment instrument according to claim 24, wherein the first filament(s) extend between the inner tube and the outer tube through an opening at the proximal end of the outer tube for expansion of the periphery of the distal bulge.

26. A deployment instrument according to any of the claims 24-25, wherein the second filament(s) extend on the outside of the outer tube.

27. A deployment instrument according to any of the claims 24-26, further comprising one or more locking members for securing the first filament(s).

28. A deployment instrument according to any of the claims 24-27, further comprising one or more locking members for securing the second filament(s).

29. A method of closing a vascular opening in a vessel wall with a deployment instrument according to any of the claims 24-28, comprising the steps of

- moving the inner tube to allow expansion of the distal bulge,

- securing the first filament

30. A method according to claim 29, further comprising the step of removing the introducer sheath prior to securing the first filament.

31. A method according to any of the claims 29-30, further comprising the step of securing at least one second filament.

32. A method according to claim 31 , further comprising the steps of - pulling the introducer sheath such that the part to form the proximal bulge is able to expand peripherally,

- removing the outer tube.

33. A method according to any of the claims 29-32, further comprising the step of injecting a fluid, such as contrast medium, through the inner tube towards the closure device.