Vascular occlusion methods, systems and devices

Described are devices, methods and systems useful for achieving occlusion of vascular vessels. Percutaneous procedures are used to occlude and obliterate the greater saphenous vein, for example in the treatment of varicose vein condition caused by venous reflux. Certain embodiments encompass the deployment of one or more vascular occlusion devices via a through-and-through percutaneous procedure that leaves the vascular occlusion device or devices in a through-and-through condition.

BACKGROUND

The present invention resides generally in the field of devices and methods useful for the occlusion of vascular vessels, and in a particular aspect relates to the occlusion of the greater or lessor saphenous vein to treat complications, such as varicose vein condition, resultant of venous reflux.

As further background, the human venous system generally includes a superficial venous system and a deep venous system, with perforating veins connecting the two systems. In human legs, the superficial system includes the great saphenous vein and the short saphenous vein. The deep system of the legs includes the anterior and posterior tibial veins which join to form the popliteal vein, which becomes the femoral vein when united with the short saphenous vein.

Such venous systems are designed to carry blood back to the heart. To facilitate this function, the venous systems contain one-way valves, which are typically bicuspid. The failure of venous valves leads to retrograde flow or reflux within the venous system. This can result in various venous diseases which include varicose veins and chronic venous insufficiency. In the varicose vein condition, the superficial veins of the leg become dilated and tortuous and can result in discoloration, pain and ulceration. The varicose vein condition commonly involves the incompetence of one or more venous valves which allow reflux of blood from the deep venous system to the superficial venous system or reflux within the superficial system. In many cases, blood from the deep vein system refluxes back down the greater saphenous vein leading to varicosity within superficial veins below the greater saphenous vein.

Surgical stripping of the greater saphenous vein is an extensively practiced technique for treating the varicose vein condition. In this technique, an incision is made in the groin to expose the sapheno-femoral junction, where the great saphenous vein and its branches are ligated. The distal portion of the greater saphenous vein has been exposed by incision interior to the medial inalleolus, and a stripping device is introduced to exit from the proximal saphenous vein. After holding the leg vertical for a time to empty the venous tree, the vein is stripped from the ankle to the groin. In cases wherein the small saphenous vein is also incompetent, it is stripped at the same time from an incision posterior to the lateral malleolus to the popliteal space. After stripping, the leg is held vertically for a time to permit vessel ends to retract, constrict and clot. The stripping procedure is commonly followed by the removal of collateral veins working through small incisions using an avulsion-extraction technique.

More recently, techniques have been developed to try to avoid the invasive stripping procedure and its associated complications. For example, techniques and devices have been developed to treat the varicose vein condition with radiofrequency (RF) energy. In these techniques a catheter having an electrode tip is used to deliver RF energy within the vein to be treated. The RF energy causes localized heating and shrinkage of the venous tissue. The electrodes can be drawn through or repositioned within the vein to treat different sections or segments of the vein. For additional information on RF treatments and devices, reference can be made for example to U.S. Pat. Nos. 6,200,312, 6,179,832, 6,165,172, 6,152,899, 6,071,277, 6,036,687, 6,033,398, 6,014,589, and 5,609,598.

Another technique which has been developed is the endovenous laser technique. This technique is typically performed under local or regional anesthesia. A bare laser fiber is inserted into the diseased vein and delivers laser light in a pulsed fashion to heat the vein to cause damage and constriction. See, e.g., Gorisch et al., “Heat Induced Contraction of Blood Vessels”, Laser Surgery Medicine 2(1), 1-13(1982). Other techniques for treating the varicose vein condition includes sclerotherapy, in which a sclerosing solution is injected into the vein to damage the interior of the vein, followed by compression wrapping to facilitate permanent closure of the damaged vein. Phlebectomy is a procedure also utilized to treat varicose veins, typically medium sized and larger veins. In this procedure, small stab incisions are made in the skin and a tool is used to hook and pull the vein out through the incision.

In view of this background, the need remains for improved and alternative techniques, devices and systems for affecting the venous system to treat venous conditions. The present invention is addressed to these needs.

SUMMARY OF THE INVENTION

Accordingly, in one aspect, the present invention provides a method for treating venous reflux in a leg of a human. The method includes percutaneously accessing a saphenous vein of the leg, and inserting a percutaneous delivery device in the saphenous vein. An occlusion device is delivered into the saphenous vein from the delivery device, so as to occlude the saphenous vein and prevent reflux therethrough.

In another aspect, the invention provides a method for occluding a vascular vessel. The method includes providing a percutaneous delivery device extending between an entry opening and an exit opening in the vessel. An occluder is delivered into the vessel from the delivery device, wherein the occluder extends between the entry opening and the exit opening.

The invention also concerns a method for occluding a vascular vessel that includes providing first and second openings in the vessel. An occluder is positioned in the vessel and extends between the first and second openings.

In another aspect, the invention provides a method for treating a refluxing greater saphenous vein in a human. The method includes delivering into the greater saphenous vein a resorbable occlusion device so as to occlude and prevent reflux through the vein.

In another embodiment, the invention provides an occlusion device useful for occluding a greater saphenous vein of a human. The occluder device has an elongated occluder body having a length of at least about 10 centimeters. The occluder body is configured for passage through a percutaneous delivery device and into the greater saphenous vein so as to cause occlusion of the vein.

The invention also provides a medical system for vascular occlusion that includes an elongate occluder body having a length of at least about 10 centimeters, and a cannulated device configured for delivery of the elongate occluder body into a vascular vessel.

In another aspect, the invention provides a system for delivery of an elongate vascular occluder. The system includes an elongate puncture device for puncturing a vascular vessel, and a guiding catheter having a lumen for receiving the elongate puncture device. This system further includes a sheath for passage over the guiding catheter, and an elongate guide wire passable through the sheath and configured for attachment to an elongate vascular occluder to pull the occluder into the sheath.

The invention also provides a medical assembly useful for the delivery of an elongate vascular occluder. The assembly includes an elongate puncture device for puncturing a vascular vessel, and a guiding catheter having a lumen for receiving the elongate puncture device. A first sheath is provided for passage over the guiding catheter, and a second sheath is provided for passage through the first sheath and configured to contain the elongate vascular occluder.

Further provided by the invention, is a vascular occluder device that includes an elongate occluder body, wherein the body also has an adaptation for attachment to a pulling device.

In another embodiment, the invention provides a method for occluding a saphenous vein of a human. The method includes accessing the saphenous vein with an introducer needle. A puncture wire is passed into the saphenous and used to exit the saphenous vein at a location spaced from the access opening. A sheath is passed from the access opening to the exit opening, and an elongate occluder device is delivered into the saphenous vein from the sheath.

The present invention provides improved methods, systems and devices for occluding venous and other vascular vessels. Additional embodiments as well as features and advantages of the invention will be apparent from the further descriptions herein.

DETAILED DESCRIPTION

As disclosed above, certain embodiments of the present invention provide methods, devices and systems for achieving occlusion of a vascular vessel such as a saphenous vein. Methods of the invention can be performed, for instance, in order to treat venous reflux through the greater saphenous vein such as that involved in the varicose vein condition.

With reference now more particularly to the figures, shown inFIG. 1is a diagram of a human leg showing certain venous structures therein. In particular, shown is human leg200having greater saphenous vein10and the femoral vein11which adjoin at the sapheno-femoral junction12. In accordance with certain aspects of the present invention, greater saphenous vein10is occluded in a region constituting substantially all of the passage between a point13occurring near the medial side of the knee to a point14occurring prior to the sapheno-femoral junction12, as illustrated by the shaded area inFIG. 2. Desirably, such occlusion is effective to prevent reflux of venous blood from the sapheno-femoral junction12in a direction down toward the medial side of the knee (e.g. at point13). Such occlusion is effective to treat varicosities that commonly occur in lower portions of the leg, e.g. portions occurring below the knee.

With reference now toFIG. 3, in certain forms of the invention, occlusion of the passage of the greater saphenous vein occurring between points13and14is achieved by an elongate occlusion device15that extends from point13to point14, and that may include end portions16and17that traverse the wall of the greater saphenous vein10. This may be achieved by deploying occlusion device15during a through-and-through percutaneous procedure, e.g. as described hereinbelow. It will be understood, however, that other occlusion devices may be used in aspects of the present invention, including those others disclosed herein as well as conventional devices such as coils.

With reference now toFIG. 4, shown is an enlarged view of that portion of the human leg occurring generally between points13and14ofFIG. 1. In an illustrative deployment procedure, percutaneous access to the greater saphenous vein10is achieved at point13using the Seldinger or any other suitable technique. For instance, an access needle can be passed through the skin to access greater saphenous vein10, and a wire guide20can be passed through the access needle and into the vein10. Prior to deployment of an occlusion device, wire guide20can be used for any number of conventional procedures including catheterization and imaging procedures in order to locate the sapheno-femoral junction12and discern a desired exit point14for a through-and-through percutaneous procedure. After any such preliminary procedures that are performed, wire guide20can be used in a deployment procedure for an occlusion device.

Specifically, referring still toFIG. 4, a deployment assembly21includes a flexible catheter22, such as a 5 French radiopaque Teflon catheter, a guide sheath23, such as a 7 French radiopaque guide sheath, a stiffening cannula received within guide sheath23(not shown inFIG. 4), and a delivery sheath24received over guide sheath23. Guide sheath23includes a tapered distal end25and a bend26adjacent the distal end25, generally corresponding to a bend in the stiffening cannula. Deployment assembly21is pre-assembled and threaded along guide wire20for the deployment procedure.

With reference now toFIG. 5, shown is deployment assembly21now received within greater saphenous vein10from point13to point14, with the tapered distal end25of the guide sheath23positioned against the wall of greater saphenous vein10using the bend26to achieve rotation and placement of the end25of the guide sheath23.

Reference will now be made toFIG. 6-12, which provide enlarged cross-sectional views in and around exit point14of greater saphenous vein10and illustrate various stages of a percutaneous exit procedure. Particularly, shown inFIG. 6is a cross-sectional view of the stage of the procedure illustrated inFIG. 5. Tapered end25of guide sheath23is shown positioned against the wall of greater saphenous vein10at point14. Received immediately within guide sheath23is stiffening cannula28, which for example may be made from 14 gauge stainless steel. Received immediately within stiffening cannula28is guide catheter22; and, received within guide catheter22is guide wire20. In a next stage of the procedure, guide wire20and guide catheter22are withdrawn from the deployment assembly leaving a condition as illustrated inFIG. 7with guide sheath23and stiffening cannula28remaining in place.

With reference now toFIG. 8, a guide catheter30and long needle31are threaded through the interior of stiffening cannula28, and needle31is used to penetrate the wall of greater saphenous vein10as illustrated. Needle31is advanced through the adjacent tissue toward the surface of the skin. In certain embodiments of the invention, needle31has a needle point of such a sharpness that the needle does not exit the skin, but rather creates a visible bump32in the skin from which the location of the needle31can be visibly discerned. The skin can be nicked at or near the apex of the bump32with a scalpel or other suitable instrument, to allow exit of the needle31, as illustrated inFIG. 9. Subsequently, needle31is grasped with forceps or any other suitable means and used to pull deployment assembly21through the skin with guide sheath23and elements internal thereof exiting first, during which tapered end25serves as a dilator to ease exit (seeFIG. 10), and eventually exposing end34of delivery sheath24externally of the skin (seeFIG. 11). Subsequently, all components except for delivery sheath24are withdrawn, leaving in place delivery sheath24with its internal cannula open35(seeFIG. 12) for use in delivering an occlusion device, for example as described below.

With reference now toFIG. 13shown is a diagram including greater saphenous vein10from points13-14, at the same stage of the procedure as that shown inFIG. 12. Delivery sheath24is in place in a through-and-through fashion, having a first end34exposed through the skin at point14occurring near the groin of the patient adjacent the sapheno-femoral junction, and a second end36exposed through the skin adjacent the medial portion of the knee of the patient. In this fashion, internal cannula35of delivery sheath24is open and available for use in delivering a vascular occlusion device.

Referring now toFIG. 14, in one embodiment, a relatively stiff guide wire37can be threaded through delivery sheath24. Guide wire37has an engaging end38including a hooked portion39or other suitable adaptation for connection to occlusion device40. Occlusion device40includes a looped structure41or any other suitable connection structure at an end thereof. Hooked portion39can be connected to looped structure41, and guide wire37can thereafter be used to draw occlusion device40through delivery sheath24, as generally shown inFIG. 15. In particular,FIG. 15illustrates occlusion device40having been drawn through delivery sheath24to expose an end27adjacent looped structure41from the skin near the groin of the patient, leaving an end42exposed through the skin near the knee of the patient. After this, delivery sheath24can be withdrawn, leaving in place only occlusion device40in a through-and-through condition with the first end27and the second end42remaining external of the skin of the patient (seeFIG. 16). Subsequently, the ends of the occlusion device40can be trimmed, and any excess length of device40remaining external of the patient can be tucked underneath the skin. The percutaneous access and exit sites can be closed by suturing or any other suitable technique, if necessary.

In some cases, it may be desirable to place more than one occlusion device40within the greater saphenous vein10of the patient. With reference again toFIGS. 14-15, if such is desired, more than one guide wire37may be passed through delivery sheath24to pull through a corresponding number of devices40, or alternatively, sequential passes can be made of one or more guide wires37in order to pull additional devices40through the sheath. On the other hand, if sheath24has insufficient internal diameter to accommodate more than one device40at a time, again referring toFIG. 15, at this stage, a second guide wire37can be threaded through sheath such that guide wire37and device40are both received through sheath24. Sheath24can then be withdrawn, leaving in place device40and guide wire37each in a through-and-through condition. The remaining guide wire37can then be used to guide a subsequent deployment assembly21, and the overall procedure repeated one or more times as described above to place a second device40, a third device40, etc.

Upon being positioned within greater saphenous vein10, occlusion device40or devices40restrict blood flow in the greater saphenous vein10so as to occlude or exclude the same. It is desired that occlusion device40be of such a dimension that the material comprising device40substantially blocks the internal lumen of greater saphenous vein10. To this end, the device40can have a compressed condition and be adapted to convert to an altered physical configuration after deployment. For example, all or a portion of device40may be adapted to expand, unfold, unroll, untwist, harden, or otherwise progress to a condition other than that which it had during deployment and which aids in occluding the vessel. Alternatively or in addition, occlusion device40can cause localized thrombus to cause or assist in occluding the lumen of greater saphenous vein10. Illustrative such expandable occlusion devices can comprise a porous sponge extracellular matrix (ECM) structure and/or a collagenous foam. For additional information concerning suitable sponge matrix materials and their preparation, reference can be made, for example, to U.S. Pat. No. 6,666,892 and International Publication No. WO03/002168, each of which is hereby incorporated herein by reference in its entirety.

With reference now toFIG. 17, shown is another view similar to that depicted inFIG. 14, except illustrating an alternative technique for delivering an occlusion device. Occlusion assembly43includes occlusion device44received within an external cannula such as a sheath45, for coaxial style delivery through delivery sheath24. For these purposes, illustratively, sheath24can be a 12 French sheath and sheath45can be a 10 French sheath. Sheath45or other external cannula desirably has an elongate slit46therein or another opening or openings along its length. Such opening or openings are beneficial, for example, in that the device44can be sterilized after loading within the sheath45using gaseous agents such as ethylene oxide (EO) which penetrate through the opening or openings to contact and sterilize device44. Procedurally, occlusion assembly43is threaded into and through delivery sheath24to achieve a through-and-through condition, whereafter sheaths24and45are withdrawn leaving occlusion device44in place in a through-and-through condition as generally described above. Device44can then be trimmed and tucked, and the procedure completed as generally described above.

With reference now toFIG. 18, shown is a view similar to that depicted inFIG. 14, except showing an alternative occlusion device and delivery system. Particularly, delivery sheath24is in place in a through-and-through condition. An occlusion assembly47includes an elongate occlusion device48received concentrically around an internal guide member49, such as a guide wire, and if desired is provided with an end piece50with a tapered end to assist in traversal of the occlusion device48through the delivery sheath24. The assembly47including occlusion device48, guide member49, and end piece50has sufficient column strength and integrity to be pushed through delivery sheath24from end36to end34, leaving occlusion device48in a through-and-through condition. Internal guide member49with end piece50and sheath24can then be withdrawn, and the occlusion device48trimmed and tucked prior to completing the procedure as described above.

With reference toFIGS. 19 and 20, illustrated are alternative methods for delivering occlusion devices by through-and-through percutaneous procedures. Taking firstFIG. 19,FIG. 19Aillustrates initial access to a vascular vessel60through the skin61via introducer needle62, which is used to deliver guide wire63to the vessel60. Guide wire63is used to guide an assembly including a dilator64and an outer sheath65into the vessel60, as shown inFIG. 19B. The guide wire63and dilator64are withdrawn, leaving in place sheath65as shown inFIG. 19C.FIG. 19Dshows a stage of the procedure in which a second percutaneous access is provided via introducer needle66, with the needle66penetrating sheath65. A guide wire68is introduced through needle66and traverses sheath65thus exiting the initial percutaneous access site. As shown inFIG. 19E, sheath65is withdrawn over guide wire68leaving in place guide wire68in a through-and-through condition as shown inFIG. 19F. An assembly including dilator69and sheath70is then introduced over guide wire68as shown inFIG. 19G, and the dilator69and guide wire68are withdrawn thereby leaving in place sheath70in a through-and-through condition as shown inFIG. 19H. Sheath70can then be used for the introduction of an occlusion device in a suitable manner including those described hereinabove.

With reference now toFIGS. 20A-20E, shown is an alternative procedure for establishing a through-and-through sheath for delivery of an occlusion device.FIG. 20Aillustrates an early stage in the procedure wherein access to vascular vessel70is provided through skin71at two locations. At a first location, introducer needle72accesses vessel70and is used to deliver a “J” guide wire73into vessel70. At another location, introducer needle74is used to access vessel70and deliver guide wire75to vessel70. As illustrated inFIG. 20B, a catheter76is advanced over the “J” guide wire73, and an assembly including catheter77and overlying sheath78is advanced over guide wire75. After introduction of the sheath78into vessel70, guide wire75and catheter77are withdrawn from sheath78. At this stage, as illustrated inFIG. 20C, “J” guide wire73and its accompanying catheter76are advanced into the cannula of sheath78. Advancement is continued until catheter76and “J” guide wire73exit the opposite end of sheath78as shown inFIG. 20D. Catheter76can optionally have a segment (e.g. about 3 to 10 cm in length) proximal to the distal tip that tapers to a slightly enlarged external diameter. This segment would fit snugly into the sheath78, and would create a transitioning external diameter that would ease exit of the sheath78from the second puncture site.FIG. 20Eshows the sheath78thereafter established in a through-and-through condition after withdrawal of the catheter76and “J” guide wire73from the sheath78. Sheath78can then be used for the deployment of an occlusion device in any suitable manner including those described above.

Although certain procedures have been described above for the delivery of occlusion devices, it will be understood that other modes of delivery of occlusion devices are also suitable in the present invention. For example, procedures involving only a single point of percutaneous access can be conducted, for instance wherein a delivery sheath is established through a percutaneous access site and into the vascular vessel to be occluded, and an occlusion device is delivered from the sheath using any suitable technique including pushing the occlusion device from the end of the sheath, e.g. as the sheath is withdrawn. In situations where needed, techniques and/or device adaptations can be employed to help to prevent withdrawal of the occlusion device as the sheath is being withdrawn from the patient over the occlusion device. These include for example the use of anchoring portions connected to the occlusion device that forcibly contact vessel walls and resist migration and/or local external compression (e.g. particularly in the case of shallow vessels) to collapse the vessel walls against a leading portion of the occlusion device exposed from the end of the sheath and/or fixing an end, or a portion of the body, of the occlusion device to the vasculature using a suitable securing means, such as one or more sutures or staples, to facilitate maintaining the position of the occluder device as the sheath is withdrawn.

As well, as a modification of a through-and-through percutaneous procedure, a single percutaneous access to a vein or other vessel through the skin can be provided, wherein at a spaced location of the accessed vessel, the vessel is again penetrated, but not the skin. One end of an elongate occlusion device can then be passed through the second penetration of the vessel and anchored in the surrounding tissue, and the percutaneous access site finished off as described above in connection with the through-and-through procedures. In the context of occluding the greater saphenous vein, such adaptations and/or techniques can be used with the percutaneous access site provided either at the knee level or near the groin in the area of the sapheno-femoral junction, or any appropriate location in between. As well, upon establishing a sheath containing a vascular occlusion device within a vessel to be occluded, a second vascular access sight can be provided near the end of the sheath, and a snare basket, or other suitable device for maintaining hold on the end of the vascular occlusion device, can be used to maintain the position of the occlusion device as its overlying sheath is withdrawn from the first percutaneous access site. Further, it is contemplated within certain embodiments of the invention that cut-down or other surgical procedures could be used in providing access to vascular vessels for delivery of vascular occlusion devices.

To illustrate further percutaneous delivery methods, shown inFIGS. 20F-20Iis one descending delivery method involving only a single point of access. As shown inFIG. 20F, a guide wire51such as a J-wire is established in the greater saphenous vein via a percutaneous entry52near the groin. Subsequently, using the wire51, a cannulated device53such as a catheter or sheath is established in the vein (FIG. 20G), and an occluder device54is delivered to the vein through the cannulated device53(FIG. 20H), e.g. by pushing or otherwise delivering the occluder device54out of the cannulated device53and withdrawing the cannulated device53, potentially in a simultaneous operation. In one mode of practice, the occluder device54can have a length sufficient to extend from the vein and out of the percutanous exit52, as shown inFIG. 20H. The occluder device can then be trimmed and if desired secured at the site of percutaneous entry52(FIG. 20I).FIGS. 20J-20Millustrate a similar one-site percutaneous delivery, except using an ascending approach with entry just above the knee.

To illustrate yet further percutaneous delivery methods and occlusion devices, shown inFIGS. 20N-20Pis an alternative occlusion device and delivery system utilizing a single point of access. In this embodiment, turning toFIG. 20N, the occlusion device186comprises a ribbon or band172attached to a fixation device174, such as a flexible tube or rod, using one or more sutures180, or other suitable securing means. Optionally, each end of the fixation device176,178can terminate with one or more barbs, or other suitable anchoring means. The occlusion device186can be deployed by first locating a deployment sheath182in a vascular vessel170. Next, the ribbon172portion of the occlusion device186can be loaded into a delivery sheath184while leaving the fixation device174external to the distal end185of the delivery sheath184. Next, the delivery sheath184, containing the occlusion device186, can be placed inside the deployment sheath182in a manner that compresses or flexes the fixation device174and the delivery sheath184can be pushed through the deployment sheath182. As the fixation device174breaches the distal end of the deployment sheath183, it will expand, thereby anchoring itself into the wall of the vessel170(seeFIG. 20O). After the fixation device174anchors, the deployment sheath182and delivery sheath184can be retracted to deploy the ribbon172into the vessel (seeFIG. 20P). Alternatively, a plurality of occlusion devices186can be deployed in the same vascular vessel170according to the above method to achieve suitable occlusion and/or thrombosis of the vascular vessel170. Still alternatively, the ribbon172can be folded over and secured to the fixation device174, thereby forming two legs or bands for achieving occlusion.

FIGS. 21 to 35Billustrate various embodiments of vascular occlusion devices of and for use in the invention.FIG. 21shows vascular occlusion device80having an occlusion body81, and first end82, and a second end83. Device80has a length “L” sufficient to occlude the length of the passage for which occlusion or ablation is desired. In accordance with certain embodiments of the invention, the device80will have a length sufficient and will be positioned so as to traverse at least one vessel that branches from the vessel to be occluded, for instance a perforator or communicator vein branching from a larger vein to be occluded such as a saphenous vein, e.g. the greater saphenous vein. In the context of greater saphenous vein occlusion procedures as described above, length “L” will be sufficient to traverse the greater saphenous vein from position13to position14, desirably having sufficient excess length to exit percutaneous access sites at those locations for processing as described. These same considerations may be applied to the other vascular occlusion devices described herein.

FIG. 22shows occlusion device84having an occlusion body85, with first and second ribbons86and87of occlusion material. Ribbons86and87are adjoined to one another integrally by an area88of occlusion material.

FIG. 23shows occlusion device89having an occlusion body90with first and second legs or ribbons of material91and92. Ribbons91and92are formed by creating a fold93in an integral longer sheet of material. If desired, a wire loop94or any other suitable tethering adaptation can be positioned around fold93or otherwise connected to the occlusion body90.

Illustrated inFIG. 24is an occlusion device95having occlusion body96with a first end97and a second end98thereof. Occlusion body96includes a plurality of cuts or slits along the length thereof to form flares or legs99which increase the surface area for contact with blood after deployment and enhance the occlusive character of the device95, e.g. by promoting thrombus.

FIG. 25shows occlusion device100having a plurality of ribbons101,102,103, and104connected by an element105such as a wire loop threaded through ends of the ribbons.

Shown inFIG. 26is occlusion device106formed as a roll of occlusion material to provide a generally cylindrical occlusion body107. Additionally, occlusion body107could be partially or completely slit along plane108and potentially additional planes, to provide modified configurations having increased surface area for blood contact.

Referring now toFIG. 27, shown is occlusion device109having an occlusion body110, formed by creating multiple folds111in a sheet of occlusion material. In this regard, it will be understood that this folded adaptation and other adaptations described herein can be designed to render the occlusion devices more compact and less voluminous for delivery, but which devices expand, unfold, or otherwise take on an increased dimension after delivery to facilitate the occlusion function.

FIG. 28shows an occlusion device112having an occlusion body113formed as a roll114of occlusion material. The external surface of occlusion body113has been contoured to create a plurality of bumps, flares or other protuberances115along the length thereof.

FIGS. 29A and 29Billustrate additional occlusion devices of the invention.FIG. 29Ashows occlusion device116having an occlusion body117formed of an occlusion material. Body117includes a plurality of cuts or slits118, for example to provide a mesh configuration, to increase surface area for blood contact. Additionally, occlusion body117can be rolled (see arrows) in order to form an alternate occlusion device119shown inFIG. 29B. Device119includes a generally cylindrical occlusion body120having irregular, raised loops or others portions of material121flaring from its surface.

Additional embodiments of occlusion devices of the invention are shown inFIGS. 30A and 30B.FIG. 30Ashows an occlusion device122including an occlusion body123having a plurality of legs or ribbons of material124established along an edge thereof by cutting or slitting material. If desired, occlusion body123can be rolled diagonally from a corner thereof (see arrows) in order to provide occlusion device125illustrated inFIG. 30B. Device125includes a generally cylindrical body126and in its rolled configuration ribbons124extend or flare from the surface thereof for increased blood contact.

In other occlusion devices of the invention, it is contemplated that occlusion material in any suitable form, such as a ribbon, band, foam, cylinder, or the like, can be combined with elements for anchoring one or both ends of the occlusion device within a vascular vessel. Illustratively, shown inFIG. 31is an occlusion device127having an occlusion body128made out of an occlusion material, and an elongate wire or other element129received within occlusion body128. Wire or other element129exits the ends of the occlusion body128, and provides coils130and131which can be configured to expand and provide points of securement of device127within a vascular vessel. As well, if desired, coils130and131may have synthetic fibers attached thereto to facilitate thrombus formation, for example as conventionally incorporated on commercial platinum or stainless steel embolization and occlusion coils. Further, while the occlusion body128is shown in tubular form, it can occupy any suitable shape or form, such as a ribbon, band, foam, or the like.

Shown inFIG. 32is occlusion device132similar to that depicted inFIG. 31, including an occlusion body133, and an internal wire or other element, and securement adaptations134and135provided by a plurality of diverging filaments or wire elements such as those found in vascular filters.

With reference toFIG. 33-35B, shown are various occlusion devices of the invention including occlusion bodies and self-expanding or forcibly (e.g. balloon) expandable stents secured to the ends of the occlusion bodies for providing points of securement within a vascular vessel.FIG. 33shows device136having occlusion body137, such as a strip or tube of occlusion material, having first and second square stents138and139attached to the ends thereof. Square-shaped stents138and139can, for example, be constructed as described in U.S. Pat. Nos. 6,200,336 and 6,508,833.FIG. 34discloses a vascular occlusion device140having an occlusion body141such as a strip or tube of occlusion material having secured at the ends thereof stents such as those ZILVER® stents sold by Cook, Inc., Bloomington, Ind. (elements142and143).FIG. 35Ashows an occlusion device144A having an occlusion body145A such as a strip or tube of occlusion material having attached to ends thereof Z-stents146A and147A such as those sold by Cook, Inc.FIG. 35Bdiscloses an occlusion device144B similar to that depicted inFIG. 35Abut further comprising barbs148attached to the struts of the stents146B,147B located at each device end. For more information on suitable barb configurations and methods of placing or mounting barbs on stents, reference can be made to U.S. Pat. No. 5,720,776 and App. 2001/0039450.

In the above-described embodiments incorporating stents, coils, filter-like elements or other anchor devices, attachment of the occluder material to the anchor device may be achieved by suturing, bonding, heat-induced welding (including laser welding), or any other suitable technique. As well, where stents are utilized, any lumen of the stent(s) may be spanned and closed by a biomaterial, including a remodelable biomaterial as described herein, to facilitate the occlusion procedure.

The material used in the formation of vascular occlusion devices of the invention can be any material suitable for occluding a vascular vessel of interest. In this regard, the occlusion material may be a synthetic material such as a polymeric material, a naturally-derived material, or a metallic material such as stainless steel. Illustrative synthetic materials may include biodegradable or non-biodegradable materials. These include, for example, synthetic biocompatible polymers such as cellulose acetate, cellulose nitrate, silicone, polyethylene teraphthalate, polyurethane, polyamide, polyester, polyorthoester, polyanhydride, polyether sulfone, polycarbonate, polypropylene, high molecular weight polyethylene, polytetrafluoroethylene, woven DACRON®, polyvinyl alcohol foam, a hydrogel, or mixtures or copolymers thereof; polylactic acid, polyglycolic acid or copolymers thereof, a polyanhydride, polycaprolactone, polyhydroxy-butyrate valerate, polyhydroxyalkanoate, or another biodegradable polymer.

Reconstituted or naturally-derived collagenous materials and/or another source of tissue, such as vascular vessels, can also be used as occlusion materials in the present invention. Such materials that are at least bioresorbable will provide advantage in the present invention, with materials that are bioremodelable and promote cellular invasion and ingrowth providing particular advantage. Bioremodelable materials may be used in this context to promote cellular growth within the lumen of the occluded vessel. This helps to guard against re-establishment of patency of the vessel through biologic processes after the occlusion procedure is completed.

Suitable bioremodelable materials can be provided by collagenous extracellular matrix materials (ECMs) possessing biotropic properties. These can be delivered to the vessel in a lyophilized or otherwise dried, or hydrated state, or additionally or alternatively in a gel or otherwise flowable (and optionally hardenable) state. For example, suitable collagenous materials include ECMs such as submucosa, renal capsule membrane, dermal collagen, dura mater, pericardium, serosa, peritoneum or basement membrane layers, including liver basement membrane. Suitable submucosa materials for these purposes include, for instance, intestinal submucosa including small intestinal submucosa, stomach submucosa, urinary bladder submucosa, and uterine submucosa.

As prepared and used, the submucosa material and any other ECM used, may optionally retain growth factors or other bioactive components native to the source tissue. For example, the submucosa or other ECM may include one or more growth factors such as basic fibroblast growth factor (FGF-2), transforming growth factor beta (TGF-beta), epidermal growth factor (EGF), and/or platelet derived growth factor (PDGF). As well, submucosa or other ECM used in the invention may include other biological materials such as heparin, heparin sulfate, hyaluronic acid, fibronectin and the like. Thus, generally speaking, the submucosa or other ECM material may include a bioactive component that induces, directly or indirectly, a cellular response such as a change in cell morphology, proliferation, growth, protein or gene expression.

Further, in addition or as an alternative to the inclusion of such native bioactive components, non-native bioactive components such as those synthetically produced by recombinant technology or other methods, may be incorporated into the submucosa tissue. These non-native bioactive components may be naturally-derived or recombinantly produced proteins that correspond to those natively occurring in the ECM tissue, but perhaps of a different species (e.g. human proteins applied to collagenous ECMs from other animals, such as pigs). The non-native bioactive components may also be drug substances. Illustrative drug substances that may be incorporated into and/or onto the occlusion devices include, for example, antibiotics, thrombus-promoting substances such as blood clotting factors, e.g. thrombin, fibrinogen, and the like. These substances may be applied to the occlusion device as a premanufactured step, immediately prior to the procedure (e.g. by soaking the material in a solution containing a suitable antibiotic such as cefazolin), or during or after deployment of the occlusion device in the patient.

Submucosa or other ECM tissue used in the invention is preferably highly purified, for example, as described in U.S. Pat. No. 6,206,931 to Cook et al. Thus, preferred ECM material will exhibit an endotoxin level of less than about 12 endotoxin units (EU) per gram, more preferably less than about 5 EU per gram, and most preferably less than about 1 EU per gram. As additional preferences, the submucosa or other ECM material may have a bioburden of less than about 1 colony forming units (CFU) per gram, more preferably less than about 0.5 CFU per gram. Fungus levels are desirably similarly low, for example less than about 1 CFU per gram, more preferably less than about 0.5 CFU per gram. Nucleic acid levels are preferably less than about 5 μg/mg, more preferably less than about 2 μg/mg, and virus levels are preferably less than about 50 plaque forming units (PFU) per gram, more preferably less than about 5 PFU per gram. The ECM material used in the invention is preferably disinfected with an oxidizing agent, particularly a peracid, such as peracetic acid. These and additional properties of submucosa or other ECM tissue taught in U.S. Pat. No. 6,206,931 may be characteristic of the submucosa tissue used in the present invention.

When used in the invention, collagenous materials such as ECMs can be in a hydrated or dried state in the product as packaged and/or when delivered. Suitable drying techniques include, for example, air drying, lyophilization techniques including freeze-drying and evaporative cooling, and vacuum-drying e.g. as occurs in vacuum pressing processes. In addition, occluder devices of the invention can include collagenous materials such as ECM materials, a portion of which have been dried by one technique and another portion of which have been dried by another, differing technique. Illustratively, an occluder device may be provided with a more pliant portion that has been dried under lyophilization conditions, and a less pliant portion that has been dried by air-drying or under vacuum pressing conditions. For instance, shown inFIG. 36is an occluder device150that includes a relatively pliant, lyophilized, fan-folded portion151attached at one end to a more rigid vacuum-pressed portion152which may be formed as a cord or rope. In this manner, the device150can be advanced into a vein or other vessel (e.g. from a sheath or other cannulated device) with the fan-folded portion151as the leading end, while using the more rigid vacuum-pressed portion152to push the fan-folded portion151. The vacuum-pressed portion152can optionally be sufficiently long to extend out of the percutaneous entry site and effectively serve as a pusher rod. After withdrawal of the sheath, the vacuum-pressed portion can be trimmed at the skin and tucked into the percutaneous access site.

FIG. 37shows another occluder device embodiment including a collagenous material such as an ECM, and a more rigid component. Occluder device153includes an elongate body154of ECM or other collagenous material, and a more rigid elongate element155connected to the body154. For example, element155can be connected to the body154at least at or near the distal end156of the body154, which will serve as the leading end of the device153during delivery, e.g. from a sheath or other cannulated device. In some embodiments, element155will be connected to body154at multiple points or continuously along the length of body154. Element155can have a length sufficient to extend from the cannulated device. Thereby, element155can be held in place during withdrawal of the cannulated device, to facilitate maintaining the position of the distal end156of body154in the vein or other vessel during such withdrawal. In this regard, in one convenient embodiment, a splitable sheath or other cannulated device can be employed during delivery, and split around rigid element155as the sheath is withdrawn from the patient.

If element155is made from a permanently implantable material, element155can be trimmed and left implanted in the patient along with body154. For example, element155may be comprised of a bioresorbable and/or bioremodelable material such as a synthetic polymer or collagen, including an ECM material. When element155and body154each comprise an ECM such as submucosa or another collagenous material, element155may for example be air-dried or vacuum pressed to be more rigid than body154, which may be lyophilized. In these embodiments, element155and body154may be formed of a single piece of material, or multiple pieces of material attached together, e.g. by bonding or suturing with a bioresorbable or other material.

Shown inFIG. 38is another occluder device embodiment157having an elongate body158and a distal anchoring end159. Distal anchoring end159is configured to expand and contact the walls of the vein or other vessel after delivery from the end of a cannulated device, sufficiently to facilitate maintaining the end159and connected body158in place during withdrawal of the cannulated device. Distal anchoring end159may be made from the same material or a different material as elongate body158. For example, body158and distal anchoring end159may both be made of a resorbable substance such as a collagenous material (e.g. containing an ECM such as submucosa), with anchoring end159being comprised of a relatively highly expandable porous material such as sponge or foam, and body158being comprised of a less expandable ribbon. The anchoring end159and body158may for example be integrally formed, or may be separate pieces attached to one another by bonding, sutures or other means. As in certain other embodiments described herein, the ribbon or other body158may be sufficiently long to extend to the percutaneous exit site, where it can be trimmed after delivery.

As illustrated inFIG. 39, in another embodiment157A similar to that described in conjunction withFIG. 38, an anchoring end159A is provided by a coiled portion that is collapsed during receipt within the cannulated delivery device, and which radially expands upon exiting the device. When an ECM-containing or other collagenous material is used for anchoring end159A, the material can be lyophilized, vacuum-pressed or otherwise dried in the coiled or other radially-expanding configuration, to set a shape memory to the material.

As shown inFIG. 40, devices157and157A may be delivered in a dual-sheath system160, in which an inner sheath161extends to the trailing edge162of the anchoring end159,159A, and an outer sheath163extends over the anchoring end159,159A. In this manner, after advancement into the vessel to be occluded, outer sheath163can be withdrawn to release anchoring end159,159A to expand and contact the vessel walls, whereafter inner sheath161can be withdrawn while anchoring end159,159A resists withdrawal of the device157,157A from the vessel. It will be understood that such a dual-sheath system may be used in conjunction with any similar occluder device having an expandable anchoring feature and an elongate portion, including expandable features such as stents, filter-type baskets, coils, and the like.

It will be also understood that devices similar to those shown inFIGS. 38 and 39, except having more than one anchoring portion, e.g. having anchoring ends at both ends, are also contemplated as being within the invention. Such devices having an anchoring portion at each end may be deployed fully into the lumen of the vein or other vessel to be occluded, with the anchoring ends contacting the vessel walls and stabilizing the position of the devices in the vessel.

Occlusion devices of the invention will generally be of sufficient dimension to achieve occlusion of the desired stretch of vascular vessel, either alone or in combination with other similar or differing devices. In certain embodiments, the occlusion device will have a length of at least about 10 cm, and in many situations at least about 20 cm. Indeed, for preferred occlusion procedures involving a significant stretch of an artery or vein, occlusion devices having lengths greater than 30 cm will be used. Illustratively, in the occlusion of the greater saphenous vein in human adolescents or adults, occlusion devices having lengths of at least about 40 cm or 50 cm can be used.

While discussions above focus upon occluding the greater saphenous vein via access at the knee level, the greater saphenous vein may also be accessed at a lower level, e.g. near the ankle. During such access, any or all of the greater saphenous vein occurring between the ankle and the sapheno-femoral junction may be subjected to occlusion. Other veins in the leg(s) that may be involved in the varicose vein condition may also be occluded, alternatively or in addition to the greater saphenous vein. For example, the lesser saphenous vein, or varicose veins themselves, may be occluded and obliterated in accordance with the invention. Further, other veins or arteries in the leg(s) or elsewhere in the body may be occluded within the scope of the present invention.

Percutaneously-conducted occlusion procedures of the invention will typically be performed under local anesthesia. In addition, after completion of the procedure, it may be beneficial to use graduated compression stockings in the occluded area, for example for a week or more. Compression of the occluded area may serve to facilitate permanent closure of the occluded vessel, for example when applied during a remodeling period during which tissue ingrowth into the occluded lumen occurs.

Sheaths, dilators, wire guides and needles used in the present invention can all be conventional marketed products or modifications thereof. For example, sheaths can be formed from PTFE (e.g. Teflon) or polyamide (e.g. Nylon) material, or a combination of materials such as an assembly including an inner layer of PTFE, a flat wire coil over the PTFE for kink resistance, and a polyamide (Nylon) outer layer to provide integrity to the overall structure and a smooth surface (e.g. as in the Flexor sheath, Cook, Inc.). Dilators can be made from conventional dilator/catheter type materials such as polyethylene, polyamide, polyurethane or vinyl, or any combination of these materials. Fittings provided for sheath/dilator assemblies can be conventional elements such as luer locks, and the dilator can have a fitting allowing it to be locked to the sheath during insertion and manipulation. Catheters can be made from conventional materials such as polyethylene, polyamide, PTFE, polyurethane, and other materials.

Delivery sheaths used in the invention will have a lumen diameter sized to allow for the introduction of a sufficient amount of occlusion material to occlude the artery or vein of interest. Illustratively, the inner diameter (I.D.) of the final delivery sheath can range from about 8 French up to about 40 French.

As is conventional, the distal ends of the catheters, sheaths, dilators, wires or other components used in percutaneous procedures can include markers that can be X-ray, sonographically, or otherwise non-invasively visualized to identify their location during the procedure. Metallic bands of stainless steel, tantalum, platinum, gold, or other suitable materials, which include a dimple pattern, can serve the purpose for both ultrasound and X-ray identification. As well, distal and/or proximal ends and/or other locations on occluder devices of the invention may include markers for non-invasive imaging, including imageable materials such as those discussed above as well as substances that can be applied to ECMs or other collagenous materials, e.g. substances containing tantalum, barium, iodine, or bismuth, e.g. in powder form.

The invention also encompasses medical kits, such as, for example, an elongate puncture device, a cannulated guiding device, a sheath, a guide wire configured for engagement of an occlusion device, and an inventive occlusion device, sealed within sterile medical packaging. The final, packaged products are provided in a sterile condition. This may be achieved, for example, by gamma, e-beam or other irradiation techniques, ethylene oxide gas, or any other suitable sterilization technique, and the materials and other properties of the medical packaging will be selected accordingly. The occlusion device may be packaged wet or after it is dried.

While the invention has been illustrated and described in detail in the foregoing description, the same is to be considered as illustrative and not restrictive in character, it being understood that only the preferred embodiment has been described and that all changes and modifications that come within the spirit of the invention are desired to be protected. All publications cited herein are hereby incorporated by reference in their entirety as if each had been individually incorporated by reference and fully set forth. In addition, U.S. Provisional Patent Application Ser. No. 60/470,611, filed May 14, 2003 and entitled, “Vessel Closure Device, Delivery Apparatus and Method of Delivering the Closure Device,” is hereby incorporated herein by reference in its entirety.