ANEURYSM OCCLUSION DEVICE

FIELD OF THE INVENTION

The present invention relates to a vaso-occlusive device for implanting into a body cavity and, in particular, to an aneurysm occlusive device.

BACKGROUND OF THE INVENTION

An aneurysm is a ballooning of a blood vessel that poses significant risk to health from the potential for rupture, clotting, or dissection. For example, hemorrhagic stroke can be caused by a ruptured brain aneurysm that is a ballooning of a weakened region of a brain artery occurring in approximately 2-5% of the population.

A variety of materials and devices have been developed for treatment of aneurysms. Vaso-occlusive devices are implants that are placed within the vasculature of the human body, typically via a catheter, either to block the blood flow through a vessel making up that portion of the vasculature through the formation of an thrombus or to form such a thrombus within an aneurysm stemming from the vessel. One widely used vaso- occlusive device is a wire coil to fill the aneurysm causing blood clotting to limit stress to the weakened vessel wall. For example, US 4,994,069 to Ritchard et al. describes a vaso-occlusive coil that assumes a linear helical configuration when stretched, and assumes a folded configuration when relaxed.

The primary goal of aneurysm treatment of brain arteries is to eliminate the risk of future hemorrhage However, even dense coil packing, achieved by multiple coil implantation, represents a filling of only 30-40% of the volume of the aneurysm dome As a result, coiling is associated with a high rate of aneurysm residua with the potential of recurrence, post-surgical re-bleeding in the long-term follow-up, and multiple exposures to the risk of repeat operations Another limitation is that, due to their lack of three- dimensional packing capability, coils are not suitable for large-sized and broad-necked aneurysms Another limitation with coils is that they can, after placement into an aneurysm, be extruded into a parent vessel and be a source of thrombosis or embolism

Three-dimensional coil designs have been described in order to increase the aneurysmal filling density Thus, US 5,645,558 to Horton describes a vaso-occlusive device having a self-forming, substantially spherical shape made from a pre-formed occlusive strand which may be helically coiled or braided US 6,159,165 to Ferrera et al describes spherical coil designs manufactured from a multi-stranded micro-cable made of a shape-memory alloy that will take on the therapeutic shape after placement into the body in another example, US 6,860,893 to Wallace et al describes three-dimensional coil structures in the approximate shape of an anatomical cavity, and a method for preforming the shape by winding and annealing a helically wound metal coil or braid on a mandrel However, none of the aforementioned designs would have the required long- term stability when implanted into aneurysms, and particularly, into large aneurysms The lack of any stable fixation or securing of the strand ends and the lack of any stable interconnection between the strands may cause unfolding and deformation of the preformed shape under physiological conditions Furthermore, the aforementioned devices are substantially hollow so that they actually occupy (and fill) a rather small volume of the aneurysm close to the aneurysmal wall Also, the loose coil designs would make it

difficult, if not impossible, to incorporate any additional elements, including vaso- occlusive members, into the hollow interior of these three-dimensional structures to enhance aneurysmal filling density or to promote early thrombosis within the aneurysm volume.

An aneurysm occlusion device made of a resilient metallic fabric permitting the device to be collapsed for deployment and resiliently self-expanding into the aneurysm has been described in US 6,168,622 to Mazzocchi. The device comprises a bulbous body portion sized to be received within the aneurysm and an anchor sized and shaped to engage the interior surface of the adjacent blood vessel wall. The usage of a metallic fabric and its fixation by clamps allows for long-term design stability of this device which is an advantage over the three-dimensional coil designs described above. However, as stated in '622, the body/anchor design of the self-expandable device makes it difficult to accurately deploy the device and prevent the anchor from being dislodged into the aneurysm. Furthermore, the body portion has to be rather small compared to the volume of the aneurysm to allow for proper positioning of the device. Another disadvantage is the shape of the anchor which fills a significant volume of the parent blood vessel of the aneurysm. As stated in '622, thrombus formation will start in the narrowest area and greatest wire density of the device which is found in the part of the device between the body portion and the anchor and in the anchor itself. Therefore, such a design would enhance thrombosis not only inside the aneurysm but also inside the adjacent blood vessel which would be of significant risk to the patient's health. Additionally, the anchor design of the device hampers any detachment by un-screwing of the delivery device from the vaso-occlusive device, as suggested in '622. Again, the interior of the device is hollow, and aneurysmal filling by thrombus formation is induced from the outer portion of the aneurysmal cavity containing the fabric of the occlusive device.

From the above, it can be seen that there remain important limitations with aneurysm occlusion devices presently known in the art. It would therefore be desirable to provide an aneurysm occlusion device, which is three-dimensional mesh structure, and which addresses the foregoing deficiencies.

SUMMARY OF THE INVENTION

According to a first aspect of the invention, an aneurysm occlusion device is provided for occluding an aneurysm cavity. The device comprises: an enclosed three-dimensional structure of resilient mesh having an interior chamber which is pre-loaded with at least one therapeutic element, the structure having: a collapsed state, in which the structure is relatively small and radially compact for delivery by a catheter into the aneurysm cavity; and an expanded state, in which the structure is relatively large and of a shape selected to substantially fill the aneurysm cavity without extending into a lumen of a vessel adjacent to the aneurysm cavity. The structure is capable of transition from the collapsed state to the expanded state within the aneurysm cavity, causing the mesh to open and progressively expose the at least one therapeutic element to the aneurysm. The at least one therapeutic element comprises a thrombus promoting element or a vessel wall healing element.

The mesh may be a woven metal, polymer, ceramic or composite mesh. The mesh may include strands of a shape memory material, such as a shape memory alloy.

The therapeutic element(s) may be loosely positioned within the interior of the structure, or they may be attached to the mesh.

In one possible embodiment, the therapeutic element is a drug delivery device. Alternatively, or in combination, the therapeutic element may be an embolization coil. Alternatively, or in combination, the therapeutic element may be a hydrogel-based particle, selected to expand under physiological conditions, such as a super-porous hydrogel. Alternatively, or in combination, the therapeutic element may be a radioactive substance. Alternatively, or in combination, the therapeutic element may be a cell.

To enhance the therapeutic effect of the device, various coatings or embedded agents may be provided. At least part of the mesh or the at least one therapeutic element may be coated or embedded with a bioactive agent. At least part of the mesh or the at least one therapeutic element may be coated or embedded with a biodegradable coating. At least part of the mesh or the at least one therapeutic element may be coated or embedded with an expandable hydrogel. At least part of the mesh or the at least one therapeutic element may be coated or embedded with a substance reactive with a liquid embolic agent to promote faster gelation or setting. At least part of the mesh or the at least one therapeutic element may be coated or embedded with a thrombogenic substance. Alternatively, at least part of the mesh or the at least one therapeutic element may be coated or embedded with a non-thrombogenic substance.

Preferably, the mesh has a weave selected to retain the at least one therapeutic element and prevent the at least one therapeutic element from migrating out of the aneurysm cavity.

According to a second aspect of the invention, a method of deploying an aneurysm occlusion device is provided. The method comprises the following steps:

a. collapsing the device, comprising an enclosed three-dimensional structure comprised of resilient mesh which defines an interior chamber containing at least one pre-loaded therapeutic element, into a relatively small and radially compact shape; b. delivering the device by a catheter into the aneurysm cavity; c. allowing the device to expand into a relatively large shape selected to substantially fill the aneurysm cavity without extending into a lumen of a vessel adjacent to the aneurysm cavity, while the device is located within the aneurysm cavity; and d. thereby causing the mesh to open and progressively expose the at least one therapeutic element to the aneurysm, wherein the at least one therapeutic element comprises a thrombus promoting element or a vessel wall healing element.

In one embodiment, the catheter may be a balloon catheter, in which case, step (c) comprises inflating a balloon on the balloon catheter to expand the device.

As mentioned previously, the mesh may be comprised of a shape memory material. In this case, in step (c), the mesh preferably self-expands into a previously memorized shape following deployment into the aneurysm cavity.

For catheter delivery, the method further comprises: step (a) further comprises inserting the collapsed device into the catheter; step (b) further comprises pushing the device through the catheter into the aneurysm cavity; and step (c) or (d) further comprises detaching the device from a delivery wire on the catheter once the device has at least begun to expand.

The device may be mechanically detached from the delivery wire, or may be electrolytically detached from the delivery wire.

The therapeutic element may be itself an expandable element, in which case, it expands concurrently with the mesh. For example, a shape memory element may be used, which self-expands into a previously memorized shape upon deployment of the device. The expandable element may be preferably a thrombus promoting drug or a vessel wall healing drug, in which case, the expansion of the element resulting in delivery of the drug into the aneurysm cavity.

According to a third aspect of the invention, a method of occluding an aneurysm cavity with an aneurysm occluding device is provided. The method comprises the following steps: a. collapsing the device, comprising an enclosed three-dimensional structure comprised of resilient mesh which defines an interior chamber containing at least one pre-loaded therapeutic element, into a relatively small and radially compact shape; b. delivering the device by a catheter into the aneurysm cavity; c. allowing the device to expand into a relatively large shape selected to substantially fill the aneurysm cavity without extending into a lumen of a vessel adjacent to the aneurysm cavity, while the device is located within the aneurysm cavity; and d. thereby causing the mesh to open and progressively expose the at least one therapeutic element to the aneurysm, wherein the aneurysm begins to occlude by forming a thrombus over the mesh as the mesh opens and the therapeutic element is exposed, wherein the at least one therapeutic element comprises a thrombus promoting element or a vessel wall healing element.

According to a fourth aspect of the invention, an aneurysm occlusion device for occluding an aneurysm cavity is provided. The device comprises: an enclosed three-dimensional structure of resilient mesh, the structure having: a collapsed state, in which the structure is relatively small and radially compact for delivery by a catheter into the aneurysm cavity; and an expanded state, in which the structure is relatively large and of a shape selected to substantially fill the aneurysm cavity without extending into a lumen of a vessel adjacent to the aneurysm cavity; the structure being capable of transition by self-expansion from the collapsed state to the expanded state within the aneurysm cavity to substantially fill the aneurysm cavity without extending into a lumen of a vessel adjacent to the aneurysm cavity.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 is a schematic diagram of the device according to a first embodiment of the present invention.

Figures 2A-2D are schematic diagrams of a deployment sequence of the device of Fig. 1 into an aneurysm cavity.

Fig. 2A illustrates the device in its collapsed form inside a delivery catheter. Fig. 2B illustrates the expanding device as it is released from the delivery catheter into the aneurysmal cavity. Fig. 2C illustrates the fully expanded device inside the aneurysmal cavity. Fig. 2D illustrates the device after detachment from the catheter.

Figures 3A-3D are schematic diagrams of a deployment sequence of a device according to a second embodiment of the present invention (containing a first type of embolism promoting element - in this case, hydrogel particles).

Figures 4A-4D are schematic diagrams of a deployment sequence of a device according to a third embodiment of the present invention (containing a second type of embolism promoting element - in this case, embolization coils)

DETAILED DESCRIPTION OF THE INVENTION

A three-dimensional mesh structure is provided Figures 1-4D illustrate various aspects of the mesh, its shape, attributes and deployment

In accordance with the present invention, the mesh for forming the three-dimensional structure may be made of a plastic or metallic fabric (or other suitable material, such as a ceramic or composite material) comprising a plurality of oriented strands Meshes and mesh designs are well-known in the art and have applications in a variety of medical devices Suitable plastic materials for forming a mesh in accordance with the present invention include non-biodegradable and biodegradable polymers, such as homopolymers, copolymers, blends, and derivatives based on poly(ester)s, poly(orthoester)s, poly(carbonate)s, poly(anhydrιde)s, poly(urethane)s, poly(phosphazene)s, poly(phosphoester)s, poly(saccharιde)s, poly(peptιde)s, polyvinyl alcohol), polyvinyl acetate), poly(N-vιnyl pyrrohdone), poly(ethylene glycol), poly(propylene glycol), poly(tetrafluorethylene), poly(chlorotrιfluoroethylene), poly(methacrylate)s, poly(acrylate)s, poly(amιde)s, poly(butadιene), poly(styrene), poly(acrylonιtrιle), poly(propylene), poly(vιnylιdene fluoride), polyvinyl chloride), poly(oxymethylene), poly(sulfone)s Highly elastic plastics and those having shape- memory properties are of particular interest for the present invention This particularly includes homopolymers and copolymers based on poly(ester)s and poly(urethane)s

Suitable metallic materials for forming the mesh are metals or metal alloys including but not limited to platinum, rhodium, palladium, indium, tungsten, gold, silver, and tantalum

Preferred is platinum or a platinum/tungsten alloy The mesh may also be formed of any of a wide variety of stainless steels Highly preferred are "super-elastic" materials and/or those having shape-memory properties such as nickel/titanium alloys, nickel/aluminum alloys or copper/zinc alloys Furthermore, bioresorbable metals including iron which may contain carbon, or a bioresorbable metal alloy or sintered metal, the main constituent of which may be selected from the group of alkaline metals, in particular lithium, alkaline earth metals, in particular magnesium, as well as iron, zinc or aluminum may be used for fabrication of the mesh

The shape of the three-dimensional structure may be imparted by heat-treatment of the mesh after preforming the desired shape, eg by fixing the mesh on the surface of a template in the desired shape during the heat-treatment The shape will in most cases be selected to correspond to the shape of the aneurysm cavity to be filled Such shape memorization techniques are well-known in the art Thus for example, nickel/titanium alloys may be treated at 500 ⁰ C for about 1-2 hours to memorize a desired shape Lower temperatures require longer, and higher temperatures shorter treatment times to achieve similar results Polymers may be treated at temperatures below their melting or decomposition temperatures which is usually below 200 ⁰ C and preferably below 10O ⁰ C, depending on the material

Alternatively, the mesh for forming the three-dimensional structure may be made by laser-cutting of a plastic or metallic object, such as a film The desired three-dimensional shape of the mesh may be imparted before or after laser-treatment Thus for example, films may be produced in the desired three-dimensional shape by any of the well-known fabrication methods, such as melt-processing (for metals and polymers) or solution- casting (for polymers), and subsequently laser-cut to provide a collapsible design Films may also be produced in a two-dimensional shape by one of the aforementioned

methods. Such films may be laser-cut to provide a collapsible design. A three- dimensional structure in the shape of an aneurysmal cavity may then be imparted by heat-treatment of the laser-cut film after preforming the desired shape as described above for a mesh made from a fabric.

The three-dimensional mesh 8, as illustrated in Fig. 1 , preferably has the shape of the cavity of the aneurysm 9 to be filled. Typical shapes include spherical, ovate, ovoid, or ellipsoid shapes, and distorted versions of these. Dependent on the chosen mesh design, the distal part 18 of the mesh may or may not contain a clamp or similar fixation to fix and/or cover distal strand ends. Three-dimensional mesh designs may contain free distal strand ends and may thus require distal fixation of these strands. Three- dimensional mesh designs may not contain open distal parts or free distal strand ends and thus may not require any distal fixation. The proximal part 20 of the mesh may or may not contain a clamp or similar fixation to fix the proximal ends of strands and/or for connecting the mesh with a delivery system. The proximal part of the mesh may preferably be shaped to fill the neck of the aneurysm. The terms "proximal" and "distal" are used herein for convenience for the reader's reference when studying the figures. However, it will be appreciated that the device could be made completely symmetrical. In such cases, the positioning of the device in a particular orientation within the aneurysm cavity will not be critical, provided that the device is positioned within the aneurysm cavity and substantially fills the cavity and neck portion of the aneurysm.

For deployment of a mesh 8, it will be inserted into a delivery catheter 10 and pushed through the catheter in a collapsed configuration (Fig. 2A). After releasing from the catheter 10 into the aneurysmal cavity 12, the mesh 8 expands to its memorized three- dimensional shape (Figs. 2B and 2C), and will finally be detached from the delivery wire 14 (Fig. 2D). It is important to note that the mesh structure does not significantly extend

into the lumen of the adjacent vessel 16 (see Fig. 2D) so that the risk of thrombosis inside the lumen of the vessel is minimized.

Deployment of the mesh from a delivery wire may be achieved by one of the methods known in the art, such as mechanical or electrolytical detachment. Mechanical detachment may simply be done by providing a thread-like clamp at the proximal end 20 of the mesh 8 and un-screwing the delivery wire from the mesh. The preferable method is the electrolytical detachment of the mesh which can easily be achieved by providing an electrolyzable connection between mesh and delivery wire. This connection may be made of stainless steel or any other electrolyzable material and may be soldered or otherwise fixed on its one end to the proximal end 20 of the mesh and on its other end to the delivery wire 14.

Occlusion of the aneurysmal cavity is imparted by thrombosis and/or foreign-body reactions induced by the inserted mesh. Thrombosis may also be imparted by providing an electrical current to the mesh for a pretermined period of time. As another method, thrombosis may be imparted by coating the mesh with a thrombotic and/or cell- proliferative agent. The agent, which may be a drug, oligosaccharide, polysaccharide, lipid, peptide or protein, radioactive substance, or derivatives and combinations of agents, may be incorporated in a polymer layer coating the mesh entirely or partially. Polymer coating can be performed in any of the well-known methods, such as dip- coating, spray-coating or brush-coating. Activation can also be by plasma modification. The polymer coating itself without any additional agent may also serve as a means to impart thrombotic and/or cell-proliferative processes in order to control aneurysmal filling. Non-degradable as well as degradable polymers such as those listed above may be suitable for coating the mesh with or without incorporation of thrombotic and/or cell- proliferative agents into the coating.

Furthermore, the three-dimensional mesh structure may contain embolization elements in its interior hollow part in order to control aneurysmal filling. Thus for example, embolization agents made from expandable particles 22 may be inserted into the cavity of mesh 8 (or attached to the mesh) and deployed, as illustrated in Figures 3A-3D. Of particular interest are hydrogel-based particles which have a reduced volume in the dried state but expand under physiological conditions. Dried particles 24 can easily be deployed inside the collapsed mesh (Fig. 3A) and expand when in contact with water inside the aneurysmal cavity (Figs. 3B and 3C). The mesh size and pattern may preferably be chosen to prevent any migration of the particles out of the mesh into the vessel (Fig. 3D). Suitable hydrogels are homopolymers or copolymers based on vinyl alcohol, vinyl acetate, N-vinyl pyrrolidone, ethylene glycol, propylene glycol, hydroxyethyl methacrylate, methyl methacrylate, as well as hydrogels based on polyesters, polysaccharides and proteins. The hydrogel may or may not be cross-linked. Of particular interest are particles made of polyvinyl alcohol). Furthermore, of particular interest are particles made of "super-porous hydrogels". Embolization particles may further contain bioactive agents or may be coated with those agents to control aneurysmal filling. Bioactive agents may additionally be embedded in drug delivery systems, such as microspheres or nanoparticles.

Another example of an embolization element which may be embedded in the interior hollow part of the three-dimensional mesh structure in order to control aneurysmal filling is embolization coils. One or more coils 26 as those well-known in the art, including those representing three-dimensional structures and those being modified with bioactive coatings, may be inserted into the cavity of mesh 8 and deployed, as illustrated in

Figures 4A-4D. The mesh size and pattern may preferably be chosen to prevent any migration of the coils out of the mesh into the adjacent vessel.

In contrast to the aforementioned methods of implantation of a mesh together with an additional embolization element in one step, embolization elements may also be inserted in a second step, from the same or a different catheter, into the mesh after it has already been deployed and expanded into the aneurysmal cavity. Thus for example, hydrogels may be inserted through the holes of the mesh into its interior part when they are in the dried state (xerogels) providing a volume small enough for insertion. Under physiological conditions, the particles gain water and expand to a bigger volume which prevents their migration out of the mesh. Similarly, coils may be inserted through the holes of the mesh into its interior part when they are in a stretched configuration. Inside the mesh, the coils relax into a memorized three-dimensional shape which prevents their migration out of the mesh. Furthermore, the mesh may provide a structure for embedding an injectable liquid embolization agent, which undergoes gelation or solidification inside the mesh preventing the agent from migration into the vasculature. The mesh can also be coated with an agent which promotes faster gelation of the injectable liquid, or preferential gelation at the mesh interface. This agent can be a cross-linker or a second reaction component or a catalyst. Meshes with appropriate size and pattern may also allow for placement of a stent through the mesh across the aneurysm and into a distal branch vessel incorporated into the wall of an aneurysm.

Additionally, any combination of one of the modification methods described above, ie mesh coating with a polymer layer with or without incorporation of bioactive agents, and embedding of embolization agents such as particles or coils, which may further be modified by coating and/or incorporation of bioactive agents, may be used in accordance with the present invention.

In an alternative embodiment of the present invention, the mesh for forming the three- dimensional structure may not be provided with a pre-memorized shape which allows for

its self-expansion inside an aneurysmal cavity, as exemplified above. Instead, the mesh may be provided with a design which allows for its expansion into a stable three- dimensional shape by means of a balloon catheter when inserted into the aneurysmal cavity.

The foregoing description illustrates only certain preferred embodiments of the invention. The invention is not limited to the foregoing examples. That is, persons skilled in the art will appreciate and understand that modifications and variations are, or will be, possible to utilize and carry out the teachings of the invention described herein. Accordingly, all suitable modifications, variations and equivalents may be resorted to, and such modifications, variations and equivalents are intended to fall within the scope of the invention as described and within the scope of the claims.