Patent Application
20060155324
Compositions and methods for repair of aneurysms are described. In particular, vaso-occlusive devices comprising polymer structures are disclosed, as are methods of making and using these devices.
An aneurysm is a dilation of a blood vessel that poses a risk to health from the potential for rupture, clotting, or dissecting. Rupture of an aneurysm in the brain causes stroke, and rupture of an aneurysm in the abdomen causes shock. Cerebral aneurysms are usually detected in patients as the result of a seizure or hemorrhage and can result in significant morbidity or mortality.
There are a variety of materials and devices which have been used for treatment of aneurysms, including platinum and stainless steel microcoils, polyvinyl alcohol sponges (Ivalone), and other mechanical devices. For example, vaso-occlusion devices are surgical implements or implants that are placed within the vasculature of the human body, typically via a catheter, either to block the flow of blood through a vessel making up that portion of the vasculature through the formation of an embolus or to form such an embolus within an aneurysm stemming from the vessel. One widely used vaso-occlusive device is a helical wire coil having windings that may be dimensioned to engage the walls of the vessels. (See, e.g., U.S. Pat. No. 4,994,069 to Ritchart et al.). Electrolytically detachable embolic devices have also been described (U.S. Pat. No. 5,354,295 and its parent, U.S. Pat. No. 5,122,136) as well as vaso-occlusive coils having little or no inherent secondary shape have also been described (see, e.g., co-owned U.S. Pat. Nos. 5,690,666; 5,826,587; and 6,458,119).
Coil devices including polymer coatings or attached polymeric filaments have also been described. See, e.g., U.S. Pat. Nos. 5,935,145; 6,033,423; 6,280,457; 6,287,318; and 6,299,627. For instance, U.S. Pat. No. 6,280,457 describes wire vaso-occlusive coils having single or multi-filament polymer coatings. U.S. Pat. Nos. 6,287,318 and 5,935,145 describe metallic vaso-occlusive devices having a braided polymeric component attached thereto. U.S. Pat. No. 5,382,259 describes braids covering a primary coil structure.
However, none of these documents describe vaso-occlusive devices comprising polymeric components as described herein, or methods of making and using such devices.
Thus, this invention includes novel occlusive compositions as well as methods of using and making these compositions.
In one aspect, described herein is a vaso-occlusive device comprising a core element having an outer surface and at least one polymer structure surrounding a substantial portion of the surface of the core element, wherein the polymer structure is selected from the group consisting of a multi-layered polymeric structure, a twisted polymer, a twill woven structure and a satin woven structure. In certain embodiments, the polymer structure is shaped into a tubular sheath. In other embodiments, the polymer structure comprises a twill weave. In other embodiments, the polymer structure comprises a satin weave. In yet other embodiments, the polymer structure comprises a twisted structure. In certain embodiments, the polymer structure is a multi-layered structure comprising at least one inner polymer member and an outer polymer member, wherein the outer polymer members covers the inner polymer member. The devices described herein are preferably radioopaque.
In any of the devices described herein the inner polymer member may be comprised of one or more monofilaments and/or one or more multi-filaments. Similarly, the outer polymer member may also be comprised of one or more monofilaments and/or one or more multi-filaments. In certain embodiments, the outer polymer member is braided into a tubular shape. In other embodiments, the outer polymer member comprises a non-woven tubular structure.
Furthermore, in any of the devices described herein, the inner and/or outer polymer members may be wound into a helical shape. The pitch of successive layers may have different magnitudes and/or directions. In certain embodiments, the inner polymer member comprises a multi-filament yarn and the outer polymer member comprises a multi-filament yarn wound in a closed pitch. In other embodiments, the inner polymer member comprises a closed pitch coil and the outer polymer member comprises a braided tubular structure.
Any of the polymer structures described herein may comprises one or more biodegradable polymers (e.g., lactide, glycolide, trimethylene carbonate and caprolactone polymers and their copolymers; hydroxybutyrate and polyhydroxyvalerate and their block and random copolymers; a polyether ester; anhydrides, polymers and copolymers of sebacic acid, hexadecandioic acid; and orthoesters) and/or one or more non-biodegradable polymers (e.g., polyethylene teraphthalate, polytetraflouroethylene, polyurethane, polypropylene and Nylon materials). In certain embodiments, at least one inner polymer member comprises a biodegradable polymer and the outer polymer member comprises a non-biodegradable polymer.
In any of the devices described herein, the core element may comprise a wire formed into a helically wound primary shape. In certain embodiments, the core element has a secondary shape (e.g., cloverleaf shaped, helically-shaped, figure-8 shaped, flower-shaped, vortex-shaped, ovoid, randomly shaped, and substantially spherical) that self-forms upon deployment. In certain embodiments, the secondary shape comprises a series of conjoined helical segments (e.g., helical segments having the same or different diameters and/or the same or different axes).
In any of the devices described herein, the core element (e.g., coil) may comprise a metal (e.g., nickel, titanium, platinum, gold, tungsten, iridium and alloys or combinations thereof such as nitinol) and/or a polymer (e.g., poly(ethyleneterephthalate), polypropylene, polyethylene, polyglycolic acid, polylactic acid, nylon, polyester, fluoropolymer, and copolymers or combinations thereof), for example one or more metal and/or polymer filaments in a braid configuration (e.g., a braid or one or more mono- and/or one or more multi-filaments). In a preferred embodiment, the core element comprises a platinum coil. In certain embodiments, the core element comprises a coil having a linear restrained configuration and a relaxed three-dimensional configuration, wherein the coil forms the relaxed three-dimensional configuration upon release from a restraining member.
Any of the devices described herein may further comprise a severable junction detachably which may be connected to a pusher element. The detachment junction can be positioned anywhere on the device, for example at one or both ends of the device. In certain embodiments, the severable junction(s) are, an electrolytically detachable assembly adapted to detach by imposition of a current; a mechanically detachable assembly adapted to detach by movement or pressure; a thermally detachable assembly adapted to detach by localized delivery of heat to the junction; a radiation detachable assembly adapted to detach by delivery of electromagnetic radiation to the junction or combinations thereof.
Furthermore, any of the devices described herein may further include one or more additional components.
In another aspect, the invention includes a method of occluding a body cavity comprising introducing any of the vaso-occlusive devices described herein into a body cavity (e.g., an aneurysm). In certain embodiments, the devices described herein are able to be packed into a selected target site (e.g., aneurysms) at packing densities greater than about 35%.
These and other embodiments of the subject invention will readily occur to those of skill in the art in light of the disclosure herein.
Occlusive (e.g., embolic) compositions are described. The compositions described herein find use in vascular and neurovascular indications and are particularly useful in treating aneurysms, for example small-diameter, curved or otherwise difficult to access vasculature, for example aneurysms, such as cerebral aneurysms. Methods of making and using these vaso-occlusive are elements also aspects of this invention. The compositions and methods described herein may achieve better occlusion and treatment outcomes than known devices, for example because they can be deployed with less friction and/or achieve higher packing densities.
Advantages of the present invention include, but are not limited to, (i) the provision of low-friction polymer covered vaso-occlusive devices; (ii) the provision of occlusive elements that can be packed into aneurysms at high densities; (iv) the provision of occlusive devices that can be retrieved and/or repositioned after deployment; and (v) cost-effective production of these devices.
All publications, patents and patent applications cited herein, whether above or below, are hereby incorporated by reference in their entirety.
It must be noted that, as used in this specification and the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to a device comprising “a polymer” includes devices comprising of two or more polymers.
The novel vaso-occlusive elements described herein comprise at least one polymer structure made up of two or more polymer filaments, for example constructs comprising filamentous elements assembled by one or more operations including coiling, twisting, braiding, weaving or knitting of the filamentous elements. Thus, non-limiting examples of polymer structures include multi-layered polymers, twisted polymer constructions, twill woven polymers, and satin woven polymers.
The polymer(s) making up the structures described herein may be selected from a wide variety of materials. One such example is a suture-type material. Synthetic and natural polymers, such as polyurethanes (including block copolymers with soft segments containing esters, ethers and carbonates), polyethers, polyamides (including nylon polymers and their derivatives), polyimides (including both thermosetting and thermoplastic materials), acrylates (including cyanoacrylates), epoxy adhesive materials (two part or one part epoxy-amine materials), olefins (including polymers and copolymers of ethylene, propylene butadiene, styrene, and thermoplastic olefin elastomers), fluoronated polymers (including polytetrafluoroethylene), polydimethyl siloxane-based polymers, cross-linked polymers, non-cross linked polymers, Rayon, cellulose, cellulose derivatives such nitrocellulose, natural rubbers, polyesters such as lactides, glycolides, trimethylene carbonate, caprolactone polymers and their copolymers, hydroxybutyrate and polyhydroxyvalerate and their copolymers, polyether esters such as polydioxinone, anhydrides such as polymers and copolymers of sebacic acid, hexadecandioic acid and other diacids, or orthoesters may be used.
Thus, the polymer structures described herein may include one or more absorbable (biodegradable) polymers and/or one or more non-absorbable polymers. The terms “absorbable” and “biodegradable” are used interchangeable to refer to any agent that, over time, is no longer identifiable at the site of application in the form it was injected, for example having been removed via degradation, metabolism, dissolving or any passive or active removal procedure. Non-limiting examples of absorbable proteins include synthetic and polysaccharide biodegradable hydrogels, collagen, elastin, fibrinogen, fibronectin, vitronectin, laminin and gelatin. Many of these materials are commercially available. Fibrin-containing compositions are commercially available, for example from Baxter. Collagen containing compositions are commercially available, for example from Cohesion Technologies, Inc., Palo Alto, Calif. Fibrinogen-containing compositions are described, for example, in U.S. Pat. Nos. 6,168,788 and 5,290,552. Mixtures, copolymers (both block and random) of these materials are also suitable.
Preferred biodegradable polymers include materials used as dissolvable suture materials, for instance polyglycolic and polylactic acids to encourage cell growth in the aneurysm after their introduction. Preferred non-biodegradable polymers include polyethylene teraphthalate (PET or Dacron), polypropylene, polytetraflouroethylene, or Nylon materials. Highly preferred is PET, for instance, in the form of 10-0 and 9-0 PET suture material or other small diameter multifilament yarns.
In addition to the polymeric component, the devices described herein also typically include a core element. The core element may be made of a variety of materials (e.g., metal, polymer, etc.) and may assume a variety of tubular structures, for examples, braids, coils, combination braid and coils and the like. Similarly, although depicted in the Figures described below as a coil, the inner member may be of a variety of shapes or configuration includes, but not limited to, braids, knits, woven structures, tubes (e.g., perforated or slotted tubes), cables, injection-molded devices and the like. See, e.g., U.S. Pat. No. 6,533,801 and International Patent Publication WO 02/096273. The core element preferably changes shape upon deployment, for example change from a constrained linear form to a relaxed, three-dimensional (secondary) configuration. See, also, U.S. Pat. No. 6,280,457.
In a particularly preferred embodiment, the core element comprises at least one metal or alloy. Suitable metals and alloys for the core element include the Platinum Group metals, especially platinum, rhodium, palladium, rhenium, as well as tungsten, gold, silver, tantalum, and alloys of these metals. The core element may also comprise of any of a wide variety of stainless steels if some sacrifice of radio-opacity may be tolerated. Very desirable materials of construction, from a mechanical point of view, are materials that maintain their shape despite being subjected to high stress. Certain “super-elastic alloys” include nickel/titanium alloys (48-58 atomic % nickel and optionally containing modest amounts of iron); copper/zinc alloys (38-42 weight % zinc); copper/zinc alloys containing 1-10 weight % of beryllium, silicon, tin, aluminum, or gallium; or nickel/aluminum alloys (36-38 atomic % aluminum). Particularly preferred are the alloys described in U.S. Pat. Nos. 3,174,851; 3,351,463; and 3,753,700. Especially preferred is the titanium/nickel alloy known as “nitinol.” These are very sturdy alloys that will tolerate significant flexing without deformation even when used as a very small diameter wire. If a super-elastic alloy such as nitinol is used in any component of the device, the diameter of the wire may be significantly smaller than that used when the relatively more ductile platinum or platinum/tungsten alloy is used as the material of construction. These metals have significant radio-opacity and in their alloys may be tailored to accomplish an appropriate blend of flexibility and stiffness. They are also largely biologically inert. In a preferred embodiment, the core element comprises a metal wire wound into a primary helical shape. The core element may be, but is not necessarily, subjected to a heating step to set the wire into the primary shape. The diameter of the wire typically making up the coils is often in a range of 0.0005 and 0.050 inches, preferably between about 0.001 and about 0.004 inches in diameter.
As shown in the Figures, the polymeric structures described herein preferably surround most, or all, of the surface of the core element and may be combined with the core element in any fashion. For example, the polymeric structures may be wound around the core element or, alternatively, may be shaped into a tubular sheath that surrounds the core element. The polymer component may adhere to the core element in one or more locations, for example by heating of the polymer or by use of adhesives (e.g., EVA) to the polymer or to the core element) or by other suitable means. Furthermore, the polymeric component may be added to the core element before or after the core element is shaped into a primary and/or secondary configuration. The use of the polymer structures as described herein on known vaso-occlusive devices (core elements) results in much less friction upon delivery and/or deployment and, in addition, allows for higher density packing of vaso-occlusive coils into vessels (e.g., aneurysms).
The resulting inner (10) and outer (20, 25) member wound construction can then be wound into another shape, for example a helically shaped coil, and optionally heat treated so as to retain the secondary shape.
Other multi-layered polymer configurations having from 2-8 layers comprising a combination of open and/or closed pitch coil constructions are also possible.
Inner (10) and/or outer (20) polymer members may be any polymer or combination of polymers, for example as described above. Furthermore, inner (10) and/or outer members (20) may comprise a braided polymer, a single polymer monofilament and/or multi-filaments (e.g., multifilament yarns, threads or sutures).
In certain embodiments, inner and outer members comprise at least one biodegradable polymer. In other embodiments, inner polymer member (10) comprises at least one biodegradable polymer and outer polymer member (20) comprises non-biodegradable polymers (e.g., Nylon). In still other embodiments, inner polymer member (10) comprises one or more non-biodegradable polymers and outer polymer member (20) comprises non-biodegradable polymers. The use of a non-biodegradable outer member (20) with a larger mesh than the inner member (10) may help prevent the premature degradation (e.g., release of particles) from an inner member (10) that includes biodegradable polymer(s). For instance if the inner member (10) comprises an absorbable polymer (e.g., braided suture) and the outer member (20) comprises an non-absorbable polymer (e.g., Nylon filament) having a slightly larger mesh or pitch than the absorbable polymer, particulate matter that is larger than the mesh size of the non-absorbable polymer cannot be released during deployment. This design does, however, allow appropriate degradation of the inner polymer (e.g., through the openings in the non-absorbable polymer) after deployment.
As noted above, the polymer structures described herein may be made to adhere to the underlying wire/coil (60) by melting the polymer(s) (e.g., outer polymer) or by the use of adhesives (e.g., by addition of adhesives such as ethylvinylacetate (EVA) to the polymer component or to the core element) or by other suitable means. In these embodiments, the secured polymer covered wire can then be wound into a helical shape.
Alternatively, the polymeric coil structure (30) can be added to an already wound helically shaped coil, for example by loading the polymeric coil onto an underlying coil, securing the polymeric coil to the underlying coil at one or more locations (e.g., by using ultraviolet glue to fix the ends of the multi-layered polymeric coil to the underlying coil and optionally heat setting the device so shrink the multi-layered polymeric coil to the underlying coil. The polymer component may completely cover the core element (as shown in
In still other embodiments, the polymeric structure comprises a twisted fiber structure. Unlike existing polymer coverings, which use braided multifilaments or monofilaments, the twisted polymers described herein comprise yarns, filaments or fibers that are twisted into a tight cable-like structure. The amount of twist, direction of twist and composition of the polymer fibers may be varied to promote greater regularity and/or stability. The twisted cable-like structures can then be wound into another shape, for example a helically shaped coil, and optionally heat-treated so as to retain the secondary shape.
In preferred embodiments, a twisted polymer as described herein comprises between about 5 and 100 (and any integer therebetween), more preferably between about 6 and 50 (or any integer therebetween) and even more preferably between about 7 and 20 (or any integer therebetween) individual filaments that are used for forming the twisted polymer structure. Although the diameter of the fibers and filaments may vary greatly, the preferred diameter of the twisted fibers is between about 0.0015 inches and about 0.0020 inches and the preferred diameter of the filaments is between about 0.0003 inches and about 0.0008 inches. In addition, although the amount of twist may vary greatly, it is preferred that the twisted structures have between about 10 and about 100 turns per inch. Furthermore, when used in coiled tube geometry, the direction of twist is preferably opposite to the direction of the coil, for instance if the polymer is formed into a coil having turns in “Z” direction, the twisted polymer has turns in an “S” direction.
Any of the aforementioned polymeric structures may be covered with a braided tubular outer (e.g., outer member (20) of
In other embodiments, the polymer component comprises a twill weave or satin weave pattern. The term “weave” refers generally to the pattern created by the weaving of warp (vertical) fibers with weft (horizontal) fibers. The twill weave shown in
As noted above, the polymer structures described herein are advantageously used in combination with a core element, for example a platinum coil. Methods of making vaso-occlusive coils having a linear helical shape and/or a different three-dimensional (secondary) configuration are known in the art and described in detail in the documents cited above, for example in U.S. Pat. No. 6,280,457. Thus, it is further within the scope of this invention that the vaso-occlusive device as a whole or elements thereof comprise secondary shapes or structures that differ from the linear coil shapes depicted in the Figures, for examples, spheres, ellipses, spirals, ovoids, figure-8 shapes, etc. The devices described herein may be self-forming in that they assume the secondary configuration upon deployment into an aneurysm. Alternatively, the devices may assume their secondary configurations under certain conditions (e.g., change in temperature, application of energy, etc.). Stretch-resistant configurations can also be designed and manufactured. For example, a fiber material can be threaded through the inside of the core element and secured to both the proximal and distal end of the device. See, e.g., U.S. Pat. No. 6,280,457.
One or more of the polymer structures described herein and core elements may also comprise additional components (described in further detail below), such as co-solvents, plasticizers, radio-opaque materials (e.g., metals such as tantalum, gold or platinum), coalescing solvents, bioactive agents, antimicrobial agents, antithrombogenic agents, antibiotics, pigments, radiopacifiers and/or ion conductors which may be coated using any suitable method or may be incorporated into the element(s) during production. In addition, lubricious materials (e.g., hydrophilic) materials may be used to coat one or more members of the device to help facilitate delivery. Cyanoacrylate resins (particularly n-butylcyanoacrylate), particular embolization materials such as microparticles of polyvinyl alcohol foam may also be introduced into the intended site after the inventive devices are in place. Furthermore, previously described fibrous braided and woven components (U.S. Pat. No. 5,522,822) may also be included, for example surrounding the polymeric structure-covered core elements described herein.
One or more bioactive materials may also be included. See, e.g., co-owned U.S. Pat. No. 6,585,754 and WO 02/051460. The term “bioactive” refers to any agent that exhibits effects in vivo, for example a thrombotic agent, an anti-thrombotic agent (e.g., a water-soluble agent that inhibits thrombosis for a limited time period, described above), a therapeutic agent (e.g., chemotherapeutic agent) or the like. Non-limiting examples of bioactive materials include cytokines; extracellular matrix molecules (e.g., collagen); trace metals (e.g., copper); and other molecules that stabilize thrombus formation or inhibit clot lysis (e.g., proteins or functional fragments of proteins, including but not limited to Factor XIII, α2-antiplasmin, plasminogen activator inhibitor-1 (PAI-1) or the like). Non-limiting examples of cytokines which may be used alone or in combination in the practice of the present invention include, basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β) and the like. Cytokines, extracellular matrix molecules and thrombus stabilizing molecules (e.g., Factor XIII, PAI-1, etc.) are commercially available from several vendors such as, for example, Genzyme (Framingham, Mass.), Genentech (South San Francisco, Calif.), Amgen (Thousand Oaks, Calif.), R&D Systems and Immunex (Seattle, Wash.). Additionally, bioactive polypeptides can be synthesized recombinantly as the sequences of many of these molecules are also available, for example, from the GenBank database. Thus, it is intended that the invention include use of DNA or RNA encoding any of the bioactive molecules. Cells (e.g., fibroblasts, stem cells, etc.) can also be included. Such cells may be genetically modified. Furthermore, it is intended, although not always explicitly stated, that molecules having similar biological activity as wild-type or purified cytokines, extracellular matrix molecules and thrombus-stabilizing proteins (e.g., recombinantly produced or mutants thereof) and nucleic acid encoding these molecules are intended to be used within the spirit and scope of the invention. Further, the amount and concentration of liquid embolic and/or other bioactive materials useful in the practice of the invention can be readily determined by a skilled operator and it will be understood that any combination of materials, concentration or dosage can be used, so long as it is not harmful to the subject.
The devices described herein are often introduced into a selected site using the procedure outlined below. This procedure may be used in treating a variety of maladies. For instance in the treatment of an aneurysm, the aneurysm itself will be filled (partially or fully) with the compositions described herein.
Conventional catheter insertion and navigational techniques involving guidewires or flow-directed devices may be used to access the site with a catheter. The mechanism will be such as to be capable of being advanced entirely through the catheter to place vaso-occlusive device at the target site but yet with a sufficient portion of the distal end of the delivery mechanism protruding from the distal end of the catheter to enable detachment of the implantable vaso-occlusive device. For use in peripheral or neural surgeries, the delivery mechanism will normally be about 100-200 cm in length, more normally 130-180 cm in length. The diameter of the delivery mechanism is usually in the range of 0.25 to about 0.90 mm. Briefly, occlusive devices (and/or additional components) described herein are typically loaded into a carrier for introduction into the delivery catheter and introduced to the chosen site using the procedure outlined below. This procedure may be used in treating a variety of maladies. For instance, in treatment of an aneurysm, the aneurysm itself may be filled with the embolics (e.g. vaso-occlusive members and/or liquid embolics and bioactive materials) which cause formation of an emboli and, at some later time, is at least partially replaced by neovascularized collagenous material formed around the implanted vaso-occlusive devices.
A selected site is reached through the vascular system using a collection of specifically chosen catheters and/or guide wires. It is clear that should the site be in a remote site, e.g., in the brain, methods of reaching this site are somewhat limited. One widely accepted procedure is found in U.S. Pat. No. 4,994,069 to Ritchart, et al. It utilizes a fine endovascular catheter such as is found in U.S. Pat. No. 4,739,768, to Engelson. First of all, a large catheter is introduced through an entry site in the vasculature. Typically, this would be through a femoral artery in the groin. Other entry sites sometimes chosen are found in the neck and are in general well known by physicians who practice this type of medicine. Once the introducer is in place, a guiding catheter is then used to provide a safe passageway from the entry site to a region near the site to be treated. For instance, in treating a site in the human brain, a guiding catheter would be chosen which would extend from the entry site at the femoral artery, up through the large arteries extending to the heart, around the heart through the aortic arch, and downstream through one of the arteries extending from the upper side of the aorta. A guidewire and neurovascular catheter such as that described in the Engelson patent are then placed through the guiding catheter. Once the distal end of the catheter is positioned at the site, often by locating its distal end through the use of radiopaque marker material and fluoroscopy, the catheter is cleared. For instance, if a guidewire has been used to position the catheter, it is withdrawn from the catheter and then the assembly, for example including the absorbable vaso-occlusive device at the distal end, is advanced through the catheter.
Once the selected site has been reached, the vaso-occlusive device is extruded, for example by loading onto a pusher wire. Preferably, the vaso-occlusive device is loaded onto the pusher wire via a mechanically or electrolytically cleavable junction (e.g., a GDC-type junction that can be severed by application of heat, electrolysis, electrodynamic activation or other means). Additionally, the vaso-occlusive device can be designed to include multiple detachment points, as described in co-owned U.S. Pat. Nos. 6,623,493 and 6,533,801 and International Patent publication WO 02/45596. They are held in place by gravity, shape, size, volume, magnetic field or combinations thereof.
Modifications of the procedure and vaso-occlusive devices described above, and the methods of using them in keeping with this invention will be apparent to those having skill in this mechanical and surgical art. These variations are intended to be within the scope of the claims that follow.
