Abstract:
Endovascular filter ( 10 ) including a plurality of struts ( 14 ) with distal ends ( 18 ) adapted to anchor the filter to the vessel wall after deployment, such as by having barbs ( 20 ), the filter being adapted to be retrieved if desired. Strut distal ends ( 18 ) are coated with an antiproliferative agent ( 40 ) that inhibits the ingrowth of tissue around the filter, thereby permitting the filter to be retrieved and removed atraumatically after a prolonged period of time, thus extending the useful life of the retrievable filter. Optionally, the proximal end ( 22 ) of the filter may also be so coated, or the entire filter.

Description:
TECHNICAL FIELD  
         [0001]    The present invention relates to medical devices and more particularly to endovascular filters.  
         BACKGROUND OF THE INVENTION  
         [0002]    In a trauma patient, orthopedic surgery patient, or neuro patient, where the patient is bedridden and not moving, clot frequently forms in the leg veins. Such clot becomes a serious risk of pulmonary embolism if it breaks loose. Recognition of this occurrence has led to the development of vena cava filters which provide protection from migrating clot. While many such filters are permanently deployed in the patient, temporary filters are known that are to be removed when it is determined that the patient is free of the risk of pulmonary embolism. Additionally, retrievable filters are known which may optionally be removed from the patient, if it is determined that the patient is free of the risk of pulmonary embolism within a short period of time after deployment. After deployment of a filter in the patient, proliferating intimal cells begin to grow around the filter struts; after a length of time, such ingrowth prevents removal of the filter without risk of trauma whereafter the filter must remain in the patient. Normally, removal of a filter is only advisable within a couple of weeks after implantation due to intimal proliferation that irreversibly anchors the filter to the vessel wall. See, for example, SCVIR March 2001, San Antonio, Tex., USA, Scientific Session 25 Abstract No. 194, Gimeno, M. S., et al.  
           [0003]    In U.S. Pat. No. 5,133,733, a collapsible filter is disclosed that is implantable in a blood vessel of a patient, and in particular in the inferior vena cava. Such filters are utilized during endovascular procedures to entrap thrombi or emboli in the blood that flows through a vein and prevent them from reaching the lungs of a patient and thereby cause pulmonary embolization. Such filters are particularly, but not exclusively, concerned with the inferior vena cava, and have legs or similar structures that anchor to the vessel wall at the desired placement site. Other filters are disclosed in U.S. Pat. Nos. 3,540,431; 3,952,747; 4,425,908 and 4,619,246.  
           [0004]    In the first-mentioned patent, a collapsible filter is provided that has limited axial length for facilitating the insertion procedure, with a moderate reduction of the blood flow area of the vein, and in its collapsed state the filter is concentrated into a slender and very narrow bundle of filter elements allowing for a correspondingly slender and narrow insertion catheter. In the expanded condition, four legs extend from an apical hub whereat they are joined together by a ferrule, and each leg of the filter comprises a central element, bent into a smooth quasi-halfsinusoidal form, and two substantially symmetrical curved side elements extending on either side of the central element are joined to the hub and to an eyelet surrounding the central element along its length that is slidable along the central element.  
           [0005]    The filter of U.S. Pat. No. 5,133,733 as a whole may be folded to a collapsed condition having an outer diameter only about as large as the thicknesses of the metal central and side elements, and then is unfolded from a collapsed insertion condition in which the central elements and side elements of all legs forms a narrow bundle for arrangement in a catheter-like insertion instrument, into a tulip-like filter configuration with the side elements interposed between the central elements of the legs to assume the shape of an apertured solid of evolution with one pointed end at the apical hub. At the free end of each leg central element is a reversely turned anchoring hook engageable with the vessel wall for anchoring the filter in place. In the unfolded tulip-like configuration, the distal ends of the filter legs, both the central and side elements, will engage the wall of the vein along a certain length, minimizing the risk of perforation of the wall, and is said to provide an optimum possibility for filter ingrowth in the vein wall and thereby an optimum long term security against migration of the filter. If the filter needs to be removed after more than fourteen days, the filter ingrowth is an undesirable effect.  
           [0006]    It is therefore desired to provide a vena cava filter that is adapted to be removable from its deployed location in a vessel of a patient without trauma to the tissue of the vessel wall and without risk of tearing of intimal tissue which could cause embolization.  
           [0007]    It is further desired to provide such a retrievable filter that is adapted for extended retrieval time in a patient, again without risk of trauma.  
         SUMMARY OF THE INVENTION  
         [0008]    The foregoing problem is solved and a technical advance is achieved in an illustrative endovascular filter for retrievable deployment in a blood vessel of a patient. A plurality of struts extend and diverge from an apical hub at a proximal end to respective distal ends adapted to anchor to the vessel wall when expanded and deployment at a treatment site in a blood vessel of a patient, and lengths of the distal ends of the struts are engageable with and against the vessel wall when deployed. The distal end lengths, and preferably the anchoring sections also, are coated with an antiproliferative agent or bioactive material that prevents or minimizes tissue growth. One such particularly useful bioactive material is paclitaxel, a drug known to have cytostatic properties and that has been shown to inhibit vascular smooth cell migration and proliferation contributing to neointimal hypoplasia.  
           [0009]    In an additional aspect, it is preferable to also coat the proximal end of the filter with the antiproliferative agent. Ingrowth would be inhibited were the proximal end to enter into engagement with the vessel wall when the filter becomes misaligned. Likewise, other surface portions of the hub body and side members between the distal and proximal filter ends are preferably coated, were these portions to engage the vessel wall upon misalignment, since the vessel wall may locally protrude inwardly from a linear configuration relative to the filter. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0010]    An embodiment of the present invention will now be described by way of example with reference to the accompanying drawings, in which:  
         [0011]    [0011]FIG. 1 discloses an elevation view of an endovascular filter of the present invention in a fully expanded condition;  
         [0012]    [0012]FIG. 2 is an end view of the expanded filter;  
         [0013]    [0013]FIG. 3 is an enlargement of one wall-engaging strut distal end that has been treated with an antiproliferative agent;  
         [0014]    [0014]FIG. 4 is a cross-sectional view through a coated strut end;  
         [0015]    [0015]FIG. 5 is a view of the filter of FIG. 1 upon deployment in the vena cava; and  
         [0016]    [0016]FIG. 6 illustrates the filter of FIG. 1 being deployed from its delivery system, in the arrangement suitable for a jugular vein approach to the treatment site. 
     
    
     DETAILED DESCRIPTION  
       [0017]    Vena cava filter  10  is shown in FIGS.  1  to  3  in its fully expanded condition to have a proximal portion  46 , a medial portion  47  and a distal portion  48 . An apical hub body  12 , in the proximal portion  46  of the filter  10 , has a first or distal end  16  and a second or proximal end  22 . A plurality of struts  14  have proximal ends  34  that are secured to the distal end  16  of hub body  12  and have distal end portions  18  that have anchoring sections  20 . The struts  14  divergingly extend distally from the distal end  16  of hub body  12 . The second or proximal end  22  of hub body  12  has a retrieval section  30  extending therefrom that terminates in a hook  31 . The specific embodiment of the filter  10  that is illustrated is shown to have pairs of side elements  24  having proximal ends  36  that are connected to the first end  16  of the hub body  12 , each pair of which is associated with a strut  14 . The side elements  24  also extend distally in diverging pairs from first end  16  of the hub body  12  and includes distal end portions  26  that converge at  28  and are slidably connected to their associated strut  14 . (see FIG. 3) The connection of side elements  24  to the struts  14  preferably being an eyelet  27  that surrounds the strut  14  and is slidable along the strut  14 .  
         [0018]    Anchoring sections  20  preferably are formed as short hooks  21  that are adapted to press slightly into the wall  52  of a vessel  50  (see FIG. 5) at the deployment site to prevent movement in the direction of blood flow. Apical hub body  12  is adapted to be engaged and retrieved by a retrieval device such as a snare, which can be remotely manipulated to snatch the hook  31  of the retrieval section  30 . The retrieval section  30  extends from the second or proximal end  22  of the hub body  12 . A ferrule  32  secures the proximal ends  34  of struts  14  and proximal ends  36  of side elements  24 , to the hub body  12 .  
         [0019]    [0019]FIG. 6 illustrates the filter  10  being deployed from the catheter  39  of delivery and deployment system  38 ; the filter has an outermost dimension when in a collapsed state essentially no greater than the combined thicknesses of the hub body, proximal ends  34 ,  36  of struts  14  and side elements  24 , and ferrule  32  therearound, to facilitate assembly into the delivery and deployment system  38  and deployment therefrom. The filter  10  must also be capable of collapsing back to this size so that it can be “swallowed” by a sheath of a retrieval device after the retrieval device snares the hook  31  of the retrieval section  30  during removal from the patient. FIG. 6 shows the arrangement suitable for a jugular vein approach to the treatment site. For a femoral approach, the filter would be reversed in orientation, with the retrieval section  30  being the forwardmost section during delivery. A quite similar filter structure is disclosed in U.S. Pat. No. 5,133,733 and a similar product is sold by William Cook Europe ApS, Bjaeverskov, Denmark as the GÜNTHER TULIP™ Filter, which is designed to be retrievable. Delivery of a filter such as that disclosed in U.S. Pat. No. 5,133,733 is described in detail in U.S. Pat. No. 5,324,304.  
         [0020]    At some point after implantation, many patients may resume their mobility and no longer need protection from migrating clot. The current maximum retrieval time after implantation for the GÜNTHER TULIP filter is fourteen days; thereafter, the filter grows into the caval wall, or more precisely, strands of organized thrombus grow around the struts and anchoring sections.  
         [0021]    In accordance with the present invention, the distal end sections  18  of struts  14  as well as their anchoring sections  20 , are coated with an antiproliferative or antiinflammatory agent  40 , shown in FIG. 4. Coating  40  inhibits or prevents the ingrowth of tissue to and around the distal end portions  18  and anchoring sections  20 , at least for an extended length of time after placement, such as for four weeks or more, thereby substantially extending the maximum retrieval time for the filter. This inhibition of ingrowth extends the protection period for the immobile patient, and yet still preserves the eventual retrievability of the filter.  
         [0022]    Occasionally an emplaced filter will become misaligned within the vessel, to the extent that the second or proximal end  22  of the hub body  12  will become engaged with the vessel wall  52 . While retrieval is still possible although it is more complicated to establish engagement by the retrieval device with the hook  31  of retrieval section  30 , it is also desirable to provide a coating of the antiproliferative or antiinflammatory agent  40  to those portions of the filter that may enter into contact with the vessel wall such as portions  42  of the second or proximal end  22  of the hub body  12  including the retrieval section  30  (FIG. 1). Similarly, it may be desirable to provide a coating of agent  40  onto surface portions in the medial portion  44  of the filter including portions of the side elements  24  and struts  14  that are spaced from the distal  48  and proximal  46  filter ends, since the vessel wall  52  may locally “protrude” inwardly because it may not remain truly coaxial around the filter.  
         [0023]    One such agent is dexamethasone and related compounds. Another is paclitaxel. Coating of an implantable medical device such as a stent, with a bioactive material, such as paclitaxel, is disclosed in U.S. Pat. No. 6,299,604. It has become well-established that paclitaxel in particular has cytotoxic properties when provided in proper dosages and concentrations, as described in U.S. Pat. No. 6,299,604, and in lower dosages and concentrations would be considered at least cytostatic and therefore able to inhibit neointimal growth, and hence very useful in preventing or inhibiting restenosis.  
         [0024]    The coating may be applied by numerous methods, including but not limited to, spraying, dipping, soaking, painting with a brush or similar tool. In the present embodiment the method of coating was spraying as a fine mist. For simplification of fabrication, the entire filter may be so coated.  
         [0025]    An excipient (e.g., matrix, binder, carrier, polymer, membrane) may be associated with the active agent and may be under the bioactive layer, over the bioactive layer, mixed with the bioactive layer, or any combination thereof. The excipient material may include, but is not limited to parylene, a cellulose based polymer or a naturally occurring basement membrane material such as Small Intestine Submucosa (SIS).  
         [0026]    In the present embodiment, because paclitaxel has low water solubility, no excipient need be used, and the coating may be entirely paclitaxel. The coated device should be handled as gently as possible with minimum scraping, abrading, rubbing, soaking or other physical challenge.  
         [0027]    A wide range of other bioactive materials can be delivered by the filter, as set forth in U.S. Pat. No. 6,096,070. Accordingly, it is preferred that the bioactive material includes at least one of heparin, covalent heparin, or another thrombin inhibitor, hirudin, hirulog, argatroban, D-phenylalanyl-L-polyL-arginyl chloromethyl ketone, or another antithrombogenic agent, or mixtures thereof; urokinase, streptokinase, a tissue plasminogen activator, or another thrombolytic agent, or mixtures thereof; a fibrinolytic agent; a vasospasm inhibitor; a calcium channel blocker, a nitrate, nitric oxide, a nitric oxide promoter or another vasodilator; Hytrin® or other antihypertensive agents; an antimicrobial agent or antibiotic; aspirin, ticlopidine, a glycoprotein Ilbilila inhibitor or another inhibitor of surface glycoprotein receptors, or another antiplatelet agent; colchicine or another antimitotic, or another microtubule inhibitor, dimethyl sulfoxide (DMSO), a retinoid or another antisecretory agent; cytochalasin or another actin inhibitor; or a remodelling inhibitor; deoxyribonucleic acid, an antisense nucleotide or another agent for molecular genetic intervention; methotrexate or another antimetabolite or antiproliferative agent; tamoxifen citrate, Taxol® or the derivatives thereof, or other anti-cancer chemotherapeutic agents; dexamethasone, dexamethasone sodium phosphate, dexamethasone acetate or another dexamethasone derivative, or another anti-inflammatory steroid or non-steroidal antiinflammatory agent; cyclosporin or another immunosuppressive agent; trapidal (a PDGF antagonist), angiopeptin (a growth hormone antagonist), angiogenin, a growth factor or an anti-growth factor antibody, or another growth factor antagonist; dopamine, bromocriptine mesylate, pergolide mesylate or another dopamine agonist;  60 Co (5.3 year half life),  192 Ir (73.8 days),  32 P (14.3 days),  111 In (68 hours),  90 Y (64 hours),  99m TC (6 hours) or another radiotherapeutic agent; iodine-containing compounds, barium-containing compounds, gold, tantalum, platinum, tungsten or another heavy metal functioning as a radiopaque agent; a peptide, a protein, an enzyme, an extracellular matrix component, a cellular component or another biologic agent; captopril, enalapril or another angiotensin converting enzyme (ACE) inhibitor; ascorbic acid, alpha tocopherol, superoxide dismutase, deferoxamine, a 21 -aminosteroid (lasaroid) or another free radical scavenger, iron chelator or antioxidant; a  14 C-,  3 H-,  131 I-,  32 P- or  36 S-radiolabelled form or other radiolabelled form of any of the foregoing; estrogen or another sex hormone; AZT or other anti polymerases; acyclovir, famciclovir, rimantadine hydrochloride, ganciclovir sodium, Norvir, Crixivan, or other antiviral agents; 5-aminolevulinic acid, meta-tetrahydroxyphenylchlorin, hexadecafluoro zinc phthalocyanine, tetramethyl hematoporphyrin, rhodamine 123 or other photodynamic therapy agents; an IgG2 Kappa antibody against Pseudomonas aeruginosa exotoxin A and reactive with A431 epidermoid carcinoma cells, monoclonal antibody against the noradrenergic enzyme dopamine beta-hydroxylase conjugated to saporin or other antibody targeted therapy agents; gene therapy agents; and enalapril and other prodrugs; Proscar®, Hytrin® or other agents for treating benign prostatic hyperplasia (BHP) or a mixture of any of these; and various forms of small intestine submucosa (SIS).  
         [0028]    In a particularly preferred aspect, the layer of bioactive material contains from about 0.1 to 10.0 μg/mm 2 , more preferably about 1.0 to 5.0 μg/mm 2 , and in the present embodiment was about 3.0 μg/mm 2  of the gross surface area of the structure. “Gross surface area” refers to the area calculated from the gross or overall extent of the structure, and not necessarily to the actual surface area of the particular shape or individual parts of the structure. In other terms, about 100 μg to about 300 μg of drug per 0.001 inch of coating thickness may be contained on the device surface.