Patent Document

CROSS-REFERENCES TO RELATED APPLICATIONS 
       [0001]    The present application is a Divisional of U.S. Pat. No. 12/383,094 filed Mar. 18, 2009 (Allowed), which application claims the benefit of priority of U.S. Provisional Appln. No. 61/037,983 filed Mar. 19, 2008. The full disclosures, each of which are incorporated herein by reference in their entirety for all purposes. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The invention described herein relates to medical devices and methods of use thereof. More particularly, the invention relates to a retrievable intravascular filter and methods for filtering embolic material within a vessel of a subject. 
       REFERENCES 
       [0003]    Berger, US Patent Application Publication No. US2007/0225644 A1, Embolic Removal for Orthopedic Procedures, Sep. 27, 2007. 
         [0004]    Clubb et al., U.S. Pat. No. 7,220,271 82, Embolic Filters Having Multiple Layers and Controlled Pore Size. 
         [0005]    McGuckin et al., U.S. Pat. No. 6,623,506, Vein Filter. 
         [0006]    Sutton, U.S. Pat. No. 7,229,462, Vascular Filter System for Carotid Endarterectomy 
         [0007]    Kimmell, U.S. Pat. No. 3,952,747, Filter and Filter Insertion Element 
         [0008]    Kimura, U.S. Pat. No. 5,935,303, Electrostatic Filter 
         [0009]    Ye et al., U.S. Pat. No. 6,241,999, Method for Producing Liposomes with Increased Percent of Compound Encapsulated. 
         [0010]    Rousseau H, Perreault-P, Otal P, Stockx L, Golzarian J, Oliva V, Reynaud P, Raat F, Szatmari F, Santoro G, Emanuelli G, Nonent M, Hoogeveen Y. The 6-F nitinol 
         [0011]    TrapEase inferior vena cava filter: results of a prospective multicenter trial. J Vasc Intery Radial. 2001 March; 12(3):299-304. 
         [0012]    Men&#39;shikova Y A, Evseeva T G, Chekina N A, Peretolchin M V, Skurkis Y O, Ivanchev S S. Synthesis of Monodisperse Polymethyl Methacrylate particles in Buffered Solutions under the Action of Carboxyl-Containing Initiator. Russian Journal of Applied Chemistry, Vol. 75, No 12, 2002 pp 1993-1998 
         [0013]    A J de Vries, Y J Gu and W van Oeveren. The rationale for fat filtration during cardiac surgery. Perfusion 2002; 17; 29 
         [0014]    De Vries A J, Gu J Y, Douglas Y L, Post W J, Lip H, Oeveren W V. Clinical evaluation of a new fat removal filter during cardiac surgery. European Journal of Cardio-thoracic Surgery. 25 (2004) 261-266 
         [0015]    Ramirez G, Romero A, Garcia-Vallejo J J, Munoz M. Detection and removal of fat particles from postoperative salvaged blood in orthopaedic surgery. Transfusion. 2002;42:66-75 
         [0016]    Taviloglu K, Yanar H. Fat embolism syndrome. Surg Today. 2007;37(1):5-8. Epub 2007 
         [0017]    Xiong Y L, Noel C, Moody W G Journal of Food Science: Textural and Sensory Properties of Low-Fat Beef Sausages with Added Water and Polysaccharides as Affected by pH and Salt. Journal of Food Science 64 (3), 550-554 
         [0018]    Peng M, Li D, Chen Y, Zheng Q. TI: Electrostatic-Assembly of Carbon Nanotubes (CNTs) and Polymer Particles in Water: a Facile Approach to Improve the Dispersion of CNTs in Thermoplastics. Macromolecular Rapid Communications. Vol 27, No. 11, p 859-864 2006 
         [0019]    Kiely L J, Olson N F. Estimate of Non-Electrostatic Interaction Free Energy Parameters for Milk Fat Globules. J. Dairy Sci. 86:3110-3112 (2003) 
         [0020]    Adrianus J. de Vries A J, Gu Y J, Douglas Y L, Post W J, Lip H, van Oeveren W. Clinical evaluation of a new fat removal filter during cardiac surgery European Journal of Cardio-Thoracic Surgery Volume 25, Issue 2, February 2004, Pages 261-266 
         [0021]    Taviloglu K, Yanar H. Fat Embolism Syndrome. Surgery Today. 2007. 37:5-8 
         [0022]    Steinbeck M. J., Robinson J. M, Karnovsky M. J. Activation of the neutrophil NADPH-oxidase by free fatty acids requires the ionized carboxyl group and partitioning into membrane lipid. J Leukoc Biol. 1991 April; 49(4):360-8 
         [0023]    Mastraneglo A. M., Jeitner T. M., Eaton J. W. Oleic acid increases cell surface expression and activity of CD 11b on human neutrophils. J Immunol. 1998 Oct. 15; 161 (8):4268-75 
         [0024]    Cnop M., Hannaert J. C., Pipeleers D. G. Troglitazone does not protect rat pancreatic beta cells against free fatty acid-induced cytotoxicity. Biochem Pharmacol. 2002 Apr. 1; 63(7): 1281-5. 
         [0025]    Kamijo A, Kimura K., Sugaya T, Yamanaouchi M, Hase H, Kaneko T, Hirata Y, Goto A, Fujita T., Omata M. Urinary free fatty acids bound to albumin aggravate tubulointerstitial damage. Kidney Int. 2002 November; 62(5): 1628-37 
         [0026]    Grotjohan H. P., van der Heijde R. M., Jansen J. R., Wagenvoort C. A., Versprille A. A stable model of respiratory distress by small injections of oleic acid in pigs. Intensive Care Med. 1996 April; 22(4):336-44 
       BACKGROUND OF THE INVENTION 
     Fat and Fat Embolism 
       [0027]    Lipids may be classified as either “anionic” (e.g. most phospholipids), “cationic” (e.g. milk fat globules (Kiely and Olson 2003)), or “neutral”. Human fat tissue is an example of a lipid which in its living, unperturbed form, is electrically neutral. But once it is surgically or metabolically disrupted, human fat begins a breakdown into several lipid fractions, some positive, some negative, and some neutral. For example, free fatty acids (FFAs) are highly polarized molecules (de Vries et al 2004). The trans form free fatty acids (FFAs) carry a negative charge (Steinbeck et al 1991). FFAs are particularly harmful in the circulation. FFAs cause vasoconstriction and granulocytes activation through surface expression and activity of CD11b (Mastraneglo et al 1998). FFAs have been implicated in b-cell damage in the pancreas (Cnop et al 2002), tubulointerstitial damage in the kidney (Kamijo et al 2002), and acute respiratory distress syndrome in the lungs (Grotjohan et al .1996). Fortunately, because a FFA molecule is a highly polarized structure, filtration as a means to remove FFAs from the blood stream holds some promise. In fact, extracorporeal, (i.e., outside the human body) mechanical blood filtration targeting fat has been demonstrated in blood from orthopedic patients (Ramirez et al 2002). Similar extracorporeal mechanical filtration during cardiac surgery has shown that FFAs are retained by the filter particularly well, a phenomenon that is thought likely to be related to the polarity of the FFA molecule (de Vries et al 2004). 
         [0028]    The embolization of fat particles into organs including the lung and brain is an important cause of medical morbidity, particularly following orthopedic trauma. When a bone is fractured, there is usually some fat released into the venous circulation. These particles are distributed downstream, particularly into the lung, but in most cases do not cause an obvious medical syndrome. Following orthopedic surgical procedures, however, the escaped fat particle load becomes very large, and a fat embolism syndrome may occur in a third of patients undergoing these procedures. Symptoms may range from mild respiratory distress with skin and eye symptoms, to severe pulmonary edema and death (Taviloglu et. al. 2007). 
       Methacrylate and Methacrylate Embolism 
       [0029]    Methacrylate is frequently used in orthopedic surgery to affix implants and to remodel lost bone. Methyl methacrylate (MMA) polymerizes and thereby hardens into polymethyl methacrylate (PMMA). The polymer PMMA is a lipophilic molecule of varying chain length, with the molecular formula (C 5 O 2 H 8 )n. It is Sold under a variety of medical and non-medical trade-names including the familiar “Plexiglas”. The two hydroxyl groups carry a negative electrostatic propensity, while the hydrogens impart positive charges. Consequently, the molecule has intrinsic electrostatic properties which become manifest under various polymerization and ambient pH conditions. Additionally, methacrylate molecules may be purposefully made to bear either a positive or a negative charge by means known in the art. For example, Peng et al. describe “a facile and organic-solvent-free method” involving the production of positively charged PMMA by emulsion polymerization, in which a cationic element such as the monomer methacryloyloxyethyltrimethylammonium chloride (METAC) is copolymerized with methacrylate. Likewise, negatively charged PMMA is produced using anionic comonomer sodium 2-acrylamido-2-methylpropanesulphonate (NaAMPS) (Peng. et al. 2006). Particles of these materials, however, are frequently taken away from the operative site by nearby veins. When the particles are brought into the fine capillaries of the lung or other regions of the body, circulatory blockages and tissue damage may result. 
       Intravascular Filter Usage and Design Considerations 
       [0030]    The engineering of vascular filters is complicated by the need to make the particle-capturing mesh tight enough to capture the targeted particles, but not so tight so as to impede circulation, or otherwise cause thrombus formation on the mesh. An excessively loose mesh (in which the spaces between the filter elements are too distant) results in failure to capture smaller emboli. Conversely, a mesh that is too tight (in which filter elements are too close to one another) increases the resistance to blood flow, and may trap particles indiscriminately, leading to early thrombosis and occlusion of paths through the filter. 
       Electrostatic Filters 
       [0031]    Electrostatic filters are known principally for use in water filtration, cleaning of fabric, air/allergen filtration, and in food processing, but have not been adapted to the unique environment and demands of intravascular use. 
         [0032]    It would be desirable to have a venous filter capable of capturing small embolic particles, including the most dangerous fatty acids, without attracting platelets and promoting thrombosis. It would also be desirable to deploy such a filter via a catheter prior to a high-embolic-risk procedure; and to be able to retrieve it at the conclusion of that procedure. 
         [0033]    The invention set forth herein relates to a retrievable protective mesh which is inserted into a blood vessel which is deemed at risk for delivering potentially harmful embolic particles to distal organs. This mesh is deployed via catheter, or by direct cut-down into the vein, and is of sufficient patency to allow normal blood cells and small clumps of cellular material through. In particular, this intravascular filter is constructed to employ electrostatic forces in a manner that permits adhesive forces to capture particles of the targeted type (for example fat or methacrylate emboli), and to retain these particles, even those which might otherwise be physically small enough to slip through the filter. Specific types of targeted particles are thereby captured and retained with improved efficiency, permitting filter elements to be more widely spaced than would otherwise be necessary, thereby decreasing both resistance and the propensity for thrombosis. The device is designed to be retrieved post-op, and the accumulated debris on the mesh analyzed in the laboratory. The device provides protection from embolism and stroke resulting from debris released by sites of tissue trauma. The device provides protection from embolism and stroke resulting from debris released by sites of tissue trauma. 
       BRIEF SUMMARY OF THE INVENTION 
       [0034]    A filter system for removal of embolic particles from a blood vessel of a subject is disclosed, where the system has a filtration element deployable within a blood vessel of the subject. At least a portion of the filtration element is electrically conductive, and either an anode or a cathode is in electrical communication with the filtration element. Embolic particles carrying an electrostatic charge opposite that of said anode or said cathode are attracted to the filtration element. The embolic particles may be lipids or methacrylate. The filtration element may further comprise a mesh, one or more struts, and/or one or more purse strings. The system may be constructed to entrap emboli and/or embolic material, some of which may comprise a diameter of 10 microns. 
         [0035]    The filter system may further comprise a delivery configuration and a deployed configuration whereby said system may be delivered and deployed in a minimally invasive percutaneous manner. The system may also be retrieved from the vessel of a subject in a minimally invasive percutaneous manner. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0036]      FIG. 1A  illustrates the venous systems of the body, which along with arteries, arterioles, venules and capillaries, constitute the vascular system. 
           [0037]      FIG. 1B  illustrates a plan view of one embodiment according to the invention in use as it is inserted into the right femoral vein of a subject, the right femoral vein shown in “see-through” mode, and a portion of the invention illustrated schematically. 
           [0038]      FIG. 2A  illustrates one embodiment according to the invention in a side view and partial schematic as it is deployed in a vessel of a subject, the vessel and attendant structures shown in cross-section. 
           [0039]      FIG. 2B  illustrates an alternative embodiment according to the invention in a side view and partial schematic as it is deployed in a vessel of a subject, the vessel and attendant structures shown in cross-section. 
           [0040]      FIG. 2C  illustrates yet another embodiment according to the invention in a side view and partial schematic as it is deployed in a vessel of a subject, the vessel and attendant structures shown in cross-section. 
           [0041]      FIG. 3A  shows an alternative embodiment according to the invention in a side view as it is deployed in a vessel of a subject, the vessel shown in cross-section. 
           [0042]      FIG. 3B  shows an alternative embodiment according to the invention in a side view as it is deployed in a vessel of a subject, the vessel shown in cross-section. 
           [0043]      FIG. 3C  shows an alternative embodiment according to the invention in a side view as it is deployed in a vessel of a subject, the vessel shown in cross-section. 
           [0044]      FIG. 4A  illustrates an alternative embodiment according to the invention in a side view during a step of deployment in a vessel of a subject, the vessel shown in cross-section. 
           [0045]      FIG. 4B  illustrates an alternative embodiment according to the invention in a side view during a step in deployment of the device in a vessel of a subject, the vessel shown in cross-section. 
           [0046]      FIG. 4C  illustrates an end view of an embodiment according to the invention during a step in deployment of the device. 
           [0047]      FIG. 4D  illustrates an end view of an embodiment according to the invention during a later step in deployment of the device. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0048]      FIG. 1A  illustrates the major anatomical aspects of the human venous system. Via this natural system, deoxygenated blood is returned to heart  100  via inferior vena cava  105 , and oxygenated blood via pulmonary veins  102 . Below renal veins  110 , inferior vena cava  105  emerges from the convergence of the left and right common iliac veins  115 . Femoral veins  120  emerge upstream (distally) from the common iliac veins  115 , and long saphenous veins  125  also arise in this region. 
         [0049]    As shown in  FIG. 1B , each of the common iliac veins  151  arises from the confluence of the femoral veins  152  and the long saphenous veins  170 . Interventional catheter  155  may be placed into this system through femoral vein  152 , for example through the lumen of guide catheter  160  which may contain electrically conductive wires  161 . Through the lumen, catheter  155  may advance to, for example, the common iliac artery, and may deploy filter mechanism  180 . Distal end of catheter  155  may be used to deploy and to retrieve filtration device  180  as will be described in the pages to follow. Conductive wires  161  within interventional catheter  155  are in electrical communication with power unit  170 . 
         [0050]      FIGS. 2A ,  2 B and  2 C illustrate use of electrostatic charges imparted upon an electrically conductive filtration mesh in order to repel platelets and red blood cells, and to attract particles and other cells and materials bearing a net positive electrostatic charge. In  FIG. 2A , battery  257  has a negative pole connected to wire  256 , which runs through the core of interventional catheter  210 , and through struts  206 , which create a conductive contact with perimeter ring  220  and mesh  207 . The positive pole of battery  257  has resister  258  and is attached to an internal or external surface  250  of the body of the patient via electrode  255 . Endogenous insulating tissue  251  generally lies between the vein walls  222  and electrode  255 . As a result of this arrangement, a net negative charge may be imparted upon filter mesh  207 . This results in the trapping of electropositive particles, such as electropositively polymerized methacrylate  231 , but not in the entrapment of electronegative particles such as platelets and red blood cells. Struts  206 , perimeter ring  220  and mesh  207  may be made of conductive materials including, for example; stainless steel, titanium and chromium or nitinol. Blood flow is shown in this embodiment in direction  213 , although the principles apply to either flow direction. In an alternative embodiment, the opposite polarity is used, in which the filtration bears a positive charge and serves to attract negatively-charged particles, for example, electronegative fat components or methacrylate that has been prepared with an anionic polymerization compound. Methods are known in the art for imparting electrostatic charges on plastics, for example using techniques similar to those described by Peng et al 2006. Positively charged methacrylate may be prepared by emulsion polymerization, in which cationic element such as monomer methacryloyloxyethyltrimethylammonium chloride (METAC) is copolymerized with methacrylate. Alternatively, negatively charged PMMA may be produced using an anionic comonomer such as sodium 2-acrylamido-2-methylpropanesulphonate (NaAMPS). Such ionic copolymerization agents are non-toxic, and may alternatively be used to impart ionic charges on many thermoplastics, rubbery polymers, or their copolymers, including PMMA, polystyrene, polyacrylonitrile, and polybutadiene, and others. 
         [0051]    In  FIG. 2B , a similar configuration is shown, in which the positive pole is placed on filtration mesh  274 , while the negative pole is placed upon the body of the guide catheter  265 , thereby trapping electronegative particles  275 . Alternatively, negative electrode  265  may be placed in another intravascular location, such as upon interventional catheter  271 .  FIG. 2C  illustrates an embodiment in which filtration elements  287 ,  288 ,  289  and  290  are each imparted with either a negative or a positive charge. Filtration element  287  and  289  are positive, while filtration elements  288  and  290  are negative. Maintaining charge on each of these elements is accomplished by sending positive wire  282  and negative wire  283 , which pass through interventional catheter  286 , on the interior of guide catheter  285 , and originate from battery  280 , with positive wire  282  receiving current limited by resistor  281 . 
         [0052]      FIG. 3A  illustrates an embodiment of the present invention in which the filtration mesh  310  is deployed via guide catheter  326  and interventional catheter  325  from upstream of the targeted filtration site. Note direction of the blood flow  301 . Red blood cells  302  are able to pass through mesh  319 , as seen with red blood cells  304 , while large materials such as methacrylate particles  303  are trapped within the mesh as methacrylate particles  327 . The same principle applies for fat cells, which, like methacrylate; are larger than the red and white blood cells, and are trapped by a 20 micron or less vessel. Lumen margin  300 ; most often the endothelium of the vein in which the device is deployed; is shown with expansible lumen perimeter ring  305  fitting against lumen margin  300 . Filtration mesh  310  is delivered by interventional catheter  325 , which passes out from guide catheter  326 , and is held in place by flexible; expansible lumen perimeter ring  305 , which is held orthogonal to the flow of blood  301  by flexible cords  328 . Perimeter ring  305  may be made of materials including; as an example, polytetrafluoroethylene (PTFE). Cords may be made of materials including for example PTFE, nylon; and suture materials including Vicryl. Filtration mesh  310  may have perforations of approximately 10 to 30 microns in size, so as to allow passage of endogeneous blood cells and very small clumps, but not of fat cells, nor of methacrylate particles. Mesh  310  may also be made of materials including nitinol. Purse string  329  serves to collapse perimeter ring  305 , closing off mesh  310  to prevent escape of trapped particles as the device is received and removed from intravascular placement, typically at the end of a surgical procedure. 
         [0053]      FIG. 3B  illustrates an embodiment of the present invention in which filtration mesh  370  is deployed via guide catheter  376  and interventional catheter  375  from downstream of the targeted filtration site; by virtue of semi-rigid struts  377  (instead of flexible cords as seen in  FIG. 2A ). Note direction of blood flow  351 . Following deployment, filtration mesh  370 , fixed upon expansible lumen perimeter ring  355 , is held into an extended position by semi-rigid struts  377 . At the convergence of struts  377 , a latched or spring-actuated mechanism may be used to assist with the deployment and retrieval processes. The closure process may be facilitated via purse string  379 : 
         [0054]      FIG. 3C  illustrates an embodiment of the present invention in which semi-rigid struts  387  are used when mesh  351  is deployed downstream of blood flow  371 , (in a manner similar to that accomplished with flexible cords in  FIG. 3A ). Use of semi-rigid struts  387  can permit greater each of deployment and closure of perimeter ring  385  and mesh  351 , optionally without need for a purse string. 
         [0055]      FIG. 4A  illustrates an embodiment of the present invention in which the collapsed filtration mesh  410  surrounds the tip of interventional catheter  425 , after being pushed forward from the interior of guide catheter  426 . This embodiment also includes semi-rigid struts  407 .  FIG. 4B  illustrates the closure and retrieval of filtration mesh  466  in one embodiment of the present invention. Purse string  461  may be used to assist with the opening and collapse of struts  460 ; which differentially move at their vertex, which extends from interventional catheter  462 . Once collapsed, the apparatus may be withdrawn through guide catheter  476 . 
         [0056]    Alternatively, if the mesh  466 , ring  465  and struts  460  are too large; or too full of filtered debris  457 , they may be retracted through the incision following the removal of guide catheter  476 . 
         [0057]      FIG. 4C  illustrates mesh  481  and perimeter ring  480  along an end view; with trapped methacrylate or fat debris  482 .  FIG. 40  illustrates the same embodiment after purse string  487  has been pulled, closing perimeter ring  486 , and trapping within mesh  485  debris  488 . 
         [0058]    The various embodiments described above are provided by way of illustration only and should not be construed to limit the invention. Based on the above discussion and illustrations, those skilled in the art will readily recognize that various modifications and changes may be made to the present invention without strictly following the exemplary embodiments and applications illustrated and described herein. Such modifications and changes do not depart from the true spirit and scope of the present invention; which is set forth in the following claims.

Technology Category: 1