Filtration device and system and method for using same

Abstract

There is provided a filter device comprising: a tubular outer member; an inner member slidably disposed within the lumen of the outer member such that a distal end of the inner member extends distally from the outer member; and a plurality of tubular porous members including a first end attached to the outer member and a second end attached to the distal end of the inner member such that axial movement of the inner member relative to the outer member axially compresses or extends the porous members to expand and collapse the porous members. Beads or other filter media are provided within the porous member that are configured to adsorb or bind one or more reagents from the fluid passing through the porous member.

Description

[0001] Relevant application data This application claims the benefit of co-pending U.S. Provisional Application Serial No. 63 / 469,511, filed May 29, 2023, the entire disclosure of which is expressly incorporated herein by reference. Technical Field

[0002] This application relates generally to medical devices, and more specifically, to filtration devices for filtering one or more reagents (e.g., for filtering one or more chemotherapy and / or other therapeutic reagents delivered to a target treatment site to reduce systemic exposure) from blood flowing within the vascular system of a subject, and to systems and methods for using such devices. Background Technology

[0003] Cancer is currently the second leading cause of death in the United States and is projected to surpass cardiovascular disease as the leading cause of death within the next decade. Intravenous chemotherapy is a common procedure for treating various cancers. However, this chemotherapy can be dose-limited by the systemic toxicity of the chemotherapeutic agents delivered to the target treatment site. For example, doxorubicin (“Dox”), a commonly used chemotherapeutic agent, has toxicities including bone marrow suppression, gastrointestinal damage, and, most notoriously, irreversible heart failure.

[0004] To limit these systemic toxicities and further increase the dosage of chemotherapy for the cancer being treated, chemotherapeutic agents such as Dox can be administered directly intra-arterially into the blood vessels feeding on the tumor (e.g., within the liver or other organs). However, a significant percentage of the chemotherapeutic agent may cross the tumor and enter the patient's systemic venous circulation, exposing other areas of the patient's body to the agent.

[0005] Therefore, devices that minimize systemic exposure to chemotherapy or other therapeutic agents would be useful. Summary of the Invention

[0006] This application generally relates to medical devices, and more specifically, to filtration devices for filtering one or more reagents from blood flowing within the vascular system of a subject, and systems and methods for using such devices. For example, the devices described herein can be specifically used to filter one or more chemotherapeutic and / or other therapeutic agents delivered to a targeted treatment site (e.g., delivered to a blood vessel communicating with a tumor within the liver or other organs) to reduce systemic exposure.

[0007] According to one example, a filtration device is provided, comprising: a tubular outer member including a proximal portion, a distal portion sized for introduction into a body cavity, and a first lumen extending between an outlet in the distal portion and the proximal portion; an elongated inner member slidably disposed within the first lumen such that a distal end of the inner member extends from the outlet and a proximal end is positioned adjacent to the proximal portion; a plurality of tubular porous members including a first end attached to the distal portion of the outer member and a second end attached to the distal end of the inner member, such that axial movement of the inner member relative to the outer member causes axial compression or extension of the porous member to cause the porous member to expand and collapse; and a filter medium within the porous member configured to adsorb or bind one or more reagents from a fluid passing through the porous member.

[0008] According to another example, a filtration device is provided, comprising: a tubular outer member including a proximal portion, a distal portion sized for introduction into a body cavity, and a first lumen extending between an outlet in the distal portion and the proximal portion; an elongated inner member slidably disposed within the first lumen such that a distal end of the inner member extends from the outlet and a proximal end is positioned adjacent to the proximal portion; a tubular porous member including a first end attached to the distal portion of the outer member and a second end attached to the distal end of the inner member such that axial movement of the inner member relative to the outer member causes axial compression or extension of the porous member to cause the porous member to expand and collapse, the porous member being divided into a plurality of segments between the first and second ends; and a filter medium within the segments of the porous member configured to adsorb or bind one or more reagents from a fluid passing through the porous member.

[0009] According to another example, a method for filtering one or more reagents introduced into a target location is provided, the method comprising: introducing a filter member into a body cavity downstream of the target location, the filter member comprising a plurality of segments of porous material spaced axially from each other; and expanding the segments to allow blood flowing through the body cavity to pass through the porous material, thereby exposing the blood to a filter medium within the segments, thereby adsorbing or binding one or more reagents to the filter medium.

[0010] Other aspects and features of the invention will become apparent from the following description taken in conjunction with the accompanying drawings. Attached Figure Description

[0011] It is believed that the invention will be better understood through the following description of certain examples taken in conjunction with the accompanying drawings, wherein like reference numerals identify like elements, and wherein: Figure 1 This is a cross-sectional view of the liver, showing a pair of filtration devices located within the hepatic veins for filtering chemotherapy agents delivered to the liver to treat tumors.

[0012] Figure 2An example of a filtration device is shown, which includes a shaft carrying a filter element, the filter element comprising a tubular mesh having four axial segments containing a filter medium.

[0013] Figure 3A and Figure 3B They are Figure 2 Details of the filter components in the collapse and expansion configurations.

[0014] Figure 4A and Figure 4B Another example of a filter element for a filter device with a collapsed configuration and an expanded configuration is shown.

[0015] Figure 4C yes Figure 4B The cross-section of the expansion filter component taken at 4C-4C.

[0016] The accompanying drawings are not intended to be limiting in any way, and it is conceivable that various examples of the invention may be implemented in a variety of other ways, including those not necessarily depicted in the drawings. The accompanying drawings, which are incorporated in and form part of this specification, illustrate several aspects of the invention and, together with the specification, serve to explain the principles of the invention; however, it should be understood that the invention is not limited to the precise arrangement shown. Detailed Implementation

[0017] The following description of certain examples of the invention is not intended to limit the scope of the invention. Other examples, features, aspects, embodiments, and advantages of the invention will become apparent to those skilled in the art from the following description, which is illustrative and contemplated as one of the best modes for carrying out the invention. As will be appreciated, the invention can have other different and obvious aspects, all of which do not depart from the invention. Therefore, the drawings and description should be considered illustrative in nature, not restrictive.

[0018] Before describing the examples, it should be understood that the invention is not limited to the specific examples described, and of course, these examples can vary. It should also be understood that the terminology used herein is for the purpose of describing specific examples only and is not intended to be limiting, as the scope of the invention will be limited only by the appended claims.

[0019] If a range of values ​​is provided, it should be understood that, unless the context explicitly specifies otherwise, every intermediate value between the upper and lower limits of that range, down to one-tenth of the lower limit unit, is also specifically disclosed. Every smaller range between any specified value or intermediate value within the specified range and any other specified value or intermediate value within that range is covered by this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range, and each smaller range in which one limit is included, two limits are included, or neither limit is included is also covered by this invention, subject to any specifically excluded limits within the specified range. Where a specified range includes one or two limits, this invention also includes ranges that exclude one or both of these included limits.

[0020] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although any methods and materials similar to or equivalent to those described herein may be used in the practice or testing of this invention, some potential and exemplary methods and materials are described hereafter.

[0021] It must be noted that, unless the context clearly specifies otherwise, the singular forms “a,” “an,” and “the” used herein and in the appended claims include plural references. Thus, for example, reference to “compound” includes a plurality of such compounds, and reference to “polymer” includes reference to one or more polymers and their equivalents known to those skilled in the art, and so on.

[0022] This document presents certain ranges, with the numerical values ​​preceded by the term "approximately". The term "approximately" is used in this document to provide textual support for the exact numbers that follow it, as well as numbers that are close to or approximate to the numbers following the term. In determining whether a number is close to or approximate to a specifically cited number, a close or approximate uncited number may be a number that provides a quantity substantially equal to the specific cited number in its presented context.

[0023] In some aspects of this disclosure, an in vivo localizable filtration device is provided that filters one or more therapeutic and / or diagnostic reagents from blood flowing in a blood vessel. The filtration device generally includes a catheter or other elongated member and a filter element coupled to the elongated member, the filter element being sized to be positioned within a blood vessel of a human or non-human subject. The filter element includes one or more tubular porous members containing a filter medium configured to filter one or more therapeutic reagents from the blood.

[0024] The filter medium may include materials that filter one or more therapeutic agents from the blood. For example, the therapeutic agents may include chemotherapy agents (such as Dox) and / or non-chemotherapy agents.

[0025] It should be understood that the term "therapeutic agent" is used extensively herein and may include therapeutic particles. Furthermore, references to "filtration of the therapeutic agent" are used extensively herein and cover the filtration of therapeutic particles. For example, particles may include free chemotherapy (or non-chemotherapy) molecules, or chemotherapy (or non-chemotherapy) loaded molecules (e.g., chemotherapy molecules bound to particles such as drug eluting resins or drug-eluting activated charcoal). Exemplary therapeutic agents may include chemotherapy agents; vasoactive agents such as verapamil, nicardipine, or milrinone; sodium tetradecyl sulfate (Sotradecol, Angiodynamics, or BioNiche Pharmaceuticals); bleomycin; X-ray or MRI contrast agents; antibiotics; dissolving agents (e.g., and thrombolytic drugs such as tPA). In some examples, particles may include unseasoned particles. Particles may include, for example, particles that block blood vessels in cancerous tissue or other diseased tissue. In some cases, particles may include polymers, adhesives, resins, activated carbon, or glass. In some examples, particles may be bound to radioactive isotopes, such as radiotherapy particles.

[0026] Filter media may include materials having properties of adsorbing, binding, capturing, or inactivating or degrading one or more therapeutic agents. For example, in some examples, filter media may include beads or other particles that adsorb, bind, capture, inactivate, and / or degrade therapeutic agents. Additional information relating to filter materials that may be included in the filtration devices described herein can be found in U.S. Patent Nos. 11,406,485 and 11,554,003, the entire disclosure of which is expressly incorporated herein by reference.

[0027] As described elsewhere in this document, in some examples, the filter media can remove therapeutic agents from the blood by adsorbing or binding them. For example, the filter media may have the property of being a magnetic carrier that adsorbs, chemically binds, and / or magnetically binds therapeutic agents without significantly binding or filtering endogenous entities in the blood. The binding between the filter media and the therapeutic agent can be irreversible or weakly reversible. Thus, the therapeutic agent can be collected by the filter media and removed from the blood, for example, when the filter is removed.

[0028] In one example, the filter medium includes a resin having the properties of adsorbing therapeutic agents, chemically binding therapeutic agents, and / or magnetically binding therapeutic agents bound to a magnetic carrier. Exemplary filter materials include resins having the properties of adsorbing and / or chemically binding therapeutic agents (such as doxorubicin), and may include strong acid cation exchange polymer resins; ion exchange resins; non-ion exchange polymer adsorption resins; resins including sulfonate groups ion-bound to therapeutic agents; chromatography-based resins; chromatography-based resins, including resins composed of polyacrylamide, polyacrylic acid, sodium acrylate, or even vinyl copolymers, or any combination thereof. Optionally, such resin may be incorporated into or incorporated thereon into other materials of the porous membrane or filter element, such as those formed from polymers or fabrics, such as Nafion (DuPont), Neosepta, CMI-7000 (Membranes International), and IONAC membranes (Sybron Chemicals).

[0029] In one example, a strong acid cation exchange polymer resin can be used for mildly positively charged drugs, such as Dox. Other examples of compounds that chemically or physically (via adsorption) bind therapeutic agents (such as doxorubicin) may include calsequestrin; cyclic oligosaccharides, such as cyclodextrins, including gamma-cyclodextrin; hNopp140; antibodies that specifically bind to the agent, such as an anti-doxorubicin monoclonal antibody (MAD 11); nucleolar phosphoproteins; Clostridium botulinum neurotoxin B; cell membrane lipids, such as cardiolipin, phosphatidylserine, and phosphatic acid; nucleic acid ligands, the so-called "aptamers," including RNA and DNA; albumin; and hemoglobin.

[0030] In other examples, various other types of ion exchange resins can be used, including weak acid cation exchange, weak base anion exchange, strong base anion exchange, etc. For example, in one example, a strong base anion exchange resin can be used for negatively charged drugs (such as heparin).

[0031] Factors such as resin functional groups and porosity / crosslinking, solution temperature, pH, concentration, and ionic strength can affect the effectiveness of resin-bound therapeutic agents. For example, in some cases, cyanogen bromide-activated resins can be used to attach functional groups. In some cases, low-crosslinked versions of these resins, such as 3% or lower, including 2% or lower, can be used. Alternatively, higher-crosslinked versions can be used if desired.

[0032] In some examples, the filter medium may include carbon combined with therapeutic agents, such as activated carbon (e.g., charcoal or activated charcoal). For example, the effectiveness of activated carbon may vary depending on factors such as pore size, shape, surface area, ash content, and hardness. In some cases, the carbon may be coated with an additional resin material. Furthermore, carbon and resin are inexpensive and can be used in small quantities while still being effective. While larger amounts may be implemented in some cases, example amounts of carbon and resin (e.g., 10 grams or less, such as 5 grams or less, and including 1 gram or less) can be implemented and are effective.

[0033] Exemplary resins used in the filtration devices described herein may include one or more of the following: HepaSphere, QuadraSphere, and Dowex 50W-X2; Dowex 50W-X4; Dowex 50W-X8; Biorad AG50W-X2; Biorad AG50W-X4; Biorad AG50W-X8; GE Sepharose Big Beads; Amberlite XAD-2; Tosoh Toyopear MegaCap II; Purolite PAD 600; and Purolite CGC100X2. Exemplary carbons used in the filtration devices may include one or more of the following: Norit C Gran; Calgon TOG NDS 20×50; and QUO-YC-1041.

[0034] In some examples, the filter media may include materials that improve biocompatibility, such as polymethyl-methacrylate (PMMA), chitosan, heparin, etc. In some cases, for example, the resin or carbon of the filter media may be coated or otherwise impregnated with PMMA, chitosan, and / or heparin. Exemplary coating methods can be found in U.S. Publication No. 2010 / 0316694, the entire disclosure of which is expressly incorporated herein by reference.

[0035] In some examples, the filter media can filter therapeutic agents from the blood by inactivating or otherwise degrading the therapeutic agent or its toxicity. For example, the filter media may include catalytic materials, such as immobilized (covalent or non-covalent) enzymes, which, for example, enzymatically degrade the therapeutic agent to reduce its toxicity level. For example, the enzymatic degradation and inactivation of Dox can occur via cleavage of its glycoskeleton by glycosidases contained in the liver.

[0036] In other examples, therapeutic agents administered to patients can be pretreated by covalently or non-covalently associating the compound with magnetic particles, such as magnetic nanoparticles. Therefore, the filter medium can include a magnetic material such that, after treatment, the magnetically bound therapeutic particles can be attracted by the magnetic material of the filter medium.

[0037] In other examples, the filter media may include a basic mechanical sieve filter that captures a variety of particles commonly used for embolizing tumors, such as resin-based particles like DC beads (DC Beads) and LC beads (LC Beads) (ion exchange resins), QuadraSpheres and HepaSpheres (sodium acrylate and vinyl copolymer resins), EmboSpheres (triacrylate resins), Bead Blocks and Cotonour Beads (polyvinyl alcohol resins), Onyx (ethylene vinyl copolymer, EVOH), TruFill or Histacryl (n-butyl cyanoacrylate (nBCA) compounds), embolization coils, or activated carbon particles. These particles may or may not be loaded with therapeutic agents that would elute within the tumor. In these examples, the filter media can capture these particles from the departing venous bloodstream to prevent their deposition in non-target organs. Furthermore, the filter media may also include a chemically based binding filtration mechanism to filter free drugs from the blood.

[0038] The reduction in toxicity levels may vary depending on the selected filter media, therapeutic agent, and specific filtration device configuration. In some examples, the reduction in toxicity levels may be in the range of 50% or greater, 75% or greater, or 90% or greater.

[0039] In some examples, the filter element may include one or more porous membranes, for example, containing resin beads or other filter media within the interior of the membrane(s). For example, the filter media may include a plurality of beads loosely dispersed within the porous membrane, such that the beads can move freely within the membrane when the filter element is deflected and / or deformed (e.g., expanded and collapsed), so that the beads do not impede the movement and / or manipulation of the filter element. The porosity of the membrane(s) may vary, but should be sufficient to allow blood to pass through it while preventing the beads or other filter media from escaping from the membrane(s). In one example, the porosity of the membrane(s) may be selected based on the size of the therapeutic agent particles, for example, to enhance the capture of therapeutic particles. Exemplary pore sizes may range from as small as forty micrometers to as large as three hundred micrometers, but other pore sizes may be implemented if desired.

[0040] In some examples, one or more porous membranes may be configured to allow blood to pass through openings in the membranes and encounter the filter medium. The membranes may be made of a variety of materials, such as fabrics, plastics, polymers, silicones, metals, metal alloys, and the like, but should allow blood to pass through.

[0041] In one example, the membrane(s) may be formed as a tubular porous member from multiple fibers woven into a tubular mesh structure, which is configured to contain a filter medium. The number of fibers may be sufficient to provide openings smaller than the filter medium, for example, while maintaining the flexibility of the filter member to facilitate introduction through tortuous anatomical structures. The resulting tubular mesh structure may be flexible enough to allow the filter membrane to be introduced into the patient (e.g., into tortuous anatomical structures within the patient's vascular system) and to facilitate guiding the filter member between collapsed and expanded configurations, for example, through axially extended and compressed mesh structures at opposite ends, as further described elsewhere herein.

[0042] Alternatively, the material of the tubular mesh structure can be biased to an expanding or collapsing configuration (e.g., by incorporating shape memory in the fiber material), while allowing the structure to expand and collapse during use. In a particular example, the tubular mesh structure can be formed from multiple axially inelastic fibers, such as metals (e.g., nitinol), plastics (e.g., polyester), and / or composite materials. In various examples, the tubular mesh structure may include about eight to two hundred and eighty-eight (8-288) fibers, about twenty-four to one hundred and forty-four (24-144) fibers, or about sixty-four (64) fibers.

[0043] Optionally, the membrane material itself may include materials having properties of adsorbing, binding, capturing, inactivating, or degrading (one or more) therapeutic agents, such as coatings and the like. For example, the membrane material may be formed, coated, and / or impregnated with resin, carbon, or other materials similar to those described elsewhere regarding filter media.

[0044] Switch to the attached image. Figure 1 An example of a patient's liver 90, including a tumor 92, is shown. Typically, a filtration device 10 can be introduced into the patient's vascular system to position a porous filtration element 40 at a location to filter one or more therapeutic agents delivered to the liver 90 to treat the tumor 92. For example, as shown, two filtration devices 10 have been introduced via the vena cava 96 to position the filtration element 40 in a corresponding hepatic vein 94, for example, to filter (one or more) therapeutic agents from the blood flowing from the liver 90 through the hepatic vein 94. While the filtration devices described herein may be specifically used for filtering agents delivered to the liver, it should be understood that the filtration devices described herein can be introduced into other organs or locations downstream of the target treatment site within the patient's vascular system to filter (one or more) agents delivered to the treatment site, thereby minimizing the patient's systemic exposure to (one or more) agents.

[0045] In some examples, the filter device 10(s) may include a conduit 20, wherein a filter element 40 is disposed at the distal end 24 of the conduit 20, such as Figure 1 As shown. The catheter 20 can be configured to fit various diameters of blood vessels of various sizes. For example, for smaller veins (such as renal veins or hepatic veins), the catheter 20 can include an outer diameter between about eight and fourteen millimeters (8-14 mm), while for larger veins (such as venous lumens), the outer diameter can be between about twenty and thirty millimeters (20-30 mm).

[0046] Optionally, any filtering device described herein may be included in a system comprising one or more additional components, such as one or more sheaths, guidewires, and the like (not shown). For example, a system described herein may include a delivery sheath sized to receive the filtering device for intravascular delivery and retrieval of the filtering device.

[0047] Go to Figure 2An example of a filtration device 110 is shown, comprising a conduit or other tubular external member 120, an elongated internal member 130, and a filtration member 140. The external member 120 includes a proximal portion or proximal end 122, a distal portion or distal end 124 sized for insertion into a body cavity, and a first lumen 126 extending between the proximal and distal portions 122 and 124, thereby defining a longitudinal axis 128. The external member 120 may have a substantially uniform configuration between the proximal and distal ends 122 and 124. Alternatively, the configuration may vary along the length of the external member 120 (e.g., between the proximal, intermediate, and distal portions) to provide desired properties. For example, the external member 120 may include a proximal portion adjacent to the proximal end 122, which may be substantially rigid or semi-rigid, for example, providing sufficient column strength to allow the distal end 124 (and the filter member 140 thereon) to be pushed or otherwise manipulated from the proximal end 122, while the distal portion may be substantially flexible to accommodate bending and / or introduce tortuous anatomical structures. Alternatively, the external member 120 may include one or more reinforcing members, for example, multiple reinforcing fibers (not shown), such as multiple fibers woven or spirally wound and / or embedded within the wall of the external member 120 along a desired length (e.g., along at least the distal portion) to prevent buckling or kinking during advancement through tortuous anatomical structures.

[0048] The internal member 130 is slidably disposed within the first lumen 126 such that the proximal end 132 of the internal member 130 extends from (or is otherwise positioned adjacent to) the proximal end 122 of the external member 120, and the distal end 134 of the internal member 130 extends from the outlet 125 in the distal end 124 of the external member 120. The internal member 130 may be a solid or hollow wire or other elongated member configured to slide freely within the lumen 126 of the external member 120. Optionally, the internal member 130 may include a lumen (not shown) extending between the proximal end 132 and the distal end 134, for example, for receiving a guidewire or other track (not shown) to facilitate the introduction of the filter device 110. Optionally, the internal member 130 may include a rounded and / or other non-invasive distal end on the distal end 134, for example, to prevent the distal end 134 from penetrating or otherwise damaging the body cavity wall in which the filter device 110 is introduced.

[0049] The filter element 140 includes a tubular porous element 142, which includes a first end 144 attached to a distal end 124 of an outer element 120 and a second end 146 attached to a distal end 134 of an inner element 130. Therefore, axial movement of the outer element 120 relative to the inner element 130 can axially compress or extend the porous element 142, for example, causing the porous element 142 to expand and collapse, as further described elsewhere herein. A filter medium 160 may be contained within the porous element 142, for example, a plurality of beads configured to adsorb or bind one or more reagents from a fluid passing through the porous element 142, also as further described elsewhere herein.

[0050] In one example, the porous member 142 is formed of multiple fibers woven into a tubular mesh structure, wherein opposite ends of the fibers define a first end 144 and a second end 146. The first end 144 and the second end 146 of the porous member 142 can be permanently attached to the distal end 124 of the outer member 120 and the distal end 134 of the inner member 130, respectively. For example, ferrules, heat shrink tubing, and the like can be positioned around and attached to the ends 144, 146 to secure them to the outer member 120 and the inner member 130. Alternatively or additionally, the ends 144, 146 can be attached by adhesive bonding, ultrasonic welding, melting, and one or more of the like. Alternatively or additionally, if the fibers are formed of plastic or other flowable materials, the ends of the fibers can be directly melted or otherwise melted to the outer member 120 and the inner member 130.

[0051] like Figure 3A and Figure 3B As best shown, the porous member 142 can be divided into a plurality of segments 149 axially spaced between a first end 144 and a second end 146. For example, the porous member 142 may include one or more waist or constriction regions 148 between the first end 144 and the second end 146, which are fixed such that the regions 148 cannot expand radially. In the example shown, the porous member 142 includes four segments 149 separated by three waist regions 148, but it should be understood that, if desired, the porous member 142 may include any desired number of segments, such as two, three, four, five, six or more (and a corresponding number of fewer than one waist region). In the example shown, the waist regions 148 are substantially uniformly spaced such that the segments 149 have substantially the same length. Alternatively, if desired, the segments 149 may have one or more different lengths.

[0052] In one example, each waist region 148 may include a collar, ring, heat-shrink wrap, or other material positioned around and permanently secured to the porous member 142. Alternatively, if the material of the porous member 142 is flowable, it may be melted or otherwise modified to melt the fibers at the waist region 148, thereby preventing their movement, and / or an adhesive or other material may be applied to melt the fibers at the waist region 147, thereby limiting the expansion of the waist region 148. The dimensions of the waist region 148 may allow the lower layer material of the porous member 142 to slide freely over the inner member 130 while preventing expansion of the confined area of ​​the porous member 142, for example, when the outer member 120 / inner member 130 is guided proximally relative to each other.

[0053] Optionally, one or more markings (not shown) may be provided on one or more of the outer member 120, the inner member 130, and / or the filter member 140. For example, radiopaque markings may be provided on or near the first end 144 and the second end 146 of the porous member 142, and on each of the waist regions 148. This may facilitate monitoring of the filter member 140 using external imaging (such as fluorescence fluoroscopy) during introduction and / or expansion. The markings may be separate loops, lines, or other radiopaque materials attached to or embedded in the desired location, and / or the radiopaque material may be included in the material of the distal end 124 of the porous member 140 and / or the outer member 120 and the distal end 134 of the inner member 130.

[0054] Further reference Figure 2 A hub or handle 150 may be provided on the proximal end 122 of the outer member 120, for example, configured and / or sized to hold and / or operate the filter device 110 from the proximal end 122. Optionally, one or more seals (not shown) may be provided on or within the hub 150, for example, around the inner member 130, to accommodate axial movement of the inner member 130 relative to the outer member 120, while preventing fluid within the lumen 126 from escaping from the hub 150 and / or external air from entering the lumen 126. For example, as shown, the hub 150 may include a Tuohy-Borst valve. Optionally, the proximal end 132 of the inner member 130 may include a hub or handle (not shown), for example, to facilitate holding or operating the inner member 130 relative to the outer member 120.

[0055] Alternatively, an actuator (not shown) may be provided on a hub or handle 150 coupled to the proximal end of the inner member 130. In this alternative, the proximal end of the inner member 130 may terminate within the hub or handle 150, rather than extending proximally from the outer member 120. For example, a slider or rotary dial (not shown) on the hub 150 may be coupled to the inner member 130, and this slider or rotary dial may be guided in the opposite direction to guide the inner member 130 proximally or distally relative to the outer member 120.

[0056] Optionally, one or more ports (not shown) may be provided on the hub 150 (or handle). For example, a side port (not shown) communicating with the lumen 126 may be provided on the hub 150, for example, for delivering one or more fluids into the lumen 126 surrounding the inner member 130. Alternatively, in an alternative where the inner member terminates within the hub or handle, an axial port may be provided opposite the proximal end 122 of the outer member communicating with the lumen 126, for example, to allow a guidewire or other instrument to pass through the hub or handle and the lumen 126. Optionally, the axial port may include one or more valves (e.g., hemostatic valves (also not shown)) that provide a substantially fluid-impermeable seal while accommodating the insertion of one or more instruments into the lumen 126.

[0057] Further reference Figure 3A and Figure 3B The outer member 120 and the inner member 130 may be axially guided relative to each other to allow the filter member 140 to selectively expand or collapse. For example, the filter device 110 may initially be provided with Figure 3A The porous member 142 (and segment 149) in the collapsed configuration shown, and the outer member 120 can be guided distally relative to the inner member 130 (or conversely, the inner member 130 is guided proximally), thereby causing the porous member 142 to be axially compressed, thereby causing the segment 149 to expand radially outward. Figure 3B The expansion configuration is shown. When needed, the outer member 120 can be guided proximally, thereby axially extending the porous member 142 to guide segment 149 back. Figure 3A The collapse configuration shown.

[0058] Optionally, the outer member 120 and / or the inner member 130 may include one or more stops (not shown) configured to restrict axial movement of the outer member 120 and the inner member 130 relative to each other. For example, a distal stop may be provided to restrict distal movement of the outer member 120 relative to the inner member 130 to prevent excessive axial compression of the porous member 142. Similarly, a proximal stop may be provided to restrict proximal movement of the outer member 120, thereby limiting axial extension of the porous member 142 to prevent excessive tension on the fibers of the porous member 142.

[0059] During use, similar to Figure 1 The illustrated device 10, with its filtration device 110, can be used to filter one or more therapeutic agents within a body cavity, such as filtering chemotherapy agents delivered to the liver 90 to treat tumor 92. For example, when the filtration member 140 is in... Figure 3A In the case of the collapsed configuration shown, the filter device 110 can be introduced into the patient's vascular system and advanced to the desired location, such as downstream of the target treatment area. For example, similar to Figure 1 The device 10 shown can be manipulated to position the distal end 134 of the internal member 130 within the hepatic vein 94 downstream of the tumor 92, thereby positioning the filter member 140 within the hepatic vein 94 downstream of the tumor 92.

[0060] Optionally, one or more additional instruments (not shown) may be used to enter the body cavity. These instruments may be part of a system or kit that includes the filter device 110, such as one or more guide sheaths, guide catheters, and / or guidewires (not shown). For example, a guidewire or other track (not shown) may be introduced from other entry sites created percutaneously, by incision, or at a peripheral location (not shown), and the guidewire may be advanced from the entry site through the patient's vascular system, either alone or with the aid of a guide catheter (not shown). For example, the distal end of the guide catheter (not shown) may be advanced over the guidewire to the desired location, and then the guide catheter may be used with the filter device 110, for example, over the guidewire or after the guidewire has been removed.

[0061] Once the distal end 134 is positioned as desired, the external member 120 can be advanced distally to guide the filter member 140 into the expanded configuration, for example, as Figure 3B As shown. Alternatively, external imaging can be used to monitor positioning and expansion, such as using fluorescence imaging to identify markings on the filter device 110, as described elsewhere herein.

[0062] Once the filter element 140 is correctly positioned and expanded, one or more therapeutic agents can be delivered to the target treatment site using conventional methods, such as delivery to... Figure 1 The liver 90 is shown in the image. Blood passing through the treatment site (e.g., entering...) Figure 1 The hepatic artery 94 shown (and any reagents carried in the blood) can encounter the expanded filter member 140, thereby entering the opening in the porous member 142 to allow the filter medium 160 to filter reagents from the blood.

[0063] After stopping the delivery of the treatment agent and allowing sufficient time, the external component 120 can be guided proximally to guide the filter component 140 back to the collapsed configuration. The filter device 110 can then be removed, and the procedure can be completed using conventional methods.

[0064] Go to Figure 4A and Figure 4B The diagram illustrates another example of a filter device 210, which is constructed in a manner generally similar to filter device 110, comprising an outer component 220, an inner component 230, and a filter component 240. Unlike filter device 110, filter component 240 comprises a plurality of tubular porous components 242 containing filter media 260 attached to the outer component 220 and the inner component 230.

[0065] As shown in the figure, each tubular porous member 242 includes a first end 244 attached to the distal end 224 of the outer member 220 and a second end 246 attached to the distal end 234 of the inner member 230. The first end 244 and the second end 246 of the porous member 242 are spaced apart from each other around the circumference of the distal ends 224, 234 of the outer member 220 and the inner member 230, such that the porous member 242 abuts against the outer wall of the inner member 230 between the first end 244 and the second end 246. Therefore, the inner member 230 is retained outside the interior of the porous member 242, and the porous members 242 are spaced apart from each other around the circumference of the inner member 230, as shown in the figure. Figure 4C As best illustrated herein. In one example, each porous member 242 may be formed by weaving multiple fibers into a tubular mesh structure, or otherwise formed to have the desired pore size, as described elsewhere herein.

[0066] exist Figure 4C In the example shown, the filter device 210 includes four porous members 242 that are substantially evenly spaced around the internal member 230. It should be understood that any desired number of porous members 242 can be provided, such as two, three, four, five, six or more.

[0067] Furthermore, each porous member 242 includes a plurality of axial segments 249 spaced apart between a first end 244 and a second end 246. For example, one or more waist regions 248 may be provided along the length of the porous member 242, such as the three waist regions 249 shown, providing four segments 249 for each of the porous members 242. For example, similar to the previous example, ferrules, rings, heat-shrink wraps, and the like may be attached around the porous member 242 to create the waist regions 248 at the same location on all the porous members 242. Alternatively or additionally, the porous member 242 may be secured at the waist regions by adhesive bonding, melting, sonic welding, and the like. The waist regions 248 may allow the porous member 242 to slide over the inner member 230, for example, such that only the first end 244 and the second end 246 of the porous member 242 are secured relative to the outer member 220 and the inner member 230.

[0068] Therefore, similar to the filter device 110, the axial movement of the inner member 230 relative to the outer member 220 can simultaneously axially compress or extend the porous member 242, causing the porous member 242 to expand and collapse. For example, as Figure 4A As shown, the filter device 210 can be provided with a porous member 242 in a collapsed configuration, for example, wherein sufficient tension is applied to the fibers or other web structure of the porous member 242 to maintain the porous member in close proximity to the inner member 230, thereby minimizing the outer cross-section of the filter member 240. Once introduced and positioned as desired, the outer member 220 can be advanced distally relative to the inner member 230 (or the inner member can be guided proximally) to axially compress the porous member 242 and cause the segment 249 to expand radially outward into an expanded configuration, such as... Figure 4B and Figure 4C As shown. After filtering one or more therapeutic agents using the filter device 210, the filter element 240 can be restored to its original state. Figure 4A The collapsed configuration shown is removed from the patient, similar to other devices described herein.

[0069] For illustrative and descriptive purposes, various examples of the above disclosure have been presented. It is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Many variations and modifications of the embodiments described herein will be apparent to those skilled in the art based on the above disclosure.

[0070] Furthermore, in describing representative embodiments, the specification may have presented methods and / or processes as a specific sequence of steps. However, the method or process should not be limited to the specific sequence of steps described herein, where the method or process does not depend on the specific sequence of steps. Other sequences of steps are possible, as will be understood by those skilled in the art. Therefore, the specific sequence of steps set forth in the specification should not be construed as a limitation of the claims.

[0071] While the invention is readily adaptable to various modifications and alternatives, specific examples have been shown in the accompanying drawings and described in detail herein. However, it should be understood that the invention is not limited to the particular forms or methods disclosed, but rather encompasses all modifications, equivalents, and alternatives falling within the scope of the appended claims.

Claims

1. A filtration device comprising: A tubular external member comprising a proximal portion, a distal portion sized for introduction into a body cavity, and a first lumen extending between an outlet in the distal portion and the proximal portion; An elongated internal member is slidably disposed within the first lumen such that the distal end of the internal member extends from the outlet and the proximal end is positioned adjacent to the proximal portion; A plurality of tubular porous members, each including a first end attached to the distal portion of the outer member and a second end attached to the distal end of the inner member, such that axial movement of the inner member relative to the outer member causes axial compression or extension of the porous member to cause the porous member to expand and collapse. and The filter medium within the porous member is configured to adsorb or bind one or more reagents from the fluid passing through the porous member.

2. The filtering device according to claim 1, wherein the porous member comprises a plurality of segments axially spaced apart from each other between the first end and the second end.

3. The filtration device according to claim 2, further comprising one or more waist regions that divide the porous member into the plurality of segments.

4. The filtering device according to claim 3, wherein one or more waist regions are slidable over the internal member, such that the porous member slides freely over the internal member between the first end and the second end.

5. The filtration device according to any one of claims 2-4, wherein the one or more waist regions include a single waist region that divides the porous member into two segments between the first end and the second end.

6. The filter device according to any one of claims 2-4, wherein the one or more collars include two waist sections that divide the porous member into three segments between the first end and the second end.

7. The filter device according to any one of claims 2-4, wherein the one or more collars include three waist regions that divide the porous member into four segments between the first end and the second end.

8. The filtration device according to any one of claims 1-4, wherein each of the porous components comprises a plurality of fibers woven together between the first end and the second end.

9. The filtration device according to claim 8, wherein the fiber comprises nickel-titanium.

10. The filtration device of claim 8, wherein the fibers are woven to define an opening smaller than the cross-section of the filter medium contained within the porous member.

11. The filtration device according to any one of claims 1-4, wherein the porous member comprises a mesh defining an opening smaller than the cross-section of the filter medium contained within the porous member.

12. The filtration device according to any one of claims 1-4, wherein the internal component includes a second lumen extending between an outlet in the distal end and the proximal end.

13. The filtering device according to any one of claims 1-4, further comprising a hub on the proximal portion of the outer member, wherein the proximal end of the inner member extends proximally from the hub such that the inner member is axially slidable relative to the hub.

14. The filtering device of claim 13, further comprising a seal that at least partially surrounds the internal component within the hub.

15. The filtering device according to any one of claims 1-4, further comprising a handle on the proximal portion of the outer member and an actuator on the handle, the actuator being coupled to the proximal end of the inner member such that movement of the actuator causes axial movement of the inner member relative to the outer member.

16. The filtration device according to any one of claims 1-4, wherein the filter medium comprises resin beads.

17. The filtration device of claim 16, wherein the resin beads are configured to adsorb or chemically bind one or more chemotherapeutic agents.

18. The filtration device of claim 16, wherein the resin beads comprise one or more of the following: ion exchange resin, strong acid cation polymer resin, non-ion exchange polymer adsorption resin, and one or more sulfonic acid groups ion-bound to the one or more chemotherapeutic agents.

19. The filtration device of claim 16, wherein the resin beads are coated with one or more of heparin, polymethyl methacrylate and chitosan.

20. A filtration device comprising: A tubular external member comprising a proximal portion, a distal portion sized for introduction into a body cavity, and a first lumen extending between an outlet in the distal portion and the proximal portion; An elongated internal member is slidably disposed within the first lumen such that the distal end of the internal member extends from the outlet and the proximal end is positioned adjacent to the proximal portion; A plurality of tubular porous members, including a first end attached to the distal portion of the outer member and a second end attached to the distal end of the inner member, and a plurality of segments axially spaced between the first end and the second end, such that axial movement of the inner member relative to the outer member causes the porous member to be axially compressed or extended, causing the segments to expand and collapse. and The filter medium within the segment of the porous member is configured to adsorb or bind one or more reagents from the fluid passing through the porous member.

21. A filtration device comprising: A tubular external member comprising a proximal portion, a distal portion sized for introduction into a body cavity, and a first lumen extending between an outlet in the distal portion and the proximal portion; An elongated internal member is slidably disposed within the first lumen such that the distal end of the internal member extends from the outlet and the proximal end is positioned adjacent to the proximal portion; A tubular porous member comprising a first end attached to the distal portion of the outer member and a second end attached to the distal end of the inner member, such that axial movement of the inner member relative to the outer member causes axial compression or extension of the porous member to cause the porous member to expand and collapse, the porous member being divided into a plurality of segments between the first end and the second end. and The filter medium inside the segment of the porous member is configured to adsorb or bind one or more reagents from the fluid passing through the porous member.

22. The filtration device of claim 21, wherein the porous member includes one or more non-expandable waist regions that divide the porous member into the plurality of segments.

23. The filtration device of claim 22, further comprising one or more collars, rings, or materials attached around the porous member to define the one or more waist regions.

24. The filtering device of claim 22, wherein one or more waist regions are slidable over the internal member, such that the porous member slides freely over the internal member between the first end and the second end.

25. The filtration device according to any one of claims 22-24, wherein the one or more waist regions include a single waist region that divides the porous member into two segments between the first end and the second end.

26. The filtration device according to any one of claims 22-24, wherein the one or more waist regions include two waist regions that divide the porous member into three segments between the first end and the second end.

27. The filtration device according to any one of claims 22-24, wherein the one or more waist regions comprise three waist regions that divide the porous member into four segments between the first end and the second end.

28. The filtration device according to any one of claims 21-24, wherein the porous member comprises a plurality of fibers woven together between the first end and the second end.

29. The filtration device of claim 28, wherein the fiber comprises nitinol.

30. The filtration device of claim 28, wherein the fibers are woven to define an opening smaller than the cross-section of the filter medium contained within the porous member.

31. The filtration device according to any one of claims 21-24, wherein the porous member comprises a mesh defining an opening smaller than the cross-section of the filter medium contained within the porous member.

32. The filtration device according to any one of claims 21-24, wherein the internal component includes a second lumen extending between an outlet in the distal end and the proximal end.

33. The filtering device according to any one of claims 21-24, further comprising a hub on the proximal portion of the outer member, wherein the proximal end of the inner member extends proximally from the hub such that the inner member is axially slidable relative to the hub.

34. The filtering device of claim 33, further comprising a seal that at least partially surrounds the internal component within the hub.

35. The filtering device according to any one of claims 21-24, further comprising a handle on the proximal portion of the outer member and an actuator on the handle, the actuator being coupled to the proximal end of the inner member such that movement of the actuator causes axial movement of the inner member relative to the outer member.

36. The filtration device according to any one of claims 21-24, wherein the filter medium comprises resin beads.

37. The filtration device of claim 36, wherein the resin beads are configured to adsorb or chemically bind one or more chemotherapeutic agents.

38. The filtration device of claim 36, wherein the resin beads comprise one or more of the following: ion exchange resin, strong acid cation polymer resin, non-ion exchange polymer adsorption resin, and one or more sulfonic acid groups ion-bound to the one or more chemotherapeutic agents.

39. The filtration device according to claim 36, wherein the resin beads are coated with one or more of heparin, polymethyl methacrylate and chitosan.

40. The filtration device according to any one of claims 21-24, wherein the porous member surrounds the internal member between the first end and the second end.

41. A method for filtering one or more reagents introduced to a target location, comprising: A filter element is introduced into a body cavity downstream of the target location, the filter element comprising multiple segments of porous material spaced axially apart from each other; The segment is expanded to allow blood flowing through the body cavity to pass through the porous material, thereby exposing the blood to a filter medium within the segment, which adsorbs or binds the one or more reagents to the filter medium.

42. The method of claim 41, wherein the filter member comprises a plurality of tubular porous membranes, the tubular porous membranes comprising opposite ends attached to an inner member and an outer member, and wherein expanding the segment comprises axially moving the other of the inner member and the outer member relative to one of the inner member and the outer member to axially compress the porous membrane, thereby causing the segment to expand radially outward.

43. The method of claim 41 or 42, further comprising introducing the one or more reagents into a target location upstream of the body cavity.

44. The method of claim 43, wherein one or more reagents comprise chemotherapy reagents.

45. The method of claim 43, wherein the target location includes blood vessels that deliver blood to an organ including a tumor, and wherein the body cavity includes blood vessels through which blood flows from the organ.

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