Filtration device, and system and method for using the same

Abstract

A filtration device is provided, comprising a tubular outer member, an inner member slidably disposed within the lumen of the outer member, the inner member having a distal end extending distally from the outer member, and a plurality of tubular porous members having a first end attached to the outer member and a second end attached to the distal end of the inner member, wherein relative axial movement of the inner member with respect to the outer member causes the porous members to be compressed or stretched axially, thereby expanding or contracting the porous members. Beads or other filtration media are disposed within the porous members and are configured to adsorb or bind one or more agents from a fluid passing through the porous members.

Description

【Technical Field】 【0001】 This application generally relates to medical devices, and more specifically, to a filtration device for filtering one or more drugs in the blood flowing within a subject's blood vessels, e.g., a device for filtering one or more chemotherapeutic agents and / or other therapeutic drugs delivered to a target treatment site to reduce systemic exposure, and systems and methods for using such a device. 【0002】 Related application data This application claims the benefit of U.S. Provisional Application No. 63 / 469,511, filed May 29, 2023, the entire disclosure of which is hereby incorporated by reference in its entirety. 【Background Art】 【0003】 Cancer is currently the second leading cause of death in the United States and is predicted to become the leading cause of death within the next 10 years, excluding cardiovascular diseases. Intravenous chemotherapy is a commonly used treatment for various cancers. However, such chemotherapy may be limited in dosage due to the systemic toxicity of the chemotherapeutic agents delivered to the target treatment site. For example, doxorubicin ("Dox") is a commonly used chemotherapeutic agent, and its toxicity includes myelosuppression, gastrointestinal disorders, and most well-known, irreversible heart failure. 【0004】 To suppress these systemic toxicities and further increase the dosage of chemotherapeutic drugs for the cancer being treated, chemotherapeutic agents such as Dox may be administered intra-arterially directly into the blood vessels that supply blood to the tumor, e.g., blood vessels within the liver or other organs. However, most of the chemotherapeutic agent passes through the tumor and enters the patient's systemic venous circulation, thereby exposing other areas of the body to the drug. 【0005】 Therefore, a device that minimizes systemic exposure to chemotherapeutic agents or other therapeutic drugs would be useful. 【Summary of the Invention】 【0006】 This application relates, in general, to medical devices, and more specifically to filtration devices for filtering one or more drugs from the blood flowing within the blood vessels of a subject, as well as to systems and methods for using such devices. For example, the devices described herein may be particularly useful for filtering one or more chemotherapeutic agents and / or other therapeutic agents delivered to a targeted therapeutic site (e.g., within blood vessels leading to a tumor in the liver or other organ) to reduce systemic exposure. 【0007】 In one example, a filtration device is provided, which includes a tubular outer member having a proximal portion, a distal portion sized to be introduced into a body cavity, and a first lumen extending between the proximal portion and the outlet of the distal portion; an elongated inner member slidably disposed within the first lumen, the elongated inner member having its distal end extending from the outlet and its proximal end positioned adjacent to the proximal portion; a plurality of tubular porous members having 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, the plurality of tubular porous members being compressed or stretched axially and expanding or contracting due to the relative axial movement of the inner members with respect to the outer member; and a filtration medium provided within the porous members and configured to adsorb or bind one or more agents from a fluid passing through the porous members. 【0008】 In another example, a filtration device is provided which includes a tubular outer member having a proximal portion, a distal portion sized to be introduced into a body cavity, and a first lumen extending between the proximal portion and the outlet of the distal portion; an elongated inner member slidably disposed within the first lumen, the elongated inner member having its distal end extending from the outlet and its proximal end positioned adjacent to the proximal portion; a tubular porous member having 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, wherein relative axial movement of the inner member with respect to the outer member causes the porous member to be compressed or stretched in the axial direction, thereby expanding or contracting the porous member, and dividing the porous member into a plurality of segments between the first end and the second end; and a filtration medium provided within the segments of the porous member and configured to adsorb or bind one or more agents from a fluid passing through the porous member. 【0009】 In yet another example, a method is provided for filtering one or more drugs administered to a target site, the method comprising the steps of introducing a filtering member into a body cavity downstream of the target site, wherein the filtering member comprises a plurality of segments of porous material spaced axially apart from one another, and expanding the segments to allow blood flowing through the body cavity to pass through the porous material, thereby bringing the blood into contact with a filtering medium within the segments, and causing one or more drugs to adsorb or bind to the filtering medium. 【0010】 Other aspects and features of the present invention will become apparent from the following description in conjunction with the accompanying drawings. [Brief explanation of the drawing] 【0011】 The present invention is expected to be better understood from the following description of specific examples in conjunction with the accompanying drawings. In the figures, similar reference numerals indicate the same elements. [Figure 1] Figure 1 is a cross-sectional view of the liver showing a pair of filtration devices placed in the hepatic vein to filter chemotherapeutic agents delivered to the liver to treat a tumor. [Figure 2] Figure 2 shows an example of a filtration device that includes a shaft holding a filtration member containing a tubular mesh having four axial segments for containing a filtration medium. [Figure 3] Figures 3A and 3B are detailed views of the filtration member of Figure 2 in its contracted and expanded configurations, respectively. [Figure 4] Figures 4A and 4B show other examples of filtration members for a filtration device, in a contracted configuration and an expanded configuration, respectively. Figure 4C is a cross-sectional view of the expanded filtration member along the line segment 4C-4C in Figure 4B. 【0012】 The drawings are not intended to limit anything in any sense, and it is assumed that various examples of the present invention may be carried out in various other ways, including those not necessarily shown in the drawings. The accompanying drawings incorporated herein and forming part thereof illustrate some aspects of the present invention and, together with the detailed description, serve to illustrate the principles of the present invention. However, it should be understood that the present invention is not limited to the exact arrangement configurations shown. [Modes for carrying out the invention] 【0013】 The following description relating to specific examples of the present invention should not be used to limit the scope of the invention. Other examples, features, aspects, embodiments and advantages of the present invention will be apparent to those skilled in the art from the following description. The following description illustrates one of the best modes intended to carry out the present invention. It will be understood that various other obvious embodiments are possible, none of which will depart from the present invention. Accordingly, the drawings and description are illustrative and should not be considered limiting. 【0014】 Before describing the examples, it should be understood that the present invention is not limited to the specific examples described and is, of course, subject to change. Furthermore, since the scope of the present invention is limited only by the appended claims, it should be understood that the terms used herein are for the sole purpose of describing specific examples and are not intended to limit them. 【0015】 Where a range of values ​​is given, unless the context explicitly indicates otherwise, each intermediate value between the upper and lower limits of that range, up to one-tenth of the lower limit, should be understood to be specifically disclosed. Each small range between any stated value or intermediate value within the stated range and any other stated value or intermediate value within the stated range is included in the present invention. The upper and lower limits of those small ranges may be independently included in or excluded from the range, and whether both or one of them are included in the small range, or neither is included in the small range, each range is included in the present invention, subject to any particularly excluded limits within the stated range. If a stated range includes one or both of the limits, the range excluding one or both of the limits that they include is also included in the present invention. 【0016】 Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art in which the present invention pertains. Any methods and materials similar to or equivalent to those described herein may be used in carrying out or testing the present invention, but several possible exemplary methods and materials are described herein. 【0017】 In this specification and the appended claims, the singular forms "a," "an," and "the" refer to multiple subjects unless the context clearly indicates otherwise. For example, a reference to "compound" includes multiple such compounds, and a reference to "polymer" includes one or more polymers and their equivalents known to those skilled in the art. 【0018】 In this specification, certain ranges are indicated by the term “approximately” preceding a number. The term “approximately” is used herein to provide literal backing for the exact number following the term and for numbers that are close to or approximate the number following the term. When determining whether a number is close to or approximates a specifically mentioned number, the close or approximate unmentioned number may be a number that, in the context in which it is presented, provides a substantially equivalent to the specifically mentioned number. 【0019】 In some aspects of this disclosure, an in vivo filtration device is provided for filtering one or more therapeutic and / or diagnostic agents from blood flowing within a blood vessel. The filtration device as a whole comprises a catheter or other elongated member and a filtration member coupled to the elongated member, which is sized to be placed within a target human or non-human blood vessel. The filtration member comprises one or more tubular porous members containing a filtration medium configured to filter one or more therapeutic agents from the blood. 【0020】 The filtration medium may include materials that filter one or more therapeutic agents from the blood. For example, therapeutic agents may include chemotherapeutic agents such as Dox, and / or non-chemotherapeutic agents. 【0021】 In this specification, the term “therapeutic agent” is used broadly and may include therapeutic particles. Furthermore, the phrase “filtering therapeutic agents” is also used broadly and may include filtering therapeutic particles. For example, particles may include free chemotherapy (or non-chemotherapy) molecules or conjugated chemotherapy (or non-chemotherapy) molecules (e.g., chemotherapy molecules conjugated to particles such as drug-releasing resins or drug-releasing activated carbon). Exemplary therapeutic agents include chemomancylominants, vasoactive agents (e.g., verapamil, nicardipine, or milrinone), sodium tetradecyl sulfate (Sotradecol, Angiodynamics, or BioNiche Pharmaceuticals), bleomycin, X-ray or MRI contrast agents, antibiotics, and solvents (e.g., thrombolytic agents such as tPA). In certain cases, particles may include inactive particles. Particles may include, for example, particles that occlude blood vessels in cancerous tissue or other diseased tissue. In some cases, particles may include polymers, adhesives, resins, activated carbon, or glass. In specific examples, these include radiation therapy particles, where particles are bound to isotopes that emit radiation. 【0022】 The filtration medium may include materials having properties that adsorb, bind, capture, inactivate, or decompose one or more therapeutic agents. For example, in certain cases, the filtration medium may include beads or other particles that adsorb, bind, capture, inactivate, and / or decompose therapeutic agents. Additional information relating to filtration materials that may be included in the filtration devices described herein is contained in U.S. Patents 11,406,485 and 11,554,003, all of which are expressly incorporated herein by reference. 【0023】 As described elsewhere in this specification, in certain examples, the filtration medium can filter therapeutic agents from the blood by being able to adsorb or bind one or more therapeutic agents and remove them from the blood. For example, the filtration medium can have the property of adsorbing therapeutic agents, chemically binding to therapeutic agents, and / or magnetically binding to the magnetic carriers of therapeutic agents without significantly capturing or filtering endogenous components in the blood. The binding between the filtration medium and the therapeutic agent can be irreversible or weakly reversible. Thus, the therapeutic agent can be collected by the filtration medium and removed from the blood when the filtration device is removed. 【0024】 In one example, the filtration medium includes a resin having the property of adsorbing therapeutic agents, chemically binding to therapeutic agents, and / or magnetically binding to the magnetic carriers bound to therapeutic agents. Exemplary filtration materials including resins having the property of adsorbing and / or chemically binding therapeutic agents such as doxorubicin include strongly acidic cation exchange polymer resins, ion exchange resins, non-ion-exchanging polymer adsorption resins, resins containing sulfonic acid groups that ionically bond to therapeutic agents, chromatography-based resins, acrylic resins composed of polyacrylamide, polyacrylic acid, sodium acrylate, and vinyl copolymers, or any combination thereof. Optionally, such resins are incorporated into porous membranes or other materials of the filtration member formed from polymers or fabrics, including, for example, Nafion (Dupont), Neosepta, CMI-7000 (Membranes International), and IONAC membranes (Sybron Chemicals). 【0025】 In one example, strongly acidic cation exchange polymer resins may be used for drugs with a weak positive charge such as Dox. Other examples of compounds that can chemically or physically (through adsorption) bind to therapeutic drugs such as doxorubicin include calcequestrin, cyclic oligosaccharides (cyclodextrins) including gamma cyclodextrin, hNopp140, antibodies that specifically bind to drugs (e.g., anti-doxorubicin monoclonal antibody (MAD11)), nucleosome phosphorylated proteins, botulinum neurotoxin B, cell membrane lipids (such as cardiolipin, phosphatidylserine, and phosphatidic acid), nucleic acid ligands (so-called "aptamers") including RNA and DNA, albumin, and hemoglobin. 【0026】 In other examples, various other types of ion exchange resins can be used, such as weak acidic cation exchange, weak basic anion exchange, and strongly basic anion exchange. For example, for negatively charged drugs (e.g., heparin), strongly basic anion exchange resins can be used. 【0027】 Factors such as the functional groups and porosity / cross-linking of the resin, solution temperature, pH, concentration, and ionic strength may affect the binding efficiency of the resin to the therapeutic drug. In some examples, activation with cyanogen bromide may be used to impart functional groups to the resin. In some examples, these resins with a low cross-linking type of 3% or less, and in some cases 2% or less, may be used. Alternatively, more highly cross-linked resins may be used as needed. 【0028】 In certain cases, the filtration medium may contain carbon, such as activated carbon (e.g., charcoal or activated charcoal), which binds to the therapeutic agent. The effectiveness of activated carbon can vary depending on factors such as pore size, shape, surface area, ash content, and hardness. In some cases, the carbon may be coated with additional resin material. Furthermore, carbon and resin are inexpensive and can be effective even in small amounts. In some cases, larger amounts of carbon and resin may be used, but even amounts of 10 grams or less, or 5 grams or less, or 1 gram or less of carbon and resin can be effective. 【0029】 Exemplary resins for filtration devices described herein include one or more of HepaSphere, QuadraSphere, 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 Toyopearl MegaCap II, Purolite PAD600, and Purolite CGC100X2. Exemplary carbons for filtration devices include one or more of Norit C Gran, Calgon TOG NDS 20×50, and QUO-YC-1041. 【0030】 In certain cases, the filter medium may contain biocompatible materials such as polymethyl methacrylate (PMMA), chitosan, and heparin. In some cases, for example, the resin or carbon of the filter medium may be coated or otherwise impregnated with PMMA, chitosan, and / or heparin. An exemplary coating method is described in U.S. Patent Publication 2010 / 0316694, the entire disclosure of which is expressly incorporated herein by reference. 【0031】 In certain cases, a filtration medium can filter a therapeutic agent from the blood by inactivating or otherwise breaking down the therapeutic agent or its toxicity. For example, the filtration medium may contain catalytic materials, such as immobilized (covalent or non-covalent) enzymes, which can enzymatically break down the therapeutic agent to reduce its toxicity level. For example, the enzymatic breakdown and inactivation of Dox can occur by cleaving its sugar backbone by glycosidases contained in the liver. 【0032】 In other examples, therapeutic agents administered to patients may be pre-treated by covalently or non-covalently bonding the compound to magnetic particles (e.g., magnetic nanoparticles). This allows the filtration medium to contain magnetic material, which, after treatment, can attract the magnetically bonded therapeutic particles to the magnetic material in the filtration medium. 【0033】 In further examples, the filtration medium may include basic mechanical sieve-like filters that capture a wide range of particles commonly used to embolize tumors, such as resin-based particles, e.g., DC Beads and LC Beads (ion exchange resins), QuadraSpheres and HepaSpheres (sodium acrylate and vinyl copolymer resins), EmboSpheres (trisacrylic resins), Bead Block 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. Such particles may or may not contain therapeutic agents that are eluted in the tumor. In such examples, the filtration medium can capture these particles from the venous bloodstream to prevent their accumulation in non-target organs. Furthermore, the filtration medium may also include chemical coupling filtration mechanisms for filtering out drugs released from the blood. 【0034】 The reduction in toxicity levels may vary depending on the selected filtration medium, therapeutic agent, and specific filtration device configuration. In certain cases, the reduction in toxicity levels may range from 50% or more, 75% or more, or 90% or more. 【0035】 In certain examples, the filtration member may include one or more porous membranes containing, for example, resin beads or other filtration media inside the membrane. For example, the filtration media may include several beads loosely arranged inside one or more porous membranes, allowing the beads to move freely inside so as not to obstruct the movement and / or operation of the filtration member when the filtration member is bent and / or deformed (e.g., expands and contracts). The porosity of the membrane can vary, but it needs to be sufficient to allow blood to pass through the membrane while preventing the beads or other filtration media from leaking out. For example, the porosity of the membrane can be selected based on the particle size of the therapeutic agent, thereby increasing, for example, the capture efficiency of the therapeutic particles. Exemplary pore sizes may include a minimum of 40 microns and a maximum of 300 microns, but other pore sizes may be used as needed. 【0036】 In certain cases, a porous membrane may be configured so that blood passes through the membrane's openings and comes into contact with a filtering medium. The membrane needs to be permeable to blood, but it can be formed from a variety of materials such as cloth, plastic, polymer, silicone, metal, and metal alloy. 【0037】 In one example, one or more membranes can be tubular porous members consisting of multiple fibers woven into a tubular mesh structure configured to contain a filtration medium. The number of fibers can be such that it provides an opening smaller than the filtration medium while maintaining the flexibility of the filtration member, for example, allowing it to be introduced through curved anatomical structures. The resulting tubular mesh structure is introduced into the patient's body, for example, into curved anatomical structures within the patient's vascular system, and is flexible enough to facilitate manipulating the filtration member between expanded and contracted configurations, for example, by axially extending and compressing both ends of the mesh structure, as further described herein. 【0038】 Optionally, the material of the tubular mesh structure can be biased to return to an expanded or contracted configuration, for example by setting shape memory in the fibrous material, while still allowing the structure to expand and contract during use. In one example, the tubular mesh structure may be formed from multiple axially immobile fibers, formed from, for example, metals such as nitinol, plastics such as polyester, and / or composite materials. In various examples, the tubular mesh structure may contain about 8 to 288 fibers, about 24 to 144 fibers, or about 64 fibers. 【0039】 Optionally, the membrane material itself may include materials having properties to adsorb, bind, capture, inactivate, or decompose therapeutic agents, such as coatings. For example, the membrane material may be formed from, coated with, and / or impregnated with resins, carbon, or other materials similar to those described elsewhere in this specification in relation to filtration media. 【0040】 Referring to the drawings, Figure 1 shows an example of a patient's liver 90 containing a tumor 92. Typically, the filtration device 10 can be introduced into the patient's vascular system and the porous filtration member 40 can be positioned 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 can be introduced via the inferior vena cava 96, with the filtration members 40 positioned in their respective hepatic veins 94, thereby filtering one or more therapeutic agents in the blood flowing from the liver 90 through the hepatic veins 94. While the filtration devices described herein are particularly useful for filtering drugs delivered to the liver, they are not limited thereto. It should be understood that the filtration devices described herein can be introduced into other organs or locations in the patient's vascular system downstream of the target therapeutic site to filter one or more drugs delivered to the therapeutic site, thereby minimizing the patient's systemic exposure to the drugs. 【0041】 In a particular example, the filtration device 10 includes a catheter 20, as shown in Figure 1, with a filtration member 40 positioned at the distal end 24 of the catheter 20. The catheter 20 can be configured with various diameters to accommodate various sizes of blood vessels. For example, for smaller veins such as renal or hepatic veins, the catheter 20 may have an outer diameter of approximately 8-14 millimeters, while for larger blood vessels such as vena cava, the outer diameter may be approximately 20-30 millimeters. 【0042】 Optionally, any filtration device described herein may be incorporated into a system comprising one or more additional components, such as one or more sheaths, guidewires, etc. (not shown). For example, the system described herein may include a delivery sheath sized to receive the filtration device and enable intravascular delivery and retrieval of the filtration device. 【0043】 Referring to Figure 2, an example of a filtration device 110 is shown, which includes a catheter or other tubular outer member 120, an elongated inner member 130, and a filtration member 140. The outer member 120 includes a proximal portion or end 122, a distal portion or end 124 of a size suitable for introduction into a body cavity, and a first lumen 126 extending between the proximal portion 122 and the distal portion 124 and defining a longitudinal axis 128. The outer member 120 may have a substantially uniform structure between the proximal end 122 and the distal end 124. Alternatively, the structure may vary along the longitudinal direction of the outer member 120, for example, between the proximal portion, intermediate portion, and distal portion, in order to provide desired properties. For example, the outer member 120 includes a proximal portion adjacent to the proximal end 122, which is substantially rigid or semi-rigid, thereby providing sufficient column strength to, for example, push the distal end 124 (and the filter member 140 located thereon) forward or otherwise manipulate it from the proximal end 122, while the distal portion may be substantially flexible to accommodate insertion into bending and / or curving anatomical structures. Optionally, the outer member 120 may include one or more reinforcing members, for example, a plurality of reinforcing fibers (not shown), which may comprise a plurality of fibers braided or spirally wound and / or embedded within the wall of the outer member 20 along a desired length, for example, along at least the distal portion, to prevent buckling or kinking when advancing through a winding anatomical structure. 【0044】 The inner member 130 is slidably positioned within the first lumen 126, with its proximal end 132 extending from (or adjacent to) the proximal end 122 of the outer member 120, and its distal end 134 extending from the outlet 125 of the distal end 124 of the outer member 120. The inner member 130 is a solid or hollow wire or other elongated member and is configured to slide freely within the lumen 126 of the outer member 120. Optionally, the inner member 130 may include a lumen (not shown) extending between the proximal end 132 and the distal end 134, which can accommodate, for example, a guide wire or other rail (not shown) to facilitate the introduction of the filtration device 110. Optionally, the inner member 130 may include a rounded end and / or other non-traumatic end at the distal end 134 to prevent the distal end 134 from puncturing or otherwise damaging the wall of the body cavity into which the filtration device 110 is introduced. 【0045】 The filtration member 140 includes a tubular porous member 142, the first end 144 of which is attached to the distal end 124 of the outer member 120, and the second end 146 of which is attached to the distal end 134 of the inner member 130. Therefore, the porous member 142 can be compressed or expanded axially by the relative axial movement of the outer member 120 with respect to the inner member 130, thereby allowing the porous member 142 to expand and contract, for example, as further described herein. The filtration medium 160 is housed inside the porous member 142 and may be a plurality of beads configured to adsorb or bind one or more agents from the fluid passing through the porous member 142, for example, as further described herein. 【0046】 In one example, the porous member 142 is formed from a plurality of fibers braided into a tubular mesh structure, with both ends of the fibers defining first and second ends 144, 146. The first and second ends 144, 146 of the porous member 142 may be permanently attached to the distal ends 124, 134 of the outer and inner members 120, 130, respectively. For example, collars, heat-shrink tubing, etc., may be positioned and attached around the ends 144, 146, thereby fixing them to the outer and inner members 120, 130. Additionally or alternatively, the ends 144, 146 may be attached by one or more of the following: adhesive bonding, ultrasonic welding, fusion bonding, etc. Additionally or alternatively, if the fibers are formed from plastic or other fusible material, the ends of the fibers may also be fused or otherwise directly fixed to the outer and inner members 120, 130. 【0047】 As is most commonly seen in Figures 3A and 3B, the porous member 142 may be divided into a plurality of segments 149 spaced axially apart between the first and second ends 144, 146. For example, the porous member 142 includes one or more constricted or restrained regions 148 between the first and second ends 144, 146, which are fixed so as not to expand radially. In the illustrated example, the porous member 142 includes four segments 149 separated by three constricted regions 148, but it will be understood that, if necessary, the porous member 142 may include any desired number of segments, e.g., two, three, four, five, six, or more segments (and one fewer constricted region than the corresponding number of segments). In the illustrated example, the constricted regions 148 are arranged substantially equally, resulting in the segments 149 having substantially the same length. Alternatively, the segments 149 may also have one or more different lengths, if necessary. 【0048】 In one example, each constricted region 148 may include a collar, ring, heat-shrink wrap, or other material positioned around the porous member 142 and permanently fixed in place. Additionally or alternatively, if the material of the porous member 142 is meltable, the material may be melted or otherwise altered to fix the fibers in place so that they do not move in the constricted region 148, and / or adhesive or other material may be added to fix the fibers in the constricted region 148, thereby limiting the expansion of the constricted region 148. The constricted region 148 can be sized so that the constrained area of ​​the porous member 142 does not expand when, for example, the outer / inner members 120, 130 are operated in a direction that brings them closer together, while still allowing the substrate of the porous member 142 to slide freely on the inner member 130. 【0049】 Optionally, one or more markers (not shown) can be provided on one or more of the outer member 120, inner member 130, and / or filtration member 140. For example, radiopaque markers can be provided on or near the first and second ends 144, 146 of the porous member 142 and on each constricted region 148, thereby facilitating monitoring of the filtration member 140 during introduction and / or expansion using external imaging methods such as fluoroscopy. The markers may be separate rings, wires, or other radiopaque materials attached or embedded at desired locations, and / or the material of the porous member 140 and / or the material of the distal ends 124, 134 of the outer and inner members 120, 130 may be impregnated with radiopaque material. 【0050】 Referring further to Figure 2, a hub or handle 150 is provided at the proximal end 122 of the outer member 120 and is configured and / or sized to, for example, hold and / or operate the filter member 110 from the proximal end 122. Optionally, one or more seals (not shown) surrounding, for example, the inner member 130, are provided in or inside the hub 150, thereby preventing fluid in the lumen 126 from leaking out of the hub 150 and / or outside air from flowing into the lumen 126, while allowing the inner member 130 to move axially relative to the outer member 120. For example, the hub 150 may include a Tuohy Borst valve. Optionally, a hub or handle (not shown) may be provided at the proximal end 132 of the inner member 130, for example, to facilitate holding and / or operating the inner member 130 relative to the outer member 120. 【0051】 Alternatively, an actuator (not shown) can 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 can terminate within the hub or handle 150, rather than extending proximal to the outer member 120. For example, a slider or rotary dial (not shown) on the hub 150 can be coupled to the inner member 130 and operated in both directions to move the inner member 130 proximal or distal to the outer member 120. 【0052】 Optionally, one or more ports (not shown) may be provided on the hub 150 (or handle). For example, a lateral port (not shown) communicating with the lumen 126 may be provided on the hub 150, thereby allowing, for example, one or more fluids to be delivered into the lumen 126 around the inner member 130. Furthermore, in an alternative example where the inner member terminates within the hub or handle, an axial port communicating with the lumen 126 may be provided opposite the proximal end 122 of the outer member 120, thereby allowing, for example, a guide wire or other device to pass through the hub or handle and the lumen 126. Optionally, the axial port may be provided with one or more valves, for example, a hemostatic valve (not shown), which can provide a substantially fluid-tight seal while allowing the introduction of one or more devices into the lumen 126. 【0053】 As shown in Figures 3A and 3B, the filtration member 140 can be selectively expanded and contracted by the axial movement of the outer member 120 and the inner member 130 relative to each other. For example, in the filtration device 110, the porous member 142 (and segment 149) is initially provided in the contracted configuration shown in Figure 3A. The porous member 142 is compressed axially by the outer member 120 being guided distally to the inner member 130 (or conversely, by the inner member 130 being guided proximal), thereby expanding the segment 149 radially outward to the expanded configuration shown in Figure 3B. If necessary, the porous member 142 can be extended axially by moving the outer member 120 proximal, returning the segment 149 to the contracted configuration shown in Figure 3A. 【0054】 Optionally, the outer member 120 and / or the inner member 130 may include one or more stops (not shown) configured to restrict the relative axial movement of the outer and inner members 120, 130. For example, by providing a distal stop, the distal movement of the outer member 120 relative to the inner member 130 can be restricted to prevent excessive axial compression of the porous member 142. Similarly, by providing a proximal stop, the proximal movement of the outer member 120 can be restricted, thereby limiting the axial elongation of the porous member 142 and preventing excessive tension on the fibers of the porous member 142. 【0055】 During use, similar to device 10 shown in Figure 1, the filtration device 110 is used to filter one or more therapeutic agents into a body cavity, for example, to filter chemotherapeutic agents delivered to the liver 90 to treat a tumor 92. For example, with the filtration member 140 in the retracted configuration shown in Figure 3A, the filtration device 110 is introduced into the patient's vascular system and advanced to a desired location, for example, downstream of the targeted therapeutic area. Similar to device 10 shown in Figure 1, the filtration device 110 can be manipulated to position the distal end 134 of the inner member 130, and thus the filtration member 140, into the hepatic vein 94 downstream of the tumor 92. 【0056】 Optionally, access to the body cavity can be made using one or more additional instruments (not shown) that are part of a system or kit including the filtration device 110, for example, one or more introducer sheaths, guide catheters and / or guidewires (not shown). For example, a guidewire or other rail (not shown) can be introduced through a percutaneous puncture site, incision site or other access site formed in a peripheral site (not shown), and the guidewire can be advanced from the introduction site through the patient's vascular system, either alone or with the help of a guide catheter (not shown). For example, the distal end of a guide catheter (not shown) can be advanced along the guidewire to a desired position, and then the filtration device 110 can be guided along the guidewire or, after the guidewire has been removed, using the guide catheter. 【0057】 Once the distal end 134 is positioned as desired, the outer member 120 can be advanced distally to move the filtration member 140 into the expanded configuration shown, for example, in Figure 3B. Optionally, the positioning and expansion can be monitored by identifying markers on the filtration device 110 using external imaging techniques such as fluorescence imaging, as described elsewhere in this specification. 【0058】 Once the filtration member 140 is properly positioned and expanded, one or more therapeutic agents can be delivered to a target therapeutic site, for example, the liver 90 shown in Figure 1, using conventional methods. Blood flowing from the therapeutic site, for example, into the hepatic artery 94 shown in Figure 1 (and any drugs carried by the blood), encounters the expanded filtration member 140 and flows into the opening of the porous member 142, where the drugs in the blood can be filtered by the filtration medium 160. 【0059】 After the delivery of the therapeutic agent is complete and a sufficient amount of time has elapsed, the outer member 120 can be moved proximal to return the filtration member 140 to its retracted configuration. Subsequently, the filtration device 110 can be removed, and the procedure can be completed using a conventional method. 【0060】 Referring to Figures 4A and 4B, another example of the filtration device 210 is shown, which is configured substantially similarly to the filtration device 110, comprising an outer member 220, an inner member 230, and a filtration member 240. However, unlike device 110, the filtration member 240 has a plurality of tubular porous members 242 containing a filtration medium 260, which are attached to the outer and inner members 220 and 230. 【0061】 As shown in the figure, each tubular porous member 242 includes a first end 244 attached to the distal end 234 of the inner member 230 and a second end 246 attached to the distal end 224 of the outer member 220. The first and second ends 244, 246 of the porous member 242 are spaced apart from each other along the circumferential direction of the distal ends 224, 234 of the outer and inner members 220, 230, so that the porous member 242 is positioned along the outer wall of the inner member 230 between the first and second ends 244, 246. As a result, the inner member 230 is located outside the interior of the porous member 242, and the porous members 242 are spaced apart from each other along the circumferential direction of the inner member 230, as shown in Figure 4C. In one example, each porous member 242 is formed by braiding a plurality of fibers into a tubular mesh structure, or by other means to have a desired pore size, as otherwise described herein. 【0062】 In the example shown in Figure 4C, the filtration device 210 includes four porous members 242 arranged at approximately equal intervals around the inner member 230. The number of porous members 242 can be any desired number, such as 2, 3, 4, 5, 6, or more. 【0063】 Furthermore, each porous member 242 includes a plurality of axial segments 249 spaced apart from each other between the first and second ends 244, 246. For example, one or more constricted regions 248 can be provided along the length of the porous member 242, for example, as shown in the figure, it is possible to provide three constricted regions 248 on each porous member 242 to form four segments 249. For example, it is possible to attach collars, rings, heat shrink wrap, etc., around the porous member 242 to form constricted regions 248 at the same positions on all porous members 242, as in the previous example. Additionally or alternatively, the porous members 242 can also be fixed in place at the constricted regions by adhesive bonding, fusion, ultrasonic welding, etc. The constricted regions 248 allow the porous member 242 to slide on the inner member 230, for example, in a configuration where only the first and second ends 244, 246 of the porous member 242 are fixed to the outer and inner members 220, 230. 【0064】 As a result, similar to the filtration device 110, the porous member 242 can be expanded and contracted by simultaneously compressing or expanding it axially by moving the inner member 230 axially relative to the outer member 220. For example, as shown in Figure 4A, the filtration device 210 is provided with the porous member 242 in a contracted configuration, in which case, for example, sufficient tension is applied to the fibers or other mesh structure of the porous member 242 so that the porous member is kept adjacent to the inner member 230 and the outer cross-section of the filtration member 240 is minimized. Once introduced and positioned in the desired location, the porous member 242 can be compressed axially by advancing the outer member 220 distally relative to the inner member 230 (or by guiding the inner member proximal), and the segment 249 can be expanded radially outward to form an expanded configuration, as shown in Figures 4B and 4C. After filtering one or more therapeutic agents using the filtration device 210, the filtration member 240 can be removed from the patient's body by returning it to the retracted configuration shown in Figure 4A, as with other devices described herein. 【0065】 The various examples disclosed above are presented for illustrative and explanatory purposes only. They are not intended to be exhaustive or to limit the invention to the exact form of the disclosure. Many variations and modifications of the embodiments described herein will be apparent to those skilled in the art in light of the above disclosure. 【0066】 Furthermore, in describing representative embodiments, this specification presents methods and / or processes as specific sequences of steps. However, a method or process should not be limited to a specific sequence of steps described herein unless the method or process depends on a specific order of steps described herein. Those skilled in the art will understand that other sequences of steps are also possible. Therefore, the specific order of steps described in the specification should not be construed as limiting the claims. 【0067】 While the present invention is capable of various modifications and alternative forms, specific examples are shown in the drawings and described in detail herein. However, it should be understood that the present invention is not limited to any particular form or method disclosed, and encompasses all modifications, equivalents, and alternatives that fall within the scope of the appended claims.

Claims

[Claim 1] A filtration device, A tubular outer member including a proximal portion, a distal portion sized to be introduced into a body cavity, and a first lumen extending between the proximal portion and the exit of the distal portion, An elongated inner member slidably disposed within the first lumen, wherein its distal end extends from the outlet and its proximal end is positioned adjacent to the proximal portion, A plurality of tubular porous members having 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, wherein the plurality of tubular porous members expand or contract by being compressed or stretched in the axial direction due to the relative axial movement of the inner member with respect to the outer member, A filter medium provided within the porous member and configured to adsorb or bind one or more drugs from the fluid passing through the porous member, A filtration device characterized by comprising the following features. [Claim 2] In the filtration device according to claim 1, A filtration device characterized in that the porous member includes a plurality of segments spaced apart from each other in the axial direction between the first end and the second end. [Claim 3] In the filtration device according to claim 2, A filtration device further comprising one or more constricted regions that divide the porous member into the plurality of segments. [Claim 4] In the filtration device according to claim 3, A filtration device characterized in that the one or more constricted regions are slidable on the inner member, and the porous member can freely slide on the inner member between the first end and the second end. [Claim 5] In the filtration device according to any one of claims 2 to 4, A filtration device characterized in that the one or more constricted regions include a single constricted region that divides the porous member into two segments between the first end and the second end. [Claim 6] In the filtration device according to any one of claims 2 to 4, A filtration device characterized in that the one or more collars include two constricted segments that divide the porous member into three segments between the first end and the second end. [Claim 7] In the filtration device according to any one of claims 2 to 4, A filtration device characterized in that the one or more collars include three constricted regions that divide the porous member into four segments between the first end and the second end. [Claim 8] In the filtration device according to any one of claims 1 to 4, A filtration device characterized in that each porous member contains a plurality of fibers braided together between the first end and the second end. [Claim 9] In the filtration device according to claim 8, A filtration device characterized in that the aforementioned fiber contains nitinol. [Claim 10] In the filtration device according to claim 8, A filtration device characterized in that the fibers are braided to define an opening smaller than the cross-section of the filtration medium contained within the porous member. [Claim 11] In the filtration device according to any one of claims 1 to 4, A filtration device characterized in that the porous member includes a mesh that defines an opening smaller than the cross-section of the filtration medium contained within the porous member. [Claim 12] In the filtration device according to any one of claims 1 to 4, A filtration device characterized in that the inner member comprises a second lumen extending between the proximal end and the outlet at the distal end. [Claim 13] In the filtration device according to any one of claims 1 to 4, A filtration device characterized in that the outer member is further provided with a hub at its proximal portion, the proximal end of the inner member extends proximal to the hub, and the inner member is axially slidable relative to the hub. [Claim 14] In the filtration device according to claim 13, A filtration device characterized by further comprising a seal within the hub that at least partially surrounds the inner member. [Claim 15] In the filtration device according to any one of claims 1 to 4, A filtration device further comprising a handle provided on the proximal portion of the outer member, and an actuator provided on the handle and coupled to the proximal end of the inner member, wherein the inner member moves axially relative to the outer member due to the movement of the actuator. [Claim 16] In the filtration device according to any one of claims 1 to 4, A filtration device characterized in that the filtration medium includes resin beads. [Claim 17] In the filtration device according to claim 16, A filtration device characterized in that the resin beads are configured to adsorb or chemically bind one or more chemotherapeutic agents. [Claim 18] In the filtration device according to claim 16, A filtration device characterized in that the resin beads include one or more of the following: an ion exchange resin, a strongly acidic cationic polymer resin, a polymer adsorption resin that does not perform ion exchange, and one or more sulfonic acid groups that ionically bond to one or more chemotherapeutic agents. [Claim 19] In the filtration device according to claim 16, A filtration device characterized in that the resin beads are coated with one or more of heparin, polymethyl methacrylate, and chitosan. [Claim 20] A filtration device, A tubular outer member including a proximal portion, a distal portion sized to be introduced into a body cavity, and a first lumen extending between the proximal portion and the exit of the distal portion, An elongated inner member slidably disposed within the first lumen, wherein its distal end extends from the outlet and its proximal end is positioned adjacent to the proximal portion, A plurality of tubular porous members having a first end attached to the distal portion of the outer member, a second end attached to the distal end of the inner member, and a plurality of segments arranged axially spaced apart between the first end and the second end, wherein the segments expand or contract as the segments are compressed or stretched axially by the relative axial movement of the inner member with respect to the outer member, A filter medium provided within a segment of the porous member and configured to adsorb or bind one or more agents from a fluid passing through the porous member, A filtration device characterized by comprising the following features. [Claim 21] A filtration device, A tubular outer member including a proximal portion, a distal portion sized to be introduced into a body cavity, and a first lumen extending between the proximal portion and the exit of the distal portion, An elongated inner member slidably disposed within the first lumen, wherein its distal end extends from the outlet and its proximal end is positioned adjacent to the proximal portion, A tubular porous member having 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, wherein the porous member is compressed or stretched in the axial direction by the relative axial movement of the inner member with respect to the outer member, causing the porous member to expand or contract, and the porous member to be divided into a plurality of segments between the first end and the second end, A filter medium provided inside the segment of the porous member and configured to adsorb or bind one or more agents from the fluid passing through the porous member, A filtration device characterized by comprising the following features. [Claim 22] In the filtration device according to claim 21, A filtration device characterized in that the porous member comprises one or more non-expandable constricted regions that separate the porous member into the plurality of segments. [Claim 23] In the filtration device according to claim 22, A filtration device further comprising one or more collars, rings, or materials attached around the porous member to define the one or more constricted regions. [Claim 24] In the filtration device according to claim 22, A filtration device characterized in that the one or more constricted regions are slidable on the inner member, and the porous member can freely slide on the inner member between the first end and the second end. [Claim 25] In the filtration device according to any one of claims 22 to 24, A filtration device characterized in that the one or more constricted regions include a single constricted region that divides the porous member into two segments between the first end and the second end. [Claim 26] In the filtration device according to any one of claims 22 to 24, A filtration device characterized in that the one or more constricted regions include two constricted regions that divide the porous member into three segments between the first end and the second end. [Claim 27] In the filtration device according to any one of claims 22 to 24, A filtration device characterized in that the one or more constricted regions include three constricted regions that divide the porous member into four segments between the first end and the second end. [Claim 28] In the filtration device according to any one of claims 21 to 24, A filtration device characterized in that each porous member contains a plurality of fibers braided together between the first end and the second end. [Claim 29] In the filtration device according to claim 28, A filtration device characterized in that the aforementioned fiber contains nitinol. [Claim 30] In the filtration device according to claim 28, A filtration device characterized in that the fibers are braided to define an opening smaller than the cross-section of the filtration medium contained within the porous member. [Claim 31] In the filtration device according to any one of claims 21 to 24, A filtration device characterized in that the porous member includes a mesh that defines an opening smaller than the cross-section of the filtration medium contained within the porous member. [Claim 32] In the filtration device according to any one of claims 21 to 24, A filtration device characterized in that the inner member comprises a second lumen extending between the proximal end and the outlet at the distal end. [Claim 33] In the filtration device according to any one of claims 21 to 24, A filtration device characterized in that the outer member is further provided with a hub at its proximal portion, the proximal end of the inner member extends proximal to the hub, and the inner member is axially slidable relative to the hub. [Claim 34] In the filtration device according to claim 33, A filtration device characterized by further comprising a seal within the hub that at least partially surrounds the inner member. [Claim 35] In the filtration device according to any one of claims 21 to 24, A filtration device further comprising a handle provided on the proximal portion of the outer member, and an actuator provided on the handle and coupled to the proximal end of the inner member, wherein the inner member moves axially relative to the outer member due to the movement of the actuator. [Claim 36] In the filtration device according to any one of claims 21 to 24, A filtration device characterized in that the filtration medium includes resin beads. [Claim 37] In the filtration device according to claim 36, A filtration device characterized in that the resin beads are configured to adsorb or chemically bind one or more chemotherapeutic agents. [Claim 38] In the filtration device according to claim 36, A filtration device characterized in that the resin beads include one or more of the following: an ion exchange resin, a strongly acidic cationic polymer resin, a polymer adsorption resin that does not perform ion exchange, and one or more sulfonic acid groups that ionically bond to one or more chemotherapeutic agents. [Claim 39] In the filtration device according to claim 36, A filtration device characterized in that the resin beads are coated with one or more of heparin, polymethyl methacrylate, and chitosan. [Claim 40] In the filtration device according to any one of claims 21 to 24, A filtration device characterized in that the porous member surrounds the inner member between the first end and the second end. [Claim 41] A method for filtering one or more drugs administered to a target site, A step of introducing a filter member into a body cavity downstream of the target site, wherein the filter member includes a plurality of segments of porous material spaced apart from each other in the axial direction; The steps include expanding the segment to allow blood flowing through the body cavity to pass through the porous material, thereby bringing the blood into contact with the filter medium within the segment, and adsorbing or binding one or more drugs to the filter medium. A method characterized by comprising: [Claim 42] In the method according to claim 41, The filtration member comprises a plurality of tubular porous membranes, the ends of which are attached to an inner member and an outer member, and the method for expanding the segment is characterized by moving one of the inner member and the outer member axially relative to the other, thereby compressing the porous membrane in the axial direction and thereby expanding the segment radially outward. [Claim 43] In the method according to claim 41 or 42, A method further comprising the step of administering the one or more drugs to a target site upstream of the body cavity. [Claim 44] In the method of claim 43, A method characterized in that the one or more drugs mentioned above include a chemotherapeutic agent. [Claim 45] In the method of claim 43, The method is characterized in that the target site includes blood vessels that carry blood into an organ containing a tumor, and the body cavity includes blood vessels from which blood flows from the organ.

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