Catheter for the local treatment of tumour tissue in intravascular and intraluminal spaces

Abstract

The invention relates to a catheter for the local treatment of tissue, more particularly tumour tissue or other unwanted tissue types, in intravascular and intraluminal spaces for insertion into a vessel for the duration of the treatment. The catheter comprises a flexible, cylindrical body (2) having a first lumen (14.1) for receiving a guide wire to control the catheter (1), a second lumen (14.2) and at least one third lumen (14.3) for separately introducing chemical and / or biological therapeutic agents into the tissue, wherein the cylindrical body (2) has radiopaque features. The catheter further comprises a conductive structure (6) for generating pulsed electrical fields, wherein the conductive structure (6) comprises at least a first and a second structure element (8.1, 8.2). Furthermore, a first and a second electrical supply line (10.1, 10.2) are provided, which are insulated from one another. The invention also relates to a catheter system.

Description

[0001] Catheter for the local treatment of tumor tissue in intravascular and intraluminal spaces

[0002] The invention relates to a catheter for the local treatment of tissue, in particular tumor tissue or other undesirable tissue types, in intravascular and intraluminal spaces for insertion into a vessel for the duration of the treatment.

[0003] The catheter's field of application is therefore not limited to tumor tissue. Any tissue can be treated with the catheter, including tissue that is not necessarily malignant (tumorous) but develops in undesirable locations. Local tumor therapy traditionally involves the surgical removal of the tumor. However, surgical removal is often not possible, particularly for tumors that grow along predefined structures or around blood vessels, due to the risk of damaging adjacent structures. This includes, for example, tumors that grow along bile ducts or at bile duct bifurcations.

[0004] Therefore, other local therapy forms are known from the state of the art, including various thermal and non-thermal ablation techniques. Examples of thermal ablation techniques include radiofrequency ablation, microwave ablation, and cryoablation. Among non-thermal ablation techniques, electroporation-based techniques are particularly noteworthy.

[0005] Electroporation describes the effect of pores forming in cell membranes as a result of pulsed electric fields. In irreversible electroporation, the cell membrane is irreversibly damaged, ultimately leading to cell death. In reversible electroporation, the formation of pores in the cell membranes is reversible. Electrochemotherapy utilizes this principle by using the pores (and thus specifically in the area of ​​reversible electroporation) to allow the chemotherapeutic agents to diffuse into the cell interior with significantly greater intensity. Another therapeutic method for treating tissue, particularly tumor tissue, that utilizes the principle of reversible electroporation is calcium electroporation. Here, calcium is introduced into the cells through electroporation. Calcium electroporation has been shown to be a safe and effective therapeutic method for treating tumorous tissue (seeStine Frandsen, Mille Vissing and Julie Gehl. "A Comprehensive Review of Calcium Electroporation - A Novel Cancer Treatment Modality". Cancers 2020, 12, 290).

[0006] The advantage of these non-thermal ablation procedures in contrast to thermal ablation procedures is that the structure of the vessels running directly next to the tumor can be preserved.

[0007] WO 2006 / 104934 A2 relates to a device and method for ablating cells. The device comprises a probe and an elongated sleeve. Electrodes for ablating the tissue using radiofrequency or microwave energy are arranged at the distal end of the probe. Furthermore, the device comprises a vacuum source coupled to a proximal end of the elongated sleeve, which can be used to generate a negative pressure for attracting the tissue to the probe.

[0008] The disadvantage of ablation using radiofrequency or microwave energy is that, in addition to the unhealthy tissue, neighboring anatomical structures can also be thermally damaged and thus irreversibly destroyed. Therefore, ablation using radiofrequency or microwave energy is not suitable for tumors that grow directly along predefined structures.

[0009] US2020 / 0405384 A1 relates to a device for treating lung tumors, comprising an ablation catheter with a radiofrequency electrode. US2020 / 0405384 A1 also describes an ablation of the tumor tissue using radiofrequency energy, although radiofrequency energy is associated with the aforementioned disadvantages.

[0010] WO 2014 / 039320 A1 relates to a device for the ablation and electroporation of tissue cells. The document discloses a catheter with a flexible body, wherein electrodes for delivering energy to the target tissue are arranged at a distal portion of the body. The device is configured such that a voltage can be generated by means of the electrodes, at which electroporation, thermal ablation, or a combination of electroporation and thermal ablation occurs. The document thus discloses a combination device for different ablation methods.

[0011] WO 2013 / 059913 A1 also relates to a device for various ablation procedures. The intravascular ablation device comprises an elongated probe with a balloon at the tip, which can be used for cryogenic treatment, and a radiofrequency or electroporation element. Furthermore, WO 2013 / 059913 A1 discloses that electroporation can be used to introduce active substances into tissue. However, WO 2013 / 059913 A1 does not disclose a way to introduce active substances separately into cellular tissue.

[0012] The object of the invention is to provide a device and a method that enables the local and separate introduction of physical, chemical and / or biological therapeutics into intravascular and intraluminal bodies for the treatment of tumor tissue without destroying the surrounding anatomy.

[0013] In a catheter of the type mentioned above, this task is achieved by a flexible, cylindrical body with a first lumen for receiving a guidewire for steering the catheter, a second lumen, and at least a third lumen for separately introducing chemical and / or biological therapeutics into the tissue. The catheter has radiopaque features so that the catheter is clearly visible during image-guided guidance.

[0014] The catheter further comprises a conductive structure for generating pulsed electric fields. The conductive structure comprises at least a first and a second structural element and extends along a distal end portion of the cylindrical body. In addition, the catheter has a first electrical supply line for connecting the first structural element to an energy source and a second supply line for connecting the second structural element to the energy source. The first and second supply lines are arranged insulated from one another. It is further preferred that the first electrical supply line connects the first structural element to a first energy source, and that the second supply line connects the second structural element to a second energy source. The first energy source and the second energy source are preferably designed independently of one another.

[0015] The energy source is designed such that it can provide different voltages, currents, a variable pulse duration and frequency, as well as a variable number of pulses. The electrical supply lines, which are made of any electrically conductive material such as stainless steel, copper, gold, silver, or conductive plastic, connect the energy source to the structural elements of the conductive structure so that the structural elements can generate pulsed electric fields. The energy source is preferably designed to provide a first potential at the first structural element and a second potential at the second structural element, wherein the first potential is higher or lower than the second potential. The energy source is preferably an electrical generator. It is further preferred that the energy source is an electrical generator approved for clinical use.The energy source is particularly preferred to be a Cliniporator® from IGEA or an AngioDynamics NanoKnife.

[0016] The catheter enables the treatment of tissue, especially tumors, in both intravascular and intraluminal spaces—that is, both in vascular structures and cavities of the human body. This catheter-based solution enables precise tumor treatment, as the flexible body of the catheter can be guided directly to the target lesion via the guidewire. The catheter is not designed to remain permanently in the human body, but is specifically designed to be inserted into the human body only for the duration of the treatment.

[0017] The invention takes advantage of the knowledge that tissue can be physically influenced using electric fields. In order to achieve the desired treatment effect without irreversibly damaging adjacent structures, the properties of the pulsed electric field must be selected to an appropriate degree. The target tissue, which is usually tumor tissue and thus pathological tissue, has electrical properties that differ from the electrical properties of the surrounding, healthy tissue. By taking into account the specific electrical properties, i.e. the permittivity and electrical conductivity of the tumor tissue and the adjacent tissue, the voltage, current intensity, pulse duration, pulse frequency, and pulse number of the electric field can be adjusted such that pore formation occurs preferably exclusively in the target tissue and the adjacent structures remain undamaged.The catheter therefore enables the treatment of tumors in the immediate vicinity of large blood vessels.

[0018] In addition, the invention enables the introduction of chemical and / or biological therapeutics into the tumor tissue, so that the catheter consequently provides a comprehensive treatment approach.

[0019] It is preferred that the second lumen and / or the third lumen is / are configured to introduce calcium. It is furthermore or alternatively preferred that the second lumen and / or the third lumen is / are configured to introduce a cytostatic agent, a saline solution, an antibiotic, an immunosuppressive agent and / or another agent that causes cell death into the tumor tissue, wherein it is preferred that the second lumen and the third lumen are configured to introduce different ones of the aforementioned therapeutic agents into the tumor tissue. However, it is also possible for the second lumen and the third lumen to be configured to introduce the same therapeutic agent, but in different amounts and / or at different locations in the tumor tissue.For example, it is preferred that the second lumen introduces calicum into a first tissue portion of the tissue to be treated, and that the second lumen introduces calicum into a second tissue portion of the tissue to be treated.

[0020] The flexible, cylindrical body of the catheter is preferably made of a thermoplastic, elastomer, and / or silicone, with the plastic preferably being a medical-grade plastic, particularly preferably a solution-grade plastic. Furthermore, the body is preferably designed to be torsionally and tensile-stable.

[0021] Furthermore, it is preferred that the catheter has more than three lumens, for example four, five, six, seven lumens, or more than seven lumens. The additional lumens can be provided for delivering additional therapeutic agents into the tissue, for supplying and removing rinsing solutions, or for conveying compressed air and other fluids. Furthermore, it is preferred that the conductive structure comprises more than two structural elements, for example three, four, five, six, seven, or more than seven structural elements, wherein the structural elements are preferably arranged at equal distances from one another. This has the advantage that electric fields with different properties can be generated, or the therapeutically effective portion of the field propagation can be more precisely adapted to the volume of the target tissue.It is therefore preferred that the energy source is configured to provide different potentials at the first, the second, and / or the further structural elements. In this way, different voltages and thus different fields can be generated between the structural elements. For example, a field can be generated between the first structural element and the second structural element that has a lower or higher field strength than a field generated between the second structural element and a third structural element. In this respect, the field distribution of the fields generated between the structural elements can be adapted to the tumor tissue to be treated. For example, a stronger field can be generated at a section of the tumor tissue that exhibits increased depth growth than at a section of the tumor tissue that is merely superficial.This method can also compensate for electrode positioning errors or inaccuracies. The generated electric field can also depend on tissue-specific electrical properties of the tumor tissue.

[0022] The conductive structure is preferably arranged on an outer surface of the cylindrical body. The advantage of this arrangement is that the conductive structure can be partially or completely pressed into the tumor tissue, or, in the case of a tumor growing around a vessel, into the vessel itself.

[0023] Alternatively, the conductive structure is preferably arranged on an inner side of the cylindrical body. The advantage of this arrangement is that the catheter has an outer side without structural elements and thus a uniformly round shape on the outside. This results in improved handling and guidance of the catheter. Furthermore, the manufacture of the catheter including the conductive structure is simplified and the catheter as a whole is more stable. It should be noted that preferably no insulating layer is arranged between the conductive structure and the tumor tissue, or in the case that the tumor tissue grows around a vessel, between the conductive structure and the vessel, so that conductivity to the tumor tissue to be treated is ensured. A further preferred embodiment is that the conductive structure is arranged on both the outer side and the inner side of the cylindrical catheter body.This also makes it possible to achieve improved stability of the catheter. In this embodiment, it is possible for the structural elements on the outside to be directly opposite the structural elements on the inside. It is also possible for the structural elements on the outside to be offset from the structural elements on the inside. For example, the structural elements can be arranged along a first partial section of the distal end section on the outside of the body and along a second partial section of the distal end section on an inside of the body. Here, too, it is preferred that no insulating layer is arranged between the conductive structure and the tumor tissue or vessel.

[0024] Another possibility to improve the stability of the catheter is that the conductive structure on the outside and / or on the inside is partially or completely embedded in a wall of the cylindrical body.

[0025] It is preferred that at least the first and second structural elements of the conductive structure are arranged parallel to a longitudinal axis of the cylindrical body. The structural elements are preferably arranged in strips along the distal end portion of the cylindrical body, with the strips preferably being of equal length. However, the strips can also have different lengths. It is preferred that the strips form straight lines, but they can also be wavy.

[0026] In an alternative embodiment, it is preferred that at least the first and second structural elements of the conductive structure are arranged elliptically along the distal end portion of the cylindrical body. The structural elements thus form closed, oval curves that wind around the cylindrical body. It is further preferred that more than two, for example, three or four, elliptical structural elements are provided. The elliptical structural elements are preferably arranged at equal distances from one another. However, it is also possible for the elliptical structural elements to be arranged at different distances from one another.

[0027] In a further alternative embodiment, it is preferred that at least the first and second structural elements of the conductive structure are arranged in a ring shape and coaxially with a longitudinal axis of the cylindrical body. The ring-shaped structural elements are preferably arranged at equal distances from one another. However, it is also possible to provide different distances between the structural elements.

[0028] In a further, alternative embodiment, the conductive structure is preferably arranged in a net-like manner along the end section of the cylindrical body. For this purpose, at least the first and the second structural element wind helically around the cylindrical body, with the first structural element winding left-handed and the second structural element right-handed around the cylindrical body. Furthermore, the first and the second structural element preferably wind around the body with a constant pitch. It is possible for the structural elements to be continuous or interrupted in sections. For this embodiment, it is preferred that the structural elements are arranged so as to be insulated from one another by an insulating intermediate layer made of an insulating material, at least at the interfaces where the two structural elements intersect.

[0029] In addition, other arrangement patterns of the structural elements of the conductive structure along the end section of the cylindrical body are possible, such as circular, semicircular, wavy, or serrated arrangement patterns. Furthermore, the arrangement patterns implemented can be combined with each other as desired. The different arrangement patterns of the structural elements enable electric fields with different properties and spatial extensions. The different arrangements of the structural elements therefore make it possible to generate electric fields that are tailored to the spatial extent of the tumor tissue to be treated.

[0030] It is preferred that the electrically conductive structure generates pulsed electric fields upon application of a voltage, which induce reversible pore formation in cell membranes of the tumor tissue. In order for the cell membranes to become reversibly permeable, the generated pulsed electric fields must have electric field strengths that exceed certain threshold values. The threshold values ​​depend in particular on the electrical properties of the target tissue, the pulse width used, and the number of pulses used. The threshold values ​​should also be adjusted so that reversible pore formation preferably occurs exclusively in the target tissue, while the adjacent structures remain undamaged. The generated pulsed electric fields (PEFs) are preferably characterized by high electric field strengths and a short duration.For reversible electroporation, millisecond pulsed electric fields (msPEF), microsecond pulsed electric fields (psPEF), and / or nanosecond pulsed electric fields (nsPEF) are preferred. Pulsed electric fields with pulse durations in the second, picosecond, and / or femtosecond ranges are also preferred. The reversible pore formation in the cell membranes also creates temporary permeability for chemical and / or biological therapeutics, allowing them to diffuse into the cell interior. For electrochemotherapy of skin tumors, pulse protocols with 8 pulses, each with a pulse width of 100 ps, ​​are known from the state of the art, with the field strength to be achieved preferably being in the range of 1 to 1.4 kV / cm (Andreas Ritter. “Strategies and electrode design for patient-specific tumor therapeutic application of electroporation.” Doctoral thesis. RWTH Aachen, Faculty of Electrical Engineering and Information Technology, May 2017).

[0031] It is particularly preferred that the electrically conductive structure generates pulsed electric fields when a voltage is applied, which bring about reversible pore formation in the cell membranes of the tumor tissue for the introduction of calcium. It has been shown that the introduction of calcium into cells is a safe and efficient therapeutic method for the treatment of tumorous tissue. A particular advantage of calcium electroporation is that the healthy surrounding tissue or structure is less affected by the calcium than the tumorous tissue itself. One reason for this could be that healthy cells, in contrast to tumorous cells, can rebuild their membrane more effectively and quickly after electroporation, whereby the permeability in healthy cells is shortened and weakened compared to tumorous cells.In addition, it has been shown that healthy cells, in contrast to tumorous cells, are better able to degrade the introduced calcium and can return more quickly to an intracellular calcium level that corresponds to the calcium level of untreated cells.

[0032] Alternatively, it is preferred that the electrically conductive structure generates electric fields upon application of a voltage that cause irreversible pore formation in cell membranes of the tumor tissue. For this to happen, the electric field strengths of the generated pulsed electric fields must also exceed threshold values, whereby the threshold values ​​for irreversible electroporation are higher than for reversible electroporation. The threshold values ​​for irreversible electroporation depend in particular on the electrical properties of the target tissue, the pulse width used, and the number of pulses. For irreversible electroporation, "millisecond pulsed electric fields" (msPEF), "microsecond pulsed electric fields" (psPEF), and / or "nanosecond pulsed electric fields" (nsPEF) are preferred. Furthermore, pulsed electric fields with a pulse duration in the second range, in the picosecond range, and / or in the femtosecond range are preferred.For irreversible electroporation of liver tumors, current state-of-the-art pulse protocols consist of 90 pulses, each with a pulse width ranging from 50 ps to 100 ps. The achievable field strength for irreversible electroporation is preferably at least 1 kV / cm (Andreas Ritter, "Strategies and Electrode Design for Patient-Individual Tumor-Therapeutic Application of Electroporation." Doctoral thesis, RWTH Aachen University, Faculty of Electrical Engineering and Information Technology, May 2017). As a result of the irreversible cell damage, the treated tissue cells die. To prevent the surrounding structures from dying, the threshold values ​​must be selected so that the electrical properties of the surrounding structure remain unaffected.

[0033] Furthermore, it is preferred that the energy source provides energy suitable for thermal ablation of the tumor tissue. For example, radiofrequency energy or microwave energy.

[0034] The conductive structure is preferably formed partially or entirely from an electrically conductive plastic. Plastics offer the advantages, among others, of being versatile in formability, highly chemically resistant, lower in density than metal, and allowing for a high degree of design freedom. Due to their ease of formability using conventional plastic molding methods and the high degree of design freedom, the diverse arrangement patterns of the conductive structure along the end section of the cylindrical body are easy to implement. A conductive structure formed partially or entirely from an electrically conductive plastic has the advantage of being significantly more flexible than a conductive structure formed from a wire and / or a conductive metal.This means that a conductive structure made of an electrically conductive plastic adapts better to the body's conditions when guiding the catheter through the body. In this respect, a conductive structure made of an electrically conductive plastic can better mimic the bends and curvatures of the vessels through which the catheter is inserted. This makes guiding the catheter significantly easier.

[0035] The conductive structure is preferably partially or completely made of a doped plastic. This means that some electrons in the polymer chains of the respective polymers are removed (p-doping) or added (n-doping). As a result, individual free electrons remain, which can glide along the molecules and thus transport the electrical charge.

[0036] Alternatively, it is preferred that the conductive structure be formed partially or entirely from a plastic containing electrically conductive additives. The additive concentration must be sufficiently high to ensure that the additives are likely to touch each other and, consequently, form continuous current paths. As the additive concentration increases, so does the conductivity of the polymer. The additives can be formed from any electrically conductive material. Examples include carbon, conductive carbon black, aluminum, or stainless steel.

[0037] Preferably, the conductive structure is formed partially or entirely from a fiber-plastic composite. When fibers are randomly arranged as additives, there is a high probability of contact even at low concentrations. It is particularly preferred for the conductive structure to be formed partially or entirely from a carbon-fiber-reinforced plastic. However, other additives with a fiber structure are also conceivable, for example, carbon fibers. A combination of different additives in the plastic is also possible, whereby additives with a fiber structure and additives without a fiber structure can also be combined.

[0038] In a further preferred embodiment, the catheter comprises a balloon, wherein in this embodiment the conductive structure extends at least partially along the balloon. The conductive structure, comprising at least two structural elements, can also be arranged on an outer side, on an inner side, or on both an outer and an inner side of the balloon. It can also be partially or completely embedded in a wall of the balloon. Furthermore, the conductive structure can be arranged according to the various arrangement patterns described above along the balloon, for example, in a strip-like, net-like, or ring-like manner, so that reference is made to the previous description in this regard.In the embodiment of the catheter with balloon, it is also preferred that the body of the catheter has a further lumen which is designed to conduct fluid and is provided for expanding the balloon by means of compressed air or liquid.

[0039] The invention further relates to a method for the local treatment of tumor tissue in intravascular and intraluminal spaces using the catheter described above. First, a percutaneous access is established and secured. The access can, for example, be to the bile duct system, a blood vessel, or another anatomical hollow organ or vascular system. Alternatively, access can be achieved via natural body openings, e.g., via the esophagus or intestine. The patient can be awake or sedated during the establishment and securing of the access. It is preferred that at least the area of ​​the percutaneous access is locally anesthetized. Furthermore, it is preferred that the percutaneous access is established using the Seldinger technique. With the Seldinger technique, a wire is first inserted through a puncture cannula, and then the puncture cannula is exchanged for an introducer (sheath) via this wire.

[0040] The procedure also includes the step of imaging the target lesion, where the target lesion is an area of ​​tumor tissue to be treated with the catheter. Possible imaging techniques include X-ray, computed tomography (CT), magnetic resonance imaging (MRI), sonography, or endoscopy.

[0041] Furthermore, the target lesion can be visualized using contrast medium. If the target lesion is located in the biliary system, contrast medium can be injected into the bile ducts. The target lesion is delineated from surrounding structures as a contrast medium void and thus becomes visible.

[0042] The method also includes the step of image-guided guidance of the catheter over the guidewire to the target lesion. The distal end portion of the catheter, comprising the conductive structure, can thus be precisely positioned at the target lesion.

[0043] In a preferred step, the method comprises the application of physical and / or chemical and / or biological measures. For this purpose, pulsed electric fields are generated using the conductive structure, which physically act on the target lesion in such a way that pores form in the cell membranes of the target lesion. The pore formation can be reversible or irreversible. Irreversible pore formation results from irreversible electroporation. Reversible pore formation results from reversible electroporation, whereby the created pores are, on the one hand, small enough to close themselves again and, on the other hand, large enough to allow molecules of a chemical and / or biological therapeutic to pass through. Chemical and / or biological therapeutics can be introduced separately and preferably independently into the porous target lesion via the second and third lumens and, if necessary, via further lumens.Possible therapeutic agents include, for example, cytostatics, saline solutions, antibiotics, calcium, immunosuppressive agents, and / or other active substances that cause cell death. The method particularly preferably comprises the introduction of calcium into the porous target lesion. It is particularly preferred that calcium be introduced into the porous target lesion in an amount of 2.5 mM to 20 mM. Amounts above 20 mM are also preferred. The introduction of just 2.5 mM of calcium into the target lesion can, after reversible electroporation, cause cell death or reduce cell viability to a range of 0% to 3%. In a further preferred embodiment of the method, the target lesion is acted upon using heat.

[0044] After treatment of the target lesion, the catheter is removed from the body in a final step.

[0045] In a preferred embodiment of the method, the treatment effect is visualized using imaging techniques. Possible imaging techniques also include X-rays, CT scans, MRI, sonography, and / or endoscopy. It is preferred that the same imaging technique be used to visualize the treatment effect as was used to localize the target lesion, thus allowing for better comparability before and after treatment of the target lesion.

[0046] In a further preferred development of the method, percutaneous access for repeated treatment of the tumor tissue is secured using the catheter and the performed procedure. Preferably, the percutaneous access is secured using a wire or a sheath. It is further preferred that the treatment effect be visualized using imaging techniques even after repeated treatments.

[0047] The invention further relates to a catheter system comprising the described catheter and a control unit for controlling the energy source, wherein the catheter system is designed to carry out the method described above. The control unit can control the energy source in such a way that variable parameter combinations of the parameters voltage, current, pulse duration, pulse frequency, and / or pulse number are possible, so that the conductive structure can consequently generate electric fields with different properties, particularly preferably with different field strengths. The invention further relates to a method for creating a three-dimensional map of an organ with a tumor. The method comprises measuring individual, tissue-specific electrical properties of the organ, preferably non-invasively, particularly preferably by electrical impedance tomography (EIT) or magnetic resonance imaging (MRI).The method further includes segmenting the tumor and the tissue surrounding it. The method further includes creating three-dimensional maps, taking into account the segmentation and the individual, tissue-specific electrical properties of the organ.

[0048] It is preferred that the control unit controls the energy source taking into account the three-dimensional map of the organ, wherein the energy source is preferably designed with one, several, or all of the features as above. Preferably, the control unit is configured to control the energy source to generate electrical fields that are adapted to the individual, tissue-specific electrical properties of the organ. Preferably, the control unit is configured to control the energy source in such a way that it provides a first potential at a first structural element of a catheter and provides a second potential at a second structural element of the catheter, wherein the first potential is higher or lower than the second potential, wherein the catheter is preferably designed with one, several, or all of the features as above.Furthermore, the control unit is preferably configured to control the energy source such that the energy source provides different potentials at the first, second, and / or further structural elements of the catheter. In this way, different voltages and thus different fields can be generated between the structural elements.

[0049] Embodiments of the invention will now be described below with reference to the drawings. These are not necessarily intended to represent the embodiments to scale; rather, the drawings are schematic and / or slightly distorted where this is useful for explanation. With regard to additions to the teachings immediately apparent from the drawings, reference is made to the relevant prior art. It should be noted that numerous modifications and changes to the form and detail of an embodiment can be made without deviating from the general idea of ​​the invention. The features of the invention disclosed in the description, in the drawings and in the claims can be essential for the further development of the invention, both individually and in any combination.Furthermore, all combinations of at least two of the features disclosed in the description, the drawings and / or the claims fall within the scope of the invention. The general idea of ​​the invention is not limited to the exact form or detail of the preferred embodiments shown and described below, or limited to an object that would be more limited than the object claimed in the claims. For specified dimensioning ranges, values ​​within the stated limits are also intended to be disclosed as limit values ​​and to be used and claimed as desired. For the sake of simplicity, the same reference numerals are used below for identical or similar parts or parts with identical or similar functions.

[0050] Further advantages, features and details of the invention will become apparent from the following description of the preferred embodiments and from the drawings, which show:

[0051] Fig. 1 is a schematic representation of a catheter with a cylindrical body and a Luer connector;

[0052] Fig. 2 shows a cross section along the AA of Fig. 1 through the catheter;

[0053] Fig.3 shows an arrangement of the conductive structure on the body according to a first arrangement;

[0054] Fig. 4 shows an arrangement of the conductive structure on the body according to a second arrangement;

[0055] Fig. 5 shows an arrangement of the conductive structure on the body according to a third arrangement;

[0056] Fig. 6 is a first schematic representation of the distal end portion B according to a first embodiment;

[0057] Fig. 7 is a second schematic representation of the distal end portion B according to the first embodiment;

[0058] Fig. 8 shows a first schematic representation of the distal end portion B according to a second embodiment; Fig. 9 shows a second schematic representation of the distal end portion B according to the second embodiment;

[0059] Fig. 10 is a schematic representation of the distal end portion B according to a third embodiment;

[0060] Fig. 11 is a schematic representation of the distal end portion B according to a fourth embodiment;

[0061] Fig. 12 is a schematic representation of the distal end section B with an expandable balloon; and in

[0062] Fig. 13 is a schematic representation of the catheter system.

[0063] Fig. 1 shows a catheter 1 with a cylindrical body 2 and a Luer connector 3 located at a proximal portion 4 of the cylindrical body 2. The Luer connector 3 is a standardized connection system through which the cylindrical body 2 of the catheter 1 can be connected to additional tubes or hoses. The length of the Luer connector 3 is variable, and the diameter of the Luer connector 3 is preferably in a range of 3 mm to 8 mm.

[0064] The cylindrical body 2 of the catheter 1 is flexible, allowing it to be easily guided to the target lesion. Furthermore, the catheter 1 is designed to be torsionally and tensile-stable. It is made of a thermoplastic, elastomer, or silicone and has radiopaque features, allowing the catheter 1 to be clearly visible during image-guided guidance. The length of the cylindrical body 2 is preferably selected to ensure that the tumor tissue to be treated is reached.

[0065] The cylindrical body 2 has a distal end section B with a conductive structure 6 (cf. Figs. 6-12). The conductive structure 6 comprises at least a first and a second structural element 8.1, 8.2, each of which is connected to an energy source 12 via an electrical supply line 10.1, 10.2. When a voltage is applied to the structural elements 8.1, 8.2, an electric field is generated. The energy source 12 can provide different voltages, currents, pulse durations and frequencies, as well as a variable number of pulses, to the structural elements 8.1, 8.2 via the supply lines 10.1, 10.2. Pulsed electric fields can thus be generated, which cause reversible electroporation, irreversible electroporation, or heat ablation (cf. Figs. 6, 8, 12). It is preferred that the energy source 12 is configured to generate different electric fields along the catheter 1.For this purpose, the energy source 12 preferably provides different potentials at the structural elements. Electric fields with different field strengths are thus formed between the structural elements, for example between the structural elements 8.1 and 8.2 and the structural elements 8.3 and 8.4 (cf. Fig. 9), whereby the higher the voltage between the structural elements, the higher the electric field strength. Fig. 2 shows a cross-section AA through the cylindrical body 2 of the catheter 1. The cross-section AA shows that the cylindrical body 2 has a first lumen 14.1, which is arranged centrally, and four further lumens 14.2-14.5, which are arranged around the first lumen 14.1. In the exemplary embodiment shown, the diameter D of the first lumen 14.1 is larger than the diameters d of the further lumens 14.2-14.5. The diameters of the lumens can also be the same size or different from one another.The arrangement and the number of lumens are not limited to the embodiment shown.

[0066] The first lumen 14.1 is preferably suitable for receiving a guide wire (not shown) and is therefore also referred to as a guide channel. The four further lumens 14.2-14.5 can be referred to as functional channels. The functional channels 14.2-14.5 are preferably suitable for conveying chemical and biological therapeutics as well as other fluids. The chemical and biological therapeutics can be conveyed together in one functional channel or separately from one another in different functional channels. In the event that the catheter 1 has an expandable balloon 16, compressed air or liquid for expanding the balloon can also be conveyed in a further functional channel. In addition, rinsing solutions can be conveyed into the lumens 14.2-14.5.

[0067] The functional channels 14.2-14.5 for conveying chemical and / or biological therapeutics and thus for introducing the therapeutics into the tumor tissue open into openings (not shown) that can be placed anywhere along the cylindrical body 2. Preferably, the functional channels 14.2-14.5 for conveying chemical and / or biological therapeutics open into openings arranged at the distal end section B of the cylindrical body 2. This enables a precise introduction of the therapeutics into the physically treated tumor tissue. It is particularly preferred that at least one of the functional channels 14.2-14.5 is configured to convey calcium. Fig. 3 shows a first cross-section along section CC in Fig. 1 through the distal end section B of the cylindrical body 2. According to this first arrangement, the conductive structure 6 is arranged on an outer surface 20 of the cylindrical body 2.In this arrangement, the conductive structure 6 comprises four structural elements 8.1 - 8.4, which are arranged at equal distances around the cylindrical body 2.

[0068] The structural elements 8.1-8.4 can be designed in the form of a wire with a partially circular cross-section, wherein the wire is made of any electrically conductive material, such as stainless steel, copper, gold, or silver, or another conductive metal or alloys thereof. The wire can be connected to the cylindrical body 2 using a suitable joining method, e.g., glued or soldered to the cylindrical body 2, or partially overmolded with the material of the body.

[0069] However, the structural elements 8.1-8.4 are particularly preferably formed from a conductive plastic that is elongated and flexible. Structural elements 8.1-8.4 made from a conductive plastic increase the flexibility of the catheter. The structural elements 8.1-8.4 made of conductive plastic can be connected to the cylindrical body 2 using a suitable joining method or can be formed directly together with the cylindrical body 2, for example, coextruded.

[0070] In this first arrangement, structural elements 8.1-8.4 have radially protruding profiles (see Fig. 3), so that structural elements 8.1-8.4 can be pressed sufficiently well into the tumor tissue or vessel. However, structural elements with significantly flatter, square, or triangular profiles are also possible and preferred.

[0071] Fig. 4 shows a further cross-section CC through the distal end section B of the cylindrical body 2. According to this second arrangement, the conductive structure 6 is arranged on an inner side 22 of the cylindrical body 2. In this arrangement, the conductive structure 6 comprises four structural elements 8.1 - 8.4 with comparatively flat, inwardly rounded profiles. On the outside, the cylindrical body 2 is uniformly round. No insulating layer is provided between the conductive structure 6 and an outer side 18 of the cylindrical body 2, so that conductivity is provided to the outside. Fig. 5 shows a further cross-section CC through the distal end section B of the cylindrical body 2. In this third arrangement, the conductive structure 6 is arranged on both the outer side 18 and the inner side 22 of the cylindrical body 2. The structural elements on the outer side 18 are directly opposite those on the inner side 22.In this third arrangement, the opposing structural elements form a closed unit. This means that there is no separating layer between the opposing structural elements; instead, they are formed as a composite. The resulting four structural elements 8.1-8.4 are circular in shape and partially embedded in a wall 24 of the cylindrical body 2. The stability of the catheter 1 can be improved by these structural elements 8.1-8.4, which are shaped both outwardly and inwardly.

[0072] Fig. 6 shows a first schematic representation of the distal end section B according to a first exemplary embodiment. The distal end section B according to the first exemplary embodiment has a conductive structure 6 with two structural elements 8.1, 8.2, which are each connected to the energy source 12 via an electrical supply line 10.1, 10.2. The two strip-shaped structural elements 8.1, 8.2 run parallel to one another and parallel to a longitudinal axis L of the cylindrical body 2 (cf. Fig. 7). The two electrical supply lines 10.1, 10.2 also run parallel to one another and parallel to the longitudinal axis L of the cylindrical body 2. The two electrical supply lines 10.1, 10.2 are formed from any electrically conductive material such as, for example, stainless steel, copper, gold, silver or conductive plastic.In addition, they are arranged in isolation from each other to ensure that the energy from the energy source 12 is transmitted undisturbed to the structural elements 8.1, 8.2.

[0073] In Fig. 6, the cross section CC in the region of the conductive structure 6 and the cross section DD in the region of the electrical supply lines 10.1, 10.2 are also shown. The conductive structure 6 is arranged on the outer surface 20 of the cylindrical body 2 according to the first exemplary embodiment (cf. cross section CC, Fig. 6). The arrangement of the conductive structure 6 therefore corresponds to the arrangement according to Fig. 3. However, it is alternatively possible for the conductive structure 6 to be arranged on the inner side 22 of the cylindrical body 2 (see Fig. 4) or on both the inner side 22 and the outer side 18 of the cylindrical body 2 (see Fig. 5). The electrical supply lines 10.1, 10.2 are partially embedded in the wall 24 of the cylindrical body 2. The wall 24 of the cylindrical body 2, which is preferably made of an insulating plastic, forms an insulating layer between the electrical supply lines 10.1, 10.2 (cf. cross-section DD, Fig. 6). However, the electrical supply lines 10.1, 10.2 can also be completely embedded in the insulating wall 24 of the cylindrical body 2.

[0074] Fig. 7 shows a second schematic representation of the distal end section B according to the first embodiment from Fig. 6. In this view, only one structural element 8.1 of the conductive structure 6 is shown. The structural element 8.1 also extends parallel to the longitudinal axis L of the cylindrical body 2 along the distal end section B and forms a straight line. The length of the strip-shaped structural element 8.1 is preferably selected depending on the tumor tissue to be treated.

[0075] Fig. 8 shows a first schematic representation of the distal end portion B according to a second embodiment. The distal end portion B according to the second embodiment also has a conductive structure 6 with two structural elements

[0076] 8.1, 8.2, each of which is connected to a power source 12 via an electrical supply line 10.1, 10.2. The two structural elements 8.1, 8.2 are arranged in a ring shape and coaxial with the longitudinal axis L of the cylindrical body 2 (see Fig. 9). The two electrical supply lines 10.1, 10.2 run parallel to each other and parallel to the longitudinal axis L of the cylindrical body 2.

[0077] Also shown in Fig. 8 is the cross section CC in the region of the conductive structure 6 and the cross section along the line DD in Fig. 6 in the region of the electrical supply lines 10.1, 10.2. The conductive structure 6 is arranged on the outer surface 20 of the cylindrical body 2 (cf. cross section CC, Fig. 8). The arrangement of the conductive structure 6 thus also corresponds to the arrangement according to Fig. 3. Here, too, it is alternatively possible for the conductive structure 6 to be arranged on the inner side 22 of the cylindrical body 2 (see Fig. 4) or on both the inner side 22 and the outer side 20 of the cylindrical body 2 (see Fig. 5). The electrical supply lines 10.1, 10.2 are partially embedded in the wall 24 of the cylindrical body 2 and arranged insulated from one another. The wall 24 here also forms the insulating layer between the two electrical supply lines.

[0078] 10.1, 10.2 (cf. cross-section DD, Fig. 8). However, the electrical supply lines 10.1, 10.2 can also be completely embedded in the wall 24 of the cylindrical body 2.

[0079] Fig. 9 shows a second schematic representation of the distal end portion B according to the second embodiment with four structural elements 8.1-8.4 arranged annularly and coaxially to the longitudinal axis L of the cylindrical body 2. The structural elements 8.1-8.4 are arranged at equal intervals along the distal end portion B. The electrical supply lines 10.1-10.4, via which the structural elements 8.1-8.4 are connected to the energy source 12, are not shown in Fig. 9.

[0080] Fig. 10 shows a schematic representation of the distal end section B according to a third exemplary embodiment. The distal end section B has three structural elements 8.1-8.3 which are elliptical in shape. The structural elements 8.1-8.3 thus form closed, oval curves that wind around the cylindrical body 2. The three structural elements 8.1-8.3 are arranged at equal distances from one another and are also each connected to the energy source 12 via an electrical supply line 10.1-10.2 (not shown). The elliptical structural elements 8.1-8.3 are arranged on the outer side 18 of the cylindrical body 2 (see Fig. 10). However, they can also be arranged on the inner side 22 or both on the inner side 22 and on the outer side 18 of the cylindrical body 2.

[0081] Fig. 11 shows a schematic representation of the distal end section B according to a fourth exemplary embodiment. In this fourth exemplary embodiment, the conductive structure 6 is arranged in a net-like manner along the distal end section B. A first and a second structural element 8.1, 8.2 wind helically around the cylindrical body 2, with the first structural element 8.1 winding right-handed and the second structural element 8.2 winding left-handed around the cylindrical body 2. The structural elements 8.1, 8.2 wind around the cylindrical body 2 with a constant and equal pitch and, when viewed together, form the shape of a net. At the interfaces 26, where the two structural elements 8.1, 8.2 intersect, the structural elements 8.1, 8.2 are arranged so as to be insulated from one another. For this purpose, an insulating intermediate layer made of a plastic is provided, for example.

[0082] Fig. 12 shows a schematic representation of the distal end section B according to a fourth exemplary embodiment. In this fourth exemplary embodiment, the catheter 1 further comprises an expandable balloon 16. The conductive structure 6 is now no longer arranged on the cylindrical body 2, but on the expandable balloon 16. In this exemplary embodiment, the conductive structure 6 comprises two structural elements 8.1, 8.2, which are arranged opposite one another and extend in the form of elongated strips along an outer balloon surface 30 (see Fig. 11, cross section CC). The structural elements 8.1, 8.2 can also be arranged on the balloon 16 in various ways according to the arrangement patterns already described, i.e., elliptical, annular, and / or net-shaped. An arrangement of the conductive structure 6 on a balloon inner side 32 or both on a balloon inner side 32 and a balloon outer side 28 is also possible and preferred.

[0083] The structural elements 8.1, 8.2 are each connected to the energy source 12 via an electrical supply line 10.1, 10.2. From the cross-section DD of Fig. 12, it can be seen that the supply lines 10.1, 10.2 are arranged on the outer side 18 of the cylindrical body 2.

[0084] Fig. 13 shows a schematic representation of the catheter system 40. The catheter system 40 comprises the catheter 1 including the energy source 12, as well as a control unit 42 connected to the energy source 12. The catheter 12 is shown only schematically and partially cut away in Fig. 13. The fewest first and fewest second supply lines 10.1, 10.2 are coupled to the energy source 12 so that the energy source can provide energy to the conductive structure (not shown in Fig. 13).

[0085] The control unit 42 is configured to control the energy source 12. Variable parameter combinations of the parameters voltage, current, pulse duration, pulse frequency, and pulse count can be controlled, thereby generating electric fields with different properties. Thus, pulsed electric fields can be generated that result in reversible or irreversible electroporation. Taking into account the specific electrical properties, i.e., the permittivity and electrical conductivity of the tumor tissue and the adjacent tissue, the parameters can also be controlled such that only the tumor tissue is subjected to electroporation. The surrounding tissue can thus retain its structure. The control unit 42 is preferably configured to control the energy source 12 to generate different electric fields between the structural elements 8.1-8.4.It is preferred that the control unit 42 controls the energy source 12 taking into account tissue-specific electrical properties of the tumor tissue. LIST OF REFERENCE SYMBOLS.

[0086] 1 catheter

[0087] 2 cylindrical body

[0088] 3 Luer connector

[0089] 4 proximal section of the catheter

[0090] 6 conductive structure

[0091] 8.1 -8.4 first, second, third and fourth structural element

[0092] 10.1 -10.4 first, second, third and fourth supply lines

[0093] 12 Energy source

[0094] 14.1 first lumen

[0095] 14.2-14.5 second, third, fourth and fifth lumen

[0096] 16 Balloon

[0097] 18 Outside of the cylindrical body

[0098] 20 Outer surface of the cylindrical body

[0099] 22 Inside of the cylindrical body

[0100] 24 Wall of the cylindrical body

[0101] 26 Interface

[0102] 28 Balloon outside

[0103] 30 Balloon surface

[0104] 32 Balloon inside

[0105] 40 Catheter system

[0106] 42 Control unit

[0107] B distal end section of the catheter

[0108] D Diameter of the first lumen d Diameter of the second, third, fourth and fifth lumen

[0109] L Longitudinal axis of the cylindrical body

Claims

Claims 1. Catheter (1) for the local treatment of tissue, in particular tumor tissue or other unwanted tissue types, in intravascular and intraluminal spaces for insertion into a vessel for the duration of treatment, comprising a flexible, cylindrical body (2) with a first lumen (14.1) for receiving a guide wire for steering the catheter (1), a second lumen (14.2) and at least a third lumen (14.3) for separately introducing chemical and / or biological therapeutics into the tissue, wherein the cylindrical body (2) has radiopaque features, a conductive structure (6) for generating pulsed electric fields, wherein the conductive structure (6) comprises at least a first and a second structural element (8.1, 8.2) and extends along a distal end section (B) of the cylindrical body (2), and a first electrical supply line (10.1) for connecting the first structural element (8.1) with an energy source (12) and a second electrical supply line (10.2) for connecting the second structural element (8.2) to the energy source (12), wherein the first and the second supply lines (10.1 , 10.2) are insulated from each other.

2. Catheter (1) according to claim 1, wherein the conductive structure (6) is arranged on an outer surface (20) of the cylindrical body (2).

3. Catheter (1) according to claim 1, wherein the conductive structure (6) is arranged on an inner side (22) of the cylindrical body (2).

4. Catheter (1) according to one of the preceding claims, wherein the conductive structure is arranged on both an outside (18) and an inside (22) of the cylindrical body (2).

5. Catheter (1) according to one of the preceding claims, wherein at least the first and the second structural element (8.1 , 8.2) of the conductive structure (6) are arranged parallel to a longitudinal axis (L) of the cylindrical body (2).

6. Catheter (1) according to any one of claims 1 to 4, wherein at least the first and the second structural element (8.1 , 8.2) are arranged elliptically along the distal end section (B) of the cylindrical body (2).

7. Catheter (1) according to one of claims 1 to 4, wherein at least the first and the second structural element (8.1 , 8.2) of the conductive structure (6) are arranged in a ring shape and coaxially to a longitudinal axis (L) of the cylindrical body (2).

8. Catheter (1) according to any one of claims 1 to 4, wherein the conductive structure (6) is arranged in a mesh-like pattern along the distal end section (B) of the cylindrical body (2).

9. Catheter (1) according to one of the preceding claims, wherein the conductive structure (6) generates pulsed electric fields when a voltage is applied, which cause reversible pore formation in cell membranes of the tissue.

10. Catheter (1) according to any one of the preceding claims 1 to 8, wherein the conductive structure (6) generates pulsed electric fields when a voltage is applied, which cause irreversible pore formation in cell membranes of the tissue.

11. Catheter (1) according to one of the preceding claims, wherein the conductive structure (6) is formed partially or completely from an electrically conductive plastic.

12. Catheter (1) according to claim 11, wherein the conductive structure (6) is formed partially or completely from a doped plastic.

13. Catheter (1) according to claim 11, wherein the conductive structure (6) is formed partially or completely from a plastic containing electrically conductive additives.

14. Catheter (1) according to claim 13, wherein the conductive structure (6) is formed partially or completely from a fiber-reinforced plastic composite.

15. Catheter (1) according to claim 14, wherein the conductive structure (6) is formed partially or completely from a carbon fiber reinforced plastic.

16. Catheter (1) according to one of the preceding claims, comprising an expandable balloon (16), wherein the conductive structure (6) extends at least sectionally along the balloon.

17. Method for the local treatment of tissue, in particular tumor tissue or other unwanted tissue types, in intravascular and intraluminal spaces with a catheter (1) according to any one of the preceding claims 1 to 16, comprising the steps: - Establishing and securing a percutaneous access; - Imaging-based localization of the target lesion; - Visualization of the target lesion using contrast medium; - Image-guided guidance of the catheter (1) over a guide wire to the target lesion; - Application of physical and / or chemical and / or biological measures; - Removal of the catheter (1).

18. The method of claim 17, further comprising the step of: - Visualizing the treatment effect using imaging techniques.

19. The method of claim 17 or 18, further comprising the step of: - Securing percutaneous access for repeated treatment of the tissue using the catheter (1).

20. Catheter system (40) with a catheter (1) according to one of claims 1 to 16, wherein the catheter system (40) further comprises a control unit (42) for controlling the energy source (12), and wherein the catheter system (40) is configured to carry out the method according to one of claims 17 to 19.

Images