Ultrasound-visible electrode needles for irreversible electroporation devices

Abstract

The present application belongs to the field of medical devices. The present application relates to an electrode needle of an irreversible electroporation device, an array of electrode needles, and an irreversible electroporation device comprising the electrode needle. The present application relates to an electrode needle for an irreversible electroporation device, the electrode needle comprising an electrode needle body, the electrode needle body being adapted to receive electric pulses and apply an electric field in a predetermined direction, and the surface of the electrode needle body comprising a conductive area and an ultrasound-developable area.

Description

Technical Field

[0001] The present application belongs to the field of medical devices. More specifically, the present application relates to an electrode needle of an irreversible electroporation device, an array of electrode needles, and an irreversible electroporation device comprising the electrode needles. Background Art

[0002] Tumors, especially malignant tumors, are major diseases that endanger human health. Traditional tumor treatments and newly developed treatments are thermal ablation physical therapies characterized by minimally invasive ablation. Due to restrictions on indications, contraindications, treatment side effects, thermal effects and other factors, its clinical application has certain limitations. In recent years, with the continuous development of pulsed bioelectrics, electric field pulses have attracted the attention of researchers with their non-thermal and minimally invasive biomedical effects. Among them, irreversible electroporation for tumor treatment has attracted widespread attention from researchers in the field of bioelectrics at home and abroad with its advantages and characteristics such as rapidity, controllability, visibility, selectivity and non-thermal mechanism, and has gradually been applied to the clinical treatment of tumors.

[0003] Irreversible electroporation is a technique that inserts an electrode needle into the patient's diseased area and applies a pulsed electric field around the cells, causing nanoscale micropores to appear on the cell membrane surface, thereby causing the exchange of substances inside and outside the cell, thereby destroying the cell homeostasis, causing permanent damage to the cell membrane, and ultimately leading to cell death. This technology has excellent application value in the treatment of tumors. The pulsed electric field can produce a non-thermal, non-chemically toxic killing effect. Moreover, the pulsed electric field only acts on the phospholipid bilayer membrane structure of the cell membrane, and does not act on components such as proteins and collagen, protecting the important vascular structures in the ablation area, and the ablation boundary is clear.

[0004] Typically, when using irreversible electroporation technology for treatment, ultrasound is used to determine the diseased area, and then electrode needles are inserted for treatment. The electrode needles used with ultrasound and inserted into the human body are one or more long needles. Currently, the electrode needles are not visible in ultrasound after being inserted into the human body. This makes it impossible to accurately measure the size of the electrode needle actually inserted into the human body (and the actual discharge size).

[0005] At present, the size of the electrode needle actually inserted into the human body (and the actual discharge size) is determined entirely by the doctor's clinical experience, which not only requires high clinical experience of the doctor, but also has inaccuracies.

[0006] There is an urgent need to design an electrode needle for an irreversible electroporation device and a method of using the electrode needle that overcomes the above-mentioned defects. Summary of the invention

[0007] The present application provides an electrode needle which is ultrasound-visible.

[0008] The electrode needle described in the present application includes an electrode needle body, which is suitable for receiving electric pulses and applying an electric field in a predetermined direction. The surface of the electrode needle body includes a conductive area and an ultrasonically developable area. The conductive area is suitable for applying an electric field in a predetermined direction to perform irreversible electroporation. The ultrasonically developable area is suitable for accurately determining the size of the electrode needle actually inserted into the human body and the actual discharge size. The conductive area is formed of a conductive material. The ultrasonically developable area is formed of an ultrasonically developable material, for example, by coating an ultrasonically developable material. Alternatively, ultrasonic developability can also be achieved by changing the surface structure of the electrode needle.

[0009] In another embodiment, the surface of the electrode needle body also includes an insulating region. The area / width of the insulating region is greater than, equal to or less than the area / width of the ultrasound developable region. Optionally, the area / width of the insulating region overlaps or partially overlaps with the area / width of the ultrasound developable region. The insulating region can inhibit the propagation of the electric field away from the target biological tissue, alleviating side effects such as muscle contraction. Preferably, the insulating region is formed of an insulating material, for example, by coating a coatable insulating material. The insulating material includes a coatable material of various organic and inorganic materials having insulation, heat resistance and biocompatibility, for example, polyparaxylene, etc. (for example, see WO2018050025). The entire contents of WO2018050025 are incorporated herein by reference.

[0010] Another aspect of the present application relates to an irreversible electroporation device, which includes: a pulse forming device configured to generate an electric pulse; and one or more electrode needles according to the present application, configured to receive the electric pulse from the pulse forming device to generate an electric field.

[0011] In another aspect, the present application provides a method for treating a tumor using an irreversible electroporation device comprising the electrode needle.

[0012] The electrode needle described in the present application can accurately determine the size of the electrode needle actually inserted into the human body and the actual discharge size when in use, avoiding inaccuracy caused by insufficient operator experience. Furthermore, since the size of the electrode needle actually inserted into the human body and the actual discharge size can be accurately determined, the irreversible electroporation device including the electrode needle described in the present application can accurately apply the electric field to the diseased part (such as a tumor), thereby improving the treatment effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 It is a schematic diagram of an electrode needle according to one embodiment of the present application.

[0014] Figure 2 It is a schematic diagram of an electrode needle according to one embodiment of the present application.

[0015] Figure 3 It is a schematic diagram of an electrode needle according to one embodiment of the present application.

[0016] Figure 4 It is a schematic diagram of an electrode needle according to one embodiment of the present application.

[0017] Description of Reference Numerals

[0018] 1: Insulation area

[0019] 2: Ultrasound imaging area

[0020] 3: Conductive area

[0021] 4: Electrode needle body DETAILED DESCRIPTION OF THE INVENTION

[0023] Ultrasound imaging means are generally used in ultrasound-guided catheter intervention procedures (for example, see CN107335099A, CN103623493A, CN204352312U). The entire contents of CN107335099A, CN103623493A, and CN204352312U are incorporated herein by reference.

[0024] At present, ultrasound imaging means have not been used in the electrode needles of irreversible electroporation devices. The inventor of this application innovatively uses ultrasound imaging means for the electrode needles of irreversible electroporation devices, solving the technical problem of not being able to accurately determine the size of the electrode needle inserted into the patient's body and the actual discharge size.

[0025] The electrode needle described in the present application includes an electrode needle body, which is suitable for receiving electric pulses and applying an electric field in a predetermined direction (for example, the direction of a tumor). The surface of the electrode needle body includes a conductive area and an ultrasonically developable area. The conductive area is suitable for applying an electric field in a predetermined direction to perform irreversible electroporation. The ultrasonically developable area is suitable for accurately determining the size of the electrode needle actually inserted into the human body and the actual discharge size. The conductive area is formed by a conductive material. The ultrasonically developable area is formed by an ultrasonically developable material, for example, by coating an ultrasonically developable material, such as a polymeric developable material. When the ultrasonically developable area is formed by coating an ultrasonically developable material, the ultrasonically developable area can also be called an ultrasonically developable coating. Alternatively, ultrasonic developability can also be achieved by changing the surface structure of the electrode needle.

[0026] In another embodiment, the surface of the electrode needle body also includes an insulating region. The area / width of the insulating region is greater than, equal to or less than the area / width of the ultrasound developable region. Optionally, the area / width of the insulating region overlaps or partially overlaps with the area / width of the ultrasound developable region. The insulating region can suppress the propagation of the electric field away from the target biological tissue, alleviating side effects such as muscle contraction. Preferably, the insulating region is formed by a coatable insulating material, for example, by coating a coatable insulating material. The coatable insulating material includes coatable materials of various organic and inorganic materials having insulation, heat resistance and biocompatibility, for example, polyparaxylene, polyetheretherketone (PEEK), etc. When the insulating region is formed by coating an insulating material, the insulating region can also be referred to as an insulating coating.

[0027] In a preferred embodiment, the electrode needle described in the present application includes a conductive region, an ultrasound-developable region, and an insulating region.

[0028] Those skilled in the art will appreciate that the electrode needle described herein may be manufactured / constructed in any manner, as long as its surface has the conductive region, ultrasound-developable region, and optional insulating region described herein.

[0029] In some embodiments, the terms "electrode needle" and "electrode needle body" described herein can be used interchangeably. In one embodiment, the electrode needle body can be formed entirely of a conductive material. The conductive material can be any conductive material that can be imagined by a person skilled in the art, in particular, a conductive material suitable for applying irreversible electroporation pulses, for example, a conductive metal material, such as (304) stainless steel.

[0030] In one embodiment, a portion of the surface of the electrode needle body has an ultrasound-developable area and an insulating area. The area / width of the insulating area is greater than, equal to, or less than the area / width of the ultrasound-developable area. Optionally, the area / width of the insulating area overlaps or partially overlaps with the area / width of the ultrasound-developable area.

[0031] Preferably, the electrode needle described in the present application includes one or more ultrasound-developable areas. The number of ultrasound-developable areas can be 1, 2, 3, 4, 5, 6 or more, preferably 2. When multiple ultrasound-developable areas are included, preferably one ultrasound-developable area overlaps with the insulating area, and the area / width of the ultrasound-developable area is smaller than the area / width of the insulating area. The area / width of the remaining ultrasound-developable areas is greater than, less than or equal to the area / width of the insulating area, and the remaining ultrasound-developable areas partially overlap, overlap, are adjacent or spaced apart by an appropriate distance from the insulating area. Further, one end of an ultrasound-developable area may overlap with one end of the insulating area, and the overlapping end of the ultrasound-developable area and the insulating area is adjacent to the conductive area. The ultrasound-developable area may be insulating.

[0032] When the insulating region overlaps or partially overlaps with the ultrasound developable region, the insulating region is located above or below the ultrasound developable region in the radial direction of the electrode needle body. Preferably, the insulating region is located above the ultrasound developable region in the radial direction of the electrode needle body, and such a setting can avoid the risk of ultrasound developable material falling off.

[0033] The conductive area is located at the top of the electrode needle, which can also be called the exposed end. The size of the conductive area is also called the actual discharge size. The insulating area and / or the ultrasound-developable area are located at the bottom of the electrode needle. The top of the electrode needle can have various shapes, such as an inclined surface shape inclined relative to the axis of the electrode needle, or a needle tip shape converging on the axis of the electrode needle. The length of the conductive end is not particularly limited, and can be 1-20 cm, preferably 1-15 cm, more preferably 1-10 cm, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 cm.

[0034] There is no particular limitation on the length of the electrode needle described in the present application. For example, the length of the electrode needle of the present application can be 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65 or 70 cm. When used, those skilled in the art can select an electrode needle of a suitable length according to actual conditions, or cut the electrode needle into a suitable length before using it. The surface of the electrode needle can be smooth or rough, preferably smooth.

[0035] The width of the insulating region is not particularly limited, for example, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65 cm. The insulating region is used to suppress the propagation of the electric field away from the target biological tissue. The width of the insulating region refers to the width of the insulating region in the direction of the electrode needle axis.

[0036] There is no particular limitation on the width of the ultrasonically developable area. Preferably, the width of the ultrasonically developable area may be 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 mm. The number of ultrasonically developable areas may be 1, 2, 3, 4, 5, 6 or more, preferably 2. Further, when a plurality of ultrasonically developable areas are included, preferably one ultrasonically developable area overlaps with an insulating area, and the area / width of the ultrasonically developable area is smaller than the area / width of the insulating area. The area / width of the remaining ultrasonically developable areas is greater than, less than, or equal to the area / width of the insulating area, and the remaining ultrasonically developable areas overlap, overlap, are adjacent, or are spaced an appropriate distance apart from the insulating area. The width of the ultrasonically developable area refers to the width of the ultrasonically developable area in the direction of the electrode needle axis.

[0037] More preferably, the electrode needle of the present application has two ultrasound-developable areas, with widths of 5-15 mm. The first ultrasound-developable area overlaps with the insulating area, wherein one end of the first ultrasound-developable area overlaps with one end of the insulating area, the width of the first ultrasound-developable area is smaller than the width of the insulating area, and the overlapping ends of the first ultrasound-developable area and the insulating area are adjacent to the conductive area. The second ultrasound-developable area also overlaps with the insulating area. The first ultrasound-developable area is separated from the second ultrasound-developable area by an appropriate distance, for example, 5-10 cm, such as 5, 6, 7, 8, 9, 10 cm.

[0038] The ultrasonic developable area is formed by an ultrasonic developable material. The ultrasonic developable material includes a material with high acoustic impedance (acoustic impedance greater than), such as one or more of aluminum oxide, titanium dioxide and silicon dioxide. Alternatively, ultrasonic developability can also be achieved by changing the surface structure of the electrode needle, for example, a part of the surface of the electrode needle can be set to have a shape different from the surface shape of other parts, such as a concave, a thread, a step, etc.

[0039] Due to the presence of the ultrasound-developable area, a person skilled in the art can easily determine the size of the electrode needle actually inserted into the human body and the actual discharge size, thereby avoiding the inaccuracy caused by the lack of operator experience, so that the irreversible electroporation device including the electrode needle described in the present application can accurately apply the electric field to the diseased part (such as a tumor), so that medical personnel can better implement the treatment plan, and ultimately improve the treatment effect. In addition, the insulating area is located above the ultrasound-developable area, which can avoid the risk of the ultrasound-developable material falling off.

[0040] The target biological tissue described in the present application includes benign or malignant tumors, for example, the malignant tumor includes rectal cancer, head and neck cancer, lung cancer, breast cancer, esophageal cancer, gastric cancer, intestinal cancer, liver cancer, pancreatic cancer, bile duct cancer, gallbladder cancer, kidney cancer, ovarian cancer, bladder cancer, or prostate cancer, and the benign tumor includes prostate hyperplasia or breast hyperplasia, etc. Those skilled in the art know that when irreversible electroporation is performed on the target biological tissue (e.g., tumor, etc.), the electric field application direction of the electrode needle is opposite to the target biological tissue, so as to apply the electric field to the target biological tissue and then ablate the target biological tissue (e.g., tumor, etc.).

[0041] The electrode needle described herein can be used in an irreversible electroporation device, such as the irreversible electroporation device described in CN106388932B and WO2018050025. When used, part or all of the length of the electrode needle described in this application is inserted into the patient's body, provided that the ultrasound imaging area should be inserted into the patient's body.

[0042] The present application also provides a method for preparing the electrode needle:

[0043] 1) providing commercially available electrode needles; and

[0044] 2) Arranging an ultrasonically developable structure or coating an ultrasonically developable material and / or an insulating material to form an ultrasonically developable area and / or an insulating area.

[0045] Another aspect of the present application relates to an irreversible electroporation device, which includes: a pulse forming device configured to generate an electric pulse; and one or more electrode needles according to the present application, configured to receive the electric pulse from the pulse forming device to generate an electric field.

[0046] In another aspect, the present application provides a method for treating tumors using an irreversible electroporation device including the electrode needle, including the step of using an ultrasonic probe to detect the size of the electrode needle inserted into the patient's body and the actual discharge size, wherein using the ultrasonic probe to detect the size of the electrode needle inserted into the patient's body and the actual discharge size is achieved by using the ultrasonic probe to detect the ultrasonically developable area on the electrode needle inserted into the patient's body.

[0047] In another aspect, the present application provides a use of the electrode needle in preparing an irreversible electroporation device for treating tumors.

[0048] In another aspect, the present application provides an electrode needle array, comprising: one or more electrode needles, the axes of the bodies of the one or more electrode needles are parallel to each other, wherein at least one of the one or more electrode needles is the electrode needle described in the present application. DETAILED DESCRIPTION

[0049] The following examples are provided to facilitate a better understanding of the present invention, but are not intended to limit the present invention. The methods in the following examples are conventional methods unless otherwise specified; the materials described are commercially available unless otherwise specified.

[0050] The electrode needles having ultrasound-visible areas described in the examples were prepared according to the following method

[0051] 1) Providing commercially available electrode needles;

[0052] 2) providing an ultrasonically developable structure or coating an ultrasonically developable material to form an ultrasonically developable area; and

[0053] 3) Optionally apply insulating material to form an insulating area.

[0054] Example 1

[0055] The electrode needle is a 304 stainless steel electrode needle with a length of 30 cm. The width of the top conductive area is 10 cm. The electrode needle has an ultrasound-developable area with a width of 20 mm. The ultrasound-developable area is formed by setting a concave shape in the area on the surface of the electrode needle. One end of the ultrasound-developable area is adjacent to the top conductive area. The bottom area adjacent to the other end of the ultrasound-developable area can also be used as a second conductive area.

[0056] Example 2

[0057] The electrode needle is a 304 stainless steel electrode needle with a length of 40 cm. The length of the top conductive area is 5 cm. The electrode needle also has an ultrasonically developable area and an insulating area. The ultrasonically developable area is formed by using a coatable material containing aluminum oxide in this area on the surface of the electrode needle. The insulating area is formed by polyparaxylene. The width of the ultrasonically developable area is 10 mm. The length of the insulating area is 35 cm. The ultrasonically developable area overlaps with the insulating area, and one end of the ultrasonically developable area coincides with one end of the insulating area, and the coincident end is adjacent to the conductive area. From the radial direction of the electrode needle body, the insulating area is located above the ultrasonically developable area.

[0058] Example 3

[0059] The electrode needle is a 304 stainless steel electrode needle with a length of 40 cm. The length of the top conductive area is 5 cm. The length of the insulating area is 35 cm. The ultrasonic developable area is formed by using a coatable material containing titanium dioxide in this area on the surface of the electrode needle. The insulating area is formed by PEEK. The electrode needle also has two ultrasonic developable areas, each of which has a width of 10 mm. The first ultrasonic developable area overlaps with the insulating area, and one end of the first ultrasonic developable area coincides with one end of the insulating area, and the overlapping end of the ultrasonic developable area and the insulating area is adjacent to the conductive area. The second ultrasonic developable area also overlaps with the insulating area. The first ultrasonic developable area and the second ultrasonic developable area are 5 cm apart from each other. In terms of the radial direction of the electrode needle body, the insulating area is located above the ultrasonic developable area.

[0060] Equivalent

[0061] The foregoing examples are only used to illustrate the present invention and should not be regarded as any limitation of the scope of the present invention. Obviously, many modifications and changes can be made to the content described in the above-mentioned specific embodiments of the present invention and the examples, and will not deviate from the principle of the present invention. All such modifications and changes are all contained in the application.

Claims

1. An electrode needle for an irreversible electroporation device, the electrode needle comprising an electrode needle body, the electrode needle body being suitable for receiving electric pulses and applying an electric field in a predetermined direction, and the surface of the electrode needle body comprising a conductive area and an ultrasound-developable area; the surface of the electrode needle body also comprising an insulating area, the conductive area being located at the top of the electrode needle body, the insulating area and the ultrasound-developable area being located at the bottom of the electrode needle body; the width of the ultrasound-developable area in the direction of the electrode needle axis is smaller than the width of the insulating area in the direction of the electrode needle axis; The number of the ultrasound-developable areas is multiple, wherein the first ultrasound-developable area overlaps with the insulating area, one end of the first ultrasound-developable area coincides with one end of the insulating area, and the coincident end of the first ultrasound-developable area and the insulating area is adjacent to the conductive area; The remaining ultrasound-visible areas partially overlap, overlap, are adjacent to, or are spaced a suitable distance apart from the insulating areas; The ultrasound imaging area is used to accurately determine the size of the electrode needle actually inserted into the human body and the actual discharge size. 2 . The electrode needle according to claim 1 , wherein the insulating region is formed of polyparaxylene. 3 . The electrode needle according to claim 1 , wherein the conductive region is formed of a conductive metal material.

4. The electrode needle according to any one of claims 1-2, wherein the ultrasound-developable area is formed by any one of the following methods: 1) formed by ultrasound-developable material; 2) formed by setting a part of the surface of the electrode needle to have a shape different from the surface shape of other parts. The electrode needle according to claim 4 , wherein the number of the ultrasound-visible areas is 2.

6. The electrode needle according to any one of claims 1 to 2, wherein the electrode needle body is entirely formed of a conductive material.

7. The electrode needle according to any one of claims 1-2, wherein the insulating region is located above or below the ultrasound-visible region in the radial direction of the electrode needle body. 8 . The electrode needle according to claim 7 , wherein the insulating region is located above the ultrasound-visible region in the radial direction of the electrode needle body. 9 . The electrode needle according to claim 5 , wherein the remaining ultrasound-visible area also overlaps with the insulating area.

10. An irreversible electroporation device, comprising: a pulse forming device configured to generate an electrical pulse; and one or more electrode needles according to any one of claims 1 to 9, configured to receive electric pulses from a pulse forming device to generate an electric field.

11. An electrode needle array, comprising: One or more electrode needles, the axes of the bodies of the one or more electrode needles are parallel to each other, wherein at least one of the one or more electrode needles is the electrode needle according to any one of claims 1 to 9.

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