Balloon catheter device for treating central lung cancer by combining irreversible electroporation and cold atmospheric pressure plasma jet

Abstract

The invention discloses a balloon catheter device for treating central lung cancer by combining irreversible electroporation and cold atmospheric pressure plasma jet. The balloon catheter device comprises a balloon structure, a multi-cavity catheter and a balloon electrode, the invention provides a balloon catheter device based on a bronchoscope. The balloon catheter device is used for achieving combined treatment of lung cancer through irreversible electroporation and atmospheric pressure cold plasma. The balloon catheter device is composed of a balloon electrode and a catheter, and the balloon electrode covers the surface of a balloon and can deliver a pulsed electric field to ablate the central lung cancer. The catheter device integrates the bronchoscope and the plasma discharge tube, can directionally convey working gas to the bronchus network under the guidance of the navigation system, generates plasma active matter after being ionized by the pulsed electric field, and can be quickly sent into the bronchus network under the action of the electric field and the flow field.

Description

Technical Field

[0001] The invention relates to the technical field of minimally invasive tumor treatment, and in particular to a balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet. Background Art

[0002] Currently, surgical resection is the gold standard for treating early-stage lung cancer. However, due to many complications and impaired cardiopulmonary function, only about one-third of lung cancer patients are eligible for surgical resection.

[0003] Traditional therapies, including stereotactic radiotherapy or fractionated radiotherapy, have been widely used in clinical practice, but these therapies have certain limitations, including heart disease and radiation pneumonia induced by long-term exposure to radiation. In addition, there is a treatment dead angle for tumor tissue remaining in the bronchus, which cannot be completely ablated or effectively inactivated. In recent years, microwave ablation and cryotherapy have been widely used in patients with peripheral lung cancer who cannot undergo surgery. However, for central lung cancer, the large blood vessels adjacent to the central trachea have a strong heat dissipation effect, which will seriously affect the ablation effect of local tumors; at the same time, hot and cold ablation will denature proteins and collagen in the ablation area, resulting in airway loss and smaller blood vessels; in addition, because the lungs are close to the heart, for example: the heat generated by microwave ablation will also form a central heat sink in the mediastinum, inducing new complications. Therefore, microwaves, cryotherapy and other methods are rarely used in clinical practice to treat central lung cancer.

[0004] Irreversible electroporation (IRE) is a minimally invasive physical therapy method for non-thermal ablation of tumors. It delivers short-term high-power energy to tumor cells, inducing the collapse of the membrane structure of the cell unit, forming a large number of perforations and causing cell death. Irreversible electroporation can preserve large blood vessels and bronchi in the ablation area, avoiding complications such as bronchopleural fistula that may occur after thermal ablation of the lungs. Clinical studies have shown that IRE ablation technology is suitable for the treatment of patients with central lung cancer. The electric field distribution is highly sensitive to the solid-liquid-gas three-phase medium of the patient's lung tissue. Therefore, it is necessary to design a precise comprehensive energy delivery method to establish an effective electric field distribution in the lung tissue to cover all tumor lesions.

[0005] Secondly, the pulmonary bronchi are branched tree-like networks, which are divided into 23 generations. Imaging methods such as CT can only detect lesions in the 6th to 8th generation bronchial structures. Therefore, image-guided physical therapy cannot effectively clear the multiple micro-lesions diffused in the bronchi. Summary of the invention

[0006] The purpose of the present invention is to provide a balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, comprising a balloon structure, a multi-lumen catheter and a balloon electrode.

[0007] The balloon structure is a hollow structure and is located at the front end of the multi-lumen catheter.

[0008] The balloon structure includes a compressed state and an expanded state.

[0009] When the balloon structure is located in the target area, the balloon structure is in an extended state, otherwise, the balloon structure is in a compressed state. The target area includes the bronchial central lung cancer area and the bronchial network micro-lesion area.

[0010] The top end of the multi-lumen catheter extends out of the balloon structure.

[0011] The multi-lumen catheter generates plasma active substances by introducing working gas and pulse electric field.

[0012] The multi-lumen catheter delivers the pulsed electric field to the balloon electrode by introducing the pulsed electric field.

[0013] The balloon electrodes are evenly distributed on the surface of the balloon structure.

[0014] The balloon electrode is used to ablate central tumors.

[0015] The working modes of the balloon catheter device include a tumor ablation mode and a bronchial network micro-lesion clearing mode.

[0016] When the balloon catheter device works in the tumor ablation mode, the balloon structure is located in the central bronchial lung cancer area and is in an extended state. At this time, the balloon electrode on the surface of the balloon structure fits closely with the tumor surface and applies electric pulses to the tumor to achieve ablation of the central tumor.

[0017] When the balloon catheter device works in the bronchial network micro-lesion cleaning mode, the balloon structure is located in the bronchial network micro-lesion area and is in an extended state, thereby expanding the bronchial duct. At this time, the multi-lumen catheter delivers plasma active substances to the bronchi by introducing working gas and pulsed electric field, thereby cleaning the diffuse micro-lesions in the bronchial network.

[0018] Furthermore, the multi-lumen catheter includes a main catheter and a plasma discharge tube.

[0019] The top end of the main catheter is connected to the balloon structure.

[0020] The plasma discharge tube is located in the main conduit, and the length of the plasma discharge tube is greater than the main conduit.

[0021] The top end of the plasma discharge tube extends out of the balloon structure.

[0022] The main conduit is used for introducing a pulse electric field.

[0023] The plasma discharge tube is used to introduce working gas, and the working gas generates plasma active substances under the action of the pulse electric field.

[0024] The plasma actives are delivered into the bronchi via a plasma discharge tube.

[0025] Furthermore, the multi-lumen catheter also includes a bronchoscope.

[0026] The bronchoscope is located in the main duct, and the length of the bronchoscope is greater than the main duct.

[0027] A balloon structure extends out of the top end of the bronchoscope.

[0028] The bronchoscope is connected to a navigation system to navigate the balloon catheter device to the corresponding area of ​​the bronchus.

[0029] Furthermore, the working gas includes one or more of helium, argon, nitrogen and oxygen.

[0030] Furthermore, when the working gas is a mixed gas, the input speed range of the working gas is 0.5 L / min-10 L / min.

[0031] Furthermore, the electric field range around the balloon electrode generated by the electric pulse applied by the balloon electrode is 500V / cm-1500V / cm.

[0032] Furthermore, the pulsed electric field includes high voltage square wave pulses.

[0033] Furthermore, when the balloon catheter device is working in the tumor ablation mode, it also monitors in real time through electric current whether the current in the tumor exceeds the threshold. If not, the pulse parameters are changed to continue to apply electric pulses to the tumor. If so, the application of electric pulses to the tumor is stopped, thereby completing the ablation of central lung cancer.

[0034] Furthermore, the pulse parameters include voltage amplitude, pulse width, and pulse frequency.

[0035] Furthermore, when the balloon catheter device operates in the bronchial network micro-lesion clearing mode, the position of the bright plasma light column is monitored in real time through a bronchoscope, and the plasma action time is recorded.

[0036] When the duration of plasma action exceeds a threshold, delivery of plasma activity to the bronchi is stopped.

[0037] The technical effect of the present invention is unquestionable. The present invention proposes a bronchoscope-based balloon catheter device for realizing irreversible electroporation and atmospheric pressure cold plasma combined treatment of lung cancer. The balloon catheter device consists of two parts: a balloon electrode and a catheter. The balloon electrode covers the surface of the balloon and can deliver pulsed electric fields to ablate central lung cancer. The catheter device integrates a bronchoscope and a plasma discharge tube. Under the guidance of the navigation system, the working gas can be delivered to the bronchial network in a directional manner. After ionization by the pulsed electric field, plasma active substances are generated, which can be quickly delivered to the bronchial network after the action of the electric field and flow field.

[0038] The balloon catheter structure based on bronchoscope guidance proposed in the present invention delivers irreversible electroporation electrical energy to improve the penetration depth of the electric field and the ablation range; the instantaneous high-power electrical energy discharge proposed in the present invention generates an atmospheric pressure cold plasma jet, and the active substances such as oxygen atoms, hydroxyl free radicals, and singlet oxygen brought by the plasma will be quickly and non-invasively delivered into the bronchial network system to induce apoptosis of tumor microlesions through oxidative stress response.

[0039] Compared with the percutaneous puncture method, the irreversible electroporation and plasma ablation technology assisted by bronchoscope guidance avoids the limitation of multiple percutaneous punctures and is significantly safer. Based on the homologous nanosecond pulse electric energy drive and combined with the bronchoscope optical navigation system, the present invention proposes a balloon catheter structure combined therapy device. The device integrates a balloon electrode that releases a pulsed electric field and a plasma discharge extension tube to achieve ablation of central lung cancer and clearance of diffuse micro-lesions in the bronchial network.

[0040] The balloon-catheter combined therapy device designed in the present invention can synchronously apply a pulsed electric field and an atmospheric pressure cold plasma jet, thereby achieving ablation of central tumors and cleaning of micro-lesions, reducing tumor residues and reducing the risk of recurrence.

[0041] The balloon-catheter combined therapy device proposed by the present invention can generate a uniform pulse electric field, a higher electric field penetration depth, and a plasma of high-density active substances in the body at the central lung cancer.

[0042] The combined therapy device proposed in the present invention can adjust the applied dose, action time, and action sequence of the pulsed electric field and plasma according to actual clinical needs.

[0043] The combined therapy device proposed in the present invention can control the uniformity of the generated pulse electric field and the concentration of plasma active substances by controlling the balloon electrode topology, working gas, and electrical parameters according to different tumor CT image data, and has the characteristics of flexibility and adjustability. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 It is a schematic diagram of the balloon-catheter combined therapy delivery device of the present invention;

[0045] Figure 2 It is a schematic diagram of the balloon catheter integrated optics and plasma discharge delivery device of the present invention;

[0046] Figure 3 Schematic diagram of plasma discharge generated by the balloon catheter in the bronchial network of the present invention, wherein Figure 3 (a) Schematic diagram of plasma generated in the bronchial model; Figure 3 (b) is a schematic diagram of the spectrum distribution of the generated plasma;

[0047] Figure 4 It is a schematic diagram of the balloon electrode electric field delivery device in the balloon catheter of the present invention;

[0048] Figure 5 A flowchart for the use of balloon catheters to ablate central lung cancer;

[0049] In the figure, there are a balloon structure 1, a multi-lumen catheter 2, a main catheter 201, a bronchoscope 202, a plasma discharge tube 203, and a balloon electrode 3. DETAILED DESCRIPTION

[0050] The present invention is further described below in conjunction with the embodiments, but it should not be understood that the above subject matter of the present invention is limited to the following embodiments. Without departing from the above technical ideas of the present invention, various substitutions and changes are made according to the common technical knowledge and customary means in the art, which should all be included in the protection scope of the present invention.

[0051] Embodiment 1:

[0052] See also Figures 1 to 5 A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet comprises a balloon structure 1, a multi-lumen catheter 2, and a balloon electrode 3.

[0053] The balloon structure 1 is a hollow structure and is located at the front end of the multi-lumen catheter 2 .

[0054] The balloon structure 1 includes a compressed state and an expanded state.

[0055] When the balloon structure 1 is located in the target area, the balloon structure 1 is in an extended state, otherwise, the balloon structure 1 is in a compressed state. The target area includes the bronchial central lung cancer area and the bronchial network micro-lesion area.

[0056] The top end of the multi-lumen catheter 2 extends out of the balloon structure 1 .

[0057] The multi-lumen catheter 2 generates plasma active substances by introducing working gas and pulse electric field.

[0058] The multi-lumen catheter 2 delivers the pulsed electric field to the balloon electrode 3 by introducing the pulsed electric field.

[0059] The balloon electrodes 3 are evenly distributed on the surface of the balloon structure 1 .

[0060] The balloon electrode 3 is used for ablating central tumors.

[0061] The working modes of the balloon catheter device include a tumor ablation mode and a bronchial network micro-lesion clearing mode.

[0062] When the balloon catheter device works in the tumor ablation mode, the balloon structure 1 is located in the central bronchial lung cancer area and is in an extended state. At this time, the balloon electrode 3 on the surface of the balloon structure 1 is closely attached to the tumor surface and applies electric pulses to the tumor to achieve ablation of the central tumor.

[0063] When the balloon catheter device works in the bronchial network micro-lesion cleaning mode, the balloon structure 1 is located in the bronchial network micro-lesion area and is in an extended state, thereby expanding the bronchial duct. At this time, the multi-lumen catheter 2 delivers plasma active substances to the bronchi by introducing working gas and pulsed electric field, thereby cleaning the diffuse micro-lesions in the bronchial network.

[0064] Embodiment 2:

[0065] A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, the main technical contents of which are shown in Example 1. Furthermore, the multi-lumen catheter 2 includes a main catheter 201 and a plasma discharge tube 203.

[0066] The top end of the main catheter 201 is connected to the balloon structure 1 .

[0067] The plasma discharge tube 203 is located inside the main conduit 201 , and the length of the plasma discharge tube 203 is greater than that of the main conduit 201 .

[0068] The top end of the plasma discharge tube 203 extends out of the balloon structure 1 .

[0069] The main conduit 201 is used to introduce a pulsed electric field.

[0070] The plasma discharge tube 203 is used to introduce working gas, and the working gas generates plasma active substances under the action of the pulse electric field.

[0071] The plasma active species is delivered into the bronchi via the plasma discharge tube 203 .

[0072] Embodiment 3:

[0073] A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, the main technical contents of which are shown in any one of Examples 1 to 2. Furthermore, the multi-lumen catheter 2 also includes a bronchoscope 202.

[0074] The bronchoscope 202 is located in the main catheter 201 , and the length of the bronchoscope 202 is greater than that of the main catheter 201 .

[0075] The top end of the bronchoscope 202 extends out of the balloon structure 1 .

[0076] The bronchoscope 202 is connected to the navigation system to navigate the balloon catheter device to the corresponding area of ​​the bronchus.

[0077] Embodiment 4:

[0078] A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, the main technical contents of which are shown in any one of Examples 1 to 3. Furthermore, the working gas includes one or more of helium, argon, nitrogen and oxygen.

[0079] Embodiment 5:

[0080] A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, the main technical contents of which are shown in any one of Examples 1 to 4. Furthermore, when the working gas is a mixed gas, the input speed range of the working gas is 0.5L / min-10L / min.

[0081] Embodiment 6:

[0082] A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, the main technical contents of which are shown in any one of Examples 1 to 5. Furthermore, the electric field range around the balloon electrode 3 generated by the electric pulse applied by the balloon electrode 3 is 500V / cm-1500V / cm.

[0083] Embodiment 7:

[0084] A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, the main technical contents of which are shown in any one of Examples 1 to 6, wherein the pulsed electric field comprises a high-voltage square wave pulse.

[0085] Embodiment 8:

[0086] A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, the main technical contents of which are shown in any one of Examples 1 to 7. Furthermore, when the balloon catheter device operates in the tumor ablation mode, it also monitors in real time through the current whether the current in the tumor exceeds the threshold value. If not, the electric pulse is continued to be applied to the tumor after changing the pulse parameters. If so, the application of the electric pulse to the tumor is stopped, thereby completing the ablation of central lung cancer.

[0087] Embodiment 9:

[0088] A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, the main technical contents of which are shown in any one of Examples 1 to 8. Furthermore, the pulse parameters include voltage amplitude, pulse width, and pulse frequency.

[0089] Embodiment 10:

[0090] A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, the main technical contents of which are shown in any one of Examples 1 to 9. Furthermore, when the balloon catheter device operates in the bronchial network micro-lesion cleaning mode, the position of the bright plasma light column is monitored in real time through a bronchoscope, and the action time of the plasma is recorded.

[0091] When the duration of plasma action exceeds a threshold, delivery of plasma activity to the bronchi is stopped.

[0092] Embodiment 11:

[0093] See also Figures 1 to 5 A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet comprises a balloon structure 1, a multi-lumen catheter 2, and a balloon electrode 3.

[0094] The balloon structure 1 is a hollow structure and is located at the front end of the multi-lumen catheter 2 .

[0095] The balloon structure 1 includes a compressed state and an expanded state.

[0096] When the balloon structure 1 is located in the target area, the balloon structure 1 is in an extended state, otherwise, the balloon structure 1 is in a compressed state. The target area includes the bronchial central lung cancer area and the bronchial network micro-lesion area.

[0097] The top end of the multi-lumen catheter 2 extends out of the balloon structure 1 .

[0098] The multi-lumen catheter 2 generates plasma active substances by introducing working gas and pulse electric field.

[0099] The multi-lumen catheter 2 delivers the pulsed electric field to the balloon electrode 3 by introducing the pulsed electric field.

[0100] The balloon electrodes 3 are evenly distributed on the surface of the balloon structure 1 .

[0101] The balloon electrode 3 is used for ablating central tumors.

[0102] The working modes of the balloon catheter device include a tumor ablation mode and a bronchial network micro-lesion clearing mode.

[0103] When the balloon catheter device works in the tumor ablation mode, the balloon structure 1 is located in the central bronchial lung cancer area and is in an extended state. At this time, the balloon electrode 3 on the surface of the balloon structure 1 is closely attached to the tumor surface and applies electric pulses to the tumor to achieve ablation of the central tumor.

[0104] When the balloon catheter device works in the bronchial network micro-lesion cleaning mode, the balloon structure 1 is located in the bronchial network micro-lesion area and is in an extended state, thereby expanding the bronchial duct. At this time, the multi-lumen catheter 2 delivers plasma active substances to the bronchi by introducing working gas and pulsed electric field, thereby cleaning the diffuse micro-lesions in the bronchial network.

[0105] When the balloon catheter device is used to ablate central lung cancer, the balloon structure 1 is compressed and inserted into the bronchus. After reaching the central lung cancer area, the balloon structure 1 is extended so that the balloon electrode 3 on the surface of the balloon structure 1 fits tightly to the tumor surface. The balloon electrode 3 applies electric pulses to the tumor to achieve ablation of the central tumor.

[0106] When the balloon catheter device is used to clean diffuse micro-lesions in the bronchial network, the balloon structure 1 is in a compressed state, and the balloon catheter device is inserted deep into the bronchus, so that the balloon structure 1 is in an extended state. While the bronchial duct is expanded, the multi-lumen catheter 2 delivers plasma active substances to the bronchi by introducing working gas and pulsed electric fields, thereby cleaning the diffuse micro-lesions in the bronchial network.

[0107] Please refer to the attached Figure 1 , which is a schematic diagram of a device for generating and delivering a pulsed electric field and plasma active substances by a balloon catheter. The system has balloon electrodes covering the surface of the balloon to apply electric pulses. The body of the device is a stretchable balloon structure, which is in a compressed state before reaching the tumor, making it easier for the device to penetrate deep into the tortuous bronchi. After reaching central lung cancer, the balloon stretches to fit the electrode tightly to the surface of the tumor. The topologically optimized electrode can penetrate the electric field deeper into the tissue and increase the ablation area. The interior of the balloon is a cavity and a hollow discharge tube structure, which will extend out of the end of the balloon. After receiving the power supply excitation of the plasma, the working gas will be ionized to produce plasma, and the active substance will be injected into the bronchi.

[0108] Embodiment 12:

[0109] A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, the main technical contents of which are shown in Example 11. Furthermore, the multi-lumen catheter 2 includes a main catheter 201 and a plasma discharge tube 203.

[0110] The top end of the main catheter 201 is connected to the balloon structure 1 .

[0111] The plasma discharge tube 203 is located inside the main conduit 201 , and the length of the plasma discharge tube 203 is greater than that of the main conduit 201 .

[0112] The top end of the plasma discharge tube 203 extends out of the balloon structure 1 .

[0113] The main conduit 201 is used to introduce a pulsed electric field.

[0114] The plasma discharge tube 203 is used to introduce working gas, and the working gas generates plasma active substances under the action of the pulse electric field.

[0115] The plasma active species is delivered into the bronchi via the plasma discharge tube 203 .

[0116] Embodiment 13:

[0117] A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, the main technical contents of which are shown in any one of Examples 11 to 12. Furthermore, the multi-lumen catheter 2 also includes a bronchoscope 202.

[0118] The bronchoscope 202 is located in the main catheter 201 , and the length of the bronchoscope 202 is greater than that of the main catheter 201 .

[0119] The top end of the bronchoscope 202 extends out of the balloon structure 1 .

[0120] The bronchoscope 202 is connected to the navigation system to navigate the balloon catheter device to the corresponding area of ​​the bronchus.

[0121] Figure 2 The bronchoscope-based navigation system and the balloon catheter device that penetrates deep into the human bronchus were demonstrated. The device uses a multi-lumen catheter as input, integrating the gas path, the power supply circuit for plasma discharge, etc. Since the bronchus is a bifurcated structure, the end of the balloon needs to be guided by the bronchoscope to treat different branches, and no additional pulsed electric field treatment is required at this time. The system also has fluid delivery components for working gases such as carrier gas connections.

[0122] Embodiment 14:

[0123] The balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet has the main technical contents shown in any one of Examples 11 to 13. Furthermore, the working gas includes one or more of helium, argon, nitrogen and oxygen. The doping ratio of oxygen and nitrogen is usually set to 1000ppm.

[0124] Embodiment 15:

[0125] A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, the main technical contents of which are shown in any one of Examples 11 to 14. Furthermore, when the working gas is a mixed gas, the input speed range of the working gas is 0.5L / min-10L / min.

[0126] The mixed working gas is connected to the plasma discharge chamber through a fast interface. The plasma discharge chamber has an inner chamber surrounded by a needle electrode and a dielectric, and a ring electrode connected to the ground, forming a dielectric barrier discharge system for generating plasma.

[0127] Embodiment 16:

[0128] A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, the main technical contents of which are shown in any one of Examples 11 to 15. Furthermore, the electric field range generated by the electric pulse applied by the balloon electrode 3 within 1 cm around the balloon electrode 3 is 500V / cm-1500V / cm, which is within the effective ablation range of irreversible electroporation and meets the application requirements of ablation of central tumors.

[0129] Embodiment 17:

[0130] A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, the main technical contents of which are shown in any one of Examples 11 to 16, wherein the pulsed electric field comprises a high-voltage square wave pulse.

[0131] Figure 3 It was demonstrated that the mixed gas was ionized by a high-voltage square wave pulse with a pulse width of 10 kV, a pulse width of 500 ns and a repetition frequency of 10 kHz to produce active particles, and the plasma propagated toward the bronchial network driven by the flow field and the electric field.

[0132] Embodiment 18:

[0133] A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, the main technical contents of which are shown in any one of Examples 11 to 17. Furthermore, when the balloon catheter device operates in the tumor ablation mode, it also monitors in real time through the current whether the current in the tumor exceeds the threshold value. If not, the electric pulse is continued to be applied to the tumor after changing the pulse parameters. If so, the application of the electric pulse to the tumor is stopped, thereby completing the ablation of central lung cancer.

[0134] The current is used to monitor in real time whether the ablation is complete. If it is detected that the current in the tumor does not exceed the threshold, the applied voltage, pulse width or pulse repetition frequency needs to be appropriately increased and the pulse needs to be continued.

[0135] Embodiment 19:

[0136] A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, the main technical contents of which are shown in any one of Examples 11 to 18. Furthermore, the pulse parameters include voltage amplitude, pulse width, and pulse frequency.

[0137] Embodiment 20:

[0138] A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, the main technical contents of which are shown in any one of Examples 11 to 19. Furthermore, in terms of plasma, a helium-air mixed working gas is introduced into the system by precisely controlling the gas flux to ensure that the medium environment for pulsed plasma transmission has an appropriate gas composition and concentration.

[0139] When the balloon catheter device operates in the bronchial network micro-lesion clearing mode, the position of the bright plasma light column is also monitored in real time through the bronchoscope, and the plasma action time is recorded.

[0140] When the duration of plasma action exceeds a threshold, delivery of plasma activity to the bronchi is stopped.

[0141] Embodiment 21:

[0142] See also Figures 1 to 5 , a balloon catheter device combining irreversible electroporation and cold atmospheric pressure plasma jet for the treatment of central lung cancer, the main technical contents are as follows:

[0143] See attached Figure 1, which is a schematic diagram of a device for generating and delivering a pulsed electric field and plasma active substances by a balloon catheter. The system has balloon electrodes covering the surface of the balloon to apply electric pulses. The body of the device is a stretchable balloon structure, which is in a compressed state before reaching the tumor, making it easier for the device to penetrate deep into the tortuous bronchi. After reaching central lung cancer, the balloon stretches to fit the electrode tightly to the surface of the tumor. The topologically optimized electrode can penetrate the electric field deeper into the tissue and increase the ablation area. The interior of the balloon is a cavity and a hollow discharge tube structure, which will extend out of the end of the balloon. After receiving the power supply excitation of the plasma, the working gas will be ionized to produce plasma, and the active substance will be injected into the bronchi.

[0144] Figure 2 The bronchoscope-based navigation system and the balloon catheter device that penetrates deep into the human bronchus are demonstrated. The device is input by a multi-lumen catheter, integrating the gas path, the power supply circuit for plasma discharge, etc. Since the bronchus is a bifurcated structure, the end of the balloon needs to be guided by the bronchoscope to treat different branches, and no additional pulsed electric field treatment is required at this time. The system also has a fluid delivery component for working gases such as a carrier gas connection. The working gas may include at least one of helium, argon, nitrogen and oxygen. The mixed gas varies in the range of 0.5L / min-10L / min, and the doping ratio of oxygen and nitrogen is usually set to 1000ppm. The mixed working gas is connected to the plasma discharge chamber through a quick interface. The plasma discharge chamber has an inner chamber surrounded by a needle electrode and a dielectric, and a ring electrode connected to the ground, forming a dielectric barrier discharge system for generating plasma.

[0145] Figure 3 The mixed gas was ionized by a high-voltage square wave pulse with a pulse width of 10kV, a repetition frequency of 500ns, and a repetition frequency of 10kHz to produce active particles. The plasma propagated to the bronchial network driven by the flow field and the electric field. The bronchial network was 3D reconstructed through CT data and obtained through 3D printing. The blue-purple glow indicated that the plasma could cover a larger component of the bronchial network. Through emission spectrum diagnosis, it can be found that there are sufficient plasma active substances in each level of bifurcation, such as hydroxyl radicals, oxygen atoms, etc.

[0146] Figure 4 The electric field distribution established by the balloon electrode in lung cancer tissue was simulated using COMSOL finite element calculation software. The model considered the bronchi, lung cancer and surrounding lung tissue in a square lung tissue unit with a side length of 3mm. A 2000V, 200ns pulse was applied. The electric field simulation showed that an electric field of 500-1500V / cm was generated within 1cm around the balloon electrode, which is within the effective ablation range of irreversible electroporation and meets the application requirements of ablation of central tumors.

[0147] Figure 5 The process of using the balloon catheter in the present invention to treat central lung cancer is demonstrated. Using a multi-parameter adjustable pulse generator, the balloon device dilates the bronchus, the electrode fits the tumor, and the central lung cancer is ablated after the parameters are applied. The current is used to monitor in real time whether the ablation is thorough. If it is detected that the current in the tumor does not exceed the threshold, it is necessary to appropriately increase the applied voltage, pulse width, or pulse repetition frequency and continue to apply the pulse. In terms of plasma, the gas flux is precisely controlled to introduce a mixed working gas of helium and air into the system to ensure that the medium environment for pulsed plasma transmission has an appropriate gas composition and concentration. The working gas is ionized and produces a high concentration of active substances. The position of the bright light column of plasma is monitored in real time through the bronchoscope lens, and the action time of the bright light column is recorded. After the plasma has acted for 10 minutes, the delivery of neutral gas and high-voltage pulses is stopped.

Claims

1. A balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet, characterized in that: It comprises a balloon structure (1), a multi-lumen catheter (2), and a balloon electrode (3); The balloon structure (1) is a hollow structure and is located at the front end of the multi-lumen catheter (2). The balloon structure (1) includes a compressed state and an extended state; When the balloon structure (1) is located in the target area, the balloon structure (1) is in an extended state, otherwise, the balloon structure (1) is in a compressed state; the target area includes a bronchial central lung cancer area and a bronchial network micro-lesion area. The top end of the multi-lumen catheter (2) extends out of the balloon structure (1); The multi-lumen catheter (2) generates plasma active substances by introducing working gas and pulse electric field; The multi-lumen catheter (2) delivers the pulsed electric field to the balloon electrode (3) by introducing the pulsed electric field; The balloon electrodes (3) are evenly distributed on the surface of the balloon structure (1); The balloon electrode (3) is used for ablating central tumors; The working modes of the balloon catheter device include a tumor ablation mode and a bronchial network micro-lesion clearance mode; When the balloon catheter device operates in the tumor ablation mode, the balloon structure (1) is located in the central bronchial lung cancer region and is in an extended state; at this time, the balloon electrode (3) on the surface of the balloon structure (1) is in close contact with the tumor surface and applies electric pulses to the tumor to achieve ablation of the central tumor; When the balloon catheter device operates in the bronchial network micro-lesion cleaning mode, the balloon structure (1) is located in the bronchial network micro-lesion area and is in an extended state, thereby expanding the bronchial duct; at this time, the multi-lumen catheter (2) delivers plasma active substances to the bronchi by introducing working gas and pulsed electric fields, thereby cleaning the diffuse micro-lesions in the bronchial network.

2. The balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet according to claim 1, characterized in that: The multi-lumen catheter (2) comprises a main catheter (201) and a plasma discharge tube (203); The top end of the main catheter (201) is connected to the balloon structure (1); The plasma discharge tube (203) is located inside the main duct (201), and the length of the plasma discharge tube (203) is greater than that of the main duct (201); The top end of the plasma discharge tube (203) extends out of the balloon structure (1); The main conduit (201) is used to introduce a pulsed electric field; The plasma discharge tube (203) is used to introduce working gas, and the working gas generates plasma active substances under the action of the pulse electric field; The plasma active species is delivered into the bronchi via a plasma discharge tube (203).

3. The balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet according to claim 2, characterized in that: The multi-lumen catheter (2) further comprises a bronchoscope (202); The bronchoscope (202) is located in the main catheter (201), and the length of the bronchoscope (202) is greater than that of the main catheter (201); The top end of the bronchoscope (202) extends out of the balloon structure (1); The bronchoscope (202) is connected to a navigation system to navigate the balloon catheter device to the corresponding area of ​​the bronchus.

4. The balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet according to claim 1, characterized in that: The working gas includes one or more of helium, argon, nitrogen and oxygen.

5. The balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet according to claim 4, characterized in that: When the working gas is a mixed gas, the input speed range of the working gas is 0.5L / min-10L / min.

6. The balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet according to claim 1, characterized in that: The electric pulse applied by the balloon electrode (3) generates an electric field in the range of 500V / cm-1500V / cm around the balloon electrode (3).

7. The balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet according to claim 1, characterized in that: The pulsed electric field includes high voltage square wave pulses.

8. The balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet according to claim 1, characterized in that: When the balloon catheter device is working in the tumor ablation mode, it also monitors in real time through electric current whether the current in the tumor exceeds the threshold. If not, it changes the pulse parameters and continues to apply electric pulses to the tumor. If so, it stops applying electric pulses to the tumor, thus completing the ablation of central lung cancer.

9. The balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet according to claim 8, characterized in that: The pulse parameters include voltage amplitude, pulse width, and pulse frequency.

10. The balloon catheter device for treating central lung cancer by combining irreversible electroporation with cold atmospheric pressure plasma jet according to claim 1, characterized in that: When the balloon catheter device is working in the bronchial network micro-lesion clearing mode, the position of the bright light column of plasma is also monitored in real time through the bronchoscope, and the action time of plasma is recorded; When the duration of plasma action exceeds a threshold, delivery of plasma activity to the bronchi is stopped.

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