Cold plasma lung cancer treatment device for combined delivery of atomized liquid-phase and gas-phase active matters

Abstract

The invention discloses a cold plasma lung cancer treatment device for combined delivery of atomized liquid-phase and gas-phase active matters. The cold plasma lung cancer treatment device comprises an activated water storage bottle, an atomizing pump, a plasma delivery conduit and a secondary activation device, according to the method and the device, plasma activated water can be excited by secondary plasma jet to form atomized liquid drops, the atomized liquid drops are synchronously mixed with gas-phase active species, and the mixed liquid drops are conveyed to the lung through a suction way. Through the gas-liquid two-phase synergistic delivery mode, the action time of the short-life active matter is prolonged, and the distribution range of the long-life active matter is expanded, so that effective treatment on central lung cancer and deep branch dispersive focuses is realized.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of tumor treatment, in particular to a cold plasma lung cancer treatment device for combined delivery of atomized liquid phase and gas phase active substances. BACKGROUND

[0002] Lung cancer is one of the malignant tumors with the highest incidence and mortality worldwide, especially central lung cancer. Due to the proximity of the tumor location to the main bronchus, large blood vessels and other key anatomical structures, traditional treatment methods have obvious limitations. Surgical resection has a low proportion of suitable population due to limited cardiopulmonary function and complications. Radiation therapy is widely used, but radiation can induce heart disease and radiation pneumonia. Thermal ablation methods such as microwave ablation, radiofrequency ablation or cryoablation have limited effect in the treatment of central lung cancer, and may cause blood vessel damage or airway necrosis due to heat diffusion.

[0003] In recent years, cold atmospheric plasma (CAP) has gradually become a research hotspot for tumor treatment due to its low temperature, non-thermal effect and the ability to generate a variety of reactive oxygen and nitrogen species (RONS). Short-lived species in gas-phase plasma (such as ) have strong oxidative activity and can induce tumor cell apoptosis; liquid-phase plasma-activated water can enrich long-lived active substances (such as ), which have been shown to have a significant inhibitory effect on cancer cells in vitro experiments. However, both gas-phase and liquid-phase plasma therapies have limitations: gas-phase active substances decay quickly during transmission and have limited depth of action; liquid-phase activated water can enrich active substances, but it is difficult to distribute uniformly in the lungs, let alone reach deep branches and alveoli.

[0004] Therefore, how to effectively combine gas-phase and liquid-phase plasma active species and deliver them to the lungs through atomization has become a key problem that needs to be solved in cold plasma tumor treatment technology. If plasma jet can be used to excite activated water again, liquid-phase species can be combined with gas-phase active substances during atomization, and inhaled into the lungs with gas flow, it is expected to achieve higher concentration, longer life and larger range of active substance delivery at the level of bronchus and even alveoli. This provides a new way of thinking for the treatment of central lung cancer and diffuse micro lesions.

[0005] Existing cold plasma tumor treatment technologies mainly rely on gas-phase jets to directly act on lesions. However, the propagation distance of these jets in the air or airways is limited, and short-lived active species decay rapidly during delivery, making it difficult to reach the deep bifurcation of the lungs, resulting in insufficient treatment coverage. On the other hand, although plasma-activated water can enrich long-lived active substances, its distribution in the lungs is uneven when directly perfused or dripped, making it difficult to reach the deep alveolar regions, and it lacks synergistic effects with gas-phase active substances. Therefore, there are two key problems: (1) the gas-phase plasma has a limited delivery distance and the active species are prone to decay, making it difficult to act on deep lesions; (2) liquid-phase activated water lacks effective delivery methods, its area of ​​action is limited, and it is difficult to cover alveoli and diffuse microlesions; (3) the delivery process is uncontrollable, and short-lived gas-phase substances are easily dissipated during the mixing and transport stages, and cannot be efficiently converted into secondary activity within droplets or at the gas-liquid interface. (4) Low safety: The existing gas phase plasma forms a non-thermal plasma plume in the bronchus, which takes advantage of the high reactivity of short-lived species to directly act on the mucosal surface or superficial lesions. Continuous near-field spraying will cause airway damage problems such as local dryness, heat accumulation or mechanical stimulation. Summary of the Invention

[0006] The purpose of this invention is to provide a cold plasma lung cancer treatment device that delivers atomized liquid and gaseous active substances in combination, comprising: an activated water storage bottle, an atomizing pump, a plasma delivery conduit, and a secondary activation device.

[0007] The activated water storage bottle contains activated water containing long-lived chemicals.

[0008] The activated water storage bottle is connected to the atomizing pump via a conduit.

[0009] The activated water in the activated water storage bottle forms an aerosol flow under the action of the atomizing pump.

[0010] The atomizing pump delivers the aerosol stream to the secondary activation device.

[0011] The plasma delivery conduit is used to generate a plasma jet containing short-lived chemicals and to deliver the plasma jet to a secondary activation device.

[0012] After the aerosol stream enters the secondary activation device, it undergoes secondary activation under the action of plasma jet to obtain a secondary activated aerosol stream.

[0013] The secondary activation device delivers the secondary activated aerosol stream into the user's respiratory system through the user terminal interface, acting on the area to be activated.

[0014] Furthermore, the activated water preparation device includes an anode, a dielectric layer, a cathode, a support, and a liquid-bearing cavity.

[0015] The preparation apparatus is arranged in a working gas mixture stream.

[0016] The anode, dielectric layer, and cathode are sequentially mounted on the support.

[0017] The support is installed on the liquid-bearing cavity.

[0018] The liquid-bearing cavity contains liquid to be activated.

[0019] An excitation pulse signal is applied to the anode and cathode. The dielectric layer restricts the instantaneous current and forms a uniform glow discharge. The working gas mixture is excited in the glow discharge region, generating electrons and active particles. The active particles diffuse through the interface and dissolve into the liquid to be activated in the liquid carrier cavity, resulting in activated water containing long-lived chemicals.

[0020] Furthermore, the working gas in the working gas mixture includes... , .

[0021] The dielectric layer is made of materials including ceramics, PTFE, FEP, PEEK, alumina, and borosilicate glass.

[0022] The support component is made of materials including polytetrafluoroethylene.

[0023] The liquid to be activated includes deionized water and physiological saline.

[0024] The amplitude range of the excitation pulse signal is 15 kV–20 kV.

[0025] The active particles include .

[0026] The long-lived chemicals include .

[0027] Furthermore, the catheter is made of materials including silicone.

[0028] The user interface includes a face mask and a bronchial tube.

[0029] Furthermore, the atomizing pump includes an ultrasonic atomizing device, a jet atomizing device, and a piezoelectric microporous atomizing device.

[0030] The atomization rate of the atomizing pump ranges from 0.3 mL / min to 0.8 mL / min.

[0031] Furthermore, the plasma delivery conduit includes a needle electrode I, a dielectric tube I, and a ring electrode I.

[0032] The needle electrode I is located inside the dielectric tube I, and the ring electrode I is sleeved on the outside of the dielectric tube I.

[0033] An ionization pulse signal is applied to the ring electrode I, forming a discharge channel I between the ring electrode I and the needle electrode I. The working gas is delivered and flows through the discharge channel, ionizing to generate a plasma jet.

[0034] Furthermore, the materials used for the needle electrode I include copper and tungsten.

[0035] The dielectric tube I is made of materials including PTFE, quartz, FEP, PEEK, alumina, and borosilicate glass.

[0036] The ring electrode I is made of stainless steel.

[0037] The peak value of the ionization pulse signal is 5 kV–12 kV, and the pulse width is 5 μs–100 ms.

[0038] The delivery working gas includes He, Ar, Mixed gas Mixed gases, air.

[0039] Furthermore, the secondary activation device includes a needle electrode II, a dielectric tube II, and a ring electrode II.

[0040] The needle electrode II is located inside the dielectric tube II, and the ring electrode II is sleeved on the outside of the dielectric tube II.

[0041] A secondary activation pulse signal is applied to the ring electrode II, forming a discharge channel II between the ring electrode II and the needle electrode II. The aerosol flow passes through the discharge channel II and undergoes secondary activation under the action of the plasma jet, resulting in a secondary activated aerosol flow.

[0042] The amplitude range of the secondary activation pulse signal is 4kV-7kV.

[0043] Furthermore, the materials used for the needle electrode II include copper and tungsten.

[0044] The dielectric tube II is made of materials including PTFE, quartz, FEP, PEEK, alumina, and borosilicate glass.

[0045] The ring electrode II is made of materials including stainless steel.

[0046] Furthermore, the short-lived chemicals include .

[0047] The secondary activated aerosol stream includes , .

[0048] The technical effectiveness of this invention is undeniable. This invention proposes a method and apparatus capable of atomizing water using a secondary plasma jet to form atomized droplets, simultaneously mixing them with gaseous active species, and delivering them to the lungs via inhalation. This gas-liquid dual-phase synergistic delivery method prolongs the action time of short-lived active substances and expands the distribution range of long-lived active substances, thereby achieving effective treatment for central lung cancer and deep, diffuse lesions.

[0049] The beneficial effects of this invention include:

[0050] 1. Gas-liquid dual-phase synergy: This invention achieves the complementary effect of short-lived gas-phase species and long-lived liquid-phase species by ionizing and atomizing plasma-activated water and mixing it synchronously with gas-phase plasma active materials, thereby significantly enhancing the killing effect on tumor cells.

[0051] 2. Increased concentration of active ingredients: Liquid droplets can carry and stabilize long-lived species, while releasing new free radicals and oxidizing molecules during secondary excitation, resulting in a higher variety and concentration of active ingredients in the gas-liquid mixture compared to single-phase treatment.

[0052] 3. Wide coverage: The droplet size is controlled at 1–5 μm, which can be deposited in the distal bronchus and alveolar region with the inhaled airflow. Combined with the diffusion expansion of gaseous species, the treatment range extends from the central airway to deep branches and diffuse microlesions.

[0053] 4. Controllable delivery process: By adjusting the gas flow rate, liquid injection rate and discharge electrical parameters, the gas-liquid ratio and active ingredient concentration can be flexibly controlled to adapt to lung cancer lesions of different sizes and locations.

[0054] 5. Enhanced safety: The temperature of the gas-liquid mixed jet is lower than that of a single gas phase plasma, and the humid atomization environment helps to avoid airway dryness or thermal damage, improving the safety and tolerability of animal experiments and future clinical applications. Attached Figure Description

[0055] Figure 1 This is a schematic diagram of the secondary activation discharge device in this invention;

[0056] Figure 2 This is a schematic diagram of the dielectric barrier discharge structure used in the preparation of activated water according to the present invention;

[0057] Figure 3 This is a schematic diagram of the spectral analysis of the active substances generated by the discharge device in this invention;

[0058] Figure 4 This is a schematic diagram illustrating the measurement of active substances in activated water according to the present invention; Figure 4 (a) is a schematic diagram of intracellular ROS measurement; Figure 4(b) is a schematic diagram of RNS measurement in the culture medium;

[0059] Figure 5 This is a schematic diagram of in vivo imaging of mouse tumors treated with the discharge device in this invention for in situ lung cancer. Figure 5 (a) is a schematic diagram of the control group imaging; Figure 5 (b) is a schematic diagram of the treatment group;

[0060] In the diagram: 1. Activated water storage bottle, 101. Anode, 102. Dielectric layer, 103. Cathode, 104. Support, 2. Atomizing pump, 3. Plasma delivery conduit, 4. Delivery working gas, 5. Plasma jet, 6. Secondary activation device, 7. Area to be activated. Detailed Implementation

[0061] The present invention will be further described below with reference to embodiments, but it should not be construed that the scope of the present invention is limited to the following embodiments. Various substitutions and modifications made based on ordinary technical knowledge and common practices in the art without departing from the above-described technical concept of the present invention should be included within the scope of protection of the present invention.

[0062] Example 1:

[0063] See Figures 1 to 5 A cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances includes: an activated water storage bottle 1, an atomizing pump 2, a plasma delivery conduit 3, and a secondary activation device 6.

[0064] The activated water storage bottle 1 contains activated water containing long-lived chemicals.

[0065] The activated water storage bottle 1 is connected to the atomizing pump 2 via a conduit.

[0066] The activated water in the activated water storage bottle 1 forms an aerosol flow under the action of the atomizing pump 2.

[0067] The atomizing pump 2 delivers the aerosol stream to the secondary activation device 6.

[0068] The plasma delivery conduit 3 is used to generate a plasma jet 5 containing short-lived chemicals and to deliver the plasma jet 5 to the secondary activation device 6.

[0069] After the aerosol stream enters the secondary activation device 6, it undergoes secondary activation under the action of the plasma jet 5 to obtain a secondary activated aerosol stream.

[0070] The secondary activation device 6 delivers the secondary activated aerosol stream into the user's respiratory system through the user terminal interface, acting on the area to be activated 7.

[0071] Example 2:

[0072] A cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances, the main technical contents of which are described in Example 1, further wherein the activated water preparation device includes an anode 101, a dielectric layer 102, a cathode 103, a support 104, and a liquid carrying chamber.

[0073] The preparation apparatus is arranged in a working gas mixture stream.

[0074] The anode 101, dielectric layer 102, and cathode 103 are sequentially mounted on the support 104.

[0075] The support member 104 is installed on the liquid-bearing cavity.

[0076] The liquid-bearing cavity contains liquid to be activated.

[0077] An excitation pulse signal is applied to the anode 101 and the cathode 103. The dielectric layer 102 restricts the instantaneous current and forms a uniform glow discharge. The working gas mixture is excited in the glow discharge region, generating electrons and active particles. The active particles diffuse through the interface and dissolve into the liquid to be activated in the liquid carrier cavity, resulting in activated water containing long-lived chemicals.

[0078] Example 3:

[0079] A cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances, the main technical contents of which are described in any one of Examples 1 to 2, further wherein the working gas of the working gas mixture includes , .

[0080] The working gas in the working gas mixture includes air. , The mass ratio is 79:21.

[0081] The dielectric layer 102 is made of materials including ceramics, PTFE, FEP, PEEK, alumina, and borosilicate glass.

[0082] The support member 104 is made of materials including polytetrafluoroethylene.

[0083] The liquid to be activated includes deionized water and physiological saline.

[0084] The amplitude range of the excitation pulse signal is 15 kV–20 kV.

[0085] The active particles include .

[0086] The long-lived chemicals include .

[0087] Example 4:

[0088] A cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances, the main technical contents of which are described in any one of Examples 1 to 3, and further, the material used for the catheter includes silicone.

[0089] The user interface includes a face mask and a bronchial tube.

[0090] Example 5:

[0091] A cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances, the main technical contents of which are described in any one of Examples 1 to 4, further wherein the atomizing pump 2 includes an ultrasonic atomizing device, a jet atomizing device, and a piezoelectric microporous atomizing device.

[0092] The atomization rate of the atomizing pump 2 ranges from 0.3 mL / min to 0.8 mL / min.

[0093] Example 6:

[0094] A cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances, the main technical contents of which are described in any one of Examples 1 to 5, further wherein the plasma delivery conduit 3 includes a needle electrode I, a dielectric tube I, and a ring electrode I.

[0095] The needle electrode I is located inside the dielectric tube I, and the ring electrode I is sleeved on the outside of the dielectric tube I.

[0096] An ionization pulse signal is applied to the ring electrode I, forming a discharge channel I between the ring electrode I and the needle electrode I. Working gas 4 is delivered and flows through the discharge channel, ionizing to generate a plasma jet 5.

[0097] Example 7:

[0098] A cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances, the main technical contents of which are described in any one of Examples 1 to 6, and further, the needle electrode I is made of copper or tungsten.

[0099] The dielectric tube I is made of materials including PTFE, quartz, FEP, PEEK, alumina, and borosilicate glass.

[0100] The ring electrode I is made of stainless steel.

[0101] The peak value of the ionization pulse signal is 5 kV–12 kV, and the pulse width is 5 μs–100 ms.

[0102] The delivery working gas 4 includes He, Ar, Mixed gas Mixed gases, air.

[0103] The The mixed gas is It accounts for 0.25%-1.5%, with the remainder being He gas. For example, He, The ratio was 99:1.

[0104] The The mixed gas is It accounts for 0.25%-1.5%, with the remainder being Ar gas.

[0105] Example 8:

[0106] A cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances, the main technical contents of which are described in any one of Examples 1 to 7, further wherein the secondary activation device 6 includes a needle electrode II, a dielectric tube II, and a ring electrode II.

[0107] The needle electrode II is located inside the dielectric tube II, and the ring electrode II is sleeved on the outside of the dielectric tube II.

[0108] A secondary activation pulse signal is applied to the ring electrode II, forming a discharge channel II between the ring electrode II and the needle electrode II. The aerosol flow passes through the discharge channel II and undergoes secondary activation under the action of the plasma jet 5, resulting in a secondary activated aerosol flow.

[0109] The amplitude range of the secondary activation pulse signal is 4kV-7kV.

[0110] Example 9:

[0111] A cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances, the main technical contents of which are described in any one of Examples 1 to 8, and further, the needle electrode II is made of copper or tungsten.

[0112] The dielectric tube II is made of materials including PTFE, quartz, FEP, PEEK, alumina, and borosilicate glass.

[0113] The ring electrode II is made of materials including stainless steel.

[0114] Example 10:

[0115] A cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances, the main technical contents of which are described in any one of Examples 1 to 9, further comprising the short-lived chemicals including .

[0116] The secondary activated aerosol stream includes , .

[0117] Example 11:

[0118] See Figures 1 to 5 A cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances, the main technical contents of which include:

[0119] Structural composition:

[0120] 1. Mechanical connection

[0121] This system, from upstream to the patient side, consists of a working gas supply, a primary discharge chamber, an atomizing / activating fluid pathway, a gas-liquid coupling and re-excitation mixing chamber, a terminal delivery component, and a monitoring and interlocking unit. It utilizes standardized interfaces for easy assembly, disassembly, and sterilization for reuse. The gas path primarily uses He / Ar with fine mixing capabilities of 0–1%. The flow rate is stabilized at 0.5–3.0 SLM. The liquid path is delivered to the ultrasonic / jet nebulizer via a PAW storage tank (PP / borosilicate glass) and a medical-grade silicone or PTFE tubing. The droplet size is controlled at 1–5 μm to accommodate both bronchial and alveolar deposition. The primary discharge chamber preferably uses a suspended electrode needle-ring design. The needle electrode is made of 0.25 mm copper / tungsten, and the ring / tube electrode is made of 304 / 316L stainless steel with an insulating layer. The dielectric sheath is made of PTFE. The gas-liquid coupling mixing chamber is a short chamber (effective length approximately 10 mm–30 mm, volume 0.2 mL–0.8 mL), coaxially parallel or staggeredly merging. A dielectric barrier ring electrode is embedded in the chamber for low-energy-density secondary excitation, while guide ribs and O-rings are used for sealing to suppress condensation backflow and leakage.

[0122] 2. Circuit connection

[0123] Activated water was prepared by a 20 kV AC-excited dielectric barrier discharge for 10 minutes. A main high-voltage pulse generator provided an adjustable pulse generation plasma stream with a peak value of 5–12 kV and a pulse duration of 100–5 μs. The generation and delivery of active components followed a pathway of "primary discharge source creation—atomization and carrying—secondary excitation and conversion—end-stage dose shaping": primary discharge enrichment in the gas phase. Short-lived species in the μs–ms range, these species are preferentially captured by droplets at the gas-liquid interface after entering the mixing chamber and transformed into a long-lived library of peroxide / nitrosyl compounds in the droplet bulk phase; parallel PAW is Long-lived materials of the min level.

[0124] Working principle and working method:

[0125] This invention uses high-purity helium as the working gas, whose low breakdown voltage and high diffusion coefficient ensure the stability of the discharge and the effective transport of active species. The gas is injected into the discharge chamber at a flow rate of 2 L / min via a mass flow controller, forming a non-thermal equilibrium plasma between the needle-ring electrodes. The prepared activated water undergoes secondary activation through the convection of the plasma jet, and the short-lived active substances enter atomized micron-sized bubbles, ultimately depositing into the bronchus.

[0126] Example 12:

[0127] See Figures 1 to 5 A cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances, the main technical contents of which include:

[0128] Please see the appendix Figure 1 This system consists of an activated water reservoir, a nebulizer pump, a secondary activation device, a delivery catheter, and a patient-end interface (mask or bronchial tube) connected in series. During operation, the activated water forms a fine aerosol under the action of the nebulizer pump. After reacting with the plasma jet in the secondary activation device, it is delivered into the respiratory system, thereby achieving the synergistic effect of short-lived and long-lived active substances in the airways and alveoli. The activated water is obtained by activating deionized water or physiological saline through an independent atmospheric pressure plasma jet (APPJ). The working gas is air, and typical discharge parameters are: AC excitation voltage of 15kV–20kV. The activated liquid is rich in... The concentrations of species with similar lifespans were approximately 100 μM–300 μM, 50 μM–200 μM, and 200 μM–500 μM, respectively. The resulting activated water was stored in a light-proof glass bottle and connected to a nebulizer pump via a silicone tube during use. The nebulizer pump employed ultrasonic or jet-type nebulization to generate micro-mist particles with a diameter of 1 μM–5 μm, ensuring they reached the bronchi and alveoli during respiration. The nebulization rate was controlled at 0.3 mL / min–0.8 mL / min, driven by helium gas, maintaining a stable flow rate (approximately 1 SLM–2 SLM) to create a continuous aerosol flow. The secondary activation device, the core of the system, was used to introduce a plasma jet during aerosol flow to achieve secondary excitation. The device employed a suspended electrode needle-ring discharge structure: the needle electrode was constructed of a 0.25 mm diameter copper wire, and the outer ring electrode was a stainless steel conduit, with a dielectric tube (PTFE or quartz tube) separating the two to form a discharge channel. The working gas is helium, with a flow rate of 1 SLM; the pulse high voltage is 7 kV, the pulse width is 200 ns, and the repetition frequency is 10 kHz.

[0129] Please see the appendix Figure 2This is a dielectric barrier discharge device for preparing plasma-activated water, as shown in the figure. Its structure consists of an anode, a ceramic dielectric layer, a cathode, a polytetrafluoroethylene (PTFE) support, and a liquid-bearing cavity. When a high-voltage pulse is applied between the anode and cathode, the ceramic dielectric layer restricts the instantaneous current and forms a uniform purple glow discharge. Working gas. / The mixed current is excited within the discharge region, generating a large number of high-energy electrons and active particles (such as... These active species diffuse into the liquid below via interfacial diffusion, reacting with water molecules to generate… Chemicals with equal lifespans are used to activate liquids.

[0130] Please see the appendix Figure 3 The paper presents the radiation spectrum in the wavelength range of 200 nm to 900 nm collected during the discharge process of the device of the present invention. It can be found that the main wavelength range in the wavelength range of 200 nm to 500 nm is... and The molecular bands, covering the wavelength range of 500 nm to 800 nm, include the spectral lines of He excited state and O atoms (at 777 nm and 866 nm), indicating that He produces sufficient oxygen molecule excitation after mixing with air.

[0131] Please see the appendix Figure 4 Different treatment groups were sprayed with atomized gas streams into well plates containing culture medium. ROS in cells and RNS in the culture medium were then detected using fluorescent probe technology. Results showed that secondary activation significantly increased intracellular ROS levels and RNS levels in the culture medium. Long-lived active substances generated by gas-liquid phase coupling (…) The dosage of (etc.) in the culture medium was increased synchronously, and the increase in ROS was greater than that in RNS.

[0132] Please see the appendix Figure 5 The tumor bioluminescence signals in mice from the control group and the plasma secondary activation atomization group showed significant differences during treatment. An orthotopic lung tumor model was established using luciferase-labeled lung cancer cells (such as LLC-Luc or A549-Luc), and in vivo imaging was performed on days 6, 10, and 17 of the treatment cycle. The intensity of the luminescence signal reflected tumor volume and metabolic activity.

[0133] In the control group, the tumor bioluminescence intensity continuously increased from day 6, and the signal range significantly expanded by day 17, indicating continued tumor growth and intensified invasion. In contrast, the plasma secondary activation nebulization group showed the most significant signal inhibition: a significant downward trend appeared as early as day 10, and by day 17, the bioluminescence signal in most mice had dropped to baseline or only focal weak spots remained; in some individuals, the tumor signal even completely disappeared. Quantitative analysis showed that the total flux at the terminal stage was approximately 20% of that in the control group (p < 0.01), significantly different from the first two groups. Overall, the bioluminescence imaging results directly validated the significant anti-tumor efficacy of the proposed "secondary activation plasma nebulization inhalation system" in animals, providing experimental evidence for subsequent mechanism research and clinical translation.

[0134] Example 13:

[0135] A cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances, the main technical contents of which are described in Example 12, further including the replacement and simplification of dielectric materials.

[0136] The ceramic or quartz dielectric used in the device can be replaced with other materials with similar dielectric constants and heat resistance, such as PTFE, FEP, PEEK, alumina, and borosilicate glass, depending on the requirements. If the ceramic sheet is simplified and omitted, and a double-layer PTFE tube is used as the dielectric separator, it can achieve one-piece molding, easy processing, and lightweight, but the heat resistance is relatively reduced, making it suitable for low-power or intermittent operation.

[0137] Example 14:

[0138] A cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances, the main technical contents of which are described in any one of Examples 12 to 13, and further, the atomization system has a replaceable design.

[0139] The nebulizer pump can be replaced with ultrasonic nebulizer, jet nebulizer, or piezoelectric microporous nebulizer, and the resulting aerosol particle size distribution within the range of 1–5 μm can meet the lung delivery requirements. If the original dual-channel gas-liquid mixing nebulizer is replaced with a single-channel jet nebulizer head, the structure can be simplified and the gas consumption can be reduced, but the activation time needs to be appropriately extended to ensure that the droplets are fully activated.

[0140] Example 15:

[0141] A cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances, the main technical contents of which are described in any one of Examples 12 to 14, further simplifying the gas types and doping ratios.

[0142] The original design adopted The mixed gas, used as the working gas for the plasma jet, can be replaced with... Alternatively, air can be used, or the oxygen doping step can be omitted, using only pure He or pure Ar for discharge. If omitted... Even with doping, the system can still produce and some However, the amount of RNS generated will decrease, making it suitable for applications with lower requirements for oxidation intensity or those that are mainly based on immune regulation.

[0143] Example 16:

[0144] A cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances, the main technical contents of which are described in any one of Examples 12 to 15, further including simplification of the power supply system and control strategy.

[0145] The main high-voltage pulse power supply can be replaced by a nanosecond pulse type with a microsecond pulse or AC high-frequency power supply; if precise phase delay control is not required, the secondary excitation independent branch can be omitted, and the system can be driven by a single power supply. Although this simplification reduces the precision of gas-liquid interfacial active substance synergistic regulation, it can significantly reduce system size and power consumption, making it suitable for miniaturized or animal experimental-grade equipment.

[0146] Example 17:

[0147] A cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances, the main technical contents of which are described in any one of Examples 12 to 16, further including the integration of an activated water preparation module.

[0148] In the original system, activated water is prepared using an independent dielectric barrier discharge device. Alternatively, an online integrated preparation module can be used, in which a micro-discharge chamber is directly embedded before the atomizing liquid inlet, achieving a "preparation and atomization simultaneously" mode. If simplified to an online mode, the storage bottle and tubing can be omitted, but an intermittent pulse or temperature control system is required to prevent the liquid from overheating.

Claims

1. A cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances, characterized in that, include: Activated water storage bottle (1), atomizing pump (2), plasma delivery conduit (3), secondary activation device (6); The activated water storage bottle (1) contains activated water containing long-lived chemicals; The activated water storage bottle (1) is connected to the atomizing pump (2) via a conduit; The activated water in the activated water storage bottle (1) forms an aerosol flow under the action of the atomizing pump (2); The atomizing pump (2) delivers the aerosol stream to the secondary activation device (6). The plasma delivery conduit (3) is used to generate a plasma jet (5) containing short-lived chemicals and to deliver the plasma jet (5) to the secondary activation device (6). After the aerosol stream enters the secondary activation device (6), it undergoes secondary activation under the action of the plasma jet (5) to obtain a secondary activated aerosol stream. The secondary activation device (6) delivers the secondary activated aerosol stream into the user's respiratory system through the user terminal interface, and acts on the area to be acted on (7).

2. The cold plasma lung cancer treatment device for combined delivery of atomized liquid and gaseous active substances according to claim 1, characterized in that, The device for preparing activated water includes an anode (101), a dielectric layer (102), a cathode (103), a support (104), and a liquid carrying chamber; The preparation apparatus is arranged in a working gas mixture stream; The anode (101), dielectric layer (102), and cathode (103) are sequentially mounted on the support (104); The support member (104) is installed on the liquid-bearing cavity; The liquid-bearing cavity contains liquid to be activated; An excitation pulse signal is applied to the anode (101) and cathode (103). The dielectric layer (102) restricts the instantaneous current and forms a uniform glow discharge. The working gas mixture is excited in the glow discharge region, generating electrons and active particles. The active particles diffuse through the interface and dissolve into the liquid to be activated in the liquid carrier cavity, resulting in activated water containing long-lived chemicals.

3. The cold plasma lung cancer treatment device for combined delivery of atomized liquid and gaseous active substances according to claim 2, characterized in that, The working gas mixture includes the working gas. , ; The dielectric layer (102) is made of materials including ceramics, PTFE, FEP, PEEK, alumina, and borosilicate glass; The material used for the support member (104) includes polytetrafluoroethylene; The liquid to be activated includes deionized water and physiological saline. The amplitude range of the excitation pulse signal is 15 kV–20 kV; The active particles include ; The long-lived chemicals include .

4. The cold plasma lung cancer treatment device for combined delivery of atomized liquid and gaseous active substances according to claim 1, characterized in that, The catheter is made of materials including silicone. The user interface includes a face mask and a bronchial tube.

5. The cold plasma lung cancer treatment device for combined delivery of atomized liquid and gaseous active substances according to claim 1, characterized in that, The atomizing pump (2) includes an ultrasonic atomizing device, a jet atomizing device, and a piezoelectric microporous atomizing device; The atomization rate of the atomizing pump (2) is in the range of 0.3 mL / min–0.8 mL / min.

6. The cold plasma lung cancer treatment device for combined delivery of atomized liquid and gaseous active substances according to claim 1, characterized in that, The plasma delivery conduit (3) includes a needle electrode I, a dielectric tube I, and a ring electrode I; The needle electrode I is located inside the dielectric tube I, and the ring electrode I is sleeved outside the dielectric tube I; An ionization pulse signal is applied to the ring electrode I, and a discharge channel I is formed between the ring electrode I and the needle electrode I. The working gas (4) is delivered and flows through the discharge channel, ionizing to generate a plasma jet (5).

7. The cold plasma lung cancer treatment device for combined delivery of atomized liquid and gaseous active substances according to claim 6, characterized in that, The needle electrode I is made of materials including copper and tungsten; The dielectric tube I is made of materials including PTFE, quartz, FEP, PEEK, alumina, and borosilicate glass; The ring electrode I is made of stainless steel; The peak value of the ionization pulse signal is 5 kV–12 kV, and the pulse width is 5 μs–100 ms. The delivery working gas (4) includes He, Ar, Mixed gas Mixed gases, air.

8. The cold plasma lung cancer treatment device for combined delivery of atomized liquid and gaseous active substances according to claim 1, characterized in that, The secondary activation device (6) includes needle electrode II, dielectric tube II, and ring electrode II; The needle electrode II is located inside the dielectric tube II, and the ring electrode II is sleeved outside the dielectric tube II; The secondary activation pulse signal is applied to the ring electrode II, and a discharge channel II is formed between the ring electrode II and the needle electrode II. The aerosol flow flows through the discharge channel II and is reactivated under the action of the plasma jet (5) to obtain the reactivated aerosol flow. The amplitude range of the secondary activation pulse signal is 4kV-7kV.

9. The cold plasma lung cancer treatment device for combined delivery of atomized liquid and gaseous active substances according to claim 8, characterized in that, The needle electrode II is made of materials including copper and tungsten; The dielectric tube II is made of materials including PTFE, quartz, FEP, PEEK, alumina, and borosilicate glass; The ring electrode II is made of materials including stainless steel.

10. The cold plasma lung cancer treatment device for the combined delivery of atomized liquid and gaseous active substances according to claim 1, characterized in that, The short-lived chemicals include ; The secondary activated aerosol stream includes , .

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