Low-temperature atmospheric pressure plasma generator and breathing device for activating cell regeneration in living organisms

Abstract

A low-temperature atmospheric pressure plasma generator (2) configured to receive air as an input substance and emit RONS, which are reactive oxygen and nitrogen species suitable for inhalation by living organisms, as an output substance, and a breathing apparatus (1) integrated with the low-temperature atmospheric pressure plasma generator (2).

Description

[Technical field]

[0001] The object of the present invention is to provide a low-temperature atmospheric pressure plasma generator and a breathing apparatus incorporating said low-temperature atmospheric pressure plasma generator. [Background technology]

[0002] In physics and engineering, plasma is defined as the fourth state of matter. This state is achieved by providing a gas with enough energy so that most of its molecules are ionized. Examples of plasma found in nature include electrical discharges during storms and the Northern Lights. In addition, plasmas are used in technology; fluorescent and neon tubes are classic examples along with plasma screens. Plasmas are also used to cut materials, as in plasma torches, which have a high ability to transfer heat at high temperatures. However, in the last two decades, devices have been developed that generate gas plasmas at low temperatures and atmospheric pressure, some of which are compatible with living tissue. The key to these plasmas not damaging tissues is the fact that they are out of thermodynamic equilibrium. This property strongly limits their ability to transfer heat to other objects they come into contact with, and they are called cold atmospheric plasmas (CAP) from their acronym. This type of plasma generates a certain concentration of activated oxygen and nitrogen molecules, called “RONS”, an acronym for Reactive Oxygen and Nitrogen Species. The importance of RONS lies in their bactericidal and regenerative effects on mammalian cells. Because of this, a new field of health called plasma medicine has developed and is in a full-fledged maturity stage, within which the present invention fits.

[0003] CAP is able to eliminate bacteria, fungi and viruses without causing any significant adverse effects on healthy cells of the organism, as evidenced by the overwhelming number of international publications on the subject. There is a broad international consensus on the scientific basis behind the clinical effects observed when using CAP. The ability of low-temperature atmospheric plasma to cause oxidative stress in the cells and microorganisms to which it is applied indicates that RONS are responsible for these effects. The difference in the level of resistance to oxidative stress between healthy cells and harmful microorganisms is the reason for the above-mentioned selectivity that CAP has. Due to structural differences between healthy cells and bacteria, fungi and viruses, such as the size of the DNA of the latter and the lack of protective functions, the resistance level is 100 times greater in healthy cells. The oxidative stress caused by RONS generated from low-temperature atmospheric plasma does not damage healthy tissues, but eliminates harmful microorganisms, including resistant bacteria.

[0004] Taking advantage of the sterilizing ability of CAP, air purification systems using CAP have been developed, for example as detailed in the following patents: US 8,529,830 B2, US 7824475 B2, US 7427313 B2, EP 2663403 B1, EP 3097750 B1. These systems incorporate various types of plasma generators that treat the air to remove microorganisms, thereby achieving a certain degree of purification of the air.

[0005] This invention is not intended to delve further into the health benefits of clean air or the need for purification systems, but to open up a new field of application for RONS to generate cold atmospheric pressure plasma for therapeutic purposes based on the concept of hormesis.

[0006] There are many identified processes in which low or sublethal doses of stressors or stimuli activate adaptive responses that make cells and organisms more resistant to high-intensity stress. This response is defined as hormesis. Normally, we are exposed to hormone-acting agents such as radiation, heat, heavy metals, antibiotics, antioxidants, exercise, and even food restriction. The hormesis response involves the expression of numerous genes that code for cytoprotective proteins such as chaperones, antioxidant enzymes, growth factors, and metallothioneins that respond to heat stress. Exposure of mammalian cells, including human cells, to low doses of RONS changes the intensity of expression of genes involved in the hormonal response in about 9 hours. The expression of constitutive, growth, and proliferation genes is decreased, while the expression of protective genes is increased, so that hormonally stimulated cells are significantly more resistant to future oxidative stress up to 15 and 30 hours after stimulation. Macroscopically, the hormonal response can be compared to the immune response to vaccination, with the major difference that the former does not retain long-term memory (more than 30 hours) and the cells or organisms must be re-exposed to the inducer in order to exert the hormonal effect again. Summary of the Invention

[0007] The present invention relates to a respiratory device that generates and projects to a human or animal patient a laminar airflow containing specific concentrations of reactive oxygen and nitrogen molecules for inhalation. These RONS are generated by a cold atmospheric pressure plasma generator that is configured to receive air as an input substance and to output the RONS as an output substance and is part of the respiratory device, and that takes advantage of the hormonal response of humans and animals to very low levels of oxidative stress in particular.

[0008] The proposed invention therefore involves a respiratory device that induces a hormonal response in humans and animals by inhaling small amounts of RONS dissolved in the air produced by a cold atmospheric pressure plasma generator.

[0009] The proposed device forms a clean air generating unit activated by cold atmospheric pressure plasma and is applied to patients both in closed rooms and in semi-open rooms specially designed for this purpose.

[0010] To better conceptually understand the present invention, it can be considered that it consists of two main parts that can integrate its functions and obtain a laminar flow of air relatively enriched in RONS produced by a low-temperature atmospheric pressure plasma generator.

[0011] Low-temperature atmospheric pressure plasma generator: Plasma is a state of matter in which ionized particles and electrons move at high speeds, generating high-energy, high-frequency impulses, promoting the creation of chemical reactions that would not occur under normal environmental conditions. This property allows the creation of RONS from oxygen and nitrogen molecules.

[0012] Respiratory equipment: This equipment may contain a cold atmospheric plasma generator, which is responsible for conditioning the air before it is additionally activated by cold atmospheric plasma. This equipment consists of a silent blower and a HEPA (High-Efficiency Particulate Arrestance) air filter. This equipment removes microorganisms and particles, including nanoparticles, from the air. The set includes a nozzle design to create a laminar airflow. The absence of turbulence in the laminar flow is one of the keys to optimal transport of RONS in the airflow. [Brief description of the drawings]

[0013] To supplement the description which follows, and to facilitate a better understanding of the characteristics of the plasma generating and breathing apparatus according to preferred examples of its practical embodiments, there is attached, as an integral part of said description, a set of drawings in which, by way of illustration and not by way of limitation, the following are represented:

[0014] [Figure 1]FIG. 1 is a conceptual diagram of a respiratory apparatus incorporating a low-temperature atmospheric pressure plasma generator according to the present invention and its application to a patient. [Diagram 2] FIG. 2 is a cross-sectional side view of a low-temperature atmospheric pressure plasma generating apparatus according to the present invention. [Diagram 3] FIG. 3 is a perspective cross-sectional view of a low-temperature atmospheric pressure plasma generating apparatus according to the present invention. [Figure 4] Figure 4 shows a cross-section of the breathing apparatus incorporating the low-temperature atmospheric pressure plasma generator, where the system was tested and measured. [Diagram 5] Figure 5 shows images obtained by measuring the tension and current signal between the electrodes of a low-temperature atmospheric pressure plasma generator. [Figure 6A] 6A and 6B show two emission spectra obtained from a low-temperature atmospheric pressure plasma generated in a low-temperature atmospheric pressure plasma generator by an optical fiber inserted into a ground electrode. [Figure 6B] 6A and 6B show two emission spectra obtained from a low-temperature atmospheric pressure plasma generated in a low-temperature atmospheric pressure plasma generator by an optical fiber inserted into a ground electrode. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] Preferred embodiments of the invention Figure 1 shows a schematic diagram in the form of a block diagram showing the location of the breathing apparatus (1) and the cold atmospheric plasma generator (2). The breathing apparatus (1) is housed in a box (6a) together with the cold atmospheric plasma generator (2) which injects a plasma activated air flow (4) into a laminar flow of clean air (3). The entire laminar flow of air is projected onto the patient (5).

[0016] The laminar flow of clean air (3) is enriched by a jet of plasma-activated air flow (4) coming from a cold atmospheric plasma generator (2). This laminar flow of air enriched with the RONS produced by the cold atmospheric plasma generator (2) is projected to the patient (5) for inhalation. The entire system is mounted in a box (6a) and connected to the domestic power grid, from which it obtains the energy it needs to operate.

[0017] If the air is not properly filtered and treated, it can carry all kinds of polluting particles, including those generated during the combustion of hydrocarbons in the cold atmospheric plasma generator (2). In this case, when the polluting molecules come into contact with the plasma, unpredictable chemical reactions can occur and compounds can also be generated. It is therefore recommended to use a pre-stage to filter the air before using it in the cold atmospheric plasma generator (2), so that the only reactive molecules generated are oxygen and nitrogen. This will prevent unknown compounds from being mixed into the air stream applied to the patient.

[0018] 2 and 3 are cross-sectional views of the low-temperature atmospheric pressure plasma generator (2).

[0019] The low-temperature atmospheric plasma generator (2) consists of two metal electrodes (6) (7) facing each other across a space (15). The cone-shaped positive electrode (6) is connected to a high-voltage source (9), while the flat metal electrode (7) is electrically connected to earth (12). Both electrodes are cylindrically symmetric and are held in a coaxial position by two centering pieces, in particular a support piece (10) made of insulating material and a metal piece (13). Both centering pieces are held in a coaxial position by a tube (8) made of insulating material adjusted with an O-ring (11). The air inlet and outlet are referenced (16) and (17), respectively.

[0020] The positive electrode (6) is connected to a voltage source (9) +V and is held by an insulating material support piece (10) that fits into the insulating material tube (8) by an O-ring (11). The positive electrode (6) is cone-shaped and has a through hole concentric with its axis, while the flat metal electrode (7) is connected to earth (12) and faces the same held at the other end of the tube of insulating material (8) by a metal piece (13) that closes the assembly with an O-ring. The flat ground electrode (12) has rounded edges and a blind hole concentric with its axis. This hole or axial drilling leaves a thin wall that forms the front face of the ground electrode, which in turn has a series of through holes (14) of smaller diameter that connect the interior of the flat metal electrode (7) with the space (15) that separates the two electrodes, as shown by the dashed circle in Figure 2.

[0021] Air activated by the cold atmospheric pressure plasma enters the system at the rear of the positive electrode (6) (air inlet (16)), reaches the space (15) between the electrodes (6) and (7), where it circulates, passes through the through-holes (14) that run through the interior of the flat metal electrode (7), and finally leaves the system through the outlet (17).

[0022] When an airflow is formed in the low-temperature atmospheric plasma generator (2), a voltage high enough to overcome the dielectric capacity of the air in the space (15) between the electrodes (6) and (7) is applied to the positive electrode (6). In this way, a column of low-temperature atmospheric plasma of circulating air is established between the electrodes (6) and (7). Inside the plasma column, RONS, reactive oxygen and nitrogen molecules, are formed and are dragged by the airflow out through the outlet (17) of the flat metal electrode (7).

[0023] As shown in FIG. 1, the low-temperature atmospheric pressure plasma generator (2) can inject an airflow activated by atmospheric pressure plasma (4) into the main laminar airflow projected onto the patient (5). FIG. 4 shows a cross-sectional view of a preferred embodiment of a breathing apparatus (1) according to the present invention.

[0024] The breathing apparatus (1) consists of a box (19) made of a material that can be insulating or metal for grounding, and includes an air impeller (18) that absorbs air (24) from the outside through an inlet opening (20) that houses an air filter (21), for example a HEPA filter, and passes an air flow completely through it. The clean air is discharged to the outside through a nozzle (22) that creates a laminar air flow. A part of the clean air is forced through a cold atmospheric plasma generator (2) that is configured to expel RONS. The main air flow and the air flow from the RONS generator are mixed at the outlet opening (23). Slats (25), preferably made of a metallic material, allow the air flow to be guided to the outlet.

[0025] In this embodiment, an air impeller (18) with cylindrical blades 30 cm long is used, which is oriented horizontally and housed in an airtight box made of insulating material. The box has a downward-facing rectangular inlet opening (20) in which a HEPA filter is housed, with dimensions of 30 cm long, 10 cm wide, and 3 cm thick. A rectangular nozzle (22) made of sheet metal is attached to the outlet of the air impeller, slightly concentrating the resulting airflow and projecting it horizontally forward in the form of a laminar air tongue. This set serves to ensure that all projected air passes through the HEPA filter and is free of nanoparticles and other contaminants. The air impeller operates at four speeds, which translate into laminar air flow velocities of 0.40, 0.70, 0.90, and 1.25 m / s measured 1 m away from the outlet opening (23) when the entire system is assembled.

[0026] A portion of the generated clean air passes through a cold atmospheric plasma generator (2) fixed in the center of the nozzle (22). This portion of air is integrated into the main flow at the outlet opening (23), which in this particular case corresponds to 5% of the total. The cross section in Figure 4 is made in the plane in which the cold atmospheric plasma generator (2) is located. Finally, thin slats (25) made of metal material arranged horizontally at the outlet are able to guide the air flow and release it in a specific direction.

[0027] Thus, air (24) is absorbed into the inlet (20) of the breathing apparatus (1) by the depression caused in the box (19) by the air impeller (18), forcing the incoming flow to pass through the HEPA filter. The air is sent forward forming a laminar flow through the rectangular nozzle (22), and a part of it is injected into the cold atmospheric plasma generator (2). Finally, the main air flow and the air flow activated by the cold atmospheric plasma generator (2) mix at the outlet opening (23) of the breathing apparatus (1) and are projected to the patient (5) for inhalation.

[0028] The low-temperature atmospheric plasma generator (2) is equipped with brass electrodes (6) and (7) with a diameter of 10 mm in the space for plasma formation (15), with a distance between the electrodes of 8 mm. The supporting piece of insulating material (10) is made of acetyl resin, and the supporting piece of the flat metal electrode (7) is made of aluminum. Both have a diameter of 39.9 mm at the height of the insert with the O-ring (11). The tube of insulating material is made of quartz, has a length of 50 mm, an inner diameter of 40 mm and a wall thickness of 2 mm. The flat metal electrode (7) has 12 through holes (14) with a diameter of 1 mm, each of which is distributed around the longitudinal axis with a diameter of 8 mm. A very important point regarding the safety of the system is that the design of the flat metal electrode (7) has the advantage that it does not allow accidental or intentional access to the space for generating plasma (15). The small diameter (1 mm) of the through holes (14) does not allow access to the plasma area, thus avoiding the risk of electrocution.

[0029] The cold atmospheric pressure plasma generator (2) is powered by a pulsed high tension source with a frequency of 60 kHz, which generates a sinusoidal output tension of 10 kV peak-to-peak without load (unloaded). Exceeding the dielectric strength of the air between the electrodes (6) and (7) results in a column of electrically conducting cold atmospheric pressure plasma with a tension achieved at a maximum peak current of 60 mA and 1.82 kV. This working situation when the cold atmospheric pressure plasma is established is shown in Figure 5, where the tension (26) and current (27) signals measured with an oscilloscope are observed. These curves show the electrical characteristics of the plasma used.

[0030] Measurements were performed using an oscilloscope and tension-current probe, with the following values ​​obtained: frequency 60 kHz, peak-to-peak tension 1.82 kV, and peak current 60 mA.

[0031] Furthermore, spectroscopic measurements were performed in the UV-visible and UV regions of the light emitted by the plasma. These measurements are crucial to confirm the presence of RONS in the plasma used and their relative abundance to non-reactive species in atmospheric pressure plasmas, such as emissions due to singly excited neutral atoms and / or molecules. For this, two fiber optic spectrometers with wavelength ranges of 200-800 nm (UV and visible) and 200-400 nm (UV) were used. The first one is used to see the full spectrum and detects the emission from RONS as well as neutral atoms and molecules. The other one has a higher resolution and allows to obtain only the emission in the UV region due to reactive oxygen and nitrogen molecules (RONS), which is the subject of this patent.

[0032] Figures 6A and 6B show the results of the spectral measurement, where in image (27a) a complete spectrum is observed in the wavelength range 200-800 nm, which corresponds to ultraviolet-visible light. In this spectrum, it can be seen that the emission in the visible spectrum (400-800 nm) is very low compared to the emission in the ultraviolet range (200-400 nm). This abundance in the ultraviolet range suggests that a relatively large amount of RONS is being produced. A more detailed spectrum in the ultraviolet range is shown in the lower image (28) of Figure 6, where the emission from 200 to 400 nm is measured.

[0033] The spectrum shows emission in the wavelength range of 200-800 nm, which corresponds to ultraviolet and visible (UV-VIS). In Figure 6B, image (28a) shows the emission spectrum only in the ultraviolet (UV) range, and shows NO (nitric oxide) (29), OH - (hydroxide ion) (30), N2 (molecular nitrogen) (31), and neutral and ionized atomic oxygen (32).

[0034] The emission of a wealth of spectral lines is clearly observed and can be divided into four characteristic groups: the first group between 200 and 275 nm, which corresponds to the release of reactive molecules of nitric oxide (NO), hydroxide ion (OH); - The second group from 275 to 310 nm corresponds to the emission of reactive molecules of , the third group of emissions in the range from 310 to 380 nm from excited neutral nitrogen molecules N2, and finally a group of low intensity emissions in the range from 380 to 400 nm from excited neutral atoms and oxygen ions. The cold atmospheric pressure plasma generator showed by the measurements carried out that both its structural parameters and the electrical supply parameters are optimized for the generation of RONS. The analyzed optical radiation was obtained from the inside of the flat metal electrode (7) by introducing an optical fiber from the outlet (17). This allowed to train the light coming from the plasma through the through hole (14).

Claims

1. A low-temperature atmospheric pressure plasma generator (2) configured to receive air as an input material and to output reactive oxygen and nitrogen species (RONS) suitable for inhalation by a living organism as an output material, the low-temperature atmospheric pressure plasma generator (2) comprising: A tube (8) of insulating material defining a cavity; an insulating support piece (10) coupled to a first end of the insulating tube (8); a metal piece (13) connected to the second end of the insulating tube (8); a cone-shaped positive electrode (6) located in the cavity of the insulating tube (8) and connectable to a voltage source (9); A flat metal electrode (7) located in the cavity of the insulating tube (8) and connectable to earth (12). Equipped with said electrodes (6, 7) face each other in a hollow pin-pepperpot configuration defining a space (15) between the electrodes (6, 7); The insulating support piece (10) is configured to hold the pyramidal positive electrode (6); The metal piece (13) is configured to hold the flat metal electrode (7); The pyramidal positive electrode (6) has a through axial bore configured to allow the passage of air into the cavity of the insulating tube (8); the flat metal electrode (7) comprises an axial cavity and a number of through holes (14) on a surface of the flat metal electrode (7) communicating the axial cavity with the cavity of the insulating tube (8); The low-temperature atmospheric pressure plasma generator (2) comprises: - establishing a circulating air flow between said electrodes (6) and (7); - applying a voltage to the pyramidal positive electrode (6) that is greater than the dielectric strength of the air in the space (15) between the electrodes (6) and (7); - generating a column of cold atmospheric pressure plasma from the air circulating between said electrodes (6) and (7); - discharging the RONS generated in the low-temperature atmospheric pressure plasma column to the outside of the low-temperature atmospheric pressure plasma generator (2) through the axial cavity of the flat metal electrode (7); It is configured as follows.

2. 2. The low-temperature atmospheric pressure plasma generator (2) according to claim 1, wherein the electrodes (6, 7) have cylindrical symmetry and are each coaxially supported by the insulating support piece (10) and the metal piece (13).

3. 3. The low-temperature atmospheric plasma generator (2) according to claim 1 or 2, wherein the insulating support piece (10) is connected to the first end of the insulating tube (8) by a first O-ring (11).

4. 2. The cold atmospheric plasma generator (2) according to claim 1, wherein the metal piece (13) is connected to the second end of the insulating tube (8) by a second O-ring (11).

5. The low-temperature atmospheric pressure plasma generator (2) according to claim 1, wherein the electrodes (6, 7) are made of brass, have a diameter of 10 mm, and the distance between the electrodes is 8 mm.

6. The low-temperature atmospheric pressure plasma generator (2) according to the preceding claim, wherein the insulating support piece (10) is made of acetyl resin and has a diameter of 39.9 mm.

7. The low-temperature atmospheric pressure plasma generator (2) according to the preceding claim, wherein the metal piece (13) is made of aluminum and has a diameter of 39.9 mm.

8. 2. The cold atmospheric plasma generator (2) according to claim 1, wherein the insulating tube (8) is made of quartz having a length of 50 mm, an inner diameter of 40 mm and a wall thickness of 2 mm.

9. 2. The low-temperature atmospheric plasma generator (2) according to claim 1, wherein the flat metal electrode (7) is provided with 12 through holes (14) each having a diameter of 1 mm, distributed around its longitudinal axis with a diameter of 8 mm.

10. A breathing apparatus (1) comprising an inlet opening (20) and an outlet opening (23), - an air impeller (18) configured to draw air through said inlet opening (20); - an air filter (21) configured to generate filtered air driven by said air impeller (18); - a plasma generator (2) according to claims 1 to 9, configured to absorb a portion of the filtered air as an input material and to emit RONS (reactive oxygen and nitrogen species) as an output material; a nozzle (22) configured to discharge the filtered air enriched with RONS in a laminar flow through an outlet opening (23); Equipped with Said laminar flow is prone to inhalation by living organisms.

11. The air-tight box made of insulating material for housing the air impeller (18) is further provided.

11. Breathing apparatus (1) according to claim 10, wherein the air impeller (18) consists of cylindrical blades having a length of 30 cm.

12. The breathing apparatus (1) according to claim 10 or 11, wherein the air filter is a HEPA (High-Efficiency Particulate Arrestance) filter and has dimensions of 30 cm length, 10 cm width and 3 cm thickness.

13. Breathing apparatus (1) according to claims 10 to 12, wherein said nozzle (22) has a rectangular shape and is made of sheet metal.

14. 14. Respiratory apparatus (1) according to any of claims 10 to 13, comprising slats (25) configured to guide the laminar airflow.

15. 15. Respiratory apparatus (1) according to claim 14, wherein the slats (25) are made of metal.

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