RU2740502C1 - Method for producing plasma-activated sterile liquids - Google Patents

Abstract

FIELD: technological processes.

SUBSTANCE: invention relates to a method of producing plasma-activated sterile liquids consisting in supplying high-voltage for time of plasma activation of liquid to working and grounding electrodes. Method is characterized by that, according to the invention, prior to supply of high-voltage, grounding electrode is fixed on outer side of vessel bottom with sterile liquid, and the working electrode is fixed on the outer side wall of the vessel at the level of the surface of the liquid and is made in form of a ring or electrically connected to each other, enclosing the vessel in place of their installation of electrically conducting tabs, wherein variable high-voltage between grounding and working electrodes is set to value from 2 to 10 kV and supplied in form of high-voltage pulses with frequency of 20-60 kHz, duration of 100 ns - 20 mcs and amplitude of 2-10 kV.

EFFECT: obtaining plasma-activated liquids with preservation of their sterility and expansion on this basis of the arsenal of technical means which can be used to produce plasma-activated sterile liquids.

1 cl, 4 dwg

Description

The invention relates to the field of medicine and biology and can be used to produce plasma-activated sterile liquids using low-temperature (cold) plasma formed by a dielectric barrier discharge.

The method can be used, in particular, for saline solutions in order to impart them various properties that can be used for the prevention and treatment of diseases (including cancer), sterilization of infected tissues, inactivation of microorganisms, acceleration of wound healing, skin regeneration and blood coagulation ...

In recent years, nonequilibrium low-temperature atmospheric pressure plasma has attracted researchers in various fields of medicine and biology. This cold plasma can handle fluids and heat-sensitive materials such as biological targets that cannot withstand high temperatures (> 40-41 ° C) and low pressures. For this purpose, gas discharges of various types are used. At the same time, two main directions can be distinguished - this is the creation of cold plasma using a flow of a working gas / gas mixture (usually argon or helium), which makes it possible to increase the size of the plasma jet and its uniformity, and the generation of low-temperature plasma at atmospheric pressure in air (without duct).

One of the widespread methods of creating a low-temperature plasma at atmospheric pressure is a dielectric barrier discharge, in which the discharge current is limited to tens of microamperes and should not lead to strong heating and high temperatures of the treated surface. The synergistic effect when exposed to the flow of electrons and radicals of the electromagnetic field, as well as the accompanying discharge of ultraviolet radiation, leads not only to surface modification, but also to a change in the properties of processed biological and liquid media, which has found application in medicine and biotechnology.

Recently, work has intensified to clarify the possibility of expanding the field of application of cold plasma in the prevention and treatment of oncological diseases. Of interest are the results of the effect of low-temperature plasma both directly on the cellular environment and on culture liquids to influence cancer cells and immunity in a living organism. A cascade of chemical reactions involving active particles generated in the plasma occurs at the liquid-gas interface, the main effect being the enrichment of the liquid with reactive oxygen species (ROS), such as hydroxyl, peroxyl and superoxide radicals, as well as reactive nitrogen species (RNS) such as nitrates, nitrites, nitrogen monoxide and peroxynitrite. In the past few years, a new line of research has emerged - plasma pharmacy. Plasma activation of liquids (its saturation with active nitrogen- and oxygen-containing radicals) has aroused interest in using it to create new drugs, as well as directly to affect a living organism. Studies show that plasma-treated fluids can retain their newly acquired properties for a long time.

A known system for producing plasma-activated liquid media [US 20190076537 A1, A61K 47/46, 03/14/2019], in which with the help of an ionizing gas, a plasma is created that processes a liquid medium in a special container. Moreover, denounced water, water-based electrolyte solution, physiological solution with phosphate buffer, glucose solution, etc. can be used as a liquid medium.

The disadvantage of this system is the inability to ensure the sterility of the liquid medium.

There is a known method [RU 2702594, C1, C02F 1/00, 08.10.2019], according to which water or an aqueous solution is exposed to plasma in a non-contact activation mode, for which water or an aqueous solution is exposed to a continuous electrodeless plasma torch, which is created by a microwave torch a plasmatron generating a directed jet of low-temperature plasma in a vapor-gas medium at atmospheric pressure.

From this technical solution, it is also known a device for the implementation of contactless plasma activation of water or aqueous solutions, which contains a torch microwave plasmatron with capacitive coupling, including a magnetron, rectangular and coaxial waveguides, a coaxial waveguide hermetically isolated from a rectangular waveguide by a radio-transparent quartz tube-insulator, while, The central conductor of the coaxial waveguide is a copper tube that serves to supply the plasma-forming gas, and ends with a nozzle with a hole 1.5 mm in diameter to form a directed jet of plasma-forming gas, and the working part of the microwave torch plasmatron is placed through a seal into a sealed chamber containing a vessel with the liquid to be processed mounted on the lift rod.

The disadvantage of this system is the impossibility of ensuring the sterility of the liquid (water or aqueous solutions), as well as the relatively high complexity caused by the use of a powerful microwave plasmatron.

The closest to the technical essence of the proposed one is a method for producing a plasma-activated saline solution [US 20190279849, 12.09.2019], including the stage of immersing the cathode in a saline solution in a container, the stage of placing the anode at a fixed distance from the surface of the specified saline solution in the specified container and the stage of applying an electric energy to the specified anode for a fixed period of time, moreover, the specified fixed distance and the specified fixed period of time are selected so as to cause a self-organizing plasma pattern on the surface of the specified saline solution with atmospheric discharge between the specified anode and the specified cathode.

The disadvantages of the closest technical solution are the complexity of ensuring the sterility of the treated liquids and the stability of the plasma treatment regime.

The objective of the present invention is to develop a method for producing plasma-activated sterile fluids while maintaining their sterility and with specified parameters for use in various biomedical applications, including in the treatment of oncological diseases, and on this basis to expand the arsenal of technical means that can be used for obtaining plasma-activated liquids.

The required technical result consists in obtaining plasma-activated liquids while maintaining their sterility and expanding on the basis of this arsenal of technical means that can be used to obtain plasma-activated sterile liquids.

The problem is solved, and the required technical result is achieved by supplying a high-voltage alternating voltage for the time of plasma activation of the liquid to the working and grounding electrodes, according to the invention, before applying the high-voltage voltage, the grounding electrode is fixed on the outer side of the bottom of the vessel (ampoule, bottle, etc.) with sterile liquid, and the working electrode is fixed on the outer side wall of the vessel at the level of the liquid surface and is made in the form of a ring or one or more electrically conductive petals, electrically connected to each other, covering the vessel in the place of their installation.

The required technical result is achieved by the fact that the alternating high-voltage voltage between the grounding and working electrodes is set in the range from 2 to 10 kV.

The required technical result is achieved by the fact that the alternating high-voltage voltage between the grounding and working electrodes is supplied in the form of an alternating sinusoidal voltage or high-voltage pulses with a frequency of 20-60 kHz, a duration of 100 ns - 20 μs and an amplitude of 2-10 kV.

The required technical result is achieved by the fact that the alternating high-voltage voltage between the grounding and working electrodes is fed simultaneously to a group of vessels with sterile liquid installed in the cassette.

The drawing shows:

in fig. 1 is a diagram of obtaining plasma-activated sterile liquids using a working electrode in the form of a ring;

in fig. 2 is a diagram of obtaining plasma-activated sterile liquids using a working electrode in the form of electrically connected electrically conductive petals covering the vessel at the place of their installation;

in fig. 3 - an example of obtaining plasma-activated sterile liquids for vessels with liquid installed in cassettes (Fig. 3a - top view, Fig. 3b - bottom view);

in fig. 4 is a graph of changes in the optical density of a liquid (saline) after adding the Griss reagent to it, where an increase in the optical density of a saline solution corresponds to an increase in the concentration of NOx (control 1 - saline in a glass ampoule without cold plasma treatment, control 2 - saline in a plastic ampoule without cold plasma treatment , treatment 1 - saline in a glass ampoule after treatment with cold plasma, treatment 2 - saline in a plastic ampoule after cold plasma treatment, the volume of saline in ampoules is 5 ml, treatment time is 15 minutes).

The drawing shows: 1 - a vessel with a liquid; 2 - working electrode; 3 - operating voltage supply terminal; 4 - grounding electrode; 5 - grounding terminal; 6 - the level of the surface of the liquid in the vessel; 7 - cassette for installation of vessels with liquid.

The proposed method for producing plasma-activated sterile liquids is implemented as follows.

On the outer side of the bottom of the vessel 1 (ampoule, vial, etc.) with a sterile liquid, the ground electrode 4 is fixed, and on the outer side wall of the vessel 1 at the level 6 of the liquid surface, the working electrode 2 is fixed in the form of a ring or electrically connected to each other covering the vessel at the place of their installation, one or more electrically conductive petals and an alternating high-voltage voltage is applied to the operating voltage supply terminal for the time of plasma activation of the liquid.

The alternating high-voltage voltage between the grounding 4 and the working 2 electrodes is set in the range from 2 to 10 kV, with a frequency of 20-60 kHz. In the case of a pulse voltage, it is supplied in the form of high-voltage pulses with a frequency of 20-60 kHz, a duration of 100 ns -20 μs and an amplitude of 2-10 kV.

The efficiency of the dielectric barrier discharge that occurs inside the treated volume is related to the dielectric material, frequency and value of the specified high voltage. For materials from which containers are created (ampoules, vials, etc.) for sterile liquids, as well as the sizes of these containers, frequencies of 20-60 kHz are optimal. It has been found experimentally that at lower and higher frequencies, the processing efficiency decreases. The voltage value is associated with the possibility of obtaining a DB discharge (about 2 kV) and a decrease in the probability of surface breakdown (10 kV). At the same time, in each specific case of obtaining PAZh (type of liquid, material and container volumes (ampoules, vials, etc.) for sterile liquids and gas inside this container), it is necessary to select the optimal processing mode and limiting the discharge current. For pulsed sources, the situation is similar, since as a result of the DBR at an alternating voltage, the liquid is processed by arising pulses with a duration of 100 ns -20 μs.

Voltage supply modes are determined by the type of liquid and gas that are in the vessel, the material from which the vessel is made (glass, polypropylene, polycarbonate, high pressure polyethylene and / or its alloy with low pressure polyethylene) and the required parameters of the liquids after their plasma activation.

Plasma activation occurs due to the use of a dielectric barrier discharge, when the wall of the vessel with the processed liquid is the dielectric barrier, which allows plasma activation without opening the vessel, using a discharge in the residual gas atmosphere.

Plasma activation of liquids can also be achieved by applying a high-voltage alternating voltage between the grounding and working electrodes simultaneously to a group of vessels 1 with sterile liquid installed in a cassette 7 (Fig. 3). This improves activation performance.

For the convenience of implementing the method, when using cassettes, the ground and working electrodes can be made spring-loaded.

As a source of high alternating voltage, piezotransformers of various types can be used, which make it possible to obtain a high-frequency 20 kHz - 60 kHz high-voltage 2 kV - 10 kV voltage on the electrodes tightly adjacent to the vessels with liquid.

The electrodes for treatment can be in the form of metal rings or several petals located at level 6, which is the liquid-gas interface in the vessel (Fig. 1). To process several ampoules, they can be combined into cassettes with a system of electrodes, to which the operating voltage is applied (Fig. 3).

The feasibility and efficiency of the proposed method is illustrated by the graph (Fig. 4), which shows the results of changes in the optical density of the liquid (saline solution) after adding the Griss reagent to it, where an increase in the optical density of the saline solution corresponds to an increase in the NOx concentration (control 1 - saline solution in a glass ampoule without cold treatment plasma, control 2 - saline in a plastic ampoule without cold plasma treatment, treatment 1 - saline in a glass ampoule after cold plasma treatment, treatment 2 - saline in a plastic ampoule after cold plasma treatment, the volume of saline in ampoules is 5 ml, processing time - 15 minutes).

Thus, thanks to the introduced improvements, the required technical result is achieved, which consists in obtaining plasma-activated liquids while maintaining their sterility and expanding on the basis of this arsenal of technical means that can be used to obtain plasma-activated sterile liquids.

Claims (2)

1. A method for producing plasma-activated sterile liquids, which consists in supplying a high-voltage voltage for the time of plasma activation of the liquid to the working and grounding electrodes, characterized in that, according to the invention, before applying the high-voltage voltage, the grounding electrode is fixed on the outer side of the bottom of the vessel with sterile liquid, and the working electrode is fixed on the outer side wall of the vessel at the level of the liquid surface and is made in the form of a ring or electrically connected to each other, covering the vessel at the place of their installation of electrically conductive petals, while the alternating high-voltage voltage between the grounding and working electrodes is set to a value of 2 to 10 kV and supplied in the form of high-voltage pulses with a frequency of 20-60 kHz, a duration of 100 ns - 20 μs and an amplitude of 2-10 kV. 2. The method according to claim 1, characterized in that the alternating high-voltage voltage between the grounding and working electrodes is supplied simultaneously to a group of vessels with sterile liquid installed in the cassette.

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