Devices for treating wounds and infected skin

Abstract

The invention relates to a system for the sequential treatment of a body surface with cold atmospheric-pressure plasma and negative-pressure therapy or negative-pressure flushing therapy. The system comprises the following components: - a flexible, substantially gas-tight cover (12) for forming a closed volume (14) over the body surface (10), - an open, nonwoven or sponge-like spacer structure (16) within the volume (14), the spacer structure being compressible under negative pressure and self-restoring in the absence of negative pressure, - at least one planar plasma applicator (20) which is arranged within the volume or gas-tightly covers an opening formed in the cover (12) and acts on the volume, - a high-voltage generator (22) connected to the plasma applicator (20) for supplying the plasma applicator (20) with an operating voltage; - at least one port (18) having a lumen (18.1) for liquid instillation and / or for aspirating gases and liquids from the volume; and - a suction pump (40) connected to the lumen (18.1) for aspirating gases and liquids from the volume.

Description

[0001] Eisenführ Speiser

[0002] Berlin, September 25, 2025

[0003] Our Ref.: CB 1327-02 WO JVO / anb / ddi

[0004] Applicant: COLDPLASMATECH GmbH

[0005] Serial Number: New Application

[0006] COLDPLASMATECH GmbH

[0007] Bahnhofstraße 31 / 32, 17489 Greifswald,

[0008] Devices and methods for the treatment of wounds and infected skin

[0009] The invention relates to various devices and methods for treating wounds and infected skin using a cold atmospheric pressure plasma. For this purpose, so-called plasma sources are used, which typically have at least one electrode operated with a voltage. Some plasma sources are additionally equipped with

[0010] 5. A further grounded electrode or a counter electrode is indicated. In plasma sources without a grounded electrode, the surface to be treated constitutes the grounded electrode or the counter electrode. If a corresponding voltage is applied to the driven electrode, an electric field is generated towards the grounded electrode or the surface to be treated. If this electric field is strong enough, a plasma can form in this electric field through the ionization of at least some of the molecules of air or a specially added gas (e.g., argon or helium). For example, so-called plasma applicators, which have two planar electrodes insulated from each other by a dialectic, can be used as plasma sources.When a suitable voltage is applied to the electrodes, a plasma can form near one of them. This plasma arises from the ionization of at least some of the air molecules near one of the flat electrodes, specifically where the electric field generated by the two electrodes is sufficiently strong. Corresponding plasma applicators are known and described, for example, in WO 2019 / 180257 A1 or Nessr Abu Rached et al., "Cold Plasma Therapy in Chronic Wounds - A Multicenter, Randomized Controlled Clinical Trial (Plasma on Chronic Wounds for Epidermal Regeneration Study): Preliminary Results", J. Clin. Med. 2023, 12, 5121.

[0011] *20250439945* Alternative plasma sources have only one active, flat electrode and use the body being treated as the counter electrode. Here, too, the plasma source is located near the surface of the body being treated.

[0012] Other plasma sources generate a gas mixture containing reactive oxygen and nitrogen species in a more remote device and then deliver the gas mixture to the body surface to be treated via a suitable line.

[0013] Plasma sources that generate a jet plasma are also described. In this process, the plasma is generated inside the source using a sufficiently strong electric field, and then transported out of the source by a gas stream (typically a noble gas such as argon or helium). The plasma or plasma-activated gas exiting the source then glides directly onto the surface to be treated.

[0014] Typical parameters of planar plasma sources and parameters of the voltage applied to the electrodes are as follows:

[0015] Treatment area: 4 to 130 cm² 2

[0016] Electrode spacing: 0.1 mm to 1.5 cm

[0017] Voltage: 1 to 8 kV

[0018] Frequency: 1 kHz to 2 MHz

[0019] A plasma applicator can have, for example, a five-layer structure. One of the layers is a dielectric layer facing the surface to be treated, covering a first, active, planar electrode. The active, planar electrode is covered on the other side by another dielectric layer, which is positioned between the planar active electrode and a similarly planar counter electrode, electrically insulating the two electrodes from each other. On its side facing away from the surface to be treated, the planar counter electrode is covered by a third dielectric layer, forming the fifth layer of the plasma applicator.

[0020] Such plasma sources can generate a plasma that ionizes the air near or within the plasma source, leading, for example, to an increased formation of reactive oxygen and nitrogen species. In addition to the gas components generated in this way, the charged particles (electrons and ions), UV radiation, and the alternating electric field itself also directly affect the surfaces being treated.

[0021] If the surface to be treated is, for example, the surface of human tissue, the effects achieved are at least partially known in principle, namely as described, for example, in Roopak Murali et al. "Cold atmospheric plasma (CAP) in wound healing: harnessing a dual-edged sword" Redox Experimental Medicine (2024) 2024 e230026.

[0022] In this context, plasma therapy is also known, in which a plasma applicator of the described type is positioned near a body surface to be treated in order to generate plasma near the surface to be treated and to treat wounds.

[0023] Plasma treatment demonstrably promotes wound healing. Plasma treatment also shows a strong effect against microorganisms such as bacteria, spores, fungi, yeasts, and viruses, including their multi-resistant forms.

[0024] To improve and / or expand the use and application of a plasma applicator, the following proposes not only an improved procedure for operating and using a plasma applicator, but also various forms of using a plasma applicator and plasma treatment in combination with other applications. One form of application involves alternating plasma treatment with vacuum or vacuum irrigation therapy.

[0025] This preferably begins with a plasma treatment in which a plasma applicator is positioned in a known manner near the surface to be treated, such that an air space exists between the electrodes of the plasma applicator and the surface to be treated. This air space is sufficiently sealed that the gas mixture generated by the cold surface plasma produced by the plasma applicator is preferably not diluted by more than 50% with ambient air for at least one minute. Preferably, at least 80% of the gas mixture generated by the plasma applicator and the cold surface plasma it produces is retained for two or more minutes – for example, four to eight minutes.To create the air space between the plasma applicator and the surface to be treated, a suitable spacer can be provided between the surface and the plasma applicator. Due to its open structure, such as porous, nonwoven, or sponge-like material, this spacer is also suitable for aspirating liquids during vacuum or vacuum irrigation therapy. In particular, the spacer can be designed to self-erect or expand in the absence of a vacuum, thus creating a gas space between the plasma applicator and the surface to be treated. For a combined application of plasma treatment and vacuum or vacuum irrigation therapy, the surface to be treated is covered or enclosed with a flexible, essentially airtight covering, such as a plastic film.A porous, non-woven, or sponge-like structure, which can also serve as a spacer, is preferably provided between the body surface to be treated and the flexible covering (e.g., the film). In addition to the body surface to be treated, the flexible covering is preferably connected as tightly as possible to the surface of the respective body surrounding the surface to be treated, in order to enclose the enclosed space at least approximately gas-tight.

[0026] Liquid can then be drawn out of the enclosed space through a lumen protruding into the sealed gas space, for example, a hose or a valve on the flexible cover, and in contact with the cavity. Due to the surrounding air pressure, the flexible cover then presses firmly against the body surface and the porous, fleece- or sponge-like structure, compressing it.

[0027] To perform plasma treatment alternating with vacuum or vacuum-irrigation therapy, air can be blown into the space enclosed by the flexible cover after each vacuum or vacuum-irrigation treatment. Alternatively, it may be sufficient to simply open the lumen to the space enclosed by the flexible cover, allowing air to flow into the enclosed space while the porous, fleece-like or sponge-like structure straightens due to its self-righting properties.

[0028] For the desired plasma treatment, the required plasma applicator can be positioned either within the space enclosed by the flexible cover, for example, between the flexible cover and the porous, non-woven, or sponge-like structure, which then also serves as a spacer between the body surface to be treated and the plasma applicator. Alternatively, the plasma applicator can be positioned outside the flexible cover opposite the body surface to be treated or integrated into the porous, non-woven, or sponge-like structure. If the flexible cover itself is thin enough, the cold surface plasma is generated on the inside of the flexible cover, i.e., within the gas space enclosed by the flexible cover, when the plasma applicator is positioned close to the cover.Preferably, the flexible cover has an opening where the plasma applicator is located, so that the plasma applicator can act directly on the air in the space enclosed by the flexible cover, rather than through the cover itself. For this purpose, the plasma applicator is tightly connected to the flexible cover at its edges.

[0029] It is also possible to first perform conventional vacuum or vacuum irrigation therapy and, after its completion, optionally delineate the remaining wound cavity with foil and seal it with an adhesive frame for a plasma applicator, then seal it with the plasma applicator to create an enclosed space. A plasma atmosphere is then created in this space for two to ten minutes, either by generating plasma within the space itself, thus creating a plasma-containing gas mixture, or by supplying a plasma-containing gas mixture from an external plasma source. In the latter case, it is not necessary to position a plasma applicator near the wound. After the plasma therapy, the necessary equipment is removed, and further vacuum therapy can be performed.

[0030] The following optional possibilities also exist for plasma treatment and vacuum or vacuum irrigation therapy:

[0031] A new plasma applicator may be used for each plasma treatment, or one plasma applicator may be used for multiple plasma treatments, alternating with several vacuum or vacuum-rinse therapies. The duration of each vacuum or vacuum-rinse therapy typically lasts several hours and / or days, while a plasma treatment itself only lasts a few minutes, for example, between one and five minutes.

[0032] If a self-erecting structure is present as a spacer, which simultaneously allows for vacuum or vacuum-irrigation therapy, it may be possible to perform plasma treatment even under reduced pressure (i.e., lower than ambient pressure) within the gas space enclosed by the flexible cover. This is possible if the self-erecting structure is not yet compressed at this low pressure, so that gas remains between the plasma applicator and the surface to be treated. Such reduced pressure promotes the ignition of a cold surface plasma.

[0033] Another combination is possible between plasma therapy and vacuum irrigation therapy. In vacuum irrigation therapy, the wound is rinsed or cleaned with different solutions between suction phases. These rinsing solutions can include, for example, Ringer's solution or a saline solution. Solutions with germicidal properties, such as polyhexanide solution, are also administered. In pure vacuum therapy, no rinsing takes place; only suctioning of wound fluid, for example, is performed.

[0034] Vacuum irrigation therapy can last between two and four hours, for example, 180 minutes, during which a negative pressure of -50 to -200 mmHg, e.g., -120 mmHg, is generated across the lumen. The surface to be treated can be rinsed regularly with a sodium chloride solution (saline solution). For a treatment area of ​​approximately 10 cm x 10 cm, rinsing with 180 ml of saline solution is recommended. The exposure time is a few minutes, for example, one to five minutes, particularly three minutes.

[0035] The saline solution intended for rinsing is then drawn out through the lumen from the space enclosed by the flexible cover.

[0036] Preferably, the porous, non-woven, or sponge-like structure through which the fluid is aspirated is cleaned or replaced before each plasma treatment. The structure can then be used for several days – for example, 3 to 8 days – for alternating plasma treatment and vacuum therapy or vacuum irrigation therapy.

[0037] Instead of rinsing the treatment area with saline solution, Ringer's solution, a polyhexanide-containing wound irrigation solution, or similar solutions can also be used. Plasma-activated water is also suitable for rinsing the treatment area. Plasma-activated water is typically water that has been in direct contact with plasma or plasma gas for a certain period of time, resulting in the formation of substances such as nitrous acid, nitric acid, and hydrogen peroxide in the water. Simultaneously, the pH value drops, sometimes to below 2. Plasma-activated water exhibits a strong antimicrobial effect, and there is good evidence that it can also positively influence wound healing.

[0038] The rinsing fluid can be introduced after suction by allowing it to flow through the lumen into the space enclosed by the flexible cover. This works particularly well if the porous, non-woven or sponge-like structure is self-erecting, enabling the rinsing fluid to be drawn in through the lumen. Alternatively, the rinsing fluid can be pumped through the lumen into the space enclosed by the flexible cover. After a contact time of, for example, three to ten minutes, the rinsing fluid can then be suctioned out again through the lumen.

[0039] During alternating plasma therapy and vacuum therapy or vacuum irrigation therapy, it is advantageous to determine the pH value of the aspirated fluid—for example, the aspirated exudate—with each change. It is also advantageous to determine the volume of aspirated fluid for each vacuum therapy or vacuum irrigation therapy session. Furthermore, it is advantageous to determine the cytokine concentration in the aspirated fluid, such as the exudate, for each vacuum therapy or vacuum irrigation therapy session. Similarly, the bacterial concentration in the aspirated fluid, such as the exudate, can also be determined.

[0040] In summary, it is advantageous for alternating plasma treatment and vacuum therapy or vacuum irrigation therapy if the plasma applicator is attached together with the flexible cover from the outset. The flexible cover ensures both a sealed gas chamber for plasma therapy and the aspiration of fluid during vacuum therapy or vacuum irrigation therapy. For plasma treatment, it is intended that gas, particularly air, is present between the plasma applicator and the body surface being treated, while this air and any fluid are aspirated during the suction phase of vacuum therapy or vacuum irrigation therapy.To perform plasma treatment again following vacuum therapy or vacuum-irrigation therapy, air can be allowed or blown into the space enclosed by the flexible cover, provided that the surface of the plasma applicator is not covered with liquid. If this is ensured, there is no need to allow or blow air into the space enclosed by the flexible cover. The residual gas remaining in the sealed gas chamber under negative pressure is suitable for plasma ignition.

[0041] Even independently of vacuum therapy or vacuum irrigation therapy, it is advantageous if the body surface to be treated with plasma therapy is enclosed by a flexible covering, such as a bag or film. Here, too, the plasma applicator should ideally be positioned opposite the body surface to be treated, although this is not strictly necessary. Ideally, the plasma applicator should not touch the body surface being treated. However, the edges of the plasma applicator can touch adjacent body surfaces, thus defining a closed gas space.

[0042] For plasma treatments, which preferably last one to ten minutes, for example two minutes, it is advantageous if the gas within the enclosed volume inside the cover is moved in some way. Gas movement can occur, for example, through natural convection, which happens when the body surface to be treated has a temperature higher than the ambient temperature. Gas movement can also be forced by deliberately deforming the flexible cover during plasma treatment using external forces, causing the volumes enclosed by the flexible cover to shift within the enclosed gas space and thus forcing a corresponding gas movement.

[0043] If the flexible cover, for example, is in the form of a pouch that encloses part of the body being treated, this pouch can be gently squeezed repeatedly at various points from the outside to create gas movement. The gas trapped by the pouch, particularly the air trapped within it, ensures that the pouch remains essentially inflated and does not touch the body surface being treated.

[0044] Plasma treatment with a bipolar plasma applicator of the type described above is preferably performed with treatment times (duration of a treatment; treatment duration) on the order of at least one minute and preferably at least two minutes. Even for smaller body surfaces to be treated, a treatment duration of approximately two minutes and a maximum of ten minutes is suitable, as this duration promotes successful treatment and, at the same time, is short enough to prevent undesirable side effects, especially with a small volume of air trapped by the covering. To achieve the desired treatment effect with larger volumes of air trapped by the covering, the treatment duration can also be longer.For example, a 2-minute treatment is sufficient for air volumes up to 101, a 4-minute treatment duration is suitable for air volumes between 101 and 201 enclosed by the cover, and a 6 to 10 or more minute treatment duration is suitable for air volumes between 201 and 301 enclosed by the cover, etc.

[0045] This makes it possible to subject smaller, but especially also large parts of the entire human body surface (more than 50% of the human body surface) to plasma treatment, which lasts, for example, four minutes, six minutes, eight minutes, ten minutes or up to twenty minutes, but is typically shorter than twenty minutes because the body is then in a correspondingly large volume of air enclosed by the cover.

[0046] For small air volumes enclosed by the cover of less than 10 liters, plasma treatment preferably lasts no more than three to five minutes; that is, the exposure time of the species generated in the plasma, as well as the electric fields and charged particles emanating from the plasma applicator, to the body surface to be treated should preferably not exceed three to ten minutes at higher, plasma-induced ozone concentrations of more than 500 ppm. For the treatment of larger body surfaces, it is also possible to use several plasma applicators with a total larger electrode surface area simultaneously in order to achieve a higher concentration in a shorter time and thus a desired effect with a shorter treatment duration, whereby the treatment duration in this case can still be at least one or two minutes.

[0047] Suitable sizes for the areas assumed by the two electrodes of the plasma applicator are, for example, 100 cm². 2 However, plasma applicators with larger or smaller electrode surfaces can also be provided. Preferably, though, the active surface area of ​​a plasma applicator – i.e., the surface area of ​​the active electrode of the plasma applicator – is between 8 cm². 2 and 120 cm 2 For larger body surfaces to be treated, several plasma applicators are preferably used simultaneously, several plasma cycles are started consecutively, or a longer treatment duration is selected. However, larger plasma applicators can also be used, in which the surface area of ​​the active electrode is 200 cm². 2and more. Another aspect concerns a combination of plasma treatment and oxygen therapy or NOx therapy and / or CO2 therapy and / or topical oxygen treatment and / or hyperbaric oxygen therapy.

[0048] In these treatments, the space enclosed by the flexible cover is filled with a gas mixture that is richer in oxygen, nitrogen, or CO2 compared to ambient air. A combination with plasma treatment is advantageous because a cold surface plasma can be ignited at the plasma applicator even in such gas mixtures.

[0049] Variants of oxygen therapy, NOx therapy or CO2 therapy include the provision of negative or positive pressure - relative to the ambient pressure - for the gas mixture enclosed in the space enclosed by the flexible cover.

[0050] The enclosed space can be very large for both ambient air plasma therapy and plasma therapy with other gases, and can, for example, be a kind of bathtub covered with a foil. In this case, almost the entire patient could be inside the gas-filled space, with only their head protruding through the foil. This allows for a kind of whole-body treatment of a patient within the framework of plasma therapy with ambient air, oxygen therapy, NOx therapy, or CO2 therapy in combination with plasma treatments. In this case, too, several plasma applicators can be used simultaneously and arranged within the enclosed space—that is, inside the bathtub, beneath the foil. When using only one plasma applicator, the treatment duration—that is, the duration for which the plasma applicator is "activated"—can be extended.

[0051] Another parameter that can be adjusted with respect to the gas in the enclosed space is the humidity of the enclosed gas. Humidity directly affects the species generated in the plasma and thus the plasma's effect. Furthermore, humidity also affects the wound. To adjust the humidity of the gas, special devices can be used that humidify dry gases. In this context, plasma-activated water, which can be nebulized, for example, can also be used to humidify the gas. Another preferred application involves the application of exogenous skin substitutes or general skin substitute products, skin equivalents, fish skin, or similar materials to wounds. Here, it has been found that pretreating the wound with plasma therapy is very advantageous.Plasma treatment leads to plasma activation of the wound surface, improves the acceptor side, provides messenger substance enrichment and disinfection.

[0052] Pretreatment of the tissue graft itself, e.g., exogenous skin substitute, using plasma treatment is also advantageous, as the plasma treatment contributes to the disinfection of the tissue graft, increases its wettability, and also promotes enrichment with active species.

[0053] Following a transplant, plasma treatment is beneficial for promoting wound healing, as it can induce and accelerate the healing process. Such plasma-assisted wound healing can be performed, for example, every two to three days or twice a week and supports standard wound care. This type of plasma-assisted wound healing is similar to conventional plasma treatment, in which the plasma applicator is positioned opposite the wound containing the tissue graft, and an almost completely sealed gas space is created between the applicator and the wound. The plasma applicator does not touch the wound, or only its edge does, to create this sealed space.

[0054] Another aspect concerns the combination of plasma therapy and ultrasound application. Ultrasound applied to the body surface being treated can help activate it. The ultrasound causes the surface to vibrate. Depending on the ultrasound frequency, the wavelength of the sound changes, reaching wavelengths smaller than the cell size. These are frequencies in the megahertz (MHz) range. With ultrasound frequencies in the megahertz range, cells can be directly stimulated, and, for example, their absorption capacity can be influenced. In combination with plasma therapy, this can enhance beneficial effects. The ultrasound can be introduced into the body surface being treated, for example, via the air, directly through skin contact, or using a porous, fleece-like, or sponge-like structure.It is intended for vacuum therapy or vacuum-irrigation therapy, or as a spacer between the plasma applicator and the body surface to be treated. Another aspect concerns a system for the sequential treatment of a body surface with cold atmospheric pressure plasma and vacuum or vacuum-irrigation therapy.The system comprises a) a flexible, substantially gas-tight cover for creating a closed volume over the body surface, b) a porous, nonwoven or sponge-like spacer structure within the volume that is compressible under pressure and self-erecting in the absence of pressure, c) at least one plasma applicator arranged within the volume or gas-tightly covering an opening formed in the cover and acting into the volume, d) a high-voltage generator for supplying the plasma applicator with the required operating voltage, which is connected to the plasma applicator, e) at least one port with a lumen for liquid instillation and / or for aspiration of gases and liquids from the volume, and f) a suction pump for or for aspiration of gases and liquids from the volume, which is connected to the lumen.

[0055] The system may include a control unit that is operatively connected to the suction pump and the high-voltage generator and is configured to effect alternating operation of a plasma therapy phase and a vacuum or vacuum flushing therapy phase.

[0056] The system can also include sensors for detecting at least one parameter such as humidity, temperature, ozone, nitrogen and oxygen species, hydrogen peroxide, pH, oxidation-reduction potential, exudate flow, or bacterial fluorescence. Preferably, the sensors additionally include a pH, oxidation-reduction potential (ORP), or cytokine measurement module for aspirated exudate. Furthermore, the system can include means for actively adjusting the gas composition within the volume, specifying a mixing ratio of oxygen, nitrogen, and / or carbon dioxide that differs from ambient air and / or a defined humidity level.

[0057] Preferably, the plasma applicator has bipolar planar electrodes separated by a dielectric and is oriented such that the active electrode faces the body surface.

[0058] Preferably the plasma applicator is unipolar and the system includes an additional neutral electrode, so that the body forms the counter electrode for the plasma applicator during application.

[0059] The plasma applicator can be designed as a jet plasma source or as a source with external generation of reactive oxygen and nitrogen species (RONS) and supply into the volume.

[0060] The cover can be designed as a film, bag, cuff, hood or tub cover that encloses a part or most of the body.

[0061] The system can have multiple plasma applicators that can be controlled simultaneously or sequentially.

[0062] In preferred embodiments, the spacer structure has flow channels or openings for gas circulation.

[0063] The system may include an ozone degradation catalyst in an exhaust or extraction line connected to the enclosed space.

[0064] The system can include a control unit that regulates plasma power, plasma duration, vacuum level, instillation volume, residence time, gas composition and humidity depending on sensor signals.

[0065] The system may include an optical sensor or imager for detecting bacterial fluorescence, connected to the high-voltage generator and configured to provide a signal to trigger additional plasma pulses depending on the detected bacterial fluorescence. The control unit may be configured to provide a mode in which plasma therapy is operated at reduced absolute pressure within the volume.

[0066] The system may include a humidifier that introduces water or plasma-activated water into the volume.

[0067] The cover is preferably locally elastically deformable in order to generate a forced gas movement during plasma therapy.

[0068] In a preferred embodiment, the system has an ultrasound transducer that can couple ultrasound into a body surface via the spacer structure, preferably during a plasma therapy phase.

[0069] Preferably, the control unit is configured to provide the following limit values ​​for the parameters suppression, plasma pulse duration, humidity and oxygen content: suppression between -50 and -200 mmHg, plasma pulse duration 1 to 10 minutes, humidity 30 to 100 percent relative humidity, oxygen content 21 to 100 volume percent.

[0070] Preferably, the system includes a safety module configured to monitor ozone concentration and reduce or stop plasma generation above a threshold for ozone concentration.

[0071] The cover is preferably designed to enclose the plasma applicator gas-tight around an opening using an adhesive frame.

[0072] The control unit preferably includes a log memory for cycle count, duration, pressure profiles, instillations and sensor signals.

[0073] The system can be designed as a portable or stationary device.

[0074] Another aspect concerns a method for treating the surface of a living body, comprising the steps of a) creating a substantially gas-tight volume over the body surface by means of a flexible cover, b) generating a cold atmospheric pressure plasma in the volume for a duration of 1 to

[0075] 10 minutes, c) applying a negative pressure of -50 to -200 mmHg and optionally instilling a rinsing solution into the volume with a residence time of 1 to 10 minutes and subsequent aspiration, d) repeating steps b) and c) in a predetermined sequence, wherein during at least one step b) or e) the gas composition and / or the humidity in the volume is controlled and adjusted to a predetermined setpoint.

[0076] The rinsing solution may include, for example, saline solution, Ringer's solution, PHMB, hypochlorous acid, hydrogen peroxide and / or plasma-activated water.

[0077] According to one variant of the procedure, photobiomodulation with electromagnetic radiation in the 600 to 900 nm range is performed before or after step b). Step e) (applying a negative pressure of -50 to -200 mmHg and optionally instilling a rinsing solution into the volume with a residence time of 1 to 10 minutes and subsequent aspiration) can then be omitted if necessary.

[0078] According to one variant of the procedure, bacteriophages and / or enzymatic debridement agents are instilled in one of the instillation phases.

[0079] According to one variant of the procedure, fluorescence is detected using an optical sensor, and additional plasma pulses are triggered if fluorescence is detected. Here, too, step c) (applying a negative pressure of -50 to -200 mmHg and optionally instilling a rinsing solution into the volume with a residence time of 1 to 10 minutes, followed by aspiration) can be omitted if necessary.

[0080] Preferably, during step b) the cover is cyclically deformed to induce gas circulation.

[0081] Preferably, step b) is performed at ambient pressure or under negative pressure within the volume. Preferably, treatment is performed prophylactically on closed incisions prior to the application of closed incision negative pressure therapy.

[0082] According to one advantageous application, the procedure is used on venous ulcers under downstream compression.

[0083] According to another advantageous application, the procedure is applied to the pin sites of percutaneous fixators, central venous catheters, or peritoneal dialysis catheters using local mini-coverage. Here, too, step c) (applying a negative pressure of -50 to -200 mmHg and optionally instilling a rinsing solution into the volume with a residence time of 1 to 10 minutes, followed by aspiration) can be omitted if necessary.

[0084] According to another advantageous application, the procedure is used on the feet or hands with a type of bag as a cover or enclosure for the treatment of onychomycosis or tinea pedis. A particular embodiment of the procedure includes the application of an exogenous skin substitute, a skin equivalent, or a tissue graft, wherein plasma therapy is performed before application and / or postoperatively. Here, too, step c) (applying a negative pressure of -50 to -200 mmHg and optionally instilling a rinsing solution into the volume with a residence time of 1 to 10 minutes and subsequent aspiration) can optionally be omitted.

[0085] In another embodiment of the method, the gas composition has an oxygen content greater than 21 percent by volume and / or a defined addition of NOx or CO2.

[0086] According to an advantageous variant of the procedure, microneedles or iontophoresis are used within the volume for drug delivery. Here, too, step c) (applying a negative pressure of -50 to -200 mmHg and optionally instilling a rinsing solution into the volume with a residence time of 1 to 10 minutes and subsequent aspiration) can be omitted if necessary.

[0087] In an advantageous embodiment of the method, a control unit adjusts the plasma duration and / or power depending on pH, ORP, exudate volume, cytokine, or fluorescence signals. In another advantageous embodiment, for treating surface areas greater than 50 percent of a body surface, a tray cover with a film or a bag large enough to accommodate the entire body is used, and the plasma pulse duration is scaled volume-dependently by the volume enclosed by the cover.

[0088] It can be advantageous to clean or replace the spacer structure between cycles of the process.

[0089] It may be advantageous to operate at least two plasma applicators simultaneously.

[0090] Preferably, the ozone concentration is monitored during plasma therapy, and if a threshold value is exceeded, operation is reduced or stopped.

[0091] Preferably, the humidity in the volume is adjusted by introducing water or plasma-activated water or water vapor or plasma-activated water vapor.

[0092] According to an advantageous variant of the method, ultrasound with frequencies in the megahertz range is delivered during at least one step b) or c) via the spacer structure or directly onto the skin next to the wound.

[0093] According to another advantageous variant of the procedure, a plasma therapy phase lasts 1 to 10 minutes and each vacuum or vacuum irrigation therapy phase lasts 30 to 240 minutes.

[0094] Preferably, the gas dilution in volume during a plasma therapy phase is limited such that at least 50 percent, preferably at least 80 percent, of the generated plasma-activated gas mixture is retained over the duration of the plasma treatment.

[0095] During a plasma therapy phase, the voltage applied to the plasma applicator is preferably between 1 kV and 10 kV and its frequency between 1 kHz and 2 MHz.

[0096] Another aspect concerns a kit for performing the procedure described above. The kit comprises a) a system of the aforementioned type, b) at least one instillation solution selected from saline, Ringer's solution, PHMB (polyhexanide), hypochlorous acid, hydrogen peroxide and / or plasma-activated water, c) optionally a phage preparation and / or an enzymatic debridement preparation, and d) instructions for use that specify a sequence of plasma therapy phases and vacuum or vacuum-rinse therapy phases with corresponding parameter values.

[0097] Additionally, the kit preferably includes disposable covers, adhesive frames and spacer structures of different geometries.

[0098] A kit containing sterile filters and catalyst units for exhaust gas treatment is preferred.

[0099] A kit containing sensors, in particular disposable sensors for pH, ORP, cytokines or fluorescence signals, is preferred.

[0100] A kit is preferred in which the instructions for use include indication pathways for closed incisions, venous ulcers, pin sites and onychomycotic areas.

[0101] Another aspect concerns uses of the system in accordance with the aforementioned aspect.

[0102] One use of the system is the sequential application of cold atmospheric pressure plasma and vacuum or vacuum irrigation therapy to a body surface within a volume formed by a flexible cover.

[0103] Preferably, the system is used for the prophylaxis of surgical wound infections at closed incisions under subsequent closed incision negative pressure therapy.

[0104] Preferably, the system is used to treat venous ulcers of the lower extremities with subsequent compression. Preferably, the system is also used to treat large burns.

[0105] The system is preferably used to treat chronic wounds.

[0106] The system is preferably used to treat pin sites, central venous catheter entry sites, or peritoneal dialysis catheters.

[0107] Preferably, the system is used to treat onychomycosis or tinea pedis. Preferably, the system is used in which the area to be treated is covered with a bag or film.

[0108] Preferably, the system is used to prepare a wound surface for the application of a skin substitute, skin equivalent or tissue graft.

[0109] When using the system, a defined humidity level is preferably set within the volume.

[0110] When using the system, a dose of plasma is preferably regulated depending on pH, ORP, exudate amount, cytokine or fluorescence signals.

[0111] Another aspect concerns a method for operating a system according to the aforementioned aspect. The method comprises the steps a) providing a substantially gas-tight volume formed by a flexible cover over a surface, b) generating a cold atmospheric pressure plasma in the volume for a predetermined pulse duration, c) applying a vacuum in the volume and instilling and aspirating a liquid, d) repeating steps b) and c), wherein a control unit regulates a plasma power and / or a vacuum and / or an instillation volume and / or a gas composition and / or an air humidity depending on sensor signals. Preferably, the method is operated at a reduced absolute pressure during the plasma therapy phase.

[0112] Preferably, the volume has a defined gas composition with oxygen, nitrogen and / or carbon dioxide, as well as a predetermined humidity range.

[0113] According to an advantageous method variant, the detection of a fluorescence-indicating signal serves as a trigger for additional plasma pulses.

[0114] Preferably, the cover is deformed to generate a forced gas movement during plasma therapy.

[0115] In one variant of the system, an ozone degradation catalyst can be installed in the exhaust pipe to facilitate the degradation of ozone in the exhaust pipe.

[0116] Preferably, ultrasound is generated during at least one step b) or c) and delivered to the body surface to be treated near the wound.

[0117] According to a beneficial treatment regimen, whole-body plasma therapy can be applied every 24 hours to reduce bacterial load and support the immune system. This leads to sepsis stabilization in cases of large-area infected tissue defects, such as burns. Further applications of plasma therapy using cold atmospheric pressure plasma include:

[0118] The system is used immediately postoperatively before or during closed incision negative pressure wound therapy (ciNPWT) for surgical site infection (SSI) prophylaxis in high-risk procedures (vascular, oncological, and obese patients). Meta-analyses and randomized controlled trials (RCTs) report reduced SSI rates with ciNPWT; a preliminary short exposure to cold atmospheric pressure plasma under a foil can further reduce the microbial load.

[0119] Percutaneous entry sites and pin sites (drivelines, fixators, central vein catheters (CVC), epidural catheters): Local, short-term application of cold atmospheric pressure plasma under a mini-film can be performed to control biofilm on metal or polymer surfaces around the insertion site. Cold atmospheric pressure plasma is effective against biofilms.

[0120] Acne areas and seborrheic / infectious dermatoses

[0121] Short-term applications of cold atmospheric pressure plasma as an adjunct to regimens that adhere to guideline-based therapies. Early clinical data exist on cold atmospheric pressure plasma in acne; cold atmospheric pressure plasma is not a replacement, but a potential booster.

[0122] Flap and graft salvage

[0123] Beyond the “skin replacement” application described above, postoperative applications of cold atmospheric pressure plasma can be used for microbial control and promotion of angiogenesis in flap margins; additionally, gases (O2 / CO2) can be controlled in the enclosed space.

[0124] Disinfection of body parts of EB patients (Epidermolysis bullosa) by enclosing the body part with a bag and contactless disinfection of the body part using cold atmospheric pressure plasma for two to six minutes.

[0125] Plasma therapy with cold atmospheric pressure plasma can be combined with and / or supplemented by other therapies as follows: complementary physical therapy:

[0126] Photobiomodulation (PBM) using red or near-infrared light-emitting diodes or low-level lasers

[0127] Photobiomodulation can follow plasma therapy with cold atmospheric pressure plasma. This can also be performed at a later time and regardless of whether vacuum or vacuum irrigation therapy is also carried out. Photobiomodulation promotes microcirculation and cell proliferation, while cold atmospheric pressure plasma reduces the initial bacterial load. Image-guided dosing with bacterial fluorescence

[0128] Integration of, for example, violet fluorescence imaging to detect high bacterial load as a trigger for cold atmospheric pressure plasma therapy. The duration and / or number of plasma therapy cycles can be controlled depending on the detected bacterial fluorescence. Studies show that fluorescence imaging detects biofilm or bacterial load at the wound bed better than purely clinical assessment. Bacterial fluorescence can be detected, for example, with the Moleculight product.

[0129] Transdermal penetration enhancement: Cold atmospheric pressure plasma temporarily increases skin permeability and can be combined with microneedles or iontophoresis in a foil space to deliver active ingredients locally. This can be done regardless of whether vacuum or vacuum irrigation therapy is being performed. Complementary pharmacological / biological therapy: Cold atmospheric pressure plasma in combination with antibiotics / antiseptics

[0130] Evidence shows synergies against biofilm when cold atmospheric pressure plasma reduces the biofilm matrix / permeability barrier. Add-on effects have been described particularly for PVP-iodine (polyvinylpyrrolidone), PHMB (polyhexanide), HOCl (hypochlorous acid), and H₂O₂; temporal separation prevents quenching of reactive oxygen and nitrogen species (RONS). Cold atmospheric pressure plasma in combination with plasma-activated water (PAW) and bacteriophages has also been shown to be effective.

[0131] Pretreatment with plasma-activated water increases phage activity against biofilms by several log units. Plasma-activated water can be used as a rinsing phase in vacuum rinsing therapy prior to phage instillation. Cold atmospheric pressure plasma in combination with antimicrobial peptides (AMPs) can be used. AMPs can be provided in hydrogels / composite dressings; cold atmospheric pressure plasma reduces bioburden and disrupts the matrix, while AMPs stabilize low-bioburden.

[0132] Enzymatic debridement agents (e.g., collagenase)

[0133] Plasma therapy and debridement can be combined by following debridement with cold atmospheric pressure plasma, or vice versa, to remove matrix / slough and marginal tissue in a more controlled manner. Enzymatic debridement is well-established and can be combined with plasma therapy; cold atmospheric pressure plasma can be used to prepare or follow up the procedure.

[0134] Biologics: PRP (Platelet Rich Plasma) / MSC (Mesenchymal Stem Cells)

[0135] Combinations with MSC and NPWT have already shown synergistic effects preclinically; cold atmospheric pressure plasma is added here as an antimicrobial, immunomodulating pulse. PRP / cold atmospheric pressure plasma concepts have been investigated in flap viability models.

[0136] Since the relative humidity in the enclosed gas space influences the generation of H₂O₂ and reactive oxygen and nitrogen species, it is advantageous to actively control the relative humidity in the enclosed gas space. PAW aerosols are beneficial as humidifiers.

[0137] The plasma applicator can have sensors that, in conjunction with a control unit, allow closed-loop control of the following parameters: pH, temperature, humidity, exudate flow, as well as H2G2 / NOx surrogate sensors in the gas and ORP (oxidation-reduction potential) in the exudate; adaptive cold atmospheric pressure plasma duration / power according to target biomarker.

[0138] The invention will now be explained using exemplary embodiments with reference to the figures. The figures show...

[0139] Fig. 1: A device for treating a body surface using a cold surface plasma; Fig. 2: A schematic top view of a larger wound covered by a flexible dressing and having an opening over which a plasma applicator is placed;

[0140] Fig. 3: a sectional view through the arrangement shown in Figure 2;

[0141] Fig. 4: illustrates an embodiment in which a body part is covered by a flexible

[0142] is enclosed in a cover, for example by a bag;

[0143] Fig. 5: a system for treating a body surface using a cold surface plasma and performing vacuum therapy using a device according to Figure 1; and

[0144] Fig. 6: a schematic representation of a process flow.

[0145] To subject a body surface 10 alternately to plasma treatment and vacuum therapy, a flexible, essentially gas-tight cover 12 in the form of a film is provided, enclosing a volume 14 containing a gas, for example, air. The cover 12 is tightly connected to the body surface 10 at its edges 12.1. Within the volume enclosed by the cover 12 is a porous, nonwoven or sponge-like structure 16, which simultaneously serves as a spacer and ensures that the volume 14 is at least partially maintained even when there is negative pressure in the space enclosed by the cover 12 relative to the surroundings. To create such negative pressure in the volume 14, a tube 18 with a lumen 18.1 is provided, through which, in particular, liquid and / or gases can be aspirated from or introduced into the volume 14 enclosed by the cover 12.

[0146] Furthermore, a plasma applicator 20 is arranged on the side of the porous, nonwoven or sponge-like structure 16 facing away from the body surface 10 to be treated, and is located within the space enclosed by the cover 12. Alternatively, the cover 12 could also have an opening, and the plasma applicator 20 could be positioned outside the cover 12 in such a way that it covers and seals the opening in the cover 12 and is in contact with the gas enclosed by the cover 12, at least with its side facing the body surface to be treated. In the illustrated embodiment, the plasma applicator 20 has a five-layer structure. The plasma applicator 20 has a first active planar electrode 20.1 and a second, also planar, counter electrode 20.2. The first active electrode 20.1 and the second, also planar, counter electrode 20.2 are electrically insulated from each other by a dielectric layer 20.3.A further dielectric layer 20.4 covers the first, active electrode 20.1 on its outer surface, which faces the body surface 10 to be treated. A third dielectric layer 20.5 covers the counter electrode 20.2 on its outer surface, which faces away from the skin surface to be treated.

[0147] During plasma treatment, a high-frequency alternating voltage with a frequency in the single-digit kHz range and a voltage in the single-digit kV range is applied to the two electrodes 20.1 and 20.2. For this purpose, the first, active electrode 20.1 and the counter electrode 20.2 are connected to a high-voltage generator 22 via electrical leads 20.6 and 20.7, so that a suitable voltage can be applied between the two electrodes 20.1 and 20.2 for the duration of a plasma treatment (treatment duration). This voltage causes a cold surface plasma to form near the side of the first, active electrode 20.1 facing outwards towards the body surface to be treated. Within the volume 14 enclosed by the cover 12, this plasma generates, among other things, reactive oxygen and nitrogen species, which can then act on the body surface 10 to be treated.The treatment duration, i.e., the duration of a plasma treatment, is preferably between two and ten minutes.

[0148] As already mentioned, fluid can be aspirated from or added to the volume enclosed by the cover 12 through the lumen 18.1 of the tube 18 as part of vacuum therapy. Preferably, vacuum therapy or vacuum irrigation therapy is used in which not only is fluid released, for example, from the body surface 10 aspirated, but also irrigation fluid is flushed through the lumen 18.1 into the volume 14 enclosed by the cover 12 and subsequently aspirated again.

[0149] Plasma treatment and vacuum therapy are performed alternately, so that as a result several plasma treatments and several vacuum therapies are carried out alternately in order to treat a body surface area 10.

[0150] Figures 2 and 3 schematically illustrate how even larger wounds 26 can be treated using a flexible cover 12 and a plasma applicator 20. The flexible cover 12 completely covers the wound 26 and has an opening 12.1 indicated by the dashed line. The plasma applicator 20 is positioned so that it completely covers the opening 12.1 and that its active electrode 20.1 points towards the gas space 14 enclosed by the flexible cover 12 and thus also towards the wound 26. This is particularly evident in the schematic sectional view in Figure 3. The plasma applicator 20 is tightly connected to the edges 12.2 of the flexible cover 12 surrounding the opening 12.1 by means of an adhesive frame 28.

[0151] Figure 4 illustrates an embodiment in which a plastic film or foil 12 is wrapped around a body part, i.e., a foot 30, to define a sealed gas space 14 around the foot 30. The gas space 14 is sealed with an elastic band 32 wrapped around the ankle of the foot 30. A plasma applicator 20 is placed in the space 14 enclosed by the plastic film 12. The plasma applicator 20 is connected via leads 20.6 and 20.7 (see Figure 1) to a power supply unit, e.g., a high-voltage generator (22; see Figure 1), which provides a voltage signal sufficient to ignite a physical plasma. A spacer 16 is located between the foot 30 and the plasma applicator 20. The spacer 16 has recesses or holes 16.1 , which allow a circulation of the gas between the surface of the plasma applicator 20 - where the plasma is ignited - and the surface to be treated - for example, the skin of the foot, as in the example shown.

[0152] It is understood that foot 20 is only an example of any body part or object to be treated. The film 12 can be a simple, flexible film wrapped around the body part, or it can be a bag.

[0153] The device from Figure 1 is preferably part of a system as shown in Figure 5. In addition to the components already mentioned in connection with Figure 1, the system from Figure 5 includes a suction pump 40 for extracting gases or liquids such as exudate from the volume 14 enclosed by the cover. Furthermore, a sensor 24 is provided in the volume 14 enclosed by the cover, with which one or more values ​​of one or more of the parameters mentioned above can be detected.

[0154] The high-voltage generator 22 and preferably also the suction pump 40 are operatively connected to a control unit, so that the high-voltage generator 22 and preferably also the suction pump 40 can be controlled by the control unit 50. Furthermore, the control unit 50 is connected to the sensor system 24. This allows both the plasma therapy using the high-voltage generator 22 and plasma applicator 20, as well as the vacuum therapy using the suction pump 40, to be controlled and, if desired, regulated depending on the measured parameter values, as mentioned above. The system can also include further components, such as an ultrasound source 60, to couple ultrasound into a volume to be treated, as mentioned above. The ultrasound source 60 is also preferably connected to the control unit 50.

[0155] Regarding the procedure (see Figure 6), plasma therapy 100 and vacuum or vacuum irrigation therapy 110 can be applied sequentially and repeated as needed. Furthermore, other therapies 120 can also be integrated into the procedure as needed, as described above.

[0156] Reference symbol list

[0157] 10 body surface areas to be treated

[0158] 12 flexible covers

[0159] 12.1 Edges of the flexible cover

[0160] 14 Volume enclosed by the cover, gas space

[0161] 16 open, fleece- or sponge-like structure, spacers

[0162] 16.1 Cutouts in the spacer

[0163] 18 hose, connection

[0164] 18.1 lumens of the hose

[0165] 20 Plasma Applicator

[0166] 20.1 active electrode of the plasma applicator

[0167] 20.2 Counter electrode of the plasma applicator

[0168] 20.3, 20.4, 20.5 dielectric layer

[0169] 20.6 and 20.7 Supply lines

[0170] 22 High-voltage generator

[0171] 24 sensors

[0172] 26 wound

[0173] 28 adhesive frames for the plasma applicator

[0174] 30 feet

[0175] 32 elastic bands

[0176] 40 Suction pump

[0177] 50 control unit

[0178] 60 ultrasound source

[0179] 100 Plasma therapy

[0180] 110 Vacuum or vacuum irrigation therapy

[0181] 120 more therapies

Claims

Claims 1. Procedure for treating the surface of a living body with the following steps: Creating a closed volume around a body surface to be treated by means of a substantially gas-tight, flexible covering, in particular a film or bag, which is substantially gas-tight and connected to the environment of the body surface to be treated, and alternating Generating a cold surface plasma in the enclosed volume for a duration of at least one minute, preferably two to four minutes (plasma treatment), and Aspiration of fluid from the sealed volume by applying negative pressure in the sealed volume (vacuum therapy), wherein the steps of generating a cold surface plasma in the sealed volume and aspiration of fluid from the sealed volume are each performed alternately at least once.

2. Method according to claim 1, wherein the cold surface plasma is generated in the enclosed volume by means of a plasma applicator in or immediately adjacent to the enclosed volume.

3. Method according to claim 2, wherein the plasma applicator has a first active planar electrode and a similarly planar counter electrode and a dielectric layer arranged between the first active planar electrode and the second, similarly planar counter electrode, and wherein the first active planar electrode faces the body surface to be treated.

4. Method according to any one of claims 1 to 3, wherein an open, nonwoven or sponge-like structure is arranged between the gas-tight, flexible cover and the body surface to be treated.

5. Method according to claim 4, wherein the plasma applicator is arranged on the side of the open, nonwoven or sponge-like structure facing away from the body surface to be treated.

6. Method according to claim 4 or 5, wherein the plasma applicator is integrated into the open, nonwoven or sponge-like structure.

7. Method according to any one of claims 4 to 6, wherein the open, nonwoven or sponge-like structure is elastically compressible and self-erecting.

8. Method according to any one of claims 4 to 7, wherein the open, nonwoven or sponge-like structure comprises electrodes of a plasma applicator.

9. Method according to claim 8, wherein the electrodes are elastically flexible electrical conductors, in particular wires, which are integrated into the open, fleece-like or sponge-like structure.

10. Method according to at least one of claims 1 to 9, wherein a mixing ratio of oxygen, nitrogen and / or CO2, which differs from that of ambient air, is set in the enclosed volume enclosed by the substantially gas-tight, flexible cover.

11. Open, non-woven or sponge-like structure (16) for vacuum therapy, which is elastically compressible and self-erecting and has electrical conductors as electrodes of a plasma applicator.

12. System for the sequential treatment of a body surface with cold atmospheric pressure plasma and vacuum or vacuum irrigation therapy, comprising a flexible, substantially gas-tight cover (12) for creating a closed volume (14) over the body surface (10), and an open, nonwoven or sponge-like spacer structure (16) within the volume (14) that is compressible under pressure and self-erecting in the absence of pressure. at least one planar plasma applicator (20) which is arranged within the volume or gas-tightly covers an opening formed in the cover (12) and acts into the volume, a high-voltage generator (22) connected to the plasma applicator (20) for supplying the plasma applicator (20) with an operating voltage, at least one connection (18) with lumen (18.1) for liquid instillation and / or for suction of gases and liquids from the volume, and a suction pump (40) connected to the lumen (18.1) for suction of gases and liquids from the volume.

13. System according to claim 12, which additionally comprises a control unit (50) which is operatively connected to the high-voltage generator (22) and preferably also to the suction pump (40) and is configured to control the operation of the high-voltage generator 22 and preferably also to the suction pump 40.

14. System according to claim 13, which additionally comprises a sensor (24) arranged in the volume (14) enclosed by the gas-tight cover (12) and connected to the control unit (50), wherein the control unit (50) is configured to control the high-voltage generator (22) and / or the suction pump (40) depending on a parameter value detected by the sensor.

15. System according to one of claims 12 to 14, which additionally comprises an ultrasound source (60) connected to the control unit (50).

Images