Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/44—Applying ionised fluids
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
  • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
  • A61B18/042—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating using additional gas becoming plasma
• • H—ELECTRICITY
  • H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
  • H05H—PLASMA TECHNIQUE; PRODUCTION OF ACCELERATED ELECTRICALLY-CHARGED PARTICLES OR OF NEUTRONS; PRODUCTION OR ACCELERATION OF NEUTRAL MOLECULAR OR ATOMIC BEAMS
  • H05H1/00—Generating plasma; Handling plasma
  • H05H1/24—Generating plasma
  • H05H1/2406—Generating plasma using dielectric barrier discharges, i.e. with a dielectric interposed between the electrodes
  • H05H1/2418—Generating plasma using dielectric barrier discharges, i.e. with a dielectric interposed between the electrodes the electrodes being embedded in the dielectric
• • H—ELECTRICITY
  • H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
  • H05H—PLASMA TECHNIQUE; PRODUCTION OF ACCELERATED ELECTRICALLY-CHARGED PARTICLES OR OF NEUTRONS; PRODUCTION OR ACCELERATION OF NEUTRAL MOLECULAR OR ATOMIC BEAMS
  • H05H1/00—Generating plasma; Handling plasma
  • H05H1/24—Generating plasma
  • H05H1/2406—Generating plasma using dielectric barrier discharges, i.e. with a dielectric interposed between the electrodes
  • H05H1/2443—Generating plasma using dielectric barrier discharges, i.e. with a dielectric interposed between the electrodes the plasma fluid flowing through a dielectric tube
  • H05H1/245—Generating plasma using dielectric barrier discharges, i.e. with a dielectric interposed between the electrodes the plasma fluid flowing through a dielectric tube the plasma being activated using internal electrodes
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
  • A61B2018/00053—Mechanical features of the instrument of device
  • A61B2018/00059—Material properties
  • A61B2018/00065—Material properties porous
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
  • A61B2018/00053—Mechanical features of the instrument of device
  • A61B2018/00059—Material properties
  • A61B2018/00071—Electrical conductivity
  • A61B2018/00083—Electrical conductivity low, i.e. electrically insulating
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
  • A61B2018/00315—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for treatment of particular body parts
  • A61B2018/00321—Head or parts thereof
  • A61B2018/00327—Ear, nose or throat
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
  • A61B2018/00315—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for treatment of particular body parts
  • A61B2018/00482—Digestive system
  • A61B2018/00494—Stomach, intestines or bowel
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
  • A61B2018/00315—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for treatment of particular body parts
  • A61B2018/00559—Female reproductive organs
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/02—Details
  • A61N1/04—Electrodes
  • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
  • A61N1/0521—Genital electrodes
  • A61N1/0524—Vaginal electrodes
• • H—ELECTRICITY
  • H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
  • H05H—PLASMA TECHNIQUE; PRODUCTION OF ACCELERATED ELECTRICALLY-CHARGED PARTICLES OR OF NEUTRONS; PRODUCTION OR ACCELERATION OF NEUTRAL MOLECULAR OR ATOMIC BEAMS
  • H05H1/00—Generating plasma; Handling plasma
  • H05H1/24—Generating plasma
  • H05H1/2406—Generating plasma using dielectric barrier discharges, i.e. with a dielectric interposed between the electrodes
  • H05H1/2441—Generating plasma using dielectric barrier discharges, i.e. with a dielectric interposed between the electrodes characterised by the physical-chemical properties of the dielectric, e.g. porous dielectric
• • H—ELECTRICITY
  • H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
  • H05H—PLASMA TECHNIQUE; PRODUCTION OF ACCELERATED ELECTRICALLY-CHARGED PARTICLES OR OF NEUTRONS; PRODUCTION OR ACCELERATION OF NEUTRAL MOLECULAR OR ATOMIC BEAMS
  • H05H2245/00—Applications of plasma devices
  • H05H2245/20—Treatment of liquids
• • H—ELECTRICITY
  • H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
  • H05H—PLASMA TECHNIQUE; PRODUCTION OF ACCELERATED ELECTRICALLY-CHARGED PARTICLES OR OF NEUTRONS; PRODUCTION OR ACCELERATION OF NEUTRAL MOLECULAR OR ATOMIC BEAMS
  • H05H2245/00—Applications of plasma devices
  • H05H2245/30—Medical applications
  • H05H2245/34—Skin treatments, e.g. disinfection or wound treatment

Definitions

• the present invention relates to a medical device for generating a plasma-activated liquid, a system having this device for generating plasma-activated liquids, and a method for generating a plasma-activated liquid. It also relates to a method for the prophylaxis and treatment of postoperative adhesions.
• Plasma refers to a mixture of particles at the atomic-molecular level. Plasma was first described in the 1920s by the chemist Irving Langmuir. It consists of a particle mixture of partially charged components, ions and electrons. Plasma can be generated artificially, for example by heating a neutral gas or exposing it to a strong electromagnetic field until an ionized gaseous substance becomes increasingly electrically conductive.
• Non-thermal or low-temperature plasma can be generated at atmospheric pressure by an electrode system by means of a so-called dielectric barrier discharge.
• This is an alternating voltage gas discharge in which at least one of the electrodes passes through the gas space galvanic isolation is electrically isolated by means of a dielectric.
• a gas- or air-filled space between the insulating encased electrodes can then be ionized or becomes plasma when an alternating voltage generates sufficient field strengths in the gas space at the electrodes.
• the alternating voltage for generating a plasma is a few kilovolts, ie a high voltage is required to generate a plasma.
• Pulsed excitation is also advantageous for generating a plasma, with voltage pulses with amplitudes in the kilovolt range with pulse durations of a few microseconds down to a few tens of nanoseconds being applied to the electrode arrangement.
• Low temperature plasma can be demonstrated on biological systems. It is described that low-temperature plasma has an efficient antiseptic effect and a positive influence on chronic and acute wounds. It is also described that treatment of tumors with low-temperature plasma can lead to inactivation of the cancer cells by initiation of apoptosis.
• biologically reactive plasma factors are held responsible for the observed effects of the plasma on biological systems. These are essentially reactive species, such as reactive nitrogen species (RNS), reactive oxygen species (ROS), free radicals, ionic compounds such as N0 2 , N0 3 , ONOO, electromagnetic radiation, etc. and possibly other so far not further characterized species.
• RNS reactive nitrogen species
• ROS reactive oxygen species
• free radicals free radicals
• ionic compounds such as N0 2 , N0 3 , ONOO, electromagnetic radiation, etc. and possibly other so far not further characterized species.
• plasma-activated media or liquids plasma-activated liquids, PAL; plasma-activated media, PAM
• PAL plasma-activated liquids
• PAM plasma-activated media
• the antiproliferative, antineoplastic and anti-inflammatory effects of plasma-activated fluids have recently been shown by various studies. Plasma-activated fluids also have an efficient antiseptic effect and a positive influence on chronic and acute wounds. Using plasma-activated fluids, wound healing can be significantly improved, and sensitivity to pain can also be reduced. In contrast to the direct use of physical plasma, the use of plasma-activated liquids allows a better metering and controllability of the biologically reactive plasma factors to be applied.
• Plasma-activated medium induces A549 cell injury via spiral apoptotic Cascade involving the mitochondrial-nuclear network, Free Radical Biology and Medicine 79, pp. 28-44; Kajiyama et al. (2017), Future perspective of strategy non-thermal plasma therapy for cancer treatment, J. Clin. Biochem. Nutr. 60, pp. 33-38; Nakamura et al. (2017), Novel intraperitoneal treatment with non-thermal plasma-activated medium inhibits metatstatic potential of ovarian cancer cells, Nature Scientific Reports 7: 6085, pp. 1-14; and Azzariti et al. (2019), Plasma-activated medium triggers cell death and the presentation of immune activating danger Signals in melanoma and pancreatic cancer cells, Nature Scientific Reports 9: 4099, pp. 1-13.
• liquids are activated by treatment with plasma.
• the known devices make use of external plasma generators. They are therefore difficult to handle and are not very suitable for immediate clinical use by a surgeon. For this reason, the devices previously used for generating plasma-activated liquids are used exclusively in experimental systems.
• the current devices also do not allow the plasma-activated liquid to be used directly on the tissue. Rather, this is made at a first point in time and only used on the tissue at a later point in time.
• plasma-activated liquids are produced "in stock", so to speak.
• the biologically reactive plasma factors are "volatile”, i.e. only stable for a limited time.
• the plasma-activated fluids currently produced are therefore often of little therapeutic value, since storage often results in only low concentrations of biologically reactive plasma factors.
• US 2008/0292497 discloses a large-scale device for disinfecting a liquid via plasma application.
• a first gas-containing compartment ment is separated from a second compartment by a phase separator.
• the phase separator can be a porous or non-porous membrane with holes, which is intended to allow gas to pass from the first into the second compartment.
• the gas is pumped into the second compartment by applying positive pressure to the first compartment.
• gas bubbles in the form of macro-bubbles form in the liquid in the second compartment.
• This device is not only unsuitable for medical use because of its large scale. Because of the accumulation of gas bubbles, there is a risk that these will be washed into the blood system and cause embolisms.
• Use in endoscopic interventions, such as hysteroscopy is also out of the question, as the gas bubbles formed make visibility difficult.
• plasma-generated species are transferred from a discharge space into a working medium, which is located in an adjacent space.
• the discharge space and the space containing the heating medium are separated by a membrane which is not further characterized.
• This device is also unsuitable for the prophylaxis and treatment of postoperative adhesions.
• the invention is based on the object of a medical
• a device for generating a plasma-activated liquid with which the disadvantages of the current devices from the prior art can be avoided or at least reduced.
• a medical device is to be provided which can be easily handled by a treating physician and can be produced on an industrial scale.
• it should preferably allow the plasma-activated liquid to be used immediately after it has been generated, without the need for lengthy storage.
• a medical device for generating a plasma-activated liquid with a plasma discharge space and a fluid-carrying space adjoining this to form an interface, the interface being one for biologically reactive plasma factors from the plasma discharge space has semipermeable membrane which is permeable and impermeable to the liquid from the liquid-carrying space.
• the constructive prerequisites for a medical device are created in an advantageous manner, which is easy for the treating doctor to handle and can be produced on a large scale.
• the plasma discharge space is designed to accommodate a medium that is suitable for generating a physical plasma, such as a gas, for example argon, helium, O 2 , N 2 , room air or other suitable gases.
• a gas for example argon, helium, O 2 , N 2 , room air or other suitable gases.
• the liquid-carrying space is designed to accommodate a liquid, such as water, saline, biological buffers, etc.
• the semipermeable membrane which can be implemented, for example, by a conventional dialysis membrane, can be used to create defined, mutually delimited plasma discharge and fluid-carrying spaces. At the same time it is ensured that the biologically reactive plasma factors accumulate in the liquid, which can migrate from the plasma through the semipermeable membrane into the liquid.
• the semipermeable membrane is designed such that the formation of gas bubbles, preferably macro-bubbles, more preferably macroscopically visible macro-bubbles, ie those with a diameter in the centimeter or millimeter range, is prevented in the liquid-carrying space .
• gas bubbles preferably macro-bubbles, more preferably macroscopically visible macro-bubbles, ie those with a diameter in the centimeter or millimeter range
• the person skilled in the art will adjust the pore diameter by suitable choice of the material of the semipermeable membrane so that essentially only the biologically reactive plasma factors are transferred from the plasma discharge space into the liquid-carrying space.
• conventional dialysis membranes or conventional biologically symmetrical dialysis membranes such as cuprophane, hemophane, or cellulose triacetate, as well as other membranes based on the natural polymer cotton cellulose.
• the average pore size dius of conventional dialysis membranes is 1.72 nm, which corresponds to a permeability limit of 1000, preferably 500 Dalton, ie larger molecules cannot penetrate the membrane; see Nowack et al. (2019), Dialysis and Nephrology for Specialists, 3rd Edition, Chapter 7, Structure of Dialysers, pp. 89-103.
• the use of conventional dialysis membranes according to the invention thus prevents (gas) bubbles from forming in the liquid in the liquid-carrying space.
• the semipermeable membrane has an average pore radius of ⁇ 5 nm, preferably of ⁇ 2 nm. This ensures that not only the formation of macro-bubbles in the liquid but also micro-bubbles is physically impossible.
• the plasma discharge space can be realized by a continuous cavity, in particular in the case of a tubular or hose-shaped configuration of the device according to the invention, in which the plasma discharge space forms an outer tube or hose body and the liquid-carrying space forms an inner tube or hose body forms or alternatively in the reverse arrangement, spacers can be provided, which ensure a spacing of the plasma discharge space from the liquid-carrying space.
• the plasma discharge space can be created by or have a gas-permeable material, such as, for example, glass fiber fabric or plastic. This has the advantage that the arrangement of the plasma discharge and liquid-carrying spaces can be implemented in a flexible manner in a layered construction and the provision of spacers is unnecessary.
• the inventor provides an easily manageable and manufacturable device for generating plasma-activated liquids with which inflammatory, chronic inflammatory, neoplastic and oncological diseases can be treated intracorporeally in an advantageous manner.
• the plasma-activated liquid can be used bar can be used after their creation on the tissue, which ensures a high level of effectiveness.
• the device according to the invention is also outstandingly suitable for the prophylaxis and treatment of postoperative, iatrogenic or inflammatory diseases caused adhesions. These represent major challenges for the health system in surgical or endoscopic / laparoscopic interventions. Due to the anti-proliferative, anti-inflammatory and wound healing-enhancing properties of plasma-activated liquids, the use of the device according to the invention is suitable as a routine therapeutic method during the end of the operation to avoid postoperative adhesions.
• the medical device according to the invention enables large-area and uniform treatment of body cavities, such as the abdominal or vaginal cavity, the oral cavity and pharynx, the thorax, gastrointestinal cavity, joint spaces, etc.
• the pressure conditions in the plasma discharge gap can be controlled in a targeted manner by providing or connecting a suitable device.
• a suitable device for example, a low pressure or even a vacuum or “near vacuum” can prevail in the plasma discharge gap. This measure has the advantage that the energy and voltage required for generating the plasma would be significantly reduced and a homogeneous plasma could be generated.
• a positive electrode insulated with a dielectric adjoins the plasma discharge space on a side opposite the interface.
• the structure of the positive electrode can be ring-shaped, lattice-shaped, spindle-shaped, meander-shaped or honeycomb-shaped. These configurations create a uniform distribution of the electrode structure, which ensures a very homogeneous plasma generation in the plasma discharge space. They also allow an advantageous flexibility or adaptability of the shape of the electrode structure.
• the dielectric can be formed from glass, ceramic or plastic, for example silicone.
• the dielectric is formed from a soft plastic such as silicone, it can exhibit flexibility, i.e. flexibility, which is advantageous in use.
• the electrode structure is not insulated with a dielectric towards the plasma discharge space, which enables a discharge, for example in the form of a corona discharge.
• a ground electrode is arranged in the plasma discharge space on and / or in the vicinity of the interface.
• the ground electrode can be integrated into the interface.
• the ground electrode is the counter electrode to the positive electrode, whereby the structural requirements for the generation of plasma by dielectric barrier discharge are created.
• the structure of the ground electrode can correspond to that of the positive electrode.
• the biologically reactive plasma factors can migrate due to Brownian motion by passive diffusion from the plasma through the membrane through into the liquid. This ensures a membrane-friendly migration of the biologically reactive plasma factors.
• the enrichment of the liquid with the reactive plasma factors can be regulated by the volume per time of the flowing liquid or the energy input of the plasma and thus adapted to the clinical conditions.
• the spacing of the positive electrode from the ground electrode is selected in such a way that, on the one hand, heat generation is avoided and, on the other hand, sufficient physical plasma can form between the positive electrode and the ground electrodes. This can be achieved by the above-mentioned spacers and / or by designing the plasma discharge space from a gas-permeable material of sufficient thickness.
• a ground electrode is arranged within the liquid-carrying space.
• the arrangement of the ground electrode "within" the liquid-carrying space means according to the invention that the ground electrode is arranged so that it can come into contact with the liquid at least on one side, preferably on both sides or completely.
• the biologically reactive plasma factors can migrate accelerated from the plasma through the membrane into the liquid not only because of the Brownian motion but rather, driven by charge. This arrangement thus ensures rapid and strong enrichment of the liquid with biologically reactive plasma factors.
• the enrichment of the liquid with the reactive plasma factors can be regulated not only by the volume per time of the flowing liquid but also by the applied voltage and adapted to the clinical conditions.
• the spacing of the positive electrode from the ground electrode is chosen so that, on the one hand, heat generation is avoided and, on the other hand, sufficient physical plasma can form between the positive electrode and the ground electrode.
• this can be achieved by the spacers discussed above and / or by designing the plasma discharge space from a gas-permeable material with sufficient thickness.
• the medical device according to the invention is tubular and / or tubular.
• hose and / or tube shape enables the individual spaces and structures to be delimited from one another in a simple manner and the electrode structures to be electrically insulated.
• a hose and / or tube shape of the device according to the invention simplifies the flexible and pliable design.
• a hose and / or tubular shape of the device according to the invention also simplifies access to body cavities through minimally invasive access and use in body cavities and / or openings, which also often have a hose and / or tubular shape.
• tubular and / or tubular means that the various spaces and structures are arranged in the form of tubes or hoses that are nested in one another. This Aus save approximately form can be particularly well integrated into existing modules, such as endoscopic Vorrichtun conditions, high pressure nebulization and / or spray unit, etc.
• So is in a first hose-shaped and / or tubular embodiment in the innermost part of the device of the liquid-carrying space, which is delimited to the outside by the semipermeable membrane, on which the ground electrode is arranged on the outside, which is outside via spacers from the plasma discharge space is limited. This is limited to the outside by the dielectric and the adjoining positive electrode.
• the positive electrode can in turn have an external insulation on its outside.
• the very outermost layer can be formed by a carrier material which gives the device structure and possibly flexibility.
• the ground electrode which is surrounded by the fluid-carrying space, is located in the innermost part of the device.
• the liquid-carrying space is delimited to the outside by the semipermeable membrane, which in turn is delimited on its outside by the plasma discharge space. This is bounded on its outside by the dielectric and the adjoining positive electrode.
• the positive electrode can in turn have an external insulation on its outside.
• the very outermost layer can be formed by a carrier material which gives the device structure and possibly flexibility.
• the positive electrode is located in the innermost part of the device according to the invention. Around this, the plasma discharge area borders on the outside, on the outside of which in turn the liquid-carrying area is provided.
• the device according to the invention is box-shaped.
• This alternative embodiment can advantageously make use of sandwich construction, the - now horizontal - arrangement and sequence of the rooms and structures essentially corresponding to those that are described for the tubular and / or hose-shaped configurations. This configuration can also be easily integrated into existing modules.
• the medical device has a support structure that surrounds it.
• the carrier represents an additional barrier in order to ensure that the generated plasma can be applied in a targeted manner to the tissue to be treated and that other areas of the body cannot come into contact with the plasma.
• the carrier can be made of metal or plastic, for example.
• the medical device according to the invention has a gas connection via which a carrier gas can be introduced into the plasma discharge space and, if necessary, discharged again.
• the medical device according to the invention has a connection for a high-pressure nebulization and / or spray unit.
• the device according to the invention is integrated into an apparatus which allows the plasma-activated liquid to be applied in a targeted and possibly flat manner.
• the connection of the device according to the invention to a high-pressure nebulization and / or spray unit enables the targeted treatment of tumor tissue.
• Postoperative adhesions can also be reduced or avoided, for example, by misting and / or spraying surgically treated tissues with the plasma-activated liquid. This can take place during or directly after the surgical intervention, so that postoperative treatment can preferably be avoided.
• the medical device has a connector for connection to an endoscopic device.
• This measure has the advantage that the device according to the invention can be integrated into endoscopic operations and into existing endoscopic systems or trocars and allows their use immediately during or after the operative intervention.
• the medical device according to the invention is designed for the intermittent and / or continuous generation of a plasma-activating liquid.
• This embodiment can be implemented, for example, by connecting a pump or a comparable device for conveying the liquid, which optionally conveys it intermittently and / or continuously through the liquid-carrying space.
• the plasma discharge can also be controlled by intermittent and / or continuous application of voltage. This measure allows the setting of a suitable treatment mode depending on the particular application.
• Another object of the invention relates to a system for generating plasma-activated liquids with the medical device according to the invention and with a high voltage source which can be connected to the medical device for applying high voltage to the electrode (s).
• Another object of the invention relates to a method for generating a plasma-activated liquid, which has the following steps:
• the gas can preferably be argon gas, helium, O 2 , N 2 , room air or other suitable gases.
• “Allowing the biologically reactive plasma factors to migrate” generally refers to the movement of the biologically reactive plasma factors through the semipermeable membrane. It includes in particular the passive diffusion of the biologically reactive plasma factors through the semipermeable membrane due to the Brownian movement and the charge-driven movement diffusion of the biologically reactive plasma factors through the semipermeable membrane.
• the medical device according to the invention is provided as the device.
• Another object of the present invention relates to the use of a plasma-activated liquid in the prophylaxis and / or treatment of postoperative adhesions.
• the plasma-activated liquid is preferably one which was produced with the device according to the invention and / or the method according to the invention.
• Fig. 1 shows a first (A) and second (B) embodiment of the device according to the invention in longitudinal section; 2 shows a first embodiment of the device according to the invention (A) in a broken plan view and (B) in cross section;
• FIG. 3 shows a second embodiment of the device according to the invention (A) in a broken plan view and (B) in cross section;
• FIG. 4 shows a third embodiment of the device according to the invention in a broken plan view
• FIG. 5 shows schematically the use of the device according to the invention during a gynecological operation
• PAL effects on mesothelial cells and fibroblasts a) PAL dose-dependent proliferation of human fibroblasts and mesothelial cells. PAL doses of 1: 2 lead to a specific inhibition of fibroblasts, with continued proliferation of mesothelial cells. b) Bright field microscopy of fibroblasts (upper field) and mesothelial cells (lower field) c) Hydroxypro- lin assay (left) and Sircol assay (right) for the quantification of extracellular insoluble collagen and procollagen. The PAL treatment results in a decreased amount of insoluble collagen with an increased amount of soluble procollagen. d) flow cytometry after PI staining.
• a PAL dose of 1: 2 leads to a fibroblast-specific G1 cell cycle arrest.
• a PAL dose of 1: 2 leads to a fibroblast-specific reduction in cell metabolism, which induces various cellular mechanisms, and to an increase in cell metabolism in mesothelial cells.
• FIG. 1A shows an enlarged longitudinal section through one with the general
• Reference numeral 10 provided medical device for generating a plasma-activated fourth liquid.
• the device 10 is suitable for the intracorporeal treatment of inflammatory, chronic inflammatory, neoplastic and oncological diseases as well as for postoperative adhesion prophylaxis.
• the medical device 10 has a plasma discharge space 12 and a fluid-carrying space 14 adjoining this on the underside in the illustration.
• physical plasma 16 in particular low or room temperature plasma, can be generated under normal atmospheric pressure or under low pressure conditions.
• the fluid-carrying space 14 is flowed through intermittently or continuously by a fluid 18, such as, for example, water, a buffer or physiological saline solution.
• the plasma discharge space 12 and the liquid-carrying space 14 adjoining the underside form an interface 20 which has a semipermeable membrane 22.
• the semipermeable membrane 22 is permeable to biologically reactive plasma factors from the plasma 16, which is formed in the plasma discharge space 12, and is impermeable to the liquid 18 from the fluid-carrying space 14.
• Electrodes 26 and 28 can be formed by a single wire or be designed in the form of a grid, spindle, meander, or wafer.
• Plasma discharge space 12 generates a physical plasma 16.
• the biologically reactive plasma factors contained therein can migrate through the semipermeable membrane 22 into the liquid 18 in the liquid-carrying space 14 due to the Brownian movement, which is indicated by the serpentine arrows.
• FIG. 1B shows a second embodiment in which the structures and features that correspond to those from FIG. 1A are represented by the same reference numerals.
• the embodiment shown in FIG. 1B differs from the embodiment shown in FIG. 1A in that the ground electrode 28 no longer rests on the upper side of the semipermeable membrane 22 with orientation towards the plasma discharge space 12, but inside the liquid-carrying space 14 is arranged.
• the biologically reactive plasma factors no longer migrate into the liquid-carrying space 14 due to Brownian motion through the semipermeable membrane 22, but are "shot" into the liquid-carrying space 14, driven by charge.
• FIG. 2 shows the medical device 10 according to the invention according to the first embodiment (corresponding to the arrangement shown in FIG. 1A).
• Partial illustration A shows the device 10 in a broken plan view
• partial illustration B shows a cross section through the device 10. Structures and features corresponding to those from FIGS. 1A and 1B are shown with the same reference numerals.
• the device 10 according to the invention has a high voltage source 30 for applying high voltage to the electrodes 26 and 28, an external insulation 32 that insulates the positive electrode 26 from the outside, and a carrier 34 surrounding this external insulation.
• FIG. 3 shows the medical device 10 according to the invention according to the second embodiment (corresponding to the arrangement shown in FIG. 1B).
• Partial illustration A shows the device 10 in a broken plan view
• partial illustration B shows a cross section through the device 10. Structures and features which correspond to those from FIG. 2 are shown with the same reference numerals.
• FIG. 4 shows the medical device 10 according to the invention in a third embodiment in which the structures and spaces are arranged in a sandwich-like manner in a horizontal layering in a carrier 34 with a box-like design. Structures and features that correspond to those of FIGS. 1, 2 and 3 are shown with the same reference numerals.
• FIG. 5 the use of the device 10 according to the invention is shown schematically during a gynecological operation.
• a pump 36 connected to the device according to the invention for supplying liquid via a hose 38, a high-voltage source or high-voltage generator 30 for applying high voltage to the electrodes via a cable 40, and a gas connection with a gas source 42 and a gas line 44 , via which a carrier gas can be introduced into the plasma discharge space 12 and possibly discharged again.
• Plasma-activated fluid enables specific inhibition of ECM-producing connective tissue cells for the prophylaxis of postoperative adhesions - experiments
• PA postoperative adhesions
• ECM extracellular matrix
• Plasma activated fluid (PAL) could prevent PA by inhibiting the dysregulation and overproliferation of fibrin and ECM-producing connective tissue cells.
• the dose-dependent PAL treatment of primary human mesothelial cells and fibroblasts with the device according to the invention showed a defined and reproducible therapeutic window (referred to here as 1: 2) (FIGS. 1a, b).
• PAL concentration it was possible to significantly inhibit the excessive cellular proliferation of the ECM and fibrin-producing fibroblasts, while the physiological cell proliferation of the mesothelial cells did not change significantly.
• the extracellular amounts of soluble procollagen (less cross-linked) were significantly increased after the PAL treatment, while insoluble (highly cross-linked) collagen decreased significantly.
• the selective antiproliferative effect on primary fibroblasts was associated with a significant G2 cell cycle arrest and a significant decrease in cellular viability.
• the same PAL dosage showed a significant increase in the viability of mesothelial cells.
• the peritoneal PAL treatment by means of the device according to the invention accordingly offers a promising medical application to target the postoperative (over) proliferation of ECM- and fibrin-producing fibroblasts and the synthesis and cross-linking of functional ECM components such as collagen to reduce.

Landscapes

• Engineering & Computer Science (AREA)
• Physics & Mathematics (AREA)
• Plasma & Fusion (AREA)
• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Spectroscopy & Molecular Physics (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Veterinary Medicine (AREA)
• Biomedical Technology (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Surgery (AREA)
• Radiology & Medical Imaging (AREA)
• Otolaryngology (AREA)
• Molecular Biology (AREA)
• Heart & Thoracic Surgery (AREA)
• Fluid Mechanics (AREA)
• Medical Informatics (AREA)
• External Artificial Organs (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Surgical Instruments (AREA)
• Materials For Medical Uses (AREA)
• Medicines Containing Material From Animals Or Micro-Organisms (AREA)
• Medical Preparation Storing Or Oral Administration Devices (AREA)

Applications Claiming Priority (2)

Publications (1)

Family

ID=74672304

Family Applications (1)

Country Status (11)

Families Citing this family (1)

Family Cites Families (6)

• 2020
  • 2020-02-18 DE DE102020104261.2A patent/DE102020104261A1/de active Pending
• 2021
  • 2021-02-17 AU AU2021224972A patent/AU2021224972A1/en active Pending
  • 2021-02-17 EP EP21706883.2A patent/EP4106652A1/de active Pending
  • 2021-02-17 BR BR112022016395A patent/BR112022016395A2/pt unknown
  • 2021-02-17 CN CN202180015000.7A patent/CN115243632A/zh active Pending
  • 2021-02-17 PE PE2022001751A patent/PE20221672A1/es unknown
  • 2021-02-17 MX MX2022010018A patent/MX2022010018A/es unknown
  • 2021-02-17 WO PCT/EP2021/053911 patent/WO2021165334A1/de unknown
  • 2021-02-17 JP JP2022549573A patent/JP7447290B2/ja active Active
• 2022
  • 2022-08-12 CO CONC2022/0011410A patent/CO2022011410A2/es unknown
  • 2022-08-17 US US17/890,222 patent/US20220387811A1/en active Pending

Also Published As

Similar Documents

Legal Events