LT6502B - Sensible plaster - Google Patents

Abstract

The multi-layer multifunctional plaster withaut the need to change during a wound healing period, it can effectively and quickly inform about a wound healing process and accelerate a wound healing process. The plaster comprises an element of adhesion to a skin, antimicrobial layer composed of metal nanoparticles, and a hydrogel membrane layer, an indicator layer, metal ions, and drug accumulation layers. The plaster may also include intelligent tools that ease the transfer of healing enhancers to skin tissues by the aid of electic charge, and measures for effective and quick stoping of wound bleeding.

Description

Field of the Invention

The invention relates to smart bandages, and more particularly multilayer smart patches for monitoring and promoting wound healing.

Description of the Related Art

Wound healing is a complex mechanism involving many processes. The main problem with the healing process is the transition of a physiologically healing wound to a chronic healing wound. This condition requires a great deal of effort to control, and the physician must be familiar with the latest techniques associated with complex molecular mechanisms to return wound healing to normal.

The wound healing process is an active and time-dependent mechanism that involves essentially three steps:

Ignition stage. It starts with the wound and lasts for about five days. During this phase, the blood vessels contract and a blood clot is formed to maintain tissue hemostasis. The blood vessels then dilate, allowing cells and important factors to enter the wound area (white blood cells, antibodies, growth factors, enzymes and nutrients). At this stage, new signs of inflammation develop: erythema, heat, edema, pain and functional disorders. At this stage, innate immune cells (neutrophils and macrophages) react immediately, phagocyting microbes, dying cells and damaged tissues.

The proliferative phase. The first few days of this phase may overlap with the inflammatory phase, then the proliferative phase lasts for about three weeks. At this stage, granulation tissue occurs, fibroblasts begin to release collagen, which acts as an astringent to reduce tissue defect. The deposition of collagen and the extracellular matrix promotes angiogenesis, which results in a better supply of nutrients to the cells, which in turn promotes the formation of granulation tissue. Healthy granulation tissue has a non-uniform texture and is naturally pink in color; if this tissue is dark, it may indicate reduced perfusion, ischemia and / or infection. At the end of this stage, epithelialization is induced, especially on the wet surface of the wound.

Stage of puberty. This stage overlaps with the previous stage, but can last as long as 2 years, depending on the type of wound and the extent of the lesion. Synthesized collagen improves skin tensile strength and contributes to scar formation. At this stage, the inflammatory cells decline to normal levels, their activity also returns to baseline, and the blood vessels slowly regress until they are restored to their original structure and volume.

The course of these stages is different and populations of dominant cells are different. Although neutrophils are the most abundant population of innate immune cells, fibroblasts act as parent cells during the proliferation phase. The inflammatory reaction is the primary response of the tissues to the lesion at which granulocytes, mainly neutrophils, monocytha macrophages, become active. If this activity is normal in the first chronic phase, then the continuous presence of neutrophils is associated with delayed wound healing and a chronic condition. The proliferative phase (epithelialization, angiogenesis, and matrix formation) begins when neutrophils are removed by activated macrophages. Thus, in the proliferative phase of a normally healing wound, fibroblasts are a major cell type. Molecules secreted by these types of cells are detected using specific biomarkers corresponding to individual healing stages, which can be used to measure the progression of wound healing.

One of the measures to sterilize a wound during its healing and thus to prevent inflammatory complications is silver-containing sterilizing agents. Silver nanoparticles, contained in cotton fabrics, proteins or polyurethane, kill Gram-negative and Gram-positive bacteria and can be used in wound healing. (F. Paladini, R. R. Picca, M. C. Sportelli, N. Cioffi, A. Sannino, M. Pollini, Surface Chemical and Biological Characterization of Flax Fabrics Modified with Silver Nanoparticles for Biomedical Applications. Materials Science & Engineering C (2015); Anh, Xing, Le, Sugavvara-Narutaki & Fong, Elastin-based silver-binding proteins with antibacterial capabilities, Nanomedicine (2013) 8 (4), 567-575; Jia Chen, Ying Peng, Zhen Zheng, Peiyu Sun, Xinling Wang, Silver -Releasing and Antibacterial Activities of Polyphenol-Based Polyurethanes. Appl. Polym. Sci. 2014, 131, 41349). Currently, the most common treatment techniques are the formation of a thin silver coating, the use of colloidal silver in solutions and other materials, and the orderly size of nanostructures in a solid matrix. There is a great deal of work that demonstrates the antibacterial activity of silver, but one of the main problems that prevents the widespread use of this material is the insecure diffusion of silver ions into aqueous media that can undergo processes such as bacterial killing (Korner E, Aguirre MH, Fortunato G, Ritter A, Ruhe J, Hegemann D. Formation and Distribution of Silver Nanoparticles in a Functional Plasma Polymer Matrix and Related AgR Release Properties (Plasma Process. Polym. 2010, 1, 619-625).

In experiments with silver-containing dressings, it was found that such a dressing does not have the strong antimicrobial effect as declared, because the bacteria accumulate in the non-silver-colored gauze gaps and do not form transparent areas in the petri dish using the standard disk method (Robert R. Calvo, Which Bandage Inhibits Bacterial Growth Most Effectively ?, California built Science fair 2006 project summary, Project number J1405). Manufacturers of similar products declare strong antibacterial activity, but the problem of silver ion diffusion remains unresolved, the patch does not work in dry environment. Also, scientists (University of Wisconsin-Madison. New Approach To Wound Healing May Be Easy On Skin, Be Hard On Bacteria. ScienceDaily. ScienceDaily, 21 August 2009) claim that such products with higher levels of silver damage fibroblasts, thus killing bacteria. ionic silver derived from, for example, nanoparticles that release small amounts of silver ions into the environment must be used.

Toxicity is also known to be one of the most important problems in products using nanotechnologies. Scientists say that 20nm nanoparticles directly (1-50 pg / ml) affect neurons by destroying their cytoskeleton, promoting decay and death. Other authors (Ouelemes PV, Araruna FB, de Faria BEF, Kuckelhaus SAS, da Silva DA, Mendonêa RZ, Eiras C, Soares MJS and Leite JRS A. Development and Antibacterial Activity of Cashevv Gum-Based Silver Nanoparticles. Int. J. Mol. Sci. 2013, 14, 4969-4981) states that from 3.37 to 13.5 pg Ag / ml no apparent toxicity was observed. The main criteria determining toxicity are the particle size and amount entering the body. Larger particles are considered less toxic.

Silver ion-saturated hydrogel dressings are also known (Bovvler PG, Cochrane CA. Progression to Healing: Wound Infection and the Role of Advanced Silver-Containing Hydrofiber® Dressing. Ostomy Wound Manage. 2003: 49 (8) (suppl): S 2 -S5; Jones S, Bovvler PG, Walker M. Antimicrobial activity of silver-containing dressings is influenced by dressing conformation with a surface surface (Wounds 2005; 17 (9): 263-270), which contain silver, kills bacteria, and helps wound heal faster. However, the functionality and effectiveness in wound healing is reduced due to the composition, arrangement and number of layers.

Although patches and bandages are used to maintain the antibacterial effect, they are coated with a thin silver film or impregnated with silver components, but such bandages can be harmful due to the higher concentration of silver, and silver salts also stain the tissues.

There are also antibiotic dressings on the market, such as polymyxin B sulfate and bacitracin zinc. The European Commission and other health authorities encourage moderate use of antibiotics, and only in the case of serious infections. The constant use of antibiotics promotes the emergence of antibiotic-resistant microorganisms.

Another very important aspect of multilayer healing patches, which allow rapid and uncomplicated wound healing, are indicators of the wound healing status. Many scientists are working to replace conventional bandages with multifunctional ones. Scientists are intensively developing systems that can detect the products and effects of bacterial activity, providing real-time patient information to prevent complications. One way to provide information about a wound's healing status is by changing the color of the bandage due to chemical indicators or fluorescent dyes. This form of dressing could react on its own by providing additional amounts of antibacterial agents (eg sodium azide) if it detects toxins and also discolor upon contact with bacteria. One major unresolved problem is the stability of such a layer (Zhou JI, Loftus AL, Mulley G, Jenkins AT. A thin film detection / response system for pathogenic bacteria. J Am Chem Soc 2010, 12; 132 (18): 6566-70). .

Although transparent hydrogels have been developed for permanent wound monitoring, which allow visual wound assessment and maintain consistent moisture on the wound surface, their functionality is very limited.

Electronic indicators used in conjunction with bandages such as patches are complex to manufacture and expensive.

In patent application no. US 11 / 936,812 discloses a wound dressing comprising materials such as a dye or a biocide enclosed within or behind a gelatin barrier. When applied to a wound, the metalloproteinase naturally present in the wound permeates the dressing and dissolves the gelatin, releasing substances inside or outside it. Such materials can be used as indicators of wound healing status or to promote wound healing. However, this method of placement of beneficial substances is not effective. There is no system in place to properly control and place all gelatin in a treatment device. Gelatin melts (melts) due to thermal effects.

The closest analogue is found in International Patent Application Ser. PCT / CA1998 / 000102. It discloses multilayer antimicrobial agents with a visible interfering color that produces a noticeable antimicrobial effect. The means include a partially reflective substrate layer, a partially permeable, top layer, balanced to form an interfering color. The top layer is formed of an antibacterial metal with a disordered atomic structure. Dissolution or alteration of the composition of the top layer due to contact with a particular alcohol or electrolyte causes a change in the optical path length, thereby producing a change in the interference color of the instrument. A multi-layer, laminated bandage is also revealed. The dressing comprises a first and a second layer, and preferably a third layer. The first and third layers are formed of perforated, non-adhesive material and most preferably have an antimicrobial coating as above. The second layer is sandwiched between the first and third layers and is formed from an absorbent material. At least one of the layers is formed of a plastic material. The layers are laminated together using ultrasonic welds at intermittent intervals on the bandage. The main disadvantages of the disclosed dressing are the inefficiently laid layers, their structure, composition and number, which prevents rapid controlled healing.

Also, this system does not provide the ability to accommodate a wider range of indicators and a smart system that controls the operation of the bandage against changed parameters. In application no. PCT / CA1998 / 000102 does not specify how additional drug agents can be added, how they are stabilized and, if necessary, dispersed throughout the surface. The bandage mentioned uses antibacterial metal instead of nanoparticles, which results in more expensive metals being used to make the bandage. Nanoparticles, by virtue of their optimum weight-to-surface ratio, can release more silver ions compared to the metallic form of antibacterial metal.

The invention allows for more effective continuous monitoring of the wound by analyzing the pH of the exudate, inflammatory mediators and proteases, toxins, antibodies without removing the patch.

It also ensures proper wound moisture, safe non-stick application on the wound, so the wound's soft tissue is not injured when removing the bandage. The patch is safer to use than its counterparts due to the structure, constituent materials and interlayer interactions of each layer.

Antibacterial agents (nanoparticles) are effectively trapped in their layers, do not enter the healing tissues, but ensure effective delivery of therapeutic agents (metal ions) to the treatment area.

The invention addresses one of the most pressing issues in the healthcare industry, treating diseases such as methicillin-resistant Staphyloccocus aureus, which often lead to complications. The invention would allow for a more effective and faster prevention of infection or healing of a wound infected with microorganisms. Advantages of the invention would allow to detect changes in wound healing and to take timely measures to eliminate wound healing complications.

Brief Description of the Invention

The described multilayer multifunctional patch can be unchanged throughout the wound healing period, can effectively and quickly inform the wound healing process and accelerate the wound healing process. The patch includes a skin adhesive, an antimicrobial layer consisting of a metal nanoparticle-saturated layer, and a hydrogel membrane layer, an indicator layer, metal ion and drug storage layers. The patch can also include smart devices that electrically facilitate the introduction of healing agents into skin tissues and measures to effectively and quickly stop wound bleeding.

Brief description of the drawings

Other features and advantages of the invention are described in the detailed description of the invention with reference to the following drawings:

Fig. the order of the layers of the patch structure is shown in Fig. a detailed view of the structure of the layers is given in Fig. the order of the layers of the patch structure with the parts of the callback system is shown in fig. is a cross-sectional view of a patch with an increased pressure on the application surface

Before referring to the detailed description of the invention, with reference to the drawings in which the invention is exemplified, it is to be understood that identical elements are designated by the same numerals throughout the drawings.

Detailed Description of the Invention

It should be understood that many specific details are set forth to provide a full and comprehensible description of an exemplary embodiment of the invention. However, it will be apparent to one skilled in the art that the level of detail of exemplary embodiments of the invention does not limit the scope of the invention, which may be practiced without such specific guidance. The well-known techniques, procedures, and ingredients have not been described in detail to avoid the confusion of exemplifying embodiments of the invention. Furthermore, this description is not to be construed as limiting the embodiments provided.

The patch may be comprised of layers comprising an outer layer (1, 1a), a stabilized layer (2) containing antimicrobial agents, at least one hydrogel membrane layer (3), an indicator layer (4, 7), a protective layer (5, 5a), and a non-adherent layer (6).

The outer layer of the bandage (1, 1a) may be made of polymeric film or natural fabric, which has holes for the removal of excess moisture. The patch is attached to the skin with a film.

Metal nanoparticles having antibacterial properties, such as silver nanoparticles, are stabilized in layer (2, 2a), and are donors of silver ions, which remain in their stabilizing layer (2, 2a), and the ions migrate to other layers.

The hydrogel membrane layer (3, 3a) accumulates and transmits silver ions to other layers and also traps the metal nanoparticles to the metal nanoparticle stabilization layer (2, 2a).

The indicator layer (4, 4a) consists of a hydrogel layer, which has vertical channels (4a.4) which are filled with a very large amount of water in the gel, so that the diffusion of substances occurs faster than through the hygrogel and is thus called rapid diffusion channels. An indicator that changes color is placed between the rapid diffusion channels (4a.3) for faster analysis of tissue fluids and skipping silver ions.

The function of the protective layer (5, 5a) is to accumulate as much silver ions as possible, to trap the nanoparticles, and to retain healing agents. Underneath it can also be fitted with a grid for additional bandage functions. The holes (5a.2) contain a gel with or without additional substances. The gel dissolves quickly into the wound, releasing all of its silver ions and healing accelerators, which, when removed, are filled with tissue fluids that can diffuse through the channels to the indicator system more quickly. The silver ions in this layer are released more slowly from the hydrogel layer (5a.1), which provides the required concentration of silver ions throughout the healing process.

The non-adherent layer (6, 6a) partially closes the cavities of the protective layer (5, 5a) and / or prevents the entire patch from adhering to the wound tissues, i.e., when the patch is adhered, separates and stays with the wound, subsequently excreted with scabs or resorbed. The patch can also be supplied without this layer.

The metal mesh (7) performs the function of transmitting and accumulating electrical charges along the layers to which they are embedded. The grid can be divided into smaller grid units by making partitions of insulating material, thus forming different electric poles (positive and negative). Alternatively, two continuous meshes are used between different dressing layers, for example, the stabilizing layer (2, 2a) and the protective layer (5, 5a) of nanoparticles with antibacterial properties.

The outer layer of the bandage (1, 1a) may be made of a polymeric film or natural fabric with holes for the removal of excess moisture. With this layer, the patch is attached to the skin. The outer layer of the patch (1, 1a) moves to the adhesive part for attaching the patch to the skin. The polymeric film can be made of silicone, PVC, and other composite materials. The outer layer (1, 1a) may also be formed as a multicomponent structure comprising porous fabric, such as cotton, which is integrated with the hydrogel at the bandage attachment site (i.e., the fabric adheres to the entire bandage upon synthesizing the unfolded hydrogel). , while the non-contacting part below the outer layer is covered with adhesive material to human skin. The hydrogel may be applied to substantially the entire outer layer (1, 1a), in the case where the fabric used acts as a moisture retention system (i.e., the adhesive film is replaced by a hydrogel). Such a layer may comprise a collagen (or analogue thereof) hydrogel with 20% microfiber cellulose and form a coating up to 1 mm thick on the inner side of the layer (1). The pairs (1a.1) of the layer (1) (holes for evaporation of excess moisture) are arranged in passes or in parallel (or possible decorative patterns) and have a diameter of 0.1 to 3 mm.

The disinfectant layer (2, 2a) of substances having antibacterial properties is enriched with metal nanoparticles (2a, 1) having antibacterial properties. Such nanoparticles may be silver nanoparticles (2a.1), silver nanoparticles together with iron nanoparticles, or silver-coated iron nanoparticles, a mixture of palladium and silver nanoparticles having a diameter of about 20 nm to about 80 nm. Their purpose is to release metal ions (2a.2). The mixture allows to reduce the amount of silver used. The layer of antimicrobial-like materials (2, 2a) also comprises a nanoparticle stabilizer which prevents the movement of the nanoparticles themselves, but only their ions. This layer provides not only sterility of the entire patch but also effective sterility of the contact surface of the patch due to moisture-distributed migration and migration of the metal ions released from the nanoparticles to other layers (3.3a, 4.4a, 5.5a, 6.6a) concentration gradient to lower, ie, skin tissues. The nanoparticulate stabilizer comprises cellulose and cotton fibers, preferably up to 10 mm in length, bonded to a solution of calogen or starch (up to 10% of the total dry weight). The prepared mass is deposited in a thin layer and the moisture removed. Thereafter, nanoparticles from the solution are deposited in the layer, or the synthesis of the particles takes place inside the layer by reduction of metal salts (silver, silver and iron, palladium and silver), which are / soaked throughout the layer. The reduction is due to UV radiation (200-400 nm). The nanoparticles are rolled at a pressure of 5 to 50 kg / cm ² . Rolling is carried out with a relief roll (roller) with a groove and pit depth of not more than 0.5 mm. The thickness of the produced layer (2, 2a) is <0.1 mm.

In the disinfectant layer (2, 2a) of such a structure, the ions of substantially uniformly distributed nanoparticles are released only in the presence of moisture, whereas the relief layer (2,

2a) The structure provides a larger surface area and faster ion migration. It also limits the release of nanoparticles into the environment beyond their stabilization layer, thus minimizing nanotoxicity.

The concentration of silver in the entire matrix of the disinfectant layer (2, 2a) may be from 3 at% to 20 at%, preferably from 3 to 15 atomic percent (at%).

The hydrogel membrane layer (3, 3a) accumulates and transmits silver ions to other layers, trapping the nanoparticles due to their viscosity to prevent them from falling into the layers below. This layer further stabilizes the thin structure of the layer of antibacterial substances (2, 2a) and distributes the migration of silver ions to other layers of the patch (4,4a, 5,5a, 6,6a). This layer (3, 3a) may be composed of collagen hydrogel or an analogue thereof. The thickness of this layer (3, 3a) is not more than 1 mm. The hydrogel forming the hydrogel membrane layer (3, 3a) fills in all relief crevices of the layer (2, 2a) having antibacterial properties. The cracks should be filled with a hydrogel due to the greater contact areas of the layer surfaces and the better migration of metal ions from the layer of antibacterial agents (2, 2a) to the layer of the hydrogel membrane (3, 3a). Additionally, the hydrogel membrane layer (3, 3a), having a high moisture content compared to the layer with antibacterial properties (2, 2a), initiates rapid migration of silver ions to the aqueous medium, i.e. migration to the hydrogel membrane layer (3, 3a). ) due to its higher water content and low metal ion concentration.

The indicator function layer (4, 4a-4e) is used to identify the occurrence of wound healing pathologies. An example of such a layer (4, 4a-4e) may be a hydrogel layer having vertical rapid diffusion channels (4a.4) filled with a gel with very high water content so that the material diffuses faster than through a portion of the hygrogel layer without such a layer. channels. The material that can be used as an indicator of certain attributes that change color, for example, is placed in the areas (4a.2) between the rapid diffusion channels (4a.4). In this way, the material effectively reacts rapidly with the liquid that reaches it, which is not a constituent of the patch and effectively passes silver ions due to different concentration gradients.

The indicator function layer (4, 4a-4e) may be formed from cellulose (microcrystalline and microfibre), cellulose cotton composite, or hydrogel-stabilized microcrystalline cellulose. Layer J is the insertion of the plates (4a.2) and the outer (upper) part is enclosed with an indicator cover (4a.1) which may be a liquid impermeable but transparent polymer. The coverings (4a. 1) on the plate are interconnected to form a mesh structure in which the joints are channels (4b. 1) having a thickness of up to 2 mm and a diameter of the horizontal channel (4b. 1) at the joint. The web of cover-plates (4c) is integrated into the composite hydrogel layer (4a) at the top.

Material that may be used as an indicator of certain endpoints may include, but is not limited to:

A chemical indicator such as bromothymol blue or other indicator with similar properties to detect changes in pH on the wound surface. Due to the smaller amount of water in the patch compared to the wound, the patch absorbs tissue fluids gradually, so pH measurements are possible behind the protective layer (5, 5a), as the indicator is less likely to diffuse to wound tissues but also detect changes. An indicator mechanism that changes color in the presence of infection and may work due to pH changes from 6 to 7-7.5 (pH of healthy tissues is about 5.5-6), altered electrical conductivity, inflammatory mediators and proteases, bacterial toxins, antibodies. The chemical indicator is contained in an indicator plate (4a.2) consisting of microcrystalline and microfiber cellulose, 60% and 40% respectively, the structure of which is stabilized by the use of calogen. The plate (4a.2) contains a 10% solution of bromothymol blue by soaking microcrystalline cellulose. Other indicators may be integrated into the indicator plate of similar structure. The indicator has a yellowish tint when the pH changes to neutral - the indicator changes color to blue. The diameter of the indicator plate (4a.2 (4c)) is 3 to 10 mm. The spaces between the elements (4a. 1,4a.2 or (4c)) are at least half the plate diameter. The elements (4a.2) are arranged in parallel, advanced, either by forming a circular structure (ring) from the plates (4c) or by using only one element (4c) per patch. The connections between the elements (4c) are formed as channels (4b. 1) having a channel diameter of up to 1mm and a diameter of the connection element (4b.1) up to 2mm.

An indicator measuring the electrical conductivity of wound fluids. This indicator is based on the measurement of variations in the electrical conductivity (resistance) of the indicator system (4d). When the resistance changes, the indicator gives a signal (color).

Indicator with chemicals that react to changes in pH and deliver electrons to the electrodes in the analyzer cell (4d) (4d 1) (feedback system indicator). The resulting reaction products change color due to the presence of a chemical indicator additive, or the resulting reaction product is naturally different in color from the original. Layer for indication functions - with feedback (4d-4e). The feedback system generates a signal of changes in the wound environment and the exudate released, and generates a weak electromotive force due to a chemical reaction in the cell (4e) transmitted to the layers of the electrical grid (7). In this way, the release of healing enhancers and their movement toward the affected tissues, as well as the movement of metal ions, are promoted. Such a layer consists of a composite hydrogel composite layer of cellulose (microcrystalline and microfibre), cellulose cotton composite or hydrogel-stabilized microcrystalline cellulose with vertical channels of 0.5 to 3 mm in diameter, arranged in a passage or parallel manner. The distance between them is arranged according to the indicator elements and opens beside them. The arrangement of the channels (4a.4) is adjacent to the cells of the analyzer (4d.2) and not under the cells (4e).

The callback elements may be formed in the indicator layer (4d.1, 4d.2, 4d.3) (Fig. 2). Such a layer consists of hydrogel wells (4d.2) (analyzer cells), water-insoluble polymer cross-linked network elements (4d.3) and rings (4d.2) at the intersections of electrodes (4d.1). Inside the ring (4d.2) are placed elements for analysis and chemical processes and reactions. There is also a duct system (4d.3) that allows fluid to circulate from the wound to the dressing layers due to diffusion.

Alternatively, the polymer is formed into a complete structure with electrodes (4d.1), channels (4d.3), and an analyzer cell (4d.2) that is embedded in the hydrogel. Such a layer becomes active, i.e., a chemical reaction occurs between the deposited active component, which begins to generate electrical charges due to a chemical reaction with the tissue fluids upon changing the pH of the tissue fluids. The electrodes (4d. 1) are connected to the metal mesh (7) thus accelerating the transfer of ions and materials through this layer. The analyzer cell (4d.2) shall have a diameter of 4 to 12 mm and a depth of not more than 2 mm.

The indicator feedback system comprising the analyzer cell (4d) and the metal mesh (7) is integral to the indicator function layer (4). The purpose of the metal mesh (7) is to carry out "electrolysis" between the layers of the patch (26, 2-5, 3-5,3-6, 4-6), thereby promoting ion migration or tissue stimulation. The patch design incorporates at least one such metal mesh (7). In one lattice, a single metal structure, or lattice (7), is separated by polymeric inserts, allowing the formation of positive and negative poles (cathode and anode) in one lattice (7). These structural members (7a, 7b) can be used together or in one of the grid variants (with or without polymer inserts).

The grids (7) are connected to the indicator layer (4, 4a-4e) to form a feedback system via the connector (7.1). The mesh (s) (7) can be connected to a source of electrical impulses to promote healing and stimulate skin muscle.

Metal ion deposition layer.

The metal ion and drug accumulation layers include a protective layer (5, 5a) and a non-adherent layer (6, 6a). The protective layer consists of hydrogel and microfibre cellulose, 80 and 20% of the total layer composition, respectively. Its function is to accumulate silver ions, to trap nanoparticles, and to retain healing agents. Using such a layer, the concentration gradient causes the metal ions to migrate from other layers, and also emits nanoparticles from the disinfectant layer (2) through the hydrogel membrane (3) and indicator (4) layers, so the system always maintains high ion concentration . The layer thickness (h) is not more than 2 mm, and usually does not exceed 1 mm. Underneath it can also be fitted with a thin metal mesh (7) for additional bandage features - smart technology. The protective layer comprises cavities (5a.2) which are rapid diffusion channels of 2 mm to 6 mm in diameter, filled with or without gel and additional healing agents. The cavities (5a.2) shall cover at least 70% of the total area of the layer. The cavities can be of any shape, for example round, rhombic, square, pentagonal or other, and arranged to form a neat structure. The soluble gel filler leaving the cavities (5a.2) quickly releases the accumulated silver ions and healing agents into the wound. As the gel leaves the cavity, its location is filled by tissue fluids which can diffuse more rapidly through the channels (5a.2, 4a.4,) to the indicator layer (4, 4a-4e). The silver ions in this layer (5, 5a) are released more slowly from the hydrogel layer (5a.1) into the cavities due to the reduced concentration of ions in them, which ensures the required concentration of silver ions in the cavity (5a.2) and wound.

The diameter of the holes (5a.2) of the protective layer (5, 5a) cannot coincide with the holes (6a.2) of the non-adhering layer (6a.2), the holes of the protective layer open to each other with different diameters, ie if the holes of one layer are the larger, the other must be smaller and vice versa. When the patch has a layer of healing agents (biocompatible materials, collagen with hyaluronic acid, analgesic, anticoagulant chemicals) along with this layer, the holes (5a.2) have a diameter of 3 to 6 mm and the layout should maximize fill and the holes in the non-adherent layer must be between 1 and 3 mm in diameter. Such a combination partially closes 5 cavities of the layer.

The non-adherent layer (6, 6a) is composed of hydrogel and cellulose, partially closing the cavities (5a.2) of the protective layer (5, 5a) and / or preventing the patch from adhering to the wound tissue. This layer (6, 6a) splits and remains at the wound when its adhesion to the adjacent layer (5, 5a) is less than the force of removal of the patch from the applied surface, where the adhesive force between this layer and its supporting layer is greater , than the force exerted on the surface of the removable patch without hardened dried healing structures, but less than the force exerted on the surface of the removable patch with hardened dried healing structures (scab).

The purpose of the non-adherent layer (6, 6a) is to prevent the wound tissues from drying on the patch and to form scabs, the removal of which causes pain and damages the wound tissues. The thickness of this layer may not exceed 0.5 mm, and the arrangement and shapes of the holes therein are analogous to the shapes and arrangement of the holes of the protective layer (5, 5a). However, the diameter of the holes in this layer (6, 6a) may be several times smaller than the diameter of the protective layer (5, 5a) when healing agents are stored in the protective layer. This layer, together with the protective layer (5, 5a), performs the function of accumulating silver ions. This layer can dissolve and fully open the protective layer (5, 5a) with healing agents. In this way, the gel of the non-adherent layer, due to the higher temperature with the therapeutic agents and Ag ions, can enter the wound tissues, spreading high concentrations of silver ions, destroying large quantities of pathogenic microorganisms in a short time.

The following are specific examples which are intended to illustrate the arrangement of the elements of the invention but should not be construed as being the only possible embodiments of the invention.

According to one embodiment of the invention, the adhesive film layer (1, 1a), the nanoparticulate layer (2, 2a), the hydrogel membrane (3, 3a), the indicator layer (4, 4a, 4b, 4c, 4d, 4e), the protective layer (5, 5a-5e) with or without drug substances, non-adherent layer (6, 6a).

According to a second embodiment of the invention, the adhesive film layer (1, 1a), the nanoparticulate layer (2, 2a), the hydrogel membrane (3, 3a), the indicator layer (4, 4a, 4b, 4c, 4d, 4e), the protective layer (5, 5a-5e) with or without drug substances, metal mesh (7), non-adherent layer (6, 6a).

The patches may be of predetermined dimensions ready for use, or may consist essentially of large area bandages which may be trimmed to individual parameters. The patch can be cut in all directions, with holes (5a.2) up to 3 mm in diameter. If the holes are larger in diameter, trimming can be done without affecting the holes in the cut patch. In such a modification, the holes in the patches are aligned parallel to each other.

The invention according to a third embodiment comprises a patch comprising an adhesive film as an outer layer (1, 1a), a nanoparticulate layer (2, 2a), a hydrogel membrane layer (3, 3a), a protective layer (5, 5a) with or without drug substances. their non-adherent layer (6, 6a), the silicone backing - the capsule (8.2). The capsule (8.2) consists of a compressed gas-filled element (8.3) with a special valve (8.4) and a gas pressure distributor (8.5) that allows the lower part (8.6) of the silicone capsule to be inflated and pressed firmly against the patch. wounds, aids in expanding and distributing pressure (8.7), completely occluding the bleeding cavity. The capsule is provided with a suitable clamping device (8.9), such as a rigid polymer strap, to which the capsule (8.2) is fixed by a sliding joint allowing the capsule (8.2) with the patch (8.1) to slide to the desired position. After tightening the strap (8.9) and activating the capsule (8.2), the air pressure presses the patch onto the wound tissues and / or presses it on. The gas actuator (8.4) is made of plastic and is molded into a gas capsule, allowing the gas to be discharged into the porous silicone cavity by breaking the plastic plate which also functions as a gas pressure distributor (8.5) (gas actuator) (8.4). 8.7), which is directly connected to the gas capsule (8.2) (located inside it), where the pressure moves in only one direction (indicated by arrows (8.8) in the drawing. The capsule (8.2) is protected against accidental damage by a plastic cap which is removable immediately The patch of this design is mounted on the inner part of the strap (8.9) where the strap is applied, and the capsule (8.2) is activated through a box in the strap (8.9) .This embodiment contains iron and silver nanoparticles which act to form sterile wound environment (due to the effects of silver) and accelerates and facilitates wound tissue adhesion and small blood vessel closure as (due to the effects of iron) The dressing modification with an electronic healing enhancement modification will also be available in this composition.

The invention according to a fourth embodiment comprises a silicone or polymer film as an outer layer (1, 1a), a metal mesh (7), a nanoparticulate layer (2, 2a), a hydrogel membrane (3, 3a), a protective layer (5, 5a), a non-adherent layer (6, 6a). The rare-mesh metal mesh (7) is mounted on the inner or outer side of the layer (6, 6a), which interacts directly with the tissue. The denser mesh structure is mounted either upstream or behind the nanoparticle-enriched layer (2, 2a), depending on which functions it exhibits more (antimicrobial or material transfer). Also, weak electrical current will shrink the smooth muscle fibers of the skin, which will promote blood flow and accelerate deepening to the non-adherent layer (6, 6a).

The invention according to a fifth embodiment comprises an outer layer (1, 1a) which may be a silicone perforated film having a thickness ranging from 1 to 4 mm, a hole arrangement and a diameter as polymeric films; a nanoparticle-enriched layer (2, 2a); a hydrogel membrane (3, 3a); a protective layer (5, 5a); a non-adherent layer (6, 6a). The bandage elements (2-6) are attached to the silicone film (1) with pores and holes for fiber optic filaments. Due to the semi-transparent structure of the bandage, laser light will reach the tissues and enhance the healing effect.

While many features and advantages have been enumerated in the description of the invention, together with the structural details and features of the invention, the description is exemplary of the invention. Changes may be made to the details, in particular the shape, size and layout of the materials, without departing from the principles of the invention, in accordance with the most widely understood meanings of the terms used in the claims. Lays out a bandage structure that can be modified by removing or adding layers or additional systems.

Claims (15)

1. A multilayer patch comprising an antimicrobial layer, an indicator layer and an adhesive layer, characterized in that: - the outer layer (1, 1a) of the patch is made of porous material; - the antibacterial layer (2, 2a) is a relief stabilizing layer of the nanoparticle having antibacterial activity; - additionally has an accumulation and transfer layer of ions separated from the nanoparticles having antibacterial action (3, 3a); - the indicator layer (4, 4a) is a channeled hydrogel layer with a chemical indicator; - additionally having a porous protective layer (5, 5a); wherein the layers of the multifunctional patch are arranged in the following sequence: outer layer (1, 1a), antibacterial layer (2, 2a), nanoparticle acquisition and transfer layer (3, 3a), indicator layer (4, 4a), protective layer (5, 5a) ). The multilayer patch of claim 1, wherein the outer layer (1, 1a) is a multicomponent derivative. The multilayer patch according to claim 1 or 2, wherein at least part of the outer layer (1, 1a) is coated with a hydrogel. The multilayer patch according to any one of claims 1 to 3, wherein the nanoparticles are selected from the group consisting of a mixture of silver nanoparticles, silver nanoparticles and iron nanoparticles, a mixture of silver-coated iron nanoparticles, palladium and silver nanoparticles. The multilayer patch according to any one of claims 1 to 4, wherein the ions accumulation and transfer layer (3, 3a) of the additional antibacterial action is a hydrogel membrane layer. The multilayer patch according to any one of claims 1 to 5, wherein the indicator layer (4) comprises an indicator (4d, 4e) for measuring the electrical conductivity of wound fluids. The multilayer patch according to any one of claims 1 to 5, wherein the indicator layer (4, 4b, 4c) comprises chemical indicators for detecting a change in pH. The multilayer patch according to any one of the preceding claims, wherein the indicator layer (4, 4d, 4e) comprises a feedback electrical system (7). The multilayer patch according to any one of the preceding claims, wherein the protective layer (5, 5a) contains dispersed metal ions and drug substances. The multilayer patch according to any one of the preceding claims, wherein a non-adherent release layer (6, 6a) is formed beneath the protective layer (5, 5a). The multilayer patch according to any one of the preceding claims, characterized in that the multilayer patch is a cut patch. A multilayer patch according to claim 1, further comprising a pressurizing means (8) and a silicone capsule (8.2) under the bandage. The multilayer patch according to claim 1, wherein the outer layer (1, 1a) is a silicone perforated film and further comprises optical fiber filaments. The multilayer patch of any preceding claim, wherein the bandage contact surface area in contact with the bandage application surface is about 1030% of the bandage contact surface. 15. A method of transporting the components of antibacterial agents through a multilayer bandage, characterized in that the components of the antibacterial agents are transported from the relief antibacterial layer (2, 2a) through the ion-collecting and transporting layer (3, 3a) of nanoparticles, a hydrogel layer with a chemical indicator (4, 4a-4e), a porous protective layer (5, 5a).