WO2018002817A1 - Timbre intelligent. - Google Patents

Timbre intelligent. Download PDF

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Publication number
WO2018002817A1
WO2018002817A1 PCT/IB2017/053826 IB2017053826W WO2018002817A1 WO 2018002817 A1 WO2018002817 A1 WO 2018002817A1 IB 2017053826 W IB2017053826 W IB 2017053826W WO 2018002817 A1 WO2018002817 A1 WO 2018002817A1
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WO
WIPO (PCT)
Prior art keywords
layer
indicator
patch according
multilayer patch
anyone
Prior art date
Application number
PCT/IB2017/053826
Other languages
English (en)
Inventor
Tadas JUKNIUS
Original Assignee
Kaunas University Of Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kaunas University Of Technology filed Critical Kaunas University Of Technology
Publication of WO2018002817A1 publication Critical patent/WO2018002817A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/00051—Accessories for dressings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/00051—Accessories for dressings
    • A61F13/00055—Saturation indicators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/00051—Accessories for dressings
    • A61F13/00063—Accessories for dressings comprising medicaments or additives, e.g. odor control, PH control, debriding, antimicrobic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/02—Adhesive bandages or dressings
    • A61F13/0203—Adhesive bandages or dressings with fluid retention members
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/26—Iron; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/38—Silver; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches

Definitions

  • This invention relates to smart bandages and, more particularly, multilayer smart patches for monitoring and promotion of wound healing.
  • Wound healing is a complex mechanism involving many processes.
  • the main problem related to the healing process is a transition of a physiologically healing wound to a chronic non-healing wound condition. This condition requires a lot of efforts to control, and, therefore, the doctor must be familiar with the latest measures associated with the complex molecular mechanisms to bring the wound healing back to normal condition.
  • the wound healing process is an active and time-dependent mechanism, substantially comprising three stages:
  • inflammation stage It begins with occurrence of the wound and extends for approximately five days. During this stage the blood vessels shrink and form a clot in order to maintain tissue hemostasis. Afterwards, the blood vessels expand allowing the ceils and critical factors to enter the wound area (white blood cells, antibodies, growth factors, enzymes and nutrients). In this stage, new signs of inflammation apear, including erythema, heat, edema, pain and functional disorders. In this stage the innate immune cells (neutrophils and macrophages) react immediately by engulfing and ingesting microbes, dying cells and damaged tissues. Proliferative stage. Several initial days of this stage may overlap with the inflammatory stage, later on the proliferative stage continues for about three weeks.
  • the granulation tissue appears and fibroblasts begin to excrete collagen, which works contractiveiy to reduce the tissue defect.
  • the collagen and extracellular matrix deposition promotes angiogenesis, which allows the ceils to be better supplied with nutrients, which, in turn, stimulate the formation of granulation tissue.
  • Healthy granulation tissue has an irregular texture and a naturally pink color; if the tissue is dark, this can mean reduced perfusion, ischemia, and (or) infection.
  • epitheliaiization is induced, in particular on the moist wound surface.
  • neutrophils are the most abundant population of innate immune cells
  • proliferative stage fibroblasts play a key role, inflammatory response is a primary tissue response to lesion, during which granulocytes, mostly neutrophils, monocytes-macrophages begin to act.
  • granulocytes mostly neutrophils, monocytes-macrophages
  • Proliferative stage episomiization, angiogenesis and matrix formation
  • proliferation stage of normally healing wound the fibroblasts are the main cell type. Molecules released by this type of cells are detected by using specific biomarkers corresponding to individual stages of healing, thus they can be used to evaluate the progress of wound healing.
  • Silver-containing sterilization substances are used as the measure for sterilization of the wound during the healing process, which allows avoiding inflammatory complications.
  • Silver nanoparticles, placed in cotton cloth, proteins or poiyurethane kill gram-negative and gram-positive bacteria and can be used in wound healing.
  • F. Paladini, R.A. Picca, M.C. Sporte!li, N. Cioffi, A, Sannino, M. Poi!ini Surface chemical and biological characterization of flax fabrics modified with silver nanoparticles for biomedical applications, Materials Science & Engineering C (2015): Anh, Xing, Le, Sugawara-Narutaki & Fong.
  • patches and bandages used for maintaining the antibacterial effects may be covered with a thin film of silver or impregnated with silver components, such bandages can be harmful due to higher silver concentrations, and, besides, silver salts act as dye on fabrics.
  • antibiotics such as polymyxin B sulfate and bacitracin zinc.
  • European Commission and other health care institutes call for moderate use of antibiotics, and in case of serious infections only. Regular use of antibiotics promotes the emergence of antibiotic-resistant microorganisms.
  • Wound healing status indicators are another very important aspect of multilayer treating patches, ensuring fast and complication-free healing of wounds.
  • Many scientists work on on a target to replace conventional dressings by multifunction ones.
  • scientists are intensively creating systems that can detect bacterial activity products and effects caused by them and inform the patient about that in real time, thus preventing complications.
  • One of the ways to provide information about the status of wound healing is to make the dressing change its color due to chemical indicators or fluorescent dyes.
  • Such kind of dressings could also further self-react by emitting additional amount of antibacterial substances ⁇ e.g. sodium azide) upon detection of toxins and also change color upon contact with bacteria.
  • Stability of such layer comprises one of the main unresolved issues among others (Zhou J1, Loftus AL, Mulley G, Jenkins AT. A thin film detection/response system for pathogenic bacteria. J Am Chem Soc. 2010 May 12;132(18):6566-70).
  • Electronic indicators for use with dressings, such as patches, are complex and expensive to manufacture.
  • Patent application No. US 1 1 / 936.812 describes wound dressings, comprising such materials as dye or biocide, enclosed in or behind the barrier of gelatin.
  • wound dressings comprising such materials as dye or biocide, enclosed in or behind the barrier of gelatin.
  • Naturally present in the wound metalloproteinase penetrates into the dressing and melts the gelatin, resulting in release of substances contained in it or behind it.
  • substances can be used as wound healing status indicators or for promotion of wound healing.
  • Such method of placement of useful substances is not effective. There is no established system to properly monitor and place all amount of gelatin in the device used for treatment. The gelatin melts due to heat exposure.
  • the closest analog is described in international patent application No. PCT/CA1998/000102. If discloses multilayer anti- microbial products, in which an interference color is visible, with the aid of which antimicrobial effect can be observed.
  • the products include partially reflective base layer and partially permeable upper layer balanced to form interference color.
  • the upper layer is formed from an antibacterial metal with a disordered atomic structure.
  • the melting or change in composition of upper layer due to contact with particular alcohol or electrolyte causes changes in optical path length and thus the changes in interference color of the product, it also discloses multi-layered laminated dressings.
  • the dressing comprises the first layer, the second layer and, preferably, the third layer.
  • the first and the third layer are formed of a perforated, non-adherent material, which, most preferably, is covered with antimicrobial coating as described above.
  • the second layer is introduced between the first and the third layer and is formed of an absorbent material.
  • At least one of the layers is formed of plastic material.
  • the layers are laminated together using ultrasonic welding seams spaced intermittently on the dressing.
  • this system does not allow introducing a wider range of indicators and an intelligent system capable to supervise the operation of the dressing according to the changed parameters.
  • Application No. PCT / CA1998 / 000102 does not describe how further drug substances can be added, how they are to be stabilized and how, where appropriate, they are released by the whole surface.
  • the described dressing uses antibacterial material instead of nanoparticles and, therefore, more expensive metals are required to manufacture it. Due to optimal weight-to-surface-area ratio nanoparticles can release more silver ions compared to the antibacterial metal form.
  • the present invention allows for more efficient continuous monitoring of the wound by analyzing exudate pH, inflammatory mediators and proteases, toxins and antibodies without removing the patch, it also ensures proper moisture for wound healing, safe use on a wound without adhering, so that removing the dressing does not traumatize the soft tissue.
  • the patch is safer to use compared with analogous solutions due to structure of each layer, constituent materials and interlayer interactions.
  • Antimicrobial substances are efficiently contained in their respective layers and are not released into healing tissue while ensuring effective delivery of treating substances (metal ions) to treated area.
  • the invention solves one of the most acute issues in the health sector - the treatment of diseases caused by methicillin-resistant bacteria, such as Staphyloccocus aureus, which often ends up with complications.
  • the invention would allow faster and more effective prevention of infections or healing an infected wound.
  • Advantages of the invention would allow to detect wound healing changes and to take timely measures to eliminate wound healing complications.
  • the described multilayer patch can be left applied during the whole wound healing period; it can efficiently and quickly provide information about wound healing process and accelerate the wound healing process.
  • the patch comprises an element for affixing the patch to the skin, a layer of antimicrobials comprising a layer saturated with metal nanoparticles and a hydrogel membrane layer, an indicator layer, a metal ion and drug accumulation layers.
  • the patch can also include intelligent means with electrical charge for facilitating faster healing by introducing healing promoters into skin tissues and means for effective and fast hemostasis.
  • Fig. 1 represents the arrangement order of patch structural layers
  • Fig. 2 represents a detailed view of the structure of layers
  • Fig. 3 represents the arrangement order of patch structural layers with parts or feedback system
  • Fig. 4 represents a cross-sectional view of the patch with means for increasing contact pressure on the surface of use
  • the patch can be composed of layers comprising the outer layer (1 , 1 a), a stabilized layer containing antimicrobials (2), 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 (1 , 1 a) of the dressing can be composed of polymeric film or natural tissue having holes/pores, designed to remove excess moisture.
  • the patch is affixed to the skin by means of the film.
  • the metal nanoparticles with antibacterial properties such as silver nanoparticles, are stabilized in the layer (2, 2a) and are silver ion donors which are maintained in the stabilizing layer (2, 2a), which ions migrate to other layers.
  • a hydrogel membrane layer (3, 3a) accumulates and transmits silver ions to the other layers and also keeps the metal nanoparticles at metal nanoparticles stabilization layer ⁇ 2, 2a).
  • the indicator layer (4, 4a) comprises a hydrogel layer having vertical channels (4a.4), filled with a gel with a very large amount of water, so the diffusion is faster than via hydrogel and they are called rapid diffusion channels.
  • the indicator that changes color is placed between the rapid diffusion channels (4a.3) to quickly carry out the analysis of tissue fluids and to transfer silver ions.
  • the function of protective layer (5, 5a) is to accumulate the maximum amount of silver ions, to catch nanoparficles and maintain the healing promoters therein. Beneath it, a mesh for additional dressing functions can also be mounted. Holes (5a.2) contain a gel with or without additional substances.
  • the gel quickly releases ail the accumulated silver ions into the wound and healing promoters and is replaced by tissue fluids, which can diffuse faster to the indicator system via the channels. Silver ions in this layer are released more slowly from hydrogel layer (5a.1 ), which ensures the required concentration of silver ions all over the healing time.
  • Non-adherent layer (6, 6a) partly seals the openings of the protective layer (5, 5a) and/or prevents the whole patch from adhering to wound tissues, i.e. when the patch adheres, this layer detaches and remains on the wound and is subsequently removed with the scab or resorbed.
  • the patch can also be supplied without this layer.
  • Metal meshes (7) are used to transfer and accumulate electrical charge next to the layers where they are inserted.
  • the mesh can be divided into smaller mesh units, making partitions of insulating material to form different electrical poles (positive and negative).
  • two seamless meshes may be used between different layers of the dressing, e.g. next to the stabilization layer (2, 2a) with nanoparficles having antibacterial properties and the protective layer (5, 5a).
  • the outer layer (1 , 1 a) of the dressing can be composed of polymeric film or natural tissue having holes/pores, designed to remove excess moisture.
  • the patch is affixed to the skin by means of this layer.
  • the outer layer of the patch (1 , 1 ) extends to the sticky portion for attachment of the patch to the skin.
  • the polymeric film can be made of silicon, PVC, and other composite materials.
  • the outer layer (1 , 1 a) can be also formed as a multicomponent structure comprising a porous fabric, such as cotton, which is integrated in the dressing attachment area using the hydrogel (i.e.
  • the fabric is adhered to the whole dressing area by placing it on the unformed gel and then synthesizing it), and the layer portion which is not in contact with the layer beneath the outer layer is covered with the material that is adhesive to human skin.
  • the outer layer (1 ,1 a) can be coated by hydrogel when the fabric is used as a system for maintaining moisture (i.e. when the adherent film is replaced by hydrogel).
  • Such layer can include collagen (or its analogue) hydrogel with 20% of microfiber cellulose, and make up to 1 mm thickness coating on the inner side of the layer (1 ).
  • Pores (1 a.1 ) of layer (1 ) (perforations for evaporation of excess moisture) of diameter from 0.1 to 0.3 mm are arranged consecutively or in parallel (or, possibly, in decorative pattern).
  • the layer of substances with anti-bacterial properties (2, 2a) is saturated with metal particles having anti-bacterial properties (2a.1 ).
  • Such nanoparticies can be silver nanoparticies (2a.1 ), silver nanoparticies in combination with iron nanoparticies or silver-coated iron nanoparticies, a mixture of palladium nanoparticies and silver nanoparticies with diameter of approximately 20 nm to 80 nm. Their purpose is to release metal ions (2a.2) into the environment. The mixture allows reducing the amount of silver used.
  • the layer of substances with anti-bacterial properties (2, 2a) also comprises stabilizer of nanoparticles, which allows the movement of ions but prevents the movement of nanoparticles.
  • This layer not only ensures the sterility of the whole patch, but also effective sterility of surface in contact with the patch due to distributed moisture migration and migration of metal ions from nanoparticles to other layers (3,3a 4,4a, 5,5a, 6,6a) from larger concentration gradient to a smaller, i.e. the skin tissues.
  • the stabilizer of nanoparticles comprises cellulose and cotton fibers, preferably up to 10 mm in length, which are bonded with collagen or starch solution (up to 10% of dry mass). The prepared mixture is deposited in a thin layer and the moisture is removed.
  • nanoparticles are deposited to the layer from the solution or a synthesis of nanoparticles takes place inside the layer by reduction of metal salts (comprising silver, silver and iron, palladium and silver) with which the whole layer is impregnated.
  • the reduction takes place due to UV radiation (200-400 nm).
  • the layer with nanoparticles is laminated using pressure of 5-50 kg / cm 2 .
  • the lamination is performed using a roll with embossed structure having grooves and holes with depth of up to 0,5 mm.
  • the manufactured layer (2, 2a) has thickness of ⁇ 0,1 mm.
  • the ions from substantially uniformly distributed nanoparticles are released when moisture is present and the embossed structure of the layer (2, 2a) ensures larger surface area and more rapid ion migration. This also limits the release of nanoparticles into the environment, behind the stabilization layer, so the nano-toxicity is reduced to a minimum.
  • the content of silver can be in range from 3 at% (atomic percent) to 20 at%, preferably from 3 at% to 15 at%.
  • the hydrogel membrane layer (3, 3a) generates and transmits silver ions to other layers, and detains the nanoparticles due to its viscosity so as to prevent them from spreading to the layers below. This layer further stabilizes the structure of thin layer of antibacteriais (2, 2a) and distributes the migration of silver ions to the other patch layers (4,4a, 5,5a, 6,6a).
  • the layer (3, 3a) can be composed of collagen hydrogel or an analogue thereof.
  • the layer (3, 3a) has a thickness of ⁇ 1 mm.
  • the hydrogel contained in hydrogel membrane layer (3, 3a) fills up ail the gaps of the layer of antibacteriais (2, 2a).
  • the gaps must be filled with hydrogel due to increased contact surface areas of the layers and better metal ion migration from the layer of antibacteriais (2, 2a) to hydrogel membrane layer (3, 3a).
  • the hydrogel membrane layer (3, 3a) having higher moisture content compared to the antibacteriais layer (2, 2a), initiates rapid silver ion migration into the aqueous medium, i.e. migration into the hydrogel membrane layer (3, 3a) due to higher amount of water therein and a low metal ion concentration.
  • the layer (4, 4a-4e) that performs indication functions is designed to identify the complications of wound healing.
  • An example of the indicator layer (4, 4a) is a hydrogel layer having vertical rapid diffusion channels (4a.4), which are filled with a gel of high water content for faster diffusion of substances compared to a hidrogel layer portion where no such channels are present.
  • the substance that can be used as an indicator of certain signs and which, for example, changes color, is placed in areas (4a.2) between rapid diffusion channels (4a.4). in this way, the substance effectively and rapidly reacts with the liquid in contact other than a patch component, and effectively and rapidly releases silver ions due to different concentration gradients.
  • the layer (4, 4a-4e) that performs indicator functions can be formed of cellulose (microcrystalline and microfiber), of cellulose or cotton composite or microcrystalline cellulose stabilized in hydrogel.
  • Plates (4a.2) are inserted into the layer with outer (upper) part surrounded by indication coating (4a.1 ), which can be liquid-impermeable, clear polymer.
  • the coatings (4a.1 ) on the plate are interconnected to form a mesh structure in which the connections are channels (4b.1 ) having a thickness of up to 2 mm and a horizontal channel (4b.1 ) in connection has a diameter of 1 mm.
  • the mesh of coatings/plates (4c) is integrated into the composite hydrogel layer (4a) at the upper part.
  • the substances used as an indicator of certain signs may include, but not limited to:
  • a chemical indicator such as bromothymol blue or another indicator with similar features, designed to detect pH changes on the surface of the wound. Due to reduced water content in the patch compared to that of the wound, the patch absorbs tissue fluids gradually, so pH measurements can be made beyond the protective layer (5, 5a), since in this portion the indicator is less likely to diffuse to the wound tissues, but at the same time is capable to detect changes.
  • Indicator mechanism that changes color upon detection of infection and is capable to react to changes in pH from 6 to 7-7.5 (pH of a healthy tissue is about 5.5-6), changes in the electrical conductivity, inflammatory mediators and proteases, bacterial toxins, and antibodies.
  • the chemical indicator is placed in the indicator plate (4a.2), which consists of microcrystalline and microfiber cellulose in proportion of 60% and 40% respectively, with structure stabilized by the use of collagen.
  • a 10% bromothymol blue solution is placed in the plate (4a.2) by impregnating microcrystalline cellulose.
  • Other indicators can also be integrated in the plate of similar structure.
  • the indicator has a yellowish tint, when the pH changes to neutral - the indicator changes color to blue.
  • the indicator plate (4a.2 (4c) has a diameter in the range from 3 to 10 mm. The spacing between elements (4a.1 ,4a.2 or (4c) is not less than half of the plate diameter.
  • the elements (4a.2) are arranged in parallel, consecutively, or forming a circular structure (ring) of the plates (4c), or using only one element (4c) in a single patch.
  • the connections between elements (4c) are formed as channels (4b.1 ), with a channel internal diameter of up to 1 mm and the connection element (4b.1 ) having a diameter of up to 2 mm.
  • An indicator that measures electrical conductivity of wound fluid. Such indicator is based on electrical conductivity (resistance) variation measurements in indicator system (4d). When resistance changes, the indicator gives a signal (color signal).
  • An indicator with chemicals that react to changes in pH and release electrons to electrodes (4d.1 ) in the analyzer cell (4d) (feedback system indicator).
  • the resulting reaction products change in color because of chemical indicator additive contained therein or the resulting reaction product has naturally different color compared to the original.
  • the layer performs indicator functions with feedback (4d-4e).
  • the feedback system generates a signal about changes in the wound environment and wound exudate, and generates a weak electromotive force due to ongoing chemical reaction in the ceil (4e), which is transmitted to the electric mesh layers (7). This way the release of healing promoters and movement thereof towards the damaged tissues, as well as movement of the metal ions is promoted.
  • Such hydrogel layer comprises a composite hydrogei layer of cellulose (microcrystalline and microfiber), cellulose or cotton composite or microcrystalline cellulose stabilized in hydrogei with vertical channels (4a.4) having diameter from 0.5 to 3 mm and arranged consecutively or in parallel. Distance between them is arranged according to indicator elements and openings are near them. Channels (4a.4) are arranged adjacent to analyzer ceils (4d.2) and there are no channels below the cells (4e).
  • the feedback elements (4d.1 , 4d.2, 4d.3) can be formed (Fig. 2).
  • Such layer comprises holes formed in hydrogei (4d.2) (analyzer cells), reticulated elements (4d.3) made of water-insoluble polymer with rings (4d.2) in points of intersection, where electrodes (4d.1 ) are installed. Inside the ring (4d.2) the elements for analysis and detection of chemical processes and reactions are placed.
  • a system of channels (4d.3) which allows the flow of liquids circulating by diffusion from the wound into the dressing layers is also designed.
  • the entire structure is designed with electrodes (4d.1 ), ducts (4d.3) and analyzer cell (4d.2), which is injected into the hydrogei.
  • This layer becomes active, i.e. there is a chemical reaction with the active component, which starts to generate electric charges due to a chemical reaction with tissue fluids upon changes in pH of tissue fluids.
  • Electrodes (4d.1 ) are connected to the metal meshes (7) to accelerate the transition of ions and substances through this layer.
  • the analyzer ceil (4d.2) should be in the range from 4 to 12 mm in diameter and not more than 2 mm in depth.
  • the feedback system of the indicator which includes an analyzer ceil (4d) and a metal grid (7), is an integral part of the layer (4) that performs an indicator function.
  • the metal mesh (7) is intended to carry out "electrolysis" between the patch layers (2-6, 2-5, 3-5,3-6, 4-6.), thereby promoting ion migration or by tissue stimulation.
  • the patch structure is equipped with at least one such metal mesh (7),
  • Each grid is a solid metal structure, or mesh (7) is separated by polymer inserts that allow forming the positive and the negative poles (cathode and anode) in a single mesh (7).
  • These structural elements (7a, 7b) can be used together or only one of the variations of the mesh (with or without polymer inserts).
  • Meshes (7) in connection with the layer (4, 4a ⁇ 4e) that performs indicator functions via a connection (7.1 ) constitute the feedback system.
  • the grid(s) (7) may be connected to a source of electrical pulses in order to make the patch that promotes healing and stimulates the skin muscles.
  • Metal ion and drug accumulation layer comprises a protective layer (5, 5a) and a non-adhesive layer (6, 6a).
  • the protective layer consists of a hydrogel and microfiber cellulose, 80 and 20% of the total layer composition respectively. It is intended to accumulate silver ions, to catch nanoparticles, and to keep the healing promoters therein. When such a layer is used, metal ions migrate from other layers due to concentration gradient, also nanoparticles of the layer containing materials with disinfectant properties (2) release ions via hydrogel membrane (3) and the indicator (4) layers, thus high ion concentration is always maintained in the system.
  • the layer thickness (h) is not greater than 2 mm and is generally less than 1 mm.
  • a thin metal grid (7) for additional smart dressing technology functions can be also mounted below it.
  • the protective layer includes openings (5a.2), which are fast diffusion channels having diameter from 2 mm to 8 mm and which are filled with a gel and, optionally, further healing promoters.
  • the area of cavities (5a.2) must be equal to at least 70% of the total layer area.
  • the cavities may be of any shape, such as circular, diamond, square, polygonal or other shapes, and arranged so as to form an ordered structure.
  • the melting gel/filling when from cavities (5a.2), quickly releases the accumulated silver ions and healing promoters. Excluded from the cavity gel is replaced by tissue fluids that can diffuse faster to indicator layer (4, 4a ⁇ 4e) through the channels (5a.2, 4a.4,).
  • Silver ions in this layer (5, 5a) are released more slowly from the hydrogel layer (5a.1 ) to the cavities due to reduced ion concentration therein, which ensures required silver ion concentration in the cavity (5a.2) and in the wound throughout the healing time.
  • Diameter of holes (5a.2) in the protective layer (5, 5a.) may be the same as of holes (6a.2) in the non-adhesive layer (6, 6a); the holes of the protective layer are open one into another with different diameters, i.e. if the holes of one layer have larger diameter, the holes of another layer must have smaller diameter and vice versa.
  • the diameter of holes is in the range from 3 to 6 mm and they must be arranged so as to maximize the filling volume, and the diameter of holes of non-adhesive layer must be in the range from 1 to 3 mm.
  • the non-adhesive layer (6, 6a) is composed of a hydrogel and cellulose and partially closes the cavities (5a.2) of the protective layer (5, 5a) and/or prevents the patch from adhering to the wound tissue.
  • This layer (6, 6a) detaches and is retained by the wound when the force of adhesion to adjacent layer (5, 5a) is less than the force of patch removal from the glued surface, wherein the force of adhesion between this layer and the supporting layer is larger than the force exerted to remove the patch from the surface without the cured dried healing structures, but less than the force exerted to remove the patch from the surface with a dried cured healing structures (scabs).
  • the non-adhesive layer (6, 6a) is intended to prevent the wound tissues from adhering to the patch and the formation of scabs, whose removal causes pain and damages the wound tissue.
  • the thickness of this must not exceed 0.5 mm, and the arrangement and shape of holes therein is similar to the shape and layout of forms in protective layer (5, 5a), However, the diameter of holes in this layer (6, 6a) can be several times smaller than of those in the protective layer (5, 5a), when the protective layer contains healing promoters.
  • This layer together with a protective layer (5, 5a) is intended for silver ion accumulation. This layer may dissolve and fully open the protective layer (5, 5a) with healing promoters.
  • the gel from the non-adhesive layer with therapeutic substances and Ag ions can get into the wound tissues resulting in higher concentration of silver ions destroying large quantities of pathogenic microorganisms in a short time.
  • the invention according to the first embodiment includes the adhesive film layer (1 , 1 a), the layer saturated with nanoparticles (2, 2a), the hydrogel membrane (3, 3a), the indicator layer (4, 4a, 4b, 4c, 4d, 4e), the protective layer (5, 5a to 5e) with or without therapeutic substances and the non- adhesive layer (6, 6a).
  • the invention according to the second embodiment includes the adhesive film layer (1 , 1 a), the layer saturated with nanoparticles (2, 2a), the hydrogel membrane (3, 3a), the indicator layer (4, 4a, 4b, 4c, 4d, 4e), the protective layer (5, 5a to 5e) with or without therapeutic substances, the metal mesh (7) and the non-adhesive layer (6, 6a).
  • Patches can have pre-defined dimensions and be ready for use, or in the form of substantially large area bandages that can be cut according to individual parameters.
  • the patch can be cut in ail directions when diameter of the holes (5a, 2) does not exceed 3 mm. For larger diameters of the holes the cutting can be done without damaging the holes of the patch that will be cut. in patches of such modification holes are arranged parallel to each other.
  • the invention according to the third embodiment includes a patch comprising the adhesive film as an externa! layer (1 , 1 a), also the layer saturated with nanoparticles (2, 2a), the hydrogei membrane layer (3, 3a), the protective layer (5, 5a) with or without therapeutic substances, the non-adhesive layer (6, 6a) and the silicone shell/capsule (8.2).
  • the capsule (8.2) comprises the compressed-gas-containing element (8.3) with the special valve (8.4) and the gas pressure distributor (8.5) that allows inflating the lower part (8.6) of the silicone capsule that moves in the direction (8.8) and tightly presses the patch against the wound and squeezes up the bleeding cavity completely with the help of further expanding and pressure distributing elements (8.7).
  • the capsule is provided with suitable tightening means (8.9), such as strong polymer belt, to which the capsule (8.2) is fitted by using a movable connector, which allows the capsule (8.2) with the patch (8.1 ) to slide into a desired position. After tightening the belt (8.9) and activating the capsule (8.2) the patch is pressed against the wound tissue and/or into it by air pressure.
  • Gas-releasing device (8.4) is made of plastic and molded into the gas capsule, allowing to release the gas by breaking the plastic plate which also serves as the gas pressure distributor (8.5) (the gas discharge element) (8.4); the released gas goes into the porous silicone chamber (8.7), which is connected directly to the gas capsule (8.2) (the chamber is inside the capsule), wherein the pressure moves only towards one direction (indicated by arrows in the drawing (8.8)). From accidental damage the capsule (8.2) is protected by a plastic cap, which is removed before use.
  • the patch of such design is affixed to the inner part of the belt (8.9) by which the banding is performed, and the capsule (8,2) is activated through the window in the belt (8.9).
  • Such embodiment includes iron and silver nanoparticles, which act to provide sterile wound environment (silver effect), speed up and facilitate the adhesion of wound tissues and tighten the small blood vessels (iron effect).
  • the bandage can also be used with electronic modification that promotes healing.
  • the invention according to the fourth embodiment comprises silicone polymer film as the external layer (1 , 1 a), also the layer saturated with nanoparticles (2, 2a), the hydrogei membrane (3, 3a), the protective layer (5, 5a), and the non-adhesive layer (6, 6a).
  • the wide-spacing metal mesh (7) is fixed on the inner or outer (6, 6a) side of the layer that directly interacts with the tissues.
  • the mesh of narrow-spacing structure is installed before or after the layer saturated with nanoparticles (2, 2a) depending on its preferred function (antimicrobial or material-transport function). Also, weak electrical currents will cause smooth skin muscles to contract thus promoting blood circulation and faster healing adjacent to the non-adhesive layer (6, 6a).
  • the invention according to the fifth embodiment comprises the outer layer (1 , 1 a) which can be a perforated silicone film with a thickness in the range from 1 to 4 mm with arrangement and diameter of holes as in the polymeric film, also the layer saturated with nanoparticles (2, 2a), the hydrogei membrane (3, 3a), the protective layer (5, 5a), and the non-adhesive layer (6, 6a).
  • the patch elements (2-6) are attached to the silicone film (1 ) with pores and holes comprising optical fibers. Due to semi-transparent patch structure, laser beam will reach the tissues and enhance the therapeutic effect.

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Abstract

Le timbre multicouche peut être laissé en place pendant toute la période de cicatrisation de la plaie. Il peut fournir des informations concernant le processus de cicatrisation et accélérer ce processus. Le timbre comprend un élément pour fixer le timbre sur la peau, une couche d'agents antimicrobiens dont une couche saturée avec des nanoparticules métalliques et une couche de membrane hydrogel, une couche indicatrice, une couche d'ions métalliques et de médicament accumulés. Le timbre comprend également un système de charge électrique accélérant la cicatrisation en ajoutant des promoteurs de cicatrisation dans les tissus et en arrêtant efficacement et rapidement l'écoulement de sang de la plaie.
PCT/IB2017/053826 2016-06-30 2017-06-27 Timbre intelligent. WO2018002817A1 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019191590A1 (fr) * 2018-03-30 2019-10-03 Kci Licensing, Inc. Pansement absorbant incorporant une indication d'état de plaie par ph
WO2020018735A1 (fr) * 2018-07-18 2020-01-23 Kci Licensing, Inc. Systèmes et méthodes de désactivation par la lumière et de retrait de champs adhésifs désactivés par la lumière
WO2023097047A3 (fr) * 2021-11-23 2023-08-03 California Institute Of Technology Systèmes et méthodes pour bandage intelligent pour la surveillance et le traitement des plaies

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WO2007046806A1 (fr) * 2005-10-21 2007-04-26 Argentum Medical, Llc Dispositif medical
US20160015962A1 (en) * 2014-07-16 2016-01-21 Mehdi Shokoueinejad Maragheh Smart Patch For Wound Management

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WO2007046806A1 (fr) * 2005-10-21 2007-04-26 Argentum Medical, Llc Dispositif medical
US20160015962A1 (en) * 2014-07-16 2016-01-21 Mehdi Shokoueinejad Maragheh Smart Patch For Wound Management

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TADAS JUKNIUS ET AL: "Antimicrobial Properties of Diamond-Like Carbon/Silver Nanocomposite Thin Films Deposited on Textiles: Towards Smart Bandages", MATERIALS, vol. 9, no. 5, 13 May 2016 (2016-05-13), pages 371, XP055404169, DOI: 10.3390/ma9050371 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019191590A1 (fr) * 2018-03-30 2019-10-03 Kci Licensing, Inc. Pansement absorbant incorporant une indication d'état de plaie par ph
WO2020018735A1 (fr) * 2018-07-18 2020-01-23 Kci Licensing, Inc. Systèmes et méthodes de désactivation par la lumière et de retrait de champs adhésifs désactivés par la lumière
US11937893B2 (en) 2018-07-18 2024-03-26 3M Innovative Properties Company Systems and methods for light deactivation and removal of light deactivated adhesive drapes
WO2023097047A3 (fr) * 2021-11-23 2023-08-03 California Institute Of Technology Systèmes et méthodes pour bandage intelligent pour la surveillance et le traitement des plaies

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