Wound dressing with embedded composite layer

Abstract

Disclosed embodiments relate to a wound dressing that can generate nitric oxide. The wound dressing can include an absorbent dressing component. The absorbent dressing component can include a composite layer, a top film layer, and a bottom film layer. The absorbent dressing component can be configured such that the composite component is embedded between the top film layer and the bottom film layer. The top film layer can include an opening such that the composite pad is exposed. The absorbent dressing component can be combined with a wound contact layer that includes the nitrite providing layer. The combination of the absorbent dressing component and the wound contact layer can be configured to generate nitric oxide.

Description

[0001] Cross-references to related applications

[0002] This application claims priority to UK Provisional Application No. 2317124.2, filed on 8 November 2023, entitled “WOUND DRESSING WITH EMBEDDED COMPOSITE LAYER”. The entire contents of the above application are incorporated herein by reference. background Technical Field

[0003] This document discloses materials, devices, methods, and systems, such as therapeutic compositions, wound care materials, their uses, and methods of treatment using them. In some instances, the materials, devices, and systems described herein include wound dressings configured for the delivery of nitric oxide (NO) and / or other active substances. Background Technology

[0004] Nitric oxide (NO) is a well-known molecule with a variety of biological functions. For example, nitric oxide affects vasodilation, stimulates angiogenesis, influences the host immune response, and exhibits potent broad-spectrum antimicrobial and antibiofilm activity. Due to these multiple effects, NO exhibits potent effects on tissues, and increasing NO levels can support accelerated wound healing, especially of chronic wounds.

[0005] Furthermore, compared to healthy individuals, people with diabetes typically have lower levels of nitric oxide, and this reduced nitric oxide supply is a contributing factor to the healing of chronic ulcers. Reduced nitric oxide supply can lead to vascular damage, such as endothelial dysfunction and vascular inflammation. Vascular damage can also reduce blood flow to the extremities, potentially making people with diabetes more likely to develop neuropathy and non-healing ulcers, and carrying a greater risk of lower limb amputation.

[0006] Therefore, there is a need for improved mechanisms for delivering effective doses of nitric oxide to wounds. Under normal conditions, nitric oxide (NO) is a free radical with a short lifespan, converting into a more stable chemical substance within seconds of its generation. Thus, for example, if gaseous nitric oxide comes into contact with air, it will be rapidly oxidized to nitrogen dioxide (NO2). Therefore, it may be difficult to maintain high concentrations of nitric oxide within wound dressings or other similar structures for extended periods. Therefore, devices or wound dressings having one or more layers containing a more stable composition can efficiently generate nitric oxide over time after activation for the stable and sustained delivery of nitric oxide to biological tissue. Of particular interest are mechanisms for delivering nitric oxide in conjunction with the use of wound dressings, especially negative pressure wound dressings, and / or during negative pressure wound therapy and / or other appropriate treatments. Summary of the Invention

[0007] Embodiments of this disclosure relate to materials, apparatus, methods, and systems for wound management. Some disclosed embodiments relate to materials, apparatus, methods, and systems for delivering nitric oxide to wounds. Those skilled in the art will understand that the applications of the materials, apparatus, methods, and systems described herein are not limited to specific tissues or specific injuries.

[0008] In some embodiments, a wound dressing for treating wounds may include: a covering layer configured to form a seal around the wound; an activator layer; a dried nitric oxide source layer that is free of or relatively free of liquid; and a collection and distribution layer.

[0009] In some embodiments, a wound dressing for treating wounds is provided, wherein the wound dressing may include an absorbent dressing component. In some embodiments, the absorbent dressing component may include a complex layer, a top membrane layer, and a bottom membrane layer. In some embodiments, the absorbent dressing component may be configured such that the complex component is embedded between the top membrane layer and the bottom membrane layer. In some embodiments, the top membrane layer may include an opening to expose the complex pad. In some embodiments, the absorbent dressing component may be combined with a wound contact layer, which further includes a nitrite-providing layer. In some embodiments, the combination of the absorbent dressing component and the wound contact layer may be configured to generate nitric oxide. In some embodiments, the complex layer may include a gelling fiber substrate loaded with an activator gel. In some embodiments, the activator gel may include a hydrogel. In some embodiments, the activator gel may contain acidic groups or portions. In some embodiments, the absorbent dressing component may also include a removable handle. In some embodiments, removal of the handle may allow the combination of the absorbent dressing component and the wound contact layer. In some embodiments, the combination may include contacting the area of ​​the absorbent dressing component exposed by the opening in the top membrane layer with the wound contact layer. In some embodiments, the wound dressing may be configured such that the wound contact layer is placed close to the wound, and an absorbent dressing component is placed above the wound contact layer. In some embodiments, the construction of the composite layer between the top and bottom membrane layers prevents delamination of the composite layer from the dressing. In some embodiments, the wound dressing may also include one or more adhesive layers.

[0010] The alternative or additional embodiments described herein provide a composition comprising one or more of the features described above or anywhere else herein.

[0011] The alternative or additional embodiments described herein provide a wound contact layer that includes one or more of the features described above or anywhere else herein.

[0012] The alternative or additional embodiments described herein provide a wound dressing that includes one or more of the features described above or anywhere else herein.

[0013] The alternative or additional embodiments described herein provide a wound treatment system that includes one or more of the features described above or anywhere else herein.

[0014] The alternative or additional implementation described herein provides a method for treating a wound, which includes one or more of the features described for the foregoing or anywhere else herein. Attached Figure Description

[0015] Figure 1 A schematic diagram of an example of a negative pressure wound therapy system;

[0016] Figure 2A An embodiment of a negative pressure wound treatment system employing a pump, a flexible fluid connector, and a wound dressing capable of absorbing and storing wound exudate is shown.

[0017] Figure 2B An embodiment of a negative pressure wound treatment system employing a flexible fluid connector and a wound dressing capable of absorbing and storing wound exudate is shown.

[0018] Figure 2C A cross-section of an embodiment of a fluid connector connected to a wound dressing is shown;

[0019] Figure 2D A cross-section of an embodiment of the wound dressing is shown;

[0020] Figures 3A to 3D An embodiment of a wound dressing capable of absorbing and storing wound exudate for use without negative pressure is shown;

[0021] Figure 3E A cross-section of an embodiment of a wound dressing capable of absorbing and storing wound exudate for use without negative pressure is shown;

[0022] Figure 4 An exploded view of an embodiment of a wound dressing that can generate nitric oxide;

[0023] Figure 5 for Figure 4 A cross-sectional view of the wound dressing;

[0024] Figure 6 An example of the equipment setup for a chemiluminescence experiment is shown;

[0025] Figure 7 The experiment on negative pressure and nitric oxide delivery is shown;

[0026] Figure 8A An example of chemiluminescence experimental results for sodium nitrate grids is described;

[0027] Figure 8B Examples of chemiluminescence experimental results are depicted for a full dressing design with pull-out tabs and self-sealing boundaries;

[0028] Figure 8C Examples of chemiluminescence experimental results for dressings containing biodegradable membranes are described;

[0029] Figure 9 An example is depicted showing the peak NO and NO2 outputs of an acrylic adhesive containing hydrogel;

[0030] Figures 10A to 10D An example of the chemiluminescence experimental results of nitric oxide-generated dressings is described;

[0031] Figures 11A to 11D An implementation scheme for a wound dressing configured to generate nitric oxide is described;

[0032] Figure 12 An exploded view of an embodiment of a wound dressing configured to generate nitric oxide is depicted.

[0033] Figure 13 A side view depicts an embodiment of a wound dressing configured to generate nitric oxide;

[0034] Figure 14 An exploded view of an embodiment of a wound dressing having multiple collection and distribution layers is depicted, the wound dressing being configured to generate nitric oxide;

[0035] Figure 15 A side view depicts an embodiment of a wound dressing having multiple collection and distribution layers, the wound dressing being configured to generate nitric oxide;

[0036] Figures 16A to 16B An embodiment of a wound dressing with a complex collection and distribution layer is described;

[0037] Figure 17 A side view depicts an embodiment of a wound dressing including a composite absorbent layer;

[0038] Figures 18A to 18C An embodiment of a wound dressing including a composite absorbent layer is described;

[0039] Figure 19 An embodiment of a wound dressing including a composite absorbent layer is described;

[0040] Figures 20A to 20D An embodiment of a wound dressing with a perforated complex collection and distribution layer is described;

[0041] Figure 21 An implementation scheme for a wound dressing with a composite layer is described;

[0042] Figure 22 An embodiment of a wound dressing with a spring composite layer is described;

[0043] Figure 23 An implementation scheme for a wound dressing having alternating complex layers and gel layers is described;

[0044] Figure 24 An implementation scheme for a wound dressing with an extended lower layer is described;

[0045] Figure 25 An implementation scheme for the complex layer is described;

[0046] Figure 26 An embodiment having a complex layer of gel surrounded by an absorbent is described;

[0047] Figure 27 An embodiment of a composite wound dressing with an absorbent nitrite-providing layer is described;

[0048] Figure 28 An embodiment of a composite wound dressing with a pleated nitrite-providing layer is described.

[0049] Figure 29 An embodiment of a wound dressing with an embedded composite layer is described. Detailed Implementation

[0050] Overview

[0051] The embodiments described herein relate to materials, apparatus, methods, and systems that have or include or utilize one or more compositions and / or materials that efficiently generate a gas (e.g., nitric oxide) over time upon activation. Embodiments herein may relate to devices and / or wound dressings having one or more layers containing compositions and / or materials that efficiently generate nitric oxide over time upon activation. For example, one or more nitric oxide generating layers may include a nitrite delivery layer containing nitrite and capable of releasing nitrite ions such that the nitrite ions can generate nitric oxide upon reaction with an acid. In some embodiments, in addition to the nitrite delivery layer, one or more nitric oxide generating layers may also include an acidic group providing layer. One or more nitric oxide generating layers may be used as standalone components individually positioned at the wound site, or may be incorporated into any number of multilayer wound dressings and wound treatment devices, such as those described below. Figures 1 to 29 As described. The embodiments of this disclosure are generally applicable to use in environmental conditions, in negative or decompression therapy systems, or in pressurization therapy systems.

[0052] Some preferred embodiments described herein include or utilize one or more nitric oxide generating layers. Such one or more nitric oxide generating layers may possess one or more of the following functional characteristics: inflammation-related activity, blood flow-related activity, antimicrobial, antiplankton, and antibiofilm activity, ease of application and / or removal as a single piece, cutability / tearability, conformability to the three-dimensional contours of the wound surface, abrasion resistance, compatibility with negative pressure wound therapy and / or pressure wound therapy, exudate management, ability to promote autolytic debridement of the wound, ability to promote wound healing, and self-indication of compositional or functional changes. Antimicrobial activity, such as in vitro antimicrobial activity, may include one or more of the following: broad-spectrum antimicrobial activity, antibiofilm activity, rapid killing of microorganisms, sustained killing of microorganisms; and the microorganisms may include one or more of the following: Gram-negative bacteria, Gram-positive bacteria, fungi, yeasts, viruses, algae, archaea, and protozoa.

[0053] Certain preferred embodiments described herein provide a wound treatment system. This wound treatment system may include a nitric oxide generating layer configured to be positioned above the wound and / or the area surrounding the wound. Those skilled in the art will understand that when the device / dressing / layer is described as being placed on or above a wound, such a device / dressing / layer may extend above and treat the area surrounding the wound. In some cases, stimulation of the area surrounding the wound and / or the wound edges may play a role in initiating the wound healing process, and the wound healing process may be activated by delivering nitric oxide to the area surrounding the wound and / or the wound edges. Delivery of nitric oxide to the area surrounding the wound and / or the wound edges may target, for example, epithelial cell activity to promote the migration of the epithelial tongue; vasodilation of the microcirculation in the skin surrounding the wound to promote perfusion by providing oxygen and nutrients; and angiogenesis to promote granulation tissue formation. The wound treatment system described herein may also include a second wound dressing configured to be positioned separately above the nitric oxide generating layer. The nitric oxide generating layer may have an adhesive that adheres to an underlying surface; and the adhesive may be configured such that the nitric oxide generating layer can be placed adjacent to the wound. A second wound dressing (if used) may adhere to the skin around the wound and may have the same size as, or may be larger than, the nitric oxide generating layer, such that the nitric oxide generating layer will be placed in contact with or adjacent to the wound and / or the surrounding area. The second wound dressing may alternatively or additionally be configured to form a seal against the skin around the wound, such that the nitric oxide generating layer will be placed in contact with or adjacent to the wound. The wound treatment system may also include a negative pressure source configured to supply negative pressure to the wound through the second wound dressing and through the wound contact layer.

[0054] Some other preferred embodiments described herein provide a multilayer wound dressing, such as those described herein. Figures 1 to 29 As described in the specification. This multilayer wound dressing may have one or more nitric oxide generating layers as its component layers, or alternatively may include a compound or lamination comprising one or more nitric oxide generating layers as part of one of its component layers. The multilayer wound dressing may include: a nitric oxide generating layer as described above or elsewhere herein; a transport layer and / or absorbent layer above / below one or more nitric oxide generating layers; a wound contact layer below one or more nitric oxide generating layers; and a covering layer above the transport layer and / or absorbent layer. The wound dressing may also include a negative pressure port positioned on or above the covering layer. One or more nitric oxide generating layers may have a peripheral shape substantially the same as the peripheral shape of the covering layer. Alternatively, one or more nitric oxide generating layers may have a peripheral shape smaller than the peripheral shape of the covering layer.

[0055] Those skilled in the art will understand that nitric oxide generating compositions, such as any nitric oxide generating compositions disclosed in this “Overview” section or elsewhere in the specification, can be loaded into one or more nitric oxide generating layers in any suitable form (such as via adsorption, absorption, chemical and / or physical adhesion entanglement) and / or via powder form. Those skilled in the art will further understand that reactive compositions, such as any reactive compositions disclosed in this section or elsewhere in the specification, can be incorporated by any suitable means into any suitable absorbent layer disclosed in this section or elsewhere in the specification, and / or any suitable transport layer disclosed in this section or elsewhere in the specification and / or any foam layer disclosed in this section or elsewhere in the specification.

[0056] In some embodiments, the wound treatment systems and multilayer wound dressings disclosed above or elsewhere herein may have or include a nitric oxide generating layer. As described herein or elsewhere in the specification, particularly below, the nitric oxide generating layer may be configured to be activated to release nitric oxide. At least a portion of the released nitric oxide may be released, for example, by diffusion. To facilitate the release and diffusion of nitric oxide, the nitric oxide generating layer may be placed adjacent to the wound.

[0057] Some preferred embodiments described in this specification provide a method for treating a wound, intact tissue, or other suitable location. This method may include placing a nitric oxide generating layer, either alone or by placing a multi-layered wound dressing having a nitric oxide generating layer over the wound. The method may include adhering a separate nitric oxide generating layer and / or a multi-layered wound dressing having a nitric oxide generating layer to healthy skin surrounding the wound. This method may also include one or more of the following steps: another wound dressing may be placed over the separate nitric oxide generating layer or over the multi-layered wound dressing having a nitric oxide generating layer placed over the wound. Wound exudate or any wet or aqueous medium other than wound exudate may be provided to reach and / or touch the nitric oxide generating layer. Wound exudate or any wet or aqueous medium other than wound exudate may diffuse or wick into the wound dressing having the nitric oxide generating layer, or diffuse or wick into the wound dressing positioned over the nitric oxide generating layer. Negative pressure can be applied to a single nitric oxide generating layer or a multi-layered wound dressing with a nitric oxide generating layer, so that wound exudate is directly aspirated into the nitric oxide generating layer, or into a wound dressing with a nitric oxide generating layer, or into a wound dressing positioned above the nitric oxide generating layer.

[0058] Those skilled in the art will understand that wound dressings, devices, and systems disclosed in this "Overview" section or elsewhere in the specification may include one or more layers, compositions, materials, or components that generate gases other than nitric oxide, in addition to or in place of a nitric oxide-generating layer, composition, or material. For example, a wound dressing or device may include one or more layers that, upon activation, effectively generate vasodilators, such as carbon monoxide or hydrogen sulfide, over time.

[0059] Those skilled in the art will further understand that, where appropriate, carbon monoxide and / or hydrogen sulfide can be used in place of nitric oxide delivery elements (such as layers) or in combination with nitric oxide delivery elements (such as layers). Further details regarding the generation and delivery of carbon monoxide and / or hydrogen sulfide can be found in Chapter 6 of the text *Inorganic and Organometallic Transition Metal Complexes with Biological Molecules and Living Cells*, ISBN 978-0-12-803814-7, which is hereby incorporated by reference. For example, hydrogen sulfide can be generated from elements / layers containing crackable / releaseable hydrogen sulfide, diallyl thiosulfinate, GYY4137, S-mesalazine ATB-429, S-naproxen ATB-346, and S-diclofenac ATB-337 / ACS-15. For example, carbon monoxide can be generated from elements / layers that provide complexes of carbon monoxide bound to suitable metals such as chromium, molybdenum, tungsten, manganese, rhenium, iron, ruthenium, cobalt, rhodium, and iridium. Such complexes can be enzymatically triggered to release carbon monoxide, photolyzed, and / or induced to release carbon monoxide in response to interactions with suitable ligands.

[0060] Methods of treating wounds

[0061] Some preferred embodiments described in this specification provide a method for treating a wound, intact tissue, or other suitable location. This method may include placing one or more nitric oxide generating layers, either alone or by placing a multilayer wound dressing having one or more nitric oxide generating layers over the wound. The method may include adhering one or more individual nitric oxide generating layers and / or a multilayer wound dressing having one or more nitric oxide generating layers to healthy skin surrounding the wound, such as the peri-wound area. The method may also include one or more of the following steps: another wound dressing may be placed over the individual one or more nitric oxide generating layers or over a multilayer wound dressing having one or more nitric oxide generating layers placed over the wound. Wound exudate or any wet or aqueous medium other than wound exudate may be provided to reach and / or touch the one or more nitric oxide generating layers. Wound exudate or any wet or aqueous medium other than wound exudate may diffuse or wick into the wound dressing having one or more nitric oxide generating layers, or diffuse or wick into the wound dressing positioned over one or more nitric oxide generating layers. Negative pressure can be applied to a single or multiple nitric oxide generating layer or a multilayer wound dressing having one or more nitric oxide generating layers, as described in the “Negative Pressure Wound Therapy (NPWT) System” section below or elsewhere in this specification, such that wound exudate is directly aspirated into one or more nitric oxide generating layers, or into a wound dressing having one or more nitric oxide generating layers, or into a wound dressing positioned above one or more nitric oxide generating layers.

[0062] Methods for treating wounds, intact tissue, or other suitable sites as described above or elsewhere herein may also include delivering negative pressure to the wound through a wound contact layer, as described in the “Negative Pressure Wound Therapy (NPWT) Systems” section below or elsewhere herein. The wound contact layer may substantially maintain the delivered negative pressure for at least about 24 hours, or at least about 48 hours, or at least about 72 hours. Alternatively, methods for treating wounds, intact tissue, or other suitable sites may include applying pressurized (positive) pressure to the wound through the wound contact layer. Alternatively, the method may include programmably varying the ambient pressure, negative pressure, and pressurized pressure delivered to the wound through the wound contact layer.

[0063] In implementation methods, methods for treating wounds, intact tissue, or other suitable locations may include using a wound contact layer in an environment not connected to a negative pressure wound therapy system as described above or elsewhere herein, or using a wound treatment system or wound dressing that includes a wound contact layer.

[0064] In some implementations, methods for treating wounds, intact tissue, or other suitable locations can reduce wound bioburden, for example, at least in vitro, by reducing the number of viable microorganisms (CFU / sample) within the first 4 hours after application of the wound contact layer. In some instances, the number of viable microorganisms can be reduced by four logarithms or more within 48 to 72 hours after the wound dressing is positioned for contact with microorganisms.

[0065] Negative Pressure Wound Therapy (NPWT) System

[0066] It should be understood that the embodiments of this disclosure are generally applicable to, but not limited to, local negative pressure (“TNP”) treatment systems. In simple terms, negative pressure wound therapy assists in the closure and healing of various forms of “refractory” wounds by: reducing tissue edema, promoting blood flow and granulation tissue formation, removing excess exudate, and reducing bacterial load (thereby lowering the risk of infection). Furthermore, this treatment allows for less disturbance to the wound, enabling faster healing. TNP treatment systems can also aid in the healing of surgically closed wounds by removing fluid and by helping to stabilize tissue immediately adjacent to the closure site. Another beneficial use of TNP treatment can be found in grafts and flaps, where removing excess fluid is important and close proximity of the graft to the tissue is necessary to ensure tissue viability.

[0067] As used herein, decompression levels or negative pressure levels (such as -X mmHg) represent pressure levels relative to normal ambient atmospheric pressure, which correspond to 760 mmHg (or 1 atm, 29.93 inHg, 101.325 kPa, 14.696 psi, etc.). Therefore, a negative pressure value of -X mmHg reflects an absolute pressure X mmHg lower than 760 mmHg, or in other words, reflects an absolute pressure of (760-X) mmHg. Additionally, negative pressures “less” or “smaller” than X mmHg correspond to pressures closer to atmospheric pressure (e.g., -40 mmHg is less than -60 mmHg). Negative pressures “more” or “larger” than -X mmHg correspond to pressures further away from atmospheric pressure (e.g., -80 mmHg is larger than -60 mmHg). In some embodiments, local ambient atmospheric pressure is used as a reference point, and this local atmospheric pressure need not be, for example, 760 mmHg.

[0068] For some embodiments of this disclosure, the negative pressure range can be approximately -80 mmHg, or between approximately -20 mmHg and -200 mmHg. It should be noted that these pressures are based on normal ambient atmospheric pressure (which can be 760 mmHg). Therefore, -200 mmHg would practically be approximately 560 mmHg. In some embodiments, the pressure range can be between approximately -40 mmHg and -150 mmHg. Alternatively, pressure ranges up to -75 mmHg, up to -80 mmHg, or exceeding -80 mmHg can be used. Additionally, in other embodiments, pressure ranges below -75 mmHg can be used. Alternatively, the negative pressure device can supply pressure ranges exceeding approximately -100 mmHg, or even -150 mmHg.

[0069] In some embodiments of the wound closure device described herein, increased wound contraction may result in increased tissue expansion in the surrounding wound tissue. This effect can be enhanced by altering the force applied to the tissue: for example, by varying the negative pressure applied to the wound over time, which can be combined with increasing the tension applied to the wound via various embodiments of the wound closure device. In some embodiments, for example, a sine wave, a square wave, or synchronization with one or more patient physiological indicators (e.g., heart rate) can be used to vary the negative pressure over time. Examples of such applications in which further disclosures relating to the foregoing can be found include U.S. Patent No. 8,235,955, published August 7, 2012, entitled “Wound treatment apparatus and method”; and U.S. Patent No. 7,753,894, published July 13, 2010, entitled “Wound cleansing apparatus with stress”. The disclosures of both patents are incorporated herein by reference in their entirety.

[0070] The embodiments of wound dressings, wound dressing components, wound treatment devices and methods described herein may also be used in combination with or supplement to those described in International Application No. PCT / IB2013 / 001469, filed on May 22, 2013 and published on November 28, 2013, entitled “APPARATUSES AND METHODS FOR NEGATIVE PRESSURE WOUND THERAPY”, and International Application No. PCT / IB2013 / 002060, filed on July 31, 2013 and published on WO2014 / 020440, entitled “WOUND DRESSING”, the entire contents of which are hereby incorporated by reference. The embodiments of the wound dressings, wound treatment devices, and methods described herein may also be used in combination with or in supplement to those described in U.S. Patent No. 9,061,095, entitled "WOUND DRESSING AND METHOD OF USE," published June 23, 2015, and U.S. Application Publication No. 2016 / 0339158, entitled "FLUIDIC CONNECTOR FOR NEGATIVEPRESSURE WOUND THERAPY," published November 24, 2016, the disclosures of which are incorporated herein by reference in their entirety, including further details regarding embodiments of wound dressings, wound dressing components and principles, and materials for use in wound dressings.

[0071] Additionally, some embodiments relating to the TNP wound management described herein (including wound dressings combined with a pump or associated electronics) may be used in combination with or supplement those described in International Publication No. WO 2016 / 174048 A1 entitled “REDUCED PRESSURE APPARATUSES”, published November 3, 2016, the entire contents of which are incorporated herein by reference. In some of these embodiments, the pump or associated electronics may be integrated into the wound dressing to provide single-article application to the wound.

[0072] Multilayer wound dressings for NPWT

[0073] Figure 1An example of a negative pressure wound therapy system 700 is shown. The system includes a wound cavity 710 covered by a wound dressing 720, which can be any of the dressings described herein. The dressing 720 can be positioned on, inside, above, or around the wound cavity 710, and further seal the wound cavity to maintain negative pressure within it. For example, a membrane layer of the wound dressing 720 can provide a substantially fluid-impermeable seal over the wound cavity 710. In some embodiments, a wound filler, such as a layer of foam or gauze, can be used to bandage the wound. The wound filler can include one or more nitric oxide generating layers (e.g., nitrite delivery layers, acidic group providing layers) as described in this section or elsewhere in the specification. For example, in conventional negative pressure wound therapy systems utilizing foam or gauze, such as the Smith + Nephew RENASYS negative pressure wound therapy system utilizing foam (RENASYS-F) or gauze (RENASYS-G), the foam or gauze can be supplemented with a nitric oxide generating layer as described above. When adding foam, gauze, or other wound packing materials, one or more nitric oxide generating layers can be inserted into the wound individually or pre-attached to the wound packing material for insertion into the wound.

[0074] A single-lumen or multi-lumen tube or conduit 740 connects the wound dressing 720 to a negative pressure device 750 configured to provide pressure reduction. The negative pressure device 750 includes a negative pressure source. The negative pressure device 750 may be a canisterless device (meaning exudate is collected in the wound dressing and / or delivered via the tube 740 for collection at another location). In some embodiments, the negative pressure device 750 may be configured to include or support a canister. Additionally, in any embodiment of the embodiments disclosed herein, the negative pressure device 750 may be wholly or partially embedded in, mounted to, or supported by the wound dressing 720.

[0075] The conduit 740 can be any suitable article configured to provide at least substantially sealed fluid flow path or passage between the negative pressure device 750 and the wound cavity 710 to provide decompression to the wound cavity. The conduit 740 can be formed of polyurethane, PVC, nylon, polyethylene, silicone, or any other suitable rigid or flexible material. In some embodiments, the wound dressing 720 may have a port configured to receive an end of the conduit 740. For example, the port may include a hole in a membrane. In some embodiments, the conduit 740 may otherwise pass through and / or beneath the membrane of the wound dressing 720 to supply reduced pressure to the wound cavity 710 to maintain a desired level of decompression within the wound cavity. In some embodiments, at least a portion of the conduit 740 is integral with or attached to the wound dressing 720.

[0076] Figure 2A An embodiment of a negative pressure wound therapy system 10 is shown, which employs a wound dressing 100 coupled with a fluid connector 110. Further examples relating to negative pressure wound therapy including wound dressings combined with pumps as described herein may also be used in combination with or complement those described in U.S. Patent No. 9,061,095, the entire text of which is incorporated herein by reference. Here, the fluid connector 110 may include an elongated conduit, more preferably a bridging member 120 having a proximal end 130 and a distal end 140, and an applicator 180 at the distal end 140 of the bridging member 120. System 10 may include a negative pressure source, such as a pump or negative pressure unit 150 capable of supplying negative pressure. The pump may include a canister or other container for storing wound exudate and other fluids that may be removed from the wound. The canister or container may also be provided separately from the pump. In some embodiments, pump 150 may be a canisterless pump, such as the PICO™ pump sold by Smith + Nephew. Pump 150 can be connected to bridge 120 via tubing, or pump 150 can be directly connected to bridge 120. In use, dressing 100 is placed over a properly prepared wound, which in some cases may be filled with wound-filling material, such as foam or gauze as described above. The applicator 180 of fluid connector 110 has a sealing surface that is positioned over an orifice in dressing 100 and seals to the top surface of dressing 100. Before, during, or after fluid connector 110 is connected to dressing 100, pump 150 is connected to a connector via tubing, or directly to bridge 120. Pump is then activated, thereby supplying negative pressure to the wound. Negative pressure can be applied until the desired level of wound healing is achieved.

[0077] like Figure 2B As shown, the fluid connector 110 preferably includes an enlarged distal end or head 140 in fluid communication with the dressing 100, as will be described in further detail below. In one embodiment, the enlarged distal end has a circular or annular shape. The head 140 is shown here positioned near the edge of the dressing 100, but can be positioned anywhere on the dressing. For example, some embodiments may provide a centered or off-center position not on or near the edge or corner of the dressing 100. In some embodiments, the dressing 10 may include two or more fluid connectors 110, each including one or more heads 140 in fluid communication with it. In a preferred embodiment, the head 140 may be measured 30 mm along its widest edge. The head 140 forms at least a portion of the applicator 180 described above, which is configured to seal the top surface of the wound dressing.

[0078] Figure 2CA cross-section through a wound dressing 100 and a fluid connector 110 is shown. This wound dressing is similar to the wound dressing 10 described in International Patent Publication WO2013175306 A2, the entire text of which is incorporated herein by reference. The wound dressing 100 (which may alternatively be any wound dressing embodiment disclosed herein or any combination of features of any number of wound dressing embodiments disclosed herein) may be positioned over the wound site to be treated. The dressing 100 may be positioned to form a sealed cavity over the wound site. In a preferred embodiment, the dressing 100 includes a top layer or overlay layer, or a backing layer 220 attached to an optional wound contact layer 222, both of which are described in more detail below. These two layers 220, 222 are preferably joined or sealed together to define an internal space or chamber. This internal space or chamber may include additional structures that may be adapted to distribute or transmit negative pressure, store wound exudate and other fluids removed from the wound, and other functions, which will be explained in more detail below. Examples of such structures described below include a transport layer 226 and an absorbent layer 221.

[0079] As used herein, the upper, top, or overlying layer refers to the layer furthest from the surface of the skin or wound when the dressing is in use and positioned above the wound. Therefore, the lower, bottom, or subsurface layer refers to the layer closest to the surface of the skin or wound when the dressing is in use and positioned on the wound.

[0080] like Figure 2C As shown, the wound contact layer 222 can be a polyurethane layer, a polyethylene layer, or other flexible layer, which is perforated or otherwise made permeable to liquids and gases, for example, via a hot needle process, ablation process, ultrasonic process, or some other method. The wound contact layer 222 has a lower surface 224 and an upper surface 223. The perforations 225 preferably include through-holes in the wound contact layer 222 that allow fluid to flow through the layer 222. The wound contact layer 222 helps prevent tissue from growing inward into other materials of the wound dressing. Preferably, the perforations are small enough to meet this requirement while still allowing fluid to flow through them. For example, perforations formed as slits or holes ranging in size from 0.025 mm to 1.2 mm are considered small enough to help prevent tissue from growing inward into the wound dressing while allowing wound exudate to flow into the dressing. In some configurations, the wound contact layer 222 can help maintain the integrity of the entire dressing 100 while also creating an airtight seal around the absorbent pad to maintain negative pressure at the wound site.

[0081] Some embodiments of the wound contact layer 222 may also serve as a carrier for optional lower and upper adhesive layers (not shown). For example, a lower pressure-sensitive adhesive may be disposed on the lower surface 224 of the wound dressing 100, while an upper pressure-sensitive adhesive layer may be disposed on the upper surface 223 of the wound contact layer. The pressure-sensitive adhesive (which may be a silicone-based, hot melt, hydrocolloid, or acrylic adhesive, or other such adhesive) may be formed on both sides of the wound contact layer, or optionally on a selected side of these sides, or not on either side. Using the lower pressure-sensitive adhesive layer can help adhere the wound dressing 100 to the skin surrounding the wound site. In some embodiments, the wound contact layer may include a perforated polyurethane membrane. The lower surface of the membrane may be provided with a silicone pressure-sensitive adhesive, and the upper surface may be provided with an acrylic pressure-sensitive adhesive, which can help the dressing maintain its integrity. In some embodiments, the polyurethane membrane layer may have adhesive layers disposed on both its upper and lower surfaces, and all three layers may be perforated together.

[0082] A transport layer 226 may be located above the wound contact layer 222. In some embodiments, the transport layer may be a porous material. As used herein, the transport layer may be referred to as a spacer layer, and the term may be used interchangeably to refer to the same component described herein. This transport layer 226 allows the transport of fluids, including liquids and gases, away from the wound site into the upper layer of the wound dressing. In particular, the transport layer 226 preferably ensures that open air passages are maintained to deliver negative pressure over the wound area, even when the absorbent layer has absorbed a significant amount of exudate. Layer 226 should preferably remain open at a typical pressure that will be applied during negative pressure wound therapy as described above, so that the entire wound site is subjected to uniform negative pressure. Layer 226 may be formed of a material having a three-dimensional structure. For example, knitted or woven spacer fabrics (e.g., Baltex 7970 weft-knitted polyester) or nonwoven fabrics may be used. Three-dimensional materials may include 3D spacer fabric materials similar to those described in International Publication WO 2013 / 175306 A2 and International Publication WO2014 / 020440, the full text of which is incorporated herein by reference.

[0083] In some embodiments, wound dressing 100 may incorporate or include one or more nitric oxide generating layers (e.g., nitrite delivery layers, acidic group providing layers) as described herein or elsewhere in the specification. Those skilled in the art will understand that wound dressing 100 may incorporate any of the one or more nitric oxide generating layers disclosed herein or elsewhere in the specification. Those skilled in the art will also understand that one or more nitric oxide generating layers may be incorporated as an integral component layer or part of a component layer. In some embodiments, one or more nitric oxide generating layers may be disposed below transport layer 226. In some embodiments, one or more nitric oxide generating layers may be disposed above wound contact layer 222. In some embodiments, one or more nitric oxide generating layers may replace transport layer 226, such that one or more nitric oxide generating layers are disposed between absorbent layer 221 (further described below) and wound contact layer 222. In some embodiments, one or more nitric oxide generating layers may supplement or replace absorbent layer 221. In some embodiments, wound dressing 100 may not have wound contact layer 222, and one or more nitric oxide generating layers may be the bottom layer of wound dressing 100. One or more nitric oxide generating layers may have the same or substantially similar size and shape as transport layer 226 and / or absorbent layer 221. In some embodiments, one or more nitric oxide generating layers or components thereof (e.g., nitrite providing layers as described herein) may be separate from wound dressing 100. For example, one or more nitric oxide generating layers or components thereof may be configured as separate layers that can be placed on a wound, and wound dressing 100 may be placed on top of them.

[0084] One or more nitric oxide generating layers may be configured to be flexible yet sufficiently rigid to withstand negative pressure, preventing excessive collapse and ensuring adequate delivery of negative pressure to the wound when supplied to the wound dressing 100. The one or more nitric oxide generating layers may be configured to include a sufficient number or size of pores to enable the delivery of negative pressure. The one or more nitric oxide generating layers may include, for example, orifices or openings below ports to deliver negative pressure and / or wound fluid. Furthermore, the one or more nitric oxide generating layers may have a suitable thickness to deliver appropriate negative pressure to the wound. For example, the one or more nitric oxide generating layers may have a thickness of about 1 mm to 10 mm, or 1 mm to 7 mm, or 1.5 mm to 7 mm, or 1.5 mm to 4 mm, or 2 mm to 3 mm. In some embodiments, the one or more nitric oxide generating layers may have a thickness of about 2 mm.

[0085] In some embodiments, an absorbent material layer 221 is disposed above the transport layer 226. This absorbent material may include foam or nonwoven natural or synthetic materials, and may optionally include superabsorbent materials, forming a reservoir for fluid (particularly liquids) removed from the wound site. In some embodiments, layer 221 may also aid in drawing fluid toward the backing layer 220.

[0086] The material of absorbent layer 221 also prevents fluid collected in wound dressing 100 from flowing freely within the dressing and is preferably used to contain any fluid collected within the dressing. Absorbent layer 221 also facilitates the distribution of fluid throughout the layer via wicking, so that fluid is absorbed from the wound site and stored throughout the absorbent layer. This helps prevent accumulation in areas of the absorbent layer. The capacity of the absorbent material must be sufficient to manage the flow rate of exudate from the wound when negative pressure is applied. Since the absorbent layer experiences negative pressure during use, the material of the absorbent layer is selected to absorb fluid under these conditions. Many materials exist that can absorb fluid under negative pressure, such as superabsorbent materials. Absorbent layer 221 can typically be made of… Foam, Freudenberg 114-224-4 or Fabrication. In some embodiments, the absorbent layer 221 may include a composite comprising superabsorbent powder, a fibrous material such as cellulose, and bonding fibers. In a preferred embodiment, the composite is an air-laid thermally bonded composite.

[0087] In some embodiments, the absorbent layer 221 is a nonwoven cellulose fiber layer having a superabsorbent material in the form of dry particles dispersed throughout. The use of cellulose fibers introduces rapid wicking elements that facilitate the rapid and uniform distribution of liquid absorbed by the dressing. The juxtaposition of the multi-stranded fibers results in strong capillary action within the fiber pad, which aids in liquid distribution. In this way, the superabsorbent material is effectively supplied with liquid. The wicking action also helps to bring the liquid into contact with the overlying layer, thereby helping to increase the evaporation rate of the dressing.

[0088] Preferably, orifices, holes, or pores 227 are provided in the backing layer 220 to allow negative pressure to be applied to the dressing 100. The fluid connector 110 is preferably attached to or sealed to the top of the backing layer 220 over the pores 227 created in the dressing 100, and transmits negative pressure via the pores 227. A tubing of a certain length can be coupled to the fluid connector 110 at a first end and to a pump unit (not shown) at a second end to allow fluid to be pumped out of the dressing. In the case where the fluid connector adheres to the top layer of the wound dressing, a tubing of a certain length can be coupled to the first end of the fluid connector such that the tubing or conduit extends parallel away from the fluid connector or substantially to the top surface of the dressing. Using adhesives such as acrylics, cyanoacrylates, epoxy resins, UV-curable or hot-melt adhesives, the fluid connector 110 can be adhered to and sealed to the backing layer 220. The fluid connector 110 can be formed of a soft polymer, such as polyethylene, polyvinyl chloride, silicone, or polyurethane, with a Shore A hardness of 30 to 90. In some implementations, the fluid connector 110 may be made of a soft or conformal material.

[0089] Optionally, the absorbent layer 221 includes at least one through-hole 228 located below the fluid connector 110. In some embodiments, the through-hole 228 may be the same size as the opening 227 in the backing layer, or it may be larger or smaller. Figure 2C As shown, a single through-hole can be used to create an opening located below the fluid connector 110. It will be appreciated that multiple openings can be used alternatively. Additionally, if more than one port is used according to certain embodiments of this disclosure, one or more openings can be created in the absorbent layer calibrated to each corresponding fluid connector. Although not essential for certain embodiments of this disclosure, the use of through-holes in the superabsorbent layer can provide fluid flow paths, which in particular remain unobstructed when the absorbent layer is near saturation.

[0090] The orifice or through-hole 228 is preferably disposed in the absorption layer 221 below the pore 227, so that the pore is directly connected to the transport layer 226, such as... Figure 2C As shown in the diagram. This allows the negative pressure applied to the fluid connector 110 to communicate with the transport layer 226 without passing through the absorbent layer 221. This ensures that the negative pressure applied to the wound site is not suppressed by the absorbent layer as it absorbs wound exudate. In other embodiments, orifices may not be provided in the absorbent layer 221, or alternatively, multiple orifices may be provided below the pores 227. In other alternative embodiments, an additional layer (such as another transport layer or a shielding layer such as that described in International Patent Publication WO2014 / 020440, the entire contents of which are incorporated herein by reference) may be provided above the absorbent layer 221 and below the backing layer 220.

[0091] The backing layer 220 is preferably gas-impermeable but water vapor-permeable, and may extend across the entire width of the wound dressing 100. The backing layer 220 (which may be, for example, a polyurethane membrane (e.g., Elastollan SP9109) with a pressure-sensitive adhesive on one side) is gas-impermeable, and this layer is thus used to cover the wound and seal the wound cavity over which the wound dressing is placed. In this way, an effective chamber is created between the backing layer 220 and the wound site, in which negative pressure can be established. For example, via adhesive or welding techniques, the backing layer 220 may preferably be sealed to the wound contact layer 222 in the boundary region surrounding the circumference of the dressing, ensuring that no air is drawn in through the boundary region. The backing layer 220 protects the wound from external bacterial contamination (bacterial barrier) and allows fluid from wound exudate to pass through this layer and evaporate from the outer surface of the membrane. The backing layer 220 preferably comprises two layers: a polyurethane membrane and an adhesive pattern dispersed on the membrane. The polyurethane membrane is preferably moisture-permeable and can be made of a material that has increased water permeability when wetted. In some embodiments, the moisture permeability of the backing layer increases as the backing layer becomes wet. The moisture permeability of the wet backing layer can be up to about ten times greater than that of the dry backing layer.

[0092] The area of ​​the absorbent layer 221 can be larger than the area of ​​the delivery layer 226, allowing the edges of the absorbent layer and delivery layer 226 to overlap, thereby ensuring that the delivery layer does not contact the backing layer 220. This provides an external channel for the absorbent layer 221, which directly contacts the wound contact layer 222, facilitating faster absorption of exudate into the absorbent layer. Furthermore, this channel ensures that no fluid can accumulate around the periphery of the wound cavity, which could otherwise permeate the seal around the dressing, leading to leakage. Figure 2C As shown, the absorbent layer 221 may define a periphery smaller than that of the backing layer 220, such that the boundary or border region is defined between the edge of the absorbent layer 221 and the edge of the backing layer 220.

[0093] like Figure 2C As shown, one embodiment of the wound dressing 100 includes an aperture 228 in an absorbent layer 221 located below the fluid connector 110. In use, for example when negative pressure is applied to the dressing 100, the wound-facing portion of the fluid connector can thus contact the delivery layer 226, which thus helps to deliver negative pressure to the wound site even when the absorbent layer 221 is filled with wound fluid. Some embodiments may have the backing layer 220 at least partially adhered to the delivery layer 226. In some embodiments, the aperture 228 is at least 1-2 mm larger in diameter than the wound-facing portion or the aperture 227 of the fluid connector 110.

[0094] In particular, for embodiments with a single fluid connector 110 and a through-hole, the fluid connector 110 and the through-hole can preferably be located in an eccentric position, such as... Figure 2B As shown in the diagram. This position allows the dressing 100 to be positioned on the patient such that the fluid connector 110 is raised relative to the rest of the dressing 100. This positioning makes it less likely that the fluid connector 110 and the filter 214 will come into contact with wound fluid that could prematurely block the filter 214, thereby impairing the delivery of negative pressure to the wound site.

[0095] Similar to the wound dressing embodiments described above, some wound dressings include a perforated wound contact layer with a silicone adhesive on the skin contact surface and an acrylic adhesive on the reverse side. In some embodiments, the wound contact layer may be made of polyurethane, polyethylene, or polyester. A transport layer is located above this boundary layer. An absorbent layer is located above the transport layer. The absorbent layer may include a superabsorbent nonwoven (NW) pad. The absorbent layer may extend approximately 5 mm beyond the transport layer at its periphery. The absorbent layer may have an opening or through-hole facing one end. The opening may be approximately 10 mm in diameter. A backing layer is located on the transport layer and the absorbent layer. The backing layer may be a high moisture permeability (MVTR) membrane coated with a pattern of acrylic adhesive. The high MVTR membrane and the wound contact layer encapsulate the transport layer and the absorbent layer, creating a peripheral boundary of approximately 20 mm. The backing layer may have a 10 mm opening, which is overlaid with the opening in the absorbent layer. A fluid connector can be bonded to a fluid connector comprising a semi-permeable membrane (SPM) that is impermeable to liquids but permeable to gases and covers the aforementioned orifice.

[0096] Figure 2D An implementation scheme for a wound dressing, which is similar to... Figures 2A to 2C Wound dressing. (Reference) Figure 2D The masking layer or shielding layer 2107 may be located below at least a portion of the backing layer 2140. In some embodiments, the shielding layer 2107 may have any of the same features, materials, or other details as any other embodiment of the shielding layer disclosed herein, including, but not limited to, having any viewing window or opening. Examples of wound dressings with shielding layers and viewing windows are described in International Patent Publication WO2014 / 020440, the entire contents of which are incorporated herein by reference. Additionally, the shielding layer 2107 may be positioned adjacent to the backing layer, or it may be positioned adjacent to any other desired dressing layer. In some embodiments, the shielding layer 2107 may be adhered to or integrally formed with the backing layer. Preferably, the shielding layer 2107 is configured to have substantially the same size and shape as the absorbent layer 2110 in order to cover the absorbent layer. Therefore, in these embodiments, the area of ​​the shielding layer 2107 will be smaller than the area of ​​the backing layer 2140.

[0097] Preferably, the absorbent layer 2110 and the shielding layer 2107 include at least one through-hole 2145 located below the port 2150. Of course, the corresponding holes through these different layers 2107, 2140, and 2110 can have different dimensions relative to each other. Figure 2D As shown, a single through-hole can be used to create an opening located below port 2150. In some embodiments, the port can utilize, for example... Figure 2C The fluid connectors depicted herein can be used in place of or in combination with them. It will be appreciated that multiple openings can be used alternatively. Additionally, if more than one port is used according to certain embodiments of this disclosure, one or more openings can be created in the absorption layer and shielding layer registered to each respective port. Although not essential for certain embodiments of this disclosure, the use of through-holes in the superabsorption layer can provide fluid flow paths, which remain unobstructed, particularly when the absorption layer 2110 is near saturation.

[0098] An orifice or through-hole 2144 may be provided in the absorbent layer 2110 and the shielding layer 2107 below the orifice 2144, such that the orifice is directly connected to the transport layer 2105. This allows negative pressure applied to port 2150 to be transmitted to the transport layer 2105 without passing through the absorbent layer 2110. This ensures that negative pressure applied to the wound site is not suppressed by the absorbent layer as it absorbs wound exudate. In other embodiments, the orifice may not be provided in the absorbent layer 2110 and / or the shielding layer 2107, or alternatively, multiple orifices may be provided below the orifice 2144.

[0099] In some embodiments, the masking layer 2107 can help reduce the unsightly appearance of the dressing during use by using a material that partially masks or covers the surface of the dressing. In one embodiment, the masking layer 2107 only partially masks the dressing to allow clinicians to obtain the information they need by observing the spread of exudate on the dressing surface. The partially masking nature of this embodiment of the masking layer allows skilled clinicians to perceive the different colors caused by exudate, blood, byproducts, etc., in the dressing, thus allowing for visual assessment and monitoring of the extent of diffusion on the dressing. However, since the color change of the dressing from its clean state to its state containing exudate is only slight, patients are unlikely to notice any aesthetic difference. The visual indication of reduced or eliminated wound exudate in a patient's wound can have a positive impact on their health, such as reducing stress.

[0100] In some embodiments, the masking layer may be formed of a nonwoven fabric (e.g., polypropylene) and may be thermally bonded using a diamond pattern with 19% bond area. In various embodiments, the masking layer may be hydrophobic or hydrophilic. Depending on the application, in some embodiments, a hydrophilic masking layer may provide increased moisture permeability. However, in some embodiments, a hydrophobic masking layer may still provide sufficient moisture permeability (i.e., through appropriate material selection and masking layer thickness) while also allowing dyes or pigments to be better retained within the masking layer. Thus, dyes or pigments can be trapped beneath the masking layer. In some embodiments, this may allow the masking layer to be colored in a lighter color or white. In a preferred embodiment, the masking layer is hydrophobic. In some embodiments, the masking layer material may be sterilized using ethylene oxide. Other embodiments may be sterilized using gamma irradiation, electron beam, steam, or other alternative sterilization methods. Additionally, in various embodiments, the masking layer may be colored or dyed, for example, with medical blue. The masking layer may also consist of multiple layers, including colored layers laminated or fused to a stronger uncolored layer. Preferably, the masking layer is odorless and exhibits minimal fiber shedding.

[0101] Multi-layer dressings used without negative pressure

[0102] Figures 3A to 3D Various embodiments of wound dressing 500 are shown, which can be used to heal wounds without negative pressure. Figure 3E It shows Figures 3A to 3D The cross-section of the wound dressing. For example... Figures 3A to 3E As shown in the dressing, the wound dressing can have a similar appearance to the reference. Figures 2A to 2D The described dressing has multiple layers, in addition to Figures 3A to 3E The dressing does not include ports or fluid connectors. Figures 3A to 3E The wound dressing may include a covering layer 501 as described herein and an optional wound contact layer 505. In some embodiments, the covering layer 501 may be permeable to moisture and / or air. The wound dressing may include various layers located between the wound contact layer 505 and the covering layer 501. For example, the dressing may include one or more absorbent layers or one or more delivery layers, as referenced herein. Figures 2A to 2D As described.

[0103] like Figures 3A to 3EAs shown, dressing 500 may include a perforated wound contact layer 505 and a top membrane 501. Additional components of the wound dressing 500 include a suitably sized foam layer 504, such as a polyurethane hydrocellular foam layer, to cover a wound of a recommended size corresponding to the selected specific dressing size. An optional activated carbon cloth layer (not shown) of similar or slightly smaller size than layer 504 may be provided to allow odor control. An absorbent layer 502, such as a layer of superabsorbent airflow mesh material containing cellulose fibers and superabsorbent polyacrylate particles, is disposed above layer 504, having a size slightly larger than layer 504, and allowing superabsorbent material overlap and serving as leak prevention. A masking or shielding layer 503, such as a three-dimensionally woven spacer fabric layer, is disposed above layer 502 to provide protection against pressure while allowing partial masking of the top surface of the superabsorbent that will retain colored exudate. In this embodiment, this layer is smaller (in the plan view) than layer 502 to allow the edges of the absorbent layer to be visible, which can be used by a clinician to assess whether dressing replacement is necessary.

[0104] Wound dressing 500 may incorporate or include one or more nitric oxide generating layers (e.g., nitrite delivery layers, acidic group providing layers) as described elsewhere in this section. Those skilled in the art will understand that wound dressing 500 may incorporate any of the one or more nitric oxide generating layers disclosed herein or elsewhere in the specification. Those skilled in the art will also understand that one or more nitric oxide generating layers may be incorporated as an integral component layer or part of a component layer. In some embodiments, the nitric oxide generating layers may be disposed below the covering layer 501. In some embodiments, one or more nitric oxide generating layers may be disposed above the wound contact layer 505. In some embodiments, dressing 500 may not include the wound contact layer 505, such that one of the nitric oxide generating layers may be the bottommost layer and configured to contact the wound surface. In some embodiments, one or more nitric oxide generating layers may be disposed below the foam layer 504. In embodiments, one or more nitric oxide generating layers may replace the foam layer 504. In some embodiments, dressing 500 may consist only of the covering layer 501 and one or more nitric oxide generating layers. In some embodiments, one or more nitric oxide generating layers or components thereof (e.g., nitrite providing layers as described herein) may be separate from the wound dressing 500. For example, one or more nitric oxide generating layers or components thereof may be configured as separate layers that can be placed on a wound, and the wound dressing 500 may be placed on top of them.

[0105] As previously described herein, one or more nitric oxide generating layers may be incorporated into or used with commercially available dressings such as ALLEVYN™ Foam, ALLEVYN™ Life, ALLEVYN™ Adhesive, ALLEVYN™ GentleBorder, ALLEVYN™ Gentle, ALLEVYN™ Ag Gentle Border, ALLEVYN™ Ag Gentle, and OpsitePost-Op Visible. In some embodiments, wound dressing 500 may include a covering layer 501, a wound contact layer 505, and a nitric oxide generating layer sandwiched therebetween. In some embodiments, wound dressing 500 may include a covering layer 501, an absorbent layer 502, a nitric oxide generating layer beneath the absorbent layer 502, and a wound contact layer 505.

[0106] Further details regarding wound dressings that may be used in conjunction with or as a supplement to the embodiments described herein can be found in U.S. Patent No. 9,877,872, entitled “WOUND DRESSING AND METHOD OFTREATMENT,” published January 30, 2018, the entire contents of which are incorporated herein by reference, including further details relating to embodiments of wound dressings, components and principles of wound dressings, and materials used in wound dressings.

[0107] Multi-layer wound dressing with integrated negative pressure source

[0108] In some implementations, the negative pressure source (such as a pump) and some or all other components of the TNP system (such as power supplies, sensors, connectors, user interface components such as buttons, switches, speakers, screens, etc.) can be integrated with wound dressings (such as those described above). Figures 1 to 3D The described dressing is integrated together. Additionally, some embodiments relating to wound treatment, including the wound dressing described herein, can also be used in combination with or in conjunction with embodiments described in the following applications: International Application WO 2016 / 174048, filed March 6, 2017, entitled “WOUND TREATMENT APPARATUSES AND METHODS WITH NEGATIVE PRESSURE SOURCEINTEGRATED INTO THE WOUND DRESSING”, and International Patent Application PCT / EP2017 / 055225, the disclosures of which are hereby incorporated herein by reference in their entirety, including further details relating to embodiments of the wound dressing, wound dressing components and principles, and materials used in the wound dressing and wound dressing components.

[0109] In some implementations, the pump and / or other electronic components may be configured to be positioned adjacent to or close to the absorbent and / or transport layers in the wound dressing, such that the pump and / or other electronic components remain part of a single device to be applied to the patient, wherein the pump and / or other electronic components are positioned away from the wound site.

[0110] Nitric oxide generation layer

[0111] Figures 4 to 5 A wound dressing 12000 including a nitric oxide generating layer is illustrated according to some embodiments. In the illustrated embodiment, the wound dressing 12000 may include a covering layer 12200, an activator layer 12400, and a nitric oxide source layer 12600. In some embodiments, the wound dressing 12000 may include additional layers as further described herein. Those skilled in the art will understand that although the various segments of the dressing may be referred to as “layers,” such segments may have other suitable shapes or configurations. As those skilled in the art will understand, the wound dressing and / or nitric oxide delivery embodiments described in this section or elsewhere in the specification may be applied over and / or over the skin surrounding a wound, such as over the peri-wound area.

[0112] The covering layer 12200 may be gas-impermeable but water vapor-permeable, and may extend across the entire width of the wound dressing 12000. The covering layer 12200 (which may be, for example, a polyurethane membrane (e.g., Elastollan SP9109 or Elastollan SP806) with a pressure-sensitive adhesive on one side) may be gas-impermeable, and this layer can therefore be used to cover the wound and seal the wound cavity over which the wound dressing is placed. Thus, a chamber or sealed wound space is created between the covering layer 12200 and the wound site. In some embodiments, negative pressure may be established within the chamber or sealed wound space created between the covering layer 12200 and the wound site. The covering layer 12200 protects the wound from external bacterial contamination (bacterial barrier) and allows fluid from wound exudate to pass through this layer and evaporate from the outer surface of the membrane. The covering layer 12200 may comprise two or more layers, for example, a polyurethane membrane and an adhesive pattern dispersed onto the membrane. In some instances, the polyurethane membrane may be moisture-permeable and may be made of a material that has increased permeability when wetted. In some embodiments, the moisture permeability of the covering increases as the covering becomes wet. The moisture permeability of a wet covering may be up to about ten times greater than that of a dry covering. In some embodiments, the covering 12200 may be replaced or supplemented with an additional wound dressing described elsewhere herein, such that the additional wound dressing is positioned above the nitric oxide generating layer. The covering may also be rainproof, such that a dressing with this covering can be used in the shower. The covering may be configured such that nitric oxide does not immediately escape through the covering, meaning the covering is nitric oxide impermeable or semi-impermeable, thereby trapping nitric oxide in the tissue so that nitric oxide can interact with the user's body. Those skilled in the art will understand that the covering can be made to be both vapor-permeable and nitric oxide impermeable.

[0113] The nitric oxide source layer 12600 can provide one or more nitric oxide releasing agents at the wound site. The nitric oxide releasing agent can include any chemical entity that, when activated or otherwise stimulated, will generate nitric oxide at the wound site. In some embodiments, the nitric oxide releasing agent can include nitrite ions, nitrites, organic and inorganic nitrites, or any pharmacologically acceptable source of nitrite, such that the nitrite ions can be reduced at the wound site to generate nitric oxide. For example, the nitric oxide source layer 12600 and / or elements can comprise one or more of ammonium nitrite, lithium nitrite, calcium nitrite, sodium nitrite, and potassium nitrite. In some embodiments, the nitric oxide source layer can be a suitable material layer or element comprising alkali metal nitrites and / or alkaline earth metal nitrites. In some embodiments, the nitrite may include: LiNO2, NaNO2, KNO2, RbNO2, CsNO2, FrNO2, Be(NO2)2, Mg(NO2)2, Ca(NO2)2, Sr(NO2)2, Ba(NO2)2, Ra(NO2)2, or any other suitable nitrite. In some embodiments, a precursor of the nitrite ion, such as nitrite, nitrate ion, nitroprusside ion, or any pharmacologically acceptable salt thereof, may be used as a source of nitrite. In some embodiments, the nitric oxide releasing agent may include nitrites such as nitro-functionalized compounds. For example, nitric oxide releasers may include nitroglycerin, isoamyl nitrite, isosorbide mononitrate, N-(ethoxycarbonyl)-3-(4-morpholinyl)silyl ketone imine; 3-morpholinosilyl ketone imine; 1,2,3,4-oxatriazolium 5-amino-3-(3,4-di-chlorophenyl)-chloride; 1,2,3,4-oxatriazolium 5-amino-3-(chloro-2-methyl-phenyl)-chloride; 1,2,3,4-oxatriazolium 3-(3-chloro-2-methyl)-chloride. Phenyl)-5-[[[cyanomethylamino]carbonyl]amino]-hydroxide inner salt; S-nitroso-N-acetyl-(D,L)-penicillamine; l-[(4',5'-bis(carboxymethoxy)-2l-nitrophenyl)methoxy]-2-oxo-3,3,diethyl-l-triazine dipotassium salt; and [l-(4',5'-bis(carboxymethoxy)-2'-nitrophenyl)methoxy]-2-oxo-3,3-diethyl-1-triazine diacetoxymethyl ester.

[0114] In some embodiments, the nitric oxide releasing agent of the nitric oxide source layer 12600 may include a diol diazepine ononium salt, including O-alkylated diol diazepine ononium salt, O-derived diol diazepine ononium salt, and non-O-derived diol diazepine ononium salt. For example, the nitric oxide releasing agent may include diethylamine / NO, V-PYRRO / NO, and / or spermine / NO. In some embodiments, the nitric oxide releasing agent of the nitric oxide source layer 12600 may include S-nitrosothiols, such as S-nitro-glutathione, S-nitroso-N-acetylcysteine, and S-nitroso-acetylpenicillamine. In some embodiments, the nitric oxide releasing agent of the nitric oxide source layer 12600 may include silica or silica nanoparticles modified with nitric oxide. In some embodiments, the nitric oxide releasing agent may be a polymer modified with nitric oxide to include nitric oxide. For example, nitric oxide can be used to modify polyethyleneimine, polypropyleneimine, polybuteneimine, polyurethane, or polyamide to form diol diazepine onium salts. In some embodiments, the nitric oxide source layer 12600 can be constructed from such nitric oxide-modified polymers. Other examples of nitric oxide releasers are provided in International Publication No. WO 2006 / 058318 and Liang et al., “Nitric oxide generating / releasing materials”, FutureScience OA, 1 (1) (2015), both of which are incorporated herein by reference in their entirety.

[0115] In some embodiments, the nitric oxide source layer 12600 may comprise a nitric oxide releasing agent (e.g., sodium nitrite) in an aqueous solution. For example, the nitric oxide source layer 12600 may comprise a material that absorbs the nitric oxide releasing agent (e.g., sodium nitrite) solution. In some embodiments, the nitric oxide source layer 12600 may comprise a dry nitric oxide releasing agent (e.g., sodium nitrite) in solid form.

[0116] The nitric oxide source layer 12600 may comprise a mesh, foam, gel, or any other material suitable for containing a nitric oxide releasing agent. For example, the nitric oxide source layer 12600 may comprise a mesh that absorbs a solution of a nitric oxide releasing agent (e.g., sodium nitrite). The mesh may be knitted, woven, or nonwoven. The mesh may be made of a polymeric material, such as viscose fiber, polyamide, polyester, polypropylene, or combinations thereof. In some embodiments, the nitric oxide source layer 12600 may comprise polypropylene, polyester, polyurethane, polyvinyl chloride, polyamide, viscose fiber, polyester, polypropylene, and / or cellulose. As described herein, the nitric oxide source layer 12600 may be composed of one or more polymers modified with nitric oxide. The nitric oxide source layer 12600 may also be made of a hydrogel without acidic groups to prevent reaction with nitrite ions to release nitric oxide. In some embodiments, the nitric oxide source layer 12600 may be made of a colored material, making it visible to aid in the positioning of the wound dressing 12000 during application to the wound and reducing the risk of incomplete removal of the nitric oxide source layer 12600 from the wound after treatment. The nitric oxide source layer 12600 may be fully or partially permeable to the diffusion of nitric oxide.

[0117] In some embodiments, the nitric oxide source layer 12600 is the bottom layer of the dressing 12000, allowing the nitric oxide source layer 12600 to contact the wound. In some embodiments, the nitric oxide source layer 12600 may be positioned within and / or above the wound. The nitric oxide source layer may be configured such that the nitric oxide source layer 12600 is substantially non-adhesive to the skin or wound, or does not damage the wound upon contact with it. In some embodiments, the dressing 12000 may include one or more layers below the nitric oxide source layer 12600, such as a wound contact layer. In some embodiments, the wound dressing 12000 may include two or more nitric oxide source layers. For example, the wound dressing 12000 may include 2, 3, 4, 5, 6, 7, or more nitric oxide source layers. In some embodiments, the nitrite providing layer 12600 may be separate from the wound dressing 12000. For example, the nitrite-providing layer 12600 can be configured as a separate layer that can be placed on a wound, and the wound dressing 12000 can be placed on it. A nitric oxide releaser can be incorporated into the nitrite-providing layer to provide a nitrite dose (e.g., a sodium nitrite dose) of about: 0.01 to 5.0, 0.5 to 4.5, 1.0 to 3.0, 1.0 to 2.0, and / or 1.0 to 1.5, in units of M (moles). For example, the dose can be about 0.50 M, about 0.01 M, about 1.5 M, about 2 M, or about 2.5 M.

[0118] The activator layer 12400 may contain chemical reagents, functional groups, or portions that can activate and / or promote the release of nitric oxide from the nitric oxide releaser. For example, a proton or acidic environment promotes the reduction of nitrite to nitric oxide, and the activator layer 12400 may include acidic groups or portions that can provide protons in an aqueous environment, thereby lowering the pH at the application site. In some embodiments, the acidic groups or portions are fixed at the activator layer 12400, for example, fixed on the surface of the activator layer 12400. The acidic groups or portions may be covalently bonded at the activator layer 12400. In some embodiments, the activator layer 12400 may comprise an acidic solution. The activator layer 12400 may comprise a mesh, foam, gel, or any other material suitable for containing acidic groups or portions. In embodiments, the activator layer 12400 is positioned above the nitric oxide source layer 12600, or the activator layer 12400 may be positioned below the nitric oxide source layer 12600. In some embodiments, the activator layer 12400 may comprise a proton source such as water, methanol, ethanol, propanol, butanol, pentanol, hexanol, phenol, naphthol, or a polyol; an aqueous acid buffer such as a phosphate, succinate, carbonate, acetate, formate, propionate, butyrate, fatty acid, amino acid, or ascorbic acid; or any suitable enzyme compound or catalytic compound. In some embodiments, bodily fluids such as blood, lymph, bile, or wound exudate may act as activators and may assist the activator layer 12400. In some embodiments, the wound dressing 12000 may not include the activator layer 12400, and wound fluid or wound exudate may act as an activator. Other examples of activators for nitric oxide releasing agents are provided in International Publication No. WO 2006 / 058318 and “Nitric oxide generating / releasing materials” by Liang et al., Future Science OA, 1 (1) (2015), both of which are incorporated herein by reference in their entirety.

[0119] In some embodiments, the wound dressing 12000 may include two or more nitric oxide source layers and / or two or more activator layers. For example, the wound dressing 12000 may include 2, 3, 4, 5, 6, 7 or more nitric oxide source layers and / or activator layers.

[0120] In some embodiments, the activator layer 12400 comprises a hydrogel, such that the activator layer 12400 can absorb wound exudate. In some instances, the activator layer 12400 may be composed of a dry gel. The activator layer 12400 may be composed of any suitable material disclosed herein. The gel of the activator layer 12400 may be presented in different physical forms. For example, the activator layer 12400 may foam during curing. The hydrogel may be poured into a foam and then cured within the foam. In some embodiments, the activator layer 12400 may be perforated through its thickness. The size of the perforation may be set to allow fluid absorption and allow the release of a required therapeutic dose of nitric oxide from the wound dressing. For example, the perforation may have a diameter set to approximately between 0.1 mm and 10 mm, between 0.15 mm and 7 mm, between 0.2 mm and 5 mm, between 0.5 mm and 4 mm, or between 0.7 mm and 3 mm. The perforation may have a circular shape, a square shape, a triangular shape, or any other suitable shape. Foamed structures and / or perforations can enhance the fluid handling capabilities of the activator layer.

[0121] In some embodiments, the activator material for the activator layer may be provided as a dispensable composition, such as as a prepolymer solution or in other extensible form, rather than as an activator layer such as Activator Layer 12400, allowing for more flexible application over and / or around the wound. For example, the activator material may be provided as a gel prepolymer solution, allowing for close application by a clinician to wounds or the area surrounding them with irregular shapes and sizes. In some embodiments, the activator material, such as a gel prepolymer solution, may be provided in and / or applied with a syringe, and the gel prepolymer solution may have a viscosity suitable for dispensing from the syringe. The activator material may also be formulated such that it can cure rapidly and no longer flow once applied to or around the wound. The activator material may include an evaporating solvent, such as isopropanol. The activator material may have a suitable second curing mechanism, such as a photoinitiating acrylate functional group. In some embodiments, the activator material may be provided as a reactive two-part system. For example, a first and a second part may be provided to be mixed immediately before dispensing to produce a polymer. In some embodiments, the first and second portions may be flowable gels with opposite charges, such that they can interact upon mixing to provide a substantially non-flowing gel. In some embodiments, the activator material may include a material that changes in response to environmental changes, such as a gel. For example, the activator material may include materials such as certain pluronics, such that it can be cured upon application to the skin from a dispenser or syringe once the temperature changes. The activator material may be applied such that it can interact with nitrite from the nitric oxide source layer 12600 (which can provide nitrite) to generate nitric oxide. Once the activator material has been applied and cured or no longer flows in any other way, the covering layer 18200 may be applied.

[0122] Once the dressing 12000 is activated, for example by placing the activator layer 12400 in contact with the nitric oxide source layer 12600, a nitric oxide releaser from the nitric oxide source layer 12600 releases nitric oxide. For example, in some embodiments, nitrite can be reduced to nitric oxide in the presence of an acidic environment provided by the activator layer 12400, as follows:

[0123]

[0124]

[0125]

[0126] The activator layer 12400 and the nitric oxide source layer 12600 may be positioned such that the nitric oxide releaser can react to provide nitric oxide. For example, the activator layer 12400 and the nitric oxide source layer 12600 may be in contact with each other within the dressing 12000 during use. In some embodiments, one or more additional layers may be positioned between the activator layer 12400 and the nitric oxide source layer 12600. In some embodiments, the activator layer 12400 and the nitric oxide source layer 12600 may be fluidly isolated from each other to prevent premature release of nitric oxide before the dressing 12000 is applied to a patient. For example, the nitric oxide source layer 12600 may be disposed in a separate package from the rest of the dressing 12000. Once the dressing 12000 is activated, the nitric oxide releaser from the nitric oxide source layer 12600 may be dispersed within the dressing 12000. In some embodiments, the nitric oxide releaser can be dissolved in wound exudate, and the wound exudate can promote the dispersion of the nitric oxide releaser. In the presence of the activator in the activator layer 12400, at least a portion of the nitric oxide releaser will react to release nitric oxide. The generated nitric oxide can diffuse into the wound or be delivered to the wound via any suitable mechanism. In some embodiments, the generated nitric oxide may not be delivered immediately or at all, but may be retained within a dressing, for example, through a selectively permeable membrane, such that the nitric oxide can prevent the growth of microorganisms within the dressing or kill microorganisms within the dressing.

[0127] In some embodiments, wound dressing 12000 may include a reducing agent to promote the reduction of a nitric oxide releasing agent (e.g., nitrite ions) to nitric oxide. Physiologically acceptable examples of such reducing agents include, but are not limited to: iodide anions, ascorbic acid, ascorbate (e.g., sodium ascorbate), isoascorbate (e.g., sodium isoascorbate), hydroquinone, butylated quinone, tocopherol, butylated hydroquinone, hydroquinone variants, butylated hydroxyanisole, butylated hydroxytoluene, β-carotene, potassium iodide, ascorbate variants, isoascorbate variants, any other suitable reducing agent, and / or any of the antioxidants and / or reducing agents described herein. The reducing agent may be included in one or more layers of wound dressing 12000. For example, the reducing agent may be included in covering layer 12200, activator layer 12400, nitric oxide source layer 12600, wound contact layer 12800, and / or any suitable layer of the nitric oxide generating wound dressing described herein. The reducing agent can be incorporated into one or more layers, for example, by physical embedding, physical blending, coating, covalent bonding, or any other suitable method. The reducing agent can be incorporated into the dressing and / or suitable layers such as hydrogel activating layers at a w / w% of about: 0.01 to 5.0%, 0.1 to 4.5%, 1.0 to 3.0%, 1.0 to 1.5%, and / or 1.5 to 2.5%. For example, the w / w% can be about 0.02%, about 0.03%, about 0.8%, about 1.2%, about 1.4%, or about 2.43%. Higher levels of reducing agent may lead to increased nitric oxide production; however, very high levels of reducing agent may become toxic.

[0128] As described herein, the nitric oxide source layer may include nitrite and may be referred to herein as a nitrite delivery layer or a nitrite providing layer. As described herein, the activator layer may include an acid and may be referred to herein as an acid providing layer or an acid delivery layer. The nitric oxide source layer / nitrite delivery layer / nitrite providing layer and the activator layer / acid providing layer may be collectively referred to herein or individually as (a plurality of) nitric oxide generating layers. As those skilled in the art will understand, the nitrite providing layer disclosed herein may be prepared and provided separately from wound dressings. For example, the nitrite providing layer may be applied to a wound, and the wound dressing may be applied over the nitrite providing layer.

[0129] Nitric oxide dressing materials and structure

[0130] As those skilled in the art will understand, the above regarding Figures 4 to 5The nitric oxide delivery dressing 1200 and the materials and dressing constructions described elsewhere in the specification may include a variety of suitable constructions and different types of materials. For example, the topmost layer furthest from the wound may be a top membrane or covering membrane, such as the top or covering layers disclosed herein, such as polyurethane materials. This top membrane or covering membrane may be constructed from the materials used in the covering layers of RENASYS drapes sold by Smith + Nephew. For example, in some embodiments, the covering layer may be an IV3000 top membrane. Below the top membrane or covering membrane may be a masking layer or fabric layer, which may be constructed from any suitable material disclosed herein as a masking layer or fabric layer. The masking layer may be constructed from stretched and unstretched polyester, polyethylene, polypropylene, polypropylene, and nonwoven fabrics and suitable blends thereof. For example, in some embodiments, the masking layer may be a 17 gsm polypropylene masking layer. Other suitable nonwoven fabrics and blends may also be utilized. In some embodiments, the masking layer may be foam. Below the masking layer or fabric layer is an activator layer, which is similar to the activator layers described herein and throughout the specification. Such activator layers can be composed of hydrogel adhesives and optionally include a central polyester support mesh and / or a support release liner. For example, in some embodiments, the activator layer can be in the form of a DURAFIBER loaded with hydrogel as described herein. In such an example, depending on the dressing size, an equivalent of about 6 grams of hydrogel can be loaded onto a 10.8 cm × 10.8 cm DURAFIBER sheet, which can be cut into 10 cm × 10 cm pieces, resulting in approximately 5.14 grams of hydrogel on a 10 cm × 10 cm DURAFIBER sheet. The activator layer can be composed of any suitable hydrogel material disclosed herein, such as acrylic hydrogels and / or sulfonic acid hydrogels. Below the activator layer may be a collection and distribution layer, which can be composed of materials described herein (such as those described in relation to...). Figures 2C to 2D The collection distribution layer may be composed of any suitable material disclosed herein (such as those used in Smith + Nephew's Acticoat Flex), for example, 3-D knitted fabric, gauze, and / or stretched polyester fibers woven into a web, similar to the materials used in Smith + Nephew's Acticoat Flex, but silver is optional. In some embodiments, the collection distribution layer may be composed of a mixture of a prepolymer solution with water, a surfactant, and polyethylene glycol (such as the foam used by Smith + Nephew in Allevyn foams). The masking layer and the collection distribution layer may use the same materials and are interchangeable. In some embodiments, the collection distribution layer may be pressed into and / or cured into the activator layer. Curing the collection distribution layer into the activator layer can increase the rate of nitric oxide formation due to faster delivery. Below the collection distribution layer, a material that can be made of materials disclosed herein (such as those used in the context of...) may be present. Figures 2C to 2DThe wound contact layer may be made of any suitable material disclosed herein. For example, the wound contact layer may include silicone adhesives and perforated polyurethane membranes. The wound contact layer may include acrylic adhesives. A nitric oxide source layer (such as a nitrite layer) made of any suitable material disclosed herein may be positioned below the wound contact layer such that the nitric oxide source layer directly abuts the wound or other tissue. In some embodiments, the nitric oxide source layer may be in other locations, such as above the activator layer and / or elsewhere in the dressing. For example, in some embodiments, the nitrite delivery layer may be a separate 17 gsm polypropylene mesh saturated with sodium nitrite solution. In some embodiments, the ALLEVYN or PICO dressing disclosed in Figures 2 and 3 may be placed directly above the activator layer and the underlying nitric oxide source layer. Placing the nitric oxide source layer directly abuts the wound, the peri-wound area, and / or other tissue may allow for increased direct release of nitric oxide into the tissue. As those skilled in the art will understand, the wound dressing and / or nitric oxide delivery embodiments described in this section or elsewhere in the specification may be applied above the wound and / or the surrounding skin, such as above the peri-wound area.

[0131] Chemiluminescence

[0132] Figure 6 The following are examples of nitric oxide delivery dressings used for testing (such as those mentioned above). Figure 4 and Figure 5 An example setup 600 of the chemiluminescence scheme disclosed herein. This setup may include a sample 602, a desiccant 604, an atmospheric air source 606, a chemiluminescence detector 608, a nitrogen supply source 610, an air pump 612, a mass flow meter 614, and a T-connector 616. In some embodiments, a ThermoFisher 42i-HL detector may be used as the chemiluminescence detector 608. After preheating the equipment with an airflow at atmospheric pressure, the sample chamber 602 and the nitrogen source can be connected to the equipment. The nitrogen flow rate via the mass flow controller can be set to a suitable value, such as between approximately: 1 to 100, 10 to 90, 25 to 75, 40 to 60 mL / min, or approximately 50 mL / min. After rinsing the system (e.g., approximately 1 to 60, 10 to 50, 20 to 40, or approximately 30 minutes), a nitric oxide source layer (such as a nitrite mesh) and an activator layer (such as a hydrogel providing acid) can be placed in the sample chamber 602. In some embodiments, the total area of ​​the nitrite mesh is smaller than that of the activator layer. In specific embodiments, the nitric oxide source layer and / or activator layer may have a length and / or width of about 0.5 to 20, 1 to 10, 2 to 8, or about 4 to 6 cm. In some embodiments, the nitric oxide source layer may be 2.5 cm × 2.5 cm, while the activator layer is 3 cm × 3 cm.

[0133] NO / NO2 release concentration can be measured at an appropriate rate using a chemiluminescence detector, checked in ppb or ppm, and monitored periodically, such as approximately every 1 second, every 2 seconds, every 5 seconds, every 10 seconds, every 30 seconds, every 60 seconds, or every 90 seconds. In some implementations, NO / NO2 concentration can be checked in ppm.

[0134] As those skilled in the art will understand, regarding the dressings disclosed herein, such as those concerning... Figures 4 to 5 The described dressings are intended to maximize NO over NO2. While nitrogen dioxide (NO2) may exert antimicrobial properties, it does not possess vasodilatory properties or the ability to activate cell proliferation. Therefore, it is generally desirable to minimize NO2 generation during nitrite acidification, such as by reducing the oxidation of dissolved nitric oxide (NO) through means such as removing oxygen from the hydrogel matrix where nitrite acidification occurs. The nitric oxide delivery dressings disclosed herein may generate both NO and NO2 simultaneously. In some embodiments, the nitric oxide dressings disclosed herein may generate both NO and NO2 at NO / NO2 ratios such as about 0.5:1 to 500:1, 1:1 to 400:1, 10:1 to 300:1, 20:1 to 200:1, or 50:1 to 100:1. For example, the ratio can be about or at least about 0.5:1, 1.01:1, 1.1:1, 1:1, 2:1, 5:1, 10:1, 20:1, 30:1, 50:1, 100:1, 200:1 or 500:1.

[0135] Figure 7 An example of experimental setup 700 and subsequent results 750 are shown, demonstrating that under negative pressure, the combination of the activator layer and the nitric oxide source layer (similar to the one described above) can be generated. Figure 4 and Figure 5 The described dressing delivers nitric oxide. Figure 7 As shown, the negative pressure wound therapy pump 702 is connected to the negative pressure wound therapy dressing 704, such as those described herein. Figures 2A to 2DAs described herein, the dressing is sealed above chamber 706 containing a nitrite test solution 708, which changes color in the presence of NO. The test solution does not change color 750 before negative pressure is applied. After running the negative pressure for a period of time to ensure no background color change occurs as shown in 760, an activator layer 710 (such as a hydrogel providing an acid), as described herein, is placed in the chamber and negative pressure is applied. Again, no color change occurs 770. Finally, a nitric oxide source layer 712 (such as a sodium nitrite mesh), as described herein, is placed on top of the activator layer 780 without exposing the nitric oxide source layer to the nitrite test solution, and negative pressure is applied. After 15 minutes of negative pressure, the indicator solution changes color 790, indicating that the interaction between the activator layer and the nitric oxide layer can produce nitric oxide, even under negative pressure.

[0136] As those skilled in the art will understand, negative pressure can be applied to any of the nitric oxide delivery dressings disclosed herein, such as Figures 4 to 5 Dressings as described elsewhere in the instructions. Dressings, such as Figures 2A to 2D The dressing described herein can be placed above the activator layer and the nitric oxide source layer placed in the wound, thereby delivering nitric oxide to the wound while applying negative pressure wound therapy.

[0137] Figures 8A to 8C Examples of chemiluminescence experiments performed using a scheme similar to that described above are shown. As those skilled in the art will understand, the measurements performed in these experimental runs are merely exemplary, and the disclosure herein is not limited to such values. Figure 8A The test showed that... Figure 8A The experimental results for the dry sodium nitrate mesh arrangement shown in the figure are as follows: This arrangement includes a polyurethane overlay layer covered with a stretched polyester ADL layer, which sits above a hydrogel activator layer sandwiched between another stretched polyester ADL layer, which sits above the dry sodium nitrite mesh. In this experimental run, after the addition of DI water, the dry sodium nitrate mesh released approximately 550 ppm NO and 75 ppm NO2 at its peak at the 25-minute mark, and the concentrations slowly decreased to approximately 80 ppm NO and 10 ppm NO2 at the 50-minute mark.

[0138] Figure 8BExperimental results are shown when testing a full dressing design with pull-out tabs and a self-sealing boundary. The pull-out tabs are used to initially separate the nitric oxide source layer from the activator layer, so that when the tabs are removed and the dressing becomes wet, the interaction between the nitric oxide source layer and the activator layer produces nitric oxide. In this experimental run, after the addition of DI water, the full dressing design with pull-out tabs and a self-sealing boundary released approximately 84 ppm NO and 15 ppm NO2 at its peak at the 17-minute mark, with the concentrations slowly decreasing to approximately 25 ppm NO and 5 ppm NO2 at the 50-minute mark.

[0139] Figure 8C An example of experimental results for a dressing containing a biodegradable membrane is shown. Here, the biodegradable membrane is placed between an activator layer and a nitric oxide source layer, so that nitric oxide is generated once the biodegradable layer breaks down. In this experimental run, after the addition of DI water, the dressing containing the biodegradable membrane released approximately 1000 ppm NO and 45 ppm NO2 at its peak at the 25-minute mark, and the concentration slowly decreased to approximately 225 ppm NO and 20 ppm NO2 at the 50-minute mark. The same experimental protocol was also used to test an activator layer containing sodium isoascorbate. In this experimental run, after the addition of DI water, the activator layer containing sodium isoascorbate released approximately 52 ppm NO and 4 ppm NO2 at its first peak at the 80-minute mark, 66 ppm NO and 5 ppm NO2 at its second and largest peak at the 110-minute mark, and the concentration slowly decreased to approximately 45 ppm NO and 2 ppm NO2 at the 160-minute mark.

[0140] Figure 9 Examples of relative peak outputs in ppm for activator hydrogels (providing acid) with or without a collection distribution layer comprising various gsm (g / m³) are shown. 2 A polypropylene, polypropylene-ethylene, or stretched polyester collection distribution layer is used. Without a collection distribution layer, the peak NO and NO2 concentrations are approximately 55 ppm and 10 ppm, respectively; however, those skilled in the art will understand that a collection distribution layer can allow for improved fluid distribution and handling over a larger area, such as a dressing. With a 17 gsm polypropylene pressed collection distribution layer, the peak NO and NO2 concentrations are approximately 20 ppm and 2 ppm, respectively. With a 17 gsm polypropylene cured collection distribution layer, the peak NO and NO2 concentrations are approximately 40 ppm and 5 ppm, respectively. As explained above, a cured collection distribution layer can allow for increased fluid delivery and increased nitric oxide formation rate. With a 30 g / m polypropylene... 2When the distribution layer was compressed and collected, the peak NO and NO2 concentrations were approximately 40 ppm and 5 ppm, respectively. With polypropylene at 30 g / m³... 2 In the case of collecting the distribution layer, the peak NO and NO2 concentrations were approximately 40 ppm and 5 ppm, respectively. With polypropylene at 40 g / m³... 2 When the distribution layer was compressed and collected, the peak NO and NO2 concentrations were approximately 30 ppm and 2 ppm, respectively. With polypropylene at 40 g / m³... 2 With the solidified collection and distribution layer, the peak NO and NO2 concentrations were approximately 38 ppm and 5 ppm, respectively. (The text abruptly ends here, likely due to an incomplete sentence or missing information.) 2 When the distribution layer was compressed and collected, the peak NO and NO2 concentrations were approximately 35 ppm and 3 ppm, respectively. With 30 g / m³ of polypropylene / ethylene... 2 With a solidified collection and distribution layer, the peak NO and NO2 concentrations are approximately 35 ppm and 3 ppm, respectively. With a stretched polyester compression collection and distribution layer, the peak NO and NO2 concentrations are approximately 35 ppm and 3 ppm, respectively. With a FLEX compression collection and distribution layer, the peak NO and NO2 concentrations are approximately 55 ppm and 8 ppm, respectively.

[0141] Figures 10A to 10D Examples of NO and NO2 concentrations over time are shown in several embodiments, including an activator layer and a nitric oxide providing layer. For example... Figures 10A to 10B As shown, activator layers containing approximately 2%–3% sodium isoascorbate were tested with and without different collection distribution layers, either pressed or cured. Gel without a collection distribution layer produced (p-indicating peak) pNO = 785 ppm and pNO2 = 78 ppm. Activator layers with stretched polyester pressed into the gel produced pNO = 506 ppm and pNO2 = 24 ppm. For the case where stretched polyester was cured onto the activator layer, pNO = 625 ppm; pNO2 = 50 ppm. For the case where polypropylene was pressed into the gel, pNO = 508 ppm and pNO2 = 26 ppm. For the case where polypropylene was cured into the gel, pNO = 624 ppm and pNO2 = 26 ppm.

[0142] Figures 10C to 10DExamples of NO and NO2 concentrations over time in activator layers containing approximately 1%–2% sodium isoascorbate, with or without different collection distribution layers, are shown. An activator layer without ADL produces pNO = 334 ppm and pNO2 = 40 ppm. For the case where the stretched polyester collection distribution layer is pressed into the activator layer, pNO = 211 ppm and pNO2 = 10 ppm. For the case where the stretched polyester collection distribution layer is cured into the activator layer, pNO = 247 ppm and pNO2 = 14 ppm. For the case where the polypropylene collection distribution layer is pressed into the activator layer, pNO = 112 ppm and pNO2 = 5 ppm. For the case where the polypropylene collection distribution layer is cured into the activator layer, pNO = 184 ppm and pNO2 = 8 ppm. As explained elsewhere in this specification, curing the collection distribution layer into the activator layer can improve fluid handling and improve nitric oxide production relative to nitrogen dioxide production.

[0143] Dry gel and hydrogel structure

[0144] Reference may be made throughout the specification to the dry gel. The dry gel can be formed from a gel by drying it under unhindered shrinkage conditions. As those skilled in the art will understand, the dry gel is a gel with a very low free water content, so low that the reaction to form nitric oxide will occur very rarely without the addition of additional water and / or liquid. For example, the dry gel may be substantially anhydrous in its dry state. Drying can be accomplished by any suitable means known in the art (e.g., freeze-drying).

[0145] In some instances, the hydrogel (which can subsequently become a dry gel upon drying) can be produced with or without glycerol and can contain, as needed, a standard amount or two, three, or four times the required amount of the crosslinking agent PEG diacrylate. A solution of sodium 2-acrylamido-2-methyl-1-propanesulfonate may be present in the dry gel. Both the hydrogel and the dry gel can be produced by converting 2-acrylamido-2-methyl-1-propanesulfonic acid (SA) (as supplied, stabilized using MEHQ) to a sodium salt by dissolving it in water, then neutralizing it to pH 7.0 with 50% NaOH and cooling it in a 10°C water bath to form a solution of neutralizing acid (NaAMPS). The hydrogel may contain approximately 5.393 wt% of 2-acrylamido-2-methyl-1-propanesulfonic acid (equivalent to 1.0 SA), approximately 4.654 wt% of 2-acrylamido-2-methyl-1-propanesulfonic acid (equivalent to 0.85 SA), approximately 2.839 wt% of 2-acrylamido-2-methyl-1-propanesulfonic acid (equivalent to 0.5 SA), and / or approximately 1.457 wt% of 2-acrylamido-2-methyl-1-propanesulfonic acid (equivalent to 0.25 SA) to approximately 7.704 wt% of 2-acrylamido-2-methyl-1-propanesulfonic acid (equivalent to 1.5 SA). The hydrogel prepolymer can be prepared by pre-dispersing a 2-hydroxy-2-methylphenylacetone photoinitiator into PEG diacrylate under low light, followed by mixing with a 58% aqueous solution of sodium 2-acrylamido-2-methyl-1-propanesulfonate (Na AMPS), sodium isoascorbate, pre-ground 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS acid), and glycerol for 10-20 minutes. The AMPS acid can be completely dissolved in the stirred Na AMPS solution, followed by the slow addition of glycerol, and then the photoinitiator / diacrylate mixture in a water bath. In some embodiments, the hydrogel can also be prepared in a mold using twice the normal amount of photoinitiator / crosslinker and / or omitting glycerol and / or using three times the amount of the prepolymer mixture to form a gel with a thickness three times greater.

[0146] Using nitric oxide from sodium nitrite to produce dressings

[0147] Figures 11A to 11D Embodiments of nitric oxide-generating wound dressings with various layer arrangements are described. As those skilled in the art will understand, the nitrite-providing layer disclosed herein can be prepared and provided separately from the wound dressing. For example, the nitrite-providing layer can be applied to the wound, and the wound dressing can be applied over the nitrite-providing layer. Those skilled in the art will also understand that... Figures 11A to 11DThe various layers depicted herein can be arranged in any suitable order, and the order depicted in the figures is merely an example. In some embodiments, the uppermost layer may be a covering layer 13002, which may have any of the same features, materials, or other details as the covering layers disclosed herein, such as being composed of a membrane. The covering layer 13002 may be adapted to seal a dressing over a wound and is adapted to be connected to a negative pressure source and / or adapted to maintain negative pressure at the wound site. In some embodiments, the boundary region of the covering layer 13002 may be attached to the skin around the wound to form a seal, allowing wound exudate to be contained within the wound dressing 13000. Below the covering layer, a masking or shielding layer 13004 (referred to herein as a “masking layer”) may be present to prevent or limit the visualization of the wound or wound exudate through the covering layer 13002. The masking layer 13004 may be located below at least a portion of the covering layer 13002. In some embodiments, the masking layer 13004 may have any of the same features, materials, or other details as any other embodiment of the masking layer disclosed herein, including but not limited to having any viewing windows or holes. Examples of wound dressings with a masking layer and an observation window are described in International Patent Publications WO2013 / 007973 and WO2014 / 020440, the entire contents of which are incorporated herein by reference. Additionally, the masking layer 13004 may be positioned adjacent to the covering layer, or adjacent to any other desired dressing layer. In the illustrated embodiment, the masking layer 13004 is located between the covering layer 13002 and the activator layer 13006. As explained elsewhere herein and as will be understood by those skilled in the art, the activator layer may be an acid-providing layer or other suitable layer. In some embodiments, the masking layer 13004 may be adhered to or integrally formed with the covering layer 13002. The masking layer 13004 may be configured to have substantially the same size and shape as the activator layer 13006 in order to cover the activator layer. The masking layer 13004 may have an area smaller than that of the covering layer 13002. In some embodiments, the shielding layer 13004 can be used to horizontally absorb core fluids and can also be used as a collection and distribution layer.

[0148] In certain embodiments, the activator layer 13006 may have any of the same features, materials, or other details as any other embodiment of the activator layer disclosed herein. For example, the activator layer 13006 may be an adhesive and may be composed of a hydrogel or degel configured to have a plurality of acidic groups or portions that can provide protons in an aqueous environment. As explained elsewhere in this specification, under such acidic conditions, nitrite ions from the nitric oxide source layer 13010 may be reduced to nitric oxide for delivery to wounds or intact skin. As explained elsewhere herein and as those skilled in the art will understand, the activator layer may also be a nitrite-providing layer or other suitable layer. The activator layer 13006 (e.g., a hydrogel layer) may include a plurality of perforations extending through the thickness of the activator layer, as described elsewhere herein. Multiple perforations allow or facilitate the passage of wound exudate through the activator layer, enabling the exudate below or around the activator layer to be transported to one or more additional absorbent layers and / or one or more evaporative layers (e.g., a covering layer) above the activator layer, thereby preventing excessive accumulation of wound exudate below the activator layer 13006. Additionally, multiple perforations can provide an increased surface area for the activator layer, thereby improving its absorption rate.

[0149] like Figure 11AAs shown, in one embodiment, a collection and distribution layer 13008 may be placed between the activator layer 13006 and the nitrite-providing layer 13010. In some embodiments, the collection and distribution layer 13008 may be configured to advantageously wick fluid horizontally as fluids (such as wound exudate) are absorbed through the layers of the dressing 13000. This lateral wicking of the fluid allows for maximum distribution of the fluid through the activator layer 13006, enabling the activator layer 13006 to achieve its full retention capacity. Furthermore, the collection and distribution layer 13008 may promote nitric oxide production because nitrite ions dissolved in the fluid can be more rapidly dispersed on the surface of the activator layer 13006. Some embodiments of the collection and distribution layer 13008 may comprise viscose fiber, polyester, polypropylene, cellulose, or a combination of some or all of these, and the material may be needle-punched. Some embodiments of the collection distribution layer 13008 may include cellulose in the range of 40-160 gsm (or about 40 to about 160 gsm), for example, 80 (or about 80) gsm. Some embodiments of the collection distribution layer 13008 may include polyethylene in the range of 40-150 g / m² (gsm). In some embodiments, the collection distribution layer 13008 may have a thickness of 1.2 mm or about 1.2 mm, or may have a thickness in the range of about 0.5 mm to 3.0 mm, about 0.5 mm to about 3.0 mm, 0.7 mm to 2.5 mm, 0.9 mm to 2.1 mm, or 1.1 mm to 1.5 mm. In some embodiments, the collection distribution layer 13008 may be composed of a material resistant to compression under the negative pressure levels typically applied during negative pressure therapy.

[0150] The collection and distribution layer 13008 may include a plurality of loosely stacked fibers arranged in a substantially horizontal fiber network. In some embodiments, the collection and distribution layer 13008 may consist of a mixture of two fiber types. One fiber may be a flat fiber with a width of 20 to 50 micrometers, or about 20 to about 50 micrometers, and may include a cellulose-based material. The other fiber may be a bicomponent fiber having an inner core with a diameter of 8 to 10 micrometers, about 8 to about 10 micrometers, 7 to 11 micrometers, 6 to 12 micrometers, or 5 to 13 micrometers, and an outer layer with a thickness of 1 to 2 micrometers, about 1 to about 2 micrometers, 1 to 2.3 micrometers, 0.8 to 2.5 micrometers, or 0.5 to 3 micrometers. The bicomponent fiber may be a mixture of polyethylene (PE) type material and polyethylene terephthalate (PET). In some embodiments, the inner core of the bicomponent fiber may be PET, and the outer layer may be PE. PE / PET fibers can have a smooth surface morphology, while cellulose fibers can have a relatively rough surface morphology. In some embodiments, the ADL material may comprise about 60% to about 90% cellulose fibers, such as about 75% cellulose fibers, and may comprise about 10% to about 40% PE / PET fibers, such as about 25% PE / PET fibers. In some embodiments, the collection distribution layer 13004 may comprise segmented microfibers.

[0151] Most of the fiber volume may extend horizontally (i.e., parallel to the plane of the top and bottom surfaces of the material), or substantially or generally horizontally. In another embodiment, 80%-90% (or about 80% to about 90%) or more of the fiber volume may extend horizontally or substantially or generally horizontally. In another embodiment, all or substantially all of the fiber volume may extend horizontally or substantially or generally horizontally. In some embodiments, most, 80%-90% (or about 80% to about 90%) of the fibers or more, or even all or substantially all of the fibers, span a distance (horizontal or lateral distance) perpendicular to the thickness of the collection distribution layer 13004, which is greater than the thickness of the collection distribution layer 13004. In some embodiments, the horizontal or lateral distance spanned by such fibers is 2 times (or about 2 times) or more, 3 times (or about 3 times) or more, 4 times (or about 4 times) or more, 5 times (or about 5 times) or more, or 10 times (or about 10 times) or more of the thickness of the collection distribution layer 13008. The orientation of these fibers can facilitate lateral wicking of fluid through the collection distribution layer 13008. This allows fluids, such as wound exudate, to be distributed more evenly throughout the collection distribution layer 13008. In some embodiments, the ratio of the amount of fluid wicked laterally across the collection distribution layer 13008 to the amount of fluid wicked vertically through the collection distribution layer 13008 under negative pressure can be 2:1 or greater, or about 2:1 or greater, or in some embodiments up to 10:1 or greater, or about 10:1 or greater.

[0152] continue Figure 11A In some embodiments, a nitric oxide source layer 13010 may be disposed below a collection and distribution layer 13004. This nitric oxide source layer 13010 may have any of the same features, materials, or other details as any other embodiment disclosed herein; for example, the nitric oxide source layer 13010 may be a nitrite-providing layer. For example, the nitric oxide source layer may be a wet net impregnated with a sodium nitrite solution. In some embodiments, the nitric oxide source layer 13010 may be dry and includes a dried nitrite source, such as dried sodium nitrite. Such dried sodium nitrite may be loaded into a material layer composed of a suitable material such as any of the materials disclosed herein. As those skilled in the art will understand, a dry material and / or substance is a material and / or substance that is free of or relatively free of liquid. For example, polypropylene, polyethylene, or melt-extruded fibers may be suitable materials for such a layer. In an implementation, when the activator layer is a hydrogel, this type of nitric oxide source layer 13010 may initially need to be separated from the activator layer 13006 to avoid reacting and generating nitric oxide before application to wounds and / or skin. Figure 11AAs depicted, a dried fluid collection layer 13008 can be used to separate the nitric oxide source layer 13010 and the hydrogel activator layer 13004 prior to application. However, such a dried sodium nitrite-providing layer can be adjacent to the dry gel activator layer 13006 because the dry gel is not wet. In the case of a dry gel, activation can occur upon contact with a fluid such as wound exudate as it passes through a dressing wick. In the case of a hydrogel, once a fluid such as wound exudate comes into contact with the collection distribution layer 13008, nitrite ions can come into contact with the acidic environment created by the activator layer, thereby generating nitric oxide, which can then be transferred to the wound and / or skin. In some embodiments, each of the layers (such as the nitric oxide source layer, the activator layer, and any other suitable layers) can be stored dry prior to use. These layers can be moistened with a suitable liquid such as saline before application to the skin or wound.

[0153] like Figure 11B As described, to maintain nitric oxide release, multiple layers containing dried sodium nitrite, such as a first nitric oxide source layer 13010 and a second oxygen nitride source layer 13012, can be present. These layers are "activated" when wound fluid reaches and wets (the multiple layers), allowing the sodium nitrite to contact the acidic groups of the hydrogel or dry gel of the activator layer 13006, thereby generating nitric oxide. In some embodiments, two, three, four, five, six, or more layers containing dried sodium nitrite can be present. Figure 11B As shown, the masking layer 13004 can be used to prevent contact between the second nitric oxide source layer 13012 and the activator layer 13004. In some embodiments, an additional collection and distribution layer and / or masking layer may be sandwiched with the activator layer to provide an additional nitric oxide source.

[0154] like Figures 11C to 11D As depicted in the embodiment, the activator layer 13006 may be positioned below the nitric oxide source layer, thereby relying on dressing soaking (such as from wound exudate) and activating the nitrite supply layer 13010.

[0155] Including ADL's nitric oxide dressing

[0156] Figures 12 to 13A wound dressing 14000 having a nitric oxide generating layer is shown. Wound dressing 14000 may be similar to wound dressing 12000. Wound dressing 14000 may include a covering layer 14200, an activator layer or acid-providing layer 14400, and a nitric oxide source layer or nitrite-providing layer 14600, each of which may be similar to the covering layer 12200, the activator layer or acid-providing layer 12400, and the nitric oxide source layer or nitrite-providing layer 12600, respectively. As those skilled in the art will understand, the nitrite-providing layers(s) disclosed herein may be prepared and provided separately from the wound dressing. For example, the nitrite-providing layer 12600 may be applied to a wound, and the wound dressing may be applied over the nitrite-providing layer.

[0157] Covering layer 14200 can be similar to covering layer 12200. Covering layer 14200 can have a greater length and width than other layers 14400, 14600, and 14800, such that covering layer 14200 defines a boundary region extending between the outer periphery of the other layers and the outer periphery of covering layer 14200. The boundary region of covering layer 14200 can be attached to the skin around the wound to form a seal, allowing wound exudate to be contained within wound dressing 14000.

[0158] In the illustrated embodiment, the wound dressing 14000 also includes a collection distribution layer (ADL) 14800. The collection distribution layer 14800 can be configured to advantageously wick fluid horizontally as it is absorbed through the layers of the dressing 14000. This lateral wicking of the fluid allows for maximum distribution of the fluid through the acid-providing layer 14400, enabling the acid-providing layer 14400 to achieve its full retention capacity. Furthermore, the collection distribution layer 14800 can promote nitric oxide production because nitrite ions dissolved in the fluid can be more rapidly dispersed on the surface of the acid-providing layer 14400. Some embodiments of the collection distribution layer 14800 may comprise viscose fiber, polyester, polypropylene, cellulose, or combinations of some or all of these, and the material may be needle-punched. Some embodiments of the collection distribution layer 14800 may include cellulose in the range of 1-220 g / m² (or about 1 to about 220 gsm), 3-200 g / m² (or about 3 to about 200 gsm), 5-190 gsm (or about 5 to about 190 gsm), 10-180 gsm (or about 10 to about 180 gsm), 20-170 gsm (or about 20 to about 170 gsm), or 40-160 gsm (or about 40 to about 160 gsm), for example 80 (or about 80) gsm. Some embodiments of the collection distribution layer 14800 may include polyethylene in the range of 3-200 gsm (or about 3 to about 200 gsm), 5-190 gsm (or about 5 to about 190 gsm), 10-180 gsm (or about 10 to about 180 gsm), 20-170 gsm (or about 20 to about 170 gsm), or 40-150 gsm. In some embodiments, the collection distribution layer 14800 may have a thickness of 1.2 mm or about 1.2 mm, or may have a thickness in the range of 0.07 mm to 7.0 mm, 0.1 mm to 5.0 mm, 0.5 mm to 3.0 mm, 0.7 mm to 2.5 mm, 0.9 mm to 2.1 mm, or 1.1 mm to 1.5 mm. The collection distribution layer 14800 may be composed of a material resistant to compression at the negative pressure levels typically applied during negative pressure therapy.

[0159] The collection and distribution layer 14800 may include a plurality of loosely stacked fibers arranged in a substantially horizontal fiber network. In some embodiments, the collection and distribution layer 14800 may consist of a mixture of two or more fiber types. One fiber may be a flat fiber with a width of 20 to 50 micrometers, or about 20 to about 50 micrometers, and may include a cellulose-based material. Another fiber may be a bicomponent fiber having an inner core with a diameter of 8 to 10 micrometers, about 8 to about 10 micrometers, 7 to 11 micrometers, 6 to 12 micrometers, or 5 to 13 micrometers, and an outer layer with a thickness of 1 to 2 micrometers, about 1 to about 2 micrometers, 1 to 2.3 micrometers, 0.8 to 2.5 micrometers, or 0.5 to 3 micrometers. The bicomponent fiber may be a mixture of polyethylene (PE) type material and polyethylene terephthalate (PET). In some embodiments, the inner core of the bicomponent fiber may be PET, and the outer layer may be PE. PE / PET fibers can have a smooth surface morphology, while cellulose fibers can have a relatively rough surface morphology. In some embodiments, the ADL material may comprise about 60% to about 90% cellulose fibers, such as about 75% cellulose fibers, and may comprise about 10% to about 40% PE / PET fibers, such as about 25% PE / PET fibers. In some embodiments, the collection distribution layer 14800 may comprise segmented microfibers.

[0160] Most of the fiber volume may extend horizontally (i.e., parallel to the plane of the top and bottom surfaces of the material), or substantially or generally horizontally. In another embodiment, 80%-90% (or about 80% to about 90%) or more of the fiber volume may extend horizontally or substantially or generally horizontally. In another embodiment, all or substantially all of the fiber volume may extend horizontally or substantially or generally horizontally. In some embodiments, most, 80%-90% (or about 80% to about 90%) of the fibers or more, or even all or substantially all of the fibers, span a distance (horizontal or lateral distance) perpendicular to the thickness of the collection distribution layer 14800, which is greater than the thickness of the collection distribution layer 14800. In some embodiments, the horizontal or lateral distance spanned by such fibers is 2 times (or about 2 times) or greater, 3 times (or about 3 times) or greater, 4 times (or about 4 times) or greater, 5 times (or about 5 times) or greater, or 10 times (or about 10 times) or greater than the thickness of the collection distribution layer 14800. The orientation of these fibers can facilitate lateral wicking of fluid through the collection distribution layer 14800. This allows fluids, such as wound exudate, to be distributed more evenly throughout the collection distribution layer 14800. In some embodiments, the ratio of the amount of fluid wicked laterally across the collection distribution layer 14800 to the amount of fluid wicked vertically through the collection distribution layer 14800 under negative pressure can be 2:1 or greater, or about 2:1 or greater, or in some embodiments up to 10:1 or greater, or about 10:1 or greater.

[0161] In some embodiments, at least some fiber volumes of the collection distribution layer 14800 may extend vertically (i.e., perpendicular to the plane of the top and bottom surfaces of the material), or substantially or generally vertically. In some embodiments, greater than 10%, greater than 20%, greater than 30%, greater than 40%, greater than 50%, greater than 60%, greater than 70% < greater than 80%, or greater than 90% of the fiber volume may extend vertically or substantially or generally vertically. The orientation of such fibers can facilitate vertical wicking of fluid through the collection distribution layer 14800. In some embodiments, the ratio of the amount of fluid vertically wicked across the collection distribution layer 14800 to the amount of fluid wicked laterally through the collection distribution layer 14800 under negative pressure may be 2:1 or greater, or about 2:1 or greater, or in some embodiments may be up to 10:1 or greater, or about 10:1 or greater.

[0162] In some implementations, the collection distribution layer 14800 can be positioned below the acid supply layer 14400, such as... Figures 12 to 13 As shown in the diagram. In some embodiments, the collection distribution layer 14800 may be located above the acid supply layer 14400.

[0163] In some implementations, a wound dressing with a nitric oxide generating layer may include two or more collection and distribution layers. Figures 14 to 15 A wound dressing 16000 is shown having two collection distribution layers (a first collection distribution layer 16820 and a second collection distribution layer 16840). The wound dressing 16000 also includes a cover layer 16200, an acid supply layer 16400, and a nitrite supply layer 16600, which are respectively similar to a cover layer 14200, an acid supply layer 14400, and a nitrite supply layer 14600. The first collection distribution layer 16820 and the second collection distribution layer 16840 are similar to the collection distribution layer 14800 of the wound dressing 14000.

[0164] like Figures 14 to 15 As shown, the acid supply layer 16400 may be sandwiched between the first collection distribution layer 16820 and the second collection distribution layer 16840. In some embodiments, both the first and second distribution layers may be positioned above or below the acid supply layer 16400.

[0165] In some embodiments, one or more layers of nitric oxide-generating wound dressings may be transparent. For example, covering layers such as covering layer 12200, covering layer 14200, and covering layer 16200 may be transparent. Furthermore, acid-providing layers such as acid-providing layers 12400, acid-providing layer 14400, and acid-providing layer 16400 may be translucent when the hydrogel material becomes wet, for example, due to contact with wound exudate. In some embodiments, a masking layer may be positioned within the wound dressing to prevent the wound or wound exudate from being visible through the covering layer or acid-providing layer.

[0166] Wound dressings with a composite layer

[0167] In some embodiments, the activator layer, such as the gel layer disclosed herein, can be integrated with another material to form a composite layer. In examples, the gel layer can be a hydrogel. Such integration can be achieved by curing a gel polymer (such as a hydrogel) or other suitable techniques. As will be described in more detail below, for example, the gel can be integrated with an ADL layer such as any ADL layer described herein to form a composite collection distribution layer. In some examples, the gel can be integrated with SLIMCORE manufactured by Libeltex or other nonwoven collection distribution layers as further described herein. For example, the ADL can be an air-bonded fiber web multilayer collection distribution layer. In some examples, the ADL can include hydrophilic PET and / or bicomponent fibers. In other examples, the gel can be integrated with an absorbent material to form a composite absorbent layer as described in more detail below, the absorbent material including materials such as fibrous gelling materials (such as cellulose fibers). For example, the cellulose / ethyl sulfonate present in DURAFIBER is manufactured by Special Fibres and Materials Ltd and incorporated into the product by Smith + Nephew. Other examples of absorbent materials include gelling fibers, such as hydrofiber produced by Convatec in AQUACEL. Such integrated composite layers can be used to provide improved fluid handling, thereby directing nitrite ions into the composite structure to improve interaction with the activator layer, thereby generating and delivering nitric oxide. As those skilled in the art will understand, the nitrite-providing layers(s) disclosed herein can be prepared and provided separately from wound dressings. For example, the nitrite-providing layer can be applied to a wound, and the wound dressing can be applied over the nitrite-providing layer.

[0168] In some instances, the gel layer and / or composite layer described herein may include interwoven fabric within the gel layer. The interwoven fabric may be in the form of a thin mesh situated within the gel layer for structural support and may be composed of polypropylene or any suitable polymer disclosed herein. The interwoven fabric may be composed of a porous structural material that provides greater integrity to a gel that would otherwise have poor cohesion. The interwoven fabric may be located at the center of the gel plate to provide cohesion for thicker samples. However, those skilled in the art will understand that the interwoven fabric can be positioned at any suitable location within the gel, such as near the top or bottom. Furthermore, the interwoven fabric may be configured not to impair the passage of fluid through the thickness of the gel.

[0169] Complex collection distribution layer

[0170] As explained above, in some embodiments, the activator layer, such as the hydrogel layer, can be embedded using a collection distribution layer to form a complex layer. Figure 16A Depicting something similar to Figures 11A to 15 The wound dressing 19000 described herein includes a complex collection and distribution layer (ADL) 19002. The complex ADL can be formed by applying an activator gel (including any suitable activator layer material described herein) in liquid form to an ADL (such as any suitable ADL described herein) or vice versa. As described elsewhere in the specification, the activator gel can be a hydrogel or a dry gel configured to have multiple acidic groups or portions capable of providing protons in an aqueous environment. In the case of a dry gel, the ADL can be embedded within the dry gel in a dry state. In the case of a hydrogel, the hydrogel can be applied in liquid and / or gel form. The activator hydrogel material can then be cured to form the complex ADL 19002. The activator layer can be cured by any suitable technique, such as by applying energy to the system in the form of UV light, irradiation (such as γ), or heat (optionally, in combination with suitable initiators such as photoinitiators and / or thermal initiators). Curing agent chemical additives can also be used for curing. A covering layer 19004 (as described herein) may be applied over the composite ADL, and a nitrite-providing layer 19006 may be disposed below or above the composite ADL layer and below the covering layer. The nitrite-providing layer 19006 may be provided as part of a dressing or applied separately. Additionally, a wound contact layer (not shown), as described elsewhere in the specification, may be positioned below the dressing and above the wound. As those skilled in the art will understand, the activator gel in liquid form may be applied in any suitable manner such that the ADL covers the bottom portion, the top portion, or the middle portion of the composite ADL layer. In embodiments, the ADL may cover the entire dimension of the composite ADL layer. In some instances, the ADL may be coated in a hydrophilic agent prior to the addition of the activator layer in liquid gel form. In some instances, the activator gel in liquid form may be cast directly onto the ADL layer to form the composite ADL and / or the ADL may be pressed onto the activator layer prior to curing the activator layer into a gel. As those skilled in the art will understand, the activator gel material and the ADL material can be combined in any suitable arrangement.

[0171] In some embodiments, the ADL is made more rigid prior to casting into the composite ADL, such as by any suitable means, such as coating or temperature treatment. Other suitable methods may include bonding methods, such as thermal bonding or adhesive bonding. Further suitable methods may include thermosetting, increasing thickness / gram weight per square meter, increasing fiber stiffness / thickness, lamination, and / or annealing. A more rigid ADL can be used to improve fluid absorption in the composite ADL by increasing surface area. Other methods for curing and forming composite ADL layers are described below.

[0172] Covering layer 19004 may be similar to covering layers disclosed elsewhere herein. Covering layer 19004 may have a greater length and width than other layers, such that covering layer 19004 defines a boundary region 19010 extending between the outer periphery of other layers and the outer periphery of covering layer 19008. The boundary region of covering layer 19010 may be attached to the skin around the wound to form a seal, allowing wound exudate to be contained within wound dressing 19000.

[0173] In some embodiments, the composite ADL 19002 can be configured to advantageously wick fluid, such as wound exudate, horizontally and / or vertically when absorbed into the wound dressing 19000. Such fluid wicking allows for maximum distribution of fluid through the composite ADL layer 19002, enabling the composite ADL 19002 to reach full or near full capacity. Furthermore, the composite ADL 19002 can promote nitric oxide production because nitrite ions dissolved in the fluid can disperse more rapidly in the composite ADL 19002 than in a separate activator gel. Some embodiments of the ADL within the composite ADL layer 19002 may include viscose fibers, polyester, polypropylene, cellulose, or combinations of some or all of these, and the material may be needle-punched. Additionally, the composite ADL layer may include fibers such as polyethylene, polyamide, and / or suitable blends thereof. Other suitable materials may include copolymers of any polymers disclosed herein and core / sheath fibers with more than one material per fiber. Any suitable ADL material disclosed herein may be used. Some embodiments of the ADL within the composite ADL layer 19002 may include cellulose in the range of 1-220 g / m² (or about 1 to about 220 gsm), 3-200 g / m² (or about 3 to about 200 gsm), 5-190 gsm (or about 5 to about 190 gsm), 10-180 gsm (or about 10 to about 180 gsm), 20-170 gsm (or about 20 to about 170 gsm), or 40-160 gsm (or about 40 to about 160 gsm), for example 80 (or about 80) gsm. Some embodiments of the composite collection distribution layer 19002 may include polyethylene in the range of 3-200 gsm (or about 3 to about 200 gsm), 5-190 gsm (or about 5 to about 190 gsm), 10-180 gsm (or about 10 to about 180 gsm), 20-170 gsm (or about 20 to about 170 gsm), or 40-150 gsm. In some embodiments, the ADL may have a thickness of 1.2 mm or about 1.2 mm, or may have a thickness in the range of 0.07 mm to 7.0 mm, 0.1 mm to 5.0 mm, 0.5 mm to 3.0 mm, 0.7 mm to 2.5 mm, 0.9 mm to 2.1 mm, or 1.1 mm to 1.5 mm. The ADL may be composed of a material resistant to compression at the negative pressure levels typically applied during negative pressure therapy, such as those described herein.

[0174] Composite ADL19002 may comprise a plurality of loosely stacked fibers arranged in a substantially horizontal fiber network. In some embodiments, the ADL within composite ADL 19002 may consist of a mixture of two or more fiber types. One fiber may be a flat fiber with a width of 20 to 50 micrometers, or approximately 20 to 50 micrometers, and may comprise a cellulose-based material. In some instances, the fiber geometry may include star-shaped, elliptical, or other suitable shapes. Another fiber may be a bicomponent fiber having an inner core with a diameter of 8 to 10 micrometers, approximately 8 to 10 micrometers, 7 to 11 micrometers, 6 to 12 micrometers, or 5 to 13 micrometers, and an outer layer with a thickness of 1 to 2 micrometers, approximately 1 to 2 micrometers, 1 to 2.3 micrometers, 0.8 to 2.5 micrometers, or 0.5 to 3 micrometers. The bicomponent fiber may be a mixture of polyethylene (PE) type material and polyethylene terephthalate (PET). In some embodiments, the inner core of the bicomponent fiber may be PET, and the outer layer may be PE. PE / PET fibers may have a smooth surface morphology, while cellulose fibers may have a relatively rough surface morphology. In some embodiments, the ADL material may comprise about 60% to about 90% cellulose fibers, such as about 75% cellulose fibers, and may comprise about 10% to about 40% PE / PET fibers, such as about 25% PE / PET fibers. In some embodiments, the ADL may comprise split microfibers.

[0175] Most of the fiber volume in the composite ADL can extend horizontally (i.e., parallel to the planes of the top and bottom surfaces of the material), or substantially or generally horizontally. In another embodiment, 80%-90% (or about 80% to about 90%) or more of the fiber volume can extend horizontally or substantially or generally horizontally. In embodiments, all or substantially all of the fiber volume can extend horizontally or substantially or generally horizontally. In some embodiments, most, 80%-90% (or about 80% to about 90%) of the fibers or more, or even all or substantially all of the fibers, span a distance (horizontal or lateral distance) perpendicular to the thickness of the collection distribution layer, which is greater than the thickness of the composite collection distribution layer 19002. In some embodiments, the horizontal or lateral distance spanned by such fibers is 2 times (or about 2 times) or greater, 3 times (or about 3 times) or greater, 4 times (or about 4 times) or greater, 5 times (or about 5 times) or greater, or 10 times (or about 10 times) or greater than the thickness of the composite ADL 19002. The orientation of these fibers can facilitate lateral wicking of fluid through the composite ADL, thereby distributing fluids such as wound exudate more evenly throughout the composite ADL 19002. In some embodiments, the ratio of the amount of fluid wicked laterally across the composite ADL 19002 to the amount of fluid wicked vertically through the composite ADL 19002 under negative pressure can be 2:1 or greater, or about 2:1 or greater, or in some embodiments up to 10:1 or greater, or about 10:1 or greater.

[0176] In some embodiments, at least some fiber volumes of composite ADL 19002 may extend vertically (i.e., perpendicular to the planes of the top and bottom surfaces of the material), or substantially or generally vertically. In some embodiments, greater than 10%, greater than 20%, greater than 30%, greater than 40%, greater than 50%, greater than 60%, greater than 70% < greater than 80%, or greater than 90% of the fiber volume may extend vertically or substantially or generally vertically. The orientation of such fibers can facilitate vertical wicking of fluid through composite ADL 19002. In some embodiments, the ratio of the amount of fluid vertically wicked across composite ADL 19002 to the amount of fluid wicked laterally through composite ADL 19002 under negative pressure may be 2:1 or greater, or about 2:1 or greater, or in some embodiments may be up to 10:1 or greater, or about 10:1 or greater.

[0177] In some implementation schemes, such as Figure 16BAs depicted herein, another separate ADL19012, such as the one described herein, can be placed below the composite ADL to further facilitate fluid wicking and nitrite distribution throughout the composite ADL. As those skilled in the art will understand, the ADL can instead be positioned above the composite ADL, or multiple ADLs can be placed on top of and below the composite ADL. Those skilled in the art will also understand that the nitrite-providing layer can be repeated, such that one or more nitrite-providing layers can be positioned elsewhere in the dressing, such as above the composite ADL. Multiple ADLs, composite ADLs, and / or nitrite-providing layers can be suitably incorporated into a single dressing.

[0178] Complex Absorbing Layer

[0179] As explained above, in other instances, the gel can be integrated with an absorbent material to form a composite absorbent layer. Such a composite absorbent layer can include materials such as fibrous gelling materials (e.g., cellulose fibers). For example, the cellulose / ethyl sulfonate present in DURAFIBER is produced by Special Fibres and Materials Ltd and incorporated into the product by Smith + Nephew. Other examples of absorbent materials include gelling fibers, such as the hydrocellulose produced by Convatec in AQUACEL. In some embodiments, the absorbent material can be a foam or another suitable material.

[0180] Figure 17 Depicting something similar to Figures 11A to 15 and Figures 16A to 18BWound dressing 19001 is described herein; however, wound dressing 19001 herein includes a complex absorbent layer 19003. The complex absorbent layer can be formed by applying an activator gel in liquid form (including any suitable activator layer material described herein) to an absorbent layer (such as any suitable absorbent described herein) or vice versa. As described elsewhere in the specification, the activator gel can be a hydrogel or a dry gel configured to have multiple acidic groups or portions capable of providing protons in an aqueous environment. In the case of a dry gel, the absorbent can be embedded within the dry gel in a dry state. In the case of a hydrogel, the hydrogel can be applied in liquid and / or gel form. The activator hydrogel material can then be cured to form the complex absorbent layer 19003. The activator layer can be cured by any suitable technique, such as by applying energy to the system in the form of UV light, irradiation (such as γ), or heat (optionally, in combination with suitable initiators such as photoinitiators and / or thermal initiators). Curing agent chemical additives can also be used for curing. A covering layer 19005 (as described herein) may be applied over the composite absorbent layer, and a nitrite-providing layer 19007 may be disposed below the composite absorbent layer or above the composite ADL layer and below the covering layer. The nitrite-providing layer 19007 may be provided as part of a dressing or applied separately. Additionally, a wound contact layer (not shown), as described elsewhere in the specification, may be positioned below the dressing and above the wound. As those skilled in the art will understand, the activator gel in liquid form may be applied in any suitable manner such that the absorbent covers the bottom portion, the top portion, or the middle portion of the composite absorbent layer. In embodiments, the absorbent may cover the entire dimension of the composite absorbent layer. In some instances, the absorbent may be coated in a hydrophilic agent prior to adding the activator layer in liquid gel form. In some instances, the activator gel in liquid form may be cast directly onto the absorbent to form the composite absorbent layer and / or the absorbent may be pressed onto the activator layer prior to curing the activator layer into a gel. As those skilled in the art will understand, the activator gel material and the absorbent material may be combined in any suitable arrangement.

[0181] In some implementations, foam can be used to form a complex absorbent layer (also known as a complex foam layer) with an activator gel, similar to the above description. Figures 16A to 17 The described implementation scheme. As those skilled in the art will understand, the composite foam layer can be as described above regarding... Figures 16A to 17 The composite layer can be incorporated into wound dressings in any manner as described. Furthermore, the composite foam layer can be combined with similar... Figure 16AAdditional ADL layers and one or more nitrite-providing layers are used in combination with other foam layers and nitrite-providing layers. In some embodiments, an uncured activator gel material in liquid form may be poured into the foam and then cured in the foam to form a composite foam layer prior to curing. Figure 18A A composite foam layer is depicted, comprising foam portions 21002 embedded in an activator gel 21004. As those skilled in the art will understand, the foam portions may extend through the entire thickness of the composite foam layer or only partially through it. The foam portions may be circular, square, disc-shaped, or any suitable shape. The foam portions may be arranged in an array as shown herein, or they may be in a random pattern.

[0182] Figure 18B An illustration depicting a side view of wound dressing 21101 is shown. Here, a composite foam layer is overlaid on a cover layer 21110, similar to other covers disclosed herein, the composite foam layer comprising alternating activator layer gel portions 21102 and foam 21104. Figure 18C The same composite foam layer is depicted, now with a wound contact layer 21112 beneath it, made of any of the materials described herein. In some embodiments, the silicone wound contact layer may extend across the entire bottom of the wound dressing or may extend only partially across the underside of the wound dressing to form a window 21012. As those skilled in the art will understand, the wound contact layer may be made of any suitable material disclosed herein. For example, the wound contact layer may be made of silicone, skin-friendly pressure-sensitive adhesive, mild acrylic adhesive, polyurethane adhesive, hydrocolloid, or other suitable materials. The window may allow convenient delivery of nitric oxide to the wound. Those skilled in the art will understand that a nitrite-providing layer may be directly attached to the underside or top side of the composite foam layer and / or provided separately and placed below or above the composite foam layer.

[0183] In some embodiments, instead of foam or ADL, a complex layer can be formed using a superabsorbent material. The superabsorbent material can be embedded within the complex superabsorbent layer by any suitable means, such as embedding it within the activator layer gel in a unique superabsorbent pattern or array. In embodiments, the superabsorbent can be distributed throughout the complex absorbent layer such that the superabsorbent particles are uniformly distributed across certain areas of the complex absorbent layer or concentrated in certain areas of the complex absorbent layer. Such embodiments can be used to absorb and trap more fluid within the superabsorbent portion. In a particular embodiment, the complex superabsorbent layer can contain approximately: between 10% and 90% superabsorbent, such as between 20% and 80%, 30% and 70%, 40% and 60%, or approximately 50% superabsorbent. In one example, the gel can be completely removed to leave only a layer of superabsorbent with embedded acid-providing portions.

[0184] Figure 19 A wound dressing 22000 is described, comprising a covering layer 22002, an absorbent layer 22004 (which may be foam), a perforating activator gel layer 22006, and a nitrite-providing layer 22008. This arrangement allows for easy interaction between the nitrite-providing layer and the activator gel layer to generate nitric oxide, while still absorbing sufficient wound exudate to prevent leakage. In some embodiments, the activator gel layer 22006 may be a complex ADL, such as those disclosed herein.

[0185] ADL perforation complex

[0186] Figures 20A to 20D A perforated wound dressing and a compound ADL are described. This type of compound ADL is similar to... Figure 16A and Figure 16B And can be prepared as described above with respect to these figures. In some embodiments, the amount of open area in the perforated ADL can range from about 25-75%, 35% to 65%, 40% to 60%, or about 50%. Perforations can be arranged and shaped to suit a particular embodiment, such as in a patterned arrangement and shaping. For example, perforations in the ADL can be arranged in lines, wherein the perforations are equidistantly spaced and positioned adjacent to each other. In some embodiments, perforations can be positioned in a checkerboard-type pattern with parallel perforation lines and rows, or perforations can be offset or staggered relative to each adjacent perforation. Perforations can have an outer perimeter of any shape, such as circular, square, rectangular, triangular, rhomboid, etc. Perforations can have different sizes as they extend through the material or layer. For example, perforations can have an overall pyramidal shape. In other words, perforations can increase or decrease their cross-sectional area as they extend through the layer or material. As those skilled in the art will understand, in some instances, perforations can take the form of slits, pits, recesses, bumps, or any suitable construction.

[0187] In this embodiment, the ADL within the complex ADL may include forked structures, such as microneedles. These microneedles can penetrate into the activator layer gel to promote capillary action within the gel.

[0188] Figure 20A A top view depicts an embodiment of a composite ADL 23002 having perforations in an ADL. Such a composite ADL may include an ADL 23004 embedded within an activator gel 23006. The perforations through the ADL layer allow the activator gel 23006 to interact directly with a nitrite-containing fluid passing through a nitrite-providing layer above or below the composite ADL.

[0189] Figure 20B A side view of an embodiment of dressing 23000 containing perforated complex ADL 23002 is depicted. The dressing includes perforated ADL 23004 and an activator gel 23006 covered by a covering layer. As described above, the perforated ADL includes perforations 23010, which allow improved direct fluid flow to the activator gel 23006. In some instances, dressing 23000 also includes a mesh interwoven fabric 23012. Figure 20C A side view depicts an embodiment of dressing 23000, which is similar to... Figure 20B The dressing. Here, the interwoven fabric 23012 includes larger perforations to allow for greater fluid flow. In some embodiments, the perforations in the interwoven fabric may have an opening area of ​​about 25%-75%, 35% to 65%, 40% to 60%, or about 50%. In some embodiments, the interwoven fabric may be completely removed to facilitate fluid flow. As shown in the figure, the fluid is distributed on the composite ADL within one minute after application.

[0190] Figure 20D Depicting something similar to Figure 20A and Figure 20B A side view of an embodiment of the wound dressing 23000. Here, the composite ADL includes a first perforation ADL 23004 and a second overlay perforation ADL 23014. In some embodiments, the second ADL 23014 may have an opening area that is the same as, more than, or less than that of the first ADL 23004. In a particular embodiment, the ratio of the opening area in the second ADL 23014 to that in the first ADL 23004 is about: .25, .5, 1, 1.5, 2, 4, 6, or 10.

[0191] Figure 21 Another embodiment of wound dressing 14001 is shown, which is similar to, for example, Figures 16A to 20DOther wound dressings described herein. Wound dressing 14001 may include a covering layer 14002, an absorbent layer 14004, a gel-perforated absorbent layer 14016 such as described elsewhere herein, a gel material or gel layer 14006, and a tissue interface layer 14012. The covering layer 14002 may be placed over the absorbent layer 14004. The gel-perforated absorbent layer 14016 may be placed under the absorbent layer 14004. The gel material or gel layer 14006 may adhere to the wound-facing surface of the gel-perforated absorbent layer 14016. Optionally, the tissue interface layer 14012 may be placed under the gel material or gel layer 14006 and adhere to a peripheral portion of the covering layer 14002.

[0192] Figure 21 The wound dressing 14001 may include one or more nitrite-providing layers, which may be separate from the dressing. In some embodiments, the wound dressing 14000 may include a collection distribution layer as described herein. Nitrite-providing layers(s) such as those described herein may be positioned above the absorbent layer 14004, between the absorbent layer 14004 and the gel-permeable absorbent layer 14016, between the gel material or gel layer 14006 and the gel-permeable absorbent layer 14016, below the gel material or gel layer 14006, below the covering layer 14002, or between the covering layer 14002 and the absorbent layer 14004. In embodiments having a collection distribution layer, the collection distribution layer may be placed between one or more nitrite-providing layers and the gel material or gel layer 14006, between the covering layer 14002 and the absorbent layer 14004, or between the absorbent layer 14004 and the gel material or gel layer 14006. Figure 21 As shown, the gel material or gel layer 14006 may have perforations 14010. The perforations can have any suitable arrangement, such as those described herein, for example, regarding... Figures 20A to 20D As described.

[0193] In manufacturing the wound dressing 14001, a gel material can permeate into the perforated absorbent layer to form a gel-through-perforated absorbent layer 14016. The gel-through-perforated absorbent layer 14016 can then be cured, for example, by using UV light or heat. The gel material or gel layer 14006 can then be adhered to the gel-through-perforated absorbent layer 14016. The size of the perforations 14026 in the gel-through-perforated absorbent layer 14016 can be adjusted according to any expansion or dilation caused by allowing the gel material to permeate into the perforated absorbent layer.

[0194] Figures 22 to 28 Implementation plan

[0195] Figure 22An embodiment of a wound dressing 24000 with a 3D spring mattress-style ADL is described, which allows the wound dressing to compress 24002 or expand vertically 24004. Such a dressing may include a bottom ADL 24006 and a top ADL 24008 separated by wicking springs 24010. In some embodiments, the top and bottom ADLs may wick horizontally, while the spring element 24010 wicks fluid vertically. As those skilled in the art will understand, the dressing may contain a suitable number of wicking springs.

[0196] Figure 23 An implementation scheme for wound dressing 25000 is described, which is similar to the one described above. Figures 16A to 16B Wound dressings disclosed elsewhere herein have alternating layers of activating gel 25002 and ADL 25004, including a top ADL 25006. A cover layer 25008 may cover this structure and may adhere to the top ADL 25006 or not. A mesh layer 25010 (which may be a wound contact layer such as those disclosed herein) may contain alternating layers and may adhere to the cover layer. In some instances, these layers may not be alternating, but may be randomly ordered or arranged in a suitable manner. In some embodiments, the wound dressing may be modified to a tea bag style, wherein randomly distributed ADL or activating gel is contained within the cover layer and the mesh layer. The ratio of ADL to activating gel in the wound dressing 25000 or tea bag may be about 25:75, 50:50, or 75:25.

[0197] Figure 24 An implementation scheme for wound dressing 26000 is described, which is similar to the one described above. Figures 16A to 16B Like wound dressings disclosed elsewhere herein, this dressing has an elongated ADL 26002 extending beyond the boundary of the overlying activated gel layer 26004. The elongated ADL can adhere to the covering layer 26006.

[0198] Figure 26Embodiments of a composite layer 27000 with channels of a hydrophilic wicking material 27002 are depicted, these channels extending vertically through the composite layer and surrounded by an activator gel 27004. In some embodiments, the hydrophilic wicking material can be composed of any suitable material, such as those disclosed herein. The hydrophilic wicking material can constitute approximately 5%, 10%, 15%, 20%, 25%, 35%, or 50% of the total volume of the composite layer 27000. At least some of the channels 27002 can be non-vertically oriented, such as horizontally or at an angle to the vertical axis. In some embodiments, the channels 27002 can be randomly oriented. In some embodiments, the wicking channels can be oriented towards the central portion of the composite layer 27000, such that fluid is guided to the center of the composite layer 27000.

[0199] Figure 26 A top view of an embodiment of dressing 28000 is depicted, which may include a complex layer 28002 (such as a complex ADL layer, a complex absorbent layer, or any suitable layer). The complex layer 28002 may be surrounded by an absorbent frame 28004, which may be used as a barrier to allow fluid to diffuse into the area surrounding the wound.

[0200] Figure 27 Embodiments of dressing 29000 are depicted, which may include a complex layer 29002 (such as a complex ADL layer, a complex absorbent layer, or any suitable layer) and a nitrite-providing layer 29004 similar to other nitrite-providing layers 29004 disclosed herein. The nitrite-providing layer 29004 may be configured such that the nitrite-providing layer is absorbent, thereby slowing fluid transfer into the complex layer 29002. In some embodiments, the nitrite-providing layer may be a perforated mesh, the perforations having an opening area of ​​approximately 10%, 25%, 50%, or 75% of the area of ​​the nitrite-providing layer 29004.

[0201] Figure 28 An embodiment of dressing 30000 is described, which may include a complex layer 30002 (such as a complex ADL layer, a complex absorbent layer, or any suitable layer) and a nitrite-providing layer 30004 similar to other nitrite-providing layers 30004 disclosed herein. Here, the nitrite-providing layer 30004 may be wrinkled, curled, or roughened to increase the surface area for fluid absorption, similar to... Figure 26 The dressing. By increasing fluid absorption, the complex layer can absorb wound fluid more slowly and therefore is not prematurely oversaturated with wound fluid.

[0202] Wound dressing with embedded composite layer

[0203] Wound dressing embodiment 32000, characterized by an embedded complex layer, is described in... Figure 29 As shown in the diagram. This embodiment may feature a composite layer 32006 embedded between a bottom membrane layer 32002 and a top membrane layer 32008. The bottom membrane layer 32002 may be adhered to the composite layer 32006 and the top membrane layer 32008 via a bottom adhesive layer 32004. An additional top adhesive layer 32010 may be present between the top membrane layer 32008 and a removable handle 32012. An opening 32014 may be present within the top membrane layer 32008 and the top adhesive layer 32010 to expose the composite layer 32006 upon removal of the handle 32012. A wound contact layer (not shown) similar to other wound contact layers disclosed herein may be positioned below the dressing and may include a handle, such as in 32012, which may be removed before the dressing is placed. The dressing may be configured such that, upon removal of the handle 32012, the dressing may be manipulated to bring the composite component 32006 into contact with the wound contact layer including a nitrite-providing component (not shown). The dressing may be configured not to generate nitric oxide before the removal of the handle 32012 and subsequent assembly of the composite component 32006 and the wound contact layer including the nitrite-providing component. In some embodiments, the wound contact layer may be placed over the wound, and the absorbent dressing component may be placed over the wound contact layer, wherein the composite component 32006 is exposed by a window 32014 configured to contact the wound contact layer. In some embodiments, the dressing may include a thickened boundary 32016 surrounding the opening 32014 exposing the composite layer 32006. In some embodiments, the thickened boundary may include two top membranes instead of one. In some embodiments, the thickened boundary may create a more rigid boundary to aid application.

[0204] Those skilled in the art will understand that, although Figure 29 Wound dressing implementations can be configured to deliver nitric oxide to the wound and / or skin surface, but Figure 29 The implementation scheme can deliver any suitable type of active ingredient, and is not limited to delivering nitric oxide. Figure 29 The implementation scheme is suitable for delivering active ingredients that require a reaction to promote the production and / or delivery of the active ingredient. For example, the active ingredient may be a molecule that has a healing effect on wounds and / or skin or some other positive physiological effect.

[0205] In some embodiments, the pad may be secured to the dressing to prevent delamination from the top film. In some embodiments, this can be achieved by using an adhesive to bond the layers of the dressing together. In some embodiments, the dressing may include a thickened border to aid application. In some embodiments, the handle will not need to be held on the dressing for application and can be removed during manufacturing. In some embodiments, the handle can be removed when the dressing is applied. In some embodiments, a single-layer (thinner) border may be more difficult to apply due to lower structural integrity, meaning the border can easily fold itself when the handle is removed. In some embodiments, a double-layer (thickened) border can provide a more rigid border, making application easier. In some embodiments, the top carrier of the top film (not on the adhesive side) may remain on to aid application and is subsequently removed as a final step in application. In some embodiments with thickened borders (two layers), the top carrier of the top film (not on the adhesive side) can be removed during manufacturing because it is not needed to aid application, thus saving the user an application step.

[0206] In some implementations, as those skilled in the art will understand, the above regarding Figure 29 The nitric oxide delivery dressing 32000 and the materials and dressing constructions described elsewhere in the specification may include a variety of suitable constructions and different types of materials. For example, the topmost layer furthest from the wound may be a top membrane or covering membrane, such as the top or covering layers disclosed herein, such as polyurethane materials. Such a top membrane or covering membrane may be constructed from the materials used in the covering layers of RENASYS drapes sold by Smith + Nephew. For example, in some embodiments, the covering layer may be an IV3000 top membrane. Below the top membrane or covering membrane may be a masking layer or fabric layer, which may be constructed from any suitable material disclosed herein as a masking layer or fabric layer.

[0207] In some embodiments, the wound dressing may be a two-component system comprising a wound contact layer and an absorbent dressing component. In some embodiments, the wound contact layer and the absorbent dressing component are held in separate packages prior to dressing application.

[0208] In some embodiments, the opening exposing the composite layer can be cut into the surface of the top membrane layer. The opening can be rectangular, elliptical, square, polygonal, or any suitable shape. Those skilled in the art will understand that... Figure 29The wound dressing can be configured to feature any openings in a top membrane layer adapted to allow interaction between the complex layer and a wound contact layer including a nitrite-providing layer. In some embodiments, the openings may be covered by a removable handle before the complex layer and the wound contact layer including the nitrite-providing layer interact. In some embodiments, multiple openings exposing the complex layer may be present.

[0209] In some embodiments, the wound dressing may further comprise one or more adhesive layers. In some embodiments, the one or more adhesive layers may contain the same adhesive. In some embodiments, the one or more adhesive layers may contain different adhesives. In some embodiments, the adhesive layers may contain skin-friendly pressure-sensitive adhesives, mild acrylic-based adhesives, polyurethane-based adhesives, hydrocolloids, or other suitable materials as described herein. In some embodiments, the adhesive may be configured to provide optimal adhesion to the layers of the dressing. In some embodiments, the adhesive may be configured to provide optimal application to the skin.

[0210] In some embodiments, additional membrane layers may be present. In some embodiments, the membrane layers may contain the same membrane material. In some embodiments, the membrane layers may contain different membrane materials. In some embodiments, the membrane layers may contain IV3000 or other suitable materials as described herein.

[0211] In some embodiments, the composite layer may comprise a gelling fiber substrate loaded with acidic hydrogel. Exemplary wound dressings may comprise a substrate such as DURAFIBER or OPSITE POST-OP pad material. Exemplary wound dressings may contain an aqueous solution of sodium 2-acrylamido-2-methyl-1-propanesulfonate and 2-acrylamido-2-methyl-1-propanesulfonic acid (SA). Exemplary wound dressings may comprise any amount of hydrogel with an acidity content ranging from 2.0 SA to 0.5 SA.

[0212] Exemplary wound dressings may include a complex layer configured to provide protons to a nitrite-providing layer to generate nitric oxide. Exemplary wound dressings may include separate ampoules of fluids in wound exudate, water provided by an aqueous hydrogel, and / or aqueous reagents to activate the nitric oxide chemical reaction.

[0213] the term

[0214] Any patents, applications, and other references mentioned above (including any references that may be listed in the accompanying application documents) are incorporated herein by reference. Where necessary, aspects of this disclosure may be modified to incorporate the systems, functions, and concepts of the various references described herein to provide other implementations.

[0215] The features, materials, characteristics, or sets described in conjunction with a particular aspect, embodiment, or example are to be understood as applicable to any other aspect, embodiment, or example described herein, unless incompatible therewith. All features disclosed in this specification (including any appended claims, abstract, and drawings), or all steps of any method or process so disclosed, may be combined in any combination, except for at least some mutually exclusive combinations of such features or steps. Protection is not limited to the details of any of the foregoing embodiments. Protection extends to any novel feature or any novel combination of features disclosed in this specification (including any appended claims, abstract, and drawings), or any novel feature or any novel combination of steps of any method or process so disclosed.

[0216] While certain embodiments have been described, these embodiments are presented by way of example only and are not intended to limit the scope of protection. In fact, the novel methods and systems described herein can be embodied in a variety of other forms. Furthermore, various omissions, substitutions, and changes can be made to the form of the methods and systems described herein. Those skilled in the art will understand that in some embodiments, the actual steps taken in the shown or disclosed process may differ from those shown in the figures. Depending on the embodiment, some of the above-described steps may be removed, and other steps may be added. For example, the actual steps or the order of steps taken in the disclosed process may differ from those shown in the figures. Depending on the embodiment, some of the above-described steps may be removed, and other steps may be added. Moreover, the features and attributes of the specific embodiments disclosed above can be combined in different ways to form other embodiments, all of which fall within the scope of this disclosure.

[0217] While this disclosure includes certain embodiments, examples, and applications, those skilled in the art will understand that the scope of this disclosure extends beyond the specific disclosed embodiments to other alternative embodiments or uses, as well as their obvious modifications and equivalents, including embodiments that do not provide all the features and advantages described herein. Therefore, the scope of this disclosure is not intended to be limited by the described embodiments and may be defined by the claims as presented herein or by claims to be presented hereafter.

[0218] Conditional language, such as “can,” “may,” “possibly,” or “can,” unless explicitly stated otherwise or otherwise understood in the context in which they are used, is generally intended to express that certain implementations include certain features, elements, or steps that are not included in other implementations. Therefore, such conditional language is not generally intended to imply that one or more implementations require a feature, element, or step in any way, or that one or more implementations must include logic for determining whether such features, elements, or steps are included in or performed in any particular implementation, with or without user input or prompting. The terms “including,” “comprise,” “have,” etc., are synonymous and used in an open-ended manner, not excluding additional elements, features, actions, operations, etc. Additionally, the term “or” is used in its inclusive sense (not in its proprietary sense) so that, when used, for example, to connect lists of elements, the term “or” indicates one, some, or all of the elements in the list. Similarly, the term “and / or” refers to a list of two or more items, encompassing all of the following interpretations of the word: any one item in the list, all items in the list, and any combination of items in the list. In addition, besides having its ordinary meaning, the term "each" as used herein can refer to any subset of a set of elements to which the term "each" is applied. Furthermore, when used in this application, the words "in this document," "above," "below," and words with similar meanings refer to the application as a whole, and not to any particular part of the application.

[0219] Unless otherwise explicitly stated, union language such as the phrase “at least one of X, Y, and Z” is understood in context as generally used to indicate that an item, term, etc., can be X, Y, or Z. Therefore, such union language generally does not imply that certain implementations require the presence of at least one of X, at least one of Y, and at least one of Z.

[0220] The degree language used herein, such as the terms “approximately,” “about,” “substantially,” and “basically”, indicates a value, quantity, or characteristic that is close to a specified value, quantity, or characteristic, which still performs the desired function or achieves the desired result. For example, the terms “approximately,” “about,” “substantially,” and “basically” can refer to a quantity that is less than 10%, less than 5%, less than 1%, less than 0.1%, and less than 0.01% of a specified quantity. As another example, in some embodiments, the terms “substantially parallel” and “basically parallel” refer to a value, quantity, or characteristic that deviates from perfect parallelism by less than or equal to 15 degrees, 10 degrees, 5 degrees, 3 degrees, 1 degree, or 0.1 degrees.

[0221] Any of the embodiments described herein may or may not be used with a dressing tank. Any dressing embodiment described herein can absorb and store wound exudate.

[0222] The scope of this disclosure is not intended to be limited by the description of certain embodiments, but may be defined by the claims. The language of the claims will be interpreted broadly based on the language used in the claims and is not limited to the examples described in this specification or during the examination of the application, which should be interpreted as non-exclusive.

[0223] Various modifications to the embodiments described in this disclosure will be apparent to those skilled in the art, and the general principles defined herein can be applied to other implementations without departing from the spirit or scope of this disclosure. Therefore, this disclosure is not intended to be limited to the embodiments shown herein, but rather to be consistent with the widest scope of the principles and features disclosed herein. Certain embodiments of this disclosure are covered by the set of claims listed below or to be presented herein.

[0224] Some embodiments of this disclosure are covered by the claims set forth at the end of this specification, or by other claims set forth at a later date.

Claims

1. A wound dressing for treating wounds, the wound dressing comprising: An absorbent dressing component comprising a complex layer, a top film layer, and a bottom film layer, the absorbent dressing component being configured such that the complex component is embedded between the top film layer and the bottom film layer, the top film layer including an opening to expose the complex pad; The absorbent dressing component is combined with a wound contact layer, the wound contact layer further comprising a nitrite-providing layer; and The combination of the absorbent dressing component and the wound contact layer is configured to generate nitric oxide.

2. The wound dressing of claim 1, wherein the composite layer comprises a gelling fiber substrate loaded with an activator gel.

3. The wound dressing of claim 2, wherein the activator gel comprises a hydrogel.

4. The wound dressing of claim 3, wherein the activator gel comprises an acidic group or portion thereof.

5. The wound dressing as claimed in any one of claims 1 to 4, wherein the absorbent dressing component further includes a removable handle.

6. The wound dressing of claim 5, wherein removal of the handle allows for combination of the absorbent dressing component with the wound contact layer.

7. The wound dressing of claim 6, wherein the combination includes contacting the area of ​​the absorbent dressing component exposed by the opening in the top membrane layer with the wound contact layer.

8. The wound dressing as claimed in any one of claims 1 to 7, wherein the wound dressing is configured such that the wound contact layer is placed close to the wound and the absorbent dressing component is placed above the wound contact layer.

9. The wound dressing of any one of claims 1 to 8, wherein the construction of the composite layer between the top membrane layer and the bottom membrane layer prevents the composite layer from delaminating from the dressing.

10. The wound dressing of any one of claims 1 to 9, wherein the wound dressing further comprises one or more adhesive layers.

11. A method for treating a wound, the method comprising: A wound dressing is provided, the wound dressing including an absorbent dressing component, the absorbent dressing component including a complex layer, a top membrane layer and a bottom membrane layer; Remove the stalk layer from the wound dressing, so that a portion of the complex layer is exposed through an opening in the top membrane layer; as well as The wound dressing is applied to the wound such that the exposed absorbent dressing component is combined with the wound contact layer, which further includes a nitrite-providing layer.

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