Activated wound dressing material

A wound dressing with an acetyl donor compound generates peracetic acid in situ using hydrogen peroxide, addressing stability issues and effectively treating multidrug-resistant infections.

JP7819924B2Active Publication Date: 2026-02-25AGA NANOTECH
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Patent Information

Application Number
JP2022552164
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2020-07-07
Filing Date
2021-02-23
Publication Date
2026-02-25
Estimated Expiration
2041-02-23

AI Technical Summary

Technical Problem

Existing wound treatment systems containing peroxygen donors face stability issues due to spontaneous reactions during storage, leading to reduced shelf life and safety concerns, and there is a need for effective treatment of multidrug-resistant infections.

Method used

A wound dressing or wound contact medium that includes an acetyl donor compound, which generates peracetic acid in situ upon application with hydrogen peroxide, avoiding reactive peroxide compounds and ensuring stability and efficacy against infections.

Benefits of technology

The system provides excellent storage stability, effective biocidal action against wound infections, including multidrug-resistant organisms, and controls reactive oxygen and nitrogen species, promoting better wound healing.

✦ Generated by Eureka AI based on patent content.
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Abstract

The present invention relates to a wound dressing or other wound contact medium that contains an acetyl donor compound but does not contain a peroxide compound and is activatable by means of applying hydrogen peroxide, the wound dressing or other wound contact medium being suitable for use in the prevention and / or treatment of wound infections in a patient, comprising applying the wound dressing or other wound contact medium to a wound in the patient, and subjecting the wound dressing or other wound contact medium to means of applying hydrogen peroxide to activate the acetyl donor compound of the wound dressing or other wound contact medium with the hydrogen peroxide to produce peracetic acid.
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Description

[Technical Field]

[0001] The present invention relates to a wound dressing or other wound contact medium suitable for use in the treatment of human or animal wound infections, as well as kits comprising the wound dressing or other wound contact medium, as well as means for applying hydrogen peroxide, and a process for preventing and / or treating wound infections in a patient. [Background technology]

[0002] Antibiotic resistance, especially the emergence of widespread multidrug-resistant infections, poses a devastating risk and carries significant costs for human health, and novel approaches to combating infectious diseases are urgently needed.

[0003] WO2015 / 150722 relates to a therapeutic agent comprising microparticles and / or nanoparticles loaded with at least one inactive precursor chemical for use in treating human or animal infectious diseases. The precursor chemical is activatable in situ by the physiological environment at the site of infection, thereby forming an antibacterial agent. In one embodiment, a peroxygen donor and an acetyl donor are combined as precursor chemicals. When activated, the peroxygen donor can form hydrogen peroxide, which in turn can activate the acetyl donor to form peracetic acid in situ.

[0004] Hydrogen peroxide and peracetic acid have strong biocidal effects against microorganisms. Therefore, the therapeutic agents of WO2015 / 150722 enable the in situ production of antibacterial agents at the site of infection, thereby providing effective treatment for infectious diseases. However, the storage stability of these therapeutic agents leaves room for improvement. This is because their precursor chemicals, particularly the peroxygen donors, are reactive compounds, and spontaneous reactions of these chemicals may already occur during storage, which may affect the properties of the agent, shorten its shelf life, or require more stringent storage conditions, such as (stronger) cooling. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] WO2015 / 150722 Summary of the Invention

[0006] It is an object of the present invention to provide a therapeutic system that is suitable for use in the prevention and / or treatment of human or animal wound infections, including multidrug-resistant infections, and at the same time has an excellent shelf life.

[0007] According to the present invention, there is provided a wound dressing or other wound contact medium comprising an acetyl donor compound but not a peroxide compound. The present invention also provides a wound dressing or other wound contact medium for use in the prevention and / or treatment of wound infection in a patient, comprising applying a wound dressing or other wound contact medium according to the present invention to a wound on a patient and subjecting the wound dressing or other wound contact medium to a means for applying hydrogen peroxide, whereby the acetyl donor compound of the wound dressing or other wound contact medium can be activated by hydrogen peroxide to generate peracetic acid in situ. Detailed Description of the Invention

[0008] Because the wound dressing or other wound contact medium does not contain reactive peroxide compounds, it has excellent storage stability, a significant improvement over systems containing peroxide compounds. At the same time, peracetic acid can be generated in situ by activation using hydrogen peroxide application. Therefore, peracetic acid, which is known to have a strong biocidal effect, can be provided to the wound site in situ, enabling effective prevention and / or treatment of wound infections. The wound dressing or other wound contact medium of the present invention offers advantages in terms of antimicrobial efficacy at the site of need, high activity against wound biofilms, and control of reactive oxygen and nitrogen species within the wound, resulting in overall better wound healing.

[0009] The acetyl donor compound, if necessary, after release from the particles, can react with hydrogen peroxide generated by plasma, as discussed below, to produce peracetic acid or a mixture of peracetic acid and hydrogen peroxide, respectively. The use of an inactive acetyl donor compound that can be activated in situ by applying hydrogen peroxide overcomes stability and safety issues associated with highly reactive antimicrobial agents. In the present invention, peracetic acid or a dynamic equilibrium mixture of hydrogen peroxide and peracetic acid is generated in situ at the wound site by using a wound dressing or other wound contact medium containing an acetyl donor in combination with a means of applying hydrogen peroxide. Peracetic acid, in particular, is known to be highly effective in disrupting biofilms and killing otherwise resistant organisms therein. Wound biofilms have been shown to be critical in impeding wound healing, particularly in chronic wounds.

[0010] The system is also flexible in that the means of applying hydrogen peroxide, such as concentration and time for each individual application, can be adjusted. The concentration of peracetic acid produced at the wound site can be adjusted regardless of the wound dressing used.

[0011] The type of wound dressing can be selected from common wound dressings. Suitable natural materials include gelatin, agarose, hypromellose, Matrigel, extracellular matrix proteins such as fibrin, fibronectin, collagen and collagen derivatives, polysaccharides such as xanthan gum, sugars, cellulose and modified celluloses such as hydroxypropyl cellulose, sodium carboxymethyl cellulose and hydroxyethyl cellulose, and polycarboxylic acids.

[0012] Other preferred wound dressings are non-porous and / or porous cross-linked and / or non-cross-linked polymeric materials, such as polyethylene oxide, polyvinyl alcohol, polyacrylic acid, polyvinylpyrrolidone, polyacrylamidomethylpropanesulfonate, polycaprolactone (PCL), polyglycolic acid (and its derivatives) and copolymers thereof.

[0013] In some embodiments, the material is Aquaform IM, Curafil IM, Granugel TM , Hypergel TM , Intrasite Gel IM, Nu-Gel TM and Purolin gel IM (Jones and Vaughan, 2005).

[0014] In other embodiments, the material comprises a polymeric material selected from the group consisting of poly(lactide-co-glycolide), poly(vinylpyrrolidone), polyvinyl alcohol), poly(hydroxyalkyl methacrylate), polyurethane foam, and hydrocolloid and alliginate coatings (Boateng et al., 2008).

[0015] Other commercially available amorphous hydrogels that may be used include Anasept TM Antimicrobial Skin & Wound Gel (Anacapa Technologies, Inc.), 3MTM Tegaderm TM Hydrogel Wound Filler(3M Health Care)、AmeriDerm Wound Gel(AmeriDerm Laboratories,Ltd.)、AquaSite TM Amorphous Hydrogel Dressing(Derma Sciences,Inc.)、Curasol TM Gel Wound Dressing(Smith & Nephew,Advanced Wound Biotherapeutics)、Dermagran TM Amorphous Hydrogel Dressing(Derma Sciences,Inc.)、DermaPlex TM Gel(MPM Medical,Inc.)、DermaSyn TM (DermaRite Industries,LLC)、DuoDERM TM Hydroactive Sterile Gel(ConvaTec)、Excel TM Gel(MPM Medical,Inc.)、Gentell Hydrogel(Gentell Wound and Skin Care)、Hydrogel Amorphous Wound Dressing(McKesson Medical-Surgical)、Hypergel TM Hypertonic Gel(Molnlycke Health Care US,LLC)、INTRASITE * Gel Hydrogel Wound Dressing(Smith & Nephew,Inc.)、Kendall TM Amorphous Hydrogel(Covidien)、LipoGel TM (Progressive Wound Care Technologies,Inc.)、MacroPro TM Gel(Molnlycke Health Care US,LLC)、MPM Regenecare TMHA Spray (MPM Medical, Inc.), Normlgel TM Isotonic Saline Gel (Molnlycke Health Care US, LLC), Purilon TM Gel (Coloplast Corp.), Regenecare TM HA (MPM Medical, Inc.), Restore TM Hydrogel (Amorphous) (Hollister Wound Care), SAF-Gel TM Hydrating Dermal Wound Dressing (ConvaTec), SilvaSorb TM Gel (Medline Industries, Inc.), SilverMed TM Amorphous Hydrogel (MPM Medical, Inc.), SilvrSTAT TM Antibacterial Wound Dressing Gel (ABL Medical, LLC), Skintegrity TM Hydrogel (Medline Industries, Inc.), SOLOSITE TM Wound Gel (Smith & Nephew, Inc.), Spand-Gel TM Primary Hydrogel (Medi-Tech International Corp.) and Woun'Dres TM Collagen Hydrogel (Coloplast Corp.) is an example.

[0016] In some embodiments, the hydrogel is in the form of a coating on a gauze pad, nonwoven sponge, rope, and / or strip. In these embodiments, the screen comprises an impregnated hydrogel, where the hydrogel is coated onto a gauze pad, nonwoven sponge, rope, and / or strip. The impregnated hydrogel may be formed by coating the gauze, sponge, rope, or strip material with a suitable hydrogel, such as gelatin.

[0017] Alternatively, AquaSite TM Hydrogel Impregnated Gauze (Derma Sciences, Inc.), DermaGauze TM (DermaRite Industries, LLC), Gentell Hydrogel Impregnated Gauze (Gentell Wound and Skin Care), Hydrogel Impregnated Gauze Dressing (McKesson Medical-Surgical), Kendall TM Hydrogel Impregnated Gauze (Covidien), MPM GelPad TM Hydrogel Saturated Gauze Dressing (MPM Medical, Inc.), Restore TM Hydrogel Dressing(Impregnated Gauze)(Hollister Wound Care), Skintegrity TM Hydrogel Dressing (Medline Industries, Inc.) and SOLOSITE TM Commercially available impregnated hydrogels of this type that may be used include Conformable Wound Gel Dressing (Smith & Nephew, Inc.).

[0018] In some embodiments, the dressing comprises a hydrogel sheet in which the hydrogel is supported by a thin fiber mesh. The hydrogel sheet can be formed by coating a fiber mesh with a suitable hydrogel (e.g., gelatin). Alternatively, commercially available hydrogel sheets, such as AquaClear® (Hartmann USA, Inc.), AquaDerm®, and others, can be used. TM (DermaRite Industries, LLC), Aquaflo TM Hydrogel Dressing(Covidien), AquaSite TMHydrogel Sheet (Derma Sciences, Inc.), Aquasorb TM and Border (DeRoyal), Avogel TM Hydrogel Sheeting for Scars (Avocet Polymer Technologies, Inc.), Comfort-Aid TM (Southwest Technologies, Inc.), CoolMagic TM Gel Sheet (MPM Medical, Inc.), Curasol TM Gel Saturated 4x4 Dressing (Smith & Nephew, Advanced Wound Biotherapeutics), Derma-Gel TM Hydrogel Sheet (Medline Industries, Inc.), Elasto-Gel TM (Southwest Technologies, Inc.), FLEXIGEL * Hydrogel Sheet Dressing (Smith & Nephew, Inc.), Hydrogel Sheet Dressing (McKesson Medical-Surgical), MediPlus TM Barrier Gel Comfort Border (MediPurpose, Inc.), MediPlus TM Barrier Gel Hydrogel Dressing (MediPurpose (registered trademark), Inc.) NU-GEL TM Wound Dressing (Systagenix), Spand-Gel TM Hydrogel Dressing Sheets (Medi-Tech International Corp.), Toe-Aid TM (Southwest Technologies, Inc.) and XCell TM Cellulose Wound Dressing (Medline Industries, Inc.) can be used.

[0019] In a specific embodiment, the hydrogel is gelatin. Gelatin can be obtained by hydrolysis of collagen by boiling skin, ligaments, tendons, etc. A mixture of 2% gelatin in water forms a firm hydrogel. The hydrogel can be formed by adding gelatin to hot water to dissolve the gelatin. When the solution is then cooled, the solid gelatin component forms submicroscopic crystalline particles that retain a significant amount of water in their interstices.

[0020] Hydrogels are usually transparent, but may also be opalescent.

[0021] In still other embodiments, the wound dressing may comprise a biological dressing (e.g., hyaluronic acid, chitosan, and elastin) or a synthetic polymer (e.g., gauze or polysiloxane) or a combination of both (e.g., Integra1 M bilayer matrix wound dressing).

[0022] In still other embodiments, the wound dressing may include GanuGEL® ConVaTec.

[0023] Examples of other wound contact media that are particularly suitable in deep or irregularly shaped wounds are plastic, fabric or foam plugs or other conformable structures, as well as gels, creams, foams or packing materials.

[0024] The wound dressing or other wound contact medium is free of peroxide compounds, i.e., does not contain any peroxide compounds. As known to those skilled in the art, peroxide compounds are those that contain a peroxo group (-OO-) or a peroxide anion (O2 2-Typical examples of peroxide compounds are hydrogen peroxide, peracids (e.g., percarbonates, perphosphates, perborates, or persulfates), metal peroxides (e.g., sodium peroxide and lithium peroxide), and organic peroxides (e.g., urea peroxide, peresters, and di-tert-butyl peroxide).

[0025] In the context of the present invention, the term "free of peroxide compounds" should be understood to mean that there is no intentional addition of peroxide compounds to the wound dressing according to the present invention. In a preferred embodiment, the term "free of peroxide compounds" should be understood to mean that the wound dressing according to the present invention does not contain peroxide compounds in any significant amount.

[0026] It should be understood that the characteristics "free of" or "free of peroxide compounds" alone do not refer to the wound dressing or other wound contact medium, as made or sold, prior to its use. As discussed below, in use, the wound dressing or other wound contact medium is subjected to a means for applying hydrogen peroxide before and / or after its application to the wound, resulting in the in situ generation of peracetic acid.

[0027] The wound dressing or other wound contact medium preferably does not contain other compounds that can liberate oxygen when activated and / or other peroxygen donors that form hydrogen peroxide when activated. Thus, the wound dressing or other wound contact medium preferably does not contain superoxide compounds, dioxygenyl compounds and ozone compounds.

[0028] The wound dressing or other wound contact medium comprises an acetyl donor compound. Preferably, the acetyl donor compound is substantially insoluble and inert. This insolubility and inertness provides the wound dressing or other wound contact medium of the present invention with even greater stability and improved shelf life. The acetyl donor compound is preferably capable of reacting with hydrogen peroxide to form peracetic acid upon addition of water. The acetyl donor preferably comprises any one or a combination of compounds from the following list: Tetraacetylethylenediamine (TAED) Methylcellulose-encapsulated TAED or encapsulated donor Acetylsalicylic acid (ASA) Diacetyldioxohexahydratriazine (DADHT) Tetraacetylglycoluril Acetylurea Diacetylurea Triacetylurea Pentaacetylglucose (PAG) Tetraacetylglycoluril (TAGU) acetyl phosphate Acetylimidazole Acetyl CoA acetic anhydride Compounds containing a hemiacetal group acetic acid Diacetylmorphine Pyruvate Acetyl chloride Acetylcaprolactam N'N'-Diacetyl-N'N'-dimethylurea.

[0029] In a preferred embodiment, the acetyl donor compound is selected from tetraacetylethylenediamine (TAED), pentaacetylglucose (PAG), acetylsalicylic acid (ASA), or a mixture thereof. PAG includes alpha-PAG and beta-PAG. It is particularly preferred to use alpha-PAG, beta-PAG, TAED, and a combination of TAED and PAG (TAED combined with alpha-PAG and TAED combined with beta-PAG) as the acetyl donor.

[0030] In a preferred embodiment, the acetyl donor compound is contained in particles so that a wound dressing or other wound contact medium contains particles containing the acetyl donor compound. It is particularly preferred that the acetyl donor compound is encapsulated in polymer particles. The polymer for the polymer particles is preferably poly(lactic-co-glycolic acid) (PLGA). The particles, especially the polymer particles, are preferably microparticles and / or nanoparticles. The loading of the acetyl donor compound into the particles as described above can be achieved by known techniques during or after the particle fabrication process.

[0031] In the case of an acetyl donor compound contained in a particle, when the particle ruptures, degrades, or changes its porosity in situ, release of the acetyl donor compound occurs, and the compound may become present on the body of the human or animal host, particularly in the body fluids in the wound being treated. Advantageously, the particles degrade over time via hydrolysis, resulting in the controlled release of the acetyl donor compound.

[0032] Examples of particles, particularly microparticles and / or nanoparticles, suitable for use in the present invention are micelles, dendrimers, buckyballs, liposomes, ethosomes, mesoporous silica, and carbon nanotubes, all of which are capable of encapsulating other chemical entities, such as acetyl donor compounds.

[0033] Advantageously, particles, preferably polymer particles, particularly microparticles and / or nanoparticles, in which an acetyl donor compound is encapsulated are produced by a thermally induced phase separation (TIPS) process, although this is not necessarily the case. Such a process minimizes the residue of solvents used in the encapsulation process, which may otherwise impair the safety and efficacy of the resulting particles. Furthermore, in some cases, the particles are preferably biodegradable to produce harmless by-products. Thus, preferably, the particles comprise a biodegradable polymer, such as poly(lactic-co-glycolic acid) (PLGA), which can be used to produce particles, particularly microparticles and / or nanoparticles, encapsulating an acetyl donor compound by the TIPS process.

[0034] Release kinetics (rate and time) can be modified by adjusting the composition of the polymer used to produce polymeric particles, such as microparticles and nanoparticles. These particles can be produced from a variety of synthetic and natural polymers. Examples of such polymers include PLGA, poly(allylamine) hydrochloride, poly(diallylmethylammonium chloride), polyethyleneimine (PEI), polyvinylpyrrolidone, poly-L-ornithine, poly-L-arginine, protamine, chitosan, alginate, polystyrene sulfonic acid, poly(acrylic acid), poly(methacrylic acid), polyvinyl sulfonic acid, polyphosphate, poly-L-glutamic acid, and dextran sulfate. Nanomicelle particles can also be produced from, for example, polyethylene oxide / polypropylene oxide diblock and triblock copolymers, phospholipids, or other surfactants.

[0035] PLGA is a preferred polymer for the particles. PLGA is a copolymer synthesized using ring-opening copolymerization of the cyclic dimer (1,4-dioxane-2,5-dione) of two different monomers, glycolic acid and lactic acid. PLGA undergoes hydrolysis in vivo to produce the original monomers, lactic acid and glycolic acid, which are by-products of various metabolic pathways in the body under normal physiological conditions. Therefore, the systemic toxicity associated with the use of PLGA for the purposes of the present invention is minimal.

[0036] As noted, the polymer particles in which the acetyl donor compounds are encapsulated are preferably produced by a thermally induced phase separation (TIPS) process, although those skilled in the art will recognize that other production methods are possible.

[0037] The TIPS process begins with the formation of a polymer solution, e.g., a PLGA solution, at elevated temperatures to produce a homogeneous solution. An acetyl donor compound is dissolved in a suitable solvent and then mixed into the polymer solution. Removal of thermal energy by quenching below the bimodal solubility curve with another immiscible cooling liquid induces phase demixing of the homogeneous polymer solution, resulting in a multiphase system containing a polymer-rich phase and a polymer-lean phase. The phase-separated polymer solution is then processed by freeze-drying to remove the solvent, producing particles, particularly microparticles and / or nanoparticles, suitable for the present invention. Conventional microencapsulators, such as the Encapsulator VAR-D unit manufactured by Nisco Engineering AG, can be used for this process.

[0038] As indicated above, the particles loaded with the acetyl donor compound may comprise microparticles, nanoparticles, or a mixture of the two. According to the IUPAC (International Union of Pure and Applied Chemistry) definition, microparticles are defined as particles with a particle size of 1×10 -7 m~1×10-4 Nanoparticles are particles of any shape with dimensions in the range of 1×10 -9 m~1×10 -7 Particles of any shape with dimensions in the range of less than 1 μm. The particle size and size distribution of microparticles and nanoparticles determine, for example, their in vivo distribution, biological fate, toxicity, and targeting ability. Furthermore, they can also affect the drug loading, drug release, and stability of the particles. Because smaller particle sizes exhibit stronger oxidative effects, particle sizes are preferably less than 250 μm, e.g., 1-250 μm.

[0039] Poly(lactic-co-glycolic acid) (PLGA)-based particles ranging in size from approximately 20 nm in diameter to micron size can be produced. The production of such particles is known and is described, for example, in WO2008 / 155558. The method for producing these particles can be used to manipulate properties such as size-to-volume ratio and surface area-to-volume ratio, porosity, payload efficiency, and drug release profile. This makes them particularly suitable for use in the present invention. The loading of these particles with acetyl donor compounds can be achieved by known techniques during or after the particle fabrication process.

[0040] Particles, such as polymer particles, in which the acetyl donor compound is encapsulated can be wetted, for example, with a surfactant, such as pluronic acid. This is advantageous for handling particles when they are hydrophobic and can be easily activated by the plasma within the hydrogel coating.

[0041] The acetyl donor compound or particles containing the acetyl donor compound can be fixed to a wound dressing or other wound contact medium by any common method. It is clear that the suitable method will depend strongly on the type of acetyl donor compound or particle used and the type of wound dressing or other wound contact medium used. In a preferred embodiment, the wound dressing comprises a coated substrate to which particles are attached, for example, by physical or chemical means. The particles are preferably attached to the coated substrate via a linking group. In this regard, bifunctional chemical compounds can be used that can react with both the coated substrate and the particles via functional groups, thereby providing a linking group between them.

[0042] The present invention also relates to a wound dressing or other wound contact medium comprising an acetyl donor for use in the prevention and / or treatment of wound infection in a patient.

[0043] The present invention also relates to a wound dressing or other wound contact medium comprising an acetyl donor for use in the prevention and / or treatment of wound infection in a patient, the prevention and / or treatment comprising applying the wound dressing or other wound contact medium to a wound in a patient, and subjecting the wound dressing or other wound contact medium to a means for applying hydrogen peroxide to activate the acetyl donor compound of the wound dressing or other wound contact medium with the hydrogen peroxide to generate peracetic acid in situ.

[0044] The present invention also relates to a wound dressing or other wound contact medium comprising an acetyl donor but not a peroxide compound for use in the prevention and / or treatment of wound infection in a patient.

[0045] The present invention also relates to a wound dressing or other wound contact medium comprising an acetyl donor but no peroxide compound for use in the prevention and / or treatment of wound infection in a patient, which prevention and / or treatment comprises applying the wound dressing or other wound contact medium to a wound in a patient, and subjecting the wound dressing or other wound contact medium to a means for applying hydrogen peroxide to activate the acetyl donor compound of the wound dressing or other wound contact medium with the hydrogen peroxide to produce peracetic acid in situ.

[0046] The wound dressing or other wound contact medium of the present invention is suitable for use in preventing and / or treating wound infections in patients. The wound dressing or other wound contact medium is as described above. Its use involves applying the wound dressing or other wound contact medium to a patient's wound. A wound may be defined as a disruption in the continuity of the epithelial layer of skin or mucous membrane, and in the case of chronic open wounds such as diabetic foot ulcers or venous leg ulcers, may be deep, affecting tissues below the epidermis.

[0047] The use further includes subjecting the wound dressing or other wound contact medium to a means for applying hydrogen peroxide. As a result, the acetyl donor compound of the wound dressing or other wound contact medium is activated by the hydrogen peroxide to generate peracetic acid in situ. Typically, a mixture of hydrogen peroxide and peracetic acid is generated. The peracetic acid, and optionally hydrogen peroxide, can exert their biocidal effects at the wound site.

[0048] In one embodiment, the means for applying hydrogen peroxide to the wound dressing or other wound contact medium comprises: means for applying hydrogen peroxide by spraying or immersion; A means of applying hydrogen peroxide by packing wipes or sterile pads containing hydrogen peroxide; means for applying hydrogen peroxide by instillation; means for applying hydrogen peroxide by striping by passing the solution over a series of holes in an applicator bar; A means for applying hydrogen peroxide by printing a solution of gel containing hydrogen peroxide by gravure printing or other techniques; Means for applying hydrogen peroxide in the form of vapor or mist is selected from.

[0049] Another means of applying hydrogen peroxide to a wound dressing or wound contact medium is by applying a microorganism that produces hydrogen peroxide in situ.

[0050] The concentration of hydrogen peroxide applied to the wound dressing by means of hydrogen peroxide can vary within a wide range. Hydrogen peroxide is readily available over the counter as a 3% or 6% solution and commercially available in concentrations up to 35%. Higher concentrations have become increasingly scarce in recent years due to their potential use in explosive devices. The concentrations mentioned above are widely used in topical treatments and dental applications. They are generally considered too high for application to open wounds. The appropriate dilution for use may be in the significantly lower millimolar range and is determined by several factors, including the amount of acetyl donor in the dressing, the nature of the wound, contact time, the absorbency of the dressing, and other factors. In one embodiment, the concentration of hydrogen peroxide applied is in the range of 0.01 to 6% by weight, e.g., 0.01 to 1% by weight, e.g., 0.01 to 3% by weight.

[0051] By subjecting a wound dressing or other wound contact medium to a means for applying hydrogen peroxide, an interaction occurs between the dressing or other medium and plasma. In particular, the acetyl donor compound of the dressing or other medium is activated by or reacts with plasma-produced hydrogen peroxide, thereby forming peracetic acid in situ and imparting biocidal properties at the wound site.

[0052] In one embodiment, the wound dressing or other wound contact medium is subjected to a means for applying hydrogen peroxide before being applied to the wound. In one embodiment, the wound dressing or other wound contact medium is subjected to a means for applying hydrogen peroxide after being applied to the wound. The treatment by a means for applying hydrogen peroxide can also be carried out before and after application to the wound. If the wound dressing or other wound contact medium is subjected to a means for applying hydrogen peroxide before being applied to the wound, it should be applied to the wound soon thereafter, for example, at most 30 minutes later. This is because the persistence of the generated active species, such as peracetic acid, which are beneficial for treatment, is relatively short.

[0053] The patient treated with the wound dressing or other wound contact medium provided as described may be a human patient or an animal patient, with human patients being preferred.

[0054] The present invention provides a) a wound dressing or other wound contact medium comprising an acetyl donor compound according to the present invention, and b) a means for applying hydrogen peroxide configured to apply hydrogen peroxide to the wound dressing or other wound contact medium; The present invention also relates to a kit comprising:

[0055] In particular, the present invention also relates to a kit comprising a wound dressing or other wound contact medium according to the present invention, which comprises an acetyl donor compound but does not comprise a peroxide compound, and a means for applying hydrogen peroxide configured to apply hydrogen peroxide to the wound dressing or other wound contact medium.

[0056] The wound dressing or other wound contact medium and the means for applying hydrogen peroxide according to the present invention have been described and referenced above. The means for applying hydrogen peroxide can direct plasma flow to the wound dressing or other wound contact medium being treated. The means for applying hydrogen peroxide can activate an acetyl donor compound in the wound dressing or other wound contact medium, thereby generating peracetic acid in situ, which results from the reaction of hydrogen peroxide with the acetyl donor compound. The means for applying hydrogen peroxide to the wound dressing or wound contact medium preferably includes: means for applying hydrogen peroxide by spraying or immersion; A means of applying hydrogen peroxide by packing wipes or sterile pads containing hydrogen peroxide; means for applying hydrogen peroxide by instillation; a means for applying hydrogen peroxide by striping the solution by passing it over a series of holes in an applicator bar that delivers the solution; A means for applying hydrogen peroxide by printing a solution of gel containing hydrogen peroxide by gravure printing or other techniques; Means for applying hydrogen peroxide in the form of vapor or mist is selected from.

[0057] The present invention also relates to a process for preventing and / or treating a wound infection in a patient, the process comprising applying a wound dressing or other wound contact medium comprising an acetyl donor to a wound of a patient according to the present invention, and subjecting the wound dressing or other wound contact medium to a means for applying hydrogen peroxide before and / or after application to the wound.

[0058] In particular, the present invention also relates to a process for preventing and / or treating a wound infection in a patient, which process comprises applying a wound dressing or other wound contact medium according to the present invention, which comprises an acetyl donor compound but no peroxide compound, to a wound on a patient, and subjecting the wound dressing or other wound contact medium to a means for applying hydrogen peroxide before and / or after application to the wound.

[0059] The process may employ a means for applying hydrogen peroxide that can direct plasma flow to the wound dressing or other wound contact medium being treated. The wound dressing or other wound contact medium of the present invention, the means for applying hydrogen peroxide to the wound dressing or other wound contact medium, and the process steps have been described and referenced above. The means for applying hydrogen peroxide may activate an acetyl donor compound in the wound dressing or other wound contact medium to produce peracetic acid in situ, which results from the reaction of hydrogen peroxide with the acetyl donor compound. The means for applying hydrogen peroxide preferably comprises: means for applying hydrogen peroxide by spraying or immersion; A means of applying hydrogen peroxide by packing wipes or sterile pads containing hydrogen peroxide; means for applying hydrogen peroxide by instillation; a means for applying hydrogen peroxide by striping the solution by passing it over a series of holes in an applicator bar that delivers the solution; A means for applying hydrogen peroxide by printing a solution of gel containing hydrogen peroxide by gravure printing or other techniques; Means for applying hydrogen peroxide in the form of vapor or mist is selected from.

[0060] The patient may be a human or an animal, with human patients being preferred.

Claims

1. 1. A wound dressing or other wound contact medium comprising an acetyl donor compound but not a peroxide compound, the acetyl donor compound is encapsulated within a polymer particle; A wound dressing or other wound contact medium, wherein the material of said wound dressing or other wound contact medium is selected from a hydrogel, a plastic, a fabric, a foam plug, a gel, a foam or a filler material.

2. 2. The wound dressing or other wound contact medium of claim 1, wherein the particles have a particle size of less than 250 μm.

3. 3. A wound dressing or other wound contact medium according to claim 1 or claim 2, wherein the wound dressing comprises a coated substrate to which the particles are attached.

4. A wound dressing or other wound contact medium as described in claim 3, wherein the wound dressing comprises a coated substrate to which the particles are attached via linking groups.

5. 5. The wound dressing or other wound contact medium of any one of claims 1 to 4, wherein the acetyl donor compound is selected from tetraacetylethylenediamine (TAED), methylcellulose-encapsulated TAED or encapsulated donor, acetylsalicylic acid (ASA), diacetyldioxohexahydratriazine (DADHT), tetraacetylglycoluril, acetylurea, diacetylurea, triacetylurea, pentaacetylglucose (PAG), tetraacetylglycoluril (TAGU), acetyl phosphate, acetylimidazole, acetyl CoA, acetic anhydride, a compound containing a hemiacetal group, acetic acid, diacetylmorphine, pyruvate, acetyl chloride, acetyl-caprolactam, N'N'-diacetyl-N'N'-dimethylurea, or a combination of two or more thereof.

6. 6. A wound dressing or other wound contact medium according to any one of claims 1 to 5, wherein the acetyl donor compound is selected from tetraacetylethylenediamine (TAED), pentaacetylglucose (PAG), acetylsalicylic acid (ASA) or mixtures thereof.

7. a) a wound dressing or other wound contact medium according to any one of claims 1 to 6, comprising an acetyl donor compound, and b) applying hydrogen peroxide to the wound dressing or other wound contact medium, which is capable of activating the acetyl donor compound of the wound dressing or other wound contact medium to generate peracetic acid in situ; Includes a kit.

8. The means for applying hydrogen peroxide to the wound dressing or other wound contact medium comprises: - means for applying hydrogen peroxide by spraying or immersion; A means of applying hydrogen peroxide by packing wipes or sterile pads containing hydrogen peroxide; - means for applying hydrogen peroxide by instillation; a means for applying hydrogen peroxide by striping it by passing it over a series of holes in an applicator bar that delivers the solution; - A means for applying hydrogen peroxide by printing a solution of gel containing hydrogen peroxide by gravure printing or other techniques; - Means for applying hydrogen peroxide in the form of vapor or mist The kit of claim 7, wherein the kit is selected from the group consisting of:

9. 7. A wound dressing or other wound contact medium according to any one of claims 1 to 6, comprising an acetyl donor compound, for use in the prevention and / or treatment of wound infections in a patient, said prevention and / or treatment comprising applying the wound dressing or other wound contact medium to a wound on the patient, and subjecting the wound dressing or other wound contact medium to a means for applying hydrogen peroxide to the wound dressing or other wound contact medium, whereby the acetyl donor compound of the wound dressing or other wound contact medium is activated by the hydrogen peroxide to produce peracetic acid in situ.

10. The means for applying hydrogen peroxide to the wound dressing or other wound contact medium comprises: - means for applying hydrogen peroxide by spraying or immersion; A means of applying hydrogen peroxide by packing wipes or sterile pads containing hydrogen peroxide; - means for applying hydrogen peroxide by instillation; a means for applying hydrogen peroxide by striping it by passing it over a series of holes in an applicator bar that delivers the solution; - A means for applying hydrogen peroxide by printing a solution of gel containing hydrogen peroxide by gravure printing or other techniques; - Means for applying hydrogen peroxide in the form of vapor or mist 10. A wound dressing or other wound contact medium for use according to claim 9 selected from:

11. 11. A wound dressing or other wound contact medium for use according to claim 9 or claim 10, wherein the wound dressing or other wound contact medium is subjected to a means for applying hydrogen peroxide to the wound dressing or other wound contact medium before and / or after it has been applied to the wound.

12. A wound dressing or other wound contact medium for use according to any one of claims 9 to 11, wherein the patient is a human or an animal.

Citation Information

Patent Citations

  • Film that controls the release of oxygen / antibacterial agents

    JP1996510155A

  • Occlusive dressing made of cellulose ester wound

    JP1999070159A

  • Therapeutic agent for use in the treatment of infections

    JP2017510648A

  • A therapeutic agent for use in the treatment of infections

    WO2015150722A1