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WO2025012618A1 - Compositions antimicrobiennes - Google Patents

Compositions antimicrobiennes Download PDF

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Publication number
WO2025012618A1
WO2025012618A1 PCT/GB2024/051760 GB2024051760W WO2025012618A1 WO 2025012618 A1 WO2025012618 A1 WO 2025012618A1 GB 2024051760 W GB2024051760 W GB 2024051760W WO 2025012618 A1 WO2025012618 A1 WO 2025012618A1
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WIPO (PCT)
Prior art keywords
composition
polymer
enzyme
substrate
weight
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PCT/GB2024/051760
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English (en)
Inventor
Thomas Hall
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Matoke Holdings Ltd
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Matoke Holdings Ltd
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Publication of WO2025012618A1 publication Critical patent/WO2025012618A1/fr
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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/40—Peroxides

Definitions

  • compositions such as powder compositions, for generating hydrogen peroxide, and their use in treating infections and wounds.
  • honey has been used for treatment of microbial infections since ancient times. In recent years there has been a resurgence of interest in the therapeutic efficacy of honey, particularly in the area of wound healing. Clinical trials have shown that honey is an effective broad-spectrum antimicrobial agent which is effective against common wound-infecting organisms, such as Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans and Escherichia coli, and is effective against antibiotic-resistant strains of bacteria. As a natural product, honey also offers an attractive alternative to drug-based treatments.
  • honey has antimicrobial activity. This activity is attributed largely to osmolarity, pH, hydrogen peroxide production and the presence of phytochemical components.
  • honey can be greatly enhanced and controlled by adding glucose oxidase to honey, and that compositions comprising honey and added glucose oxidase are applicable in the treatment of a number of infections, and notably in the treatment of infections caused by biofilms (see WO 2015/166197, WO 2016/083798 and WO 2016/124926).
  • honey is a natural product, its composition can vary greatly depending on its source.
  • the difference in antimicrobial potency among honeys can be more than one hundred-fold, depending on the geographical, seasonal and botanical source of the honey, as well as the harvesting, processing and storage conditions. Consequently, the antimicrobial efficacy may also vary depending on the type of honey used.
  • honey may also contain other components, such as allergens e.g. trace amounts of pollen, which may cause adverse reactions when applied to certain subjects and make it unsuitable for certain pharmaceutical applications.
  • allergens e.g. trace amounts of pollen
  • Honey is sticky and can be difficult to apply and remove from a patient. Honey may also require processing such that it is in a suitable form for application to subjects, which can add cost and complexity to the production process. Such processing may include creaming or pasteurisation.
  • compositions which provide enhanced antimicrobial efficacy compared to honey, and which also overcome some of honey’s disadvantages.
  • compositions with improved stability The applicant has formulated synthetic liquid and gel compositions which ma improvements over honey-based compositions, such as those disclosed in WO 2020/193993 and WO 2021/186165.
  • liquids and gels may be advantageous for certain applications, they may not be optimal for other applications.
  • powders may be more advantageous in certain circumstances. For instance, powders may be more readily applied to dressing materials to form antimicrobial dressings. In certain circumstances, powders could be applied directly to a wound.
  • Superabsorbent powder compositions comprising superabsorbent polymer are disclosed in WO 2019/077335. However, it is desired to provide powders that are not necessarily superabsorbent, and which have improved stability. For example, it is desired to provide dry compositions, such as powders, which maintain the ability to generate hydrogen peroxide at effective levels and which maintain their consistency, minimising clumping or aggregation, after being stored for extended periods of time.
  • the invention concerns compositions which include enzyme that is able to convert a substrate to release hydrogen peroxide.
  • such compositions are able to generate hydrogen peroxide on addition of water.
  • Such compositions may also include substrate for the enzyme.
  • the invention also concerns methods of making such compositions that are able to generate hydrogen peroxide.
  • this may include combining enzyme that is able to convert a substrate to release hydrogen peroxide and substrate for the enzyme.
  • the composition is a dry composition.
  • a dry composition comprising enzyme that is able to convert a substrate to release hydrogen peroxide; polymer; and optionally substrate for the enzyme.
  • the composition is a solid composition.
  • a solid composition comprising enzyme that is able to convert a substrate to release hydrogen peroxide; polymer; and optionally substrate for the enzyme.
  • dry, solid compositions includes granular compositions or powdt herein to a “powder” may be used interchangeably with a “granular composition”. Dry compositions may also include films. Compositions of the invention may thus not be liquids or gels.
  • the composition is a powder composition, or a dry powder composition.
  • a powder composition comprising enzyme that is able to convert a substrate to release hydrogen peroxide; polymer; and optionally substrate for the enzyme.
  • compositions of the invention are able to generate hydrogen peroxide on contact with water.
  • compositions may comprise substrate for the enzyme, and/or they could comprise precursor substrate.
  • compositions of the invention may comprise a plurality of enzymes that are able to convert a substrate to release hydrogen peroxide.
  • compositions may comprise two enzymes, such as glucose oxidase and galactose oxidase.
  • compositions of the invention may comprise only one enzyme that is able to convert a substrate to release hydrogen peroxide.
  • the only enzyme in the composition that is able to convert a substrate to release hydrogen peroxide may be glucose oxidase.
  • the enzyme is a purified enzyme.
  • purified enzyme is used herein to include an enzyme preparation in which the enzyme has been separated from at least some of the impurities originally present when the enzyme was produced.
  • impurities that have been removed or reduced include those that would otherwise interfere with the ability of the enzyme to convert the substrate to release hydrogen peroxide.
  • the enzyme is at least 95% pure. Even more preferably, the enzyme is at least 98% pure. Most preferably, the enzyme is at least 99% pure.
  • the enzyme may have been produced by recombinant or non-recombinant means, and may be a recombinant or non-recombinant enzyme.
  • the enzyme may be purified from a microbial source, preferably from a non-genetically modified microbe.
  • the level of purity of the enzyme may be selected as appropriate depending on the intended use of the composition.
  • a medical grade or medical device grade of purity should be used.
  • a pharmaceutical grade of purity should be used.
  • the total amount of all the hydrogen peroxide-generating enzyme in composi invention may be 0.0005% to 0.5% (by weight), 0.001 % to 0.2% (by weight), 0.001% to 0.1 % (by weight), or 0.0005% to 0.05% (by weight).
  • composition includes more than one enzyme that is able to convert a substrate to release hydrogen peroxide
  • at least one of those enzymes may be present in an amount of 0.0005% to 0.5% (by weight), 0.001% to 0.2% (by weight), 0.001 % to 0.1 % (by weight), or 0.005% to 0.05% (by weight).
  • the amount of enzyme may vary depending on the desired level of hydrogen peroxide production on dilution, or the particular application of the composition. In some applications, the amount of enzyme may be higher. For example, if the composition (e.g. a powder) is to be used to coat or impregnate a dressing material, higher enzyme concentrations may be desirable to compensate for a lower coating density.
  • the composition e.g. a powder
  • higher enzyme concentrations may be desirable to compensate for a lower coating density.
  • the total amount of hydrogen peroxide generating enzyme in compositions of the invention may be 0.5 % to 10% (by weight), 0.5% to 7.5% (by weight), or 0.5% to 5% (by weight).
  • composition includes more than one enzyme that is able to convert a substrate to release hydrogen peroxide, at least one of those enzymes may be present in an amount of 0.5 % to 10% (by weight), 0.5% to 7.5% (by weight), or 0.5% to 5% (by weight).
  • a suitable amount of enzyme can be readily determined by a person of ordinary skill in the art, if necessary using a well diffusion assay, to determine the extent of hydrogen peroxide release for different amounts of enzyme.
  • the amount of enzyme used may be selected so as to produce a composition for generating antimicrobial activity that is equivalent to a selected phenol standard (for example a 10%, 20%, or 30% phenol standard).
  • compositions of the invention may comprise at least 1 unit, and preferably up to 1500 units, of the enzyme per gram of the composition.
  • a “unit” is defined herein as the amount of enzyme (e.g. glucose oxidase) causing the oxidation of 1 micromole of substrate (e.g. glucose) per minute at 25 degrees centigrade at pH 7.0.
  • the enzyme is, or comprises, an oxidoreductase enzyme.
  • oxidoreductase enzymes include glucose oxidase, hexose oxidase, cholesterol oxidase, galactose oxidase, pyranose oxidase, choline oxidase, pyruvate oxidase, glycollate oxidase, amino acid oxidase, or mannose oxidase.
  • the oxidoreductase enzyme is glucose oxidase and the substrate for the oxidoreductase enzyme is glucose.
  • a composition according to the invention comprises rr for example at least 30 units, at least 50 units, or at least 100 units, and suitably less than 685 units, for example 100-500 units, of enzyme (e.g. glucose oxidase) per gram of the composition.
  • a composition according to the invention comprises at least 500 units, for example 500-1000 units, or 685-1000 units, of enzyme (e.g. glucose oxidase) per gram of the composition.
  • compositions of the invention may only be able to generate hydrogen peroxide at a significant level following dilution by water. Addition of water may thus initiate hydrogen peroxide production. Consequently, compositions of the invention should not comprise sufficient free water to allow the enzyme to convert the substrate.
  • Addition of water which may include contact with wound exudate, may result in sustained release of hydrogen peroxide at a specific level or concentration for a sustained period of time.
  • the level may be affected by the amount of enzyme in the composition.
  • the level of hydrogen peroxide production may be chosen so that the level is not too high, and thus cytotoxic, but is not too low and thus ineffective.
  • compositions of the invention may provide for sustained release of hydrogen peroxide at a level of 0.1 mM to 20 mM for a period of at least twenty four hours, preferably at least 72 hours, following dilution of the composition.
  • the level may be 0.5 mM to 10 mM .
  • the level may be 1 mM to 7.5 mM .
  • the water activity (a w ) may be 0.4 or less, or 0.3 or less.
  • a low water activity may be advantageous in preventing microbial proliferation, and it may be advantageous in minimising hydrogen peroxide production prior to activation by dilution.
  • Water activity is typically measured using a hygrometer, such as a resistive electrolytic hygrometer, a capacitance hygrometer or a dew point hygrometer. Measurement of water activity would typically take place at ambient temperature, such as normal temperature and pressure. Measurement of water activity may take place according to ISO 18787:2017.
  • compositions of the invention there is less than 10 ppm, less than 6 ppm, or less than 3 ppm hydrogen peroxide in compositions of the invention.
  • hydrogen peroxide is preferably not detectable using a hydrogen peroxide test strip, such as a Quantofix® peroxide test stick (Sigma Aldrich, UK).
  • hydrogen peroxide may present at a level less than 1 ppm or at a level less than 0.5 ppm.
  • Hydrogen peroxide may be at a level less than 0.1 ppm.
  • Compositions of the invention could feasibly contain low levels, or trace amoi
  • compositions of the invention may be manufactured by lyophilisation, for example, which would remove water from the compositions. So, the composition may be a lyophilised composition.
  • compositions of the invention may comprise a plurality of substrates.
  • compositions of the invention may comprise only one substrate.
  • the only substrate present may be glucose.
  • the substrate is a purified substrate.
  • the term “purified substrate” is used herein to include a substrate which has been separated from at least some of the impurities originally present when the substrate was obtained or produced.
  • the purified substrate may be obtained from a natural source or may be synthetically produced.
  • the purified substrate may be a processed, extracted, or refined substrate (i.e. a substrate in which impurities or unwanted elements have been removed by processing).
  • the purified substrate is at least 90%, 95%, or 99% pure (mass purity).
  • the substrate is pharmaceutical grade.
  • the substrate is, or comprises, sugar.
  • sugar is used herein to refer to a carbohydrate with the general formula Cm(H 2 O) n .
  • the purified sugar may be obtained from a natural source (for example a processed, extracted, or refined natural sugar), or be synthetically produced.
  • the sugar is preferably at least 90%, 95%, or 99% pure (mass purity).
  • the sugar is preferably a pharmaceutical grade sugar.
  • the sugar may be a monosaccharide or a disaccharide, preferably a monosaccharide.
  • the sugar may include, for example purified D-glucose, hexose, or D-galactose.
  • the purified sugar may be medical grade, medical device grade, or pharmaceutical grade D-glucose, hexose, or D- galactose.
  • the sugar may be an anhydrous sugar.
  • the glucose may be anhydrous glucose.
  • the composition may comprise a precursor substrate. Any disclosure herein which relates to the substrate, such as amounts and purity, may also apply to the precursor substrate.
  • compositions of the invention which comprise a precursor-substrate
  • the composition may comprise one or more enzymes for converting the precursor-substrate to the substrate for the enzyme.
  • the precursor-substrate may not necessarily be converted to the substrate enzymatically.
  • addition of water may be sufficient for conversion.
  • compositions of the invention may comprise non-enzymatic catalysts.
  • Compositions which comprise a precursor-substrate may comprise a first enz convert the substrate to release hydrogen peroxide, and a second enzyme that is able to convert the precursor-substrate to the substrate for the first enzyme.
  • the precursor-substrate is preferably a carbohydrate, such as a polysaccharide, or a sugar e.g. a disaccharide, or sugar derivative.
  • the precursor-substrate may be sucrose
  • the first enzyme may be glucose oxidase and the second enzyme may be invertase.
  • the precursor-substrate may be maltose
  • the first enzyme may be glucose oxidase
  • the second enzyme may be maltase.
  • compositions of the invention which comprise a precursor-substrate may comprise an enzyme (preferably a purified enzyme) that is able to convert the substrate to release hydrogen peroxide, and at least two enzymes (e.g. second and third enzymes, preferably purified enzymes) that are able to convert the precursor-substrate to the substrate for the first enzyme.
  • the precursor-substrate may be starch
  • the first enzyme may be glucose oxidase
  • the second and third enzymes may be amylase and maltase.
  • the precursorsubstrate may be cellulose
  • the first enzyme may be glucose oxidase
  • the second and third enzymes may be cellulose and beta-glucosidase.
  • the enzyme is at least 95% pure, and the substrate is at least 95% pure (all with reference to mass purity).
  • the enzyme is at least 98% pure, and the substrate is at least 98% pure (all with reference to mass purity).
  • the enzyme is at least 99% pure, and the substrate is at least 99% pure (all with reference to mass purity).
  • compositions of the invention may be pharmaceutical grade.
  • pharmaceutical grade is used herein to refer to include reference to a purity standard for a reagent that has been established by a recognized national or regional pharmacopeia (e.g., the U.S. Pharmacopeia (USP), British Pharmacopeia (BP), National Formulary (NF), European Pharmacopoeia (EP), or Japanese Pharmacopeia (JP)).
  • USP U.S. Pharmacopeia
  • BP British Pharmacopeia
  • NF National Formulary
  • EP European Pharmacopoeia
  • JP Japanese Pharmacopeia
  • the substrate there is 10% or less, by weight, of the substrate in compositions of the invention. There may be 15% or less by weight, of the substrate. There may be 10% or less, by weight, of the substrate. There may be less than 5%, by weight, of the substrate, e.g. about 3%, by weight, of the substrate.
  • the total amount of all substrate in the composition may be at least 1 %, by weight, of the substrate.
  • compositions of the invention may have 1 % to 10%, by weight, of the substrate, preferably 1 to 5% by weight of the substrate.
  • the total amount of example be about 3%, by weight.
  • low amounts of total substrate may be preferred, higher amounts of substrate are also contemplated.
  • the total amount of substrate may be from 1% to 25%, by weight, of the composition.
  • a composition of the invention comprises more than one substrate, at least one of those substrates may be at least 1%, by weight, of the composition.
  • at least one of the substrates may be 1 % to 10%, by weight, 1 to 5%, or about 3% by weight of the composition.
  • At least one of the substrates may be from 1 % to 25%, by weight, of the composition.
  • a powder composition comprising enzyme that is able to convert a substrate to release hydrogen peroxide, substrate for the enzyme, and polymer, wherein the total amount of substrate in the composition is less than 5%, by weight.
  • the total amount of all sugar is preferably 10% or less by weight.
  • the total amount of fructose and glucose may not exceed 10%, by weight, of the composition.
  • the total amount of sugar is 7.5% or less, by weight.
  • the total amount of sugar in compositions of the invention is 1% to 10% by weight.
  • the total amount of sugar in the composition is 1 to 7.5% by weight.
  • the total amount of sugar in the composition is 1 to 5%, by weight.
  • the total amount of sugar in the composition is less than 5%, by weight.
  • a powder composition comprising enzyme that is able to convert a substrate to release hydrogen peroxide, substrate for the enzyme, and polymer, wherein the total amount of sugar in the composition is less than 5%, by weight.
  • compositions of the invention preferably do not include fructose.
  • Fructose is hygroscopic and is quicker to absorb moisture and slower to release it to the environment than sugars such as sucrose and glucose.
  • Fructose is an effective humectant and can retain moisture for extended periods of time. This may lead to instability because compositions including fructose may lead to greater water absorption, and increased hydrogen peroxide production, during storage. It may also lead to an inferior powder consistency. For example, it may increase clumping or aggregation of the powder.
  • compositions of the invention do not include any sugar other than glucose.
  • Compositions of the invention may not include any sugar derivative.
  • the term is used herein to refer to a sugar that has been modified by addition of one or more substituents other than a hydroxyl group.
  • Sugar derivatives thus encompass amino sugars, acidic sugars, deoxy sugars, sugar alcohols, glycosylamines and sugar phosphates.
  • sugar derivatives may include glucose-6-phosphateglucosamine, glucoronate, gluconate, galactosamine, glucosamine, sialic acid, deoxyribosefucose, rhamnose glucuronic acid, polyols (e.g. sorbitol, erythritol, xylitol, mannitol, lactitol and maltitol) and sucralose.
  • polyols e.g. sorbitol, erythritol, xylitol
  • compositions of the invention may not include sugars or sugar derivatives that have a high solubility in water, for example a solubility which is greater than glucose.
  • Glucose has a solubility of 90g/100g water at 20°C and 1 atm.
  • compositions of the invention may not include a sugar or sugar derivative with a solubility greater than or equal to 100g/100g water at 20°C and 1 atm, greater than or equal to 200g/100g water at 20°C and 1 atm, greater than 300g/100g water at 20°C and 1 atm.
  • compositions of the invention may not include a sugar or sugar derivative that is more hygroscopic than glucose.
  • Polymer in compositions of the invention may be any medically acceptable polymer, such as any Food and Drug Administration-approved (FDA-approved) polymer.
  • FDA-approved Food and Drug Administration-approved
  • compositions of the invention may comprise a plurality of polymers with distinct chemical structures, which are distinct from one another other than just by their molecular weight.
  • structurally distinct polymers may comprise structurally distinct monomer units.
  • the total amount of all polymer in the composition may be greater than 50%, by weight, of the composition.
  • the total amount of all polymer may be greater than 75%, by weight, of the composition.
  • the total amount of all polymer may be at least 80%, by weight, of the composition.
  • the total amount of all polymer may be at least 85%, by weight, of the composition.
  • the total amount of all polymer may be at least 90%, by weight, of the composition.
  • the total amount of all polymer may be at least 95%, by weight, of the composition.
  • a powder composition comprising enzyme that is able to convert a substrate to release hydrogen peroxide, substrate for the enzyme, and polymer, wherein the total amount of polymer in the compositior 75% by weight.
  • a composition of the invention comprises more than one polymer
  • at least one of those polymers may be at least 5%, by weight, of the composition, at least 10%, by weight, of the composition or at least 20%, by weight, of the composition.
  • the composition includes two polymers with a combined weight % of more 80, the first polymer may have a weight % of 25, whilst the second polymer may have a weight % of 55.
  • compositions of the invention may include different types of the same polymer with the same molecular structure, such as the same monomer.
  • the same monomer such as polyethylene glycols with differing molecular weights.
  • the polymer comprises a water-soluble polymer, which is soluble in water at normal temperature and pressure (NTP).
  • NTP normal temperature and pressure
  • suitable water-soluble synthetic polymers include polyacrylic acid, polyethylene oxide, polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylamide, poly (isopropyl acrylamide) and poly(cyclopropyl methacrylamide).
  • the polymer comprises a synthetic polymer.
  • the polymer comprises a non-ionic polymer.
  • the polymer comprises a biocompatible polymer.
  • the polymer comprises a biodegradable polymer.
  • the polymer comprises a polymer with a carbon chain backbone, such as a vinyl polymer.
  • the polymer comprises a polymer with a hetero chain backbone, such as a polyether.
  • the polymer comprises a plasticising polymer.
  • the polymer comprises a semi-crystalline polymer, which is semi-crystalline at NTP.
  • the polymer comprises a thermoplastic polymer.
  • the polymer may comprise a polymer with a glass transition temperature (Tg) of 30 e C or higher, 50 e C or higher, or 60 e C or higher. Such polymers may afford a degree of hardness or granularity to the powder. Polymers with low Tg may not provide the desirabh hardness.
  • Tg glass transition temperature
  • a preferred example of a polymer with a Tg of at least 50 e C or more is polyvinyl alcohol.
  • Other examples of polymers with Tg of at least 50 e C include polyacryilic acid, polvinyl pyrrolidone and polyacrylamide.
  • the polymer may comprise a polymer with a Tg which is less than 50 e C, preferably less than 30 e C, more preferably less than 25 e C.
  • Polymers with such Tg values, such as polyethylene glycol, or polypropylene glycol may have plasticising properties.
  • the polymer comprises polyvinyl alcohol.
  • Polyvinyl alcohol may be present in the composition in an amount of at least 10%, by weight, at least 25% by weight, at least 50% by weight, at least 75% by weight, or at least 90% by weight.
  • Polyvinyl alcohol may be present in an amount of 50 to 90% by weight, or 55 to 80% by weight.
  • the polyvinyl alcohol may have a molecular weight of 20,000 to 75,000, such as 25,000 to 60,000, e.g. 31 ,000 to 50,000.
  • the polyvinyl alcohol may be at least 80% hydrolysed, preferably at least 85% hydrolysed.
  • the polymer comprises polyethylene glycol.
  • Polyethylene glycol may be present in the composition in an amount of at least 10%, by weight, at least 25% by weight, at least 50% by weight, at least 75% by weight, or at least 90% by weight.
  • Polyethylene glycol may be present in an amount of 10 to 50% by weight, or 15 to 45% by weight.
  • the polymer comprises polyvinyl alcohol and polyethylene glycol.
  • Polyvinyl alcohol and polyethylene glycol may each be present in an amount of at least 10% by weight or at least 20% by weight.
  • the amount of polyvinyl alcohol may be more than the amount of polyethylene glycol.
  • Polyethylene glycol in compositions of the invention may have a molecular weight of 10000 or less (i.e. PEG 10000), 7500 or less, or 5000 or less (i.e. PEG 5000).
  • the polyethylene glycol may have a molecular weight of at least 2000 (i.e. PEG 2000), or at least 3000 (i.e. PEG 3000).
  • the polyethylene glycol may have a molecular weight of 2000 to 10000, 2000 to 7500 or 3000 to 5000.
  • the polymer may comprise one or more water-insoluble, synthetic polymers. These may include polyesters, such as aliphatic polyesters. Examples may include polylactic acid, poly(lactic-co-glycolic acid) or polycaprolactone.
  • the polymer may comprise one or more natural polymers.
  • the one or more r may comprise a protein-based polymer such as albumin, collagen or gelatin.
  • the one or more natural polymers may comprise a polysaccharide-based polymer such as agarose, alginate, carrageenan, chitosan, cyclodextrins, dextran, hyaluronic acid, polysialic acid, starch or cellulose.
  • the polymer may comprise one or more cellulose-based polymers, such as methyl cellulose, ethyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxyethylmethyl cellulose hydroxypropyl cellulose, hydroxypropyl methyl cellulose or cellulose acetate phthalate, or microcrystalline cellulose.
  • cellulose-based polymers such as methyl cellulose, ethyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxyethylmethyl cellulose hydroxypropyl cellulose, hydroxypropyl methyl cellulose or cellulose acetate phthalate, or microcrystalline cellulose.
  • the polymer may comprise a starch-based polymer, such as sodium starch glycolate.
  • the polymer may comprise a hydrocolloid, such as alginic acid, carrageenan, chitosan, hyaluronic acid or pectinic acid.
  • a hydrocolloid such as alginic acid, carrageenan, chitosan, hyaluronic acid or pectinic acid.
  • the polymer may comprise a co-polymer.
  • the co-polymer may be a graft co-polymer, such as Polyethylene glycol/polyvinyl alcohol (PEG/PVA).
  • a graft co-polymer may combine properties of the constituent polymers used to form the graft co-polymer.
  • the composition comprises a first polymer and a second polymer.
  • the composition may thus comprise a blend of first and second polymer.
  • the applicant has appreciated that certain beneficial properties may be afforded by a polymer blend including the first and second polymer.
  • the specific blend may assist in stabilisation, such as maintaining the ability of the composition to generate effective levels of hydrogen peroxide for an extended period after the composition has been made.
  • the specific blend may also impart a desirable texture to the composition, for example the first polymer may impart hardness to enable easier milling or granulation.
  • the second polymer may act a plasticiser.
  • the first polymer is preferably a water-soluble, synthetic polymer.
  • the first polymer preferably has a Tg of at least 30 e C, at least 50 e C, more preferably at least 60 e C.
  • the first polymer is preferably a vinyl polymer, more preferably polyvinyl alcol
  • the second polymer is preferably a water-soluble synthetic polymer.
  • the second polymer preferably has a Tg of less than 50 e C, more preferably less than 30 e C, even more preferably less than 25 e C.
  • the first polymer preferably has a Tg which is higher than the second polymer.
  • the second polymer is preferably a polyether, more preferably polyethylene glycol.
  • Polyethylene glycol for example, has been found to highly compatible with hydrogen peroxide generating enzymes, such as glucose oxidase, and has a particularly beneficial effect on maintaining stability.
  • the first polymer may be present in an amount greater than the second polymer.
  • the first polymer may be present in an amount of 50 to 90%, by weight, preferably 55 to 85%, by weight.
  • the second polymer may be present in an amount 10 to 50%, by weight, preferably 15 to 45% by weight.
  • a powder composition comprising enzyme that is able to convert a substrate to release hydrogen peroxide, substrate for the enzyme, and polymer, wherein the polymer comprises a first water-soluble, synthetic polymer and a second water-soluble, synthetic polymer, the first polymer having a Tg of 50 e C or higher and the second polymer having a Tg less than 50 e C, preferably wherein the first polymer comprises a vinyl polymer and the second polymer comprises a polyether polymer, more preferably wherein the first polymer is polyvinyl alcohol and the second polymer is polyethylene glycol.
  • compositions of the invention comprise less than 10%, less than 5% or less than 0.5%, by weight, superabsorbent polymer (SAP). Even more preferably, the composition preferably comprises substantially no SAP.
  • SAPs are polymers that can absorb and retain extremely large amounts of liquid relative to their own mass. Inclusion of SAPs may thus have an adverse effect on powder consistency, by promoting aggregation by absorption of atmospheric water.
  • SAPs are usually made from hydrophilic polymers containing anionic water-holding groups, such as carboxylic acid groups. Commonly, SAPs are produced from acrylic acid, its salts, or acrylamide. SAPs are preferably cross-linked, with the degree and type of cross-linking affecting its properties. For example, low-density cross-linked SAPs generally have higher water-retention capacity and swell to a larger degree, but may have a softer and stickier gel formation. High cross-link density polymers may exhibit lower water retention provide a firmer gel that is able to retain its shape more readily. SAPs may be classified according to the charge in the cross-linked chains. For example, SAPs may be non-ionic, ionic, amphoteric or zwitterionic. In some preferred embodiments, the SAPs are anionic.
  • compositions of the invention may thus include one of more SAPs selected from sodium polyacrylate; hydrolysed cellulose-polyacrylonitrile; a starch-polyacrylonitrile copolymer; a cross-linked co-polymer of maleic anhydride, such as ethylene maleic anhydride copolymer; cross-linked carboxymethyl cellulose; polyvinyl alcohol co-polymer; and cross-linked polyethylene oxide; polysaccharide-based SAPs; and poly(amino acid)-based.
  • SAPs selected from sodium polyacrylate; hydrolysed cellulose-polyacrylonitrile; a starch-polyacrylonitrile copolymer; a cross-linked co-polymer of maleic anhydride, such as ethylene maleic anhydride copolymer; cross-linked carboxymethyl cellulose; polyvinyl alcohol co-polymer; and cross-linked polyethylene oxide; polysaccharide-based SAPs; and poly(amino acid)-based.
  • compositions of the invention may exclude polymers with such an absorption capacity.
  • compositions of the invention may exclude SAPs with an absorption capacity of at least 15 g/g, at least 20 g/g, at least 30 g/g, at least 50 g/g, at least 100 g/g at least 200 g/g, at least 500 g/g, or at least 1000 g/g.
  • Absorption capacity may also be termed centrifuge retention capacity.
  • the absorption capacity of a water-absorbing material can be measured by methods known to the skilled person.
  • a water-absorbing material such as a SAP
  • the ‘tea bag’ method an amount of the material is placed into a tea bag (acrylic/polyester gauze with fine meshes) and the bag is dipped in an excess amount of water or saline solution for one hour to reach equilibrium swelling. The excess solution is removed by hanging the bag until no more liquid drops off. The tea bag is then weighed and the swelling capacity is calculated as follows:
  • Wi is the weight of the swollen sample and W o is the original weight of the material.
  • Water-retention capacity may be measured in deionised water.
  • water-retention capacity may be measured in a saline solution, such as a 0.9 wt% saline solution.
  • the centrifuge method 0.2g (Wi), of the material is placed into a bag (60 x 60 mm) made of non-woven fabric.
  • the bag is dipped in 100 mL of saline solution (0.9% by weight) for half an hour at room temperature. It is taken out, and then excess solution is removed by a centrifugal separator for 3 minutes at 250g, then the weight of the bag (W 2 ) is measured.
  • the same stages are carried out with an empty bag and the weight of the bag (W o ) is measured.
  • the water-absorbing capacity is measured as follows:
  • NWSP 241 .0R2 This test (W 2 -W 0 -Wi)/Wi This test (NWSP 241 .0R2) is standardised by the European Disposables and Association (EDANA). Testing may be done in accordance with ISO 17190-6. Absorption capacity may be assessed at NTP.
  • compositions of the invention include a salt.
  • Including a salt may be beneficial during the process of manufacturing the composition and help maintain stability.
  • the salt may help protect the enzyme during freezing and/or drying. It may, for instance, protect during lyophilisation.
  • the salt may be present in an amount of 10% or less, preferably 7.5% or less, more preferably 5% or less, by weight.
  • the salt may be present in an amount of about 3%, by weight.
  • the composition may comprise a buffer, for example a buffer salt.
  • buffer salts include: PBS, TBS, Bis-Tris.
  • PBS may be preferred because it may provide superior biocompatibility.
  • the particle size may be adjusted to optimise the composition according to its intended application. For example, the smaller the particle size, the more easily it may become solubilised or absorb fluid. However, it may be undesirable for the particle size to be too small such that a significant amount becomes aerosolised upon dispensing.
  • the powder may have a mean particle size of 3000 pm or less.
  • the powder may have a mean particle size of 2000 pm or less.
  • the powder may have a mean particle size of 1000 pm or less.
  • the powder may have a mean particle size of 500 pm or less.
  • the powder may have a mean particle size of 50 pm or more.
  • the powder may have a mean particle size of 100 pm or more.
  • the powder may have a mean particle size of 200 pm or more.
  • the powder may have a mean particle size of 50 to 3000 pm.
  • the powder may have a mean particle size of 100 to 2000 pm.
  • the powder may have a mean particle size of 100 to 1000 pm.
  • the powder may contains less than 10% of particles with a size of 1000 pm or more.
  • the powder may contain less than 10% of particles with a size of 50 pm or less.
  • the powder may have a modal particle size of 3000 pm or less.
  • the powder may have a modal particle size of 2000 pm or less.
  • the powder may have a modal particle size of 1000 pm or less.
  • the powder may have modal particle size of 500 pm or less.
  • the powder may have a modal particle size of 100 pm or more.
  • the powder may have a modal particle size of 200 pm or more.
  • the powder may have a modal particle size of 50 to 3000 pm.
  • the powder may have a modal particle size of 100 to 2000 pm.
  • the powder may have a modal particle size of 100 to 1000 pm.
  • the powder may have a median particle size of 3000 pm or less.
  • the powder may have a median particle size of 2000 pm or less.
  • the powder may have a median particle size of 1000 pm or less.
  • the powder may have median particle size of 500 pm or less.
  • the powder may have a median particle size of 50 pm or more.
  • the powder may have a median particle size of 100 pm or more.
  • the powder may have a median particle size of 200 pm or more.
  • the powder may have a median particle size of 50 to 3000 pm.
  • the powder may have a median particle size of 100 to 2000 pm.
  • the powder may have a median particle size of 100 to 1000 pm.
  • Particle size may be analysed using laser diffraction.
  • Laser diffraction may employ the Mie or Fraunhofer model.
  • Particle size may be measured in accordance with ISO 13320:2020.
  • Particle size is conventionally reported in terms of diameter irrespective of the actual particle shape; commonly the equivalent spherical diameter.
  • Particle size results may be represented in accordance with ISO 9276-1 and ISO 9276-2.
  • the median particle size may be a mass median diameter.
  • compositions of the invention are substantially free of catalase.
  • compositions of the invention are substantially free of peroxidase, such as lactoperoxidase.
  • compositions of the invention are substantially free of lactoferrin.
  • compositions of the invention are substantially free of zinc oxide.
  • compositions of the invention are substantially free of honey.
  • compositions of the invention are substantially free of antioxidant.
  • compositions of the invention may comprise a haemostat or a blood clotting agent.
  • compositions of the invention may comprise a coagulation factor.
  • Potential coagulation factors include fibrinogen or thrombin.
  • Artificial blood clotting agents could be included in compositions of the invention. Examples of such agents include carriers, such as albumin carriers, to which fibrinogen-binding peptides are immobilised.
  • Compositions of the invention are preferably sterile. Compositions of the inve sterilised by any suitable means.
  • Preferably compositions of the invention have been sterilised by irradiation. Irradiation may be achieved by gamma, electron beam or X-ray. Electron beam may be preferred.
  • the Applicant has found that compositions can retain glucose oxidase activity (and, therefore, the ability to release hydrogen peroxide on dilution) following sterilisation by exposure to gamma irradiation or electron beam irradiation.
  • a suitable level or dose of irradiation may be 10-100 kGy, preferably 10-50 kGy, more preferably 15-40 kGy, such as 20-40 kGy, or 20-25 kGy.
  • compositions of the invention may be adequately sterilised using lower doses than required for SurgihoneyRO®.
  • SurgihoneyRO® is typically sterilised with a dose of 35-70 kGy.
  • compositions of the invention may be in a container or sachet.
  • the container may assist in maintaining the sterility of the composition.
  • the container is sealed or airtight.
  • the container may have a removable and/or replaceable cap or seal.
  • the container is preferably opaque.
  • a composition of the invention may be provided with a dressing material.
  • the dressing material may be coated with the composition.
  • suitable dressing materials include gauzes, bandages, tissues, films, gels, foams, hydrocolloids, alginates, hydrogels, or polysaccharide pastes, granules, beads or tulle. It may comprise carboxymethylcellulose.
  • the composition may be present together with a wound-dressing matrix, such as a collagen or collagenglycosaminoglycan matrix.
  • the dressing material may be a fabric.
  • Compositions in combination with a dressing are preferably sterile, and may be sterilised using irradiation, e.g. gamma irradiation or electron beam irradiation.
  • the dressing material may be impregnated with the powder.
  • the powder may adhere to a surface of the dressing material.
  • a liquid or a gel such as a hydrogel
  • the polymer may absorb water to form the gel.
  • the gel may thus generate hydrogen peroxide because it contains sufficient free water to allow the enzyme to convert the substrate.
  • composition in the form of a gel comprising an enzyme, a substrate for the enzyme, polymer and water.
  • the enzyme, substrate and polymer may be in any form as described herein.
  • the gel preferably includes the form of a buffer salt, as described herein.
  • compositions of the invention can be used to treat any microbial infection that can be treated by hydrogen peroxide.
  • examples include infection caused by gram positive bacteria, gram negative bacteria, acid-fast bacteria, viruses, yeasts, parasitic or pathogenic micro-organisms or fungi.
  • infections caused by the following micro-organisms may be treated: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophytics, Beta haemolytic Streptococci Group A or B, Campylobacter coli, Campylobacter jejuni, Methicillin Resistant Staphylococcus Aureus (MRSA), Methicillin Sensitive Staphylococcus Aureus (MSSA), Botrytis cinerea, Mycobacterium tuberculosis, Cryptosporidium, Plasmodium, Streptococcus pyogenes, Streptococcus zooepidemicus and Toxoplasma.
  • MRSA Methicillin Resistant Staphylococcus Aureus
  • MSSA Methicillin
  • composition of the invention for use in the prevention or treatment of a microbial infection, for example a microbial infection that comprises a biofilm, or a microbe that is capable of forming a biofilm.
  • a composition of the invention for use in the prevention or treatment of a microbial infection that comprises a biofilm or a microbe that is capable of forming a biofilm.
  • the biofilm may comprise bacteria, fungi and/or viruses.
  • composition of the invention in the manufacture of a medicament for the prevention or treatment of a microbial infection, for example a microbial infection that comprises a biofilm, or a microbe that is capable of forming a biofilm.
  • the invention also provides a method of preventing or treating a microbial infection, for example a microbial infection that comprises a biofilm, or a microbe that is capable of forming a biofilm, wherein the method comprises administering an effective amount of a composition of the invention to a site of the infection.
  • a microbial infection for example a microbial infection that comprises a biofilm, or a microbe that is capable of forming a biofilm
  • the method comprises administering an effective amount of a composition of the invention to a site of the infection.
  • composition of the invention to prevent or inhibit microbial growth.
  • composition of the invention for use as a medicament.
  • compositions of the invention may be used to treat animals.
  • Compositions of the invention may be used to treat humans.
  • the invention also provides use of a composition of the invention in the manufacture of a medicament for the prevention, treatment, or amelioration of a microbial infection.
  • compositions of the invention may be topically administered.
  • compositions of the invention for use in the treatment of a microbial infection that comprises a biofilm.
  • a composition of the invention may be used in a method of wound care, including the treatment of a wound, or the treatment or management of wound sepsis.
  • the wound may be an acute wound, chronic wound, surgical wound (for example, a Caesarean wound), chronic burn, or an acute burn.
  • a composition of the invention may be used in the prophylactic prevention of wound sepsis. If a storage-stable composition of the invention is used, it will be appreciated that this may be diluted by liquid present at the wound site, which thereby leads to the release of hydrogen peroxide by the diluted composition.
  • composition of the invention for treatment of a wound.
  • method of treating a wound which comprises administering a composition of the invention to a subject in need of such treatment.
  • use of a composition of the invention in the manufacture of a medicament for the treatment of a wound is also provided.
  • compositions of the invention may be used to treat chronic wounds or wounds that are critically colonized.
  • critically colonized is often used to refer to a wound that has reached a critical point at which bacteria begin to negatively affect the wound and begin to elicit signs of their presence.
  • a critically colonized wound may indicate the presence of a biofilm.
  • a bacterial load of greater than 10 5 organisms/gram of tissue is often accepted as impeding wound healing (Siddiqui AR, Bernstein JM (2010) Chronic wound infection: Facts and controversies. Clinics in Dermatology 28: 519-26; Edmonds, M., & Foster, A. (2004). The use of antibiotics in the diabetic foot. Am J Surg, 187(5A), 25S-28S.
  • compositions of the invention may be used to treat wounds that have a bacterial load of greater than 10 5 organisms/gram of tissue.
  • Compositions of the invention may be administered to a patient, such as placed on the wound of a patient, for a period of at least 24 hours or 48 hours or, more preferably, 72 hours.
  • composition of the invention in the manufacture of a medicament for treatment of a wound.
  • a method of treating inflammation which comprises administering a composition of the invention to a site of inflammation.
  • composition of the invention for treatment of inflammation.
  • composition of the invention in the manufacture of a medicament for treatment of inflammation.
  • a method of stimulating tissue growth which comprises administering a composition of the invention to a site in need of such stimulation.
  • composition of the invention for stimulating tissue growth is also provided according to the invention a composition of the invention for stimulating tissue growth.
  • composition of the invention in the manufacture of a medicament for stimulating tissue growth.
  • a method of debriding a wound which comprises administering a composition of the invention to a wound in need of debridement.
  • composition of the invention for debriding a wound.
  • composition of the invention in the manufacture of a medicament for debriding a wound.
  • a method of deodorising a wound which comprises administering a composition of the invention to a wound in need of deodorising.
  • composition of the invention for deodorising a wound.
  • use of a composition of tf manufacture of a medicament for deodorising a wound is also provided according to the invention.
  • a composition of the invention may be provided with instructions for use of the composition.
  • a composition of the invention may be packaged as a kit with the instructions.
  • the present invention also concerns methods of making compositions of the invention.
  • a method of preparing a composition comprising: forming a solution comprising polymer and enzyme that is able to convert a substrate to release hydrogen peroxide; and drying the solution to form a dried mixture comprising the enzyme and the polymer.
  • the method may comprise adding the substrate in dried form (such as powder form), to the dried mixture.
  • the composition may not necessarily include substrate for the enzyme.
  • the composition could be manufactured and sold separately from the substrate, possibly as an intermediate product.
  • a user could, for instance, add substrate at the point of use.
  • compositions of the invention do comprise substrate, and so it is preferable that the substrate is added in dried form to the dried mixture.
  • Contacting the enzyme with polymer may advantageously coat or protect the enzyme and help to stabilise the enzyme.
  • compositions of the invention may thus comprise granules or particles of substrate interspersed with granules or particles comprising enzyme and polymer. This may assist in separating enzyme and substrate and prevent premature generation of hydrogen peroxide.
  • the enzyme may thus be suspended in, or coated with, polymer.
  • the polymer may form a matrix within which enzyme is dispersed or suspended.
  • compositions of the invention may be heterogenous powders.
  • the compositions may thus comprise a first set of particles or granules which include the enzyme but which do not include the substrate, and a second set of particles or granules which include the substrate but which do not include the enzyme. This may differ from homogeneous powders in which each particle or granule comprises both enzyme and substrate.
  • the first and second set of particles or granules may be mixed in the powder.
  • the first set of particles may comprise polymer.
  • the second set of particles may not comprise polymer.
  • a powder composition comprising enzyme that is able to convert a substrate to release hydrogen peroxide, substrate for the enzyme, and polymer, wherein the powder comprises a first set of particles which include the enzyme but which do not include the substrate, and a second set of particles substrate but which do not include the enzyme.
  • the first set of particles comprise polymer.
  • the second set of particles may not comprise polymer.
  • the solution is an aqueous solution.
  • the polymer is water-soluble.
  • the solution preferably comprises a salt.
  • the salt may comprise a buffer salt.
  • the buffer may comprise PBS, TBS or Bis-Tris. PBS may be preferred.
  • the solution may have an ionic strength of 5 to 100 mM, preferably 10 to 75 mM, more preferably 25 to 50 mM.
  • ionic strengths may maintain stability of the composition.
  • the method may comprise a milling or grinding step to form a powder.
  • the dried mixture may be milled before the substrate is added.
  • the substrate may then be added in powder form.
  • the substrate may be added to the dry mixture and then milled.
  • the solution is dried by lyophilisation to form the dried mixture.
  • the solution may be stored at freezing conditions, preferably at a temperature of less than -60 e C, such as around - 80 e C for at least 24 hours before being lyophilisation.
  • the method may comprise a sterilisation step, to form a sterile composition, optionally wherein the sterilisation step comprises exposuree to gamma or electron beam radiation. Sterilisation preferably occurs after milling.
  • the method includes adding a purified enzyme.
  • the enzyme may have a mass purity at least 95%, preferably at least 98%.
  • the method includes adding a purified substrate.
  • the substrate may have a mass purity of at least 95%, preferably at least 98%.
  • Figure 1 shows the ability of various compositions (Blend 1 , see Example 1 ) to generate hydrogen peroxide on dilution, on the day of manufacture (DOM), after 28 days, and after 56 days;
  • Figure 2 shows the ability of compositions to generate hydrogen peroxide on dilution, 4.5 months after manufacture
  • Dulbecco’s Phosphate buffered saline (Gibco, DPBS) was supplied by Fisher scientific, UK. Deionised (DI) water was created using a Purite Fusion water purification system. Anhydrous D-Glucose was supplied by Thermo Scientific Chemicals, UK. Glucose oxidase (GOx) was supplied by BBI Solutions, UK. Poly (ethylene glycol) with a molecular weight (M.W.) of 4000 (PEG) was supplied by Sigma Aldrich, UK. Poly (vinyl alcohol), 87.0-89.0% hydrolysed with a M.W. of approximately 31 ,000-50,000 (PVA) was supplied by Thermo Scientific Chemicals, UK. All materials were used as delivered with no further purification or modifications made.
  • DI Deionised
  • DPBS was first diluted to an ionic concentration of 50 mM to create a working solution (W- PBS).
  • a 10% PVA solution was then formed in W-DPS. This was achieved by continually stirring and heating the solution at 80°C for 1 hour or until full dissolution was observed. Once fully dissolved the PVA solution was allowed to cool to room temperature (RT).
  • RT room temperature
  • a 10% PEG solution was also formed in W-DPS by mixing at RT.
  • a third solution was then created, also at RT, and consisted of 0.05% GOx in W-DPS.
  • the 10% PEG solution was then combined with the GOx solution in a 24:1 ratio and mixed thoroughly. This combined PEG-GOx solution was then added to the cooled PVA solution, whilst stirring, at a ratio of 1 :3 until mixed.
  • the powders are stored at room temperature under normal atmospheric conditions. Testing of hydrogen peroxide production is conducted using Amplex red reagents (See Example 2).
  • HRP horseradish peroxidase stock
  • Example 2 The powders from Example 1 incorporating PBS buffer salts were tested for their ability to generate hydrogen peroxide over even longer periods of time. The results are shown in Figure 2. No significant reduction in the ability to generate hydrogen peroxide was observed after 4.5 months of storage.
  • Example 1 The materials are as indicated in Example 1 .
  • DPBS was first diluted to an ionic concentration of 25 mM to create a working solution (W- PBS).
  • a 10% PVA solution was then formed in W-DPS. This was achieved by continually stirring and heating the solution at 80°C for 1 hour or until full dissolution was observed. Once fully dissolved the PVA solution was allowed to cool to room temperature (RT).
  • RT room temperature
  • a 10% PEG solution was also formed in W-DPS by mixing at RT.
  • a third solution was then created, also at RT, and consisted of 0.05% GOx in W-DPS.
  • the 10% PEG solution was then combined with the GOx solution in a 34:1 ratio and mixed thoroughly. This combined PEG-GOx solution was then added to the cooled PVA solution, whilst stirring, at a ratio of 35:65 until mixed.
  • Blend 2 demonstrates greater inelastic properties, making it more amenable to milling, to potentially allow smaller particle sizes.
  • aureus was assessed immediately postproduction, and then again after 10 and 18 days, complimentary to that of the hydrogen peroxide assay. It was found that the zone produced initially were large (24.7 ⁇ 1 .5 mm) that decreased to (11 .3 ⁇ 1 .5 mm) after 10 days and after 18 days no zone of inhibition was detected (Figure 3c). Controls of both glucose and water produced no capacity to inhibit bacteria inferring that activity is due to the presence of GOx and the enzymatic reaction that occurs.
  • a powder composition comprising enzyme that is able to convert a substrate to release hydrogen peroxide; and polymer.
  • composition according to clause 1 which is a powder or a granular composition.
  • composition according to clause 2 comprising particles in which enzyme is suspended in, or coated with, the polymer.
  • composition according to any preceding clause which is a powder or a granular composition comprising a first set of particles interspersed with a second set of particles, the first set of particles comprising enzyme and polymer, but substantially no substrate, and the second set of particles comprising substrate but substantially no enzyme, and optionally substantially no polymer.
  • composition according to clause 4 wherein the first set of particles comprise the enzyme suspended in, or coated with, the polymer.
  • composition according to any preceding clause which is able to generate hydrogen peroxide on contact with water.
  • composition according to any preceding clause comprising substrate.
  • composition according to any preceding clause in which the total amount of the polymer is greater than 50%, by weight, greater than 75%, by weight, or at least 90%, by weight, of the composition.
  • composition according to any preceding clause in which the substrate is less than 10%, by weight, or less than 5%, by weight, of the composition.
  • composition according to any preceding clause, wherein the total amount of sugar is 10% or less, by weight, or less than 5%, by weight, of the composition.
  • composition according to any preceding clause which is substantially free of fructose.
  • composition according to any preceding clause wherein the polymer comprises a plurality of distinct polymers.
  • composition according to any preceding clause wherein the polymer comprises a water-soluble polymer.
  • composition according to any preceding clause wherein the polymer comprises a non-ionic polymer. 16. The composition according to any preceding clause, wherein the poly biodegradable polymer.
  • composition according to any preceding clause in which the polymer comprises a semi-crystalline polymer.
  • composition according to any preceding clause in which the polymer comprises a polymer with a glass transition temperature of 50 e C or higher.
  • composition according to any preceding clause in which the polymer comprises a polymer with a glass transition temperature of less than 50 e C, preferably less then 20 e C.
  • composition according to any preceding clause in which the polymer comprises a polymer with an organic carbon chain backbone, optionally a vinyl polymer.
  • composition according to any preceding clause in which the polymer comprises a polymer with a heterochain backbone.
  • composition according to any preceding clause in which the polymer comprises a polyether.
  • composition according to any preceding clause in which the polymer comprises one or more of polyacrylic acid, polyethylene oxide, polyethylene glycol, polyvinyl pyrrolidone, polyvinyl alcohol and polyacrylamide.
  • composition according to any preceding clause in which the polymer comprises polyvinyl alcohol.
  • composition according to clause 24 in which the polyvinyl alcohol is present in an amount of at least 10%, by weight, at least 25% by weight, at least 50% by weight, at least 75% by weight, or at least 90% by weight. .
  • composition according to any preceding clause in which the polymer comprises polyethylene glycol.
  • composition according to clause 26 in which the polyethylene glycol is present in an amount of at least 10%, by weight, at least 25% by weight, at least 50% by weight, at least 75% by weight, or at least 90% by weight.. 28.
  • the composition according to any preceding clause comprising less weight, superabsorbent polymer, preferably substantially no superabsorbent polymer.
  • composition according to any preceding clause which does not include a polymer which has a water absorption capacity of at least 10 g/g.
  • composition according to any preceding clause comprising salt.
  • composition according to clause 30 wherein the total amount of salt present in the composition is less than 10% by weight, preferably less than 5% by weight.
  • composition according to clause 30 or clause 31 wherein the salt comprises a buffer.
  • composition according to clause 32 wherein the buffer comprises PBS, TBS or Bis-Tris, preferably wherein the buffer comprises PBS.
  • composition according to any preceding clause wherein the enzyme comprises glucose oxidase and the substrate comprises glucose.
  • composition according to any preceding clause which has a water activity of 0.3 or less.
  • composition according to any preceding clause comprising less than 1 %, by weight, of water.
  • composition according to any preceding clause which comprises substantially no hydrogen peroxide.
  • composition according to any preceding clause comprising less than 10 ppm, less than 6 ppm or less than 3 ppm hydrogen peroxide.
  • composition according to any preceding clause which is sterile.
  • composition according to any preceding clause wherein there is 0.001 % to 10%, by weight, of the enzyme in the composition, or 0.0025% to 5%, by weight, of the enzyme in the composition.
  • composition according to any preceding clause comprising substantially no honey.
  • composition according to any preceding clause wherein the com powder or is granular, with an average particle size of 3000 pm or less.
  • composition according to any preceding clause wherein the composition is a powder or is granular, with an average particle size of 2000 pm or less.
  • composition according to any preceding clause wherein the composition is a powder or is granular, with an average particle size of 1000 pm or less.
  • composition according to any preceding clause wherein the composition is a powder or is granular, with an average particle size of 500 pm or less.
  • composition according to any preceding clause wherein the composition is a powder or is granular, with an average particle size of 50 pm or more.
  • composition according to any preceding clause wherein the composition is a powder or is granular, with an average particle size of 100 pm or more.
  • composition according to any preceding clause wherein the composition is a powder or is granular, with an average particle size of 200 pm or more.
  • a wound dressing which comprises a dressing material for dressing a wound, and a composition according to any preceding clause.
  • a package or container comprising a composition as defined in any of clauses 1 to 51 , which is air-tight or hermetically sealed.
  • composition according to any of clauses 1 to 51 for use as a medicament.
  • composition according to any of clauses 1 to 51 for use in prevention, treatment or amelioration of a microbial infection.
  • composition according to any of clauses 1 to 51 for use in treatment of a wound.
  • a method of preparing a composition optionally wherein the composition is as defined in any of clauses 1 to 51 , comprising: forming a solution comprising polymer, and enzyme that is able to coi to release hydrogen peroxide; drying the solution to form a dried mixture comprising the enzyme and the polymer; and optionally adding substrate in dried form, to the dried mixture.
  • the polymer comprises one or more of polyacrylic acid, polyethylene oxide, polyethylene glycol, polyvinyl pyrrolidone, polyvinyl alcohol and polyacrylamide.
  • composition is formulated such that the polyvinyl alcohol is present in an amount of at least 10%, by weight, at least 25% by weight, at least 50% by weight, at least 75% by weight, or at least 90% by weight.

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Abstract

L'invention concerne des compositions de poudre qui comprennent une enzyme qui est capable de convertir un substrat pour libérer du peroxyde d'hydrogène, un substrat pour l'enzyme, et un polymère. La composition comprend un premier ensemble de particules dispersées dans un second ensemble de particules. Le premier ensemble de particules comprend l'enzyme et le polymère, mais sensiblement pas de substrat. Le second ensemble de particules comprend le substrat, mais sensiblement pas d'enzyme.
PCT/GB2024/051760 2023-07-07 2024-07-05 Compositions antimicrobiennes Pending WO2025012618A1 (fr)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015166197A1 (fr) 2014-04-30 2015-11-05 Matoke Holdings Limited Compositions antimicrobiennes
WO2016083798A1 (fr) 2014-11-24 2016-06-02 Matoke Holdings Limited Prévention et traitement d'infections microbiennes
WO2016124926A1 (fr) 2015-02-03 2016-08-11 Matoke Holdings Limited Compositions et fibres antimicrobiennes
WO2019077335A1 (fr) 2017-10-16 2019-04-25 Matoke Holdings Limited Compositions antimicrobiennes superabsorbantes
WO2020193993A2 (fr) 2019-03-27 2020-10-01 Matoke Holdings Limited Compositions antimicrobiennes
WO2021186165A1 (fr) 2020-03-16 2021-09-23 Matoke Holdings Limited Compositions antimicrobiennes

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015166197A1 (fr) 2014-04-30 2015-11-05 Matoke Holdings Limited Compositions antimicrobiennes
WO2016083798A1 (fr) 2014-11-24 2016-06-02 Matoke Holdings Limited Prévention et traitement d'infections microbiennes
WO2016124926A1 (fr) 2015-02-03 2016-08-11 Matoke Holdings Limited Compositions et fibres antimicrobiennes
WO2019077335A1 (fr) 2017-10-16 2019-04-25 Matoke Holdings Limited Compositions antimicrobiennes superabsorbantes
WO2020193993A2 (fr) 2019-03-27 2020-10-01 Matoke Holdings Limited Compositions antimicrobiennes
WO2021186165A1 (fr) 2020-03-16 2021-09-23 Matoke Holdings Limited Compositions antimicrobiennes

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
EDMONDS, M.FOSTER, A.: "The use of antibiotics in the diabetic foot", AM J SURG, vol. 187, no. 5A, 2004, pages 25S - 28S
SIDDIQUI ARBERNSTEIN JM: "Chronic wound infection: Facts and controversies", CLINICS IN DERMATOLOGY, vol. 28, 2010, pages 519 - 26

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