Antimicrobial device

Abstract

A dispensing device is described which comprises a first chamber in which there is a first composition and a second chamber in which there is a second composition. The first and second compositions are formulated such that hydrogen peroxide production is possible only when the first composition is mixed with the second composition.

Description

[0001] Antimicrobial Device

[0002] The present invention relates to devices for generating antimicrobial activity, and their use in preventing and treating infection.

[0003] The applicant has found that compositions that are able to release hydrogen peroxide are particularly effective at preventing or inhibiting a microbial infection.

[0004] Surgihoney™ (also known as SurgihoneyRO™) is a chemical engineered honey that has the ability to deliver variable and sustained doses of reactive oxygen species (ROS). Studies in vitro and in vivo have demonstrated Surgihoney’s efficacy in eradication of infection. This has included drug resistant strains, such as methicillin-resistant S. aureus (MRSA) and vanomycin- resistant Enterococcus faecium (Dryden, M., Lockyer, G., Saeed, K., & Cooke, J. (2014). Engineered Honey: In Vitro Antimicrobial Activity of a Novel Topical Wound Care Treatment. Journal of Global Antimicrobial Resistance, 2, 168-172). It was also shown to be effective against fungi and prevented or reduced the seeding of biofilms (Dryden, M., Halstead, F., & Cooke, J. (2015). Engineered Honey to Manage Bacterial Bioburden and Biofilm in Chronic Wounds. EWMA Free Paper Session: Infection and Antimicrobials). Engineered honeys, such as honey with added glucose oxidase, and related compositions, are described in WO 2015 / 166197 A1 , WO 2016 / 083798 A1 , WO 2016 / 124926 A1 and WO 2017 / 013448 A1 .

[0005] At present, Surgihoney™ is available in the form of a sachet or tube for topical administration. However, the applicant has found that, in certain circumstances, administration of Surgihoney™ in these forms may be inconvenient. For example, applying a viscous composition evenly to a wound may be difficult and may require the applier to physically spread the composition on the wound. Honey is also sticky and can be difficult to apply and remove from a patient.

[0006] 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. Furthermore, 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. There is also considerable variability in physical characteristics such as viscosity and colour.

[0007] There is a desire to provide improved compositions which provide enhanced antimicrobial efficacy compared to honey, and which also overcome some of honey’s disadvantages. In a broad sense, the invention concerns a dispensing device for producing, or generating, hydrogen peroxide. The device may produce, or allow production of, a hydrogen-peroxide- generating composition.

[0008] According to the invention, there is provided a dispensing device comprising a first chamber in which there is a first composition and a second chamber in which there is a second composition, in which the first and second compositions are formulated such that hydrogen peroxide production is possible only when the first composition is mixed with the second composition.

[0009] This may be achieved by separating components between the first and second compositions, such as separating enzyme and corresponding substrate and / or enzyme and corresponding precursor substrate.

[0010] Separating the first and second compositions may ensure that no hydrogen peroxide production can occur until the user desires it, and until the user effects, or activates, the device to allow the mixing to occur.

[0011] By keeping the first and second compositions separate, the stability of those compositions may be enhanced because hydrogen peroxide production may be prevented from occurring until it is required. Hydrogen peroxide is generally unstable at ambient temperature. The separation of the enzyme and the substrate prevents the enzyme converting the substrate to release hydrogen peroxide, and thus helps to maintain the stability of the composition for extended periods at ambient temperature.

[0012] WO2019 / 077336A1 discloses a dual dispenser. In a first chamber is a composition comprising glucose oxidase and glucose, and in a second chamber is water. The present invention may provide advantages over this known device. For example, compositions comprising both glucose and glucose oxidase may be more difficult to keep stable because they must not include sufficient free water to allow the enzyme to convert the substrate. This may be achieved by including high levels of sugars, such as the compositions disclosed in Example 2 of

[0013] WO2019 / 077336A1 . Including high levels of sugars may make the compositions susceptible to precipitation. In addition, including high levels of sugars or other components which reduce the amount of free water may significantly increase the viscosity of the composition, making it more challenging to administer, particularly in a spray format.

[0014] Although the first and second compositions are formulated such that hydrogen peroxide production is possible only on mixing, the mixing of the first and second compositions may not necessarily result in the generation of hydrogen peroxide. For example, a mixture resulting from mixing the first and second compositions may not comprise sufficient free water to allow hydrogen peroxide production to take place. For instance, neither the first nor the second composition may comprise water. Water may thus be provided separately. For example, water may already be present at the site of administration of the mixture, such as at a wound site. Alternatively, the device itself may provide a source of water. For instance, the device may comprise the first composition, the second composition and water in separate compartments. The first composition, second composition and water may be mixed prior to dispensing of the mixture from the device, or the first composition, second composition and water may form a mixture once each has been dispensed from the device.

[0015] It is also possible that the device may be substantially free of air or oxygen, such that even if the first and second compositions are mixed prior to dispensation, the mixture does not generate hydrogen peroxide. This may be achieved by purging the device (including purging the first and second chambers) to remove air. Air may be replaced with nitrogen, argon or another inert gas. The compositions could be treated to remove oxygen or reduce oxygen content.

[0016] Hydrogen peroxide production may take place only when the first and second compositions, or a mixture of the first and second compositions, have been dispensed from the device and exposed to air.

[0017] However, it is preferable that the first and second compositions are formulated, and the device is configured, such that mixing the first and second compositions initiates hydrogen peroxide production.

[0018] The generation of hydrogen peroxide may thus occur without the need for separate addition of other components such as water. The resulting mixture from mixing the first and second compositions may thus include sufficient free water to allow hydrogen peroxide generation.

[0019] The first composition may comprise water. For example, the first composition may be an aqueous solution.

[0020] The second composition may comprise water. For example, the second composition may be an aqueous solution.

[0021] Although it is preferable that both the first composition and second composition comprise water, it is possible that only one of the compositions comprises water. If only one of the compositions comprises water, the other, water-free composition may comprise a non-aqueous solvent. For example, it may be a non-aqueous solution.

[0022] The first and / or second composition may be a liquid or gel.

[0023] In a preferred example, the first composition comprises enzyme that is able to convert a substrate to release hydrogen peroxide, and the second composition comprises substrate for the enzyme. So, hydrogen peroxide production may not be able to take place until the first and second compositions are mixed because the first composition does not include substrate and the second composition does not include enzyme.

[0024] According to the invention there is provided a dispensing device comprising a first chamber in which there is a first composition and a second chamber in which there is a second composition, the first composition comprising enzyme that is able to convert a substrate to release hydrogen peroxide, and the second composition comprising substrate for the enzyme.

[0025] References herein to “enzyme” or “the enzyme” may refer to one or more enzyme. For example, in some embodiments, the first composition may comprise a plurality of enzymes that are able to convert a substrate to release hydrogen peroxide. In some embodiments, the first composition may comprise only one enzyme that is able to convert a substrate to release hydrogen peroxide.

[0026] References herein to “substrate” or “the substrate” may refer to one or more substrates. For example, in some embodiments, the second composition may comprise a plurality of substrates. In some embodiments, the second composition may comprise only one substrate.

[0027] In some embodiments the enzyme is an oxidoreductase enzyme. Examples of oxidoreductase enzymes that can convert a substrate to release hydrogen peroxide include glucose oxidase, hexose oxidase, cholesterol oxidase, galactose oxidase, pyranose oxidase, choline oxidase, pyruvate oxidase, glycollate oxidase, and amino acid oxidase. The corresponding substrates for these oxidoreductase enzymes are D-glucose, hexose, cholesterol, D-galactose, pyranose, choline, pyruvate, glycollate and amino acid, respectively.

[0028] In a preferred example, the oxidoreductase enzyme is glucose oxidase, and the substrate is D- glucose.

[0029] A mixture of one or more oxidoreductase enzymes and one or more substrates for the oxidoreductase enzymes may be present in compositions of devices of invention.

[0030] In the first composition, the enzyme that is able to convert the substrate to release the hydrogen peroxide (e.g. glucose oxidase) 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) enzyme, or 0.01% to 0.05% (by weight).

[0031] In the first composition, there may be 10 to 5000 ppm, 15 to 3000, 20 to 2500 ppm, 25 to 2000, 50 to 1000 ppm of the enzyme that is able to convert the substrate to release hydrogen peroxide (e.g. glucose oxidase). Compositions of the invention may comprise 750 to 2000 ppm of the enzyme that is able to convert the substrate to release hydrogen peroxide. In the first composition, the enzyme activity of the enzyme that is able to convert the substrate to release hydrogen peroxide (e.g. glucose oxidase) may range, for example, from 1 -400 lU / mg, or 1 -300 lU / mg, for example 250-280 lU / mg. The amount of enzyme used is likely to depend on several factors, including the desired use of the composition, the desired level of hydrogen peroxide release, and the desired length of time for hydrogen peroxide release. A suitable amount of enzyme can readily be 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).

[0032] In the first composition, the invention may comprise at least 1 unit, and preferably up to 1500 units, of the enzyme that is able to convert the substrate to release hydrogen peroxide (e.g. glucose oxidase), per gram of the composition. A “unit” is defined herein as the amount of enzyme causing the oxidation of 1 micromole of substrate per minute at 25 degrees centigrade at pH 7.0.

[0033] The substrate (e.g. glucose) is preferably present in the second composition in an amount less than 20%, by weight. For example, the substrate (e.g. glucose) may be present in an amount of 1 -10%, or 1 -5%, by weight.

[0034] Preferably, the total amount of sugar in the second composition is less than 20%, by weight, for example 10% or less, by weight.

[0035] The first and second compositions are preferably synthetic. The first and second compositions preferably do not include honey.

[0036] For example, the first composition may be formed by including a purified enzyme, such as a food grade, medical grade or pharmaceutical grade enzyme. The enzyme used to make the first composition may be an enzyme that has at least 95% mass purity, preferably at least 99% mass purity. The enzyme may have been produced by recombinant or non-recombinant means, and may be a recombinant or non-recombinant enzyme. The enzyme may have been purified from a microbial source.

[0037] The second composition may be formed by including a purified substrate, such as a food grade, medical grade or pharmaceutical grade substrate. The substrate used to make the second composition may be a substrate that has at least 95% mass purity, preferably at least 99% mass purity.

[0038] Devices of the invention may comprise a precursor-substrate. The precursor substrate may be in the second composition. The precursor-substrate may be in addition to, or as an alternative to, the substrate. If the device comprises a precursor substrate, the device may also comprises an enzyme for converting the precursor-substrate to the substrate for the enzyme.

[0039] The enzyme for converting the precursor substrate may be in the first composition. For example, the first composition may comprise an enzyme for converting the precursor-substrate to the substrate for the enzyme, optionally in addition to an enzyme that is able to convert the substrate to generate hydrogen peroxide. The second composition may comprise the precursor substrate (in addition to, or as an alternative to, the substrate).

[0040] So, devices of the invention may comprise a second composition which comprises a precursorsubstrate, and a first composition that comprises a first enzyme that is able to 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.

[0041] Alternative devices of the invention may have other configurations. For instance, the first composition may have a first enzyme that is able to convert the substrate to generate hydrogen peroxide, and a precursor substrate. The second composition may have a second enzyme that is able to convert the precursor substrate to the substrate.

[0042] The precursor-substrate may be a carbohydrate, such as a polysaccharide, or a sugar e.g. a disaccharide, or sugar derivative. For example, the precursor-substrate may be sucrose, the first enzyme may be glucose oxidase and the second enzyme may be invertase. In another example, the precursor-substrate may be maltose, the first enzyme may be glucose oxidase and the second enzyme may be maltase.

[0043] In a preferred example, the device is configured to dispense a mixture of the first and second compositions from the device. In other words, the first and second compositions may be premixed prior to dispensation. For instance, the device may comprise a mixing chamber (or mixing zone) having a first inlet for the first composition, a second inlet for the second composition, and an outlet for a mixture of the first and second compositions.

[0044] The first inlet may comprise a conduit from the first chamber to the mixing chamber; the second inlet may comprise a conduit from the second chamber to the mixing chamber. The outlet may comprise a conduit from the mixing chamber. The outlet from the mixing chamber may form at least part of a device outlet, permitting dispensing of the mixture from the device. Dispensing of the mixture from the device may occur through an exit hole or aperture.

[0045] The device may be configured to dispense the mixture under pressure. For example, the device may be arranged to dispense the mixture as a spray or atomised liquid. Rather than the device being configured to dispense a mixture, the device may be configured to dispense the first and second compositions separately. So, a mixture of the first and second compositions could be formed after dispensing the first and second compositions. For instance, the first and second compositions may mix on a surface, such as a wound. In one example, the device may comprise a first device outlet for the first composition and a second device outlet for the second composition. The first device outlet may comprise a first tube for passage of the first composition from the first chamber, and through a first exit hole or aperture. The second outlet may comprise a second tube for passage of the second composition from the second chamber, and through a second exit hole or aperture.

[0046] The device may be arranged to dispense the first and second compositions under pressure. For example, the device may be arranged to dispense both the first and second compositions as a spray or atomised liquid.

[0047] The device of the invention is preferably a spraying device, such as a pump-action spray or trigger spray, an atomiser or an aerosol.

[0048] The device may be configured, or shaped and sized for a particular purpose. For example, the device may be a nasal spray which has an elongated neck suitable for intranasal insertion.

[0049] The device may be a sachet or a pouch. The sachet or pouch may be manufactured from a plastics or polymer material. The sachet or pouch may be flexible or deformable to enable a user to squeeze the sachet or pouch.

[0050] Although the device may have an outlet, such as a nozzle, to allow the first and second compositions, or a mixture of the first and second compositions to be dispensed from the device, it may not be necessary. This is because a user may be able to manually create an outlet by, for instance, cutting, piercing or tearing a portion of the device, or by breaking a seal. This may be particularly applicable if the device is a sachet or pouch.

[0051] The device of the invention may be configurable from a first state to a second state. In the first state, the first composition in the first chamber and the second composition in the second chamber cannot mix. In the second state, the first composition in the first chamber and the second composition in the second chamber can mix.

[0052] For example, the device may be configurable to provide an opening, such as an opening between the first chamber and second chamber, to permit mixing of the first and second compositions. The device may comprise a barrier (or seal or septum). In one example, the barrier may separate the first chamber and second chamber. In another example the barrier may separate first and second chambers from a mixing chamber. The barrier may be openable, breakable or frangible. The user may manually open or break the barrier to permit mixing of the first and second compositions prior to dispensation.

[0053] The first and second compositions in devices of the invention, are preferably sterile. Sterilisation may occur by any suitable means. Preferably the composition and / or water compositions are sterilised by irradiation, such as gamma radiation or elnaohectron beam radiation.

[0054] Compositions in devices of the invention preferably have not been sterilized by ozonation, and do not include ozone, or any components that have been subjected to sterilisation by ozonation. In particular, the compositions in devices of the invention should not comprise ozonized honey or ozonated oil.

[0055] The first and / or second compositions are preferably substantially free of catalase, or comprise substantially no catalase. Preferably, the first and second compositions are substantially free of catalase.

[0056] The first and / or second compositions are preferably substantially free of peroxidase, or comprise substantially no peroxidase. Preferably, the first and second compositions are substantially free of peroxidase.

[0057] The first and / or second compositions are preferably substantially free of zinc oxide, or comprise substantially no zinc oxide. Preferably, the first and second compositions are substantially free of zinc oxide.

[0058] The first and / or second compositions in devices of the invention may comprise a buffer, or a component that may be capable of acting as act as a buffer in an aqueous solution. Preferably, Preferably, the first and second compositions comprise a buffer. Examples of suitable buffers include PBS (phosphate buffered saline), citric acid / NaOH, HEPES (4-(2-hydroxyethyl)-1 - piperazineethanesulfonic acid) and TRIS (trisaminomethane). The compositions of devices of the invention may be buffered (or may be capable of being buffered in an aqueous solution) at a pH of 5 or less, e.g. 3 to 5 (such as about pH 4). Alternatively, compositions of devices the invention may be buffered (or may be capable of being buffered in an aqueous solution) at a pH greater than 5, e.g. 6 to 8 (such as about pH 7).

[0059] The first and / or second compositions may comprise a viscosity modifier. If a viscosity modifier is present, preferably the first and second compositions comprise a viscosity modifier. Inclusion of a viscosity modifier may allow the viscosity of the first and / or second compositions, or of the mixture of the first and second compositions, to have a higher viscosity. A higher viscosity may assist in topical retention. For instance, a more viscous composition may enable the mixture to remain on a wound, or at a site of infection, for a longer period of time. Viscosity may be adjusted accordingly to assist tissue retention but to also permit spraying. This may be achieved by adjusting the amount and / or type, of the viscosity modifier. This may also be achieved by including agents which permit the first and / or second compositions to undergo shear thinning.

[0060] Viscosity modifiers may include polymer. The polymer may comprise a synthetic polymer and / or a natural polymer. Preferably, the polymer is water soluble. The polymer may be soluble in an organic, or non-aqueous, solvent. The polymer may be biodegradable or bioerodable. The polymer in the composition may be any medically acceptable polymer, such as any Food and Drug Administration-approved (FDA-approved) polymer.

[0061] The viscosity modifier may be saccharide-based, such as a polysaccharide. The viscosity modifier may be peptide-based. Suitable viscosity modifiers may include Guar gum, Xanthan gum, Gellan, Alginate, A-carrageenan, cellulose (or cellulose derivatives such as hydroxyethyl cellulose), Konjac, cyclodextrins, chitosan, gelatin or hyaluronic acid.

[0062] A suitable synthetic polymer may be polyethylene oxide (or polyethylene glycol), polyvinyl alcohol or polyvinylpyrrolidone. Other polymers may include poly(lactic-co-glycolic acid), polyglycolic acid, polylactic acid, polycaprolactone, polymeric surfactants, polyacrylic acid, polyacrylamide, N-(2-hydroxypropyl) methacrylamide (HPMA), polyoxazolines, polyphosphates or polyphosphazenes. Another suitable polymer may be phosphino-carboxylic acid (PCA).

[0063] The first and / or second composition may contain polymer in an amount greater than 10% or 20% by weight. Polymer may be present in the first and / or second composition in an amount of 60% or less by weight.

[0064] According to the invention, there is provided a method of dispensing from a device, the device as described herein. The method comprises dispensing a mixture of the first and second compositions from the device; or dispensing, separately, the first and second compositions from the device.

[0065] If the first and second compositions are dispensed separately, the first and second compositions may be dispensed concurrently. In other words, the first and second compositions may be dispensed at the same time and so may be applied to a surface, such as a wound site, at the same time. In one example, the device may be a trigger spray in which effecting one trigger initiates the dispensing of both the first and second compositions simultaneously through separate outlets.

[0066] Alternatively, the application of the first composition may precede the application of the second composition, or vice versa. In other words, dispensing of the compositions may be sequential. In one example, the device may be a trigger spray in which effecting a first trigger initiates the dispensing of the first composition, and effecting a second trigger initiates the dispensing of the second composition. Methods of the invention may comprise dispensing on to a wound or on to a site of infection. The method may comprise dispensing on to, or in, a human or animal body. For example, the compositions, or the mixture, may be applied intranasally, to the throat or to the lungs. Consequently, the device may be a nasal spray or throat spray.

[0067] The method may comprise treating a wound, treating inflammation, stimulating tissue growth, debriding a wound, deodorising a wound, which comprises administering a composition of the invention to a wound in need of deodorising, or treating, or ameliorating a microbial infection. The microbial infection may comprise a biofilm.

[0068] The method may comprise dispensing on to a surface which is not on a human or animal body.

[0069] According to the invention there is provided a kit comprising: a first dispensing device in which there is a first composition; and a second, separate, dispensing device in which there is a second composition, in which the first and second compositions are formulated such that hydrogen peroxide production is possible only when the first composition is mixed with the second composition.

[0070] If the dispensing devices are separate, the user may apply the first and second compositions sequentially, or simultaneously.

[0071] According to the invention, there is provided a kit comprising a device comprising a first chamber and a second chamber; and separately a first composition and a second composition, in which the first and second compositions are formulated such that hydrogen peroxide production is possible only, when the first composition is mixed with the second composition.

[0072] According to the invention there is provided a kit comprising: a first dispensing device in which there is a first composition; and a second dispensing device in which there is a second composition, in which the first and second compositions are formulated such that hydrogen peroxide production is possible only when the first composition is mixed with the second composition.

[0073] Kits in which the first and second compositions are separate from the devices may permit the addition of the first composition to the first chamber and the second composition to the second chamber. For example, the first and second chamber may be refillable with the first and second compositions respectively.

[0074] In any of the kits described above, the device and the first and second compositions may be in any form as disclosed herein. For example, in a preferred embodiments of kits of the invention, the first composition may comprise enzyme that is able to convert a substrate to release hydrogen peroxide, and the second composition may comprise substrate for the enzyme.

[0075] Embodiments of the invention are now described, by way of example only, with reference to the accompanying drawings in which:

[0076] Figure 1 shows a schematic drawing of trigger spray device; and

[0077] Figure 2 shows a schematic drawing of a pouch comprising a frangible septum positioned between a first chamber and a second chamber.

[0078] Example 1 - Spravable Device

[0079] A spray device 1 as shown in Figure 1 , has a first chamber 3 and a second chamber 7. In the first chamber is a first composition 5 of 0.005% glucose oxidase dissolved in PBS. In the second chamber is a second composition 9 of 3% glucose dissolved in PBS.

[0080] A first tube 11 connects the first chamber 3 to a mixing chamber 15 in a neck 14 of the device, and a second tube 13 connects the second chamber to the mixing chamber. The mixing chamber is connected to a nozzle 17, which defines an outlet hole (not shown). A trigger 19 is located on the neck of the device.

[0081] In use, the user operates the trigger 17, which draws the first composition 5 from the first chamber 3 through the first tube 11 to the mixing chamber 15, and simultaneously draws the second composition 9 from the second chamber 7 through the second tube 13 to the mixing chamber 15. The first and second compositions mix in the mixing chamber to form a mixture 21 and the mixture is ejected through the hole defined in the nozzle 17, as a spray. The mixture generates hydrogen peroxide.

[0082] Example 2 - Pouch

[0083] A dispensing device 20 in the form of a flexible pouch formed from a plastics material (as shown in Figure 2) has a first compartment 23 and a second compartment 27. In the first compartment is a first composition 22 of 0.005% glucose oxidase dissolved in PBS. In the second compartment 27 is a second composition 29 of 3% glucose dissolved in PBS. The dispensing device comprises a frangible septum 22 positioned between the first compartment and the second compartment, and one outlet 21 in the form of a closed nozzle, which is in connection with the second compartment.

[0084] In use, a user applies pressure to the first compartment 23 and / or the second compartment 27. The resulting pressure causes the frangible septum 22 to rupture and open, allowing the first composition 22 and the second composition 29 to form a mixture and initiate hydrogen peroxide production. The user then opens the nozzle 21 and squeezes the pouch such that the mixture may be dispensed from the pouch to the desired site, such as a wound.

Claims

Claims1 . A dispensing device, comprising: a first chamber in which there is a first composition; and a second chamber in which there is a second composition, in which the first and second compositions are formulated such that hydrogen peroxide production is possible only when the first composition is mixed with the second composition.

2. A dispensing device according to claim 1 , in which the first and second compositions are formulated such that hydrogen peroxide production is initiated when the first composition is mixed with the second composition.

3. A dispensing device according to claim 1 or claim 2, in which the first composition comprises enzyme that is able to convert a substrate to release hydrogen peroxide, and the second composition comprises substrate for the enzyme.

4. A device according to any preceding claim, in which the first composition comprises water.

5. A device according to claim 4, in which the first composition is an aqueous solution.

6. A device according to any preceding claim, in which the second composition comprises water.

7. A device according to claim 6, in which the second composition is an aqueous solution.

8. A device according to any preceding claim configured to dispense a mixture of the first and second compositions.

9. A device according to claim 8, comprising a mixing chamber having a first inlet for the first composition from the first chamber, a second inlet for the second composition from the second chamber, and an outlet for the mixture.

10. A device according to claim 8 or claim 9, comprising a device outlet for permitting dispensation of the mixture.

11. A device according to any of claims 1 to 8, configured to dispense, separately, the first composition and second composition from the device.

12. A device according to claim 11 , comprising a first device outlet for dispensation of the first composition from the device and a second device outlet for dispensation of the second composition from the device.

13. A device according to any preceding claim configured to dispense the mixture under pressure, or configured to dispense the first and second compositions under pressure.

14. A device according to any preceding claim configured to dispense the mixture as a spray, or configured to dispense the first and second compositions as a spray.

15. A device according to claim 14, which is a pump-action or trigger spray.

16. A device according to claim 3, or any claim dependent on claim 3, in which the enzyme is glucose oxidase and the substrate is glucose.

17. A device according to any preceding claim, in which the first and second compositions are sterile.

18. A device according to any preceding claim, in which the first and second compositions are substantially free of catalase.

19. A device according to any preceding claim, in which the first and second compositions are substantially free of peroxidase.

20. A device according to any preceding claim, in which the first and / or second composition comprises a viscosity enhancer.21 . A device according to claim 20, in which the viscosity enhancer comprises a polymer.

22. A device according to claim 20 or claim 21 , comprising a saccharide-based viscosity enhancer.

23. A device according to claim 22, in which the viscosity enhancer is Guar gum, Xanthan gum, gellan, alginate, A-carrageenan, hydroxyethyl cellulose, or konjac.

24. A device according to any preceding claim, in which the first and / or second composition comprises a buffer.

25. A device according to claim 3, or any claim dependent on claim 3, in which the enzyme is one enzyme.

26. A device according to claim 3, or any claim dependent on claim 3, in which the enzyme is present in the first composition in an amount of 0.001 -0.1%%, by weight.

27. A device according to claim 3, or any claim dependent on claim 3, in which the substrate is one substrate.

28. A device according to claim 3, or any claim dependent on claim 3, in which the substrate is present in the second composition in an amount of 1 -10%, by weight.

29. A method of dispensing from a device, the device as defined in any preceding claim, the method comprising: a) dispensing a mixture of the first and second compositions from the device; or b) dispensing, separately, the first and second compositions from the device.

30. A method according to claim 29, comprising dispensing the first and second compositions from the device, concurrently.31 . A method according to claim 29, comprising dispensing the first and second compositions from the device, sequentially.

32. A method according to any of claims 29 to 31 , wherein the dispensing comprises spraying.

33. A kit comprising: a first dispensing device in which there is a first composition; and a second, separate, dispensing device in which there is a second composition, wherein the first and second compositions are formulated such that hydrogen peroxide production is possible only when the first composition is mixed with the second composition.

34. A kit comprising: a first dispensing device; a second dispensing device; a first composition; and a second composition. wherein the first device, second device, first composition and second composition are separate, and wherein the first and second compositions are formulated such that hydrogen peroxide production is possible only when the first composition is mixed with the second composition.

35. A kit comprising: a) a device comprising a first chamber and a second chamber; and separately b) a first composition and a second composition, wherein the first and second compositions are formulated such that hydrogen peroxide production is possible only when the first composition is mixed with the second composition.

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