WO2004064881A1 - Formulations de traitement de la peau - Google Patents

Formulations de traitement de la peau Download PDF

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Publication number
WO2004064881A1
WO2004064881A1 PCT/GB2004/000179 GB2004000179W WO2004064881A1 WO 2004064881 A1 WO2004064881 A1 WO 2004064881A1 GB 2004000179 W GB2004000179 W GB 2004000179W WO 2004064881 A1 WO2004064881 A1 WO 2004064881A1
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WO
WIPO (PCT)
Prior art keywords
formulation according
hydrogen peroxide
light
skin
gel
Prior art date
Application number
PCT/GB2004/000179
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English (en)
Inventor
Paul James Davis
Andrew John Austin
Original Assignee
Insense Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
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Publication of WO2004064881A1 publication Critical patent/WO2004064881A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0015—Medicaments; Biocides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/11—Peroxy compounds, peroxides, e.g. hydrogen peroxide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents

Definitions

  • This invention relates to skin treatment formulations, particularly skin dressings, for application to a part of a human or animal body for treatment of skin, and relates particularly (but not exclusively) to wound dressings for treatment of compromised skin, particularly skin lesions, i.e. any interruption in the surface of the skin, whether caused by injury or disease, including ulcers, burns, cuts, punctures, lacerations, blunt traumas etc.
  • the invention also relates to a method of in situ generation of hydrogen peroxide.
  • Iodine is an efficient microbiocide but at high concentrations it is toxic to the body's own cells (epithelial cells, keratinocytes and white blood cells etc) which are needed to heal and reconstruct the wound. It is difficult to provide a sustained flux of these substances at an optimal level, and even more difficult to control the flux rate over an extended time to match the changing individual needs for antisepsis as a wound or other lesion progresses.
  • the only way to control flux rates from a conventionally dosed wound dressing product is to change the dressing, replacing one with another having a different starting dose. In fact, dressings with a pre-dosed supply of anti-microbial substance must normally be changed frequently, yet this is expensive of nursing time and can interfere with the healing process itself.
  • Hydrogen peroxide (H 2 O 2 ) is a known antimicrobial substance with many advantages. It is produced naturally in the body by white blood cells as part of the immune defence activities in response to infection. There are no known microbial evasion mechanisms by which microbes can escape its effects and it has a short lifetime, very rapidly breaking down to water and oxygen in the tissues. It therefore does not accumulate to dangerous levels. When it is to be applied topically (e.g. to treat acne), its effectiveness is enhanced by the fact that it readily penetrates the skin surface to reach underlying sites of infection. The oxygen liberated when hydrogen peroxide is decomposed in the wound can itself be helpful in the process of healing, by inhibiting anaerobic bacteria and supporting cells that are engaged in the healing process, (e.g. white blood cells, keratinocytes and epithelial cells etc).
  • hydrogen peroxide As hydrogen peroxide is so beneficial, it has been used for many years as an anti-microbial substance for cleansing wounds of all kinds and as a biologically compatible general antiseptic.
  • hydrogen peroxide-containing ointments are used, e.g. , for treatment of leg ulcers, pressure sores, minor wounds and infection.
  • Hydrogen peroxide solution is very unstable and is readily oxidised to water and oxygen; further, hydrogen peroxide at high concentration can be damaging to normal skin.
  • hydrogen peroxide tends to be restricted to initial clean-up and sterilisation of wounds. Even so, it is a natural defence substance, produced by the body's own cells (at lower concentrations) and it is increasingly recognised as an intercellular and intracellular messenger molecule, involved in cell to cell molecular signalling and regulation.
  • hydrogen peroxide is potentially a very beneficial molecule, if it can be used at the right concentrations and in the appropriate time course.
  • US 4576817 discloses an absorbent pad or bandage comprising serum-activated oxidoreductase enzyme, e.g. glucose oxidase, for producing hydrogen peroxide on contact with serum.
  • serum-activated oxidoreductase enzyme e.g. glucose oxidase
  • the enzyme catalyses reaction of the substrate (e.g. ⁇ -D-glucose for glucose oxidase) with water and oxygen in the serum to produce hydrogen peroxide (and gluconic acid when using glucose oxidase).
  • a pad comprising glucose oxidase is shown in Example 1 to have bacteriostatic properties.
  • the pad or bandage may also include a peroxidatic peroxidase enzyme, e.g. lactoperoxidase, for interacting with hydrogen peroxide thus produced and an oxygen- accepting anion in the serum (e.g. iodide ions) to produce an oxidised anionic bacterial inhibitor (plus e.g. hypoiodite from iodide ions).
  • a peroxidatic peroxidase enzyme e.g. lactoperoxidase
  • an oxygen- accepting anion in the serum e.g. iodide ions
  • an oxygen- accepting anion in the serum e.g. iodide ions
  • Fibres comprising glucose oxidase and lactoperoxidase are shown in Example 2 to have bacteriostatic properties.
  • the present invention concerns an alternative approach to production of hydrogen peroxide, and possibly also substances produced by reaction with hydrogen peroxide.
  • the present invention provides a skin treatment formulation comprising a photocatalytic agent and an electron donor substance.
  • the photocatalytic agent When exposed to light in the presence of oxygen, the photocatalytic agent acts to cause conversion of oxygen to hydrogen peroxide, with corresponding oxidation of the electron donor substance. If this reaction occurs on or in the vicinity of skin, the hydrogen peroxide so produced can have a localised antibacterial effect. By controlling exposure to light, hydrogen peroxide can be generated in situ in the vicinity of skin in a way that has not hitherto been possible. In a typical wound there is a plentiful supply of catalase from the body's own cells. This catalase instantly converts hydrogen peroxide to oxygen, so use of a formulation of the invention has the effect of supplying oxygen to the wound.
  • the arrangement responds rapidly to the presence or absence of light, rapidly starting or stopping production of hydrogen peroxide.
  • the rate of production of hydrogen peroxide is directly proportional to the intensity of light, within limits, permitting ready control of hydrogen peroxide levels.
  • the invention can thus provide a readily controlled source of active antimicrobial agent for skin treatment purposes.
  • the skin treatment formulation may be in the form of an ointment or gel, e.g. having an otherwise conventional composition suited to application to skin.
  • the formulation is in the form of a skin dressing.
  • the invention thus provides a skin dressing comprising a photocatalytic agent and an electron donor substance.
  • the formulation e.g. dressing
  • the formulation is used by being located on the skin of a human or animal, e.g. over a wound or on a region of skin to be treated for cosmetic or therapeutic purpose, e.g. for treatment of acne or other skin conditions.
  • the formulation should be kept away from light until required for use, e.g. by being sealed in a suitable light-tight enclosure or packaging.
  • the formulation requires access to oxygen, e.g. in ambient air.
  • the formulation may be left exposed to the atmosphere in use or, more preferably, may include or be used in conjunction with an oxygen-permeable covering that may adhere to the skin of a human or animal subject, e.g. in known manner. At least part of the covering is of oxygen-permeable material e.g.
  • the oxygen-permeable material may be in the form of a "window" set in an otherwise relatively oxygen-impermeable covering, e.g. of possibly thicker more dense material.
  • Exposure of the formulation, e.g. dressing, to light may be controlled and regulated in a number of different ways.
  • the formulation includes or is used in conjunction with a covering (possibly constituted by the oxygen-permeable covering discussed above) at least part of which is transparent to light, e.g. with the covering including a light-transparent region or window, so light from the surroundings can pass through the covering to cause the hydrogen peroxide-generating reaction.
  • Means are preferably provided for regulating passage of light through the covering.
  • a light-opaque cover or shutter means (operable manually or by automated means) may be provided for occluding at least the light transparent part of covering.
  • the light transmission properties of the covering may be variable in known manner (e.g.
  • the covering is variably transparent in a controllable manner (again being operable manually or automatically, e.g. by electronic control means).
  • Such embodiments may rely on ambient light or light from an associated light source to drive the hydrogen peroxide-generating reaction in a controllable manner.
  • the formulation e.g. dressing
  • an internal, dedicated light source such as one or more light emitting diodes (LEDs) or an electroluminescent polymer film, with associated power supply, e.g. batteries.
  • LEDs light emitting diodes
  • electroluminescent polymer film with associated power supply, e.g. batteries.
  • the photocatalytic agent and electron donor are shielded in use from light from the surroundings, e.g. by use of a light-opaque (but oxygen-permeable) covering over these components and the light source, so the only exposure to light is from the light source which can readily be precisely regulated (again being operable manually or by automated means).
  • control means e.g. an electronic controller, for controlling the light source and hence controlling the timing and rate of generation of hydrogen peroxide to suit requirements.
  • these components are conveniently housed in a separate module, linked by wires, infra red connection etc to the light source etc.
  • the module conveniently includes attachment means, such as a strap or self-adhesive strip, to facilitate attachment to a person or animal being treated in the vicinity of the area of skin to be treated.
  • the invention can be used to generate hydrogen peroxide as appropriate for treatment, either as a continuous flux at an appropriate rate, at varying rates, as intermittent pulses, or at a rate regulated in a feedback loop, responding to signs or symptoms detectable in or associated with the region being treated, e.g. local heat or redness.
  • the invention can thus provide a controllable means for generating hydrogen peroxide in situ at a site of skin to be treated (e.g. at the surface of a wound, burn etc), possibly delivering a sustained flux of changing concentrations, matched to the changing needs and conditions of a particular region being treated.
  • Hydrogen peroxide levels, in dressings and formulations of the invention, in use, are suitably in the micromolar to low millimolar range.
  • the photocatalytic agent conveniently comprises flavine mononucleotide (FMN).
  • FMN flavine mononucleotide
  • the electron donor substance conveniently comprises ethylene diamine tetra acetic acid (EDTA).
  • EDTA ethylene diamine tetra acetic acid
  • the photocalytic agent may comprise zinc oxide particles, e.g. in the form of quantum sized particles with an organic electron donor e.g. ascorbic acid, as described by Bruemann et al J. Phys Chem 1987 91, 3789-3798.
  • a layer of barrier material is preferably included, to be located in use between the skin and photocatalytic agent and electron donor substance, with the layer for example forming part of the dressing of the invention, to prevent undesired migration of materials.
  • a barrier has the effect, inter alia, of preventing possibly interfering substances such as catalase, iron ions etc. being taken up into the formulation from a wound site.
  • Suitable barrier material includes e.g. a semi-permeable sheet or membrane e.g. of cellulose acetate or cellulose ester, such as one that is permeable only to molecules of molecular weight less than, say, 350 Da (possibly having a nominal molecular weight cut-off of 500 Da but with an actual limit of less than 350 Da).
  • Suitable membranes include cellulose acetate membrane code Z368024 supplied by Sigma and Spectrum SpectraPor cellulose ester membrane code 131054 supplied by NBS Biologicals. (Spectrum and SpectraPor are Trade Marks).
  • the photocatalytic agent and electron donor substance are preferably present in the form of one or more gels, suitably hydrated gels, preferably together in a single hydrated gel.
  • the or each hydrated gel conveniently comprises a polyacrylamide gel, an agar gel or an alginate gel, e.g. formed from alginic acid cross-linked in known manner, e.g. by use of calcium chloride.
  • Most cross-linked gels of this type form a biopolymer matrix that retains very high molecular weight reagents or particles such as ZnO particles within the gel, preventing escape of such materials from the point of use.
  • a barrier material such as described above is required to prevent escape.
  • the gel may be in the form of beadlets, beads, slabs or extruded threads etc.
  • the gel may be cast around a mechanical reinforcing structure, such as a sheet of cotton gauze or an inert flexible mesh, e.g. to provide a structurally reinforced hydrogel layer or slab.
  • a mechanical reinforcing structure such as a sheet of cotton gauze or an inert flexible mesh, e.g. to provide a structurally reinforced hydrogel layer or slab.
  • a dressing in accordance with the invention may further comprise an enclosure such as a sachet or bag, preferably made from barrier material e.g. membrane-like material that is permeable only to molecules of MW less than about 350 Da and that is transparent to light.
  • barrier material e.g. membrane-like material that is permeable only to molecules of MW less than about 350 Da and that is transparent to light.
  • the contents of the enclosure can be in the form of a simple aqueous solution (optionally with buffer salts etc.), or as a viscous solution of gel formed by the presence of suitable gelling materials (e.g. polysaccharides or synthetic polymers).
  • the enclosure can be filled with aqueous liquid, with or without thickening/gelling polymers, having an appropriate pH and ionic content, but in which the photocatalytic ingredients are supplied within particles or (preferably) microcapsules (e.g. liposomes or polymerised liposomes) suspended or dispersed in the liquid.
  • particles or microcapsules e.g. liposomes or polymerised liposomes
  • the enclosure is conveniently made of barrier material as discussed above.
  • the gel may be in the form of a shear-thinning gel, e.g. of suitable gums such as xanthan gum (e.g. available under the Trade Mark Keltrol), in this case preferably without a mechanical reinforcing structure.
  • suitable gums such as xanthan gum (e.g. available under the Trade Mark Keltrol)
  • Such gums are liquid when subjected to shear stress (e.g. when being poured or squeezed through a nozzle) but set when static.
  • the gel may be in the form of a pourable component, facilitating production of a gel in the dressing.
  • Such a shear-thinning gel may also be used in combination with a preformed, mechanically reinforced gel.
  • the reagents may be present in a gel in a number of possible forms, including in solution as free molecules.
  • the reagents may be chemically conjugated to each other, chemically conjugated to other molecules (e.g. polyethylene imine), or incorporated in a solid support such as beads.
  • Gels of different types e.g. cross-linked alginate and shear-thinning, may be used together with a single formulation, e.g. dressing.
  • Formulations e.g. dressings, in accordance with the invention (or components thereof) are suitably supplied in sterile, sealed, water-impervious, light-opaque packages, e.g. foil pouches.
  • Dressings in accordance with the invention can be manufactured in a range of different sizes and shapes for treatment of areas of skin e.g. wounds of different sizes and shapes. Appropriate amounts of reagents for a particular dressing can be readily determined by experiment.
  • the formulation e.g. dressing, can be used to generate hydrogen peroxide in situ in the vicinity of the skin of a person or animal being treated, adjacent a site for treatment, with the hydrogen peroxide exerting known antimicrobial or oxygen delivering action as discussed above.
  • the hydrogen peroxide generated in this way may be used in a two stage arrangement (e.g. as disclosed in US 4576817), in conjunction with a peroxidatic peroxidase enzyme, e.g. lactoperoxidase, to produce reactive oxygen intermediates that have antimicrobial properties and that can therefore assist in skin treatment and promoting wound healing.
  • a peroxidatic peroxidase enzyme e.g. lactoperoxidase
  • Peroxidase enzymes useful in the invention include lactoperoxidase, horseradish peroxidase, chloroperoxidase and myeloperoxidase, with lactoperoxidase currently being favoured.
  • a mixture of peroxidase enzymes may be used.
  • the peroxidase enzyme where used, is conveniently present in one or more hydrated gels, e.g. as discussed above.
  • the antimicrobial efficiency of the system can be further enhanced by the inclusion of iodide ions, which can be oxidised to iodine by the action of hydrogen peroxide, especially in the presence of the enzyme lactoperoxidase.
  • the formulation desirably includes a supply of iodide ions, e.g. potassium iodide or sodium iodide.
  • iodine is also relatively toxic to host cells in the wound (e.g.
  • the supply of iodide ions e.g. iodide salt
  • a membrane or gauze or other suitable layer interposed between the skin surface and the hydrogen peroxide-producing part of the formulation.
  • iodine surge can be very useful in quickly ridding a wound of a microbial burden, and its relatively short duration allows healing by minimising damage to growing cells and their repairing activity.
  • the source of iodide ions may be such as to provide, in use, a sustained flux of iodine (and/or hypoiodous acid) for release into a wound, in addition (and in proportion) to hydrogen peroxide.
  • the invention also includes within its scope a method of in situ generation of hydrogen peroxide for skin treatment, comprising locating in the vicinity of skin to be treated a photocatalytic agent and an electron donor substance; and exposing the reagents to light in the presence of oxygen, resulting in production of hydrogen peroxide.
  • Figure 1 illustrates schematically one embodiment of a skin dressing in accordance with the invention
  • Figure 2 illustrates schematically an experimental arrangement for demonstrating functioning of a skin dressing in accordance with the invention
  • Figure 3 is a chronoamperotometry graph of current (in nA) versus time (in seconds) obtained using apparatus as illustrated in Figure 2;
  • Figure 4 is a further graph of current (in nA) versus time (in seconds) obtained using apparatus as illustrated in Figure 2, showing light-dependent hydrogen peroxide production;
  • Figure 5 is a schematic illustration of the apparatus of Figure 2 in a light-tight enclosure
  • Figure 6 is a graph similar to Figure 4 obtained using the apparatus illustrated in Figure 5;
  • Figure 7 is a graph of current (in ⁇ A) versus time (in minutes).
  • the skin dressing 10 illustrated schematically in Figure 1 is of layered construction and comprises a gel slab 12 containing in solution flavine mononucleotide (FMN) and ethylene diamine tetra acetic acid (EDTA); an LED array 14 on one side of slab 12 with associated miniaturised electronic controller and battery 16; an oxygen-permeable polytetrafluoroethylene (PTFE) cover 18 covering the LED array 14 and gel slab 12; and a sheet 20 of Sigma semi-permeable barrier material on the side of slab 12 remote from the LED array 14.
  • the dressing is shown on an area of skin 22 of a human or animal to be treated, including a wound site 24.
  • the dressing 10 is located over the wound site 24, with barrier sheet 20 in contact with the skin, and with the dressing being held in position by adhesion of peripheral parts of the cover 18 to surrounding skin (not shown in Figure 1).
  • the dressing also includes in gel slab 12 a sensor 26 linked to the controller 16 for feedback control.
  • the dressing may be operated manually, with a user turning the LED array on or off as required.
  • the controller 16 can be programmed to regulate automatically operation of the LED in accordance with one or more programs.
  • a program may produce a preset pattern of peroxide flux rates over time.
  • a number of other programs may each produce a different, usually simpler, pattern of peroxide production rates, to be selected as appropriate by a user according to an ongoing assessment of treatment required e.g. based on wound type and state.
  • the controller 16 may respond to feedback signals from the sensor, varying hydrogen peroxide production rates and timing appropriately.
  • the dressing will be used to generate hydrogen peroxide to the extent that concentrations within the dressing will be in the micromolar to low millimolar range.
  • a typical example of a gel slab 12 was produced as follows:
  • Gels containing the active components were prepared in the dark, or under minimal illumination, by the following procedure: 1 % agar (Sigma product No. A9539) was dissolved in boiling deionised water. The agar solution was cooled to about 45 °C (just above the gelling temperature) and had dissolved therein 25mM FMN (Riboflavin 5'- monophosphate (sodium salt dihydrate), supplied by Fluka, code 83810) and 25mM EDTA (EDTA Na 2 , supplied by Sigma, code E1644). The resulting warm, ungelled solution was poured over a cotton gauze (which acted as a support for the gel) and allowed to cool and set. Pads of approximately 1 cm x 1 cm were cut, a size sufficient to allow them to cover the end of the electrode. Pads were kept in the dark at all times, to prevent the initiation of hydrogen peroxide production.
  • Figure 2 illustrates an experimental arrangement used to demonstrate photocatalytic production of hydrogen peroxide, using a FMN and EDTA-containing gel slab 12 and semi-permeable barrier sheet 20 located on a proprietary screen-printed carbon electrode 30, the terminals of which are linked to a Perkin Elmer DLK-60 electrochemical analyser 32 constituting a peroxide sensing system.
  • the semi-permeable barrier sheet 20 is either cellulose acetate membrane, 500 Da nominal molecular weight cut off 350 Da actual cut off, supplied by Sigma (code Z368024) or Spectrum SpectraPor cellulose ester membrane, 500 Da nominal molecular weight cut off, 350 Da actual cut off, supplied by NBS Biologicals (code 131054) (Spectrum and SpectraPor are Trade Marks).
  • Figure 3 is a chronoamperotometry graph of results obtained using the set up of Figure 2 (with special software in place of that normally used with the DLK-60 analyser), showing results for different concentrations of hydrogen peroxide and demonstrating the ability to detect concentrations as low as 10 ⁇ M.
  • the dark chamber was initially rapidly removed and replaced with a transparent chamber (to maintain humidity) with a 20 Watt halogen lamp placed over the arrangement to provide a light source.
  • a 20 Watt halogen lamp placed over the arrangement to provide a light source.
  • hydrogen peroxide was produced, as monitored by analyser 32.
  • the lamp was then switched off, and the dark chamber replaced.
  • the production of hydrogen peroxide stopped, as indicated by the level trace in Figure 4.
  • the dark chamber was again swapped for a transparent chamber and the arrangement left exposed to ambient light, whereupon slow production of hydrogen peroxide began.
  • the halogen lamp was again switched on, resulting in an increase in the rate of hydrogen peroxide, as indicated by the increased slope of the graph of Figure 4.
  • Figure 4 shows the rapid change in peroxide production in response to changing light conditions. It should be noted that the software analysis program used produces an inverse graph.
  • dark chamber 40 has a small hole 42 in the upper wall thereof, located above the gel 12.
  • An LED 44 powered by a 6V battery (not shown) is located above the chamber with the bulb 46 of the LED 44 passing through the hole 42, for illuminating the gel 12.
  • the only light to which gel 12 can be exposed is light coming from the bulb 46 of the LED 44 when switched on.
  • a 7cm length of pre-wetted dialysis tube (Spectrum Labs, code 131054, of 500 Da nominal molecular weight cut off, with a flat diameter of 16mm) was taken, and clamped shut at one end.
  • EDTA ethylene diamine tetra acetic acid, supplied by Sigma, code E1644
  • FMN flavin mononucleotide, supplied by Fluka, code 83810
  • Test plates consisted of nutrient agar No. 2 (supplied by Oxoid), cast to a depth of approximately 5mm. The plates were left to stand for a minimum of 18 hours. A culture of Staphylococcus aureus was prepared to an optical density of between 6-7. 200 microlitres of the suspension was applied to each plate, and spread in several directions to ensure an even spreading was produced. The plates were allowed to dry for at least 15mins before use.
  • Illumination apparatus was constructed by suspending 2 ultrabright blue LEDs (supplied by Maplins Electronics, code L53MBC, light output of 90mcd each, with a peak wavelength of 430nm), 1 cm above the reactant bag.
  • the LEDs were wired in parallel, and powered by 3x Duracell AA-sized batteries.
  • One plate was set up as above, and the sealed dialysis tube containing the reactants laid onto the plate, in one movement, to prevent scraping the bacteria from the surface.
  • the plate was wrapped in aluminium foil to prevent light ingress, and placed in an incubator maintained at 37°C.
  • a second plate was set up as previously described, but not wrapped in foil. The plate was placed into the 37 °C incubator, and the illuminated LEDs placed over the top of the bag, at a height of 1 cm. The LEDs were positioned so that they were shining directly onto the bag. The plates were left for 24 hours before being examined. Results
  • Electrode buffer (lOOmM sodium phosphate pH6 + lOOmM potassium chloride) was placed, covering the reference, working and outer electrodes.
  • 80 ⁇ l of reaction solution was placed (125mM FMN + 37mM EDTA). The apparatus was set up in a dark box to minimise external light activation. 2 blue ultrabright LEDs were suspended directly above the reactants, at a height of 1 cm. The LEDs were not powered.
  • the electrode was connected to a Whistonbrook Technologies "Ezescan” (Ezescan is a Trade Mark) electrochemical analyser and control unit, and a potential of 1150 mN was applied. The baseline was allowed to stabilise. The reaction was initiated by powering up the LEDs, with 3 Duracell AA batteries. The FMN/EDTA was illuminated for 30 minutes. Data was recorded via the "Ezescan” system by the procedures recommended by the manufacturer..

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Abstract

Une formulation de traitement de la peau, se présentant sous la forme d'un onguent ou d'un gel ou d'un pansement pour la peau, comprend un agent photocatalytique, par exemple un mononucléotide de flavine ainsi qu'une substance donneuse d'électrons, par exemple de l'acide éthylène diamine tétracétique, avantageusement sous la forme d'un gel d'agar (10). Lors de l'exposition à la lumière en la présence d'oxygène (par exemple de l'atmosphère ambiante) l'agent photocatalytique a pour effet de provoquer la conversion d'oxygène en peroxyde d'hydrogène. Si cette réaction se produit sur ou à proximité de la peau, le peroxyde d'hydrogène ainsi produit peut avoir un effet antibactérien localisé. Par une régulation de l'exposition à la lumière, du peroxyde d'hydrogène peut ainsi être généré in situ au voisinage de la peau d'une manière jusqu'alors impossible.
PCT/GB2004/000179 2003-01-24 2004-01-21 Formulations de traitement de la peau WO2004064881A1 (fr)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102006053656A1 (de) * 2006-11-13 2008-05-15 Kronos International, Inc. Verfahren zur Bestimmung der Photoaktivität von im sichtbaren Licht photoaktiven Photokatalysatoren und Messapparatur hierfür
WO2018102463A1 (fr) * 2016-11-30 2018-06-07 Christopher Duke Composés réactifs avec des radicaux libres et des dérivés réactifs de l'oxygène
EP3322451A4 (fr) * 2015-07-14 2019-03-13 Washington State University Réduction ou prévention électrochimique d'infections
WO2020148642A1 (fr) 2019-01-14 2020-07-23 Tompa Majcen Dominika Formulations contenant des composés actifs d'oxygène et dispositifs pour leur application

Citations (2)

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US4576817A (en) * 1984-06-07 1986-03-18 Laclede Professional Products, Inc. Enzymatic bandages and pads
WO1994013333A1 (fr) * 1992-12-08 1994-06-23 University College Cardiff Consultants Limited Pansements

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DE102006053656A1 (de) * 2006-11-13 2008-05-15 Kronos International, Inc. Verfahren zur Bestimmung der Photoaktivität von im sichtbaren Licht photoaktiven Photokatalysatoren und Messapparatur hierfür
EP3322451A4 (fr) * 2015-07-14 2019-03-13 Washington State University Réduction ou prévention électrochimique d'infections
US11229714B2 (en) 2015-07-14 2022-01-25 Washington State University Electrochemical reduction or prevention of infections
WO2018102463A1 (fr) * 2016-11-30 2018-06-07 Christopher Duke Composés réactifs avec des radicaux libres et des dérivés réactifs de l'oxygène
WO2020148642A1 (fr) 2019-01-14 2020-07-23 Tompa Majcen Dominika Formulations contenant des composés actifs d'oxygène et dispositifs pour leur application

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