GB2508237A

GB2508237A - An ozone releasing wound dressing

Info

Publication number: GB2508237A
Application number: GB1221296.5A
Authority: GB
Inventors: Nigel Parker
Original assignee: EMCO PACKAGING SYSTEMS Ltd
Current assignee: EMCO PACKAGING SYSTEMS Ltd
Priority date: 2012-11-27
Filing date: 2012-11-27
Publication date: 2014-05-28
Anticipated expiration: 2032-11-27
Also published as: GB2508237B; GB201221296D0

Abstract

An ozone-releasing wound dressing, comprises an outer fabric cover 1; a first pad secured within the outer fabric sheet and containing a fill material 4, which is arranged to release ozone on exposure to body heat and a second pad, also secured within the outer fabric layer, containing a fill material 6 of high absorbance to effectively manage wound exudates. The outer fabric cover is comprised of a composite material with both a low water vapour transmission rate and a low oxygen transmission rate to prevent the escape of ozone from the wound-site, the outer fabric cover further carries a self adhesive coating in order to allow it to be secured to the skin surrounding the area of the wound site, ensuring that the wound is fully enclosed. The fill material formulation preferably comprises ozone, present in an amount of 0.2-1.0% w/v, dissolved in a non-ionising organic solvent selected from refined rapeseed oil, grape seed oil, ground nut oil, maize oil, linseed oil, olive oil, safflower oil, sesame seed oil, soya oil, sunflower oil, argan oil, 100% glycerol of a blend of two or thereof.

Description

AN OZONE RELEASING WOUND DRESSING

Field of the Invention

The invention relates to an ozone releasing wound dressing,

Description of the Related Art

The successful treatment of wounds, whether post operative, traumatic or those produced by diabetic, venous, pressure and mixed vascular aetiology ulcers can be highly demanding on health services, especially in the case of ulcers and as a consequence carry high cost implications.

In the economically advanced western nations, increased longevity together with the rise in obesity and associated diabetes has led to some nearly two million or roughly one in two hundred Europeans suffering from chronic wounds such as pressure induced sores and venous leg ulcers, as well as diabetic lesions. With these populations projected to show increased longevity into the foreseeable future, the number of sufferers is likely to rise substantially.

Chronic wounds can take from weeks to even years to heal, with over 30% taking more than two years and many never healing. This inevitably leads to considerable suffering and consequential incapacity for those afflicted.

In addition, the onset of wound infection can lead rapidly to sepsis, septic shock, and if treatment is unsuccessful, eventual death. Considering the high costs of hospitalization and the added trauma and discomfort to the patient, and despite the availability of many treatment systems, clinicians remain obstructed and frustrated by both the persistent slow healing and the increasing treatment costs of these wounds.

Of the treatment systems available, however, one that has been used as a wound management tool, largely on the fringes of orthodox medical practice for more than 40 years, is ozone.

Ozone (03) is a highly reactive chemical element and occurs in nature as a colourless gas. It is an allotrope of oxygen, of which the latter can be present in one of its three forms: Monatomic oxygen -occurring as single atom of oxygen (0), which is highly reactive, very unstable with two free covalent bonds, resulting in a very short free or un-reacted lite.

Diatomic oxygen -occurring as a molecule with two atoms of oxygen (02), which is the most abundant and stable form, having no free bonds (0-0) Triatomic oxygen or Ozone -occurring as a molecule with three atoms of oxygen (03), having a free bond resulting in its high reactivity.

Ozone is a more powerful oxidant than diatomic oxygen and can oxidize practically all organic and non-organic compounds. Regarding bio-organic compounds, ozone is found to have a selective reactivity with compounds having double bonds such as amino acids, peptides, proteins, nucleic acids and particularly unsaturated fatty acids, which make up the basis for the lipid bio-layer of cell membranes and the lipoprotein complexes of blood plasma. In biological media, ozone reactions with unsaturated fatty acids pre-dorninate. Ozone has been shown to be effective against a range of gram negative and gram positive bacteria and studies with various mimetic wound systems have shown that with controlled delivery, ozone can be utilized as either a disinfectant or as a biostat.

Ozone has been shown to be effective against a range of gram negative and gram positive bacteria and studies with various mimetic wound systems have shown that with controlled delivery, ozone can be utilized as either a disinfectant or as a biostat.

Ozone is an effective antagonist to an enormous range of pathogenic organisms and in this regard, cannot be equalled. It is capable of inactivating aerobic, facultative and anaerobic bacteria, a wide spectrum of viruses and a comprehensive range of fungal and protozoan pathogens. There is also evidence that ozone, through its oxidizing properties, inactivates bacterial toxins, whose function is to destroy tissues, providing bacteria with colonizing advantage.

The medical use of ozone is based on its oxidative, disinfection and micro-biocidal properties. As discussed above, ozone disables bacteria and fungi much more effectively than does either chlorine or chlorine based biocide compounds. It is also very effective in destroying viruses and carcinogenic agents, which in most cases are not destroyed by those chemicals generally used for water sanitisation.

Ozone exerts its anti pan-pathogenic actions through mechanisms entirely different to those of conventional antibiotic agents. The latter must be constantly restructured or replaced to surmount mutated pathogen resistance. Ozone, on the other hand, presents a direct and powerful oxidative challenge that pathogens are incapable of circumventing.

Recently, ozone as a wound management tool has become more mainstream within the medical establishment, as evidenced by the recent publication in 2006 of Ozone Therapy in Practice, Health Manual, by the State Medical Academy of Nizhny Novogorod on behalf of the Ministry of Health Service of the Russian Federation, authors Oleg V. Maslennikov, Claudia N. Kontorshchikova and Inn A. Gribkova.

Additional, recent publications promoting or endorsing the medical use of topically applied ozone include: Biological and clinical effects of ozone. Has ozone therapy a future in medicine?, byV. Bocci, British Journal of Biomedical Science 1999; 56: 270-279, Therapeutic Effects of Ozonized Olive Oil in the Treatment of Intractable Fistula and Wound after Surgical Operation, by Akiyo Matsumoto et al., presented to the Ozone Medical Conference, London, 14th September 2001 Evaluation of an Ozone-Based Wound Management System, by A. J. Denvir et al., Wound Repair and Regeneration, Vol. 12, Issue 2, page A5, April 2004, Modulation of cutaneous wound healing by ozone; Differences between young and aged mice, by Y. Lim etal., Toxicology Letters, 2006, Vol. 160, Issue 2, pgs 127 -134 (ISSN 0378-4274), Therapeutic Effects of Topical Applications of Ozone on Acute Cutaneous Wound Healing by Hee Su Kim et al., J. Korean Medical Sci. 2009 June; 24(3): 368-374' Ozonated sesame oil enhances cutaneous wound healing in SKH1 mice by Guiseppe Valacchi et al., Wound Repair and Regeneration, Vol. 19, Issue 1, pages 107 -115, January/February 2011, As pointed out by A. J. Denvir in his article in Wound Repair and Regeneration above, ozone offers a specific solution to the problem of effective management of microbial wound contamination. Despite the advantages, several technical barriers have prevented ozone-based disinfection treatments from becoming more widely investigated.

Negative press from years of unsubstantiated medical successes has made the medical community wary of even legitimate ozone technologies. Because there has until recently been only limited research into using ozone in infection prevention, much of the hardware has not been developed to the stage where the technology can be used in clinical trials.

The local treatment of infected wounds, such as may easily occur with open bed sores (decubitus), ulcers of the lower leg (ulcus cruris), diabetic gangrene or delayed/disturbed wound healing processes, belong to the classical application fields of medical ozone, where use can be made of its disinfectant effects, both bactericidal and fungicidal, to achieve a germ-free and clean wound.

In the case of diabetes suffers, the advantage of topical ozone therapy lies in its ease of administration, as once the principles of ozone dynamics and the art of adapting ozone dosages and treatment protocols are mastered by the clinician, topical ozone therapy can safely be applied to a broad range of diabetes-related afflictions.

In order to replicate this potential for overall therapeutic action, ulcerative conditions require to be treated with an assortment of various systemic antibiotic agents and in the context of accepted contemporary medical practice, the latter is becoming increasingly less feasible.

Externally or topically applied ozone is both a preventive, acute care and chronic care therapeutic agent and ozone therapy, applied in a timely and appropriate fashion, may obviate the need for systemic anti-pathogen therapies and the potential side effects and organ stresses to be suffered by the patient that this option entails.

Topically applied ozone is, however, entirely compatible with systemically administered antibiotics, as it is with debridement and other local wound care procedures.

The disadvantages of current topical ozone therapy for decubitus, diabetic and other ulcerative conditions is that ozone is not transportable and needs to be generated on the site at the time of administration and as ozone needs to be administered serially in the treatment of these wounds, this may require, in many circumstances, daily applications until the lesions are resolved.

Such procedures can be time consuming and costly in terms of medical staff deployment as well as being stressful to the patient Apart from topical treatments with ozone generated electronically in situ, ozone is also administered to wounds dissolved in a range of vegetable oils, with the latter either in a liquid state or in a semi-solid state, similar in consistency and appearance to Vaseline petroleum jelly.

There is documented evidence that ozone application to superficial tissues whose blood supply is reduced enhances tissue blood and oxygen perfusions.

In vivo laboratory trials with direct applications of ozonated vegetable oil to acute cutaneous wounds have indicated accelerated repair, with the promotion of collagen synthesis and fibroblast proliferation at the injury site, in association with the increased expression of platelet derived growth factor (PDGF), transforming growth factor-13 (TGF-13) and vascular endothelial growth factor (VEGF).

Topical ozonated oil application, however, is effectively restricted in ozone therapy to wounds without heavy exudation and therefore excludes this mode of treatment for chronic wounds such as pressure induced sores (decubitus), venous leg ulcers and diabetic, ulcerative conditions.

Summary of the Invention

According to the invention,, there is provided a wound dressing, comprising: -an outer fabric cover (1) with a both a low water vapour transmission rate (WVTR) and a low oxygen transmission rate (OTR), which carries, on its inner face, a medically approved, non-allergenic, self-adhesive coating in order to allow it to be secured to surface of the skin surrounding the wound site, fully enclosing the latter, a first pad, in a multi-cellular sachet format, integrally secured within the outer fabric sheet and containing a fill material (4), which is caused by the temperature elevation produced by the body heat of the patient under treatment, to release ozone and wherein the first, or ozone releasing pad has an outer or backing sheet (2) that is a high barrier to both liquids and gases and an inner cover face (3) comprising a spun-bonded polymer support layer laminated to a gas permeable but liquid impermeable, polymer film, acting as a diffusion rate control' layer and a second pad, also integrally secured within the outer fabric layer, which is in direct contact with the wound, comprising a fully liquid and gas permeable backing sheet and cover face (5), the later overlaid with a fully liquid permeable, non-adherent fabric (7) to allow atraumatic, pain-free removal from the wound bed, wherein the second pad contains a fill material (6) of an high absorbance composition to effectively manage wound exudates, a peelable cover sheet (8), for the complete dressing, of a gas permeable, easy-peel, polymer laminate, attached to the adhesive coated, edge facing of the outer fabric layer and designed to maintain the sterility of the dressing up to the point of its application.

The wound dressing thus incorporates a fully liquid impermeable but gas permeable pad in a multi-cellular sachet format, containing a non-aqueous, non-ionising organic solvent in which ozone is dissolved.

This device has been designed so that when applied to the wound, the body heat produced by the patient under treatment, promotes and maintains ozone release.

The present invention is designed to provide a wound dressing of a generally conventional format, although integrally incorporating a liquid impermeable but gas permeable, cellular envelope containing a solvent, in which ozone is dissolved. When subjected to an elevation in temperature, such as the body heat produced by the patient receiving treatment, the ozone comes out of solution and effectively bathes the wound site at a controllable, pre-determined concentration within the wound site headspace atmosphere.

The dressing in the present invention, when deployed, is designed to enclose both the wound site itself, together with the area of skin immediately surrounding it, thus creating a restricted headspace above the wound, into which the ozone is released and contained.

The inventor understands that the OTR of the control' layer of the ozone releasing pad must be great enough to provide sufficient gas permeability without allowing permeability to the liquid solvent.

The inventor also understands that the selection of the material composition and gauges of the components of the control' layer of the first pad can be used to control the OTR of this layer and thus regulate the level of ozone within the wound site headspace atmosphere.

The control' layer may have an OTR in the range 2500cm3-1 5000cm3/m2 in 24 hours at 1 bar at 23°C.

In a preferred embodiment of the invention, the permeable support layer is a spun-bonded, high density polyethylene (HDPE) fabric, the density of which may be 42.5 gIm2-61.OgIm2.

A polyurethane adhesive may be used to bond the layers of the laminate together.

The inventor understands that the wound types that the device is designed to treat require dressings to be changed at relatively frequent intervals. In order to minimize redundancy in performance capacity, which will aid in both reducing the weight and size of the dressing and as a consequence contribute to patient comfort when worn, the mass of the fill material will be closely tailored to meet the ozone delivery requirements of the headspace atmosphere of the wound site during these intervals.

In relation to the above, the inventor has achieved significant improvements in the performance, during the operational life of the wound dressing, by introducing control' layer polymer and gauge selection to optimally regulate the OTR of the ozone releasing pad, against a range of wound requirements. The inventor has, moreover, additionally discovered that further benefits may be obtained by selectively modifying the relative concentration of dissolved ozone within the fill material.

The fill material formulation may comprise a range of non-ionising, inorganic solvents, wherein the selected solvent can be a single product, or as a blend of two or more from those available from the range, as determined to be appropriate, in terms of ozone solubility, for the particular application concerned and the specific performance that the latter requires.

Ozone will be dissolved in the selected solvent, or blend of solvents, to achieve a predetermined target concentration.

wherein the multi-cellular sachet of the ozone releasing pad is in two parts, with a lower, cover face comprising a laminate material of a permeable, mechanical support layer and a liquid impermeable but gas permeable control' layer, this latter layer having an OTR in the range 2500cm3-15000cm31m2 in 24 hours at 1 bar at 23°C.

In a further aspect of the invention there is provided a wound dressing device, comprising: a multi-cellular sachet of the ozone releasing pad, fully impermeable to liquid and permeable to gases, a fill material contained in the above sachet, which is caused by body heat to release ozone; wherein the till material formulation comprises, a medical grade, refined vegetable oil or glycerol in which ozone is dissolved to a level of 2.Og/l to bOg/I, wherein the dissolved ozone is present in an amount from 0.002% to 0.01 0% wiw.

In its deployment, the ozone releasing wound dressing in this invention is similar to the standard absorbent dressings as conventionally applied to chronic wounds, in that it is first removed from its sealed, protective, liquid and gas impermeable storage pack and the cover face sheet removed to expose the self adhesive facing of outer fabric cover.

The ozone releasing wound dressing is then placed carefully over the wound site (Fig 2), ensuring that the adhesive facing (9) of the outer fabric has made good contact with the skin surrounding the wound (10) and that the latter (11) is fully enclosed.

Body heat radiated from both the wound itself and the surrounding area of enclosed skin (10) produces a marked elevation in the level of ozone coming out of solution and diffusing through the cover face control' layer of the multi-cellular sachet, then passing through the wound contact and exudate absorbing pad into the headspace (Fig. 2.), establishing the ozone composition of the atmosphere therein contained at a pre-determined target optimum for the wound type concerned.

With the wound dressing in this invention correctly applied to the surface of the skin, studies have shown that within the multi-cellular sachet of the ozone releasing pad, the temperature of an ozonated, refined rapeseed oil fill material can be elevated by body heat, from an ambient of 20°C to between 27.0°C and 32.5°C and then maintained within this temperature range over a monitored period of l2hours.

The target levels of 0.O75ppm to 0.l5Oppm for ozone in the wound site headspace atmosphere are significantly below the current UK HSE Guidance Note EH (Environmental Hygiene) 38 -Ozone: health hazards and precautionary measures. The occupational exposure standard (OES) requires that the ozone concentration should be cO.2ppm in atmospheres where personnel are to be exposed and not exceed 0.2ppm in air when averaged over a 15 minute reference period, although if proved to be medically beneficial, there could be a case for exceeding these levels, under appropriate medical supervision.

The potential for overpressure of the wound by continuous delivery of ozone to the wound site headspace atmosphere, is minimal as the levels of ozone released, although effective, are still very low and even after dissociation to oxygen, will contribute less than O.2ppm.

During manufacture, which is carried out under aseptic conditions with ambient production temperatures controlled at between 4°C and 6°C, the ozone will be generated electronically, by means of a high voltage plasma, from a medical grade, pure oxygen source in order to avoid any content of nitrogen oxides, which can prove harmful to epithelial cells.

The ozone thus produced is then dissolved, by means of a sintered ceramic diffuser or, for preference, an inline venturi system, to a level of 2.OgIl to 10.Og/l in a non-ionizing, organic solvent, which, again for preference, will be a medical grade, refined rapeseed oil, the latter also being maintained at between 4°C and 6°C throughout the operation in order to minimise any ozone loss through the gas coming out of solution due to temperature elevation.

The non-ionising, organic solvent, once ozonated to the level required, will, as part of an inline process, be deposited immediately, on a volumetric basis, into a vertical form, fill and seal packing machine adapted to produce the multi-cellular sachet of the upper, ozone releasing pad of the wound dressing.

While still being held at between 4°C and 6°C, the finished ozone releasing pad will enter the assembly phase of the wound dressing production, where it is combined, within the cover fabric, with the wound contact and exudate absorbing pad and the whole sealed with the easy-peel', protective cover face.

Completed wound dressings will them be packed individually into liquid impermeable but gas permeable packs with hermetic closures to await a sterilisation procedure and final sealing.

Post-production storage and distribution will require temperature controlled conditions of between -20°C and -25C to ensure a minimal loss of ozone through the gas coming out of solution Once delivered to the hospital or wound clinic, the wound dressings will again need to be stored under temperature controlled conditions within a conventional, domestic deep freeze at between -17°C and -20C, until required for use. The effective storage life of the ozone releasing wound dressing under these frozen conditions is 26 weeks.

When required, the ozone releasing wound dressing should be removed from temperature controlled storage and, under normal ambient conditions, allowed to gain in temperature until, by employing an infra-red thermometer, it is judged warm enough to apply to the patient, without causing the latter thermal discomfort.

At this point, the wound dressing should be withdrawn from its pouch, prepared by removing the easy-peel' protective cover face layer and applied to the wound site, all the time observing those normal procedures employed for handling conventional wound dressings.

In application, the temperature of the fill material within the multi-cellular sachet of the ozone releasing pad will be elevated, within approximately 60 minutes, by the body heat radiating from the wound site area and with retention aided by the reflective surface of the backing sheet, to between 27.0°C and 32.5°C, effectively raising the rate that ozone will come out of solution and diffuse through the cover face control' layer and then through the wound contact and exudate absorbing pad, to the wound site headspace, where it will establish a maintained, predetermined concentration within the range of 0.O75ppm to 0.lSOppm.

In a further embodiment of the wound dressing of this invention, there may be the additional inclusion of an oxygen releasing pad, the initiation of which will be water vapour produced by both the wound site and the enclosed, surrounding area of skin. In construction, this additional pad will be a parallel insertion between the ozone releasing pad and the wound contact and exudate absorbing pad. This would be designed to supplement the action of the ozone by bathing the wound site in supra-atmospheric levels of oxygen.

Detailed Description

An embodiment of the invention is an ozone releasing wound dressing, as shown in the sectional side elevation in Fig. 1., having an outer fabric cover of a composite material (1), with both a low water vapour transmission rate (WVTR) and low oxygen transmission rate (OTR), to minimise the loss of ozone from the head space atmosphere of the wound-site. The loss of released ozone from the wound site is therefore prevented both by the selection of the OTR of the composite material of the outer fabric cover and the restricted surface area available for gas transmission.

The outer fabric cover comprises a composite water impermeable but water vapour and gas permeable layer, which has a WVTR of lOg to 30g1m2 in 24 hours at 23 °C and 85% relative humidity and an OTR in the range 20cm3 to 80cm3/m2 in 24 hours at 1 bar at 23°C.

The outer fabric cover additionally carries, on its inner surface, a medically approved, non-allergenic, self-adhesive coating in order to allow it to be securely applied to the surface of the skin surrounding the wound site, as shown in Fig. 2., ensuring that the latter is fully enclosed.

Within the outer fabric cover, integrally contained and secured, is both an upper, ozone releasing pad in a multi-cellular sachet format, and a lower, high capacity, fluid absorbent pad. These are positioned in a parallel, long axis alignment, as shown in Fig. 1.

The multi-cellular sachet of the ozone releasing pad contains a fill material (4), of a non-ionising, organic solvent in which ozone is dissolved to a predetermined concentration. The fill material will, with an elevation in temperature provided by the patient's body heat, release ozone at levels designed to maintain a predetermined percentage composition within the enclosed headspace atmosphere of the wound site.

The multi-cellular sachet of the ozone releasing pad is fabricated from an upper or backing sheet (2) comprising a fully liquid impermeable and gas impermeable laminate material and a lower, cover face (3) comprising a non-woven, polymer support layer laminated to a gas permeable but fully liquid impermeable polymer film control' layer.

The upper or backing sheet of the multi-cellular sachet will, for preference, be either a polyethylene terethphalate (PET) l2pm/Aluminium Foil 7pmllow density polyethylene (LDPE) 2Opm laminate or a Heat Resistant Lacquer/Aluminium Foil 9pm/LDPE 2Opm laminate, which has a reflective inner surface and is capable of reflecting back radiated body heat, thus reducing heat loss from the dressing, allowing the performance of the fill material, in terms of ozone release, to be more efficient.

As an alternative to the foil/polymer laminates above, the following may also be used: -a non-woven or spun-bonded, 42.SgmIm3 HDPE fabric, such as Tyvek 1 025B, laminated with a PET 1 5pm film, or a PET l5pm/polyvinyhdene chodde (PVDC) lOpm/LDPE l5pm co-extrusion film, or a PET l5pm/ethyl vinyl alcohol (EVOH) lOpm/LDPE l5pm co-extrusion film, or a material of equivalent characteristics and performance.

The cover face of the multi-cellular sachet will be a low porosity, spun-bonded, 42.5g/m3 -61.0 g/m3 HDPE fabric, such as Tyvek 1025B or 2058L, laminated to a LDPE l5pm -25pm film control' layer.

The multi-cellular sachet above has been designed in this format in order to control the movement of the liquid fill material and effect its uniform distribution within the ozone releasing pad, thus ensuring an even diffusion of ozone, per unit area, from the control' sheet and at the same time avoiding uneven pressure on the wound site and any consequent discomfort to the patient.

The structure of the above multi-cellular sachet is produced as a number of individual cells, in an approximate size range of 20mm x 20mm to 25mm x 25mm, by modified vertical, form, fill and seal packing technology, employing a series of narrow vertical lanes with short cycle, transverse seals.

The deposited weight of the fill material formulation within individual cells of the above multi-cellular sachet, will range from O.8g to 1.2g.

The lower of the two pads within the wound dressing comprises an envelope (5), which may be fabricated from medical grade non-woven, 35.Og/m2 polypropylene (PP) fabric and contain a fill material (6), in the form of super-absorbent acrylate beads laminated within layers of medical grade, non-woven, 35.OgIm2 PP fabric, or a material of equivalent specification and performance, which is designed to fully absorb and retain wound exudates in order to allow the wound itself to remain relatively dry.

In another embodiment of the invention, the fill material in the envelope of the above pad may alternatively contain a fill material comprising a highly liquid absorbent mixture of alginate and carboxymethylcellulose, to absorb wound exudates.

In the above pad, the envelope on its lower or wound contact surface, may be overlaid by and attached to a silicone-based mesh (7) providing a fully exudate-permeable, non-adherent layer, which will allow dressing changes with the minimum of pain and trauma.

Alternatively, in the above pad, the envelope, on its lower or wound contact surface, may have attached a perforated polymer film, such as Systagenix's Easy-LIFT® precision film, to allow atraumatic dressing removal.

The multi-cellular sachet of the ozone releasing pad of the embodiment contains a fill material formulation of ozone dissolved in a non-ionising, organic solvent, which, for preference, will be a medical grade of refined rapeseed oil.

Alternative non-ionizing, organic solvents may include the following: -grape seed oil groundnut oil maize oil linseed oil olive oil safflower oil sesame seed oil soya oil sunflower oil argan oil 100% glycerol or a blend of two or more of the above.

The formulation of the fill material of the above multi-cellular sachet, in terms of the relative composition of the constituent compounds, is designed to deliver the level of ozone required within the headspace atmosphere of the wound site and is thus broadly tailored to the nature of the wound concerned, with a range of formulations available to meet these particular requirements.

The mass of the fill material formulation of the above multi-cellular sachet, while avoiding excessive redundancy, is designed to deliver the performance life required and is also tailored, within the range discussed above, to the size and particular nature of the wound being treated.

In order to allow the fill material formulations to perform optimally, the cover face control' layer of the above multi-cellular sachet is required to be impermeable to liquids but also to have an appropriately high OTR.

To achieve this, the cover-face of the above multi-cellular sachet is fabricated from a bi-laminate material, with an inner polymer film control' layer supported by an outer membrane of a dense, low porosity, spun-bonded polymer fabric.

The cover-face of the above multi-cellular sachet therefore comprises an outer, permeable support layer and an inner, fully liquid impermeable but gas permeable control' layer, which, in combination, have an OTR in the range 2500cm3- 15000cm31m2 in 24 hours at 1 bar at 23°C.

In order to retain fully the fill material formulation selected and to restrict outward diffusion of ozone to the cover face only, the upper or backing sheet of the above multi-cellular sachet is a fully liquid impermeable laminate material with a high barrier to gas transmission.

In a particular embodiment, the upper or backing layer of the multi-cellular sachet, which comprises the upper ozone releasing pad of the device, is a tn-laminate material, comprising an outer, gas impermeable layer of a PET 12pm film, bonded by a 4g/m2 of a mono-component, polyurethane based, solvent-less adhesive to an middle gas impermeable layer of aluminium 7pm foil, which in turn is bonded by 4g1m2 of a mono-component, polyurethane based, solvent-less adhesive, to an inner, bond layer of PE 2Opm film.

The cover face of the above multi-cellular sachet, which comprises the upper ozone releasing pad of the device, is a bi-laminate material, comprising an outer, permeable layer of Tyvek 2FS, 1025B or 2058L, a spun-bonded, opaque 42.5g1m2 - 61.OgIm2 HDPE fabric, bonded with a 4g/m2 of a mono-component, polyurethane based, solvent-less adhesive to an inner, fully liquid impermeable but gas permeable, polymer film control' layer The above polymer film, depending on the OTR requirements demanded by the nature of the wound to be dressed, will be either PP, with a thickness of l5pm - 2Opm or PE, with a thickness of l5pm -25pm or an appropriately performing co-extrusion of the two polymers. For the majority of applications, however, PE is the preferred choice.

The supporting layer in the control' sheets is Tyvek, a permeable, non-woven, HDPE fabric, which in this case will have a density in the range of 42.5g1m2 - 61.OgIm2. This material is not an effective barrier to oxygen. The grades of TYVEK selected would include Tyvek 2FS, 1025B, and 2058L, although for the majority of applications Tyvek 2FS, a medical specification with microbial barrier properties is the preferred choice.

The inner and outer layers of the cover face control' layer are bonded together with a 4g/m2 of a mono-component, polyurethane based, solvent-less adhesive, or a material of equivalent properties and performance, the composition and thickness of which will have a negligible effect on the OTR of either the inner layer or the laminate overall.

The WVTR of the afore mentioned fabrics, films and laminates may be measured, where applicable, by employing a commercially available water permeation analyser such as the MOCON PERMATRAN-W Model 3/33, which is designed with integral, automatic, relative humidity generation to test this property of packaging films. The machine measures according to the ASIM standard F -1249.

The OTR of the afore mentioned fabrics, films and laminates may be measured by employing a commercially available oxygen transmission rate analyser, such as the MOCON OX-TRAN Model 1/50, which is designed to test this property of packaging films. The machine measures according to the ASTM standard F-1927.

In its simplest construction, the materials forming the backing and cover face are fabricated into the multi-cellular sachet comprising the upper ozone releasing pad of the device, which allows the outward diffusion of ozone at a predetermined, controlled rate and at a pressure that will not perceptibly exceed ambient atmospheric.

In this format, the above multi-cellular sachet is capable of being manufactured using existing vertical, form, fill and seal technology, where the seals themselves can be heat bonded or dielectrically or ultrasonically welded.

In this format, the multi-cellular sachet, which comprises the upper ozone releasing pad of the device is intended to be placed with precision and secured within the outer fabric cover of the wound dressing.

The envelope of the lower, wound contact and exudate absorbing pad of the embodiment contains a fill material in the form of a die-cut, multi-laminate pad comprising layers of a medical, wound contact specification, liquid water permeable, non-woven PP fabric, between which are dispersed, at low density, fine beads of super-absorbent acrylate, also of a medical, wound contact specification.

The envelope of the lower, wound contact and exudate absorbing pad of an alternative embodiment contains a fill material in the form of a comprising a highly liquid absorbent mixture of alginate and carboxymethylcellulose of a medical, wound

contact specification.

The envelope of the lower, wound contact and exudate absorbing pad of the embodiment is fabricated, in its cover face and backing sheets, from a medical, wound contact specification, liquid water permeable, non-woven PP fabric, or a material of equivalent properties and performance.

The envelope of the wound contact and exudate absorbing pad of the embodiment, on its lower or wound contact surface is overlaid with a silicone-based mesh providing a fully exudate-permeable, non-adherent layer, or other material of equivalent properties and performance, which will allow dressing changes with the minimum of pain and trauma.

The envelope of the wound contact and exudate absorbing pad of an alternative embodiment, on its lower or wound contact surface is covered with a non-adherent, fully exudate-permeable, perforated polymer film, such as Systagenix's Easy-LIFT® precision film, or others of equivalent properties and performance, to allow atraumatic dressing removal.

The lower wound contact and exudate absorbing pad of both of the above embodiments are designed to allow unimpeded diffusion of ozone, from the upper, ozone releasing pad of the device, to the wound site headspace.

In this format, the lower, wound contact and exudate absorbing pad of the embodiment can be manufactured using existing vertical, or horizontal, form, fill and seal technology, where the seals themselves can be heat bonded or dielectrically or ultrasonically welded.

In this format, the lower, wound contact and exudate absorbing pad of the device is intended to be placed with precision and secured within the outer fabric cover of the wound dressing.

The device is designed for deployment as a self-adhesive wound dressing, in conventional format for the protection and treatment of chronic wounds such as pressure induced sores and decubitus, venous leg ulcers, as well as diabetic lesions, in which there is the possibility of the presence of free water and where the ozone composition of the wound site headspace atmosphere is required to be maintained at predetermined supra-atmospheric levels.

The criteria, which this device aims at, are:-to be fully compliant with all required medical certification to provide ease of application to the wound site, with minimal additional training beyond that already required for the conventional dressing of chronic wounds to protect the wound site from physical contact to protect the wound site from chemical and microbial contamination S to effectively remove wound exudates in order to allow the wound to remain dry, to protect the wound site by retaining fully the fill materials and any reaction products produced, to be flexible in that it can be applied at any orientation that the location of the wound requires, to be comfortable when worn by the patient, to produce and maintain pre-determined supra-atmospheric levels of ozone within the wound site headspace atmosphere.

In order to address the latter requirement, alternative formulations of the fill material may be used, which fall within the range of 2g -lOg of dissolved ozone per litre of the non-ionising organic solvent.

The formulation of the fill material, in terms of the relative composition of the fill material, in respect of the amount of ozone in solution, is designed to effect the wound site headspace atmosphere ozone level required and is thus specific to the type of wound treated and, within a limited range, will vary between specific wound type.

Control over the rate of release of ozone and the period over which this release will continue, is effected by a selected combination of the relative mass of ozone in solution within the non-ionising, organic solvent, the mass/volume of the solvent, the OTR and surface area of the control' sheet of the multi-cellular sachet of the ozone releasing pad.

Target level of ozone within the wound-site headspace atmosphere is 0.O75ppm to O.l5ppm, although higher or lower levels can be delivered if informed medical treatment regimes indicate that such are both beneficial and safe Correspondingly, apart from the composition, the mass of a fill material formulation in the envelope of the ozone releasing pad is also determined by the particular demands placed on the headspace atmosphere of the wound site by the size, type and nature of the chronic wound concerned and the requirements the latter imposes on the former in order to maintain the predetermined, optimum ozone composition demanded.

Typically, the mass of the fill material contained within the multi-cellular sachet of the ozone releasing pad will equate to O.2gIcm2 for the overall area of the control' sheet.

The dimensions of the upper, ozone releasing pad and the lower, wound contact and exudate absorbing pad secured within a dressing and thus the respective, effective surface areas, will reflect the size of the chronic wound to be dressed. It is anticipated by the inventors that the device in the present invention will be produced in a limited but appropriately informed, range of sizes.

Studies have shown that wound dressings containing the ozone releasing pad, as an integral component as described, can develop and maintain target range, supra-atmospheric levels of ozone within the headspace atmosphere of the wound site atmosphere for periods exceeding eight days.

In particular, the selective use of the polymers and their gauges, in the fabrication of the control' sheet of the multi-cellular sachet of the ozone releasing pad, to regulate ozone release allows a degree of precision in the provision of a range of performances that more closely meet the particular dressing requirements of the wounds under treatment.

Claims

CLAIMS1. An ozone-releasing wound dressing, comprising an outer fabric cover, a first pad contained within the outer fabric cover, the first pad comprising a fill material formulation arranged to relase ozone in the case of an elevation in temperature produced by body heat and a second pad contained within the outer fabric cover, the second pad being an absorbent pad for absorbing aqueous liquids, wherein the outer fabric cover is comprised of a composite material with both a low water vapour transmission rate and low oxygen transmission rate, OTR, the latter to prevent the escape of ozone from the wound-site head space atmosphere, wherein the outer fabric cover carries a self-adhesive coating in order to allow it to be secured to the skin surrounding the area of the wound site, ensuring that the latter is fully enclosed.
2. An ozone releasing wound dressing according to claim 1, wherein the outer fabric cover has a water vapour transmission rate of lOgIm2 to 30g1m2 in 24 hours at 23 °C and 85% relative humidity and an oxygen transmission rate in the range 20cm3/m2 to 80cm3/m2 in 24 hours at 1 bar at 23°C.
3. An ozone releasing wound dressing according to claim 1, wherein the first pad contained within the outer cover is a multi-cellular sachet with a plurality of cells and having a cover face sheet and a backing sheet each of a different material.
4. An ozone releasing wound dressing according to claim 3, wherein the backing sheet is fully impermeable to liquids and impermeable to gases.
5. An ozone releasing wound dressing according to claim 3, wherein the backing sheet comprises an outer liquid and gas impermeable support layer, a middle highly liquid and gas impermeable layer and an inner, liquid impermeable but gas permeable, thermo-bond layer, which in combination have an OTR in the range of 5cm3/m2-1 Ocm3/m2 in 24 hours at 1 bar at 23°C.
6. An ozone releasing wound dressing according to claim 3, wherein the backing sheet is of a tn-laminate material, comprising an outer, gas and liquid impermeable layer of a polymer film bonded, with a polyurethane adhesive, to a middle, highly gas and liquid impermeable aluminium foil bonded in turn, on its inner face, with a polyurethane adhesive, to an inner, thermo-bond layer of a liquid impermeable but gas permeable polymer film.
7. An ozone releasing wound dressing according to claim 3, wherein the backing sheet is of a tn-laminate material, in which the middle layer is a highly gas and liquid impermeable aluminium foil reflective to infra-red radiation on it inner face for reflecting back radiated body heat.
8. An ozone releasing wound dressing according to claim 3, wherein the cover backing sheet is of a tn-laminate material, comprising an outer liquid and gas impermeable layer of a polyethylene terethphalate fabric, bonded with a polyurethane adhesive to a middle layer of a highly liquid and gas impermeable aluminium foil.
9. An ozone releasing wound dressing according to claim 3, wherein the backing sheet is of a tn-laminate material, comprising an outer liquid and gas impermeable layer of a heat resistant lacquer applied to a middle layer of a highly liquid and gas impermeable aluminium foil.
10. An ozone releasing wound dressing according to claim 3, wherein the backing sheet is of a tn-laminate material, having a middle layer of a highly liquid and gas impermeable aluminium foil with a thickness of 6 to 8pm.
11. An ozone releasing wound dressing according to claim 3 or 10, wherein the backing sheet is of a tn-laminate material, wherein, inner, thermo-bond layer is an liquid impermeable but gas permeable low density polyethylene film of thickness 15 pm to 25pm.
12. An ozone releasing wound dressing according to claim 3, 10, or 11 wherein the backing sheet is of a tn-laminate material, in which a 3 g/m2to 5g/m2 of a mono-component, polyurethane based, solvent-less adhesive, or a material of equivalent properties and performance, bonds the three layers of the laminate together.
13. An ozone releasing wound dressing according to any of claims 3 to 12 wherein the first pad has a cover face sheet that is impermeable to liquids and permeable to gases.
14. An ozone releasing wound dressing according to claim 3 or 13, wherein the first pad has a cover face sheet comprising an outer permeable support layer and an inner, fully liquid impermeable but gas permeable layer, which in combination have an 0Th in the range of 2500cm3-1 5,000cm3/m2 in 24 hours at 1 bar at 23°C.
15. An ozone releasing wound dressing according to claim 3, 13 or 14 wherein the first pad has a cover face sheet of a bi-laminate material, comprising an outer, permeable layer of a spun-bonded, opaque 42.5g/m2 -6i.Og/m2 high density polyethylene fabric, bonded with a polyurethane adhesive to an inner, control' layer of liquid impermeable but gas permeable polymer film.
16. An ozone releasing wound dressing according to claim 3, 13, 14, or 15 wherein the first pad has a cover face sheet of a bi-laminate material, with an inner or control' layer of polymer film of either low density polyethylene, with a thickness of l5pm -2Opm or polypropylene, with a thickness of l5pm -2Opm or an appropriately performing co-extrusion of the polyethylene and polypropylene.
17. An ozone releasing wound dressing according to claim 3, 13, 14, 15 or 16 wherein the first pad has a cover face sheet of a bi-laminate material, in which a 4g/m2 of a mono-component, polyurethane based, solvent-less adhesive bonds the two layers of the laminate together.
18. An ozone releasing wound dressing according to any preceding claim wherein the fill material formulation comprises: an active ingredient, ozone, dissolved in a non-ionising organic solvent, wherein the active ingredient is present in an amount from 0.2% -1.0% w/v.
19. An ozone releasing wound dressing according to any preceding claim, wherein the fill material formulation comprisesa non-ionising organic solvent component including medical grade, refined rapeseed oil, grape seed oil, groundnut oil, maize oil, linseed oil, olive oil, safflower oil, sesame seed oil, soya oil, sunflower oil, argan oil, 100% glycerol or a blend of two or more thereof.
20. An ozone releasing wound dressing according to any preceding claim, wherein the fill material formulation is arranged, when the dressing is applied and the temperature is elevated to between 27.0°C and 32.5°C by radiant body heat from the patient, to release ozone into the headspace atmosphere of the wound site at a concentration of between 0.OJ5ppm and 0.l5Oppm.
21. An ozone releasing wound dressing according to any preceding claim, wherein the fill material formulation comprises a concentration of ozone dissolved in a non-ionising, organic solvent pre-determined to allow a pre-selected ozone delivery to the wound site headspace atmosphere required to meet a specific therapeutic regime for a predetermined type of wound under treatment.
22. An ozone releasing wound dressing according to any preceding claim, wherein the first pad comprises a plurality of individual cells, and wherein the volume of the fill material formulation within the individual cells is pre-selected to allow controlled ozone delivery to the wound site headspace atmosphere required to meet the therapeutic regime demands for a predetermined type of wound under treatment.
23. An ozone releasing wound dressing according to any preceding claim, wherein the first pad comprises a cover face control layer of polymer pre-selected to allow a controlled ozone delivery to the wound site headspace atmosphere required to meet the therapeutic regime demands for a predetermined type of wound under treatment.
24. An ozone releasing wound dressing according to any preceding claim, wherein the first pad comprises a cover face control layer of polymer pre-selected to allow controlled ozone delivery to the wound site headspace atmosphere required to meet the therapeutic regime demands for a predetermined type of wound under treatment.
25. A method of manufacturing an ozone releasing wound dressing according to any preceding claim, wherein the fill material formulation is comprises a non-ionizing organic solvent and an ozone component, including of electronically generating the ozone component only from a medical grade, pure oxygen source.S