AU2004249259A1 - Method and apparatus for supplying gas to an area - Google Patents

Description

WO 2004/112649 PCT/US2004/019599 METHOD AND APPARATUS FOR SUPPLYING GAS TO AN AREA This application claims the benefit of U.S. Application Serial No. 60/479,745, filed on 5 June 18, 2003, U.S. Application Serial No. 10/781,965, filed on February 18, 2004, and U.S. Application Serial No. 60/551,638, filed on March 8, 2004, which are herein incorporated by reference in their entirety. FIELD OF THE INVENTION 10 The present invention relates generally to supplying a gas to an area. BACKGROUND OF THE INVENTION Throughout this application various publications are referenced by arabic numerals within parentheses. Full citations for these publications may be found at the end of the 15 specification immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains. The healing of wounds and the effect of oxygen tension has been intensively studied (1). Among the components important in the healing process are fibroblast proliferation, 20 angiogenesis, collagen synthesis, and reepithelialization. Soon after injury, whether accidental or surgically induced, undifferentiated mesenchymal cells transform to migratory fibroblasts, which migrate into and across the injured wound. It is known that fibroblasts are aerobic in nature. Fibroblasts are stimulated to produce collagen. While experiments from cultured fibroblasts suggest that high lactate 25 and ascorbic acid concentration typical of hypoxic conditions may activate some of the fibroblast collagen-synthesizing enzymes, animal studies involving low, normal, and high oxygen tensions nevertheless demonstrate increased rates of collagen synthesis under hyperoxic rather than hypoxic conditions. Angiogenesis, on the other hand, appears to be stimulated by a hypoxic tissue 30 gradient, with new capillaries extending in the direction of lower oxygen concentration. When a hypoxic gradient no longer exists, angiogenesis is minimized or static. Epithelialization is also known to be related to oxygen tension, with higher rates of epithelial proliferation observed under hyperoxic as opposed to hypoxic conditions. 1 WO 2004/112649 PCT/US2004/019599 The supply of oxygen to healing wound tissue may be derived from three sources: oxygen chemically bound to hemoglobin in whole blood; oxygen dissolved in plasma; and oxygen which diffuses into plasma or tissue from the exterior. In deep wounds, the latter is of little importance. The studies of R. P. Gruber et al., for example, indicate that oxygen 5 tension, measured polarographically, increases markedly at 3 bar of 100% 02 in the superficial dermis (0.30-0.34 mm), while the relative oxygen concentration of the deep dermis (1.8-2.2 mm) is unchanged under the same conditions (2). In surface wounds, all sources of oxygen are important. In wounds of large surface area, however, for example ulcers, only the tissue at the edges of the ulcer or at its base are 10 well supplied with blood, and the growing granulation tissue, in the absence of oxygen diffusing from the exterior, must be supplied by diffusion from blood vessels and plasma, a relatively inefficient process. It is well established, also, that occlusive coverings that maintain a moist environment promote wound healing (3). Furthermore, it is well known that the changing of wound 15 dressings may interfere with the healing process by disrupting the healing tissue where granulation and collagen synthesis has not imparted sufficient tensile strength to avoid rupture upon dressing removal. However, due to the inability of the blood and plasma to supply optimal oxygen concentration, and due to the further reduction in oxygen from the exterior brought about by the presence of the occluding dressing, a hypoxic condition may 20 rapidly be reached. Although this condition may encourage angiogenesis, it negatively affects collagen synthesis and epithelialization. Moreover, various clostridium species, e.g., C. perfringens and C. septicum, are induced to germinate under hypoxic conditions, which can also support other anaerobic flora (4). In addition to minimizing anaerobic flora by discouraging germination, hyperoxic conditions are known to reduce the concentration of 25 other pathogens as well. Past treatment of chronic ulcers and gangrenous tissue has, in many cases, involved extensive debridement in combination with antibiotics and systemic hyperbaric oxygen. Room size hyperbaric oxygen chambers or chambers sized for the individual patient have employed pure oxygen at pressures of 2 to 3 bar. Treatment time is limited, as oxygen 30 toxicity and central nervous system (CNS) disorders may result from the increased oxygen content of the blood. Such treatments have met with a great deal of success, but the success may not be due to the increased systemic blood and plasma-derived oxygen supply. The blood and plasma already contain sufficient oxygen for the healing process. Rather, it is the diffusion-limited access of oxygen to the wound that limits the oxygen supply required for 2 WO 2004/112649 PCTIUS2004/019599 optimal healing and minimization of infection. The increased oxygen tension in the wound most likely results directly from increased diffusion into the wound surface from the oxygen in the chamber. Gruber, for example, indicates that rate of oxygen absorption from the skin is roughly proportional to oxygen concentration from nearly 0% to 30% (2). Gruber further 5 indicates, however, that oxygen absorption tends to level off at higher oxygen concentrations. Due to the expense of large hyperbaric chambers and the systemic effects of oxygen toxicity that they may engender, topical hyperbaric chambers have been proposed. Topical chambers operating at "normal" hyperbaric pressures of 2-3 bar are difficult to seal to the body or extremity being treated, however, without interfering with blood supply to the wound 10 locus. Thus, hyperbaric chambers operating at only modestly elevated pressure have been manufactured, such as a device operating at 22 mm Hg pure oxygen (1.03 bar) (5). However, such chambers are expensive and difficult to sterilize (6). Cross-infection is stated to be common. Heng and others have proposed a simple hyperbaric oxygen treatment chamber 15 consisting of a polyethylene bag that may be secured to the body or extremity with adhesive tape (6), or a transparent nylon bag with straps and VELCRO® closures (7). Pressure is maintained at between 20 mm Hg and 30 mm Hg. However, the leakage associated with the sealing of such bags requires a relatively high rate of oxygen flow. Thus, this method is useful only in facilities with sufficient oxygen supply, or in controlled home environments 20 where a large oxygen tank is pennissible. A disposable hyperbaric treatment bag with improved closure is disclosed in U.S. Pat. No. 5,029,579. Another disposable hyperbaric treatment bagis disclosed in U.S. Pat. No. 5,478,310. In U.S. Pat. No. 4,875,483, a combination layered dressing having an external low oxygen-permeability layer and an abutting internal oxygen permeable layer has been 25 proposed. The relatively low permeability exterior layer is left attached for 3 to 72 hours creating hypoxia, and hopefully stimulating angiogenesis, following which this layer is removed. However, although the remaining, and now exterior layer is oxygen permeable, the layer nevertheless decreases oxygen transport, and thus hyperbaric treatment, by one of the methods previously described, may be necessary to elevate oxygen levels sufficiently to 30 provide optimal healing. Ischemia compromises wound healing and wounds in aging populations are more ischemic than those in younger populations (8). It has been demonstrated in ischemic rabbit ear models that topical or hyperbaric oxygen can convert a non-healing wound into a healing 3 WO 2004/112649 PCTIUS2004/019599 wound, and that growth factors (PDGF) provide a synergistic benefit when used with oxygen (9). It is well known that the speed of epidermal migration on the normal wound is critically dependent on the amount of oxygen available, and this is the rate-limiting step. The 5 control of the local environment is dependent on the local blood supply and the diffusion of oxygen from the atmosphere. Any form of treatment that encourages an increase in the wound fluid and reduces the time during which the wound is non-perfused will tend to increase the rate of healing (10, 11). It is generally agreed that the tissue surrounding a wound does not alone supply 10 sufficient oxygen for wound repair, and that atmospheric oxygen is required for the formation of hydroxyproline, a key element in epidermal wound healing. It has been demonstrated that 93% of the oxygen incorporated into the hydroxyl groups of newly synthesized hydroxyproline is derived from the atmosphere (12). It is further generally known that it is likely that oxygen reaches the epidermal cells 15 directly by diffusion through the scab rather than via the vascular or tissue supply. Prior studies of wounds covered with plastic films found that the higher the oxygen permeability of the film, the greater the healing rate (13, 14). Furthermore, the films prevented scab formation, thereby altering the mode of epidermal regeneration. The use of wound dressings that prevent scab formation and have increased oxygen permeability are thought to improve 20 wound healing. The increased presence of oxygen speeds the re-establishment of epithelial continuity. Direct access of pure oxygen to open wounds promotes epidermal cell migration. Kaufman et al. showed a continuum in wound healing improvement when changing humidified oxygen levels from 21 to 60, and 80-96% on full thickness burns on guinea pigs (15). Niinikoski also suggested that collagen accumulation in the dead space of animal 25 wounds increases with oxygen concentration of the environment, peaking at 70% (16). A review of topical oxygen and burn wound healing states that oxygen is essential for the contraction, the dominant healing process (17). Topical oxygen has also been shown to improve the healing rate of skin ulcers and wounds where an inadequate supply of oxygen results from peripheral vascular disease or local injury to the microcirculation. Fischer 30 showed topical hyperbaric oxygen treatment improved epithelialization and contraction of decubitus ulcers (5). Utkina demonstrated that moderate increases in oxygen levels at normal atmospheric pressure increases the closure rate of open wounds (18). He showed healing rate improved with continuous exposure to 45%. 4 WO 2004/112649 PCTIUS2004/019599 A number of patents have been issued that disclose the use of local generation of oxygen at the wound site to treat wounds in bandage systems using chemical reactions, oxygen saturated solutions, or electrochemical generators (see U.S. Patent Nos. 5,855,570, 5,578,022, 5,788,682, 5,792,090 and 6,000,403). These concepts have not been 5 commercialized. The present invention allows for gas to be contained simply into the wound dressing, which creates a wound environment with continuous exposure to preset oxygen levels, without need for a gas source such as a generator, saturated solution or a chemical reaction. Since the amount of oxygen consumed by metabolic processes in the wound is relatively small, the materials for the dressing and the volume of the oxygen cavity in the 10 dressing can be selected to maintain the desired oxygen concentration for the practical life of the dressing Prior to this invention, larger amounts of oxygen were believed to be required to benefit wound healing, which justified the need for an oxygen releasing source However, the actual amount of oxygen that the wound consumes in cell metabolism is quite small, and 15 simply requires a design that assures a large diffusion gradient for oxygen into the wound during the healing period. Hyperbaric approaches that use elevated pressure to further enhance the oxygen diffusion gradients to transfer more oxygen into the tissue are only used briefly, and once the patient is withdrawn from the high-pressure environment, the oxygen levels in the wound drop down to pre-exposure limits quickly. The present invention 20 operates as a hyperoxic environment without the need for using elevated pressure to create the oxygen diffusion gradient. Supplying oxygen to a wound on a continuous and ambulatory basis is of benefit to speed healing and reduce infection. The oxygen dressing described below can be complimentary to other therapies and can address a rate-limiting step for various types of 25 wounds. SUMMARY OF THE INVENTION The present invention is an apparatus that is capable of providing one or more gases to a target area. One embodiment of the invention is a multi-layer wound dressing comes 30 pre-filled with high levels of oxygen between the layers. The top layer is a barrier film that holds the oxygen over the wound, while the bottom layer is a high transfer rate film, attached over the wound. This self-contained dressing is applied to the wound like conventional wound dressings, and can be manufactured with a similar size, weight and feel of conventional dressings or transdermal patches. The dressing can also envelop the target area, 5 WO 2004/112649 PCTIUS2004/019599 such as an appendage, in a controlled environment. For example, the dressing can be in the form of a glove or mitten for hand treatments or wounds or in the form of a sock for foot or leg treatments or wounds. The barrier layer holds the oxygen in the vicinity of the wound, while the permeable 5 or porous layer allows the oxygen to diffuse into the wound fluid at a rate proportional the gradient, until the wound fluid is saturated. The dressing acts like an oxygen reservoir, and as oxygen is consumed by the wound, there is a local abundant supply to be used as needed. While oxygen is a rate-limiting component in the wound healing process, the oxygen transfer across intact skin is insignificant, and oxygen consumption by a wound is a relatively 10 small number, estimated to be 10~ 4 cc/mL fluid-hr. Therefore the design of the dressing is influenced most significantly by the diffusion rates of the relevant gases through the barrier material, the target gas concentration range on the patient, the length of time the dressing may be worn, and the seal integrity of the dressing to itself and to the patient The dressing would be removed by the user from a package that uses controlled 15 atmospheric packaging (CAP) to maintain the product integrity. CAP is specifically a package with high barrier properties that contains the desired ratio of gases to preserve the product. CAP is well known in the food industry and examples of the types of CAP that may be used are described in U.S. Patent No. 4,895,729 and in the published literature (19, 20, 21, 22, 23). 20 The dressing will accelerate healing of acute and chronic wounds, as well as provide antibacterial and antifungal benefits. BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are incorporated in and constitute a part of this 25 specification, illustrate one embodiment of the invention and, together with the description, explain one embodiment of the invention. In the drawings, Figure 1 illustrates one embodiment of a dressing system. Figure 2 illustrates one embodiment of a packaging system. Figure 3 illustrates one embodiment of a gas emitting pouch system. 30 Figure 4 illustrates a flow diagram for utilizing a packaging system according to one embodiment of the invention. Figure 5 illustrates a flow diagram for utilizing a dressing system according to one embodiment of the invention. Figure 6 illustrates one embodiment of a pouch system. 6 WO 2004/112649 PCTIUS2004/019599 Figure 7 illustrates the embodiment of a glove. Figure 8 illustrates the embodiment of a sock. DETAILED DESCRIPTION 5 The following detailed description of the invention refers to the accompanying drawings. The detailed description merely provides exemplary embodiment of the invention and is not intended to limit the invention. Figure 1 illustrates an apparatus for supplying one or more gases, also referred to herein as a dressing system 100. The dressing system 100 is shown as an exemplary 10 perspective cut-away view to more clearly illustrate the invention. In one embodiment, the dressing system 100 is configured to contain a gas that is dispensed to a user wearing the dressing system 100. For example, the different gases contained within the dressing system 100 may include but is not limited to oxygen, carbon dioxide, and/or nitrogen. As used herein, the term "gas" includes any gas or volatile. 15 The dressing system 100 includes a seal 110, an external barrier (or top layer) 120, a reservoir 130, an absorbent ring 140, an adhesive backing 150, a permeable film (or bottom layer) 160, and a compliant porous insert 170. The seal 110 is configured to bond the external barrier 120 and the permeable film 160 together such that the reservoir 130 is formed. 20 The external barrier 120 is selected to be non-permeable to gases. For example, the external barrier 120 may be constructed of metallized polyester, ceramic coated polyester, polyvinylidene chloride laminates such as Saranex@, EVOH laminates such as Oxyshield@, or polyamide laminates such as Capran@. In one embodiment, the external barrier 120 may be configured to conduct heat or electrical stimulation from an external source to the user. 25 For example, polyethylene or another infrared transmittable material may be utilized as the external barrier 120. The permeable film 160 is configured to be permeable to gases. For example, the permeable film 160 may be constructed of polyurethane, silicone, polyvinylchloride, polyolefins, and the like, preferably ethylene vinyl alcohol (EVA) or EVA/polyethylene. 30 The reservoir 130 is configured to store a gas while the dressing system 100 is worn by a user. In one embodiment, the stored gas within the reservoir 130 is controllably released to the user through the permeable film 160. 7 WO 2004/112649 PCTIUS2004/019599 The amount of gas released to the user while wearing the dressing system 100 may vary according to the concentration of the gas contained within the reservoir 130 and the material used as the permeable film 160. Other factors such as temperature and atmospheric pressure may also affect the amount of gas released to the user. 5 The absorbent ring 140 may be located adjacent to the permeable film 160 and may be configured to wick away moisture from the user. The adhesive backing 150 is configured to adhere the dressing system 100 to the user. Further, the adhesive backing 150 may also be utilized to prevent the gas that is delivered through the permeable film 160 to the user from escaping. In one embodiment, the adhesive 10 backing 150 may cover the perimeter of the dressing system 100. In another embodiment, the adhesive backing may cover the entire dressing system 100 and may be integrated with the permeable film 160. Examples of the types of adhesive that may be used in the present invention are described in U.S. Patent Nos. 6,284,941 and 5,308,887. In one embodiment, the adhesive 15 backing may be comprised of adhesive used in commercially available adhesive bandages. In another embodiment, the adhesive backing may be comprised of a gel adhesive. The gel adhesive may be comprised of a hydrogel. The gel adhesive may also be reusable, such that the dressing system could be removed from the user and replaced more than once. The compliant porous insert 170 is configured to prevent gas debt in areas caused by 20 pressing the external barrier 120 directly on to the permeable film 160. In one embodiment, the compliant porous insert 170 placed within the reservoir 130 and between the external barrier 120 and the permeable film 160. The elements comprising the dressing system 100 are shown for illustrative purposes only. Deletion or substitution of any shown elements does not depart from the spirit and 25 scope of the invention. Similarly, the addition of new elements does not depart from the spirit and scope of the invention. In one embodiment, the dressing system 100 is configured to be pre-filled with high levels of oxygen within the reservoir 130. In this embodiment, the dressing system 100 is configured to be placed over a wound of the user to help the wound heal. In one 30 embodiment, the external barrier 120 is configured to hold the oxygen within the dressing system 100 and the permeable film 160 is a high transfer rate film and is configured to provide oxygen over the wound. In other words, the external barrier 120 holds the oxygen in the vicinity of the wound, while the permeable film 160 allows the oxygen to diffuse into the wound fluid at a rate proportional the gradient, until the wound fluid is saturated. 8 WO 2004/112649 PCTIUS2004/019599 Subsequent to the saturation, the dressing system 100 acts as an oxygen reservoir; as oxygen is consumed by the wound, there is a local abundant supply of oxygen to be provided to the wound as needed. The proportions of the dressing system 100 may be influenced by the diffusion rates 5 of the relevant gases through the permeable film 160, the target gas concentration range on the user, the length of time the dressing system 100 may be worn, and the seal integrity between the dressing system 100 and the user. The dressing system 100 may accelerate healing acute and chronic wounds, as well as provide antibacterial and antifungal benefits. 10 In another embodiment, in addition to providing gas to a user, the dressing system 100 may be configured to deliver biologically beneficial agents such as drugs, minerals, nutrition, amino acids, pH modifiers, anti-microbials, growth factors, enzymes to the user. In one embodiment, integrating the delivery systems of the gas with the beneficial agent additives may lead to synergistic effects that are not achieved by just the gas or the beneficial agent 15 additives alone. In one embodiment, these biologically beneficial agents may be delivered as microencapsulated agents incorporated in the adhesive backing 150. In another embodiment, the microencapsulated agents may be available in a gel matrix in the dressing cavity 180, accessible to the wound through pores or perforations, or using conventional transdermal technologies. 20 In an alternate embodiment, instead of filling the reservoir 130 with gas, a substance is included within the reservoir 130 to generate gas within the reservoir 130. For example, oxygen-releasing agents may be included within the reservoir 130. Oxygen releasing agents include oxygen releasing inorganic salts, hydrogen peroxide containing formulations, intercalated magnesium peroxide, sodium percarbonate, sodium carbonate and hydrogen 25 peroxide, and the like. In yet another embodiment, the permeable film 160 may be deleted and the compliant porous insert 170 may be utilized to hold a substance for generating a gas within the dressing system 100. In yet another embodiment, the external barrier 120 is comprised of Saranex@, the 30 permeable film 160 is a polyurethane high oxygen permeability film, these two layers are hermetically sealed around the perimeter, and the reservoir 130 contains 98% oxygen. One method of achieving the specified oxygen concentration in the reservoir 130 and to create the controlled atmospheric packaging is to (1) assemble dressing, sealing the reservoir 9 WO 2004/112649 PCTIUS2004/019599 with normal atmospheric conditions (about 21% oxygen); (2) place the dressing in the metallized film package; (3) flush the package with 100% oxygen; and (4) seal the package. In storage, the gas in the reservoir 130 will come to equilibrium with the gas in the package via the permeable film 160. When the product is received by the customer and opened, the 5 gas in the reservoir will achieve 98% oxygen. The materials and dimensions used are determined by taking into account these objectives. In another embodiment, the dressing system as described herein may further comprise a septum, which is defined herein as a septum, a valve, a Luer-type fitting or any resealable opening through which one or more gases can be introduced into the dressing system, then 10 resealed to prevent the one or more gases from escaping. The dressing system of this embodiment may be applied to the wound, and then the one or more gases in the desired ratio may be introduced into the dressing system, e.g., with a syringe. The septum would also allow for refilling of the dressing system, if desired. Figure 2 illustrates a packaging system 100. The packaging system 100 is shown as 15 an exemplary perspective cut-away view to more clearly illustrate the invention. In one embodiment, the packaging system 200 is configured to contain a gas within an enclosed container 210, which is within the packaging system. For example, the different gases contained within the dressing system 100 may include but is not limited to oxygen, carbon dioxide, and/or nitrogen. 20 The enclosed container 210 is also configured to hold the dressing system 100 as shown and described corresponding to Figure 1. Once the enclosed container 210 is sealed, the enclosed container is substantially impermeable; the gas within the enclosed container 210 substantially remains within the enclosed container 210. Further, the enclosed container 210 utilizes controlled atmospheric packaging (CAP) to maintain the environment within the 25 enclosed container 210. In one embodiment, CAP is a package with high barrier properties that contains the desired ratio of gases to preserve the internal environment. The gas within the enclosed container 210 may penneate the dressing system 100 through the permeable film 160. In one embodiment, the packaging system 200 may be utilized to store the dressing 30 system 100 without degrading the gas stored within the reservoir 130 within the dressing system 100 when the gas within the reservoir 130 and the gas within the enclosed container 210 are the same. In another embodiment, the packaging system 200 may be utilized to change the concentrations of gases in the dressing system 100. The gas constituents stored within the 10 WO 2004/112649 PCTIUS2004/019599 enclosed container 210, diffuse into the dressing system 100 when the concentration of the gas within the container 210 is higher in concentration compared to the gas within the dressing system 100. Similarly, the gas constituents stored within the dressing system 100, diffuse into the container 210 when the concentration of the gas within the container 210 is 5 lower in concentration compared to the gas within the dressing system 100. The gases may diffuse through the permeable film 160 until the constituents reach equilibrium, the same concentrations on both sides of the permeable film. Figure 3 illustrates a gas emitting pouch system 300. The gas emitting pouch system 300 is shown as an exemplary perspective cut-away view to more clearly illustrate the 10 invention. In one embodiment, the gas emitting pouch system 300 is configured to contain a gas that is dispensed to the local area surrounding the gas emitting pouch system 300. For example, the different gases contained within the gas emitting pouch system 300 may include but is not limited to oxygen, carbon dioxide, and/or nitrogen. The gas emitting pouch system 300 includes a first permeable film 310, a second 15 permeable film 320, and a reservoir 330. In one embodiment, the first permeable film 310 is coupled with the second permeable film 320 and forms the reservoir 330 for storing gas within the gas emitting pouch system 300. For example, the first and second permeable films 310 and 330 maybe constructed of polyurethane, polyethylene, silicone films, polyvinylchloride, and the like. 20 The reservoir 330 is configured to store a gas while the gas emitting pouch system 300 is being used. In one embodiment, the stored gas within the reservoir 330 is controllably released to the area surrounding the gas emitting pouch system 300 through the first and second permeable films 310 and 320. The amount and rate of gas released through the gas emitting pouch system 300 may 25 vary according to the concentration gradients of the gas across the permeable films that comprise the walls of reservoir 330 and the materials used as the first and second permeable films 310 and 320. 310 and 320 can be the same or different materials. The amount and rate of release of gas can be different on the opposite sides, this can occur when 310 and 320 have different permeabilities. Other factors such as temperature, humidity, and atmospheric 30 pressure may also affect the amount of gas released. The elements comprising the gas emitting pouch system 300 are shown for illustrative purposes only. Deletion or substitution of any shown elements does not depart from the spirit and scope of the invention. Similarly, the addition of new elements does not depart from the spirit and scope of the invention. 11 WO 2004/112649 PCTIUS2004/019599 In one embodiment, the gas emitting pouch system 300 is configured prefilled with the desired gas concentrations and is stored within the packaging system 200 (Figure 2) prior to releasing gas into the surrounding environment, also prefilled with the same gas concentrations as in the gas emitting pouch, in order to maintain the levels in the pouch. In 5 another embodiment, the gas within the reservoir 330 within the gas emitting pouch system 300 comes to equilibrium within the packaging system 200 so that both the pouch and the package reach the target concentrations In one embodiment, the gas emitting pouch system 300 is configured to be placed in an environment where the gas stored within the reservoir 330 is released steadily into the 10 surrounding environment, as the gradient doesn't change appreciably. In another embodiment, the release rate of gas from the reservoir 330 into the surrounding environment slows as the surrounding environment becomes saturated with the gas. Subsequent to the saturation, the gas emitting pouch system 300 acts as a gas reservoir; as gas is dissipated from the surrounding environment, there is a local supply of gas within the reservoir 330 to be 15 provided to the surrounding environment, governed by the transfer rate across the permeable film. The gas emitting pouch 300 has many applications which may include non- medical applications such as applying the gas emitting pouch 300 to effect environments in containers for any purpose such as lab experiments, food preservation, to accelerate degradation, to 20 prevent corrosion, and the like. The flow diagrams as depicted in Figures 4, and 5 illustrate merely one embodiment of the invention. The flow diagrams in Figures 4 and 5 are one particular use of the invention based on a specific application. In other embodiments, the invention may be utilized with other applications. The blocks within the flow diagrams may be performed in a different 25 sequence without departing from the spirit of the invention. Further, blocks may be deleted, added, or combined within each of the flow diagrams without departing from the spirit of the invention. The flow diagram in Figure 4 illustrates an exemplary process of utilizing the packaging system 200 according to one embodiment. 30 In Block 410, a gas-retaining object is placed within the packaging system 200. In one embodiment, the gas-retaining object is the dressing system 100. In another embodiment, the gas-retaining object is gas emitting pouch system 300. In yet another embodiment, the gas-retaining object may be any item that is configured to retain and controllably release a gas from the object. 12 WO 2004/112649 PCTIUS2004/019599 In Block 420, the packaging system 200 is flushed with a gas. In one embodiment, the packaging system 200 is flushed with the same gas contained with the gas-retaining object. For example, the dressing system 100 may be pre-filled with oxygen and placed within the packaging system. By flushing the packaging system 200 with oxygen, the 5 packaging system 200 ensures that the dressing system 100 retains the pre-filled oxygen content. In another embodiment, the packaging system 200 is flushed with a different gas than the gas contained with the gas-retaining object. For example, the dressing system 100 may contain air that contains other gases in addition to oxygen and may be placed within the 10 packaging system 200. By flushing the packaging system 200 with pure oxygen, the packaging system 200 diffuses the dressing system 100 with additional oxygen until the gas within the packaging system 200 and the gas within the dressing system 100 have reached an equilibrium. In Block 430, the packaging system 200 is sealed after placing the gas-retaining 15 object within the packaging system 200 and flushing the packaging system 200 with a gas. In Block 440, if the gas within the gas retaining device and the gas within the packaging system 200 differ, then an exchange of gas occurs until an equilibrium is achieved. For example, by using the above example describing a dressing system 100 that contains air which is sealed within the packaging system 200 flushed with pure oxygen, the oxygen 20 diffuses into within the dressing system 100, while nitrogen diffuses out of the dressing system 100 into the package 200 until an equilibrium is achieved between the gas within the dressing system 1100 and the packaging system 200. In this embodiment, the gas may be exchanged through the permeable film 160 (Figure 1). In Block 550, the packaging system 200 may be opened to remove the gas-retaining 25 object. The packaging system 200 may be utilized to store the gas-retaining object without degrading the gas within the gas-retaining object. In another embodiment, the packaging system 200 may be utilized to infuse the gas-retaining object with a gas. The flow diagram in Figure 5 illustrates an exemplary process of utilizing the dressing system 100 according to one embodiment. 30 In Block 510, the dressing system 100 is removed from a packaging. In Block 520, the dressing system 100 is adhered to a user. In one embodiment, the dressing system 100 may cover a wound or broken skin of the user. In one embodiment, the dressing system 100 utilizes the adhesive backing 150 to adhere the dressing system 100 to the user. 13 WO 2004/112649 PCTIUS2004/019599 In Block 530, a seal is formed between the dressing system 100 and the user. In one embodiment, the adhesive backing 150 forms the seal between the dressing system 100 and the user. In Block 540, gas is supplied from the dressing system 100 to the user. In one 5 embodiment, the penneable film 160 is positioned over the wound or broken skin of the user and allows the gas from the dressing system 100 to be supplied to wound of the user. In another embodiment, the permeable film 160 may be positioned over intact skin of the user and allows the gas from the dressing system 100 to be supplied to the skin of the user. There are numerous practical applications in supplying oxygen to intact skin such as 10 treating sun or radiation damaged skin, exfoliated skin, dermabraded skin, or providing nourishment to aged skin. There may be a synergistic effect with topical agents as well. In Block 550, the gas within the reservoir 130 of the dressing system 100 maybe stored until additional gas is supplied to the user through the permeable film 160. Another embodiment of the packaging system comprises any of the packaging 15 systems described herein and further comprises a septum, which as defined herein may be a septum, a valve, Luer lock or any resealable opening, through which one or more gases can be introduced into the packaging system, then resealed to prevent gases from escaping. The packaging system may be charged with the one or more gases in the desired ratio on site (e.g., hospital, doctor's office). 20 In another embodiment, the adhesive layer may comprise a gel. The gel may have semi-adhesive properties, such that the same dressing system can be removed and replaced repeatedly. Examples of gels that may be used are described in U.S. Patent Nos. 4,839,345, 5,354,790 and 5,583,114. The foregoing descriptions of specific embodiments of the invention have been 25 presented for purposes of illustration and description They are not intended to be exhaustive or to limit the invention to the precise embodiments disclosed, and naturally many modifications and variations are possible in light of the above teaching. The embodiments were chosen and described in order to explain the principles of the invention and its practical application, to thereby enable others skilled in the 30 art to best utilize the invention and various embodiments with various modifications as are suited to the particular use contemplated. Figure 6 illustrates a pouch system 600. The pouch system 600 is configured to emit gas into a local environment, similar to the gas emitting pouch system 300. The pouch system 600 includes a first layer 610 and a second layer 630. The first layer 610 and the 14 WO 2004/112649 PCTIUS2004/019599 second layer 630 may be permeable to gases. In one embodiment, the first layer 610 and the second layer 630 are bonded through an intermediate layer 620. The intermediate layer 620 provides the pouch system 600 a more resilient and durable seal between the first layer 610 and the second layer 630 by diverting the load so that more robust shear force is applied to a 5 higher bond strength seal rather than strictly a design that puts all the internal pressure and load on a peel strength surface. By adding the intermediate layer 620 with a narrower diameter than the first layer 610, the seal between the first layer 610 and the second layer 630 is reinforced. Another embodiment of the invention is an apparatus that envelops a target area, such 10 as an appendage, in a controlled environment. Once the appendage requiring treatment is placed in the apparatus, the opening is secured around the appendage. For example, the apparatus can be in the form of a glove or mitten for hand treatments or wounds or in the form of a sock for foot or leg treatments or wounds. A glove or mitten would be secured around a patient's hand or arm and a sock would secured around a patient's ankle or leg. The 15 apparatus can be prefilled in the reservoir, as described herein and packaged in a CAP environment. The apparatus can also be packaged in a CAP environment that facilitates the exchange of gases such that the reservoir achieves the target ratios of gases passively through diffusion in storage, as described herein. The apparatus can also be filled or recharged according to any of the methods described herein. 20 Figure 7 illustrates a glove for use in hand/arm treatments or wounds. A side view 700A and a cross-section 700B of section A-A of the glove are shown. The inner layer 710 is a permeable film, as described herein, which is permeable to oxygen and/or other gases. The outer layer 720 is an external barrier, as described herein, selected to be less permeable to oxygen and/or other gases. The two layers form a reservoir 730 between them that may 25 contain one or more gases, gel, fluid, cushioning material, resilient porous material, or a combination thereof, or as described herein. Figure 8 illustrates a sock for use in foot/leg treatments or wounds. A top view 800A, a side view 800C and a front view 800D are shown. A cross-section 800B of section A-A of the sock is also shown. The inner layer 810 is a permeable film, as described herein, which is 30 permeable to oxygen and/or other gases. The outer layer 820 is an external barrier, as described herein, selected to be less permeable to oxygen and/or other gases. The two layers form a reservoir 830 between them that may contain one or more gases, gel, fluid, cushioning material, resilient porous material, or a combination thereof or as described herein. 15 WO 2004/112649 PCTIUS2004/019599 A further embodiment of the invention is an apparatus wherein the inner and/or outer layers further comprise ribs. The ribs allow the one or more gases in the reservoir to be applied to the target area even when pressure is exerted on the apparatus from an external source. 5 Other embodiments of the invention can also be an apparatus in the form of a blanket, an oxygen mask, a wrap, or an eye patch. These other embodiments may be use to supply oxygen or other gases to target areas such as the face or eye by placing the permeable layer on the target area and securing the apparatus to a patient either externally by mechanical means, i.e., gravity, by wrapping a securing tape or material around it, or by sealing the 10 apparatus directly to the target area with an adhesive seal around the perimeter or other surfaces. Any of the embodiments of the invention described herein may be used in combination with existing technologies. The present invention is useful for wound healing for human and animal patients, for 15 use in laboratories, and anywhere a specific gas or combination of gases is required to reach a specific, discrete site. The foregoing descriptions of specific embodiments of the invention have been presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the invention to the precise embodiments disclosed, and naturally many 20 modifications and variations are possible in light of the above teaching. The embodiments were chosen and described in order to explain the principles of the invention and its practical application, to thereby enable others skilled in the art to best utilize the invention and various embodiments with various modifications as are suited to the particular use contemplated. 25 References: 1. Whitney JD, "Physiological Effects of Tissue Oxygenation on Wound", Heart & Lung, Vol. 18., No. 5, pp. 466-474, Sep. 1989. 2. Gruber RP, et al., "Skin Permeability to Oxygen and Hyperbaric Oxygen", ARCH. SURG., Vol. 101, pp. 69-70, July 1970. 30 3. Eaglstein WH, "Experiences with Biosynthetic Dressings", J. AmM. Acad. Dermatol., Vol. 12 (2 Pt 2), pp. 434-40, February 1985. 4. Niinikoski J, et al., "Combination of Hyperbaric Oxygen, Surgery, and Antibiotics in the Treatment of Clostridial Gas Gangrene", Infections in Surgery, pp. 23-37, January 1983. 16 WO 2004/112649 PCTIUS2004/019599 5. Fischer BH, "Treatment of Ulcers on the Legs with Hyperbaric Oxygen", J. Derm. Surg., Vol. 1, No. 3, pp. 55-58, Oct. 1975. 6. Heng M, et al., "A Simplified Hyperbaric Oxygen Technique for Leg Ulcers", Arch Dermatol, Vol. 120, pp. 640-645, May 1984. 5 7. Olejniczak S, et al., "Topical Oxygen Promotes Healing of Leg Ulcers", Medical Times, Vol. 104, No. 12, pp. 114-121, Dec. 1976. 8. * Transcript of United States Food & Drug Administration, Center for Drug Evaluation & Research, Dermatologic and Ophthalmic Drugs Advisory Committee, 4 6 th Meeting, pp. 15-28, July 14, 1997 10 (http://www.fda.gov/ohrms/dockets/ac/97/transcpt/3308t1.pdf). 9. Zhao LL, Davidson JD, Wee SC, Roth S, Mustoe TA, "Effect of Hyperbaric Oxygen and Growth Factors on Rabbit Ear Ischemic Ulcers," Arch Surg/Vol. 129, Oct 1994. 10. Winter GD, Perins DJD, Proceedings of the 4 th Intl Congress on Hyperbaric Medicine, Igaku Shoin Ltd, p. 363, 1970. 15 11. Silver IA, in Wound Healing & Wound Infection, ed. Hunt TK, Appleton Century-Crofts, NY, p 2 6, 1980. 12. 'Prockop DJ, et al., "Oxygen-18 studies on the conversion of proline to collagen hydroxyproline", Arch Biochem BioPhys VI01, p. 499, 1963. 13. Winter GD., Advances in Exp Med and Bio, V94, p. 673-8, July 4, 1977. 20 14. Silver IA, in Epidermal Wound Healin , ed. Maibach H & Rovee D, Year Book Medical Publishers, Inc, Chicago, p. 291-305, 1972. 15. Kaufman T, et al., Surgical Forum V34, pp. 111-113,1983. 16. Niinikoski J, Clin Plast. Surg, V4, p. 361, 1977. 17. Kaufman T, et al., Bums, V9, pp.169-173,1983. 25 18. Utkina OT, Biol. Abstr., V45, 6289, 1964. 19. Brody AL, Food Technology, Vol. 55, No. 9, pp. 104-106, Sept. 2001. 20. Hoogenwerf SW, et al., Letters in Applied Microbiology, Vol. 35, Issue 5, p. 419, Nov. 2002. 21. Devlieghere F, et al., "Modified atmosphere packaging: state of the art", 30 http://www.ifis.co.uk/hottopics/MAParticle2.PDF, Sept. 2000. 22. Labell, "Controlled & Modified Atmosphere Packaging", Food Processing, p. 152, Jan. 1985. 23. "Biobased Packaging Materials for the Food Industry", ed. CJ Weber, http://www.nf-2000.org/publications/f4046fin.pdf, Nov. 2000. 17

Claims (62)

1. An apparatus for supplying one or more gases to a target area, comprising a top layer and a bottom layer sealed around the perimeter of the layers to form a reservoir between the layers, wherein the top layer has gas barrier properties and the bottom layer has high gas transfer properties, said reservoir containing one or more gases.

2. The apparatus of claim 1, wherein the apparatus further comprises an adhesive backing configured to affix the apparatus to the target area.

3. The apparatus of claim 1, wherein the top layer is comprised of a metallized polyester.

4. The apparatus of claim 1, wherein the top layer is comprised of a ceramic coated polyester.

5. The apparatus of claim 1, wherein the top layer is comprised of a polyvinylidene chloride laminate.

6. The apparatus of claim 5, wherein the polyvinylidene chloride laminate is Saranex@.

7. The apparatus of claim 1, wherein the top layer is comprised of an EVOH laminate.

8. The apparatus of claim 7, wherein the EVOH laminate is Oxyshield@.

9. The apparatus of claim 1, wherein the top layer is comprised of a polyamide laminate.

10. The apparatus of claim 9, wherein the polyamide laminate is Capran@.

11. The apparatus of claim 1, wherein the top layer is comprised of ethylene vinyl alcohol or ethylene vinyl alcohol/polyethylene.

12. The apparatus of claim 1, wherein the top layer conducts heat or electrical stimulation from an external source to the target area.

13. The apparatus of claim 1, wherein the bottom layer is comprised of polyurethane, silicone, polyvinylehloride, or polyolefins. 18 WO 2004/112649 PCTIUS2004/019599

14. The apparatus of claim 1, wherein the bottom layer is porous or perforated

15. The apparatus of claim 14, wherein the bottom layer is porous or perforated in a manner sufficient to allow non-gas entities to pass through.

16. The apparatus of claim 15, wherein the non-gas entities comprise nutritional or therapeutic agents.

17. The apparatus of claim 1, wherein the gas contained in the reservoir is controllably released through the bottom layer to the target area.

18. The apparatus of claim 1, wherein an absorbent layer is attached to the bottom layer and said absorbent layer is between the bottom layer and the target area.

19. The apparatus of claim 1, wherein an absorbent layer is attached to the bottom layer and said absorbent layer is between the top layer and the bottom layer.

20. The apparatus of claim 18 or 19, vAherein the absorbent layer is ring-shaped.

21. The apparatus of claim 2, wherein the adhesive backing covers the perimeter of the bottom layer.

22. The apparatus of claim 2, wherein the adhesive backing covers the entire apparatus.

23. The apparatus of claim 22, wherein the adhesive backing is integrated with the bottom layer.

24. The apparatus of claim 1, wherein a compliant porous insert is contained within the reservoir.

25. The apparatus of claim 23, wherein the compliant porous insert is comprised of a sponge-like material.

26. The apparatus of claim 24, wherein an absorbent layer is incorporated into the compliant porous insert.

27. The apparatus of claim 24, wherein the compliant porous insert fills the entire reservoir and is adjacent to both the top layer and the bottom layer. 19 WO 2004/112649 PCTIUS2004/019599

28. The apparatus of claim 18, wherein a compliant porous insert is incorporated in the absorbent layer.

29. The apparatus of claim 1, wherein the gas in the reservoir is oxygen.

30. The apparatus of claim 1, wherein the gas in the reservoir is nitrogen.

31. The apparatus of claim 1, wherein the gas in the reservoir is carbon dioxide.

32. The apparatus of claim 1, wherein said reservoir further contains a biologically beneficial agent.

33. The apparatus of claim 32, wherein the biologically beneficial agent is a drug, mineral, nutrient, amino acid, pH modifier, anti-microbial, growth factor or enzyme.

34. The apparatus of claim 33, wherein the biologically beneficial agent is contained in microcapsules incorporated in the adhesive backing.

35. The apparatus of claim 33, wherein the biologically beneficial agent is contained in a gel matrix in the reservoir.

36. The apparatus of claim 1, wherein the one or more gases are generated in the reservoir by a substance capable of producing one or more gases.

37. The apparatus of claim 36, wherein the substance in the reservoir is an oxygen releasing agent.

38. The apparatus of claim 37, wherein the oxygen-releasing agent is an inorganic salt, a hydrogen peroxide containing formulation, intercalated magnesium peroxide, sodium percarbonate, sodium carbonate, or hydrogen peroxide.

39. The apparatus of claim 36, wherein the substance in the reservoir is a nitrogen releasing agent.

40. The apparatus of claim 36, wherein the substance in the reservoir is a carbon dioxide-releasing agent.

41. The apparatus of claim 1, wherein either the top layer or the bottom layer or both further comprise a plurality of spaced apart ribs. 20 WO 2004/112649 PCTIUS2004/019599

42. The apparatus of claim 1, which is in a form of a glove or mitten.

43. The apparatus of claim 1, which is in a form of a sock.

44. An apparatus for supplying one or more gases to a target area, comprising a top layer, an absorbent layer and a bottom layer sealed around the perimeter of the layers to form a reservoir between the top and bottom layers, wherein the top layer has gas barrier properties, the bottom layer has high gas transfer properties and the absorbent layer is attached to the bottom layer, said reservoir containing one or more gases.

45. An apparatus for supplying one or more gases to a target area, comprising a top layer, an absorbent layer, a bottom layer and a gel layer sealed around the perimeter of the layers to form a reservoir between the top and bottom layers and filled with the absorbent layer, said reservoir containing one or more gases, wherein the top layer has gas barrier properties, the absorbent layer is attached to the bottom layer and has high gas transfer properties, the bottom layer has high gas transfer properties, and the gel layer is attached to the bottom layer and contacts the target area.

46. An apparatus for supplying one or more gases to a target area, comprising a top layer having gas barrier properties and an adhesive layer, wherein the adhesive layer having gas barrier properties is attached to the perimeter of the top layer, such that the adhesive layer adheres to the surface around the target area, forming a reservoir between the top layer and the target area such that the adhesive layer comprises the sides of the reservoir.

47. The apparatus of claim 46, wherein the top layer is convex when placed over the target area.

48. The apparatus of any of claims 1-47, further comprising a gasket that seals the top and bottom layers together around the perimeter.

49. The apparatus of claim 48, wherein the gasket is a reinforced gasket that extends into the reservoir. 21 WO 2004/112649 PCTIUS2004/019599

50. The apparatus of any of claims 1-49, further comprising a septum.

51. A packaging system comprising a substantially gas-impermeable enclosed container containing an apparatus of any of claims 1-50 and one or more gases, wherein the desired ratio of the one or more gases is preserved in the apparatus reservoir.

52. A packaging system comprising a substantially gas-impermeable enclosed container containing an apparatus of any of claims 1-50 and a gas, wherein the gas in the container is different from the gas in the apparatus and the two gases diffuse through the bottom layer of the apparatus to reach equilibrium within the enclosed container.

53. A method of delivering one or more gases to a target area comprising the step of applying to the target area the apparatus of any one of claims 1-50.

54. A method of charging an apparatus of claims 1-50 with one or more gases, comprising the steps of: a. placing the apparatus within a substantially gas-impermeable container, wherein the apparatus contains air within the reservoir; b. flushing the container with one or more gases sufficient to produce a desired ratio of gases; and c. sealing the container and allowing said gases to permeate the reservoir of said apparatus via the bottom layer such that the one or more gases reach equilibrium in the apparatus and the container.

55. A method of charging an apparatus of claims 1-50 with one or more gases, comprising the steps of: a. placing the apparatus within a substantially gas-impermeable container, wherein the apparatus contains one or more gases in a desired ratio within the reservoir; b. flushing the container with one or more gases in the same desired ratio; and c. sealing the container to maintain the desired ratio. 22 WO 2004/112649 PCTIUS2004/019599

56. A method of charging an apparatus of claims 1-50 with one or more gases, comprising the steps of: a. placing the apparatus within a substantially gas-impermeable container wherein the container comprises a septum; b. sealing the container; c. connecting a gas source to the septum; d. flushing the container with one or more gases sufficient to produce a desired ratio of gases; and e. allowing said gases to permeate the reservoir of said apparatus via the bottom layer such that the one or more gases reach equilibrium in the apparatus and the container.

57. A method of charging an apparatus of claims 1-50 with one or more gases, comprising the steps of: a. placing the apparatus within a substantially gas-impermeable container, wherein both the apparatus and the container are in a controlled environment having the desired ratio of gases; b. sealing the container in the controlled environment to capture the desired ratio of gases in the container; and c. I allowing said gases to pemieate the reservoir of said apparatus via the bottom layer such that the desired ratio gases are contained in the apparatus.

58. A kit comprising any of the apparatus of claims 1-50 and instructional material which describes application of the apparatus to a target area to effect delivery of one or more gases to the target area.

59. A method of charging an apparatus of claims 1-50 with one or more gases, comprising the steps of: a. placing the apparatus over the target area; 23 WO 2004/112649 PCTIUS2004/019599 b. sealing the apparatus around the target area by applying pressure to the adhesive layer; c. inserting a gas-introducing component connected to a source of one or more gases in a desired ratio through the top layer into the reservoir; d. introducing the one or more gases into the reservoir; and e. removing the gas-introducing component from the apparatus.

60. An apparatus for wound healing, comprising a top layer and a bottom layer sealed around the perimeter of the layers to form a reservoir between the layers, wherein the top layer has gas barrier properties and the bottom layer has high gas transfer properties, said reservoir containing one or more gases.

61. Use of the apparatus of any one of claims 1-50 and 60 as a therapeutic device for treatment of a wound in a mammal.

62. The use of claim 61, wherein the wound is selected from the group consisting of ulceration, gangrenous damage, sun damage, radiation damage, exfoliation damage, dermabrasion damage, and skin damage due to aging. 24