Abstract:
A portable, self-contained device is described for the topical application of oxygen and the removal of wound exudates to promote the healing of skin wounds. The device includes a wound dressing that incorporates at least one electrochemical cell for generating oxygen. The device can regulate the supply of oxygen to the wound at various concentrations, pressures and dosages and is used to produce a high concentration of oxygen at the wound site. By reversing the polarity of the power source a reduced pressure can be created in a reservoir attached to our device. The reduced pressure in the reservoir draws naturally flowing exudates away from the wound. Alternately, two reverse polarity cells are used to alternately supply oxygen and draw away exudates.

Description:
BACKGROUND 
     The present exemplary embodiments relate to the expeditious removal of exudates from a wound site and the concurrent or subsequent delivery of pure oxygen to the Wound site to promote healing of venous stasis and diabetic foot ulcers and other wounds. 
     Accumulation of wound exudate increases patient discomfort and the potential for bacterial infection, and, thereby, affects adversely the healing process. In particular, chronic wound fluid blocks the proliferation and activity of fibroblasts and keratinocytes. In addition, it prevents easy reach of pure oxygen to the wound bed due to poor oxygen solubility in aqueous fluids, and, hence, the effectiveness of topical intermittent and transdermal sustained oxygen therapies. Chronic wounds are often heavily colonized with bacterial organisms and, therefore, timely removal of exudate is essential to minimize bio-burden. Wound cleansing removes contaminants from the wound surface and renders the wound less conducive to microbial growth. Wounds with foul smelling drainage are generally infected or filled with necrotic debris, and healing time is prolonged as tissue destruction progresses. The fluid of wound edema contains proteolytic enzymes, bacterial toxins, prostaglandins, and necrotic debris, all of which contribute to prolonged chronic inflammation. 
     Various types of wound dressings and drainage devices have been reported in the patent literature. Thus, a multi-purpose wound dressing is described by Ewall, in U.S. Pat. No. 5,607,388. This patent teaches the use of a multiple layer wound dressing with sequentially removable layers that can be used to control the accumulation of exudate. 
     A general purpose surgical drain is described in U.S. Pat. No. 3,753,439. This device is a drainage conduit packed inside with soft, non-friable absorbent material. A suction line can be connected to the top of the fixture to drain the exudate. 
     Argenta and Morykwas (U.S. Pat. Nos. 5,636,643 and 5,645,081) patented a method of treating tissue damage by applying a negative pressure to a wound sufficient in time and magnitude to promote tissue migration and thus facilitate wound closure. Negative pressures in the range of 2-7 inches of Hg are applied over the wound and the surrounding areas. The area around most wounds becomes swollen with intercellular fluid, which is not removed due to insufficient blood circulation, and further compromises blood circulation as time progresses. Application of vacuum over the wound and surrounding area forces the intercellular fluid to flow towards the negative pressure region. Since the wound is open and perhaps sees the most negative pressure, all the intercellular fluid ends up accumulating in the wound. A tube properly placed in the wound and connected to the external vacuum source removes the liquid as it accumulates. Application of negative pressure over the wound site enhances both blood circulation and tissue migration. 
     The present embodiments herein described differ substantially from that of Argenta and Morykwas in at least two important respects: first, it simply allows better access of oxygen to the tissue bed by removing the naturally secreted wound exudates, and, second, it does not produce a negative pressure directly at a wound site, unlike the Argenta and Morykwas device. It therefore does not induce gross fluid flow from the wound area (from the surrounding tissue bed) or migration of epithelial and/or subcutaneous tissue toward the wound. Any reduced pressure at the wound site is generally less than that experienced in the Argenta and Morykwas device. 
     Sustained oxygen delivery has been suggested (see, e.g., U.S. Pat. No. 5,578,022) as an effective tool to accelerate the healing process even in the case of chronic wounds. In order to realize the benefits of delivered oxygen, it is important that the access to the tissue bed by oxygen be uninhibited. Exudate accumulation normally prevents such easy access of oxygen to the tissue bed. The present embodiments relate to electrochemical, light-weight devices, capable of both removing exudates from the wound bed, and also of delivering oxygen to the wound. These devices use no mechanical pumps or compressed gases and can be directly attached to the affected limb/area allowing the patient to be ambulatory. 
     BRIEF SUMMARY 
     In accordance with one aspect, there is provided one type of such dual action device including a single cell that can alternately remove exudates from the wound bed and deliver purified oxygen to the wound. A second type of device incorporates two such cells, in which one of the cells removes the exudates from the wound to expose the tissue bed, whereas the other delivers oxygen to the wound either intermittently or continuously. 
     In accordance with a second aspect, there is provided a device for supplying oxygen and removing exudates for treatment of a skin wound comprising a sealed housing; a conduit fluidly connecting the housing to the skin wound; and an electrochemical cell incorporated within the housing for alternately supplying oxygen to the skin wound and drawing exudates away from the skin wound, the cell including: a) a first electrode; b) a membrane for diffusing the negative ions and/or neutral species therethrough; and c) a second electrode communicating with the electrolyte; wherein in a first operating mode, the first electrode reduces oxygen in a feed gas to negative ions and/or neutral species and the second electrode oxidizes the negative ions and/or neutral species to produce a high concentration of oxygen for supply to the skin wound; and further wherein in a second operating mode, the operation of the electrodes is reversed, producing a reduced pressure in the housing resulting in removal of exudates from the wound. 
     In accordance with a third aspect, there is provided a device for supplying oxygen and removing exudates for treatment of a skin wound comprising: first and second sealed housings; first and second conduits fluidly connecting the first and second housings to the skin wound; an oxygen generating cell positioned in the first housing for supplying oxygen to the skin wound according to an electrochemical process; an oxygen consuming cell positioned in the second housing for drawing exudates away from the skin wound by generating a reduced pressure at the wound site; a valve positioned in the second conduit; a wound dressing patch adapted to form an occlusive seal over the skin wound; and a third conduit equipped with an absorbing media fluidly connecting the second housing and a wound bed of the wound. 
     In a fourth aspect, there is provided a method for treating skin wounds, comprising the steps of: placing an oxygen generating device having first and second associated electrochemical cells in fluid communication with a skin wound; and a) using the first cell to generate oxygen from the atmosphere and supplying the oxygen to the skin wound; and b) using the second cell to consume oxygen present in a vicinity of the wound, thereby generating a reduced pressure that acts to suction exudates from the site of the wound. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a schematic representation of a side view of an oxygen producing patch suitable for use with various embodiments of the invention. 
         FIG. 2  is a schematic representation of a dual action oxygen delivery and wound exudates removal device according to one embodiment. 
         FIG. 3  is a schematic representation of a dual action oxygen delivery and wound exudates removal device according to another embodiment. 
         FIG. 4  is a schematic representation of a dual action oxygen delivery and wound exudates removal device according to still another embodiment. 
     
    
    
     DETAILED DESCRIPTION 
     One present embodiment involves a device incorporating two single cells, one which removes by suction exudates from the wound site, and the other, which generates oxygen to be delivered to the wound site. As envisioned, in this dual cell device, two cells are mounted on individual single chambers connected via passages to a main chamber where the exudates are collected. 
     Each of the units, or cells, used in the present embodiments may operate based on similar principles as those described in our earlier patent, U.S. Pat. No. 5,578,022, (incorporated herein by reference in its entirety) which has been commercialized by Ogenix Corporation under the name EpiFLO, and approved by FDA for the treatment of certain types of wounds. More specifically, it uses oxygen reduction at a high area gas permeable cathode yielding water as a product, and water oxidation at a high area gas permeable anode to generate pure oxygen. Both electrodes are attached to opposite surfaces of a thin polymer electrolyte membrane (PEM), e.g., Nafion®, in much the same way as in PEM fuel cells. As the gas permeability of the assembly is very low, operation of the device enriches the oxygen content of the side facing the anode, and, at the same time, depletes the oxygen content of the side facing the cathode. 
     With reference to  FIG. 1 , a side view of a basic oxygen producing device and patch assembly suitable for use with various aspects of the present embodiments is shown. The device includes a porous cathode  10 , an ion conducting membrane  14  and a porous anode  16  inside a housing  18 . The cathode is exposed to the atmosphere, such as through a vent  20 , and the anode is exposed to or in communication with the skin wound  36 . An impermeable barrier  24  separates the cathode and anode sides of the housing. Attached to a perimeter of an underside of the housing  18  is an adhesive strip  22 , which completely encircles the base and is used to secure the device to the patient&#39;s skin  34  or a bandage  26  around the wound. 
     The adhesive strip  22  does not touch the wound, but serves to cause the housing of the device to stand off a slight distance from the wound itself, such that a cavity  28  is formed between a bottom of the housing  30  and the wound. This cavity  28  becomes filled with gaseous oxygen emitted from the interior of the housing through holes  32  on the bottom of the housing  30 . Alternately, instead of holes  32 , the bottom of the housing  30  may be formed of a material permeable to oxygen. The adhesive strip may be permeable to oxygen gas to prevent undue gas pressure from building up in the cavity  28 . This permeability may be obtained by having formed valves or capillary holes through the adhesive layer (not shown) but preferably will be obtained by having the adhesive material itself be somewhat porous, since the formed passageways may have a greater tendency to allow contaminants to enter cavity  28  when the device is not operating. The oxygen pressure in the cavity  28  will vary depending on the permeability of the housing bottom, the number of valves and the identity of the adhesive material, and the rate of oxygen production. However, the pressure will preferably not exceed about 20-30 mm Hg to prevent vasoconstriction. 
     Adhesive is depicted at  22  for affixing the patch over a skin wound such that oxygen cannot flow readily out of the treatment area. As stated, the patch will generally have one or more one-way valves or small capillary holes to permit outflow of air. The patch may be incorporated into, include, or be deployed on top off or underneath one or more bandage layers  26 . The bandage itself may have multiple layers to promote patient comfort and healing, including but not limited to layers of cotton gauze, polyethylene oxide-water polymer, as well as layer(s) containing topical ointments and other medicines including antibiotics, antiseptics, growth factors and living cells. Preferably, the bandage is occlusive on all sides and offers anti-microbial control without antibiotics or antiseptics, although these can still be used for added protection. 
     Positioned between the anode  16  and the cathode  10  is an ion conducting membrane  14 . At electrode  10  a cathodic reaction occurs to combine the ambient oxygen from the air into water, in which it is present as reduced oxygen. The voltage differential created by electrodes  10  and  16  drives the species across the membrane  14 , which is specific to passage of that species. At anode  16 , an anodic reaction occurs to convert the species to release the reduced oxygen as gaseous oxygen onto the wound site. 
     With this unit, dioxygen supplied from the atmospheric air is reduced at the gas-permeable cathode  10  to negatively charged ions i.e. superoxide and peroxide and their various unprotonated and protonated states (HO 2   0 , HO 2   − , O 2   2− ) or hydroxyl ions or undissociated H 2 O 2  according to a one, two or four electron process. The cathode may be of the type used in fuel cells. One or more of these species then travel through the thin separator/electrolyte structure or membrane  14  to the gas permeable anode  18 , where they are reconverted into dioxygen. The dioxygen flows out of the anode and is intended to be directed to a skin wound. 
     The unit as shown in  FIG. 1  may be powered by a variety of primary or secondary power sources, including alkaline manganese-dioxide, zinc-air, lithium thionyl chloride, lithium manganese dioxide, lithium ion, nickel metal hydride and the like. 
     With reference now to  FIG. 2 , a device according to one embodiment of the present invention having a similar housing design as in  FIG. 1 , but utilizing two such electrochemical units or cells is shown. A first cell  112  has its anode  114  (oxygen generating electrode) exposed to an associated first chamber  116 , while a second cell  118  has its cathode  120  (oxygen reducing electrode) exposed to its own adjoining chamber  122 . Although the two devices are shown mounted on different side walls of the device, other configurations may also be envisioned, and as such are also covered by this invention. Regardless of their geometrical disposition, the entire device is so designed to prevent wound exudate from contacting the cells in almost any orientation, thus making the device wearable and portable. The second cell  118  or pump cell, when powered by a constant voltage, consumes oxygen from the main reservoir  124 , thereby reducing the pressure therein, drawing by suction, exudates from the wound through an inlet  126  into its main reservoir  124 . The consumed oxygen is evacuated to the atmosphere via an exhaust port  128 . First or oxygen generating cell  112 , when powered at constant current, continuously generates oxygen at rates of several ml/hr. The current flow in the pump cell  118  is preferably many times larger than the oxygen-generating cell  112 . 
     The device can be designed so that the main reservoir  124  with the collected exudate can be easily detached from the cells and power/control electronics. In this respect, a drain port  130  in fluid contact with the main reservoir  124  can be incorporated into the device for easy draining of the collected exudates. Alternately, or in addition to this, the reservoir and/or other parts of the housing can be made disposable, such that a user would merely need to remove the cells from one housing and put them in a new housing, without the need to drain or remove the collected exudates. 
     This will allow a single device to provide exudate collection for extended periods. Also, a gas permeable membrane or membranes (not shown) impervious to liquids can be added between the cells and main reservoir  124  and/or inlet  126  to further ensure water or exudates from contacting the cell and its components. In a preferred mode of operation, the oxygen generating cell  112 , is preferably constantly “ON” and provides a uniform oxygen flow to the wound, except for brief periods during which the suction mode of the first device is in operation, while the suction cell  118  preferably operates only for a short period of time, e.g., 2 minutes, and then switched off, in a cyclic fashion. 
     In a second embodiment as shown in  FIG. 3 , there is provided a device incorporating a single cell that removes exudates from the wound site using suction created by the device itself, and then generates oxygen which is delivered to bare wound, in an alternating fashion. An electrochemical cell as detailed above with associated power supply  40  is mounted on one of the walls of a hermetically sealed box  42 . In an exemplary device, the box may be of approximately 30 ml capacity. The cell is sealed to the wall of the box such that an electrode of the cell is in contact with the sealed interior of the box. A gas permeable barrier layer  44  (e.g., EPTFE, see dotted line in the figure above) is placed adjacent to the cell and separates the cell from the main interior volume of the box to prevent exudates from contaminating cell components. The box  42  is fitted with a cannula or conduit  46  such as a flexible tubing, which is sealed on one of the walls of the box below the barrier layer, in a leak-free manner and provides fluid communication between the interior of the box and the wound. The cannula may include a Luer type connection or similar type. The cannula is preferably made from a polymeric material suitable for use in hospital applications. Suitable materials for use in the cannula include, but are not limited to, silicone, polyethylene, polypropylene, polyurethane and various other thermoplastics. 
     The device will have either an integral or removable trap arrangement  48  for the exudates. In a preferred arrangement, the cell  40  is preferably mounted on the top or an upper wall of the box, while the exudates collects at the bottom of the box. Such an arrangement allows for the free-flow of gaseous oxygen between the wound and the cell, which will bypass the accumulated exudate in the box. 
     The power supply associated with the cell  40  is capable of operating in either a constant current or a constant voltage mode. In a typical operation cycle, the power supply is switched to a constant voltage mode, with the voltage pre-set at a prescribed level to limit the current to a 50-100 mA range, with the electrode facing the holes polarized at a potential negative enough to reduce oxygen in the box, and thereby decrease the pressure therein. This creates a suction through the cannula, which is placed in a wound bed  50 . This draws exudates  52  accumulated in the wound bed into the box. This suction cycle is expected to last only 2-4 minutes. If there is no exudate left, then a partial vacuum of very low magnitude will be created, which will be equalized either by leak of air into the wound or by incoming oxygen during the oxygen generation cycle. 
     In the second stage, operation of the device is switched into a constant current mode with the polarity reversed such that the electrode facing the holes will generate oxygen, which will then be carried to the wound via the cannula tubing. The cycles can be repeated at pre-set periods of suction and oxygen generation using conventional electronic circuitry. 
     Depending on the type of wound and the dressing used to cover it, the tubing can contact the dressing in various ways. For example, the end of the cannula may be placed directly above the wound and under fully occlusive dressings, thereby making an ordinary bandage “oxygen enriched”. 
     For in vivo uses, the end of the cannula can be implanted to the site where treatment is desired. The implanted end of the cannula may be perforated with multiple holes or made of material that would allow oxygen to diffuse through the tubing wall into ischemic tissue or the bloodstream. In addition, a syringe can be attached to the end of the tubing to facilitate the introduction of oxygen subdermally. Site specific oxygen delivery to promote localized angiogenesis or ischemic reperfusion and elevated metabolism is beneficial for orthopedic and organ repair as well as tissue, bone, tendon, and cartilage regeneration. Localized oxygenation of tissue and tumors for improved radiological oncology applications may benefit with the present device. 
     Thus, the present device may be considered a universal remote supply of oxygen in that it can be used with a wide variety of bandages or dressings already on the market. Additional types of dressings with which the present invention may be used include fully occlusive thin film dressings, hydrocolloid dressings, alginate dressings, antimicrobial dressings, biosynthetic dressings, collagen dressings, foam dressings, composite dressings, hydrogel dressings, warm up dressings, and transparent dressings. 
     In a third embodiment, there is provided a dual action device including two cells and a snorkel or valve arrangement. This example uses first and second cells  70  and  72  and incorporates in addition a snorkel or valve type arrangement to prevent interference of operation of the first cell from the second cell and vice versa. First and second cells  70  and  72  are housed in first and second sealed boxes  74  and  76 . The wound site  78  is covered with a wound dressing patch that forms an occlusive seal  80  that at least substantially prevents air from the atmosphere from contacting the wound. Cannulas  82  and  84  connecting the boxes  74  and  76  with the wound are provided. Cells  70  and  72  are configured such that first cell  70  is configured to produce oxygen within the box  74 , while second cell  72  is configured to consume oxygen from the box  76 . If first cell  70  is turned on, oxygen will be produced within the box  74  and the partial pressure of oxygen will increase therein. Pressurization is avoided by allowing the gas to flow through the cannula  82 , into the wound site  78  and through cannula  84  into cell  72 . A check valve  86  positioned in cannula  84  is opened. The pressurized oxygen is allowed to escape through a small hole incorporating a snorkel type arrangement (not shown) in the seal  80 . 
     Once cell  70  has been in operation for a while, thereby exposing the wound and cell  72  to a highly enriched oxygen atmosphere, it is then turned off, cell  72  is turned on, and the valve  86  is closed. Oxygen consumption at the cathode in cell  72  will decrease the total pressure within the compartment which, aided by the snorkel which closes the hole in the seal  80  upon a reduction in pressure, provides an occlusive seal over the wound. An absorbing media  86  immersed in the exudates is interposed between cell  72  and the wound, such that exudate is forced by the pressure differential out of the wound area and accumulates in the absorbent  86 . Alternate use of this dual device arrangement will allow, as stated above, both bathing the wound with oxygen and removal of the exudate as required for wound healing. In one embodiment, the negative pressure at the wound is less than 2 inches of Hg. 
     Other similar arrangements can be thought of with one or two cells. In one example, an electrochemical cell is sealed in a two chamber (A and B) box, thus isolating the anode from the cathode compartments. The cathode compartment is equipped with a solenoid-actuated valve, which in turn is controlled by a control circuit. The control circuit energizes the solenoid on a pre-programmed duty cycle. The solenoid is normally open and energized to close. 
     A cannula from the anode chamber delivers pure oxygen to the wound. Another cannula is placed in the bottom of the wound either by itself or inserted into a capillary bed (e.g., a piece of absorbent material or hydrogel dressing). The distal end of this cannula in the wound exudate is then connected to an exudate waste container. The container houses an absorber that can take up the wound exudate. The exudate container also houses an outlet (with a goose neck arrangement) which is connected to the cathode chamber of the device through a one-way check valve. The exudate container is so designed as to make removal and disposal easy. When the device operates, the wound bed is delivered pure oxygen. During normal operation (or oxygen delivery cycle), the solenoid is open to atmosphere, allowing air access to the cathode of the cell. 
     During the exudate removal cycle, the solenoid is closed for a predetermined time, during which the oxygen in the cathode chamber is consumed, thus allowing a decrease in pressure. This causes the wound exudate to be drained into the exudate waste container. The solenoid valve is opened at a predetermined duty cycle to alternately allow air access and to create pressure differential between the cathode chamber and the wound. By this means, the wound is allowed access to pure oxygen, while removing excess exudate from the wound bed. 
     In another example, two cells are employed in series. The anode chamber of the first device is connected to the wound in substantially the same manner as described above. The anode outlet of a second oxygen-concentrating device is connected to the cathode chamber of the first device via a conduit or connecting tube. A check valve is placed in the connecting tube, with the flow direction allowing flow from the second device to the first. The second device is operated intermittently (at a pre-determined duty cycle) so as to periodically fill the cathode chamber of the first device with oxygen. The cathode chamber of the first device is also fitted with a check valve to allow purging of the cathode chamber initially and subsequently, when necessary. When the oxygen is consumed in the cathode chamber of the first device, due to the presence of pure oxygen, the pressure differential generated is substantially more than that in the previous example. Thus, when the polarity of the first device is reversed in order to draw exudates away from the wound, due to the higher pressure differential, the exudate suction is accomplished more efficiently. The exudate flow is contained in a disposable container in much the same way as described in the previous example.