Patent Description:
There is also widespread acceptance that cleansing a tissue site can be highly beneficial for new tissue growth. For example, a wound can be washed out with a stream of liquid solution, or a cavity can be washed out using a liquid solution for therapeutic purposes. These practices are commonly referred to as "irrigation" and "lavage" respectively. "Instillation" is another practice that generally refers to a process of slowly introducing fluid to a tissue site and leaving the fluid for a prescribed period of time before removing the fluid. For example, instillation of topical treatment solutions over a wound bed can be combined with negative-pressure therapy to further promote wound healing by loosening soluble contaminants in a wound bed and removing infectious material. As a result, soluble bacterial burden can be decreased, contaminants removed, and the wound cleansed.

While the clinical benefits of negative-pressure therapy and/or instillation therapy are widely known, there is an ongoing need to develop improved therapy systems, components, and processes.

<CIT> discloses an apparatus for cleansing wounds using reduced pressure and irrigant fluid.

Notwithstanding references below to a method or methods, no method is claimed (similarly, no dressing is claimed).

New and useful systems and dressings for treating wounds with negative pressure and instillation of an antimicrobial solution comprising a peroxy α-keto carboxylic acid, such as peroxy pyruvic acid, in a negative-pressure and instillation therapy environment are set forth in the appended claims. Illustrative embodiments are also provided to enable a person skilled in the art to make and use the claimed subject matter.

For example, in some embodiments, instillation and negative pressure therapy systems and methods are especially effective for improving tissue granulation when used in conjunction with antimicrobial solutions of the present technology that have demonstrated efficacy against a broad range of healthcare-associated infections (HAIs), biofilms and planktonic microbes that are categorized and described below. To combat the growing threat of infections, antimicrobial solutions may be used as an instillation fluid in conjunction with the automated instillation and negative pressure therapy systems and methods described herein. For example, without limiting the mechanism, function or utility of present technology, it has been found that antimicrobial solutions comprising peroxy pyruvic acid have demonstrated unique safety and efficacy properties that can mitigate or treat the increasing threat of HIAs, including the most resistant pathogens such as methicillin resistant Staphylococcus aureus (MRSA), CRE and C. difficile spores.

More specifically, a system for treating a tissue site is provided according to claim <NUM>.

Also disclosed herein is a method (unclaimed) for treating a tissue site is disclosed comprising positioning a tissue interface to contact the tissue site, covering the tissue interface and the tissue site with a drape to provide a fluid seal between the therapeutic environment and the local external environment, and delivering an antimicrobial solution comprising an antimicrobial agent containing peroxy α-keto carboxylic acid (e.g., peroxy pyruvic acid) the therapeutic environment before providing negative pressure to the therapeutic environment. The method may further comprise a providing negative pressure to the therapeutic environment in pressure control modes after or during the time period that the antimicrobial solution is provided to the therapeutic environment.

As used herein, the words "preferred" and "preferably" refer to embodiments of the technology that afford certain benefits, under certain circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful and is not intended to exclude other embodiments from the scope of the technology.

The present technology provides solutions comprising a peroxy α-keto carboxylic acid ("antimicrobial solutions") for use in a negative pressure treatment regime. Such peroxy α-keto carboxylic acids include peroxyacids of the general formula
<CHM>
wherein R is alkyl, such as C<NUM>-C<NUM> alkyl. In various embodiments, antimicrobial solutions comprise a peroxy α-keto carboxylic acid selected from the group consisting of peroxy puryvic acid, peroxy α-keto butyric acid, peroxy α-keto valeric acid, and mixtures thereof. A preferred α-keto carboxylic acid is peroxy peruvic acid. Peroxy α-keto carboxylic acids among those useful herein are disclosed in <CIT>; <CIT>; and <CIT>.

Antimicrobial solutions of the present technology may comprise pharmaceutically acceptable carriers, optional active materials, and excipients. As used herein, such a "pharmaceutically acceptable" component is one that is suitable for use with humans and/or animals without undue adverse side effects (such as toxicity, irritation, and allergic response) commensurate with a reasonable benefit/risk ratio. The antimicrobial solutions comprise water or physiological saline as a pharmaceutically acceptable carrier. In general, the peroxy α-keto carboxylic acid is present in the antimicrobial solution at a level of from about <NUM>,<NUM> ppm or less.

In various embodiments, the antimicrobial solution comprises an aqueous solution of peroxy pyruvic acid at a concentration of from about <NUM>% to about <NUM>% (by weight). For example, the peroxy pyruvic acid about <NUM>% or less, about <NUM>% or less, about <NUM>% or less, about <NUM>% or less, about <NUM>% or less, about <NUM>% or less, about <NUM>% or less, about <NUM>% or less, about <NUM>% or less, about <NUM>% or less, about <NUM>% or less, or about <NUM>% or less, or about <NUM>% or less, or about <NUM>% or less. For example, in some embodiments the peroxy pyruvic acid concentration may be about <NUM>%, or about <NUM>%, or about <NUM>%. Expressed as parts per million (ppm), the concentration of peroxy pyruvic acid may be from about <NUM> ppm to about <NUM> ppm, about <NUM> ppm to about <NUM> ppm, or from about <NUM> ppm to about <NUM> ppm, or from about <NUM> ppm to about <NUM> ppm, or from about <NUM> ppm to about <NUM> ppm. For example, in various embodiments, the concentration of peroxy pyruvic acid is about <NUM> ppm, about <NUM> ppm, about <NUM> ppm, about <NUM> ppm, about <NUM> ppm, about <NUM> ppm, about <NUM> ppm, about <NUM> ppm, about <NUM> ppm, about <NUM> ppm or about <NUM> ppm. In various embodiments, the molarity of peroxy pyruvic acid may be from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, or from about <NUM> to about <NUM>.

In some embodiments, the antimicrobial solution comprises peroxy pyruvic acid, pyruvic acid and hydrogen peroxide. In one embodiment, the antimicrobial solution is, or comprises, the VERIOX™ antimicrobial agent, comprising peroxy pyruvic acid, available from CHD Bioscience of Fort Collins, Colorado.

In some embodiments, the antimicrobial solution comprises one or more optional antimicrobial agents, such as hypochlorite, silver nitrate, sulfur-based based antimicrobials, biguanides, and cationic antimicrobials. In some embodiments, the antimicrobial solution comprises an α-keto ester, preferably an alkyl α-keto ester such as an alkyl pyruvate ester. Such esters and compositions are described in <CIT>.

The present technology also provides negative pressure therapy devices and systems, and methods of treatment (unclaimed) using such systems with antimicrobial solutions. <FIG> is a schematic diagram of an example embodiment of a negative-pressure and instillation therapy system for delivering treatment solutions to a dressing at a tissue site. <FIG> is a simplified functional block diagram of an example embodiment of a therapy system <NUM> that can provide negative-pressure therapy with instillation of treatment solutions in accordance with this specification. The therapy system <NUM> may be packaged as a single, integrated unit such as therapy system <NUM>. The therapy system <NUM> may be, for example, a V. Ulta™ System available from Kinetic Concepts, Inc.

The term "tissue site" in this context broadly refers to a wound, defect, or other treatment target located on or within tissue, including but not limited to, bone tissue, adipose tissue, muscle tissue, neural tissue, dermal tissue, vascular tissue, connective tissue, cartilage, tendons, or ligaments. A wound may include chronic, acute, traumatic, subacute, and dehisced wounds, partial-thickness burns, ulcers (such as diabetic, pressure, or venous insufficiency ulcers), flaps, and grafts, for example. The term "tissue site" may also refer to areas of any tissue that are not necessarily wounded or defective, but are instead areas in which it may be desirable to add or promote the growth of additional tissue. For example, negative pressure may be applied to a tissue site to grow additional tissue that may be harvested and transplanted.

The therapy system <NUM> includes a negative-pressure supply, and includes a distribution component, which is a dressing. A distribution component is preferably detachable, and may be disposable, reusable, or recyclable. For example, a dressing <NUM> is fluidly coupled to a negative-pressure source <NUM>, as illustrated in <FIG>. The dressing <NUM> includes a cover <NUM> and a tissue interface <NUM>. A regulator or a controller, such as a controller <NUM>, may also be coupled to the negative-pressure source <NUM>. The therapy system <NUM> may optionally include a fluid container, such as a container <NUM>, coupled to the dressing <NUM> and to the negative-pressure source <NUM>.

The therapy system <NUM> also includes a source of instillation solution. For example, a solution source <NUM> may be fluidly coupled to the dressing <NUM>, as illustrated in the example embodiment of <FIG>. The solution source <NUM> is fluidly coupled to a positive-pressure source such as the positive-pressure source <NUM>. A regulator, such as an instillation regulator <NUM>, may also be fluidly coupled to the solution source <NUM> and the dressing <NUM>. In some embodiments, the instillation regulator <NUM> may also be fluidly coupled to the negative-pressure source <NUM> through the dressing <NUM>, as illustrated in the example of <FIG>. In some embodiments, the negative-pressure source <NUM> and the positive-pressure source <NUM> may be a single pressure source or unit as indicated by dashed line <NUM>.

As illustrated in <FIG>, for example, the therapy system <NUM> may include a pressure sensor <NUM>, an electric sensor <NUM>, or both, coupled to the controller <NUM>. The pressure sensor <NUM> may also be coupled or configured to be coupled to a distribution component and to the negative-pressure source <NUM>.

Components may be fluidly coupled to each other to provide a path for transferring fluids (i.e., liquid and/or gas) between the components. For example, components may be fluidly coupled through a fluid conductor, such as a tube. A "tube," as used herein, broadly includes a tube, pipe, hose, conduit, or other structure with one or more lumina adapted to convey a fluid between two ends. Coupling may also include mechanical, thermal, electrical, or chemical coupling (such as a chemical bond) in some contexts. For example, a tube may mechanically and fluidly couple the dressing <NUM> to the container <NUM> in some embodiments.

For example, the negative-pressure source <NUM> may be directly coupled to the controller <NUM>, and may be indirectly coupled to the tissue interface <NUM> of the dressing <NUM> through the container <NUM> by conduits <NUM> and <NUM>. Additionally, the positive-pressure source <NUM> may be directly coupled to the controller <NUM>, and may be indirectly coupled to the tissue interface <NUM> through the solution source <NUM> and the instillation regulator <NUM> by conduits <NUM>, <NUM> and <NUM>.

The fluid mechanics of using a negative-pressure source to reduce pressure in another component or location, such as within a sealed therapeutic environment, can be mathematically complex. However, the basic principles of fluid mechanics applicable to negative-pressure therapy and instillation are generally well-known to those skilled in the art, and the process of reducing pressure may be described illustratively herein as "delivering," "distributing," or "generating" negative pressure, for example.

In general, exudates and other fluids flow toward lower pressure along a fluid path. Thus, the term "downstream" typically implies something in a fluid path relatively closer to a source of negative pressure or further away from a source of positive pressure. Conversely, the term "upstream" implies something relatively further away from a source of negative pressure or closer to a source of positive pressure. Similarly, it may be convenient to describe certain features in terms of fluid "inlet" or "outlet" in such a frame of reference. This orientation is generally presumed for purposes of describing various features and components herein. However, the fluid path may also be reversed in some applications (such as by substituting a positive-pressure source for a negative-pressure source) and this descriptive convention should not be construed as a limiting convention.

"Negative pressure" generally refers to a pressure less than a local ambient pressure, such as the ambient pressure in a local environment external to a sealed therapeutic environment provided by the dressing <NUM>. In many cases, the local ambient pressure may also be the atmospheric pressure at which a tissue site is located. Alternatively, the pressure may be less than a hydrostatic pressure associated with tissue at the tissue site. Unless otherwise indicated, values of pressure stated herein are gauge pressures. Similarly, references to increases in negative pressure typically refer to a decrease in absolute pressure, while decreases in negative pressure typically refer to an increase in absolute pressure. While the amount and nature of negative pressure applied to a tissue site may vary according to therapeutic requirements, the pressure is generally a low vacuum, also commonly referred to as a rough vacuum, between -<NUM> Hg (-<NUM> Pa) and -<NUM> Hg (-<NUM> kPa). Common therapeutic ranges are between -<NUM> Hg (-<NUM> kPa) and -<NUM> Hg (-<NUM> kPa).

A negative-pressure supply, such as the negative-pressure source <NUM>, may be a reservoir of air at a negative pressure, or may be a manual or electrically-powered device that can reduce the pressure in a sealed volume, such as a vacuum pump, a suction pump, a wall suction port available at many healthcare facilities, or a micro-pump, for example. A negative-pressure supply may be housed within or used in conjunction with other components, such as sensors, processing units, alarm indicators, memory, databases, software, display devices, or user interfaces that further facilitate therapy. For example, in some embodiments, the negative-pressure source <NUM> may be combined with the controller <NUM> and other components into a therapy unit, such as therapy system <NUM>. A negative-pressure supply may also have one or more supply ports configured to facilitate coupling and de-coupling the negative-pressure supply to one or more distribution components.

The tissue interface <NUM> can be generally adapted to contact a tissue site. The tissue interface <NUM> may be partially or fully in contact with the tissue site. If the tissue site is a wound, for example, the tissue interface <NUM> may partially or completely fill the wound, or may be placed over the wound. The tissue interface <NUM> may take many forms, and may have many sizes, shapes, or thicknesses depending on a variety of factors, such as the type of treatment being implemented or the nature and size of a tissue site. Moreover, any or all of the surfaces of the tissue interface <NUM> may have projections or an uneven, course, or jagged profile that can induce strains and stresses on a tissue site, which can promote granulation at the tissue site,.

In some embodiments, the tissue interface <NUM> may be a manifold <NUM>. A "manifold" in this context generally includes any substance or structure providing a plurality of pathways adapted to collect or distribute fluid across a tissue site under pressure. For example, a manifold may be adapted to receive negative pressure from a source and distribute negative pressure through multiple apertures across a tissue site, which may have the effect of collecting fluid from across a tissue site and drawing the fluid toward the source. In some embodiments, the fluid path may be reversed or a secondary fluid path may be provided to facilitate delivering fluid across a tissue site.

In some illustrative embodiments, the pathways of a manifold may be interconnected to improve distribution or collection of fluids across a tissue site. In some illustrative embodiments, a manifold may be a porous foam material having interconnected cells or pores. For example, cellular foam, open-cell foam, reticulated foam, porous tissue collections, and other porous material such as gauze or felted mat generally include pores, edges, and/or walls adapted to form interconnected fluid channels. Liquids, gels, and other foams may also include or be cured to include apertures and fluid pathways. In some embodiments, a manifold may additionally or alternatively comprise projections that form interconnected fluid pathways. For example, a manifold may be molded to provide surface projections that define interconnected fluid pathways.

The average pore size of a foam may vary according to needs of a prescribed therapy. For example, in some embodiments, the tissue interface <NUM> may be a foam having pore sizes in a range of <NUM>-<NUM> microns. The tensile strength of the tissue interface <NUM> may also vary according to needs of a prescribed therapy. For example, the tensile strength of a foam may be increased for instillation of topical treatment solutions. In one non-limiting example, the tissue interface <NUM> may be an open-cell, reticulated polyurethane foam such as GranuFoam® dressing or VeraFlo® foam, both available from Kinetic Concepts, Inc.

The tissue interface <NUM> may be either hydrophobic or hydrophilic. In an example in which the tissue interface <NUM> may be hydrophilic, the tissue interface <NUM> may also wick fluid away from a tissue site, while continuing to distribute negative pressure to the tissue site. The wicking properties of the tissue interface <NUM> may draw fluid away from a tissue site by capillary flow or other wicking mechanisms. An example of a hydrophilic foam is a polyvinyl alcohol, open-cell foam such as V. WhiteFoam® dressing available from Kinetic Concepts, Inc. Other hydrophilic foams may include those made from polyether. Other foams that may exhibit hydrophilic characteristics include hydrophobic foams that have been treated or coated to provide hydrophilicity.

The tissue interface <NUM> may further promote granulation at a tissue site when pressure within the sealed therapeutic environment is reduced (i.e., below ambient pressure). For example, any or all of the surfaces of the tissue interface <NUM> may have an uneven, coarse, or jagged profile that can induce microstrains and stresses at a tissue site if negative pressure is applied through the tissue interface <NUM>.

In some embodiments, the tissue interface <NUM> may be constructed from bioresorbable materials. Suitable bioresorbable materials may include, without limitation, a polymeric blend of polylactic acid (PLA) and polyglycolic acid (PGA). The polymeric blend may also include without limitation polycarbonates, polyfumarates, and capralactones. The tissue interface <NUM> may further serve as a scaffold for new cell-growth, or a scaffold material may be used in conjunction with the tissue interface <NUM> to promote cell-growth. A scaffold is generally a substance or structure used to enhance or promote the growth of cells or formation of tissue, such as a three-dimensional porous structure that provides a template for cell growth. Illustrative examples of scaffold materials include calcium phosphate, collagen, PLA/PGA, coral hydroxy apatites, carbonates, or processed allograft materials.

In some embodiments, the cover <NUM> may provide a bacterial barrier and protection from physical trauma. The cover <NUM> may also be constructed from a material that can reduce evaporative losses and provide a fluid seal between two components or two environments, such as between a therapeutic environment and a local external environment. The cover <NUM> may be, for example, an elastomeric film or membrane that can provide a seal adequate to maintain a negative pressure at a tissue site for a given negative-pressure source. The cover <NUM> may have a high moisture-vapor transmission rate (MVTR) in some applications. For example, the MVTR may be at least <NUM>/m^<NUM> per twenty-four hours in some embodiments. In some example embodiments, the cover <NUM> may be a polymer drape, such as a polyurethane film, that is permeable to water vapor but impermeable to liquid. Such drapes typically have a thickness in the range of <NUM>-<NUM> microns. For permeable materials, the permeability generally should be low enough that a desired negative pressure may be maintained.

An attachment device, such as an attachment device <NUM>, may be used to attach the cover <NUM> to an attachment surface, such as undamaged epidermis, a gasket, or another cover. The attachment device may take many forms. For example, an attachment device may be a medically-acceptable, pressure-sensitive adhesive that extends about a periphery, a portion, or an entire sealing member. In some embodiments, for example, some or all of the cover <NUM> may be coated with an acrylic adhesive having a coating weight between <NUM>-<NUM> grams per square meter (g. Thicker adhesives, or combinations of adhesives, may be applied in some embodiments to improve the seal and reduce leaks. Other example embodiments of an attachment device may include a double-sided tape, paste, hydrocolloid, hydrogel, silicone gel, or organogel.

In some embodiments, a dressing interface may facilitate coupling the negative pressure source <NUM> to the dressing <NUM>. The negative pressure provided by the negative-pressure source <NUM> may be delivered through the conduit <NUM> to a negative-pressure interface <NUM>, which may include an elbow port <NUM>. In one illustrative embodiment, the negative-pressure interface <NUM> is a T. ® Pad or Sensa T. ® Pad available from KCI of San Antonio, Texas. The negative-pressure interface <NUM> allows the negative pressure to be delivered to the cover <NUM> and realized within an interior portion of the cover <NUM> and the manifold <NUM>. In this illustrative, non-limiting embodiment, the elbow port <NUM> extends through the cover <NUM> to the manifold <NUM>, but numerous arrangements are possible.

The therapy system <NUM> may also include a particulate filter <NUM>, which may be positioned in fluid communication between the fluid container <NUM> and/or the negative-pressure source <NUM> and the dressing <NUM>. The particulate filter <NUM> may function to remove particulate matter from the effluent that has circulated through the dressing <NUM>. For example, fluid delivered to the dressing <NUM> and to a tissue site may be drawn out of the dressing <NUM> through the negative-pressure interface <NUM> and transported through negative-pressure conduit <NUM> to the particulate filter <NUM>. The fluid may be filtered to remove particulate matter in the particulate filter <NUM>, before being recollected in the fluid container <NUM>.

The therapy system <NUM> may also include a second interface that may facilitate coupling of the positive-pressure source <NUM> to the dressing <NUM>, such as fluid-delivery interface <NUM>. The positive pressure provided by the positive-pressure source <NUM> may be delivered through the conduit <NUM>. The fluid-delivery interface <NUM> also may be fluidly coupled to the dressing <NUM> and may pass through a hole cut in the cover <NUM>. The hole cut in the cover <NUM> for the fluid-delivery interface <NUM> may be separated as far apart as possible from its location or other hole cut in the cover <NUM> through which the negative-pressure interface <NUM> may pass. The fluid-delivery interface <NUM> may allow for a fluid, such as an antimicrobial solution of the present technology, to be delivered by the therapy system <NUM> through the cover <NUM> and to the manifold <NUM>. In some embodiments, the fluid-delivery interface <NUM> may include an inlet pad. The inlet pad may be a non-dampening material or a material that is not sound-absorbing. In some embodiments, the inlet pad may be an elastomer. For example, the inlet pad may be an elastic polymer, such as polyurethane, thermoplastic elastomers, polyether block amide (PEBAX), polyisoprene, polychloroprene, chlorosulphonated polythene, and polyisobutylene, blends and copolymers. In one illustrative embodiment, the fluid-delivery interface <NUM> and the negative-pressure interface <NUM> may be integrated into a single pad for the delivery and removal of solutions from the tissue site <NUM>, such as a V.

Sensors, such as the pressure sensor <NUM> or the electric sensor <NUM>, are generally known in the art as any apparatus operable to detect or measure a physical phenomenon or property, and generally provide a signal indicative of the phenomenon or property that is detected or measured. For example, the pressure sensor <NUM> and the electric sensor <NUM> may be configured to measure one or more operating parameters of the therapy system <NUM>. In some embodiments, the pressure sensor <NUM> may be a transducer configured to measure pressure in a pneumatic pathway and convert the measurement to a signal indicative of the pressure measured. In some embodiments, for example, the pressure sensor <NUM> may be a piezoresistive strain gauge. The electric sensor <NUM> may optionally measure operating parameters of the negative-pressure source <NUM>, such as the voltage or current, in some embodiments. Preferably, the signals from the pressure sensor <NUM> and the electric sensor <NUM> are suitable as an input signal to the controller <NUM>, but some signal conditioning may be appropriate in some embodiments.

The solution source <NUM> may also be representative of a container, canister, pouch, bag, or other storage component, which can provide a solution for instillation therapy, such as an antimicrobial solution of the present technology. As discussed above, the compositions of the antimicrobial solutions may vary according to a prescribed therapy, comprising optional antmicrobial actives in addition to a peroxy α-keto carboxylic acid. In some examples, methods of the present technology employ only (consist essentially of administering) an antimicrobial solution comprising peroxy puryvic acid or other peroxy α-keto carboxylic acid. In other examples, methods may further comprise administration of other therapeutic solutions. Examples of such other therapeutic solutions that may be suitable for some prescriptions include hypochlorite-based solutions, silver nitrate (<NUM>%), sulfur-based solutions, biguanides, cationic solutions, and isotonic solutions. In one illustrative embodiment, the solution source <NUM> may include a storage component for the solution and a separate cassette for holding the storage component and delivering the solution to the tissue site <NUM>, such as a V. VeraLink™ Cassette available from Kinetic Concepts, Inc.

In operation, the tissue interface <NUM> may be placed within, over, on, or otherwise proximate to a tissue site, such as tissue site <NUM>. The cover <NUM> may be placed over the tissue interface <NUM> and sealed to an attachment surface near the tissue site <NUM>. Thus, the dressing <NUM> can provide a sealed therapeutic environment proximate to a tissue site, substantially isolated from the external environment, and the negative-pressure source <NUM> can reduce the pressure in the sealed therapeutic environment. Negative pressure applied across the tissue site through the tissue interface <NUM> in the sealed therapeutic environment can induce macrostrain and microstrain in the tissue site, as well as remove exudates and other fluids from the tissue site, which can be collected in container <NUM>.

As discussed above, the tissue site <NUM> may include, without limitation, any irregularity with a tissue, such as an open wound, surgical incision, or diseased tissue. The therapy system <NUM> is presented in the context of a tissue site that includes a wound <NUM>, which is through the epidermis <NUM>, or generally skin, and the dermis <NUM> and reaching into a hypodermis, or subcutaneous tissue <NUM>. The therapy system <NUM> may be used to treat a wound of any depth, as well as many different types of wounds including open wounds or other tissue sites. The tissue site <NUM> may be the bodily tissue of any human, animal, or other organism, including bone tissue, adipose tissue, muscle tissue, dermal tissue, vascular tissue, connective tissue, cartilage, tendons, ligaments, or any other tissue. Treatment of the tissue site <NUM> may include removal of fluids originating from the tissue site <NUM>, such as exudates or ascites, or fluids instilled into the dressing to cleanse or treat the tissue site <NUM>, such as antimicrobial solutions. The wound <NUM> may include undesirable tissue <NUM>, biofilm <NUM> formed on any living or nonliving surface of the dressing <NUM> or the tissue site <NUM>, and planktonic microbes <NUM> floating or swimming in liquid medium in and around the dressing <NUM>. Such undesirable tissue may include, necrotic, damaged, infected, contaminated, or adherent tissue, foreign material within the wound <NUM>. In many instances, it may be desirable to remove the undesirable tissue <NUM> or treat the biofilm <NUM> and planktonic microbes <NUM> with antimicrobials in order to promote healing of the wound <NUM>. The illustrative, non-limiting embodiment shows the therapy system <NUM> in the context of the wound <NUM> and the tissue site <NUM> having a localized discrete area of undesirable tissue <NUM>, biofilm <NUM>, or planktonic microbes <NUM> within the wound <NUM>. The therapy system <NUM> may be used in broader contexts, including with any type of tissue site including wounds, defects, or other treatment target located on or within living or nonliving tissue.

In one embodiment, controller <NUM> receives and processes data, such as data related to the pressure distributed to the tissue interface <NUM> from the pressure sensor <NUM>. The controller <NUM> may also control the operation of one or more components of therapy system <NUM> to manage the pressure distributed to the tissue interface <NUM> for application to the wound <NUM> at the tissue site <NUM>, which may also be referred to as the wound pressure (WP). In one embodiment, controller <NUM> may include an input for receiving a desired target pressure (TP) set by a clinician or other user and may be program for processing data relating to the setting and inputting of the target pressure (TP) to be applied to the tissue site <NUM>. In one example embodiment, the target pressure (TP) may be a fixed pressure value determined by a user/caregiver as the reduced pressure target desired for therapy at the tissue site <NUM> and then provided as input to the controller <NUM>. The user may be a nurse or a doctor or other approved clinician who prescribes the desired negative pressure to which the tissue site <NUM> should be applied. The desired negative pressure may vary from tissue site to tissue site based on the type of tissue forming the tissue site <NUM>, the type of injury or wound <NUM> (if any), the medical condition of the patient, and the preference of the attending physician. After selecting the desired target pressure (TP), the negative pressure source <NUM> is controlled to achieve the target pressure (TP) desired for application to the tissue site <NUM>.

Referring more specifically to <FIG>, a graph illustrating an illustrative embodiment of pressure control modes <NUM> that may be used for the negative-pressure and instillation therapy system of <FIG> and <FIG> is shown wherein the x-axis represents time in minutes (min) and/or seconds (sec) and the y-axis represents pressure generated by a pump in Torr (mmHg) that varies with time in a continuous pressure mode and an intermittent pressure mode that may be used for applying negative pressure in the therapy system. The target pressure (TP) may be set by the user in a continuous pressure mode as indicated by solid line <NUM> and dotted line <NUM> wherein the wound pressure (WP) is applied to the tissue site <NUM> until the user deactivates the negative pressure source <NUM>. The target pressure (TP) may also be set by the user in an intermittent pressure mode as indicated by solid lines <NUM>, <NUM> and <NUM> wherein the wound pressure (WP) is cycled between the target pressure (TP) and atmospheric pressure. For example, the target pressure (TP) may be set by the user at <NUM> mmHg below ambient pressure for a specified period of time (e.g., <NUM>) followed by the therapy being turned off for a specified period of time (e.g., <NUM>) as indicated by lines <NUM> by venting the tissue site <NUM> to the atmosphere, and then repeating the cycle by turning the therapy back on as indicated by line <NUM> which consequently forms a square wave pattern between the target pressure (TP) level and no pressure. In various embodiments the steps of providing negative pressure and providing the antimicrobial solution are sequentially repeated two or more times.

The decrease of the wound pressure (WP) at the tissue site <NUM> from ambient pressure to the target pressure (TP) is not instantaneous, but rather gradual depending on the type of therapy equipment and the dressing. For example, the negative pressure source <NUM> and the dressing <NUM> may have an initial rise time as indicated by the dashed line <NUM> that may vary depending on the type of dressing and therapy equipment being used. For example, the initial rise time for one therapy system may be in the range between about <NUM>-<NUM> mmHg/second or, more specifically, equal to about <NUM> mmHg/second, and in the range between about <NUM>-<NUM> mmHg/second for another therapy system. When the therapy system <NUM> is operating in the intermittent mode, the repeating rise time <NUM> may be a value substantially equal to the initial rise time <NUM>.

The target pressure may also be a variable target pressure (VTP) controlled or determined by controller <NUM> that varies in a dynamic pressure mode. For example, the variable target pressure (VTP) may vary between a maximum and minimum pressure value that may be set as an input determined by a user as the range of negative pressures desired for therapy at the tissue site <NUM>. The variable target pressure (VTP) may also be processed and controlled by controller <NUM> that varies the target pressure (TP) according to a predetermined waveform such as, for example, a sine waveform or a saw-tooth waveform or a triangular waveform, that may be set as an input by a user as the predetermined or time-varying reduced pressures desired for therapy at the tissue site <NUM>.

Referring more specifically to <FIG>, a graph illustrating an illustrative embodiment of another pressure control mode for the negative-pressure and instillation therapy system of <FIG> and <FIG> is shown wherein the x-axis represents time in minutes (min) and/or seconds(sec) and the y-axis represents pressure generated by a pump in Torr (mmHg) that varies with time in a dynamic pressure mode that may be used for applying negative pressure (i.e., reduced pressure, below ambient pressure) in the therapy system. For example, the variable target pressure (VTP) may be a reduced pressure that provides an effective treatment by applying reduced pressure to tissue site <NUM> in the form of a triangular waveform varying between a minimum and maximum pressure of <NUM>-<NUM> mmHg below ambient pressure with a rise time <NUM> set at a rate of +<NUM> mmHg/min. and a descent time <NUM> set at -<NUM> mmHg/min, respectively. In another embodiment of the therapy system <NUM>, the variable target pressure (VTP) may be a reduced pressure that applies reduced pressure to tissue site <NUM> in the form of a triangular waveform varying between <NUM>-<NUM> mmHg with a rise time <NUM> set at a rate of +<NUM> mmHg/min and a descent time <NUM>. set at -<NUM> mmHg/min. Again, the type of system and tissue site determines the type of reduced pressure therapy to be used.

<FIG> is a flow chart illustrating an illustrative example of a therapeutic method <NUM> that may be used for providing negative-pressure and instillation therapy for delivering an antimicrobial solution or other treatment solution to a dressing at a tissue site. In one embodiment, the controller <NUM> receives and processes data, such as data related to fluids provided to the tissue interface. Such data may include the type of instillation solution prescribed by a clinician, the volume of fluid or solution to be instilled to the tissue site ("fill volume"), and the amount of time needed to soak the tissue interface ("soak time") before applying a negative pressure to the tissue site. The fill volume may be, for example, between <NUM> and <NUM>, and the soak time may be between one second to <NUM> minutes. The controller <NUM> may also control the operation of one or more components of the therapy system <NUM> to manage the fluids distributed from the solution source <NUM> for instillation to the tissue site <NUM> for application to the wound <NUM> as described in more detail above. In one embodiment, fluid may be instilled to the tissue site <NUM> by applying a negative pressure from the negative pressure source <NUM> to reduce the pressure at the tissue site <NUM> to draw the instillation fluid into the dressing <NUM> as indicated at <NUM>. In another embodiment, fluid may be instilled to the tissue site <NUM> by applying a positive pressure from the negative pressure source <NUM> (not shown) or the separate positive pressure source <NUM> to force the instillation fluid from the solution source <NUM> to the tissue interface <NUM> as indicated at <NUM>. In yet another embodiment, fluid may be instilled to the tissue site <NUM> by elevating the solution source <NUM> to height sufficient to force the instillation fluid into the tissue interface <NUM> by the force of gravity as indicated at <NUM>. Thus, the therapy method <NUM> includes instilling fluid into the tissue interface <NUM> by either drawing or forcing the fluid into the tissue interface <NUM> as indicated at <NUM>.

The (unclaimed) therapy method <NUM> may control the fluid dynamics of applying the fluid solution to the tissue interface <NUM> at <NUM> by providing a continuous flow of fluid at <NUM> or an intermittent flow of fluid for soaking the tissue interface <NUM> at <NUM>. The therapy method <NUM> may include the application of negative pressure to the tissue interface <NUM> to provide either the continuous flow or intermittent soaking flow of fluid at <NUM>. The application of negative pressure may be implemented to provide a continuous pressure mode of operation at <NUM> as described above to achieve a continuous flow rate of instillation fluid through the tissue interface <NUM> or a dynamic pressure mode of operation at <NUM> as described above to vary the flow rate of instillation fluid through the tissue interface <NUM>. Alternatively, the application of negative pressure may be implemented to provide an intermittent mode of operation at <NUM> as described above to allow instillation fluid to soak into the tissue interface <NUM> as described above. In the intermittent mode, a specific fill volume and the soak time may be provided depending, for example, on the type of wound <NUM> being treated and the type of dressing <NUM> being utilized to treat the wound <NUM>. After or during installation of fluid into the tissue interface <NUM> has been completed, the therapy method <NUM> may begin may be utilized using any one of the three modes of operation at <NUM> as described above. The controller <NUM> may be utilized to select any one of these three modes of operation and the duration of the negative pressure therapy as described above before commencing another installation cycle at <NUM> by instilling more fluid at <NUM>.

The therapy method <NUM> provides irrigation, i.e., the practice of washing out a wound or bodily opening with a stream of liquid solution, and lavage, i.e., the practice of washing out a cavity or organ, using a liquid solution for therapeutic purposes. Instilled fluid is slowly introduced into the wound and remains in the wound bed for a defined period of time before being removed by applying negative pressure as described above. Automated installation helps with wound cleansing by loosening soluble contaminants in the wound bed followed by subsequent removal of infectious material during negative pressure therapy. As a result, soluble bacterial burden can be decreased, contaminants removed, and the wound thus cleansed, all without interaction from a user or clinician, The therapeutic method including therapeutic method <NUM> as generally described above (i) cleanses the wound with instillation of topical wound cleansers in a consistent, controlled manner, (ii) treats the wound with the instillation of appropriate topical antimicrobials and antiseptic solutions and the removal of infectious material, and (iii) heals the wound and prepares for primary or secondary closure of the wound.

<FIG> is a bar chart illustrating the increase in granulation tissue thickness ("GTT") after (i) providing negative-pressure and instillation therapy for delivering instillation fluids to a dressing at a tissue site, (ii) providing such therapy using a saline solution, and (iii) providing such therapy using an antimicrobial that may be accomplished with the example embodiment of therapy system of <FIG> and <FIG> in the therapy method of <FIG>. Several preclinical studies have been conducted on animals utilizing the improved installation technology as described above to determine the effect on granulation tissue formation. In one study, an in vivo porcine full-thickness wound model (n=<NUM>) was used to evaluate granulation tissue thickness. The therapy method included the following steps: (i) Each animal received contralateral <NUM> diameter full-thickness excisional dorsal wounds that were treated with the negative pressure and instillation therapy using the tissue interface and, more specifically, V. VeraFlo™ Therapy using the V. VeraFlo™ Dressing, (ii) The V. VeraFlo™ Therapy was set to instill <NUM> of normal saline, soak for <NUM> minutes and apply negative pressure of -125mmHg continuously for <NUM> hours for <NUM> cycles per day. (iii) The V. ® Therapy was set at -125mmHg continuous pressure. (iv) After <NUM> days, tissue samples were processed for histology and stained with Masson's tri-chrome. (v) Granulation tissue thickness was measured from the base of the wound to the surface of the wound.

The results were quite unexpected and impressive. A significant increase in granulation thickness of about <NUM>% (<NUM> ± <NUM>; p<<NUM>) was observed using the V. VeraFlo™ Therapy with V. VeraFlo™ Dressings compared to using only negative pressure therapy with the V. ® GranuFoam™ Dressings (<NUM> ± <NUM>; p<<NUM>). Results of the histological findings showed that the increase in granulation thickness was the result of new tissue deposition, not swelling. Optimization of instillation and negative pressure therapy parameters, such as instillation volume, soak time, and cycle frequency may allow for further improvement in tissue granulation. However, it is uncertain how these swine results may correlate to human results.

Instillation and negative pressure therapy systems and (unclaimed) methods are especially effective for improving tissue granulation when used in conjunction with antimicrobial solutions that have demonstrated efficacy against a broad range of healthcare-associated infections (HAIs), biofilms and planktonic microbes that are categorized and described above. Healthcare-associated infections, also known as hospital-acquired infections, include fungal, viral and bacterial infections that patients contract during the course of receiving healthcare treatment for other conditions. HAIs can cause severe pneumonia and infections of the urinary tract, bloodstream and other parts of the body. Some common HAIs include hospital-acquired pneumonia, Methicillin resistant Staphylococcus aureus (MRSA), Clostridium difficile spores, tuberculosis and gastroenteritis. These HAIs and biofilms survive on surfaces in the hospital and enter the body through wounds, catheters and ventilators, while the planktonic microbes survive in fluids associated with the tissue site.

To combat the growing threat of infections, antimicrobial solutions may be used as an instillation fluid in conjunction with the automated systems and methods described above including, for example, instilling the antimicrobial solutions to the tissue interface <NUM> in a continuous or intermittent mode followed by negative pressure therapy for treating the wound <NUM> at the tissue site <NUM>.

Antimicrobial solutions comprising an antimicrobial agent containing a peroxy α-keto carboxylic acid as the active ingredient have demonstrated unique safety and efficacy properties that can mitigate or treat the increasing threat of HIAs, including the most resistant pathogens such as methicillin resistant Staphylococcus aureus (MRSA), CRE and C. difficile spores. Such antimicrobial agents are not only capable of destroying the bacteria that cause biofilms, but also capable of breaking down the biofilm matrix and reducing the total dry weight of the biofilm by almost <NUM>% according to certain in vitro test results. One embodiment of an antimicrobial agent containing peroxy pyruvic acid as the active ingredient that may be utilized as an instillation fluid for the present therapeutic system and methods is the VERIOX™ antimicrobial agent available from CHD Bioscience of Fort Collins, Colorado. The VERIOX™ antimicrobial agent has demonstrated in pre-clinical animal studies its ability to disinfect and enhance the healing response in wounds, especially in conjunction with the installation and negative pressure therapy systems and methods described above.

For example, an ex vivo study was undertaken using an installation and negative pressure therapy method similar to the V. Ulta™ System available from Kinetic Concepts, Inc. of San Antonio, Texas, to determine how VERIOX™ antimicrobial agent, containing peroxy peruvic acid, performs on human wound pathogens. In this study, sponges that were used to remove debris from chronic infected wounds in human subjects were exposed to various concentrations of VERIOX™ and then tested for residual antimicrobial growth. VERIOX™ resulted in complete bacterial kill at <NUM>-hours and <NUM>-hours, post treatment, thus confirming the product's capability of destroying difficult-to-kill pathogens in a highly contaminated environment at low concentrations. Furthermore, the results were the same regardless of the wound type (diabetic, non-diabetic and drug-resistant wounds). This study demonstrated that antimicrobial solutions of the present technology can kill highly resistant pathogens (such as MRSA, CRE and C. difficile spores) without harming healthy cells or tissue at clinically efficacious levels.

In yet another example, an in vivo animal study was undertaken using an installation and negative pressure therapy method similar to the V. Ulta™ System to treat a histomorphometry of porcine wounds with different antimicrobial solutions including the VERIOX™ antimicrobial agent as the instillation fluid. The results of this study are set forth in <FIG>. This study demonstrates that the treatment not only did not harm healthy cells or tissue associated with the wound, but also greatly increased granulation tissue thickness by a remarkable <NUM>% (<NUM>; p<<NUM>) over instillation therapy without using the antimicrobial agent (<NUM>; p<<NUM>).

Without limiting the mechanism, function or utility of present technology, the systems and methods described herein may provide significant advantages relative to treatment modalities among those known in the art. For example, a single antimicrobial solution comprising peroxy pyruvic acid or other peroxy α-keto carboxylic acid may perform multiple functions in wound care thereby eliminating the serial healing method of debriding, washing with antiseptic, and granulation. Even though antimicrobial and/or antiseptic solutions used for wound cleansing may, in general, be toxic to cells at some level, the antimicrobial solution of the present technology comprising peroxy α-keto carboxylic acid combined with negative pressure therapy provides antimicrobial efficacy to kill biofilms and planktonic microbes while expediting granulation tissue growth. This single solution may also mitigate the need for a physician to frequently inspection the wound by removing the dressing to determine the next level of treatment and the timing of such treatments.

Claim 1:
A system for treating a tissue site, comprising:
a dressing including a tissue interface adapted to contact the tissue site and a cover adapted to provide a fluid seal between a therapeutic environment including the tissue interface proximate one side of the cover and a local external environment on the other side of the cover;
a positive-pressure source fluidly coupled to a solution source comprising an antimicrobial solution and adapted to actuate the solution source for delivering the solution to the tissue interface; and
a negative-pressure source fluidly coupled to the dressing and adapted to provide negative pressure to the therapeutic environment after delivery of the antimicrobial solution to the therapeutic environment;
characterized in that the solution comprises an aqueous solution of a peroxy α-keto carboxylic acid.