WO2017015208A1

WO2017015208A1 - Wound dressing and method for treating acute and chronic wounds

Info

Publication number: WO2017015208A1
Application number: PCT/US2016/042788
Authority: WO
Inventors: Abra JANIS
Original assignee: Hollister Incorporated
Priority date: 2015-07-17
Filing date: 2016-07-18
Publication date: 2017-01-26

Abstract

The present invention provides a wound dressing and method for treating wounds that introduces and/or promotes the growth of non-pathogenic bacteria or single-celled eukaryotes such as fungi, yeast, or algae over pathogenic bacteria or saprophytic fungi within a would or on the skin. It is intended that the non-pathogenic species will compete with the pathogenic organisms and reduce their relative proportion of the total bioburden population. A single microbial or algal species or a mixture of organisms can be delivered at one time, or in sequence. Organisms can be in the planktonic form in a liquid suspension that is sprayed or poured onto the wound, or immobilized as spores on a solid or semi-solid substrate that is applied to the wound (e.g., in a wound dressing). In addition dressings that modulate the skin or wound environment to select one or one group of organisms over another are described.

Description

WOUND DRESSING AND METHOD FOR TREATING ACUTE

AND CHRONIC WOUNDS

CROSS-REFERENCE TO RELATED APPLICATIONS

[oooi] This application claims the benefit of U.S. Provisional Application Serial No. 62/193,774, filed on July 17, 2015, which is herein incorporated by reference in its entirety.

FIELD OF THE INVENTION

[0002] The present invention relates generally to wound care and, more particularly, to the treatment of acute and chronic wounds utilizing a single or combination of nonpathogenic bacterium, fungus, algae or yeast.

BACKGROUND OF THE INVENTION

[0003] Colonization, infection and biofilm formation by pathogenic bacteria and/ or fungi has been typically believed to impair acute and chronic wound healing. In particular, negative effects of bacterial infection may include impairment of granulation, epithelialization and cellular migration as well as increasing chronicity. Spread of infection can lead to even more complications. The bacteria and fungi responsible for such negative effects have been identified as both aerobic and anaerobic species, however, the correlation of anaerobic species of bacteria with wound chronicity has led some researchers to hypothesize that the interaction between aerobic and anaerobic microbes is as or more important than the strains of bacteria or fungi.

In connection with the above, the presence of bacteria in a chronic wound does not necessarily mean that the wound is infected. Historically, wounds have been classified as infected once bioburden has increased to greater than 10⁶ (10⁵ for Staphylococcus) colony forming units (cfu) per gram of tissue. Recent studies, however, have cautioned against relying on cfu numbers alone. Based on the relative bioburden level, a wound can be generally classified on the wound infection continuum from sterility at one end, to contaminated, to colonized, to critically colonized, and ultimately to infected at the other end. Therefore, it is well accepted wounds are not sterile therefore bacteria are likely to already be present in a wound, and that the presence of bacteria does not necessarily mean that the wound is infected.

[0004] Of note, antimicrobial resistance has been gaining awareness as a growing public health issue. In particular antibiotic resistance, due to use in agriculture, inappropriate use, over-prescription, and slowing of development of new formulations, is of particular interest, as the field of medicine, including acute and chronic wound care, is seeking novel therapeutic modalities to increase the armamentarium against pathogenic species.

[0005] In view of recent research regarding wounds and bacteria, the present invention seeks to provide a wound dressing and methods for treating acute and chronic wounds in a manner currently not contemplated or seen in the art.

SUMMARY OF THE INVENTION

[0006] It is an object of the present invention to provide a wound dressing for treating acute and/ or chronic wounds.

[0007] It is another object of the present invention to provide a wound dressing for treating acute and/ or chronic wounds that introduces specific species of bacteria, algae, yeast or fungi to a wound. [0008] It is another object of the present invention to provide a wound dressing for treating acute and/ or chronic wounds that modulates existing populations of bacteria, algae, yeast or fungi within a wound.

[0009] It is another object of the present invention to provide a wound dressing for treating acute and/ or chronic wounds that selects or encourages the survival or growth of certain organisms over others within or around a wound.

[ooio] It is another object of the present invention to provide a method for treating acute and/ or chronic wounds.

[ooii] It is another object of the present invention to provide a method for treating acute and/ or chronic wounds that includes introducing specific species of bacteria to a wound, modulating existing populations of bacteria within a wound, and/ or selecting or encouraging the growth of certain organisms over others.

[0012] These and other objects are achieved by the present invention.

[0013] The present invention provides a wound dressing and method for treating wounds that introduces and/ or promotes the growth of non-pathogenic bacteria or single-celled eukaryotes over pathogenic bacteria or saprophytic fungi within a wound or on the skin. It is intended that the non-pathogenic species will compete with the pathogenic organisms and reduce their relative proportion of the total bioburden population. A single bacterial, algae, yeast or fungal species or a mixture of bacteria, algae, yeast or fungi can be delivered at one time, or in sequence. Bacteria, algae, yeast or fungi can be in the planktonic form in a liquid suspension that is sprayed or poured onto the wound, delivered in a paste or gel-like biofilm state, or immobilized as storage stable dry spores on a solid substrate that is applied to the wound (e.g., in a wound dressing). BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The present invention will be better understood from reading the following description of non-limiting embodiments, with reference to the attached drawings, wherein below:

[0015] FIG. 1 is a perspective view of a wound dressing according to an embodiment of the present invention.

[0016] FIG. 2 is a perspective view of a wound dressing according to another

embodiment of the present invention.

DESCRIPTION OF PREFERRED EMBODIMENTS

[0017] The present invention is directed to a wound dressing and method for treating a wound that involves applying a bacterial, alga, yeast or fungal culture or inoculum of non-pathogenic bacteria, algae, yeast or fungi to an at-risk or infected wound in order to competitively colonize the wound bed and prevent adhesion and proliferation of pathogenic bacteria such as, for example, S. aureus, S. epidermidis, and P. aeruginosa, that could lead to infection. The present invention contemplates various methods for applying such bacteria culture or inoculum of non-pathogenic bacteria, algae, yeast or fungi such as, for example, through the use of sprays, swabs, dressing-immobilized cultures or spore strips. Regardless of the particular method of application, selective nutrition or conditions for the selected non-pathogenic organism(s) may be

incorporated into each to aid in the proliferation of the selected bacteria, algae, yeast fungi, or the like. Similarly, biofilm forming cocktails of organisms or specific species that limit the growth of others through the release of natural antibiotics or compete for nutrients or attachment sites may also be introduced to the wound bed utilizing the wound dressing or methods disclosed herein.

[0018] In an embodiment, once the population of desirable bacteria, algae, yeast or fungi are applied to a wound through one of the above-described methods, a dressing configured to maintain the proper conditions for the specific species of bacteria, algae, yeast or fungi selected can be applied over the wound. Alternatively, the dressing itself may contain the population of bacteria, algae, yeast or fungi to be applied to the wound in the form of a gel or the like. In particular, the present invention contemplates a wound dressing that contains or releases specific growth medium or otherwise alters the environment at the wound site to preserve or encourage growth of one species of bacteria while discouraging the growth of others. As used herein, "environment" may include the temperature, pH and humidity or hydration level present at the wound site. Reservoirs, gels or degradable microspheres can be utilized to deliver or alter the wound conditions over time, as discussed in detail hereinafter. In an embodiment, the bacteria selected for introduction may be of the genus lactobacillus, although the use of other bacteria or fungal species may also be utilized without departing from the broader aspects of the present invention.

[0019] For example, in an embodiment, the desired temperature at the wound site may controlled to be within a range of temperatures that is selective for the differential survival of bacteria of the genus Lactobacillus (e.g., 43-46°C, which is, importantly, outside the temperature range for successful growth of pathogenic Staphylococcus aureus (optimum temperature 37 °C) and Staphylococcus epidermidis (optimum temperature between 26-37°C), or Pseudomonas aeruginosa (optimum temperature 37

°Q).

[0020] Alternatively, or in addition to controlling temperature, the pH may be controlled to within a pH range that is selective for the differential survival of bacteria of the genus Lactobacillus (e.g., below pH 5.0, which is outside the pH range for successful growth of pathogenic Staphylococcus aureus (pH optimum 7.4-7.6) and Staphylococcus epidermidis (pH optimum 6.8), or Pseudomonas aeruginosa (pH optimum 6.6-7.0)).

[0021] With respect to humidity, for example, Pseudomonas aeruginosa is typically a waterborne bacterium, therefor desiccation would differentially select dehydration tolerant species over this common pathogenic species.

[0022] Further to the above, hypertonicity (high salt) is differentially selective for lactobacillus over other bacterial species such as Pseudomonas and Staphylococcus. This is the same mode of action for the production of fermented foods such as kimchi or sauerkraut. Hypertonic conditions are created (through the brining process with NaCl) that select for the survival of lactobacillus species over other bacterial flora on the substrate. As the material is metabolized, the metabolite leads to a lowering of pH that further selects for the survival of lactobacillus species.

[0023] In addition, or alternative to, the introducing bacteria of the genus lactobacillus, yeast or algae may be introduced to a wound and the environment controlled to encourage growth of such yeast or algae. For example, the present invention

contemplates the utilization of the yeast Saccharomyces cerivisae (used in brewing of beer), which has a pH optimum of 4 and a temperature optimum of 26°C. Moreover, algae species contemplated include those commonly used in food production such as Clorella (pH optimum 10-10.5, temperature optimum 15°C, low salinity) and Spirulina (temperature optimum 32°C, pH 9-9.5). Marine species that have evolved in seawater likely will have optimal growth in hypertonic (~2M) conditions

[0024] In an embodiment, polymeric microspheres containing bacterial, algal or fungal spores, medium, media components, or the like may be timed to release based on degradation of the carrier, which could be tuned based on ionic conditions in the wound (e.g., hypotonic, isotonic, hypertonic), temperature or pH. Protein carriers may also be utilized, where breakdown would occur in the presence of endogenous, fungal or bacterial proteases that may increase in acute and chronic or infected wounds.

[0025] For example, with reference to FIG. 1, a wound dressing 10 according to an embodiment of the present invention is illustrated. The dressing 10 includes a base layer 12 of a type commonly known in the art such as a film, hydrogel or hydrocolloid. The dressing 10 also includes a reservoir 14 formed therein having a re-sealable opening or port 16 providing a passageway allowing for fluid communication between the exterior of the dressing 10 to the underside of base layer 12 at the wound site. Either the base layer 12 or the reservoir 14 may contain the population of selected bacteria or fungi to be applied to the wound, as indicated above. Where the bacteria or fungi is first applied utilizing a spray, gel or the like, the dressing 10 may be placed over the wound thereafter.

[0026] Importantly, the port 16 allows for the introduction of additional or different nutritional medium as needed to facilitate the growth of the selected bacteria, algae, fungi, or yeast that have been introduced to the wound. Alternative or additional inoculation with bacteria, algae, yeast or fungi could also be could also be performed without changing the dressing by introducing the bacteria or fungi through the port 16.

[0027] With reference to FIG. 2, a wound dressing 100 according to another

embodiment of the present invention is illustrated. The wound dressing 100 is generally similar to wound dressing 10 and includes a body 110 configured to be placed over a wound 102 after a selected population of bacteria, algae, yeast or fungi is introduced to the wound via the methods hereinbefore described. Alternatively, the dressing 100 may itself contain the bacteria, algae, yeast or fungi to be introduced. The dressing 100 is configured to provide a substantially sealed cavity or chamber 112 surrounding the wound 102 and may include a plurality of ports including, for example, an inlet port 114 and an outlet port 116 in selective fluid communication with the chamber 112.

[0028] The ports 114, 116 allow for the selective introduction or removal and monitoring of gases in the chamber 112 surrounding the wound 102. This allows the temperature, humidity or concentrations of gases surrounding the wound 102 to be precisely controlled. For example, the ports 114, 116 may be utilized to selectively introduce or remove oxygen from the area surrounding the wound. In an embodiment, the dressing 100 may include a gauge or sensor 118 configured to monitor the humidity level or the concentration of various gases within the chamber 112 surrounding the wound 102. Importantly, the dressing 100 can be utilized to select for one species or a class of organisms while limiting the growth of others either through nutritional composition, induced hyperoxia, hypoxia, or anoxia, or changes in pH. For example, the wound dressing 100 may be utilized to produce an anaerobic environment that would limit the growth of aerobic bacteria but allow or encourage the growth of anaerobes.

Alternatively, the wound dressing 100 may be utilized to produce an aerobic

environment that would limit the growth of anaerobic bacteria but allow or encourage the growth of aerobes.

[0029] Examples of selective media, beyond the high salt selection for lactobacillus described above, include Pseudomonas isolation agar and mannitol salts agar for selection of Staphylococcus.

[0030] As discussed above, dressing 10 or 100 may be applied to an at risk, infected or inoculated wound to selectively establish, limit or preserve a differential population of bacteria or fungi that have been delivered to the wound. In some embodiments, the wound dressing may contain deliver or promote the growth of yeast or algae. [0031] In connection with the above-described embodiments, the goal of the introduction of competitive organisms is the occupation of binding sites within the exposed extracellular matrix (ECM) of the wound and competition for nutrients and other resources to limit the proliferation of pathogenic species. In certain embodiments, extremophilic archaebacteria could also be utilized, as these bacteria thrive in non- physiologic conditions that may not be detrimental to wound healing. In particular, these species can persist in high salt and high or low pH environments, as well as in temperature extremes that would be selective against typical pathogenic wound bacteria or fungi.

[0032] The present invention therefore provides a wound dressing and method for treating wounds that introduces and/ or promotes the growth of non-pathogenic bacteria or single-celled eukaryotes (fungi, yeast, or algae) over pathogenic bacteria or saprophytic fungi within a wound or on the skin. It is intended that the non-pathogenic species will compete with the pathogenic organisms and reduce their relative

proportion of the total bioburden population. A single bacterial or fungal species or a mixture of bacteria, algae, yeast or fungi or bacteria and fungi can be delivered at one time, or in sequence. Bacteria or fungi can be in the planktonic form in a liquid suspension that is sprayed or poured onto the wound, or immobilized as spores on a solid substrate that is applied to the wound (e.g., in a wound dressing).

[0033] As indicated above, a dressing according to the present invention may

alternatively not contain or deliver live microbes, but may instead selectively encourage the growth of a preferred species or selectively discourage the growth of a non- desirable species. The preferred species may have been previously introduced utilizing the methods described herein, or may be naturally present within a wound or on or in the skin. [0034] In addition to the benefits described above, the wound dressing and methods of the present invention offer a novel treatment for infection or reduction of bioburden without the use of antimicrobials or antibiotics, which have been widely accepted to encourage the evolution of resistant populations over time, an increasingly urgent public health issue.

[0035] While the embodiments described above allude to the use of monocultures, co- cultures or multi-cultures of more than one bacterial or fungal species may also be utilized to competitively colonize a wound bed and prevent adhesion and proliferation of pathogenic bacteria or fungi without departing from the broader aspects of the present invention. In addition, while the present invention has been described as being applicable to wounds, generally, the present invention is particularly suited for the treatment of acute and chronic dermal wounds.

[0036] Although this invention has been shown and described with respect to the detailed embodiments thereof, it will be understood by those of skill in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiments disclosed in the above detailed description, but that the invention will include all embodiments falling within the scope of this disclosure.

Claims

WHAT IS CLAIMED IS:

1. A method for treating a wound, comprising the steps of:

introducing a non-pathogenic bacteria, fungi, algae or yeast to the wound; and promoting growth of the non-pathogenic bacteria, fungi, algae or yeast.

2. The method according to claim 1, wherein:

the step of introducing the non-pathogenic bacteria, fungus, algae or yeast to the wound includes at least one of spraying a liquid containing the bacteria, fungus, algae or yeast on the wound, applying a spore strip over the wound, and covering the wound with a dressing containing the non-pathogenic bacteria, fungus, algae or yeast.

3. The method according to claim 2, further comprising the step of:

applying a wound dressing over the wound.

4. The method according to claim 3, wherein:

the wound dressing is configured to deliver a growth medium for the nonpathogenic bacteria, algae, yeast or fungus onto the wound.

5. The method according to claim 2, wherein:

the wound dressing is configured to alter an environment of or surrounding the wound in a manner that encourages growth of the non-pathogenic bacteria, fungus, algae or yeast while discouraging growth of a pathogenic bacteria or fungus.

6. The method according to claim 5, wherein:

the wound dressing includes at least one of a reservoir, a gel or a degradable microsphere for delivering the growth medium onto the wound or altering the environment surrounding the wound.

7. The method according to claim 5, wherein:

the non-pathogenic bacteria is of the genus lactobacillus.

8. The method according to claim 1, further comprising the step of:

introducing at least one biofilm forming cocktail of organisms or species to the wound;

wherein the at least one biofilm forming cocktail is configured to at least one of limit the growth of pathogenic bacteria or fungus through the release of naturally occurring antibiotics and compete with the pathogenic bacteria or fungus for nutrients.

9. The method according to claim 6, wherein:

the environment includes at least one of a humidity level and temperature.

10. The method according to claim 6, wherein:

the step of promoting the growth of the non-pathogenic bacteria, algae, yeast or fungi includes modifying at least one of a temperature, hydration and pH of the wound using the wound dressing.

11. The method according to claim 3, wherein:

the wound dressing includes a base layer formed from a film, hydrogel, or hydrocolloid; and

a reservoir having a re-sealable opening allowing fluid communication between an exterior of the wound dressing and an underside of the base layer adjacent to the wound.

12. The method according to claim 3, further comprising the step of:

introducing a second, non-pathogenic bacteria, algae, yeast or fungi to the wound through the re-sealable opening in the wound dressing without removing or changing the wound dressing, the second, non-pathogenic bacteria, algae yeast or fungi being different from the non-pathogenic bacteria, algae, yeast or fungi first introduced to the wound.

13. A wound dressing, comprising:

a base layer;

a reservoir; and

at least one port providing a passageway to the reservoir from an exterior of the dressing, the reservoir being in fluid communication with a wound when the dressing is placed over the wound;

wherein the wound dressing is configured to deliver at least one of deliver nonpathogenic bacteria, algae, yeast or fungi to the wound, and promote growth of the non-pathogenic bacteria or fungi, algae, yeast or fungi.

14. The wound dressing of claim 13, wherein:

the at least one port includes an inlet port and an outlet port.

15. The wound dressing of claim 14, further comprising:

a gauge within the reservoir, the gauge being configured to monitor at least one of a hydration, humidity level and a pH at the wound within the reservoir.

16. The wound dressing of claim 13, wherein:

the wound dressing is configured to deliver a selective growth medium for the non-pathogenic bacteria, algae, yeast or fungi onto the wound via at least one of the at least one port and the reservoir, a gel or a degradable microsphere.

17. The wound dressing of claim 16, wherein:

the wound dressing is configured to alter an environment surrounding the wound in a manner that encourages growth of the non-pathogenic bacteria, algae, yeast or fungi while discouraging growth of a pathogenic bacteria or fungi.

18. The wound dressing of claim 17, wherein:

the environment includes a plurality of parameters including specific media or wound exudate components, hydration, humidity level, temperature and pH; and

the wound dressing is configured to alter at least one of the specific media or wound exudate components, hydration, humidity level, temperature and pH at the wound.

19. A method for treating a wound, comprising the steps of:

at least one of identifying a preferred species of non-pathogenic bacteria or fungi within the wound or introducing a non-pathogenic bacteria, algae, yeast or fungi to the wound;

applying a wound dressing over the wound; and

utilizing the wound dressing, promoting growth of the non-pathogenic bacteria, algae, yeast or fungi while discouraging growth of the a pathogenic bacteria or fungi by altering at least one parameter of an environment surrounding the wound or delivering a selective growth medium for the non-pathogenic bacteria, algae, yeast or fungi onto or into the wound.

20. The method according to claim 19, further comprising the step of:

introducing a different, non-pathogenic bacteria, algae, yeast or fungi to the wound without removing the wound dressing.