Prebiotic, probiotic and / or postbiotic treatments, ostomy barriers and adhesives, and methods for improving peristomal skin health

Abstract

The ostomy barrier, skin adhesive, accessory, or peristomal skin treatment comprises a population of non-pathogenic bacteria, fungi, algae, yeasts, or lysates thereof configured to limit the growth of pathogenic organisms in or on the peristomal skin or other body site skin and / or maintain a healthy skin flora. The ostomy barrier, adhesive, accessory, or peristomal skin treatment may also be configured to alter the peristomal or other skin environment to inhibit the growth of pathogenic organisms while promoting the growth of desirable or commensal populations.

Description

[Technical field]

[0001] The present disclosure relates to skin adhesives and methods and devices for ostomy peristomal skin care, and more particularly to ostomy barriers, adhesives, accessories and treatments that introduce, maintain and / or promote the growth of non-pathogenic bacteria or unicellular eukaryotes rather than pathogenic bacteria or saprophytic fungi. [Background technology]

[0002] Skin adhesives are used to secure transcutaneous interfaces to the body for a wide variety of medical devices and wearable sensor technologies. One example is the ostomy barrier, which is used to secure an ostomy appliance, such as an ostomy pouch, to the skin surrounding the user's stoma, i.e., the "peristomal skin." Typically, current ostomy barriers include a skin barrier formed from an adhesive, a backing layer, and an entrance opening that receives the stoma. The ostomy barrier can be attached to the ostomy pouch for a one-piece pouch system. Alternatively, the ostomy barrier can be configured as a faceplate for a two-piece pouch system that includes a body-side coupling configured to engage with a pouch-side coupling attached to the ostomy pouch. Ostomy accessories are used with the ostomy barrier to aid in the correct "fitting" of the barrier, including attachment, sealing, removal, and reapplication.

[0003] Ostomy barriers may remain attached to the skin of the user for extended periods of time to secure the ostomy pouch. The peristomal skin environment beneath the ostomy barrier is warm, dark, moist, and may be intermittently soiled by urine, feces, or other excretions, providing an ideal environment for the growth of microorganisms that may lead to peristomal skin dysbiosis and / or infection. Studies have found that peristomal skin swabs show a variety of viral, bacterial, and fungal infections, as well as colonization with bacterial and fungal microorganisms. Reported adverse effects of infection with pathogenic species include impaired re-epithelialization and cell migration, and epidermal viability, which may affect the healing of peristomal skin complications and conditions. Additionally, many ostomy patients may be immunosuppressed due to comorbidities, including but not limited to diabetes, adjunctive cancer therapy / chemotherapy, or immunosuppressants / immunomodulators used to treat inflammatory bowel disease, which may further increase the risk of peristomal infection and other complications.

[0004] The microbiome is the collective genomic population of microorganisms in a particular environment, e.g., the human body or body part, and its impact on health and disease is an active area of ​​research. Probiotics have been used, e.g., in the gastrointestinal tract and in topical skin care formulations for acne, atopic dermatitis, and other conditions, to selectively promote the growth of non-pathogenic microorganisms over pathogenic microorganisms. It is hypothesized that the non-pathogenic microorganisms change the environment and / or compete with the pathogenic microorganisms, reducing their relative proportion to the total population. Furthermore, differential culture media, nutrients, and / or conditions have been widely used historically to identify and / or isolate microorganisms and are well characterized in the literature. These same media, nutrients, and / or conditions can be used to selectively promote or inhibit certain bacterial, fungal, and / or viral species over others.

[0005] The present disclosure provides improved skin adhesives, ostomy barriers, appliances, accessories and peristomal treatments that contain ingredients and / or conditions that selectively promote and / or maintain non-pathogenic bacteria, fungi, algae, and / or healthy peristomal skin. Summary of the Invention

[0006] Peristomal skin treatments, ostomy accessories, ostomy appliances, skin adhesives or ostomy skin barriers, according to various embodiments, may be configured to promote peristomal skin health by introducing selected species of non-pathogenic bacteria, fungi, algae or yeast, or modulating existing bacterial populations, or by preferentially selecting or encouraging the growth of certain non-pathogenic microorganisms over others.

[0007] In one aspect, the skin adhesive or ostomy barrier can include a skin barrier or adhesive and a population or lysate of non-pathogenic bacteria, fungi, algae or yeast configured to limit the growth of pathogenic organisms in or on the peristomal skin or to maintain a healthy skin flora. The population or lysate of non-pathogenic bacteria, fungi, algae or yeast can be selected from the group consisting of, for example, but not limited to, Lactobacillus, Lactobacillus plantarum, other lactic acid bacteria and Bifidobacterium, and lysates thereof.

[0008] The skin adhesive or ostomy barrier may further comprise a nutrient medium configured to promote the growth of populations of non-pathogenic bacteria, fungi, algae or yeast while inhibiting the growth of pathogenic organisms, hi one embodiment, the ostomy barrier or adhesive may comprise a resealable opening or port for introducing the nutrient medium.

[0009] In one embodiment, the population or lysate of non-pathogenic bacteria, fungi, algae or yeast may be provided on the skin-facing surface of the skin barrier adhesive or incorporated into the barrier or adhesive formulation. For example, the population of non-pathogenic bacteria, fungi, algae or yeast may be provided on a release liner and transferred to the skin-facing surface of the skin barrier or adhesive when the release liner is laminated to the skin barrier or adhesive and removed prior to use.

[0010] In one embodiment, the ostomy barrier or skin adhesive can be configured to deplete oxygen or provide an airtight peristomal area, creating an anaerobic environment that allows for the growth of anaerobic bacteria while limiting the growth of aerobic bacteria. Alternatively, an aerobic environment may be provided to limit the growth of anaerobic bacteria. In another embodiment, the ostomy barrier or adhesive can be configured to maintain a peristomal skin temperature of about 38°C to 48°C with an integrated heating element. A heating pad thereon may be utilized to provide selective temperature conditions. In yet another embodiment, the ostomy barrier or adhesive can be configured or formulated to control the humidity and / or pH of the peristomal skin area within selected ranges to promote the growth of populations of non-pathogenic bacteria, fungi, algae, or yeasts while inhibiting the growth of other organisms or pathogenic organisms. Buffer conditions may also be included to maintain a specific pH that promotes a healthy skin microflora over introduced (e.g., gut or fecal bacteria) or pathogenic species.

[0011] In another aspect, the peristomal skin treatment, ostomy accessory or skin adhesive may comprise a lysate or population of non-pathogenic bacteria, fungi, algae or yeast configured to limit the growth of pathogenic organisms in / on the peristomal skin.

[0012] In some embodiments, the non-pathogenic bacteria, fungi, algae, or yeast populations or lysates may be contained in degradable polymer microspheres or protein carriers that may be configured to degrade or disintegrate upon exposure to a particular range of ionic conditions or a particular range of pH, or in the presence of endogenous or pancreatic proteases known to be present in ileostomy and colostomy waste. In one embodiment, the non-pathogenic bacteria, fungi, algae, or yeast populations may be incorporated and immobilized in a water-soluble carrier formed from polyvinyl alcohol or gelatin or other functional polymers that provide a favorable environment. In one embodiment, the ostomy accessory or peristomal skin treatment may be provided as a stoma powder or paste. In some embodiments, the peristomal skin treatment, ostomy accessory, or skin adhesive may further include a protease inhibitor, such as ethylenediaminetetraacetic acid (EDTA).

[0013] In yet another aspect, a method of improving or maintaining peristomal skin health may include applying a lysate or population of non-pathogenic bacteria, fungi, algae, or yeast to the peristomal or other skin site via a vehicle, and attaching an ostomy barrier or adhesive, respectively, configured to promote growth of the population of non-pathogenic bacteria, fungi, algae, or yeast.

[0014] In one embodiment, the lysate and / or population of non-pathogenic bacteria, fungi, algae or yeast may be provided in a liquid form that can be sprayed or applied to the peristomal skin or other skin site, or may be provided in the form of a gel, paste or powder. The adhesive or ostomy barrier may include a nutrient medium configured to promote the growth of the population of non-pathogenic bacteria, fungi, algae or yeast while inhibiting the growth of pathogenic organisms. In one embodiment, the adhesive or ostomy barrier may be configured to alter at least one aspect of the peristomal skin, such as nutrition, oxygenation, ion concentration, temperature, moisture, humidity or pH, to promote the growth of the population of non-pathogenic bacteria, fungi, algae or yeast while inhibiting the growth of selected pathogenic organisms.

[0015] In one embodiment, the adhesive or ostomy barrier may incorporate solid, gel and / or liquid additives to regulate microclimate humidity. For example, desiccants or vapor pressure regulating additives may be incorporated into the ostomy barrier, allowing for regulation of humidity within the peristomal skin microenvironment. The barrier can be tailored to specific humidity conditions by the selection of different additives and / or desiccants and their proportions within the barrier. Additional humidity specifications can be expanded by combinatorial mixtures of additives with different chemical identities and proportions within the barrier. In another embodiment, the humidity regulating adhesive, skin protectant or device may be applied as an adjunct to peristomal care. Humidity regulation can be customized to promote the growth of beneficial microbial populations, suppress pathogenic organisms, or a combination thereof. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0016] While the present disclosure is applicable to embodiments in various forms, presently preferred embodiments are described below, where it is understood that the disclosure is considered to be illustrative and that it is not intended to limit the disclosure to the specific embodiments illustrated.

[0017] The human skin microbiome differs by anatomical site due to microclimates, e.g., dry, sebum, and wet microclimates. Surgically created stomas may disrupt the gut and / or skin microbiome to different degrees, altering the native microbiome therein. The stoma also creates a unique microclimate at the interface between the skin and gut for a potentially unique dysbiotic mixed skin / gut microbiome. The present disclosure discloses methods and devices to maintain, regulate, or alter the ostomy environment to maintain and / or re-establish peristomal skin health, according to various embodiments.

[0018] As used herein, probiotics are live microorganisms that are administered to confer a health benefit on the host. The health benefit of probiotics can vary depending on the bacterial strain, the method of delivery or application, and the clinical condition.

[0019] As used herein, a prebiotic is a compound or ingredient that can selectively stimulate the growth and / or activity of one or more strains of microorganisms that are beneficial to the health of the host.

[0020] Postbiotics, as used herein, refer to soluble factors (products or metabolic by-products) secreted by live microorganisms or released following lysis of the microorganism, such as enzymes, peptides, teichoic acids, muropeptides derived from peptidoglycan, polysaccharides, cell surface proteins and organic acids.

[0021] In this disclosure, for simplicity, monocultures are described, however, co-cultures or polycultures of two or more bacterial species, fungal, algal species, or combinations thereof may also be used.

[0022] In one embodiment, peristomal skin treatments (e.g., skin protectants, skin conditioners, lotions, liquids, etc.) or ostomy appliances or accessories (e.g., ostomy barriers, stoma rings, stoma powders, etc.) can be configured to deliver a single bacterial species or a mixture of bacteria, or a single lysate or a mixture of lysates, either at once or in sequence, to maintain and improve peristomal skin health. The bacteria can be delivered in various forms, such as in suspension (e.g., in a liquid suspension that can be sprayed, painted, or poured onto the skin), lyophilized powder, and / or spores immobilized on a solid substrate that can be applied to the peristomal skin and isolate the skin from ostomy effluent, such as an ostomy barrier comprising a hydrocolloid or other biomaterial. Genera of microorganisms suitable for application to peristomal skin can include, but are not limited to, Lactobacillus, Lactobacillus plantarum, Lactobacillus acidophilus, and Bifidobacterium, or lysates thereof. Such microorganisms are currently used as over-the-counter (OTC) probiotics and are therefore readily available. Many other bacterial, fungal and eukaryotic species, including algae, such as Staphylococcus and / or Streptococcus, may also be suitable for application to the peristomal skin.

[0023] Bacterial cultures or inocula of non-pathogenic bacteria, or lysates thereof, can be applied to at-risk, irritated, lacerated, colonized, or infected peristomal skin to competitively colonize the area and prevent attachment, colonization, and growth of pathogenic bacteria. Examples of application methods can include sprays, swabs, dressings, immobilized cultures, or spore strips. In some embodiments, selective nutrients or conditions for the selected non-pathogenic organism(s) can be incorporated into the delivery vehicle to support the growth of selected bacteria, algae, yeast, fungi, etc. In one embodiment, organisms or biofilm-forming cocktails of specific species that limit the growth of other species by release of natural antibiotics or competition for nutrients or attachment sites can be introduced to the peristomal skin by ostomy barriers, attachments, or other application methods according to various embodiments.

[0024] In one embodiment, the ostomy skin barrier may include a lysate or population of bacteria, algae, yeast or fungi that is applied to the peristomal skin in the form of an additive, gel or ingredient. In another embodiment, the bacteria or bacterial lysate may be formulated into a spray-dried powder format that can be used directly as a stoma powder or incorporated into wipe formulations, adhesive compositions, adhesive tape compositions, seal or paste formulations, etc. Reservoirs, gels or degradable microspheres may be utilized as delivery vehicles to change peristomal conditions over time.

[0025] In some embodiments, bacterial formulations can be incorporated into the ostomy pouch film to reduce odor-causing bacteria and / or promote a skin-friendly environment. For example, the ostomy pouch can include a population of non-pathogenic bacteria, fungi, algae, yeast, or lysates thereof. In another example, the ostomy pouch can be formed from a polymer film that includes a population of non-pathogenic bacteria, fungi, algae, yeast, or lysates thereof. Such an ostomy pouch can promote a healthy microbiome environment even if the user experiences reflux of the pouch contents. In one embodiment, the ostomy pouch can be formed from a multi-layer film that includes an inner layer that includes a population of non-pathogenic bacteria, fungi, algae, yeast, or lysates thereof.

[0026] In one embodiment, a lysate or population of selected bacteria, algae, yeast or fungi may be first applied to the peristomal skin, for example by spray or powder application, followed by application to an ostomy barrier configured to maintain desirable conditions for the applied population of bacteria, algae, yeast or fungi.

[0027] In one embodiment, the peristomal skin treatment, or ostomy appliance or accessory, may be configured to selectively promote the growth of a preferred species or mixture of preferred species, or selectively inhibit the growth of an undesirable species or mixture of undesirable species. For example, the peristomal skin treatment, or ostomy appliance or accessory, may include prebiotics, postbiotics, and / or selective modulation of interface / environmental conditions to control the microflora in the peristomal skin, and in acute or chronic skin wounds and skin conditions, such as atopic dermatitis or psoriasis. The peristomal treatment, or ostomy appliance or accessory, may or may not contain or deliver live bacteria or microorganisms.

[0028] In some embodiments, the ostomy barrier may contain a specific growth medium or otherwise alter the peristomal skin environment to maintain or promote the growth of certain types of bacteria while inhibiting the growth of others. As used herein, the peristomal skin environment may include, but is not limited to, the ion concentration, temperature, pH, humidity and moisture levels of the peristomal skin. For example, a hydrocolloid ostomy barrier may include a material that provides a selective nutritional composition, induces hyperoxia / hypoxia / anoxia, or alters the pH of the peristomal skin to promote the growth of certain species or classes of organisms while restricting the growth of others. Such an ostomy barrier may be applied to at-risk, infected or inoculated peristomal skin sites to establish, restrict or maintain differential organism populations. In one embodiment, the ostomy appliance may include a skin barrier material that includes a nutrient medium configured to selectively promote the growth of non-pathogenic bacterial, fungal, algae, yeast populations or their lysates while inhibiting the growth of pathogenic organisms.

[0029] In one embodiment, a peristomal treatment, or ostomy barrier or accessory, may be configured to modulate the relative populations of aerobic and anaerobic bacteria to improve peristomal skin health. For example, an ostomy barrier may be configured to deplete oxygen or provide an airtight peristomal region, creating an anaerobic environment that limits the growth of aerobic bacteria but permits or encourages the growth of anaerobic bacteria.

[0030] In one embodiment, the ostomy barrier may be configured to use an integrated heating element powered by a battery, capacitor or other power source to control the peristomal skin temperature within a range selected for differential survival of bacteria of the Lactobacillus genus (e.g., 43°C to 46°C) that is outside the temperature range for successful growth of pathogenic Staphylococcus aureus (optimum temperature 37°C) and Staphylococcus epidermidis (optimum temperature 26°C to 37°C) or Pseudomonas aeruginosa (optimum temperature 37°C).

[0031] In one embodiment, the ostomy barrier may include a resealable opening or port for introducing a nutrient medium configured to promote the growth of selected bacteria as desired. In such an embodiment, bacterial inoculation may also be performed without altering the ostomy barrier.

[0032] In one embodiment, the ostomy barrier may include an inlet port, an outlet port, a humidity regulation reservoir, or a combination thereof that may be configured to control humidity or gas concentration. In such an embodiment, the ostomy barrier may include a meter for measuring or detecting the humidity or gas level. Regulation of environmental humidity may allow dynamic modification of the peristomal microbiome environment. For example, by lowering the relative humidity of the peristomal area, the driving pressures for the dry skin microbiome may be upregulated, as these driving pressures may more closely resemble the microenvironment of healthy non-sebaceous skin tissue. In one embodiment, the peristomal treatment may dry the peristomal skin to differentially select for dehydration-tolerant species over pathogenic species that thrive in moist environments, such as water-borne bacteria (e.g., Pseudomonas aeruginosa).

[0033] In one embodiment, the ostomy barrier may include a material that contains or releases a specific carbon source to maintain or promote the growth of one or more bacterial species while inhibiting the growth of other bacterial species. In some embodiments, reservoirs, gels, or degradable microspheres can be used to generate or change peristomal skin conditions over time. For example, degradable polymer microspheres containing bacteria, spores, culture medium, and culture medium components may be triggered to release based on the degradation of the carrier, which may be adjusted based on the ionic conditions (hypotonic / isotonic / hypertonic) or pH level of the skin. In another example, a protein carrier may contain bacteria, spores, culture medium, and / or culture medium components, and the protein carrier may be configured to disintegrate in the presence of endogenous proteases, which may be elevated in concentrations in irritated, inflamed, or infected peristomal skin, or exogenous proteases, such as those found in ileostomy and, to a lesser extent, colostomy output. The protein carrier may be configured to disintegrate in the presence of enzymes introduced from the stoma, such as pancreatic proteases. Alternatively, degradable carbohydrate- or lipid-based polymers can be used to deliver bacteria, spores, media, or media components in the presence of endogenous or pancreatic amylases or lipases, respectively.

[0034] The probiotic organisms or prebiotic compounds may also be incorporated and immobilized in water-soluble carriers, such as polyvinyl alcohol (PVOH) or gelatin, or other functional polymer microcapsules. In one embodiment, the immobilized probiotic organisms or prebiotic compounds may be applied to a release liner and laminated to the ostomy barrier, and the probiotic organisms or prebiotic compounds may be transferred to the skin-facing surface of the ostomy barrier when the release liner is removed prior to use. When the ostomy barrier is attached to the peristomal skin of the user, the immobilized probiotic organisms or prebiotic compounds may be disposed at the interface between the ostomy barrier and the skin of the user, and the probiotic organisms or prebiotic compounds may be released by exposure to moisture, sweat, or stoma effluent. In some embodiments, a mixture of prebiotic organisms and probiotic compounds may be provided on the skin-facing surface of the ostomy barrier to promote the growth of beneficial microorganisms.

[0035] The pH level of the peristomal skin can be controlled within a range selective for the differential survival of Lactobacillus bacteria (e.g., below pH 5.0, which is outside the pH range for successful growth of pathogenic Staphylococcus aureus (optimum pH 7.4-7.6), Staphylococcus epidermidis (optimum pH 6.8), or Pseudomonas aeruginosa (optimum pH 6.6-7.0). In some embodiments, both the pH level and temperature of the peristomal skin can be controlled within a selected range. In one embodiment, the skin adhesive, peristomal treatment, ostomy barrier, or accessory can include a material that is metabolized to produce a metabolic product that lowers the pH for the selective survival of Lactobacillus species.

[0036] In one embodiment, the skin adhesive, peristomal treatment, ostomy barrier or accessory may be configured to provide hypertonicity (high salinity) that may be differentially selective for Lactobacillus over other bacterial species such as Pseudomonas and Staphylococcus. Hypertonic conditions can be created, for example, by brining with NaCl, for the selective survival of Lactobacillus species over other bacterial flora.

[0037] In some embodiments, yeast or algae may be introduced to the peristomal skin in addition to or instead of bacteria of the Lactobacillus genus. In such embodiments, the peristomal treatment or ostomy barrier may be configured to provide a peristomal environment conducive to yeast or algae growth. Suitable yeast species for peristomal skin application may include Saccharomyces cerivisae (used in brewing beer), which has an optimum pH of 4 and an optimum temperature of 26° C. Suitable algae species may include species commonly used in food production, such as Chlorella (optimum pH 10-10.5, optimum temperature 15° C., low salinity), Spirulina (optimum temperature 32° C., pH 9-9.5), and marine species evolved in seawater that may have optimal growth in hypertonic (approximately 0.6 M) conditions.

[0038] According to various embodiments of the present disclosure, to limit the growth of pathogenic species, competitor organisms may be introduced that occupy binding sites in the exposed extracellular matrix (ECM) of the peristomal skin and compete for nutrients and other resources. In some embodiments, extremophilic archaea may also be utilized because these bacteria thrive under non-physiological conditions that may not be detrimental to the healing or maintenance of healthy peristomal skin. These species can survive high salinity and high or low pH environments, as well as extreme temperatures that may be selective for typical pathogenic wound bacteria or fungi.

[0039] All patents referenced herein are hereby incorporated by reference in their entirety, whether or not expressly stated within the text of this disclosure.

[0040] In this disclosure, the words "a" or "an" are to be construed as including both the singular and the plural. Conversely, references to the plural shall, where appropriate, include the singular.

[0041] From the foregoing description, it will be seen that numerous modifications and variations can be made without departing from the true spirit and scope of the novel concepts of the present disclosure. It is understood that no limitation to the specific embodiments shown is intended or should be inferred. The present disclosure is intended to cover, by the appended claims, all modifications that fall within the scope of the claims.

Claims

1. An ostomy appliance comprising a skin barrier material and a population of non-pathogenic bacteria, fungi, algae, yeasts, or lysates thereof ("population"), the population configured to limit the growth of pathogenic organisms and / or selectively enhance the growth and maintenance of non-pathogenic or commensal bacteria in the peristomal skin environment.

2. The ostomy appliance of claim 1 , wherein the mass is provided on a skin-facing surface of the skin barrier material or incorporated into the skin barrier material.

3. 10. The ostomy appliance of claim 1, further comprising a nutrient medium configured to selectively promote growth of the population while inhibiting growth of the pathogenic organisms.

4. 10. The ostomy appliance of claim 1, wherein the mass is provided on a release liner, the release liner is laminated to the skin barrier material, and the mass is transferred to the skin-facing surface of the skin barrier material.

5. 10. The ostomy appliance of claim 1, wherein the skin barrier material is formed from a skin barrier formulation incorporating the population, and the population migrates to the skin-facing surface of the skin barrier material.

6. 2. The ostomy appliance of claim 1, wherein the population is selected from the group consisting of Lactobacillus, Lactobacillus plantarum, Lactobacillus acidophilus, and Bifidobacterium, and lysates thereof.

7. 2. The ostomy appliance of claim 1, wherein the population is selected from the group consisting of Saccharomyces cerevisiae, Chlorella, Spirulina, Archaea, and lysates thereof.

8. 10. The ostomy appliance of claim 1, configured to create an anaerobic environment that depletes oxygen or provides an airtight peristomal area to limit the growth of aerobic bacteria while allowing the growth of anaerobic bacteria.

9. 10. The ostomy appliance of claim 1, configured to provide oxygen and create an aerobic environment, allowing the growth of aerobic bacteria while limiting the growth of anaerobic bacteria.

10. 10. The ostomy appliance of claim 1, configured to maintain a peristomal skin temperature of about 38°C to 48°C.

11. 10. The ostomy appliance of claim 1, further comprising a resealable opening or port for introducing a nutrient medium configured to promote growth of the population while inhibiting growth of other organisms or pathogenic organisms.

12. 10. The ostomy appliance of claim 1, configured to control humidity of the peristomal skin area within selected ranges to promote growth of the population while inhibiting growth of the pathogenic organisms.

13. 10. The ostomy appliance of claim 1, configured to control a pH level of the peristomal skin area within a selected range to promote growth of the population while inhibiting growth of the pathogenic organisms.

14. The ostomy appliance of claim 1 which is an ostomy barrier or an ostomy ring.

15. 10. The ostomy appliance of claim 1, wherein the ostomy appliance is an ostomy pouch system, the ostomy pouch system comprising an ostomy pouch formed from a polymeric film containing the mass.