Background

Technical Field

The present disclosure relates to antibiofilm compositions, the methods of disruption of biofilms, and reduction and/or elimination of microbes, especially related to wounds, and medical device surfaces that are in contact with biological tissue.

Background

Wounds can be categorized as acute or chronic wounds. Examples of acute wounds are surgical incision, cuts, abrasions and trauma wounds. Chronic wounds include pressure ulcers, diabetic foot ulcers, arterial ulcers, venous leg ulcers, and mixed etiology ulcers among others. Regardless of etiology, all chronic wounds have a similar biochemical profile in relation to elevated proinflammatory cytokines, elevated matrix metal loproteases and diminished growth factors. Additionally, the cellular profile of a chronic wound, irrespective of wound type, demonstrates a constant excess of neutrophils, suggesting a persistent state of inflammation exists. Combining this common biochemistry and cellularity with the observation that biofilms are prevalent in chronic wounds raises the possibility of biofilm presence being the common factor that induces a state of chronic inflammation leading to non-healing and the principal cause of wound decreased sensitivity to antimicrobials.

One of the main challenges in achieving wound closure is that of infection. Infection can result from the formation of biofilms where a clinical inflammatory response is not generated. Biofilms form when planktonic (free floating) microorganisms attach to a surface, alter their phenotype, form micro colonies and self-express a matrix of extracellular polymeric substance (EPS). This EPS provides the microbial communities with protection from cellular, antibiotic and chemical attack, Within these communities the bacteria communicate with each other through a chemical signaling pathway - "quorum sensing" (Qs) that can lead to the expression of virulence factors.

In addition to wounds, biofilms are also known to form on other abiotic surfaces such as medical devices e.g. orthopaedic implants, catheters, and other devices that dwell in the body temporarily or permanently.

The presence of biofilms in wounds, tend to be the cause of delayed wound healing resulting in increased patient morbidity, longer hospital stay, and increased cost of care. Similarly, biofilm formation on indwelling devices can lead to infection that can only be resolved through removal of the implant and has major implications for future patient well-being

In order to promote wound healing and to minimize the risk of infection, it is important to either prevent the formation of biofilms or to promptly disrupt the biofilms and reduce the bioburden in a wound bed. In the latter case, a combination of regiment is required, namely, removing the slough of biofilm and to disrupt the EPS, and attacking the microbial colonies with an effective antibiofilm composition. Example antibiofilm methods and compositions include US

2008/0118573 that describes a method of treating a biofilm comprising a composition containing a heavy metal. US 8,784,790 describes a method to treat chronic wounds, which include steps of debriding the necrotic or devitalized tissue, and then applying an aqueous solution that solvates the EPS comprising a metal ion sequestering agent, a surfactant, and a buffering agent. US 2014/0005605 describes a coating for a device comprising a polymer and an agent that inhibits biofilm formation such as a quorum sensing inhibitor.

However, there is a need for an antibiofilm composition and method to disrupt biofilms in wounds and medical devices that is more effective and advantageous over conventional systems. SUMMARY

One objective of the present invention is to provide antibiofilm composition and method that is effective to disrupt biofilms in wounds and medical devices. A further objective of the present invention is to inhibit and/or reduce the growth of biofilms in wounds and medical devices.

According to a first aspect of the present invention there is provided an antibiofilm composition comprising: at least one quorum sensing inhibitor, at least one iron-chelating agent, and at least one antimicrobial agent; wherein the composition reduces the microbial count by at least one order of magnitude in 24 hours. Further, the composition may comprise at least one extracellular polymeric substance disrupting agent. The extra-cellular disrupting agent enables quicker access to the bacteria within the biofilm by the antimicrobial agent and hence a reduction in the proliferation of bacteria and the promotion of wound healing.

Optionally, the quorum sensing inhibitor may be nitro-pyridine N-oxide, pyridine N-oxide, polypyridine N-oxide and its copolymers, synthetic and natural peptides, sulfur-based compounds such as S-phenyl-L-cysteine sulfoxide and diphenylsulfide, meta-bromo-thiolactone (mBTL), and/or combinations thereof.

Advantageously, the present combination of components and in particular the synergy associated with the present combination enables lower concentrations of antimicrobially active substances that is currently demanded for wound treatment. Accordingly, the subject invention is advantageous to reduce adverse effects for patients by exposure to wound treatment formulations in addition to increasing biocompatibility of the formulation so as to minimize irritation and disruption to healthy tissue and patient wellbeing generally.

Optionally, the quorum sensing inhibitor may be present in the antibiofilm composition in the range of 0.0001 to 10 wt%, preferably 0.001 to 5 wt%, 0.005 to 4 wt%, or 0.01 to 3 wt%, 0.01 to 1 wt%, 0.05 to 1 wt%, or 0.08 to 0.8 wt% of the total composition. Optionally, the iron chelating agent may be selected from polycarboxylic acids such as ethylenediaminetetraacetic acid (EDTA), HEDTA, diethylenetriaminepentoacetic acid (DTP A), and their salts, phytic acid, citric acid, oxalic acid, tartaric acid, galactonic acid, and their salts, esters, acid chlorides, anhydrides, and the like, sodium pyrophosphate, pyridoxal isonicotinoyl hydrazine (PIH), oxachelin, curcumin, and/or combinations thereof.

The iron chelating agent may be present in the antibiofilm composition in the range of 0.0001 to 20 wt%, preferably 0.0001 to 10 wt%, 0.0001 to 5 wt%, 0.001 to 10 wt%, 0.001 to 5 wt%, 0.005 to 3.5 wt%, 0.05 to 3.5 wt%, or 0.1 to 3.5 wt% or 0.01 to 5 wt% of the total composition.

The antimicrobial agent may be selected from silver and silver salts, silver sulfadiazine, iodine, povidone-iodine, cedexomer-iodine, chlorohexidine gluconate, chloramine T, quaternary ammonium compounds, Poly(hexam ethylene biguanide)hydrochloride [PHMB], zinc and its salts, copper and its salts, ceragenins, octenidene hydrochloride, benzalkonium chloride and/or combinations thereof.

Optionally, the antimicrobial agent may be present in the antibiofilm composition in the range of 0.00001 to 5 wt%, preferably 0.0001 to 4 wt%, 0.0001 to 3 wt%, 0.001 to 2 wt%, 0.01 to 2 wt%, 0.08 to 1.8 wt%, 0.08 to 0.8 wt% or 0.8 to 2 wt% of the total weight % of the composition.

Optionally, the antibiofim composition may be a liquid, solid, powder, foam, mousse, liquid gel, solid gel, semi-solid, hydrogel, pad, fibre, film, woven fabric, non-woven fabric, mesh, an adhesive, and/or combinations thereof. Further, the antibiofilm composition may be sprayed onto the wound or surface of a medical device with or without a propellant.

Optionally, the antibiofilm composition comprises: Quorum sensing inhibitor: Nitro-pyridine N- oxide at 0.005-2 wt%; Iron chelating agent: EDTA at 0.001-3 wt%; Antimicrobial: Silver nitrate at 0.00001 - 2 wt%; and DI water at Qs. Optionally, the antibiofilm composition comprises: Quorum sensing inhibitor: meta

bromo-thiolactone (mBTL),at 0.005 - 2 wt%; Iron chelating agent: Citric acid at 0.001 - 3 wt%; Antimicrobial: Silver citrate at 0.00001 - 2 wt%; and DI water at Qs.

Optionally, the antibiofilm composition comprises: Quorum sensing inhibitor: Nitro- pyridine N-oxide at 0.005 - 2 wt%; Iron chelating agent: Citric acid at 0.001 - 3 wt%;

Antimicrobial: Silver citrate at 0.00001 - 2 wt%; Biosurfactant: R90L (Rhamnolipid) at 0.03 - 0.5 wt%; DI water at Qs.

Optionally, the antibiofilm composition comprises: Quorum sensing inhibitor: S-phenyl L-cysteine sulfoxide at 0.005 - 2 wt%; Iron chelating agent: Citric acid at 0.001 - 3 wt%;

Antimicrobial: PHMB at 0.00001 - 2 wt%; Biosurfactant: R90L (Rhamnolipid) at 0.03 - 0.5 wt%; and DI water at Qs.

Optionally, the antibiofilm composition comprises: Quorum sensing inhibitor: S-phenyl L- cysteine sulfoxide at 0.005 - 2 wt%; Iron chelating agent: Citric acid at 0.001 - 3 wt%;

Antimicrobial: PHMB at 0.00001 - 2 wt%; Extra-cellular polymer substance disrupting agent: Xylitol at 0.01 - 5 wt%; and DI water at Qs.

Optionally, the antibiofilm composition comprises: Quorum sensing inhibitor: Nitro-pyridine N- oxide at 0.005 - 4 wt%; Iron chelating agent: EDTA at 0.0001 - 5 wt%; Antimicrobial:

octenidine hydrochloride at 0.0001 - 4 wt%; and Solvent: DI water at Qs.

Optionally, the antibiofilm composition comprises: Quorum sensing inhibitor: meta-bromo- thiolactone at 0.005 - 4 wt%; Iron chelating agent: citric acid at 0.0001 - 5 wt%; Antimicrobial: PHMB at 0.0001 - 4 wt%; Extra-cellular polymer substance disrupting agent: rhamnolipid at 0.001 - 3 wt%; and Solvent: DI water at Qs.

Optionally, the antibiofilm composition comprises: Quorum sensing inhibitor: meta-bromo- thiolactone at 0.005 - 4 wt%; Iron chelating agent: EDTA at 0.005 - 2.5 wt%; Antimicrobial: PHMB at 0.0001 - 4 wt%; Extra-cellular polymer substance disrupting agent: rhamnolipid at 0.001 - 3 wt%; and Solvent: DI water at Qs.

Optionally, the antibiofilm foam composition comprises: Quorum sensing inhibitor: S- phenyl-L-cysteine sulfoxide at 0.005 - 2 wt%; Iron chelating agent: Citric acid at 0.001 - 3 wt%; Antimicrobial: PHMB at 0.00001 - 2 wt%; Extra-cellular polymer substance disrupting agent: Xylitol at 0.01 - 5 wt%; Soma Foama® Flexible Silicone Castable Foam (Part A + Part B) (from Smooth-On, Inc.) at min. 20 wt%. Soma Foama® Flexible Silicone Castable Foam is a two- component platinum-cured silicone foaming composition from Smooth-on Inc. The components are added to Part B of the silicone foam, and then mixed with Part A to cure and form the final foam-in-place solid.

Optionally, a hydrogel adhesive-based antibiofilm composition comprises: Quorum

sensing inhibitor: S-phenyl-L-cysteine sulfoxide at 0.005 - 2 wt%; Iron chelating agent: Citric acid at 0.001 - 3 wt%; Antimicrobial: PHMB at 0.00001 - 2 wt%; Extra-cellular polymer substance disrupting agent: Xylitol at 0.01 - 5 wt%; PVP:PEO: Water hydrogel adhesive* at Qs. *The PVP:PEO: Water hydrogel adhesive is prepared according to US patent 4,750,482.

Optionally, a powder-based antibiofilm composition comprises: Quorum sensing

inhibitor: S-phenyl-L-cysteine sulfoxide at 0.005 - 5 wt%; Iron chelating agent: Citric acid at 0.001 - 5 wt%; Antimicrobial: Povidone-Iodine at 0.0001 - 10 wt%; Superabsorbent:

WasteLock 770 (from M2 Technologies) at 0.01 - 20 wt%; Others (hydrocolloid powders) at Qs.

According to a second aspect of the present invention there is provided a method of disrupting biofilms in wounds include the steps of: i. debriding the wound; and ii. applying an anti-biofilm composition to the wound, comprising: at least one quorum sensing inhibitor, at least one iron- chelating agent, and at least one antimicrobial; wherein the composition reduces the microbial count by at least one order of magnitude in 24 hours. According to a third aspect of the present invention there is provided a method of disrupting biofilms in wounds that may include the steps of: i. applying antibiofilm composition directly to the wound, and; ii. attaching an article to the wound; wherein the antibiofilm composition comprises: at least one quorum sensing inhibitor, at least one iron chelating agent, and at least one antimicrobial; wherein the composition reduces the microbial count by at least one order of magnitude in 24 hours.

According to a fourth aspect of the present invention there is provided a method of disrupting biofilms in wounds include the steps of: i. applying antibiofilm composition to an article and; ii. attaching the article to the wound; wherein the antibiofilm composition comprises: at least one quorum sensing inhibitor, at least one iron chelating agent, and at least one antimicrobial;

wherein the composition reduces the microbial count by at least one order of magnitude in 24 hours.

Optionally, the article attached to the wound may be gel, lotion, powder, pad, dressing, film, fabric, non-woven, foam, mesh, adhesive, and/or combinations thereof.

According to a fifth aspect of the present invention there is provided a method of disrupting biofilms in wounds that may include the steps of: i. debriding the wound; and ii. applying an anti-biofilm composition to the wound, comprising: at least one agent that disrupts the extracellular polymer substance, at least one quorum sensing inhibitor, at least one iron chelating agent, and at least one antimicrobial; wherein the composition reduces the microbial count by at least one order of magnitude in 24 hours.

Optionally, the extra-cellular polymer substance disrupting agent may be xylitol, lactoferrin, combinations of xylitol and lactoferrin, citric acid, surfactants, and/or combinations thereof.

Optionally, the extra-cellular polymer substance disrupting agent may be present in the antibiofilm composition in the range of 0.0001 to 20 wt%, preferably, 0.001 to 10 wt%, 0.001 to 3 wt%, 0.01 to 5 wt%, 0.01 to 3 wt%, 0.01 to 1 wt%, or 0.08 to 0.8 wt% of the total composition. According to a sixth aspect of the present invention there is provided a method of disrupting biofilms in wounds according to any one of the above embodiments, wherein the antibiofilm composition may be used before, after, or during negative pressure wound therapy treatment (NPWT).

According to a seventh aspect of the present invention there is provided a wound cleanser composition comprising an antibiofilm composition, which comprises at least one quorum sensing inhibitor, at least one iron chelating agent, at least one surfactant, and at least one antimicrobial; wherein the composition reduces the microbial count by at least one order of magnitude in 24 hours.

According to an eighth aspect of the present invention there is provided a wound cleanser composition comprising an antibiofilm composition, which comprises at least one agent that disrupts the extra-cellular polymer substance, at least one quorum sensing inhibitor, at least one iron chelating agent, at least one surfactant, and at least one antimicrobial; wherein the composition reduces the microbial count by at least one order of magnitude in 24 hours.

According to a ninth aspect of the present invention there is provided a wound dressing comprising: i. a wound contacting article and; ii. an antibiofilm composition applied to the article, wherein the antibiofilm composition further comprises at least one quorum sensing inhibitor, at least one iron chelating agent, at least one surfactant, and at least one antimicrobial; wherein the composition reduces the microbial count by at least one order of magnitude in 24 hours.

According to a tenth aspect of the present invention there is provided a wound dressing comprising: i. a wound contacting article and; ii. an antibiofilm composition applied to the article, wherein the antibiofilm composition further comprises at least one agent that disrupts the extra-cellular polymer substance, at least one quorum sensing inhibitor, at least one iron chelating agent, at least one surfactant, and at least one antimicrobial; wherein the composition reduces the microbial count by at least one order of magnitude in 24 hours. The wound dressing may be a contacting article that may be a foam, film, mesh, fibers, non-woven fabric, woven fabric, gel, and the like. The dressing may be an adherent dressing with a pressure sensitive adhesive, or a non-adherent dressing. Further the dressing may be part of another cover dressing that holds this dressing in place.

In aspects, the antibiofilm composition may be a paste, liquid, powder, foam, solid, fabric, fiber, film, liquid gel, curing gel and/or combinations thereof.

In aspects, the antibiofilm composition may be delivered to the wound or surface of a medical device in a flowable state such as a liquid, paste, foam, gel, which then changes to a non- flowable state. This transition from flowable to non-flowable may be triggered by drying, polymerization, chemical reaction, hydration, energy activated such as thermal, electromagnetic radiation (example: radio waves, microwaves, infrared radiation, visible light, ultraviolet radiation, X-rays and gamma rays).

In aspects, the debridement of the wound may be achieved by enzymatic, mechanical, chemical, biologic, electrical, ultrasound, radio frequency (RF), microwave, and/or other energy induced.

In aspects, the method of disrupting biofilms in a wound may include applying the antibiofilm composition directly without debriding the wound.

In aspects, the antibiofilm composition may be allowed to stay in contact with the wound for a period less than 24 hours. The antibiofilm composition could be part of a wound cleanser. By wound cleanser is meant any liquid that can be used to remove dead or necrotic tissue, debris, and other extraneous matter from a wound.

In other aspects, the antibiofilm composition may be in contact with the wound for a period greater than 24 hours. The antibiofilm composition may further comprise at least one surfactant, biosurfactant of synthetic and/or natural origin. The surfactants could be anion, cationic, amphoteric or non-ionic, and/or combinations thereof. Suitable examples of surfactants are glycolipids, rhamnolipids, lipopeptides, polysaccharide-protein complexes, phospholipids, fatty acids, neutral lipids, phosphoryl choline, esters of sodium, alkybenzyl sulfonates, sulfosuccinates, alkyl phosphates, long chain alcohols, polyalkyleneoxides, sodium alkyl sulfates, and alkyl sulfates. Biosurfactants include mannoserythritol lipid B, sodium surfactin, and/or combinations thereof.

In aspects, the antibiofilm composition may be applied to an article, such as a dressing or a patch prior to applying to the tissue.

In other aspects, the antibiofilm composition may be applied as a liquid directly to the wound, such that the composition cures in place to a solid or semi-solid or gel consistency.

In aspects, the antibiofilm composition may be delivered to the wound on a polymer matrix, wherein the polymer matrix may be hydrophobic or hydrophilic or amphiphilic. The polymer matrix may be a scaffold, which may be degraded by the wound bed, thereby exposing or releasing the antibiofilm composition.

In other aspects, the antibiofilm composition may include pain relieving agents or other active substances.

In another aspect, the antibiofilm composition may be delivered to the wound as a hydrogel.

In other aspects, the antibiofilm composition may be used before, after, or during negative pressure wound therapy treatment (NPWT).

In aspects, the antibiofilm composition may be delivered to wound or surface of a medical device as a film forming coating. By film forming, it is meant that the composition may be a liquid or semi-solid, or paste, which then transforms to a film on the surface applied either by drying, polymerization, chemical reaction, hydration, curing, heating, or other energy activation, and/or combinations thereof.

According to an eleventh aspect of the present invention there is provided a wound cleanser comprising an antibiofilm composition, comprising at least one quorum sensing inhibitor, at least one iron chelating agent, at least one surfactant, and at least one antimicrobial; wherein the composition reduces the microbial count by at least one order of magnitude in 24 hours.

In other aspects, the antibiofilm composition may comprise other components such as superabsorbent polymers, hydrocolloid powders, nanoclay, and other fillers to absorb the fluid.

Furthermore, in aspects the antibiofilm composition may be delivered to the wound in a woven and/or non-woven fabric, pad, foam, mesh, film, and/or combinations thereof.

According to a twelfth aspect of the present invention there is provided a kit comprising an antibiofilm composition, a debrider or surface roughness increasing agent, and a dressing, wherein the antibiofilm composition comprises at least one quorum sensing inhibitor, at least one iron chelating agent, at least one surfactant, and at least one antimicrobial; wherein the composition reduces the microbial count by at least one order of magnitude in 24 hours.

According to a thirteenth aspect of the present invention there is provided a kit comprising an antibiofilm composition, a debrider or surface roughness increasing agent, and a dressing, wherein the antibiofilm composition comprises at least one agent that disrupts the extra-cellular polymer substance, at least one quorum sensing inhibitor, at least one iron chelating agent, at least one surfactant, and at least one antimicrobial; wherein the composition reduces the microbial count by at least one order of magnitude in 24 hours. DETAILED DESCRIPTION

Particular embodiments of the present disclosure are described herein below; however, the disclosed embodiments are merely examples of the disclosure and may be embodied in various forms. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present disclosure in virtually any appropriately detailed structure.

The term "biofilm" refers to a layer of extracellular polymeric substances (EPS) with microbial colonies buried within the EPS on or in a wound, soft tissue, or medical device. The term "extracellular polymeric substances" (or EPS) refers to biopolymers and other compounds that are produced by microorganisms such as bacteria. The EPS is mainly polysaccharides, as well as proteins, nucleic acids, lipids and humic substances. The exact composition depends on the type of microorganisms, the age of the biofilm, and the environment in which they exist. The EPS is known to play an important role in cell aggregation, cell adhesion, and biofilm formation, and protect cells from a hostile environment. The term "antibiofilm" means preventing, eliminating, or reducing the microbial count. The term disrupting biofilms means breaking the matrix hosting the microbial colonies and subsequently killing the microbes to reduce or eliminate their count.

The term quorum sensing inhibitor refers to any molecule, chemical, compound, protein, or amino acid that can inhibit the communication between bacteria/microbial colonies within in a biofilm or a biofilm precursor zone. The quorum sensing inhibitor accordingly weakens a biofilm community by disrupting the biofilm as well as inhibiting biofilm reformation. Accordingly, wound healing is beneficially affected.

The term "chelating" agent refers to any chemical or compound that can bind or chelate an ion, such as a metal ion. For example, an iron-chelating agent is an agent that chelates iron, and traps the metal. The action of such chelating agents could be temporary or permanent. As will be appreciated in wounded tissue, high iron concentrations can be expected as iron is essential for microorganisms proliferation. The subject invention is effective to chelate free iron and impede microbial growth.

The term "antimicrobial agent" refers to a substance that has the ability to cause at least a 1 -log order reduction in one or more aerobic or anaerobic bacteria present which accordingly is beneficial for wound healing.

The subject invention is particularly beneficial in that the inventors have identified a synergy between the quorum sensor inhibitor, the iron chelating agent and antimicrobial agent that leads to an enhancement of performance of the antibiofilm composition relative to the effect that would otherwise be provided by the individual components. In particular, disruption of the biofilm community by the quorum sensor inhibitor leads to a more planktonic bacteria that can be killed more rapidly by the antimicrobial agent. Additionally, chelation of iron reduces the effective survival rate of bacteria to greatly facilitate wound healing.

The subject invention is further advantageous in that the combination of components of the antibiofilm composition as a formulation does not provide negative or adverse side effects during or following wound treatment. The subject invention is advantageous to minimize or eliminate a requirement for disinfecting solutions that otherwise increase the burden of patient care and the potential irritation caused to unaffected tissue resulting from over or prolonged exposure to such disinfecting formulations.

Antibiofilm compositions, and articles efficacy testing

There are several known assays to quantify the microbial count, and to determine the efficacy of an antimicrobial in a sample. One such disclosure is described in US 2010/0120915. Another suitable microbial count assay is described in US 2013/0150451. There are also standard tests that could be used to determine the efficacy of the antibiofilm compositions and/or articles thereof, such as ASTM E2783 - Standard Test Method for Assessment of Antimicrobial Activity for Water Miscible Compounds Using a Time-Kill Procedure, and ASTM E2149 - Standard Test Method for Determining the Antimicrobial Activity of Antimicrobial Agents Under Dynamic Contact Conditions.

Examples

The general mix procedure for preparing a liquid antibiofilm composition: about 100 grams of deionized (DI) or deionized and distiller water may be weighed in a container such as a glass beaker. Then, the other components of the composition are added slowly to the water under constant stirring. Heat may be applied to the water to help dissolution of ingredients. After adding all the ingredients, the contents may be stored in a sealed jar or plastic container until further use. Optionally, the components could be added to a pH buffered solution, and/or saline to improve the solubility and/or stability of the components.

The antibiofilm composition may be evaluated using known assays for inhibition, re-growth, etc. The bacterial strain of Gram positive bacteria such as Enterococcus faecalis, Staphylococcus aureus, etc. and Gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, etc. may be evaluated according to well known standard assays. In a typical test, the bacteria are cultured in an assay cell, and the excess washed off. The cells are then exposed to the antibiofilm composition for a period of time, i.e. 24 hours, after which the cells are exposed to a suitable medium for bacterial regrowth. In another procedure for biofilm formation and subsequent evaluation of the antibiofilm composition, the procedure disclosed by Ammons et. al., in International Wound Journal, Volume 8, Number 3, pages 268-273 may be used.

Without limiting the invention, the following examples provide compositions, which are expected to reduce the bacterial count by at least one log order in 24 hours of exposure to the antibiofilm composition and/or articles comprising such compositions. One skilled the art would appreciate that the concentration of different components can vary due to the nature of the biofilm, the microbial type(s) present in the biofilm, and the suitability for the application (wounds or medical device surfaces). To arrive at an optimal concentration of each component, it is necessary to perform a minimum inhibitory concentration (MIC) test from which the minimal dosage can be determined for each target microbe.

Example 1

Example 2

Example 3

Example 4

Example 5

Example 7

Example 9. Foam composition according to the present invention.

Soma Foama® Flexible Silicone Castable Foam is a two-component platinum-cured silicone foaming composition from Smooth-on Inc. The components are added to Part B of the silicone foam, and then mixed with Part A to cure and form the final foam-in-place solid.

Example 10. Example of a hydrogel adhesive-based antibiofilm composition according to the present invention.

*The PVP:PEO: Water hydrogel adhesive is prepared according to US patent 4,750,482. About 20 wt% of polyvinylpyrrolidone (PVP) PVP -90 from Ashland Inc. is mixed with 30 wt% CARBOWAX™ Polyethylene Glycol (PEG) 300 or 400 and 50 wt% water under shear using a stirrer in a mixing vessel. The remaining components of Example 11 are added in any order into this mixture under shear. The contents are then poured onto a release coated paper or suitable film or fabric, and dried overnight. Then the top surface is protected with another release-coated paper. The coating is then subjected to electron beam (e-beam radiation) to crosslink the adhesive coating. The resulting adhesive antibiofilm composition is expected to disrupt the biofilm and reduce the antimicrobial count by at least one log order after 24-hours exposure.

Example 11. Example of powder-based antibiofilm composition according to the present invention.