ANTIMICROBIAL ADHESIVE DRESSINGS

Abstract

An adhesive transparent antimicrobial sheet or film cured from a liquid containing silicone includes dispersed particulates of polyhexamethylene biguanide hydrochloride (PHMB) present at up to about 5% by weight. The dispersed particulates of PHMB are not soluble in the liquid containing silicone, and the PHMB has a molecular weight range of from 400 to 8000. Dispersed particulates of ethylenediamine tetraacetic acid (EDTA) are present at about 0.01% to about 1% by weight. The dispersed particulates of EDTA are not soluble in the liquid containing silicone. Up to 2% v/v glycerin can be included. A backing layer is on one side of the sheet or film, The sheet or film is flexible and maintains adhesiveness such that it is repositionable on tissue and/or skin with little or no tissue or skin trauma. The sheet or film does not contain chlorhexidine.

Claims

1. An adhesive transparent antimicrobial sheet or film cured from a liquid containing silicone, the sheet or film comprising: dispersed particulates of polyhexamethylene biguanide hydrochloride (PHMB) present at up to about 5% by weight, wherein the dispersed particulates of PHMB are not soluble in said liquid containing silicone, and wherein said PHMB has a molecular weight range of from 400 to 8000; dispersed particulates of ethylenediamine tetraacetic acid (EDTA) present at about 0.01% to about 1% by weight, wherein the dispersed particulates of EDTA are not soluble in said liquid containing silicone; up to 2% v/v glycerin; and a backing layer on one side of said sheet or film, wherein said sheet or film is flexible and maintains adhesiveness such that it is repositionable on tissue and/or skin with little or no tissue or skin trauma, wherein the sheet or film does not comprise chlorhexidine.

2. The sheet or film of claim 1, wherein said dressing has a thickness of up to about 5 mm.

3. The sheet or film of claim 1, wherein said dressing is washable.

4. The sheet or film of claim 1, wherein said backing layer is made of a material selected from the group consisting of polyurethane, polyester, vinyl, cellulose, oxycellulose, rayon, and viscose.

5. A method for treating wound areas and surgical incisions or for preventing or minimizing infection of a wound or incision site or needle puncture, the method comprising contacting the wound, the surgical incision or the needle puncture with the adhesive antimicrobial dressing of claim 1.

6. The method of claim 5, further comprising applying said adhesive antimicrobial dressing to an indwelling therapeutic device as a protective dressing.

7. The sheet or film of claim 1, wherein said sheet or film has a thickness of about 0.18 mm to about 0.5 mm.

8. The sheet or film of claim 1, further comprising a liner on a tissue and/or skin contact side of the sheet or film.

9. The sheet or film of claim 8, wherein said liner is made of a polycarbonate material.

10. The sheet or film of claim 1, wherein said dressing is moisture and gas permeable.

11. The sheet or film of claim 1, wherein the sheet or film further comprises an additional antimicrobial agent.

12. An adhesive antimicrobial dressing configured as a transparent and adhesive silicone sheet or film cured from a liquid containing silicone, wherein the sheet or film comprises humectant, dispersed particulates of polyhexamethylene biguanide hydrochloride (PHMB) that are not soluble in said liquid containing silicone and dispersed particulates of EDTA that are not soluble in said liquid containing silicone; and a backing layer on one side of said sheet or film, wherein a molecular weight range of the polyhexamethyle biguanide hydrochloride is from 400 to 8000, wherein the sheet or film does not comprise chlorhexidine.

13. The dressing of claim 12, wherein the amount of PHMB in said sheet or film is up to about 5% by weight relative to total amount of said dressing.

14. The dressing of claim 12, wherein the amount of EDTA in said sheet or film is from about 0.01% to about 0.5% by weight relative to total amount of said dressing.

15. The dressing of claim 12, wherein said humectant is glycerin provided in an amount of up to 2% v/v relative to total amount of said dressing.

16. The dressing of claim 12, wherein said dressing has a thickness of up to about 5 mm.

17. The dressing of claim 12, wherein said dressing is one or more of tacky, flexible, repositionable and washable.

18. The dressing of claim 12, wherein said backing layer is made of a material selected from the group consisting of polyurethane, polyester, vinyl, cellulose, oxycellulose, rayon, and viscose.

19. The dressing of claim 12, further comprising a liner on a tissue and/or skin contact side of the sheet or film.

20. A method for making the adhesive antimicrobial dressing according to claim 1, the method comprising: mixing together a liquid containing silicone with a silicone dispersion of polyhexamethylene biguanide hydrochloride (PHMB) and ethylenediamine tetraacetic acid (EDTA) that are not soluble in said liquid and remain as particulates, and an optional humectant; and allowing the mixture to cure under suitable temperature and pressure.

21.-29. (canceled)

30. A sheet or film of adhesive silicone exhibiting antimicrobial activity solely as a result of containing a combination of dispersed insoluble particulates of polyhexamethylene biguanide hydrochloride (PHMB) and dispersed insoluble particulates of EDTA; and optional humectant.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0093] FIG. 1 shows oligomers of PHMB.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0094] While the present description sets forth specific details of various embodiments, it will be appreciated that the description is illustrative only and should not be construed in any way as limiting.

[0095] Herein described are novel wound dressings that are antimicrobial and adhesive. The dressings have a layer that adheres to skin and tissue. The dressing can be further fabricated to have a film backing material and further formulated to have a liner laminated to the adhesive surface.

[0096] The antimicrobial silicone adhesive dressings in general comprise a tissue contact layer that is a hydrophobic material. An antimicrobial is dispersed with the tissue contact layer in a manner that the antimicrobial is not soluble therein and instead forms particulate antimicrobial particles dispersed therein. To the antimicrobial is provided a chelator, humectant and optionally other antimicrobial agents. In certain desired embodiments of the invention, the dressings are silicone based, in aspects, a silicone gel material that can be provided in a variety of formats.

[0097] In embodiments of the invention, PHMB is utilized as the antimicrobial and is used in conjunction with EDTA in order to deter microbial ingress and growth on or with a wound dressing, the wound bed, the surface surgical wound excision site, or dermal and/or tissue exit-sites of a medical device such as a topical surgical dressing, negative pressure wound therapy dressing or contact layer, or ostomy wound contact devices or covering film and/or catheter exit site wounds such as those of venous catheters and the like.

[0098] Surprisingly, the silicone-based adhesive dressing of the present invention retains the desired adhesive and beneficial properties while admixed with a dispersion of insoluble PHMB and EDTA, it is known that EDTA is a metal chelating compound.

[0099] The present invention is the first to realize that a transparent tacky silicone gel can be combined with an antimicrobial in combination with a metal chelating agent and humectant to form a stable composition for the manufacture of a dressing for covering surgical incisions, i.v. site wounds, wounds requiring NPWT and other wounds. Still other antibiotics may be further combined with metal chelators and silicone compositions to manufacture medical devices such as surgical dressings, i.v. dressings, surgical drapes, NPWT dressings, and the like for treating wounds; for example, chlorhexidine in combination with EDTA may be combined with the silicone as described in this invention to provide a composition that may be manufactured into a medical devices noted above.

[0100] The invention provides a transparent silicone sheet dressing such as a wound dressing, that includes PHMB and EDTA that are insoluble in the silicone polymer used to form the adhesive dressing skin or tissue contact layer, resulting in insoluble particles dispersed throughout the resulting adhesive dressing. A PHMB and EDTA dispersion in the tacky silicone adhesive mixture allows for incorporation of antiseptic PHMB and EDTA combination into the adhesive wound dressing or skin covering thus providing a preservative function within the adhesive contact layer and antimicrobial action of the dressing when placed on human skin and tissue.

[0101] The antimicrobial silicone adhesive dressings of the invention provide gentle, atraumatic adhesiveness, and topical antiseptic activity for several days. The dressings are transparent and this allows for visibility of a wound site or other surgical incisional site, or i.v. needle puncture site, skin surface or wound without having to lift the dressing from the skin, wound or incision site. Its gentle adhesion and flexibility allow it to be easily lifted and removed cleanly from patients' without skin trauma or damage to sensitive and/or inflamed wounded tissue, no matter how long the silicone adhesive has been on the skin. As silicone gel does not lose adhesion when removed from the skin, it can be washed with water, air dried, and reapplied to the skin if required.

[0102] In other embodiments of the invention, the tissue contact layer is a hydrophobic silicone material formatted as a silicone adhesive, silicone gel, silicone thin film, silicone pad, or silicone foam.

[0103] Silicones are polymers consisting of alternate atoms of silicon and oxygen with organic groups attached to the silicon atoms. The degree of polymerisation determines the physical form of the silicone, which can vary from thin oils to relatively hard rubbers or soft sticky resins. Soft silicones are soft and tacky and adhere well to dry surfaces. A soft silicone wound dressing is coated with a soft silicone adhesive or a wound contact layer that can be removed without causing trauma to the wound or to the surrounding skin. The dressing may be easily lifted from the skin and re-applied to the dry skin with no appreciable reduction to the adhesive strength.

[0104] The invention as an antimicrobial silicone adhesive dressing is transparent and comprises: 1) an anti-microbial component comprising at least PHMB; 2) a hydrophobic silicone polymer; 3) at least EDTA in combination with PHMB, 4) optional humectant such as glycerin where the polymer comprises a medical grade silicone that can be platinum-cured to a tacky adhesive used in medical applications such as a wound dressing for surgical wounds, i.v. needle insertion sites, surgical drapes, negative pressure wound therapy (NPWT) adhesive coverings, NPWT tissue contact layers, surgical drapes and the like. It should be recognized by those experienced in the art that other suitable medical devices may be produced by the invention herein.

[0105] Suitable silicone adhesive material for use in the invention are platinum-catalyzed, fillerless, silicones elastomer adhesives such as Dow Corning BIO-PSA class of silicone adhesives and Dow Corning silicone Soft Skin Adhesives (SSAs) MG 7-9800, MG 7-9850 and MG 7-9900. In one aspect MG 7-9900 a desirable silicone. Other examples of adhesive silicone gel compositions of clear, tacky silicones suitable to practice the invention herein include the two component MED-6345 tacky silicone gel by Nusil Technology LLC, CA, USA, and Wacker SILPURAN 2112 A/B, 2120 A/B and 2130 A/B, 2-part, addition-curing silicone compositions curing to soft, tacky silicone adhesives by Wacker Chemie GmbH, Munich, Germany. Components A and B of SILPURAN 2110 A/B and 2120 A/B for example are mixed homogeneously in a ratio A:B=1:1 and cure rapidly at temperatures over 100 C. The cured composition has good tackiness and adhesive properties. Increasing the proportion of component A results in a softer silicone gel and increased tackiness. Increasing the proportion of component B results in a harder gel with reduced tackiness. The platinum catalyst is in component A.

[0106] A solventless silicone adhesive for use in the present invention is a cross-linked silicone soft skin adhesive (SSA) elastomer technology. SSA materials are known as tacky gel or silicone gel. They differ from analogous silicone elastomers by the absence of reinforcing silica filler. As a result, they have the consistency of a gel but they are not truly polymeric gel because they are not based on an insoluble polymer network swollen with low molecular weight fluids. SSAs are cross-linked polydimethylsiloxanes with low amounts of free extractable molecules. Despite low consistency and some compressibility, SSAs show resilience and quick recovery under cyclic deformation. The pressure sensitive adhesive property of SSA is mainly based on the capacity of the surface to quickly wet the substrate and conform to its relief without excessive flow. Because the viscous component is minimal, the material does not flow, and only small dissipation of the energy occurs when deformation pressure is applied. The result is an immediate debonding, which happens at low peel or shear force. The advantage in skin adhesion is the atraumatic removal obtained with SSA: no skin stripping and no painful skin or hair pulling. Another advantage lies in the fact that SSAs have a low viscous component that limits their flow and consequently the readiness to absorb materials at the surface of the skin such as stratum corneum cells and lipids. The adhesive surface of SSAs remains relatively clean. It can be removed and re-adhered easily to the same location (Silicone Adhesives in Healthcare Applications, Thomas, X. Dow Corning Technical Brochure and references therein).

[0107] Cross-linking of SSAs is based on an addition reaction (hydrosilylation), between vinyl functional PDMS and hydrogen functionalsiloxanes (e.g. dimethyl, methylhydrogen siloxane copolymers, hydrogen dimethylsiloxy terminated PDMS) as shown in the FIG. 6. The cure reaction is catalyzed by a platinum complex. It can occur at room temperature or be accelerated at elevated temperature (80 C. to 145 C.), without the formation of by-products.

[0108] In one embodiment of the present invention silicone adhesives (SSAs) are utilized as they are two-part, platinum-catalyzed, fillerless, high adhesion elastomeric silicone adhesives. They are clear and soft skin adhesives suitable for wound care applications, as they provide the following characteristics: [0109] Tack for quick bonding to various skin types, and wet skin; [0110] Suitable adhesiveness and cohesiveness; [0111] Gentle adhesion and atraumatic removal from fragile and compromised skin; [0112] No skin stripping or peeling for hair; [0113] Ability to reposition easily and re-apply easily and effectively; [0114] High degree of flexibility; [0115] Moisture and gas permeable; [0116] Compatibility with many therapeutic molecules; and [0117] Co-formulation with pharmaceutical excipients to adjust the kinetics of drug efflux.

[0118] Surprisingly is it now for the first time demonstrated that silicone elastomer solutions (such as for example but not limited to MG 7-9800, MG 7-9850 and MG 7-9900) may be combined with a polymeric biguanide, such as PHMB and at least EDTA to form a stable composition that can be cured by platinum-based catalysis. Prior to the present invention, it was not realized or demonstrated that PHMB and EDTA in combination could be effectively combined with a silicone liquid solution in a stable manner to form a stable solution with particulates that could be cured to form a transparent dressings for use in treating various wounds.

[0119] The backing onto which the silicone adhesive layer laid is preferably flexible film-like polymer material such as but not limited to polyurethane. The added soft silicone adhesive material will be the skin adhesive contact layer. The backing is preferably substantially permeable to air and moisture vapor. The backing is also preferably substantially impermeable to liquids and microorganisms and viruses. Examples of suitable materials for backing layer include, but are not limited to, polyurethanes, polyesters, and vinyls, cellulose, oxycellulose, rayon, viscose, collagen foams, pads, thin films, and composite biomaterials, and flexible thin films of any medically suitable and materials biocompatible with human skin and tissues.

[0120] Antimicrobial agents that may be used for the purposes of the invention may be any such agent which is suitable for use in the dressing. In addition, to the PHMB and EDTA, as a desired embodiment, at least one other antimicrobial agent may optionally be included in the dressing, with or without EDTA. Non-limiting examples include compounds of metals such as silver, copper, or zinc, iodine based compounds, polyhexamethylene biguanide (PHMB) and derivatives, chlorohexidine gluconate/acetate, and Octenidine and derivatives. Further alternative anti-microbial agents are possible. Suitable anti-microbial agents include, but are not limited to, a triclosan, a polymoxin, a tetracycline, an amino glycoside (e.g., gentamicin or Tobramycin), a rifampicin, a bacitracin, an erythromycin, a neomycin, a chloramphenicol, a miconazole, a quinolone, a penicillin, a nonoxynol 9, a fusidic acid, a cephalosporin, a mupirocin, a metronidazole, a secropin, a protegrin, a bacteriolcin, a defensin, a nitrofurazone, a mafenide, a acyclovir, a vanocmycin, a clindamycin, a lincomycin, a sulfonamide, a norfloxacin, a pefloxacin, a nalidizic acid, an oxalic acid, an enoxacin acid, a ciprofloxacin, a biguanide, combinations thereof and the like. In certain embodiments the anti-microbial agent comprises polyhexamethylene biguanide (PHMB) and/or derivatives thereof.

[0121] In one particular embodiment of the invention, PHMB is utilized. Polyhexamethylene biguanide (PHMB, N-(3-aminopropyl)-imidodicarbonimidic diamide, or also known also known as polyhexanide Poly(hexamethylenebiguanide hydrochloride), Poly(iminocarbonimidoy liminocarbonimidoylimino-1,6-hexanediyl) hydrochloride, Poly(iminoimidocarbonyl-iminoimidocarbonyl-iminohexamethylene) hydrochloride, Poly(iminoimidocarbony liminoimidocarbonyliminohexamethylene) hydrochloride, with the following trade names, Baquacil, Caswell No. 676, Cosmocil CQ, EPA Pesticide Chemical Code 111801, Polihexanido, Polihexanidum, Polyhexanide, PP 073 and UNII-322U039G has a proven efficacy against pathogens commonly found in wounds.

[0122] PHMB is an aqueous-based cationic compound used as a preservative and antimicrobial agent, it is active against microorgansims, and is compatible with a wide range of aqueous-based cosmetics and personal-care products. Preparations of PHMB (FIG. 1, where n is an integer) are mixtures of polymeric biguanides with a molecular weight range of 400-8,000 representing polymers with 2-40 repeating subunits, with an average number 11 repeating subunits (FIG. 1, n=11) (Cationic Antimicrobial Polymers and Their Assemblies A. M. Carmona-Ribeiro, L. Dias de Melo Carrasco, Int. J. Mol. Sci. 2013, 14, 9906-9946).

[0123] Due to dynamic equilibrium of polymerization/depolymerization in step-growth synthesis, commercial PHMB has three possible groups at its chain ends: nitrile, guanidine or amine. Oligomers of PHMB (FIG. 1) generally available from commercial sources may be used to fabricate the dressing, where n=6 to 100, preferably 6-20. Mixtures of oligomers, in commercial PHMB have three possible groups at the polymer chain ends: nitrile, guanidine or amine, and mixtures of these can be used as may be purchased from commercial sources according to the present invention. Suitable salts of PHMB include, but are not limited to salts of hydrochlorides, hydrobromides, gluconates, acetates, ascorbates and citrates.

[0124] The chain length (FIG. 1, n) of PHMB may have a maximum size of 40-42 subunits. There exists an equilibrium of polymerization/depolymerization, with depolymerization occurring by biguanide break resulting in one cyanamide chain-end and one guanidine chain-end. Longer chains (FIG. 1, n>40 subunits) will break up into smaller chains that can undergo interchange reactions, complicating the estimation of the true molecular weight distribution. This process can explain the maximum chain length around n=40 subunits with a weight-averaged degree of polymerization of n=12 [cited in G. F. de Paula, Physical and Chemical Characterization of Poly(hexamethylene biguanide) Hydrochloride Polymers 2011, 3, 928-941].

[0125] PHMB is soluble in water, alcohols and glycols, and is incompatible with anionic surfactants and soaps; it is not soluble in oils and hydrocarbons and silicone elastomers. It should be kept at a pH below 8.0, and should not be heated above 80 C. It is however, stable in the presence of light, pH 4-10, and up to 80 C. In the silicone adhesive of this invention PHMB is stable to the curing temperature of 140 C., and to autoclaving at 121 C. PHMB is a heterogeneous mixture of polymers. The basic molecular chain of PHMB can be repeated from two to about forty times with increasing polymer chain length correlating with increasing antiseptic/antimicrobial efficacy. While the effect of PHMB on managing bioburden is well-known, exposure of viral particles to PHMB causes them to clump together as aggregates. Comparative tests of PHMB's biocompatibility (measurement of an antiseptic/antimicrobial agent's activity in relation to its cytotoxicity) against other commonly used standard of care therapies have demonstrated its superiority over chlorhexidine, povidone-iodine, triclosan, silver and sulfadiazine.

[0126] While EDTA is the preferred chelating agent, other suitable chelating agents may be used as is generally known in the art, and may be selected from, but not limited to, the group consisting of non-toxic salts of diethylenetriaminepentaacetic acid, 1,2-diaminocyclohexane-N,N-tetraacetic acid, beta.-mercaptoethyliminodiacetic acid, tetrakis (2-aminoethyl)-ethylenediamine, B,B,B-triaminotriethylamine, N-hydroxyethylethylenediaminetriacetic acid and ethylenediamine N,N-dipropionic acid N,N-diacetic acid and polymeric chelating agents such as polyethyleneimine. A wound dressing of the present invention may further include a chelating agent. Any suitable chelating agent may be utilized. By way of non-limiting example, chelating agents such as ethylenediaminetetraacetic acid (EDTA), variations of EDTA such as, for example, disodium EDTA or tetrasodium EDTA, combinations thereof and the like, are contemplated. Chelating agents can heighten the susceptibility of bacteria and other organisms to the antiseptic effects of the anti-microbial agent, thereby rendering the wound dressing more effective in combating and/or preventing infection, without the necessity of increasing the levels of anti-microbial agent contained therein. This aspect of the present invention advantageously avoids problems caused by the irritating effects of certain anti-microbial agents, such as CHG, especially when applied to the skin that higher concentration levels.

[0127] In aspects of the invention to the silicone is also added a surfactant (surface active agent) which reduces the surface tension of a fluid allowing it to better wet a surface. Any amphoteric surfactant having this property can be utilized in the silicone adhesive of the invention such as betaine and glycerin. The amphoteric surfactant is present in an amount of up to about 2%. In aspects about 0.1% to about 2% v.v. In aspects up to about 1%, up to about 1.5%, and up to about 2%. In aspects the silicone adhesive comprises glycerin, in aspects about 2.0% glycerin is utilized.

[0128] The amount of antimicrobial for use in the present invention, in aspects PHMB, can range from about 0.1 to about 1%, or from about 0.3 to about 0.5% or about 0.3%. The amount of chelator for use in the dressing of the invention, such as the EDTA, can range from about 0 to about 1%, or from about 0.1 to about 0.5% or about 0.01%. One of skill in the art can determine the effective amounts with the teachings of these ranges. By effective is meant that the dressings of the invention can serve their purpose for wound care management and are substantially antimicrobial.

[0129] In aspects of the invention, chlorhexidine can be used as the antimicrobial in conjunction with the EDTA combination and glycerin.

[0130] In an aspect of the invention, the antimicrobial silicone adhesive dressing is made by loading each of PHMB and EDTA in the mixture and glycerin prior to curing.

[0131] The silicone adhesive is formulated from two parts. Part A is the primary silicone polymer with catalysts, and Part B contains the crosslinking agent. The silicone is a two part platinum cure silicone adhesive product supplied from the Dow Corning Corporation. The antimicrobial chemicals (PHMB, and EDTA) and humectant (glycerin) are added to the silicone through an addition to the Part B component. In an aspect, the mixing ratio of Part A:Part B is 0.99:1 but may vary. The ingredients are added to Part A component in a container and mixed uniformly. Once the silicone is mixed thoroughly, it is coated onto a polyurethane backing that is fed through a convection oven. As the polyurethane backing is pulled through the oven, the silicone mixture is coated to a specific thickness. The oven subjects the silicone mixture to a specified temperature for a given length of time. The elevated temperature aids in the cure of the silicone coating. Oven temperatures for curing may be from about 130 C. to about 150 C., in aspects about 140 C. As the coated substrate leaves the oven a polycarbonate liner is laminated to the cured silicone surface.

[0132] The thickness of the silicone coating is about 0.1 mm to about 0.5 mm, in aspects about 0.18 mm. The dressing range can be from about 0.01 mm to about 5 mm, preferably for thin film SSA application it can range from about 0.01 to about 1 mm, and in aspects from about 0.1 to about 0.5 mm, and in further aspects from about 0.14 to about 0.2 mm, and in aspects about 0.18 mm thick; the polyurethane backing layer is up to about 28 microns thick. One of skill in the art would understand that the backing layer thickness may be dependent on the particular application and thus can vary and in aspects be thicker than 28 microns.

[0133] The silicone adhesive dressings of the invention can be fabricated onto the backing material and an optional liner is applied to the tissue contact surface for use prior to packaging such that the dressing does not adhere to the packaging material per se. Thus a dressing for clinical use may be made with a backing layer that is substantially air permeable and substantially permeable to moisture vapour, yet substantially impermeable to liquids, microorganisms and viruses; having a silicone antimicrobial thin film thereon as described herein; and a liner such as a polycarbonate or similar type liner to protect the tacky surface as packaged. The dressings can be packaged as kits for wound care/would management use.

[0134] The invention will be further illustrated by reference to the following non-limiting Examples. All parts and percentages are expressed as parts by weight unless otherwise indicated.

EXAMPLES: THESE ARE NON-LIMITING AND ENCOMPASS EMBODIMENTS OF THE INVENTION

Example 1: Formation of Silicone Gel Adhesive Dressing

[0135] A mixture was formed of; (1) a liquid containing silicone elastomer composition, in which the adhesive elastomers are based on a platinum-catalyzed polydimethyl-siloxane composition that cures at a variety of temperatures from ambient to 140 C., without the formation of by-products, and (2) a PHMB compound plus the metal chelator, EDTA, in the hydrophobic silicone mixture. Glycerol was added in some of the mixtures. The mixture was allowed to form a transparent adhesive material under appropriate and suitable conditions of temperature and pressure in the presence or absence of the catalyst, such as platinum. The gel material was applied to a polyurethane backing layer.

[0136] The cured silicone tacky gel adhesive contact layer contained 0.01% tetramethylvinylcyclosilioxane, had a total thickness of about 0.18 mm on a polyurethane backing carrier of about 28 micron (0.028 mm) thickness. The thickness of the contact layer may be modified to be more or less than 0.18 mm in thickness as may be required.

[0137] A cured silicone tacky gel adhesive contact layer containing 0.01% tetramethylvinylcyclosilioxane, having a total thickness of about 0.18 mm on a polyurethane backing carrier was also formed without catalyst. The thickness of the contact layer may be modified to be more or less than 0.18 mm in thickness as may be required.

Methodology

[0138] a. Weighed out 249 grams of Part B silicone (Dow Corning: DC7-9900) for compounding a 500 gram total weight sample size of the mixture. [0139] b. Weighed out 0.05 gm EDTA and 1.5 gm PHMB. [0140] c. Added 2% v/v glycerin [0141] d. Added b) and c) chemicals one at a time to the silicone under constant mixing and after thorough mixing, vacuum mix mixture. [0142] e. Mixed the material of step d) above with 249 gm of Part A silicone. [0143] f. Coated the material onto a polyurethane sheet to a thickness of up to about 28 microns in at an oven temperature of 140 C. at a dwell time of two minutes.
Loading of each of PHMB and EDTA in the cured final dressing. [0144] PHMB amount in final coating=0.3% wgt [0145] EDTA amount in final coating=0.01% wgt [0146] Glycerin amount in final coating=2% v/v [0147] Silicone gel=97.69% [0148] Total=100%

[0149] The composition had excellent and instantaneous tack, atraumatic removal from skin, is hypoallergenic, had the ability to be removed and repositioned, and is transparent. Curing times, temperature and pressures for forming the silicone adhesive composition containing the PHMB and EDTA are known to one of skill in the art. For example, cohesive and self-adhering silicone materials may be produced from platinum catalyzed polydimethyl-siloxane that will cure at a variety of temperatures from ambient to 140 C.

[0150] A single-coated wound dressing is made with adhesive side exposed on only one side of polyurethane backing layer. Backings can be made of cloth, various films, foams, and a range of other materials. Single-coated products may be manufactured either with or without a release liner as is well-known in the art. Silicone adhesion and release test methods utilized ASTM D3330. The silicone coat weight test procedure was developed using ASTM D899-00.

Example 2: Formation of Silicone Gel Adhesive Dressing

[0151] To Part B as described above was added the following: [0152] 2% glycerin; [0153] 0.3% PHMB; [0154] 0.01% EDTA.

[0155] Part A as described above was then added to Part B mixture and mixed as described above. The composition had excellent and instantaneous tack, atraumatic removal from skin, is hypoallergenic, had the ability to be removed and repositioned, and is transparent.

Antimicrobial Assay

[0156] Test samples of the antimicrobial silicone adhesive with PHMB and EDTA were cut into 5 cm5 cm pieces and placed with the adhesive side facing up on LB agar microbiology plates; control silicone adhesive samples had no PHMB or EDTA. A microliter droplet of microorganism adjused to 105 CFU/mL of either Staphylococcus aureus or Candida albicans was placed directly onto the adhesive surface in 4 replicate locations. The plates with adhesive pieces and microorganisms were incubated at 37 C. for 18 hours. After 18 hours the droplets were taken up with a pipette and transferred directly onto the surface of new LB plates and incubated for 18 hours at 37 C. Growth of microorganism was assessed visually. No growth of either microorganism was indicative of antimicrobial activity.

[0157] Liquid samples on PHMB and EDTA-containing silicone adhesive with microbes taken up after 18 hours and transferred to new LB plates showed no growth after incubation for 18 hours, indicating antimicrobial activity of the silicone adhesive. Antimicrobial activity was assessed for longer periods and it was found to providemicrobiocidal activity for at least up to 7 days.

[0158] Since many possible embodiments may be made of the invention without departing from the scope thereof, it is to be understood that all matters herein set forth are to be interpreted as illustrative, and not in a limiting sense. While specific embodiments have been shown and discussed, various modifications may of course be made, and the invention is not limited to the specific forms or arrangement of elements and steps described herein, except insofar as such limitations are included in the following claims. Further, it will be understood that certain features and subcombinations are of utility and may be employed without reference to other features and subcombinations. This is contemplated by and is within the scope of the claims.

[0159] Further although embodiments of these inventions have been disclosed in the context of certain examples, it will be understood by those skilled in the art that the present inventions extend beyond the specifically disclosed embodiments to other alternative embodiments and/or uses of the inventions and modifications and equivalents thereof. In addition, while several variations of the inventions have been shown and described in detail, other modifications, which are within the scope of these inventions, will be readily apparent to those of skill in the art based upon this disclosure. It is also contemplated that various combinations or sub-combinations of the specific features and aspects of the embodiments may be made and still fall within the scope of the inventions. It should be understood that various features and aspects of the disclosed embodiments can be combined with or substituted for one another in order to form varying modes of the disclosed inventions.

[0160] In understanding the scope of the present application, the articles a, an, the, and said are intended to mean that there are one or more of the elements. Additionally, the term comprising and its derivatives, as used herein, are intended to be open ended terms that specify the presence of the stated features, elements, components, groups, integers, and/or steps, but do not exclude the presence of other unstated features, elements, components, groups, integers and/or steps. The foregoing also applies to words having similar meanings such as the terms including, having and their derivatives.

[0161] It will be understood that any aspects described as comprising certain components may also consist of or consist essentially of, wherein consisting of has a closed-ended or restrictive meaning and consisting essentially of means including the components specified but excluding other components except for materials present as impurities, unavoidable materials present as a result of processes used to provide the components, and components added for a purpose other than achieving the technical effect(s) described herein. For example, a composition defined using the phrase consisting essentially of encompasses any known pharmaceutically acceptable additive, excipient, diluent, carrier, and the like. Typically, a composition consisting essentially of a set of components will comprise less than 5% by weight, typically less than 3% by weight, more typically less than 1% by weight of non-specified components.

[0162] It will be understood that any component defined herein as being included may be explicitly excluded from the claimed invention by way of proviso or negative limitation. For example, in aspects, certain of the recited components if desired can be explicitly excluded from the compositions and methods described herein.

[0163] In addition, all ranges given herein include the end of the ranges and also any intermediate range points, whether explicitly stated or not.

[0164] Finally, terms of degree such as substantially, about and approximately as used herein mean a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree should be construed as including a deviation of at least 5% of the modified term if this deviation would not negate the meaning of the word it modifies.