Novel antibacterial topical skin occlusive compositions and systems

Abstract

Novel compositions and systems for wound closure with antimicrobial efficacy are disclosed. The compositions provide improved flexibility and stretchability for devices that are easily applied to the wound site or wound closure device. The invention also relates to novel platinum catalysts for use in such compositions. The catalysts provide rapid curing on topical surfaces, such as skin, bonding to such surfaces in approximately 2 to 5 minutes.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application is related to U.S. patent application Ser. Nos. 16 / 885,413 (Attorney Docket No. ETH6068USNP1), 16 / 885,426 (Attorney Docket No. ETH6069USNP1), 16 / 885,361 (Attorney Docket No. ETH6070USNP1), 16 / 885,375 (Attorney Docket No. ETH6085USNP1), all of which were filed on May 28, 2020, and ________ (Attorney Docket No. ETH6070USCIP1, filed concurrently with the present application), all of which have a common assignee and are hereby incorporated by reference in their entirety for all purposes.

[0002] FIELD OF THE INVENTION The technical field to which this invention pertains is silicone-based wound closure compositions and silicone-based topical skin adhesive (TSA) devices and systems. [Background technology]

[0003] There is a need for elastomeric topical skin adhesives, particularly for skin closure of moving body joints such as knees, wrists, and elbows.

[0004] An elastic version of the TSA is particularly needed in orthopedic surgery. Vigorous movement of the joint can compromise the quality of the closure at the interface between the adhesive and the skin. A watertight closure is also desirable for the product to reduce the possibility of post-operative infection. Silicone-type adhesives are one solution to both of these two major customer requirements due to their elasticity and sealing properties.

[0005] Silicones are known to be inert and are commonly used in OTC scar reduction products. Reduced skin reactions and improved cosmetic appearance are additional benefits offered by silicone-based TSAs. Summary of the Invention [Problem to be solved by the invention]

[0006] Thus, there is a need for an elastomeric topical skin adhesive, particularly for closure of moving body parts and joints such as knees, wrists, elbows, etc.

[0007] Due to the potential for microbial contamination and infection of wounds, there is a further need to provide an antimicrobial agent as part of any new TSA.

[0008] There is also a need to absorb liquid discharge from the wound during the healing process. A typical TSA seals the wound and is less susceptible to wound discharge or exudate leakage. There is also a need to detect the status of the wound, especially for draining exudate. Indicators of wound status are important for addressing potential problems with wound management, including anti-infective treatment, dressing changes, etc. [Means for solving the problem]

[0009] Thus, novel catalyst compositions, silicone-based curable adhesive compositions, and wound closure systems are disclosed that further comprise antimicrobial agents and / or indicators, such as for wound exudate drainage or wound moisture detection.

[0010] The composition includes a mixture of vinyl-terminated polydimethylsiloxane and polydimethylhydro-co-polydimethylsiloxane crosslinker, surface-treated silica particles as a binder, and a novel, unconventional platinum catalyst, optionally along with a common low-boiling organic solvent such as an aliphatic organic solvent (e.g., hexane or its commercial derivatives) and a SiH-terminated polydimethylsiloxane chain extender, and further includes an antimicrobial agent. The proposed silicone adhesive can dry on skin within 3 minutes at body temperature. The skin retention between the proposed silicone adhesive and skin is comparable to or better than that of typical cyanoacrylate-based TSA products. Unlike conventional cyanoacrylate-based TSA products, the invented silicone-based TSA, when combined with a conventional wound closure device, can be stretched up to 160% of its original length and fully recover to its original, unstretched dimensions. When treated with an antimicrobial agent, the conventional wound closure device was stretched up to 145% of its original length and fully recovered to its original, unstretched dimensions, as demonstrated below.

[0011] Bond formation is enabled by a condensation reaction between silanol functional groups on the surface of silica particles and OH functional groups on the skin. Silanol condensation tends to be slow at ambient temperatures, and the new, unconventional catalyst allows this reaction to occur in a short period of time. The new platinum-based catalyst also activates the vinyl silylation reaction, allowing vinyl-terminated silicone polymers to crosslink simultaneously with the condensation reaction.

[0012] In one embodiment, the present invention relates to a composition, comprising: a crosslinkable silicone polymer having reactive functional groups; a silica-containing composition; a silicone crosslinker; The following formula: a catalyst comprising a platinum tetramethyldivinyldisiloxane diethylmaleate complex having Pt[(CH2=CH)(CH3)2Si]2O·(COCH=CHCO)(C2H5O)2; Antibacterial agents, including

[0013] In the foregoing embodiment, the silica-containing composition can be added as a separate component, but more preferably it is contained in the crosslinkable silicone polymer. The coating composition can also contain a platinum catalyst.

[0014] Another aspect of the present invention is a medical device having a surface, at least a portion of which is coated with the novel silicone coating composition described above.

[0015] Yet another aspect of the present invention is a novel platinum catalyst for use in crosslinkable silicone coatings. The catalyst has the following formula: Contains platinum complexes with Pt[(CH2=CH)(CH3)2Si]2O·(COCH=CHCO)(C2H5O)2.

[0016] A further aspect of the present invention is the use of the composition of the present invention as a topical skin adhesive and in combination with a wound closure device as a system or kit for closing a wound, further having incorporated therein an antimicrobial agent and / or an indicator for detecting wound exudate discharge or wound moisture.

[0017] These and other aspects and advantages of the present invention will become more apparent from the following description. [Brief explanation of the drawings]

[0018] [Figure 1] NMR peak comparison of Karstedt's catalyst compared to the NMR peaks of the novel catalyst of the present invention. [Figure 2a] 1 illustrates the steps of the stretching test used to demonstrate the stretchability of the present invention without an antimicrobial agent. [Figure 2b] 1 illustrates the steps of the stretching test used to demonstrate the stretchability of the present invention without an antimicrobial agent. [Figure 2c] 1 illustrates the steps of the stretching test used to demonstrate the stretchability of the present invention without an antimicrobial agent. [Figure 3a]1 illustrates the steps of a stretching test used to demonstrate the stretchability of the present invention containing an antimicrobial agent. [Figure 3b] 1 illustrates the steps of a stretching test used to demonstrate the stretchability of the present invention containing an antimicrobial agent. [Figure 3c] 1 illustrates the steps of a stretching test used to demonstrate the stretchability of the present invention containing an antimicrobial agent. [Figure 4a] 1 shows a comparative example of the Zone of Inhibition of antimicrobial-containing and nonantimicrobial-containing compositions on S. aureus. [Figure 4b] 1 shows a comparative example of the Zone of Inhibition of antimicrobial-containing and nonantimicrobial-containing compositions on S. aureus. [Figure 5a] 1 shows a comparative example of the zone of inhibition of antimicrobial-containing and antimicrobial-free compositions on E. coli. [Figure 5b] 1 shows a comparative example of the zone of inhibition of antimicrobial-containing and antimicrobial-free compositions on E. coli. [Figure 6a] It is noted that absorbents and / or indicators may be incorporated into the compositions of the present invention at or on the surface of the underlying wound closure device. [Figure 6b] It is noted that absorbents and / or indicators may be incorporated into the compositions of the present invention at or on the surface of the underlying wound closure device. [Figure 6c] It is noted that absorbents and / or indicators may be incorporated into the compositions of the present invention at or on the surface of the underlying wound closure device. [Figure 7] 1 is a schematic diagram showing water penetration into the underside of a film of the present invention, the color change of embedded absorbent / indicator particles upon absorption of water or moisture into the film, and the water repellency of the top surface of the film. [Figure 7a]1 shows the color change of a composition of the present invention before and after exposure to moisture when an absorbent and / or indicator is included in the composition. [Figure 7b] 1 shows the color change of a composition of the present invention before and after exposure to moisture when an absorbent and / or indicator is included in the composition. [Figure 7c] 1 shows the hydrophobicity of the surface of the composition of the present invention. [Figure 7d] 1 illustrates the flexibility and stretchability of the compositions of the present invention for embodiments when an absorbent and / or indicator is included in the composition. [Figure 7e] 1 illustrates the flexibility and stretchability of the compositions of the present invention for embodiments when an absorbent and / or indicator is included in the composition. [Figure 7f] 1 illustrates the flexibility and stretchability of the compositions of the present invention for embodiments when an absorbent and / or indicator is included in the composition. [Figure 7g] 1 illustrates the water absorption and indicator capacity of the compositions of the present invention when an absorbent and / or indicator is included in the composition. [Figure 7h] 1 illustrates the water absorption and indicator capacity of the compositions of the present invention when an absorbent and / or indicator is included in the composition. DETAILED DESCRIPTION OF THE INVENTION

[0019] The terms silicone and siloxane are conventionally used interchangeably in the art, and that usage is adopted herein.

[0020] Topical skin adhesive compositions and wound closure systems One aspect of the present invention is directed to novel wound closure compositions that are particularly useful for closing lacerations and surgical incisions. These compositions are suitable for use as topical skin adhesives and as adhesives in combination with wound closure devices.

[0021] In one embodiment, the composition comprises a mixture of a crosslinkable siloxane polymer and a silica-containing composition, which may be added as a separate component, but more preferably is contained within the crosslinkable silicone polymer, a conventional silicone crosslinker, and a platinum catalyst. The silicone polymer component is blended with a conventional aromatic organic solvent, including, for example, an aliphatic organic solvent, such as hexane, heptane, or their commercial derivatives, to form a coating solution or composition. Other solvents suitable for coating solutions include, but are not limited to, low molecular weight siloxanes, such as hexamethyldisiloxane.

[0022] The crosslinkable siloxane polymers useful in the composition of the present invention have reactive functional groups or terminal functional groups, including, but not limited to, vinyl-terminated, hydroxyl, and acrylate functional groups. The crosslinkable siloxane polymers that can be used in the composition of the present invention preferably include vinyl-terminated polydialkylsiloxanes or vinyl-terminated polyalkylarylsiloxanes. Examples include, but are not limited to, the following vinyl-terminated siloxane polymers: polydimethylsiloxane, polydiphenylsilane-dimethylsiloxane copolymer, polyphenylmethylsiloxane, polyfluoropropylmethyl-dimethylsiloxane copolymer, and polydiethylsiloxane. It is particularly preferred to use vinyl-terminated crosslinkable polymethylsiloxanes.

[0023] Crosslinking agents that can be used in the compositions of the present invention include conventional silicone crosslinking agents, such as polymethylhydrosiloxane, polymethylhydro-co-polydimethylsiloxane, polyethylhydrosiloxane, polymethylhydrosiloxane-co-octylmethylsiloxane, and polymethylhydrosiloxane-co-methylphenylsiloxane. Preferred conventional crosslinking agents for use in the compositions of the present invention are polymethylhydrosiloxane and polymethylhydro-co-polydimethylsiloxane. Accurate control of the crosslink density in the coatings of the present invention is achieved by accurately controlling the ratio of non-crosslinkable silicone polymer (e.g., polydimethylsiloxane) to the total crosslinked polymer. The total crosslinked polymer is formed by the reaction of a functionalized crosslinkable polymer with a crosslinking agent, for example, the vinylsilylation reaction of vinyl-terminated polydimethylsiloxane with polymethylhydrosiloxane, optionally in the presence of a platinum complex catalyst. Examples of such polymers include, but are not limited to, Gelest product code numbers DMS-V31, DMS-V33, DMS V-35, DMS V42, DMS-V46, DMS-V52, etc., available from Gelest, Inc., Morrisville, Pa. 19067. A typical molecular structure of vinyl-terminated polydimethyldisiloxane is as follows:

[0024] [ka] where n is defined by the molecular weight.

[0025] The molecular weight of the silicone polymer used can be estimated based on the relationship between viscosity and molecular weight (page 11, SILICONE FLUIDS: STABLE, INERT MEDIA ENGINEERING AND DESIGN PROPERTIES, catalog published by Gelest, Inc., 11 East Steel Rd., Morrisville, PA 19067). Using A.J. Barry's relationship for molecular weights (M) > 2,500, which correlates to kinematic viscosity μ (expressed in centistokes (cSt) at 25°C), the molecular weight M of a silicone can be estimated as follows: log μ cSt =1.00+0.0123M 0.5 (Published by A.J. Barry in the Journal of Applied Physics 17, 1020 (1946)).

[0026] Under appropriate conditions, vinyl-terminated polydimethylsiloxane reacts with a polymethylhydrosiloxane crosslinker in the presence of a platinum catalyst, resulting in the vinyl-terminated polydimethylsiloxane linear polymers being fully crosslinked to one another. The amount of polymethylhydrosiloxane crosslinker is in large stoichiometric excess relative to the vinyl-terminated polydimethylsiloxane-based polymer. It is believed that the excess SiH functional groups in the crosslinker react with OH functional groups on a surface (e.g., human skin) to form Si-O-C bonds (e.g., polymer sutures) or Si-O-Fe bonds (e.g., steel needles) at elevated temperatures. Thus, the covalent bond created between the silicone coating and the device adhesively attaches the coating to a given surface as a result of this reaction.

[0027] The polymethylhydrosiloxane crosslinkers used in the practice of the present invention have a molecular weight of about 1000 to about 3000, preferably about 1400 to about 2100. Examples of such polymeric crosslinkers include, but are not limited to, Gelest product code numbers HMS-991 and HMS-992, available from Gelest, Inc. (Morrisville, Pa. 19607). A typical molecular structure of a polymethylhydrosiloxane crosslinker is as follows:

[0028] [ka] where n is defined by the molecular weight.

[0029] Polymethylhydro-co-polydimethylsiloxane can also be used as a crosslinker in the novel coatings of the present invention. Examples of this polymer include, but are not limited to, Gelest product code numbers HMS-301 and HMS-501. The molecular weight of this siloxane polymer crosslinker is typically about 900 to about 5,000, preferably about 1,200 to about 3,000. A typical molecular structure of a polymethylhydro-co-polydimethylsiloxane crosslinker is as follows:

[0030] [ka] where n and m are defined by the molecular weight.

[0031] Silica-containing composition As used herein, silica-containing compositions described for use with the present invention include silica materials from commercially available compositions that contain silica either as a separate component (such as surface-treated silica) or in a crosslinkable silicone polymer mixture.

[0032] As a separate component, silica is incorporated into the compositions of the present invention to act as a binder to skin and other substrate materials. It is believed that the OH groups on the surface of the silica particles react with OH functional groups on the surface of substrate materials, including human skin, under certain conditions, as illustrated below.

[0033] [ka]

[0034] Silica particles were incorporated into crosslinkable silicone polymers. To enable compatibility with the polysiloxane polymer matrix, which prevents phase separation, the silica particles require a hexamethylsilyl surface treatment. An example of a treated silica is hexamethyldisilazane-treated silica (i.e., trimethylsilyl-surface-treated silica) filler (Gelest SIS6962.0).

[0035] For silicone polymers that already contain silica, these can be obtained from commercially available sources, such as silica-containing compositions selected from reactive silica-containing silicone bases, including HCR (high consistency rubber) bases and LSR (liquid silicone rubber) bases, with LSR bases being preferred. Other commercially available examples of this material include, but are not limited to, Wacker 401-10, 401-20, and 401-40 bases, and liquid silicone rubber bases. Commercially available examples of this material include, but are not limited to, Bluestar Silbione LSR 4370 bases. These types of commercially available silicone rubber bases are prepared by mixing surface-treated silica fillers with vinyl-terminated polydimethylsiloxane polymers of various molecular weights. Surface treatments can be performed in situ during the mixing process to improve compatibility between the filler and the polysiloxane polymer.

[0036] catalyst Karstedt of GE Silicone invented a highly active platinum catalyst in the early 1970s (U.S. Patent No. 3,775,452). Vinyl-terminated polydimethylsiloxane can react with polymethylhydrosiloxane crosslinkers in less than one minute at ambient temperature using only 10 ppm of Karstedt catalyst. Conventional platinum catalysts do not allow the reaction between OH groups on the surface of silica particles and OH functional groups on the surface of a substrate. This type of condensation reaction tends to be slow at ambient conditions and with typical catalysts for this reaction, including organic amines and catalysts such as tin dilaurate. Trace amounts of condensation catalyst will terminate the catalytic ability of the platinum catalyst (known as platinum poisoning in the silicone industry). Novel platinum-equivalent catalysts are needed to activate OH condensation between silica particles and substrate materials to enable rapid adhesion formation between silicone and a given substrate material. The novel platinum-based catalyst of the present invention can simultaneously activate both vinyl silylation and OH condensation.

[0037] The new catalyst is prepared by reacting Karstedt's catalyst with diethyl maleate according to Scheme 1. The new platinum tetramethyldivinyldisiloxane diethyl maleate catalyst enables both vinylsilylation and condensation reactions. It is called a "dual-functional silicone catalyst."

[0038] [ka]

[0039] The novel catalyst of the present invention can be prepared by mixing Karstedt's catalyst in a xylene solution with a low concentration of vinylcyclohexanol in a xylene solution at ambient temperature for a time effective to complete the reaction, e.g., 30 minutes, which is indicated by a change in color of the reaction mixture from clear to light brown.

[0040] The resulting catalyst solution containing the novel catalyst of the present invention is ready for use in compositions useful as topical skin adhesives. The formula of the resulting platinum complex catalyst (platinum tetramethyldivinyldisiloxane diethylmaleate complex) is: Pt[(CH2=CH)(CH3)2Si]2O·(COCH=CHCO)(C2H5O)2.

[0041] It should be noted that the resulting catalytic reaction mixture contains a small amount of the reaction product divinyltetramethyldisiloxane. This component is a low-boiling component that does not affect the catalyst and evaporates quickly. Therefore, purification of the catalytic mixture to remove divinyltetramethyldisiloxane is optional, and its presence at ultra-low concentrations is believed to have no effect on the crosslinking reaction of the crosslinkable silicone polymer. The novel catalyst of the present invention also activates bond formation between silanol groups on the surface of the silica filler and OH functional groups on a given surface, i.e., the catalyst can activate two reactions. This allows the crosslinkable components in the silicone coating to cure, rapidly forming a coating film at the desired curing temperature and providing bonding to a given substrate, such as human skin.

[0042] Solvents for viscosity reduction Some commercially available filler-reinforced cross-linkable silicone polymers (silicone rubbers) have high viscosities, typically greater than 500,000, up to several million cP. Mixing and spreading such high-viscosity materials on the skin is impossible, and mild organic solvents are required to reduce their viscosity.

[0043] For this purpose, a low-temperature aliphatic solvent is used. Typical examples include, but are not limited to, pentane, heptane, hexane, and mixtures thereof. The organic solvent is added at a concentration sufficient to effectively blend the silicone polymer components into a homogeneous solution. The total solvent concentration is 10% to 30%, depending on the original viscosity of the base rubber. Ultra-low boiling point solvents, such as n-butane and isopentane, can also be used to provide a sprayable formulation of the silicone adhesive.

[0044] Chain extenders for low viscosity vinyl-terminated polydimethylsiloxane-based polymers These commercially available filler-reinforced crosslinkable silicone polymers (silicone rubbers) have high viscosities ranging from 100,000 centipoise (cP) to several million cP (e.g., 1 to 20 million cP). Therefore, a (low molecular weight) vinyl-terminated polydimethylsiloxane (<300 cP) can be added together with a low-temperature aliphatic solvent to improve its mixability and spreadability. SiH-terminated polydimethylsiloxane is added as a chain extender to polymerize the low-molecular weight vinyl-terminated polydimenthylsiloxane. The SiH-terminated polydimethylsiloxane-based polymer has a molecular weight of 1,000 to 100,000, preferably 3,000 to 10,000.

[0045] Examples of this type of polymer include, but are not limited to, Gelest product code numbers DMS-H21, DMS-H31, etc. A typical molecular structure of a SiH terminated polydimethyldisiloxane is illustrated below:

[0046] [ka]

[0047] The silicone polymer and novel platinum catalyst are dispersed in a low-boiling organic solvent to form a coating solution. Low-temperature aliphatic solvents are used for silicone dispersions. Aromatic solvents and hexamethyldisiloxane are commonly used for silicone dispersions. Typical examples include, but are not limited to, pentane, heptane, hexane, and mixtures thereof. The organic solvent is added at a concentration sufficient to effectively blend the silicone polymer components into a homogeneous coating solution. The total solvent concentration is about 80% to about 99% by weight, more typically about 85% to about 93% by weight, depending on the coating thickness requirements. Those skilled in the art will understand that the coating thickness can be manipulated by varying the solids content of the coating solution.

[0048] antibacterial agents The compositions described above further comprise at least one antibacterial agent. The antibacterial agent can be an antibiotic or antimicrobial agent or any agent with antipathogen function, including, for example, triclosan, chlorhexidine, polyhexamethylene biguanide (PHMB), octenidine, elemental silver, and silver salts. In a preferred embodiment, the compositions of the present invention comprise triclosan.

[0049] Wound fluid / moisture absorbing particles and indicators The compositions described above may further comprise at least one wound exudate or wound moisture absorbent and / or indicator.

[0050] Suitable absorbents are those having water or moisture or exudate absorbent particles that are capable of absorbing water in an amount of at least 10% by weight of the particle, more preferably at least 30% of the absorbed water relative to the weight of the particle. When present in the compositions of the present invention, the absorbent particles may have the property of changing color to indicate the presence of wound exudate or moisture, as described hereinafter.

[0051] Advantageously, prior to curing, silica-based desiccant particles containing an indicator are incorporated into the silicone matrix described above. After curing, the composition forms a thin layer suitable as a TSA / bandage with good adhesive, absorbent, and indicator properties.

[0052] Examples of absorbent materials include silica and anhydrous inorganic salts. Examples of anhydrous inorganic salts include copper(II) sulfate and cobalt(II) chloride. These types of absorbent materials change color when they come into contact with water and are used as indicators in commercially available desiccants that have indicating properties; the indicators are typically mixtures of silica and an inorganic salt indicator (e.g., cobalt(II) chloride).

[0053] Examples of commercially available desiccants include the® desiccants produced by EMD Millipore Corporation and Drierite™ indicating absorbents produced by WA Hammond.

[0054] Advantageously, superabsorbent materials can be utilized instead of or in combination with salt-based desiccants and absorbent materials. While the color change is due to salt hydration, most of the water absorption is due to the superabsorbent particles. In some embodiments, superabsorbent materials can be utilized as absorbent or desiccant particles in the present invention, including (a) crosslinked polyacrylates and polyacrylamides, (b) hydrolyzed cellulose-polyacrylonitrile, and c) crosslinked copolymers of maleic anhydride. Materials useful for such applications are exemplified by crosslinked sodium polyacrylate, various acrylonitrile- and acrylamide-based polymers (e.g., starch-g-polyacrylonitrile). Other superabsorbent materials that may be useful are based on various polysaccharides, such as starch, chitosan, and guar gum. Composite superabsorbents can also be made by incorporating kaolin, attapulgite, humates, mica, bentonite, montmorillonite, and sodium silicate.

[0055] Typically, the amount of absorber / indicator will be in the range of 5-25% by weight of the total formulation.

[0056] The inventors have discovered that, as described below, incorporating silica-based desiccant particles (with or without an indicator) into a film formed from the cured silicone matrix composition of the present invention results in a film having a hydrophobic upper surface and a water-permeable lower (substrate-facing) surface. Figure 7 is a schematic diagram illustrating water penetration into the lower surface of the film (e.g., a surface in constant, intimate contact with the substrate, such as a moist or exudate-producing wound or tissue surface), the color change of the embedded absorbent / indicator particles upon absorption of water or moisture from wound exudate, etc., into the film, and the water-repellent properties of the upper surface of the film. Intimate and prolonged contact of the lower surface with wound secretions / moisture allows absorption into the silicone film over time, while the hydrophobic upper surface repels water, preventing prolonged immersion of the film in moisture. The moisture-resistant properties of the upper surface of the film are ideally suited for patients who may wish to shower after the film has cured.

[0057] With reference to Figures 7a, 7b, and 7c, the above principles can be observed with compositions of the present invention. In one example, a silica-containing composition of the present invention was immersed in water to simulate intimate contact with a moisture source on its surface. Before immersion, a blue coloration was observed (Figure 7a). After immersion, the coloration changed to red / pink, indicating water intrusion (Figure 7b). The hydrophobic nature of compositions of the present invention is further illustrated by, for example, simulating prolonged, intimate contact (e.g., splashes in a shower) and viewing the surface of the cured composition, where drops of moisture (e.g., element 500) appear as beads, as shown in Figure 7c.

[0058] In various embodiments, the absorbent / indicator component may be incorporated into the compositions of the present invention in various ways. Referring to Figure 6a, a wound 360 in tissue 340 is approximated with a wound closure device 300. A topical skin adhesive 320 containing absorbent / indicator particles is applied over the top and sides of the wound closure device 300. Alternatively, as shown in Figure 6b, the absorbent / indicator particles may be applied to the wound closure device 400, or as a coating 450 on the wound closure device 400, as shown in Figure 6c.

[0059] array The order of component addition is important. A typical coating composition is prepared in the following manner: If silica is added as a separate component, the vinyl-terminated polydimethylsiloxane is dispersed with the surface-treated silica in a first solution, such as hexamethyldisiloxane, for up to two hours until completely homogenous (Solution 2). Heptane is then added (Solution 3) and mixed for an additional hour before adding the polymethylhydrosiloxane crosslinker. After all catalysts are added as the final component, the solution is thoroughly blended for an additional hour.

[0060] In the following paragraphs, weight percent refers to the weight percent of the total solids content in the coating solution. The novel coating compositions of the present invention will contain sufficient amounts of polymeric components, silica-containing compositions, crosslinkers, catalysts, and solvents to effectively provide silicone coatings with high flexibility and durability.

[0061] Typically, the amount of silica in the coating solution is about 5% to about 40% by weight (total solids), more typically about 10% to about 30% by weight (total solids), and preferably about 15% to about 25% by weight (total solids). The amount of crosslinkable silicone polymer is typically about 60% to about 95% by weight (total solids), more typically about 70% to about 90% by weight (total solids), and preferably about 75% to about 85% by weight (total solids). The amount of silicone crosslinker is typically about 1% to about 15% by weight (total solids), more typically about 2% to about 10% by weight (total solids), and preferably about 3% to about 8% by weight (total solids). The amount of platinum catalyst, based on the total solids in the novel silicone coating composition of the present invention (elemental platinum of total solids), is typically about 0.06% to about 0.003%, more typically about 0.04% to about 0.008%, and preferably about 0.03% to about 0.01% by weight. The amount of antimicrobial agent, based on the total solids in the novel silicone coating composition of the present invention, is typically about 0.05% to about 2%, more typically about 0.1% to about 1.5%, and preferably about 0.2% to about 1% by weight.

[0062] The amount of organic solvent in the compositions of the present invention is typically about 0% to about 30% by weight, more typically about 10% to about 20% by weight, and preferably about 12% to about 18% by weight. Those skilled in the art will understand that the amount of solvent present in the novel coating compositions of the present invention will vary depending on several factors, and that the amount of solvent in the coating composition will be selected to produce an effective coating. Typical factors to consider include the application method, curing method, coating equipment used, ambient conditions, thickness, etc. It will be understood that each component of the coating composition of the present invention can be a blend of these components. For example, two or more crosslinkable silicone polymers with different functional groups and / or molecular weights can be used.

[0063] In practice, like most commercially available platinum-cured silicone materials, the silicone-based topical skin adhesives of the present invention are delivered in a two-part kit by mixing equal amounts of the Part A and Part B components, as described hereinafter.

[0064] Briefly, a high-speed mixer is used to mix vinyl-terminated polydimethylsiloxane with platinum tetramethyldivinyldisiloxane diethylmaleate catalyst, silica particles, and optionally an aliphatic organic solvent to form kit Part A. A high-speed mixer is used to mix vinyl-terminated polydimethylsiloxane with polymethylhydro-co-polydimethylsiloxane crosslinker, silica particles, an antimicrobial agent (if desired), and optionally an aliphatic organic solvent to form kit Part B.

[0065] When applied to a substrate, equal amounts of the two-part kit were mixed using a static mixer and then spread onto the surface of the substrate, such as skin. The compositions of the present invention are well suited for wound closure applications, such as topical skin adhesives. In general, these compositions have been demonstrated to cure to a non-tacky character or feel at temperatures of about 19°C. At temperatures of about 28°C, the compositions cure in about 2-5 minutes.

[0066] As described above and as will be understood by those skilled in the art, the silicone composition of the present invention cures into a film that is neither tacky nor sticky within a few minutes. In contrast, some silicone adhesives, such as silicone pressure-sensitive adhesives (PSAs), are inherently tacky or sticky and are intended to remain so throughout the adhesive's useful life. Such a useful life of a sticky silicone PSA can extend to several years. The non-stickiness of the compositions and examples of the present invention is measured by ASTM C679.

[0067] Generally, ASTM C679 involves lightly touching the surface of a curable sealant to a polyethylene film at regular intervals until the sealant itself does not adhere to the film and the film appears clean when peeled from the surface. More specifically, a strip of polyethylene film is placed on the surface of the curable elastomer, and a 30g weight is placed on the film. The weight is left in place for 30 seconds, then removed, the polyethylene strip is removed, and the film is examined for sealant adhesion. The length of time from when the sealant is first applied to a given surface until the sealant no longer adheres to the film is called the tack-free time, and is the point at which the film exhibits a non-tacky nature, proving that the sealant has cured.

[0068] Upon hardening, the hardenable compositions of the present invention exhibit extensibility, flexibility, and stretchability properties that are particularly useful for application to wound closure over flexible joints, such as knees, elbows, etc. The hardenable compositions of the present invention, optionally in combination with various wound closure devices, can be applied to any wound closure, including wounds over flexible joints or wounds not over flexible joints, for example, general surgical closure of any tissue region (such as the body, abdomen, arms, legs, shoulders, back regions, etc.).

[0069] The compositions of the present invention may be applied directly onto the wound as a settable liquid or semi-liquid, flowable composition, or may be applied onto a porous, flowable composition-permeable wound closure device.

[0070] Wound Closure System As noted above, the compositions of the present invention are suitable for use in combination with wound closure devices.

[0071] Wound closure devices suitable for use in the present invention include any suitable device configured to close a wound. The most useful wound closure devices are wound closure strips, tapes, patches, or any other material suitable for closing a wound, most preferably strips. Preferably, the wound closure device is porous to allow the flowable polymerizable adhesive to penetrate the device and allow proper bonding of the device to the tissue surface to be bonded.

[0072] The wound closure device includes a wound-facing side and an upper side. The wound-facing side further includes an adhesive, such as a pressure-sensitive adhesive (PSA), applied to at least a portion of the wound-facing side. The PSA is useful for initial wound closure. The wound closure device is preferably porous. As used herein, "porous" means either that a majority of the wound closure device has pores, so that a subsequently applied polymerizable adhesive composition is soaked up or absorbed by the bulk material, or that a majority of the wound closure device has voids (such as a mesh or screen), so that a subsequently applied polymerizable adhesive composition passes directly through the bulk material, with or without being soaked up or absorbed by the bulk material. For example, in the case of a woven material, "porous" is generally used to mean that the applied adhesive composition penetrates and passes through the gaps between the fibers, but does not necessarily pass into and through the fibers themselves. Preferably, the wound closure device is a mesh strip.

[0073] Such porosity (or other properties, such as hydrophobicity or hydrophilicity) also allows for polymerization initiators or rate modifiers to be loaded into or onto the wound closure device prior to use to initiate the subsequently applied polymerizable adhesive composition. Such porosity also preferably allows air and liquid to pass through the wound closure device, either through the pores themselves or through voids in the bulk material. Depending on the degree of porosity and / or the size of the openings, the porosity of such meshes, or the ability of air and liquid to permeate through the mesh, can be tailored to remain or be absent after formation of the final composite material. Because they are intended to be used to cover wounds, such as on biological tissue, wound closure devices are also preferably non-toxic. Therefore, wound closure devices should be biocompatible with the desired substrate (e.g., tissue, skin, organs, etc.), preferably of a material that is government-approved or generally considered safe for the desired purpose. By way of example, a suitable wound closure device is a mesh material, as disclosed in US Patent Application Nos. 2006 / 0009099 and 2005 / 0182443, which are incorporated herein by reference in their entireties.

[0074] The wound closure device may be a woven fabric or mesh / web material. Suitable woven fabric materials may be formed of either synthetic or natural materials. Such woven fabric materials may be formed of either woven or nonwoven fabrics, or woven or nonwoven materials. The wound closure device may be, for example, any suitable polymeric film, plastic foam (including open-cell foam), woven fabric, knitted fabric, nonwoven fabric, or mixtures thereof. Thus, among other materials, suitable wound closure devices may be prepared from, for example, nylon, polyolefins (e.g., polyethylene, polypropylene, ethylene propylene copolymers, and ethylene butylene copolymers), acrylic, rayon, polyurethane, polyurethane foam, polystyrene, plasticized polyvinyl chloride, polyesters (e.g., polyethylene terephthalate (PET), polyamides, polylactic acid, polyglycolic acid, polycaprolactone, and copolymer mixtures of the above), natural materials (e.g., cotton, silk, and linen), polytetrafluoroethylene (PTFE), biovascular materials, collagen, Gore-Tex®, DACRON®, and the like. Preferred wound closure device materials are those that contain OH functional groups on their surfaces, whether naturally occurring or resulting from a surface treatment that imparts OH functional groups ("OH surface treatment"). These materials include, but are not limited to, polyester, nylon, acrylic, rayon, polyurethane, polyurethane foam, polystyrene, polyester, polyethylene terephthalate (PET), polyamide, polylactic acid, polyglycolic acid, polycaprolactone, copolymer blends of the above, as well as cotton, silk, and linen. Suitable OH surface-treated materials that impart OH functional groups to their surfaces include, but are not limited to, OH surface-treated PTFE, OH surface-treated polypropylene, and OH surface-treated polyethylene.

[0075] The wound closure device may be formed from synthetic, semi-synthetic, or natural organic materials. Thus, for example, the mesh may be formed from a synthetic or natural polymeric material that is not made from materials such as metal (e.g., silver, steel, etc.) or glass or ceramic. The wound closure device may or may not be biodegradable. The wound closure device is preferably tear-resistant.

[0076] The wound closure device may have a thickness of about 0.1 mm to about 25 mm, hi another embodiment, the wound closure device has a thickness of about 0.5 mm to about 20 mm, preferably about 0.7 mm to about 10 mm, and most preferably about 1 mm to about 5 mm.

[0077] The wound closure device is a strip, and the length of the strip may be about 2 cm to about 40 cm, preferably about 10 cm to about 30 cm, and most preferably 25 cm. The width of the strip may be 0.1 cm to about 8 cm, preferably about 2 cm to about 6 cm, and more preferably about 4 cm.

[0078] The wound closure device may be selected to be stretchable or to have some memory effect. In such embodiments, the stretchable properties of the mesh may desirably provide some pressure or stress at the application site, for example, to hold the wound edge coapted. Similarly, in embodiments where such an additional degree of pressure or stress at the application site is not desired, the mesh may be selected to have less stretch or no stretch.

[0079] Wound closure devices may or may not be biodegradable. "Biodegradable" means that the mesh biodegrades in vivo over time, thereby eliminating the need for physical removal of the mesh after a certain period of time. Thus, for example, a biodegradable mesh would biodegrade in an in vivo environment over a period of about one week to about five years. A non-biodegradable material would not biodegrade in an in vivo environment within about five years. Such non-biodegradable materials would therefore require physical removal of the wound closure device at a desired time, rather than slowly degrading over time or being able to naturally slough off from the tissue.

[0080] The wound closure device may preferably include one or more chemicals disposed therein or thereon. For example, one or more chemicals may be dispersed within or on the wound closure device, such as chemically bonded, physically bonded, absorbed, or adsorbed to the wound closure device. Such chemicals that may be present in or on the wound closure device include, but are not limited to, any suitable, preferably compatible, additive that enhances the performance of the composite structure. Such additional chemicals may be bioactive or non-bioactive. Accordingly, suitable other chemicals include, but are not limited to, colorants (such as inks, dyes, and pigments), fragrances, protective coatings that do not chemically strip, temperature-sensitive agents, pharmaceuticals, wound healing agents, antimicrobial agents, etc. [Example]

[0081] Example 1, Platinum Catalyst (Synthesis Procedure) 44.50 g of Gelest SIP6831.2 (2.2% platinum divinyltetramethyldisiloxane complex in xylene, Karstedt catalyst) was mixed with 2 g of diethyl maleate at ambient temperature for 24 hours. Samples were removed after 3, 18, and 24 hours of NMR testing. Figure 1 shows the NMR spectrum of the 3-hour sample.

[0082] The formation of the new catalyst is evidenced in Scheme 1, which is based on NMR spectroscopic identification. The Karstedt catalyst has a characteristic peak at approximately -6111 ppm. 195 It is known to have a Pt signal.

[0083] After mixing the mixture of Example 1 for 3 hours, the original signal of the Karstedt catalyst at -6111 ppm, along with a new signal at -6082 ppm, was observed, as illustrated in the NMR spectrum of this mixture at 3 hours in Figure 1. 195 A Pt signal was observed, and the intensity of the new signal increased over time, while the intensity of the Karstedt catalyst signal simultaneously decreased.

[0084] Preparation of test sample compositions As described above, the silicone-based topical skin adhesive is delivered in a two-part kit by mixing equal amounts of ingredients Part A and Part B. The following examples illustrate the ingredients of each part of the composition as they are prepared and then mixed together.

[0085] Example 2. Preparation of a Silicone-Based Topical Skin Adhesive—No Antimicrobial Agent Part A 40 g of vinyl-terminated polydimethylsiloxane (Gelest DMSV41) was mixed with 10 g of surface-treated silica particles (Gelest SIS6962.0) and 2.6 g of the resulting catalyst from Example 1 using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.

[0086] Part B 40 g of vinyl-terminated polydimethylsiloxane (Gelest DMSV41) was mixed with 10 g of surface-treated silica particles (Gelest SIS6962.0) and 3.34 g of polymethylhydro-co-polydimethylsiloxane (Gelest HMS301) using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.

[0087] Example 3. Preparation of a silicone-based topical skin adhesive using a commercially available silica-containing silicone raw material—without an antimicrobial agent Part A 90 g of Elkem 44 experimental base (containing vinyl-terminated polydimethylsilicone-based polymer and fumed silica particles) was mixed with 4.72 g of the resulting catalyst of Example 1, 9.0 g of low molecular weight vinyl-terminated polydimethylsilicone-based polymer (Gelest DMS V21), and 26 g of hexane using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.

[0088] Part B 81 g of Elkem 44 experimental base (containing a vinyl-terminated polydimethylsilicone-based polymer and fumed silica particles) was mixed with 8.1 g of polymethylhydrosiloxane crosslinker (Gelest DMS H991), 2.7 g of SiH-terminated polydimethylsiloxane chain extender (Gelest DMS H21), and 10.2 g of hexane using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.

[0089] Control: Control using conventional Karstedt catalyst without silica binder - no antimicrobial agent Part A 40 g of vinyl-terminated polydimethylsiloxane (Gelest DMSV41) was mixed with 2.6 g of Karstedt catalyst xylene solution (1% Gelest SIP6831.2 in xylene) using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.

[0090] Part B 40 g of vinyl-terminated polydimethylsiloxane (Gelest DMSV41) was mixed with 3.34 g of polymethylhydro-co-polydimethylsiloxane (Gelest HMS301) using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.

[0091] Example 4A. Preparation of a Silicone-Based Antimicrobial Topical Skin Adhesive of the Present Invention Loaded with 0.25% Triclosan Part A 90 g of Elkem 55 experimental base (containing a vinyl-terminated polydimethylsilicone-based polymer and fumed silica particles) was mixed with 0.62 g of Example 1, 0.90 g of Gelest SIP6831.2 (2.2% platinum divinyltetramethyldisiloxane complex in xylene), and 9.0 g of a low molecular weight vinyl-terminated polydimethylsilicone-based polymer (Gelest DMS V21) using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.

[0092] Part B 90 g of Elkem 55 experimental base (containing a vinyl-terminated polydimethylsilicone-based polymer and fumed silica particles) was mixed with 9.0 g of polymethylhydro-co-polydimethylsiloxane crosslinker (Gelest DMS H301), 3.0 g of SiH-terminated polydimethylsiloxane chain extender (Gelest DMS H21), and 0.5 g of triclosan using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.

[0093] Example 4B. Preparation of a Silicone-Based Antimicrobial Topical Skin Adhesive of the Present Invention Loaded with 0.50% Triclosan Part A 90 g of Elkem 55 experimental base (containing a vinyl-terminated polydimethylsilicone-based polymer and fumed silica particles) was mixed with 0.62 g of Example 1, 0.90 g of Gelest SIP6831.2 (2.2% platinum divinyltetramethyldisiloxane complex in xylene), and 9.0 g of a low molecular weight vinyl-terminated polydimethylsilicone-based polymer (Gelest DMS V21) using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.

[0094] Part B 90 g of Elkem 55 experimental base (containing a vinyl-terminated polydimethylsilicone-based polymer and fumed silica particles) was mixed with 9.0 g of polymethylhydro-co-polydimethylsiloxane crosslinker (Gelest DMS H301), 3.0 g of SiH-terminated polydimethylsiloxane chain extender (Gelest DMS H21), and 1.0 g of triclosan using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.

[0095] Example 4C. Preparation of a Silicone-Based Antimicrobial Topical Skin Adhesive of the Present Invention Loaded with 0.75% Triclosan Part A 90 g of Elkem 55 experimental base (containing a vinyl-terminated polydimethylsilicone-based polymer and fumed silica particles) was mixed with 0.62 g of Example 1, 0.90 g of Gelest SIP6831.2 (2.2% platinum divinyltetramethyldisiloxane complex in xylene), and 9.0 g of a low molecular weight vinyl-terminated polydimethylsilicone-based polymer (Gelest DMS V21) using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.

[0096] Part B 90 g of Elkem 55 experimental base (containing a vinyl-terminated polydimethylsilicone-based polymer and fumed silica particles) was mixed with 9.0 g of polymethylhydro-co-polydimethylsiloxane crosslinker (Gelest DMS H301), 3.0 g of SiH-terminated polydimethylsiloxane chain extender (Gelest DMS H21), and 1.5 g of triclosan using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.

[0097] Example 4D, Control Example: Preparation of a Silicone-Based Topical Skin Adhesive with 0% Triclosan Loading Part A 90 g of Elkem 55 experimental base (containing a vinyl-terminated polydimethylsilicone-based polymer and fumed silica particles) was mixed with 0.62 g of Example 1, 0.90 g of Gelest SIP6831.2 (2.2% platinum divinyltetramethyldisiloxane complex in xylene), and 9.0 g of a low molecular weight vinyl-terminated polydimethylsilicone-based polymer (Gelest DMS V21) using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.

[0098] Part B 90 g of Elkem 55 experimental base (containing a vinyl-terminated polydimethylsilicone-based polymer and fumed silica particles) was mixed with 9.0 g of polymethylhydro-co-polydimethylsiloxane crosslinker (Gelest DMS H301), 3.0 g of SiH-terminated polydimethylsiloxane chain extender (Gelest DMS H21) using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.

[0099] Example 5. Test Sample Preparation and Description of Test Procedures Test Procedures Preparation of Wound Closure Strip Test Samples An 8 inch by 11 inch synthetic substrate (or biosubstrate) was cut in two halves measuring 4 inches by 11 inches. A 1 inch wide PSA (pressure sensitive adhesive) coated polyester mesh was placed along the cut line to hold the two halves together. The two-part silicone TSA composition described above was mixed and applied evenly onto the mesh using a conventional rubber spatula to cover the entire area of the mesh.

[0100] Holding strength test: This test evaluated the force required to separate a PSA-coated mesh and a substrate that was applied with a silicone TSA composition. The method was based on ASTM F2458: Standard Test Method for Wound Closure Strength of Tissue Adhesives and Sealants.

[0101] A synthetic substrate (Mylar) was used for testing, and selected samples were also tested on pig skin. The width of the synthetic substrate was 1 inch, the pig skin was 2 inches, and the strain rate was 20 inches per minute.

[0102] Peel test. T-peel strength testing was performed according to ASTM F2256: Standard Test Method for Strength Properties of Tissue Adhesives in T-peel with Tension Loading.

[0103] The average peel strength of the mesh coated with the silicone-based TSA in a T-peel configuration is performed at a strain rate of 10 inches per minute.

[0104] Zone of Inhibition Test: A triclosan-containing silicone TSA test article is placed on an agar plate inoculated with the test organism. When the antimicrobial agent triclosan diffuses through the silicone carrier into the agar plate, susceptible microorganisms will not grow on or around the disk for a distance as long as the concentration of the antimicrobial agent exceeds the minimum inhibitory concentration (MIC). This distance is called the Zone of Inhibition (ZOI). Assuming the antimicrobial agent has a diffusion rate in the medium, the presence of a ZOI around the test article indicates that the organism would be inhibited by the presence of the antimicrobial agent in a satisfactory growth medium in its absence. The diameter of the ZOI is inversely proportional to the MIC.

[0105] Using this ZOI test, triclosan-containing silicone-coated test articles were tested for antimicrobial properties. The ZOI test is a conventional method for estimating the inhibitory effect of an antimicrobial substance against a specific bacterial strain of interest. The ZOI assay is useful for testing diffusible agents. As the agent diffuses away from the disk, the concentration decreases logarithmically. The susceptibility of the organism to the agent is determined by the appearance and size of a zone where no growth occurs (i.e., the zone of inhibition).

[0106] The triclosan-containing silicone-coated test articles were aseptically placed into individual sterile Petri dishes and exposed to 100 microliters of inoculum containing 10 colony-forming units (CFU) of Staphylococcus aureus or Escherichia coli. Trypticase soy agar was poured into each dish and allowed to solidify. The plates were incubated at 37°C for 48 hours. After incubation, the plates were examined in a dark-field colony counter and the zone of inhibition was measured.

[0107] Holding strength test sample Synthetic backing, polyester film, 0.05 inch thick Duralar® film (Grafix Plastics, Maple Heights, OH) A 1.0 inch wide PSA (pressure sensitive adhesive) coated polyester mesh (Lot No. 16204, Innovize, St. Paul, MN) was placed along the cut line to hold together two halves of the 4 inch x 11 inch Duralar film described above. In each of the following examples, the two-part silicone TSA composition was mixed (Example 2, Example 3, Control, Examples 4A-4C, and Control 4D) and applied evenly onto the mesh, covering the entire area of the mesh using a conventional rubber spatula. The samples were allowed to dry at 31°C for 2-5 minutes. Five 1 inch wide strips of each coated mesh sample were cut for testing.

[0108] Bio-based material (pig skin) A 2 inch by 8 inch pigskin sample was cut into two halves measuring 2 inches by 4 inches. A 1.5 inch wide PSA (pressure sensitive adhesive) coated polyester mesh was placed along the cut line to hold the two halves together. A two-part silicone TSA composition (Example 3) was mixed and applied evenly onto the mesh using a conventional rubber spatula to cover the entire area of the mesh.

[0109] Peel test sample Synthetic substrate (polyester film, 0.05 inch thick Duralar® film) (Grafix Plastics, Maple Heights, OH) A 5" x 5" PSA (pressure-sensitive adhesive) coated polyester mesh (Lot No. 16204, Innovize, St. Paul, MN) was placed on a polyester substrate of the same dimensions. Each of the two-part silicone TSA compositions from the following examples (Example 2, Example 3, Control, Examples 4A, 4B, 4C, and Control 4D) was mixed and applied to the mesh using a conventional rubber spatula to evenly cover the entire area of the mesh. Each coated mesh sample was dried and maintained at 31°C overnight (i.e., at least 8 hours), after which five 1-inch wide specimens were cut for testing.

[0110] Bio-based material (arm of a 55-year-old Asian male) A 3" x 1" PSA (pressure sensitive adhesive) coated onto polyester mesh was placed on the left arm of a 55-year-old Asian male. Each of the two-part silicone TSA compositions of the following examples was mixed (Example 3 and Control) and applied onto the mesh using a conventional rubber spatula to cover the entire area of the mesh.

[0111] Bio-based material (pig skin) A 5" x 1.5" PSA (pressure sensitive adhesive) coated polyester mesh (Lot #16204, Innovize, St. Paul, MN) was placed on a piece of porcine skin. The two-part silicone TSA composition of Example 3 was mixed and applied onto the mesh using a conventional rubber spatula to cover the entire area of the mesh.

[0112] Stretching test sample A 5-inch x 5-inch PSA (pressure-sensitive adhesive) coated polyester mesh (Lot No. 16204, Innovize, St. Paul, MN) was placed on a Teflon substrate. A two-part silicone TSA composition was mixed (Example 3 and Example 4C) and applied evenly onto the mesh using a conventional rubber spatula to cover the entire area of the mesh. After 1 hour, the silicone-coated polyester mesh was peeled from the Teflon substrate. Five 1-inch wide silicone-coated mesh specimens were cut for testing.

[0113] Performance test results: 1a: Retention test results (synthetic substrate) Retention tests on polyester film were performed for the compositions of Examples 2 and 3, along with a control, and the results are summarized in Table 1.

[0114] [Table 1]

[0115] Referring to Table 1, it can be seen that retention on polyester substrates is significantly better for the inventive examples made from polysiloxane polymers and commercial bases compared to the conventional crosslinked silicone polymer using Karstedt's catalyst (control). Additionally, a decrease in retention is observed between the antimicrobial-containing examples (Examples 4A, 4B, and 4C) and the non-antimicrobial-containing examples (Examples 2, 3, and 4D).

[0116] 1b: Retention test results (biosubstrate) The composition of Example 3 was subjected to a pig skin retention test. Table 2 summarizes the results.

[0117] [Table 2]

[0118] Referring to Table 2, it is shown that the holding strength of the silicone-based TSA on pig skin is comparable to the holding strength of a cyanoacrylate-based commercial product, which is about 10 pounds.

[0119] 2a: Peel test results (synthetic substrate) Peel testing of TSA compositions on synthetic substrates (polyester) was performed using the compositions of Examples 2 and 3, as well as Control and Examples 4A-4C and Control 4D. Table 3 summarizes the results.

[0120] [Table 3]

[0121] Referring to Table 3, it can be seen that the average and maximum peel forces for polyester substrates are significantly superior for the inventive examples made from polysiloxane polymers and commercial bases compared to the conventional crosslinked silicone polymers using Karstedt's catalyst (Control Example). Furthermore, peel forces are observed to be approximately equal or slightly lower between the antimicrobial-containing examples (Examples 4A, 4B, and 4C) and the non-antimicrobial-containing examples (Examples 2, 3, and 4D).

[0122] 2b: Peel test results (bio-based substrate) Stripping tests of TSA on human skin were performed for Example 3 and the control. Table 4 summarizes the results.

[0123] [Table 4]

[0124] The release force of the silicone TSA made in Example 3 of the present invention is significantly higher than the control, and the release force of the silicone TSA on human skin is very similar to the release force of the same material on a polyester substrate (see Table 3).

[0125] 2b: Peel test results (bio-based substrate) Peel testing of TSA on pig skin was performed in Example 3 and the results are summarized in Table 4a.

[0126] [Table 5]

[0127] 3: Results of extension test Example 3 was stretched to 160% of its original length. The dimensions of the test specimen were measured before and after stretching, and images are shown in Figures 2a, 2b, and 2c.

[0128] Example 4C was stretched to 145% of its original length. The dimensions of the test specimen were measured before and after stretching, and images are shown in Figures 3a, 3b, and 3c.

[0129] With reference to these figures, the test results show that Example 3 can be stretched to 160% of its original dimensions and fully recover, while the Example 4C sample can be stretched to 145% and fully recover. In a separate test (not shown), the cyanoacrylate-coated polyester mesh sample could only be stretched to 101% of its original dimensions. That is, 1% stretch was sufficient to cause permanent deformation.

[0130] Example 6 - Zone of Inhibition Test Duplicate test articles (1 x 1 cm silicone-coated polyester mesh specimens) cut from each Example were aseptically placed into individual sterile Petri dishes and exposed to 100 microliters of inoculum containing 10 colony-forming units (CFU) of Staphylococcus aureus (S. aureus) or Escherichia coli (E. coli). Trypticase soy agar was poured into each dish and allowed to solidify. The plates were incubated at 37°C for 24 hours. After incubation, the plates were examined in a dark-field colony counter and the zone of inhibition was measured. The results are shown in Tables 4 and 5.

[0131] [Table 6]

[0132] Referring to Table 4, it can be seen that the compositions containing antimicrobial agents (Examples 4A-4C) are effective against S. aureus, whereas the non-antimicrobial composition (Control Example 4D) is not effective against S. aureus.

[0133] Figures 4a and 4b show the ZOIs for Example 4C (0.75% triclosan loading) and Control Example 4D (no antimicrobial agent), respectively, exposed to A. aureus on trypticase soy agar plates. As can be seen by comparing these two figures, Example 4C demonstrates that the composition of the present invention can effectively load an antimicrobial agent.

[0134] [Table 7]

[0135] Referring to Table 5, it can be seen that the compositions containing an antimicrobial agent (Examples 4A-4C) are effective against E. coli, whereas the non-antimicrobial composition (Control Example 4D) is not effective against E. coli.

[0136] Figures 5a and 5b show the ZOIs for Example 4C (0.75% triclosan loading) and Control Example 4D (no antimicrobial agent), respectively, exposed to E. coli on trypticase soy agar plates. As can be seen by comparing these two figures, Example 4C demonstrates that the compositions of the present invention can effectively load antimicrobial agents.

[0137] Example - Solventless (SF) In some embodiments, the use of organic solvent-free mixed compositions is more desirable. Such embodiments include situations where the contents of a mixing device, such as a dual-barrel syringe, may be prepared using a solvent, resulting in the syringe contents leaking past the syringe seal or the solvent evaporating. The inventors have discovered that suitable compositions without organic solvents are possible by substituting low molecular weight (3000-9000) vinyl-terminated polydimethylsiloxanes and / or low molecular weight (3000-9000) hydride-terminated polydimethylsiloxanes. Both of these types of low molecular weight vinyl-terminated or hydride-terminated polydimethylsiloxane compounds have viscosities in the range of 40-150 cP. The inventors have demonstrated that these solvent-free formulations can reduce the viscosity of high-viscosity silicone bases, which typically have viscosities of over 500,000 up to several million centipoise.

[0138] In these embodiments, the Part A composition will typically contain in the range of 60-95 wt. % silicone base (including vinyl terminated polydimethylsilicone base polymer and fumed silica particles) for controlling the viscosity of Part A between 45,000-75,000 cP (or 30-100 wt. % for controlling the viscosity of Part A between 15,000-45,000 cP, or 0-40 wt. % for controlling the viscosity of Part A between 75,000-105,000 cP), 5-15 wt. % vinyl terminated polydimethylsiloxane for 3000-9000 cPs, and 100-250 ppm elemental platinum contributed by the catalyst of the present invention. Pt[(CH2=CH)(CH3)2Si]2O·(COCH=CHCO)(C2H5O)2.

[0139] The Part B composition will typically contain in the range of 60-80 wt. % silicone base (including vinyl terminated polydimethylsilicone base polymer and fumed silica particles) if the viscosity of Part B is controlled to 45,000-75,000 cP base (or 0-30 wt. % base if the viscosity of Part B is controlled to 15,000-45,000 cP, or 70-100 wt. % base if the viscosity of Part B is controlled to 75,000-105,000 cP), 10-40 wt. % polymethylhydro-co-polydimethylsiloxane crosslinker, and 3-12 wt. % hydride terminated polydimethylsiloxane.

[0140] Typically, the viscosity of both the Part A and Part B compositions, independently, before mixing, will be in the range of 25,000 to 100,000 cP, and will be similar when Parts A and B are used in combination with each other at around low, medium, or high viscosity levels.

[0141] Example 1 - Novel Platinum Catalyst (Synthesis Procedure) 2.7g of diethyl maleate was mixed with 3.6g of diethyl ether and 3.6g of Gelest SIP6830.3 (3.0% platinum divinyltetramethyldisiloxane complex in vinyl-terminated polydimethylsiloxane, Karstedt catalyst - no xylene solvent) for 24 hours at ambient temperature. 64.9g of Gelest SIP6830.3 was then added to the mixture, and the mixture was mixed for an additional 72 hours with the container cap open. Finally, 928.8g of vinyl-terminated polydimethylsiloxane (Gelest DMS V21) was added and mixed for an additional 4 hours. The new platinum catalyst masterbatch contained the new catalyst with 2055ppm elemental platinum, with the remainder essentially vinyl-terminated polydimethylsiloxane.

[0142] Example 2-SF, (low viscosity) (15,000 to 45,000 cP) Part A Using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 3 minutes, 90 g of Elkem 55 experimental base (also known as Elkem Silbione 4020-55, containing vinyl-terminated polydimethylsilicone-based polymer and fumed silica particles) was mixed with 10 g of Example 1-SF. This composition had a viscosity of 32,090 cP (see Example 7a-SF).

[0143] Part B Using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 3 minutes, 90 g of Elkem 55 experimental base was mixed with 9.0 g of polymethylhydro-co-polydimethylsiloxane crosslinker (Gelest HMS H301) and 3.0 g of SiH-terminated polydimethylsiloxane chain extender (Gelest DMS H21). The composition had a viscosity of 31,160 cP (see Example 7a-SF).

[0144] Example 3-SF, medium viscosity (45,000-75,000 cP) Part A Using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 3 minutes, 115 g of Elkem 55 experimental base was mixed with 20 g of Elkem 44 experimental base (also known as Elkem Silbione 4020-55, containing vinyl-terminated polydimethylsilicone-based polymer and fumed silica particles) and 15 g of Example 1-SF. This composition had a viscosity of 57,900 cP (see Example 7a-SF).

[0145] Part B Using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 3 minutes, 80 g of Elkem 44 experimental base was mixed with 20 g of Elkem 55 experimental base, 42 g of polymethylhydro-co-polydimethylsiloxane crosslinker (Gelest HMS 151), and 8.0 g of SiH-terminated polydimethylsiloxane chain extender (Gelest DMS H21). The composition had a viscosity of 61,500 cP (see Example 7a-SF).

[0146] Example 4-SF, high viscosity (75,000-105,000 cP) Part A Using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 3 minutes, 90 g of Elkem 55 experimental base was mixed with 45 g of Elkem 44 experimental base and 15 g of Example 1-SF. This composition had a viscosity of 84,000 cP. (See Example 7a-SF.)

[0147] Part B Using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 3 minutes, 100 g of Elkem 44 experimental base was mixed with 42 g of polymethylhydro-co-polydimethylsiloxane crosslinker (Gelest HMS H151) and 8.0 g of SiH-terminated polydimethylsiloxane chain extender (Gelest DMS H21). The composition had a viscosity of 94,800 cP (see Example 7a-SF).

[0148] Example 5-SF: Adhesion Performance Test Sample Preparation: Holding strength test sample Synthetic backing, polyester film, 0.05 inch thick Duralar® film (Grafix Plastics, Maple Heights, OH) A 1.5-inch wide PSA (pressure-sensitive adhesive) coated polyester mesh (Lot No. 16204, Innovize, St. Paul, MN) was placed along the cut lines to hold together two halves of the 4-inch by 11-inch Duralar film described above. In each of the following examples, the two-part silicone TSA composition was mixed (Example 2-SF, Example 3-SF, Example 4-SF) and applied to the mesh using a conventional rubber spatula, covering the entire area of the mesh. The samples were cured at 31°C for 1-3 minutes and maintained at this temperature overnight. Five 1-inch wide strips of each coated mesh sample were cut for testing.

[0149] Peel test sample Synthetic substrate (polyester film, 0.05 inch thick Duralar® film) (Grafix Plastics, Maple Heights, OH) A 5" x 5" PSA (pressure-sensitive adhesive) coated polyester mesh (Lot No. 16204, Innovize, St. Paul, MN) was placed on a polyester substrate of the same dimensions. Each of the two-part silicone TSA compositions from the following examples was mixed (Example 2-SF, Example 3-SF, Example 4-SF) and applied to the mesh using a conventional rubber spatula to cover the entire area of the mesh. Each coated mesh sample was allowed to cure and maintained at 31°C overnight (i.e., at least 8 hours), after which five 1-inch wide specimens were cut for testing.

[0150] Stretching test sample A 5" x 5" PSA (pressure-sensitive adhesive) coated polyester mesh (Lot No. 16204, Innovize, St. Paul, MN) was placed on a polyethylene substrate. Two-part silicone TSA compositions were mixed (Examples 2-SF, 3-SF, and 4-SF) and applied evenly onto the mesh using a conventional rubber spatula to cover the entire area of the mesh. After 1 hour, the silicone-coated polyester mesh was peeled from the Teflon substrate. Five 1-inch wide silicone-coated mesh specimens were cut for testing.

[0151] Example 6-SF. Description of Test Procedure Viscosity measurement: Viscosity measurements were performed on Examples 2-SF, 3-SF, and 4-SF using a Brookfield DV II+CP viscometer. Spindle 12 was used for all measurements, and the speed was 1 RPM.

[0152] Curing time measurement ASTM C679: Standard Test Method for Tack-Free Time of Elastomeric Sealant. The test consists of lightly touching the surface of the curable sealant to a polyethylene film at regular intervals until the sealant itself does not adhere to the film and the film appears clean when peeled from the surface. More specifically, a strip of polyethylene film is placed on the surface of the curable elastomer and a 30 g weight is placed on the film. The weight is left in place for 30 seconds, then removed, the polyethylene strip is removed, and the film is examined for sealant adhesion. The length of time from when the sealant is first applied to a given surface until the sealant no longer adheres to the film is called the tack-free time, and is the point at which the film exhibits a non-tacky nature, proving that the sealant has cured.

[0153] Peel test. T-peel strength testing was performed according to ASTM F2256: Standard Test Method for Strength Properties of Tissue Adhesives in T-peel with Tension Loading.

[0154] The average peel strength of the mesh coated with the silicone-based TSA in a T-peel configuration is performed at a strain rate of 10 inches per minute.

[0155] Holding strength test: This test evaluated the force required to separate a PSA-coated mesh and a substrate that was applied with a silicone TSA composition. The method was based on ASTM F2458: Standard Test Method for Wound Closure Strength of Tissue Adhesives and Sealants.

[0156] The test used a synthetic substrate (Mylar) with a width of 1 inch and a strain rate of 20 inches / minute.

[0157] Example 7-SF. Performance test results: 7a-SF. Viscosity measurement. Table 1a-SF summarizes the results of the viscosity measurements for Examples 2-SF, 3-SF, and 4-SF.

[0158] [Table 8]

[0159] 7b-SF. Measurement of curing time Cure time measurements for the compositions of Examples 2-SF, 3-SF, and 4-SF were performed during the preparation of the peel test specimens, and the results are summarized in Table 1b-SF.

[0160] [Table 9]

[0161] The foregoing demonstrates that the compositions of the present invention can cure in less than two minutes.

[0162] 7c-SF: Retention test results (synthetic substrate) Retention tests on polyester film were performed for the compositions of Examples 2-SF, 3-SF, and 4-SF, and the results are summarized in Table 1c-SF.

[0163] [Table 10]

[0164] Referring to Table 1c-SF, it can be seen that retention on polyester substrates is significantly better for the inventive examples made from polysiloxane polymers and commercial bases (Control, Table 1) compared to the conventional cross-linked silicone polymers using Karstedt's catalyst (Control).

[0165] 7d-SF: Peel test results (synthetic substrate) Peel testing of TSA compositions on synthetic substrates (polyester) was performed using compositions of Examples 2-SF, 3-SF, and 4-SF, and the results are summarized in Table 1d-SF.

[0166] [Table 11]

[0167] Referring to Table d-SF, it can be seen that the average peel force for polyester substrates is significantly better for the inventive examples made from polysiloxane polymers and commercial bases compared to the conventional crosslinked silicone polymers using Karstedt catalysts (see Control, Table 3).

[0168] 7e-SF: Results of extension test Examples 2-SF, 3-SF, and 4-SF were able to be stretched to 160% of their original length and recover to their original dimensions.

[0169] As demonstrated, the novel compositions, wound closure systems, and catalysts of the present invention have many advantages over the prior art. The compositions enable the formation of medical-grade silicone adhesives that are particularly suitable for human skin. The compositions provide a durable, stretchable structure that offers both mechanical and adhesive properties. The catalyst provides dual-cure catalysis, allowing polysiloxane chains to crosslink rapidly to form films while also forming adhesive properties on a given hydroxyl-containing substrate. In the presence of this novel dual-functional catalyst, silanol functional groups on the surface of silicone fillers in the composition react with hydroxyl functional groups on a given surface, providing adhesive properties to the novel silicone adhesive.

[0170] Example 7 - Wound Exudate / Hygroscopic Particles and Indicator The following examples demonstrate the feasibility of embodiments of the compositions of the present invention incorporating wound exudate / moisture absorbent particles and / or indicators to absorb moisture when in intimate contact with a moisture source, while maintaining the important adhesive and flexibility characteristics required for use as a wound closure device.

[0171] Like most commercially available platinum-cured silicone materials, the water-absorbent silicone-based topical skin adhesives (TSAs) of the present invention are delivered in a one-to-one volume, two-part kit.

[0172] Preferably, the aforementioned composition is made with the solventless silicone composition described above.

[0173] Generally, a high-speed mixer is used to mix vinyl-terminated polydimethylsiloxane with platinum tetramethyldivinyldisiloxane diethylmaleate catalyst, silica particles, and optionally an aliphatic organic solvent to form Part A of the kit. A high-speed mixer is used to mix vinyl-terminated polydimethylsiloxane with polymethylhydro-co-polydimethylsiloxane crosslinker, silica particles, and optionally an aliphatic organic solvent to form Part B of the kit. Silica desiccant particles are blended into Part B during the preparation process. These water-absorbing particles are commercially available and have an indicator property where a color change indicates absorbed water / moisture.

[0174] Example 7a: Preparation of a silicone-based water-absorbing TSA with 23% desiccant loading Absorbent TSA with 23% desiccant Part A 90 g of E-Kem 55 experimental base (containing a vinyl-terminated polydimethylsilicone-based polymer and fumed silica particles) was mixed with 0.62 g of Example 1, 0.60 g of Gelest SIP 6830.3 (a 3% platinum divinyltetramethyldisiloxane complex in vinyl-terminated polydimethylsiloxane), and 9.0 g of a low molecular weight vinyl-terminated polydimethylsilicone-based polymer (Gelest DMS V21) using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.

[0175] Part B Using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes, 32 g of E-Kem55 experimental base (containing a vinyl-terminated polydimethylsilicone-based polymer and fumed silica particles) was mixed with 20.5 g of polymethylhydro-co-polydimethylsiloxane crosslinker (Gelest DMS H071), 1.6 g of SiH-terminated polydimethylsiloxane chain extender (Gelest DMS H21), and 45.8 g of silica desiccant (the® Desiccant, 100% indication, EMD Millipore Corporation, Billerica, MA).

[0176] Control Example 7b: Preparation of a silicone-based TSA with 0% desiccant loading Part A 90 g of E-Kem 55 experimental base (containing a vinyl-terminated polydimethylsilicone-based polymer and fumed silica particles) was mixed with 0.62 g of Example 1, 0.62 g of Example 1, 0.60 g of Gelest SIP 6830.3 (a 3% platinum divinyltetramethyldisiloxane complex in vinyl-terminated polydimethylsiloxane), and 9.0 g of a low molecular weight vinyl-terminated polydimethylsilicone-based polymer (Gelest DMS V21) using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.

[0177] Part B 64 g of E-Kem55 experimental base (containing a vinyl-terminated polydimethylsilicone-based polymer and fumed silica particles) was mixed with 41 g of polymethylhydro-co-polydimethylsiloxane crosslinker (Gelest DMS H071) and 3.2 g of SiH-terminated polydimethylsiloxane chain extender (Gelest DMS H21) using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.

[0178] Example 7c - Preparation of Test Samples Holding strength test sample An 8-inch by 11-inch synthetic substrate (polyester film, 0.05-inch thick Duralar film, Grafic Plastics, Maple Height, Ohio) was cut into two halves measuring 4 inches by 11 inches. A 1-inch-wide PSA (pressure-sensitive adhesive)-coated polyester mesh (Lot No. 16204, Innovize, St. Paul, Minn.) was placed along the cut line to hold the two halves together. In each of the following examples, the two-part silicone TSA compositions were mixed (Example 7a and Control Example 7b) and applied to the mesh using a conventional rubber spatula, covering the entire area of the mesh. In accordance with ASTM 678, the samples were dried at 31°C for 3 minutes. After 1 hour at 31°C, 1-inch-wide strips were cut for testing.

[0179] Peel test sample Synthetic substrates (polyester film, 0.05-inch-thick Duralar film) (Grafic Plastics, Maple Heights, OH)

[0180] A 5" x 5" PSA (pressure-sensitive adhesive) coated polyester mesh (Lot No. 16204, Innovize, St. Paul, MN) was placed on a Mylar substrate with the same dimensions. In each of the following examples, the two-part silicone TSA composition was mixed (Example 7a and Control 7b) and applied to the mesh using a conventional rubber spatula to cover the entire area of the mesh. The samples were allowed to dry and rest overnight at 31°C, after which 1-inch wide specimens were cut for testing.

[0181] Stretching test sample A 5" x 5" PSA (pressure-sensitive adhesive) coated polyester mesh (Lot No. 16204, Innovize, St. Paul, MN) was placed on a Teflon substrate. In each of the following examples, a two-part silicone TSA composition was mixed (Example 7a and Control 7b), respectively, and applied to the mesh using a conventional rubber spatula to cover the entire area of the mesh. After 1 hour, the silicone-coated polyester mesh was peeled from the Teflon substrate. 1" x 5" silicone-coated mesh specimens were cut for extension testing.

[0182] Example 7d - Performance Test Results Retention test (synthetic substrate) Retention tests on polyester film were performed on test samples of Example 7a and Control 7b, and the results are summarized below.

[0183] [Table 12]

[0184] For the water-absorbing silicone-based TSA (Example 7a, containing desiccant), retention on a polyester substrate is comparable to that of the non-drying silicone-based TSA (Control Example 7b).

[0185] Peel test (synthetic substrate) Peel testing of TSA on synthetic substrates was performed on test samples using the compositions of Example 7a and Control 7b, and the results are summarized below.

[0186] [Table 13]

[0187] As can be seen, the release force of the water-absorbing silicone-based TSA (Example 7a) on a polyester substrate is slightly lower than the release force of the non-drying silicone-based TSA (Control Example 7b).

[0188] Extension test The sample of Example 7a was stretched to 150% of its original length. The dimensions of the test sample were measured before and after stretching, and images are shown in Figures 7d, 7e, and 7f.

[0189] Water absorption test: A test specimen of Example 7a, measuring approximately 3.5 x 3.5 x 0.1 cm, was immersed in water at ambient temperature for 24 hours. After immersion in water, a weight gain of 4.82% was observed. A test specimen of control sample 7b was tested at the same time, and no weight gain was observed. As illustrated in Figures 7G and 7h, the color of the test specimen (Example 7a) changed from blue to brown.

[0190] As illustrated in the examples above, the incorporation of a silica-based desiccant into a silicone TSA can exhibit a color change when immersed in water. Quite unexpectedly, the hydrophobic nature of crosslinked polydimethylsiloxane does not appear to prevent water penetration into the silicone TSA matrix when the silicone TSA is in full contact with water via immersion; the same would be expected to be true when the silicone TSA is in intimate contact with a moisture source over a period of time, such as a wound closure device in contact with wound exudate / drainage. Of particular note is the finding that the incorporation of a desiccant does not appear to affect the adhesive and mechanical properties of the silicone TSA when compared to a control that does not contain a desiccant.

[0191] As demonstrated, the novel composition, wound closure system, and catalyst of the present invention offer numerous advantages over the prior art. The composition allows for the formation of a medical-grade silicone adhesive, particularly suitable for human skin. The composition provides a durable, stretchable structure that offers both mechanical and adhesive properties. The catalyst provides dual-cure catalysis, allowing for rapid crosslinking of polysiloxane chains to form a film while also forming adhesive properties on a given hydroxyl-containing substrate. Silanol functional groups on the surface of silicone fillers in the composition react with hydroxyl functional groups on a given surface in the presence of this novel dual-functional catalyst, providing adhesive properties to the novel silicone-based adhesive. Furthermore, as illustrated in the above examples, triclosan-containing silicone TSAs provide an effective means for delivering antimicrobial agents through skin closure devices. The incorporation of triclosan does not appear to significantly affect the adhesive properties of the adhesive or the surgical performance of the silicone-based TSA.

[0192] While the present invention has been shown and described with reference to specific embodiments thereof, it will be understood by those skilled in the art that various changes in form and detail of the invention may be made without departing from the spirit and scope of the invention as claimed.

[0193] [Embodiment] (1) A composition comprising: a crosslinkable silicone polymer having reactive functional groups; a silica-containing composition; a silicone crosslinker; 1. A catalyst having the formula: a catalyst comprising a platinum tetramethyldivinyldisiloxane diethylmaleate complex having Pt[(CH2=CH)(CH3)2Si]2O·(COCH=CHCO)(C2H5O)2; and an antibacterial agent. (2) The composition of claim 1, wherein the crosslinkable silicone polymer is selected from the group consisting of vinyl-terminated polydialkylsiloxanes, vinyl-terminated polydimethylsiloxanes, vinyl-terminated polydiphenylsilane-dimethylsiloxane copolymers, vinyl-terminated polyphenylmethylsiloxanes, vinyl-terminated polyfluoropropylmethyl-dimethylsiloxane copolymers, vinyl-terminated polydiethylsiloxanes, and SiH-terminated polydimethyldisiloxanes. (3) The composition of claim 1, wherein the crosslinkable silicone polymer comprises a vinyl-terminated polydimethylsiloxane. 4. The composition of claim 1, wherein the silica-containing composition comprises a trimethylsilyl surface-treated silica filler. (5) The composition of claim 1, wherein the silica-containing composition is selected from commercially available reactive silica-containing silicone bases, including HCR (high consistency rubber) bases and LSR (liquid silicone rubber) bases.

[0194] (6) The composition of claim 5, wherein the silica-containing composition is a liquid silicone rubber base. 7. The composition of claim 1, wherein the silicone crosslinker is selected from the group consisting of polymethylhydrosiloxane, polymethylhydro-co-polydimethylsiloxane, polyethylhydrosiloxane, polymethylhydrosiloxane-co-octylmethylsiloxane, and polymethylhydrosiloxane-co-methylphenylsiloxane. (8) The composition of claim 1, wherein the silicone crosslinker comprises polymethylhydrosiloxane, polymethylhydro-co-polydimethylsiloxane, and combinations thereof. (9) The composition of embodiment 1, wherein the composition further comprises about 0% to about 30% by weight of an organic solvent, based on the weight of the composition. 10. The composition of claim 1, wherein the composition comprises from about 1 wt. % to about 15 wt. % of the silicone crosslinker based on total solids, and the coating composition further comprises from about 0 wt. % to about 30 wt. % of an organic solvent based on the weight of the coating composition.

[0195] 11. The composition of claim 1, wherein the coating composition comprises from about 0.003 wt. % to about 0.06 wt. % of a platinum catalyst based on total solids, and the coating composition further comprises from about 0 wt. % to about 30 wt. % of an organic solvent based on the weight of the coating composition. 12. The composition of claim 1, wherein the coating composition further comprises a solvent selected from the group consisting of pentane, hexane, heptane, a mixture of low molecular weight olefins, and combinations thereof. (13) The composition of embodiment 1, wherein the antibacterial agent is selected from the group consisting of triclosan, chlorhexidine, polyhexamethylene biguanide (PHMB), octenidine, elemental silver, and silver salts. 14. The composition of claim 13, wherein the antibacterial agent is triclosan. 15. The composition of claim 14, wherein the triclosan comprises about 0.05% to about 2.0% by weight of the composition.

[0196] 16. The composition of claim 15, wherein the triclosan comprises about 0.1% to about 1.5% by weight of the composition. 17. The composition of claim 16, wherein the triclosan comprises about 0.2% to about 1.0% by weight of the composition. 18. The coating composition of claim 1, wherein the composition is curable at a temperature of about 19°C. 19. The coating composition of claim 18, wherein the composition is curable at a temperature of about 28° C. for about 2 to 5 minutes. (20) A kit comprising: a) a wound closure device; b) a composition according to embodiment 1.

[0197] (21) The kit of embodiment 20, wherein the wound closure device is a wound closure strip. (22) The kit of embodiment 21, wherein the wound closure strip is selected from the group consisting of mesh, polymeric film, plastic foam (including open cell foam), woven fabric, knitted fabric, nonwoven fabric, and combinations thereof. (23) The kit of embodiment 22, wherein the wound closure strip is a mesh. (24) The kit of embodiment 23, wherein the wound closure device comprises a material selected from the group consisting of polyester, nylon, acrylic, rayon, polyurethane, polyurethane foam, polystyrene, polyester, polyethylene terephthalate (PET), polyamide, polylactic acid, polyglycolic acid, polycaprolactone, and mixtures thereof; cotton, silk, and linen; and surface-treated materials that impart OH functional groups to their surfaces, including, but not limited to, OH-surface-treated PTFE, OH-surface-treated polypropylene, and OH-surface-treated polyethylene. 25. The kit of embodiment 24, wherein the antibacterial agent is triclosan.

[0198] (26) A composition comprising: a crosslinkable silicone polymer having reactive functional groups; a silica-containing composition; a silicone crosslinker; 1. A catalyst having the formula: a catalyst comprising a platinum tetramethyldivinyldisiloxane diethylmaleate complex having Pt[(CH2=CH)(CH3)2Si]2O·(COCH=CHCO)(C2H5O)2; and a wound exudate or wound moisture absorbent and / or indicator. 27. The composition of claim 26, wherein the absorbent and / or indicator is silica. 28. The composition of claim 26, wherein the absorbent and / or indicator is a superabsorbent. 29. The composition of claim 26, wherein the absorbent and / or indicator is an anhydrous inorganic salt. (30) A kit comprising: a) a wound closure device; b) a composition according to embodiment 26.

[0199] (31) The kit of embodiment 30, wherein the wound closure device is a wound closure strip. (32) The kit of embodiment 31, wherein the wound exudate or wound moisture absorbent and / or indicator is applied or coated onto the wound closure strip.

Claims

1. A composition for cutaneous administration for wound closure applications, comprising: a crosslinkable silicone polymer having reactive functional groups; a silica-containing composition; a silicone crosslinker; 1. A catalyst having the formula: Formula Pt[(CH ２ =CH)(CH ３ ) ２ Si] ２ O・(COCH=CHCO)(C ２ H ５ O) ２ a catalyst comprising a platinum tetramethyldivinyldisiloxane diethylmaleate complex having the formula: and an antibacterial agent.

2. 2. The composition of claim 1, wherein the crosslinkable silicone polymer is selected from the group consisting of vinyl-terminated polydialkylsiloxanes, vinyl-terminated polydimethylsiloxanes, vinyl-terminated polydiphenylsilane-dimethylsiloxane copolymers, vinyl-terminated polyphenylmethylsiloxanes, vinyl-terminated polyfluoropropylmethyl-dimethylsiloxane copolymers, vinyl-terminated polydiethylsiloxanes, and SiH-terminated polydimethyldisiloxanes.

3. The composition of claim 1 , wherein the crosslinkable silicone polymer comprises a vinyl-terminated polydimethylsiloxane.

4. The composition of claim 1 , wherein the silica-containing composition comprises a trimethylsilyl surface-treated silica filler.

5. 10. The composition of claim 1, wherein the silica-containing composition is selected from commercially available reactive silica-containing silicone bases, including HCR (high consistency rubber) bases and LSR (liquid silicone rubber) bases.

6. The composition of claim 5 , wherein the silica-containing composition is a liquid silicone rubber base.

7. 2. The composition of claim 1, wherein the silicone crosslinker is selected from the group consisting of polymethylhydrosiloxane, polymethylhydro-co-polydimethylsiloxane, polyethylhydrosiloxane, polymethylhydrosiloxane-co-octylmethylsiloxane, and polymethylhydrosiloxane-co-methylphenylsiloxane.

8. The composition of claim 1, wherein the silicone crosslinker comprises polymethylhydrosiloxane, polymethylhydro-co-polydimethylsiloxane, and combinations thereof.

9. The composition of claim 1 , wherein the composition further comprises from about 0% to about 30% by weight of an organic solvent, based on the weight of the composition.

10. 10. The composition of claim 1, wherein the composition comprises from about 1% to about 15% by weight of the silicone crosslinker based on total solids, and the composition further comprises from about 0% to about 30% by weight of an organic solvent based on the weight of the composition.

11. 10. The composition of claim 1, wherein the composition comprises from about 0.003 wt. % to about 0.06 wt. % of a platinum catalyst based on total solids, and the composition further comprises from about 0 wt. % to about 30 wt. % of an organic solvent based on the weight of the composition.

12. 10. The composition of claim 1, wherein the composition further comprises a solvent selected from the group consisting of pentane, hexane, heptane, a mixture of low molecular weight olefins, and combinations thereof.

13. 10. The composition of claim 1, wherein the antimicrobial agent is selected from the group consisting of triclosan, chlorhexidine, polyhexamethylene biguanide (PHMB), octenidine, elemental silver, and silver salts.

14. 14. The composition of claim 13, wherein the antibacterial agent is triclosan.

15. 15. The composition of claim 14, wherein the triclosan comprises from about 0.05% to about 2.0% by weight of the composition.

16. 16. The composition of claim 15, wherein the triclosan comprises from about 0.1% to about 1.5% by weight of the composition.

17. 17. The composition of claim 16, wherein the triclosan comprises from about 0.2% to about 1.0% by weight of the composition.

18. The composition of claim 1 , wherein the composition is curable at a temperature of about 19° C.

19. The composition of claim 18, wherein the composition is curable at a temperature of about 28°C for about 2 to 5 minutes.

20. A kit for wound closure applications, comprising: a) a wound closure device; b) the composition of claim 1.

21. 21. The kit of claim 20, wherein the wound closure device is a wound closure strip.

22. 22. The kit of claim 21, wherein the wound closure strip is selected from the group consisting of mesh, polymeric film, plastic foam (including open cell foam), woven fabric, knitted fabric, nonwoven fabric, and combinations thereof.

23. 23. The kit of claim 22, wherein the wound closure strip is a mesh.

24. 24. The kit of claim 23, wherein the wound closure device comprises a material selected from the group consisting of polyester, nylon, acrylic, rayon, polyurethane, polyurethane foam, polystyrene, polyester, polyethylene terephthalate (PET), polyamide, polylactic acid, polyglycolic acid, polycaprolactone, and mixtures thereof; cotton, silk, and linen; and surface-treated materials that impart OH functional groups to their surfaces, including, but not limited to, OH-surface-treated PTFE, OH-surface-treated polypropylene, and OH-surface-treated polyethylene.

25. 25. The kit of claim 24, wherein the antimicrobial agent is triclosan.

26. A composition for cutaneous administration for wound closure applications, comprising: a crosslinkable silicone polymer having reactive functional groups; a silica-containing composition; a silicone crosslinker; 1. A catalyst having the formula: Pt[(CH ２ =CH)(CH ３ ) ２ Si] ２ O・(COCH=CHCO)(C ２ H ５ O) ２ a catalyst comprising a platinum tetramethyldivinyldisiloxane diethylmaleate complex having the formula: and a wound exudate or wound moisture absorbent and / or indicator.

27. 27. The composition of claim 26, wherein the absorbent and / or indicator is silica.

28. 27. The composition of claim 26, wherein the absorbent and / or indicator is a superabsorbent.

29. 27. The composition of claim 26, wherein the absorbent and / or indicator is an anhydrous inorganic salt.

30. A kit for wound closure applications, comprising: a) a wound closure device; b) the composition of claim 26.

31. 31. The kit of claim 30, wherein the wound closure device is a wound closure strip.

32. 32. The kit of claim 31, wherein the wound exudate or wound moisture absorbent and / or indicator is applied or coated onto the wound closure strip.

Images