Novel topical skin closure compositions and systems

Abstract

Novel compositions and systems for closure of wounds are disclosed. The compositions provide devices of improved flexibility and elasticity and are readily applied to wound sites or over wound closure devices. The present invention is also directed to a novel platinum catalyst for use in such compositions. The catalyst provides for rapid curing on topical surfaces such as skin and bonds to such surfaces in about 2 -5 minutes.

Description

TECHNICAL FIELDThe field of art to which this invention pertains is silicone-based wound closure compositionsand devices, in particular, silicone-based topical skin adhesives (TSA's) and systems.BACKGROUND OF THE INVENTIONThere is a need for elastomeric topical skin adhesives, especially for skin closure of themoving body joints such as knees, wrists, elbow, etc.Elastic versions of the TSA are especially needed in orthopedic surgery. Aggressive motionof joints may compromise the quality of the closure at the interface between the adhesive andthe skin. Watertight closure is also desirable in a product in order to lessen the possibility ofpost-surgical infections. Silicone types of adhesives are one solution for both these two keycustomer requirements due to its elasticity and sealing properties.Silicone is known for its inertness and commonly used as OTC scar reduction products.Reducing skin reactions and improvement of cosmesis are the extra benefits provided bysilicone-based TSA.Thus, there is a need for elastomeric topical skin adhesives, especially for the closure of themoving body parts and joints, such as knees, wrists, elbows, etc.3SUMMARY OF THE INVENTIONAccordingly, novel catalytic compositions, silicone based curable adhesive compositions, andwound closure systems are disclosed.The compositions comprise a mixture of vinyl terminated polydimethylsiloxane, and5 polydimethylhydro-co-polydimethylsiloxane cross linker, surface treated silica particles asbonding agent, and a novel, non-conventional platinum catalyst, optionally with common lowboiling point organic solvent such as aliphatic organic solvent such as hexane or itscommercial derivatives, and SiH terminated polydimethyl siloxane chain extender. Theproposed silicone adhesive can be dried on skin at body temperature in less than 3 minutes.10 The skin holding forces between the proposed silicone adhesive and skin is comparable orbetter than the typical cyanoacrylate-based TSA products. Unlike the traditionalcyanoacrylate-based TSA products, the invented silicone-based TSA when combined withtraditional wound closure devices can be stretched to 160% of its original length and fullyrecover to its original dimension.15 The bonding formation is enabled by the condensation reaction between the silanol functionson the surface of silica particle and the OH functions on the skin. Silanol condensation tendsto be sluggish at ambient temperature and the novel non-conventional catalyst enables thisreaction to occur in a short period of time. The platinum based novel catalyst also activatesvinyl silylation reaction to allow vinyl terminated silicone polymer to cross link20 simultaneously to the condensation reaction.In one embodiment, the invention relates to a composition comprising:a cross-linkable silicone polymer having reactive functionalities;a silica-containing composition;a silicone cross-linking agent; and25 a catalyst, wherein said catalyst comprises a platinum tetramethyldivinyl disiloxane diethylmaleate complex having the formula:Pt[(Clli= CH)(CH3)2Si]20·(COCH = CHCO)(C2Hs0)2.4In the foregoing embodiment, the silica-containing composition may be added as a separatecomponent, but more preferably it is contained in the cross-linkable silicone polymer. Thecoating compositions may also contain a platinum catalyst.Another aspect of the present invention is a medical device having a surface, wherein at least5 part of the surface is coated with the above-described novel silicone coating composition.Still yet another aspect of the present invention is a novel platinum catalyst for use withcross-likable silicone coatings. The catalyst comprises a platinum complex having thefollowing formula:10 A further aspect of the present invention is use of the compositions of this invention as atopical skin adhesive and as a topical skin adhesive in conjunction with wound closuredevices as systems or kits to close wounds.In other embodiments, the compositions of this invention are made under controlled viscosityrequirements limiting or eliminating the need for organic solvent(s) as hereinafter described.15 These and other aspects and advantages of the present invention will become more apparentfrom the following description.BRIEF DESCRIPTION OF THE DRAWINGSFIG. 1 is an NMR peak comparison of the Karstedt Catalyst compared with the NMR peak of20 the novel catalyst of this invention.FIGS. 2A, 2B and 2C show the steps of a stretch test used to demonstrate to elasticity ofthepresent invention.DETAILED DESCRIPTION OF THE INVENTIONThe terms silicone and siloxane are conventionally used interchangeably in this art, and that25 usage has been adopted herein.Topical Skin Adhesive Compositions & Wound Closure SystemsOne aspect of the present invention is directed to novel wound closure compositions whichare particularly useful for closing lacerations and surgical incisions. These compositions are5suitable for use as topical skin adhesives and as adhesives in conjunction with wound closuredevices.In one embodiment, the compositions include a mixture of a cross-linkable siloxane polymerand a silica-containing composition which may be added as a separate component, but more5 preferably contained in the cross-linkable silicone polymer, a conventional silicone crosslinkingagent, and a platinum catalyst. The silicone polymer components are blended withconventional aromatic organic solvents, including, for example, aliphatic organic solvents(such as, for example, hexane, heptane or its commercial derivatives) to form coatingsolutions or compositions. Other solvent suitable for coating solution includes and not limited10 to low molecular weight siloxane, e.g., hexamethyldisiloxane.The cross-linkable siloxane polymers useful in the compositions of the present invention willhave reactive functionalities or terminal functional groups, including but not limited to vinylterminated, hydroxyl and acrylate functional groups. The cross-linkable siloxane polymersthat can be used in the compositions of the present invention preferably include vinyl15 terminated polydialkylsiloxane or vinyl terminated polyalkyarylsiloxane. Examples includebut are not limited to the following vinyl terminated siloxane polymers: polydimethylsiloxane, polydiphenylsilane-dimethylsiloxane copolymer, polyphenylmethylsiloxane,polyfluoropropylmethyl-dimethylsiloxane copolymer and polydiethylsiloxane. It isparticularly preferred to use vinyl terminated cross-linkable polymethyl siloxane.20 The cross-linking agents that can be used in the compositions of the present invention includeconventional silicone cross-linking agents such as, for example, polymethylhydro siloxane,polymethylhydro-co-polydimethylsiloxane, polyethyhydrosiloxane,polymethylhydrosiloxane-co-octylmethylsiloxane, polymethylhydrosiloxane-comethylphenylsiloxane.The preferred conventional crosslinkers for use in the compositions of25 the present invention are polymethylhydro siloxane and polymethylhydro-copolydimethylsiloxane.Precise control of cross-link density in the coatings of the presentinvention is achieved by precise control of the ratio of non-cross-linkable silicone polymer(e.g., polydimethylsiloxane) to fully cross-linked polymer. The fully cross-linked polymer isformed by a reaction between the functionalized cross-linkable polymer and the cross-linking30 agent, for example, a vinylsilylation reaction between vinyl-terminated polydimethylsiloxaneand polymethylhydrosiloxane optionally in the presence of a platinum complex catalyst.Examples of this polymer include but are not limited to: Gelest Product Code No. DMS-V31,6DMS-V33, DMS V-35, DMS V42, DMS-V46, DMS-V52, etc., available from Gelest, Inc.,Morrisville, Pa. 19067. The typical molecular structure of vinyl terminatedpolydimethyldisiloxane is the following:=~Si-o t-o s(-= CH3 -tCH3 1 CH3CH3 6H3 n CH35 wherein n is defined by the molecular weight.The molecular weights of the silicone polymers used wherein can be estimated basedon the relationship between viscosity and molecular weight (page 11, SILICONE FLUIDS:STABLE, INERT MEDIA ENGINEERING AND DESIGN PROPERTIES, Catalogpublished by Gelest, Inc. 11 East Steel Rd. Morrisville, PA 19067). Using A.J. Barry's10 relationship for molecular weights (M) >2,500 correlating the kinematic viscosity !lexpressed in centistokes (eSt) at 25 C, the molecular weight M of silicones can be estimatedas follows:15log J.lcSt = 1.00 + 0.0123M0·5(as published by A.J. Barry in the Journal of Applied Physics 17, 1020 (1946))Vinyl terminated polydimethylsiloxane reacts with polymethylhydrosiloxane cross-linker inthe presence of platinum catalyst under appropriate conditions; the vinyl terminatedpolydimethylsiloxane linear polymers are fully cross-linked to each other as the result of thisreaction. The amount of polymethylhydrosiloxane cross-linker is in large stoichiometric20 excess compared to vinyl terminated polydimethylsiloxane base polymer. It is believed thatthe extra SiH functions in the cross-linker react with the OH functions on the surface such ashuman skin, e.g., polymeric sutures, to form Si-0-C bonds at elevated temperature or inthe case of steel needles, to form Si-0-Fe bonds. Covalent bonds thus created between thesilicone coating and the device, as the result of this reaction, result in the adhesive attachment25 of the coating to a given surface.The polymethyhydrosiloxane cross-linkers, or cross-linking agents, used in the practice of thepresent invention will have a molecular weight between about 1000 and about 3000, andpreferably between about 1400 and about 2100. An example of this polymer cross-linkerincludes, but is not limited to, Gelest Product Code No. HMS-991, HMS-992, available from7Gelest, Inc., Morrisville, Pa. 19607. The typical molecular structure of thepolymethylhydrosiloxane cross-linker is the following:CH:lCH~3S i-0 -tS' i-0t s (C-CH3H :lCH3 6H3 n CH35 wherein n is defined by the molecular weight.Polymethylhydro-co-polydimethylsiloxane can also be used as cross-linker or cross-linkingagent in the novel coatings ofthe present invention. Examples ofthis polymer include, butare not limited to, Gelest Product Code No. HMS-301, HMS-501. The molecular weight ofthis siloxane polymer cross-linking agent will typically be between about 900 and about10 5,000, and preferably about 1,200 to about 3,000. The typical molecular structure ofpolymethylhydro-co-polydimethylsiloxane cross linker is the following:CH3 -tCH3 nCH3 t CH3~Si-o L-o CH3 L-o l-cmCIH 3 CIH 3 I \ n H m CH3wherein n and m are defined by the molecular weight.15 Silica-Containing CompositionsAs used herein, the silica-containing compositions described for use with this inventioninclude silica materials as a separate component (such as surface treated silica) or fromcommercially available compositions that contain silica in a cross linkable silicone polymermixture.20 As a separate component, silica is incorporated into composition of this invention to act as abonding agent to skin and other substrate materials. It is believed that the OH groups on thesurface of silica particles react with the OH functions on the surface of substrate materialincluding human skin under a certain condition, as illustrated below.8OH OH,.O.yH . OH OH I ISi Si Sio / 1 "'-o / 1 '-.... o / 1 '-..o / 0 0 0Si / '-.... Si / '-.... Si / ' Si / I / si , I / si, I / Si , I / o I o I o I o1Silica particles were incorporated into the cross linkable silicone polymers. Hexamethyl silylsurface treatment is needed for the silica particles to enable its compatibility to the5 polysiloxane polymer matrix which prevents phase separation. An example of treated silicaincludes hexamethyldisilazane treated silica i.e., trimethyl silyl surface treated silica filler(Gelest SIS6962.0).In the case of silicone polymers already containing silica, these may be obtained fromcommercially available sources such as silica-containing composition selected from reactive10 silica-containing silicone bases including HCR (high consistent rubber) bases and LSR(liquid silicone rubber) bases, preferred are LSR bases. Other commercial examples of thismaterial include and is not limited to Wacker 401-10, 401-20, 401-40 base; and a liquidsilicone rubber base, a commercial example of this material includes and is not limited toBluestar Silbione LSR 4370 base. These type of commercial silicone rubber bases are15 prepared by mixing a surface-treated silica filler with various molecular weights of vinylterminated polydimethylsiloxane polymer. In-situ surface treatment may be performed duringthe mixing process to improve the compatibility between filler and polysiloxane polymer.CatalystKarstedt of GE Silicone invented a highly active platinum catalyst at the beginning ofthe20 1970's (US 3775452). Vinyl terminated polydimethylsiloxane can react withpolymethylhydrosiloxane containing cross linker in less than 1 minute at ambient temperaturewith as little as 10 ppm of the Karstedt catalyst. The traditional platinum catalyst does notenable the reaction between OH groups on the surface of silica particles reacts and the OH9functions on the surface of substrate. This type of condensation reaction tends to be slow atambient condition and the typical catalyst for this reaction including organic amine andcatalyst such as tin dilaurate. Trace amount of condensation catalyst will terminate thecatalytic ability of platinum catalyst which is referred as platinum poisoning in the silicone5 industry. A novel platinum comparable catalyst is needed to activate the OH condensationbetween silica particle and substrate material, to enable rapid adhesion formation betweensilicone and a given substrate material. A platinum based novel catalyst of the presentinvention is able to activate both vinyl silylation and OH condensation simultaneously.The novel catalyst is prepared by reacting Karstedt' s catalyst with diethyl maleate according10 to scheme 1. The novel platinum tetramethyldivinyl disiloxane diethyl maleate catalystenables both vinyl silylation and condensation reaction. This is referred to as "dualfunctional silicone catalyst".15Scheme 1¢0 0~0~0CH3 / ... 0\I ..._ ¢ s· . / \ ..... 0~CH3 ! h·······lem,. . / 0~ / '51 . / CH3 ~ 0+CH3 CH3 CH3 CH3 . / ' \ / C H3\( \I ... .- );~, / s\ .. ~{ o emII 0 \• .... \ \ / CH3 II ~ ·.. Si..... _ / '-... / CH3105CH3 CH3 CH3 C)i3 ,.-~ / H3\ ( \ I .-· Si / " / / CH3SJ" s\· / / '- I 0 , ... ··~·.... ~(_...CH3+...... ..~-....... j:9 CI-!3¢0 0~0'-. / 0CH3 CH3 CH3 C}I3\I \ I / \ / s·I o The novel catalyst of the present invention may be prepared in the following manner.Karstedt catalyst in xylene solution is mixed with a low concentration of vinylcyclohexanolin a xylene solution at ambient temperature for a sufficiently effective time to complete thereaction, e.g., a half an hour, and completion of the reaction is indicated by a change of the10 color of the reaction mixture, from clear to light brown.15The resulting catalyst solution containing the novel catalyst of the present invention is readyto use in a composition useful as a topical skin adhesive. The formula of the resultingplatinum complex catalyst (platinum tetramethyldivinyl disiloxane diethyl maleate complex)IS:Pt[(CH2 = CH)(CHJ)2Si]20·(COCH = CHCO)(C2Hs0)2.It should be noted that the resulting catalyst reaction mixture will contain a small amount ofthe reaction product divinyltetramethyldisiloxane. This component does not affect thecatalyst and is a low boiling point component that is rapidly evaporated. Accordingly,11purification of the catalyst mixture to remove divinyltetramethyldisiloxane is optional, and itis believed that its presence at ultra low concentrations will not affect the cross-linkingreaction of a cross-linkable silicone polymer. The novel catalyst of the present invention alsoactives the bonding formation between silanol groups on the surface of silica fillers and OH5 functions on a given surface, that is, the catalyst is capable to activate two reactions. Thisallows for curing the cross-linkable components in silicone coatings to rapidly form coatingfilms at desired curing temperatures and provides bonding to a given substrate such as humanskin.Solvents for Viscosity Reduction10 Some commercially produced filler reinforced cross linkable silicone polymers (silicone baserubber) have high viscosity, typically higher than 500,000 and up to many millions of cP. It isimpossible to mix and spread such high viscosity material onto skin and low hazardousorganic solvent is needed to reduce its viscosity.Low temperature aliphatic solvents are used for this purpose. Typical examples include, but15 are not limited to, pentanes, heptanes, hexanes and their mixtures. The organic solvents areadded at a concentration sufficient to allow effective blending of the silicone polymercomponents into a homogeneous solution. The total solvent concentration is between 10%and 30%, depending upon the original viscosity of the base rubber. Ultra-low boiling pointsolvent such as n-butane and isopentane can also been used to provide sprayable formulation20 of silicone adhesive.Chain Extender for Low Viscosity Vinyl Terminated Polydimethylsiloxane Base PolymerFor those commercially produced filler reinforced cross linkable silicone polymers (siliconebase rubber) that have a high viscosity in the range from 100,000 centipoise (cP) to severalmillion cP (e.g., 1-20 million cP) viscosity, (low molecular weight) vinyl terminated25 polydimethylsiloxane (<300 cP) may be also added together with low temperature aliphaticsolvents to improve its mixability and spreadability. A SiH terminated polydimethylsiloxaneis added as a chain extender to polymerize the low molecular weight vinyl terminatedpolydimentylsiloxane. The SiH terminated polydimethylsiloxane base polymer hasmolecular weight between 1000 and 100,000, preferably between 3,000 to 10,000.125Examples of this type of polymer include, but are not limited to: Gelest Product Code No.DMS-H21, DMS-H31, etc. The typical molecular structure ofSiH terminatedpolydimethyldisiloxane is illustrated belowCH3 (1H3 t lH3H-7si-o\~i-o s~-HCH3 \ CH311CH3The above silicone polymers and novel platinum catalyst are dispersed into low boiling pointorganic solvents to form the coating solution. Low temperature aliphatic solvents are used for10 the silicone dispersion. Aromatic solvents and hexamethyldisiloxane are commonly used forsilicone dispersion. Typical examples include, but are not limited to, pentane, heptanes,hexane and their mixtures. The organic solvents are added at a concentration sufficient toallow effective blending of the silicone polymer components into a homogeneous coatingsolution. The total solvent concentration is from about 80 wt.% to about 99 wt.%, and is more15 typically from about 85 wt. %to about 93 wt. %, depending upon the coating thicknessrequirement. Those skilled in the art will appreciate that the coating thickness can beengineered by changing the solids content of the coating solution.The sequence of the addition of components is important. The typical coating composition isprepared in the following manner. In the case when the silica is added as a separate20 component, the vinyl terminated polydimethylsiloxane is dispersed into the first solution suchas hexamethyldisiloxane together with surface treated silica for up to two hours until fullyhomogeneous (solution 2). Heptane is then added (solution 3) and further mixing for onehour prior to the addition of polymethylhydrosiloxane cross linker. The solution is fullyblended for one more hour after all of the catalyst is added as the final component25 In the following paragraph, the wt. % is the wt. % of total solid content in the coatingsolution. The novel coating compositions of the present invention will contain sufficientamounts ofthe polymeric components, silica-containing composition, cross-linking agent,catalyst, and solvent to effectively provide a silicone coating having high flexibility anddurability.13Typically, the amount of the silica in the coating solution will be about 5 wt. %to about 40wt.% (total solids), more typically about 10 wt. %to about 30 wt.% (total solids), andpreferably about 15 wt. %to about 25 wt. %(total solids). The amount of the cross-linkablesilicone polymer will typically be about 60 wt.% to about 95 wt.% (total solids), more5 typically about 70 wt.% to about 90 wt.% (total solids), and preferably about 75 wt.% toabout 85 wt. %(total solids). The amount of the silicone cross-linking agent will typically beabout 1 wt. %to about 15 wt. % (total solids), more typically about 2 wt. %to about 10 wt.%(total solids), and preferably about 3 wt.% to about 8 wt.% (total solids). The amount ofthe platinum catalyst based upon the total solids in the novel silicone coating compositions10 (platinum element in total solids) of the present invention will typically be about 0.06 wt.%to about 0.003wt. %, more typically about 0.04 wt.% to about 0.008 wt. %, and preferablyabout 0.03 wt.% to about 0.01 wt. %.The amount of organic solvent in the compositions of the present invention will typically beabout Owt. %to about 30 wt. %, more typically about 10 wt. %to about 20 wt. %, and15 preferably about 12 wt. %to about 18 wt. %. Those skilled in the art will appreciate that theamount of solvent present in the novel coating compositions of the present invention willvary with several factors, and that the solvent quantity in the coating compositions will beselected to engineer an efficacious coating. The factors typically considered include themethod of application, the method of cure, the coating equipment utilized, ambient20 conditions, thickness, etc. It will be appreciated that each of the components of the coatingcompositions of the present invention may consist of blends of those components. Forexample, two or more cross-linkable silicone polymers having different functionalities and / ormolecular weights may be used, etc.The compositions of this invention are well suited for wound closure applications such as25 topical skin adhesives. Generally, these compositions have been demonstrated to cure to anon-tacky nature or touch at temperatures at about 19 C. At temperatures of about 28 C, thecompositions cure in about 2-5 minutes.As noted above and as would be appreciated by one of skill in the art, the siliconecompositions of this invention cure in several minutes to films that are neither sticky nor30 tacky. In contrast, some silicone adhesives, such as silicone pressure sensitive adhesives(PSA's), are by nature sticky or tacky and are intended to be such for the entire usable life ofthe adhesive. Such useable life of the tacky silicone PSA's may be upwards to several years.14The non-tackiness of the compositions and examples of this invention is measured by ASTMC679.In general ASTM C679 consists of lightly touching a surface of a curing sealant with apolyethylene film at regular intervals until the sealant does not attach itself to the film and the5 film appears clean when peel from the surface. More specifically a strip of polyethylene filmis placed on the surface of the curing elastomer and a 30g weight is placed on the film. Theweight is left in place for 30 seconds, then removed and the polyethylene strip is removedand examined for sealant attachment to the film. The length of time from when the sealantwas first applied onto a given surface until the time the sealant is no longer picked up by the10 film is called tack-free time and is the time point at which the film exhibits a non-tackynature which evidences that the sealant has cured.Upon curing the curable compositions of the present invention exhibit stretchable, flexibleand elastic properties especially useful for applications over wound closure on bendable15 joints, such as knees, elbows. The curable compositions of the present invention, optionallyin combinations with various wound closure devices can be applied over any wound closures,including wounds over bendable joints or wounds not over bendable joints, such a generalsurgical closures such over any tissue area, e.g. body, abdominal, arm, leg, shoulder, backareas and similar.20 The compositions of this invention can be applied onto wounds directly as a curable liquid orsemi-liquid, flowable composition, or applied over a porous, flowable compositionpermeablewound closure device.Wound Closure SystemsAs noted above, the compositions of this invention are suitable for use in combination with25 wound closure devices.Wound closure devices suitable for use in this invention comprise any device that isconfigured to close a wound. The wound closure devices most useful are wound closurestrips, tapes, patches or any other materials suitable for closing a wound, most preferably astrip. Preferably, the wound closure device is porous and will allow a flowable,30 polymerizable adhesive to permeate the device and to allow adequate bonding of the deviceto a tissue surface being bonded.15The wound closure device comprises a wound facing side and a top side. The wound facingside may further comprise an adhesive such as a pressure sensitive adhesive (PSA) appliedover at least a portion of the wound facing side. The PSA is useful for initially approximatingthe wound. The wound closure device is preferably porous. By "porous" is meant herein5 either that the bulk of the wound closure device has pores, such that subsequently appliedpolymerizable adhesive composition is soaked up or absorbed by the bulk material, or thatthe bulk of the wound closure device has voids (like a net or screen), such that thesubsequently applied polymerizable adhesive composition passes directly through the bulkmaterial, with or without being soaked up or absorbed by the bulk material. For example, in10 the case of textile materials, "porous" is generally used to mean that the applied adhesivecomposition permeates and passes through interstices between the fibers, but does notnecessarily pass into and through the fibers themselves. Preferably the wound closure deviceis a mesh strip.Such porosity (or other properties such as hydrophobicity or hydrophilicity) will also allow a15 polymerization initiator or rate modifier to be loaded in or on the wound closure device priorto use, to initiate the subsequently applied polymerizable adhesive composition. Suchporosity will also preferably allow air and fluid to pass through the wound closure device,either through pores per se, or through voids in the bulk material. Depending upon the degreeof porosity and / or the size of the openings, such porosity of the mesh or ability of air and20 fluid to permeate through the mesh may be tailored either to remain after a final compositematerial is formed, or to be absent therefrom. The wound closure device is also preferablynon-toxic, as it is intended to be used cover a wound, such as on biological tissues. As such,the wound closure device should be biologically compatible with the desired substrate (suchas tissue, skin, organ, or the like), and is preferably a material that is governmentally25 approved or generally regarded as safe for the desired purpose. By way of example, suitablewound closure devices are mesh materials and are disclosed in United States PatentApplications 2006 / 0009099 and 2005 / 0182443, incorporated herein by reference in theirentirety.The wound closure device may be a textile or mesh / web material. Suitable textile materials30 may be formed of either synthetic or natural materials. Such textile material may be formedof either woven or non-woven fabrics or materials. The wound closure device may be, forexample, any suitable polymeric film, plastic foam (including open celled foam), a wovenfabric, knitted fabric, a non-woven fabric, mixture thereof, or the like. In particular, suitable16wound closure devices may thus be prepared, for example, from nylons, polyolefins such aspolyethylene, polypropylene, ethylene propylene copolymers, and ethylene butylenecopolymers, acrylics, rayons, polyurethanes, polyurethane foams, polystyrenes, plasticizedpolyvinylchlorides, polyesters such as polyethylene terephthalate (PET), polyamides,5 polylactic acids, polyglycolic acids, polycaprolactones, copolymer mixtures of the above,natural materials such as cotton, silk and linen, polytetrafluoroethylene (PTFE), biovascularmaterial, collagen, Gore-Tex®, DACRON®, etc. The preferred wound closure devicematerials are those that contain an OH functionality on its surface whether occurringnaturally or by surface treatment to impart an OH functionality ("OH surface-treated"). These10 materials include and are not limited to polyesters, nylons, acrylic, rayon, polyurethanes,polyurethane foams, polystyrenes, polyesters, polyethylene terephthalate (PET), polyamides,polylactic acid, polyglycolic acid, polycaprolactone, copolymer mixtures of the above, andcotton, silk and linen. Suitable OH surface-treated materials that impart an OH functionalityto their surfaces include but are not limited to OH surface-treated PTFE, OH surface-treated15 polypropylene and OH surface-treated polyethylene.The wound closure device may be formed of a synthetic, semi-synthetic, or natural organicmaterial. Thus, for example, the mesh may be formed of a synthetic or natural polymermaterial, but not from a material such as metal (such as silver, steel or the like) or glass or20 ceramic. The wound closure device may be either biodegradable, or not biodegradable. Thewound closure device is preferably resistant to tearing.The thickness of the wound closure device may be from about 0.1 mm to about 25 mm. Inanother embodiment, the thickness of the wound closure device is from about 0.5 mm toabout 20 mm, preferably from about 0.7 mm to about 10 mm, most preferably from about 125 mm to about 5 mm.When the wound closure device is a strip, the strip may be from about 2 em to about 40 em,preferably from about 10 to about 30 em, most preferably 25 em in length. The strip may befrom 0.1 to about 8 em, preferably from about 2 to 6 em, more preferably about 4 em inwidth.30 The wound closure device may be selected to be elastic or have some memory effect. In suchembodiments, the elastic properties of the mesh may desirably provide a degree of pressureor stress at the application site, for example, to maintain wound edge approximation.17Likewise, in embodiments where such additional degree of pressure or stress at theapplication site is not desired, the mesh may be selected to have less or no elasticity.The wound closure device may be either biodegradable, or not biodegradable. By"biodegradable" is meant that the mesh biodegrades over time in vivo, such that it does not5 require physical removal of the mesh after a set period of time. Thus, for example, abiodegradable mesh is one that, in the in vivo environment, will biodegrade over a period offrom about one week to about five years. A nonbiodegradable material is one that does notbiodegrade in an in vivo environment within about five years. Such a nonbiodegradablematerial thus would require physical removal of the wound closure device at a desired time,10 rather than slowly deteriorating over time or may slough off naturally from the tissue.The wound closure device may include one or more chemical materials located in or on it.For example, one or more chemical substances may be dispersed in or on the wound closuredevice, such as being chemically bound, physically bound, absorbed, or adsorbed to it. Such15 chemical materials that may be present in or on the wound closure device include, but are notlimited to, any suitable and preferably compatible additive that enhances performance of thecomposite structure. Such additional chemical substances may be bioactive or non-bioactive.Suitable other chemical substances thus include, but are not limited to, colorants (such asinks, dyes and pigments), scents, protective coatings that do not chemically detach,20 temperature sensitive agents, drugs, wound-healing agents, anti-microbial agents and the like.ExamplesExample l, Novel Platinum Catalyst (Synthesis Procedure)44.50g of Gelest SIP 6831.2 (2.2% platinum divinyl tetramethyldisiloxane complex in25 xylene, Karstedt catalyst) was mixed with 2g of diethyl maleate for 24 hours at ambienttemperature. Samples were taken out after 3 hours, 18 hours, and 24 hours for NMR testingand the NMR spectra for the 3 hour sample is shown in FIG. 1.18The formation of the novel catalyst is the evidence for scheme 1, which rests on NMRspectroscopic identification. Karstedt catalyst is known with a characteristic 195Pt signal atapproximately -6111 ppm.After 3 hours of mixing of the mixtures of Example 1, a new 195Pt signal at -6082 ppm was5 observed along with the original signal for the Karstedt catalyst at -6111 ppm as illustrated inthe NMR spectra of this mixture at 3 hours in FIG. 1. The intensity of the new signalincreases over time while the intensity of the Karstedt catalyst signal reduced at the sametime.10 Example 2, Preparation of Silicone-Based Topical Skin AdhesiveIn general and similar to most of commercially available platinum cured silicone materials,the silicone-based topical skin adhesive is delivered in a two-part kit by mixing equalvolumes of the Part A and Part B components.As an overview, vinyl terminated polydimethylsiloxane is mixed with Platinum15 tetramethyldivinyl disiloxane diethyl maleate catalyst, silica particles and optionally aliphaticorganic solvent using a high-speed mixer to form part A of the kit. Vinyl terminatedpolydimethylsiloxane were mixed with polymethylhydro-co-polydimethylsiloxane crosslinker, silica particle and optionally aliphatic organic solvent using high speed mixer to formpart B of the kit.20 Equal amounts of the two-part kit were mixed using a static mixer and then spread onto thesurface of a substrate, such as skin. The mixture of the two-part kit cured within 5 minutes atbody temperature as determined by the loss of stickiness or tackiness of the applied silicone.40g of vinyl terminated polydimethylsiloxane (Gelest DMSV41) was mixed with lOg of25 surface treated silica particles (Gelest SIS6962.0), together with 2.6g of the resulting catalystof Examplel using a high-speed centrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpmfor 5 minutes.40g of vinyl terminated polydimethylsiloxane (Gelest DMSV41) was mixed with lOg of30 surface treated silica particles (Gelest SIS6962.0), together with 3.34g ofPolymethylhydro19co-polydimethylsiloxane (Gelest HMS301) using a high-speed centrifugal mixer (FlackTekDAC150 FV-K) at 3470 rpm for 5 minutes.Example 3, Preparation of Silicone-Based Topical Skin Adhesive using Commercial Silica-5 containing Silicone Raw Material.90g ofE-Kem 44 experimental base (containing vinyl terminated polydimethyl silicone basepolymer and fume silica particles) was mixed with 4.72g of the resulting catalyst of Example1, 9.0g oflow molecular weight vinyl terminated polydimethyl silicone base polymer (Gelest10 DMS V21) and 26g of hexane using a high-speed centrifugal mixer (FlackTek DAC150 FVK)at 34 70 rpm for 5 minutes.8lg ofE-Kem 44 experimental base (containing vinyl terminated polydimethyl silicone basepolymer and fume silica particles) was mixed with 8 .lg of polymethyl hydro siloxane cross15 linker (Gelest DMS H991), 2.7g of SiH terminated polydimethylsiloxane chain extender(Gelest DMS H21) and 10.2g of hexane using a high speed centrifugal mixer (FlackTekDAC150 FV-K) at 3470 rpm for 5 minutes.Control Example: Control Example without Silica Bonding Agent and Using Conventional20 Karstedt CatalystPart A40g of vinyl terminated polydimethylsiloxane (Gelest DMSV41) was mixed with 2.6g ofKarstedt catalyst xylene solution (1% of Gelest SIP 6831.2 in xylene) using a high-speedcentrifugal mixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.25 Part B40g of vinyl terminated polydimethylsiloxane (Gelest DMSV41) was mixed 3.34g ofPolymethylhydro-co-polydimethylsiloxane (Gelest HMS301) using a high-speed centrifugalmixer (FlackTek DAC150 FV-K) at 3470 rpm for 5 minutes.20Example 4, Preparation of Test Samples and Description of Test ProceduresTest ProceduresWound Closure Strip Testing Sample Preparation:5 An 8 inch by 11 inch synthetic substrate (or bio substrate) was cut in two halves withdimensions of 4 inches by 11 inches. A 1 inch wide PSA (pressure sensitive adhesive) coatedpolyester mesh was placed along the cutting line to hold the two half pieces together. Thetwo-part silicone TSA compositions described above were mixed and applied onto the meshevenly to cover the entire area of the mesh using a conventional rubber spatula.10 Holding Strength Test:This test evaluated the force required to separate the substrate approximated with the PSAcoated mesh and the applied silicone TSA compositions .. This method was based onASTMF2458: Standard test method for wound closure strength in tissue adhesive and sealant.Synthetic substrate (Mylar) were used for the test, selected samples were also tested on15 porcine skin. The width of the synthetic substrate was 1 inch and porcine skin was 2 inch andthe strain rate was 20 inches / minute.Peel Test.The T-peel strength test was performed following ASTM F2256: Standard test method for20 Strength Properties of Tissue Adhesives in T-Peel by Tension Loading.The average peel strength of mesh coated with silicone-based TSA in T -peel configuration isperformed at a strain rate of 10 inches / minute.Holding Strength Test Sample25 Synthetic substrate, Polyester film (0.05 inch thick Duralar® film), Grafix Plastics, MapleHeights, OHAn 8 inch by 11 inch piece of the Duralar® polyester film was cut in two half withdimensions of 4 inch by 11 inch. Al.5inch wide PSA (pressure sensitive adhesive) coated21polyester mesh (Lot# 16204, Innovize, St Paul, MN) was placed along the cutting line to holdthe two half pieces together. The two-part silicone TSA compositions in each ofthefollowing examples were respectively mixed (Example 2, Example 3 and Control Example)and evenly applied onto the mesh to cover the entire area of the mesh using a conventional5 rubber spatula. The samples were dried between 2 to 5 minutes at 31 C. 5, 1 inch wide stripsof each of the covered mesh samples were cut for testing.Bio Substrate (Porcine skin)A 2 inch by 8 inch sample of porcine skin was cut in two halves with the dimensions of 210 inches by 4 inches. A 1.5 inch wide PSA (pressure sensitive adhesive) coated polyester meshwas placed along the cutting line to hold the two half pieces together. The two-part siliconeTSA composition was mixed (Example 3) and evenly applied onto the mesh to cover theentire area of the mesh using a conventional rubber spatula.Peel Test Sample15 Svnthetic substrate (Polyester film, 0.05 inch thick Duralar® film, Grafix Plastics, MapleHeights, OH)A 5 inch by 5 inch PSA (pressure sensitive adhesive) coated on polyester mesh (Lot# 16204,Innovize, St Paul, MN) was placed on the polyester substrate of the same dimensions. Thetwo-part silicone TSA compositions of each of the following examples were respectively20 mixed (Example 2, Example 3, and Control Example) and applied onto the mesh evenly tocover the entire area of the mesh using a conventional rubber spatula. 5, 1 inch widespecimens were cut for testing after each of the covered mesh samples were dried.Bio substrate (Arm of a 55 year-old Asian male)A 3 inch by 1 inch PSA (pressure sensitive adhesive) coated on polyester mesh was placed on25 the left arm of a 55 year old Asian male. The two-part silicone TSA compositions of each ofthe following examples were respectively mixed (Example 3 and Control Example) andapplied onto the mesh evenly to cover the entire area of the mesh using a conventional rubberspatula.

Claims

We Claim:

331. A composition comprising:a cross-linkable silicone polymer having reactive functionalities;a silica-containing composition;a silicone cross-linking agent; and,a catalyst, wherein said catalyst comprises a platinum tetramethyldivinyl disiloxane diethylmaleate complex having the formula:Pt[(CH2 = CH)(CHJ)2Si]20·(COCH = CHCO)(C2Hs0)2.

2. The composition of claim 1, wherein the cross-linkable silicone polymer is selected fromthe group consisting of vinyl terminated polydialkylsiloxane, vinyl terminatedpolydimethylsiloxane, vinyl terminated polydiphenylsilane-dimethylsiloxane copolymer,vinyl terminated polyphenylmethylsiloxane, vinyl terminated polyfluoropropylmethyldimethylsiloxanecopolymer, vinyl terminated polydiethylsiloxane, and SiH terminatedpolydimethyldisiloxane.

3. The composition of claim 1, wherein the cross-linkable silicone polymer comprises vinylterminated polydimethylsiloxane.

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

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

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

7. The composition of claim 1, wherein the silicone cross-linking agent is selected from thegroup consisting ofpolymethylhydrosiloxane, polymethylhydro-co-polydimethylsiloxane,34polyethyhydrosiloxane, polymethylhydrosiloxane-co-octylmethylsiloxane, andpolymethylhydrosiloxane-co-methylphenylsiloxane.

8. The composition of claim 1, wherein the silicone cross-linking agent comprisespolymethylhydrosiloxane, polymethylhydro-co-polydimethylsiloxane and combinationsthereof.

9. The composition of claim 1, wherein the composition additionally comprises about 0 wt.%to about 30 wt. %of an organic solvent, based upon the weight of the composition.

10. The composition of claim 1, wherein the composition comprises about 1 wt.% to about15 wt. %of the silicone cross-linking agent based on total solids, wherein the coatingcomposition additionally comprises about 0 wt. %to about 30 wt. %of an organic solvent,based upon the weight of the coating composition.

11. The composition of claim 1, wherein the coating composition comprises about 0.003 wt.%to about 0.06 wt.% of the platinum catalyst, based on total solids, wherein the coating12. The composition of claim 1, wherein the coating composition additionally comprises asolvent selected from the group consisting of pentane, hexane, heptanes, mixtures of lowmolecular weight olefins, and combinations thereof.

13. A composition comprising a platinum tetramethyldivinyl disiloxane diethyl maleate14. The coating composition of claim 1, wherein the composition is curable at temperaturesat about 19 C.

15. The coating composition of claim 14, wherein the composition is curable at temperaturesof about 28 C in about 2-5 minutes.

16. A kit comprising:a) a wound closure device; andb) the composition of claim 1.3517. The kit of claim 16, wherein the wound closure device is a wound closure strip.

18. The kit of claim 17, wherein the wound closure strip is selected from the group consistingof meshes, polymeric films, plastic foams (including open celled foam), woven fabrics,knitted fabrics, a non-woven fabrics and combinations thereof.

19. The kit of claim 18, wherein the wound closure strip is a mesh.

20. The kit of claim 19, wherein the wound closure device comprises materials selected fromthe group consisting of polyesters, nylons, acrylics, rayons, polyurethanes, polyurethanefoams, polystyrenes, polyesters, polyethylene terephthalate (PET), polyamides, polylacticacids, polyglycolic acids, polycaprolactones, and mixtures thereof; cotton, silk and linen; andsurface-treated materials that impart an OH functionality to their surfaces including but notlimited to OH surface-treated PTFE, OH surface-treated polypropylene and OH-surfacetreated polyethylene.

21. The composition of claim 1, comprising the combination of equal volumes of a Part Aand a Part B, wherein:Part A comprises 60 to 95 wt. % vinyl terminated polydimethyl silicone base polymer andfumed silica particles,5 to 15 wt. %vinyl terminated polydimethylsiloxane having a molecular weight rangmgfrom 3,000 to 9,000, and100 to 250 ppm of elemental platinum contributed from the catalyst Pt[(CH2 =CH)(CH3)2Si]20·(COCH = CHCO)(C2Hs0)2; andPart B comprises 60 to 80 wt. %vinyl terminated polydimethyl silicone base polymer and10 to 40 wt.% polymethylhydro-co-polydimethyl siloxane cross linker, and3 to 12 wt. %hydride terminated polydimethylsiloxane having a molecular weight ranging5 from 3,000 to 9,000.

22. The composition of claim 1, comprising the combination of equal volumes of a Part Ath day of December, 2022ETHICON, INC.By their agentAbhinav Agarwal(IN / PA 2850)OF LALL & SETHI36 AGENT FOR THE APPLICANTDated this 12Part A comprises 30- 100 wt.% vinyl terminated polydimethyl silicone base polymer and5 to 15 wt. %vinyl terminated polydimethylsiloxane having a molecular weight rangingCH)(CHJ)2Si]20·(COCH = CHCO)(C2Hs0)2; andPart B comprises 0 to 30 wt. %vinyl terminated polydimethyl silicone base polymer and23. The composition of claim 1, comprising the combination of equal volumes of a Part APart A comprises 0 to 40 wt. %vinyl terminated polydimethyl silicone base polymer and100 to 250 ppm of elemental platinum contributed from the catalyst of Pt[(CH2=Part B comprises 70 - 100 wt. % vinyl terminated polydimethyl silicone base polymer and10 from 3,000 to 9,000.