CA2202264A1 - Low trauma wound dressing with improved moisture vapor permeability - Google Patents

Abstract

We have discovered a low trauma wound dressing including a moisture-vapor permeable backing and a contiguous particulate adhesive layer comprised of tacky, substantially solvent-insoluble, solvent-dispersible, acrylate-based, elastomeric, pressure-sensitive adhesive microspheres.

Description

W O96/14094 PCTrUS95112193 LOW TRAI lMA WOUND DRESSING
WITH IMPRO~7ED MOISTU~E VAPOR
PERMEABILITY

~IELD OF TE~E INVENTION
' This invention relates to wound dressings. More specifically, this invention relates to wound dressing tapes having a pressure sensitive adhesive layer for securing the dressing over the wound.
BACKGROUND OF lrHE INVENTION
Wound dressing tapes intçnded for application to wounds that exude bodily fluids should prevent the introduction of bacteria or other pathogens into the wound while pe. ~ ing maximum evaporation of exuded fluids. At the same time, such tapes should also provide good initial adhesion -- in order to prevent prematurerelease.of the tape -- and minim~l build-up of adhesion -- so as to ~ skin 15 trauma upon removal of the tape.
Commercially available wound dressing tapes typically include either a rubber-based or an acrylic-based adhesive with acrylic-based adhesives generallyfavored because of their hypoallergenic nature.
While the hypoallergenic nature of an adhesive is one factor to be

2 0 considered in a~s~ssing acceptability of the adhesive for use in a wound dressing tape, tr~um~ti7~tion of slcin upon nemoval of a wound dressing tape is primarilycorrelated to ch~nges in the cohesion of slcin cells resulting from prolonged coverage of the skin with an occlusi~fe tape or bandage. The type and severity of skin injury res~-lting from the removal of many conventional wound dressing tapes 2 5 varies with the length of time the taple is worn. The longer a tape is worn, the more hydrated and thus macerated the outer layer of the stratum corneum becomes. The internal strength of the stratum corneum can be significantly reduced when macerated in this manner, res~llting in deep and irregular fractures within the stratum corneum upon removal of a wound dressing tape. When occlusive medical

3 0 tape is worn for short intervals of time -- such as a few minlltes -- the upper layer of the stratum corneum will not gain significant fluid from the underlying skin layers and the tape can be removed without significant trauma to the skin. However, W O96/14094 PCTrUS95/12193 when occlusive medical tape is worn on the skin for prolonged periods -- such astwenty four hours -- fluids will build-up in the upper layers of the stratum corneum and frequently result in severe skin fractures upon removal of the tape.
Trauma to the skin can be le~sene~l when the wound dressing tape permits evaporation of fluids from underneath the tape. This fact has led to the development and sale of wound dressing tapes which provide a high moisture vaportr~n~mi.~sion rate.
Potter (United States Patent No. 4,595 001) discloses formation of a moisture vapor tran~mi.c.sive wound dressing tape by pattern coating an adhesiveonto a backing so as to leave a significant p~. ;en~age of the backing in direct contact with the skin.
R~wli-.gs (United States Patent No. 4 798 201) discloses formation of a porous, moisture vapor permeable adhesive film for use in a wound dressing whichis formed by coating a mixture of an emulsion adhesive and petroleum spirits onto a silicone release liner or backing film.
T~k~oto (European Patent Application Publication 0 353 972) discloses formation of a moisture vapor tr~n~mi~ive wound dressing tape by dot coating an adhesive onto a ba~1~ing so as to leave a significant percentage of the backing available for direct contact with the skin.
Silver (United States Patent No. 3 691 140) discloses formation of a porous moisture vapor permeable adhesive film for use in a wound dressing which is formed by solvent coating a swelled solid microsphere adhesive onto a backing at a coating weight effective for pe.",illing particle to particle discontinuities to form between microspheres in the adhesive layer as the swelled microspheres shrink due to evaporation ofthe solvent.
These tapes advantageously m~int~in a relatively normal moisture content of the outermost skin layers so that any fractures in the skin caused by removal of the wound dressing tape will develop near the surface of the naturally desqll~m~tinglayers of the stratum corneum. However, such tapes tend to lack sufficient initial 3 0 adhesion to the skin and frequently fall off. In addition such tapes typically exhibit W O96/14094 PCTrUS95/12193 significant build-up of adhesion which counteracts the reduced trauma benefit achieved from the enhanced breathability of the tape.
In summary, the prior art offers a choice between aggressive adhesive tapes which result in significant injury to the skin upon removal and minim~lly aggressive 5 adhesive tapes that allow for IllOiSlU~ e tr~n~mi~cion but are prone to premature release from the skin. Consumer pl erel ~nce has resulted in most conventional adhesive tapes using the minim~lly aggressive adhesives.
Hence, a substantial need exists for a moisture vapor L~ Je, low trauma wound dressing tape exhibiti~g good initial adhesion and minim~l build-up10 of adhesion.
SUM~IARY OF TH]E INVlENTION
We have discovered a low trauma wound dressing possessing the advantageous co...bi..aLion of improved moisture vapor permeability, acceptable initial adhesion, minim~l build-up of adhesion and effective antimicrobial 15 performance. The wound dressing inçl~des a moisture-vapor permeable backing and a contiguous particulate adhesive layer. The adhesive is comprised of tacky,substantially solvent-insoluble, solvent-dispersible, aclylate-based, elastomeric, pressure-sensitive adhesive microspheres. The adhesive may optionally be impregn~ted with an antimicrobial system of an antimicrobial agent and a transfer 2 0 agent wherein the Ll ~nsrer agent is effective for allowing migration of theantimicrobial agent from the interior of the adhesive layer to the surface of the adhesive layer in contact with the wound.

W 096/1409~ . PCT~US95/12193 DETALLED DESC~UCP110 N OF THE n~ENTIO N
LNCLuDn~G A BEST M O DE
DEF ~ TIONS
As utilized herein, inc~ ing the claims, the term "critical micelle concentration" means the minimllm concentration of emlllcifier neCess~ry for formation of the submicroscopic a~ lion of ~mul.~ifier molecules known as micelles. It is understood that the critical micelle concentration is dependent upon the specific emulsifier used and the aqueous environment into which the em~ ifier is placed. Generally, critical micelle concentrations will range from about 0.0001 to 3.0 moles/liter.
As utilized herein, including the claims, the phrase "contiguous particulate adhesive layer" means a particle cont~ining adhesive layer (such as a microsphere adhesive) which is coated onto a surface at a particulate density such that the particles form a substantially contiguous surface over the entire coated surface with substantially all particles in physical contact with several other particles in the adhesive layer. Adhesive layers having minim~l particle to particle contact, such as described in Silver (United States Patent No. 3,691,140), and those which are pattern coated, such as disclosed in European Patent Application 353972, are notcontiguous particulate adhesive layers.
2 0 As utilized herein, incl~ ing the claims, the phrase "solvent irlsoluble "
means that the compound is sparingly dissolved on a molecular level in the specified solvent.
As utilized herein, in~ ing the claims, the phrase "solveot swellable "
means that the compound expands in size when contacted by the specified solvent 2 5 and forms a dispersion when immersed in the solven~ which consisting substantially of individual particles.
COMPOSITION
Wound Dressing Backings Substrates suitable for use in the m~nllf~cture of a wound dressing intended for ~tt~hment to the skin include woven, nonwoven and knit fabrics and conformable synthetic polymeric films. Suitable polymeric films are those formed of -W O96/14094 PCTrUS9~/12193 such polymers as polypropylene, polyethylene, polyvinyl chloride, polyurethane, polyetheramide, polyester, and ethyl cellulose. P-~re,.ed synthetic films are those of the moisture vapor permeable type.
Suitable woven and nonwoven fabrics include those formed from threads of 5 synthetic or natural materials inclu~lin~ cotton, nylon, rayon, polyester, and the like.
Synthetic fabrics suitable for use are those constructed from fibers having a tensile modulus of less than about 400,000 psi, preferably less than about 300,000 psi, measured in accordance with ASTM D-63 8. The fabric should be sufficiently continuous to prevent pathogens as large as a single cell, such as bacteria, from 10 entering the wound.
Suitable substrates are moisture vapor permeable so as to permit the evaporatlon of body fluids, such as pe. ~pi. ~lion and wound exudate, from underneath the dressing. Preferred materials are those which possess a twenty four hour moisture vapor tr~n~mi~sion rate ~VTRUp) of at least about 500 glm2/24 hours, most pl e~l ~bly at least about 1000 glm2124 hours when measured in accordance with ASTM E 96-80 at 40C with a humidity di~~ ial of 80%.
Preferred substrates also perrnit visual inspection of the wound without removal of the dressing.
A superior backing posses~in~ the desired attributes of con~l Illability, 2 0 continuity, strength and moisture vapor permeability is a film of hydrophilic polyurethane with a thickness of from about 15 to 80 microns, preferably 20 to 60 microns, and most preferably 25 to 50 microns.
A continuous film of polyurethane sold by B. F. Goodrich under the trademark "EstaneO" and a continuous film Or polyester sold by E. I. Dupont de 2 5 Nemours sold under the trademark "~IytrelO" each have an acceptable MVTRyp value of about 1000 to 1500 glm2124hrs. Woven substrates, such as that used by Minnesota Mining and ~mlf~ch~ring; Company in the construction of "DuraporeO"
surgical tape possess even higher MV7~up.
Adhesive 3 0 The pressure-sensitive adhesives of the invention comprise at least about 70 wt% solid or hollow microspheres and optionally about 1 wt% to 30 wt% of a W O 96/14094 PCTrUS95/12193 binder. Preferably, those formulations which do not include an antimicrobial agent comprise hollow microspheres a.lmixed with a solvent-soluble, macromonomer-co"~ binder copolymer.
The major component of the adhesive rnicrospheres is a hydrophobic 5 acrylate monomer which contributes to the visco-elastic pl ope- lies of the copolymer. The monomer is selected from the group consisting of (i) an acrylate or methacrylate ester of a non-tertiary C4 l2 alcohol, and (ii) an acrylate or methacrylate ester of a mixture of non-tertiary Cl l4 alcohols with an average of between about 4-12 carbon atoms per alcohol molecule. Such acrylate and 10 methacrylate alcohol esters are generally oleophilic, water Pmul~ifi~hle monomers having restricted water solubility. The homopolymers of these acrylate and methacrylate alcohol esters generally have glass transition temperatures below about -20C.
Useful acrylate and mçth~crylate alcohol esters include specifically, but not 15 exclusively, the acrylic acid and methacrylic acid esters of l-butanol, l-pentanol, 3 -pentanol, 2-methyl- 1 -butanol, 1 -methyl- 1 -butanol, 1 -methyl- 1 -pentanol, 2-methyl- 1 -pentanol, 3-methyl- 1 -pentanol, 2-ethyl- 1 -butanol, 2-ethyl- 1 -hexanol, 3,5,5-trimethyl-1-hexanol, 3-heptanol, 2-octanol, 1-decanol, and l-dodecanol.
Mixtures of these alcohols are available from Exxon under the Exxal family mark.2 0 A preferred alcohol mixture for use in synth~ci~ing the acrylate monomer is Exxal~-8.
Specific acrylate and methacrylate monomers include n-butyl acrylate, sec-butyl acrylate, 2-methyl butyl acrylate, 4-methyl-2-pentyl acrylate, 2-ethyl hexyl acrylate, isooctyl acrylate, isononyl acrylate, isoamyl acrylate, isodecyl acrylate, and 2 5 isodecyl methacrylate Other vinyl monomers which have a homopolymer glass transition temperature of greater than about -20C may be inc.lllded with the acrylate or methacrylate alcohol ester provided that the glass transition temperature of theresultant polymer is below about -20C. Examples of suitable vinyl monomers 3 0 include specifically, but not exclusively, tert-butyl acrylate, isobornyl acrylate, W O96114094 PCTrUS95J12193 n-butyl meth~crylate, iso-butyl methacrylate, tert-butyl methacrylate, vinyl acetate, and acrylamide.
A first optional monomer is a polar monomer which is copolymerizable with the other monomers used to form the adhesive microspheres. Representative 5 examples of suitable polar monomers include moderately ionized compounds such as acrylic acid, meth~crylic acid, itaconic acid, crotonic acid, maleic acid, fumaric acid and sulfoethyl meth~crylate; and ionic monomers such as sodium meth~rylate, ammonium acrylate, sodium aclylate, trimethylamine p-vinylbenzimide, 4,4,9-trimethyl-4-azonia-7-oxo 8-oxa-9-decene-1-sulphonate, N,N-dimethyl-N-(b-meth~cryloxyethyloxy-ethyl) ammonium propionate betaine, trimethylamine metll~crylimide, l,l-diethyl-l-(2,3-dihydroxypropyl)aminemethacrylimide, acrylonitrile, meth~crylonitrile and maleic anhydride. The prere,led polar monomers are the monocarboxylic and dicarboxylic acids and salts thereof.
The microspheres can include up to about 25 wt % polar monomers -- based upon the total weight of all monomers in the polymer -- with a loading of about 1 to 10 wt% p~t;~l~c;d. Such loading provides microspheres with b~l~nced pressure-sensitive adhesive properties. Inclusion of greater than about 25 wt% tends to produce an adhesive with insufficient tack and poor pressure sensitive adhesive pe. r.,..... .....,ance.
2 0 A second optional monomer is an N-vinyllactam which is copolymerizable with the other monomers used to form the adhesive microspheres. Inclusion of this monomer, ei~rOI ~;es the adhesive and contributes improved cohesiveness to the microspheres. Plere..ed N-vinyll~ct~m~ are N-vinylpyrrolidone and N-vinyl-2-caprolactam.
2 5 The microspheres can include up to about 25 wt % of an N-vinyllactammonomer -- based upon the total weight of all monomers in the polymer -- with a Ioading of about 3 to 15 wt% pl~re--ed. Inclusion of greater than about 25 wt%
tends to produce an adhesive with reduced tack and reduced conformability.
A third optional monomer is a hydrophilic alkylene oxide acrylate. The 3 0 synthesis of such alkylene oxide acrylates employs commercially available starting materials and widely known and accepted conventional techniques such as CA 02202264 1997-04-o9 W O96/14094 PCTrUS95/12193 described in United States Patent Application Serial No. 84/00506 and International Patent Publication WO 84/03837. For example, the alkylene oxide acrylate monomer may be prepared by reacting an a,b-unsaturated carboxylic acid, such as acrylic acid or meth~crylic acid, with an equimolar amount of a monoalcohol of a5 poly(lower alkylene oxide). The esterification reaction is generally con lucted under anhydrous conditions in an organic solvent, such as toluene, which plt;re.~bly forms an azeotropic mixture with the water generated by the esterification reaction.
Typically, the alcohol is combined with the organic solvent and the unsaturated carboxylic acid is added to the alcohol/solvent mixture.
The reaction is conventionally conducted in the presence of an acid catalyst, such as para-toluenesulfonic acid, and a free-radical inhibitor, such as copper powder. The reaction mixture is refluxed for several hours under a nitrogen atmosphere and the resultant water removed by azeotropic rlictill~tion.
Suitable poly(alkylene oxides) which may be used to prepare the alkylene oxide acrylate monomers using the above-described procedure include CarbowaxO
350, CarbowaxO 550, CarbowaxO 750, CarbowaxO 2000 and CarbowaxO 5000 commercially available from Union Carbide Corp. The C~arbowaxO family of monomers are methoxy-poly(ethylene oxide) ethanols possessing an average molecular weight expressed by the numeral provided in conjunction with the 2 0 CarbowaxO mark (i.e. . CarbowaxO 5000 has an average molecular weight of five thousand). The poly(alkylene oxide) of choice is poly(ethylene oxide) having an average of from 3 to 40 poly(ethylene oxide) (EO) units, preferably 5 to 20 EO
units, per molecule; including CarbowaxesO 350, 550 and 750.
A suitable commercially available poly(alkylene oxide) acrylate ester is NK-2 5 Ester AM-90GO available from Shin-Nakamura.
The microspheres can include up to about 15 wt % of a hydrophilic alkylene oxide acrylate monomer -- based upon the total weight of all monomers in the polymer -- with a loading of about 3 to 10 wt% p. ef~" ed. Inclusion of greater than about 15 wt% tends to produce an adhesive having reduced tack.
3 0 The microspheres can be synthesized as either hollow or solid spheres. The microspheres are normally tacky, elastomeric, solvent dispersible and insoluble --W O96/14094 PCTrUS9S/12193 but swellable -- in organic solvents. Individual spheres generally have a diameter of at least 1 micrometer with ~ meters of about 1 to about 250 micrometers pl~rt:lled. A majority ofthe hollow-type microspheres prepared by the methods ofthis invention have at least one void that has a ~i~meter of at least about 10% the 5 ~ eter of the microsphere, with void diameters of up to 30% readily achievable although larger void ~ m~tçrs are obtainable.
The adhesive may optionally include a minor amount of a binder copolymer.
Suitable binder copolymers are those co.~ g l~p~a~ g units of the A and B
monomers described below. The binder copolymer may optionally include the C
10 monomer also described below.
Monomer A is a hydrophobic acrylate monomer of the same type which forms the major con.ctit~lent of the mierospheres. The acrylate monomer contributes to the visco-elastic properties of the binder copolymer. Briefly, the monomer isselected from the group consisting of (i) an acrylate or methacrylate ester of a15 non-tertiary C4.l2 alcohol, and (ii) an acrylate or methacrylate ester of a mixture of non-tertiary C, l4 alcohols with an average of between about 4-12 carbon atoms per alcohol molecule.
The binder copolymer can include about 50 to 98 wt%, preferably about 85 to 95 wt%, monomer A -- based upon the total weight of all monomers in the 2 0 copolymer.
Monomer B is a polar monomer copolymerizable with the monomeric acrylic acid ester and of the same type described as an optional component of the microspheres.
The binder copolymer can include about 1 to 20 wt%, preferably about 1 to 2 5 15 wt%, monomer B -- based upon the total weight of all monomers in the copolymer.
Monomer C has the general formula X-(Y)n-Z wherein: X is a vinyl group copolymerizable with the A and B monomers; Y is a divalent linking group; n is zero or one; and Z is a monovalent polymeric moiety having a Tg greater than 20C, 3 0 an average molecular weight of between about 2,000 to 30,000, and is essenti~lly unreactive under copolymerization conditions. The vinyl group of the C monomer W O 96/14094 PCT~US9~J12193 is copolynl~- i~ble with the A and B monomers to form an elastomeric backbone having the polymeric moieties pendant therefrom.
The p,~re" ed C monomer has an X group of the general formula: -R R' ^-C = C -H
10 wherein: R is hydrogen or a COOH group and R' is hydrogen or methyl.
The double bond between the carbon atoms provides a copolymerizable moiety capable of copolymerizing with the A and B monomers.
. The pl erel, ed C monomer has a Z group of the general formula:

-(C ~ CH2)n-R3 l/2 0 wherein:
n is an integer from 20 to S00, R2 is hydrogen or a lower alkyl, R3 is a lower alkyl, and R4 is a monovalent radical CO2R5 or wherein: R5 is a lower alkyl and R6 is hydrogen or lower alkyl.
Preferably the C monomer has a general formula selected from the group 3 0 consisting of W 096/14094 PCTrUS95/12193 C) H
l/2 l/2 l/2 and O O H

l/2 15 whelein R7 is hydrogen atom or lower alkyl.
The vinyl termin~ed polymeric monomers are sometimes known as macromolecular monomers or macror~nonomers. Such monomers are well known and may be prepared by the method dlisclosed in United States Letters Patent Nos.
3,786,116 and 3,842,059 issued to Milkovich et al. The disclosures ofthe 2 0 Milkovich et al. Letters Patent are incorporated herein by reference.
The binder copolymer can include about 1 to 30 wt%, preferably about 2 to 10 wt%, monomer C -- based upon the total weight of all monomers in the copolymer.
The combination of B and C monomers in the copolymer should be within 2 5 the range of about 2 to 50 wt% basecl upon the total weight of all monomers in the copolymer.
A polymeric suspension stabilizer may op~-lonally be e~corporated into the aqueous suspension to f~çilit~te formation of the microspheres. The use of a - polymeric ~u~pen~ion stabilizer is particularly useful where homopolymer 3 0 microspheres are formed without the presence of an ionic copolymer. Many ionic and nonionic polymeric suspension stabilizers are effective for use in preparation of CA 02202264 1997-04-o9 W O 96/14094 PCTrUS95/12193 the microspheres. For example, polymeric stabilizers, such as those listed in United States Letters Patent No. 4,166,152 and incorporated herein by reference, would be useful suspension stabilizers according to the present invention. Polymeric stabilizers disclosed in United States Letters Patent No. 4,166,152 inrlude, but are 5 not limited to; polyoxyethylene, polyacrylic acid, polymeth71crylic acid, polyacrylamide, poly(N-vinylpyrrolidone), polyethylene imine, polyvinyl methyl ether, salts thereof, and mixtures thereof.
Typically, stabilizer concentrations of greater than about 10 wt% -- based on the monomers present in the suspension -- tend to provide less than optimum 10 properties to the resultant suspension. While certain stabilizers may function .s~ti.cf~ctorily at concentrations of greater than 10 wt% -- based upon the monomers present in the suspension -- concentrations of greater than about 10 wt% generally tend to produce excessive amounts of undesirable latex in the polymerized suspension, interfere with control of final particle size, and result in microspheres 15 having reduced tack.
Exemplary polymeric suspension stabilizers include (i) neutralized polycarboxylic acids inclurlin~ polyacrylic acid salts having a molecular weight of greater than about 5000 such as ammonium polyacrylate, sodium polyacrylate, lithium polyacrylate, and potassium polyacrylate; (ii) acrylamides inclu~ling carboxyl 2 0 modified polyacrylamides such as CyanamerO A-370 available from American Cyanamid; (iii) copolymers of acrylic acid and dimethylaminoethyl methacrylate;
(iv) quaternary amines such as GafquatO (a quaternized poly(N-vinylpyrrolidone))copolymer available from General Aniline) and JRO-400 (a quaternized amine substituted cellulosic available from Union Carbide); (v) cro.s~linked polyvinyl2 5 alcohols; and (vi) carboxy modified cellulosics such as NateosolO CMC Type 7L (a sodium carboxymethylcellulose available from Hercules). Set forth below is a table indicating representative stabilizers and the concentration level found to be effective for succes.~fi~l microsphere prt;pa,~lion.

. CA 02202264 1997-04-09 W O96/14094 PCTrUS95/12193 TABLE ONE
Trade Name Class [rn~erf~ TenSionl Pr~rc.. ~,d Level (dynes/cm) (wt o/o) None 50/50 copolymer of acrylic 21.2 1.0 acid and ~lim~th~ l.yl metha.,--~ldt~;
GOOD RITE K714 Pol~ ylic acid (n~--tr~1i7.od 21.0 1.0 with ~
GAF GAFQUAT 755 Q~ l.i~d poly(N-vinyl) 18.2 1.0 pyrrolidone copolvmer UNION CARBIDE Qudt~ .lu~d c~lh~ r 18.5 1.0 CYANAMER A-370 Carboxyl modified 21.0 3.0 polydc.yL.I,.ide NATROSOL CMC Sodium 19.8 5.0 ~,I,o~y".ell,ylcellu'ose Type 7L GANTREZ Copolymer of 15.4 1.0 HYM polyvinylmethyl ether and maleic anhydride (neutralized with .s~....o W O96/14094 PCTrUS95/12193 Antimicrobial System An antimicrobial system may optionally be incorporated into the pressure-sensitive adhesive for purposes of red-lcin~ the likelihood that infectious microbes will be introduced through the wound covered by the wound dressing. A suitable 5 antimicrobial system incl~ldes a pharnl~eutically acceptable, topical antimicrobial agent and a transfer agent. The antimicrobial agent destroys or other~,vise hinders growth and reproduction of pathogenic microbes while the transfer agent permits the antimicrobial agent to migrate from the interior of the adhesive layer to the exposed surface where it can contact and control pathogens before they are 10 introduced into the wound.
Suitable antimicrobials include any of the pharrn~ce~1tically acceptableantimicrobial agents approved for topical application to open sores and wounds.
The antimicrobial agent should also be compatible with the other conctihllonts ofthe adhesive composition. Examples of suitable antimicrobial agents include 15 OTTASEPT~ (chloroxylenol available from the Bedford Chemicals Division of Ferro Corporation); SUMQUAT~) 6020 (cetyl dimethyl ethyl ammonium bromide available from the Chemical Products Division of Hexcel Corporation);
SUMQUAT(~ 6030 (cetyl trimethyl ammonium bromide available from the Chemical Products Division of Hexcel Corporation); SUMQUAT~ 6110 (myristyl 2 0 trimethyl ammonium bromide available from the Chemical Products Division of Hexcel Corporation); TCC(~ BACTERIOSTAT (3,4,4'-trichlorocarbanilide available from Monsanto Company); chlorhexidine gl~lcon~t~ iodine, lauricidin, triclosan, and the like. Because of its superior compatibility with the other components in the adhesive composition, limited adverse effect upon the other 2 5 desired properties and characteristics of the adhesive, and exceptional antimicrobial performance, the antimicrobial agent of choice is chlorhexidine gluconate.
Suitable t, ~ re, agents should facilitate migration of the antimicrobial agent from the interior volume of the adhesive layer to the surface of the adhesive layer in contact with the wound. Without intçn-1ing to be unduly limited thereby, it is 3 0 believed that transfer agents of the type described herein f~cilit~te movement of the antimicrobial agent to the exposed surface of the adhesive layer by softening or CA 02202264 1997-04-o9 W O96114094 PCTrUS95112193 plasticizing the adhesive composition ~nd thereby permitting limited leaching of the antimicrobial to the surface of the adhesive layer.
Suitable ~,~ns~r agents include aliphatic, aromatic and cyclic hydrocarbons having at least one pendant hydroxyl group such as glycerin, poly(allylene oxides), alkoxylated sucrose, alkoxylated glycerol, nonyl phenol, octyl phenol, and the like.
Because of its low cost, ease of availability, superior compatibility with the other components in the adhesive composition, limited deleterious effect upon the other desired properties and characteristics of the adhesive, and exceptional pe. ro""ance in f~r.ilit~ting migration of the antimicrobial agent to the surface of the adhesive layer, the L~ns~ agent of choice is glycerine.
The adhesive composition can include about 0.5 to 5 wt% of the antimicrobial agent and about S to 30 wt% ofthe transfer agent -- based upon thetotal weight of all components in the adhesive. While dependent upon the type ofantimicrobial agent used, a loading of less than about 0.5 wt% antimicrobial agent is generally ine~ective for controlling microbial growth at the site of the wound while a loading of greater than about 5 wt% antirnicrobial agent tends to adversely affect the other desired properties and characteristics of the adhesive with little increase in the antimicrobial effectiveness of the adhesive. Similarly, dependent upon the specific transfer agent used, a loading of less than about 5 wt% l, ansîel agent is 2 0 generally ineffective for allowing the antimicrobial agent to migrate towards the surface of the adhesive layer to an ext,ent sufficient to control microbial growth for r"ct.?nrled periods of time, while a loading of greater than about 30 wt% L,~nsrel agent tends to adversely affect the other desired properties and characteristics of the adhesive with little increase in the antimicrobial effectiveness of the adhesive.
2 5 The pressure-sensitive adhesive of the invention may also include a tackifying resin and/or additional pl~1iri~Pr to obtain the well known properties and characteristics attributable to such additives. Tackifiers suitable for use herein include hydrogen~ted rosin esters co",n,e~ cially available from various co",panies inr,lu~1ing the ForalO and PentalynO families of rosin esters available from Hercules, 3 0 Inc. Specific tackifiers acceptable for use in the adhesive of the invention include ForalO 65, ForalO 85 and ForalO 105. Other useful tackifiers include those based W O96/14094 PCTAUS9~112193 on t-butyl styrene disclosed in United States Patent No. 5,045,569. Suitable plasticizers include the widely available plasticizers dioctyl phth~l~tP, 2-ethyl hexyl phosphate, and tricresyl phosphate.
It is also within the scope of this invention to include various other 5 bioco"")dlible components, such as pigments, fillers, stabilizers, rheological modifiers, and various polymeric additives.
Release Liner The release liner may be any of the commercially available paper and film liners which have been treated to provide a release surface (such as a surface 10 coating of an aliphatic fluorochemical or silicone) having acceptable h~ntllin~
characteristics (such as limited transfer of adhesive to the liner).
MANUFACTURE
Adhesive Aqueous suspensions of hollow microspheres may be prepared by a 15 "two-step" emulsification process. The first step involves formation of a water-in-oil emulsion by combining an aqueous solution of the polar monomer(s) and an oil-phase emulsion ofthe other monomer(s) (i.e., the acrylate or meth~rylate alcohol ester) emulsified by an emulsifier having a low hydrophilic-lipophilic balance (HLB) value. In those situations where a polar monomer is not2 0 in~lude(l in the microsphere, water may be mixed directly into the oil phase to form the water-in-oil emulsion.
Suitable emulsifiers are those having an HLB value below about 7, with pl e~ d emulsifiers having an ~B value of about 2 to 7. Emulsifiers having an HLB value of greater than about 7 tend to produce an oil-in-water emulsion rather 2 5 than the desired water-in-oil emulsion. Examples of suitable emulsifiers are the anionic emulsifiers of sorbitan monoleate, sorbitan trioleate, and ethoxylated oleyl alcohol, such as BRIJO 93, available from Atlas Chemical Industries, Inc.
The other components, such as the free radical initiator and any cros.clinki~g monomer, are dissolved in the oil-phase, along with the oil-phase monomers, prior 3 0 to formation of the oil-in-water emulsion W O 96/14094 PCT~US95/12193 A thickening agent, such as mel:hyl cellu~o. ~ may be incorporated into the aqueous phase, prior to formation of the water-in-ull emulsion.
The second step involves formation of a water-in-oil-in-water emulsion by dispersing the water-in-oil emulsion fol~ed in the first step into a second aqueous-5 phase co,~ g a second ~m~ ifier having an ~B value above about 6. Thesecond aqueous phase may contain that portion of the polar monomer(s) which was not incorporated into the water-in-oil emulsion with the first aqueous-phase.
F.mlllcifiers suitable for use in forming the water-in-oil-in-water emulsion of this invention are those having an E~ value of greater that about 6. F.m~ ifiers10 having an HLB value of less than about 6 tend to produce an oil-in-water emulsion rather than a water-in-oil emulsion witlh the disadvantage ~i.ccllssed infra.
Examples of suitable emulsifiers include ethoxylated sorbitan monoleate, ethoxylated lauryl alcohol, and alkyl sulfates.
The emulsifier used in both steps should be incorporated at a concentration 15 which is greater than its critical micelle concentration. Additional details concerning the prepal ~ion of multiple emulsions, such as the water-in-oil-in-water emulsions used herein, may be found in various literature references, inc~ ing Surfactant Systems: Their Chemist~y. Phannacy & Biology~ (D. Attwood and A. T.
Florence, Chapman & Hall T.imite~l7 New York, New York, 1983). Heat and/or 2 0 radiation is then applied to the water-in-oil-in-water emulsion to initiate polymerization of the monomers.
Following polymerization, an aqueous suspension of hollow microspheres is obtained which is stable to agglomera~ion or coagulation under room temperature conditions. The suspension may have a non-volatile solids contents of from about25 10 to about 70 wt%. Upon prolonged st~n~ling, the suspension separates into two phases. one phase beis~ aqueous and substantially free of polymer, the other phase being an aqueous suspension of microspheres. Both phases may contain a minor portion of small latex particles. Dec~ ;on of the microsphere-rich phase provides - an aqueous suspension having a non-volatile solids content on the order of 40-50 3 0 wt% which, if shaken with water, will readily redisperse. This aqueous suspension of microspheres may be utilized without further treatment.

W O 96/140~4 PCTrUS9~/12193 Alternatively, the aqueous suspension may be coagulated with a co~ ting agent, washed and than dried to form dry microspheres. Suitable co~ ting agents include (i) polar organic solvents, such as methanol, iSOpl opallol and the like, (ii) ionic emulsifiers having a charge opposite to that of the em~ ifier used in the polymerization process, and (iii) saturated salt solutions. The dried microspheres can be readily dispersed in common organic liquids, such as ethyl acetate, tetrahydrofuran, heptane, 2-butanone, ben7ene, cyclohexane, and various esters. It is, however, not possible to readily resuspend them in water.
Aqueous suspensions of solid microspheres may also be prepared by a "one-step" emulsification process. The one-step process is conrillcted by aqueous suspension polymerization of (i) at least one alkyl acrylate, alkyl methacrylate, and/or vinyl ester monomer, (ii) at least one free radically reactive hydrophilic monomer, (iii) at least one polymeric suspension stabilizer, such as polyvinyl alcohol, and (iv) an optional polar monomer. It is believed that other polymericsuspension stabilizers, such as the neutralized polycarboxylic acids described previously herein and in United States Patent No. 4,166,152, issued to Baker et al., and other steric or electrosteric polymeric stabilizers could also be usefully incorporated into the microspheres. Suitable polymeric suspension stabilizers include specifically, but not exclusively, one or more of polyoxyethylene, poly(N-2 0 vinylpyrrolidone), polyethyl~neimin~, poly(vinyl methyl ether), and salts thereof.
The methods described herein may be modified by withholding the addition of all or a portion of the free radically reactive hydrophilic monomer(s) and/or the polar monomer(s) until after polymerization of the oil emulsion is initi~ted This alternative procedure may be used provided the withheld components are added to 2 5 the polymerizing mixture prior to complete polymerization of the monomers in the water-in-oil emulsion. According to this alternative procedure, the formulator may add any portion of the free radically reactive hydrophilic monomer(s) and/or polar monomer(s) at any convenient point in prepa~ g the pressure-sensitive adhesive microspheres.
3 0 In addition to the processes described hereinabove, microspheres can beprepared according to the processes described in U.S. Patent Nos. 5,053,436 and CA 02202264 1997-04-o9 W O96/14094 PCTrUS95/12193 5,045,569 and European Patent Applic:ation WO 94/13751, the descriptions of which are incorporated herein by reference.
Polymerization ofthe emulsified monomers is effected by standard free radical polymerization ~ltili~ing a suitable free radical initiator. Suitable initiators 5 are those which are both fairly oil-soluble and fairly water-insoluble. Use of a water-soluble poly.,.e. i;c~Lion initiator ~ends to cause the formation of excessive amounts of latex which -- due to its small particle size -- tends to destroy the desired prop~- ~ies and characteristics of the microspheres.
Numerous suitable free radical initiators are well known in the industry.
10 Preferred free radical initiators are those which are freely soluble in oil with limited water solubility. Exemplary of those free radical initiators suitable for use in the present invention are those described in United States Patent No. 4,994,322 and such description is incorporated herein by reference. Suitable thermally activated initiators include specifically, but not exclusively: azo compounds such as 2,2'-azo-15 bis(isobutyronitrile); and hydroperoxides and peroxides such as tert-butyl hydroperoxide, benzoyl peroxide, and cyclohexanone peroxide. Suitable photoinitiators include specifically, but not exclusively, benzophenone, benzoin ethyl ether and 2,2-dimethoxy-2-phenylacetophenone.
The concentration of initiator ~may affect sphere quality and should be 20 carefully monitored. Generally, about 0.15 to 0.70 wt%, preferably about 0.25 to 0.5 wt%, initiator -- based upon the total weight of all monomers -- is effective for initi~ting poly"~ ion and providing superior quality microspheres. Initiator concentrations below about 0.15 wt% tend to result in slow polymerization rates while concentrations of greater than about 0.70 wt% tend to increase the rate of 2 5 polymerization and thereby complicate control of the exothermic reaction.

The suspension from which the microspheres of the invention are made may also contain a mllltifil~ctional crocclinking agent. The-term "mllltifi~nctional", as used herein, refers to crosslinking agents which possess two or more free radically - polymerizable ethylenically unsaturated groups. Useful ml~ltifilnc.tional crosclinking 3 0 agents include (i) acrylic or methacrylic diol esters such as butanediol diacrylate, dec~nediol diacrylate and hexane diol diacrylate; (ii) acrylic triol esters such as W O96/14094 PCTrUS95/12193 glycerol triacrylate, and (iii) acrylic tetrol esters such as pentaerythritol tetracrylate.
Other useful cro.sslinkin~ agents include (iv) polymeric ml-1tifi-nctional (meth)acrylates such as poly(ethylene oxide) diacrylate and poly(ethylene) oxidedimethacrylate; (v) polyvinylic crosslinking agents such as substituted and 5 unsubstituted divinyl~n7:etle; and (vi) difunctional urethane acrylates, such as EbecrylO 270 (a mixture of acrylated urethanes with a result~nt average molecular weight of 1500 available from Radcure Specialties) and EbecrylO 230 (a mixture of acrylated urethanes with a resultant average molecular weight of 5000 available from Radcure Specialties).
The crosslinker can be added to the suspension at any time prior to complete polymerization. The crosslinker is preferably added prior to initiation of polymerization.
The crosslinker may be incorporated at a level of up to about 0.15 equivalent wt %, preferably up to about 0.1 equivalent wt% -- based upon the weight of the total polymerizable composition. The term "equivalent wt %" of a given compound is defined as the number of equivalents of that compound divided by the total number of equivalents in the total composition wherein an equivalent is the number of grams divided by the equivalent weight. The term "equivalent weight" is defined as the molecular weight divided by the number of polymerizable 2 0 groups in the monomer (in the case of those monomers with only one polymerizable group, equivalent weight = molecular weight).
Microspheres formed solely from a methacrylate monomer generally require the inclusion of a cro,sslinking agent. Failure to include a cro.sslinkin~ agent in such cases can result in the synthesis of solvent soluble microspheres.
2 5 The binder copolymer can be prepared by standard free radical polymerization of the A, B and optional C monomers. Such techniques are further described in D. Satas, Handbook of PSA Technolo~y. 2nd Ed., p. 908, Van-Norstrand-Rheinhold, New York, 1989. The relevant disclosures ofthese references are hereby incorporated by reference.
3 0 The antimicrobial system may be conveniently formed and uniformly dispersed throughout the adhesive composition by simply blending the antimicrobial .

W O96/14094 PCTrUS9~/12193 agent into the transfer agent and then introducing the blend into the adhesive composition. Alternatively, the antimicrobial agent and llansre, agent may be indep~ndP.ntly blended into the adhesive composition with s -fficient agitation to ensure dispersion of the antimicrobial agent throughout the adhesive composition.
The pressure-sensitive adhesive of the invention may be made by colllbilfillg a dispersion of microspheres with a solution of the binder copolymer at a dry weight ratio of microspheres to binder of abcut 2:1 to 100:1 with a pl erel I ed weight ratio of about 3:1 to 10:1. When employed, the antimicrobial system is preferably incorporated into the adhesive composition so as to provide about 0.5 to about ~wt% antimicrobial agent - based upon the total weight of all other components inthe adhesive composition, in~ ing transfer agent. Concentrations of about 5 to about 30 wt% transfer agent -- based upon the total weight of all other components in the adhesive composition, incl~lding transfer agent -- have been found to be effective for producing the necessary level of surface migration without significantly imp~CCting the other desired attributes of the adhesive.
Since the adhesive is intentled for use in a wound dressing, the adhesive should be sterilized. A widely accepted method of sterilizing wound dressings is to subject the dressing to about 25 to 50 kilograys of gamma radiation. The wound dressing may also be sterilized by the ethylene oxide sterilization method.
2 0 Wound Dressing Tape Solvent-based adhesive compositions can be coated onto the substrate by any of a variety of conventional techniques such as roll coating, spray coating,extrusion co~ting, coextrusion, hot-melt coating and the like. The process of choice depends upon the nature of the substrate employed. For example, a prc;rel, ed 2 5 method for coating the adhesive upo:n a nonwoven fabric is to disperse the adhesive copolymer microspheres in an organic solvent, spread the dispersed copolymer onto a release liner, and then l~min~te the adhesive coating onto the nonwoven fabricbefore the adhesive is completely dry. Alternatively, the adhesive microspheres can be coated directly from water.

CA 02202264 l997-04-09 W O96/14094 PCTrUS95/12193 Application The dressing may be easily applied by simply removing the release liner and applying the exposed adhesive-conl~h-;n~ surface over the wound.
PROPERTIES &
5 CHARACTE~STICS
Moisture Vapor Tr~r~ ion Rate The wound dressings of this invention possess a superior moisture vapor tr~n~miCsion rate which permits the evaporation of pel~l,i,alion and wound exudate 10 from underneath the dressing. Preferred adhesives for use in the dressing are those with a moisture vapor tr~n.cmis,sion rate (A~f~TR,~p) of at least about 500 g/m2/24 hours, most preferably at least about 1000 g/m2/24 hours, when measured in accordance with ASTM E 96-80 at 40C with a humidity differential of 80%.
Skin Adhesion The adhesives used in this invention exhibit an initial skin adhesion (To) of between about 0.01 to about 0.2 N/cm width, preferably between about 0.03 to about 0.15 N/cm width; and a twenty four hour skin adhesion (T24) of between about 0.07 to about 0.5 N/cm width, preferably between about 0.15 to about 0.3 N/cm width. Adhesives with an adhesion of less than about 0.01 N/cm width at any2 0 time during normal periods of use tend to peel prematurely from the skin while adhesives with an adhesion of greater than about 0.5 N/cm width at the time of removal will frequently produce significant skin irritation upon removal despiteeffective evaporation of fluids from beneath the dressing.
Microbial Control 2 5 The wound dressings of this invention which include the optional antimicrobial system also provide effective antimicrobial properties to the exposed surface of the wound covered by the dressing. The antimicrobial-cont~ining adhesive compositions of this invention are effective for achieving a 2.5 to 6 log reduction in bacteria as tested in accordance with the microbial assay described3 0 i~7J;a, with a log reduction of greater than about 2.5 generally considered effective for controlling the growth of bacteria under the dressing.

W O96/14094 PCTrUS95112193 TESTING PROTOCOLS
Moisture Vapor Tr~r~ sio- Rate (Upright) The Moisture Vapor Tr~n~mi~ion Rate (MVTl~p) is measured in accordance with ASTM E 96-80 as modified below.
Thirty five millimeter ~ m~tçr samples of a 0.025 cm thick film of the adhesive is l~min~te~l to a 0.0275 cm thick polyurethane web having aMV~up of 2,000 to 2,400 g/m2/24 hours measured at 40C and a relative humidity di~-e,-~ial 1 0 of 80%.
The l~min~ted samples are sand~wiched between the adhesive surfaces of two axially aligned foil adhesive rings having 2.54 cm cli~meter holes. Each sample is pulled to ensure a flat, wrinkle-free and void-free foil/sample/foil l~min~te.
` A four-ounce (0.14 liters) glass jar is filled half-full with distilled water. The jar is fitted with a screw-ol-~ ap having a 3.8 cm rli~metçr hole concentricallyaligned with a rubber washer having a 4.445 cm outside-diameter and a 2.84 cm inside-tli~met~r.
The foil/sample/foil l~min~te is concentrically positioned on the rubber washer and the sample-co..l~;..;..g sub-assembly screwed loosely onto the jar.
2 0 The assembly is placed into a chamber .. ~ ed at a temperature of 40Cand 20% relative humidity. The assembly is removed from the chamber after four hours, weighed to the nearest 0.01 gram (W,), and immetli~tçly returned to the chamber. The cap is nc ~ screwed tightly onto the jar without bulging of the sample. The assembly is again removed from the chamber af-ter an additional 2 5 çi~hteen hours and weighed to the nearest 0.01 gram (W2).
The MVTRt,p of the l~min~ted samples (measured in grams of water tran~mitted per square meter of sample area over a twenty four hour period) may then be calculated according the formula set forth below:
MVTR"p = (W~ - W2~(4.74 ' 104)/t where:
(W,) is the initial wei,ght of the assembly (grams) CA 02202264 l997-04-09

4 PCTnUS95/12193 (W~ is the final weight of the assembly (grams), and (l) is the time period between Wl and W2 (hrs).
Three samples of each adhesive were run and the average of the three samples reported.

5 Moisture Vapor Tr~ ics~on Rate (Inverted) The protocol for measuring "Inverted" MVTR ~RjnvJ is the same as the "Upright" protocol except that the assembly is inverted inside the chamber once the 10 cap is tightly screwed onto the jar so that the water within the jar directly contacts the foil/sample/foil l~min~te while the assembly is within the chamber.
Skin Adhesion Evaluation of the adhesiveness of an adhesive composition to human skin is an inherently temper~ment~l but essenti~lly reproducible dett;l.,-hlalion so long as 15 the conditions established below are observed. Human skin possesses wide variations in composition, topography, and the presence/absence of various body fluids. However, controlled and co~ )a,~Li~e values of adhesion are attainable by selecting a panel of individuals which is sufficiently large to provide statistically significant data and one or more evaluators trained to recognize the normal skin2 0 variations encountered in medical practice.
Initial skin adhesion (To) and skin adhesion after 24 hours of continuous contact with the skin (T24) is measured in accordance with the widely accepted PSTC-l Peel Adhesion Test for single coated adhesive tape con~lucted at a removal angle of 180. The PSTC-l Peel Adhesion Test is a testing protocol established by 2 5 the Specifications and Technical Committee of the Pressure Sensitive Tape Council located at 5700 Old Orchard Road, Skokie, Illinois. The test is modified for ourpurposes by applying the tape to the skin of a living human.
The adhesive is tested as a 0.025 mm film coated onto a 0.0275 mm thick polyurethane web having aMV~2yp T2~ of 2,000 to 2,400 g/m2/24 hours measured 30 at 40C and a relative humidity di~e,elllial of 80%. Three samples measuring 2.5 cm wide by 7.6 cm long are applied to the back of each of six human subjects (three men and three women). The subjects are placed in a prone positioned with arms at W O 96/14094 PCTrUS95/12193 their sides and heads turned to one side. Samples are applied to both sides of the spinal colurnn with the length of each sample positioned at a right angle to thespinal column. The samples are appliecl without tension or pulling of the skin.
The samples are pressed into place with a 2 kg roller moved at a rate of - 5 ap~,o~."ately 2.~ cm/sec with a single forward and reverse pass. No manual pressure should be applied ~o the roller during application.
The samples are then removed either immedi~tely after application (To) or a~cer 24 hours of continuous contact with the skin (T24), at a removal angle of 180 and removal rate of 15 cm per minute, using an adhesion tester equipped with 25 Ib (11.4 kg) test line ~tt~rlled to a 2.5 cm clip. The clip is ~tt~c.hed to the edge ofthe sample furthest from the spinal column by m~nll~lly lifting about 1 cm ofthe sample from the skin and att~ching the clip to the raised edge. The adhesion tester is a strain-gauge mounted on a motor-driven carriage.
Th~ n~e~su~e~fo~c~xer~ed to ~et remo~al i~ rep~rt~d ~n Ne~.cns pe~
1 5 cçntimetçr.
Microbial Assay Culture plates are prepared ~om a solution of3% B ACTO agar, available from Difco Laboratories of Detroit, Michigan, in distilled water. The plates are2 0 dried for 20-30 mimltçs at 37C in an incub~tQr prior to use.
Onto a 25 millimeter di~meter ~elman metricel filter having a 0.45 micrometer pore size is filtered five mi~liliters of a 3 ' 106 CFU/ml suspension of Enterococcus feacalis. The co.~ ted filter is air dried and placed on the surface of one of the previously pl epared cult~sre plates.
A 11/2 inch (3.81 cm) square sample ofthe wound dressing to be tested is p,t;pa~ed and placed into contact with the co~ ted filter resting on the cultureagar plate with the adhesive side of the wound dressing physically contacting the co..l~"~ ed filter. The plates are then inc.ub~ted for 30 minutes at 37C in an arid incub~tor after which the wound dressing and co~ ed filter are removed.
3 0 The co"l~-";l-~ted filter is submerged in 100 millilitt~rs of a neutralizer and processed for three to five minutçs in a Waring blender. The neutralizer is selected W O 96/14094 PCT~US95/12193 based upon the anti-microbial agent incorporated in the wound dressing adhesive with Difco Neutralizing Buffer used when the wound dressing includes chlorh~ line gluconate as the anti-microbial agent and 0 1 wt% sodium thiosulfate solution used when the wound dressing in~.luded iodine as the anti-microbial agent.
The processed samples are then diluted with phosphate buffered saline, plated onto an m-entococcus agar culture plate, and incubated at 37C for 24 hours, after which the number of bacterial colonies are counted and recorded EXPERIMENTAL
Exp~- I.t 1 Syn~hesis of Microspheres (Adhesives #1-19) Into a one-liter resin reactor equipped with a mecll~nical stirrer, a condenser, and inlet-outlet lines was charged (i) 450 grams of deionized water, (ii) 5 6 grams of StandapolO A (an ammonium lauryl sulfate emulsifier purchased firomHenkel AG), (iii) 0.72 grams LucidolO-70 (benzoyl peroxide purchased from Pennwalt Corporation), and (iv) 150 grams of a mixture of monomers isooctyl acrylate, isodecyl acrylate, acrylic acid, N-vinylpyrrolidone and poly(ethylene oxide) acrylate with the ratio of monomers specified in TABLE TWO and TABLE FOUR.
2 0 This monomer suspension was homogenized in an OmniO mixer (available from Omni International Inc.) prior to polymerization for adhesives 15 and 16. The mixture was then stirred at 400 rpm for the remainder of the polymerization reaction. The atmosphere in the reactor vessel was eva-~u~ted by application of vacuum and the vessel purged with argon through colllpl~,~ion of the polymerization 25 reaction. The telllpe,~L~lre ofthe reactor was raised to between 55 and 65C and m~int~ined at that elevated temperature for a time period specified in TABLE TWOfor purposes of completing polymerization. The polymerized suspension was then allowed to cool to room temperature and the suspension removed from the reactor and filtered. Optical microscopy revealed microspheres with an average diameter 3 0 reported in TABLE TWO suspended in water.

CA 02202264 1ss7-04-og WO 96/140g4 PCTIUS9~J12193 Blxperlment 2 ~dhesive Testing (Adhesives #1-19) - The initial Moisture Vapar Tr~nsmi~sion Rate (Upright~ (MVTR"p), Skin 5 Adhesion (Initial~ (~0,), and Skin Adhesion (Twenty Four EIours) (~2J ofthe samples was then measured in accordance with the testing protocols set forth herein. The results of such testing are set forth in TABLE T~EE below.

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--E~ t 3 Synt*esis of Microspheres (Adhesives #20-40) Into a one-liter resin reactor equipped with a mechanical stirrer, a condenser, and inlet-outlet lines was charged (i) 450 grams of deionized water, (ii)

6 grams of StandapolO A (an ammonium lauryl sulfate emulsifier purchased from Henkel AG), (iii) 0.72 grams LucidolO 70 (benzoyl peroxide purchased from Pennwalt Corporation), and (iv) 150 grams of a mixture ofthe monomers isooctyl acrylate, N-vinylpyrrolidone, acrylic acid, and poly(ethylene oxide) acrylate with the ratio of monomers specified in TABLE TWO and TABLE FOUR. This monomer suspension was homogenized in an OmniO mixer (available from Omni International Inc.) prior to polyllleli~a1ion for adhesives 20, 23-26 and 32-36. The mixture was stirred at 400 rpm for the rem~in~r of the polymerization reaction. The atmosphere in the reactor vessel was ev~c~l~ted by application of vacuum and thevessel purged with argon through completion of the polymerization reaction. The temperature of the reactor was raised to between 55 and 65C and l?~ ed at that elevated twnpe- al~lre for a time period specified in TABLE FOI~R for purposes of completing polymerization. The polymerized suspension was then allowed to 2 0 cool to room temperature and the suspension removed from the reactor and filtered.
Optical microscopy revealed microspheres with an average ~ meter as reported in TABLE FOUR suspended in water.
The adhesive was form~ ted from the microspheres by inclutiing an antimicrobial system into the adhesive. The antimicrobial system included (i) an2 5 ~ntimicrobial agent selected from chlorhexidine gluconate (TABLE FIVE) and iodine (TABLE SIX), (ii) a transfer agent selected from glycerol, CarbowaxO 200 and CarbowaxO 400 as set forth in TABLE FIVE and TABLE SIX, and (iii) the optional coating promoter poly(N-vinylpyrrolidone). The chlorhexidine gluconate was incorporated at a conce-".a~ion of 4 parts chlorh~xi-iine gluconate per 100 3 0 parts combination of microspheres, poly(N-vinylpyrrolidone) and glycerine. The iodine was incorporated at a concenl,alion of 2 parts chlorllPYic~ine gluconate per 100 parts combination of microspheres, poly(N-vinylpyrrolidone) and glycerine.

W O 96/14094 PCT~US95/12193 Experiment 4 Adhesive Testing (Adhesives #20~0) The Skin Adhesion (Initial) (Ta), Skin Adhesion (Twenty Four Hours) (T24), 5 and Log Bacteria Reduction of the samples was then measured in accordance with the testing protocols set forth herein. The results of such testing are set forth in TABLE FIVE and TABLE SIX below.

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Symbol Meaning (Units) AA Acrylic Acid CBX200 C~l,u~O 200 CBX4oo CarbowaxO 400 EOA Poly(ethylene oxide) acrylate v~Le1ei1l the number of ethoxy units per acrylate is indic~ted by the subscripted number provided in conj~ clion with the wt% (i.e., 516 means 5 wt% of a poly(ethylene oxide) acrylate having an average of 16 ethoxy units) EOAI6 is the acrylate ester of CarbowaxO 550 purchased from Union Carbide Corp. EOA9 is NK-Ester AM-9OG
purchased from Shin-Nakamura.
GLY Glycerin IDA Isodecyl acrylate IOA Isooctyl acrylate KGray Sterilizing Gamma Radiation MVIRUp Moisture Vapor Tr~n.cmi~ion Rate Measured with Upright Cup (g/cm2/24hr) MVI~Vt Moisture Vapor T1~-n~ ;on Rate Measured w/ an Inverted Cup (g/cm2/24hr) NVP N-~d~ylpy~olidone PVP Poly(N-vinylpyrrolidone) To Skin Adhesion at time (t) = O hrs (Newtons/cm width) T24 Skin Adhesion at time (tJ = 24 hrs (Newtons/cm width) SUBSTITUTE SHEET ~RULE 26)

Claims (31)

1. claim 1 1. A low trauma wound dressing having improved moisture vapor permeability comprising layers of a moisture-vapor permeable backing and a contiguous particulate adhesive layer comprising at least 70 wt.% tacky, substantially solvent-insoluble, solvent-dispersible, acrylate-based, elastomeric, pressure-sensitive adhesive microspheres.
   
   We claim:
2. 2. The wound dressing of claim 1 wherein the adhesive layer further comprises an antimicrobial system which provides a layer of the adhesive with the capability of effecting at least a 2.5 log reduction in bacteria.
3. 3. The wound dressing of claim 2 wherein the antimicrobial system includes at least an antimicrobial agent and a transfer agent.
4. 4. The wound dressing of claim 3 wherein the antimicrobial agent is chlorhexidine.
5. 5. The wound dressing of claim 4 wherein the transfer agent is glycerin.
6. 6. The wound dressing of claim 2 wherein a layer of the adhesive is effective for achieving at least a 5 log reduction in bacteria.
7. 7. The wound dressing of claim 2 wherein a majority of the adhesive microspheres contain at least one interior void having a diameter of at least about 10% of the diameter of the microsphere.
8. 8. The wound dressing of claim 2 wherein a majority of the adhesive microspheres contain at least one substantially spherical interior void having a diameter of at least about 30% of the diameter of the microsphere.
9. 9. The wound dressing of claim 1 wherein the adhesive microspheres have an average diameter of at least 1 micrometer.
10. 10. The wound dressing of claim 1 wherein the adhesive microspheres are formed from an acrylate polymer having a glass transition temperature of less than about -20° C.
11. 11. The wound dressing of claim 1 wherein the adhesive microspheres are comprised of at least one alkyl acrylate or alkyl methacrylate ester selected from the group consisting of n-butyl acrylate, sec-butyl acrylate, 2-methyl butyl acrylate, 4-methyl-2-pentyl acrylate, 2-ethyl hexyl acrylate, isooctyl acrylate, isononyl acrylate, isoamyl acrylate, isodecyl acrylate, and isodecyl methacrylate.
12. 12. The wound dressing of claim 1 wherein the adhesive microspheres include (a) at least about 75 wt% of at least one alkyl acrylate or alkyl methacrylate ester, and (b) a balance of at least one polar monomer.
13. 13. The wound dressing of claim 12 wherein the alkyl acrylate is selected from the group consisting of (a) an acrylate or methacrylate ester of a non-tertiary C4-12 alcohol, and (b) an acrylate or methacrylate ester of a mixture of non-tertiary C1-14 alcohols with a resultant average of between about 4-12 carbon atoms per alcohol molecule.
14. 14. The wound dressing of claim 12 wherein the polar monomer is selected from the group consisting of acrylic acid, methacrylic acid, itaconic acid, crotonic acid, maleic acid, fumaric acid, and salts thereof.
15. 15. The wound dressing of claim 1 wherein the adhesive microspheres include (a) at least about 75 wt% of at least one alkyl acrylate or alkyl methacrylate ester, and (b) up to 25 wt% of a combination of (A) a polar monomer selected from the group consisting of acrylic acid, methacrylic acid, itaconic acid, crotonic acid, maleic acid, fumaric acid, and salts thereof, (B) a hydrophilic N-vinyllactam, and (C) a hydrophilic alkylene oxide acrylate having an average of about 3 to 40 alkylene oxide units.
16. 16. The wound dressing of claim 1 wherein the adhesive comprises:
    (a) about 70 to 90 wt% microspheres, and (b) about 10 to 30 wt% binder copolymer comprising an elastomeric polymeric backbone having pendant polymeric moieties with the backbone comprised of:
    (A) about 50 to 98 wt% of a first monomer comprising an acrylate or methacrylate ester of a non-tertiary C4-12 alcohol or an acrylate or methacrylate ester of a mixture of non-tertiary C1-14 alcohols with a resultant average of between about 4-12 carbon atoms per alcohol molecule, (B) about 1 to 20 wt% of a second polar monomer copolymerizable with the first monomer, and (C) about 0 to 30 wt% of a third monomer having the general formula X-(Y)n-Z where (1) X is a vinyl group copolymerizable with monomers A and B, (2) Y is a divalent linking group, (3) n is 0 or 1, and (4) Z is a monovalent polymeric moiety having a glass transition temperature of greater than 20°C with a molecular weight of about 2,000 to about 30,000 and being essentially unreactive under copolymerization conditions.
17. 17. The wound dressing of claim 16 wherein the adhesive microspheres further include at least one polar monomer.
18. 18. The wound dressing of claim 1 wherein the microspheres comprise (a) at least about 85 wt% of an alkyl acrylate ester selected from the group consisting of n-butyl acrylate, sec-butyl acrylate, 2-methyl butyl acrylate, 4-methyl-2-pentyl acrylate, 2-ethyl hexyl acrylate, isooctyl acrylate, isononyl acrylate, isoamyl acrylate, isodecyl acrylate, and isodecyl methacrylate, and (b) up to 15 wt% of at least one polar monomer selected from the group consisting of acrylic acid, methacrylic acid, itaconic acid, crotonic acid, maleic acid, fumaric acid, and salts thereof.
19. 19. The wound dressing of claim 17 wherein the second monomer is selected from the group consisting of acrylic acid, methacrylic acid, itaconic acid, N-vinylpyrrolidone, acrylamide, methacrylamide, acrylonitrile and methacrylonitrile.
20. 20. The wound dressing of claim 17 wherein a majority of the adhesive microspheres contain at least one substantially spherical interior void having a diameter of at least about 10% of the diameter of the microsphere.
21. 21. The wound dressing of claim 10 wherein (a) the adhesive microspheres are formed from non-ionic monomers and comprise a major portion of at least one oleophilic, water-emulsifiable alkyl acrylate or methacrylate ester.
22. 22. The wound dressing of claim 1 wherein (a) the adhesive microspheres consist essentially of:
    (A) about 90 to about 99.5 wt% of one or more oleophilic, water-emulsifiable alkyl acrylate esters, at least one of said esters being selected from the group consisting of isooctyl acrylate, 4-methyl-2-pentyl acrylate, 2-methylbutyl acrylate, sec-butyl acrylate, n-butyl acrylate and 2-ethyl hexyl acrylate, and (B) about 10 to about 0.5 percent by weight of one or more additional monomers selected from the group consisting of trimethylamine methacrylimide, trimethylamine p-vinylbenzimide, ammonium acrylate, sodium acrylate, N,N-dimethyl-N-(b-methacryloxyethyl) ammonium propionate betaine, 1,1-dimethyl-1-(2,3-dihydroxypropyl)amine methacrylimide, 4,4,9-trimethyl-4-azonia-7-oxo-8-oxa-9-decene- 1 -sulphonate, 1 ,1 -dimethyl- 1 -(2,3-dihydroxypropyl) amine methacrylimide, and maleic anhydride; and (b) the adhesive microspheres are prepared by aqueous suspension polymerization in the presence of a suitable emulsifier at a level above said emulsifier's critical micelle concentration.
23. 23. The wound dressing of claim 22 wherein the adhesive microspheres consist essentially of about 98 to about 99.5 wt% alkyl acrylate esters and 0.5 to 2 wt% additional monomers.
24. 24. The wound dressing of claim 1 wherein the backing is polyurethane.
25. 25. The wound dressing of claim 24 wherein the backing is transparent polyurethane having a MVTRup of at least 500 g/m.
26. 26. A low trauma wound dressing having improved moisture vapor permeability comprising laminated layers of a moisture-vapor permeable backing and a multiple stratum adhesive layer of tacky, substantially solvent-solvent-insoluble, solvent-dispersible, acrylate-based, elastomeric, pressure-sensitive adhesive microspheres
27. 27. The wound dressing of claim 26 wherein a majority of the adhesive microspheres contain at least one interior void having a diameter of at least about 10% of the diameter of the microsphere.
28. 28. The wound dressing of claim 26 wherein the adhesive microspheres include (a) at least about 75 wt% of at least one alkyl acrylate or alkyl methacrylate ester, and (b) up to 25 wt% of a combination of (A) a polar monomer selected from the group consisting of acrylic acid, methacrylic acid, itaconic acid, crotonic acid, maleic acid, fumaric acid, and salts thereof, (B) a hydrophilic N-vinyllactam, and (C) a hydrophilic alkylene oxide acrylate having an average of about 3 to 40 alkylene oxide units.
29. 29. The wound dressing of claim 26 wherein the adhesive comprises:
    (a) about 70 to 99 wt% microspheres, and (b) about 1 to 30 wt% binder copolymer comprising an elastomeric polymeric backbone having pendant polymeric moieties with the backbone comprised of:
    (A) about 50 to 98 wt% of a first monomer comprising an acrylate or methacrylate ester of a non-tertiary C4-12 alcohol or an acrylate or methaclylate ester of a mixture of non-tertiary C1-14 alcohols with a resultant average of between about 4-12 carbon atoms per alcohol molecule, (B) about 1 to 20 wt% of a second polar monomer copolymerizable with the first monomer, and (C) about 1 to 30 wt% of a third monomer having the general formula X-(Y)n-Z where (1) X is a vinyl group copolymerizable with monomers A and B, (2) Y is a divalent linking group, (3) n is 0 or 1, and (4) Z is a monovalent polymeric moiety having a glass transition temperature of greater than 20°C with a molecular weight of about 2,000 to about 30,000 and being essentially unreactive under copolymerization conditions.
30. 30. The wound dressing of claim 26 wherein (a) the adhesive microspheres are formed from non-ionic monomers and comprise a major portion of at least one oleophilic, water-emulsifiable alkyl acrylate or methacrylate ester, and (b) the adhesive microspheres are prepared by aqueous suspension polymerization in the presence of at least one suitable emulsifier at a concentration level above the emulsifier's critical micelle concentration and a suitable polymeric suspension stabilizer.
31. 31. The wound dressing of claim 26 wherein the backing is polyurethane.