AU773532B2 - Intrinsically bactericidal absorbent dressing and method of fabrication - Google Patents

Description

WO 00/33778 WO 0033778PCT/US99/29091 intrisicaly Bactericd Absorbent Dressing and Mehod of Fabrkation Field mf the 113eninn S Thlis invienton relates generally to absorbent dresings, and more partlcuLariy highlyabsorbent synthetic polymer dresigs having azidmicrobWa agents attached th==t.

PknJrn f hg ngo Bacterial growth in absorbent dressings for wounds, uinary ineontnmncs diapmr, and mcn=--dzon pads can lead to saeious medica' complications as well as socia difficultie. For example, bacteiaL growth in urinary incotince diapers or mcazsuadon pads usually produce strung, unpleasant odors tha ane moially unaceeptable ad can cause p=nos to alter thei lifetyle. Conventiona absorbent pads for unnary ncntineac* and zumw=aa ame not inbcretly bactecdal. Conuently, fth only way to avoid growth of bacteria in fth absorbent dressings is to clange them at freuet in=vals, even if the absorbent capacity of the pad has not bee reached. in the area of wound dresdqns, bacterial onuomination of acute wounds and infrcdon of chronic skin wounds =r major clinical Problems that can result in sigifct morbidity and, in sav=r c&se, Mortality. conventionally, wound drcssings have been designed to absorb wound fluids and yet provide a mois environment for prOVomtn wound hteling. aowever, such most envircnmts create a nutrient rich resr for bactrWa growth in the druing. Bamtria. growing in fth can be shed back into the wound, increaing the risk of wound infecion, or rcponse to toxins, and producing strog, foul odor:.

In an effort to addrms tWes problem, a=iOdc or chemIcal disinfectanu. Mr frequently applied topically to wounds prior to covering t wound with a dresdnS..

WO 00/33778 WO 0033778PCT/US99/2909 I Almeratively, topical agents Mr sometim applie directly to the =izaec of the dmssing. To control foul Odom~ so m dresings incrprae charcool powder to absorb molecules generating the foul odor. For some applicaton topilzl aVplicaion of andba terial agcnts is tendency to seep into fte weousu being rreatad. Purlietmore, many andicrobia dzrzg, such as iodine, =r cytotoxic and will zrerd wound healing if used repeiively or at high A composition comprising a tueisobi polya=e having a monolayer (or near monolayer) of slae antimicrbial agent in a covalent bonding relatonship with the bas polymer, Is disclosed. in U.S. Paten No. 5,045,322. The composition may be in the fom of flakes, strps, powders, filamneits, fibers ot films, and may be applied to a substrate in the form of a coating. The aliozemenzinned composition is leow apt to intr a wound vis-a-vis conventional topical went sysML lIn tha zespect, the disclosed composition provides an improvenmt over conventional, topical ura~int m1:yes. However, uilanes contain siloxane is bonds which can be cleaved by acids and bases. produced by inftio or bact:-.-W growth. In turn, Omee nmons may weaken or destroy bonds btweezi the aloen aumicrobial. aget and the underlying polymer. Consequently, anti obIaL agent may seep into a wound and retad wound healing, The need exists for an impoved =ntmicrobial dressing composition having an antimicrobial agent which can be maintaind securey ahed to a superabsorbeit polymer upon exposur to aci& and bases produced by nftdo and bacterial growth. In addition to reducing di. propenslty ftr detachment of the an nicrobia1 agent, it would be deiable to provide a surfaw a=e enhanced dresWSi mctur for iacng the eecvenezs of -the anuzia'oialagent.

Summary of the Invention It is an object of the present invention to provide an inherently bactericidal superabsorbant dressing having an enhanced surface area.

It is another object of the present invention to provide an inherently bactericidal superabsorbant dressing having an improved bactericidal attachment structure that resists degradation upon exposure to acids or bases produced, for instance, during bacterial growth.

At least one of these and other objects are achieved by the inherently bactericidal polymer composition of the present invention. In the preferred embodiment, the composition comprises a polymer matrix having quaternary ammonium groups tethered to its surface through non-siloxane bonds. The surface area of the polymer matrix is enhanced, for instance, by electrostatically spinning a fiber-forming synthetic polymer to form a frayed fiber or filament. Alternatively, the polymer solution can be wet- or dryspun to create a roughened fiber surface by controlling the choice of solvent and the polymer solution temperature. Additional surface area enhancement is provided by tethering molecular chains of quaternary ammonium-pendent groups to the surface of the polymer matrix. Tethering may be accomplished by known techniques such as grafting and selective absorption.

In an alternate embodiment of the invention, non-ionic bactericidal molecules are 20 coupled to the surface of the polymer matrix, in lieu of ionically-charged molecules.

Ilonically-charged molecules are prone to being neutralized upon encountering oppositely- *charged molecules. For instance, positively charged quaternary ammonium groups may be neutralized by negatively-charged chloride ions present in physiological fluids. In instances were such neutralization is significant enough to reduce the bactericidal properties of the dressing below an acceptable level, non-ionic surface groups may be preferable.

Disclosure of the Invention According to a first aspect of this invention there is provided a dressing for ::absorbing biological fluids, comprising: a superabsorbant polymer matrix having an 30 enhanced surface area; and a plurality of antimicrobial compounds coupled by none siloxane bonds to said polymer matrix.

According to a second aspect of this invention there is provided a method for fabricating an intrinsically antimicrobial absorbent dressing, comprising the steps of: forming a superabsorbent synthetic polymer matrix having an enhanced surface area; and attaching by non-siloxane bonds a plurality of antimicrobial compounds to the enhanced surface area of said polymer matrix.

[R IBUU]027.docin3 [R\L1BUUJ]02750.doc~jin WO 00/33778 WO 0033778PCT[US99/29091 Thrjim~4 neMmintinn of th fi.ri CWrnhodirints A novel aibaetezial polymer compositicn is fabricated to have an echanced surfacc are and superabsorbent capacity for biological fluids, including urine, blood, and wound In the preferred embodiment of the present invention, the composition includes a polymecr ma~ix having quaternazy aminonium compounds attacbed to the surface of the polymer ratrix. The polymer matri is comprised of a plurality of hydrophilic fibers or fllament$ wich can be fabricared in any suitable mannr. For example, suitable fibers or can be fabricated by viet- or dzy-spizwilg a fiber-forznulg synthetic polymer from a spinning solvent. The resifing polymer has superabsorbent capacity. Generally, polymer capable of absiorbing from about thirty tw sixty gramns of water per gram of polymer are considered to be superabsorbent. Examplus of superasarbent polinm which can be fabricated in thWs umnner incld pa TCTyli acds, polyethyleneO oxides and polyvinyl alcohols. For example, methods for spinning polyethyiczne oxid usig acetone solvent arc well known.

Signifimaty, *he polymer matrix is fabricaed tw have an enhanced surhmc arms Enhaincing the sue ana of the polymer inarii resuli in improved absorption of biological fluid, and i=UMse t avalaility of sites for at~cbwit of the adtimimobial quarenUY ammoniumf conmnd. A conespon ding increase in te quantity and density of antimicrobial site, in turn, enhances the efficacy of the composition in kIllig ogAniSs sucE as bacteria and viruses.

at =y occu to one skilled in the at of pO~yWw~rsig=c that a variety Of methods are available for accmplishig surfta sme modification. rrefersbly, surfac ame enhancemen, is acomlished by a modified spilning or casting method. FoV instance, electroSstainnking is a odified spinning techique which results in fraying of the faber as it exits the sPinrtte.

AlternaivelY, a polymIcr solution can be wet- or dry-spun to crea a roughened fiber surfae by controlling the solvent t"p and the polymer solunon £empezr This technoo is well known and his been applied, for exal, in the manUfacur of asymmeti membranes havng ouhened porns for dialysis. The size of the roughened pores is prirnaroiitdle WO 00/33778 WO 0033778PCTfUS99/29091 by the speed of Precipitation which, in tuzn, is controll by solvent intcracticn paz~mes, tepezn=z,

C&C.

The surf=-- a= of the polymer composition is further enhan=d by tethcring ch~ains of anM"=b UPS to d.0 outc sur*ee of the iudividui Poiy--er Iizers. P---fae-iy, molecular chains of quaternary ammoniuzm PeidCnt IV~p ame fabn-caed to hwle at l.eat cric end adapted for attachment to a fiber suirfaceC. For instnce, Surize gtafdng may be accomplished by crating surface free, radicals as initation sizc from Peroxide gccrdon (0=6n or mi~owavc). Al=flatvely, jurface achment of an aepn gnetwork may be achieved using a monomer which swells the "Ubale polymer. The uncrporation of tethmrd andiirbial chains has the fuzrther bmnefi of enhancing f th uctionality of the composiidi. in Particular, the ttcrecd andimrbial chains extend into the particula biological Soludion to bind to harmful bacterial ad vital orgais In contrast to known diressics compositions in which a monolayer (or mer monolayer) of bactricidial compound is directy attached to a fiber surb"c, the chain sUUcwr Of the prosen invention, which fution liko arms euending outwardly from thc fiber =uface, more effectively bind the Ud~crobia ime go haxmful organim. Prejzably, ezhcing is accomplshed by gtAfting the antimicrba -chai directy to fte surhmc, or by selective adsorqtio of a copolymer to the matiX Sirface.

Graftns rechniue are well known in the al For ewnmple, quav5W ammoflIum compound graftig usig the monomer tzimcthylamiflum ethyl niulwcRyltB to graft polymerize to a modified polyezhyle= surh=c is descrbed by Yahaioui (l4astcs Thesis, Univesity of Forida, 1986). yahioui dencrbes a gzafdng technique in which a plasm discharge is used to cem t fr aca s which inidiae PolymleriatiOn Of GW2OPTrtc mnomems Seletive adsoptio of appropriate block copolymez can also be used.

In coflw2st to know compositions in whic:h an =dtiniciobiii is achieved by.

covualandy bonding Al=*e groups to the surfa= of the WOs polymer, the Pr"=et invozzdoa incorporate a chemicaj which is based on polyminziZof uinfae gzafting) Of mmoofl= containin& all crbon-carbon, carbogOXygef =nd ce -nitroge main bonds, such as the diallY, diallyl, qmaenaaY =aminoi compound. consequently, the composition of WO 00/33778 WO 0033778PCTfUS99/29091I the preset invOei results in a strucbt which is loss proe to reacting with acids and base produced by bacteial growth. As previously rnioncd, such feactions, can degrade the a2tchment between the matrx and aniicobial groups. Tn instances where the conrosidcn Is aiie-d '0 a Wound Such degrdation ;;ui4 ru-ui.c i antirmcroba ageni~ euahn from -the polymer mrnix and entering. a wound site. In some mses, this can have the deleterious effec of retarding wound healing.

Xn an altenate embodimnt of the present invendon, anionic antibactenicidal groups are immobibyced on the SU!fWAc Of a .super bsorban dresing to improve the antibactericidai efflcaey of the dressing. The positve charge assodated with quatesnary ammoniun groups, for example, can be neutralized by negative i=n, Such as chloride ions present in phy~ological fluids such as urine and plasma. For applicadons wher the degree of ne~l~inwinl significantly reduce t&e effectivecou of the an-bactaridda agent, anionic suxtace groups can be substituted for qua=erY aMMOrm poupa. Example Of Chemical cOOMPoIMds that can be used to produce immobilized anionic snfce groups include Tzhwn-100, Tweeji 20 and deoxycholate. For instance. Tri=o-1QO contains a free hydroxyl group which can be.

dernvatized into a good leaving group, suel as tosyl or chloride, and subsequently rected with a base-treated polymer, such as methyl cellulose, to yield a surac immoblllzd non-ionic surta4 .uqt Dirnethyldialyl amumonium chlorid is one example of a suitable monomer which may be used with fth present invention. This monomra. omonly reter=e to is DMWAC Or DADMAC, is used in dhe farication of oQMMerc iQCCu~zdng polymers. bUKciions of sziakyl(p-vinylbefzyl) mmmoniurn cloride or the P-trialkylaminOehYl StYrCIC monomer ame aLso suitable, Ono such eample is tzlmezhyl(p-vnyI beazy) aMMOnluU chloride the metyl groups of this monomer can be replwde bi other Alyl groups to impart desired Properues Alteratively, meshacyLat.-baad monomcar may be used; however, they may suffer from hydrolytic ingwbility undar aidic, and basic couidoas in a fashion simila to the AI4-ae tments of fte prior amt Consequeat!y, niebacrYL-Atba56d monometi are not preferred.

While th prefere embo"=mcts of the invention have been illustrated and described, it will be clear that the invention is not so limited. Numerous =&ftcliOfls, chages, WO 00/33778 PCT/US99/29091 vali2~am2, substitudans =nd equivaients will occur to those sWdlld iii the art without depar g from fth spirt and scope of fte prmt invant~fl as dwibed in the lims.

Claims (11)

1. A dressing for absorbing biological fluids, comprising: a superabsorbent polymer matrix having an enhanced surface area; and a plurality of antimicrobial compounds coupled by non-siloxane bonds to said polymer matrix.

2. A dressing as recited in claim 1, wherein said plurality of antimicrobial compounds comprise quaternary ammonium compounds.

3. A dressing as recited in claim 1, wherein said antimicrobial compounds comprise chain-like structures tethered at one end to said polymer matrix.

4. A dressing as recited in claim 1, wherein said plurality of antimicrobial compounds are non-ionic compounds.

A dressing as recited in any one of claims 1 to 4, wherein said dressing comprises a sanitary pad.

6. A dressing as recited in any one of claims 1 to 4, wherein said dressing comprises a tampon.

7. A dressing as recited in any one of claims 1 to 4, wherein said dressing comprises a bandage.

8. A method for fabricating an intrinsically antimicrobial absorbent dressing, comprising the steps of: 20 forming a superabsorbent synthetic polymer matrix having an enhanced surface area; and attaching by non-siloxane bonds a plurality of antimicrobial compounds to the enhanced surface area of said polymer matrix.

9. A dressing for absorbing biological fluids, said dressing substantially as hereinbefore described.

10. A method for fabricating an intrinsically antimicrobial absorbent dressing, said method substantially as hereinbefore described.

11. A dressing prepared by the method according to claim 8 or claim 30 Dated 2 March 2004 Quick-Med Technologies, Inc. and University of Florida Research Foundation, Inc Patent Attorneys for the Applicant/Nominated Person SPRUSON FERGUSON 8 [R:\LIBUU]02750.doc:jin