OA11725A - Intrinsically bactericidal absorbent dressing and method of fabrication. - Google Patents

Abstract

A superabsorbent polymer dressing having antimicrobial properties for use in fabricating wound dressings, sanitary napkins, tampons and the like, includes a synthetic polymer matrix fabricated to have an enhanced surface area. Antimicrobial compounds are coupled to the surface of the polymer matrix by non-siloxane bonds.

Description

I 117 2 5

Intrinsically Bactericidal absorbent Dressing and Method of Fabrication

Field of the Invention

This invention relates generally to absorbent dressings, and more particularly highlv-absorbent synthetic polvmerdressings having antimicrobial agents attached thereto. 5 Backgjound of the Invention

Bacterial growth in absorbent dressings for wounds. urinary incontinence diapers. and menstruation pads can lead to serious medical complications as well as social difiïculties. For example, bacterial growth in urinary incontinencediapers or menstruation pads usually produces strong, unpleasant odors that are socially unacceptable and can causepersons to aller their lifestyle. Conventional absorbent pads for urinary incontinence and menstruation are not θ inherently bactericidal. Consequently, the only way to avoid growth of bacteria in the absorbent dressings is to change them at frequent intervals, even if the absorbent capacity of the pad has not been reached. In the area ofwound dressings. bacterial contamination of acute wounds and infection of chronic skin wounds are major clinicalproblems that can rcsult in sigruficant morbidity and. in scvere cases, mortality. Conventionally, wound dressingshâve been designed to absorb wound fluids and yet provide a moist environment for promoting wound healing I 5 However. such moist environments create a nutricnt rich réservoir for bacterial growth in the dressing. Bacteria growing in the dressing can be shed back into the wound. increasing the risk of wound infection or response totoxins, and producing strong. foui odors.

In an effort to address these problems, antibiotics or Chemical disinfectanls are frequentlv applied topically towounds prior to covering the wound with a dressing 2 117 2 5

Altemativelv, topical agents are sometimes applied directly to the surface of the dressing To control fouiodors, some known dressings incorporate charcoal powder to absorb molécules generating the foui odor. Forsome applications, topical application of antibacterial agents is not désirable. For instance, bactericidal agentsapplied topically to wound dressings hâve a tendency to seep into the wound being treated. Furthermore, 5 many antimicrobial drugs, such as iodine, are cytotoxic and will retard wound healing if used repetitively or at high concentrations. A composition comprising a superabsorbent polymer having a monolayer (or near monolayer) of silaneantimicrobial agent in a covalent bonding relationship with the base polymer is disclosed in U S. Patent No.5,045,322. The composition may be in the form of flakes, strips, powders, filaments, fibers or films, and may 10 applied to a substrate in the form of a coating The aforemenlioned composition is less apt to enter a wound vis-a-vis conventional topical treatment Systems, In lhat respect, the disclosed composition providesan improvement over conventional topical treatment Systems. However, silanes contain siloxane bonds whichcan be cleaved by acids and bases produced by infection or bacterial growth. In tum, these reactions mayweaken or destroy bonds between the silane antimicrobial agent and the underlying polymer. Consequently, 15 antimicrobial agent may seep into a wound and retard wound healing.

The need exists for an improved antimicrobial dressing composition having an antimicrobial agent which can be maintained securelv attached to a superabsorbent polymer upon exposure to acids and bases producedby infection and bacterial growth In addition to reducing the propcnsitv for detachmenl of the antimicrobialagent, it would be désirable to provide a surface area cnhanced dressing structure for incrcasing the 20 cffectiveness of the antimicrobial agent. 3 11725

Summarv of (he Invention

It is an object of the présent invention to provide an inherentiy bactericidal superabsorbant dressinghaving an enhanced surface area.

It is anolher object of the présent invention to provide an inherentiy bactericidal superabsorbant dressing 5 having an improved bactericidal attachment structure that resists dégradation upon exposure to acids or bases produced. for instance, during bacterial growth.

These and other objects are achieved by the inherentiy bactericidal polymer composition of the présentinvention. In the preferred embodiment, the composition comprises a polymer matrix having quatemaryammonium groups tethered to ils surface through non-siloxane bonds. The surface area of the polymer 10 matrix is enhanced. for instance, by electrostatically spinning a ftber-forming synthetic polymer to form a frayed fiber or filament.

Altematively, the polymer solution can be wet- or dry-spun to create a roughened fiber surface bycontrolling the choice of solvent and the polymer solution température. Additional surface areaenhancement is provided by tethering molecular chains of quatemary ammonium pendent groups to the 15 surface of the polymer matrix. Tethering may be accomplished by known techniques such as grafting and sélective adsorption.

In an altcmate embodiment of the invention, non-ionic bactericidal molécules are coupled to the surfaceof the polymer matrix, in lieu of ionically-charged molécules. Ionically-charged molécules are prone tobeing neutralized upon cncountering oppositely-charged molécules. For instance, positively-charged 20 quatemary ammonium groups may be neutralized by negativelv-charged chloride ions présent in physiological fluids. In instances were such neutralization is significanl enough to reduce the bactericidalproperties of the dressing below an acceptable level. non-ionic surface groups may be préférable. 4 11725

Detailed Description of the Preferred Embodiments A novel aniibacteriaJ polymer composition is fabricated to hâve an enhanced surface area andsuperabsorbent capacity for biological fluids, including urine, blood, and wound exudate.

In the preferred embodiment of the présent invention, the composition includes a polvmer matrix having 5 quatemary ammonium compounds attached to the surface of the polymer matrix. The polymer matrix is comprised of a plurality of hydrophilic fibers or filaments which can be fabricated in anv suitable manner. Forexample, suitable fibers or filaments can be fabricated by wet- or dry-spinning a fiber-forming syntheticpolymer from a spinning solvent. The resulting polymer has superabsorbent capacity Generally. polymerscapable of absorbing from about thirtv to sixty grams of water per gram of polymer are considered to be 10 superabsorbent. Examples of superabsorbent polymère which can be fabricated in this manner include polyacrylic acids, polyethylene oxides and polyvinyl alcohols. For example, methods for spinning polyethyleneoxide using acetone solvent are well known.

Significantly, the polymer matrix is fabricated to hâve an enhanced surface area. Enhancing the surfacearea of the polymer matrix results in improved absorption of biological fluids, and increases the availability of 15 sites for attachment of the antimicrobial quatemary ammonium compounds. A corresponding increase in thequantity and density of antimicrobial sites, in tum, enhances the efficacv of the composition in killingorganisms such as bacteria and viruses.

Il mav occur to one skillcd in the art of polymer science lhat a vanety of methods are available foraccomplishing surface area modification. Preferably, surface area enhancement is accomplished by a modified 20 spinning or casting method. For instance, electrostatic spinning is a modified spinning technique which results in fraying of the fiber as it exils the spinerette. Altemalivelv. a polymer solution can be wet- or dry-spun to create a roughened fiber surface by controlling the solvent type and the polymer solution température. This technologv is well known and has been applied. for example, in the manufacture of asymmetric membranes having roughened pores for dialysis. The size of the roughened pores is primarily conlrolled 5 H 725 by the speed of précipitation which, in tum, is controlled by solvent interaction parameters, température, etc.

The surface area of the polymer composition is further enhanced by tethering chains of antimicrobial groups to the outer surface of the individual polymer fibers. Preferably, molecular chains of quatemary ammonium pendent groups arefabricated to hâve at least one end adapted for attachment to a fiber surface. For instance, surface grafiting may be 5 accomplished by creating surface free radicals as initiation sites from peroxide génération (ozone or microwave).

Altematively, surface attachment of an interpenetrating network may be achieved using a monomer which swells thesubstrate polymer. The incorporation of tethered antimicrobial chains has the further benefit of enliancing the functionalityof the composition. In particular, the tethered antimicrobial chains extend into the particular biological solution to bind toharmful bacterial and viral organisms. In contrast to known dressing compositions in which a monolayer (or near 10 monolayer) of bactericidal compound is directly attached to a fiber surface, the chain structures of the présent invention,which function like amis extending outwardly from the fiber surface, more effectively bind the antimicrobial sites toharmful organisms. Preferably, tethering is accomplished by grafting the antimicrobial chains directly to the matrix surface,or by sélective adsorption of a copolymer to the matrix surface.

Grafting techniques are well known in the art. For example, quatemary-ammonium compound grafting 15 using the monomer trimethylammonium ethyl méthacrylate to graft polymerize to a modified polyethylene surface is described by Yahaioui (Master’s Thesis, University of Florida, 1986). Yahioui describes a grafting technique in which aplasma discharge is used to create free radicals which initiate polymerization of appropriate monomers. Sélectiveadsorption of appropriate block copolymers can also be used.

In contrast to known compositions in which an antimicrobial structure is achieved by covalently bonding 20 silane groups to the surface of the base polymer, the présent invention incorporâtes a Chemical structure which is based onpolymerization (i.e., surface grafting) of monomers containing ail carbon-carbon, carbon-oxygen and caibon-nitrogenmain bonds, such as the dialkly, diallyl, quatemary ammonium compounds. Consequently, the composition of 6 117 2 5 the présent invention results in a structure which is less prone to reacting with acids and bases produced by bacterialgrowth. As previously mentioned, such reactions can dégradé the attachment between the matrix and antimicrobialgroups. In instances where the composition is applied to a wound dressing such dégradation could resuit inantimicrobial agents detaching from the polymer matrix and entering a wound site. In some cases, this can hâve the 5 deleterious effect of retarding wound healing

In an altemate embodiment of the présent invention, anionic antibactericidal groups are immobilized on the surface of a superabsorbant dressing to improve the antibactericidal efficacy of the dressing The positive chargeassociated with quatemary ammonium groups, for example, can be neutralized by négative ions, such as chlorideions présent in physiological fluids such as urine and plasma. For applications where the degree of neutralization 10 will significantly reduce the effectiveness of the antibactericidal agent, anionic surface groups can be substituted for quatemary ammonium groups. Examples of Chemical compounds that can be used to produce immobilized anionicsurface groups include Triton-100, Tween 20 and deoxycholate. For instance, Triton-100 contains a free hydroxylgroup which can be derivatized into a good leaving group, such as tosyl or chloride, and subsequently reacted with abase-treated polymer, such as methyl cellulose, to yield a surface immobilized non-ionic surfactant. 15 Dimethyldiallyl ammonium chloride is one example of a suitable monomer which may be used with the présent invention. This monomer, commonly referred to as DMDAC or DADMAC, is used in the fabrication ofcommercial flocculating polymers. Modifications of trialkyl(p-vinylbenzyl) ammonium chloride or the p-trialkylaminoethvl styrene monomers are also suitable. One such example is trimethyl(p-vinyl benzyl) ammoniumchloride; the methyl group» of this monomer can be replaced by other alkyl groups to impart desired prop^erties. 20 Altematively, methacrylate-based monomers may be used; however, they may suffer from hydrolytic instability under acidic and basic conditions in a fashion similar to the silane-based treatments of the prior art. Consequently,methacrylate-based monomers are not pxeferred.

While the preferred embodiments of the invention hâve been illustrated and described, it will be clear thatthe invention is not so limited. Numerous modifications, changes, 7 ΐ ΐ 7 2 5 variations, substitutions and équivalents will occur to those skilled in the art without departing from the spiritand scope of the présent invention as described in the claims.

Claims (8)

1. f 1 7 2 5 8 We claim:

   1. A dressing for absorbing biological fluids, comprising: a superabsorbent polymer matrix having an enhanced surface area; and5 a plurality of antimicrobial compounds coupled by non-siloxane bonds to said polymer matrix.
2. 2. A dressing as recited in claim 1, wherein said plurality of antimicrobial compoundscomprise quatemary ammonium compounds. 10
3. 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. 4. A dressing as recited in claim 1, wherein said plurality of antimicrobial compounds are15 non-ionic compounds.
5. 5. A dressing as recited in claim 1, wherein said dressing comprises a sanitary pad.
6. 6. A dressing as recited in claim 1, wherein said dressing comprises a tampon. 20
7. 7. A dressing as recited in claim 1, wherein said dressing comprises a bandage.
8. 8. A method for fabricating an intrinsically antimicrobial absorbent dressing, comprising thesteps of: 25 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.