the present invention is based on the surprising and unexpected discovery that zeolites with silver ions exchanged onto internal acidic sites of the zeolite are highly efficacious in imparting anti - microbial character to hyaluronan coatings and other polysaccharide coatings . the coating system comprising a bi - laminar , biocompatible , lubricious coating including a base coat and a top - coat , and containing a silver zeolite as a source of broad spectrum anti - microbial ions , provides a highly useful coating for device structures and surfaces . illustrative articles that are amenable to coating include , without limitation , medical devices such as catheters , stents , medical grafts , artificial implants , orthopedic devices , etc ., as well as consumer products such as contact lenses , drinking containers , apparel articles , place mats , furniture , telecommunications and computational equipment , etc . the base coat in the aforementioned bi - laminar biocompatible lubricious coating can be of any suitable type , including for example acrylic copolymers as well as other polymeric and copolymers , and other film - forming materials , as will be appreciated by those skilled in the art , and readily determinable without undue experimentation for a given end use application of the coating system . the acrylic copolymer is a preferred material for various applications , and provides excellent adhesion to metal or polymeric wires or other substrates such as polymeric catheters , etc . the base coat in such bi - laminar biocompatible lubricious coating provides reactive chemical groups for grafting the biocompatible topcoat to the base coat . the top - coat in one preferred embodiment comprises hyaluronan , a glycosaminoglycan material found in all mamalian cells , provide a biocompatible coating system . such hyaluronan topcoat make the coated surface extremely slippery or lubricious in character , when wetted with aqueous fluids , and the top - coat is fully compatible in in vivo usage and corporeal contact . there are many other desirable top - coat materials including glycosaminoglycans and mucopolysaccharides such as chondroitin sulfate and heparin , the latter being able to confer desirable anti - thrombogenic character to a coated surface . the silver zeolite is usefully employed in any suitable form , e . g ., in a powder ( e . g ., in 1 - 4 microns diameter particles ) or slurry form . the zeolite is a 100 %. inorganic carrier and the silver ions therein are released through ion exchange in the use environment . the zeolite is a cation exchanger that binds silver ions . in the absence of a mobile counterion , the silver is not released , but in a use environment such as blood or other physiological fluid , containing mobile ions such as sodium ions , calcium ions , potassium ions , etc ., and a mobile counterion for the silver ion such as chloride , phosphate or bicarbonate ion , the silver ions are released from the zeolite by ion exchange . the ion - exchange type antimicrobial agents of the present invention all have a ceramic or ceramic - like support with passages within and throughout the support . in the case of zeolites , the passages are three - dimensional . in the case of zirconium phosphate , they are two - dimensional . in essence , the former is more sponge - like whereas the latter looks more like an “ oreo ” cookie , wherein the passages go through the filling but not through the cookie . the supports have incorporated into them various anionic sites to which pendant cations are bound . most often , these are na +. to render the materials antimicrobial , an ion - exchange is conducted in a silver ionic solution whereby all or a portion of the na + cations ( or other cations ) are exchanged for the silver cations . because of the large amount of ag + in the support , each individual support particle serves as a large reservoir for ag + ions , thus providing the long - term viability of the antimicrobial . the latter compares to the use of metal salts or organic antimicrobials which have no concentrated reservoir , and which quickly deplete . in hyaluronan coatings containing the silver zeolite , good coating film properties are maintained , including lack of adverse effect of the silver active ingredient in the silver - containing zeolite , with respect to viscosity and coating chemistry and the process of coating film curing . the silver zeolite is an effective anti - microbial agent in hyaluronan coatings and other polysaccharide coatings . the coating composition containing the silver zeolite therefore achieves a substantial advance in the art , over prior art coatings containing silver salts , free silver or other forms of silver which compromise the film formation and the lubricity , durability , and biocompatibility of the hyaluronan or other mucopolysaccharide coating system . by contrast , the coating compositions of the present invention provide a silver delivery system for biocompatible hyaluronan coatings , in which an inorganic , silver - based antimicrobial is incorporated in the hyaluronan coating without loss or deterioration of the excellent lubricity , durability , and biocompatibility inherent to such hyaluronan coatings . the features of the invention are more fully appreciated with respect to the following discussion and non - limiting examples . the purpose of this example is to show the effect of silver ion , silver salts , and silver zeolite on the hydak coatings mentioned above . a hydak g23 coating solution , obtained from biocoat incorporated , was formulated by mixing 100 g hydak g23 stock acrylic polymer solution ( 30 % solids ) with 5 . 8 g desmodur n75 trifunctional isocyanate cross - linking agent ( obtained from bayer ) and 124 g propyleneglycol methyl ether acetate solvent ( pma ), available from aldrich chemical and other suppliers ). this base coat coating solution was applied to polymethylmethacrylate test panels as a layer nominally 0 . 003 - in . deep , with a coating knife , and the coat was cured for 40 min in a 60 ° c . oven . in this specification , the abbreviation “ des n ” means desmodur n75 defined above . the top - coat coating solution contained 0 . 60 % sodium hyaluronate ( obtained from lifecore biomedical ) plus 0 . 10 % triton cf10 surfactant ( obtained from union carbide ) and applying a nominally 0 . 006 - in . deep layer by coating knife onto the cured base coat . the panels were cured for 16 h at 60 ° c . after curing , the panels were washed by soaking for 30 min . in deionized water . this was the basic coating procedure used for all the solution polymer - based coatings on test panels . the influence of silver ion was tested by adding silver ( i ) oxide , silver acetate ( obtained from aldrich chemical ) or silver zeolite ( obtained from agion technologies , ak10d grade , in the form of a dry powder , 2 - 3 microns average particle size ) to the base or the top - coat coating solutions . to add silver compounds to the base coat coating solution , the desired weight of silver salt or silver zeolite was suspended in a portion of the pma solvent used to formulate the base coat coating solution , and this suspension was mixed with the other components of the formulation . for the top - coat , the desired weight of silver salt was added directly to the coating solution and mixed with a paddle bladed mixer except that silver zeolite in the top - coat was added from a stabilized 20 % silver zeolite commercial slurry , ( from agion technologies , product number ak10n - 20w ) rather than the dry powder . the resulting cured and washed coatings were examined for finger feel lubricity and for durability in a gardner abrader . table 1 shows the results : panel coatings amended with 1 % silver acetate or 1 % or 6 % silver oxide were fragile , surviving less than 200 , 000 cycles in the abrasion tester . moreover , panels with the highest silver oxide levels were noticeably less lubricious than controls . by contrast , the control panels without silver and all the formulations containing silver zeolite were robust , surviving over 500 , 000 cycles in the abrader without loss of hydrophilic character or lubricity . this example contains two parts , and deals with the release of silver from silver zeolite - acrylic - polysaccharide coatings : a series of samples were prepared by coating ethyl vinyl acetate catheter tubing , 1 . 5 mm . nominal diameter ( microline brand , available from cole - parmer ). in all cases , the tubing was cleaned by wiping five times with a lint - free pad wetted with 2 - propanol and dried at 60 ° c . for 2 hours before coating . the samples were coated with various biocoat bilaminar coatings also containing various agion silver zeolites . for this example , all coatings were applied by dipping the tubing into the coating solution and withdrawing at a controlled rate . for samples a - d , the base coat was withdrawn at 0 . 22 in / sec and the top - coat at 2 . 0 in / sec . for all other examples , both base and top - coat were withdrawn at 0 . 20 in / sec . curing conditions and the nature and amount of the silver zeolite are specified for each coating . cured samples were assayed for the release of silver ion as described below . for samples a - d , the unamended base coat coating solution was prepared by mixing 5 . 76 g hydak g23 ( 30 % solids ), 6 . 34 g pma and 0 . 33 g des n for 30 min using a flat - bladed mixing paddle . the unamended top - coat was an aqueous solution containing 0 . 60 % sodium hyaluronate , 0 . 10 % triton cf10 and 0 . 60 % triethylene glycol ( aldrich chemical ). base coats were cured at 60 ° c . for 40 min and topcoats were cured for 12 hours at 60 ° c . top - coats were applied less than 2 hours after completion of base coat curing , and top - coat curing was begun immediately after withdrawal of the tubing from the coating bath . individual samples a - d were prepared by modifications of this basic coating scheme as indicated in table 2 . to assess the release of silver ion from the zeolite in these coatings , 1 . 0 - in sections of the coated tubing were eluted in 10 ml 0 . 80 % nano 3 at 37 ° c . with gentle shaking . the resulting fluid was analyzed periodically for silver concentration using a perkin - elmer grafite furnace atomic absorption spectrometer . the results are given in table 3 : the results reveal that the silver in the top - coat is most available for exchange with the external medium . in the body , however , such rapidly released silver must be expected to migrate rapidly from the catheter site . in contrast , silver ion from the base coat was barely released from the 5 % silver zeolite , sample a , but showed a sustained release over several days from the 10 % silver zeolite , sample d . sustained release of silver is preferable to maintain anti - microbial activity at the catheter site . silver zeolite of high silver content , in the base coat , is clearly preferable for producing sustained silver release . zeolite containing 5 - 10 % silver is effective , but zeolite containing 10 - 20 % is more preferred . it should be noted that ability to sustain silver release is obviously also dependent upon the total silver reservoir deposited in a coating . the size of such silver reservoir can be varied , especially increased relative to the examples above , as is well known in the art , by increasing the thickness of a coating . coat thickness ( independently both top - coat and basecoat ) is controlled by varying ( increasing or decreasing ) the percent solids of the coating solutions , keeping the proportions of the non - solvent components the same . it is also varied , increasing or decreasing , by changing the coating withdrawal speeds . such changes always entail a balance of factors , however , since the overall characteristics of the coating , such as flexibility , durability and extensibility , for example , may also be altered by changes of coating thickness . in this part , three other bilaminar hydak coatings were amended with various silver zeolites , coated onto ethyl vinyl acetate tubing , and examined for silver release . tubing samples were cleaned as described in part one ; all coatings were done at 0 . 20 in / sec withdrawal speed for both base and top - coats . all formulations were agitated for 20 min using a flat bladed mixer before coating . other coating conditions are given below . sample e base coat consisted of hydak s103 , a solvent - based acrylic copolymer particularly designed for adhesion to silicone substrates . the coating solution consisted of 100 g hydak s103 ( 30 % solids ), 4 g des n , 36 g pma and 110 g of a 20 % slurry of ag10n zeolite al85h in acetone . the base coat was cured for 40 min at 60 ° c . the top - coat coating solution consisted of 18 . 54 g hydak a14 ( a formulated , crosslinkable solution of hyaluronic acid , prepared according to the method described in u . s . pat . no . 5 , 789 , 571 , the disclosure of which is incorporated by reference herein ) plus 0 . 203 g of a 0 . 20 % aqueous solution of neocryl cx100 trifunctional aziridine crosslinking agent ( neocryl resins , inc .). the top - coat was cured for 15 hours at 60 ° c . sample f consisted of an acrylic copolymer aqueous emulsion , hydak dc8 , a coating noted for its adhesion to metals . the base coat consisted of 22 . 5 g of dc8 ( 29 % solids ), 1 . 65 g neocryl cx100 ( 100 % solids ), 0 . 75 g nh 4 oh ( 20 %), 22 . 5 g water , and 15 g agion ak10n - sw20 zeolite suspension ( 20 %). the top - coat was 42 g hydak a16 ( a formulated , crosslinkable solution of hyaluronic acid , of a type described in u . s . patent application ser . no . 09 / 880 , 476 , filed jun . 12 , 2001 , the disclosure of which is incorporated by reference ) plus 2 . 10 g of 0 . 20 % aqueous solution of neocryl cx100 . the dc8 base coat was cured for 20 min at 80 ° c . and the top - coat for 5 hours at 80 ° c . sample g was another acrylic copolymer aqueous emulsion , hydak b10195 , a general purpose emulsion coating . this sample was prepared exactly as sample f , substituting the stock hydak b10195 for dc8 and eliminating the nh 4 oh . curing times , temperatures and top - coat were exactly as for sample f . analysis of silver release involved soaking 1 . 0 - in . segments of the cured coated tubing in 50 ml 0 . 80 % nano 3 at 37 ° c . with gentle shaking , and analyzing the silver concentration after 24 hours by atomic absorption . table 4 gives the results : first , note that these samples were eluted into five times the volume of nano 3 used in table 3 . thus , the values for silver concentration in table 4 must be adjusted ( increased ) by a factor of 5 to compare them to table 3 . on that basis , silver is most readily released from the s103 base coat , but is probably released too rapidly to sustain an anti - microbial effect . next best is b10195 aqueous emulsion which appears to offer a sustained release rate , and the least release is from the dc8 system . to complement these sustained silver releases with an initial burst of anti - microbial soluble silver ion , it was recalled that hyaluronan , a common component of the top - coats of these coatings , is itself a cation exchange medium . therefore , a charge of soluble silver was applied to samples e - g by briefly soaking the cured coating with 10 % agno 3 , rinsing with deionized water , and drying . this process loaded all accessible surface exchange sites with silver . when 1 . 0 - in samples of these materials were analyzed by extraction into 50 ml nano 3 as for table 4 , the following results were obtained : it is interesting to note that sample f , which showed no release of silver from the base coat in 24 hours , showed a distinctly higher capacity to release silver from surface accessible exchange sites . apparently , other cation exchange sites are available in this coating , relative to the other coatings . these additional sites both increase sample f &# 39 ; s capacity for surface exchange of soluble silver and provide a barrier or sink for silver released from zeolite in the emulsion , delaying or preventing rapid release from the base coat reservoir . this example shows the effectiveness of silver ion as a biocide . to assess the anti - microbial effectiveness of the zeolite - amended coatings , samples were exposed to bacteria and bacterial viability determined . one - foot ( 12 - in .) sections of samples a and b of example 2 , and uncoated ethyl vinyl acetate tubing were separately added to 70 ml of phosphate buffered saline ( pbs , 0 . 90 % nacl plus 10 mm sodium phosphate , ph 7 . 4 ). at time zero , 5 ml of a fresh stationary phase broth culture of s . aureus ( atcc 25923 ) was added . the contents were mixed and aliquots plated on nutrient agar to determine the viable count . the mixture was incubated with gentle shaking for 24 hours at 37 ° c . and re - assayed for viable bacteria . table 6 shows the results : table 6 shows that the coatings exert an anti - microbial effect . sample a is most interesting , since it defines an approximate minimal level of silver release that shows anti - microbial activity in these assays . recall in table 3 that sample a only released 5 . 5 ppb silver after 24 hours incubation , compared to 416 ppb for sample b . nevertheless , this sample reduced the s . aureus content of this assay by 91 %. the invention thus provides hyaluronan coatings with a compatible source of silver ion that can provide a rapidly released , effective concentration of broad spectrum anti - microbial action supplemented by a substantial , longer acting reservoir of the effective agent available for sustained release during the operating or service life of the structure incorporating the silver ion zeolite - containing hyaluronan coating . moreover , in such coating , the effective anti - microbial agent concentrates transiently in the surface layer of the coating , where it can be highly effective in preventing surface colonization by pioneer biofilm formers . further , the anti - microbial agent is supplied in an inherently anti - fouling surface ( with respect to the hyaluronan coating ). this example shows the effect of zeolite coatings on biofilms . samples of polyurethane stick ( estane 58284 , b . f . goodrich ) nominally 3 mm diameter were coated with the same agion al85h - amended base coat composition exactly as described for the sample d base coat , and top coated with unamended hydak a14 / cx exactly as described for the sample e top - coat . these samples were submitted to a flow - cell biofilm assay conducted by bacterin , inc ., bozeman mont . briefly , in this assay , the coated sticks are placed in a flow - through cell and exposed over a 7 - day period to a continuous one - way flow of bacteria ( s . aureus clinical isolate from a central venous catheter related infection ) diluted into sterile defibrinated sheep &# 39 ; s blood ( bbl cat # 212391 ). the study provided 21 such flow - through chambers so that three samples could be taken daily . samples were assayed for percent coverage of the stick surface by confocal laser scanning microscopy ( clsm ) and for viability using the baclight live / dead molecular probe ( molecular probes , eugene , oreg .) and clsm . sticks were aseptically scraped , the scrapings sonicated and plated on nutrient agar for viable counts . the results are in tables 7 , 8 , and 9 . the data show that the coated stick resisted biofilm attachment , reduced the overall viable count , and limited the viable cells in the biofilm . the fact that the numbers established by day 1 were relatively the same over the 7 - day period may be explained by the fact that the coated stick had zeolite only in the base coat , and as illustrated in example 2 , sample d , it requires several hours before an effective level of silver is released . if this sample contained silver exchanged onto surface exchange sites , as further illustrated in example 2 , sample e , the strong immediate burst of silver may even have reduced the day 1 levels for the coated sample . while the invention has been described with respect to various exemplary embodiments , the scope of the invention is not intended to be limited thereby , and variations , modifications and other embodiments of the expressly described features and aspects are readily effected , as will be apparent to the skilled artisan based on the disclosure herein , with all such variations , modifications and other embodiments contemplated as being within the scope of the present invention as hereinafter claimed .
an article including a surface having a coating thereon , in which the coating includes a base coat , firmly adhered to the surface , and a hydrophilic , biocompatible top - coat . an antibiotic ceramic component is dispersed in one or both of the base coat and top - coat . preferably , the ceramic component is dispersed in the base coat . in a preferred embodiment , the ceramic component is a zeolite with silver ions exchanged onto internal acidic sites of the zeolite , and the top - coat includes a polysaccharide , such as hyaluronan . the zeolite is highly effective in imparting anti - microbial character to the coating .