Patent Application
20050129929
The present invention relates to a medium containing a combination of iron sequestering agents and antimicrobial materials that is able to limit the growth of harmful microorganisms and prevent microbial contamination. The medium also provides a means of indicating the effectiveness of antimicrobial activity. The medium further has an adhesive layer so it can be adhered to a surface such as a counter top and/or changes visual appearance as the material reaches a predetermined state.
In recent years people have become very concerned about exposure to the hazards of bacterial contamination. For example, exposure to certain strains of Eschericia coli through the ingestion of under-cooked beef can have fatal consequences. Exposure to Salmonella enteritidis through contact with unwashed poultry can cause severe nausea and exposure to Staphylococcus aureus, Klebsiella pneumoniae, yeast (Candida albicans) can cause skin infections. In some instances bacterial contamination alters the taste of the food or drink or makes the food unappetizing. With the increased concern by consumers, manufacturers have started to produce products having antimicrobial properties.
In the area of food preparation, counter tops, table and cabinets are made using high-pressure laminates as discussed in U.S. Pat. No. 6,248,342. When used in food preparation areas, high-pressure laminates often come in contact with food and are a breeding ground for bacteria, fungi, and other microorganisms. Therefore, attempts have been made to develop high-pressure laminates having antimicrobial properties. For example, the organic compound triclosan has been incorporated in countertops to provide a surface having antimicrobial properties.
Nobel metal ions such as silver and gold ions are known for their anti-microbial activities and have been used in medical care for many years to prevent and treat infection.
Patents U.S. Pat. No. 5,556,699 and U.S. Pat. No. 6,436,422 disclose antibiotic materials containing zeolites for use as materials for packaging foods, medical equipment and accessories. U.S. Pat. No. 6,555,599 discloses an antimicrobial vulcanized EPDM rubber-containing article having sufficient antimicrobial activity and structural integrity to withstand repeated use without losing either antimicrobial power or modulus strength.
It has also been recognized that small concentrations of metal ions play an important role in biological processes. For example, Mn, Fe, Ca, Zn, Cu and Al are essential bio-metals, and are required for most, if not all, living systems. Metal ions play a crucial role in oxygen transport in living systems, and regulate the function of genes and replication in many cellular systems. It has been recognized that iron is an essential biological element, and that all living organisms require iron for survival and replication. Although the occurrence and concentration of iron is relatively high on the earth's surface, the availability of “free” iron is severely limited by the extreme insolubility of iron in aqueous environments. As a result, many organisms have developed complex methods of procuring “free” iron for survival and replication; and depend directly upon these mechanisms for their survival. United states patent application Ser. Nos. 10/822,940 filed Apr. 13, 2004 entitled DERIVATIZED NANOPARTICLE COMPRISING METAL-ION SEQUESTRANT by Joseph F. Bringley, 10/823,443 filed Apr. 13, 2004 entitled USE OF DERIVATIZED NANOPARTICLES TO MINIMIZE GROWTH OF MICRO-ORGANISMS IN HOT FILLED DRINKS by Richard W. Wien, et al., Ser. No. 10/823,446 filed Apr. 13, 2004 entitled CONTAINER FOR INHIBITING MICROBIAL GROWTH IN LIQUID NUTRIENTS by David L. Patton et al., Ser. No. 10/822,929 filed Apr. 13, 2004 entitled COMPOSITION OF MATTER COMPRISING POLYMER AND DERIVATIZED NANOPARTICLES by Joseph F. Bringley et al., Ser. No. 10/822,939 filed Apr. 13, 2004 entitled COMPOSITION COMPRISING INTERCALATED METAL-ION SEQUESTRANTS by Joseph F. Bringley, et al., Ser. No. 10/823,453 filed Apr. 13, 2004 entitled ARTICLE FOR INHIBITING MICROBIAL GROWTH by Joseph F. Bringley et al., Ser. No. 10/822,945 filed Apr. 13, 2004 entitled ARTICLE FOR INHIBITING MICROBIAL GROWTH IN PHYSIOLOGICAL FLUIDS by Joseph F. Bringley et al. describe materials and methods for sequestering iron, and other bio-essential elements, and preventing microbial growth. The materials and methods limit the availability of bio-essential elements to microbial organisms and hence retard or prevent their growth.
There is a problem in that antimicrobial films may quickly be depleted of antimicrobial active materials and become inert or non-functional. Depletion results from rapid diffusion of the active materials into the biological environment with which they are in contact. Once the film and the contacting environment is depleted of antimicrobial materials, microorganisms may resume growth. There is a further problem in that it is heretofore impossible to distinguish a depleted or inactive film from a working film using common human senses such as sight, smell or touch. Thus, users are unable to determine if a surface is antimicrobially safe for continued operation. When surface such as countertops lose this effectiveness in preventing bacterial growth, they are expensive and difficult to replace.
There remains a need for antimicrobial films which are more effective in their ability to inhibit or prevent microbial contamination. There remains a need to provide a perceivable indication to the user that the antimicrobial material is depleted or has worn away, thus prompting the user that the film needs to be replaced. The film also can be easily applied to a surface such as a countertop or other work surface and easily removed when the antimicrobial properties have been depleted.
The present invention is also directed to the problem of the growth of micro-organism in liquids that occur and remain on food preparation surfaces that adversely affects food quality.
In accordance with one aspect of the present invention there is provided a flexible multi-layer medium comprising:
In accordance with another aspect of the present invention there is provided a multi-layer medium comprising:
In accordance with still another aspect of the present invention there is provided a multi-layer medium comprising:
In accordance with still another aspect of the present invention there is provided a plurality of multi-layer sheets layered together to form a stack of flexible multi-layer medium comprising: a flexible support layer having a first side and a second side; a
In accordance with another aspect of the present invention there is provided a flexible multi-layer medium comprising:
These and other aspects, objects, features and advantages of the present invention will be more clearly understood and appreciated from a review of the following detailed description of the preferred embodiments and appended claims, and by reference to the accompanying drawings.
In the detailed description of the preferred embodiments of the invention presented below, reference is made to the accompanying drawings in which:
Referring to
The antimicrobial active material of antimicrobial layer 15 may be selected from a wide range of known antibiotics and antimicrobials. An antimicrobial material may comprise an antimicrobial ion, molecule and/or compound, metal ion exchange materials exchanged or loaded with antimicrobial ions, molecules and/or compounds, ion exchange polymers and/or ion exchange latexes, exchanged or loaded with antimicrobial ions, molecules and/or compounds. Suitable materials are discussed in “Active Packaging of Food Applications” A. L. Brody, E. R. Strupinsky and L. R. Kline, Technomic Publishing Company, Inc. Pennsylvania (2001). Examples of antimicrobial agents suitable for practice of the invention include benzoic acid, sorbic acid, nisin, thymol, allicin, peroxides, imazalil, triclosan, benomyl, metal-ion release agents, metal colloids, anhydrides, and organic quaternary ammonium salts. Preferred antimicrobial reagents are metal ion exchange reagents such as silver sodium zirconium phosphate, silver zeolite, or silver ion exchange resin which are commercially available. The antimicrobial layer 15 generally has a thickness “y” of between 0.1 microns and 100 microns, preferably in the range of 1.0 and 25 microns. In the embodiment illustrated the thickness “y” is about 5 microns.
The adhesive used to form the adhesive layer 20 is typical of the adhesive layer found on the back shelving papers such as a reposition adhesive such as the adhesive used in 3M™ Scotch® 859 Removable Mounting Squares and 3M™ Scotch® Repositionable Glue Tape 928-100.
In another embodiment of the antimicrobial multilayer medium 5, the adhesive layer 20 may be a flexible static-cling vinyl such as Trans-Flex-Cast commercially available from Transilwrap Co., Inc., 9201 W. Belmont Ave., Franklin Park, Ill.
A second embodiment of the antimicrobial multilayer medium 5, made in accordance the present invention, is shown in
Depending upon the material chosen for the support layer, an additional layer called a subbing layer 40 may be coated on the top surface 18 of the support layer 10. The subbing layer 40 is used to insure proper adhesion of the antimicrobial layer 15 to the support layer 10. Likewise, a subbing layer 45 maybe coated on the bottom surface 22 of the support layer 10. The subbing layer 45 is used to insure proper adhesion of an adhesive layer 20 to the support layer 10. As previously discussed, depending on what material is used for the base 10, the subbing layer 45 may or may not be required. Preparing a support surface (hydrophobic) such as cellulose triacetate to accept an aqueous cast polymer such as polyvinyl alcohol may require chemical and/or an interlayer coating (subbing layer) to improve adhesion. An example of this could be found in photographic patent literature where gelatin based hydrophilic photographic materials are commonly attached to hydrophobic supports such as polyethylene terephthalate. In the embodiment illustrated, an optional peelable protective release layer 50 is provided over adhesive layer 20 for protecting the adhesive layer 20 until it is to be used for securing the multilayer medium 5 to a surface. Preferred protective release materials include polyester, cellulose paper, and biaxially oriented polyolefin. The release layer 50 is peeled off the adhesive layer 20 as indicated by arrow 52 whereby the multilayer medium 5 is secured to the desired surface.
A web (not shown) of the antimicrobial medium 5 can be made by several possible methods. In one embodiment, the antimicrobial web is made by coating the surface 18 of a plastic, paper or fabric support 10 with a polymeric layer containing one or more antimicrobial compounds. The antimicrobial is typically dispersed or dissolved in a medium or solvent. The medium or solvent may contain a binder to allow the antimicrobial to adhere to the support 10 and may contain other addenda such as coating aids, surfactants, plasticizers, etc. to aid the coating process. The coating may be applied by painting, spraying or casting. It is preferred to apply the coating via a solvent assisted process (aqueous or organic) such as blade, rod, knife or curtain coating. The antimicrobial web may also be made by extrusion, or coextrusion of polymeric layers such that at least one layer comprises an antimicrobial compound and the color indicating chemistry described below. The antimicrobial web may also be prepared by blow molding.
Now referring to
Now referring to
In a preferred embodiment, the multilayer medium 5 contains an antimicrobial material comprising a metal ion exchange material which is exchanged with at least one antimicrobial metal ion selected from silver, copper, gold, nickel or zinc, and is additionally exchanged with at least one colored metal ion, or colored metal ion complex. The colored metal ion or metal ion complex may be antimicrobial or may be inert. The colored metal ion or metal ion complex imparts color to the antimicrobial sheet and upon exposure to a biological medium, diffuses into the medium, and is depleted in the same manner that the antimicrobial metal ion is depleted. As the colored metal ion or colored metal-ion complex is depleted, the web changes color. The amount of exchanged colored metal ion or metal ion complex is determined such the rate of depletion of the colored metal ion is similar to the rate of depletion of the antimicrobial metal ion, and thus, the loss of color from the web indicates a loss of antimicrobial activity. In a further preferred embodiment, the antimicrobial material consists of metal ion exchanged zirconium phosphate, zeolite or other metal ion exchanged resin, which is exchanged with at least one antimicrobial metal ion selected from silver, copper, gold, nickel or zinc, and is additionally exchanged with at least one highly colored metal ion or metal ion complex. Colored metal ions or metal ion complexes suitable for practice of the invention are Cu(II), Co(II), Co(III), Ni(II), Manganese ion, Cr(III), Fe(II), Fe(III), Ni(II) and metal ion complexes such as Co(NH3)63+, Cu(NH3)42+.
Alternatively, color indication can be provided in the diffusion control layer 30 shown in
Another approach to providing color indication for the antimicrobial web is to incorporate a colorless, or colored, precursor material which then reacts with a diffusible species such as antimicrobial ions, to form a colored molecule or material, or a material of a different color than the precursor. In this manner, as more antimicrobial ions diffuse through the web, more dye is produced thus producing a visual color indication. In a preferred embodiment the dye precursor is contained in the diffusion control layer 30 and reacts with diffusing antimicrobial metal ions selected from silver, copper, gold, zinc and nickel to produce a colored material. A working example of the color indicating chemistry 70 is illustrated below in which a metalized dye is formed by reaction of a metal ion with the ligand, 2-methyl-5-hydroxy-8-(2-pyridylazo)-quinoline-3-carboxylic acid. The reaction forms a very highly colored dye having the stoichiometry M(ligand) or M(Ligand)2. Examples of suitable metal ions are copper, zinc, cobalt and nickel.
Now referring again to
Now referring to
Yet another embodiment of the present invention is illustrated in
The mulitilayer medium of the invention comprises an immobilized metal-ion sequestering agent. The term immobilized, as used herein, defines the metal-ion sequestrant as being attached to a rigid or semi-rigid object, and as such, the metal-ion sequestrant is not free to diffuse away from the object or to dissolve into the liquid medium in which the object is immersed. The metal-ion sequestrant may be immobilized by means of a covalent chemical bond, or may be electrostatically immobilized on a support such as by mordant polymers, or may be immobilized via intercalation chemistry. The object may be a support such as glass, paper, plastic, cellulose, textiles, metal or wood. It is preferred that the sequestering agent is immobilized on a particle or a polymer. It is preferred that the sequestering agent has a high stability constant for a target metal-ion. It is further preferred that the metal-ion sequestrant has a high-affinity for biologically significant metal-ions, such as, Zn, Cu, Mn and Fe.
A measure of the “affinity” of metal-ion sequestrants for various metal-ions is given by the stability constant (also often referred to as critical stability constants, complex formation constants, equilibrium constants, or formation constants) of that sequestrant for a given metal-ion. Stability constants are discussed at length in “Critical Stability Constants”, A. E. Martell and R. M. Smith, Vols. 1-4, Plenum, N.Y. (1977), “Inorganic Chemetal-ion sequestranttry in Biology and Medicine”, Chapter 17, ACS Symposium Series, Washington, D.C. (1980), and by R. D. Hancock and A. E. Martell, Chem. Rev. vol. 89, p. 1875-1914 (1989). The ability of a specific molecule or ligand to sequester a metal-ion may depend also upon the pH, the concentrations of interfering ions, and the rate of complex formation (kinetics). Generally, however, the greater the stability constant, the greater the binding affinity for that particular metal-ion. Often the stability constants are expressed as the natural logarithm of the stability constant. Herein the stability constant for the reaction of a metal-ion (M) and a sequestrant or ligand (L) is defined as follows:
M+n L⇄MLn
where the stability constant is βn=[MLn]/[M][L]n, wherein [MLn] is the concentration of “complexed” metal-ion, [M] is the concentration of free (uncomplexed) metal-ion and [L] is the concentration of free ligand. The log of the stability constant is log βn, and n is the number of ligands which coordinate with the metal. It follows from the above equation that if βn is very large, the concentration of “free” metal-ion will be very low. Ligands with a high stability constant (or affinity) generally have a stability constant greater than 1010 or a log stability constant greater than 10 for the target metal. Preferably the ligands have a stability constant greater than 1015 for the target metal-ion. Table 1 lists common ligands (or sequestrants) and the natural logarithm of their stability constants (log βn) for selected metal-ions.
EDTA is ethylenediamine tetraacetic acid and salts thereof,
DTPA is diethylenetriaminepentaacetic acid and salts thereof,
DPTA is Hydroxylpropylenediaminetetraacetic acid and salts thereof,
NTA is nitrilotriacetic acid and salts thereof,
CDTA is 1,2-cyclohexanediamine tetraacetic acid and salts thereof,
PDTA is propylenediammine tetraacetic acid and salts thereof.
Desferroxamine B is a commercially available iron chelating drug, desferal ®.
MECAMS, 4-LICAMS and 3,4-LICAMS are described by Raymond et al. in “Inorganic Chemetal-ion sequestranttry in Biology and Medicine”, Chapter 18, ACS Symposium Series, Washington, D.C. (1980). Log stability constants are from “Critical Stability Constants”, A. E. Martell and R. M. Smith, Vols. 1-4,
In some instances, it may be necessary to remove specific metal-ion(s) from a target environment. The target environment is a liquid environment, e.g., food extrudates or residues containing nutrients left behind after the preparation of foods and beverages. In such cases it may be desirable to immobilize a metal-ion sequestrant with a very high specificity or selectivity for a given metal-ion. Immobilized metal-ion sequestrants of this nature may be used to control the concentration of the target metal-ion. One skilled in the art may prepare such immobilized metal-ion sequestrants by selecting a metal-ion sequestrant having a high specificity for the target metal-ion. The specificity of a metal-ion sequestrant for a target metal-ion is given by the difference between the log of the stability constant for the target metal-ion, and the log of the stability constant for the interfering metal-ions. For example, if a treatment required the removal of Fe(III), but it was necessary to leave the Ca-concentration unaltered, then from Table 1, DTPA would be a suitable choice since the difference between the log stability constants 28-10.8=17.2, is very large. 3,4-LICAMS would be a still more suitable choice since the difference between the log stability constants 43-16.2=26.8, is the largest in Table 1.
It is preferred that the immobilized metal-ion sequestrants have a high stability constant for the target metal-ion(s). The stability constant for the immobilized metal-ion sequestrant will largely be determined by the stability constant for the attached metal-ion sequestrant. However, the stability constant for the immobilized metal-ion sequestrants may vary somewhat from that of the attached metal-ion sequestrant. Generally, it is anticipated that metal-ion sequestrants with high stability constants will give immobilized metal-ion sequestrants with high stability constants. For a particular application, it may be desirable to have an immobilized metal-ion sequestrant with a high selectivity for a particular metal-ion. In most cases, the immobilized metal-ion sequestrant will have a high selectivity for a particular metal-ion if the stability constant for that metal-ion is about 106 greater than for other ions present in the system.
It is preferred that the immobilized metal-ion sequestrant of the invention has a high-affinity for iron, and in particular iron(III). It is preferred that the stability constant of the sequestrant for iron(III) be greater than 1010. It is still further preferred that the metal-ion sequestrant has a stability constant for iron greater than 1020.
Metal-ion sequestrants may be chosen from various organic molecules. Such molecules having the ability to form complexes with metal-ions are often referred to as “chelators”, “complexing agents”, and “ligands”. Certain types of organic functional groups are known to be strong “chelators” or sequestrants of metal-ions. It is preferred that the sequestrants of the invention contain alpha-amino carboxylates, hydroxamates, or catechol, functional groups. Hydroxamates, or catechol, functional groups are preferred. Alpha-amino carboxylates have the general formula:
R—[N(CH2CO2M)—(CH2)n—N(CH2CO2M)2]x
where R is an organic group such as an alkyl or aryl group; M is H, or an alkali or alkaline earth metal such as Na, K, Ca or Mg, or Zn; n is an integer from 1 to 6; and x is an integer from 1 to 3. Examples of metal-ion sequestrants containing alpha-amino carboxylate functional groups include ethylenediaminetetraacetic acid (EDTA), ethylenediaminetetraacetic acid disodium salt, diethylenetriaminepentaacetic acid (DTPA), Hydroxylpropylenediaminetetraacetic acid (DPTA), nitrilotriacetic acid, triethylenetetraaminehexaacetic acid, N,N-bis(o-hydroxybenzyl) ethylenediamine-N,N′ diacteic acid, and ethylenebis-N,N′-(2-o-hydroxyphenyl)glycine.
Hydroxamates (or often called hydroxamic acids) have the general formula:
where R is an organic group such as an alkyl or aryl group. Examples of metal-ion sequestrants containing hydroxamate functional groups include acetohydroxamic acid, and desferroxamine B, the iron chelating drug desferal.
Catechols have the general formula:
Where R1, R2, R3 and R4 may be H, an organic group such as an alkyl or aryl group, or a carboxylate or sulfonate group. Examples of metal-ion sequestrants containing catechol functional groups include catechol, disulfocatechol, dimethyl-2,3-dihydroxybenzamide, mesitylene catecholamide (MECAM) and derivatives thereof, 1,8-dihydroxynaphthalene-3,6-sulfonic acid, and 2,3-dihydroxynaphthalene-6-sulfonic acid.
The combination antimicrobial metal-ion sequestering multilayer medium 7 similar to the multilayer medium 5, like numerals indicating like elements and function as previously discussed. The multilayer medium 7 which includes a support layer 10 with an antimicrobial layer 15 as previously described is preferably coated on the top surface 170 of a polymeric layer 150 with an adhesive layer 20 coated on the bottom surface 22 of the support layer 10. The polymeric layer 150 contains an immobilized metal-ion sequestering agent or sequestrant such as EDTA. In the embodiment illustrated, the immobilized metal-ion sequestering agent or sequestrant is provided in a separate layer. It is of course understood that the metal-ion sequestrant 145 may be placed in the diffusion layer 30 and/or the antimicrobial layer 15. If the metal-ion sequestrant 145 is placed in the diffusion layer 30, an additional barrier layer 152 maybe added. The metal-ion sequestrant 145 removes designated essential bio-metal ions from any nutrient residue 155 deposited on the surface 35 during the preparation of food as shown in
Referring now to
Still referring again to
It is to be understood that various other changes and modifications may be made without departing from the scope of the present invention, the present invention being defined by the following claims.
Parts List:
This is a Continuation-in-Part of Ser. No. 10/737, 346 filed Dec. 16, 20003 entitled Antimicrobial Web For Application to a Surface by David Patton et al. Reference is made to commonly assigned U.S. patent application Ser. No. ______ filed Jun. 15, 2004 entitled “An Iron Sequestering Antimicrobial Composition” by Joseph F. Bringley, et al. (Docket 88081), and commonly assigned U.S. patent application Ser. No. ______ filed Jun. 15, 2004 entitled “Composition Comprising Metal-Ion Sequestrant” by Joseph F. Bringley (Docket 88079) incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| Parent | 10737346 | Dec 2003 | US |
| Child | 10868730 | Jun 2004 | US |
