Widespread attention has been focused in recent years on the consequences of bacterial contamination contracted by food consumption or contact with common surfaces and objects. Some noteworthy examples include the sometimes fatal outcome from food poisoning due to the presence of particular strains of Eschericia coli in undercooked beef; Salmonella contamination in undercooked and unwashed poultry food products; as well as illnesses and skin irritations due to Staphylococcus aureus and other micro-organisms. Anthrax is an acute infectious disease caused by the spore-forming bacterium bacillus anthracis. Allergic reactions to molds and yeasts are a major concern to many consumers and insurance companies alike. Respiratory infections due to viruses such as SARS (severe acute respiratory syndrome) coronavirus, and the return of the H5N1 virus and mutations thereof, now commonly referred to as the avian flu or bird flu, which was responsible for the great pandemic influenza of 1918, have become major public health issues. In addition, significant fear has arisen in regard to the development antibiotic-resistant strains of bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). The Centers for Disease Control and Prevention estimates that 10% of patients contract additional diseases during their hospital stay and that the total deaths resulting from these nosocomially-contracted illnesses exceeds those suffered from vehicular traffic accidents and homicides. In response to these concerns, manufacturers have begun incorporating antimicrobial agents into materials used to produce objects for commercial, institutional and residential use.
The antimicrobial properties of silver have been known for several thousand years. The general pharmacological properties of silver are summarized in “Heavy Metals” and “Antiseptics and Disinfectants: Fungicides; Ectoparasiticides”—by Stewart C. Harvey in The Pharmacological Basis of Therapeutics, Fifth Edition, by Louis S. Goodman and Alfred Gilman (editors), published by MacMillan Publishing Company, NY, 1975. It is now understood that the affinity of silver ion for biologically important moieties such as sulfhydryl, amino, imidazole, carboxyl and phosphate groups are primarily responsible for its antimicrobial activity.
The attachment of silver ions to one of these reactive groups on a protein results in the precipitation and denaturation of the protein. The extent of the reaction is related to the concentration of silver ions. The diffusion of silver ion into mammalian tissues is self-regulated by its intrinsic preference for binding to proteins through the various biologically important moieties on the proteins, as well as precipitation by the chloride ions in the environment. Thus, the very affinity of silver ion to a large number of biologically important chemical moieties (an affinity which is responsible for its action as a germicidal/biocidal/viricidal/fungicidal/bacteriocidal agent) is also responsible for limiting its systemic action—silver is not easily absorbed by the body. This is a primary reason for the tremendous interest in the use of silver containing species as an antimicrobial i.e. an agent capable of destroying or inhibiting the growth of microorganisms, including bacteria, yeast, fungi and algae, as well as viruses.
In addition to the affinity of silver ions for biologically relevant species, which leads to the denaturation and precipitation of proteins, some silver compounds, those having low ionization or dissolution ability, also function effectively as antiseptics. Distilled water in contact with metallic silver becomes antibacterial even though the dissolved concentration of silver ions is less than 100 ppb. There are numerous mechanistic pathways by which this oligodynamic effect is manifested i.e. by which silver ion interferes with the basic metabolic activities of bacteria at the cellular level, thus leading to a bacteriocidal and/or bacteriostatic effect.
A detailed review of the oligodynamic effect of silver can be found in “Oligodynamic Metals” by I. B. Romans in Disinfection Sterilization and Preservation, C. A. Lawrence and S. S. Bloek (editors), published by Lea and Fibiger (1968) and “The Oligodynamic Effect of Silver” by A. Goetz, R. L. Tracy and F. S. Harris, Jr. in Silver in Industry, Lawrence Addicks (editor), published by Reinhold Publishing Corporation, 1940. These reviews describe results that demonstrate that silver is effective as an antimicrobial agent towards a wide range of bacteria.
While it is well known that silver-based agents provide excellent antimicrobial properties, aesthetic problems due to discoloration are frequently a concern. This is believed to be due to several root causes, including the inherent thermal and photo-instability of silver ions, along with other mechanisms. A wide range of silver salts are known to be thermally and photolytically unstable, discoloring to form brown, gray or black products. Silver ion may be formally reduced to its metallic state, assuming various physical forms and shapes (particles and filaments), often appearing brown, gray or black in color. Reduced forms of silver that form particles of sizes on the order of the wavelength of visible light may also appear to be pink, orange, yellow, beige and the like due to light scattering effects. Alternatively, silver ion may be formally oxidized to silver peroxide, a gray-black material. In addition, silver ion may simply complex with environmental agents (e.g. polymer additives, catalyst residues, impurities, surface coatings, etc.) to form colored species without undergoing a formal redox process. Silver ion may attach to various groups on proteins present in human skin, resulting in the potentially permanent dark stain condition known as argyria. Silver ion may react with sulfur to form silver sulfide, for which two natural mineral forms, acanthite and argentite, are known to be black in color. Pure silver sulfate (white in color) has been observed to decompose by light to a violet color.
In any given practical situation, a number of mechanisms or root causes may be at work in generating silver-based discoloration, complicating the task of providing a solution to the problem. For example, Coloplast, as describe in U.S. Pat. No. 6,468,521 and U.S. Pat. No. 6,726,791, disclose the development of a stabilized wound dressing having antibacterial, antiviral and/or antifungal activity characterized in that it comprises silver complexed with a specific amine and is associated with one or more hydrophilic polymers, such that it is stable during radiation sterilization and retains the activity without giving rise to darkening or discoloration of the dressing during storage. Registered as CONTREET®, the dressing product comprises a silver compound complexed specifically with either ethylamine or tri-hydroxymethyl-aminomethane. These specific silver compounds, when used in conjunction with the specific polymer binders carboxymethylcellulose or porcine collagen, are said to have improved resistance to discoloration when exposed to heat, light or radiation sterilization and contact with skin or tissue.
The point in time when discoloration of a composition associated with a silver-based additive appears can range from early in the manufacturing process to late in a finished article's useful life. For example, thermal instability can set in shortly after introduction of the silver-based additive into a high temperature melt-processed polymer, or much later during long-term storage of the material or finished article at lower (e.g. ambient) temperatures, sometimes referred to as long-term heat stability (LTHS). Likewise, photo-instability can result from short-term exposure to high-energy radiation processing or radiation sterilization, or later from long-term exposure of the material or finished article to ambient light (e.g. requiring ultraviolet (UV) stabilization). In addition, polymeric materials are well known to inherently discolor to some degree either during high temperature melt processing, or later due to aging in the presence of light, oxygen and heat. Thermoplastic polymers such as polyolefins are typically processed at temperatures between about 200-280° C. and will degrade under these conditions by an oxidative chain reaction process that is initiated by free-radical formation. Free radicals (R*) formed either along the polymer backbone or at terminal positions will react quickly with oxygen (O2) to form peroxy radicals (ROO*), which in turn can react with the polymer to form hydroperoxides (ROOH) and another free radical (R*). The hydroperoxide can then split into two new free radicals, (RO*) and (*OH), which will continue to propagate the reaction to other polymer chains. It is known in the art that antioxidants and light stabilizers can prevent or at least reduce the effects of these oxidative chain reactions. Several types of additives are added to polymers to protect them during processing and to achieve the desired end-use properties. Additives are generally divided into groups: stabilizers and modifiers. Typical modifiers are antistatic-and antifogging agents, acid scavengers, blowing agents, cling agents, lubricants and resins, nucleating agents, slip- and anti-blocking agents as well as fillers, flame retardants, compatibilizers and crosslinkers. Antioxidant stabilizers are typically classified as (1) free-radical scavengers or primary antioxidants, and (2) hydroperoxide decomposers or secondary antioxidants. While not being held to any particular microscopic theory, the mechanism of antioxidants is described in “Rubber Chemistry and Technology” 47 (1974), No. 4, pages 988 and 989. The instant invention is directed primarily at reducing discoloration often seen in melt-processed thermoplastic polymers immediately following compounding, extrusion or molding at high temperature.
Primary antioxidants are added to polymers mainly to improve long-term heat stability of the final fabricated article. Primary antioxidants are often called free radical scavengers because they are capable of reacting quickly with peroxy or other available free radicals to yield an inert or much less reactive free radical species, thus halting or slowing down the oxidative chain reaction process that leads to degradation. Primary antioxidants typically include, for instance, sterically hindered phenols, secondary aromatic amines, hydroquinones, p-phenylenediamines, quinolines, hydroxytriazines or ascorbic acid (vitamin C). Although aromatic amines are the strongest primary antioxidant, they are highly staining and seldom used in thermoplastics. Sterically hindered phenols are diverse in number as well as commercially available in high purity. Hindered phenols have been structurally classified as (1) alkylphenols, (2) alkylidinebisphenols, (3) thiobisphenols, (4) hydroxybenzyl compounds, (5) acylaminophenols, and (6) hydroxyphenyl propionates.
Secondary antioxidants are added to polymers mainly to provide needed short-term stability in melt flow and color during high temperature melt processing of the plastic material. They are believed to function by reacting with hydroperoxides to yield stable products that are less likely to fragment into radical species. Secondary antioxidants can usually be classified chemically as either a phosphorous-containing or a sulfur-containing compound. Phosphites such as triesters of phosphoric acid (P(OR′)3) are believed to react with hydroperoxides (ROOH) to form phosphates (OP(OR′)3) and alcohols (ROH). Elemental sulfur compounds and diaryl disulfides are reported to decompose hydroperoxides by generating sulfur dioxide. Thioethers (R1SR2) are believed to react with hydroperoxides (ROOH) to yield sulfoxides (R1 SOR2) and alcohols (ROH). Sulfoxides may in turn destroy several equivalents of hydroperoxide through the intermediate formation of sulfenic acids and sulfur dioxide.
A third group of antioxidant stabilizers is commonly referred to as synergists. These materials may not be effective stabilizers when used alone, but when used in combination with another antioxidant a cooperative action results wherein the total effect is greater than the sum of the individual effects taken independently. Carbon black acts synergistically when combined with elemental sulfur, thiols or disulfides, whereas these materials are largely ineffective when used alone under the same conditions. Homosynergism is used to describe two stabilizers of unequal activity that work by the same mechanism. For example, two radical scavenging primary antioxidants might function synergistically if one were to transfer a hydrogen atom to the radical formed by the other, thus regenerating the latter stabilizer and extending its effectiveness. Alternatively, heterosynergism might result between a free radical scavenger and a nonradical hydroperoxide decomposer that act on different portions of the oxidative chain reaction process that leads to decomposition. Ultraviolet absorbers or metal deactivators in combination with radical scavengers have also been report to be heterosynergists. Some common thiosynergists include the esters of β-thiodipropionic acid, for example the lauryl, stearyl, myristyl or tridecyl esters. A widely used antioxidant package for polyolefins is the primary antioxidant 2,6-di-tert-butyl-4-methylphenol (BHT) with the thiosynergist dilauryl thiodipropionate (DLTDP), as both components of this combination are approved by the U.S. Food and Drug Administration for use in packaging materials for food products.
A conventional preferred antioxidant stabilizer combination known in the art to reduce discoloration in melt-processed polyolefins, and polypropylene in particular, includes a sterically hindered phenolic primary antioxidant with an organic phosphite or phosphonite secondary antioxidant. Bolton suggested using derivatives of phosphonic or phosphinic acids as stabilizers for polyolefins (U.S. Pat. No. 2,230,371, German Pat. No. 1,210,855, and Belgian Pat. No. 617,194) and Heinrich et al disclosed using diphosphonic and diphosphinic acid derivatives in combination with phenolic stabilizers in U.S. Pat. No. 4,024,103. More recently, the consensus view that a phenolic primary antioxidant with an organic phosphite or phosphonite secondary antioxidant is the preferred stabilizer combination to improve color and reduce melt flow instability during high temperature melt processing of polyolefins has been expressed many times, for instance, in U.S. Pat. No. 6,015,854, U.S. Pat. No. 6,022,946, U.S. Pat. No. 6,197,886, U.S. Pat. No. 6,770,693, and U.S. Pat. No. 6,881,744.
While combinations of antioxidant stabilizers are frequently employed in thermoplastic resins, often very specific combinations are optimized to address particular problems. Webster in U.S. Pat. No. 6,538,056 and U.S. Pat. No. 6,774,170 discloses that polyethylene melt-phase compounded with oxidized, non-cationized, non-silylated sulfur black pigment, a phenolic antioxidant, a sulfur-containing secondary antioxidant (specifically the thiosynergist compound distearyl-thiodipropionate), and optionally containing carbon black or other inorganic fillers, exhibits improved long-term oxidative thermal stability in accelerated heating tests. Nakajima in JP10120833 disclose that the long-term thermal stability of a flame-retardant polyolefin comprising 30-70% by weight magnesium hydroxide, a polyol ester of a condensed aliphatic hydroxy acid, calcium stearate and a phenolic antioxidant, can be further improved by the addition of a thioether antioxidant. Oeysaed et al in WO2004033545 disclose that the long-term thermal stability of polypropylene is improved when a phosphite/phosphonite-type antioxidant is added along with a hindered phenol antioxidant and a sulfur-containing antioxidant (specifically the thiosynergist distearyl-thiodipropionate, IRGANOX PS-802) in accelerated heating tests. Inada et al in JP62270642 disclose improved adhesion to aluminum and stainless steel plates by polypropylene resin grafted with maleic acid and further containing calcium stearate, phenolic antioxidant (tetrakis[methylene-3-(3,5-di-t-butyl-4-hydroxyphenyl)propionate]methane, IRGANOX 1010) and dithioether antioxidant (distearyldisulfide, HOSTANOX SE-10).
A rapidly emerging application for silver based antimicrobial agents is inclusion in polymers used in plastics and synthetic fibers. A variety of methods is known in the art to render antimicrobial properties to a target fiber. The approach of embedding inorganic antimicrobial agents, such as zeolite, into low melting components of a conjugated fiber is described in U.S. Pat. No. 4,525,410 and U.S. Pat. No. 5,064,599. In another approach, the antimicrobial agent may be delivered during the process of making a synthetic fiber such as those described in U.S. Pat. No. 5,180,402, U.S. Pat. No. 5,880,044, and U.S. Pat. No. 5,888,526, or via a melt extrusion process as described in U.S. Pat. No. 6,479,144 and U.S. Pat. No. 6,585,843. Alternatively, deposition of antimicrobial metals or metal-containing compounds onto a resin film or target fiber has also been described in U.S. Pat. No. 6,274,519 and U.S. Pat. No. 6,436,420. Still, the formation of colored species of silver that impart discoloration to a plastic composition or fiber is clearly undesirable from both an aesthetic and a practical materials performance perspective, and the prior art has not adequately addressed formation of thermoplastic polymer and silver compositions with desired color stability and low discoloration.
In addition to the color instabilities inherent to silver and to polymeric materials themselves, silver ion imbedded in polymer composites may react with polymer decomposition products (e.g. free radicals, peroxides, hydroperoxides, alcohols, hydrogen atoms and water), modifiers (e.g. chlorinated flame retardants), stabilizers and residual addenda (e.g. titanium tetrachloride, titanium trichloride, trialkylaluminum compounds and the like from Ziegler-Natta catalysts) to form potentially colored byproducts. This greater complexity of potential chemical interactions further challenges the modern worker in designing an effective stabilizer package for polymers containing silver species.
A number of approaches have been taken in the past to reduce discoloration resulting from the inclusion of silver-based compounds in melt-processed polymers. Niira et al in U.S. Pat. No. 4,938,955 disclose melt-processed antimicrobial resin compositions comprising a silver containing zeolite and a single stabilizer (discoloration inhibiting agent) selected from the group consisting of a hindered amine (CHIMASSORB 944LD or TINUVIN 622LD), a benzotriazole, a hydrazine, or a hindered phenol (specifically octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate, commercially available as IRGANOX 1076). Reduction in long-term discoloration from exposure to 60 days of sunlight in the air was the only response reported.
Ohsumi et al in U.S. Pat. No. 5,405,644 disclose two fiber treatment processes in which the addition of a benzotriazole, preferably methylbenzotriazole, to treatment solutions subsequently inhibits discoloration in fibers comprising a silver containing tetravalent-metal phosphate antimicrobial agent. More specifically, addition of a benzotriazole to an ester spinning oil reduces discoloration in treated fibers following one day exposure to outdoor sunlight; and secondly, the addition of a benzotriazole to an alkali treatment solution reduces discoloration in treated fibers when examined immediately following treatment. It is suggested that the benzotriazole either retards the dissolution of silver ions or inhibits the reaction of small amounts of soluble silver ion with the various chemicals present in the fiber treatment solutions.
Lever in U.S. Pat. No. 6,187,456 discloses reduced yellowing of melt-processed polyolefins containing silver-based antimicrobial agents silver zirconium phosphate or silver zeolite when sodium stearate is replaced with aluminum magnesium hydrotalcite. Tomioka et al in JP08026921 disclose that discoloration from high temperature can be prevented for polypropylene compounded with a silver mixture containing specific amounts of sulfite and thiosulfate ion, if the antimicrobial silver mixture is impregnated on silica gel support. Dispersing silver-based antimicrobial agents into a wax or low molecular weight polymer as a carrier that is intern blended into a higher molecular weight polymer is disclosed in JP03271208A and JP2841115B2 as a safe means to handle higher concentrations of silver-based antimicrobial agents without staining the skin.
Some workers report reducing discoloration by simply combining silver-based antimicrobial agents with other antimicrobial agents in hopes of reducing the total amount of silver in a given formulation. Ota et al in JP04114038 combine silver sulfate with the organic antifungal agent TBZ (2-(4-thiazolyl)benzimidazole) to reduce discoloration in injection molded polypropylene. Herbst in U.S. Pat. No. 6,585,989 combines a silver containing zeolite and the organic antimicrobial agent TRICLOSAN® (2,4,4′-trichloro-2′-hydroxydiphenyl ether) in polyethylene and polypropylene to yield improved UV stabilization (less yellowness) in accelerated weathering tests. Kimura in U.S. Pat. No. 7,041,723 discloses that for polyolefins containing an antimicrobial combination consisting of (A) a silver containing zeolite and either (B) a silver ion-containing phosphate or (C) a soluble silver ion-containing glass powder, some drawbacks of each antimicrobial agent are mitigated, including the reduction of discoloration from UV light exposure in accelerated weathering tests.
There is a need to provide improved compositions comprising silver-based antimicrobial agents and thermoplastic polymers that substantially reduce the degree of unwanted discoloration within the resultant article due to the introduction of silver metal or silver ion salts.