MX2008002848A - Antimicrobial substrates - Google Patents

Abstract

A synergistic antimicrobial composition containing at least two kinds of antimicrobial agents, including poly-hexamethylene biguanide (PHMB), stably associated to a material substrate is described. The substrate can take the forms of an anti-infection face mask, medical devices, or surgical instruments.

Description

SUBSTRATES TO TIMICROBIANS Field of the Invention The present invention relates to a chemical treatment that can be applied to a protective article. In particular, the invention relates to compositions of material for controlling the spreading of pathogens and infectious diseases.

Antecedent-bes In recent years, the prevalence of infections in hospitals has had serious implications for both patients and workers for health care. Infections in hospitals are those that originate or occur in a hospital or hospital-type establishment for long-term care. In general, infections in hospitals are more serious and dangerous than external infections acquired in the community because the pathogens in hospitals are more virulent and resistant to typical antibiotics. Hospital infections are responsible for around 20,000-100,000 deaths in the United States of America per year. About 5% to 10% of patients in American hospitals (about 2 million per year) develop a clinically significant hospital infection. These hospital acquired infections (HAI) are usually related to a procedure or treatment used to diagnose or treat the patient's illness or injury.

The mechanism of action of hospital infections, as in any other infectious disease, is dependent on host, agent or environmental factors. Risk factors for the host such as age, nutritional status and existing disorders. Hospital infections are influenced by the intrinsic virulence of microbes as well as their ability to colonize and survive within institutions. Diagnostic procedures, medical devices, medical and surgical treatments are risk factors in the hospital environment. Infections acquired in the hospital can be caused by bacteria, viruses, fungi, or parasites. These microorganisms may already be present in the patient's body or may come from the environment, contaminated hospital equipment, health care workers, or other patients. Depending on the causative agents involved, an infection can start anywhere in the body. A localized infection is limited to a specific part of the body and has local symptoms.

Infections acquired in the hospital can also develop from surgical procedures, catheters placed in the urinary tract or blood vessels, or material for the nose or mouth that are inhaled in the lungs. The most common types of infections acquired in hospitals are urinary tract infections (UTI), pneumonia due to the use of endotracheal ventilators, pathogenic blood pollutants, and infections in surgical wounds. For example, if a surgical wound in the abdomen becomes infected, the area of the wound becomes red, hot, and painful. A generalized infection is one that enters the bloodstream and causes general systemic symptoms such as fever, chills, low blood pressure, or mental confusion.

Hospitals and other health care facilities have developed extensive infection programs to prevent hospital infections. Some standard precautionary measures to prevent infections include hand washing, which remains an effective method to prevent the spread of the disease, or should be routinely performed. Frequent hand washing by workers for health care and visitors is necessary to avoid passing infectious microorganisms to hospitalized patients, via the contact transfer mechanism. Gloves should be worn when touching blood, body fluids, secretions, excretions and contaminated items. The gloves should also be worn before touching the mucous membrane and the skin not intact. Gloves should be changed after tasks and procedures in the same patient who is heavily contaminated. Gloves should be removed quickly after use, before touching non-contaminated environmental surfaces and before seeing another patient. The hands should be washed subsequently. Masks, eye shields and face shields should be used to protect the mucous membranes of the eye, nose and mouth during procedures and patient care activities that are similarly exposed to the health care worker. through splashes and sprinkling of blood, secretions or excretions of body fluids. Gowns should be used to protect the skin and prevent contamination of clothing during splashes of blood or body fluids. Instruments and medical equipment must be properly sterilized to ensure they are not contaminated.

In the current environment for health care, the battle against hospital infections has not yet been won. Even when hospital infection control programs and more conscious efforts on the part of health care workers to take adequate precautions when caring for patients can prevent about 25% to 33% of these infections, a significant number of infections still occur. Current procedures are not enough. Despite the application of precautionary measures (for example, hand washing, use of gloves, face masks and dressing gowns), hospital acquired infections (HAI) still occur mainly via the transfer contact. That is, individuals who contact a surface contaminated by pathogens such as hands, clothing, and / or medical instruments can still transfer pathogens from one surface to another immediately or within a short time after initial contact. Researchers have used numerous ways to attack the problems related to microbes. Antiseptics and disinfectants are used extensively in hospitals and other health care facilities for a variety of topical and hard surface applications. In particular, they are an essential part of infection control practices and help in the prevention of hospital infections. Conventional antimicrobial agents currently available, however, are not very effective in killing and immobilizing pathogens on the surfaces to which the antimicrobial agents are applied.

The problem of antimicrobial resistance to biocides has made the control of unwanted bacteria and fungi somewhat complex. The widespread use of antiseptic and disinfectant products has raised concerns about the development of microbial resistance, particularly cross-resistance to antibiotics. A wide variety of active chemical agents (or "biocides") are found in these products, many of which have been used for hundreds of years for antisepsis, disinfection, and preservation. Despite this, less is known about the mode of action of these active agents than about antibiotics. In general, biocides have a broader spectrum of activity than antibiotics, and while antibiotics tend to have specific intracellular objectives, biocides can have multiple objectives. The wide use of antiseptic and disinfectant products has initiated some speculation about the development of microbial resistance, in particular the cross resistance to antibiotics. This review considers what is known about the action of, and the mechanisms of microbial resistance to, antiseptics and disinfectants and attempts, when possible, to relate current knowledge to the clinical environment.

Antibiotics should only be used when necessary. The use of antibiotics creates favorable conditions for infection with the fungal organism Candida. The overuse of antibiotics is also responsible for the development of bacteria that are resistant to antibiotics. In addition, excessive use and leaching of antimicrobial agents or antibiotics can cause bioaccumulation in living organisms and can also be cytotoxic to mammalian cells.

To better protect both patients and health care providers, protective articles, such as clothing, gloves, and other covers that have rapid, highly efficient performance, antimicrobial properties, including antiviral properties, are necessary for a variety of different Applications for a broad spectrum of antimicrobial protection. The industry needs antimicrobial materials that can control or prevent the transfer by contact of pathogens from area to area and from patient to patient. In view of the resistance problems that can arise with conventional antimicrobial agents that kill when the bacteria ingest the antibiotics, an antimicrobial that virtually kills on contact and has minimal or no leachate from the substrate with which it is applied can be better appreciated by workers in the field. Therefore, it is important to develop materials that do not provide a means for pathogens to still intermittently survive or grow, and that are stably associated with the surfaces of the substrate on which the antimicrobial agent is applied. In addition, antimicrobial protective articles must be relatively inexpensive to manufacture. It is also desirable to have an antimicrobial material that simultaneously has adequate fluid barrier and antistatic properties. Additionally, it is also desirable to have an antimicrobial and antiviral material to control infections of growth pathogens in blood and / or air, such as human immunodeficiency virus (HIV), severe acute respiratory syndrome (SARS), hepatitis B , etc.

Synthesis of the Invention The present invention describes in part a composition of antimicrobial material that can be applied to substrates of material and protective articles. The antimicrobial composition includes a mixture of at least one component selected from Group A, Group B, and optionally Group C. Group A includes a first or major antimicrobial agent, such as polyhexamethylene biguanide (PHMB). Group B includes at least one second antimicrobial agent, and / or an organic acid, or a processing aid. Group C includes an antistatic agent or fluoropolymer. Alternatively, the antimicrobial composition can be characterized as a mixture, in terms of percentage by weight of active agents either in solution or on a substrate, of about 0.1-99.9 percent by weight of polyhexamethylene biguanide (PHMB), and about 0.1-99.9 percent by weight concentration of a synergistic co-active agent X, wherein X is at least one of the following: a second antimicrobial agent, an organic acid, an active surface agent, or a surfactant. The primary and secondary agents are present in a ratio in the range from about 1000: 1 to about 1: 1000, respectively.

The composition exhibits a killing efficiency of at least 1 x 103 cfu / gram (colony formation unit per gram) (or 3 Logio (log reduction)) within a period of about 30 minutes. Desirably, the composition exhibits at least one Logio (log reduction) within a period of about a period of 5-10 minutes. Also, the composition is stable on the surfaces of the substrate to which it can be applied, so that it does not tend to leach out of the applied surface, and can achieve a uniform coating of active agents on the surface.

The second antimicrobial agent is at least one of the following: another biguanide, a chlorhexine, an alexidine, and relevant salts thereof, stabilized oxidants such as chlorine dioxide, stabilized peroxide (urea peroxide, mannitol peroxide) that is: sulfites (metasulfites) sodium), bis-phenols (triclosan, hexachlorophene, etc.), quaternary ammonium compounds (chloro benzalkonium, cetrimide, chlorine cetylpyridium, quaternized cellulose, and other quaternized polymers, etc.), various agents that "occur naturally" (polyphenols) of green or black tea extract, citric acid, chitosan, anatase titanium dioxide, tourmaline, bamboo extract, neem oil, etc.), hydrotropes (strong emulsifiers) and chaotropic agents (alkyl polyglycosides) and synergistic combinations thereof .

The processing aids may include an alcohol (e.g., octanol, hexanol, isopropanol), wetting agent surfactant, viscosity modifier (e.g., polyvinyl pyrrolidone (PVP), ethyl hydroxyethyl cellulose) surface modifier of binding agent, salts, or pH modifiers. The surface active agent may include a cellulose or a cellulose derivative material modified with quaternary ammonium groups.

According to another aspect, the present invention also relates to protective articles having a substrate with at least one surface having a treatment of the present antimicrobial composition in solution. In certain embodiments, the first treated antimicrobial surface is oriented away from the user's body. The at least one part of the substrate can be composed of either an elastomeric, polymeric, woven or non-woven material. In particular, the substrate can be either a natural or synthetic elastomeric membrane or sheet, cellulose-based fabric, polymer film, or polyolefin material, or combinations thereof. When the substrate is a non-woven material, the non-woven material may have a coating of the antimicrobial solution on one side of the material, or the antimicrobial solution may permeate up to about 15 nanometers of the non-woven material, but it is also possible to completely saturate the material throughout its volume if desired.

The protective article may take the form of a garment for use by patients, health care workers, or other persons who may come into contact with potentially infectious agents or microbes, including an article of clothing such as a gown, Toga, face mask, head cover, shoe cover, or glove. Alternatively, the protective article may include a surgical cover, a fenestration or surgical cover, a cover, sheets, bedding or linens, pads, gauze dressing, cleaning cloth, sponge or other cleaning, disinfecting or sanitation articles for applications at home, institutional, for health and industrial care.

The invention also discloses a method for treating a substrate, the method comprising: a) providing a substrate and an antimicrobial solution comprising a mixture of an antimicrobial agent containing polyhexamethylene biguanide (PHMB) and a synergistic coacting agent; b) either submerging the substrate in a liquid bath or spraying a coating of the antimicrobial solution onto a surface of the substrate. The method may involve exposing the substrate to an incandescent discharge treatment (e.g. corona or plasma) of an excited gas so that a surface of the substrate is functionalized to receive the antimicrobial solution.

The substrate may encompass both woven and non-woven fabrics made of either natural or synthetic fibers or combinations of mixtures of the two, elastic and non-elastic, porous and non-porous membranes or films, and of laminates or combinations thereof. . Other substrates may include rubber, plastic, or other synthetic polymer materials, or metal, steel, glass or ceramic materials. These substrates can be prepared for use in various applications for health care, personal care, institutional, industrial and other applications where the potential exists for the spread of infectious diseases.

Additional features and advantages of the present protective and / or sanitation articles and associated manufacturing methods will be described in the following detailed description. It is understood that both the above synthesis and the following detailed description and examples are merely representative of the invention, and are intended to provide a general view to understand the invention as claimed.

Brief Description of the Figures Figure 1 is an exemplary process for applying a treatment composition of the present invention to one or both sides of the displacement tissue.

Figure 2 is an alternative arrangement and method for applying a treatment composition of the present invention.

Figures 3A-C are schematic representations of a roll process 3- and 4- of reverse coating roll.

Figures 4A and 4B are schematic representations of typical arrangements of engraving coaters.

Figure 5 is a schematic representation of a wire rod measuring rod or rod fixed.

Detailed description of the invention Section I - Definitions and Technical Terms In this specification and the appended claims, the singular form of "a", "one", and "the" includes the plural reference unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood or are generally accepted by one of ordinary skill in the art to which this invention pertains.

As used herein, the terms "antimicrobial agent" or "antimicrobial agents" refer to chemicals or other substances that either kill or slow the growth of microbes. Among the antimicrobial agents in use today are antibacterial agents (that kill bacteria), antiviral agents (that kill viruses), antifungal agents (that kill fungi), and antiparasitic agents (that kill parasites). The two main classes of antimicrobial agents are "antibiotics" and surface disinfectants, otherwise known as "biocides". Biocides and antibiotics are both antimicrobial agents.

The term "biocides" is a general term that describes a chemical agent, such as a pesticide, usually broad-spectrum, that inactivates living microorganisms. Due to the range of biocides in antimicrobial activity, other terms may be more specific, including static, "with reference to growth-inhibiting agents (eg, bacteriostatic, fungistatic, or sporastatic), and" -cida ", with reference to the agents that kill the target organism (for example, bactericidal, fungicidal, sporadic, or virucidal).

The term "antibiotics" refers to a naturally occurring or synthetic organic chemical substance, most often used in low concentrations, in the treatment of infectious diseases of man, animals, and plants, which prevent or inhibit the growth of microorganisms. Examples of antibiotics include therapeutic drugs, such as penicillin, while biocides are disinfectants or antiseptics such as iodine. Antibiotics typically have a single objective and a very specific mode of action, therefore interacting with any receptors in the cell membrane, or the metabolic or nucleic functions of the cell, causing the inhibition of enzymatic or metabolic processes, similar to a "deadbolt" and key "to achieve microbicidal action, while biocides have multiple objectives and modes of action, which for example, may include physical disruption and permanent damage to the outer cell membrane of a bacterial microbe. Antibiotics and biocides are in different ways from one another as they try to open a door with a key against a hammer. Due to its specific mode of action, antibiotics are more closely associated with the spread and development of new microorganisms resistant to multiple drugs. As a result, the use of a biocide is the preferable embodiment of the invention. Some examples of biocide chemistries include biguanides (e.g., chlorhexine, alexidine, polyhexamethylene biguanide, and relevant salts thereof), halogen-releasing agents (e.g., iodine, iodophors, sodium hypochlorite, N-halamin, etc.). .), stabilized oxidants such as chlorine dioxide, stabilized peroxide (e.g. urea peroxide, peroxide mannitol), metal-containing species and oxides thereof (e.g., silver, copper, selenium, etc. Either in the form of a particle or embedded in the support matrix such as a zeolite or polymer), sulfides (eg, sodium metasulfide), bis-phenols (eg, triclosan, hexachlorophene, etc.), quaternary ammonium compounds (eg, chloro benzalkonium, cetrimide , chlorinated cetylpiridium, quaternized cellulose, and other quaternized polymers, etc.), various agents that "occur naturally" (eg, polyphenols from green or black tea extract, citric acid, chitosan, anata sa, titanium oxide, bamboo extract, neem oil, etc.), hydrotropes (e.g., strong emulsifiers) and chaotropic agents (e.g., alkyl polyglycosides) and synergistic combinations thereof. Depending on the chemistry of the substrate (polyolefin against cellulose-based materials) and the method of incorporating it into the product (topical versus grafted), many of the above chemicals can be used alone or in concert to achieve the final properties of the claimed product of interest.

As used herein, the term "containing" refers to the product generated in accordance with any method of incorporating an antimicrobial agent into a desired article. This can result in the molten addition of the active agent to a polymer melt during the extrusion and spinning of the fibers and the manufacture of the non-woven materials used in making the products; Topical application methods that may or may not impart "sides" to the fabrics used in building the finished products; and other non-standard methods such as plasma treatment, electrostatic bonding, surface graft copolymerization by radiation using for example ultraviolet, gamma, and electron beam radiation sources, or the use of chemical initiation to produce graft copolymerized surfaces which have antimicrobial activity, etc.

As used herein, the phrase "broad spectrum of microorganisms" is defined to include a minimum gram-positive and gram-negative bacterium, including resistant strains thereof, eg, strains of methicillin-resistant Staphilococus aureus (MRSA), Vancomycin-resistant enterococci (VRE) and strains of Streptococcus pneumoniae resistant to penicillin. Preferably, it is defined to include all bacteria (gram +, gram and fast acid strains) and yeasts such as Candida albicans. More preferably, it is defined to include all bacteria (gram +, gram-, and fast acid), yeast, and both enveloped and clean viruses such as human influenza, rhinovirus, poliovirus, adenovirus, hepatitis, human immunodeficiency virus ( HIV), herpes simplex, severe acute respiratory syndrome (a type of viral pneumonia) (SARS), and avian fever.

As used herein, the phrase "rapidly inhibits and controls growth" is defined to mean that the article in question leads to a reduction in the concentration of a broad spectrum of microorganisms by a magnitude of at least 1 logio (reduction of registration ), as measured by the bottle agitator method, the liquid drop challenge test, and / or the aerosol challenge test within 30 minutes. Preferably, it leads to a reduction in microbial concentration by a factor of 3 logio (record reduction) (eg, reduction by 103 units of colony formation per gram of material (cfu / g)) within about 30 minutes. More preferably, it leads to a reduction in microbial concentration by a factor of 4 logio (log reduction) or more within about 30 minutes.

As used herein, the phrase "prevents or minimizes contact transfer" is defined to mean that the article in question will lead to a reduction of 1 logio (reduction of registration) in the transfer of a broad spectrum of viable microorganisms when they contact another surface as compared to an untreated control article as measured by the contact transfer protocol outlined in the publication of United States of America patent application number 2004/0151919. Preferably, it leads to a reduction in the transfer of viable microorganisms by a factor of 3 logio (log reduction). More preferably, it leads to a reduction of viable microorganisms transferred by a factor of 4 logio (log reduction) or greater.

An "unleaded" antimicrobial surface is one that passes the test protocol of the American Society for Testing and Materials (ASTM) E2149-01 entitled "Standard Test Method for Determining the Antimicrobial Activity of Immobilized Antimicrobial Agents Under Dynamic Contact Conditions " The lack of a zone of inhibition with the chosen treatment agents demonstrates that the active species do not leach from the treated substrate.

Section II- Description Antiseptics and disinfectants are widely used in hospitals and other health care facilities for a variety of topical and hard surface applications. In particular, they are an essential part of infection control practices and help in the prevention of hospital infections. In recent years, the assembly is concerned about potential microbial contamination and the risks of infection that have increased the use of antimicrobial products containing chemical biocides. In general, biocides have a broader spectrum of activity than antibiotics, and while antibiotics tend to have specific intracellular objectives, biocides can have multiple objectives. However, some conventional biocides typically either need to be ingested by the pathogen or leached from a contacted surface to be effective against microbes.

In view of the need for a composition and articles treated with the composition, the present invention provides an approach to address the problems associated with bacterial and viral transmission and infection. According to the present invention, the antimicrobial composition can produce a death efficiency of 1 logio (log reduction) immediately after contact, and at least a death efficiency of about 3 logio (log reduction) in about less than about 30 minutes, typically under about 10 or 15 minutes. The composition can be stably applied to a variety of substrates or materials, such as either woven or non-woven fabrics, and to organic or inorganic surfaces.

Section A - Antimicrobial Composition The compositions according to the present invention adapt a combination of antimicrobial re-agents to produce a synergistic effect that is non-additive to the individual components. We consider several compounds as potential antimicrobial agents and / or processing aids. In particular, we consider several cationic polymers, such as quaternary ammonium compounds and polymeric biguanide alcohols, and surfactants as the main candidates for possible application on protective substrates. We have found that a combination of cationic polymers such as quaternary ammonium compounds (eg, quaternary ammonium cellulose and quaternary ammonium siloxane), polymeric biguanides, surfactants, alcohols, and organic acids, such as acetic, citric, benzoic acids, can produce non-additive synergistic systems with broad pathogenic efficacy. The combination with other antimicrobial compounds, surfactants, seems to improve the antimicrobial efficacy of the polymeric biguanides on the treatments that use polymer biguanides alone. These synergistic formulas allow for a rapid action of multiple mechanism of action that can make them less prone to develop bacterial resistance than the simple formula of the biguanide component. In addition, biocidal component actives in the formulas of the present invention can be more effective at relatively lower concentrations than if individual components alone were used at the same corresponding concentrations. These synergistic formulas allow not only improved efficiency, but also allow for potentially less leachate, less cyto-toxicity, and lower costs. Thus, with the present compositions one can use polymeric biguanides at lower concentrations than conventionally observed ones.

Biguanide poly-hexamethylene hypochloride (PHMB) is a cationic biguanide that strongly attracts and disrupts the negatively charged membrane of most microorganisms. Poly-hexamethylene biguanide (PHMB) is a polymer with a repeating unit consisting of highly basic biguanide groups bonded with hexamethylene spacers. Traditionally, the activity of poly-hexamethylene biguanide (PHMB) increases over a basis weight with increased polymerization levels, which have been linked to improved disruption of the inner membrane, the poly-hexamethylene biguanide (PHMB) agglutinates to receptor sites on the surface of bacterial cell membranes and extensively disrupts the two-layer membrane, causing greater interference to the detriment of bacterial metabolic processes. It is believed that poly-hexamethylene biguanide (PHMB) causes the formation of acid phospholipid domain of the cytoplasmic membrane. The permeability changes immediately, and it is believed to be an altered function of some enzymes associated with the membrane.

According to certain theories, a proposed sequence of events during the interaction of poly-hexamethylene biguanide (PHMB) with a cell envelope is as follows: (i) the rapid attraction of the biguanide poly-hexamethylene (PHMB) towards the surface of the negatively charged bacterial cell, with a strong and specific adsorption to the phosphate-containing compounds; (ii) the integrity of the outer membrane is deteriorated, and the poly-hexamethylene biguanide (PHMB) is attracted to the inner membrane; (iii) the binding of poly-hexamethylene biguanide (PHMB) to the phospholipids occurs, with an increase in the permeability of the inner membrane (K + loss) accompanied by bacteriostatic; and (iv) complete loss of membrane function, followed by precipitation of the intracellular constituents and a bactericidal effect. The mechanism of action of poly-hexamethylene biguanide (PHMB) in bacteria and fungi is the disruption of the outer cell membranes by means of 1) displacement of divalent cations that provide structural integrity and 2) agglutination of the phospholipids of the membrane. These actions provide the disorganization of the membrane and subsequently the closure of all the metabolic processes that rest on the structure of the membrane such as the generation of energy, the force of proton movement, as well as the transporters. The poly-hexamethylene biguanide (PHMB) is particularly effective against pseudomonas.

There is a substantial amount of microbiological evidence that disruption of the cell membrane is a lethal event. This can be modeled in the laboratory by the production of small unilamellar phospholipid vesicles (50-100 nanometers in diameter) that are loaded with a dye. The addition of poly-hexamethylene biguanide (PHMB) in the physiological concentration range causes a rapid interruption of the vesicles (observed by the monitored release of the dye) and the constant time for the reaction corresponds to the rapid death rate. Once the outer membrane has been opened, the poly-hexamethylene biguanide (PHMB) molecules can access the cytoplasmic membrane where they bind to the negatively charged phospholipids. The physical disruption of the bacteria's membrane leads to the filtration of critical cellular components from the cell, thereby killing the bacteria.

The very strong affinity of the poly-hexamethylene biguanide (PHMB) for the negatively charged molecules means that they can interact with some common anionic (but non-cationic or non-ionic) surfactants used in the coating formulas. However, it is compatible with polyvinyl alcohol, cellulose thickeners and starch-based products and works well on polyvinyl acetate and vinyl acetate-ethylene emulsion systems. It also provides good performance in silicone emulsions and electro-coated cationic systems. Simple compatibility tests quickly show whether poly-hexamethylene biguanide (PHMB) is compatible with a given formula and stable systems can often be developed by fine-tuning anionic components.

The poly-hexamethylene biguanide molecule (PHMB) can bind to the surface of the coated layer, such as in gloves, cover coats, face masks, or medical and surgical instruments, through hydrophobic interaction with apolar substrates and a complex load interaction associated with the regions of the substrate that have a negative charge. Once the bacteria become within a close proximity of the molecule of the polyalkylmethylene biguanide (PHMB) the poly-hexamethylene biguanide (PHMB) is preferably transferred to the most highly negatively charged bacterial cell. Alternatively, the hydrophobic regions of the biguanide can interact with the hydrophobic regions of the substrate allowing the cationic regions of the biguanide molecule poly-hexamethylene (PH B) accessibility to interact with the membrane of the negatively charged bacteria. The true mechanism is also a mixture of both types of interactions. Even though, the particular mechanism of retention of substrates is not well understood at present, our most recent leachate data imply that it actually sticks to the substrate and does not leach out as defined by the testing methods of the American Testing Society and Materials (ASTM), described in the empirical section, below. Since it does not show evidence of leachate from the applied substrate, poly-hexamethylene biguanide (PHMB) is less likely to lead to organism resistance or cytotoxic effects.

Commercially available Iteractions of poly-hexamethylene biguanide (PHMB), such as under the brand names of Cosmocil CQ (20 percent by weight of poly-hexamethylene biguanide (PHMB) in water) or of Vantocil, a hetero-dispersed mixture of poly-hexamethylene biguanide (PHMB) with a molecular weight of about 3,000, are active against bacteria in positive gram and in negative gram, but are not sporicidal.

The second antimicrobial active agent may include a quaternary ammonium compound, a quaternary ammonium siloxane, a polyquaternary amine; species containing metal and oxides thereof, either in the form of a particle or incorporated in a matrix or polymer support; halogen, a halogen-releasing agent or a halogen-containing polymer, a bromine compound, a chlorine dioxide, a thiazole, a thiocinate, an isothiazoline, a cyanobutane, a dithiocarbamate, a thion, a triclosan, an alkylsulfosuccinate, a alkyl-amino-alkyl glycine, a dialkyl-dimethyl-phosphonium salt, a cetrimide, hydrogen peroxide, 1-alkyl-1, 5-diazapentane, or chloro-cetyl pyridinium.

Table 1 synthesizes several biocides and processing aids that can be used in the present antimicrobial compositions. It also lists their common chemical names or trade names. Quaternary ammonium compounds, such as those commercially available under the names of Aegis ™ AEM 5700 (from Dow Corning, Midland, Michigan) and Crodacel QM (from Croda, Inc., of Parsippany, New Jersey), with certain surfactants such as alkyl polyglycosides, commercially available under the name of Glucopon 220 UP (from Cognis Corp., of Ambler, Pennsylvania), and chitosan glycolate, available under the name of Hydagen CMF and Hydagen HCMF (from Cognis Corp., of Cincinnati , Ohio), can mean improving the killing efficiency of poly-hexamethylene biguanide (PHMB) in a synergistic manner as will be demonstrated in the tables here. One should note that many of the biocides described here can be used alone or in combination in a variety of products that vary considerably in activity against microorganisms.

Table 1. Table of active reagents and Processing Aids * Used as aditi '/ or internal fades. These additives 30? typically compounds in terrooplastic resins (eg, polypropylene (PP) | to produce a concentrate which is then mixed dry with the virgin resin and co-extruded to produce fibers and fabrics that contain additive tails.) The additive is generally distributed throughout the volume of the fiber and enough of the additive is present on the surface of the fiber to provide antimicrobial activity.The concentration of the additive present on the surface of the fiber depends on several factors including the concentration of the additive in the melt in relation to the main body of the resin or type of resin, processing conditions and thermal history, resin cri.stalinity, and relative thermodynamic compatibility of the resin and the additive.It is understood that the additive must be compatible with the thermoplastic resin in the melt. for processing, and it is still desirable that the additive be ueno3 compatible with the resin in environmental conditions in such a way that the additive does not reach a certain extension to the surface of the thermoplastic fiber. The processing aids case amorphous compounds can be added to the main resin to facilitate the migration of the additive to the surface of the fiber. It is also understood that other active ingredients such as poly-hexaraethylene biguanide (PHHBi) can be compounded and co-extruded into various other thermoplastic resins.

Table 2 summarizes a number of exemplary composition examples according to the present invention containing various percentage combinations of the reagents listed in Table 1. Each reagent is presented in terms of percent by weight of the active agents in the total formula . Other components such as processing aids (eg hexanol, octanol, alkyl polyglycoside, or other surfactants) to highlight the wetting and / or uniformity of the treatment coating can be incorporated into the formula in a range from about 0.1 to about of 1 percent by weight, with respect to the total amount of the ingredients in the composition. In certain additions, processing aids are present in about 0.2 to 0.75 percent by weight concentration. The respective formulas are mixed in an aqueous solution. The formula can be diluted to any desired or required concentration level, depending on the treatment process to achieve the desired 0 predetermined added to the amount on the substrate for antimicrobial efficacy. For example, when a saturation process is used and the objective is to collect 100% wetting, one can prepare a solution that will be similar in amount added to the concentration added to the substrate. In other words, if one is targeting a one percent addition to the substrate, the concentration of the active agents in the solution of the treatment composition will also be 1 percent by weight. The individual components are listed using the trademark or common brand name only as a short form for identifying individual chemical reagents, and should not be constructed to limit the invention to any particular embodiment or commercial formula. The composition examples of Table 2, all can be used as topical coatings on a predetermined organic or inorganic substrate, and each is effective in producing at least 3 Logio (log reduction) in colony forming units (CFU) / ml) (CFU / g) within about 15-30 minutes. Desirably, the compositions are fast acting to kill the microbes within about 10 minutes, and in some cases within 5 minutes While poly-hexamethylene biguanide (PHMB) is a constituent of all the compositions in Table 2, Examples 1-6, and 16 illustrate formulas containing a mixture of at least two or three other useful active antimicrobial agents or aids of processing. Examples 7-13 show the formulas containing the poly-hexamethylene biguanide (PHMB) at a significant level (= 70-75 percent by weight). Examples 14-26 contain moderate levels of poly-hexamethylene biguanide (PHMB). In addition to exhibiting some antimicrobial properties, the quaternary ammonium compounds and surfactants help in wetting the materials of the treated substrate. It is believed that this can help to provide a more uniform treatment surface for the poly-hexamethylene biguanide (PHMB) on the substrate when used in combination. It is also thought that an improved wetting of the material allows the target organism to enter in better proximity and contact with the active halves of the antimicrobial agents on the surface of the material. Alcohol can also induce a similar effect on the antimicrobial properties of the material. A material treated with the solution, which combines the various agents, may exhibit greater efficiency in killing the organism than with poly-hexamethylene biguanide (PHMB) alone.

Examples 27-31 in Table 2A combine fast acting topical compositions with relatively slow acting biocides that are either embedded on the surface of the substrates or incorporated molten with the polymer based nonwoven fibers. The two types of antimicrobial formulas work in a complementary way. Fast acting topical antimicrobial compositions provide a rapid, sharp response against (eg, immobilizing and killing) any microbes that may contact an antimicrobial treated substrate, and the slower acting biocides embedded or incorporated on the substrate maintain the level of protection over an extended period of time of at least an additional 6-12 hours, more commonly of around 24 hours or even longer.

In certain embodiments, the antimicrobial composition includes combinations of biocide active agents that work against bacteria and viruses. For example, a composition may include: poly-hexamethylene biguanide (PHMB), quaternary ammonium cellulose, xylitol, citric acid, benzoic acid, surfactant, complex agent (for example polyvinyl pyrrolidone (PVP)), antistatic agent (eg example, Nicepole FL) as in Examples 1-6. A desirable antistatic agent is one that does not reduce the surface tension of the water by more than 20 dynes per centimeter. The present composition is desirably moderately hydrophilic; therefore, a drop of a formula applied to a surface can produce a contact angle of less than about 90 degrees with respect to, for example, a surface of the polypropylene substrate. The compositions have a pH in a range of about 2 to about 5 or 6. Preferred pH ranges are around 2.5-4 or 2.5-3.5, depending on the desired particular environmental conditions for use. Examples 1, 3, 22, and 23, contain an acrylic copolymer and isopropyl alcohol compound, which serves as an antistatic agent useful for treating non-woven fabrics such as those commonly found in medical fabrics.

An antimicrobial solution comprising a major active agent, including at least 0.1-99.9% by weight of poly-hexamethylene biguanxide (PHMB) by weight of active agents, and a secondary active agent selected from at least one of the following: alkyl polyglycosides, quaternized cellulose derivatives, quaternized siloxanes, surfactants, and organic acids. The final concentration for each of the active reagents and the processing aids on a treated substrate can be in the range of about 0.01-20 percent by weight. The exact concentrations may depend on the specific type of microorganism that is the target against and / or the nature of the coated substrate material. As an illustration, the general concentration ranges for each component individually in the examples are summarized in Table 22.

Table 22- Final Concentration of the Components of the Composition on a Substrate Treated The antimicrobial composition should be odorless for humans; that is, the composition is undetectable at least to the human olfactory system. This feature is important if the antimicrobial composition is used on face masks or other substrates that are in close proximity to the human nose.

Section B- Substrates and Their Properties A variety of different types of substrates can be treated or coated with the present antimicrobial composition. In accordance with certain embodiments, the substrate materials may include, for example, elastomeric membranes, films or foams, such as natural rubber or synthetic polymer latex, soft or hard rubber or plastic, plastics, or metal, glass or ceramic surfaces , such as they are with medical devices and / or surgical equipment and instruments, or physical hospital facilities. Alternatively, other embodiments may have substrate materials that are selected from either woven or non-woven fabrics. The woven fabrics can be made of natural fibers (for example, cellulose, cotton, linen, wool, silk) or a mixture of natural and synthetic fibers (for example, thermoplastics, polyolefin, polyester, nylon, aramid, polyacrylic materials). A wide variety of elastic or non-elastic thermoplastic polymers can be used to construct non-woven substrate materials. For example, without limitation, polyamides, polyesters, polypropylene, polyethylene, ethylene and propylene copolymers, polymers and copolymers of polylactic acid and polyglycolic acid, polybutylene, styrenic co-block polymers, catalyzed matalocene polyolefins, preferably with a density of less of 0.9 grams per cubic centimeter, and other types of polyolefins, for the production of various types of elastic or non-elastic fibers, filaments, films or sheets, or combinations and laminations thereof.

The beneficial attributes of the present invention are illustrated with the nonwoven materials treated with the antimicrobial compositions described in Section A, above. The treated non-woven fabrics can be made into a variety of products, which may include, for example, protective garments, gowns or aprons, and industrial clothing, as well as cover materials that can be used in the manufacture of bedding fabrics, fenestration covers , wrappers or pads. Other uses may be for various items of medical use, such as face masks, hand gloves, or foot covers, as well as personal care products, including swimwear, diapers, underpants, absorbent articles, cleaning cloths , and items for adult incontinence. The present antimicrobial compositions can be placed in a number of strategic locations to prevent bacterial activity. For example, in medical absorbent or personal care products, the compositions may be placed on either the outer or inner layer outside the surface contacting the skin, such as either a liner or matrix of an absorbent medium.

Another beneficial aspect of an article of the present invention is that the substrates and non-woven articles or fabrics subject of the present treatment can have durable antimicrobial characteristics. According to Table 3 shows, the present compositions do not produce zones of inhibition on the treated substrates. The antimicrobial coating formed on the surface of a substrate is not leached in the presence of aqueous substances or with aqueous bases and organic solvents under typical conditions of hospital use or for health care. Because antimicrobial agents are strongly absorbed or bound to the surface of the glove, the antimicrobial effect appears to be chemically more durable, thus providing a longer lasting antimicrobial benefit.

In addition, the non-fugitive nature of the antimicrobial coating can minimize microbial transmission and the development of resistant tensions of the so-called "super-insect". Traditional agents leach from the surface of the article, such as a glove, and must be consumed by the microbe to be effective. When such traditional agents are used, the microbe is poisoned and destroyed only if the dose is lethal. If the dose is sub-lethal, the microbe can adapt and become resistant to the agent. As a result, hospitals are reluctant to introduce such agents in areas with immunocompromised patients. In addition, because these antimicrobial agents are consumed in the process, the effectiveness of the antimicrobial treatment decreases with use. The antimicrobial compounds or polymers used with the present invention are not consumed by microbes. Instead, the antimicrobial agents break the membrane of the microbes that are present on the surface of the substrate treated with the antimicrobial. One problem with some conventional antimicrobial immobilization formulas is that immobilized microbes still remain alive and continue to produce cytotoxins or other pathogens. The present compositions immobilize and kill organisms, thereby preventing further potential contamination.

Unlike conventionally observed, the nonwoven materials treated with the present antimicrobial compositions greatly maintain their liquid barrier properties when they are segregated to the surface of the materials. It is believed that by controlling the topical placement of the antimicrobial composition, in which the poly-hexamethylene biguanide (PHMB) is confined to the bonded layer with superior or outermost spinning of a meltblown-melt-bonded substrate. Spunbonded (SMS), for example, one can prevent the creation of a liquid conduit in the underlying capable of the substrate material, thereby achieving the beneficial combination of barrier and antimicrobial properties. For example, in certain embodiments, one can manipulate the rheology of the antimicrobial composition during the treatment application process such that the composition is not transmitted in the inner layers of the treated substrate material. In addition, it is desirable to use a formula that exhibits a relatively high surface tension, greater than about 40 or 50 dynes per centimeter. Water-soluble polymers that are neither surface active or minimally active, such as ethyl hydroxyethyl cellulose or polyvinyl pyrrolidone, can be incorporated into the composition to minimize aqueous penetration into the substrate and preserve an acceptable level of barrier properties of the substrate. substratum. These types of water soluble polymer compounds are of good film formation and viscosity increase agents. A combination of film formation, low surface tension, and higher composition viscosity characteristics helps to create a uniform functional layer that limits the permeability of the treatment of the antimicrobial composition in the volume body of the non-woven structure bonded with spin-blown with fusion-linked with yarn (SMS), resulting in minimum detrimental impact on the barrier properties of the spunbond-melt-bonded knitted fabric as measured by the hydrostatic head pressure. Some examples of this concept can be found in Table 4, which shows that the impact of the antimicrobial treatment on the barrier properties of the spunbond-melt-bonded spin-bonded fabric is minimal. The treated substrate acquires a barrier protection performance measurement of = 55 millibars of hydrostatic head pressure, which is defined as level 3 barrier protection in accordance with the standards of the Association for the Advancement of Instrumentation. Medical (AAMI). A spunblown-melt-spunbonded (SMS) fabric of 1.5 ounces per square yard (~ 50 grams per square meter) with no treatment was used as a control and possesses an average hydrostatic head of 83.5 millibars. A similar fabric bonded with melt-spun yarn-bound yarn (SMS) treated by a conventional filling method with an iteration of the present antimicrobial composition containing only one poly-hexamethylene biguanide (PHMB) and a wetting agent, octanol , was shown to have a hydrostatic head pressure of around 62 millibars, or a drop of barely 26% as compared to the control. Desirably, the hydrostatic head pressure is around 64-68 or 69 millibars. By incorporating a viscosity modifying agent and applying the composition via a Meyer rod, however, the hydrostatic head is observed to improve to around 66-67 millibars, or a drop of around only 20% compared to the control . Therefore, with the present invention, one can make a fabric that maintains good barrier properties as well as good antimicrobial properties by using the appropriate composition and application technique. In addition, placing the antimicrobial chemistry on the surface of the substrate will make the biocides more readily available to interact with the pathogens, thus improving overall efficacy. Despite the use of film forming chemistries in the composition, the spunbond-melt-bonded, spunbond (SMS) coated substrate also maintains its good air permeability characteristics to ensure the thermal comfort of the wearer.

Another attribute of the present invention is that the coated nonwoven substrate imparts antistatic properties when an antistatic agent, such as an acrylic copolymer and isopropyl alcohol or guanidine hydrochloride and sorbitol, are added to the composition. Table 5 synthesizes the resulting barrier and antistatic properties of a 1-ounce substrate per square yard of spunbond-meltblown-bonded (SMS) bond treated with a polyhexamethylene biguanide (PHMB) and film-forming agents and antistatic co-actives in accordance with a version of the present composition. The treated substrate achieves a barrier protection performance measure of at least standard AAMI barrier level 2, which is accepted as = 20 mbar head pressure. To the extent that Examples C and D in the Table exhibit very fast static decay (<0.5 seconds) and good barrier properties (~ 42-47 mbar, which is ~ 15-23% drip compared to the control), These examples are preferable.

Embodiments of the present antimicrobial composition may include a protective article, such as gloves, face masks, surgical or medical gowns, covers, shoe covers, or fenestration covers. For purposes of illustration, the beneficial properties of the present invention may be incorporated in a face mask containing a combination of one or more antimicrobial agents and co-active agents that rapidly inhibit and control the growth of a broad spectrum of microorganisms on the surface of the product both in the presence and absence of dirt loading. The antimicrobial coating, which quickly kills or inhibits, can be selectively placed on the outer nonwoven that faces the mask rather than across the entire product. The antimicrobial agents are unleached from the surface of the mask in the presence of fluids, and / or are non-recoverable on particles that can be peeled off by the mask in use and potentially inhaled by the user as measured using the blow-off test protocol. he.

The cross-blow test and analytical work produce evidence that the present combination antimicrobial solution treatment is safe to use with face masks and will not fall out of the mask liner under normal conditions of use. By using samples of yarn-bound material treated with the present antimicrobial solution, we performed blow-through tests to simulate respiration for the use of face mask products for a period of 8 hours. The materials for masks, including the samples bound with treated yarn, were compressed and kept fixed between two conduits. Humidified air is blown through the duct apparatus and any chemical treatment that can delaminate from the material is collected in a jar.

In some embodiment, the antimicrobial agents include a variety of biocides (as opposed to antibiotics), in particular, for example, polymeric bigunaids, such as biguanide polyhexamethylene (PHMB) sold under various brand names, such as Cosmocil CQ, Vantocil, etc. . Alternatively, the face mask may contain an antimicrobial agent or agents that prevent or minimize the transfer by contact of a broad spectrum of viable microorganisms from the surface of the mask to another surface that comes in contact with the mask both in the presence and absence of dirt load. The face mask can be adapted to have bacterial filtration efficiency (BFE) of greater than or equal to about 85-90% as measured in accordance with test number F2101 of the American Society for Testing and Materials (ASTM). Preferably, the mask exhibits a bacterial filtration efficiency (BFE) of greater than or equal to about 95%. More preferably, the mask has a bacterial filtration efficiency of more than or equal to about 99%. The face mask may exhibit a differential pressure of less than or equal to 5 millimeters of water per square centimeter, as measured by the F2101 test of the American Society for Testing and Materials (ASTM) to ensure the respiratory comfort of the product. Desirably, the differential pressure is less than or equal to 2.5 millimeters of water per square centimeter. The face mask can have a particle filtration efficiency (PFE) of greater than or equal to about 85-90% as measured by the Latex Particle Challenge test (test number F2299 of the American Society for Testing and Materials (ASTM)). Preferably, the particle filtration efficiency (PFE) is greater than or equal to 95%. More preferably, the particle filtration efficiency (PFE) is greater than or equal to 99%. The face mask may have a fluid penetration resistance of greater than or equal to 80 millimeters (Hg) against synthetic blood as measured in accordance with Test F1862 of the American Society for Testing and Materials (ASTM). Preferably, the mask exhibits a fluid penetration resistance of greater than or equal to about 120 mm Hg. More preferably, the mask exhibits a fluid penetration resistance of greater than or equal to about 160 mm Hg.

In another iteration, the advantages of the present invention can be incorporated in an antimicrobial cover gown. The gown contains a combination of antimicrobial agents and co-active agents that rapidly inhibit and control the growth of a broad spectrum of microorganisms on the surface of the product both in the presence and absence of dirt loading. The gown may contain, prevent or minimize the transference by contact of a broad spectrum of viable microorganisms from the surface of the gown to other surfaces that come in contact with the gown both in the presence and absence of dirt loading. As with the face mask, the antimicrobial agents that cover the surface of the gown are also stable associated with the substrate and do not leach from the surface of the gown in the presence of fluids. The gown may possess a fluid barrier characteristic, as measured by the hydrostatic head test, of equal to or more than about 20 mbar (level 2 AAMI). Preferably, the fluid barrier is measured to be equal to or greater than about 50 millibars (level 3 AAMI). More preferably, the fabric of the gown is also resistant to blood and viral penetration, as defined by standards of tests numbers F1670 and F1671 of the American Society for Testing and Materials (ASTM). The fluid barrier can be equal to or greater than about 100 millibars.

Antimicrobial-treated gowns can dissipate 50% of an electrostatic charge of 5000 volts in less than 0.5 seconds as measured by the static decay test using Standard Test Method No. 40.2 (95) of the Association of Industries. Nonwoven Fabrics (INDA). Generally described, a 3.5-inch by 6.5-inch sample is conditioned, including the removal of any existing load. The sample is then placed in an electrostatic decay test kit and charged to 5000 volts. Once the sample has accepted the charge, the charging voltage is removed and the electrodes are grounded. The time it takes for the sample to lose a previously fixed amount of the load (for example, 50% or 90%) is recorded. The electrostatic decay times for the samples referred to herein were tested using the calibrated static decay meter model number SD 406C and 406D, available from Electro-Tech Systems, Inc., of Glenside, Pennsylvania. Preferably, the gown material can dissipate 90% of a 5000 volt load in less than 0.5 seconds. More preferably, the gown will dissipate 99% of a charge of 5000 volts in less than 0.5 seconds. In addition, the gown material has a Class I flammability rate as measured by the flame propagation protocol (CPSC 1610 and NFPA 702). Both static decay and flame propagation requirements are critical in a hospital facility to minimize the same potential of a fire due to accidental static discharges. It is important to note that not all the options of the substrate and the antimicrobial composition will lead to this advantageous fixation of the properties and codes that pass both of these criteria in addition to having antimicrobial properties that are the preferable additions.

Section C - Process Methods for Achieving the Desired Properties The antimicrobial compositions can be applied topically to the outer surfaces of the filaments of the non-woven fabric after they are formed. Desirably, a uniform coating is applied on the surfaces of the substrate. A uniform coating refers to a layer of antimicrobial agents that do not aggregate only at selected sites on a surface of the substrate, but have a relatively homogeneous or even distribution over the surface of the treated substrate. Desirably, the processing aid must evaporate or quench once the antimicrobial composition dries on the surface of the substrate. Suitable processing aids may include alcohols, such as hexanol or octanol. Note that the terms "surface treatment", "surface modification", and "topical treatment" refer to an application of the present antimicrobial formula to a substrate and are used interchangeably, unless otherwise indicated.

The non-woven fabrics that are treated with an antimicrobial coating of the present invention can be manufactured in accordance with a number of processes. In an illustrative example, a method for preparing an antimicrobial-treated substrate involves providing a hydrophobic polymer substrate and exposing at least a portion of the substrate to a mixture that includes at least one antimicrobial active agent (e.g., polyhexamethylene biguanide (PHMB )) and at least one co-active agent (e.g., AEGIS AM 5700) and at least one processing aid (e.g., alkyl-polyglycoside, or other surfactants). A suggested combination includes contacting the substrate with a mixture that includes an antimicrobial agent, a wetting agent, a surfactant, and a rheology control agent. These components of the treatment composition can be combined in a water mixture and applied as an aqueous treatment. The composition of the treatment may also include other components, such as antistatics, skin care ingredients, antioxidants, vitamins, botanical extracts, essences, odor control agents, and color. The final amount of the active reagents on the treated substrate can be diluted to a desired or predetermined concentration.

In accordance with an embodiment, the antimicrobial composition can be applied to the material substrate via conventional saturation processes such as the so-called "dip and squeeze" or "fill" technique. The "dip and squeeze" or "fill" processes can coat both sides of and / or through the volume of the substrate with the antimicrobial composition. When immersed in a bath, the antimicrobial solution is a unit medium containing all the components, or in a process of subsequent multiple steps, other desired components can then be added to the antimicrobial base layer. For example, a formula of a unitary antimicrobial solution may include leveling and / or antistatic agents. On substrates containing polypropylene, an antistatic agent can help dissipate the accumulated static charge of mechanical friction. An antistatic agent can be added to the antimicrobial solution, and the mixture can be introduced simultaneously to the material substrate in an application step. Alternatively, the antistatic solution can be applied using a spray, then the antimicrobial solution in a second step.

In certain product forms, where one wishes to treat only one side and not the inner layers or the opposite side of the sheet substrate, in which the substrate material is layered to another sheet layer (eg, filter media). or barrier) which is without the antimicrobial treatment, other processes are preferable such as in a rotary grid, reverse roller, Meyer rod (or wire rod), engraving, slot matrix, aperture coating, or other similar techniques , relatives to people in the nonwovens industry. (See, for example, detailed descriptions of these and other techniques available from Faustel Inc. of Germantown, Wis. (Www.faustel.com). One may also consider printing techniques such as flexographic or digital techniques. one may use a combination of more than one coating to achieve controlled placement of the treatment composition Such combination may include, but is not limited to, a reverse etching process, followed by a Meyer rod process.Alternatively, the antimicrobial composition can be applied through an aerosol spray on the surface of the substrate The spray apparatus can be used to apply the antimicrobial solution and / or antistatic agent only on one side of the substrate sheet or on both sides separately if desired. Antistatic agent can be applied to the substrate in a secondary step, for example, using a spray system or any other conventional application process. On sheet materials, treated nonwoven substrates can achieve at least one hydrostatic head greater than 20 millibars. The antimicrobial coatings are applied in at least a single layer on the fabrics joined with spunblown-melt-spunbonded (SMS) yarns. Alternatively, one can use a molten extrusion process to incorporate an antimicrobial agent into the material followed by topical application of a second antimicrobial agent or co-active agent of an aqueous solution. In addition, other ingredients may also be added during the molten extrusion to improve for example: a) wetting of the material if desired, b) electrical conductivity or antistatic properties, c) skin emollient, d) antioxidants, etc.

With reference to Figure 1, an exemplary process for the application of a treatment composition of the present invention to one or both sides of a displaced tissue will be described. It should be appreciated by those skilled in the art that the invention is equally applicable to an online treatment or a separate step out of line of treatment. The fabric 12, for example, a non-woven laminate bonded with meltblown or meltblown or spunbond-meltblown-spunbond (SMS), is directed under a support roll 15 to a treatment station including headstocks. Rotary spray 22 for the application to a side 14 of the fabric 12. An optional treatment station 18 (shown in phantom) which may include rotary spray heads (not shown) may also be used to apply the same treatment composition or other composition treatment to the opposite side 23 of the tissue 12 directed on the support rollers 17 and 19. Each treatment station receives a supply of treatment liquid 30 from a container (not shown). The treated fabric can then be dried if needed when passing over drying drums (not shown) or other drying means and then under the supporting roll 25 to roll up like a roll or to be converted for use for which it is intended. For a polypropylene fabric, drying can be achieved by heating the treated fabric at a temperature from about 220 degrees Fahrenheit to 300 degrees Fahrenheit, most desirably at a temperature from 270 degrees Fahrenheit to 290 degrees Fahrenheit, by passing over a heated drum to fix the treatment composition and complete the drying. The drying temperatures for other polymers will be apparent to those skilled in the art. Alternative drying media include ovens, air dryers, infrared dryers, microwave dryers, air blowers, etc.

Figure 2 illustrates an alternative arrangement and method of applying a treatment composition of the present invention. The alternative arrangement and the method use a saturation application step or dip and squeeze. As shown in Figure 2, the fabric 100 which for example can be a carded and bonded fabric of 2. 50 ounces per square yard of a nonwoven surfacing material passes over guide roll 102 and into bath 104 containing a mixture of the antimicrobial water treatment composition. The treatment time can be controlled by the guide rollers 106. The pressure point between the tightening rollers 108 removes the excess treatment composition that is returned to the bath by a collection tray 109. Drying drums 110 remove the remaining moisture. If more than one treatment composition is employed, the dip and squeeze may be repeated and the fabric 100 may be advanced to and immersed in additional baths (not shown).

Various other methods can be used to contact a substrate with the composition or treatment compositions according to the invention. For example, a substrate can be printed by means of printing rollers or other coating steps, or spray techniques that can be employed. Preferably, the composition or treatment compositions are applied as a cover layer on the substrate by a Meyer rod, reverse gravure or flexographic techniques, for example, such that the treatment composition forms a uniform and homogeneous layer on the substrate with minimal penetration of the treatment composition into the volume of the substrate. The coating of the overlayer, in general, results in a more uniform distribution of the antimicrobial treatment on the substrate and allows the antimicrobial agents to be more readily available on the surface of the substrate. The overcoat coating technique also results in maintaining better barrier properties of the substrate.

As Table 5 shows, the restriction of antimicrobial and antistatic agents in certain layers of the substrate (for example, the spun-bonded layer in the spunblown-melt-bonded (SMS) bonded structure) helps maintain the barrier and improve the antistatic properties of the substrate. The hydrostatic head is improved and the antistatic decay achieved with the use of viscosity modifiers with minimal surface activity. The use of processes that apply a coating on a surface layer that minimally penetrates the volume of the substrate also promotes improved barrier properties as compared to a saturation process for example.

A nonwoven fabric or laminate can be treated with compositions and methods of the present invention to impart a broader antimicrobial spectrum and antistatic properties as desired or at predetermined locations on the substrate, while maintaining desired barrier properties. In addition, the components of the treatment composition can be applied in separate steps or in a combined passage. It should also be understood that the antimicrobial surface treatment method and treatment of the non-woven materials with topical application of the ingredients of this invention can incorporate not only multiple ingredients for improved antimicrobial performance but can also be used to incorporate antistatic agents that can be allowed to dissipate. the accumulated static charge.

The selection of the coating process is dependent on a number of factors, including, but not limited to: 1) viscosity, 2) solution concentration or solids content, 3) the current coating addition on the substrate, ) the surface profile of the substrate to be coated, etc. Frequently, the coating solution will require some modifications in the formula of the concentration (or solids content), viscosity, wetting or drying characteristics to optimize the treatment or coating performance.

The present invention is further illustrated by the following examples which are representative of the invention.

Example 1. Topical treatment of a substrate using a saturation process.

For illustration purposes, typically, an aqueous formula of 500 milliliters is prepared containing 0.5 percent by weight of polyhexamethylene biguanide (PHMB) + 3 percent by weight of citric acid + 0.3 percent by weight of Glucopon 220 UP + 96.6 by percent by weight of water, as shown in Table 3. The relative concentrations of the examples in Table 3 are normalized to 100% solids for each ingredient. For example, 0.5 percent by weight of the polyhexamethylene biguanide (PHMB) in Example 1, indicates that 2.5 grams of Cosmocil CQ (which is 20% biguanide polyhexamethylene solids (PHMB)) was in fact used in 100 grams of solution to achieve in fact 0.5 percent by weight of polyhexamethylene biguanide (PHMB) in the final composition.

The aqueous formula is completely mixed for about 20 minutes using a laboratory shaker (Stirrer RZR 50 from Caframo Ltd., Wiarton, Ontario, Canada). Alternatively a high cut mixer can also be used. After the aqueous composition (or bath) has been mixed and homogenized, it is poured into a glass pan or coated with Teflon. Then, typically an 8 inch by 11 inch hand sheet substrate is immersed in the bath for saturation. Generally, complete saturation of the substrate is achieved when the substrate becomes translucent. After complete saturation, the substrate is pressed between two rollers, with a stationary roller and a rotating roller, of a laboratory drainer no. LW-849, type LW-1, made by Atlas Electrical Device Co. , from Chicago, Illinois. After the sample is pressed and passed through the rollers, the excess saturant is removed and the wet weight (Ww) is immediately measured using a Mettler PE 360 balance. The saturated and pressed sample is then placed in a drying oven at about 80 degrees centigrade for about 30 minutes or until that a constant weight is reached. After drying, the weight of the treated and dried sample (d) is measured. The amount of treatment that is on the substrate can be measured gravimetrically by first calculating the percentage of collected moisture (% WPU) using equation 1,% WPU = (Ww-Wd / Wd) x 100 (Equation 1) where, w = wet weight of the saturated sample after the pressure, Wd = dried weight of the treated sample, Then, the percentage added on the sheet is calculated using equation 2 below. % added =% WPU x bath concentration (% by weight) (Equation 2) For example, if the total concentration of the bath is 3.8 percent by weight, and the calculated percentage of collected moisture (% WPU) is 100% then the addition in the substrate is 3.8 percent by weight. Now it is possible to control the addition on the substrate by controlling the percentage of moisture collected (% WPU) and the concentration of the bath. At a given concentration of the bath the percentage of collected moisture (% WPU) can be varied to a certain extent by the variation of the pressure of the pressure point of the laboratory drainer. Generally, higher the pressure of the pressure point, more saturation (or treated composition) is squeezed from the substrate, the lower the percentage of collected moisture (% WPÜ) and the lower is the final addition on the substrate.

Example 2. Topical treatment of a substrate using overcoating processes to. Reverse Roller Coating: In the coating of the reverse roller, the coated composition is measured on the roller of the applicator by the precision setting of the opening between the upper measuring roller and the application roller below it. The coating is removed from the application roller by the substrate as it passes around the support roller at the bottom. The diagrams in Figures 3A-C illustrate a reverse roll roller coating process 3, even when roll versions 4 are common. In the reverse engraving coating, the actual coating material is measured by the engraving on the roller before being cleaned as in a conventional reverse roller coating process.

Photogravure Coating The photogravure coating depends on the engraving roller that runs in a coating bath that fills the printed dots or lines of the roller with the coating material. The excess coating on the roller is removed by the doctor blade and the coating is then deposited on a substrate as it passes through the engraving roller and a pressure roller. Figures 4A and 4B illustrate a schematic representation of the typical arrangements of gravure coaters. Photogravure offset is common, where the coating is deposited primarily on an intermediate roller before being transferred to the substrate. c. Meyer rod coating (measuring rod) In a dipstick coating, the wire-wound measuring rod, sometimes referred to as the Meyer rod, allows the desired amount of coating to remain on a substrate. The excess coating is deposited on the substrate as it passes over the bath roll. The amount is determined by the diameter of wire used on the rod. This process is considerably tolerant of the non-precision engineering of the other components of the coating machine. Figure 5 shows a schematic representation of a typical placement.

In another embodiment, typical antimicrobial compositions can be applied cooperatively with slow acting or biocidal agents that are either incorporated during extrusion with melt as part of the polymer melt formulation of certain nonwoven fibers or filaments, or by generating fibers with biocides embedded in the surface of each fiber. As mentioned above, examples 27-31 in Table 2 are formulations cooperatively bringing together topically fast topical antimicrobial compositions with biocidal formulations embedded and extruded together from slower acting internal melt. Adjustment of the concentration of the incorporated biocides can control the distribution and overall prevalence of the biocidal agents on the surface of the fiber.

Section III- Antimicrobial Test Methods.

A. Sample preparation The test organisms are cultured in 25 mL of an appropriate broth medium for about 24 + 2 hours at 37 + 2 ° C on a wrist-action shaker. The bacterial culture is then transferred by placing about 25% of aliquot in 25 ml of broth and cultivating again for about 24 + 2 hours at 37 24 + 2 ° C. The organisms are then centrifuged and washed three times with salt water buffered with phosphate (PBS). The organisms are then suspended in salt water buffered with phosphate to obtain an inoculum of approximately lxlO8 CFU / mL.

Test items and control samples are exposed to the ultraviolet light source for about 5-10 minutes per side before the test to ensure that the samples are healthy before inoculation with the bacteria. The test materials are contacted with a known population of test bacteria from the inoculum for a specific period of time. A sample is then coated at the end of the exposure time to list the surviving bacteria. The logio reduction forms the control material and the original population is calculated using the following formula: Logio control * -Logio CFU / sample test article = reduction Logio- * CFU / sample of control or theoretical samples CFU / sample.

After exposure of the bacteria to the surface of our treated product for a designated amount of time (~ 10-30 minutes), the substrate is placed in a bottle and a buffer is added to elute the microorganisms off the substrate before cover them to see how many remain alive. This buffer contains a chemical to deactivate or "neutralize" the antimicrobial agent to (a) stop the active agent from killing the organisms after a designated period of time and (b) prevent artifacts from arising from the exposure of microorganisms to the antimicrobial in the solution rather than only on the substrate. Because each chemical used as an antimicrobial agent is a little different (for example: cationic, non-ionic, metal etc.), a different neutralizer was feasibly added in each case to close the antimicrobial at the desired endpoint of the experiment . These neutralizers are pre-screened to ensure that they do not affect microorganisms.

The neutralizer used can be selected from a list that is commonly used in the field. These media, non-ionic detergents, bisulfate, lecithin, lefin broth, thiosulfate, thioglycolate and pH buffers, a method similar to those described in the American Society for testing and materials, standard practices for evaluating inactivators of antimicrobial agents used in disinfectants, antiseptics or preserved products, American Society for Testing Materials 1054-91 (1991) can be used.

B. Dynamic agitator bottle protocol This test was used to quickly analyze different antimicrobial combinations to look at the synergistic effects. The experimental procedure is based on the ASTM E 2149-01 standard. In short, the test is carried out by first adding a 2"x 2" sample of treated material to a bottle containing 50 mL of a buffered salt water solution. The bottle is then inoculated with the challenge organism (6.5-7 logio total) and agitated by mechanical means for a designated period of time. At specific time points, a sample of the solution is then removed and coated. Finally, the plate is incubated, examined for microbial growth, and the number of colony forming units counted. The reduction of log in organisms is measured by comparing the growth on the experimental plate with the control plates without antimicrobial treatment.

C. Zone of inhibition protocol to measure runoff.

ASTM dynamic agitation bottle test and zone inhibition protocols ASTM E 2149-01 and AATCC 147-1998 to be used to analyze the leachate of the test material. To establish if the antimicrobial coating applied on the materials is truly stable and does not drain from the substrate surface, two tests were used. First according to the American Textile Chemicals Association and colouristic test protocol (ATCC) -147, in a dry runoff test, the treated antimicrobial material is placed on an agar plate sown with a known amount of organism population on the plate surface. The plate is then incubated for about 18-24 hours at around 35 ° C or 37 ° C + 2 ° C. Then the agar plate is evaluated. Any runoff of the antimicrobial from the treated material will result in a zone of inhibited microbial growth. As summarized in the data from the examples that follow, we did not find zones of inhibition, indicating that there were no antimicrobial agents that would run off from any of the samples tested.

Secondly, in a wet runoff area of the inhibition test, according to the test protocol of the American Test Society and Materials (ASTM) E 2149-01, involving a dynamic agitation bottle, we placed several pieces of a substrate coated with antimicrobial in a solution of 0.3 mM phosphate (KH2P04) at a buffer pH ~ 6.8. The piece of material was allowed to settle for 24 hours in solution and then the supernatant of the solution was extracted. The extraction conditions involved where 30 minutes at room temperature (~ 23 ° C) with 50 ml of buffer in an Erlenmeyer 250 ml bottle. The bottle was shaken on a wrist shaker for one hour + 5 minutes. About 100 microliters (pL) of supernatant were added to an 8 millimeter well cut into a second sown agar plate and allowed to dry. After 24 hours at 35 ° C + 2 ° C, the agar plate was examined for any indication of activity inhibition or microbial growth. The absence of any zones of inhibition suggests that there was no runoff of the antimicrobial from the surface of the glove into the supernatant, or its effect on the microorganism on the agar plate.

In summary, these protocols are carried out by incubating an inoculated placar containing either the current treated material or a solution that has been exposed to the treated material. This plate is then analyzed for areas of inhibition of organism growth to detect if the antimicrobial has run off the material or into the solution.

D. Rapid Death Protocol In another aspect, to assess the effectiveness of how quickly killed applied antimicrobial agents, we employ a rapid germicidal direct contact test developed by Kimberly-Clark Corporation, this test better simulates real-world work situations in which Microbes are transferred from one substrate to another through direct contact of short duration. This test also allows to assess whether contact with the surface of material treated in one position will kill microbes quickly, while the solution-based test of the ASTM E 2149-01 protocol tends to provide multiple opportunities to make contact and kill microbes, which is less realistic in practice.

Briefly, microorganisms (6.5-7 logio total) suspended in the salt-buffered water solution are placed on a substrate with or without the antimicrobial coating. The microbial suspension (250μl for bacteria, 200μl for virus) is spread over an area of 32 cm2 per minute using a Teflon® spreader device. After the spreading, the substrate is allowed to sit for a specific contact time. After the contact time, the substrate is placed in an appropriate neutralizer and is stirred and swirled thoroughly. The samples are taken from the neutralizer and coated on the appropriate means to obtain the number of viable microbes recovered. The number of microbes recovered from an untreated substrate is compared to the number recovered from a treated substrate to determine the effectiveness of the antimicrobial coating. The data in Tables 6-10 indicate the reduction in viable microbes recovered from a spunbonded or one SMS material compared to an SMS material or bound with untreated yarn.

D .1 Rapid Death Protocol for Masks and Robes A supply culture used to challenge both coated and uncoated materials was prepared according to the following. Organisms evaluated included S. aureus (MRSA) ATCC 33591, S. aureus ATCC 27660, Enterococcus faecalis (VRE) ATCC 51299, and / or Klebsiella pneumoniae ATCC 4352. The appropriate organism of freezer supply and culture in 25 milliliters of TSB medium in a conical tube of 50 milliliters capped loose, stirred at 200 revolutions per minute 24 + 6 hours at 35 + 2 ° C. After 24 hours of incubation ??? of culture were used to inoculate a few seconds 25 ml of TSB media in a 50 ml conical tube. This is incubated and stirred at 200 revolutions per minute, 24 + 6 hours, at 35 + 2 ° C. After another 24 hours, the suspension is centrifuged at 9000 revolutions per minute (4 + 2 ° C for 10 minutes). The resulting supernatant is replaced with 25 ml of sterile PBS and swirled for one minute to resuspend the cells. The resulting cell suspension is diluted with PBS to achieve an objective inoculum concentration of approximately 107 CFU / ml. This final work inoculum solution may or may not contain a 5% dirt load (bovine serum albumin).

The samples of material are challenged with 250 μ? of the inoculum added to half the material attached to the test material challenge device (50 milliliter conical tube). The challenge of inoculum is spread over the material for one minute using a sterile Teflon® police. After which the suspension is allowed to sit for the additional time necessary to reach the desired contact time of 10 or 30 minutes. Upon completion of the contact time, the material is aseptically transferred to the individual sample containers containing 25 milliliters of LEB extractant and swirled thoroughly. The sample is removed by placing the containers on an orbital shaker (200 revolutions per minute) for 10 minutes. After which the number of microbes is measured by a viable plate count.

E. Transfer Protocol of Concho Microorganisms (total of 6.5-7 logio) suspended in a buffered salt water solution are placed on a substrate with or without an antimicrobial coating. The microbial suspension (250 μ? For bacteria; 200 μ? For virus) is spread over an area of 32 cm2 for one minute using a Teflon® spreading device. After spreading, the substrate is allowed to sit for a specified contact time. After the contact time, the substrate is inverted and placed on a porcine skin for one minute. While it is on the skin, a continuous weight of ~ 75 g is applied evenly to the substrate on the skin. After a minute on the skin, the substrate is removed, placed in an appropriate neutralizer and swirled and swirled thoroughly. The samples are taken from the neutralizer and coated with an appropriate medium to obtain the number of viable microbes recovered. The number of microbes recovered from an untreated substrate is compared to the number recovered from the treated substrate to determine the effectiveness of the antimicrobial coating. To examine the difference in microbes transferred to porcine skin from a treated substrate against an untreated one, two 2-milliliter aliquots of an extractant-buffered solution were placed on the skin where the substrate was contacted. The skin surface was scraped using a Teflon® spreading device with each two milliliter aliquot being harvested after scraping. The extractant collected from the skin was then smoothed with respect to the number of viable microbes in the same manner as the substrate. The effective reduction in contact transfer was determined by comparing the number of microbes extracted from the skin contacted with an untreated substrate against the number extracted from the skin contacted with the treated substrate. Tables 11A and 11B present the reduction in contact transfer for the spunbond and SMS substrates. The data in these tables indicate that the material bonded with treated yarn was able to reduce the transfer of bacteria to the pig skin by more than 4 log (>99.99%) compared to the one with untreated yarn. Similar results were seen with the SMS material treated with more than one reduction of 5 Log in transfer being observed (> 99.999%). These tests show the effectiveness of the material treated to reduce the spread of microbes through physical contact.

F. Blow Test Protocol through Using a proprietary Kimberly-Clark test method, we were able to analyze the acceptance of non-woven substrates for face mask applications. In the blow-through test, a 125 ml beater (from ACE Glass Inc.) containing approximately 60 ml of deionized water is contacted with an air supply using the pipeline (eg Nalgene pipe). The output of the kicker is connected to a second and a third puncher in parallel each of which contained approximately 40 milliliters of deionized water, in order to moisten the air. The outputs of the second and third tappers are linked and directed to a flow regulator. The sample to be tested is cut into a diameter of 10 centimeters and placed between two funnels; a front funnel and a posterior funnel having an upper internal diameter of 102 millimeters. A first puncher containing about 60 milliliters of deionized water (for example Milli-Q water) is connected to an air barb on a cover with a Nalgene tube (5/16"). An outlet pipe (1/4") ) from the first beater is equipped with a "tee" to make contact with a second and third puncher in parallel, both containing about 40 milliliters of deionized water. A second joins the output lines from the two tappers to an input of a flow regulator. The outlet from the flow regulator (5/16") is connected to a stem of the funnel with the sample, and the tube from a subsequent funnel is directed to a bottle that receives 500 milliliters volume containing about 120 milliliters of deionized water.

The air is supplied to the first beater and is adjusted to 30 SLPM with the flow regulator in line. An air valve is open on the cover and the air flow is adjusted to 30 SLPM. Moistened air is blown through the sample material for about 8 hours at a constant flow rate. After about 8 hours, the air valve is closed and the tubing is removed from the posterior funnel. The pipe is then pulled upward of the water in the receiving bottle and washed internally and externally inside the receiving bottle with small amounts of deionized or purified water (eg Milli-Q water). The extracted water is poured into three 60 ml I-CHEM vessels and placed in the vacuum evaporation system (Labconco RapidVap® Model 7900002 at 100% speed, 85 ° C, 90 minutes, 180 mbar vac) until it is dry The extract is reconstituted in about 1.0 milliliters of deionized water, filtered and injected onto a high pressure liquid chromatograph (HPLC). The high-pressure liquid chromatograph system was an Agilent 1100 quaternary high-pressure liquid chromatograph with a SynChropak Catsec 100A (4.6 x 250 mm) coluum, an eluent of 0.1% trifloroacetic acid / acetonitrile (95/5), a flow rate of 0.5 milliliters / minute, an injection of 25 microliters, an improved Sedex detector 55, 43 ° C, N2 at 3.4 bar and elusion with Cosmocil at 5.7 minutes and with Crodacel at 6.3 minutes. The antimicrobial agents are detected and quantified using liquid chromatography.

G. Electrostatic decay test The following describes the static or electrostatic decay test method employed in the present invention. This method has also been reported in U.S. Patent No. 6,562,777, column 10, lines 1-16, incorporated herein. This test determines the electrostatic properties of the material by measuring the time required to dissipate a charge from the surface of the material. Except, as specified, this test was carried out in accordance with the INDA standard test methods: IST 40.2 (95). Generally described, a specimen of 3.5 inches by 6.5 inches is conditioned, including the removal of any existing load. The specimen is then placed in an electrostatic decay test kit and charged to 5, 000 volts. Once the specimen has accepted the charge, the charging voltage is removed and the electrodes are grounded. The time it takes the sample to lose a pre-set amount of charge (eg 50% or 90%) is recorded. The electrostatic decay times for the samples mentioned herein were tested using a calibrated static decay meter model No. SDM 406C and 406D available from Electro-Tech Systems, Inc., of Glenside, PA.

Section IV-Empirical Examples. A. The following tables present illustrative examples of the beneficial synergistic effect of the present invention compared to some common antimicrobials currently available.

Tables 12-15 provide a baseline reference of the relative efficacy of the individual antimicrobial compounds alone at a concentration of 1.0%, when applied topically to samples of different woven fabrics (eg spunbonded, spunbonded- blown with fusion-linked with spinning (SMS), blown with fusion); against a broad spectrum of microorganisms (eg gram-positive and gram-negative bacteria and fungi, mold and yeast) after a contact time of 1.5 or 15 minutes for each kind of substrate. The baseline data shows that a composition containing 1% by weight of PHMB can provide a reduction of > 3 logio in the colony forming units (CFU) within minutes.

Table 12- Reduction results Logio of dynamic agitation bottle against S. aureus (ATCC 6538) Table 13- Logio reduction results of dynamic agitation bottle against P. Aeruginosa (ATCC 9027).

Table 14- Log10 reduction results of dynamic agitation bottle against A. Niger (ATCC 16404).

Table 15- Logio reduction results of dynamic agitation bottle against C. Albicans (ATCC 10231).

We have discovered that the combination of other agents allows the use of less PH B, which provides competitive cost savings, while still achieving the same or better level of antimicrobial activity as before. Tables 10-14 below show the synergistic effect of the present compositions of the invention against gram positive and gram negative bacteria on a nonwoven fabric. The data in Tables 16-20 certify the rapid kill kinetics of the present compositions, at lower PHMB levels in the presence of selected co-active agents (Table 1) when compared to the PHMB acting alone. The antimicrobial action can achieve a significant microbial reduction within a few minutes.

Table 16- Logio reduction of dynamic agitation bottle against S. aureus (ATCC 6538).

Table 17- Logio reduction results of dynamic agitation bottle against A. aureus (ATCC-6538).

Table 18-Logi0 reduction results of dynamic agitation bottle against P. Aeruginosa (ATCC 9027) Table 19-Logy reduction results of dynamic agitation bottle against S. aureus (ATCC 6538) Table 20-Logi0 reduction results of dynamic agitation bottle against P. Aeruginosa (ATCC 9027) The particular compositions of the tables are examples of the present invention to illustrate their non-additive effect, and do not necessarily limit the invention.

In addition, the inclusion of organic acids and alcohols has a significant beneficial impact against viruses. As shown in Table 21, the efficacy against viruses and against microbes of PHMB is enhanced when combined with other organic acids, such as citric, benzoic, propionic, salicylic, glutaric, maleic, ascorbic acids. or acetic and other joint additives. The data showed an anti-viral / anti-microbial reduction in the order of > 3 log10 CFU against common pathogens.

Table 21-Logy reduction results of dynamic agitation bottle for (0.5% PHMB, 7.5% citric acid, 2% N-polyglycoside alkyl) against positive gram and negative gram bacteria.

According to another embodiment, gloves made of either woven or nonwoven textiles, leather or elastomeric materials (for example natural rubber latex or synthetic polymer) can be either sprayed with a heated solution or immersed in a heated bath containing a antifoaming agent, and a repetition of the present antimicrobial compositions. The solution is heated by the spray atomizer or in a heated canister before entering the atomizer while spinning in a forced air dryer. This method only allows the outside of the glove to be treated more efficiently with less solution and still provide the desired antimicrobial efficacy, better adhesion of the antimicrobial to to mitigate any runoff of the agent off the surface, and also eliminates the potential for irritation of the user's skin due to the constant contact between the biocide and the user's skin.

To further elaborate the inhibition test zone and the contact transfer test protocols, a desired inoculum can then be placed aseptically on a first surface. Any desired inoculum quantity can be used, and in some embodiments, an amount of about 1 milliliter is applied to the first surface. In addition, the inoculum can be applied to the first surface over any desired area. In some cases, the inoculum can be applied over an area of about 178 millimeters by 178 millimeters. The first surface can be made of any material capable of being sterilized. In some embodiments, the first surface may be made of stainless steel, glass, porcelain, ceramic, natural or synthetic leather, such as pig skin or the like. inoculum can then be left to remain on the first surface for a relatively short amount of time, for example, about 2 or 3 minutes before the article is evaluated, for example the transfer substrate comes into contact with the first surface. The transfer substrate can be any type of article. The particular application may in some cases be for examination or surgical gloves. The transfer substrate, for example, the glove must be handled aseptically. Where the transfer substrate is a glove, a glove can be placed on the left and right hands of the experimenter. A glove can then be contacted with the first inoculated surface, ensuring that the contact time is firm and direct to minimize the error. The test glove can then be removed immediately using the other hand and placed in a bottle containing a desired amount of sterile buffered water (prepared as before) to extract the transferred microbes. In some cases, the glove can be placed in a bottle containing about 100 milliliters of sterile buffered water and tested within a specified amount of time. Alternatively, the glove can be placed in a bottle containing an adequate amount of Letheen Agar base (available from Alpha Biosciences, Inc. of Baltimore Md.) To neutralize the antimicrobial treatment for further evaluation. The bottle containing the glove can then be placed on a reciprocating agitator and agitated at a rate of from about 190 cycles / minute to about 200 cycles / minute. The bottle can be stirred for any desired time and in some cases it is stirred for about 2 minutes.

The glove can then be removed from the bottle, and the solution diluted as desired. A desired amount of the solution can then be placed on at least one sample plate Agar. In some cases, around 0.1 mi. of the solution can be placed on each sample plate. The solution on the sample plates can then be incubated for a desired amount of time to allow the microbes to propagate. In some cases, the solution may incubate for at least 48 hours. The incubation can take place at any optimum temperature to allow the growth of microbes and in some cases can take place at from about 33 ° C to 37 ° C. In some cases, incubation can take place at around 35 ° C.

After the incubation is completed, microbes present are counted and the results reported as CFU / ml. The percentage of recovery can then be calculated by dividing the microbes extracted in CFU / ml by the number present in the inoculum in (CFU / ml.) And multiplying the value by 100.

In another aspect, to evaluate the effectiveness of how fast they kill the applied antimicrobial agents, we employ a rapid germicidal direct contact test, developed by Kimberly-Clark Corporation. This test best simulates real-world work situations in which microbes are transferred from a substrate to a glove through direct contacts of short duration. This test also allows the evaluation of contact with the surface of the glove in a position to kill microbes quickly, while the solution-based test of the ASTM E 2149-01 protocol tends to provide multiple opportunities for contact and killing microbes, which is less realistic in practice.

We apply an inoculum of a known quantity of microbes to the surface treated with antimicrobials from a glove. After 3-6 minutes, we evaluated the number of microbes that remained on the surface of the treated glove. Any sample with a logarithmic reduction (Logio) of around 0.8 or greater is effective and exhibits a satisfactory level of performance. As with the contact transfer tests carried out according to the current ASTM protocols, a reduction in the concentration of microbes on the order magnitude of around Logio 1 is effective. Desirably, the level of microbial concentration can be reduced to a magnitude of about 3 Logio or more desirably of about 4 Logio or greater. Table 2 reports the relative effectiveness of killing after contact with the coated glove. The concentration of organisms on the surface is given at an initial zero point of time and points of three, five and thirty minutes. As one can see, the reduction of the resulting percentage in the number of organisms to time zero and after three, five and thirty minutes is dramatic. Significantly, within the first few minutes of contact with the antimicrobial it kills virtually all (96-99% or more) of the microorganisms present.

To test the antimicrobial efficacy of a polyhexamethylene biguanide, we treated the nitrile examination gloves according to the ASTM 04 / 123409-106"Rapid Germicide Time Death" protocol. In short, about 50] i of a night culture of S. aureus (ATCC # 27660, 5xl08CFU / ml) was applied to the glove material. After a contact time of about 6 minutes the glove fabric was placed in a neutralizing buffer. The surviving organisms were extracted and diluted in a Letheen broth. The aliquots were scattered and coated on the Tryptic Soy Agar plates. The plates were incubated for 48 hours at 35 ° C. After incubation the surviving organisms were counted and the colony forming units (CFU) were recorded. The reduction (logio) in the surviving organisms of the test material against the control fabric was calculated.

Logio CFU / sample control / Logio CFU / sample test item = Logio reduction.

We found in the microtexturized nitrile glove samples evaluated, the treatment with polyhexamethylene biguanide produced a greater reduction of 4 log of S. aureus ATCC 27660 when it was applied to a machine at 0.03 g / glove. The results are summarized in table 23 below: TABLE 23 The treatment of nitrile gloves with polyhexamethylene biguanide showed a greater reduction of 1 log of organisms when sprayed by hand without heat and a reduction greater than 5 log when machine sprayed under heated conditions.

The nitrile control material demonstrated an inherent antimicrobial efficacy of three and four logs. These results are comparing the reduction in applied organisms (estimate of latex control material table 24).

TABLE 24. Latex gloves samples evaluated: TABLE 25. Nitrile glove samples evaluated T without reduction = less than 0.5 log of test glove reduction in comparison to control glove Inoculum: 8.08 The inhibition test zone was completed to evaluate the adherence of the antimicrobial agent. The results are summarized below in tables 26 and 27.

Table 26.

Sample description Level of Organism Zone of Size of 8 Inoculum inhibition Test of the cadaver 1 Substrate of 1.1 X 10 * CFU / mI None Staphylococcus? Μ? golden nitrile 2 Substrate of 1.1 X 10'CFU / ml No Staphylococcus ??? μ? golden nitrile 3 Substrate of 1.1 X 10sCFU / ml No Staphylococcus? μ? golden nitrile 4 Substrate of 1.1 X 10sCPU / ml No Staphylococcus ??? μ? Golden nitrile 5 Control 1.1 X lO'CFU / ml No Staphylococcus ≥ μ? negative-gold Nitrile substrate 6 Control 1.1 X 10'CFO / ral 5 iwn Staphylococcus? μ? positive -05 * golden Amphyl. { v: v) Table 27 Description description Body Size Zone Size d < # Inoculum inhibition Test sample 1 Substrate of 1.3 x ío'cru / mi No Staphylococcus ??? μ? Natural golden rubber latex 2 Substrate of 1.1 X 105 CFU / ral None Staphylococcus? μ? natural golden rubber latex 3 Substrate of 1.3 x iosmi / mi No Staphylococcus ??? μ? Natural golden rubber latex 4 Substrate of 1.3 X 10sCFU / nl None Staphylococcus ??? μ? Natural golden rubber latex 5 Substrate of 1.3 X 10'CFU / ml No Staphylococcus ??? μ? Natural golden rubber latex 6 Control 1.3 X lO'CFU / ml No Staphylococcus ??? μ? negative golden Natural rubber latex substrate 7 Control 1.3 X 13 'FU / mi 5 rare Staphylococcus? μ? positive-0.5 * golden Araphyl (v: v) The present invention has been described in general in detail by way of examples. The words used are words of description rather than delimitation. Those of ordinary skill in the art understand that the invention is not necessarily limited to the embodiments specifically described herein, but that modifications and variations may be made without departing from the scope of the invention as defined by the following claims or their equivalents, including its equivalent components currently known, or to be developed, which may be used within the scope of the present invention. Therefore, unless the changes otherwise depart from the scope of the invention, such changes should be considered as being included herein and the appended claims should not be limited to the description of the preferred versions given herein. 101 O O 101 Table 2A. Illustrative Examples of Compositions including the addition of internal and topical melting of biocidal agents EXAMPLE 5 Ingredient 27 26 29 31 Topical PHMB 50 20% 35% 20% Crodacel QM 10% 5% Chitosan CMF 20% Aegis ABM S? 00 Glucopon 220 UP Xylitol 10% 10 Citrus Acid Benzoic acid PVP iodo E 481 Nicepole FC 1 - hexanol 5% 5% Internal 15 Al fagan RC 2000 50% 75% Irgaguard B 7S20 They were 20% 7S% 0 102 Non-Woven Coat with Barrier and Antimicrobial Properties Table 3.- Results of dynamic agitation bottle log reduction for several co-formulations PHMB with common pathogens * Treatment Compositions Contained 5 w / v% Bovine Serum Albumin (BSA) ** AATCC # 147-1998 modified to use dried agar instead of wet agar on which the fabric is placed *** ASTM E2149-01 (100 my) 103 Table . Effective results of dynamic bottle agitation and impact of surface treatment on barrier properties of an SMS fabric of 1.5 ounces per square yard.

Note: Z0I is zone of inhibition E481 is Bermcoll EBS 481 FQ - Ethyl hydroxyethyl cellulose PVP is polyvinyl pyrrolidone (1) Modified AATCC method # 147-1998 (2) Method ASTM E2149-01 (3) Hydrostatic head - (100 cm "Head) mbar STM 4507 (4) Air permeability STM 3801 (38 cm 2 Head) cfm 104 Comment: E481 and PVP are water soluble polymers and which are poorly active surface. But E481 and PVP are also good viscosity enhancement and good film agents. A combination of film formation, low surface tension reduction and high composition viscosity allows to limit the flow of the treatment composition within the volume of the SMS structure and makes the treatment less feasible to affect the barrier property of said SMS as measured by the hydrostatic head pressure. 105 Table 5. Antistatic and barrier properties results for 0.6% by weight of PHMB and joint co-formulations applied on 1 ounce per square yard of SMS through various processes. c 5 0 Etode of static decay: 0 106 Table 6. Efficacy of binding with yarn treated with antimicrobials against several organisms. Average log reduction values of = 2 duplicates. All materials connected with microbes for 10 minutes at 25 ° C. Inhibition zone measured with S. aureus ATCC 27660. 10 15 0 107 Table 7. Efficacy of binding with yarn treated with antimicrobial against several organisms, average log reduction of = 2 duplicates. All materials contacted the microbes for 30 minutes at 25 ° C in the presence of 5% bovine serum albumin. 108 Table 8. Efficacy of binding with yarn treated with antimicrobial against virus. Average log reduction values of 3 duplicates. All materials contacted the microbes for 30 minutes at 25 ° C the presence of 5% bovine serum albumin.

Table 9. Efficacy of SMS treated with antimicrobial against several organisms. Average log reduction values of = 2 duplicates. All materials made contact with the microbes for 10 minutes at 25 ° C. 109 Table 10. Efficacy of SMS treated with antimicrobial against several organisms. The average log reduction values of = 2 duplicates. All materials contacted with microbes for 30 minutes at 25 ° C in the presence of 5% bovine serum albumin. 110 Table 11A + B. Joint capacity with spinning and SMS treated to reduce the transfer of microbes from the treated material to the porcine skin. All materials contacted with microbes for 30 minutes at 25 ° C in the presence of 5% bovine serum albumin. After making the contact the materials touched the porcine skin for a minute. The numbers of bacteria transferred to the porcine skin were enumerated and log reductions were calculated. All values are average of 9 duplicates.

Claims (1)

1. CLAIMS 5 1. An article that comprises first surface with an associated antimicrobial coating stably with said first surface, and said antimicrobial coatings reduce a concentration of microbes by a magnitude of at least 1 logio of 10 colony forming units as measured by a method of agitator bottle, liquid drop challenge test and / or Spray challenge test within about 30 minutes under ambient conditions. 15 2. The article as claimed in the clause 1 characterized in that said article exhibits a reduction in contact transfer of 3 Logio from within about 30 minutes from the initial contact time 112 except one of the following: elastomeric membranes, films or foams, thermoplastic materials, metal, glass or ceramic surfaces. 4. The article as claimed in clause 2 characterized in that the substrate is either natural rubber or a synthetic polymer latex. 5. The article as claimed in clause 2 characterized in that said substrate is made of steel. 6. The article as claimed in clause 2 characterized in that said substrate is a medical device or surgical instrument. 7. A mask for the face having a body material with an antimicrobial coating on at least a portion of a first surface, said antimicrobial coating comprises a first antimicrobial agent and a coactive agent, wherein said antimicrobial coating rapidly inhibits and controls growth of a broad spectrum of microorganisms. 113 8. The mask for the face as claimed in clause 7 characterized in that the first coated surface exhibits a reduction of colony forming units of three Logio within a period of about 30 minutes as measured using a death test protocol rapid, when an inoculum either in the presence or in the absence of 5% load of bovine serum albumin (BSA) soils makes contact with said first surface, of any of the following microorganisms: Staphylococcus aureus, Enterococcus faecalis, Moraxella catarrhalis, Klebsiella pneumoniae or Candida albicans. 9. The mask for the face as claimed in clause 7, characterized in that the reduction of 3 logio of colony forming units occurs within a period of about 15 minutes. 10. The mask for the face as claimed in clause 7 characterized in that said body material is selected from one of the following: a) cellulose-based sheet, b) synthetic polymer non-woven sheet, c) a polymeric film or ) a laminated sheet of any combination of any of two classes of the preceding a) -c). 11. The mask for the face as claimed in clause 7 characterized in that the antimicrobial agents are a biocide that includes polymeric biguanide. 12. The mask for the face as claimed in clause 11 characterized in that said biocide is poly-hexamethylene biguanide (PHMB) at a final concentration of about 0.05-5% by weight of active agent. 13. The mask for the face as claimed in clause 7 characterized in that said antimicrobial coating forms either a uniform coating or is selectively deposited along an exterior face of said mask. 14. The mask for the face as claimed in clause 7 characterized in that said antimicrobial coating permeates around 5μ ?? of said outer face. 1 15 15. The mask for the face as claimed in clause 7 characterized in that said antimicrobial agents are not leaching from said first surface of said mask in the presence of liquid fluids. 16. The mask for the face as claimed in clause 7 characterized in that said mascara for the face exhibits a bacterial filtration efficiency (BFE) of greater than or equal to 80%. 17. The mask for the face as claimed in clause 7 characterized in that said chew exhibits a bacterial filtration efficiency of greater than or equal to about 85% as measured by ASTM F2101. 18. The mask for the face as claimed in clause 7 characterized in that said mask for the face exhibits a bacterial filtration efficiency of greater than or equal to 95%. 19. The mask for the face as claimed in clause 7 characterized in that said mask 116 for the face exhibits a bacterial filtration efficiency of greater than or equal to 99%. 20. The mask for the face as claimed in clause 7 characterized in that said mask has a differential pressure of less than or equal to 5 millimeters water / cm2, as measured by the ASTM F 2101 standard. 21. The mask for the face as claimed in clause 7 characterized in that said mask has a differential pressure of less than or equal to 2.5 millimeters water / cm2 ' 22. The mask for the face as claimed in clause 7 characterized in that said mask has a particle filtration efficiency (PFE) greater than or equal to 85% as measured by the latex particle challenge test (ASTM F 2299 ). 23. The mask for the face as claimed in clause 7 characterized in that said mask has a particle filtration efficiency greater than or equal to 95%. 117 24. The mask for the face as claimed in clause 7 characterized in that said mask has a particle filtration efficiency greater than or equal to 99%.