Polymer-based antimicrobial composition and method of use thereof

Abstract

Provided are polymer-based antimicrobial compositions that reduce the transmission of infectious diseases from surfaces that are non-toxic, water-soluble, exhibit broad-spectrum antimicrobial activity, and can be easily adapted to different environments, surfaces, and application complexities. The composition includes a cationic polymer, at least one adhesion promoter, optionally organic and / or inorganic particles that are photocatalytically active in visible light, and a carrier, wherein the components of the composition are not covalently bonded to each other. Also provided is an antimicrobial composition including at least (i) a polyethyleneimine-based polymer and a carrier, or (ii) organic and / or inorganic particles that are photocatalytically active in visible light, an adhesion promoter, and a carrier. The antimicrobial composition can be applied to disinfect a surface and to form a removable, residual, self-disinfecting film on the surface.

Description

[Technical Field]

[0001] Background of the Invention Infectious diseases kill more people worldwide each year than any other single cause. Minimizing infections caused by pathogenic microorganisms is a major concern in many fields, particularly in medical devices, drugs, hospital surfaces / furniture, dental restorative and surgical instruments, healthcare products and sanitary applications, water purification systems, textiles, food packaging and storage, industrial or household electrical appliances, and aircraft. Hospitals, in particular, bear a great deal of effort and expense in combating infections. [Background technology]

[0002] Infections occur through contact with, ingestion of, ingestion of, or inhalation of pathogens. It is estimated that 80% of human infections result from contact with microbially contaminated surfaces (Salwiczek et al., Trends Biotechnol 32:82-90 (2014)). Generally, antimicrobial agents that target pathogens are used to combat these infections. However, a particular problem is microorganisms that can rapidly and easily mutate their own genes to become resistant to these drugs, making them difficult to eliminate. For example, Staphylococcus aureus (S. aureus) generally colonizes human skin and mucous membranes without causing serious problems, but if the bacteria enter the body, they can cause illnesses ranging from mild to life-threatening, including skin and wound infections, infectious eczema, abscess infections, heart valve infections or endocarditis, pneumonia, and bloodstream infections or bacteremia. Some strains of S. aureus are resistant to methicillin and other beta-lactam antibiotics—methicillin-resistant S. aureus (MRSA)—and require a different type of antibiotic to treat. Furthermore, spore-forming Clostridium difficile (C. difficile), a superbug of the gut that causes symptoms ranging from diarrhea to life-threatening colon inflammation, is the most common bacterial infection that occurs in hospitals.

[0003] Over the past few years, the number of researchers working on developing new antimicrobial systems aimed at mitigating, eradicating, and / or eliminating costly debilitating infections has continued to grow. Much of this research focuses on polymers due to their inherent properties: polymers can act as a matrix for holding antimicrobial agents, and their properties, such as their hydrophilicity and / or molecular weight, can significantly influence the resulting antimicrobial activity. Consequently, the use of polymer materials with antimicrobial properties is attracting increasing interest from both academia and industry.

[0004] Known antimicrobial polymer coatings have been prepared by impregnating, adsorbing, or covalently bonding antimicrobial agents to various surfaces to provide a film layer. For example, U.S. Patent No. 9,127,173 discloses the preparation of layer-by-layer coatings on a substrate, where the coating contains quaternary amine groups that impart antimicrobial properties to the substrate. Non-leaching surfaces are often considered preferable because microorganisms are exposed to higher surface concentrations of antimicrobial agents compared to sustained-release surfaces. Furthermore, leaching surfaces make it difficult to pass cytotoxicity tests by the Environmental Protection Agency (EPA). As a general principle, non-leaching antimicrobial coatings and methodologies for their preparation are very complex and impractical for large-scale production and commercialization. Moreover, this technique is generally surface-specific. Another approach to preparing antimicrobial coatings involves using coatings that are non-covalently bonded to the surface. However, like covalent coatings, these methodologies generally require multiple complex synthesis steps and need to be adapted to coat different substrates, and therefore not for commercial use. This makes it difficult to achieve.

[0005] Therefore, despite active research in this field, there is still a need for novel antimicrobial materials that exhibit broad-spectrum antimicrobial activity and can easily adapt to the complexities of different environments (e.g., homes, medical facilities, schools, agriculture), surfaces (e.g., wood, stainless steel, marble, glass, and fabrics), and applications (e.g., food packaging, water or air filters, or even the protection of fruits and vegetables). Furthermore, such antimicrobial residual self-sanitizing films or coatings should ideally offer a very high mortality rate, be viable for several weeks, be non-toxic, and be easily removed. It would also be desirable to obtain versatile and inexpensive methods for preparing such surface coatings on a commercial scale. [Overview of the project]

[0006] The present invention is based on a polymer-based antimicrobial composition that is non-toxic, water-soluble, and significantly reduces the transmission of infectious diseases from surfaces such as glass, plastic, granite, and metallic substrates, as well as skin. The polymers used in the composition can perform two functions: (i) the ability to disinfect surfaces by killing existing pathogens (kill-now); and (ii) providing a removable residual self-disinfecting film that prevents future microbial growth (kill-later). The polymer-based composition is effective against bacteria, viruses, and spores, including Clostridium difficile (C. difficile). Furthermore, unlike most commercially available disinfectants, the polymer-based composition inactivates non-enveloped viruses, which are typically the cause of common colds and gastrointestinal viral illnesses. Since the antimicrobial composition does not require pathogenic chemicals or metals, unlike many other commercially available disinfectants, this composition is safe for humans, animals, and the environment.

[0007] The present invention provides a polymer-based antimicrobial composition comprising a cationic polymer, at least one adhesion promoter, a carrier, and optionally organic and / or inorganic particles that are photocatalytically active in visible light, wherein the components of the composition are not covalently bonded to each other. The antimicrobial composition is subjected to the following tests: (i) Meets the EPA requirements for log3 reduction against viruses and log5 reduction against bacteria, Pathogenic agent spray testing in accordance with International Law E1153 of the (ASTM) (and Materials) (ii) Suspension test in accordance with ASTM International Code E1052-96 (2002) or ASTM International Code E2315 (2016) (iii) A film formed from the composition (iii) Within 30 minutes, at least 95% of the log5 population of Gram-positive or Gram-negative bacteria, (iii-b) At least 95% of the log4 population of enveloped viruses within 30 minutes of contact. (iii-c) at least 95% of non-enveloped viruses within 30 minutes of contact, and / or (iii-d) Within 24 hours of contact, at least 94% of the log4 population of Clostridium difficile bacteria, The antimicrobial activity is determined according to the Japanese Industrial Standard (JIS) Z 2801 (2006) test, or a modified version of such test as described herein, to kill the organism. (iv) A film formed from the composition conforms to the International Organization for Standardization (ISO) 10993-5 According to the in vitro cytotoxicity test, the value is 2 or less. (v)(va) The film formed from the composition is subject to EPA Protocol #01-1A (vb) A durability test in which, after waiting 7 days following film formation, the film formed from the composition kills at least 99.9% of Gram-positive and Gram-negative bacteria according to a residual self-disinfecting activity test, or (vb) a durability test in which, after waiting 7 days following film formation, the film formed from the composition kills at least 95% of Gram-positive and Gram-negative bacteria or enveloped and non-enveloped viruses, according to a modified version of Protocol #01-1A of the residual self-disinfecting activity test described herein. It follows at least one of the following.

[0008] The present invention also provides a method for killing microorganisms on a surface, comprising applying an antimicrobial composition to the surface, which comprises a cationic polymer, at least one adhesion promoter, a carrier, and optionally organic and / or inorganic particles that are photocatalytically active in visible light.

[0009] The present invention further provides a method for killing microorganisms on a surface, comprising applying an antimicrobial composition containing a high molecular weight polydiallyldimethylammonium salt and a carrier to the surface.

[0010] The present invention further provides compositions comprising a polyethyleneimine polymer, optionally a second cationic polymer selected from polydiallyldialkylammonium salts, poly(acrylamide-co-diallyldialkylammonium halide), chitosan, or a combination thereof, optionally a polyacid, and a carrier. Antimicrobial compositions are also provided comprising at least one organic and / or inorganic particle photocatalyzed in visible light, at least one adhesion promoter, and a carrier. These compositions can be used in methods for killing microorganisms on a surface. [Brief explanation of the drawing]

[0011] [Figure 1] Figure 1 shows counterion exchange in polydiallyldimethylammonium chloride (polyDADMAC) by LiTFSI in one embodiment of the present invention. [Figure 2]Figure 2A shows a small pore size from a filter containing uncharged 5 μm glass. Figure 2B shows a filter containing positively charged alumina with a larger pore size, and a cationic polymer bound to the alumina.

Mode for Carrying Out the Invention

[0012] Detailed Description of the Invention The present invention provides a polymer-based antibacterial composition comprising a cationic polymer, at least one adhesion promoter, optionally organic and / or inorganic particles that are photocatalytically active in visible light, and a carrier, wherein the components of the composition are not covalently bonded to each other. The antibacterial composition is as follows: (i) A pathogen-killing spray test according to ASTM E1153 that meets the EPA requirements of a log3 reduction against viruses and a log5 reduction against bacteria, (ii) A suspension test according to ASTM E1052-96(2002) or ASTM E2315(2016), (iii) The film formed from the composition (iii-a) At least 95% of the log5 population of gram-positive or gram-negative bacteria within 30 minutes, (iii-b) At least 95% of the log4 population of enveloped viruses within 30 minutes of contact, (iii-c) At least 95% of non-enveloped viruses within 30 minutes of contact, and / or (iii-d) At least 94% of the log4 population of Clostridium difficile bacteria within 24 hours of contact, Kill according to the JIS Z 2801(2006) test for antibacterial activity, or a modified version of such a test described herein, (iv) The film formed from the composition has a value of 2 or less according to the in vitro cytotoxicity test of the International Organization for Standardization (ISO) 10993-5 (v)(va) A film formed from the composition kills at least 99.9% of Gram-positive and Gram-negative bacteria according to the EPA Protocol #01-1A residual self-disinfecting activity test, or (vb) A durability test is performed, selected from the following, in which, after waiting 7 days after film formation, the film formed from the composition kills at least 95% of Gram-positive and Gram-negative bacteria or enveloped and non-enveloped viruses, according to a modified version of the Protocol #01-1A residual self-disinfecting activity test described herein. Follow at least one of the following tests.

[0013] The efficacy of the antimicrobial compositions described herein is best appreciated in terms of the following advantages: The compositions have the ability to “kill now” without the presence of conventional pathogenic chemicals that may be toxic when applied to surfaces as conventional disinfectants. The compositions have the ability to “kill later,” i.e., to continuously kill (sanitize) in the future after application, by forming a residual self-sanitizing film that passes EPA permissible durability tests and EPA approved toxicity tests as described herein. The residual self-sanitizing film is removable with water (e.g., warm soapy water), alcohol, or a water-alcohol mixture. The technology is highly adaptable for the following reasons: i) the compositions can be adjusted to create films of varying thicknesses, solubility, and adhesion; ii) one or more cationic polymers can be mixed in specific proportions to target specific pathogens and / or to design products with various cost profiles; and / or iii) the natural “kill now” property derived from the cationic polymers can be enhanced, if desired, by adding one or more conventional antimicrobial agents to the composition. These and other advantages of the present invention, as well as further features of the invention, will become apparent from the description of the invention provided herein.

[0014] The antimicrobial composition comprises at least one cationic polymer. The cationic polymer may be any suitable cationic polymer of molecular weight and charge density that exhibits antimicrobial properties and allows the composition or a film formed from the composition to pass at least one of tests (i) to (v). It has been found that the charge density is affected by the molecular weight and pH of the formulation. For example, the charge tends to increase with higher molecular weight. Alternatively, the charge tends to increase with lower pH. Thus, the molecular weight and / or pH can be modified to provide the desired charge density and / or antimicrobial activity. Suitable molecular weights of various cationic polymers are described herein. The pH of the composition is typically less than about 7, for example, between about 3 and 7, more preferably between about 4 and 6.

[0015] While we do not wish to be bound by any particular theory, cationic polymers are highly effective, in particular, in targeting Gram-positive and / or Gram-negative bacteria, as well as enveloped and unenveloped viruses. In particular, positively charged polymers are thought to attract and bind to microbial particles such as viral particles. The polymer continues to encapsulate the microorganism. Once the polymer has completely encapsulated the microorganism, the capsid is broken, resulting in the harmless release of genomic material.

[0016] Specific examples of suitable cationic polymers include polydiallyldialkylammonium salts, acrylicoxyalkyltrialkylammonium salts (e.g., acrylicoxyethyltrimethylammonium halide, methacrylateoxyethyltrimethylammonium halide), and vinylphenalkyltrialkylammonium salts. salt (e.g., vinylbenzyltrimethylammonium halide), acrylamide Alkyltrialkylammonium salts (e.g., 3-acrylamido-3-methylbutyltrimethylammonium halide), poly(acrylamido-co-diallyldialkyla This includes ammonium salts (e.g., poly(acrylamide-co-diallyldimethylammonium chloride)), polyethyleneimine polymers, chitosan, or combinations thereof. In any of the aforementioned polymers, each alkyl group may be the same or different, and the linear C group may be different. 1-6 Or branch C 3-6 The group is (e.g., methyl, ethyl, t-butyl), and the salt is an anion such as a halide (e.g., chloride, fluoride, bromide), a halide-containing anion (e.g., bis(trifluoromethane)sulfonimide, trifluoroacetate), a sulfate, or a phosphate. Preferably, the cationic polymer is a polydiallyldialkylammonium salt (e.g., polydiallyldimethylammonium halide), poly(acrylamide-co-diallyldialkylammonium halide) (e.g., poly(acrylamide-co-diallyldimethylammonium chloride)), and / or polyethyleneimine polymer (e.g., linear, chemically unmodified PEI). In some embodiments, the composition does not contain a crosslinked polycyclic compound (e.g., a cavity structure) containing a polymer-linked crosslinked polycyclic compound (e.g., a polymer-linked cavity). In some embodiments, the cationic polymer is not a hybrid material containing one or more divalent metals and siloxane crosslinks.

[0017] In some examples, polydiallyldialkylammonium salts (e.g., polydiallyldimethylammonium halide), acryloxylalkyltrialkylammonium salts, vinylphenalkyltrialkylammonium salts, acrylamide alkyltrialkylammonium salts, and poly(acrylamide-co A combination of two or more cationic polymers selected from (-diallyldialkylammonium halide), polyethyleneimine polymers, and chitosan is used in the composition. In certain embodiments, polydiallyldialkylammonium salts (e.g., polydiallyldimethylammonium halide) are used in combination with polyethyleneimine polymers (e.g., linear or branched polyethyleneimine (PEI)). In preferred embodiments, polydiallyldimethylammonium chloride or poly(acrylamide-co-diallyldialkylammonium chloride) is used in combination with chemically unmodified linear PEI.

[0018] Cationic polymers may or may not be used in combination with anionic polymers to form polyelectrolyte complexes (PECs). As used herein, a PEC refers to a complex that is automatically formed when one or more cationic polymers are added in combination with one or more anionic polymers. PECs tend to be hydrophilic and water-soluble. In some embodiments, the composition does not contain anionic polymers. When the cationic polymer is a polydiallyldialkylammonium salt (e.g., polydiallyldialkylammonium halide), the formation of a PEC is optional, i.e., the anionic polymer is optional in the composition. In some embodiments, the composition does not contain anionic polymers in combination with polydiallyldialkylammonium salts (e.g., polydiallyldimethylammonium halide).

[0019] In one embodiment, the cationic polymer is a polydiallyldialkylammonium salt such as polydiallyldialkylammonium halide (e.g., halide or halide-containing anion), polydiallyldialkylammonium sulfate, or polydiallyldialkylammonium phosphate. In polydiallyldialkylammonium halide, the halide is any suitable compound in which the anion is a halide or contains a halide (e.g., bis(trifluoromethane)sulfonimide, trifluoroacetate), for example, polydiallyldimethylammonium fluoride, polydiallyldimethylammonium chloride, polydiallyldimethylammonium bromide, polydiallyldimethylammonium iodide, polydiallyldimethylammonium It may be ammonium bis(trifluoromethane)sulfonimide or a combination thereof. In a preferred embodiment, the polydiallyldimethylammonium halide is polydiallyldimethylammonium fluoride, polydiallyldimethylammonium chloride (polyDADMAC), or a mixture of polydiallyldimethylammonium chloride and polydiallyldimethylammonium fluoride and / or polydiallyldimethylammonium bis(trifluoromethane)sulfonimide.

[0020] A preferred polydiallyldialkylammonium salt is a polymer produced from the polymerization of a diallyldialkylammonium compound, which can be represented by the following formula.

[0021] [ka]

[0022] Here, R1 and R2 are the same or different, each being hydrogen or a C1-C6 alkyl group; R3 and R4 are independently hydrogen or an alkyl, hydroxyalkyl, carboxyalkyl, carboxyamidalkyl, or alkoxyalkyl group having 1 to 12 carbon atoms; Y- This represents anions such as halides, halide-containing anions (e.g., bis(trifluoromethane)sulfonimide), sulfates, or phosphates. Preferred examples of diallyldialkylammonium monomers include diallyldimethylammonium chloride (DADMAC), diallyldimethylammonium fluoride, diallyldimethylammonium bis(trifluoromethane)sulfonimide, diallyldimethylammonium bromide, diallyldimethylammonium sulfate, diallyldimethylammonium phosphate, dimethylallyldimethylammonium chloride, dimethylallyldimethylammonium fluoride, dimethylallyldimethylammonium bis(trifluoromethane)sulfonimide, diethylallyldimethylammonium chloride, diethylallyldimethylammonium fluoride, and diethylallyldimethylammonium This includes nium bis(trifluoromethane)sulfonimide, diallyl di(beta-hydroxyethyl)ammonium chloride, diallyl di(beta-hydroxyethyl)ammonium fluoride, diallyl di(beta-hydroxyethyl)ammonium bis(trifluoromethane)sulfonimide, diallyl di(beta-ethoxyethyl)ammonium chloride, diallyl di(beta-ethoxyethyl)ammonium fluoride, diallyl di(beta-ethoxyethyl)ammonium bis(trifluoromethane)sulfonimide, diallyl diethylammonium chloride, diallyl diethylammonium fluoride, and diallyl diethylammonium bis(trifluoromethane)sulfonimide. In preferred embodiments, the cationic polymer is polyDADMAC.

[0023] In certain embodiments, some of the polyDADMAC molecular chloride counterions can be converted to insoluble fluoride-containing counterions. Such conversion can occur, for example, by adding a diluted mixture of lithium bis(trifluoromethane)sulfonimide (LiTFSI). LiTFSI and polyDADMAC carry an electrostatic charge that imparts a portion of the poly(poly)electrolyte behavior in solution. This counterion exchange in polyDADMAC by LiTFSI is shown in Figure 1. LiTFSI is converted to water It is known to have good solubility and stability in the environment. The exchange reaction consists of mixing two solutions: one containing positively charged polyDADMAC and the other containing negatively charged TFSI - Contains anions. A sufficient ratio of polymer to anion is TFSI - When exchanged with anions, the polymer becomes insoluble and precipitates from the solution. TFSI in solution - Anions can either bind to polymer chains or become part of micelles. The present invention seeks to utilize an ion exchange strategy to generate only enough micelles to slightly reduce the solubility of cationic polymers, whether used alone or in a PEC film. As described herein, TFSI - The addition of anions reduces the solubility of the polymer, but improves the durability of the resulting film compared to the EPA Protocol #01-1A residual self-disinfecting activity test or a modified version thereof. TFSI will result in the desired reduction in solubility. -The desired solubility is achieved by experimentally determining the amount. In a specific example, the following steps can be used: 1) First, reduce the water added to the polyDADMAC solution by 125 ml; 2) Generate a diluted solution of TFSI by mixing 0.125 to 0.250 grams of TFSI solution per 2.4 grams of polyDADMAC; then 3) Drop this diluted solution into the polyDADMAC solution. This method is carried out with vigorous stirring at room temperature for 24 hours, which is necessary to ensure a uniform distribution. If desired, this mixture can be used to produce a PEC having one or more anionic polymers. In such an embodiment, if a PEC is desired, before introducing the anionic polymer to produce the PEC, TFSI - A partial substitution of the counterion Cl - in water-soluble polyDADMAC is achieved by adding a diluted solution of.

[0024] The counterion conversion strategy of polyDADMAC does not adversely affect its antibacterial activity. To test the activity, an excess of TFSI - was used to generate a precipitate, which was then dissolved in dimethyl sulfoxide (DMSO). This solution was then placed on a slide to form a film, which was held for 7 days and then inoculated with a log6 population of Escherichia coli (E. coli). PolyDADMAC converted using a mixture of fluoride ions and chloride ions provided a film that could kill >99.99% of the E. coli population within 30 minutes.

[0025] Polydiallyldialkylammonium salts (e.g., polydiallyldimethylammonium halide), acryloxyalkyltrialkylammonium salts, vinylphenalkyltrialkylammonium salts, and / or Acrylamide alkyltrialkylammonium salts preferably have a number-average molecular weight of 25,000 g / mol to 20,000,000 g / mol. Typically, higher molecular weights are preferred to reduce the solubility of films formed from antimicrobial compositions. Polydiallyldialkylammonium salts (e.g., polydiallyldimethylammonium halide), acrylicoxyalkyltrialkylammonium salts, vinylphenalkyltrialkylammonium salts, and / or acrylamide alkyltrialkylammonium salts are also preferred. Acrylamide alkyltrialkylammonium salts may have a number average molecular weight of 20,000,000 g / mol or less, for example, 15,000,000 g / mol or less, 10,000,000 g / mol or less, 5,000,000 g / mol or less, or 1,000,000 g / mol or less. Alternatively, polydiallyldialkylammonium salts, acrylicoxyalkyltrialkylammonium salts, vinylphenalkyltrialkylammonium salts, and / or Crilamidoalkyltrialkylammonium salts are available in concentrations of 25,000 g / mol or more, for example, 50,000 g / mol or more, 100,000 g / mol or more, 150,000 g / mol or more, 200,000 g / mol or more, 250,000 g / mol or more, 300,000 g / mol or more, 350,000 g / mol or more, 400,000 g / mol or more, 450,000 g / mol or more, 500,000 g / mol or more, and 550,000 g They can have a number average molecular weight of 600,000 g / mol or more, 650,000 g / mol or more, 700,000 g / mol or more, 750,000 g / mol or more, or 800,000 g / mol or more. Therefore, polydiallyldialkylammonium salts, acryloxyalkyltrialkylammonium salts, vinylphenalkyltrialkylammonium salts, and / or acrylamidealkyltrialkylammonium salts can have a number average molecular weight limited by any two of the aforementioned endpoints. For example, polydiallyldialkylammonium salts, acryloxyalkyltrialkylammonium salts, vinylphenalkyltrialkylammonium salts, and / or acrylamidealkyltrialkylammonium Salt is available in the following ranges: between 25,000 g / mol and 20,000,000 g / mol, between 25,000 g / mol and 15,000,000 g / mol, between 25,000 g / mol and 10,000,000 g / mol, between 25,000 g / mol and 5,000,000 g / mol, between 25,000 g / mol and 1,000,000 g / mol, between 50,000 g / mol and 1,000,000 g / mol, and between 100,000 g / mol and 1,000,000 g / mol. The number average molecular weight can be between 150,000 g / mol and 1,000,000 g / mol, between 200,000 g / mol and 1,000,000 g / mol, between 250,000 g / mol and 1,000,000 g / mol, between 300,000 g / mol and 1,000,000 g / mol, between 350,000 g / mol and 1,000,000 g / mol, or between 400,000 g / mol and 1,000,000 g / mol. In some embodiments, polydiallyldialkylammonium salts, acryloxylalkyltrialkylammonium salts, vinylphenalkyltrialkylammonium salts, and / or acryl Midoalkyltrialkylammonium salts have a number average molecular weight between 250,000 g / mol and 1,000,000 g / mol or between 800,000 g / mol and 1,000,000 g / mol, and include a number average molecular weight between 900,000 g / mol and 1,000,000 g / mol.

[0026] In some embodiments, polydiallyldialkylammonium salts are "ultra-high molecular weight" polydiallyldialkylammonium salts such as ultra-high molecular weight polydiallyldimethylammonium halide. Ultra-high molecular weight polydiallyldialkylammonium salts (e.g., polydiallyldimethylammonium halide) are typically between about 800,000 g / mol and about 20,000,000 g / mol (e.g., between about 1,000,000 g / mol and 15,000,000 g / mol, between about 1,000,000 g / mol and 10,000,000 g / mol, between about 1,000,000 g / mol and 5,000,000 g / mol, and between about 2,000,000 g / mol and 5,000,000 g / mol). The number average molecular weight is between 1000,000 g / mol, between approximately 3,000,000 g / mol and 5,000,000 g / mol, between approximately 4,000,000 g / mol and 10,000,000 g / mol, between approximately 5,000,000 g / mol and 20,000,000 g / mol, between approximately 5,000,000 g / mol and 15,000,000 g / mol, between approximately 6,000,000 g / mol and 20,000,000 g / mol, and between approximately 6,000,000 g / mol and 15,000,000 g / mol. In these embodiments, the halide in polydiallyldialkylammonium halide generally contains a fluoride, a chloride, or an anion containing a fluoride and / or chloride. In particular, polydiallyldialkylammonium halide is polyDADMAC, or a mixture of polyDADMAC and polydiallyldimethylammonium fluoride and / or polydiallyldimethylammonium bis(trifluoromethane)sulfonimide.

[0027] In another embodiment, the cationic polymer is a polyethyleneimine polymer, which is typically an ene-free polymer that makes up a number of pathogenic microorganisms such as rhinovirus, poliovirus, adenovirus, coxsackievirus, parvovirus, and rotavirus. It is effective against bellovarian viruses. The polyethyleneimine polymer can be any suitable polyethyleneimine polymer, which is linear or non-linear, preferably linear.

[0028] Numerous studies have reported on the chemical modification of polyethyleneimines (PEI) to produce antimicrobial agents. For example, Gao et al. (J. Biomaterial Science, Polymer Edition, 2007, 18, 531-544) (see reference) reported that quaternated branched PEI (BPEI) was antimicrobial against E. coli at low concentrations. Pasquier et al. (Biomacromolecules, 2007, 8, 2874-2882) reported that quaternated BPEI with various long alkyl groups showed some antimicrobial activity against E. coli, while linear PEI grafted with long alkyl chains (LPEI) produced a series of hydrophobically modified, water-insoluble LPEI derivatives that effectively killed both E. coli and Staphylococcus aureus. See also U.S. Patent No. 9,399,044 and WO2008 / 127416A2. For example, the chemically modified PEI described in U.S. Patent No. 9,399,044 is effective only against bacteria (e.g., Mycobacterium tuberculosis, Gram-negative E. coli, and Pseudomonas aeruginosa, and Gram-positive Staphylococcus aureus) and the fungus Candida albicans, but not against viruses. WO 2008 / 127416 A2 demonstrates that antimicrobial coatings containing chemically modified PEI can kill enveloped viruses but not non-enveloped viruses, as shown in Table 1.

[0029] [Table 1]

[0030] However, chemical modification requires expensive, low-yield organic chemical processes that use toxic chemicals harmful to humans and the environment. Therefore, in some embodiments of the present invention, the polyethyleneimine polymer is linear PEI that is not chemically or structurally modified (e.g., does not contain alkyl groups and / or quaternary ammonium groups). Furthermore, it has been discovered that chemically unmodified linear PEI can kill non-enveloped viruses. In particular, films of chemically unmodified linear PEI described herein have demonstrated not only the killing of Gram-positive and Gram-negative bacteria, but also at least a log4 (99.99%) reduction against both enveloped and non-enveloped viruses, including rhinovirus, poliovirus, and adenovirus. Many non-enveloped viruses, such as Russ, Coxsackievirus, Parvovirus, and Rotavirus, are pathogenic microorganisms that cause the common cold and gastrointestinal viral illnesses, making them particularly important. Table 2 shows the ability of antimicrobial compositions containing chemically unmodified linear PEI to reduce MS2 bacteriophages, which are considered to be surrogates for non-enveloped viruses.

[0031] [Table 2]

[0032] In other embodiments, the polyethyleneimine polymer is deacylated PEI or quaternized N-alkyl-N-methylpolyethyleneimine. Deacylated polyethyleneimines may be available from commercial suppliers such as Polysciences, Inc. (Warrington, PA). As used herein, “deacylated polyethyleneimine” refers to polyethyleneimine having a protonable nitrogen atom of the following formula:

[0033] [ka]

[0034] In the formula, the polymer is partially (at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 80%, or at least 90%) or completely (about 98–100%) hydrolyzed (deacylated). While we do not wish to be bound by any particular theory, dealkylation is thought to enhance PEI's ability to kill viruses and reduce its cytotoxicity.

[0035] As used herein, “quaternized-N-alkyl-N-methylpolyethyleneimine” refers to a polyethyleneimine that has been partially (at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90%) or completely (about 98–100%) hydrolyzed, methylated, and then quaternized with an alkyl substituent. The alkyl substituent in this embodiment may be any suitable alkyl substituent, whether linear or branched. Generally, alkyl substituents are selected for chain lengths that are most effective against viruses, for example, C 8-14 and C 10-12 C including 1-18 It has the following characteristics. In one embodiment, the alkyl substituent is decane, dodecane, or hexadecane.

[0036] A synthetic route for providing PEI that is completely hydrolyzed (deacylated), methylated, and then quaternized includes the following method steps.

[0037] Step 1: Prepare linear PEI completely deacetylated by acid-catalyzed hydrolysis of commercially available PEOZ (e.g., 500 kDa, 200 kDa, and 50 kDa, preferably 50 kDa). For example, 10.0 g of PEOZ was added to 400 mL of 24% (wt / vol) HCl and subsequently refluxed for 96 hours. The POEZ crystals dissolved completely in 2 hours, but a white precipitate appeared after 3 hours (i.e., a total of 5 hours). In each case, the precipitate was isolated by filtration and then air-dried.

[0038] Next, protonated PEOZ (2-ethyl-2-oxazoline) was deprotonated using an aqueous solution of a base (e.g., KOH). Briefly, 10 g of protonated linear PEI was dissolved in 50 mL of distilled water, and 6 M KOH was added until the pH of the solution was approximately 11. The completely deprotonated PEI appeared as a white precipitate, which was filtered and repeatedly washed with distilled water until it became neutral (pH approximately 7). The final product was linear PEI without N-acyl groups, having a molecular weight of approximately 217 kDa, 87 kDa, or preferably 22 kDa.

[0039] Step 2: The E. Clarke methylation technique (Clarke et al., JACS, 55(11):4571(1933)) can be used to prepare linear N-methyl-PEI. A 50% aqueous solution of 10 g of 22 kDa PEI prepared in Step 1 was transferred to a round-bottom flask, to which 90% formic acid (24.5 mL, 0.48 mol) was added, followed by 37% formaldehyde (29.3 mL, 0.36 mol) and 20 mL of water. The reaction mixture was stirred at 90°C for 96 hours. After cooling to room temperature, the pH of the reaction mixture was adjusted to 11 using an 8 M KOH solution. The deprotonated N-methylated PEI was extracted several times with chloroform, and the entire organic solution was repeatedly washed with water. Then the chloroform was removed to obtain yellow, viscous N-methylated PEI with 100% methylation.

[0040] Step 3: N-alkylN-methylPEI was then quaternized to make it water-soluble and to target viruses. Specifically, 1 g (17.5 mmol / repeating unit) of N-methylated PEI was dissolved in 75 ml of tert-butanol in a screw-top pressure tube. 1-bromohexadecane was added to obtain the side chain length most effective against viruses. The reaction mixture was then heated at 105°C for 48 to 96 hours, depending on the desired solubility of the final product. After the reaction was complete, the solvent was removed to one-tenth of its original volume. Then, excess acetone (200 mL) was added to the reaction mixture and the precipitate was filtered off. To further purify the product, the precipitate was dissolved in chloroform and acetone was added to reprecipitate the product. The excess solvent was decanted and the precipitate was dried using a high vacuum pump to obtain a linear N-alkylN-methylPEI polymer.

[0041] Polyethyleneimine polymers typically have a number average molecular weight between 15,000 g / mol and 250,000 g / mol. Polyethyleneimine polymers can have a number average molecular weight of 250,000 g / mol or less, for example, 230,000 g / mol or less, 210,000 g / mol or less, 190,000 g / mol or less, or 170,000 g / mol or less. Alternatively, polyethyleneimine polymers can have a number average molecular weight of 15,000 g / mol or more, for example, 30,000 g / mol or more, or 60,000 g / mol or less. Polyethyleneimine polymers can have a number average molecular weight of 15,000 g / mol or more, 90,000 g / mol or more, 100,000 g / mol or more, 120,000 g / mol or more, or 150,000 g / mol or more. Therefore, polyethyleneimine polymers can have a number average molecular weight limited by any two of the aforementioned endpoints. For example, polyethyleneimine polymers can have a number average molecular weight between 15,000 g / mol and 250,000 g / mol, between 15,000 g / mol and 230,000 g / mol, between 15,000 g / mol and 210,000 g / mol, between 15,000 g / mol and 190,000 g / mol, between 15,000 g / mol and 170,000 g / mol, and 30,000 g / mol. It can have a number average molecular weight between 100,000 g / mol, between 60,000 g / mol and 170,000 g / mol, between 90,000 g / mol and 170,000 g / mol, between 120,000 g / mol and 170,000 g / mol, or between 150,000 g / mol and 170,000 g / mol, for example, approximately 160,000 g / mol.

[0042] One aspect of the present invention is an antimicrobial composition comprising (a) a polydiallyldialkylammonium salt (e.g., polydiallyldimethylammonium halide) used in combination with a polyethyleneimine polymer (e.g., linear or branched polyethyleneimine (PEI), preferably linear PEI), (b) at least one adhesion promoter, (c) optionally photocatalytically active organic and / or inorganic particles in visible light, (d) optionally at least one salt, and (e) a carrier (each of which is described herein). The antimicrobial composition passes at least one of tests (i) to (v). The weight ratio of the polydiallyldialkylammonium salt to the polyethyleneimine polymer is any suitable amount, but is typically in the range of 80 / 20 to 20 / 80 (e.g., 30 / 70, 33 / 67, 40 / 60, 45 / 55, 50 / 50, 55 / 45, 60 / 40, 67 / 33, 70 / 30). In certain cases, the weight ratio of polyDADMAC:PEI is 50 / 50 or 33 / 67.

[0043] When the cationic polymer is a polyethyleneimine polymer, the composition may further contain an anionic polymer such that the cationic polymer and the anionic polymer combine to form a PEC. In some embodiments, a polyethyleneimine polymer, such as a chemically unmodified linear PEI, is used without an anionic polymer such as a polyacrylate. In other embodiments where a PEC is desired, the composition contains both a polydiallyldialkylammonium salt (e.g., polydiallyldimethylammonium halide) and PEI, such as branched PEI. Two approaches have been proposed to add PEI to the system. One approach is to first complex the polydiallyldialkylammonium halide with the anionic polymer, then complex the PEI with the anionic polymer, and then mix the two complexes. A second, and preferred, approach is to complex both cationic polymers simultaneously with the anionic polymer in a one-pot synthesis.

[0044] Those skilled in the art know that non-enveloped viruses are resistant to ethanol, the alcohol most commonly used in hand sanitizers and other disinfectants. The inventors have discovered that a composition of ethanol and chemically unmodified linear PEI is effective in killing non-enveloped viruses, and that its antimicrobial activity can be further improved by the addition of small organic polyacids such as citric acid. While not wishing to be bound by any theory, it is thought that protonated linear PEI can bind to anionic polyacids (e.g., citrates) to form a complex. Suitable organic polyacids include polycarboxylic acids containing at least three carboxylic acid groups (e.g., 3, 4, 5, and / or 6 carboxylic acid groups), such as organic tribasic acids. Specific examples of polycarboxylic acids include citric acid, isocitric acid, aconitic acid, and propane-1,2,3-tricarboxylic acid. This includes hemimeltic acid, trimellitic acid, trimesic acid, prehnitic acid, mealalanophanic acid, pyromellitic acid, benzenepentacarboxylic acid, meritol acid, ethylenediamine-N,N'-dimalonic acid (EDDM), 2,2'-azandiyldisuccinic acid, 2,2'-oxydisuccinic acid (ODS), ethylenediaminedisuccinic acid (EDDS), diethylenetriaminepentaacetic acid (DTPA), ethylenediaminetetraacetic acid (EDTA), 2,2'-((((1,2-dicarboxyethyl)azandiyl)bis(ethane-2,1-diyl))bis(oxy))disuccinic acid, and any combination thereof. Preferably, the polyacid is citric acid. The PEI-citric acid complex forms a stable colloid when the ratio of protonated linear PEI to citrate is in the range of approximately 70:30 to 90:10 (e.g., approximately 70:30, 75:25, 80:20, 85:15, or 90:10). If more citrate is desired in the complex, e.g., 60:40, the colloid may become unstable. However, the colloid can be stabilized by filtering out the larger citrate complex.

[0045] In another embodiment, the cationic polymer is chitosan. When the cationic polymer is chitosan, PEC formation is optional, meaning that the anionic polymer is optionally present in the composition. In some examples, deacetylated chitosan (e.g., trimethylchitosan) with less than 95% deacetylation and / or quaternization results in a more soluble, high molecular weight chitosan. Thus, it is possible to create low-solubility films that are durable enough not to require PEC formation.

[0046] Chitosan typically has a number-average molecular weight between 20,000 g / mol and 2,000,000 g / mol. Chitosan can have a number-average molecular weight of 2,000,000 g / mol or less, for example, 1,750,000 g / mol or less, 1,500,000 g / mol or less, or 1,250,000 g / mol or less. Alternatively, chitosan can have a number-average molecular weight of 20,000 g / mol or more, for example, 50,000 g / mol or more, 100,000 g / mol or more, 250,000 g / mol or more, 500,000 g / mol or more, or 1,000,000 g / mol or more. Thus, chitosan can have a number-average molecular weight limited by any two of the aforementioned endpoints. For example, chitosan is available in concentrations between 20,000 g / mol and 2,000,000 g / mol, between 20,000 g / mol and 1,750,000 g / mol, between 20,000 g / mol and 1,500,000 g / mol, between 20,000 g / mol and 1,250,000 g / mol, between 20,000 g / mol and 1,000,000 g / mol, and 50,000 g It can have a number-average molecular weight between / mol and 2,000,000 g / mol, between 100,000 g / mol and 2,000,000 g / mol, between 250,000 g / mol and 2,000,000 g / mol, between 500,000 g / mol and 2,000,000 g / mol, or between 1,000,000 g / mol and 2,000,000 g / mol.

[0047] If the antimicrobial composition optionally includes at least one anionic polymer that forms a PEC together with a cationic polymer, the PEC can offer two important advantages to the present invention: 1) Polymer assembly using PEC eliminates the use of chemical crosslinking agents, thereby reducing the potential toxicity and other undesirable effects of the reagents; 2) PEC formed between polyacids and polybases is resistant to pH fluctuations in the dissolution medium.

[0048] Anionic polymers include polyacrylates, polysulfates, polysulfonates, polycarboxylates, polyoxometalates, sulfonated or carboxylated metalloporphyrins, xanthan gum, alginates, or lignin compounds (e.g., ligninsulfonic acid, Any suitable anionic polymer that can form a PEC with a cationic polymer may be an anionic polymer selected from pectin, carrageenan, humicates, fulvate, angico gum, gum Kondagogu (Cochlospermum gossypium DC), sodium alkylnaphthalene sulfonate (e.g., MORWET®), poly-γ-glutamic acid, starch maleate half ester, carboxymethylcellulose, chondroitin sulfate, dextran sulfate, and hyaluronic acid. The anionic polymer may be linear, branched, dendritic, grafted, or exist as a copolymer (e.g., a block copolymer).

[0049] In preferred embodiments, the anionic polymer is a polyacrylate (PAAS). Specific examples of PAAS include alkali metal polyacrylates (e.g., sodium polyacrylate) and ammonium polyacrylate. The polyacrylate has a number average molecular weight of at least 10,000 g / mol. For example, the polyacrylate can have a number average molecular weight of 20,000 g / mol or more, for example, 40,000 g / mol or more, 60,000 g / mol or more, 80,000 g / mol or more, 100,000 g / mol or more, 120,000 g / mol or more, or 140,000 g / mol or more.

[0050] The size and internal structure of PEC particles are controlled, for example, by the formation process, medium and structural parameters, specific mixing sequence, mixing ratio, PEC concentration, pH, and molecular weight. Controlling the size of PEC particles is important because it affects 1) the overall stability of the pickering PEC; 2) the solubility of the film formed by the dispersion; and 3) the adhesive strength of the film to the substrate. The solubility and adhesion of the film can be adjusted by controlling the size of the final PEC colloid. Some applications require films that are less soluble and more adhesive. However, adjusting these two properties is always constrained by stability issues. If too many anionic polymers are used, the PEC colloid will become too large and precipitate.

[0051] The final PEC particle size can be determined by the ratio of anionic polymer electrolyte (n-) to cationic polymer electrolyte (n+). A high n- / n+ ratio will result in larger PEC particles. However, doping cationic polymers to anionic polymers promotes growth, followed by a decrease in size. The preferred doping method is to dope anionic polymers to cationic polymers, even if the doping order cannot produce the smallest particles (assuming an n- / n+ ratio of less than 0.8).

[0052] The size of PEC particles is also affected by the mixing order. When anionic polymers are added to cationic polymers, the PEC particles become larger. Nevertheless, there are techniques to counteract this undesirable growth. Firstly, by limiting the concentration of the polyelectrolyte in the forming solution; in other words, by working with a very dilute solution, the size of the PEC emulsion particles can be kept small. Given that a preferred mixing order has a detrimental effect on particle size, the counteracting strategy presented in this invention is to work with a dilute solution, i.e., limit the concentration of the polymer and then evaporate the excess water after the formation of the PEC. In certain embodiments of this invention, the method is not limited to cationic polymers (e.g., polydiallyldialkylammonium salts, acrylicoxyalkyltrialkylammonium salts, vinylphenalkyltrialkylammonium salts, acrylamidealkyltrialkylammonium salts) (Tium salts, PEI, and / or chitosan) at approximately 0.001-0.1M (e.g., 0.0 It is preferable to use it at a concentration of 0.5M.

[0053] A second method to counteract the tendency for PEC growth is to control the pH of the cationic polymer mixture relative to the pH of the anionic polymer mixture. For example, a lower pH (around pH 4) for the cationic polymer and a higher pH (around pH 10) for the anionic polymer will result in smaller particle sizes. Therefore, cationic polymers for generating PEC (e.g., polydiallyldialkylammonium salts, acrylicoxyalkyltrialkylammonium salts, vinylphenalkyltrialkylammonium salts, acrylamidealkyltrialkylammonium salts) The (but not essential) preferred pH of the PEC solution (containing PEI and / or chitosan) is maintained at approximately 4, and the anionic pH is maintained at approximately 10. The pH of the final PEC solution is approximately 4.5, and after evaporation, the pH is adjusted to approximately 7.4. The lower pH of the cationic polymer fluid is thought to contribute to smaller particle sizes and thus help offset the adverse effects of dosing order and molecular weight, which promote larger particle sizes.

[0054] To pass the EPA cytotoxicity test, the antimicrobial composition should be maintained at a pH of around 7. Even slight dissolution of the film during testing can cause leaching, and pH levels far above or below 7 will kill the mammalian cells used in the test, causing the film to fail. A pH of 7 should also help ensure that the anionic polymer is maintained in its ionized form. If necessary, the pH can be adjusted by adding a suitable acid (e.g., hydrochloric acid, sulfuric acid, citric acid, etc.) or base (e.g., sodium hydroxide, potassium hydroxide). The final pH is recommended to be adjusted after dispersing any organic and / or inorganic particles in the PEC.

[0055] In relation to the present invention, it is important that the PEC surface remains strongly positive. Since the antimicrobial action is thought to be related to a positively charged cationic polymer(s) that attracts and punctures negatively charged microbial films, for example, if an excess amount of anionic polymer is added (i.e., if (n- / n+) is too high), the PEC particle charge will become negative, which will destroy the effectiveness of the antimicrobial composition. Therefore, it is important that the PEC particle charge remains positive. For the purposes of the present invention, it is recommended that the (n- / n+) value not exceed 0.3, and preferably less than 0.2.

[0056] Generally, ppm relative to film thickness is determined by the amount of carrier (e.g., water) that evaporates from the mixed solution (e.g., PEC solution). When working with very dilute concentrations, a considerable excess of carrier needs to be evaporated to reach the desired ppm of solid in the film-forming composition.

[0057] In one embodiment of the present invention, the PECs are assembled such that they have an average aggregate size in solution of less than approximately 500 nm (e.g., less than 400 nm, less than 300 nm, less than 200 nm). In some embodiments, the aggregate size is less than approximately 100 nm in diameter (e.g., less than 80 nm, less than 50 nm, less than 25 nm, less than 10 nm). The particle size and molecular weight of the associated PECs can be measured by static or dynamic light scattering.

[0058] The antimicrobial composition preferably also includes at least one adhesion promoter that adheres the composition to the surface of a substrate to form a residual self-disinfecting film that cannot be immediately washed away. In some embodiments, the residual self-disinfecting film is not covalently bonded to the surface of the substrate. In some examples, the adhesion promoter may be described as a coupling agent. The adhesion promoter is typically one or more compounds having at least one functional group that is attractive to the surface of the desired substrate, at least one cationic polymer, or both. Suitable examples of adhesion promoters include titanates, carboxylated branched or linear PEIs, and syl The materials include ran compounds, cationic block copolymers, and other polymers that produce "adhesive" reactive groups such as acyl or carboxylic acids and carboxylic acid derivatives. Preferably, the adhesion promoter is a carboxylated branched PEI, as it does not impair the cationic charge of the polymer.

[0059] The titanate may be any suitable titanate that enhances the ability of the composition to adhere to a surface and / or allows the composition or a film formed from the composition to pass one or more of tests (i) to (v). Typically, the titanate is selected from alkoxy titanates, neoalkoxy titanates, oxyacetate chelate titanates, ethylene chelate titanates, pyrophosphate titanates, and combinations thereof.

[0060] In a preferred embodiment, the titanate is titanium IV2,2(bis-2-propenolatemethyl)butanolate, trisneodecanoate-O, titanium IV2,2(bis-2-propenolatemethyl)butanolate, tris(dodecyl)benzenesulfonate-O, titanium IV2,2(bis-2-propenolatemethyl)butanolate, tris(dioctyl)phosphat-O, titanium IV2,2(bis-2-propenolatemethyl)butanolate, The titanates are selected from tris(dioctyl)pyrophosphate-O, titanium IV2,2(bis2-propenolatemethyl)butanolate, tris(2-ethylenediamino)ethylate, titanium IV2,2(bis2-propenolatemethyl)butanolate, tris(3-amino)phenylate, titanium IV2,2(bis2-propenolatemethyl)butanolate, tris(6-hydroxy)hexanoate-O, or any combination thereof. Typically, the titanates are titanium IV2,2(bis2-propenolatemethyl)butanolate and trisneodecanoate-O.

[0061] The antimicrobial composition may contain any suitable amount of titanate to form a residual self-disinfecting film. The antimicrobial composition may contain titanate in an amount of 0.1% by weight ("wbm") or more based on the monomer of the cationic polymer, for example, 0.2%wbm or more, 0.3%wbm or more, 0.4%wbm or more, or 0.5%wbm or more. Alternatively, the antimicrobial composition may contain titanate in an amount of 6%wbm or less of the cationic polymer, for example, 5%wbm or less, 4%wbm or less, 3%wbm or less, 2%wbm or less, 1%wbm or less, 0.9%wbm or less, 0.8%wbm or less, or 0.7%wbm or less. Thus, the antimicrobial composition may contain titanate in an amount limited by any two of the aforementioned endpoints. For example, an antimicrobial composition may contain titanate in an amount between 0.1% wbm and 6% wbm of cationic monomers, for example, between 0.2% wbm and 6% wbm, between 0.3% and 6%, between 0.4% wbm and 6% wbm, between 0.5% wbm and 6% wbm, between 0.5% wbm and 5% wbm, between 0.5% wbm and 4% wbm, between 0.5% wbm and 3% wbm, between 0.5% wbm and 2% wbm, between 0.5% wbm and 1% wbm, between 0.5% wbm and 0.9% wbm, between 0.5% wbm and 0.8% wbm, or between 0.5% wbm and 0.7% wbm, for example, 0.6% wbm.

[0062] The adhesion promoter may be carboxylated PEI (PEI-COOH), which is either branched, linear, or a mixture of branched and linear. PEI-COOH can be commercially purchased or prepared from PEI. For example, bromoacetic acid in water can be added to PEI in water. The resulting mixture is then stirred, and then filtered to isolate the polymer and remove any unreacted acid. PEI-COOH can have any suitable molecular weight, but typically has a number-average molecular weight between 15,000 g / mol and 250,000 g / mol. PEI-COOH can be used in suitable amounts, usually in the range of 0.001% to 3% by weight, with endpoints including 0.01%, 0.1%, 0.5%, 1%, 1.5%, 2%, and / or 2.5%. Preferred amounts are in the range of 0.001% to 0.01% by weight, for example, 0.001% by weight.

[0063] As adhesion promoters, silane compounds such as silane coupling agents can be used. Generally, silane coupling agents have functional groups at both ends that bond organic groups, such as cationic polymers, to inorganic groups, such as substrates. Silane compounds have the formula R-(CH2) n -Si-X3 can be present in the formula, where R is an organic functional group (for example, a linear or branched C1-C that can be optionally substituted). 20The group is an alkyl, an aryl such as phenyl or naphthyl which is optionally substituted, an amino such as -NH(CH2)3NH2, an epoxy, or a methacrylate (m(NH2)3NH2), where n is an integer from 0 to 6, and X is a hydrolyzable group (e.g., alkoxy, acyloxy, halo, or amino). Suitable examples include trialkoxysilanes and monoalkoxysilanes (where the alkoxy is a C1-C6 alkoxy (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy, or a combination thereof)), dipodal (branched) silanes having two alkoxy-silane branches, cyclic azasilanes, vinylsilanes, acryloxysilanes, epoxysilanes, and aminosilanes, or any combination thereof. Specific examples of silane compounds include methyltrimethoxysilane, methyltriethoxysilane, isobutyltrimethoxysilane, n-octyltriethoxysilane, phenyltrimethoxysilane, vinyltrichlorosilane, vinyltris(β-methoxyethoxy)silane, vinyltriethoxysilane, vinyltrimethoxysilane, 3-methacryloxypropyl-trimethoxysilane, β-(3,4-epoxycyclohexyl)-ethyltrimethoxysilane, γ-glycidoxypropyltrimethoxysilane, γ-glycidoxypropyl-methyldiethoxysilane, and N-β This includes (aminoethyl)-γ-aminopropyl-trimethoxysilane, N-β(aminoethyl)-γ-aminopropyl-methyldimethoxysilane, 3-aminopropyl-triethoxysilane, and N-phenyl-γ-aminopropyl-trimethoxysilane, or combinations thereof.

[0064] Adhesion promoters can also be cationic block copolymers, such as high molecular weight polyethylene copolymers having basic or acidic adhesion groups such as amino and / or hydroxyl groups. Commercial products of this type include BYK® 4500, BYK® 4510, BYK® 4509, BYK® 4512, and BYK® 4513, which are available from BYK Chemie GmbH (Wesel, Germany). Suitable amounts of block copolymers range from 0.001% to 5% by weight, including endpoints of 0.01%, 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, or 5%. Preferred amounts range from 0.5% to 2% by weight, for example, 1% by weight.

[0065] The adhesion promoter may also be a polymer that naturally has or is modified to have “sticky” reactive groups such as acyl groups, carboxylic acids, carboxylic acid derivatives, sulfur-containing moieties (e.g., thio), amino groups, hydroxyl groups, and / or halo-containing groups. The polymer itself is any suitable part, preferably charge-free, such as polyethylene, polypropylene, poly(ethylene-vinyl acetate), polyester, polyurethane, polyamide, polyvinyl acetate, polyvinyl alcohol, polyvinyl butyral, polyvinyl chloride, polyvinyl ether, or combinations thereof. Suitable amounts of polymer are in the range of 0.001% to 3% by weight, including endpoints in the ranges of 0.01%, 0.1%, 0.5%, 1%, 1.5%, 2%, and / or 2.5%. Preferred amounts are in the range of 0.5% to 2% by weight, for example, 1% by weight.

[0066] In some embodiments, the antimicrobial composition may be any suitable organic particles (e.g., graphene or graphitic carbon nitride (g-C3N4)) and / or inorganic particles that are photocatalytically active in visible light (e.g., between 390 and 700 nm). The composition contains organic and / or inorganic particles. Photocatalytically active organic and / or inorganic particles can destroy pathogenic microorganisms (e.g., C. difficile, bacteria, and / or viruses, including triple influenza and SARS) and generate reactive oxygen species that enhance the bactericidal properties of the composition. Generally, organic and / or inorganic particles that are photocatalytically active in visible light are selected from graphene, g-C3N4, transition metal oxides, transition metal sulfides, transition metal selenides, dye sensitizers, conjugated polymers, noble metals, or mixtures thereof. A mixture of particles means that two or more different types of particles are present in the antimicrobial composition. In contrast, in polyjunctional complexes, the various components of the complex are closely bonded to ensure electron transfer and minimize hole recombination.

[0067] As used herein, the term “particle” includes spherical particles (e.g., spheres), as well as other shapes, such as plates, rods, cubes, and flakes, or combinations of various shapes and forms.

[0068] Graphene is an allotrope of carbon, in which carbon atoms are bonded to each other in a sheet-like structure with a thickness of one atom. Graphene can be selectively functionalized with oxygen-containing groups and / or nitrogen-containing groups. An analogue of graphite is graphite carbon nitride (g-C3N4), which is photocatalytic.

[0069] Transition metal oxides, sulfides, and selenides may be any suitable compounds comprising at least one metal atom and at least one anion of oxygen, sulfur, or selenium having an oxidation state of -2. In some embodiments, the transition metal oxide is selected from the group consisting of silicon dioxide (including fumed silica, amorphous silica, precipitated silica, hydrophilic silica, and hydrophobic silica), titanium dioxide, zinc oxide, iron oxide, aluminum oxide, cerium oxide, zirconium oxide, and combinations thereof; the transition metal sulfide is selected from cadmium sulfide, molybdenum disulfide, tungsten sulfide, silver sulfide, zinc sulfide, selenium sulfide, iron disulfide, nickel sulfide, ruthenium sulfide, cobalt sulfide, and combinations thereof; and / or the transition metal selenide is cadmium selenide, copper selenide, copper geranium selenide, copper indium gallium selenide, copper titanium selenide, indium selenide, manganese diselenium, titanium selenide, tungsten diselenium, silver selenide, disilver selenide, digold triselenium Selected from triselenide, zinc sulfide, iron selenide, nickel selenide, ruthenium selenide, cobalt selenide, and combinations thereof.

[0070] Tungsten doping and other metal doping have been shown to suppress charge recombination and improve the photocatalytic activity of photocatalysts (Rozenberg et al., Prog Polym Sci, 2008, 33:40-112). In a specific embodiment... Transition metal oxide / sulfide / selenium particles can be doped with suitable metals such as tungsten, nitrogen, or a combination of tungsten and nitrogen.

[0071] In one embodiment, the transition metal oxide is titanium dioxide (TiO2). TiO2 particles can be obtained from any suitable mineral form of TiO2. For example, TiO2 particles can maintain an anatase crystal structure, a brookite crystal structure, or a rutile crystal structure. In a preferred embodiment, TiO2 maintains an anatase crystal structure.

[0072] TiO2 particles can be of any suitable structural form. Typically, TiO2 particles are TiO2 nanoparticles ("NPs"). TiO2 nanoparticles can be synthesized by any suitable method. For example, TiO2 nanoparticles can be synthesized in liquid or gas. In a preferred embodiment, TiO2 nanoparticles are synthesized in liquid, as liquid synthesis tends to produce soft aggregates, thereby making it easier to disperse the TiO2. Exemplary TiO2 nanoparticles are tungsten-doped 25 nm anatase, liquid phase synthesis These are TiO2 nanoparticles, which can be purchased from Nanostructured & Amorphous Materials, Inc. (Houston, TX).

[0073] In a specific example of functionalized TiO2 particles, W-doped liquid synthetic TiO2 (20 nm) is calcined with urea at 400°C for 1 hour, which produces a poly(amino-tri-s-triazine) polymer covalently bonded to the TiO2 particles. Next, the W / N-doped TiO2 particles are pulverized with powdered urea. The hard material produced by calcination is pulverized into a powder so that it can be placed in a planetary ball mill with the urea. The milling specification is to pulverize at 300 rpm for 30 minutes using balls weighing 10 times the weight of 10% urea and TiO2. After 30 minutes, the milling drum is filled 3 / 4 with 200 ml of H2O and pulverized for a further 5 minutes to capture and disperse the TiO2 nanoparticles. The contents are then placed in a beaker and mixed under 150 W UV light for 1 hour. At this point, the highly dispersed nanopowder is available for addition to antimicrobial compositions. It is important to note that the nanopowder is highly dispersed in water, which helps to maintain it in a non-aggregated nanostate. Thus, the functionalization process described herein makes it possible for TiO2 to be dispersible in water (typically, TiO2 is dispersible only in alcohol). Creating such a stable nanodispersion without surfactants means that when the particles are dispersed in a cationic polymer solution or PEC, the particles will not be contaminated by surfactants, which can weaken their ability to respond to visible light.

[0074] High-energy milling of TiO2 particles achieves two things: 1) de-agglomerate the powder to produce nanoparticles; and 2) double-dope the particles with urea along with nitrogen, particularly doping newly exposed particle facets as high-energy milling breaks down aggregates and aggregates. Essentially, the milling is thought to push nitrogen into the pores and cover facets that were not previously exposed during the calcination process. After calcination with urea and milling with urea, the TiO2 nanoparticles are irradiated with 150 watts of UV light. While we do not wish to be bound by any theory, it is thought that UV irradiation improves the visible light responsiveness of the TiO2 nanoparticles by introducing hydroxyl groups onto the surface of the TiO2 nanoparticles. This is one explanation for why the particles disperse easily in water. The ability of the functionalized nanoparticles to decompose methylene blue was tested, and it was observed that the total of all four functionalization steps significantly decomposed the dye within 90 minutes.

[0075] Finally, after calcination, pulverization, washing, and light irradiation, the particles can be dye-sensitized. The theory and practice of using dyes to enhance the visible light sensitivity of transition metal oxide particles (e.g., TiO2) is important for "dye-sensitized solar cells" (DSSCs) technology. DSSCs have attracted considerable attention in recent years due to their relatively low cost and high efficiency. A DSSC is essentially a photoelectrochemical system, where light focusing is achieved by dye molecules adsorbed on the surface of oxide nanostructures that form a photoelectrode film. Surface sensitization of wide-bandgap semiconductor photocatalysts such as TiO2 with chemisorbed or physicosorbed dyes can increase the efficiency of the excitation process and expand the excitation wavelength range of transition metal oxide particles (e.g., TiO2). This occurs through the excitation of a sensitizer that can inject holes or, more generally, electrons into the particles. When a monolayer of dye is dispersed on a photocatalyst with a high surface area, very efficient charge injection is observed. This sensitization expands the wavelength response range of the photocatalyst, which is important for it to operate under natural sunlight. The electron injection and reverse electron transfer rates from the dye to transition metal oxide particles (e.g., TiO2) depend on the properties of the dye molecule, the characteristics of the transition metal oxide particles (e.g., TiO2), and the interaction between the dye and the transition metal oxide particles. Dyes include fluorescein, fluorescein isothiocyanate, cyanine, merocyanine, hemicyanine, perylene, xanthene, porphyrin (e.g., tetraphenylporphyrin), phthalocyanine (e.g., copper phthalocyanine), polyene, and polythiofone. Any suitable compound such as ester, coumarin (e.g., NKX-2677, NKX-2587, NKX-2697, NKX-2753, NKX-2586, or NKX-2311) and ruthenium-based dyes (e.g., (Bu4N)2[Ru(dcbpyH)2(NCS)2](N719), (Bu4N)2[Ru(dcbpy)2(NCS)2], cis-di(thiocyanato)bis(2,2'-bipyridyl-4,4'-dicarboxylate)ruthenium(II)(N3), tri(thiocyanato)-2,2',2''-terpyridyl-4,4',4''-(tricarboxylate)ruthenium(II) (black dye), K8, K9, K19, and Z907). In a particular embodiment of the present invention, the N719 dye is applied by mixing calcified / milled / UV-photofunctionalized transition metal oxide particles (e.g., TiO2) with a mixture of 0.5 mM N719 dye in ethanol in the dark for 1 hour. Other dyes may also be used. The functionalized particles are decanted, centrifuged, and added back to water.

[0076] In any of the embodiments described herein, TiO2 particles are doped with tungsten and nitrogen and hydrolyzed under ultraviolet (UV) light. The resulting particles are visible light-responsive TiO2 particles that are effective as antimicrobial agents, particularly when such particles are embedded in a film formed from the antimicrobial composition of the present invention. Accordingly, the present invention provides a method for killing microorganisms on a surface (e.g., sterilization of the surface, provision of a residual self-disinfecting film, or both), comprising applying an antimicrobial composition comprising (i) visible light-responsive TiO2 particles doped with tungsten and nitrogen, (ii) at least one adhesion promoter (e.g., titanate, carboxylated branched PEI), and (iii) a carrier to the surface. The adhesion promoter is as described herein, and the carrier may be, for example, water, alcohol, or a combination of water and alcohol, as described herein.

[0077] While not wishing to be bound by any particular theory, the electronic structure of TiO2 is characterized by a filled valence band and an empty conduction band. When the band gap energy is excited, electrons are propelled from the valence band to the conduction band, creating electron-hole pairs. These electron-holes react with water to produce reactive oxygen species, such as hydroxyl radicals, sometimes called reactive oxygen species (ROS). The holes in TiO2 decompose water molecules to form hydrogen gas and hydroxyl radicals. The negative electrons react with oxygen molecules to form superoxide anions (O2). - It forms a superoxide anion. The superoxide anion further reacts with water molecules to produce hydroxyl radical peroxide (·OOH) and hydrogen peroxide (H2O2). ·OH, O2 - ·OOH and H2O2 can react with pathogenic microorganisms and destroy their cellular structures.

[0078] Furthermore, electron holes themselves can directly react with microbial cell walls, cell membranes, and cellular components. In microzymes and bacilli, intracellular coenzyme A (CoA) is oxidized by TiO2, resulting in the loss of activity of CoA dimers, which halts cellular respiration and ultimately leads to microbial death. In this process, an electron shift between the dead cell and TiO2 passes through CoA. Consequently, the CoA content decreases and the number of CoA dimers increases.

[0079] Dye sensitizers include fluorescein, fluorescein isothiocyanate, cyanine, merocyanine, hemicyanine, perylene, xanthene, porphyrin (e.g., tetraphenylporphyrin), phthalocyanine (e.g., copper phthalocyanine), polyene, polythiophene, coumarin (e.g., NKX-2677, NKX-2587, NKX-2697, NKX-2753, NKX-2586, or NKX-2311) and ruthenium-based dyes (e.g., (Bu4N)2[Ru(dcbpyH)2(NCS)2](N719), (Bu4N)2[Ru(dcbpy)2(NCS)2], cis-di(thiocyanato)bis(2,2'-bipyridyl-4,4'-dicarboxylate)ruthenium(II)(N3), tri(thiocyanato)-2,2',2''-terpyridyl-4,4',4''-(tricarb) Any suitable compound such as xylate ruthenium(II) (black pigment), K8, K9, K19, and Z907.

[0080] Organic and / or inorganic photocatalytic particles may contain conductive conjugated polymers. Suitable conjugated polymers include polypyrrole (Ppy), poly(3-hexylthiophene) (P3HT), polycarbazole, polyindole, polyazepine, polyaniline, polyfluorene, polyphenylene, polypyrene, polyazulene, polynaphthalene, polythiophene (Ptp), poly(3,4-ethylenedioxythiophene), poly(p-phenylene sulfide), polyacetylene, poly(p-phenylene vinylene), and any combination thereof. Conjugated polymers can be incorporated into nanocomposite materials specifically designed to react with normal indoor lighting to generate reactive oxygen species (ROS). ROS destroys spore-like microorganisms that are difficult to kill, such as C. difficile and fungi. ROS also oxidizes microbial debris, thereby performing a continuous cleaning function. In certain embodiments, the photocatalytic nanocomposite material comprises a multi-junction composite material including WTiO2 / CN heterojunction / Ppy, where WTiO2 is tungsten-doped TiO2 nanoparticles as described herein, CN is graphic carbon nitride (g-C3N4), and Ppy is polypyrrole.

[0081] Historically, most photocatalytic materials have been designed around various metal sulfides and metal oxides rather than polymers. Titanium dioxide (TiO2) was the optimal metal oxide because it is readily available, inexpensive, stable, non-toxic, and highly reactive in the ultraviolet (UV) spectrum. The inventors wanted to go beyond the use of TiO2, as their objective was to create a photocatalytic material that would be reactive under normal indoor lighting. Because TiO2 has a broad band gap (3–3.2 eV), it absorbs only light in the UV spectrum that is not present in indoor lighting. Therefore, the present invention provides a polymer-based, i.e., metal-free or very limited, photocatalytic nanocomposite material. Such nanocomposite materials are likely to be less toxic to humans and the environment when incorporated into cationic polymer-containing residual self-disinfecting films as described herein, and do not have anionic charges that counteract cationic charges. In more polymer-based nanocomposite materials, WTiO2 in WTiO2 / CN heterojunction / Ppy multijunction composites is replaced with acid-modified or protonated graphic carbon nitride (g-C3N4). Protonation of CN gives CN a band gap with valence and conductivity bands very close to those of TiO2. The inventors have developed several techniques to generate protonated CN, called acidified carbon nitrate (ACN), and then strongly bond the protonated CN to heterogeneous CN and conjugated polymers (such as polypyrrole (Ppy), poly(3-hexylthiophene) (P3HT), polythiophene (Ptp)), thereby obtaining photocatalytic composite materials specifically designed to capture low levels of indoor light. This method is described in detail in U.S. Provisional Patent Application No. 62 / 367,981 and the inventors' concurrent provisional patent applications, the entirety of which is incorporated herein by reference.

[0082] The advantages of this new polymer-based photoreactive material include one or more of the following: (i) maximum photon focusing by multi-junction band slicing; (ii) maximum photon utilization by using materials with appropriate band edges, ordering assembly and tight bonding to facilitate rapid electron transport, and minimizing electron-hole recombination; and (iii) assembly using low-cost and easily scalable manufacturing processes that create nano, mesoporous materials with extremely high surface area, producing mixed morphologically stable dispersions of micro, nano, and crystalline particles and platelets, without using toxic chemicals or generating waste, maximizing the optical path of incident light and preserving all "invisible" nano / crystalline particles and platelets.

[0083] Organic and / or inorganic photocatalytic particles may contain precious metals such as ruthenium, rhodium, palladium, silver, osmium, iridium, platinum, gold, or mixtures thereof. In some embodiments, the precious metal is platinum.

[0084] The average diameter of organic and / or inorganic particles that are photocatalytically active in visible light is not particularly limited and may be in the range of 5 nm to 1,000 nm. Organic and / or inorganic particles may have an average diameter of 1,000 nm or less, for example, 750 nm or less, 500 nm or less, 250 nm or less, or 100 nm or less. Alternatively, organic and / or inorganic particles may have an average diameter of 5 nm or more, for example, 10 nm or more, or 15 nm or more. Thus, organic and / or inorganic photocatalytic particles may have an average diameter limited by any two of the aforementioned endpoints. For example, organic and / or inorganic photocatalytic particles may have an average diameter of 5 nm to 1,000 nm, 5 nm to 750 nm, 5 nm to 500 nm, 5 nm to 250 nm, 5 nm to 100 nm, 10 nm to 100 nm, or 15 nm to 100 nm.

[0085] The antimicrobial composition may contain any appropriate amount of organic and / or inorganic photocatalytic particles to form a residual self-disinfecting film. The antimicrobial composition may contain organic and / or inorganic photocatalytic particles in amounts of 1% by weight ("wbm") or more, based on the monomer of the cationic monomer, for example, 1.5%wbm or more, 2%wbm or more, 2.5%wbm or more, 3%wbm or more, 4%wbm or more, or 5%wbm or more. Alternatively, the antimicrobial composition may contain organic and / or inorganic particles in amounts of 20%wbm or less, or less, based on the cationic polymer, for example, 18%wbm or less, 15%wbm or less, 12%wbm or less, 10%wbm, 9%wbm or less, 8%wbm or less, 7%wbm or less, 6%wbm or less, or 5%wbm or less. Thus, the antimicrobial composition may contain organic and / or inorganic particles in amounts limited by any two of the aforementioned endpoints. For example, an antimicrobial composition may contain organic and / or inorganic particles in amounts between 1% wbm and 20% wbm of cationic monomers, such as between 1% wbm and 15% wbm, between 1% wbm and 10% wbm, between 1% wbm and 7% wbm, between 1% wbm and 6% wbm, between 1% wbm and 5% wbm, between 4% wbm and 20% wbm, between 5% wbm and 15% wbm, between 4% wbm and 8% wbm, or between 5% wbm and 8% wbm.

[0086] In one aspect of the present invention, the antimicrobial composition comprises at least one organic and / or inorganic particle that is photocatalytically active in visible light, at least one adhesion promoter, and a carrier. The organic and inorganic photocatalytic particles, adhesion promoter, and carrier are described herein. Under the conditions of the modified protocol of JIS Z 2801 (2006 edition, updated in 2010), a film formed from the antimicrobial composition containing the photocatalytic particles kills microorganisms. For example, an antimicrobial composition containing at least one organic and / or inorganic particle that is photocatalytically active in visible light kills at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 97%, at least 98%, at least 99%) of a log4 population of Clostridium difficile bacteria, fungi, or yeasts within 24 hours of contact. Thus, the composition may be used according to any of the methods described herein to kill microorganisms on a surface.

[0087] In some embodiments, the antimicrobial composition contains salts, which may affect the ability of the cationic polymer to adsorb to the surface of the substrate and form a film. While we do not wish to be bound by any theory, it is thought that high salt concentrations induce conditions similar to those experienced by polymers in a preferred solvent. Polyelectrolytes, even when charged, are still primarily nonpolar due to their carbon backbone. While charges on the polymer backbone exert electrostatic forces that drive the polymer into a more open, loose stereostructure, if the surrounding solution has a high concentration of salts, the charge repulsion will be screened. This charge is screened ( When screened, the polyelectrolyte will begin to function like any other nonpolar polymer in a high ionic strength solution, minimizing its interaction with the solvent. This can lead to the deposition of a much more aggregated, high-density polymer on the surface, potentially resulting in improved adsorption or adhesion.

[0088] The salt is any inorganic salt, such as any salt containing a cation of a Group I metal (lithium, sodium, potassium, rubidium, or cesium), a Group II metal (beryllium, magnesium, calcium, strontium, or barium), ammonium, or aluminum. The counteranion may be a halide, carbonate, bicarbonate, sulfate, thiosulfate, phosphate, nitrate, nitrite, acetate, bromate, chlorate, or iodate. Specific examples of salts include lithium bromide, lithium chloride, lithium iodate, lithium iodide, lithium hydroxide, lithium sulfate, lithium phosphate, sodium bromide, sodium chloride, sodium acetate, sodium bicarbonate, sodium bisulfate, sodium bromate, sodium chlorate, sodium hydrosulfide, sodium hydroxide, sodium hypophosphite, sodium iodate, sodium iodide, potassium acetate, potassium bicarbonate, potassium bromate, potassium bromide, potassium chloride, potassium carbonate, potassium chlorate, potassium hydroxide, potassium iodide, potassium phosphate, potassium thiosulfate, rubidium bromide, rubidium chloride, rubidium fluoride, rubidium iodide, rubidium nitrate, rubidium sulfate, cesium bromide, cesium chloride, cesium carbonate, cesium nitrate, beryllium nitrate, beryllium sulfate, magnesium acetate This includes strontium, magnesium bromide, magnesium chloride, magnesium iodate, magnesium iodide, magnesium nitrate, magnesium phosphate, magnesium sulfate, calcium acetate, calcium bromide, calcium chloride, calcium iodide, calcium iodate, calcium nitrite, calcium nitrate, calcium phosphate, calcium sulfate, strontium bromide, strontium chloride, strontium hydrogen phosphate, strontium iodide, strontium nitrate, strontium sulfate, barium acetate, barium bromide, barium chloride, barium iodide, barium nitrate, barium phosphate, barium sulfate, barium thiosulfate, ammonium acetate, ammonium bicarbonate, ammonium bromide, ammonium chloride, ammonium nitrate, aluminum chloride, aluminum phosphate, and any combination thereof. In some embodiments, the salt is a group I halide salt such as sodium chloride or potassium chloride.

[0089] The antimicrobial composition may contain any suitable amount of salt, such as 0.01M to 0.1M, including any combination of endpoints at 0.01M, 0.02M, 0.03M, 0.04M, 0.05M, 0.06M, 0.07M, 0.08M, 0.09M, and 0.1M. In a particular example, the antimicrobial composition contains 0.01M to 0.05M of salt.

[0090] If desired, the cationic polymer can be mixed with one or more non-electrolyte (non-ionic) polymers. Suitable non-electrolyte (non-ionic) polymers are preferably water-soluble and include, for example, polyacrylamide, polyamine, polyamidoamine, polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, and polyacrylate (e.g., poly(methyl)methacrylate), or any combination thereof.

[0091] The antimicrobial composition contains a carrier. The carrier can be any suitable carrier that evaporates when the composition is applied to a desired surface. Generally, the carrier is selected from alcohol, water, or a combination thereof. In some embodiments, the carrier contains a combination of water and alcohol. Suitable alcohols include methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, and t-butanol, or a combination thereof. In preferred embodiments, the carrier contains ethanol (for example, the carrier is a combination of ethanol and water). When an alcohol-water combination is used as the carrier, the alcohol:water ratio is preferably 10:90 to 99:1 (e.g., 10:90, 20:80, 30:70, 40:60, 50:50, 60:40, 70:30, 80: (These are in the ranges of 20, 90:10, 95:5, and 99:1). In certain embodiments, the alcohol:water ratio is in the range of 70:30 to 80:20.

[0092] In general, antimicrobial compositions do not contain pathogenic small molecule compounds (i.e., nonpolymers) or antimicrobial metals, including conventional pathogenic agents registered with the EPA, because such components have a significant impact on the composition. EPA-approved pathogenic agents that can be excluded from a composition include, for example, glutaraldehyde, halazon, hexachlorophene, nitrofurazone, nitromersol, povidone-iodine, thimerosol, C1-C5-parabens, hypochlorites, clofucarban, chlorophene, poloxamer-iodine, phenols, mafenide acetate, aminacline hydrochloride, quaternary ammonium salts, oxychlorocene, metabromsaran, merbromin, dibromsaran, glyceryl laurate, sodium and / or zinc pyrithione, (dodecyl)(diethylenediamine)glycine, (dodecyl) N-(high molecular weight)C12 10 -C 24This includes alkyl-N-benzyl-quaternary ammonium salts. Suitable quaternary ammonium compounds are described in U.S. Patent No. 8,067,403 and include benzalkonium chloride (e.g., benzalkonium chloride), substituted benzalkonium chloride (e.g., alkyldimethylbenzylammonium chloride), double quaternary ammonium compounds (e.g., containing an equimolar mixture of alkyldimethylbenzylammonium chloride and alkyldimethylethylbenzylammonium chloride), twin or double-chain quaternary ammonium compounds such as dialkylmethylamines (e.g., didecyldimethylammonium chloride or dioctyldimethylammonium chloride), and mixtures of second-generation quaternary ammonium compounds and fourth-generation quaternary ammonium compounds (e.g., didecyldimethylammonium chloride and alkyldimethylbenzylammonium chloride). In one embodiment, the pathogenic agent is at least one member selected from the group consisting of sodium hypochlorite, chloride, chlorine dioxide, sodium chloride, potassium persulfate, potassium permanganate, silver nitrate, chlordexidine, hexachlorophene, hydrogen peroxide, acetic acid, peracetic acid, betadine, povidone-iodine, formaldehyde, glutaraldehyde, benzalkonium chloride, triclosan, boric acid, phenol, cresol acid, thymol, and polyhexamethyl biguanide.

[0093] However, if desired, one or more additional chemical pathogenic agents, such as those described above, may be added to any of the aforementioned embodiments of the antimicrobial composition. This option provides further chemical killing mechanisms to further enhance the antimicrobial activity of the antimicrobial composition. Once one or more pathogenic agents are incorporated into the antimicrobial composition, they are captured by the antimicrobial residual self-disinfecting film and gradually released as the coated surface comes into contact with moisture. When the film is exposed to a larger amount of water, such as when the surface is wiped, wet with food residue, or washed with water, this can result in the release of a larger amount of pathogenic agents. Therefore, whatever pathogenic agents are used, they must not be toxic to humans, nor should they make the film sticky, cloudy, or impair the appearance of the surface to which they are applied. Pathogenic agents are typically added at low concentrations. Therefore, such additives preferably consist of 0.001% by weight ("wbm") to 5% by weight ("wbm") based on the monomer of a cationic polymer.

[0094] In a particular embodiment, the antimicrobial composition is polydiallyldimethylammonium haly. The antimicrobial composition comprises or consists of polydiallyldimethylammonium halide, polyethyleneimine polymer, anionic polymer, at least one adhesion promoter (e.g., titanate, carboxylated branched PEI), optionally, organic and / or inorganic particles that are photocatalytically active in visible light, and a carrier, each of which is described herein. In some embodiments of this embodiment, the organic and / or inorganic particles that are photocatalytically active in visible light are present in the composition. In certain embodiments, the antimicrobial composition comprises or consists of polydiallyldimethylammonium halide, polyethyleneimine polymer, at least one adhesion promoter, optionally, anionic polymer, optionally, organic and / or inorganic particles that are photocatalytically active in visible light, and a carrier, each of which is described herein. In certain embodiments, the antimicrobial composition comprises or consists of polydiallyldimethylammonium halide, at least one adhesion promoter (e.g., titanate, carboxylated branched PEI), organic and / or inorganic particles that are photocatalytically active in visible light, and a carrier, each of which is described herein.

[0095] Another aspect of the present invention is an antimicrobial composition comprising a polyethyleneimine polymer, optionally a second cationic polymer selected from polydiallyldialkylammonium salts, poly(acrylamide-co-diallyldialkylammonium halide), chitosan, or a combination thereof, optionally a polyacid, optionally at least one adhesion promoter, and a carrier. The polyethyleneimine polymer is typically linear or branched polyethyleneimine (PEI) as described herein, but preferably linear PEI that is not chemically or structurally modified.

[0096] In some examples, the second cationic polymer is absent. In other examples, the second cationic polymer is a polydiallyldialkylammonium salt, which is a polydiallyldimethylammonium halide (e.g., polydiallyldimethylammonium chloride and / or polydiallyldimethylammonium fluoride). In one embodiment, the second cationic polymer is a poly(acrylamide-co-diallyldialkylammonium halide), such as poly(acrylamide-co-diallyldimethylammonium chloride). In other embodiments, the second cationic polymer is chitosan.

[0097] The polyacid and at least one adhesion promoter are as described herein.

[0098] The carrier used in the composition is any suitable carrier (e.g., water, propanol, isopropanol, and / or ethanol) as described herein. Typically, the composition will contain a mixture of various alcohols in 20% to 80% by volume, with the remainder supplemented with water. To enhance the antiviral effect, a mixture of various alcohols in amounts between 3% and 10% of a diol, preferably propanediol (1,2-propanediol and 1,3-propanediol) or butanediol (1,3-butanediol), having a chain length of 3 to 5 carbon atoms, can be added to the composition. Preferably, the diol is 1,2-propanediol and / or the alcohol is ethanol.

[0099] Proton donors can be added to the composition in appropriate amounts (for example, about 0.015 to about 1 percent of the total weight of alcohol, including about 0.05 to about 1 percent, about 0.08 to about 0.8 percent, and about 0.1 to about 0.8 percent). Proton donors include hydrochloric acid, nitric acid, phosphoric acid, phosphonic acid, boric acid, sulfuric acid, adipic acid, benzene 1,3,5-tricarboxylic acid, chlorosuccinic acid, choline chloride, cis-aconitic acid, citramaric acid, citric acid, cyclobutane 1,1,3,3-tetracarboxylic acid, cyclohexane 1,2,4,5-tetracarboxylic acid, cyclopentane 1,2,3,4-tetracarboxylic acid, diglycolic acid, fumaric acid, glutamic acid, glutaric acid, glyoxylic acid, isocitric acid, ketomalonic acid, lactic acid, maleic acid, malic acid, malonic acid, nitrilotriacetic acid, oxalacetic acid, oxalic acid, phytomethyl The proton donor is any suitable compound such as citric acid, p-toluenesulfonic acid, salicylic acid, succinic acid, tartaric acid, tartonic acid, tetrahydrofuran 2,3,4,5-tetracarboxylic acid, tricarbaryl acid, bercenic acid, 3-hydroxyglutaric acid, 2-hydroxypropane, 1,3-dicarboxylic acid, glyceric acid, furan 2,5-dicarboxylic acid, 3,4-dihydroxyfuran-2,5-dicarboxylic acid, 3,4-dihydroxytetrahydrofuran-2,5-dicarboxylic acid, 2-oxo-glutaric acid, dl-glyceric acid, 2,5-furan-dicarboxylic acid, or a mixture thereof. Preferably, the proton donor is citric acid, tartaric acid, malonic acid, and / or malic acid. More preferably, the proton donor is citric acid.

[0100] If desired, the composition may also contain other components, such as propylene glycol, thickeners (e.g., polyacrylic acid), humectants (e.g., glycerin, aloe vera), essential oils (e.g., tea tree oil), fruit extracts, fragrances (e.g., carbomer, aminomethylpropanol, isopropyl myristate, tocopheryl acetate), and / or dyes (e.g., Blue 1, Red 33, Yellow 5). Depending on the carrier, the polymer used, and the presence of additional components, the composition may be in any desired formulation, including liquids, creams, gels, or foams.

[0101] In certain examples, the composition comprises unmodified linear PEI, polyDADMAC, optionally citrate, carboxylated branched PEI, and a water / alcohol carrier.

[0102] In one embodiment, a polyethyleneimine polymer and a second cationic polymer form a crystalline miscible mixture that provides a stable dispersion in a carrier. The miscible mixture is stable, i.e., it provides a clear crystalline solution from which there is no precipitate or byproduct. The miscible mixture is different from PEC. Furthermore, although we do not wish to be bound by any theory, it is thought that the crystallinity of the polymers in the mixture has a larger surface area and can provide more interfaces between the cationic polymer and microbial pathogens, both in solution and as a film.

[0103] Miscible crystalline mixtures can be prepared by any suitable method. In a particular example, a miscible mixture of chemically unmodified linear PEI and another cationic polymer can be prepared as follows: A suitable amount of water / PEI dispersion (e.g., about 4000 ppm PEI) is heated to a temperature slightly above the glass transition temperature of PEI (e.g., at least 1°C above the glass transition temperature, at least about 2°C above the glass transition temperature, at least about 3°C ​​above the glass transition temperature, at least about 4°C above the glass transition temperature, at least about 5°C above the glass transition temperature; including temperatures of 65-80°C or 68-78°C or 70-75°C, or temperatures of about 70°C, about 72°C, or about 74°C). A suitable amount of a solution of a second cationic polymer (e.g., polyDADMAC) having a lower pH (e.g., pH about 5-6, including pH about 5, pH about 5.5, or pH about 6) is then added. This lower pH further helps ensure that the PEI remains in solution. After vigorous mixing, the solution is cooled to room temperature. Next, an appropriate amount (e.g., 25-100 ppm) of adhesion promoter (e.g., carboxylated branched PEI) is added. Carboxylated branched PEI is very basic, and this will raise the pH of the solution. The pH should be readjusted to 6.5 to prevent the linear PEI from solidifying. Next, the solution is reheated to a temperature slightly above the glass transition temperature of PEI (e.g., at least 1°C above the glass transition temperature, at least about 2°C above the glass transition temperature, at least about 3°C ​​above the glass transition temperature, at least about 4°C above the glass transition temperature, at least about 5°C above the glass transition temperature; including temperatures in the range of 65-80°C or 68-78°C or 70-75°C, or about 72°C or about 75°C). An appropriate amount of alcohol is added dropwise while vigorous stirring of the mixture. The mixture is continuously stirred while cooling to room temperature. Then the solution is heated to room temperature. Stir the liquid for another 24 hours.

[0104] PEI-containing compositions may have one or more bactericidal, virucidal, and / or germicidal properties and, if desired, can be used as antimicrobial compositions, particularly as hand sanitizers, according to the tests, substrates, and / or methods described herein. Accordingly, provided is a method for disinfecting a surface, comprising applying a composition to the surface comprising a polyethyleneimine polymer, optionally a second cationic polymer selected from polydiallyldialkylammonium salt, poly(acrylamide-co-diallyldialkylammonium halide), chitosan, or a combination thereof, optionally a polyacid, optionally at least one adhesion promoter, and a carrier. In one embodiment of this method, a composition comprising chemically unmodified linear PEI, optionally a polyacid, and a carrier comprising water and alcohol is used as a hand sanitizer particularly effective against non-enveloped viruses.

[0105] Since linear PEI is sensitive to pH and temperature, special techniques have been developed to produce stable, transparent, non-sticky hand sanitizer mixtures containing a linear PEI colloidal dispersion. In a specific example, the method for preparing the hand sanitizer composition includes the following steps: At room temperature, a suitable amount of linear PEI in water is vigorously stirred to produce a PEI dispersion. While vigorously stirring, the PEI in the dispersion is then protonated with a suitable acid, thereby lowering the pH to 6 and obtaining a transparent liquid. The transparent liquid is then heated to a temperature slightly above the glass transition temperature of PEI (e.g., at least 1°C above the glass transition temperature, at least about 2°C above the glass transition temperature, at least about 3°C ​​above the glass transition temperature, at least about 4°C above the glass transition temperature, at least about 5°C above the glass transition temperature; including temperatures in the range of 65-80°C or 68-78°C or 70-75°C, or about 70°C, about 72°C, or about 74°C). A suitable amount of alcohol is then added dropwise to maintain the temperature of the transparent liquid at about 65°C. The clear hand sanitizer mixture was cooled to avoid excessive alcohol evaporation, and then stirred for several hours (e.g., at least 2 hours, at least 3 hours, at least 4 hours, or at least 5 hours) while covered.

[0106] The antimicrobial composition of the present invention satisfies or exceeds at least one of the following antimicrobial tests: (i) Pathogenic spray testing in accordance with ASTM E1153, meeting EPA requirements for log3 reduction against viruses and log5 reduction against bacteria. (ii) Suspension test in accordance with ASTM E1052-96 (2002) or ASTM E2315 (2016) (iii) A film formed from the composition (iii) Within 30 minutes, at least 95% of the log5 population of Gram-positive or Gram-negative bacteria, (iii-b) At least 95% of the log4 population of enveloped viruses within 30 minutes of contact. (iii-c) at least 95% of non-enveloped viruses within 30 minutes of contact, and / or (iii-d) Within 24 hours of contact, at least 94% of the log4 population of Clostridium difficile bacteria, Inhibitory activity is determined by the JIS Z 2801 (2006) test, or a modified version of such test as described herein. (iv) A film formed from the composition conforms to the International Organization for Standardization (ISO) 10993-5 According to the in vitro cytotoxicity test, the value is 2 or less. (v)(va) Films formed from composition (v)(va) exhibit at least 99.9% of Gram-positive and Gram-negative bacteria according to the EPA Protocol #01-1A residual self-disinfecting activity test. (vb) A durability test in which, after waiting 7 days following film formation, the film formed from the composition kills at least 95% of Gram-positive and Gram-negative bacteria or enveloped and non-enveloped viruses, according to a modified version of Protocol #01-1A Residual Self-Disinfecting Activity Test described herein.

[0107] Test (i) refers to ASTM E1153, whose entire content is incorporated by reference, and is a pathogen-killing spray test used to evaluate the antimicrobial efficacy of a one-step cleaner disinfectant formulation recommended for use on lightly soiled, animate, non-porous, non-food-contact surfaces (i.e., a "kill now" claim). ASTM E1153 (last revised in 2014) states that the antimicrobial efficacy of a disinfectant is tested against Staphylococcus aureus, Klebsiella pneumoniae, Enterobacter aerogenes, or a combination thereof, on a pre-cleaned, animate, hard, non-porous, non-food-contact surface.

[0108] Table 3 shows the results of pathogenic spray tests for the miscible mixture formulation of the present invention, along with a comparison with three commercially available products. Pathogenic spray tests for MS2, MRSA, and E. coli were performed using two cationic polymer compositions. Composition A was a miscible mixture containing 3000 ppm of chemically unmodified linear PEI, 3000 ppm of polyDADMAC, 25 ppm of carboxylated branched PEI, 35% ethanol, and the remainder water. Composition B was a miscible mixture containing 200 ppm of chemically unmodified linear PEI, 200 ppm of polyDADMAC, 25 ppm of carboxylated branched PEI, 70% ethanol, and the remainder water (operational pH was approximately 7.6).

[0109] [Table 3]

[0110] The results in Table 3 demonstrate that composition B, containing 400 ppm of cationic polymer, passed the MS2 pathogen-killing spray test within 5 minutes of contact, which is noteworthy as the EPA's maximum ppm standard for quaternary ammonium compounds is 400 ppm according to ASTM E1153. Furthermore, the antimicrobial efficacy of some quaternary ammonium compounds is significantly reduced by soil or organic matter loading. As seen in Table 3, composition B was also highly effective against MRSA and E. coli in the spray test (ASTM E1153) in the presence of a 5% soil loading.

[0111] Test (ii) is a suspension test according to ASTM E1052-96 (2002) or ASTM E2315 (2016) to determine the efficacy of an antimicrobial solution in the form of a suspension against specific viruses such as adenovirus, coronavirus, influenza virus, rhinovirus, and rotavirus. The test virus is inoculated into aliquots of the test substance and held for a required exposure time. At each predetermined exposure time, the aliquots are taken out, neutralized by serial dilution, and assayed for viral infectivity using an assay method specific to the test virus. Appropriate virus, cytotoxicity of the test substance, and neutralization controls are performed simultaneously. The percentage and logarithmic reduction of viral infectivity are calculated in comparison to the corresponding viral control. ASTM E1052-96 (2002) and ASTM E2315 (2016) are most suitable for antimicrobial compositions that are suspensions, such as hand sanitizer compositions.

[0112] For test (iii), the film formed from the antimicrobial composition was found to be effective against Gram-positive bacteria and Gram-negative bacteria, as well as enveloped viruses, non-enveloped viruses, and / or chloroforms. The ability to kill Stridium difficile bacteria can be tested according to the conditions described in JIS Z 2801 (2006 edition, updated in 2010), which is known as a Japanese Industrial Standards test for antimicrobial activity and efficacy in antimicrobial products and whose entire contents are incorporated by reference. In particular, as described herein, according to JIS Z 2801 (2006) or a modified version thereof, a film formed from the antimicrobial composition of the present invention kills (iii-a) at least 95% of the log5 population of Gram-positive or Gram-negative bacteria within 30 minutes, (iii-b) at least 95% of the log4 population of enveloped viruses within 30 minutes of contact, (iii-c) at least 95% of non-enveloped viruses within 30 minutes of contact, and / or (iii-d) at least 94% of the log4 population of Clostridium difficile bacteria within 24 hours of contact. In a preferred embodiment, a film formed from the antimicrobial composition of the present invention satisfies two or more, three or more, or all four of requirements (iii-a) to (iii-d).

[0113] For example, under the conditions of this test, the JIS Z 2801 protocol showed a log4 reduction in E. coli on a film containing only polyDADMAC after 30 minutes in response to a log5 challenge (Table 4).

[0114] [Table 4]

[0115] The same film, subjected to a log7 challenge, showed a log4 reduction in MRSA after 10 minutes (Table 5).

[0116] [Table 5]

[0117] In particular when testing antiviral activity, an additional self-disinfecting ("later kill") test was devised for residual self-disinfecting films, which is considered more practical for real-world applications. This test is based on the assumption that, in real-world applications, the antimicrobial residual self-disinfecting film will not be covered. This test modifies JIS Z 2801 (2006 edition, updated in 2010) by eliminating the need to cover the inoculated film and by starting the test time after the inoculation has dried. 3000 ppm Table 6 shows the results of tests using the modified JIS Z 2801 to measure the solubility of MS2 on films prepared from a non-toxic, miscible mixture of chemically unmodified linear PEI, 3000 ppm polyDADMAC, 79% ethanol, 25 ppm carboxylated branched PEI, and the remainder water. "Post-kill" data for Gram-positive and Gram-negative bacteria were prepared using standard JIS tests.

[0118] [Table 6]

[0119] Furthermore, the test was conducted under illumination conditions, and the sample surface area was set to 1600 mm². 2 From 2500mm 2 By increasing the amount, when testing against Clostridium difficile bacteria, JIS It is possible to modify Z 2801 (2006 version, updated in 2010).

[0120] Test (iv) relates to ISO 10993-5 (last updated in 2009), whose entire content is incorporated by reference, and which tests the in vitro cytotoxicity of medical device materials. This method relates to the incubation of cultured cells in contact with the device and / or an extract of the device, either directly or by diffusion. In particular, the test material, positive control and negative control are extracted according to method ISO 10993-12. The original extract is serially diluted, and five concentrations are used for the test. L-929 cells (mouse, C3H / An, connective tissue) are treated with the sample extract, reagent control, and either the negative control or the positive control. A triplicate plate is prepared for each treatment. Cells are incubated for 24 hours and observed under a microscope for cytotoxic activity. The cultures are observed under a microscope and graded on a scale of 0 to 4 for reactivity ("4" means severe cytotoxicity; "3" means moderate cytotoxicity; "2" means mild cytotoxicity; "1" means slight cytotoxicity; and "0" means non-cytotoxicity). If the result is grade 2 or lower (i.e., 0, 1, or 2), the test sample meets the requirements of the test.

[0121] The residual self-disinfecting films formed from PEC, miscible mixtures, or individual cationic polymers described herein are non-leaching and, as shown by the following test results in Table 7, score 0 in ISO 10993-5 (2009 edition) It passes the in vitro cytotoxicity test.

[0122] [Table 7]

[0123] Test (v) relates to Protocol #01-1A, commonly known as the "Clorox Test," a method approved by the EPA for the claim of long-term disinfection (i.e., the claim of "later killing" durability). Protocol #01-1A, whose entire contents are incorporated by reference, measures the residual self-disinfecting activity of a dried chemical residue (film) on an inanimate, hard, non-porous surface against only the bacteria: Staphylococcus aureus, Klebsiella pneumoniae, and / or Enterobacter aerogenes. Specifically, the surface is inoculated, treated with the test product, dried, and then rubbed under alternating wet and dry conditions, with several re-inoculations dotted thereto. At the end of the test and at least 24 hours later, the ability of the test surface to kill 99.9% of microorganisms within 5 minutes is measured. To pass this test, the film formed from the composition must maintain its antimicrobial efficacy during and after 12 alternating wet and dry abrasions with a loaded cloth.

[0124] Protocol #01-1A, a modified version of the EPA durability test, can be used. Since Protocol #01-1A relies on killing microorganisms by releasing pathogenic chemicals from the film and is designed for products that are depleted over time, the modified protocol is considered more appropriate for evaluating residual self-disinfecting films formed from the antimicrobial composition of the present invention. The antimicrobial composition of the present invention contains a charged cationic polymer whose killing mechanism is not expected to be depleted over time and does not require pathogenic chemicals. The modified test consists of subjecting the film to three friction cycles daily (one dry, one wet, one dry) using the load and cycle times of the EPA #01-1A protocol. This modified test captures the antimicrobial effect of the antimicrobial composition over several days compared to a single 24-hour measurement in standard Protocol #01-1A. To pass the modified test, the polymer-based film must be resistant to glass or stucco after 4–7 days. It will be necessary to continue demonstrating a reduction of at least 95% (e.g., at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9%) of Gram-positive bacteria, Gram-negative bacteria, enveloped viruses, and / or non-enveloped viruses on stainless steel substrates.

[0125] The present invention also provides a method for killing microorganisms on a surface, comprising applying an antimicrobial composition to the surface comprising a cationic polymer (alone or encapsulated in PEC), at least one adhesion promoter (e.g., titanate, carboxylated branched PEI), optionally, organic and / or inorganic particles that are photocatalytically active in visible light, and a carrier (each of these components is as described herein). The method may include disinfecting the surface, providing a residual self-disinfecting film, or both. The term “microorganism” includes any unicellular or multicellular organism such as bacteria, viruses, fungi, archaea, and protists (e.g., algae, amoebas, protozoa). As used herein, the term “apply” means any suitable technique used to transfer the antimicrobial composition to the surface. For example, the techniques for application may include, but are not limited to, brushing, rolling, spraying, wiping, mopping, injecting, painting, absorbing, adsorption, imbibing, immersion, saturation, penetration, immersion, and combinations thereof.

[0126] Further provided is a method for killing microorganisms on a surface (e.g., sterilizing the surface, providing a residual self-disinfecting film, or both), comprising applying an antimicrobial composition comprising a high molecular weight (preferably very high molecular weight) polydiallyldimethylammonium salt (e.g., polydiallyldimethylammonium halide) and a carrier to the surface, as described herein. The antimicrobial composition of this embodiment may further include (i) polyethyleneimine polymers, chitosan, or combinations thereof, and / or (ii) anionic polymers, and / or (iii) organic and / or inorganic particles that are photocatalytically active in visible light, and / or (iv) at least one adhesion promoter (e.g., titanate, carboxylated branched PEI), and / or (v) at least one salt. Each of these optional components is as described herein.

[0127] Once applied to a surface, the carriers in the composition described herein evaporate, leaving an antimicrobial residual self-disinfecting film on the surface. The antimicrobial residual self-disinfecting film makes the surface bactericidal, virucidal, and / or germicidal. As used herein, the term “making a surface bactericidal, virucidal, and / or germicidal” means reducing the presence of bacteria, viruses, and / or pathogens (including fungi such as Aspergilla brasliensis) to any appropriate degree (e.g., removing, killing, preventing and / or inhibiting their growth). As used herein, the term “any appropriate degree” means a reduction of 50% or more, including a reduction of 60% or more, a reduction of 70% or more, a reduction of 80% or more, a reduction of 90% or more, a reduction of 92% or more, a reduction of 94% or more, a reduction of 95% or more, a reduction of 97% or more, a reduction of 98% or more, a reduction of 99% or more, or a removal of 99.5% or more.

[0128] According to this embodiment, the present invention provides a coated surface comprising a surface (e.g., the surface of a substrate) and an antimicrobial residual self-disinfecting film applied to the surface as described herein. The resulting film provides a non-leaching surface that is not easily removed. In most embodiments, the antimicrobial residual self-disinfecting film is not covalently bonded to the surface (e.g., the surface of a substrate).

[0129] Surfaces to be made bactericidal, virucidal, and / or germicidal include any biocompatible material. The surface may be made of suitable materials. The surface may be used in or derived from any suitable form, such as powder, dust, aggregates, amorphous solids, sheets, fibers, tubes, cloths, etc. In embodiments, the surface may include metal, glass, glass fiber, silica, sand, wood, fibers, natural polymers, synthetic polymers, plastics, rubber, ceramics, porcelain, stone, marble, cement, human or animal body (e.g., skin), or any hybrids, alloys, copolymers, blends, or combinations thereof.

[0130] Suitable metal surfaces for use in the present invention include, for example, stainless steel, nickel, titanium, tantalum, aluminum, copper, gold, silver, platinum, zinc, nickel-titanium alloy (nitinol), nickel, chromium, and iron alloy (INCONEL®, Special Metals, Corporation, Elkhart, IN), iridium, tungsten, silicon, magnesium, tin, galvanized steel, hot-dip galvanized steel, electro-galvanized steel, annealed hot-dip galvanized steel, alloys of any of the aforementioned metals, coatings containing any of the aforementioned metals, and combinations thereof.

[0131] Suitable glass surfaces for use in the present invention include, for example, soda-lime glass, strontium glass, borosilicate glass, barium glass, lanthanum-containing glass ceramics, glass fibers, and combinations thereof.

[0132] Suitable silica surfaces for use in the present invention include, for example, quartz, fused silica, crystalline silica, fumed silica, silica gel, silica aerogel, and mixtures thereof.

[0133] Suitable sand surfaces for use in the present invention include, for example, sands made of silica (e.g., quartz), calcium carbonate (e.g., aragonite), and mixtures thereof. The sand may also contain other components such as minerals (e.g., magnetite, chlorite, eiolite, gypsum, olivine, garnet), metals (e.g., iron), seashells, coral, limestone, and / or rocks.

[0134] Suitable wood surfaces include, for example, hardwoods and softwoods, as well as materials processed from wood, wood chips, or fibers (e.g., plywood, oriented strand board, laminated veneer, composite materials, strand material, chipboard, hardboard, medium-density fiberboard), and combinations thereof. Types of wood include alder, birch, elm, maple, willow, walnut, cherry, oak, hickory, poplar, pine, fir, and combinations thereof.

[0135] Suitable fiber surfaces for use in the present invention include, for example, natural fibers (e.g., derived from animals, plants, or minerals) and synthetic fibers (e.g., derived from cellulose, minerals, or polymers). Suitable natural fibers include cotton, hemp, jute, flax, ramie, sisal, bagasse, wood fibers, silkworm silk, spider silk, sinew, intestinal gland, wool, sea silk, mohair, angora, and asbestos. Suitable synthetic fibers include rayon (e.g., lyocell), modal, and metallic fibers (e.g., copper, gold, silver, nickel, aluminum, iron), carbon fibers, silicon carbide fibers, bamboo fibers, seacell, nylon, polyester, polyvinyl chloride fibers (e.g., vinylon), polyolefin fibers (e.g., polyethylene, polypropylene), acrylic polyester fibers, aramid (e.g., TWARON®, KEVLAR®, NOMEX®), spandex, and combinations thereof.

[0136] Natural polymer surfaces suitable for use in the present invention include, for example, polysaccharides (e.g., cotton, cellulose), shellac, amber, wool, silk, natural rubber, biopolymers (e.g., proteins, extracellular matrix components, collagen), and combinations thereof.

[0137] Suitable synthetic polymer surfaces for use in the present invention include, for example, polyvinylpyrrolidone, acrylic, acrylonitrile-butadiene-styrene, polyacrylonitrile, acetal, polyphenylene oxide, polyimide, polystyrene, polypropylene, polyethylene, polytetrafluoroethylene, polyvinylidene fluoride, polyvinyl chloride, polyethyleneimine, polyester, polyether, polyamide, polyorthoester, polyanhydride, polysulfone, polyethersulfone, polycaprolactone, polyhydroxybutyrate valerate, polylactone, polyurethane, polycarbonate, polyethylene terephthalate, and copolymers and combinations thereof.

[0138] Typical rubber surfaces suitable for use in the present invention include, for example, silicone, fluorosilicone, nitrile rubber, silicone rubber, polyisoprene, sulfur-cured rubber, butadiene-acrylonitrile rubber, isoprene-acrylonitrile rubber, and combinations thereof.

[0139] Suitable ceramic surfaces for use in the present invention include, for example, boron nitride, silicon nitride, alumina, silica, combinations thereof, and combinations thereof.

[0140] Suitable stone surfaces for use in the present invention include, for example, bauxite, calcite, feldspar, gypsum, slate, granite, quartz, quartzite, limestone, dolomite, sandstone, marble, soapstone, serpentinite, and combinations thereof.

[0141] For the purposes of the present invention, the animal body includes, but is not limited to, the order Rodentia (e.g., mice), Lagomorpha (e.g., rabbits), Carnivora (e.g., felines (cats) and canines (dogs)), Artiodactyla (e.g., cows) and swines (pigs)), Perissodactyla (e.g., horses)), Primates, Ceboids, or Simioids (e.g., monkeys), Aves (e.g., birds), Arthropoda (e.g., insects), Fish (e.g., fish), or Apes (e.g., humans and apes). Typically, the skin of an animal's body (including intact skin, wounded or broken skin, and / or skin otherwise damaged, for example by burns) and / or mucous tissue (e.g., oral cavity, nose, eye, or genital tissue) serve as suitable surfaces for application of antimicrobial compositions. The skin and / or mucous tissue may be associated with any part of the animal's body, including the limbs, tail, abdomen, chest, head, neck, face, genital area (e.g., mammary glands), buttocks, or back. Generally, the types and amounts of components of the antimicrobial composition are selected to ensure biocompatibility, minimize toxicity, minimize irritation, and / or have a desired level of surface tackiness and / or adhesion of the formed film.

[0142] Surfaces are typically components of larger structures. For example, surfaces include: medical devices, diagnostic equipment, implants, gloves, masks, curtains, mattresses, sheets, blankets, gauze, bandages, tissues, surgical drapes, tubes, surgical instruments, safety equipment, cloth, clothing, floors, handles, walls, sinks, showers or bathtubs, toilets, furniture, wall switches, toys, exercise equipment, playground equipment, shopping carts, countertops, electrical appliances, handrails, doors, air filters, pipes, tools, plates, cups, containers, object labeling containers, food, food labeling containers, food packaging, food processing equipment, food handling equipment, food transport equipment, food vending machines, and food storage. Warehouse equipment, food packaging equipment, plants, telephones, mobile phones, remote controls, computers, mice, keyboards, touchscreens, leather, cosmetics, cosmetic manufacturing equipment, cosmetic storage equipment, cosmetic packaging equipment, personal care products, personal care product manufacturing equipment, personal care storage equipment, personal care packaging equipment, animal husbandry supplies, animal husbandry product manufacturing equipment, veterinary equipment, powders, creams, gels, ointments, eye care products, eye care product manufacturing equipment, contact lenses, eyeglasses, eye care storage equipment, contact lens cases, jewelry, jewelry manufacturing equipment, jewelry storage equipment, animal shelters It may be part of a base material for things like jigs, agricultural machinery, animal food handling equipment, animal food storage spaces, animal food storage equipment, animal food containers, aircraft, land vehicles, air treatment equipment, air filters, water vehicles, water storage spaces, water storage equipment, water treatment equipment, water storage containers, water filters, hands, hair, feet, legs, arms, torso, head, or other parts of an animal's body, pharmaceutical labeling containers, pharmaceutical packaging, pharmaceutical processing equipment, pharmaceutical handling equipment, pharmaceutical transport equipment, pharmaceutical vending machines, pharmaceuticals, pharmaceutical storage equipment, pharmaceutical packaging equipment, etc.

[0143] "Medical devices" include any devices having surfaces that come into contact with tissue, blood, or other bodily fluids found in or subsequently used in a mammal (e.g., a human) during their use or operation. Medical devices also include extracorporeal devices used in surgery that come into contact with blood that is later returned to the patient or mammal, such as blood oxygenators, blood pumps, blood storage bags, blood collection tubes, blood filters including filtration media, dialysis membranes, and tubes used to carry blood. Medical devices also include internal prostheses implanted in mammals (e.g., humans) that are implanted in blood vessels or the heart, such as vascular grafts, stents, pacemaker leads, surgical conduits, and heart valves. Medical devices also include devices for temporary intravascular use that are placed in blood vessels, the heart, organs, or tissues for monitoring, repair, or treatment purposes, such as catheters, guidewires, amniocentesis needles and biopsy needles, cannulas, drainage tubes, shunts, sensors, transducers, and probes. Medical devices also include prostheses such as artificial joints, such as those for the hip or knee, as well as artificial hearts. Furthermore, medical devices include penile implants, condoms, tampons, sanitary napkins, eyepieces, surgical slings, sutures, hemostatic agents, antimicrobial materials, surgical mesh, percutaneous patches, and wound dressings / bandages.

[0144] "Diagnostic equipment" includes any devices or instruments used to diagnose or monitor a medical condition. Examples include ultrasound machines, magnetic resonance imaging (MRI) machines, positron emission tomography (PET) scanners, computed tomography (CT) scanners, ventilators, cardiopulmonary bypass machines, extracorporeal membrane oxygenation (ECMO) machines, dialysis machines, blood pressure monitors, otoscopes, ophthalmoscopes, stethoscopes, blood pressure monitor cuffs, electrocardiographs, thermometers, defibrillators, microscopes, sigmoidoscopy, and anoscopes.

[0145] "Surgical instruments" include any instruments or devices used to perform surgical procedures or operations. Examples include scalpels, lancets, trocars, hemostatic agents, grippers, forceps, clamps, retractors, stretchers, positioners, tracheostomy devices, dilators, staplers, irrigation needles, hypodermic needles, drills, scopes, endoscopes, probes, rulers, and calipers.

[0146] "Safety equipment" includes devices used to protect people, animals, or objects. Examples of "safety equipment" include masks, face shields, sunshades, goggles, glasses, gloves, shoe covers, foot guards, leg guards, belts, smocks, aprons, coats, vests, rain gear, hats, helmets, chin straps, hairnets, shower caps, hearing protection (earplugs, earmuffs, hearing bands), ventilators, gas masks, accompanying air hoods, collars, straps, and first-aid kits.

[0147] "Fabric" includes any type of suitable fabric, such as bedding, curtains, towels, table covers, protective sheets, and dishcloths.

[0148] "Clothing" includes clothing, footwear, or other items that someone wears on themselves. Examples include uniforms, coats, shirts, trousers, waders, surgical gowns, socks, shoes or boot liners, insoles, gloves, hats, boots, and sandals.

[0149] The surface is part of the building structure, or floors, walls, electrical appliances (e.g., refrigerators, ovens, stoves, dishwashers, washing machines, clothes dryers, furnaces, water heaters, air conditioners, heaters), sinks, showers or bathtubs, toilets, furniture (e.g., mattresses, benches, sofas, chairs, tables, etc.) This may include items found within the building structure, such as shelves, cabinets, beds, dressing tables, countertops, handrails, air filters, air treatment equipment, water treatment equipment, water filters, pipes, doors, handles, lighting, light switches, thermostats, sprinklers, air conditioner evaporators and / or condensers.

[0150] The surface may also be an exercise machine, playground equipment, or a toy or exercise equipment including a swimming pool.

[0151] The surface may be a tool (e.g., knife, fork, spoon, ladle, spatula, whisk, etc.), a plate (e.g., food storage container, food serving piece, etc.), food packaging (e.g., bag, box, foil, plastic wrap, etc.), or other items that come into contact with food (e.g., cutting board, food display container, food processing equipment, food handling equipment, food transport equipment, food vending machine, animal food handling equipment, animal food storage space, food storage equipment, animal food container, animal food storage equipment). The surface may also be part of food processing equipment such as food processing tanks, stirrers, conveyor belts, knives, grinders, packaging machines, and labeling machines.

[0152] "Food" is any food product for which it is desirable to provide an antimicrobial residual self-disinfecting film. In such embodiments, the antimicrobial residual self-disinfecting film and its composition should be nontoxic to human and animal consumption. "Food" may be, for example, any fruit, vegetable, meat, or egg.

[0153] "Plants" are any suitable plants, including angiosperms (flowering plants), gymnosperms (seed-producing plants), conifers, ferns, and mosses. Suitable angiosperms include Amborella (e.g., Amborella trichopoda Baill), Nymphaeales (e.g., water lilies), Austrobaileiales (e.g., Illicium), Chloranales (e.g., from the genera Ascarina, Chalanthus, Hediosum or Chloranthus), Magnolias (e.g., The group consists of plants such as magnolias, laurels, and black pepper, monocots (e.g., grasses, orchids, and palm trees), the genus Ceratophyllum (e.g., aquatic plants), or eudicots (e.g., sunflowers, petunias, and apples). Appropriate gymnosperms are derived from the subclasses Cycadidae, Ginkgoidae, Gnetidae, or Pinidae.

[0154] The surface may be part of an electronic device such as a telephone, mobile phone, remote control, computer, mouse, keyboard, or touchscreen.

[0155] The surface may further be part of cosmetics (e.g., eyeshadow, eyeliner, primer, foundation, lipstick, lip gloss, blush), cosmetic manufacturing equipment, cosmetic storage equipment, cosmetic packaging equipment, personal care products (creams, gels, ointments, lip balm, body soap, facial soap, lotion, cologne, perfume, antiperspirant, deodorant, cosmetic paper, cotton swabs, cotton pads, mouthwash, toothpaste, nail polish, shampoo, conditioner, hairspray, talcum powder, shaving cream, contact lenses, contact lens cases, eyeglasses), personal care product manufacturing equipment, personal care storage equipment, personal care packaging equipment, jewelry (e.g., necklaces, rings, earrings, bracelets, watches), jewelry manufacturing equipment, or jewelry storage equipment.

[0156] "Animal care supplies" and "veterinary equipment" can be any products used in settings involving animals, such as homes, dormitories, and animal hospitals. Of course, veterinary equipment can be used outside of hospital settings. Animals are any animals generally considered to be pets, non-pets, domesticated, veterinarian-treated, and wild animals. Examples include dogs, cats, reptiles, birds, rabbits, ferrets, guinea pigs, hamsters, rats, mice, fish, and more. This includes horses, goats, cattle, and pigs. Suitable animal husbandry supplies include personal care supplies, toys, beds, crates, kennels, carriers, bowls, dishes, ropes, spits, trash cans, and grooming supplies (e.g., clippers, scissors, brushes, combs, dematting tools, deshedding tools). Suitable veterinary equipment includes any medical and surgical instruments described herein, as well as other equipment such as tables, bathtubs, stretchers, sinks, scales, cages, carriers, and ropes.

[0157] "Animal housing" can be any suitable housing such as a shed, stable, shelter, grab bag shelter, hatch, barn, shed, cage, nest box, feeder, post, cage, carrier, or bed.

[0158] "Agricultural equipment" is any device used in agricultural settings, including farms or pastures, in particular farms or pastures for housing animals, processing animals, or both. Domestic animals may be housed or processed as described herein and include, for example, horses, cattle, bison, and small animals such as poultry (e.g., chickens, quail, turkeys, geese, ducks, pigeons, doves, pheasants, swans, ostriches, guinea fowl, Indian peafowl, emus), pigs, sheep, goats, alpacas, llamas, deer, donkeys, rabbits, and fish. Examples of agricultural equipment include wagons, trailers, carts, barns, sheds, fencing equipment, sprinklers, shovels, scrapers, ropes, restraints, feeders, water dispensers, feeders, water filters, water treatment systems, stock tanks, fountains, buckets, pails, hay racks, scales, poultry flooring, egg processing systems, barn curtains, tractors, seeders, planters, plows, rotators, tillers, sprayers, agitators, sorters, balers, harvesters, cotton pickers, threshing machines, lawnmowers, backhoe loaders, squeeze chutes, hydraulic chutes, head chutes, head gates, crowding tubs, and corral tubs. Includes a tub, alley, calving pen, calf table, and milking machine.

[0159] The surface may be part of a vehicle such as an aircraft, land vehicle, or water vehicle. Suitable vehicles include cars, vans, trucks, buses, ambulances, recreational vehicles, campervans, motorcycles, scooters, bicycles, wheelchairs, trains, trams, ships, boats, canoes, submarines, unmanned underwater vehicles (UUVs), personal watercraft, airplanes, jets, helicopters, unmanned autonomous vehicles (UAVs), and hot air balloons.

[0160] If desired, surfaces to which the antimicrobial residual self-disinfecting film is applied can be regenerated by removing the antimicrobial residual disinfecting film, as the film is typically not covalently bonded to the surface. The removal process can be carried out by any suitable method, such as washing or rinsing with a solvent (e.g., water and / or alcohol). Thus, the antimicrobial coating on a surface (e.g., the surface of a substrate) described herein can be considered temporary (e.g., removable). In one embodiment, the antimicrobial residual self-disinfecting film is water-soluble and removable with water (e.g., hot soapy water).

[0161] The antimicrobial residual self-disinfecting film makes a surface bactericidal to any suitable bacteria to any suitable degree. In other words, the antimicrobial composition of the present invention can form an antimicrobial residual self-disinfecting film on a surface (e.g., the surface of a substrate) that kills at least 75% (e.g., at least 80%, at least 85%, at least 90%, at least 92%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5%) of bacteria that come into contact with the antimicrobial residual self-disinfecting film. For example, bacteria such as Staphylococcus Staphylococcus aureus, Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus saprophyticus, Pseudomonas erginosa, Listeria monocytogenes, Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Haemophilus influenzae, Helicobacter pylori The antimicrobial agents may be *Salmonella pylori*, *Salmonella*, *Shigella*, *Clostridium*, *Enterobacter aerogenes*, *Gram-negative Escherichia coli*, *Clostridium difficile*, or combinations thereof. In certain embodiments, the antimicrobial composition is effective in reducing (e.g., by removal, death, or prevention and / or inhibition of growth) *Gram-positive methicillin-resistant Staphylococcus aureus* (MRSA), *Gram-negative Escherichia coli* (ATCC 8739), *Clostridium difficile* (ATCC 43598), or combinations thereof.

[0162] In one embodiment of the present invention, an antimicrobial residual self-disinfecting film formed from the antimicrobial composition described herein makes the surface bactericidal against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) bacteria. Preferably, the antimicrobial residual self-disinfecting film kills at least 95% (e.g., at least 96%, at least 97%, at least 98%, at least 99%) of the log5 population of Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) bacteria within 30 minutes of contact (e.g., within 20 minutes, 15 minutes, 10 minutes, or 5 minutes). In a particularly preferred embodiment, the antimicrobial residual self-disinfecting film kills at least 99.8% of the log5 population of Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) bacteria within 5 minutes of contact.

[0163] In another embodiment of the present invention, an antimicrobial residual self-disinfecting film formed from the antimicrobial composition described herein makes a surface bactericidal against Gram-negative Escherichia coli (ATCC 8739) bacteria. In particular, the antimicrobial residual self-disinfecting film kills at least 95% (e.g., at least 96%, at least 97%, at least 98%, at least 99%) of the log5 population of Gram-negative Escherichia coli (ATCC 8739) bacteria within 30 minutes of contact (e.g., within 20 minutes, 15 minutes, 10 minutes, 5 minutes). In a preferred embodiment, the antimicrobial residual self-disinfecting film kills at least 99.7% of the log5 population of Gram-negative Escherichia coli (ATCC 8739) bacteria within 5 minutes of contact.

[0164] In yet another embodiment of the present invention, an antimicrobial residual self-disinfecting film formed from the antimicrobial composition described herein makes a surface bactericidal against Clostridium difficile (ATCC 43598) bacteria. More specifically, the antimicrobial residual self-disinfecting film kills at least 75% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99%) of the log4 population of Clostridium difficile (ATCC 43598) bacteria within 24 hours of contact (e.g., within 18 hours, 12 hours, 10 hours, 8 hours, 6 hours). In a preferred embodiment, the antimicrobial residual self-disinfecting film kills at least 99.7% of the log4 population of Clostridium difficile (ATCC 43598) bacteria within 8 hours of contact.

[0165] Viruses, especially non-enveloped viruses, such as norovirus, rotavirus, and adenovirus. Viruses, and polioviruses in particular, are far more difficult to kill. Generally, the only way to kill a range of non-enveloped viruses is to use large quantities of extremely harsh chemicals, such as hypochlorites, acids, and peroxides, all of which are highly cytotoxic. Notably, the techniques described in the present invention can form antimicrobial residual self-disinfecting films that kill non-enveloped viruses. Accordingly, the present invention provides antimicrobial residual self-disinfecting films formed from the antimicrobial compositions described herein that make a surface virucidal to any suitable virus to any suitable degree, for example, to reduce (e.g., remove, kill, or prevent and / or inhibit the proliferation) at least 75% of the virus (e.g., at least 80%, at least 85%, at least 90%, at least 92%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5%). In certain cases, an antimicrobial residual self-disinfecting film formed from the antimicrobial compositions described herein makes the surface virucidal against at least one enveloped virus (e.g., varicella virus, influenza, herpes simplex, severe acute respiratory syndrome (SARS), flavivirus, togavirus) or a non-enveloped virus (e.g., Levivirus, norovirus, rotavirus, adenovirus, parvovirus, and poliovirus).

[0166] In another embodiment of the present invention, an antimicrobial residual self-disinfecting film formed from an antimicrobial composition described herein makes the surface virucidal against influenza A (e.g., H1N1, H1N2, and H5N1) enveloped viruses. In one embodiment, the antimicrobial residual self-disinfecting film kills at least 95% (e.g., at least 96%, at least 97%, at least 98%, at least 99%) of the log4 population of influenza A (H1N1) (ATCC CCL-34) enveloped viruses within 60 minutes of contact (e.g., within 45 minutes, 30 minutes, or 20 minutes). In a preferred embodiment, the antimicrobial residual self-disinfecting film kills at least 99% of the log4 population of influenza A (H1N1) (ATCC CCL-34) enveloped viruses within 30 minutes of contact.

[0167] In yet another embodiment of the present invention, the antimicrobial residual self-disinfecting film makes a surface virucidal against non-enveloped viruses such as Levivirus (e.g., MS2), norovirus, rotavirus, adenovirus, parvovirus, or poliovirus. In one embodiment, the antimicrobial residual self-disinfecting film kills at least 95% (e.g., at least 96%, at least 97%, at least 98%, at least 99%) of non-enveloped viruses within 30 minutes of contact (e.g., within 20 minutes, 15 minutes, 10 minutes, 5 minutes). In a preferred embodiment, the antimicrobial residual self-disinfecting film kills at least 97% of non-enveloped viruses within 5 minutes of contact. In some examples of this embodiment, the non-enveloped virus is MS2 (ATCC 15597-B1).

[0168] One embodiment of the present invention relates to a treated filter material comprising one or more insoluble cationic polymers, as described herein, bonded to a positively charged nonwoven filter material. The filter material is suitable for filtering liquids (e.g., water) and air, and can be made from any suitable material such as alumina (Al2O3), polyester (e.g., PET), polyethylene, polypropylene, polyamide (e.g., nylon 6,6), polyimide, polyacrylic, glass, metal, dextran, cellulose, jute, wood pulp, cotton, or a combination thereof (e.g., cellulose coated with microglass fibers and / or nanoalumina fibers). If the material is not positively charged in its natural form, the material can be modified as needed, for example, by adding one or more quaternary ammonium groups, to provide the desired positive charge. The nonwoven filter material can be purchased commercially. It can be prepared by any suitable method (e.g., wetlaid, airlaid, drylaid, meltblown, spunbond, nanofiber web spinning, and continuous draw fiberization). See, for example, Argonide (Sanford, FL), Pall Corporation (Port Washington, New York), GE Infrastructure Water and Process Technologies (Trevose, PA), and Meissner Filtration Products (Camarillo, CA). Adhesion promoters acting as coupling agents can be used as described herein. Embodiments in which the adhesion promoter is cationic, such as branched carboxylated PEI, are preferred.

[0169] Most filter media reduce pathogenic microorganisms through simple sorting by size, but such filters require high pressure (e.g., fluid) to effectively sort the material, are easily soiled, and require frequent maintenance. As described herein, treated filters that are positively charged and bonded to one or more insoluble cationic polymers can effectively kill microorganisms under reduced pressure and / or with less contamination. Figure 2A shows a small pore size from a filter containing 5 μm glass that is not positively charged. Figure 2B shows a filter containing positively charged alumina with a larger pore size. However, due to the cationic polymer bonded to the alumina (e.g., insoluble polyDADMAC, linear PEI), the filter behaves like the small-pore microglass filter in Figure 2A.

[0170] In one example of a treated water filter, polyDADMAC, made insoluble (for example, by substituting some of the chloride counterions with fluoride), is bonded to a positively charged Al2O3 nonwoven filter media having branched carboxylated PEI. The resulting treated filter media has a very high positive zeta value. In another example, a treated air filter is manufactured by bonding linear PEI to a positively charged Al2O3 nonwoven filter media using an adhesion promoter such as branched carboxylated PEI.

[0171] Highly contaminated (log7) metalworking fluids, as described herein, that passed through the treated filter showed a 99.9% reduction in microorganisms, including non-enveloped viruses, during testing.

[0172] The present invention can be further described by the following embodiments. (1)An antimicrobial composition comprising (a) a cationic polymer, (b) at least one adhesion promoter, (c) organic and / or inorganic particles that are optionally photocatalytically active in visible light, and (d) a carrier, wherein the components of the composition are not covalently bonded to each other, and the antimicrobial composition is subjected to the following tests: (i) a pathogenic spray test in accordance with ASTM International Code E1153, satisfying the EPA requirements for log3 reduction against viruses and log5 reduction against bacteria; (ii) a suspension test in accordance with ASTM International Code E1052-96 (2002) or ASTM International Code E2315 (2016); (iii) a film formed from the composition (iii-a) at least 95% of the log5 population of Gram-positive or Gram-negative bacteria within 30 minutes; (iii-b) contact of (iv) A film formed from a composition that kills at least 95% of the log4 population of enveloped viruses within 30 minutes of contact, (iii-c) at least 95% of non-enveloped viruses within 30 minutes of contact, and / or (iii-d) at least 94% of the log4 population of Clostridium difficile bacteria within 24 hours of contact, according to the Japanese Industrial Standard (JIS) Z 2801 (2006) test for antimicrobial activity, or a modified version of such test described herein, according to the International Organization for Standardization (ISO) 10993-5 in (v)(va) a film formed from the composition kills at least 99.9% of Gram-positive and Gram-negative bacteria according to the U.S. Environmental Protection Agency (EPA) Protocol #01-1A residual self-disinfecting activity test, or (vb) a durability test in which, after waiting 7 days after film formation, the film formed from the composition kills at least 95% of Gram-positive and Gram-negative bacteria or enveloped and non-enveloped viruses, according to a modified version of Protocol #01-1A residual self-disinfecting activity test described herein. An antimicrobial composition that conforms to one or more of the following.

[0173] (2) Cationic polymers include polydiallyldialkylammonium salt, acrylicoxyalkyltrialkylammonium salt, vinylphenalkyltrialkylammonium salt, and acrylamide alkyltrialkyl The antimicrobial composition according to Embodiment 1, which is an ammonium salt, poly(acrylamide-co-diallyldialkylammonium salt), polyethyleneimine polymer, chitosan used in combination with an optionally selected anionic polymer, or a combination thereof.

[0174] (3) The antimicrobial composition according to Embodiment 2, wherein the polydiallyldialkylammonium salt is polydiallyldimethylammonium halide, and the halide is a chloride, a fluoride, a chloride-containing anion, a fluoride-containing anion, or a combination thereof.

[0175] (4) The antimicrobial composition according to any one of embodiments (1) to (3), wherein the cationic polymer is a chemically unmodified linear polyethyleneimine (PEI).

[0176] (5) The antimicrobial composition according to any one of embodiments (1) to (4), wherein at least one adhesion promoter is selected from titanates, carboxylated branched or linear PEIs, silane compounds, cationic block copolymers, polymers comprising at least one acyl group, carboxylic acid group, or carboxylic acid derivative, and combinations thereof.

[0177] (6) The antimicrobial composition according to any one of embodiments (1) to (5), wherein the organic and / or inorganic particles that are photocatalytically active in visible light are selected from the group consisting of graphene, g-C3N4, transition metal oxides, transition metal sulfides, transition metal selenides, dye sensitizers, conjugated polymers, precious metals, or mixtures thereof.

[0178] (7) The antimicrobial composition according to any one of embodiments (1) to (6), wherein the organic and / or inorganic particles that are photocatalytically active in visible light are W and N-doped TiO2 particles hydrolyzed under ultraviolet (UV) light.

[0179] (8) The antimicrobial composition according to any one of embodiments (1) to (7), wherein the antimicrobial composition does not contain pathogenic small molecule compounds.

[0180] (9) The antimicrobial composition according to any one of embodiments (1) to (7), wherein the antimicrobial composition further comprises at least one pathogenic agent.

[0181] (10) The antimicrobial composition according to any one of embodiments (1) to (9), wherein the antimicrobial composition further comprises one or more non-electrolyte polymers.

[0182] (11) The antimicrobial composition according to embodiment (10), wherein one or more non-electrolyte polymers include polyacrylamide.

[0183] (12) Polyethyleneimine polymer, optionally polydiallyldialkylane An antimicrobial composition comprising a monium salt, a second cationic polymer selected from poly(acrylamide-co-diallyldialkylammonium halide), chitosan, or a combination thereof, optionally a polyacid, optionally at least one adhesion promoter, and a carrier.

[0184] (13) The antimicrobial composition according to embodiment (12), wherein the polyethyleneimine polymer is linear PEI.

[0185] (14) The antimicrobial composition according to embodiment (12) or (13), wherein the composition comprises chemically unmodified linear PEI, polydiallyldimethylammonium chloride (polyDADMAC), optionally citric acid, carboxylated branched PEI, and a water-alcohol carrier.

[0186] (15) The antimicrobial composition according to any one of embodiments (12) to (14), wherein the composition comprises citric acid.

[0187] (16) An antimicrobial composition comprising at least one organic and / or inorganic particle that is photocatalytically active in visible light, at least one adhesion promoter, and a carrier, wherein the film formed from the antimicrobial composition does not need to cover the inoculated film, and kills microorganisms under conditions of JIS Z 2801 modified by starting the test time after the inoculation has dried.

[0188] (17) A method for killing microorganisms on a surface, comprising applying an antimicrobial composition described in any one of embodiments (1) to (16) to the surface.

[0189] (18) The method according to embodiment (17), wherein the carrier evaporates and leaves a residual self-disinfecting film on the surface.

[0190] (19) The method according to embodiment (18), wherein the residual self-disinfecting film makes the surface bactericidal, virucidal, and / or germicidal.

[0191] (20) The residual self-disinfecting film has reduced the following: (i) at least 95% of the log5 population of Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) bacteria within 30 minutes of contact; (ii) at least 95% of the log5 population of Gram-negative Escherichia coli (ATCC8739) bacteria within 30 minutes of contact; (iii) at least 95% of the log4 population of influenza A (H1N1) (ATCC CCL-34) enveloped virus within 60 minutes of contact; (iv) at least 95% of non-enveloped viruses within 30 minutes of contact; and / or (v) at least 75% of the log4 population of Clostridium difficile (ATCC 43598) bacteria within 24 hours of contact. The method according to embodiment (18) or (19), which kills one or more of the following.

[0192] (21) The method according to embodiment (20), wherein the non-enveloped virus is MS2 (ATCC 15597-B1).

[0193] (22) A method for killing microorganisms on a surface, comprising applying an antimicrobial composition comprising a high molecular weight polydiallyldialkylammonium salt and a carrier to the surface.

[0194] (23) The antimicrobial composition is a polyethyleneimine polymer, chitosan, or a combination thereof. The method according to embodiment (22), further including a combination.

[0195] (24) The method according to embodiment (22) or (23), wherein the antimicrobial composition further comprises organic and / or inorganic particles that are photocatalytically active in visible light.

[0196] (25) The method according to any one of embodiments (22) to (24), wherein the antimicrobial composition does not contain pathogenic small molecule compounds.

[0197] (26) The method according to any one of embodiments (22) to (25), wherein the carrier evaporates and leaves a residual self-disinfecting film on the surface.

[0198] (27) The residual self-disinfecting film has reduced the following: (i) at least 95% of the log5 population of Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) bacteria within 30 minutes of contact; (ii) at least 95% of the log5 population of Gram-negative Escherichia coli (ATCC8739) bacteria within 30 minutes of contact; (iii) at least 95% of the log4 population of influenza A (H1N1) (ATCC CCL-34) enveloped virus within 60 minutes of contact; (iv) at least 95% of non-enveloped viruses within 30 minutes of contact; and / or (v) at least 75% of the log4 population of Clostridium difficile (ATCC 43598) bacteria within 24 hours of contact. The method according to embodiment (26), which kills one or more of the following.

[0199] The following embodiments further illustrate the present invention, but of course, they should not be interpreted as limiting its scope. [Examples]

[0200] Examples The antimicrobial compositions for the following examples were prepared according to the following general procedure: (1) Prepare a highly diluted mixture of one or more cationic polymers. (2) Add photocatalytic particles as a weight percentage (%wbcm) based on the cationic monomer. (3) Prepare a highly diluted mixture of one or more anionic polymers. (4) Mix the diluted cationic polymer and the diluted anionic polymer to create a PEC. (5) If used, add a titanate adhesion promoter as a weight percentage (%wbtm) based on the total monomer. (6) Concentrate the cationic / anionic PEC (i.e., partially evaporate the solvent) to obtain a desired concentration, for example, used to determine the film thickness and film durability. (7) Further dilute the antimicrobial composition for the desired modification. Steps 2-7 are optional depending on the desired bactericidal composition and concentration.

[0201] Example 1 This example illustrates the preparation of an antimicrobial composition in an embodiment of the present invention.

[0202] Table 8 lists the individual components and their relative amounts necessary to form polyDADMAC / PEI / PAAS PEC. In addition to calculating the solution concentration (ppm), the amounts of each individual component are listed.

[0203] [Table 8]

[0204] The antimicrobial compositions that produce PECs, as described in Table 8, include two cationic polymers (i.e., polyDADMAC and PEI), an anionic polymer (PAAS), titanate, TiO2 particles (photocatalyst), and water as a carrier. Alcohol is not required for the creation of PECs. After the PECs are formed, a certain percentage of water is replaced with alcohol. When the composition is used as a spray disinfectant, the alcohol helps to kill bacteria. The alcohol also helps the composition dry faster and form a residual self-disinfecting film. This water replacement with alcohol can range from 5% to 90% alcohol, preferably from 35% to 70%.

[0205] Example 2 This example demonstrates future antimicrobial protection against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) bacteria and Gram-negative Escherichia coli (ATCC8739) bacteria, as shown by an antimicrobial composition according to one embodiment of the present invention.

[0206] As shown in Table 9, bactericidal compositions were prepared containing either 250 kDa pDADMAC or ultra-high molecular weight (1,000,000 g / mol) pDADMAC, a water-methanol mixture, titanate, and functionalized TiO2 particles. The reported mortality rates and times are from films inoculated with bacteria after 7 days. Bacterial testing was performed by an independent testing laboratory, BioSan Laboratories, Inc. (Warren, MI), and the results for 4.8 kppm films are shown in Table 10. The simulated EPA durability test used herein consists of the required 12 alternating wet and dry wipes under a specified load. Organisms recovered from each sample were measured after 5 minutes. The results are shown in row 4 of Table 10.

[0207] [Table 9]

[0208] [Table 10]

[0209] As is evident from the results presented in Table 10, ultra-high molecular weight pDADMAC is highly effective in preventing the future growth of both Gram-positive bacteria (MRSA) and Gram-negative bacteria (E. coli), killing over 99.5% in 5 minutes. Furthermore, these results were measured after a 7-day period, demonstrating that the antimicrobial residual self-disinfecting film sustainably kills bacteria at this efficient level. Moreover, ultra-high molecular weight polyDADMAC is equally effective in killing Gram-negative (E. coli) bacteria after EPA durability testing. Therefore, the antimicrobial residual self-disinfecting film is not easily wiped off from surfaces.

[0210] Example 3 This embodiment demonstrates future antimicrobial protection against influenza A (H1N1) (ATCC CCL-34) enveloped virus and MS2 (ATCC 15597-B1) non-enveloped virus, as shown by an antimicrobial composition according to an embodiment of the present invention. ru.

[0211] Bactericidal compositions containing pDADMAC and / or PEI, titanate, and optionally functionalized TiO2 in a water-methanol mixture were prepared according to Table 8, 9, or 11. The reported mortality rates and times are from after inoculation of films with the virus for 7 days. Virus testing was performed by an independent testing laboratory, Antimicrobial Test Laboratories (Round Rock, TX), and the results are shown in Table 12.

[0212] [Table 11]

[0213] [Table 12]

[0214] As is evident from the results presented in Table 12, antimicrobial compositions containing pDADMAC and TiO2 dissolve 98.2% of the log4 population of influenza A (H1NI) virus within 30 minutes of contact, and 99% within 60 minutes. Furthermore, antimicrobial compositions containing PEI kill 97.4% of the log4 population of non-enveloped virus MS2 within 5 minutes, and 99% within 30 minutes. Table 12 also demonstrates that the bactericidal compositions containing polyDADMAC, TiO2, and PEI become more antiviral, particularly against non-enveloped MS2, when 33% PEI is added. Without PEI, 82.3% are killed within 30 minutes, but with 33% PEI, 95% are killed within 30 minutes. Furthermore, Table 12 demonstrates that the antimicrobial composition containing pDADMAC and TiO2 killed only 82.3% of non-enveloped MS2 viruses within 30 minutes of contact, which increased to 97.8% after 24 hours.

[0215] Example 4 This embodiment demonstrates future antimicrobial protection against spore-producing Clostridium difficile (ATCC 43598) bacteria provided by an antimicrobial composition according to one embodiment of the present invention.

[0216] As shown in Table 9, antimicrobial compositions containing ultra-high molecular weight pDADMAC, titanate, and functionalized TiO2 were prepared in a water-methanol mixture. The reported elimination rates and times are from after inoculation of bacteria onto films 7 days later. Bacterial testing was performed by an independent testing laboratory, Antimicrobial Test Laboratories (Round The study was conducted by Rock (TX), and the results are shown in Table 13.

[0217] [Table 13]

[0218] As is evident from the results shown in Table 13, the antimicrobial composition containing ultra-high molecular weight pDADMAC and TiO2 kills 98% of the log5 population of Clostridium difficile (ATCC 43598) bacteria in 8 hours.

[0219] Example 5 This embodiment demonstrates future antimicrobial protection against the fungus Aspergilla brasliensis, as shown by an antimicrobial composition according to an embodiment of the present invention.

[0220] Antimicrobial compositions containing ultra-high molecular weight pDADMAC, titanate, and functionalized TiO2 in a water-methanol mixture were prepared using the formulations listed in Table 9. The reported mortality rates and times were obtained after inoculating films with fungi for 7 days. Fungal tests were performed by an independent testing laboratory, BioSan Laboratories, Inc. (Warren, MI), and the results are shown in Table 14.

[0221] [Table 14]

[0222] As is evident from the results shown in Table 14, an antimicrobial composition containing ultra-high molecular weight pDADMAC, titanate, and TiO2 kills 86% of the log4 population of Aspergilla brasliensis fungi in 8 hours.

[0223] Example 6 This example demonstrates future antimicrobial protection against Gram-positive, methicillin-resistant Staphylococcus aureus (MRSA) bacteria provided by an antimicrobial composition according to an embodiment of the present invention.

[0224] The bactericidal composition was prepared according to the components described in Table 9, except that titanium dioxide was not present. The simulated EPA durability test used herein consists of 12 alternating wet and dry wipes with a specified load applied. The organisms recovered from each sample were measured after 5 minutes. The results are described in Table 15.

[0225]

Table 15

[0226] This example demonstrates the "kill later" antibacterial protection against MRSA shown by a film formed from an antibacterial composition containing polyDADMAC, titanate, and a carrier.

[0227] Example 7 This example demonstrates the antibacterial activity shown by a composition containing pDADMAC and a carrier.

[0228] An antibacterial composition containing either low molecular weight polyDADMAC (250,000 g / mol) or ultra-high molecular weight (1,000,000 g / mol) polyDADMAC in a water-methanol (80 / 20) mixture was prepared. The composition was coated on a transparent glass slide and dried to form a film. The killing power of the polyDADMAC film was tested against methicillin-resistant Staphylococcus aureus (MRSA). The organisms recovered from each sample were measured after 5 minutes. The results are described in Table 16.

[0229]

Table 16

[0230] Unexpectedly, films made using ultra-high molecular weight polyDADMAC were found to be considerably more effective than those made with low molecular weight (250,000 g / mol) in killing Gram-positive and Gram-negative bacteria. As shown in Table 16, after 5 minutes of exposure to a log7 MRSA population, the 250,000 g / mol molecular weight film yielded only 2.08 antimicrobial activity. In comparison, the 1,000,000 g / mol molecular weight film, using the same amount of polymer in each case, yielded 5.7, or more than twice the antimicrobial activity. The difference in killing rates between low molecular weight polyDADMAC and high molecular weight polyDADMAC is thought to be due to differences in film formation rather than differences in charge density.

[0231] Example 8 This embodiment demonstrates the provision of a residual self-disinfecting film on a fabric surface using the antimicrobial composition according to an embodiment of the present invention.

[0232] An antimicrobial composition in the form of PEC was prepared containing 6,000 ppm pDADMAC, 1,500 ppm polyacrylic acid, 400 ppm titanate, and 0.1% w / w functionalized TiO2 particles. The composition was applied to a fabric in a rinse cycle and then tested for antimicrobial resistance using the American Association of Textile Chemists and Colorists (AATCC) Test Method 100, which is designed to evaluate the performance of the antimicrobial finish on the fabric. The test demonstrated that the polymer-based composition could dissolve 99.58% of the log4 MRSA population on the fabric after 4 hours (Table 17). Although the AATCC does not specify a standard, a similar test method, ISO 20743, specifies 2-Log 10 Alternatively, a 99% reduction is recommended.

[0233] [Table 17]

[0234] A second antimicrobial composition was prepared containing 4000 ppm PEI, 2000 ppm poly(acrylamide-co-diallyldimethylammonium chloride), and 25 ppm carboxylated branched PEI in a carrier, with a pH of approximately 6. The composition was applied to fabrics in a rinse cycle, and then tested for antimicrobial resistance under the same conditions as above. The results are summarized in Table 18.

[0235] [Table 18]

[0236] Example 9 This example demonstrates the antimicrobial protection against E. coli provided by an antimicrobial composition containing titanate.

[0237] A composition containing titanate was applied to a glass slide in water. The coated slides were cured for 5 days, and then a log6E. coli population was inoculated onto the slides. The pure titanate film resulted in 88.72% mortality after 24 hours, as shown in Table 19.

[0238] [Table 19]

[0239] Example 10 This embodiment demonstrates the antibacterial activity of the hand sanitizer composition in the embodiment of the present invention.

[0240] A PEI dispersion was prepared by vigorously stirring 4000 ppm of linear PEI in water at room temperature. The PEI in the dispersion was then protonated with citric acid while vigorously stirring, thereby lowering the pH to 6 and obtaining a clear liquid. The clear liquid was then heated to 70°C. To maintain the temperature of the clear liquid at 65°C, ethanol and 1,2-propanediol were then added dropwise. The clear mixture was cooled to avoid excessive alcohol evaporation, and then stirred with a cover for at least 4 hours. The resulting miscible mixture contained 4000 ppm of chemically unmodified linear PEI, 72% ethanol, 5% 1,2-propanediol, 0.25% by weight of citric acid, and the remainder water.

[0241] The activity of the hand sanitizer compositions against non-enveloped viruses was assessed according to ASTM E 1052-96 (2002) ("Standard Test Methods for Evaluating the Activity of Bactericides Against Viruses in Suspension"). Using this test, the hand sanitizer formulations inactivated MS2 (a surrogate for non-enveloped viruses) by reducing its levels by 99.9% (log3) within 60 seconds of contact. The activity of the hand sanitizer compositions against MRSA (Gram-positive bacteria) and E. coli (Gram-negative bacteria) was assessed according to ASTM E 2315. The hand sanitizer compositions inactivated both bacteria by reducing their levels by 99.999% (log5) within 30 seconds of contact. The results of these tests are summarized in Table 20.

[0242] [Table 20]

[0243] Example 11 This example demonstrates the synthesis of functionalized TiO2 particles according to one embodiment of the present invention.

[0244] TiO2 particles were functionalized using the following method. Starting with 1 g of tungsten-doped, 20 nm liquid-synthesized TiO2, 5 g of urea was added and the mixture was calcined at 400 °C for 40 minutes to obtain NTiO2. Next, the NTiO2 was pulverized into fine powder, to which 1 g of NTiO2 plus 10 g of milling balls with respect to 10% urea was added. The mixture was pulverized at 300 rpm for 30 minutes. After 30 minutes, 200 mL of water was added and the mixture was further pulverized for 5 minutes. Then the pulverized mixture was exposed to 160 W of UV light. After 1 hour, the mixture was decanted and centrifuged, and 0.5 mM of dye was added in the dark. The mixture was decanted and centrifuged again, and then water was added once more.

[0245] All references, including publications, patent applications, and patents cited herein, are hereby incorporated by reference as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein as fully as if it were so set forth.

[0246] In the context describing the present invention (particularly in the context of the following claims), the use of the terms “a,” “an,” “the,” and “at least one,” and similar references, should be interpreted as encompassing both singular and plural forms, unless otherwise indicated herein or unless clearly contradicted by the context. The use of the term “at least one” with the enumeration of one or more items (for example, “at least one of A and B”) should be interpreted as meaning one item (A or B) selected from the enumerated items, or any combination of two or more enumerated items (A and B), unless otherwise indicated herein or unless clearly contradicted by the context. The terms “comprising,” “having,” “including,” and “containing” should be interpreted as unrestricted terms (i.e., “including, but not limited to”), unless otherwise specified herein. The enumeration of value ranges in this specification is intended to serve as a concise way of referring individually to each separate value that falls within that range, unless otherwise specified herein, and each separate value is incorporated herein as if it were individually enumerated herein. All methods described herein may be performed in any suitable order unless otherwise indicated herein or unless it is clearly inconsistent in particular by context. The use of any examples or exemplary language (e.g., "etc.") provided herein is merely for the purpose of better illustrating the invention and does not limit the scope of the invention unless specifically claimed. No language herein should be construed as indicating that any unclaimed element is essential for the practice of the invention.

[0247] To carry out the present invention, the inventors have included the best mode known to them, and preferred implementation of the present invention. The embodiments are described herein. Variations of these preferred embodiments may become apparent to those skilled in the art by reading the foregoing description. The inventors anticipate that those skilled in the art will use such variations as appropriate, and the inventors intend to carry out the invention in ways other than those specifically described herein. Accordingly, the invention includes all modifications and equivalents of the subject matter enumerated in the claims appended herein, as permitted by applicable law. Furthermore, any combination of the above elements in all possible variations thereof is incorporated herein unless otherwise indicated herein or is clearly contradictory in particular by context.

Claims

1. Cationic, chemically unmodified linear polyethyleneimine (PEI), Polydiallyldialkylammonium salts, Carrier, and Polyacids selected from isocitrate, aconitate, propane-1,2,3-tricarboxylic acid, hemimellitic acid, trimellitic acid, trimesic acid, 1,2,3,5-benzenetetracarboxylic acid, pyromellitic acid, benzenepentacarboxylic acid, meritolic acid, ethylenediamine-N,N'-dimalonic acid (EDDM), 2,2'-azandiyldisuccinic acid, 2,2'-oxydisuccinic acid (ODS), diethylenetriaminepentaacetic acid (DTPA), and any combination thereof. An antimicrobial composition containing [the specified ingredient].

2. The antimicrobial composition according to claim 1, wherein the polydiallyldialkylammonium salt is polydiallyldimethylammonium halide, polydiallyldialkylammonium sulfate, or polydiallyldialkylammonium phosphate.

3. The antimicrobial composition according to claim 2, wherein the polydiallyldialkylammonium salt is polydiallyldimethylammonium chloride (polyDADAMAC).

4. The antimicrobial composition according to any one of claims 1 to 3, wherein the carrier is selected from ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, t-butanol, water, and combinations thereof.

5. The antimicrobial composition according to any one of claims 1 to 4, wherein the polyacid is selected from aconitic acid, propane-1,2,3-tricarboxylic acid, hemimellitic acid, trimellitic acid, trimesic acid, 1,2,3,5-benzenetetracarboxylic acid, pyromellitic acid, benzenepentacarboxylic acid, meritolic acid, ethylenediamine-N,N'-dimalonic acid (EDDM), 2,2'-azandiyldisuccinic acid, 2,2'-oxydisuccinic acid (ODS), diethylenetriaminepentaacetic acid (DTPA), and any combination thereof.

6. The antimicrobial composition according to any one of claims 1 to 5, further comprising a pH adjusting agent.

7. The antimicrobial composition according to any one of claims 1 to 6, further comprising one or more non-electrolyte polymers.

8. The antimicrobial composition according to claim 7, wherein one or more non-electrolyte polymers contain polyvinylpyrrolidone.

9. The antimicrobial composition according to any one of claims 1 to 8, further comprising at least one adhesion promoter.

10. The antimicrobial composition according to claim 9, wherein at least one adhesion promoter is selected from titanate, branched or linear PEI having a carboxylic acid group, silane compounds, cationic block copolymers, polymers containing at least one acyl group, carboxylic acid group, or carboxylic acid derivative, and combinations thereof.

11. Water, ethanol, or a combination thereof can be used as a carrier. The antibacterial composition according to claim 1, comprising:

12. A method for killing microorganisms on a surface, comprising applying an antimicrobial composition according to any one of claims 1 to 11 to the surface, wherein the surface includes metal, glass, glass fiber, silica, sand, wood, fiber, natural polymer, synthetic polymer, plastic, rubber, ceramic, porcelain, stone, marble, cement, alloy, copolymer, blend, or a combination thereof.

13. The method according to claim 12, wherein the carrier evaporates and leaves a residual self-disinfecting film on the surface.

14. The residual self-disinfecting film is as follows: (i) at least 95% of the log5 population of Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) bacteria within 30 minutes of contact; (ii) At least 95% of the log5 population of Gram-negative Escherichia coli (ATCC8739) bacteria within 30 minutes of contact; (iii) Within 60 minutes of contact, at least 95% of the log4 population of influenza A (H1N1) (ATCC CCL-34) enveloped virus; (iv) at least 95% of non-enveloped viruses within 30 minutes of contact; and / or (v) At least 75% of the log4 population of Clostridium difficile (ATCC 43598) bacteria within 24 hours of contact The method according to claim 13, wherein one or more of the following are killed.

15. The method according to claim 14, wherein the non-enveloped virus is MS2 (ATCC 15597-B1).

16. The method according to any one of claims 12 to 15, wherein the surface is in the form of a fabric.

17. The method according to any one of claims 12 to 15, wherein the surface is part of the filter.

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