Polymer-based antimicrobial compositions and methods of use thereof

Abstract

A polymer-based antimicrobial composition is provided that is non-toxic, water-soluble, and reduces the transmission of infectious diseases from a surface. The composition comprises a cationic polymer, at least one adhesion promoter, optionally organic and / or inorganic particles having photocatalytic activity under visible light, and a carrier, wherein the components of the composition are not covalently bound to each other. Also provided are antimicrobial compositions comprising at least (i) a polyethyleneimine-based polymer and a carrier, or (ii) organic and / or inorganic particles having photocatalytic activity under visible light, an adhesion promoter and a carrier. An antimicrobial composition may be applied to disinfect a surface and form a removable residual self-disinfecting film on the surface.

Description

[0001] This application is a divisional application of the Chinese invention patent application with the application date of July 27, 2017, application number 201780052448.X, and invention name “Polymer-based antimicrobial composition and method of use thereof”. Technical Field

[0002] The present invention relates to polymer-based antimicrobial compositions. Background Art

[0003] Infectious diseases cause more deaths worldwide each year than any other single cause. Minimizing infections caused by pathogenic microorganisms is an important issue in many fields, especially in medical devices, pharmaceuticals, hospital surfaces / appliances, dental restorations and surgical equipment, health care products and hygiene applications, water purification systems, textiles, food packaging and storage, industrial or household appliances, aviation, etc. Especially in hospitals, great efforts and huge costs are spent in combating infections.

[0004] Infections occur by touching, eating, drinking, or breathing materials containing pathogens. It is estimated that 80% of human infections occur as a result of contact with surfaces contaminated with microorganisms (Salwiczek et al., Trends Biotechnol 32: 82-90 (2014)). Typically, these infections are combated with antimicrobial agents that target the pathogens. However, what is particularly problematic is that these microorganisms can quickly and easily undergo genetic mutations to become resistant to these agents, making their elimination difficult. For example, Staphylococcus aureus (S. aureus) usually colonizes human skin and mucous membranes without causing serious problems, but if the bacteria enter the body, diseases ranging from mild to life-threatening can occur, including skin and wound infections, infected eczema, abscess infections, heart valve infections or endocarditis, pneumonia, and bloodstream infections or bacteremia. Some S. aureus are resistant to methicillin and other β-lactam antibiotics, i.e., methicillin-resistant S. aureus (MRSA), and alternative types of antibiotics are needed to treat them. Additionally, spore-forming Clostridium difficile (C. difficile), an intestinal superbug that causes symptoms ranging from diarrhea to life-threatening colon inflammation, is the most common bacterial infection in hospitals.

[0005] Over the past few years, an increasing number of researchers have devoted their efforts to the development of new antimicrobial systems aimed at helping to mitigate, combat and / or eliminate costly and debilitating infections. Much of this research has focused on polymers due to their inherent properties: polymers can serve as substrates that retain antimicrobial agents, and their characteristics, such as their hydrophilicity and / or molecular weight, can have a large impact on the resulting antimicrobial activity. Therefore, the use of polymeric materials with antimicrobial properties has attracted increasing attention from both academia and industry.

[0006] Known antimicrobial polymer coatings have been prepared by impregnating, adsorbing or covalently attaching antimicrobial agents to various surfaces to provide film-forming layers. For example, U.S. Pat. No. 9,127,173 discloses the preparation of layer-by-layer coatings on substrates, wherein the coatings contain quaternary amine groups that impart antimicrobial properties to the substrate. Non-leaching surfaces are generally considered to be preferred compared to sustained-release surfaces because microorganisms are exposed to high surface concentrations of antimicrobial agents. In addition, leaching surfaces make it difficult to pass the cytotoxicity test of the Environmental Protection Agency (EPA). As a general rule, non-leaching antimicrobial coatings and preparation methods are extremely complex and impractical for large-scale production and commercialization. In addition, the technology is generally surface-specific. Alternative methods for preparing antimicrobial coatings include using coatings that are non-covalently attached to the surface. However, similar to covalently attached coatings, these methods generally require complex multiple synthesis steps and need to be adjusted to coat different substrates, thus making them unsuitable for commercial use.

[0007] Therefore, despite active research in this area, there is still a need for novel antimicrobial materials that have broad spectrum antimicrobial activity and can easily adapt to the complexity of different environments (e.g., families, health care providers, schools, agriculture), surfaces (e.g., wood, stainless steel, marble, glass, and textiles), and applications (e.g., food packaging, water or air filters, and even protection of fruits and vegetables). In addition, such antimicrobial residual self-disinfecting films or coatings should ideally provide very high kill rates, be viable for several weeks, be nontoxic and easy to remove. It is also desirable to have a general and inexpensive method for preparing such surface coatings on a commercial scale. Summary of the invention

[0008] The present invention relates to polymer-based antimicrobial compositions that are non-toxic, water-soluble, and significantly reduce the transmission of infectious diseases from surfaces such as glass, plastic, granite and metal substrates, as well as skin. The polymers used in the compositions can perform two functions: (i) they can disinfect surfaces by killing existing germs (immediate kill); and (ii) they provide a removable residual self-disinfecting film to prevent future microbial growth (subsequent kill). The polymer-based compositions are effective against bacteria, viruses, and spores including Clostridium difficile. In addition, unlike most commercial disinfectants, the polymer-based compositions inactivate non-enveloped viruses, which are often responsible for the common cold and gastrointestinal cold. Because the antimicrobial compositions do not require germicidal chemicals or metals, unlike many other commercial disinfectants, the compositions are safe for humans, animals, and the environment.

[0009] 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 having photocatalytic activity under visible light, wherein the components of the composition are not covalently bound to each other. The antimicrobial composition meets at least one of the following tests:

[0010] (i) according to the American Society for Testing and Materials (ASTM) International Method E1153 Germicidal Spray Test, which meets EPA requirements for log 3 reduction of viruses and log 5 reduction of bacteria,

[0011] (ii) Suspension test according to ASTM International Method E1052-96 (2002) or ASTM International Method E2315 (2016),

[0012] (iii) a film formed from the composition having an antimicrobial activity as determined by the Japanese Industrial Standard (JIS) Z 2801 (2006) test or a modified version of such test as described herein.

[0013] (iii-a) kills at least 95% of the log5 population of Gram-positive or Gram-negative bacteria within 30 minutes,

[0014] (iii-b) kills at least 95% of the log4 population of enveloped viruses within 30 minutes of contact,

[0015] (iii-c) kills at least 95% of non-enveloped viruses within 30 minutes of contact, and / or

[0016] (iii-d) kills at least 94% of the log4 population of Clostridium difficile within 24 hours of contact,

[0017] (iv) a film formed from the composition has a value of 2 or less according to the International Organization for Standardization (ISO) 10993-5 in vitro cytotoxicity test,

[0018] (v) a durability test selected from (va) a film formed from the composition kills at least 99.9% of Gram-positive and Gram-negative bacteria according to EPA Protocol #01-1A Residual Self-Disinfecting Activity Test, or (vb) a film formed from the composition kills at least 95% of Gram-positive and Gram-negative bacteria, or enveloped and non-enveloped viruses, after waiting 7 days after film formation according to a modified version of Protocol #01-1A Residual Self-Disinfecting Activity Test as described herein.

[0019] The present invention also provides a method of killing microorganisms on a surface, comprising applying to the surface an antimicrobial composition comprising a cationic polymer, at least one adhesion promoter, a carrier and optionally organic and / or inorganic particles having photocatalytic activity under visible light.

[0020] The present invention also provides a method of killing microorganisms on a surface, comprising applying to the surface an antimicrobial composition comprising a high molecular weight polydiallyldimethylammonium salt and a carrier.

[0021] The present invention also provides a composition comprising a polyethyleneimine-based polymer, an optional second cationic polymer, an optional polyacid, and a carrier, wherein the second cationic polymer is selected from polydiallyldialkylammonium salts, poly(acrylamide-co-diallyldialkylammonium halides), chitosan, or a combination thereof. An antimicrobial composition is also provided comprising at least one organic and / or inorganic particle having photocatalytic activity under visible light, at least one adhesion promoter, and a carrier. These compositions can be used in methods for killing microorganisms on surfaces. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 The counter ion exchange of polydiallyldimethylammonium chloride (polyDADMAC) by LiTFSI in an embodiment of the present invention is shown.

[0023] Figure 2 A shows the small pore size of a filter comprising non-positively charged 5 μm glass. Figure 2 B shows a filter comprising positively charged alumina with larger pore size and a cationic polymer coupled to the alumina. DETAILED DESCRIPTION

[0024] The present invention provides a polymer-based antimicrobial composition comprising a cationic polymer, at least one adhesion promoter, optionally organic particles and / or inorganic particles having photocatalytic activity under visible light, and a carrier, wherein the components of the composition are not covalently bound to each other. The antimicrobial composition meets at least one of the following tests:

[0025] (i) Germicidal spray testing according to ASTM E1153, which meets EPA requirements for log3 reduction of viruses and log5 reduction of bacteria,

[0026] (ii) Suspension test according to ASTM E1052-96 (2002) or ASTM E2315 (2016),

[0027] (iii) a film formed from the composition according to the JIS Z 2801 (2006) test for antimicrobial activity or a modified version of such test as described herein

[0028] (iii-a) kills at least 95% of the log5 population of Gram-positive or Gram-negative bacteria within 30 minutes,

[0029] (iii-b) kills at least 95% of the log4 population of enveloped viruses within 30 minutes of contact,

[0030] (iii-c) kills at least 95% of non-enveloped viruses within 30 minutes of contact, and / or

[0031] (iii-d) kills at least 94% of the log4 population of Clostridium difficile within 24 hours of contact,

[0032] (iv) a film formed from the composition has a value of 2 or less according to the International Organization for Standardization (ISO) 10993-5 in vitro cytotoxicity test,

[0033] (v) a durability test selected from (va) a film formed from the composition kills at least 99.9% of Gram-positive and Gram-negative bacteria according to EPA Protocol #01-1A Residual Self-Disinfecting Activity Test, or (vb) a film formed from the composition kills at least 95% of Gram-positive and Gram-negative bacteria, or enveloped and non-enveloped viruses, after waiting 7 days after film formation according to a modified version of Protocol #01-1A Residual Self-Disinfecting Activity Test as described herein.

[0034] The effectiveness of the antimicrobial compositions described herein is best reflected in the following advantages. When applied to a surface as a traditional disinfectant, the composition has the ability to "kill immediately", even in the absence of potentially toxic conventional disinfectant chemicals. The composition has the ability to "kill later", that is, to lastingly kill (disinfect) in future later applications by forming a residual self-disinfecting film that passes the EPA acceptable durability test and EPA approved toxicity test as described above. The residual self-disinfecting film can be removed with water (e.g., warm soapy water), alcohol, or a water-alcohol mixture. The technology is highly adjustable because: i) the composition can be adjusted to produce films with a variety of thicknesses, solubility, and adhesion, ii) one or more cationic polymers can be mixed in specific proportions to target specific pathogens and / or design products with various cost characteristics, and / or iii) if desired, the natural "kill immediately" characteristics derived from the cationic polymer can be enhanced by adding one or more conventional antimicrobial agents to the composition. These and other advantages of the present invention and additional inventive features are apparent from the description of the invention provided herein.

[0035] The antimicrobial composition comprises at least one cationic polymer. The cationic polymer can be a cationic polymer with any suitable molecular weight and charge density that exhibits antimicrobial properties and enables the composition or a film formed by the composition to pass at least one of the tests (i)-(v). It has been determined that the charge density is affected by the molecular weight and the pH of the formulation. For example, as the molecular weight increases, the charge tends to increase. Alternatively, or in addition, as the pH decreases, the charge tends to increase. Therefore, the molecular weight and / or pH can be changed to provide the desired charge density and / or antimicrobial activity. The suitable molecular weight of a variety of cationic polymers is described herein. The pH of the composition is generally less than about 7, for example, the pH is about 3 to 7, and more preferably the pH is about 4 to 6.

[0036] Without wishing to be bound by any particular theory, cationic polymers are particularly effective in targeting Gram-positive and / or Gram-negative bacteria and enveloped and non-enveloped viruses. In particular, it is believed that positively charged polymers attract and bind to microbial particles, such as viral particles. The polymer continues to encapsulate the microorganism. Once the polymer completely encapsulates the microorganism, the capsid is destroyed, resulting in harmless release of genomic material.

[0037] Specific examples of suitable cationic polymers include polydiallyldialkylammonium salts, acryloyloxyalkyltrialkylammonium salts (e.g., acryloyloxyethyltrimethylammonium halide, methacryloyloxyethyltrimethylammonium halide), vinylphenylalkyltrialkylammonium salts (e.g., vinylbenzyltrimethylammonium halide), acrylamidoalkyltrialkylammonium salts (e.g., 3-acrylamido-3-methylbutyltrimethylammonium halide), poly(acrylamide-co-diallyldialkylammonium salts) (e.g., poly(acrylamide-co-diallyldimethylammonium chloride)), polyethyleneimine-based polymers, chitosan, or combinations thereof. In any of the foregoing polymers, each alkyl group is the same or different and is a linear C 1-6 or branched C 3-6 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 a polyethyleneimine-based polymer (e.g., linear, non-chemically modified PEI). In some embodiments, the composition is free of bridged polycyclic compounds (e.g., cavitand structures), including bridged polycyclic compounds bound to polymers (e.g., cavitands bound to polymers). In some embodiments, the cationic polymer is not a hybrid material comprising one or more than one divalent metal and a siloxane bridge.

[0038] In some cases, a combination of two or more cationic polymers selected from polydiallyldialkylammonium salts (e.g., polydiallyldimethylammonium halides), acryloxyalkyltrialkylammonium salts, vinylphenylalkyltrialkylammonium salts, acrylamidoalkyltrialkylammonium salts, poly(acrylamide-co-diallyldialkylammonium halides), polyethyleneimine-based polymers, and chitosan is used in the composition. In a specific embodiment, polydiallyldialkylammonium salts (e.g., polydiallyldimethylammonium halides) are used in combination with polyethyleneimine-based polymers (e.g., linear or branched polyethyleneimine (PEI)). In a preferred embodiment, polydiallyldimethylammonium chloride or poly(acrylamide-co-diallyldialkylammonium chloride) is used in combination with a non-chemically modified linear PEI.

[0039] Cationic polymers can be used together with anionic polymers or not together with anionic polymers to form polyelectrolyte complexes (PECs). As used herein, PEC refers to a complex that is automatically formed when one or more than one cationic polymers are added together with one or more than one anionic polymers. PECs are generally hydrophilic and tend to be water-soluble. In some embodiments, the composition does not include anionic polymers. When the cationic polymer is a polydiallyldialkylammonium salt (e.g., polydiallyldialkylammonium halide), the formation of PEC is optional, i.e., the anionic polymer is optional in the composition. In some embodiments, the composition does not include a combination of anionic polymers and polydiallyldialkylammonium salts (e.g., polydiallyldimethylammonium halide).

[0040] In one embodiment, the cationic polymer is a polydiallyldialkylammonium salt, such as a polydiallyldialkylammonium halide (e.g., a halide ion or an anion containing a halide), a polydiallyldialkylammonium sulfate, or a polydiallyldialkylammonium phosphate. In the polydiallyldialkylammonium halide, the halide can be any suitable compound wherein the anion is a halide ion or comprises a halide ion (e.g., bis(trifluoromethane)sulfonylimide, trifluoroacetate), such as polydiallyldimethylammonium fluoride, polydiallyldimethylammonium chloride, polydiallyldimethylammonium bromide, polydiallyldimethylammonium iodide, polydiallyldimethylammonium bis(trifluoromethane)sulfonylimide, 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.

[0041] Preferred polydiallyldialkylammonium salts are those polymers formed by polymerization of a diallyldialkylammonium compound, which can be represented by the formula:

[0042]

[0043] wherein R1 and R2 are the same or different and are each hydrogen or a C1-C6 alkyl group; R3 and R4 are independently hydrogen or an alkyl group, a hydroxyalkyl group, a carboxyalkyl group, a carboxyamide alkyl group or an alkoxyalkyl group having 1 to 12 carbon atoms; Y -represents an anion, such as a halide, a halogen-containing anion (e.g., bis(trifluoromethane)sulfonyl imide), a sulfate, or a phosphate. Examples of preferred diallyldialkylammonium monomers include diallyldimethylammonium chloride (DADMAC), diallyldimethylammonium fluoride, diallyldimethylammonium bis(trifluoromethane)sulfonyl imide, diallyldimethylammonium bromide, diallyldimethylammonium sulfate, diallyldimethylammonium phosphate, dimethylallyldimethylammonium chloride, dimethylallyldimethylammonium fluoride, dimethylallyldimethylammonium bis(trifluoromethane)sulfonyl imide, diethylallyldimethylammonium chloride, diethylallyldimethylammonium fluoride, diethylallyldimethylammonium In a preferred embodiment, the cationic polymer is polyDADMAC.

[0044] In a specific embodiment, some of the chloride counterions of the polyDADMAC molecules can be converted to insoluble fluoride counterions. This conversion can be performed, for example, by adding a diluted mixture of lithium bis(trifluoromethane)sulfonyl imide (LiTFSI). LiTFSI, as well as polyDADMAC, has an electrostatic charge, which gives the moiety (poly)electrolyte behavior in solution. This counterion exchange of LiTFSI in polyDADMAC is Figure 1 As shown in Figure 2. LiTFSI is known to have good solubility and stability in water. The exchange reaction consists of mixing two solutions: one containing positively charged polyDADMAC and the other containing negatively charged TFSI. - When a sufficient proportion of the polymer counter anion has been reacted with TFSI - During anion exchange, the polymer becomes insoluble and precipitates from the solution. TFSI in solution - The anion may be attached to the polymer chain or may be part of a micelle. The present invention seeks to use an ion exchange strategy to create just enough micelles to slightly reduce the solubility of the cationic polymer, whether used alone or in a PEC membrane. TFSI - The addition of anions reduces the solubility of the polymer but increases the durability of the resulting membrane according to the EPA Protocol #01-1A Residual Self-Disinfecting Activity Test or a modified version thereof as described herein. The TFSI that will produce the desired solubility reduction is determined experimentally. -The desired solubility can be achieved by adjusting the amount of water added to the polyDADMAC solution. In a specific example, the following steps can be used: 1) initially reduce the water added to the polyDADMAC solution by 125 ml; 2) prepare a diluted TFSI solution by mixing 0.125 g to 0.250 g of TFSI into the solution for every 2.4 g of polyDADMAC; and then 3) drip this diluted solution into the polyDADMAC solution. Vigorous stirring for 24 hours at room temperature is required to carry out this process to ensure uniform distribution. If desired, this mixture can be used to produce a PEC with one or more than one anionic polymer. If a PEC is desired in such an embodiment, the TFSI is added before the anionic polymer is introduced to produce the PEC. - dilute the solution to achieve water-soluble poly-DADMAC in Cl - Partial replacement of counterions.

[0045] The counterion conversion strategy of polyDADMAC does not adversely affect its antimicrobial activity. To test the activity, an excess of TFSI was used. - To produce a precipitate, the precipitate was then dissolved in dimethyl sulfoxide (DMSO). The solution was then placed on a glass slide to produce a membrane, which was kept for 7 days and then inoculated with a log6 population of E. coli. The converted polyDADMAC with a mixture of fluoride and chloride ions provided a membrane capable of killing >99.99% of the E. coli population within 30 minutes.

[0046] Polydiallyl dialkyl ammonium salt (for example, polydiallyl dimethyl ammonium halide), acryloyloxy alkyl trialkyl ammonium salt, vinyl phenyl alkyl trialkyl ammonium salt and / or acrylamido alkyl trialkyl ammonium salt preferably have the number-average molecular weight of 25000g / mole to 20000000g / mole.Usually preferred higher molecular weight is to reduce the solubility of the film formed by antimicrobial composition.The number-average molecular weight of polydiallyl dialkyl ammonium salt (for example, polydiallyl dimethyl ammonium halide), acryloyloxy alkyl trialkyl ammonium salt, vinyl phenyl alkyl trialkyl ammonium salt and / or acrylamido alkyl trialkyl ammonium salt can be 20000000g / mole or lower, for example 15000000g / mole or lower, 10000000g / mole or lower, 5000000g / mole or lower or 1000000g / mole or lower. Alternatively or additionally, the number average molecular weight of the polydiallyldialkylammonium salt, acryloxyalkyltrialkylammonium salt, vinylphenylalkyltrialkylammonium salt, and / or acrylamidoalkyltrialkylammonium salt can be 25,000 g / mole or more, for example, 50,000 g / mole or more, 100,000 g / mole or more, 150,000 g / mole or more, 200,000 g / mole or more, 250,000 g / mole or more, 300,000 g / mole or more, 400,000 g / mole or more, 500,000 g / mole or more, 600,000 g / mole or more, 700,000 g / mole or more, 800,000 g / mole or more, 900,000 g / mole The molecular weight of the polydiallyl dialkyl ammonium salts, acryloxy alkyl trialkyl ammonium salts, vinyl phenyl alkyl trialkyl ammonium salts, and / or acrylamido alkyl trialkyl ammonium salts may be selected from the group consisting of:For example, the number average molecular weight of the polydiallyldialkylammonium salt, acryloxyalkyltrialkylammonium salt, vinylphenylalkyltrialkylammonium salt, and / or acrylamidoalkyltrialkylammonium salt can be 25000 g / mole to 20000000 g / mole, 25000 g / mole to 15000000 g / mole, 25000 g / mole to 10000000 g / mole, 25000 g / mole to 5000000 g / mole, 25000 g / mole to 10000000 g / mole, 50000 g / mole to 15000000 g / mole, 50 ...5000000 g / mole, 50000 g / mole to 15000000 g / mole, From about 100 g / mole to about 1000000 g / mole, from about 1000000 g / mole to about 1000000 g / mole, from about 150000 g / mole to about 1000000 g / mole, from about 200000 g / mole to about 1000000 g / mole, from about 250000 g / mole to about 1000000 g / mole, from about 300000 g / mole to about 1000000 g / mole, from about 350000 g / mole to about 1000000 g / mole, or from about 400000 g / mole to about 1000000 g / mole. In some embodiments, the number average molecular weight of the polydiallyldialkylammonium salt, acryloxyalkyltrialkylammonium salt, vinylphenylalkyltrialkylammonium salt, and / or acrylamidoalkyltrialkylammonium salt is 250,000 g / mole to 1,000,000 g / mole, or 800,000 g / mole to 1,000,000 g / mole, including 900,000 g / mole to 1,000,000 g / mole.

[0047] In some embodiments, the polydiallyldialkylammonium salt is an "ultra-high molecular weight" polydiallyldialkylammonium salt, such as an ultra-high molecular weight polydiallyldialkylammonium halide. The number average molecular weight of the ultra-high molecular weight polydiallyldialkylammonium salt (e.g., polydiallyldialkylammonium halide) is typically from about 800,000 g / mole to about 20,000,000 g / mole (e.g., from about 1,000,000 g / mole to 15,000,000 g / mole, from about 1,000,000 g / mole to 10,000,000 g / mole, from about 1,000,000 g / mole to 5,000,000 g / mole, from about 2,000,000 g / mole to 50,000,000 g / mole). In some embodiments, the polydiallyldialkylammonium halide may be present in an amount of about 100 g / mol, about 3000000 g / mol to 5000000 g / mol, about 4000000 g / mol to 10000000 g / mol, about 5000000 g / mol to 20000000 g / mol, about 5000000 g / mol to 15000000 g / mol, about 6000000 g / mol to 20000000 g / mol, about 6000000 g / mol to 15000000 g / mol). In these embodiments, in general, the halide ions in the polydiallyldialkylammonium halide are fluoride ions, chloride ions, including fluoride and / or chloride-containing anions. Specifically, the polydiallyldimethylammonium halide is polyDADMAC, or a mixture of polyDADMAC and polydiallyldimethylammonium fluoride and / or polydiallyldimethylammonium bis(trifluoromethane)sulfonimide.

[0048] In another embodiment, the cationic polymer is a polyethyleneimine-based polymer, which is generally effective against non-enveloped viruses, which account for the majority of pathogenic microorganisms, such as rhinovirus, poliovirus, adenovirus, coxsackievirus, parvovirus, and rotavirus. The polyethyleneimine-based polymer can be any suitable polyethyleneimine-based polymer, which is linear or non-linear, preferably linear.

[0049] There are many reports that polyethyleneimine (PEI) has been chemically modified to produce antimicrobial agents. See, for example, Gao et al. (J. Biomaterial Science, Polymer Edition, 2007, 18, 531-544) reported that quaternized branched PEI (BPEI) has antimicrobial activity against Escherichia coli (E. coli) at low concentrations. Pasquier et al. (Biomacromolecules, 2007, 8, 2874-2882) reported that BPEI quaternized by various long alkyl groups showed a certain degree of antimicrobial activity against Escherichia coli, while linear PEI (LPEI) grafted with long chain alkyl chains produced a series of hydrophobically modified water-insoluble LPEI derivatives that effectively killed Escherichia coli and Staphylococcus aureus. See also U.S. Patent 9399044 and WO2008 / 127416A2. For example, the chemically modified PEI described in U.S. Pat. No. 9,399,044 is only effective against bacteria (e.g., Mycobacterium tuberculosis, Gram-negative Escherichia coli and Pseudomonas aeruginosa, Gram-positive Staphylococcus aureus) and fungi Candida albicans, but not against viruses. WO 2008 / 127416 A2 demonstrates that an antimicrobial coating comprising chemically modified PEI can kill enveloped viruses but not non-enveloped viruses, as shown in Table 1.

[0050] Table 1

[0051]

[0052] However, chemical modification requires expensive, low-yield organic chemical processes that use toxic chemicals that are harmful to humans and the environment. Therefore, in some embodiments of the present invention, the polyethyleneimine-based polymer is a linear PEI that has not been chemically modified or structurally modified (e.g., does not include alkyl and / or quaternary ammonium groups). In addition, it has been found that non-chemically modified linear PEI can kill non-enveloped viruses. In particular, the membranes of the non-chemically modified linear PEI described herein not only kill Gram-positive and Gram-negative bacteria, but also show at least a log4 (99.99%) reduction for enveloped and non-enveloped viruses, which is particularly important because many non-enveloped viruses are pathogenic microorganisms that cause the common cold and gastrointestinal cold, such as rhinovirus, poliovirus, adenovirus, coxsackievirus, parvovirus and rotavirus. The ability of an antimicrobial composition comprising a non-chemically modified linear PEI to reduce MS2 bacteriophage is shown in Table 2, which is considered a substitute for non-enveloped viruses.

[0053] Table 2

[0054]

[0055] In other embodiments, the polyethyleneimine-based polymer is a deacylated PEI or a quaternized N-alkyl-N-methyl polyethyleneimine. Deacylated polyethyleneimine can be provided by commercial sources, such as Polysciences, Inc. (Warrington, Pennsylvania). As used herein, "deacylated polyethyleneimine" refers to a polyethyleneimine having a protonatable nitrogen and having the formula:

[0056]

[0057] Wherein 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 90%) or completely (about 98% to 100%) hydrolyzed (deacylated). Without wishing to be bound by any particular theory, it is believed that dealkylation enhances the ability of PEI to kill viruses and reduces its cytotoxicity.

[0058] As used herein, "quaternized N-alkyl-N-methylpolyethyleneimine" refers to a polyethyleneimine that 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 90%) or completely (about 98% to 100%) hydrolyzed, methylated, and then quaternized with an alkyl substituent. The alkyl substituent in this embodiment can be any suitable linear or branched alkyl substituent. Typically, the chain length of the alkyl substituent is selected to be most effective against viruses, such as C 1-18 , including C 8-14 and C 10-12 In one embodiment, the alkyl substituent is decane, dodecane or hexadecane.

[0059] A synthetic route to provide a fully hydrolyzed (deacylated), methylated, and then quaternized PEI comprises the following process steps:

[0060] Step 1: Prepare fully deacetylated linear PEI by acid-catalyzed hydrolysis of commercial PEOZ (e.g., 500 kDa, 200 kDa and 50 kDa, preferably 50 kDa). For example, 10.0 g of PEOZ is added to 400 mL of 24% (weight / volume) HCl and then refluxed for 96 hours. POEZ crystals are completely dissolved within 2 hours, but white precipitates appear after 3 hours (i.e., 5 hours in total). The precipitates in each case are separated by filtration and then air-dried.

[0061] The protonated PEOZ (2-ethyl-2- In brief, 10 g of protonated linear PEI was dissolved in distilled water (50 mL), and 6 M KOH was added until the pH of the solution became about 11. The completely deprotonated PEI was a white precipitate, which was filtered and repeatedly washed with distilled water until it became neutral (pH was about 7). The final product was a linear PEI without N-acyl groups, with a molecular weight of about 217 kDa, 87 kDa, or preferably 22 kDa.

[0062] Step 2: The E. Clarke methylation technique (Clarke et al., JACS, 55(11):4571(1933)) can be used to produce linear N-methyl-PEI. A 50% aqueous solution of PEI consisting of 10 g of 22 kDa PEI produced in step 1 was transferred to a round-bottom flask, to which 90% formic acid (24.5 mL, 0.48 mole) was added, followed by 37% formaldehyde (29.3 mL, 0.36 mole) 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 8M KOH solution. The deprotonated N-methylated PEI was extracted several times with chloroform, and the entire organic solution was repeatedly washed with water. The chloroform was then removed to obtain a yellow viscous N-methylated PEI with a methylation degree of 100%.

[0063] Step 3: N-alkyl-N-methyl PEI is then quaternized to water-soluble and targeted to viruses. In particular, 1 g (17.5 mmol / repeat unit) of N-methylated PEI is dissolved in 75 mL of tert-butyl alcohol in a screw cap pressure tube. 1-bromohexadecane is added to the screw cap pressure tube to provide the most effective side chain length for killing viruses. The reaction mixture is then heated at 105 ° C for 48 to 96 hours, depending on the desired solubility of the final product. After the reaction is completed, the solvent is removed to reach one-tenth of its initial volume. Then, an excess of acetone (200 mL) is added to the reaction mixture and the precipitate is filtered out. In order to further purify the product, the precipitate is dissolved in chloroform, and acetone is added to reprecipitate the product. Excess solvent is decanted and the precipitate is dried using a high vacuum pump to obtain a linear N-alkyl N-methyl PEI polymer.

[0064] The number-average molecular weight of the polymer based on polyethyleneimine is generally 15000g / mole to 250000g / mole.The number-average molecular weight of the polymer based on polyethyleneimine can be 250000g / mole or lower, for example 230000g / mole or lower, 210000g / mole or lower, 190000g / mole or lower or 170000g / mole or lower.Or, or additionally, the number-average molecular weight of the polymer based on polyethyleneimine can be 15000g / mole or higher, for example, 30000g / mole or higher, 60000g / mole or higher, 90000g / mole or higher, 100000g / mole or higher, 120000g / mole or higher or 150000g / mole or higher.Therefore, the polymer based on polyethyleneimine can have the number-average molecular weight limited by any of the above-mentioned two endpoints. For example, the number average molecular weight of the polyethyleneimine-based polymer can be 15,000 g / mole to 250,000 g / mole, 15,000 g / mole to 230,000 g / mole, 15,000 g / mole to 210,000 g / mole, 15,000 g / mole to 190,000 g / mole, 15,000 g / mole to 170,000 g / mole, 30,000 g / mole to 170,000 g / mole, 60,000 g / mole to 170,000 g / mole, 90,000 g / mole to 170,000 g / mole, 120,000 g / mole to 170,000 g / mole, 150,000 g / mole to 170,000 g / mole, or 160,000 g / mole.

[0065] One aspect of the invention is an antimicrobial composition comprising (a) a polydiallyldialkylammonium salt (e.g., a polydiallyldimethylammonium halide) in combination with a polyethyleneimine-based polymer (e.g., a linear or branched polyethyleneimine (PEI), preferably a linear PEI); (b) at least one adhesion promoter; (c) optionally organic and / or inorganic particles having photocatalytic activity under 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)-(v). The weight ratio of the polydiallyldialkylammonium salt to the polyethyleneimine-based polymer is any suitable amount, but is typically 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 one embodiment, the weight ratio of polyDADMAC:PEI is 50 / 50 or 33 / 67.

[0066] When the cationic polymer is a polymer based on polyethyleneimine, the composition may also include an anionic polymer so that the cationic polymer and the anionic polymer are combined to form a PEC. In some embodiments, a polymer based on polyethyleneimine, such as a non-chemically modified linear PEI, is used in the absence of an anionic polymer such as a polyacrylate. In other embodiments where a PEC is required, the composition includes a polydiallyldialkylammonium salt (e.g., polydiallyldimethylammonium halide) and PEI, such as a branched PEI. Two methods of adding PEI to the system are proposed. One method is to first compound the polydiallyldialkylammonium halide and the anionic polymer, then compound the PEI with the anionic polymer, and then blend the two complexes. The second and preferred method is to compound the cationic polymer with the anionic polymer simultaneously in a one-pot synthesis.

[0067] It is known to those skilled in the art that non-enveloped viruses are resistant to ethanol, which is the most commonly used alcohol in hand disinfectants and other disinfectants. The inventors have found that compositions of ethanol and non-chemically modified linear PEI can effectively kill non-enveloped viruses, and the antimicrobial activity can be further improved by adding organic small molecule polyacids such as citric acid. Without wishing to be bound by any theory, it is believed that protonated linear PEI combines with anionic forms of polyacids (e.g., citrate) to form complexes. 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, propane-1,2,3-tricarboxylic acid, trimellitic acid, trimellitic acid, trimesic acid, pyromellitic acid, mellanophanic acid, mellitic acid, mellitic acid, ethylenediamine-N,N'-dimaleic acid (EDDM), 2,2'-azadisuccinic acid, 2,2'-oxydisuccinic acid (ODS), ethylenediamine disuccinic acid (EDDS), diethylenetriaminepentaacetic acid (DTPA), ethylenediaminetetraacetic acid (EDTA), 2,2'-((((1,2-dicarboxyethyl)azadiyl)bis(ethane-2,1-diyl))bis(oxy))disuccinic acid, and any combination thereof. Preferably, the polyacid is citric acid. When the ratio of protonated linear PEI to citric acid is about 70:30 to 90:10 (e.g., about 70:30, about 75:25, about 80:20, about 85 / 15, or about 90:10), the PEI-citrate complex forms a stable colloid. If more citric acid is required in the complex, such as 60:40, the colloid becomes unstable. However, the colloid can be stabilized by filtering out the larger citrate complex.

[0068] In another embodiment, the cationic polymer is chitosan. When the cationic polymer is chitosan, the formation of PECs is optional, i.e., the anionic polymer is optionally present in the composition. In some cases, chitosan with 95% or less deacetylation and / or deacetylation with quaternization (e.g., trimethyl chitosan) produces a more soluble high molecular weight chitosan. Thus, a low soluble film that is sufficiently durable and does not require the formation of PECs can be produced.

[0069] The number-average molecular weight of chitosan is generally 20000g / mole to 2000000g / mole. The number-average molecular weight of chitosan can be 2000000g / mole or lower, for example 1750000g / mole or lower, 1500000g / mole or lower or 1250000g / mole or lower. Or, or additionally, the number-average molecular weight of chitosan can be 20000g / mole or higher, for example, 50000g / mole or higher, 100000g / mole or higher, 250000g / mole or higher, 500000g / mole or higher or 1000000g / mole or higher. Therefore, chitosan can have the number-average molecular weight limited by any two above-mentioned endpoints. For example, the number average molecular weight of chitosan can be 20,000 g / mole to 2,000,000 g / mole, 20,000 g / mole to 1,750,000 g / mole, 20,000 g / mole to 1,500,000 g / mole, 20,000 g / mole to 1,250,000 g / mole, 20,000 g / mole to 1,000,000 g / mole, 50,000 g / mole to 2,000,000 g / mole, 100,000 g / mole to 2,000,000 g / mole, 250,000 g / mole to 2,000,000 g / mole, 500,000 g / mole to 2,000,000 g / mole, or 1,000,000 g / mole to 2,000,000 g / mole.

[0070] When the antimicrobial composition optionally comprises at least one anionic polymer, which forms a PEC with a cationic polymer, the PEC can provide two important advantages to the present invention: 1) the use of PECs to assemble polymers eliminates the use of chemical cross-linking agents, thereby reducing the potential toxicity and other adverse effects of the agents; 2) the PECs formed between the polyacid and the polybase are resistant to pH changes in the dissolution medium.

[0071] The anionic polymer can be any suitable anionic polymer capable of forming a PEC with a cationic polymer, for example, selected from polyacrylates, polysulfates, polysulfonates, polycarboxylates, polyoxometalates, sulfonated or carboxylated metalloporphyrins, xanthan gum, alginate, or lignin compounds (e.g., lignin sulfonates, pectin, carrageenan, humates, fulvic acid salts, brazil gum, Kondagogu gum (Cochlospermum gossypium DC.), sodium alkylnaphthalene sulfonates (e.g., MORWET TM ), poly-γ-glutamic acid, maleic acid starch half ester, carboxymethyl cellulose, chondroitin sulfate, dextran sulfate and hyaluronic acid). The anionic polymer can be linear, branched, dendritic, grafted or present as a copolymer (e.g., a block copolymer).

[0072] In a preferred embodiment, the anionic polymer is a polyacrylic acid salt (PAAS). Specific examples of PAAS include polyacrylic acid alkali metal salts (e.g., polyacrylic acid sodium salt) and polyacrylic acid ammonium salt. The number average molecular weight of the polyacrylic acid salt is at least 10000 g / mole. For example, the number average molecular weight of the polyacrylic acid salt can be 20000 g / mole or higher, such as 40000 g / mole or higher, 60000 g / mole or higher, 80000 g / mole or higher, 100000 g / mole or higher, 120000 g / mole or more, or 140000 g / mole or higher.

[0073] The size and internal structure of the PEC particles are regulated by, for example, the formation process, medium and structural parameters, specific mixing sequence, mixing ratio, PEC concentration, pH and molecular weight. Controlling the size of the PEC particles is important because the particle size affects: 1) the overall stability of the Pickering PEC; 2) the solubility of the film formed from the dispersion; and 3) the adhesion 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 may require a film with lower solubility and greater viscosity. However, adjusting these two properties will always be limited by stability issues. If too much anionic polymer is used, the PEC colloid will become too large and precipitate out.

[0074] The size of the final PEC particle can be determined by the amount of anionic polyelectrolyte (n-) relative to the amount of cationic polyelectrolyte (n+). If the n- / n+ ratio is high, the PEC particle will grow. However, when a cationic polymer is added to an anionic polymer, there is a problem of accelerated growth followed by size reduction. The preferred method of doping is to add anionic polymer to cationic polymer, even though this order of addition does not produce the smallest particles (assuming n- / n+ is below 0.8).

[0075] The size of PEC particles is also affected by the mixing order. When anionic polymers are added to cationic polymers, PEC particles become larger. However, there are some techniques that can offset this undesirable growth. First, by limiting the concentration of polyelectrolytes in the forming solution, that is, using very dilute solutions, the size of PEC emulsion particles can be kept very small. Considering that the preferred mixing order has an adverse effect on particle size, the offset strategy proposed in the present invention is to use a dilute solution, that is, to limit the concentration of the polymer, and then evaporate the excess water after the PEC is formed. In a specific embodiment of the present invention, the method preferably, but not limited to, uses a cationic polymer (e.g., polydiallyldialkylammonium salt, acryloxyalkyltrialkylammonium salt, vinylphenylalkyltrialkylammonium salt, acrylamidoalkyltrialkylammonium salt, PEI and / or chitosan) with a concentration of about 0.001M to 0.1M (e.g., 0.005M).

[0076] A second method to counteract the growth tendency of PECs is to control the pH of the cationic polymer mixture relative to the pH of the anionic polymer mixture. For example, lower pH cationic polymers (pH of about 4) and higher pH anionic polymers (pH of about 10) produce smaller particle sizes. Therefore, the pH of the cationic polymer (e.g., polydiallyldialkylammonium salts, acryloxyalkyltrialkylammonium salts, vinylphenylalkyltrialkylammonium, acrylamidoalkyltrialkylammonium salts, PEI and / or chitosan) solution used to produce PECs is preferably, but not necessarily, maintained at about 4, and the anionic pH is maintained at about 10. The pH of the final PEC solution is about 4.5, and after evaporation, the pH is adjusted to about 7.4. It is believed that the lower pH of the cationic polymer fluid contributes to the production of smaller particle sizes, thereby helping to counteract the negative effects of the addition order and molecular weight, thereby promoting the production of larger particle sizes.

[0077] The antimicrobial composition should be maintained at a pH close to 7 to pass the EPA cytotoxicity test. Even slight dissolution of the membrane during the test will result in leaching, and a pH much higher or much lower than 7 will kill the mammalian cells used in the test and the membrane will fail. In addition, a pH of 7 should help ensure that the anionic polymer remains in 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). It is recommended to adjust the final pH after any organic and / or inorganic particles are dispersed in the PEC.

[0078] With respect to the present invention, it is important that the PEC surface remain strongly positive. For example, if an excess of anionic polymer is added (i.e., if (n- / n+) is too high), the PEC particle charge can become negative, which can undermine the effectiveness of the antimicrobial composition, since the antimicrobial mode of action is believed to be associated with the positively charged cationic polymer, which attracts and pierces the negatively charged microbial membrane. Therefore, it is important that the PEC particle charge remain positive. For the purposes of the present invention, it is recommended that the (n- / n+) value does not exceed 0.3, and is preferably less than 0.2.

[0079] Typically, the ppm of film thickness is determined by the amount of carrier (e.g., water) evaporated from the combined solution (e.g., PEC solution). When very dilute concentrations are used, a considerable amount of carrier needs to be evaporated to achieve the desired solids ppm in the film-forming composition.

[0080] One aspect of the invention is to assemble PECs in a manner such that the average aggregate size of the PECs in solution is less than about 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 about 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.

[0081] The antimicrobial composition preferably also comprises at least one adhesion promoter, so that the composition can adhere to the substrate surface to form a residual self-disinfecting film that cannot be immediately washed off. In some embodiments, the residual self-disinfecting film is not covalently bound to the surface of the substrate. In some cases, the adhesion promoter can be described as a coupling agent. The adhesion promoter is generally one or more than one compound with at least one functional group, and the functional group is attractive to the surface of the substrate, at least one cationic polymer, or both of the substrate. Suitable examples of adhesion promoters include titanates, carboxylated branched or linear PEI, silane compounds, cationic block copolymers, and other polymers that will produce "stickiness", reactive groups such as acyl or carboxylic acids, and carboxylic acid derivatives. Preferably, the adhesion promoter is a carboxylated branched PEI because it does not damage the cationic charge of the polymer.

[0082] The titanate may be any suitable titanate which increases the ability of the composition to adhere to a surface and / or enables the composition or a film formed from the composition to pass one or more of the tests (i) to (v). Typically, the titanate is selected from alkoxy titanates, neoalkoxy titanates, glycolate chelate titanates, ethylene chelate titanates, pyrophosphate titanates, and combinations thereof.

[0083] In a preferred embodiment, the titanate is selected from 2,2 (bis 2-propylene oxymethyl) butoxy-tri neodecanoate-0 titanium IV, 2,2 (bis 2-propylene oxymethyl) butoxy-tri (dodecyl) benzene sulfonic acid-0 titanium IV, 2,2 (bis 2-propylene oxymethyl) butoxy-tri (dioctyl) phosphoryloxy-0 titanium IV, 2,2 (bis 2-propylene oxymethyl) butoxy-tri (dioctyl) pyrophosphoryloxy-0 titanium IV, 2,2 (bis 2-propylene oxymethyl) butoxy-tri (2-ethylene diamino) ethoxy titanium IV, 2,2 (bis 2-propylene oxymethyl) butoxy-tri (3-amino) phenoxy titanium IV, 2,2 (bis 2-propylene oxymethyl) butoxy-tri (6-hydroxy) hexyl-0 titanium IV, or any combination thereof. Typically, the titanate is 2,2 (bis-2-propylene oxymethyl) butoxy-tri neodecanoate-0 titanium IV.

[0084] Antimicrobial compositions can include any suitable amount of titanate to form a residual self-disinfecting film. Antimicrobial compositions can include, for example, 0.1% of the weight of the cationic polymer based on monomer ("wbm") or more titanate, for example, 0.2% wbm or more, 0.3% wbm or more, 0.4% wbm or more, or 0.5% wbm or more. Alternatively, or additionally, antimicrobial compositions can include 6% wbm or less titanate, 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, of the cationic polymer. Therefore, antimicrobial compositions can include titanate in an amount limited by any two aforementioned endpoints. For example, the antimicrobial composition can include a titanate in an amount of 0.1% wbm to 6% wbm of the cationic monomer, for example, 0.2% wbm to 6% wbm, 0.3% wbm to 6% wbm, 0.4% wbm at least 6% wbm, 0.5% wbm to 6% wbm, 0.5% wbm to 5% wbm, 0.5% wbm to 4% wbm, 0.5% wbm to 3% wbm, 0.5% wbm to 2% wbm, 0.5% wbm to 1% wbm, 0.5% wbm to 0.9% wbm, 0.5% wbm to 0.8% wbm, or 0.5% wbm to 0.7% wbm, for example 0.6% wbm.

[0085] Adhesion promoter can be carboxylated PEI (PEI-COOH), which is branched, linear or branched and linear mixture. PEI-COOH can be purchased commercially or prepared by PEI. For example, bromoacetic acid aqueous solution can be added to the PEI aqueous solution. Then the resulting mixture is stirred, and then filtered to separate the polymer and remove the unreacted acid. PEI-COOH can have any suitable molecular weight, but generally has a number average molecular weight of 15000g / mol to 250000g / mol. PEI-COOH can be used in a suitable amount, generally 0.001 wt % to 3 wt %, including endpoints of 0.01 wt %, 0.1 wt %, 0.5 wt %, 1 wt %, 1.5 wt %, 2 wt % and / or 2.5 wt %. Preferred amount is 0.001 wt % to 0.01 wt %, for example 0.001 wt %.

[0086] Silane compounds such as silane coupling agents can be used as adhesion promoters. Generally, silane coupling agents have functional groups at both ends, allowing organic groups such as cationic polymers to bind to inorganic groups such as substrates. Silane compounds can have the formula R-(CH2) n -Si-X3, wherein R is an organic functional group (e.g., an optionally substituted linear or branched C1-C 20 alkyl, optionally substituted aryl such as phenyl or naphthyl, amino such as -NH(CH2)3NH2, epoxy or methacryloxy), n is an integer from 0 to 6, and X is a hydrolyzable group (e.g., alkoxy, acyloxy, halogen or amino). Suitable examples include trialkoxysilanes and monoalkoxysilanes (wherein the alkoxy is a C1-C6 alkoxy (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy, or a combination thereof)), bidentate (branched) silanes having two alkoxy-silane branches, cyclic azasilanes, vinyl silanes, acryloxysilanes, epoxysilanes and aminosilanes, or any combination thereof. Specific examples of the silane compound include methyltrimethoxysilane, methyltriethoxysilane, isobutyltrimethoxysilane, n-octyltriethoxysilane, phenyltrimethoxysilane, vinyltrichlorosilane, vinyltri(β-methoxyethoxy)silane, vinyltriethoxysilane, vinyltrimethoxysilane, 3-methacryloxypropyl-trimethoxysilane, β-(3,4-epoxycyclohexyl)-ethyltrimethoxysilane, γ-glycidoxypropyl-trimethoxysilane, γ-glycidoxypropyl-methyldiethoxysilane, N-β(aminoethyl)-γ-aminopropyl-trimethoxysilane, N-β(aminoethyl)-γ-aminopropyl-methyldimethoxysilane, 3-aminopropyl-triethoxysilane, and N-phenyl-γ-aminopropyl-trimethoxysilane, or a combination thereof.

[0087] The adhesion promoter may be a cationic block copolymer, for example a high molecular weight polyethylene copolymer having basic or acidic adhesion groups such as amino and / or hydroxyl groups. Commercial products of this type include BYK Chemie GmbH (Wiesel, Germany) and BYK TM 4500, BYK TM 4510、BYK TM 4509, BYK TM 4512 and BYK TM 4513. Suitable amounts of the block copolymer are from 0.001 wt % to 5 wt %, including ranges with endpoints of 0.01 wt %, 0.1 wt %, 0.5 wt %, 1 wt %, 1.5 wt %, 2 wt %, 2.5 wt %, 3 wt %, 3.5 wt %, 4 wt %, or 5 wt %. Preferred amounts are from 0.5 wt % to 2 wt %, such as 1 wt %.

[0088] Adhesion promoters can also be polymers that naturally have or have been modified to have "sticky" reactive groups, such as acyl, carboxylic acid, carboxylic acid derivatives, sulfur-containing moieties (e.g., thio), amino, hydroxyl and / or halogen-containing groups. The polymer itself is any suitable part, preferably uncharged, such as polyethylene, polypropylene, poly(ethylene-vinyl acetate), polyester, polyurethane, polyamide, polyvinyl acetate, polyvinyl alcohol, polyvinyl butyral, polyvinyl chloride, polyvinyl ether or a combination thereof. The suitable amount of polymer is 0.001% by weight to 3% by weight, including endpoints of 0.01%, 0.1%, 0.5%, 1%, 1.5%, 2% by weight and / or 2.5% by weight. Preferred amount is 0.5% by weight to 2% by weight, such as 1% by weight.

[0089] In some embodiments, the antimicrobial composition comprises organic and / or inorganic particles having photocatalytic activity under visible light, and the organic and / or inorganic particles can be any suitable organic (e.g., graphene or graphite phase carbon nitride (g-C3N4)) and / or inorganic particles having photocatalytic activity under visible light (e.g., 390nm to 700nm). The organic and / or inorganic particles having photocatalytic activity produce reactive oxygen species that can destroy pathogenic microorganisms (e.g., kill Clostridium difficile, bacteria and / or viruses, including avian influenza and SARS), thereby enhancing the disinfection properties of the composition. Typically, the organic and / or inorganic particles having photocatalytic activity under 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 particles are present in the antimicrobial composition, whereas in a multijunction complex, the various components of the complex are tightly bound to ensure electron transfer and minimize recombination of holes.

[0090] As used herein, the term "particle" includes spherical particles (eg, spheres) and other shapes, such as platelets, rods, cubes, and flakes, or combinations of various shapes and morphologies.

[0091] Graphene is an allotrope of carbon in which carbon atoms are bonded to each other in sheets one atom thick. Graphene can optionally be functionalized with oxygen- and / or nitrogen-containing groups. An analogue of graphite is photocatalytic graphitic carbon nitride (g-C3N4).

[0092] Transition metal oxides, sulfides and selenides can be any suitable compound comprising at least one metal atom and at least one anion of oxygen, sulfur or selenium in an oxidation state of -2. In some aspects, the transition metal oxide is selected from 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 selected from cadmium selenide, copper selenide, copper germanium selenide, copper indium gallium selenide, copper titanium selenide, indium selenide, manganese diselenide, titanium selenide, tungsten diselenide, silver selenide, silver selenide, gold triselenide, zinc selenide, iron selenide, nickel selenide, ruthenium selenide, cobalt selenide and combinations thereof.

[0093] 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 some embodiments, the transition metal oxide / sulfide / selenide particles can be doped with a suitable metal such as tungsten, nitrogen, or a combination of tungsten and nitrogen.

[0094] In one embodiment, the transition metal oxide is titanium dioxide (TiO2). The TiO2 particles can be obtained from any suitable TiO2 mineral form. For example, the TiO2 particles can maintain anatase crystal structure, a brookite crystal structure, or a rutile crystal structure. In a preferred embodiment, the TiO2 maintains anatase crystal structure.

[0095] The TiO2 particles can be of any suitable structural type. Typically, the TiO2 particles are TiO2 nanoparticles ("NP"). The TiO2 nanoparticles can be synthesized by any suitable method. For example, the TiO2 nanoparticles can be liquid-phase synthesized or gas-phase synthesized. In a preferred embodiment, the TiO2 nanoparticles are liquid-phase synthesized because liquid-phase synthesis tends to produce soft aggregates, which makes it easier to disperse the TiO2. Exemplary TiO2 nanoparticles are 25nm anatase, liquid-phase synthesized TiO2 nanoparticles doped with tungsten, which can be purchased from Nanostructured & Amorphous Materials, Inc. (Houston, Texas, USA).

[0096] In a specific example of functionalizing TiO2 particles, W-doped liquid-phase synthesized TiO2 (20 nm) was calcined with urea at 400°C for 1 hour, which produced a poly(amino-tri-s-triazine) polymer covalently attached to the TiO2 particles. Next, the W / N-doped TiO2 particles were ground together with powdered urea. The hard material produced by the calcination was ground into a powder so that it could be placed in a planetary ball mill with urea. The grinding specifications were 300 rpm with 10% urea and balls weighing 10 times the weight of TiO2 for 30 minutes. After 30 minutes, three-quarters of the grinding drum was filled with 200 mL of H2O and ground for another 5 minutes to capture and disperse the TiO2 nanoparticles. The contents were then placed in a beaker and mixed under 150 W of UV light for 1 hour. The highly dispersed nanopowder can then be added to the antimicrobial composition. It is important to note that the nanopowder is highly dispersed in water, which keeps it in a non-aggregated nano state. Thus, the functionalization method described herein enables TiO2 to be dispersed in water, whereas TiO2 is typically only dispersible in alcohols. Producing this stable nanodispersion in the absence of surfactants means that when the particles are dispersed into a cationic polymer solution or PEC, the particles are not contaminated by surfactants that could inhibit their ability to respond to visible light.

[0097] The high energy grinding of the TiO2 particles achieves two purposes: 1) deagglomerates the powder to produce nanoparticles; and 2) urea dual doping of the nitrogen-containing particles, in particular, any newly exposed facets of the particles are doped as the high energy grinding breaks up agglomerates and aggregates. Basically, it is believed that grinding forces nitrogen into the pores and covers facets that were previously unexposed during the calcination process. After calcination with urea and grinding with urea, the TiO2 nanoparticles were irradiated with 150 watts of UV light. Without wishing to be bound by any theory, it is believed that UV irradiation improves the visible light responsiveness of the TiO2 nanoparticles because hydroxyl groups are introduced on the surface of the TiO2 nanoparticles. This is one explanation for why the particles are easily dispersed in water. The ability of the functionalized nanoparticles to degrade methylene blue was tested, and it was observed that the sum of all four functionalization steps significantly degraded the dye within 90 minutes.

[0098] Finally, after calcination, grinding, 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 the core of the "dye-sensitized solar cell" (DSSC) technology. DSSC has attracted much attention in recent years due to its relatively low cost and high efficiency. DSSC is basically a photoelectrochemical system in which light capture is completed by dye molecules, which are adsorbed on the surface of the oxide nanostructure forming the photoelectrode film. Surface sensitization of wide-bandgap semiconductor photocatalysts such as TiO2 by chemical adsorption or physical adsorption of dyes can improve the efficiency of the excitation process and expand the excitation wavelength range of transition metal oxide particles (e.g., TiO2). This is done by exciting the sensitizer, which can inject holes or more common electrons into the particles. When a monolayer dye is dispersed on a photocatalyst with a high surface area, efficient charge injection is observed. This sensitization increases 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 the transition metal oxide particles (e.g., TiO2) depend on the nature of the dye molecule, the nature of the transition metal oxide particles (e.g., TiO2), and the interaction between the dye and the transition metal oxide particles. The dye is any suitable compound, such as 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-bis(thiocyanato)bis(2,2′-bipyridine-4,4′-dicarboxylate)ruthenium(II) (N3), tris(thiocyanato)-2,2′,2″-terpyridine-4,4′,4″-tricarboxylate)ruthenium(II) (black dye), K8, K9, K19 and Z907). In one embodiment of the invention, N719 dye is applied by mixing calcined / milled / UV light functionalized transition metal oxide particles (e.g., TiO2) with 0.5 mM of the N719 dye mixture in ethanol for 1 hour in the dark. Other dyes may also be used. The functionalized particles are decanted, centrifuged and added back to the water.

[0099] In any of the embodiments described herein, the TiO2 particles are doped with tungsten and nitrogen and hydrolyze under ultraviolet (UV) light. The resulting particles are visible light responsive TiO2 particles, which are effective as antimicrobial agents, particularly when such particles are embedded in a film formed by the antimicrobial composition of the present invention. Thus, the present invention provides a method for killing microorganisms on a surface (e.g., disinfecting a surface, providing a residual self-disinfecting film, or both), comprising applying an antimicrobial composition to a surface, the 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. The adhesion promoter is as described herein, and the carrier is as described herein, and can be, for example, water, alcohol, or a combination of water and alcohol.

[0100] Without 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. The band gap energy is excited and electrons are driven from the valence band to the conduction band and an electron-hole pair is generated. The electron hole reacts with water to produce reactive oxygen species, such as hydroxyl radicals, sometimes referred to as reactive oxygen species (ROS). The positive holes of TiO2 separate water molecules to form hydrogen and hydroxyl radicals. The negative electrons react with oxygen molecules to form superoxide anions (O2 - ). Superoxide anions further react with water molecules to generate peroxyhydroxyl radicals (·OOH) and hydrogen peroxide (H2O2). ·OH, O2 - Each of OOH and H2O2 can react with pathogenic microorganisms and destroy their cell structures.

[0101] In addition, the electron holes themselves can directly react with the microbial cell wall, cell membrane, and cell components. In yeast and bacilli, intracellular coenzyme A (CoA) is oxidized by TiO2, making CoA dimers inactive, which leads to the cessation of cell respiration and ultimately the death of the microorganisms. In this process, the electron transfer between the killed cells and TiO2 is carried out through CoA. As a result, the content of CoA decreases and the CoA dimers increase.

[0102] The dye sensitizer is any suitable compound, such as 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-bis(thiocyanato)bis(2,2′-bipyridine-4,4′-dicarboxylate)ruthenium(II) (N3), tris(thiocyanato)-2,2′,2″-terpyridine-4,4′,4″-tricarboxylate)ruthenium(II) (black dye), K8, K9, K19 and Z907).

[0103] Organic and / or inorganic photocatalytic particles may include conductive conjugated polymers. Suitable conjugated polymers include polypyrrole (Ppy), poly (3-hexylthiophene) (P3HT), polycarbazole, polyindole, polyaza, 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 nanocomposites that are specifically designed to react with ordinary indoor lighting systems to produce reactive oxygen species (ROS). ROS destroy spore-like microorganisms that are difficult to kill, such as Clostridium difficile and fungi. ROS also oxidize microbial debris, thereby performing a continuous cleaning function. In a specific embodiment, the photocatalytic nanocomposite is composed of a multi-junction composite, which includes: WTiO2 / CN heterojunction / Ppy, wherein WTiO2 is tungsten-doped TiO2 nanoparticles as described herein, CN is graphitic carbon nitride (g-C3N4), and Ppy is polypyrrole.

[0104] Historically, most photocatalytic materials have been designed around various metal sulfides and metal oxides rather than polymers. Titanium dioxide (TiO2) is the metal oxide of choice because it is readily available, cheap, stable, non-toxic, and highly reactive in the ultraviolet (UV) spectrum. The inventors hope to go beyond the use of TiO2 because the goal is to produce photocatalytic materials that are reactive in ordinary indoor lighting systems. Since TiO2 has a wide band gap (3eV to 3.2eV), it only absorbs light in the UV spectrum, which is not present in indoor lighting. Therefore, the present invention provides a polymer-based photocatalytic nanocomposite, i.e., no or very limited use of metals. As described herein, such nanocomposites may be less toxic to humans and the environment, and when incorporated into residual self-disinfecting films containing cationic polymers, there is no anionic charge to offset the cationic charge. In the polymer-based nanocomposite, the WTiO2 in the WTiO2 / CN heterojunction / Ppy multijunction composite is replaced by acid-modified or protonated graphite phase carbon nitride (g-C3N4). Protonation of CN results in a band gap of CN with a valence and conduction band very close to that of TiO2. The inventors have developed several techniques to produce protonated CN, known as acidified carbon nitride (ACN), and then strongly couple the protonated CN to heterogeneous CN and conjugated polymers (e.g., polypyrrole (Ppy), poly(3-hexylthiophene) (P3HT), polythiophene (Ptp), etc.), thereby obtaining photocatalytic composites specifically designed for capturing low-level indoor light. This method is explained in detail in U.S. Provisional Patent Application 62 / 367,981 and concurrently filed provisional patent applications by the inventors, the entire contents of which are incorporated herein by reference.

[0105] Advantages of this new class of polymer-based photoreactive materials include one or more of the following: (i) maximum light harvesting using multi-junction band segments, (ii) maximum photon utilization by using materials with appropriate band edges, ordering the assemblies and tightly coupling them to promote fast electron transport and minimize electron-hole recombination, (iii) assembly using a low-cost, easily scalable manufacturing process that does not use toxic chemicals and produces no waste and produces nano-mesoporous materials with extremely high surface areas, which produces stable dispersions of mixed morphologies of micro-, nano- and crystalline particles and platelets, thereby maximizing the optical path of the incident light and retaining all "invisible" nano / crystalline particles and platelets.

[0106] The organic and / or inorganic photocatalytic particles may include a noble metal, such as ruthenium, rhodium, palladium, silver, osmium, iridium, platinum, gold, or mixtures thereof. In some embodiments, the noble metal is platinum.

[0107] The average diameter of the organic and / or inorganic particles having photocatalytic activity in visible light is not particularly limited and may be 5nm to 1000nm. The average diameter of the organic and / or inorganic particles may be 1000nm or less, such as 750nm or less, 500nm or less, 250nm or less, or 100nm or less. Alternatively, or in addition, the average diameter of the organic and / or inorganic particles may be 5nm or greater, such as 10nm or greater, or 15nm or greater. Therefore, the organic and / or inorganic photocatalytic particles may have an average diameter defined by any two of the aforementioned endpoints. For example, the average diameter of the organic and / or inorganic photocatalytic particles may be 5nm to 1000nm, 5nm to 750nm, 5nm to 500nm, 5nm to 250nm, 5nm to 100nm, 10nm to 100nm, or 15nm to 100nm.

[0108] The antimicrobial composition may include any suitable amount of organic photocatalytic particles and / or inorganic photocatalytic particles to form a residual self-disinfecting film. The antimicrobial composition may include organic and / or inorganic photocatalytic particles in an amount of 1% by weight ("wbm") or more of the cationic monomer, such as 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, or additionally, the antimicrobial composition may include organic and / or inorganic particles in an amount of 20% wbm or less of the cationic polymer, such as 18% wbm or less, 15% wbm or less, 12% wbm or less, 10% wbm or less, 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 can include organic and / or inorganic particles in an amount defined by any two of the aforementioned endpoints. For example, the antimicrobial composition can include organic and / or inorganic particles in an amount of 1% wbm to 20% wbm of the cationic monomer, for example, 1% wbm to 15% wbm, 1% wbm to 10% wbm, 1% wbm to 7% wbm, 1% wbm to 6% wbm, 1% wbm to 5% wbm, 4% wbm to 20% wbm, 5% wbm to 15% wbm, 4% wbm to 8% wbm, 5% wbm to 8% wbm.

[0109] In one aspect of the invention, the antimicrobial composition comprises at least one organic particle and / or inorganic particle having photocatalytic activity under visible light, at least one adhesion promoter and a carrier. Organic photocatalytic particles and inorganic photocatalytic particles, adhesion promoters and carriers are described herein. The film formed by the antimicrobial composition comprising photocatalytic particles kills microorganisms under the conditions of the revised scheme of JIS Z2801 (2006 edition, which was updated in 2010). For example, the antimicrobial composition comprising at least one organic particle and / or inorganic particle having photocatalytic activity under 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 the log4 population of Clostridium difficile, fungi or yeast within 24 hours of contact. Therefore, the composition can be used according to any method described herein to kill microorganisms on the surface.

[0110] In some embodiments, the antimicrobial composition comprises a salt that can affect the ability of the cationic polymer to be adsorbed to the substrate surface and produce a film. Without wishing to be bound by any theory, it is believed that high salt concentrations result in conditions similar to the interactions experienced by polymers in favorable solvents. Although polyelectrolytes are charged, they are still mainly non-polar with a carbon skeleton. Although the charges on the polymer backbone exert electrostatic forces, causing the polymer to enter a more open and loose conformation, if the surrounding solution has a high concentration of salt, the charge repulsion will be shielded. Once this charge is shielded, the polyelectrolyte will act as any other non-polar polymer in a high ionic strength solution and begin to minimize the interaction with the solvent, which can cause more aggregation and dense polymer deposition on the surface and improve adsorption or adhesion.

[0111] The salt is any inorganic salt, for example 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 counter anion can be a halide, carbonate, bicarbonate, sulfate, thiosulfate, phosphate, nitrate, nitrite, acetate, bromate, chlorate, iodate, etc. Specific examples of the salt 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, magnesium bromide, sodium 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.

[0112] The antimicrobial composition can include any suitable amount of salt, such as 0.01 M to 0.1 M, including any combination of endpoints such as 0.01 M, 0.02 M, 0.03 M, 0.04 M, 0.05 M, 0.06 M, 0.07 M, 0.08 M, 0.09 M, and 0.1 M. In a specific example, the antimicrobial composition includes 0.01 M to 0.05 M salt.

[0113] If desired, the cationic polymer can be blended with one or more than one non-electrolyte (non-ionic) polymer. Suitable non-electrolyte (non-ionic) polymers are preferably water-soluble and include, for example, polyacrylamide, polyamine, polyamidoamine, polyethylene glycol, polyvinyl pyrrolidone, polyvinyl alcohol and polyacrylate (e.g., polymethyl methacrylate), or any combination thereof.

[0114] Antimicrobial composition comprises carrier.Carrier can be any suitable carrier, and this carrier just evaporates after composition is applied to desired surface.Usually, carrier is selected from alcohol, water or its combination.In some embodiments, carrier comprises the combination of water and alcohol.Suitable alcohol comprises methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, sec-butyl alcohol and tert-butyl alcohol or its combination.In preferred embodiments, carrier comprises ethanol (for example, carrier is the combination of ethanol and water).When using the combination of alcohol and water as carrier, alcohol: the ratio of water is preferably 10:90 to 99:1 (for example, 10:90, 20:80, 30:70, 40:60, 50:50, 60:40, 70:30, 80:20, 90:10, 95:5 and 99:1).In some embodiments, alcohol: the ratio of water is 70:30 to 80:20.

[0115] Typically, the antimicrobial composition does not contain bactericidal small molecule compounds (i.e., non-polymers) or antimicrobial metals (including those EPA-registered conventional bactericides) because these components have a substantial impact on the composition. EPA-approved bactericides that can be excluded from the composition include, for example, glutaraldehyde, halazon, hexachlorophene, furazolidinone, nitrocresol mercuric, polyvinylpyrrolidone iodine, thimerosal, C1-C5-parahydroxybenzoic acid esters, hypochlorites, halocarban, chlorobenzylphenol, poloxamer iodine, phenoplasts, mafenide acetate, amiloride hydrochloride, quaternary ammonium salts, oxyclosan, bromosalan, mercurochrome, dibromosalan, glyceryl laurate, pyrithione sodium and / or zinc pyrithione, (dodecyl)(diethylenediamine)glycine, (dodecyl)(aminopropyl)glycine, phenolic compounds (e.g., m-cresol, o-cresol, p-cresol, o-phenylphenol, 4-chloro-m-cresol, chloroxylenol, 6-n-pentyl-m-cresol, resorcinol, resorcinol monoacetate, p-tert-butylphenol, and o-benzyl-p-chlorophenol), alkaline glutaraldehyde, and quaternary ammonium salts (e.g., N-(higher)C 10 -C 24-alkyl-N-benzyl-quaternary ammonium salts, which contain water-soluble anions, such as halides (such as chloride, bromide and iodide); sulfates and methylsulfates, and heterocyclic imides, such as imidazolinium salts). Suitable quaternary ammonium compounds are described in U.S. Pat. No. 8,067,403 and include: benzalkonium chloride (e.g., benzalkonium chloride), substituted benzalkonium chlorides (e.g., alkyl dimethyl benzyl ammonium chloride), diquaternary ammonium compounds (e.g., containing an equal mixture of alkyl dimethyl benzyl ammonium chloride and alkyl dimethyl ethyl benzyl ammonium chloride), di- or di-chain quaternary ammonium compounds, such as dialkyl methyl amines (e.g., didecyl dimethyl ammonium chloride or dioctyl dimethyl ammonium chloride), and mixtures of fourth generation quaternary ammonium compounds with second generation quaternary ammonium compounds (e.g., didecyl dimethyl ammonium chloride and alkyl dimethyl benzyl ammonium chloride). In one embodiment, the antiseptic is at least one selected from the group consisting of sodium hypochlorite, chloride, chlorine dioxide, sodium chloride, potassium persulfate, potassium permanganate, silver nitrate, chlorhexidine, hexachlorophene, hydrogen peroxide, acetic acid, peracetic acid, betadine, povidone-iodine, formaldehyde, glutaraldehyde, benzalkonium chloride, triclosan, boric acid, phenol, cresylic acid, thymol, and polyhexamethylbiguanide.

[0116] However, if desired, one or more than one additional chemical bactericide, such as those agents described above, can be added to any of the aforementioned embodiments of the antimicrobial composition. This selection provides an additional chemical killing mechanism to further enhance the antimicrobial activity of the antimicrobial composition. When one or more than one bactericide is incorporated into the antimicrobial composition, these agents are retained in the residual self-disinfecting film of the antimicrobial and are gradually released when the coated surface is in contact with moisture. When the film is exposed to a large amount of water, such as when the surface is wetted by wiping, food residues or dishwashing water, an increased amount of bactericide can be released. Therefore, it is important that no matter what bactericide is used, the agent must be non-toxic to the human body and should not make the film sticky, blurry or in any way damage the appearance of the surface to which they are applied. Bactericides are usually added in lower concentrations. Therefore, these additives preferably account for 0.001% to 5% of the weight ("wbm") based on monomers of the cationic polymer.

[0117] In some embodiments, the antimicrobial composition consists essentially of or consists of polydiallyldimethylammonium halides, polyethyleneimine-based polymers, anionic polymers, at least one adhesion promoter (e.g., titanates, carboxylated branched PEI), optionally organic and / or inorganic particles having photocatalytic activity under visible light, and a carrier, wherein each component is described herein. In some aspects of this embodiment, organic and / or inorganic particles having photocatalytic activity under visible light are present in the composition. In some embodiments, the antimicrobial composition consists essentially of polydiallyldimethylammonium halide, a polyethyleneimine-based polymer, at least one adhesion promoter, an optional anionic polymer, optional organic and / or inorganic particles having photocatalytic activity under visible light, and a carrier, or consists of polydiallyldimethylammonium halide, a polyethyleneimine-based polymer, at least one adhesion promoter, an optional anionic polymer, optional organic and / or inorganic particles having photocatalytic activity under visible light, and a carrier, wherein each component is described herein. In some embodiments, the antimicrobial composition consists essentially of polydiallyldimethylammonium halide, at least one adhesion promoter (e.g., titanate, carboxylated branched PEI), organic and / or inorganic particles having photocatalytic activity under visible light, and a carrier, or consists of polydiallyldimethylammonium halide, at least one adhesion promoter (e.g., titanate, carboxylated branched PEI), organic and / or inorganic particles having photocatalytic activity under visible light, and a carrier, wherein each component is described herein.

[0118] Another aspect of the invention is an antimicrobial composition comprising a polyethyleneimine-based polymer, an optional second cationic polymer (selected from polydiallyldialkylammonium salts, poly(acrylamide-co-diallyldialkylammonium halides), chitosan, or a combination thereof), an optional polyacid, an optional at least one adhesion promoter, and a carrier. The polyethyleneimine-based polymer is typically a linear or branched polyethyleneimine (PEI) as described herein, but is preferably a linear PEI that has not been chemically or structurally modified.

[0119] In some cases, there is no second cationic polymer. In other cases, 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.

[0120] The polyacid and at least one adhesion promoter are as described herein.

[0121] The carrier used in the composition is any suitable carrier as described herein (e.g., water, propanol, isopropanol and / or ethanol). Typically, the composition comprises 20% to 80% by volume of various alcohol blends and a balance of water. In order to enhance the virucidal effect, 3% to 10% of various glycols (preferably those with a chain length of 3 to 5 carbon atoms, such as propylene glycol (1,2-propylene glycol and 1,3-propylene glycol) or butylene glycol (1,3-butylene glycol)) blends can be added to the composition. Preferably, the glycol is 1,2-propylene glycol and / or the alcohol is ethanol.

[0122] The proton donor can be added to the composition in a suitable amount (e.g., about 0.015% to about 1%, including about 0.05% to about 1%, about 0.08% to about 0.8%, about 0.1% to about 0.8%, based on the total weight of the alcohol). The proton donor is any suitable compound, such as hydrochloric acid, nitric acid, phosphoric acid, phosphonic acid, boric acid, sulfuric acid, adipic acid, benzene 1,3,5-tricarboxylic acid, chlorosuccinic acid, choline chloride, aconitic acid, citramalic 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, oxalic acid, oxalic acid Preferably, the proton donor is citric acid, tartaric acid, malonic acid, tetrahydrofuran-2,3,4,5-tetracarboxylic acid, tricarballylic acid, ethylenediaminetetraacetic acid (verseneacid), 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.

[0123] If desired, the composition may contain other components, including, for example, 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, aminomethyl propanol, isopropyl myristate, tocopheryl acetate), and / or dyes (e.g., blue 1, red 33, yellow 5). Depending on the presence of the carrier, the polymer used, and other components, the composition may be any desired formulation, including liquid, cream, gel, or foam.

[0124] In one embodiment, the composition comprises a non-chemically modified linear PEI, polyDADMAC, optionally citric acid, a carboxylated branched PEI, and a water / alcohol carrier.

[0125] In one embodiment, the polyethyleneimine-based polymer and the second cationic polymer form a crystalline miscible blend, resulting in a stable dispersion in a carrier. The miscible blend provides a stable clear crystalline solution, i.e., without precipitation or settling. A miscible mixture is different from a PEC. In addition, without wishing to be bound by any theory, it is believed that the crystalline nature of the polymer in the blend is to have a larger surface area and be able to provide more interface between the cationic polymer and the microbial pathogen in solution or as a membrane.

[0126] Crystallization miscible blends can be prepared by any suitable method. In a specific example, the miscible blends of non-chemically modified linear PEI and other cationic polymers can be prepared as follows. An appropriate amount of water / PEI dispersion (e.g., about 4000ppm of PEI) is heated to a temperature slightly higher than the glass transition temperature of PEI (e.g., at least 1°C higher than the glass transition temperature, at least about 2°C higher than the glass transition temperature, at least about 3°C ​​higher than the glass transition temperature, at least about 4°C higher than the glass transition temperature, at least about 5°C higher than the glass transition temperature; including a temperature of 65°C to 80°C, or 68°C to 78°C, or 70°C to 75°C, or about 70°C, about 72°C, or about 74°C). Next, an appropriate amount of a second cationic polymer (e.g., poly-DADMAC) solution with a relatively low pH (e.g., pH is about 5 to 6, including pH being about 5, pH being about 5.5, or pH being about 6) is added. This relatively low pH further helps to ensure that PEI remains in a solution state. After vigorous mixing, the solution is cooled to room temperature. Next, an appropriate amount (e.g., 25ppm to 100ppm) of adhesion promoter (e.g., carboxylated branched PEI) is added. Carboxylated branched PEI is very alkaline, thereby increasing the pH of the solution. The pH should be adjusted back to 6.5 so that the linear PEI is not solidified. Next, the solution is reheated to a temperature slightly higher than the glass transition temperature of PEI (e.g., at least 1°C higher than the glass transition temperature, at least about 2°C higher than the glass transition temperature, at least about 3°C ​​higher than the glass transition temperature, at least about 4°C higher than the glass transition temperature, at least about 5°C higher than the glass transition temperature; including a temperature of 65°C to 80°C, or 68°C to 78°C, or 70°C to 75°C, about 72°C or about 75°C). While the blend is vigorously stirred, an appropriate amount of alcohol is dripped in. The blend is continuously stirred while being cooled to room temperature. The room temperature solution is then stirred for another 24 hours.

[0127] The composition containing PEI can have one or more than one bactericidal, virucidal and / or pathogenicidal properties, and if desired, the substrate can be used as an antimicrobial composition in accordance with the tests, substrates and / or methods described herein, in particular as a hand sanitizer. Thus, the present invention also provides a method for disinfecting a surface, comprising applying to the surface a composition comprising a polyethyleneimine-based polymer, an optional second cationic polymer (selected from polydiallyldialkylammonium salts, poly(acrylamide-co-diallyldialkylammonium halides), chitosan, or a combination thereof), an optional polyacid, an optional at least one adhesion promoter, and a carrier. In one aspect of the method, a composition comprising a non-chemically modified linear PEI, an optional polyacid, and a carrier comprising water and an alcohol is used as a hand sanitizer that is particularly effective against non-enveloped viruses.

[0128] Since linear PEI is sensitive to pH and temperature, specific techniques have been developed to produce a stable, completely clear, non-viscous hand sanitizer blend containing a linear PEI colloidal dispersion. In one specific example, the method for preparing a hand sanitizer composition comprises the following steps: at room temperature, vigorously stirring an appropriate amount of a linear PEI aqueous solution to produce a PEI dispersion. Under vigorous stirring, the PEI in the dispersion is then protonated with an appropriate acid to reach a pH of 6 and produce a clear liquid. Next, the clear liquid is heated to a temperature slightly higher than the glass transition temperature of PEI (e.g., at least 1°C higher than the glass transition temperature, at least about 2°C higher than the glass transition temperature, at least about 3°C ​​higher than the glass transition temperature, at least about 4°C higher than the glass transition temperature, at least about 5°C higher than the glass transition temperature; including a temperature of 65°C to 80°C, or 68°C to 78°C, or 70°C to 75°C, about 70°C, about 72°C, or about 74°C). Then, an appropriate amount of alcohol is dripped in to keep the temperature of the clear liquid at about 65°C. The clear hand sanitizer mixture is removed from heat to avoid evaporation of excess alcohol and then stirred while covered for several hours (e.g., at least 2 hours, at least 3 hours, at least 4 hours, or at least 5 hours).

[0129] The antimicrobial compositions of the present invention meet or exceed at least one of the following antimicrobial tests:

[0130] (i) Germicidal spray testing according to ASTM E1153, which meets EPA requirements for log3 reduction of viruses and log5 reduction of bacteria,

[0131] (ii) Suspension test according to ASTM E1052-96 (2002) or ASTM E2315 (2016),

[0132] (iii) a film formed from the composition according to the JIS Z 2801 (2006) test for antimicrobial activity, or a modified version of such test as described herein.

[0133] (iii-a) kills at least 95% of the log5 population of Gram-positive or Gram-negative bacteria within 30 minutes,

[0134] (iii-b) kills at least 95% of the log4 population of enveloped viruses within 30 minutes of contact,

[0135] (iii-c) kills at least 95% of non-enveloped viruses within 30 minutes of contact, and / or

[0136] (iii-d) kills at least 94% of the log4 population of Clostridium difficile bacteria within 24 hours of contact,

[0137] (iv) a film formed from the composition has a value of 2 or less according to the International Organization for Standardization (ISO) 10993-5 in vitro cytotoxicity test,

[0138] (v) a durability test selected from (va) a film formed from the composition kills at least 99.9% of Gram-positive and Gram-negative bacteria according to EPA Protocol #01-1A Residual Self-Disinfecting Activity Test, or (vb) a film formed from the composition kills at least 95% of Gram-positive and Gram-negative bacteria, or enveloped and non-enveloped viruses, after waiting 7 days after film formation according to a modified version of Protocol #01-1A Residual Self-Disinfecting Activity Test as described herein.

[0139] Test (i) refers to ASTM E1153, the entire contents of which are incorporated by reference, which is a germicidal spray test used to evaluate the antimicrobial efficacy of one-step cleaning sanitizer formulations for lightly soiled, inanimate, non-porous, non-food contact surfaces (i.e., "kill immediately" claim). In ASTM E1153 (most recent revision in 2014), the antimicrobial efficacy of sanitizers is tested against Staphylococcus aureus, Klebsiella pneumoniae, Enterobacter aerogenes, or a combination thereof, on pre-cleaned, inanimate, hard, non-porous, non-food contact surfaces.

[0140] The results of the germicidal spray test of the miscible blend formulations of the present invention are listed in Table 3 and compared with three commercially available products. Two cationic polymer compositions were used to perform MS2, MRSA and E. coli germicidal spray tests. Composition A is a miscible blend comprising 3000ppm of non-chemically modified linear PEI, 3000ppm of polyDADMAC, 25ppm of carboxylated branched PEI, 35% ethanol and the balance of water. Composition B is a miscible blend comprising 200ppm of non-chemically modified linear PEI, 200ppm of polyDADMAC, 25ppm of carboxylated branched PEI, 70% ethanol and the balance of water (operating pH is about 7.6).

[0141] Table 3

[0142]

[0143] The results in Table 3 show that Composition B contains 400 ppm of cationic polymer and passes the MS2 germicidal spray test within 5 minutes of contact, which is noteworthy because the EPA's maximum ppm standard for quaternary ammonium compounds according to ASTM E1153 is 400 ppm. In addition, the antimicrobial efficacy of some quaternary ammonium compounds is significantly reduced by soil or organic loading. As shown in Table 3, Composition B is also very effective against MRSA and E. coli spray tests (ASTM E1153) in the presence of 5% soil loading.

[0144] Test (ii) is a suspension test according to ASTM E1052-96 (2002) or ASTM E2315 (2016) for determining the effectiveness of an antimicrobial solution in the form of a suspension against specific viruses such as adenovirus, coronavirus, influenza virus, rhinovirus and rotavirus. An aliquot of the test substance is inoculated with the test virus and maintained for the desired exposure time. At each predetermined exposure time, an aliquot is removed, neutralized by serial dilution, and the viral infectivity is determined by an assay specific for the test virus. Appropriate viral, test substance cytotoxicity and neutralization controls are performed simultaneously. The percentage and log reduction of viral infectivity are calculated compared to the corresponding viral control. ASTM E1052-96 (2002) and ASTM E2315 (2016) are most suitable for antimicrobial compositions in the form of suspensions, such as hand sanitizer compositions.

[0145] For test (iii), the ability of the film formed by the antimicrobial composition to kill Gram-positive and Gram-negative bacteria and enveloped viruses, non-enveloped viruses and / or Clostridium difficile can be tested according to the conditions set forth in JIS Z 2801 (2006 edition, updated in 2010), which is known as the Japanese Industrial Standard Test for Antimicrobial Activity and Efficacy of Antimicrobial Products, the entire contents of which are incorporated herein by reference. In particular, according to JIS Z 2801 (2006) or a modified version thereof as described herein, the film formed by the antimicrobial composition of the present invention: (iii-a) kills at least 95% of the log5 population of Gram-positive or Gram-negative bacteria within 30 minutes, (iii-b) kills at least 95% of the log4 population of enveloped viruses within 30 minutes of contact, (iii-c) kills at least 95% of the non-enveloped viruses within 30 minutes of contact, and / or (iii-d) kills at least 94% of the log4 population of Clostridium difficile within 24 hours of contact. In preferred embodiments, the film formed from the antimicrobial composition of the present invention meets two or more, three or more, or all four of requirements (iii-a) to (iii-d).

[0146] For example, under the conditions of this test, the JIS Z 2801 protocol showed a log 4 reduction of E. coli on a membrane containing polyDADMAC alone after 30 minutes against a log 5 challenge (Table 4).

[0147] Table 4

[0148]

[0149] *cfu / sample – colony forming units per recovered sample

[0150] The same membranes showed a log 4 reduction of MRSA after 10 minutes, but with a log 7 challenge (Table 5).

[0151] Table 5

[0152]

[0153] *cfu / sample – colony forming units per recovered sample

[0154] An additional self-disinfecting ("subsequent kill") test was designed for residual self-disinfecting films, which was considered more practical for practical applications, particularly when testing antiviral activity. This test is based on the assumption that in realistic applications, residual self-disinfecting films of antimicrobial activity will not be covered. The test improves JIS Z 2801 (2006 edition, which was updated in 2010) by not requiring covering of the inoculated film and starting the test time after the inoculum has dried. The test results obtained using the modified JIS Z 2801 are listed in Table 6 for determining cell lysis of MS2 on films formed from a non-toxic miscible blend of 3000 ppm non-chemically modified linear PEI, 3000 ppm poly-DADMAC, 79% ethanol, 25 ppm carboxylated branched PEI, the balance being water. "Subsequent kill" data for Gram-positive and Gram-negative bacteria were obtained using the standard JIS test.

[0155] Table 6

[0156]

[0157] In addition, the test can be performed under light conditions and the sample surface area can be increased from 1600 mm 2 Increased to 2500mm 2 To improve JIS Z 2801 (2006 edition, updated in 2010) when testing for Clostridium difficile.

[0158] Test (iv) relates to ISO 10993-5 (last updated in 2009), the entire contents of which are incorporated by reference, wherein the in vitro cytotoxicity of medical device materials is tested. The method involves incubating cultured cells in contact with the device and / or extracts of the device, either directly or by diffusion. In particular, test articles, positive controls and negative controls are extracted according to the ISO 10993-12 method. The original extract is serially diluted and tested using 5 concentrations. L-929 cells (mouse, C3H / An, connective tissue) are treated with sample extracts, reagent controls and negative controls or positive controls. Three copies of each treatment are prepared. The cells are incubated for 24 hours and the cytotoxic effects are observed under a microscope. The culture is observed under a microscope and the reactivity is assessed using a 0 to 4 scale ("4" means severe cytotoxicity; "3" means moderate cytotoxicity; "2" means mild cytotoxicity; "1" means microcytotoxicity; "0" means no cytotoxicity). When the result is less than or equal to grade 2 (i.e., 0, 1 or 2), the test article meets the test requirements.

[0159] As described herein, the residual self-disinfecting film formed from PECs, miscible blends or cationic polymers alone is non-leaching and therefore passes the ISO 10993-5 (2009 edition) in vitro cytotoxicity test with a score of 0, as shown in the test results below in Table 7.

[0160] Table 7

[0161]

[0162] Test (v) involves Protocol #01-1A, commonly referred to as the "Clorox Test," which is an EPA-approved method for determining long-term disinfection claims (i.e., "follow-up kill" durability claims). Protocol #01-1A (the entire contents of which are incorporated by reference) determines the residual self-disinfecting activity of dry chemical residues (films) on inanimate, hard, non-porous surfaces against only the following bacteria: Staphylococcus aureus, Klebsiella pneumoniae, and / or Enterobacter aerogenes. Specifically, the surface is inoculated, treated with the test product, allowed to dry, and then scraped under alternating wet and dry conditions, interspersed with several re-inoculations. At the end of the study and at least 24 hours later, the ability of the test surface to kill 99.9% of microorganisms in 5 minutes is determined. In order to pass this test, the film formed by the composition must maintain antimicrobial efficacy between and after 12 alternating wet and dry rubs with a weighted fabric.

[0163] Can use EPA durability test, i.e. the improved version of scheme #01-1A.Think that the modified scheme is more suitable for assessing the residual self-disinfecting film formed by antimicrobial composition of the present invention, because scheme #01-1A is designed to rely on the product that kills microorganisms and chemical can be exhausted over time by releasing sterilizing chemicals from film.Antimicrobial composition of the present invention does not need sterilizing chemicals, but comprises charged cationic polymer, and its killing mechanism is considered not to be exhausted over time.The improved test comprises the weight and cycle time using EPA#01-1A scheme, and the film is rubbed three times (once dry, once wet, once dry) every day.Compared with the single 24-hour measurement of standard scheme #01-1A, this improved test captures the antimicrobial efficacy of antimicrobial composition in a few days. Passing this modified test requires that after 4 to 7 days, the polymer-based film will continue to exhibit 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%) reduction in Gram-positive bacteria, Gram-negative bacteria, enveloped viruses and / or non-enveloped viruses on a glass or stainless steel substrate.

[0164] The present invention also provides a method for killing microorganisms on a surface, comprising applying an antimicrobial composition to the surface, the antimicrobial composition comprising a cationic polymer (alone or encapsulated in a PEC), at least one adhesion promoter (e.g., titanate, carboxylated branched PEI), optionally organic particles and / or inorganic particles having photocatalytic activity under visible light, and a carrier, each of these components 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 "application" refers to any suitable technique for transferring the antimicrobial composition to a surface. For example, the technique for application may be, but is not limited to, brushing, rolling, spraying, wiping, mopping, pouring, painting, absorbing, adsorbing, absorbing, soaking, impregnating, penetrating, impregnating, and combinations of these methods.

[0165] Also provided is a method for killing microorganisms on a surface (e.g., disinfecting the surface, providing a residual self-disinfecting film, or both), comprising applying to the surface an antimicrobial composition comprising a high molecular weight (preferably ultra-high molecular weight) polydiallyldimethylammonium salt (e.g., polydiallyldimethylammonium halide) and a carrier as described herein. The antimicrobial composition of this embodiment may also include (i) a polyethyleneimine-based polymer, chitosan, or a combination thereof, and / or (ii) anionic polymers, and / or (iii) organic and / or inorganic particles having photocatalytic activity under 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.

[0166] As described herein, after being applied to the surface, the carrier in the composition evaporates, thereby leaving an antimicrobial residual self-disinfecting film on the surface. The antimicrobial residual self-disinfecting film makes the surface have a bactericidal, virucidal and / or germicidal effect. As used herein, the term "making the surface have a bactericidal, virucidal and / or germicidal effect" refers to reducing the presence of bacteria, viruses and / or germs (including fungi, such as Aspergillus brasiliensis) (e.g., eliminating, killing or preventing and / or inhibiting growth) to any suitable extent. As used herein, the term "any suitable extent" refers to reducing by 50% or more, including reducing by 60% or more, reducing by 70% or more, reducing by 80% or more, reducing by 90% or more, reducing by 92% or more, reducing by 94% or more, reducing by 95% or more, reducing by 97% or more, reducing by 98% or more, reducing by 99% or more, or eliminating by 99.5% or more.

[0167] According to this embodiment, the present invention provides a coated surface comprising a surface (e.g., a surface of a substrate) and an antimicrobial residual self-disinfecting film as described herein applied to the surface. 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 bound to the surface (e.g., the surface of the substrate).

[0168] The surface with bactericidal, virucidal, and / or germicidal effect can be any suitable material, including biocompatible materials. The surface can be used in any suitable form or derived from any suitable form, such as powder, dust, aggregate, amorphous solid, sheet, fiber, tube, fabric, etc. In an embodiment, the surface includes metal, glass, glass fiber, silica, sand, wood, fiber, natural polymer, synthetic polymer, plastic, rubber, ceramic, porcelain, stone, marble, cement, human or animal body (such as skin), or any hybrid, alloy, copolymer, blend, or combination thereof.

[0169] Metal surfaces suitable for use in the present invention include, for example, stainless steel, nickel, titanium, tantalum, aluminum, copper, gold, silver, platinum, zinc, nickel titanium alloy (Nitinol), alloys of nickel, chromium and iron (INCONEL TM , Special Metals Company, Elkhart, Indiana, USA), iridium, tungsten, silicon, magnesium, tin, galvanized steel, hot-dip galvanized steel, electrogalvanized steel, annealed hot-dip galvanized steel, alloys of any of the foregoing metals, coatings containing any of the foregoing metals, and combinations thereof.

[0170] Glass surfaces suitable 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.

[0171] Silica surfaces suitable for use in the present invention include, for example, quartz, fused quartz, crystalline silica, fumed silica, silica gel, silica aerogel, and mixtures thereof.

[0172] Sand surfaces suitable for use in the present invention include, for example, sand composed of silicon dioxide (e.g., quartz), sand composed of calcium carbonate (e.g., aragonite), and mixtures thereof. Sand may contain other components, such as minerals (e.g., magnetite, chlorite, glauconite, gypsum, olivine, garnet), metals (e.g., iron), shells, corals, limestone, and / or rocks.

[0173] Suitable wood surfaces include, for example, hardwoods and softwoods, and materials made from wood, wood chips or fibers (e.g., plywood, oriented strand board, laminated veneer, composites, lumber, particle board, 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.

[0174] Fiber surfaces suitable 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, silk, spider silk, sinew, gut, wool, sea silk, yarn, mohair, angora goat wool, and asbestos. Suitable synthetic fibers include man-made fibers (e.g., lyocell fibers), modal and metal fibers (e.g., copper, gold, silver, nickel, aluminum, iron), carbon fibers, silicon carbide fibers, bamboo fibers, seaweed fibers, nylon, polyester, polyvinyl chloride fibers (e.g., vinion), polyolefin fibers (e.g., polyethylene, polypropylene), acrylic polyester fibers, aramids (e.g., Twaron fibers), and polyurethane fibers. TM 、KEVLAR TM or NOMEX TM), spandex, and combinations thereof.

[0175] Natural polymer surfaces suitable for use in the present invention include, for example, polysaccharides (eg, cotton, cellulose), shellac, amber, wool, silk, natural rubber, biopolymers (eg, proteins, extracellular matrix components, collagen), and combinations thereof.

[0176] Synthetic polymer surfaces suitable for use in the present invention include, for example, polyvinyl pyrrolidone, acrylic resins, acrylonitrile-butadiene-styrene copolymers, polyacrylonitrile, acetals, polyphenylene oxides, polyimides, polystyrene, polypropylene, polyethylene, polytetrafluoroethylene, polyvinylidene fluoride, polyvinyl chloride, polyethyleneimine, polyesters, polyethers, polyamides, polyorthoesters, polyanhydrides, polysulfones, polyethersulfones, polycaprolactones, polybutylhydroxyvalerate, polylactones, polyurethanes, polycarbonates, polyethylene terephthalate, and copolymers and combinations thereof.

[0177] 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.

[0178] Ceramic surfaces suitable for use in the present invention include, for example, boron nitride, silicon nitride, aluminum oxide, silicon dioxide, and combinations thereof.

[0179] Stone surfaces suitable for use in the present invention include, for example, bauxite, calcite, feldspar, gypsum, slate, granite, quartz, quartzite, limestone, dolomite, sandstone, marble, soapstone, serpentine, and combinations thereof.

[0180] For purposes of the present invention, the animal body includes, but is not limited to, rodents (such as mice), lagomorphs (such as rabbits), carnivores (e.g., felines (cats) and canines (dogs)), even-toed ungulates (such as cattle and pigs), odd-toed ungulates (such as horses), primates, platyrrhines or anthropoids (such as monkeys), aves (such as birds), arthropods (such as insects), fishes (such as fish), or simians (such as humans and apes). Typically, the skin (including intact skin, injured or broken skin, and / or other skin damaged by, for example, burns) and / or mucosal tissue (e.g., oral, nasal, ocular or genital tissue) of the animal body serves as a surface suitable for applying the antimicrobial composition. The skin and / or mucosal tissue can be associated with any part of the animal body, including limbs, tail, abdomen, chest, head, neck, face, genital area (e.g., breasts), buttocks, or back. Generally, the types and amounts of components of the antimicrobial composition will be selected to ensure biocompatibility, minimize toxicity, minimize irritation, and / or achieve a desired level of surface tack and / or adhesion of the resulting film.

[0181] A surface is typically a component of a larger structure. For example, a surface can be part of a substrate such as a medical device, diagnostic equipment, implant, glove, mask, curtain, mattress, sheet, blanket, gauze, dressing, tissue, surgical drape, tubing, surgical instrument, safety device, fabric, clothing item, floor, handle, wall, sink, shower or bathtub, toilet, furniture, wall switch, toy, sports equipment, playground equipment, shopping cart, countertop, appliance, railing, door, air filter, tube, utensil, plate, cup, container, object display container, food, food display container, food packaging, food processing equipment, food handling equipment, food transportation equipment, food vending equipment, food storage equipment, food packaging equipment, plant, phone, cell phone, remote control, computer, mouse, keyboard, touch screen, leather, cosmetics, cosmetics making equipment, cosmetics storage equipment, cosmetics packaging equipment, personal care products, personal care products manufacturing equipment, personal care storage equipment, personal care packaging equipment, animal care products, animal care product manufacturing equipment, veterinary equipment, powders, creams, gels, ointments, eye care products, eye care product manufacturing equipment, contact lenses, glasses, eye care product storage equipment, contact lens cases, jewelry, jewelry manufacturing equipment, jewelry storage equipment, animal housing, agricultural equipment, animal food handling equipment, animal food storage space, animal food storage equipment, animal food containers, aircraft, land vehicles, air handling equipment, air filters, water vehicles, water storage space, water storage equipment, water treatment equipment, water storage containers, water filters, hands, hair, feet, legs, arms, torso, head, or animal body parts, pharmaceutical display containers, pharmaceutical packaging, pharmaceutical processing equipment, pharmaceutical handling equipment, pharmaceutical transportation equipment, pharmaceutical vending equipment, pharmaceuticals, pharmaceutical storage equipment, pharmaceutical packaging equipment.

[0182] "Medical device" includes any device having a surface that contacts tissue, blood or other body fluids during use or operation, the tissue, blood or other body fluids being present in a mammal (e.g., a human) or subsequently used in a mammal (e.g., a human). Medical devices include, for example, extracorporeal devices for surgical operations, such as blood oxygenators, blood pumps, blood storage bags, blood collection tubes, blood filters including filter media, dialysis membranes, pipes for transporting blood, etc., which contact blood and then return blood to the patient or mammal. Medical devices also include endoprostheses implanted in mammals (e.g., humans), such as vascular grafts, stents, pacing electrodes, surgical prosthetic catheters, heart valves, etc. implanted in blood vessels or hearts. Medical devices also include devices for temporary intravascular use, such as catheters, guidewires, amniocentesis and biopsy needles, cannulas, drainage tubes, shunts, sensors, transducers, probes, etc. placed in blood vessels, hearts, organs or tissues for monitoring, repair or treatment. Medical devices also include prostheses, such as artificial joints such as artificial hips or knees and artificial hearts. Additionally, medical devices include penile implants, condoms, tampons, sanitary napkins, ophthalmic lenses, sling materials, sutures, hemostatic agents used in surgery, antimicrobial materials, surgical mesh fabrics, transdermal patches, and wound dressings / bandages.

[0183] "Diagnostic equipment" includes any device or tool used to diagnose or monitor a medical condition. Examples include ultrasound, magnetic resonance imaging (MRI) machines, positron emission tomography (PET) scanners, computed tomography (CT) scanners, ventilators, heart-lung machines, extracorporeal membrane oxygenation (ECMO) machines, dialysis machines, sphygmomanometers, otoscopes, ophthalmoscopes, stethoscopes, sphygmomanometers, blood pressure cuffs, electrocardiographs, thermometers, defibrillators, specula, sigmoidoscopes, and anoscopes.

[0184] "Surgical instruments" include any tool or device used to perform a surgical procedure or procedure. Examples include scalpels, lancets, trocars, hemostats, graspers, forceps, clamps, retractors, spreaders, positioners, tracheostomies, dilators, staplers, irrigation needles, injection needles, drills, scopes, endoscopes, probes, rulers, and calipers.

[0185] "Safety equipment" includes equipment used to protect a person, animal or object. Examples of "safety equipment" are masks, face shields, visors, goggles, glasses, gloves, overshoes, toe guards, gaiters, belts, overalls, aprons, coats, vests, rain gear, hats, helmets, chin rests, hair nets, shower caps, hearing protection (ear plugs, earmuffs, hearing belts), respirators, gas masks, hoods, collars, belts and first aid kits.

[0186] "Fabric" includes any type of suitable fabric, such as bedding, curtains, towels, tablecloths, protective sheets and dishcloths.

[0187] "Apparel articles" include clothing, footwear, or other items worn on his or her person. Examples include uniforms, coats, shirts, pants, high boots for wading, surgical gowns, socks, shoe or boot liners, insoles, gloves, hats, shoes, boots, and sandals.

[0188] A surface can be an item that is part of or may be present in a building structure, such as a floor, wall, appliance (e.g., refrigerator, oven, stove, dishwasher, washer, dryer, furnace, water heater, air conditioner, heater), sink, shower or bathtub, toilet, furniture (e.g., mattress, couch, sofa, chair, table, shelf, mantle, bed, dresser), countertop, railing, air filter, air handling unit, water handling unit, water filter, pipe, door, handle, light, light switch, thermostat, sprinkler, air conditioner evaporator and / or condenser.

[0189] The surface can also be a toy or sports equipment, including gym equipment, playground equipment or a swimming pool.

[0190] The surface can be a utensil (e.g., knife, fork, spoon, ladle, spatula, whisk, etc.), a dish (e.g., food storage container, food serving piece, etc.), food packaging (e.g., bag, box, foil, plastic wrap), or other item that comes into contact with food (e.g., cutting board, food display container, food processing equipment, food handling equipment, food transport equipment, food vending equipment, animal food handling equipment, animal food storage space, food storage equipment, animal food container, animal food storage equipment). The surface can be part of food processing equipment, such as a food processing tank, blender, conveyor belt, knife, grinder, packaging machine, labeling machine, etc.

[0191] "Food" is any food that is desired to be provided with an antimicrobial residual self-disinfecting film. In such an embodiment, the antimicrobial residual self-disinfecting film and its composition should be non-toxic to human and animal consumption. "Food" can be, for example, any fruit, vegetable, meat or egg.

[0192] "Plant" is any suitable plant, including angiosperms (flowering plants), gymnosperms (plants that produce seeds), conifers, ferns and bryophytes. Suitable angiosperms are from Amborella trichopoda Baill (e.g., Amborella trichopoda Baill), Nymphaeales (e.g., Water Lily), Magnoliasales (e.g., Illicium verum), Chrysanthemiales (e.g., from Ascaris, Chrysanthemi, Snow Scented Orchid, or Nine-section Tea), Magnolias (e.g., Magnolia, Laurel, Black Pepper), Monocots (e.g., Gramineae, Orchids, Palms), Dermatophytes (e.g., Aquatic Plants), or True Dicots (e.g., Sunflower, Petunia, Apple). Suitable gymnosperms are from Cycadidae, Ginkgo, Gnetidae or Pinidae.

[0193] The surface can be part of an electronic device such as a phone, cell phone, remote control, computer, mouse, keyboard and touch screen.

[0194] The surface can also be part of a cosmetic product (e.g., eye shadow, eyeliner, primer, foundation, lipstick, lip gloss, blush), cosmetics manufacturing equipment, cosmetics storage equipment, cosmetics packaging equipment, personal care products (e.g., creams, gels, ointments, lip balms, body wash, facial cleansers, lotions, colognes, perfumes, antiperspirants, deodorants, facial tissues, cotton swabs, cotton pads, mouthwash, toothpaste, nail polish, shampoo, conditioner, hair spray, talcum powder, shaving cream, contact lenses, contact lens cases, glasses), personal care product manufacturing equipment, personal care storage equipment, personal care packaging equipment, jewelry (e.g., necklaces, rings, earrings, bracelets, watches), jewelry making equipment, or jewelry storage equipment.

[0195] "Animal care products" and "veterinary equipment" can be any product used in an environment including animals, such as a house, a storage place or a veterinary hospital. Of course, veterinary equipment can be used in places outside a hospital environment. Animals are any animals that are usually regarded as pets, non-pets and wild animals provided with board and lodging by a veterinarian. Examples include dogs, cats, reptiles, birds, rabbits, ferrets, guinea pigs, hamsters, rats, mice, fish, turtles, horses, goats, cattle and pigs. Suitable animal care products include individual care products, toys, beds, baskets, doghouses, brackets, bowls, dishes, belts, collars, small boxes and combing products (for example, pliers, scissors, brushes, combs, knot untanglers and depilatory tools) as described herein. Suitable veterinary equipment includes any medical device and surgical instrument as described herein and other equipment, such as tables, bathtubs, stretchers, sinks, scales, cages, brackets and belts.

[0196] "Animal housing" may be any suitable housing, such as a coop, stable, shelter, grab bag shelter, hut, barn, shed, pen, nest box, feeder, stand, cage, rack or bed.

[0197] "Agricultural equipment" is any device used in an agricultural setting, including a farm or ranch, particularly a farm or ranch where animals are raised, processed, or both. Animal livestock that can be raised or processed as described herein 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, peacocks, emus), pigs, sheep, goats, alpacas, llamas, deer, donkeys, rabbits, and fish. Examples of agricultural equipment include trucks, trailers, carts, barns, sheds, fences, sprinklers, shovels, scrapers, slings, ropes, restraints, feeders, waterers, troughs, water filters, water treatment equipment, tanks, fountains, buckets, pails, hay racks, scales, poultry flooring, egg handling equipment, barn curtains, tractors, seed drills, planters, plows, rotators, tillers, spreaders, sprayers, mixers, sorters, balers, harvesters, cotton pickers, threshers, mowers, backhoe loaders, squeeze chutes, hydraulic chutes, head chutes, sluice gates, milking tubs, corral basins, troughs, calving pens, calving stalls, and milking machines.

[0198] The surface can be part of a vehicle, such as an aircraft, a land vehicle, or a water vehicle. Suitable vehicles include cars, vans, trucks, buses, ambulances, recreational vehicles, campers, motorcycles, scooters, bicycles, wheelchairs, trains, trams, ships, boats, canoes, submarines, unmanned underwater vehicles (UUVs), personal watercrafts, airplanes, jets, helicopters, unmanned autonomous vehicles (UAVs), and hot air balloons.

[0199] Because the residual self-disinfecting film of antimicrobial is not usually covalently bonded to the surface, the surface to which the residual self-disinfecting film of antimicrobial is applied can be regenerated by removing the residual self-disinfecting film of antimicrobial, if necessary. The removal step can be performed by any suitable method, such as washing or rinsing with a solvent (e.g., water and / or alcohol). Therefore, the antimicrobial coating on the surface (e.g., the surface of the substrate) described herein can be considered temporary (e.g., removable). In one embodiment, the residual self-disinfecting film of antimicrobial is water-soluble and can be removed with water (e.g., hot soapy water).

[0200] The antimicrobial residual self-disinfecting film allows the surface to have any suitable degree of bactericidal effect on any suitable bacteria. 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), killing 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 the bacteria in contact with the antimicrobial residual self-disinfecting film. For example, the bacterium can be, for example, Staphylococcus aureus, Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus saprophyticus, Pseudomonas aeruginosa, Listeria monocytogenes, Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Haemophilus influenzae, Helicobacter pylori, Salmonella, Shigella, Clostridium, Enterobacter aerogenes, Gram-negative Escherichia coli, Clostridium difficile, or a combination thereof. In some embodiments, the antimicrobial composition can be effective in reducing (e.g., eliminating, killing or preventing and / or inhibiting the growth of) Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), Gram-negative Escherichia coli (ATCC 8739), Clostridium difficile (ATCC 43598), or a combination thereof.

[0201] In one aspect of the invention, the antimicrobial residual self-disinfecting film formed by the antimicrobial composition described herein makes the surface bactericidal to Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). 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) within 30 minutes of contact (e.g., within 20 minutes, within 15 minutes, within 10 minutes, within 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) within 5 minutes of contact.

[0202] In another aspect of the invention, the antimicrobial residual self-disinfecting film formed by the antimicrobial composition described herein makes the surface bactericidal to Gram-negative Escherichia coli (ATCC 8739). 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) within 30 minutes of contact (e.g., within 20 minutes, within 15 minutes, within 10 minutes, within 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) within 5 minutes of contact.

[0203] In another aspect of the invention, the antimicrobial residual self-disinfecting film formed by the antimicrobial composition described herein makes the surface bactericidal to Clostridium difficile (ATCC 43598). 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) within 24 hours of contact (e.g., within 18 hours, within 12 hours, within 10 hours, within 8 hours, within 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) within 8 hours of contact.

[0204] Viruses are more difficult to kill, especially non-enveloped viruses, such as norovirus, rotavirus, adenovirus and poliovirus. In general, the only way to kill a large number of non-enveloped viruses is to use a large amount of very irritating chemicals, such as hypochlorite, acid and peroxide, all of which have very high cytotoxicity. It is worth noting that the technology described in the present invention can form an antimicrobial residual self-disinfecting film that kills non-enveloped viruses. Therefore, the present invention provides an antimicrobial residual self-disinfecting film formed by an antimicrobial composition as described herein, which makes the surface have any suitable degree of virucidal effect on any suitable virus, for example, reducing (for example, eliminating, killing or preventing and / or inhibiting growth) at least 75% (for example, 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 the virus. In one embodiment, the antimicrobial residual self-disinfecting film formed by the antimicrobial composition described herein renders the surface virucidal to at least one enveloped virus (e.g., varicella virus, influenza virus, herpes simplex virus, severe acute respiratory syndrome (SARS) virus, flavivirus, togavirus) and / or non-enveloped virus (e.g., smooth bacteriophage, norovirus, rotavirus, adenovirus, parvovirus, and poliovirus).

[0205] In another aspect of the invention, the antimicrobial residual self-disinfecting film formed by the antimicrobial composition described herein makes the surface have a virucidal effect on 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, within 30 minutes, within 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.

[0206] In another aspect of the invention, the antimicrobial residual self-disinfecting film renders the surface virucidal to non-enveloped viruses, such as smooth bacteriophages (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, within 15 minutes, within 10 minutes, within 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 cases of this embodiment, the non-enveloped virus is MS2 (ATCC 15597-B1).

[0207] One embodiment of the present invention relates to a treated filter medium comprising one or more than one insoluble cationic polymer as described herein coupled to a positively charged non-woven filter medium. The filter medium is suitable for filtering liquids (e.g., water) and air, for example, and can be made of any suitable material, such as alumina (Al2O3), polyester (e.g., PET), polyethylene, polypropylene, polyamide (e.g., nylon 6,6), polyimide, polyacrylic acid, glass, metal, dextran, cellulose, jute, wood pulp, cotton, or a combination thereof (e.g., microglass fibers and / or cellulose coated with nano-alumina fibers). If the natural form of the material is not positively charged, the material can be modified as desired, such as by adding one or more than one quaternary ammonium groups, thereby providing the necessary positive charge. The non-woven filter medium can be purchased commercially and can be prepared by any suitable method (e.g., wet-laid, air-laid, dry-laid, melt-blown, spunbonded, nanofiber web spinning, and continuous stretch fiberization). See, for example, Argonide (Sanford, FL), Pall Corporation (Port Washington, NY), GE Infrastructure Water and Process Technologies (Trevose, PA), and Meissner Filtration Products (Camarillo, CA). Adhesion promoters as described herein may be used as coupling agents. Embodiments in which the adhesion promoter is a cationic such as a branched, carboxylated PEI are preferred.

[0208] Most filter media reduce pathogenic microorganisms by simple size screening, but such filters require high pressure to effectively screen materials (e.g., fluids), are susceptible to fouling, and require frequent maintenance. As described herein, treated filters that are positively charged and coupled to one or more insoluble cationic polymers can effectively kill microorganisms with reduced pressure and / or less fouling. Figure 2A shows the small pore size of a filter comprising 5 μm glass that is not positively charged. Figure 2 B shows a filter comprising positively charged alumina and having a larger pore size. However, due to the coupling of a cationic polymer (e.g., insoluble polyDADMAC, linear PEI) to the alumina, the filter acts similarly to Figure 2 A is a micro glass filter with a smaller pore size.

[0209] In one example of a treated water filter, polyDADMAC that has been rendered insoluble (e.g., by replacing a portion of the chloride counterions with fluoride) is coupled to a positively charged non-woven filter Al2O3 media with a branched carboxylated PEI. The resulting treated filter media has a very high positive zeta value. In another example, a treated air filter is made by coupling a linear PEI to a positively charged non-woven filter Al2O3 media using an adhesion promoter (e.g., a branched carboxylated PEI).

[0210] When tested, a highly contaminated (log 7) metal working fluid passed through a treated filter as described herein reduced microorganisms, including non-enveloped viruses, by 99.9%.

[0211] The present invention is further illustrated by the following embodiments.

[0212] (1) An antimicrobial composition comprising: (a) a cationic polymer, (b) at least one adhesion promoter, (c) optionally organic and / or inorganic particles having photocatalytic activity under visible light, and (d) a carrier, wherein the components of the composition are not covalently bound to each other and the antimicrobial composition meets one or more of the following tests: (i) a germicidal spray test according to the American Society for Testing and Materials (ASTM) International Method E1153, which meets the EPA requirements for log3 reduction of viruses and log5 reduction of bacteria; (ii) a suspension test according to ASTM International Method E1052-96 (2002) or ASTM International Method E2315 (2016); (iii) a film formed from the composition according to the Japanese Industrial Standard (JIS) Z2801 (2006) test for antimicrobial activity or a modified version of such a test as described herein, (iii-a) kills at least 95% of Gram-positive or Gram-negative bacteria within 30 minutes. The invention relates to a method for preparing a film of the present invention to provide a film having a log5 population of at least 99.9% of gram-negative bacteria, (iii-b) kills at least 95% of the log4 population of enveloped viruses within 30 minutes of contact, (iii-c) kills at least 95% of non-enveloped viruses within 30 minutes of contact, and (iii-d) kills at least 94% of the log4 population of Clostridium difficile within 24 hours of contact; (iv) a film formed from the composition has a value of 2 or less according to the International Organization for Standardization (ISO) 10993-5 in vitro cytotoxicity test; and (v) a durability test selected from (va) according to the Environmental Protection Agency (EPA) protocol #01-1A residual self-disinfecting activity test, the film formed from the composition kills at least 99.9% of gram-positive bacteria and gram-negative bacteria, or (vb) according to a modified version of the protocol #01-1A residual self-disinfecting activation test as described herein, after waiting 7 days after film formation, the film formed from the composition kills at least 95% of gram-positive bacteria and gram-negative bacteria, or enveloped viruses and non-enveloped viruses.

[0213] (2) An antimicrobial composition according to embodiment (1), wherein the cationic polymer is a polydiallyldialkylammonium salt, an acryloxyalkyltrialkylammonium salt, a vinylphenylalkyltrialkylammonium salt, an acrylamidoalkyltrialkylammonium salt, a poly(acrylamide-co-diallyldialkylammonium salt), a polyethyleneimine-based polymer, chitosan optionally used in combination with an anionic polymer, or a combination thereof.

[0214] (3) The antimicrobial composition according to embodiment (2), wherein the polydiallyldialkylammonium salt is polydiallyldimethylammonium halide, and the halide ion is a chloride ion, a fluoride ion, a chloride-containing anion, a fluoride-containing anion, or a combination thereof.

[0215] (4) The antimicrobial composition according to any one of embodiments (1) to (3), wherein the cationic polymer is a non-chemically modified linear polyethyleneimine (PEI).

[0216] (5) An 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, and polymers comprising at least one of acyl groups, carboxylic acid groups or carboxylic acid derivatives, and combinations thereof.

[0217] (6) An antimicrobial composition according to any one of embodiments (1) to (5), wherein the organic particles and / or inorganic particles having photocatalytic activity under 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.

[0218] (7) The antimicrobial composition according to any one of embodiments (1) to (6), wherein the organic particles and / or inorganic particles having photocatalytic activity under visible light are W-doped and N-doped TiO2 particles that are hydrolyzed under ultraviolet (UV).

[0219] (8) The antimicrobial composition according to any one of embodiments (1) to (7), wherein the antimicrobial composition does not contain a small molecule compound that kills pathogens.

[0220] (9) The antimicrobial composition according to any one of embodiments (1) to (7), wherein the antimicrobial composition further comprises at least one bactericide.

[0221] (10) The antimicrobial composition according to any one of embodiments (1) to (9), wherein the antimicrobial composition further comprises one or more than one non-electrolyte polymers.

[0222] (11) The antimicrobial composition according to embodiment (10), wherein the one or more than one non-electrolyte polymers include polyacrylamide.

[0223] (12) An antimicrobial composition comprising a polyethyleneimine-based polymer, an optional second cationic polymer (selected from polydiallyldialkylammonium salts, poly(acrylamide-co-diallyldialkylammonium halides), chitosan, or a combination thereof), an optional polyacid, an optional at least one adhesion promoter, and a carrier.

[0224] (13) The antimicrobial composition according to embodiment (12), wherein the polyethyleneimine-based polymer is linear PEI.

[0225] (14) An antimicrobial composition according to embodiment (12) or (13), wherein the composition comprises non-chemically modified linear PEI, polydiallyldimethylammonium chloride (polyDADMAC), optionally citric acid, carboxylated branched PEI and a water-alcohol carrier.

[0226] (15) The antimicrobial composition according to any one of embodiments (12) to (14), wherein the composition comprises citric acid.

[0227] (16) An antimicrobial composition comprising at least one organic particle and / or inorganic particle having photocatalytic activity under visible light, at least one adhesion promoter, and a carrier, wherein a film formed from the antimicrobial composition kills microorganisms under conditions of, wherein JIS Z2801 is modified by not requiring the inoculated film to be covered and starting the test time after the inoculum has dried.

[0228] (17) A method for killing microorganisms on a surface, comprising applying the antimicrobial composition of any one of embodiments (1) to (16) to the surface.

[0229] (18) The method according to embodiment (17), wherein the carrier evaporates to leave a residual self-disinfecting film on the surface.

[0230] (19) A method according to embodiment (18), wherein the residual self-disinfecting film renders the surface bactericidal, virucidal and / or germicidal.

[0231] (20) The method according to embodiment (18) or (19), wherein the residual self-disinfecting film kills one or more of the following: (i) at least 95% of the log5 population of methicillin-resistant Staphylococcus aureus (MRSA) within 30 minutes of contact; (ii) at least 95% of the log5 population of group Gram-negative Escherichia coli (ATCC 8739) within 30 minutes of contact; (iii) at least 95% of the log4 population of influenza A (H1N1) (ATCC CCL-34) enveloped viruses 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) within 24 hours of contact.

[0232] (21) The method according to embodiment (20), wherein the non-enveloped virus is MS2 (ATCC 15597-B1).

[0233] (22) A method of killing microorganisms on a surface, comprising applying to the surface an antimicrobial composition comprising a high molecular weight polydiallyldialkylammonium salt and a carrier.

[0234] (23) The method according to embodiment (22), wherein the antimicrobial composition further comprises a polyethyleneimine-based polymer, chitosan, or a combination thereof.

[0235] (24) The method according to embodiment (22) or (23), wherein the antimicrobial composition further comprises organic particles and / or inorganic particles having photocatalytic activity under visible light.

[0236] (25) The method according to any one of embodiments (22) to (24), wherein the antimicrobial composition does not contain small molecule pathogenicidal compounds.

[0237] (26) The method according to any one of embodiments (22) to (25), wherein the carrier evaporates to leave a residual self-disinfecting film on the surface.

[0238] (27) A method according to embodiment (26), wherein the residual self-disinfecting film kills one or more of the following: (i) kills at least 95% of the log5 population of methicillin-resistant Staphylococcus aureus (MRSA) within 30 minutes of contact; (ii) kills at least 95% of the log5 bacterial population of Gram-negative Escherichia coli (ATCC 8739) within 30 minutes of contact; (iii) kills at least 95% of the log4 population of influenza A (H1N1) (ATCC CCL-34) enveloped viruses within 60 minutes of contact; (iv) kills at least 95% of non-enveloped viruses within 30 minutes of contact; and / or (v) kills at least 75% of the log4 population of Clostridium difficile (ATCC 43598) within 24 hours of contact.

[0239] The following examples further illustrate the invention but, of course, should not be construed as limiting its scope in any way.

[0240] Example

[0241] The antimicrobial compositions of the following examples are prepared according to the following general procedure: (1) preparing a highly diluted mixture of one or more cationic polymers, (2) adding photocatalyst particles as a weight percentage based on cationic monomer (% wbcm), (3) preparing a highly diluted mixture of one or more anionic polymers, (4) blending the diluted cationic polymer and the diluted anionic polymer to produce a PEC, (5) adding a titanate adhesion promoter as a weight percentage based on total monomer (% wbtm), if used, (6) condensing the cationic / anionic PEC (i.e., partially evaporating the solvent) to obtain the desired concentration for determining, for example, film thickness and film durability, and (7) further diluting the antimicrobial composition to effect the desired modification. Steps 2-7 are optional depending on the desired disinfectant composition and concentration.

[0242] Example 1

[0243] This example illustrates the preparation of an antimicrobial composition according to an embodiment of the present invention.

[0244] The components and their relative amounts used to form the polyDADMAC / PEI / PAAS PEC are tabulated and listed in Table 8. In addition to the calculated solution concentration (ppm), the amounts of the individual components are also listed.

[0245] Table 8

[0246]

[0247] The antimicrobial composition for producing PECs listed in Table 8 comprises two cationic polymers (i.e., polyDADMAC and PEI), an anionic polymer (PAAS), a titanate, TiO2 particles (photocatalyst), and water as a carrier. Alcohol is not required for the production of PECs. After the PECs are formed, a certain proportion of the water is replaced by alcohol. When the composition is used as a disinfectant spray, the alcohol helps to kill bacteria. The alcohol also helps the composition to dry faster to form a residual self-disinfecting film. The replacement of water with alcohol can be 5% alcohol to 90% alcohol, preferably 35% to 70%.

[0248] Example 2

[0249] This example demonstrates that antimicrobial compositions according to embodiments of the present invention exhibit future antimicrobial protection against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli (ATCC 8739).

[0250] Disinfecting compositions were prepared comprising polyDADMAC of 250 kDa or polyDADMAC of ultra high molecular weight (1000000 g / mole) listed in Table 9, water-methanol mixtures, titanate, and functionalized TiO2 particles. The reported kill rates and times were measured using 7-day-old films inoculated with bacteria. Bacterial testing was performed by an independent testing laboratory, BioSan Laboratories, Inc. (Warren, Michigan), and the results for the 4.8K ppm films are listed in Table 10. The simulated EPA durability test used herein consisted of the required 12 alternating wet and dry wipes of specified weight. The organisms recovered from each sample were measured after 5 minutes. The results are listed in Table 10, row 4.

[0251] Table 9

[0252]

[0253] Table 10

[0254]

[0255] As is evident from the results listed in Table 10, the ultra-high molecular weight poly-DADMAC is very effective in preventing future growth of Gram-positive (MRSA) and Gram-negative (E. coli) bacteria, with a kill rate of greater than 99.5% in 5 minutes. In addition, these results measured after a period of 7 days demonstrate that the antimicrobial residual self-disinfecting film continues to kill at this effective level. In addition, the ultra-high molecular weight poly-DADMAC is also effective in killing Gram-negative (E. coli) bacteria after EPA durability testing. Therefore, the antimicrobial residual self-disinfecting film is not easily removed from the surface.

[0256] Example 3

[0257] This example demonstrates that antimicrobial compositions according to embodiments of the present invention exhibit future antimicrobial protection against Influenza A (H1N1) (ATCC CCL-34) enveloped viruses and MS2 (ATCC 15597-B1) non-enveloped viruses.

[0258] Disinfecting compositions comprising polyDADMAC and / or PEI, titanate, and optionally functionalized TiO2 were prepared in water-methanol mixtures according to Table 8, Table 9, or Table 11. The reported kill rates and times were measured using 7-day-old films inoculated with virus. Virus testing was performed by an independent testing laboratory, Antimicrobial Test Laboratories (Round Rock, Texas), and the results are listed in Table 12.

[0259] Table 11

[0260]

[0261] Table 12

[0262]

[0263] As is apparent from the results listed in Table 12, the antimicrobial composition comprising polyDADMAC and TiO2 lyses 98.2% of the log4 population of influenza A (H1N1) virus within 30 minutes of contact and 99% within 60 minutes. In addition, the antimicrobial composition comprising PEI kills 97.4% of the log4 population of non-enveloped virus MS2 within 5 minutes and 99% within 30 minutes. Table 12 also shows that the disinfecting composition comprising polyDADMAC, TiO2 and PEI with the addition of 33% PEI becomes more antiviral, particularly against non-enveloped MS2. In the absence of PEI, 82.3% is killed within 30 minutes, but with 33% PEI, 95% is killed within 30 minutes. In addition, Table 12 shows that the antimicrobial composition comprising polyDADMAC and TiO2 kills only 82.3% of non-enveloped MS2 virus within 30 minutes of contact, a value that increases to 97.8% after 24 hours.

[0264] Example 4

[0265] This example demonstrates that antimicrobial compositions according to embodiments of the present invention exhibit future antimicrobial protection against spore-forming Clostridium difficile (ATCC 43598).

[0266] Antimicrobial compositions comprising ultra-high molecular weight poly-DADMAC, titanate, and functionalized TiO2 were prepared in a water-methanol mixture as shown in Table 9. The reported kill rates and times were measured using 7-day-old membranes inoculated with bacteria. Bacterial testing was performed by an independent testing laboratory, Antimicrobial Test Laboratories (Round Rock, Texas), and the results are listed in Table 13.

[0267] Table 13

[0268] Test for Clostridium difficile Materials and / or special test conditions Initial Log Kill % in 8 hours ATC#43598 <![CDATA[Ultra-high molecular weight polyDADMAC / TiO2]]> <![CDATA[6.75×10 5 ]]> 98％

[0269] As is apparent from the results listed in Table 13, the antimicrobial composition comprising ultra high molecular weight poly-DADMAC and TiO2 killed 98% of the log5 population of Clostridium difficile (ATCC 43598) within 8 hours.

[0270] Example 5

[0271] This example demonstrates that antimicrobial compositions according to embodiments of the present invention exhibit future antimicrobial protection against the fungus Aspergillus brasiliensis.

[0272] Antimicrobial compositions comprising ultra-high molecular weight poly-DADMAC, titanate, and functionalized TiO2 were prepared in a water-methanol mixture using the formulations shown in Table 9. The reported kill rates and times were measured using 7-day-old films inoculated with fungi. Fungal testing was performed by an independent testing laboratory, BioSan Laboratories, Inc. (Warren, Michigan), and the results are listed in Table 14.

[0273] Table 14

[0274] Tested fungi Materials and / or special test conditions Initial Log Kill % in 8 hours Aspergillus brasiliensis <![CDATA[Ultra-high molecular weight polyDADMAC / TiO2]]> <![CDATA[2.15×10 4 ]]> 86％

[0275] As is apparent from the results listed in Table 14, the antimicrobial composition comprising ultra high molecular weight poly-DADMAC, titanate, and TiO2 killed 86% of the log4 population of Aspergillus brasiliensis within 8 hours.

[0276] Example 6

[0277] This example demonstrates that antimicrobial compositions according to embodiments of the present invention exhibit future antimicrobial protection against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA).

[0278] The disinfecting composition was prepared according to the components listed in Table 9, except that titanium dioxide was not present. The simulated EPA durability test used herein consisted of 12 alternating wet and dry wipes of the required weight. The organisms recovered from each sample were measured after 5 minutes. The results are shown in Table 15.

[0279] Table 15

[0280]

[0281] *cfu / sample – colony forming units per recovered sample

[0282] This example demonstrates that films formed from an antimicrobial composition comprising polyDADMAC, a titanate, and a carrier exhibit "post-kill" antimicrobial protection against MRSA.

[0283] Example 7

[0284] This example demonstrates that a composition comprising polyDADMAC and a carrier exhibits antimicrobial activity.

[0285] Antimicrobial compositions containing low molecular weight polyDADMAC (250,000 g / mole) or ultrahigh molecular weight (1,000,000 g / mole) polyDADMAC were prepared in a water-methanol (80 / 20) mixture. The compositions were coated on a transparent glass slide and dried to form a film. The polyDADMAC film was tested for its ability to kill methicillin-resistant Staphylococcus aureus (MRSA). The organisms recovered from each sample were measured after 5 minutes. The results are shown in Table 16.

[0286] Table 16

[0287]

[0288] *cfu / sample – colony forming units per recovered sample

[0289] Unexpectedly, it was found that the films produced with ultra-high molecular weight polyDADMAC were more effective than low molecular weight (250,000 g / mole) in killing gram-positive and gram-negative bacteria. As shown in Table 16, after being exposed to log 7 MRSA population for 5 minutes, the film of 250,000 g / mole molecular weight provided only 2.08 antimicrobial activity. In contrast, using the same amount of polymer in each case, the film of 1,000,000 g / mole molecular weight produced 5.7 antimicrobial activity, i.e. more than twice. It is believed that the difference in the killing rate of polyDADMAC with lower molecular weight and polyDADMAC with higher molecular weight may be due to the difference in film formation rather than the difference in charge density.

[0290] Example 8

[0291] This example illustrates the use of an antimicrobial composition according to an embodiment of the present invention to provide a residual self-disinfecting film on a fabric.

[0292] An antimicrobial composition in the form of a PEC was prepared containing 6000 ppm of polyDADMAC, 1500 ppm of polyacrylic acid, 400 ppm of titanate, and 0.1 wt % of functionalized TiO2 particles. The composition was applied to the cloth in the 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 antimicrobial surface materials on fabrics. The test showed that the polymer-based composition was able to lyse 99.58% of the log4 MRSA population on the cloth after 4 hours (Table 17). Although the AATCC does not specify a standard, a similar test method ISO 20743 recommends 2-Log 10 Or 99% reduction.

[0293] Table 17

[0294]

[0295] A second antimicrobial composition comprising 4000 ppm PEI, 2000 ppm poly(acrylamide-co-diallyldimethylammonium chloride) and 25 ppm carboxylated branched PEI in a carrier was prepared at a pH of about 6. The composition was applied to the cloth in the rinse cycle and then tested for antimicrobial resistance under the same conditions as above. The results are shown in Table 18.

[0296] Table 18

[0297]

[0298] Example 9

[0299] This example demonstrates that the antimicrobial composition containing titanate exhibits antimicrobial protection against E. coli.

[0300] A composition containing titanate in water was applied to a glass slide. The coated slide was left for 5 days and then inoculated with a log 6 population of E. coli. After 24 hours the pure titanate film achieved a kill of 88.72%, as shown in Table 19.

[0301] Table 19

[0302]

[0303] *cfu / sample – colony forming units per recovered sample

[0304] Example 10

[0305] This example demonstrates the antimicrobial activity of the hand sanitizer compositions according to embodiments of the present invention.

[0306] At room temperature, 4000ppm linear PEI in water was vigorously stirred to produce a PEI dispersion. Under vigorous stirring, the PEI in the dispersion was then protonated with citric acid to reach a pH of 6 and produce a clear liquid. The clear liquid was then warmed to 70°C. Ethanol and 1,2-propylene glycol were then dropped so that the temperature of the clear liquid was maintained at 65°C. The clear mixture was removed from the heat to avoid evaporation of excess alcohol and then stirred for at least 4 hours while covered. The resulting miscible blend contained 4000pm non-chemically modified linear PEI, 72% ethanol, 5% 1,2-propylene glycol, 0.25% by weight citric acid, and the remainder of water.

[0307] The activity of the hand sanitizer composition against non-enveloped viruses complies with ASTM E 1052-96 (2002) ("Standard Test Method for Evaluating the Activity of Microbicides Against Viruses in Suspension"). Using this test, the hand sanitizer formulation inactivated MS2 (a surrogate for non-enveloped viruses) with a 99.9% (log 3) reduction in MS2 within 60 seconds of contact. The activity of the hand sanitizer composition against MRSA (Gram-positive bacteria) and E. coli (Gram-negative bacteria) complies with ASTM E 2315. The hand sanitizer composition inactivated both bacteria with a 99.999% (log 5) reduction in both bacteria within 30 seconds of contact. Table 20 summarizes the results of these tests.

[0308] Table 20

[0309]

[0310] Embodiment 11

[0311] This example illustrates the synthesis of functionalized TiO2 particles according to an embodiment of the present invention.

[0312] The TiO2 particles were functionalized using the following method. 1 g of tungsten-doped 20 nm liquid-phase synthesized TiO2 was used as the starting material, 5 g of urea was added, and the mixture was calcined at 400 ° C for 40 minutes to obtain NTiO2. The NTiO2 was then ground into a fine powder, 10 g of grinding balls were added for each gram of NTiO2, and 10% urea was added. The mixture was ground at 300 rpm for 30 minutes. After 30 minutes, 200 mL of water was added, and the mixture was ground for another 5 minutes. The ground mixture was then subjected to 160 W of UV light. After 1 hour, the mixture was decanted and centrifuged, and 0.5 mM dye was added in the dark. The mixture was decanted and centrifuged again, and then water was added.

[0313] All references, including publications, patent applications, and patents, cited herein are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein.

[0314] The use of the terms "one" and "the" and "at least one" and similar expressions in the context of describing the present invention (particularly in the context of the following claims) should be interpreted as covering one and more than one, unless otherwise specified herein or explicitly contradicted with the context. The use of the term "at least one" (e.g., "at least one of A and B") in the enumeration of one or more items should be interpreted as indicating that one item (A or B) or any combination of two or more of the listed items (A and B) is selected from the listed items, unless otherwise specified herein or explicitly contradicted with the context. Unless otherwise specified, the terms "comprising", "having", "including" and "containing" should be interpreted as open terms (i.e., meaning "including but not limited to"). Unless otherwise specified herein, the description of the numerical range herein is intended only to be used as a shorthand method for individually referring to each individual value falling within the range, and each individual value is incorporated into this specification as if it is quoted separately in this article. Unless otherwise specified herein or the context is obviously contradictory, all methods described herein can be performed in any suitable order. Unless otherwise stated, the use of any and all examples or exemplary language (e.g., "such as") provided herein is intended only to better illustrate the present invention rather than to limit the scope of the present invention. No language in the specification should be construed as indicating that any unclaimed element is essential to the practice of the present invention.

[0315] Preferred embodiments of the present invention are described herein, including the best mode of implementing the present invention known to the inventor. After reading the foregoing description, variations of those preferred embodiments may become apparent to those of ordinary skill in the art. The inventor expects that skilled technicians will appropriately adopt these variations, and the inventor hopes that the present invention will be implemented in a manner different from that specifically described herein. Therefore, the present invention includes all modifications and equivalents of the subject matter described in the appended claims as allowed by applicable law. In addition, unless otherwise specified herein or the context is clearly contradictory, the present invention encompasses any combination of all possible variations of the above-mentioned elements.

Claims

1. An antimicrobial film coating having antibacterial, antiviral and antifungal properties applied to a substrate, comprising: (a) a cationic non-chemically modified linear polyethyleneimine (PEI) having a number average molecular weight of 15000 g / mole or higher; (b) at least one adhesion promoter selected from titanates, branched polyethyleneimine-based polymers having carboxylate groups, polyDADMAC or other cationic quaternary ammonium polyelectrolytes, and combinations thereof; and (c) optionally a pH adjusting acid comprising a synthetic acid or an organic acid or a combination thereof; in, The antimicrobial film coating maintains at least 96% microbial reduction after 24 hours of exposure to the friction cycle and microbial challenge of EPA #01-1A durability test, The components of the antimicrobial film coating are not covalently bonded to each other, The antimicrobial film coating is not covalently bonded to the surface of the substrate, and The antimicrobial film coating does not contain anionic polymers.

2. The antimicrobial film coating of claim 1, wherein the antimicrobial film coating further comprises a cationic polymer selected from polydiallyldialkylammonium salts, acryloxyalkyltrialkylammonium salts, vinylphenylalkyltrialkylammonium salts, acrylamidoalkyltrialkylammonium salts, poly(acrylamide-co-diallyldialkylammonium salts), chitosan optionally in combination with anionic polymers, and combinations thereof.

3. The antimicrobial film coating of claim 2, wherein the antimicrobial film coating further comprises a polydiallyldialkylammonium salt, the polydiallyldialkylammonium salt being a polydiallyldimethylammonium halide, wherein the halide ion is a chloride ion, a fluoride ion, a chloride-containing anion, a fluoride-containing anion, or a combination thereof.

4. The antimicrobial film coating of claim 3, wherein the halide ion is a chloride ion or a chloride-containing anion.

5. The antimicrobial film coating according to any one of claims 1 to 3, wherein the antimicrobial film coating does not contain an antimicrobial metal.

6. The antimicrobial film coating according to any one of claims 1 to 3, wherein the antimicrobial film coating further comprises at least one small molecule compound that kills pathogens.

7. The antimicrobial membrane coating according to any one of claims 1 to 3, wherein the antimicrobial membrane coating further comprises one or more than one non-electrolyte polymer.

8. The antimicrobial film coating of claim 7, wherein the one or more than one non-electrolyte polymer comprises polyvinyl pyrrolidone.

9. The antimicrobial film coating according to claim 1, wherein the microorganism is a substitute for a non-enveloped virus and is MS2 (ATCC 15597-B1).

10. A method of killing microorganisms on a surface, comprising contacting the microorganisms with the antimicrobial film coating of any one of claims 1 to 9.

11. The method according to claim 10, wherein: The antimicrobial film coating kills one or more of the following: (i) kills at least 95% of the log5 population of methicillin-resistant Staphylococcus aureus (MRSA) within 30 minutes of contact; (ii) kills at least 95% of the log5 population of Gram-negative Escherichia coli (ATCC 8739) within 30 minutes of contact; (iii) kills at least 95% of the log4 population of influenza A (H1N1) (ATCC CCL-34) enveloped viruses within 60 minutes of contact; (iv) kills at least 75% of the log4 population of Clostridium difficile (ATCC 43598) within 24 hours of contact.

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