Coated substrate and method for producing coated substrate

Abstract

To provide a method for producing a coating base material having excellent antiviral and antibacterial properties, and to provide the coating base material obtained by the method.SOLUTION: The coated substrate includes a substrate and a surfactant coated on a surface of the substrate, and an element constituting the surfactant is covalently bonded to an element derived from the substrate on the surface of the substrate. The covalent bond is selected from the group consisting of a carbon-carbon covalent bond, a carbon-nitrogen covalent bond, and a carbon-oxygen covalent bond. An analog of a compound having a biguanide-type structure is chlorhexidine.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] One embodiment of the present invention relates to a coated substrate and a method for making the coated substrate. [Background technology]

[0002] The novel coronavirus disease (COVID-19) that began spreading worldwide in 2020 has prompted the development of a variety of antiviral agents and components. Furthermore, the emergence of drug-resistant bacteria has led to a strong demand for antibacterial measures that do not use antibiotics. With growing awareness of hygiene worldwide, there is a demand for the development of component surfaces that exhibit antibacterial and antiviral properties without the use of special chemicals, targeting components used in living environments.

[0003] Known methods for fixing substances having antibacterial and antiviral activity to the surface of a component include a method of fixing an antibacterial and antiviral agent using a binder (Patent Document 1, Non-Patent Documents 1 and 2), a method of fixing an antibacterial and antiviral agent by heat treatment under normal or increased pressure (Patent Document 2), a method of fixing an antibacterial and antiviral agent after pre-treating the material surface by plasma treatment (Patent Document 3), a method of fixing an antibacterial and antiviral agent using an adhesive (Patent Document 4), and a method of fixing an antibacterial and antiviral agent via hydroxyl groups already present on the material surface (Patent Document 5). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2012-002869 [Patent Document 2] Re-tabled publication 2016 / 009928 [Patent Document 3] Special Publication No. 2022-537362 [Patent Document 4] Special Publication No. 2023-521043 [Patent Document 5] Japanese Patent Application Publication No. 2019-072974 [Non-patent literature]

[0005] [Non-Patent Document 1] K. Ozaltin, A. Di Martino, Z. Capakova, M. Lehocky, P. Humpolicek, T. Saha, D. Vesela, M. Mozetic, P. Saha, Polymers, 13, 1201 (2021) [Non-patent document 2] T.-S. Kim, S.-H. Park, D. Park, J.-H. Lee, S. Kang, J. Membr. Sci., 576 17 (2019) Summary of the Invention [Problem to be solved by the invention]

[0006] In conventional methods for immobilizing antibacterial or antiviral agents on a substrate, damage to the substrate must be considered when using heat or plasma treatment. Furthermore, when immobilizing antibacterial or antiviral agents via hydroxyl groups already present on the material surface, the surface chemical structure of the substrate is limited.

[0007] When a conventional binder or adhesive is used to fix an antibacterial or antiviral substance to a substrate, the types of substrates that can be used and the applications of the substrates to which the antibacterial or antiviral substance is fixed using a binder or adhesive are limited. Furthermore, when a binder or adhesive is used, the thickness of the antibacterial or antiviral substrate increases.

[0008] In view of the above problems, one object of one embodiment of the present invention is to provide a method for producing a coated substrate having excellent antiviral or antibacterial properties, and a coated substrate obtained thereby. [Means for solving the problem]

[0009] A coated substrate according to one embodiment of the present invention comprises a substrate and a surfactant coated on the surface of the substrate, and elements constituting the surfactant are covalently bonded to elements derived from the substrate on the surface of the substrate.

[0010] In the above configuration, the covalent bond may be selected from the group consisting of a carbon-carbon covalent bond, a carbon-nitrogen covalent bond, and a carbon-oxygen covalent bond.

[0011] In the above configuration, the surfactant may be selected from the group consisting of sodium dodecyl sulfate, sodium stearate, sodium dodecyl phosphate, dodecylamine hydrochloride, octadecylamine hydrochloride, octylamine hydrobromide, benzalkonium chloride, benzethonium chloride, cocamidopropyl hydroxysultaine, cocamidopropyl betaine, sodium laurylaminodipropionate, alkyldiaminoethylglycine hydrochloride, and analogs of compounds having a biguanide structure.

[0012] In the above configuration, the analog of the compound having a biguanide structure is chlorhexidine.

[0013] In the above configuration, the chlorine / nitrogen ratio in the spectrum obtained by X-ray photoelectron spectroscopy of the surface of the substrate at a sample tilt angle of 45° may be 0.15 or less.

[0014] In the above-described configuration, the surface of the coating substrate may have a contact angle with water of 55° or less.

[0015] In the above configuration, the substrate may be selected from the group consisting of resin, ceramic, metal, and natural fiber.

[0016] In the above configuration, the form of the substrate may be selected from the group consisting of a plate, a film, a fiber, a powder, and a pellet.

[0017] In a method for producing a coated substrate according to one embodiment of the present invention, a surfactant is attached to the substrate, and the substrate to which the surfactant has been attached is irradiated with ultraviolet light, thereby coating the substrate with the surfactant.

[0018] In the above manufacturing method, the ultraviolet light may have a wavelength of 170 nm to 300 nm.

[0019] In the above manufacturing method, the amount of ultraviolet light is 0.1 mW / cm 2 ~100mW / cm 2 may be.

[0020] In the above-described production method, an element constituting the surfactant may be covalently bonded to an element derived from the substrate on the surface of the substrate.

[0021] In the above-mentioned manufacturing method, the surfactant may be selected from the group consisting of sodium dodecyl sulfate, sodium stearate, sodium dodecyl phosphate, dodecylamine hydrochloride, octadecylamine hydrochloride, octylamine hydrobromide, benzalkonium chloride, benzethonium chloride, cocamidopropyl hydroxysultaine, cocamidopropyl betaine, sodium laurylaminodipropionate, alkyldiaminoethylglycine hydrochloride, and analogs of compounds having a biguanide structure.

[0022] In the above manufacturing method, the covalent bond may be selected from the group consisting of a carbon-carbon covalent bond, a carbon-nitrogen covalent bond, and a carbon-oxygen covalent bond.

[0023] In the above production method, the analog of the compound having a biguanide structure is chlorhexidine.

[0024] In the above manufacturing method, the substrate may be selected from the group consisting of resin, ceramic, metal, and natural fiber.

[0025] In the above-mentioned manufacturing method, the form of the substrate may be selected from the group consisting of a plate, a film, a fiber, a powder, and a pellet. [Effects of the Invention]

[0026] According to one embodiment of the present invention, it is possible to provide a method for producing a coated substrate having excellent antiviral and antibacterial properties, and a coated substrate obtained thereby. [Brief explanation of the drawings]

[0027] [Figure 1] FIG. 1 is an end view of a coated substrate according to one embodiment of the present invention. [Figure 2] 1A to 1C are schematic diagrams illustrating a method for producing a coated substrate according to one embodiment of the present invention. [Figure 3] 1A to 1C are schematic diagrams illustrating a method for producing a coated substrate according to one embodiment of the present invention. [Figure 4] 1A to 1C are schematic diagrams illustrating a method for producing a coated substrate according to one embodiment of the present invention. [Figure 5] This is the chemical formula for chlorhexidine. [Figure 6] 1 is a schematic diagram of the chemical formula of chlorhexidine. [Figure 7] The results are obtained by XPS measurement of the surface of a polyester fiber piece and the surface of a polyethylene fiber piece before UV irradiation. [Figure 8] The graph shows the results of XPS measurement of the surface of a polyester fiber piece and the surface of a polyethylene fiber piece after ultraviolet irradiation. [Figure 9] The results are obtained by XPS measurement of the surface of a polyester fiber piece and the surface of a cotton fiber piece before UV irradiation. [Figure 10] The results are obtained by XPS measurement of the surface of a polyester fiber piece and the surface of a cotton fiber piece after ultraviolet irradiation. [Figure 11] The graph shows the results of XPS measurements on the surface of a polyethylene terephthalate film before and after ultraviolet irradiation. [Figure 12] 1 is a photograph of a polyethylene terephthalate film before ultraviolet irradiation. [Figure 13] 1 is a photograph of a polyethylene terephthalate film after ultraviolet irradiation. DETAILED DESCRIPTION OF THE INVENTION

[0028] An embodiment of the present invention will be described in detail below with reference to the drawings. The present invention is not limited to the following embodiment, and various modifications can be made within the scope of the invention.

[0029] A coating substrate according to one embodiment of the present invention will be described with reference to FIGS.

[0030] <Configuration of coating substrate 10> 1 is an end view of a coated substrate 10 according to one embodiment of the present invention. The coated substrate 10 includes a substrate 101 and a surfactant 102 coated on the surface of the substrate 101.

[0031] The substrate 101 is selected from the group consisting of resins, ceramics, metals, and natural fibers.

[0032] When a resin is used for the substrate 101, thermoplastic resins such as polyethylene (PE), polypropylene (PP), polystyrene / styrene resin (PS), vinyl chloride resin / polyvinyl chloride (PVC), ABS resin (ABS), AS resin (SAN), polyethylene terephthalate (PET), methacrylic resin (PMMA), polyamide (PA), polycarbonate (PC), polyacetal (POM), polybutylene terephthalate (PBT), polyphenylene ether (PPE), fluororesin, polyimide (PI), polyethersulfone (PES), polyetherimide (PEI), etc. Alternatively, thermosetting resins such as urea resin (UF), melamine resin (MF), unsaturated polyester (UP), epoxy resin (EP), silicone resin (SI), polyurethane (PUR), etc. may be used.

[0033] Furthermore, when ceramics are used for the substrate 101, alumina (Al2O3), zirconia (ZrO2), aluminum nitride (AlN), silicon carbide (SiC), and silicon nitride (Si3N4) can be used. When a metal is used for the substrate 101, aluminum, copper, stainless steel, or the like can be used. Silicon may also be used for the substrate 101. Natural fibers such as cotton and hemp may also be used for the substrate 101.

[0034] The substrate 101 may be in the form of a plate, film, fiber, powder, or pellet. When the substrate 101 is a plate-shaped metal or resin, the thickness of the substrate 101 may be 1 mm or more. When the substrate 101 is a film-shaped resin, the thickness of the substrate 101 may be 1 μm to less than 1 mm. When the substrate 101 is a fibrous resin or natural fiber, the thickness may be 1 μm to less than 1 mm. When the substrate 101 is a powdered ceramic, the average particle size may be 3 μm to less than 1 mm. When the substrate 101 is a pellet-shaped resin, the average particle size may be 1 mm or more.

[0035] The surfactant 102 is preferably a drug with low skin irritation and oral toxicity and high immediate release. Ionic surfactants (anionic surfactants, cationic surfactants, amphoteric surfactants) can be used as the surfactant 102. Examples of anionic surfactants that can be used include sodium dodecyl sulfate, sodium stearate, and sodium dodecyl phosphate. Examples of cationic surfactants that can be used include dodecylamine hydrochloride, octadecylamine hydrochloride, octylamine hydrobromide, and quaternary ammonium salts. Examples of quaternary ammonium salts that can be used include benzalkonium chloride and benzethonium chloride. Examples of amphoteric surfactants that can be used include cocamidopropyl hydroxysultaine, cocamidopropyl betaine, sodium laurylaminodipropionate, and alkyldiaminoethylglycine hydrochloride.

[0036] Alternatively, a nonionic surfactant can be used as the surfactant 102. Analogues of compounds having a biguanide structure can be used as the nonionic surfactant. Examples of analogues of compounds having a biguanide structure include chlorhexidine, alexidine, polyaminopropyl biguanide, polyhexanide, olanexidine, proguanil, and chloroproguanil.

[0037] In the coated substrate 10, elements constituting the surfactant 102 are covalently bonded to elements of the substrate 101 on the surface of the substrate 101. For example, an analog of a compound having a biguanide structure is a drug with high immediate action, but it can be irritating on contact with the skin and can be orally toxic on contact with mucous membranes. However, in the coated substrate 10 according to one embodiment of the present invention, elements constituting the analog of a compound having a biguanide structure are covalently bonded to elements derived from the substrate 101 on the surface of the substrate 101. This prevents the analog of the compound having a biguanide structure from being released, thereby limiting skin irritation to the area in contact with the coated substrate 101 and the duration of contact. Therefore, skin irritation is thought to be lower than when the analog of a compound having a biguanide structure is released from the substrate. Furthermore, preventing contact with mucous membranes on the coated substrate 10 reduces oral toxicity.

[0038] The surfactant 102 exerts at least one of antiviral, antibacterial, antifungal, and antiparasitic effects.

[0039] The surfactant 102 has an antiviral effect. In this specification and the like, the antiviral effect means the inactivation of pathogenic viruses.

[0040] The coated substrate 10 according to one embodiment of the present invention exhibits antiviral effects against enveloped and non-enveloped viruses. The surfactant 102 inactivates enveloped viruses by damaging their envelopes. The surfactant 102 inactivates non-enveloped viruses by damaging their capsid structures.

[0041] The coated substrate 10 can be used to inactivate enveloped viruses, such as SARS coronavirus, highly pathogenic avian influenza virus, MARS coronavirus, Ebola virus, novel coronavirus, smallpox virus, hepatitis B virus, measles virus, and rabies virus. The coated substrate 10 also exhibits a virus inactivation effect against these enveloped viruses.

[0042] The coated substrate 10 exhibits a high virus inactivation effect against non-enveloped viruses, such as viruses of the Caliciviridae family, and exhibits a higher virus inactivation effect against viruses of the genus Vesivirus and / or Norovirus, and exhibits a particularly high virus inactivation effect against at least one virus selected from the group consisting of feline calicivirus, murine norovirus, and human norovirus. Furthermore, the coated substrate 10 is not limited to the above-mentioned non-enveloped viruses, and also exhibits a virus inactivation effect against rotavirus, poliovirus, adenovirus, and the like.

[0043] Viruses are prone to errors in their genetic information during proliferation and replication. Therefore, viruses are known to mutate rapidly, resulting in the emergence of new mutant strains. Such mutations often occur in the spike protein, affecting the effectiveness of vaccines that primarily target the spike protein. The coating substrate 10 according to one embodiment of the present invention acts on the envelope and capsid, which are less susceptible to mutations, and therefore exhibits virus inactivation effects even against mutant virus strains.

[0044] The surfactant 102 has an antibacterial effect. In this specification and the like, the term "antibacterial effect" is a concept that encompasses a bactericidal effect and a bacteriostatic effect. In other words, the surfactant is considered to have an "antibacterial effect" not only when it has the effect of reducing the viable cell count of a specific bacterium, but also when it has the effect of suppressing the growth rate of the specific bacterium. The surfactant 102 kills bacteria by damaging the cell membrane of the bacteria.

[0045] The coated substrate 10 according to one embodiment of the present invention exhibits an antibacterial effect against, for example, methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, vancomycin-intermediate-resistant Staphylococcus aureus, wild-type Pseudomonas aeruginosa strains, quadruple-disrupted strains of Pseudomonas aeruginosa resistance genes, Enterobacter faecalis, and vancomycin-resistant Enterobacter faecalis, etc. The coated substrate 10 according to one embodiment of the present invention also exhibits an antibacterial effect against resistant bacteria such as carbapenem-resistant Enterobacteriaceae, penicillin-resistant Streptococcus pneumoniae, extended-spectrum beta-lactamase-producing bacteria, AmpC-producing bacteria, multidrug-resistant Pseudomonas aeruginosa, and drug-resistant Acinetobacter.

[0046] When chlorhexidine is used as the surfactant 102, the site of action of chlorhexidine is the bacterial cell membrane (lipid membrane). Therefore, the coating substrate 10 according to one embodiment of the present invention similarly exhibits antibacterial effects against bacteria and resistant bacteria other than those exemplified above.

[0047] The surfactant 102 has an antifungal effect. In this specification and the like, the term "antifungal effect" is a concept that encompasses a fungicidal effect and a fungal growth inhibitory effect. In other words, an "antifungal effect" is considered to exist not only when it has the effect of reducing the number of live bacteria of a specific fungus but also when it has been confirmed that it has the effect of inhibiting the growth rate of a specific fungus. The surfactant 102 kills fungi by damaging their cell membranes.

[0048] The coated substrate 10 according to one embodiment of the present invention also exhibits antifungal effects against the genera Aspergillus, Cryptococcus, Pneumocystis, Trichosporon, Trichophyton, Malassezia, Sporothrix, black fungi, Fusarium, Trichothecium, Cepharosporium, Rhzioctonia, Ceratobasidium, Magnaporthe, Ophiostoma, Cryphonectria, Ustilago, and Alternaria. Specifically, the coated substrate 10 according to one embodiment of the present invention exhibits antifungal effects against Candida.

[0049] When chlorhexidine is used as the surfactant 102, the site of action of chlorhexidine is the cell membrane (lipid membrane) of the fungus. Therefore, the coating substrate 10 according to one embodiment of the present invention similarly exhibits antifungal effects against fungi other than those exemplified above.

[0050] The surfactant 102 has an antiparasitic (anti-vector) effect. In this specification, the term "antiparasitic effect" is a concept that encompasses a parasitic killing effect and a parasitic proliferation inhibitory effect. The surfactant 102 reduces parasitic infection by damaging the surface structure of the parasite itself or the organism that transmits the parasite.

[0051] The coated substrate 10 according to one embodiment of the present invention exhibits a parasite growth inhibitory effect against parasites, including protozoa and helminths. Because organisms that transmit parasites are smaller than humans, they are highly susceptible to drugs. Therefore, by affecting these organisms, it is possible to affect the parasites as well.

[0052] The coated substrate 10 according to one embodiment of the present invention is effective against protozoan rhizopods such as the genera Entamoeba, Naegleria, Acanthamoeba, and Balamuthia; flagellates such as Giardia, Trichomoniasis, Trypanosoma, and Leishmania; ciliates such as Balantidiasis; and sporozoans such as Cryptosporidium, Plasmodium, Toxoplasma, Babersia, and Kudoa. The coated substrate 10 according to one embodiment of the present invention is also effective against nematodes of helminths such as the genera Enterobius, Ascaris, Trichuris, Ancylostoma, Necater, Strongyloides, Capillaria, Trichinella, Anisakis, Gnathostoma, Loa, Toxocara, Dracunculus, Angiostrongylus, Wuchereria, Brugia, and Onchocerca, as well as cestodes of the genera Taenia, Echinococcus, Diphyllobothrium, Spirometra, Diplogonoporus, and Vampirolepsis, and trematodes of the genera Paragonimus, Clonorchis, Fasciola, Schistosoma, Metagonimus, Heterophyes, Fasciolopsis, and Echinostoma.

[0053] In the coated substrate 10, elements constituting the surfactant 102 are covalently bonded to elements originating from the substrate 101 on the surface of the substrate 101. The covalent bond is selected from the group consisting of a carbon-carbon covalent bond, a carbon-nitrogen covalent bond, and a carbon-oxygen covalent bond. The covalent bond between the elements constituting the surfactant 102 and the elements originating from the substrate 101 can be confirmed by X-ray photoelectron spectroscopy (also known as XPS analysis).

[0054] <Method of manufacturing the coating substrate 10> Next, a method for producing the coating substrate 10 according to one embodiment of the present invention will be described with reference to FIGS.

[0055] As shown in FIG. 2, a surfactant solution 103 is applied to a substrate 101. The surfactant solution 103 is a mixture of a surfactant 102 and a solvent. The surfactant 102 described in FIG. 1 may be used as the surfactant 102. The solvent may be at least one of ethyl acetate, acetone, alcohol, and water. The concentration of the surfactant 102 in the surfactant solution 103 is preferably 1 mM to 500 mM. For example, when a sodium dodecyl sulfate aqueous solution is used as the surfactant solution 103, the concentration is preferably 5 mM to 500 mM or 100 mM to 400 mM. When a chlorhexidine ethyl acetate solution is used as the surfactant solution 103, the concentration is preferably 1 mM to 50 mM or 2 mM to 10 mM. The surfactant solution 103 can be attached to the substrate 101 by impregnating the substrate 101 with the surfactant solution 103. Alternatively, the surfactant solution 103 may be sprayed or applied to the substrate 101.

[0056] It is preferable to evaporate the solvent contained in the surfactant solution 103 attached to the substrate 101 before irradiating with ultraviolet rays. If ultraviolet rays are irradiated before evaporating the solvent, the solvent itself will absorb the ultraviolet light and inhibit the reaction between the surfactant and the substrate. Methods for evaporating the solvent include drying under reduced pressure, natural drying, and infrared irradiation.

[0057] Next, as shown in FIG. 3, ultraviolet light 104 is irradiated onto the substrate 101 and surfactant solution 103. When the solvent in the surfactant solution 103 has evaporated, ultraviolet light 104 is irradiated onto the substrate 101 and surfactant 102. A low-pressure mercury lamp, a high-pressure mercury lamp, an ArF or XeCl excimer laser, or an excimer lamp can be used as the light source for the device that irradiates ultraviolet light 104. Here, the wavelength of the ultraviolet light 104 is 170 nm or more and 300 nm or less. The light intensity of the ultraviolet light 104 is usually 0.1 mW / cm. 2 ~100mW / cm2 , preferably 0.5 mW / cm 2 ~50mW / cm 2 , more preferably 1 mW / cm 2 ~10mW / cm 2 The irradiation time of the ultraviolet light 104 is preferably about 10 seconds to 30 minutes.

[0058] Irradiating the substrate 101 and surfactant 102 with ultraviolet light 104 increases the reactivity of both the surfactant 102 and the substrate 101 due to excitation and radical induction of the components of the surfactant 102 and excitation of the components of the substrate 101. This allows covalent bonding between elements originating from the substrate 101 and elements constituting the surfactant 102. When an analog of a compound having a biguanide structure is used as the surfactant 102, elements constituting the analog of the compound having a biguanide structure are covalently bonded to elements originating from the substrate on the surface of the substrate. This reaction proceeds easily at room temperature or under cooling. Therefore, even when a resin is used as the substrate 101, deterioration of the resin due to heating can be suppressed.

[0059] When irradiating the substrate 101 and the surfactant 102 with ultraviolet light, the substrate 101 may be heated as needed. When heating the substrate 101, the heating temperature is preferably equal to or lower than the heat-resistant temperature of the substrate 101, for example, preferably 200°C or lower.

[0060] In Figure 3, when polyester fiber is used as substrate 101 and chlorhexidine ethyl acetate is used as surfactant solution 103, surfactant solution 103 is applied to a polyester fiber piece, the ethyl acetate solvent is evaporated, and then the chlorhexidine adhering to the polyester fiber piece is irradiated with ultraviolet light. This causes the chlorine contained in the chlorhexidine to be desorbed, and the hydrogen contained in the polyester to be desorbed. As a result, as shown in Figure 4, carbon from chlorhexidine can be covalently bonded to carbon from the polyester.

[0061] The surface of the coated substrate 10 thus manufactured is subjected to X-ray photoelectron spectroscopy at a sample tilt angle of 45°. The elemental composition ratio of the spectrum obtained is determined to be chlorhexidine (molecular formula: C 22 H 30 Cl2N 10 ) reflecting the chemical structure in which one chlorine atom has been removed, the chlorine / nitrogen ratio is 0.15 or less.

[0062] In this embodiment, the covalent bond is described as a carbon-carbon covalent bond, but it may be a carbon-nitrogen covalent bond or a carbon-oxygen covalent bond depending on the surfactant 102 used. Therefore, the covalent bond is selected from the group consisting of a carbon-carbon covalent bond, a carbon-nitrogen covalent bond, and a carbon-oxygen covalent bond.

[0063] In one embodiment of the present invention, the surfactant structure is covalently bonded to the substrate by detaching weakly bonded atoms upon irradiation with the high-energy vacuum ultraviolet light used in the present technology. When chlorhexidine is used as the surfactant, the C-Cl bond is cleaved by ultraviolet irradiation, resulting in a radical reaction with the substrate. At this time, it is believed that the covalent bond occurs due to electron transfer from the functional group contained in the substrate.

[0064] For example, as in Patent Document 2, when a substrate and a quaternary ammonium halide are heat-treated, the chemical bond between the quaternary ammonium halide and the substrate is thought to be an ionic bond, hydrogen bond, or coordinate bond, based on the chemical structure of the quaternary ammonium halide. When a quaternary ammonium halide is used, even with low thermal energy compared to high-energy ultraviolet light, weak bonds in the quaternary ammonium halide are broken and the quaternary ammonium halide bonds with the substrate, resulting in an ionic, hydrogen, or coordinate bond rather than a covalent bond. Furthermore, in order to form a covalent bond between the substrate and the quaternary ammonium halide, it is expected that the bond will occur via various auxiliary agents or additives in the treatment liquid, and it is thought that the quaternary ammonium halide and the substrate will not directly form a covalent bond.

[0065] Furthermore, when a surfactant is fixed to a substrate via oxygen by performing an oxygen plasma treatment on the substrate surface, as in Patent Document 3, an increase in oxygen components may be observed by XPS analysis. On the other hand, in one embodiment of the present invention, UV light is irradiated onto the substrate and surfactant, covalently bonding elements of the surfactant and elements of the substrate, so there is little change in the element ratio before and after UV irradiation, and no increase in oxygen components is observed.

[0066] Chlorhexidine, a compound having a biguanide structure, may be used as gluconate, hydrochloride, or acetate.When chlorhexidine gluconate is used as a surfactant, for example, it is estimated that not only chlorhexidine but also the gluconic acid moiety will be fixed to the substrate by irradiating ultraviolet light.Even if the gluconic acid moiety is fixed to the substrate, it is unlikely to have any adverse effects, but it is expected that the amount of the chlorhexidine moiety, which is the active ingredient, fixed will decrease.

[0067] In addition, the active ingredient of cationic surfactants (e.g., dodecylamine hydrochloride, octadecylamine hydrochloride, and octylamine hydrobromide) is presumed to be the alkylammonium moiety, and the counter anion, chlorine or bromine, is a single element. Therefore, the amount of the counter anion fixed to the substrate is very small compared to the case where the gluconic acid moiety is fixed to the substrate when chlorhexidine gluconate is used, and the impact is presumed to be limited.

[0068] The surface of the coated substrate 10 has a contact angle with water of 55° or less. In other words, the surface of the coated substrate 10 to which the hydrophilic functional group biguanide structure is fixed has high wettability. As a result, droplets spread over the surface of the coated substrate 10, increasing the contact area, and the surfactant 102 contained in the coated substrate 10 can further inactivate viruses contained in the droplets and kill bacteria.

[0069] Through the above steps, the coated substrate 10 according to one embodiment of the present invention can be manufactured.

[0070] According to the method for producing a coated substrate 10 according to one embodiment of the present invention, the components constituting the surfactant 102 can be chemically bonded directly to the surface of the substrate 101 in a single step. Because heat treatment or plasma treatment is not required, there is no need to worry about damage to the substrate 101. The components constituting the surfactant 102 can be chemically fixed via covalent bonds without being limited by the surface structure of the substrate 101.

[0071] Furthermore, by spraying the surfactant solution 103 onto the surface of the substrate 101, the surfactant solution 103 can be applied to a substrate 101 with a large area or a substrate 101 with a complex shape. Thereafter, the area of ​​the substrate 101 to which the surfactant solution 103 has been applied can be dried and then irradiated with ultraviolet light at room temperature. In this way, irradiation with high-energy ultraviolet light eliminates the need for processing using a heating device, plasma device, or the like, and therefore the surfactant 102 can be chemically fixed to the surface of the substrate 101 regardless of the size or shape of the substrate 101.

[0072] Furthermore, since no binder or adhesive is required, the type of substrate 101 is not limited, and the coating substrate 10 can be used in a wide range of applications. Furthermore, since no extra material is required, the properties of the substrate 101 itself can be maintained. For example, when a fiber is used as the substrate 101, the texture of the substrate 101 can be maintained. Furthermore, when a light-transmitting material is used as the substrate 101, the light-transmitting properties of the substrate 101 can be maintained.

[0073] <Virus destruction mechanism> Next, the mechanism by which chlorhexidine destroys viruses will be described with reference to FIGS. 5 and 6. FIG. 5 is the chemical formula of chlorhexidine 150 bound to substrate 101. Because chlorhexidine 150 shown in FIG. 5 is bound to substrate 101, it has a structure in which one Cl has been removed. As shown in FIG. 5, chlorine from chlorhexidine has been removed. FIG. 6 is a schematic diagram of the chemical formula of chlorhexidine. In FIG. 6, chlorhexidine has structures 51a and 51b with many positive charges, large structures 52a and 52b, and a highly hydrophobic structure 53 connecting structures 51a and 51b. Large structures 52a and 52b are six-membered rings.

[0074] First, we will explain the mechanism by which chlorhexidine 150 destroys the envelope of enveloped viruses. Chlorhexidine 150 is positively charged due to its high N content. For example, the surface of the envelope of an enveloped virus is negatively charged. Therefore, when an enveloped virus approaches the coating substrate 10, chlorhexidine 150 utilizes the negative charge of the envelope to attract it. However, a large number of positive charges are required to firmly bind to the envelope surface. Next, large structures such as 6-membered rings (52a, 52b, and 53) can be inserted into the membrane surface, significantly disrupting the stability of the lipid membrane. Furthermore, the strong bond between the positive charge of chlorhexidine and the negative charge on the envelope surface makes chlorhexidine less likely to peel off from the envelope surface. Furthermore, the hydrophobic groups of chlorhexidine can destabilize the envelope.

[0075] Next, we will explain the mechanism by which chlorhexidine 150 destroys membrane proteins (e.g., spikes) of enveloped viruses. When chlorhexidine 150 utilizes the envelope of the enveloped virus to pull it in, the large structures 52a and 52b of chlorhexidine 150, such as the six-membered ring, and the positively charged and highly hydrophobic structures 53, bind to the spikes of the enveloped virus, significantly disrupting the stability of the spikes. This allows chlorhexidine to destroy the virus.

[0076] In the coated substrate 10 according to one embodiment of the present invention, elements constituting the surfactant 102 are covalently bonded to elements originating from the substrate 101 on the surface of the substrate 101. This prevents the surfactant 102 from eluting from the substrate 101 due to droplets containing viruses that adhere to the surface of the coated substrate 10. Furthermore, even if a drug that may be harmful to the human body is used as the surfactant 102, it prevents the surfactant 102 from eluting from the substrate 101 in droplets that adhere to the surface of the coated substrate 10. Due to the surfactant 102 covalently bonded to the surface of the substrate 101, the coated substrate 10 can exhibit an effect at a lower dose than when a drug is carried on the substrate 101, and can maintain at least one of an antiviral effect, an antibacterial effect, an antifungal effect, and an antiparasitic effect for a long period of time. [Example]

[0077] Example 1 In this example, the results of verifying that a surfactant 102 can be immobilized on a substrate 101 by a method for producing a coated substrate 10 according to one embodiment of the present invention will be described.

[0078] A polyester fiber piece conforming to JIS L0803 was used as the substrate. The polyester fiber piece was immersed in a 300 mM aqueous solution of sodium dodecyl sulfate and dried. Next, the polyester fiber piece was irradiated with light from an excimer lamp (10 mW / cm 2) was irradiated at room temperature (25°C) for 30 minutes. The polyester fiber pieces were then washed with pure water and dried under reduced pressure. XPS measurements were performed on the surfaces of the polyester fiber pieces before and after UV irradiation.

[0079] A polyethylene fiber piece was used as the substrate. The polyethylene fiber piece was immersed in a 300 mM aqueous solution of sodium dodecyl sulfate and dried. Next, the polyethylene fiber piece was irradiated with an excimer lamp (10 mW / cm 2 ) was irradiated at room temperature (25°C) for 30 minutes. The polyethylene fiber pieces were then washed with pure water and dried under reduced pressure. XPS measurements were performed on the surfaces of the polyethylene fiber pieces before and after UV irradiation.

[0080] Figure 7 shows the results of XPS measurements on the surface of a polyester fiber piece and the surface of a polyethylene fiber piece before UV irradiation. Figure 8 shows the results of XPS measurements on the surface of a polyester fiber piece and the surface of a polyethylene fiber piece after UV irradiation. As shown in Figure 8, sulfur and sodium derived from sodium dodecyl sulfate were observed. The results of the XPS measurements showed that UV irradiation of the substrate caused sodium dodecyl sulfate to covalently bond to the substrate.

[0081] Example 2 A polyester fiber piece conforming to JIS L0803 was used as the substrate. The polyester fiber piece was immersed in a 7.5 mM chlorhexidine ethyl acetate solution, and the ethyl acetate was evaporated. Next, the polyester fiber piece was irradiated with light from an excimer lamp (100 mW / cm 2 ) was irradiated at room temperature (25°C) for 1 minute. The polyester fiber pieces were then washed with a solvent and dried under reduced pressure. XPS measurements were performed on the surfaces of the polyester fiber pieces before and after UV irradiation.

[0082] A cotton fiber piece conforming to JIS L0803 was used as the substrate. The cotton fiber piece was immersed in a 7.5 mM chlorhexidine ethyl acetate solution, and the ethyl acetate was evaporated. Next, the cotton fiber piece was irradiated with light from an excimer lamp (100 mW / cm 2 ) was irradiated at room temperature (25°C) for 1 minute. The cotton fiber pieces were then washed with a solvent and dried under reduced pressure. XPS measurements were performed on the surfaces of the cotton fiber pieces before and after UV irradiation.

[0083] Figure 9 shows the results of XPS measurements of the surface of a polyester fiber piece and the surface of a cotton fiber piece before UV irradiation. Figure 10 shows the results of XPS measurements of the surface of a polyester fiber piece and the surface of a cotton fiber piece after UV irradiation. As shown in Figure 10, nitrogen and chlorine derived from chlorhexidine were observed. The results of the XPS measurements showed that chlorhexidine was covalently bonded to the substrate by UV irradiation.

[0084] Example 3 A 50 μm thick polyethylene terephthalate (PET) film was used as the substrate. For ultraviolet irradiation, the PET was immersed in a 7.5 mM chlorhexidine ethyl acetate solution, and the ethyl acetate was dried. Next, the PET was irradiated with ultraviolet light from an excimer lamp (100 mW / cm 2 ) was irradiated at room temperature (25°C) for 1 minute. The PET was then washed with a solvent and dried under reduced pressure. XPS measurements were performed on the PET surface before and after UV irradiation.

[0085] Figure 11 shows the results of XPS measurements of the PET surface before and after UV irradiation. As shown in Figure 11, nitrogen and chlorine derived from chlorhexidine were observed. The XPS measurements showed that chlorhexidine was covalently bonded to the substrate by irradiating it with UV light.

[0086] From the results of XPS measurement described in Example 3 and the results of XPS measurement of chlorhexidine alone, it was found that chlorhexidine (molecular formula: C 22 H 30Cl2N 10 The chlorine / nitrogen ratio derived from the PET was calculated. The chlorine / nitrogen ratio of chlorhexidine alone was 0.22, while the chlorine / nitrogen ratio of the PET with chlorhexidine immobilized was 0.15. These results indicate that after UV irradiation, one chlorine atom is released from the chlorhexidine molecule, which reacts with the substrate via a radical, immobilizing the chlorhexidine, reducing the chlorine content by approximately half.

[0087] In Example 3, water was dropped onto the surface of PET before and after UV irradiation to measure the contact angle. The water contact angle of the PET before UV irradiation was 79°, and the water contact angle of the PET after UV irradiation was 54°. It is believed that UV irradiation of the surfactant-coated substrate sufficiently introduced biguanide groups, which are hydrophilic nitrogen-containing groups in chlorhexidine molecules, into the substrate. This is thought to be the reason why the water contact angle of the substrate after UV irradiation was lower than that of the substrate before UV irradiation.

[0088] Furthermore, in Example 3, the transparency of PET before and after UV irradiation was compared. Figure 12 is a photograph of PET before UV irradiation, and Figure 13 is a photograph of PET after UV irradiation. As shown in Figure 13, PET remained transparent even after UV irradiation. This confirmed that the introduction of a surfactant into the substrate had little effect after UV irradiation.

[0089] Example 4 Next, the results of an antiviral test performed on the coated substrate 10 according to one embodiment of the present invention will be described.

[0090] First, a coated substrate 10A was prepared by immobilizing chlorhexidine on the surface of a polyester fiber piece according to the method described in Example 2. Then, a coated substrate 10B was prepared by immobilizing chlorhexidine on the surface of a cotton fiber piece according to the method described in Example 2.

[0091] The coated substrates 10A and 10B were subjected to an antiviral test in accordance with ISO 18184. The antiviral test was carried out by placing test pieces (coated substrates 10A and 10B) in a container and measuring 1 to 10 × 10 7 0.2 mL of influenza A virus suspension 302 containing PFU / mL was dropped per 0.4 g, and the container was sealed.

[0092] The test piece was then left to stand at 25°C for 2 hours. The test piece was then washed with 20 mL of SCDLP to recover any remaining virus. The recovered solution was then serially diluted 10-fold with SCDLP.

[0093] Next, 0.1 mL of each diluted solution was applied to a petri dish in which MDCK cells (canine kidney cells) had been cultured, and the cells were subsequently cultured (this is called the plaque method).

[0094] Next, live cells were stained, and the unstained areas (cells that had died and detached) were counted. Finally, the virus infectivity was calculated from the counts and the dilution ratio.

[0095] The virus infectivity was calculated using the following formula (1). V = 10 × C × D (1) V: viral infectivity titer (PFU / mL) C: Number of plaques D: Dilution ratio of the washing solution

[0096] The antiviral activity value R was calculated according to the following formula (2). Antiviral activity value = log(Vb) - log(Vc) (2) Log(Vb): Common logarithm of the virus infectivity per 0.4 g of Comparative Example 1 after 24 hours Log(Vc): Common logarithm of the viral infection value per 0.4 g of Example 1 after 24 hours

[0097] When the antiviral activity value was 2.0 or higher, it was evaluated as having an antiviral effect.

[0098] Next, according to the method described in Example 3, chlorhexidine was immobilized on the surface of the PET to prepare a coated substrate 10C.

[0099] The coated substrate 10C was subjected to an antiviral test in accordance with ISO 21702. The antiviral test was carried out by applying 1 × 10 7 A virus suspension containing influenza A virus containing PFU / mL was placed in a 25cm 2 0.4 mL was dropped per tube and covered with film.

[0100] The test specimen was then left to stand at 25°C for 24 hours while preventing drying. The surface of the test specimen was then washed with 10 mL of SCDLP to recover any remaining virus. A 10-fold dilution series of the recovered solution was then prepared using SCDLP.

[0101] Next, each diluted solution was applied to a petri dish in which MDCK cells (canine kidney cells) had been cultured, and the cells were subsequently cultured.

[0102] Next, live cells were stained, and the unstained areas (cells that had died and detached) were counted. Finally, the virus infectivity was calculated from the counts and the dilution ratio.

[0103] According to the above formula (1), the viral infectivity (PFU / cm 2 ) was calculated, and the antiviral activity value R was calculated according to formula (2).

[0104] Table 1 summarizes the results of the antiviral tests on coated substrates A to C. Here, the inactivation rate refers to the rate of virus inactivation calculated from the number of active viruses (PFU / mL) in each of the control sample and the test sample. The inactivation rate was calculated using the following formula (3):

[0105]

number

[0106] [Table 1]

[0107] As shown in Table 1, it was confirmed that the coated substrates 10A, 10B, and 10C according to one embodiment of the present invention all had a high antiviral effect with an inactivation rate of 99.97% or more.

[0108] It was shown that the coated substrates 10A to 10C according to one embodiment of the present invention provide a high antiviral effect.

[0109] Example 5 The results of an antibacterial test performed on the coated substrate 10 according to one embodiment of the present invention will be described below.

[0110] According to the method described in Example 3, chlorhexidine was immobilized on the surface of PET to prepare a coated substrate 10D.

[0111] An antibacterial test was conducted on the coated substrate 10D in accordance with JIS Z 2801 (ISO 22196). For the antibacterial test, 0.4 mL of bacterial solution was dropped onto a 50 mm x 50 mm (0.1 mm thick) test piece (coated substrate 10D) and covered with a 40 mm x 40 mm film. This test piece was cultured for 24 hours at 35 ± 1°C and a relative humidity of 90% or higher. After leaving it to stand, the test bacteria on the test piece were washed out and collected, and then 1 cm 2 The number of viable bacteria per unit area was measured.

[0112] The antibacterial activity value R was calculated according to formula (4). R = Ut - At (4) R: Antibacterial activity value Ut: 1cm of the unprocessed test piece after 24 hours 2 Average logarithm of viable bacteria count per At: 1cm after 24 hours of antibacterial treatment 2 Average logarithm of viable bacteria count per

[0113] The bacteria used were methicillin-susceptible Staphylococcus aureus 209P, methicillin-resistant Staphylococcus aureus N315, methicillin-resistant Staphylococcus aureus OM584, vancomycin-intermediately resistant Staphylococcus aureus Mu50, Enterococcus faecalis ATCC29212, vancomycin-resistant Enterococcus faecalis ATCC51299, vancomycin-resistant Enterococcus faecalis NCTC12201, Pseudomonas aeruginosa wild-type strain PAO1, and Pseudomonas aeruginosa resistance gene quadruple disruptant strain YM64.

[0114] Table 2 summarizes the results of the antibacterial test for coated substrate D.

[0115] [Table 2]

[0116] As shown in Table 2, it was confirmed that coated substrate D according to one embodiment of the present invention has a high antibacterial effect against all bacteria. Furthermore, as shown in Table 2, the antibacterial test showed sufficient antibacterial activity not only for 24 hours but also for 2 hours.

[0117] It was shown that the coated substrate 10D according to one embodiment of the present invention provides a high antibacterial effect.

[0118] Although embodiments of the present invention have been described in detail above, it should be understood that modifications, variations and changes can be made without departing from the scope of the appended claims.

[0119] In the present invention, even if there are other effects and advantages different from those brought about by the above-described embodiments, if they are clear from the description in this specification or can be easily predicted by a person skilled in the art, they are naturally understood to be brought about by the present invention. [Explanation of symbols]

[0120] 10: coating substrate, 51a: positively charged structure, 51b: positively charged structure, 52a: large structure, 52b: large structure, 53: highly hydrophobic structure, 101: substrate, 102: surfactant, 103: surfactant solution, 150: chlorhexidine

Claims

1. A substrate; a surfactant coated on the surface of the substrate, A coated substrate, wherein an element constituting the surfactant is covalently bonded to an element originating from the substrate on the surface of the substrate.

2. 2. The coated substrate of claim 1, wherein the covalent bond is selected from the group consisting of a carbon-carbon covalent bond, a carbon-nitrogen covalent bond, and a carbon-oxygen covalent bond.

3. 2. The coated substrate according to claim 1, wherein the surfactant is selected from the group consisting of sodium dodecyl sulfate, sodium stearate, sodium dodecyl phosphate, dodecylamine hydrochloride, octadecylamine hydrochloride, octylamine hydrobromide, benzalkonium chloride, benzethonium chloride, cocamidopropyl hydroxysultaine, cocamidopropyl betaine, sodium laurylaminodipropionate, alkyldiaminoethylglycine hydrochloride, and analogs of compounds having a biguanide structure.

4. The coated substrate according to claim 3 , wherein the analog of the compound having a biguanide structure is chlorhexidine.

5. 4. The coated substrate according to claim 3, wherein the chlorine / nitrogen ratio in a spectrum obtained by X-ray photoelectron spectroscopy of the surface of the substrate at a sample tilt angle of 45° is 0.15 or less.

6. 6. The coated substrate according to claim 5, wherein the surface of the coated substrate has a contact angle with water of 55° or less.

7. The coated substrate according to claim 1 , wherein the substrate is selected from the group consisting of resins, ceramics, metals, and natural fibers.

8. The coated substrate according to claim 1 , wherein the substrate has a form selected from the group consisting of a plate, a film, a fiber, a powder, and a pellet.

9. A surfactant is applied to the substrate, The method for producing a coated substrate includes irradiating the substrate to which the surfactant has been attached with ultraviolet light, thereby coating the substrate with the surfactant.

10. The method for producing a coated substrate according to claim 9, wherein the ultraviolet light has a wavelength of 170 nm to 300 nm.

11. The amount of ultraviolet light is 0.1 mW / cm ２ ~100mW / cm ２ The method for producing a coated substrate according to claim 9, wherein

12. The method for producing a coated substrate according to claim 9 , wherein an element constituting the surfactant is covalently bonded to an element originating from the substrate on the surface of the substrate.

13. The method for producing a coated substrate according to claim 12, wherein the covalent bond is selected from the group consisting of a carbon-carbon covalent bond, a carbon-nitrogen covalent bond, and a carbon-oxygen covalent bond.

14. 10. The method for producing a coated substrate according to claim 9, wherein the surfactant is selected from the group consisting of sodium dodecyl sulfate, sodium stearate, sodium dodecyl phosphate, dodecylamine hydrochloride, octadecylamine hydrochloride, octylamine hydrobromide, benzalkonium chloride, benzethonium chloride, cocamidopropyl hydroxysultaine, cocamidopropyl betaine, sodium laurylaminodipropionate, alkyldiaminoethylglycine hydrochloride, and analogs of compounds having a biguanide structure.

15. The method for producing a coated substrate according to claim 14, wherein the analogue of a compound having a biguanide structure is chlorhexidine.

16. The method for producing a coated substrate according to claim 9 , wherein the substrate is selected from the group consisting of resins, ceramics, metals, and natural fibers.

17. The method for producing a coated substrate according to claim 9 , wherein the substrate has a form selected from the group consisting of a plate, a film, a fiber, a powder, and a pellet.

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