Antimicrobial composition

Abstract

To provide an antibacterial agent composition that exhibits excellent antibacterial effects, particularly in wet environments. [Solution] The following components (A), (B), and (C); (A) Water-insoluble acylated cellulose derivatives (B) Antimicrobial agents (C) Solvent An antimicrobial composition containing the following:

Description

Technical Field

[0001] The present invention relates to an antibacterial agent composition and an antibacterial method.

Background Art

[0002] The administration of antibacterial drugs greatly contributes to the cure of infectious diseases caused by microorganisms and the improvement of the prognosis of patients. On the other hand, in recent years, various drug-resistant bacteria having resistance to antibacterial drugs have been confirmed, and the number of cases where the treatment of infectious diseases has become difficult is increasing. It is estimated that if no countermeasures are taken, the annual death toll will reach 10 million by 2050 (Non-Patent Document 1). In particular, in order to suppress the infection of drug-resistant bacteria in hospitals, it is necessary to regularly clean the surfaces that are frequently contacted by various humans such as patients and medical staff, as well as the areas around water that are regarded as reservoirs of drug-resistant bacteria (Non-Patent Document 2), in order to remove drug-resistant bacteria from the target surfaces. However, the complexity and the re-growth on the target surfaces after cleaning have become problems. The cleaning interval of the target hospital water area is generally once a day, which is insufficient to maintain a low bacterial count in the water area where drug-resistant bacteria adhere frequently. Therefore, an antibacterial technique for suppressing the growth of bacteria on the target surface is required between cleanings. In addition, water durability is required to suppress the growth of bacteria in the water environment.

[0003] Cellulose is a natural polymer in which glucose is polymerized by β-glycosidic bonds and is the main component of the cell walls of plant cells and fibers. Cellulose is insoluble in both water and organic solvents, but cellulose derivatives obtained by chemically treating cellulose can be dissolved and are used as films and coating agents. Using cellulose with a low environmental impact as a raw material is considered to be one of the efforts contributing to the sustainability of society.

[0004] Typical cellulose derivatives include nitrocellulose and acetylcellulose. Considering their application as coating agents for water areas, the former has problems such as flammability and aging deterioration, and the latter has problems such as deterioration due to hydrolysis and strange odors caused by released acetic acid.

[0005] Other cellulose derivatives include water-soluble compounds such as methylcellulose, carboxymethylcellulose, and hydroxymethylcellulose. However, the surfaces formed by these compounds dissolve in water, making them unsuitable as coating agents for areas exposed to water.

[0006] On the other hand, cellulose nanofibers, obtained by breaking down cellulose to the nanoscale, can be functionalized by introducing functional groups, just like cellulose itself, and can be dispersed in water. Cellulose nanofibers have a wide range of applications, including ballpoint pen ink and plastic reinforcing agents.

[0007] However, since the safety of cellulose nanofibers, particularly in relation to inhalation exposure, is still under investigation, it is necessary to use materials to immobilize the cellulose nanofibers in combination. For example, in a technology in which modified cellulose nanofibers are mixed in an organic medium (Patent Document 1), it is possible to immobilize antibacterial agents in the organic medium, but there are concerns that because the treated surface is an organic medium, it may promote the retention of solid contaminants on the treated surface. [Prior art documents] [Patent Documents]

[0008] [Patent Document 1] Japanese Patent Publication No. 2023-94520 [Non-patent literature]

[0009] [Non-Patent Document 1] Tackling a crisis for the health and wealth of nations: The review on antimicrobial resistance (2016) [Non-Patent Document 2] Nature medicine (2020) 941-951 [Overview of the Initiative] Problems to be Solved by the Invention

[0010] The present invention particularly relates to providing an antibacterial agent composition that exhibits excellent water durability and antibacterial effect in an environment around water. Means for Solving the Problems

[0011] The inventor has found that when a solution obtained by dissolving a water-insoluble acylated cellulose derivative as a base and an antibacterial agent are mixed and surface treatment is performed, a treatment film with high water durability is formed and an excellent antibacterial effect is exhibited.

[0012] That is, the present invention relates to the following 1) to 3). 1) The following components (A), (B) and (C); (A) Water-insoluble acylated cellulose derivative (B) Antibacterial agent (C) Solvent An antibacterial agent composition containing the above. 2) A treatment film formed on a target surface using the above antibacterial agent composition. 3) An antibacterial method of applying the above antibacterial agent composition to a target surface. [[ID=SS]]Effects of the Invention

[0013] According to the present invention, high water durability and antibacterial properties can be imparted to a target surface, and infection of drug-resistant bacteria and the like through the target surface can be suppressed. Brief Description of the Drawings

[0014] [Figure 1] [[ID=TT]]Shows the measurement results of the particle size of silver oxide. [Figure 2] Shows the measurement results of the particle size of benzisothiazolinone. [Figure 3] Shows the measurement results of the particle size of zinc pyrithione. Modes for Carrying Out the Invention

[0015] The antibacterial composition of the present invention contains a water-insoluble acylated cellulose derivative as component (A). Here, in this specification, "water-insoluble" means a property of not dissolving in pure water.

[0016] The water-insoluble acylated cellulose derivative is not limited as long as it has an acylated cellulose derivative skeleton and is water-insoluble. Hereinafter, the cellulose derivative before acylation, which is the raw material for producing the water-insoluble acylated cellulose derivative, is referred to as the raw material cellulose derivative. As the raw material cellulose derivative, in addition to cellulose, short-chain acylated celluloses such as acetyl cellulose and acetyl butyl cellulose, short-chain alkyl etherified celluloses such as methyl cellulose and ethyl cellulose, and cellulose modified with a hydroxyalkyl group, a glyceryl ether group, or a (mono)alkyl glyceryl ether group are preferable. More specifically, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, glyceryl cellulose, methyl glyceryl cellulose, etc. can be mentioned. Furthermore, as the raw material cellulose derivative of the water-insoluble acylated cellulose derivative of component (A), those having the following structural units are preferable.

[0017]

Chemical formula

[0018] (In the formula, R' represents a linear or branched alkylene group having 2 to 8 carbon atoms, and n represents a number such that the average addition molar number of R'O per glucose unit is 0.1 to 10)

[0019]

[0020] ​Preferred raw material cellulose derivatives include hydroxyethylcellulose and hydroxypropylcellulose, with hydroxypropylcellulose being more preferred. Furthermore, the mass-average molecular weight (Mw) of the raw material cellulose derivative is preferably 10,000 to 4,000,000, more preferably 100,000 to 3,000,000, and even more preferably 300,000 to 2,000,000, from the viewpoint of solubility in component (C).

[0021] Water-insoluble acylated cellulose derivatives are compounds in which at least a portion of the hydroxyl groups of the above-mentioned raw material cellulose derivative are substituted with the group -O-CO-R, and the cellulose derivative skeleton is acylated. As water-insoluble acylated cellulose derivatives, it is preferable that in the -O-CO-R group, which is a substituent on the hydroxyl groups of the raw material cellulose derivative, R is a linear or branched alkyl or alkenyl group having 3 to 40 carbon atoms.

[0022] Examples of R in the -O-CO-R group of water-insoluble acylated cellulose derivatives include the following (i) to (iv). (i) Examples of linear alkyl groups include butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group, tridecyl group, tetradecyl group, pentadecyl group, hexadecyl group, heptadecyl group, octadecyl group, nonadecyl group, icosyl group, henicosyl group, docosyl group, tricosyl group, tetracosyl group, pentacosyl group, hexacosyl group, heptacosyl group, octacosyl group, nonacosyl group, triacontyl group, hentriacontyl group, dotriacontyl group, tritriacontyl group, tetratriacontyl group, pentatriacontyl group, hexatriacontyl group, heptatriacontyl group, octatriacontyl group, nonatriacontyl group, and tetracontyl group.

[0023] (ii) Examples of branched alkyl groups include methylpentyl group, methylhexyl group, methylheptyl group, methyloctyl group, methylnonyl group, methylundecyl group, methylheptadecyl group, ethylhexadecyl group, methyloctadecyl group, propylpentadecyl group, 2-hexyldecyl group, 2-octyldodecyl, 2-heptylundecyl group, 2-decyltetradecyl group, 2-dodecylhexadecyl group, 2-tetradecyloctadecyl group, and 2-hexadecylicosyl group.

[0024] (iii) Examples of linear alkenyl groups include dodecenyl, tridecenyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, octadecenyl, nonadecenyl, icocenyl, henicocenyl, dococenyl, tricocenyl, tetracocenyl, pentacocenyl, hexacocenyl, heptacocenyl, and octacocenyl groups.

[0025] (iv) Examples of branched alkenyl groups include isotridecenyl group, isooctadecenyl group, isotriacontenyl group, 2-butyloctenyl group, 2-hexyldecenyl group, 2-octyldodecenyl group, 2-decyltetradecenyl group, and 2-dodecylhexadecenyl group.

[0026] Of these, from the viewpoint of film-forming properties, R is preferably a linear alkyl group. Also from the same viewpoint, the number of carbon atoms is preferably 9 to 21, more preferably 11 to 19, even more preferably 13 to 17, and still more preferably 15.

[0027] From the viewpoint of solubility in solvents, the -O-CO-R substitution rate of the hydroxyl group is preferably 45 mol% or more, more preferably 60 mol% or more, and even more preferably 75 mol% or more. From the viewpoint of improving water resistance, it is preferably 96 mol% or less, more preferably 94 mol% or less, and even more preferably 92 mol% or less. Furthermore, the -O-CO-R substitution rate of the hydroxyl group is preferably 45 to 96 mol%, more preferably 60 to 94 mol%, and even more preferably 75 to 92 mol%. A moderate amount of hydroxyl groups remaining is preferable from the viewpoint of the dispersibility of the antibacterial agent, preferably 5 mol% or more, more preferably 6 mol% or more, even more preferably 8 mol% or more, even more preferably 10 mol% or more, preferably 55 mol% or less, more preferably 52 mol% or less, even more preferably 48 mol% or less, and even more preferably 45 mol% or less. Furthermore, the residual rate of hydroxyl groups is preferably 5 to 55 mol%, more preferably 6 to 52 mol%, even more preferably 8 to 48 mol%, and even more preferably 10 to 45 mol%.

[0028] The mass-average molecular weight of the water-insoluble acylated cellulose derivative is preferably 100,000 or more, more preferably 200,000 or more, even more preferably 300,000 or more, even more preferably 500,000 or more, preferably 4,000,000 or less, more preferably 3,000,000 or less, even more preferably 2,000,000 or less, and even more preferably 1,500,000 or less, from the viewpoint of solubility in solvents. The mass-average molecular weight (Mw) is determined by gel permeation chromatography (using chloroform solvent, a calibration curve defined with linear polystyrene as the standard, and a refractive index detector).

[0029] Water-insoluble acylated cellulose derivatives can be purchased commercially, or they can be produced by known chemical synthesis methods. Water-insoluble acylated cellulose derivatives are produced, for example, by reacting a raw material cellulose derivative with an acid halide having a linear or branched alkyl or alkenyl group with 3 to 40 carbon atoms, thereby substituting at least some of the hydroxyl groups of the raw material cellulose derivative.

[0030] Examples of water-insoluble acylated cellulose derivatives include hydroxyethylcellulose laurate, hydroxyethylcellulose myristic acid, hydroxyethylcellulose palmitate, hydroxyethylcellulose stearate, hydroxyethylcellulose behenate; hydroxypropylcellulose laurate, hydroxypropylcellulose myristic acid, hydroxypropylcellulose palmitate, hydroxypropylcellulose stearate, hydroxypropylcellulose behenate; hydroxyethylmethylcellulose laurate, hydroxyethylmethylcellulose myristic acid, hydroxyethylmethylcellulose palmitate, hydroxyethylmethylcellulose stearate, hydroxyethylmethylcellulose behenate; hydroxypropylmethylcellulose laurate, hydroxypropylmethylcellulose myristic acid, hydroxypropylmethylcellulose palmitate, hydroxypropylmethylcellulose stearate, hydroxypropylmethylcellulose behenate, and the like. In particular, from the viewpoint of film-forming properties, hydroxypropylcellulose laurate, hydroxypropylcellulose myristicate, hydroxypropylcellulose palmitate, hydroxypropylcellulose stearate, and hydroxypropylcellulose behenate are preferred, with hydroxypropylcellulose palmitate being more preferred. One or more water-insoluble acylated cellulose derivatives may be used.

[0031] The content of component (A) in the antimicrobial agent composition of the present invention is preferably 0.03% by mass or more, more preferably 0.1% by mass or more, from the viewpoint of antimicrobial agent support, and preferably 40% by mass or less, more preferably 10% by mass or less, from the viewpoint of the stability of the antimicrobial agent composition. Furthermore, the content of component (A) is preferably 0.03 to 40% by mass, and more preferably 0.1 to 10% by mass.

[0032] The antimicrobial composition of the present invention contains an antimicrobial agent as component (B). The antimicrobial agent is not particularly limited, and inorganic antimicrobial agents, natural extract antimicrobial agents, organic, aliphatic, or aromatic compound antimicrobial agents can be used. One or more types of antimicrobial agents can be used. Examples of inorganic antimicrobial agents include metal oxides such as zinc oxide, silver oxide, aluminum oxide, titanium oxide, calcium oxide, and magnesium oxide, as well as silver complexes. Examples of naturally derived antibacterial agents include hinokitiol, chitosan, and catechin. Examples of organic, aliphatic, and aromatic compound antimicrobial agents include quaternary ammonium salts such as dialkyldimethylammonium salts and alkyldimethylammonium salts, isothiazoline antimicrobial agents such as 5-chloro-2-methyl-4-isothiazolin-3-one and 1,2-benzoisothiazolin-3-one (benzisothiazolinone), biguanide antimicrobial agents such as polyhexamethylene biguanide (PHMB), and pyrithione. Here, the alkyl group of the quaternary ammonium salt is a linear alkyl group having 8 to 18 carbon atoms, such as octyl, decyl, dodecyl (lauryl), tetradecyl (myristyl), hexadecyl (cetyl), heptadecyl, and octadecyl (stearyl), with octyl, decyl, and dodecyl being preferred. Furthermore, the ammonium salt is F - Cl - , Br - , I - Halide ions such as NO - SO4 2- Examples include salts with the following substances, preferably salts with halide ions, and more preferably salts with chloride ions.

[0033] The solubility of component (B) in water at room temperature (25°C) is preferably 10 g / L or less, and more preferably 1 g / L or less, from the viewpoint of sustained release.

[0034] When component (B) is a solid at room temperature (25°C), the average particle size of component (B) is preferably 1 μm to 100 μm, and more preferably 5 μm to 60 μm, from the viewpoint of supportability. The average particle size of component (B) can be measured according to conventional methods, for example, by a wet method using a commercially available particle size analyzer. In this specification, the average particle size of component (B) can be measured by the method described in the examples below.

[0035] From the viewpoint of effectiveness, the antibacterial agent of component (B) is preferably an isothiazolinoline-based antibacterial agent (e.g., 1,2-benzoisothiazolin-3-one), zinc pyrithione, or silver oxide.

[0036] The content of component (B) in the antibacterial agent composition of the present invention can be appropriately set depending on the type, but from the viewpoint of antibacterial activity, it is preferably 0.03% by mass or more, and more preferably 0.1% by mass or more.

[0037] The mass ratio of component (A) to component (B) [(B) / (A)] in the antibacterial composition of the present invention is preferably 0.1 or higher, and more preferably 1 or higher, from the viewpoint of antibacterial activity.

[0038] The antimicrobial composition of the present invention contains a solvent as component (C). In this specification, the solvent is a solvent that dissolves a water-insoluble acylated cellulose derivative. Examples of solvents include polar organic solvents and non-polar organic solvents. Examples of polar organic solvents include alcohols such as methanol, ethanol, propanol, isopropanol, butanol, and isobutanol; ketones such as acetone, methyl ethyl ketone, diethyl ketone, and methyl propyl ketone; and polyols such as propylene glycol and triethylene glycol. Examples of non-polar organic solvents include aliphatic hydrocarbons such as paraffinic hydrocarbons, isoparaffinic hydrocarbons, cyclic paraffinic hydrocarbons, olefinic hydrocarbons, and naphthenic hydrocarbons; aromatic hydrocarbons; halogenated hydrocarbons; and ethers such as dimethyl ether, diethyl ether, tetrahydrofuran, and dioxane. From the viewpoint of solubility, nonpolar organic solvents are preferred, aliphatic hydrocarbons are more preferred, and volatile aliphatic hydrocarbons are even more preferred from the viewpoint of quick drying and non-residual properties on the treated surface. Volatility means having a flash point of 35 to 87°C. Examples of volatile aliphatic hydrocarbons include paraffinic hydrocarbons such as n-decane, n-undecane, and n-dodecane; isoparaffinic hydrocarbons such as isodecane, isododecane, and hydrogenated polyisobutene; and cyclic paraffinic hydrocarbons such as cyclodecane and cyclododecane. Of these, volatile aliphatic hydrocarbons having 10 to 16 carbon atoms are preferred, and volatile aliphatic hydrocarbons having 12 carbon atoms are more preferred. Among these, isoparaffinic hydrocarbon oils are preferred, isododecane and hydrogenated polyisobutene with 12 carbon atoms are more preferred, and isododecane is even more preferred. A commercially available example is isododecane (isomer mixture) from Fujifilm Wako Pure Chemical Industries, Ltd. One or more solvents can be used.

[0039] The content of component (C) in the antibacterial agent composition of the present invention is preferably 50% by mass or more, and more preferably 70% by mass or more, from the viewpoint of dissolving component (A) and antibacterial effect.

[0040] In the antibacterial composition of the present invention, the mass ratio of component (A) to component (C) [(C) / (A)] is preferably 10 or more, more preferably 30 or more, from the viewpoint of the solubility of component (A).

[0041] In addition to the components mentioned above, the antibacterial composition of the present invention may contain, in appropriate combinations, additives such as surfactants, polymers, chelating agents, humectants, lubricants, builders, buffers, abrasives, electrolytes, bleaching agents, fragrances, dyes, foaming control agents, corrosion inhibitors, essential oils, thickeners, pigments, gloss enhancers, enzymes, detergents, dispersants, silicones, and hydrophobic substances, as long as they do not impair the effects of the present invention. The content of the additives can be appropriately set within a range that does not impair the objectives of the present invention.

[0042] The antimicrobial composition of the present invention can be manufactured by any suitable method. For example, it can be manufactured by mixing components (A), (B), and (C), and other components as needed. The mixing order of each component is not particularly limited and can be mixed in any order, but from the viewpoint of dissolving component (A), it is preferable to mix component (A) and component (C) first, and then mix component (B).

[0043] The antibacterial composition of the present invention may be in liquid or gel form, but a liquid form is preferred. If a gel form is desired, it can be prepared by appropriately adding a natural gelling agent or a synthetic gelling agent, such as a water-soluble gelling agent like carrageenan or gellan gum, or an oil-soluble gelling agent like a metal soap or aluminum octylate, according to conventionally known methods.

[0044] As shown in the examples below, surface treatment using a composition containing a water-insoluble acylated cellulose derivative, an antibacterial agent, and a solvent forms a highly water-resistant treated film that exhibits excellent antibacterial effects against various microorganisms, including various Gram-positive and Gram-negative bacteria. For example, it shows excellent antibacterial effects against Staphylococcus aureus, Enterococcus faecium, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloacae, and Stenotrophomonas maltophilia. Therefore, a combination of a water-insoluble acylated cellulose derivative, an antimicrobial agent, and a solvent can serve as an active ingredient in an antimicrobial composition and can also be used to manufacture such a composition. Furthermore, by applying a composition containing a water-insoluble acylated cellulose derivative, an antibacterial agent, and a solvent to the target surface, antibacterial properties can be imparted to the target surface.

[0045] The microorganisms targeted by the antimicrobial agent composition of the present invention include a variety of species, such as Gram-positive bacteria, Gram-negative bacteria, or drug-resistant strains thereof. Examples of Gram-positive bacteria include: Bacillus species such as Bacillus subtilis, Bacillus anthracis, and Bacillus cereus; Listeria species such as Listeria monocytogenes, Listeria ivanovii, and Listeria seeligeri; Alicyclobacillus species such as A. acidoterrestris (formerly B. acidoterrestris); Staphylococcus species such as S. aureus; and Streptococcus species such as S. pyogenes. Examples include Clostridium bacteria such as C. botulinum (C. botulinum), C. perfringens (C. perfringens), and C. sporogens; Clostridioides bacteria such as C. difficile; Leuconostoc bacteria such as L. mesenteroides; Desulfotomaculum bacteria such as D. nigrificans; Enterococcus bacteria such as E. faecalis, E. faecium, E. gallinarum, and E. casseriflavus; and Streptococcus bacteria such as Streptococcus pneumoniae. Examples of Gram-negative bacteria include Shigella bacteria such as S. dysenteria (Shigella subgroup A), S. flexneri (Shigella subgroup B), S. boydii (Shigella subgroup C), and S. sonnei (Shigella subgroup D); Brucella bacteria; Escherichia coli such as E. coli O157; S. typhi (S. typhi), S. paratyphi A (S. paratyphi A), and S. paratyphi Examples include Salmonella bacteria such as Salmonella paratyphi B, Salmonella typhimurium, and Salmonella enteritidis; Vibrio bacteria such as Vibrio cholerae and Vibrio parahaemolyticus; Pseudomonas bacteria such as Pseudomonas aeruginosa; Acinetobacter bacteria such as A. baumannii; Klebsiella bacteria such as Klebsiella pneumoniae; Stenotrophomonas bacteria such as S. maltophilia; and Enterobacter bacteria such as E. cloacae. Drug-resistant bacteria include those that exhibit resistance to specific or multiple antibacterial agents, such as MRSA (methicillin-resistant Staphylococcus aureus), PRSP (penicillin-resistant Streptococcus pneumoniae), VRE (vancomycin-resistant enterococci), extended-spectrum β-lactamase (ESBL) producing bacteria, AmpC producing bacteria, MDRP (multidrug-resistant Pseudomonas aeruginosa), CRE (carbapenem-resistant Enterobacteriaceae), CPE (carbapenemase-producing Enterobacteriaceae), and MDRA (multidrug-resistant Acinetobacter). In particular, the present invention is suitable for bacteria of the genera Staphylococcus, Escherichia coli, Enterococcus, Klebsiella, Acinetobacter, Pseudomonas, Enterobacter, and Stenotrophomonas.

[0046] In this invention, "antibacterial" is a term that includes all of the concepts of "sterilization" and "disinfection," which kill microorganisms, and "bacteriostatic" and "antimicrobial" actions, which suppress the occurrence, growth, and proliferation of microorganisms.

[0047] The antibacterial composition of the present invention can be applied to surfaces such as animal skin or mucous membranes to which bacteria adhere, and hard or soft surfaces of inanimate objects. In particular, it is suitable for hard or soft surfaces of inanimate objects. Examples of surfaces of inanimate objects include hard surfaces such as counters, sinks, restrooms, washbasins, toilets, bathtubs, showers, floors, windows, doorknobs, walls, drains, faucets, and pipes in homes and hospitals, as well as handrails and tables; hard surfaces such as kitchenware, furniture, telephones, personal computers, calculators, air purifiers, humidifiers, medical equipment, buttons on various devices, toys and other various tools, tools, miscellaneous goods, and stationery; and soft surfaces such as textile products (carpets, area rugs, curtains, bedding, fabric furniture, clothing, masks, etc.).

[0048] The manner in which the antimicrobial agent composition of the present invention is applied to a target surface is not particularly limited, and any of the following methods may be used: applying the antimicrobial agent composition directly to the target surface; diffusing the antimicrobial agent composition and sprinkling it onto the target surface; or wiping the target surface with a sheet, gauze, towel, wet wipe, tissue, or the like impregnated with the antimicrobial agent composition. Another method involves filling a known spray container, such as a trigger spray container (direct pressure or stored pressure type), a dispenser-type pump spray container, or an aerosol spray container equipped with a pressure-resistant vessel, with the antibacterial composition, and then spraying it onto the target object while appropriately adjusting the spray volume. After applying the antibacterial composition to the target surface, it is preferable to leave it to dry. For example, in areas with water, such as washbasins, it is preferable to leave it for 10 minutes or more. This allows for the formation of a treated film on the target surface that possesses both high water resistance and antibacterial properties.

[0049] The amount of antibacterial agent composition used in the present invention can be appropriately adjusted depending on the treatment method, ambient temperature and humidity, etc., but preferably 25 g / m². 2 That's all. [Examples]

[0050] <Example of manufacturing: Synthesis of hydroxypropylcellulose palmitate> Under nitrogen, at 50°C in a mixed solvent of toluene and methyl ethyl ketone, 57.8 g (0.165 mol) of hydroxypropyl cellulose (Cellney M; manufactured by Nippon Soda Co., Ltd.) was dissolved in 232.8 g (2.5 mol) of 3-methylpyridine. 300.0 g (1.09 mol) of palmitoyl chloride was added dropwise over 0.5 hours. The mixture was then reacted at 50°C for 5 hours, precipitated in ethanol, purified, and dried to obtain hydroxypropyl cellulose palmitate, a water-insoluble acylated cellulose derivative (mass-average molecular weight 870,000, average acyl substitution degree 90 mol% of total hydroxyl groups).

[0051] (Measurement of mass-average molecular weight) The average molecular weight (Mw) of the polymer was measured by gel permeation chromatography (GPC) using a Hitachi L-6000 high-performance liquid chromatography system. A Hitachi L-6000 eluent flow channel pump was used, a Schodex RI SE-61 differential refractive index detector was employed, and a double-connected GMHHR-H column was used. The sample was adjusted to a concentration of 0.5 g / 100 mL with the eluent, and 20 μL was used. The eluent was a chloroform solution of 1 mmol / L N,N-dimethyldodecylamine (Farmin DM20, Kao Corporation). The column temperature was 40°C, and the flow rate was 1.0 mL / min.

[0052] (Measurement of average acyl (ester) substitution degree) In 1H-NMR, the proton of the methyl group adjacent to the carbonyl group of esterified cellulose appears at around 5 ppm, while the sum of the protons adjacent to the oxygen of the 6-membered ring of cellulose and the methylene group adjacent to the hydroxyl group of cellulose appears at around 3.5 ppm. The integral value was calculated from these values.

[0053] <Measurement of particle size of antibacterial agents> The apparatus used was a particle size analyzer LA-950V2 (manufactured by HORIBA). Silver oxide (manufactured by Fujifilm Wako Pure Chemical Industries) was dispersed in ion-exchanged water using a wet method and subjected to measurement while circulating in a flow system. Measurements were performed with N=5, and data were obtained in volume distribution. The average value of the median diameter of three points (d1, d2, d3) after removing the maximum and minimum values ​​was used as the volume-average particle size.

[0054] Test example: Antimicrobial test The information on the components used in the examples is summarized below. Hydroxypropylcellulose palmitate: See the manufacturing example above. Benzisothiazolinone: Manufactured by Fujifilm Wako Pure Chemical Industries, water solubility: 1 g / L, solid at room temperature. Zinc pyrithione: Manufactured by Fujifilm Wako Pure Chemical Industries, water solubility: 15 mg / L, solid at room temperature. Silver oxide: Manufactured by Fujifilm Wako Pure Chemical Industries, water solubility: 13 mg / L, solid at room temperature. Isododecane (isomer mixture): Manufactured by Fujifilm Wako Pure Chemical Industries.

[0055] <Preparation of test specimens> Test specimens made of glass slides and polyethylene terephthalate (PET) were used. For the glass slide specimens, 130 μL of each composition was applied to the transparent portion (61 × 26 [mm]) of a glass slide (MATSUNAMI, Super Frost Glass Slide 76 × 26 [mm] S2441) and air-dried at room temperature. For the PET specimens, PET (Engineering Test Service, 75 × 25 [mm]) was cut in half, 65 μL of each composition was applied to the entire surface, and air-dried at room temperature. After drying, to examine the water resistance of the coating, 200 mL of deionized water was filled into a sterile 200 mL screw-top cup (Eiken Chemical), and each of the obtained test specimens was immersed in it. The white portion of the glass slide and the edges of the PET test specimen were held and shaken for 5 seconds to wash them. This was repeated 10 times per test specimen, and then air-dried at room temperature. On the other hand, a substrate with no coating was used as a control for this slide glass and PET test piece.

[0056] <Antibacterial Testing> [Preparation of bacterial suspension] The following bacterial cells were used for the test. Table 1 shows a list of bacteria used in the antimicrobial testing.

[0057] [Table 1]

[0058] The glycerol stock solutions stored at -80°C shown in Table 1 were pre-cultured at 37°C for 24 hours using Soybean Casein Digest Agar (manufactured by Nippon Pharmaceutical Co., Ltd., SCD agar medium "Daigo"). The following day, colonies were picked and streaked onto fresh SCD agar, and cultured at 37°C for 24 hours. The following day, the colonies were suspended in sterile physiological saline, and the absorbance at a wavelength of 600 nm (OD600nm) was measured using a spectrophotometer (Hitachi High-Technologies Corporation, U-5100) to prepare a solution with OD=1. This solution was then diluted 100-fold with Soybean Casein Digest Broth (Nippon Pharmaceutical Co., Ltd., SCD medium "Daigo") to prepare the bacterial suspension for evaluation.

[0059] [Contact between bacterial solution and treated surface] 100 μL of bacterial suspension was dropped onto each test specimen, and the specimens were sandwiched between other specimens treated with the same agent. These specimens were then placed in a sterile No. 2 square petri dish (140 × 100 × 14.5 [mm]: Eiken Chemical Co., Ltd.) and incubated at 37°C for 18 to 24 hours. The slide glass containing the bacterial suspension was washed with sterile deionized water using a 5 mL pipette, ensuring that the surface with the bacterial suspension was exposed. The surface of the test specimens was swabded using a wipe-check II (Eiken Chemical Co., Ltd.), and the container was vortexed for 30 seconds to suspend the bacterial cells. Bacterial suspensions were prepared by serial dilution in 10-fold increments, and 3 μL of each was added to SCD agar medium packed in a sterile No. 2 square petri dish. These were incubated at 37°C for 18 to 24 hours. In addition, 50 μL of the suspension stock solution was added to SCD agar medium packed in a sterile petri dish (Φ90 × 15 [mm]: manufactured by Ina Optica) to allow detection down to a lower limit of 1.313 [log(cfu / mL)]. The antibacterial activity value was calculated using the following method. Antimicrobial activity value = log{(Number of viable bacteria after 24 hours of incubation in untreated specimen) - (Number of viable bacteria after 24 hours of incubation in treated specimen)}

[0060] Figures 1-3 show the particle size measurements of the antibacterial agents. The average particle size of silver oxide was 29.80 ± 1.37 μm (Figure 1), the average particle size of benzisothiazolinone was 52.82 ± 2.05 μm (Figure 2), and the average particle size of zinc pyrithione was 5.16 ± 0.04 μm (Figure 3). Table 2 shows the results of antibacterial tests for S. aureus and E. coli when they were brought into contact with test specimens that had undergone a water resistance test on a glass surface. Table 3 shows the results of antibacterial tests to determine the lower limit of the concentration of the antibacterial agent used, using test specimens that had undergone a water resistance test on a glass surface. Table 4 shows the results of antibacterial tests targeting combinations of multiple drug-resistant or susceptible bacterial strains using test specimens that had undergone a water resistance test on a glass or PET surface. In the tables, "nt" indicates "not tested."

[0061] [Table 2]

[0062] [Table 3-1]

[0063] [Table 3-2]

[0064] [Table 4]

[0065] <Result> As shown in Tables 2-4, treated films mixed with isododecane, a water-insoluble acylated cellulose derivative, and an antibacterial agent showed remarkable antibacterial effects regardless of whether the bacteria were Gram-positive or Gram-negative, or whether they were drug-resistant or susceptible strains. On the other hand, when the surface was treated with a water-insoluble acylated cellulose derivative without an antibacterial agent, no reduction in bacterial count was observed. This confirms that antibacterial properties are ensured on the surface of treated films mixed with a water-insoluble acylated cellulose derivative and various antibacterial agents.

Claims

1. The following components (A), (B), and (C); (A) Water-insoluble acylated cellulose derivatives (B) Antimicrobial agents (C) Solvent An antimicrobial composition containing the following:

2. The antimicrobial composition according to claim 1, wherein the content of component (A) is 0.03 to 40% by mass.

3. The antibacterial composition according to claim 1, wherein the content of component (B) is 0.03% by mass or more.

4. The antibacterial composition according to claim 1, wherein the content of component (C) is 50% by mass or more.

5. The antimicrobial agent composition according to any one of claims 1 to 4, wherein component (A) is a cellulose derivative having a cellulose skeleton in its main chain, and 45 mol% or more of the total hydroxyl groups are substituted with -O-CO-R (where R represents a linear or branched alkyl or alkenyl group having 3 to 40 carbon atoms).

6. The antibacterial composition according to any one of claims 1 to 4, wherein component (B) is one or more selected from isothiazolinine-based antibacterial agents, zinc pyrithione, and silver oxide.

7. The antimicrobial agent composition according to any one of claims 1 to 4, wherein component (C) is a nonpolar organic solvent.

8. The antimicrobial agent composition according to any one of claims 1 to 4, wherein component (C) is an aliphatic hydrocarbon having 10 to 16 carbon atoms.

9. An antimicrobial composition according to any one of claims 1 to 4 for use against microorganisms including drug-resistant bacteria.

10. The antimicrobial composition according to claim 9, wherein the microorganism is selected from Staphylococcus bacteria, Escherichia coli, Enterococcus bacteria, Klebsiella bacteria, Acinetobacter bacteria, Pseudomonas bacteria, Enterobacter bacteria, and Stenotrophomonas bacteria.

11. A treated film formed on a target surface using the antibacterial composition according to any one of claims 1 to 4.

12. An antimicrobial method comprising applying the antimicrobial agent composition according to any one of claims 1 to 4 to a target surface.

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