Classifications

• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
  • A01N37/06—Unsaturated carboxylic acids or thio analogues thereof; Derivatives thereof
• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N61/00—Biocides, pest repellants or attractants, or plant growth regulators containing substances of unknown or undetermined composition, e.g. substances characterised only by the mode of action
• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
  • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
  • A01P3/00—Fungicides
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
  • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
  • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
  • C08F220/10—Esters
  • C08F220/12—Esters of monohydric alcohols or phenols
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
  • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
  • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
  • C08F220/10—Esters
  • C08F220/34—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate

Definitions

• One aspect of the present invention relates to an antibacterial polymer or an antibacterial polymer composition.
• cationic polymers adsorb to negatively charged cell membranes of bacteria and other organisms, and then cause physical destruction of the cell membranes due to the hydrophobic sites. Therefore, cationic polymers have an antibacterial effect against drug-resistant bacteria and are attracting attention as antibacterial agents that do not produce drug-resistant bacteria. For example, it is known that in methacrylic polymers having cationic groups, the antibacterial properties improve as the alkyl chain length of the side chain becomes longer and the hydrophobicity becomes higher (for example, Non-Patent Documents 1 and 2).
• Non-Patent Documents 1 and 2 report that it has high hemolytic properties that destroy red blood cells in the blood, and low blood compatibility.
• One aspect of the present invention provides an antibacterial polymer that is both antibacterial and blood compatible and suppresses the elution of components into the body, and an antibacterial polymer composition that contains the antibacterial polymer.
• An example embodiment of the present invention is as follows.
• An antibacterial polymer having a cationic group and an alkyl group having 8 to 30 carbon atoms The content of the structural unit having a cationic group relative to 100% by mass of the antibacterial polymer is 10% by mass or more and less than 51% by mass, The content of the structural unit having an alkyl group having 8 to 30 carbon atoms is 30% by mass or more and less than 90% by mass.
• An antibacterial polymer composition comprising the antibacterial polymer described in any one of [1] to [10].
• an antibacterial polymer and an antibacterial polymer composition which have both antibacterial properties and blood compatibility and exhibit extremely low elution of components into the body.
• the antibacterial polymer according to one embodiment of the present invention has excellent flexibility and conformability, and therefore can be suitably used as a material for attaching to biological surfaces such as curved surfaces, movable parts, and wounds (for example, wound dressings).
• (meth)acrylic is used as a general term for acrylic and methacrylic, and may be either acrylic or methacrylic.
• (meth)acrylate is used as a general term for acrylate and methacrylate, and may be either acrylate or methacrylate.
• (meth)acryloyl is used as a general term for acryloyl and methacryloyl, and may be either acryloyl or methacryloyl.
• the antibacterial polymer according to one embodiment of the present invention (hereinafter also referred to as "the present polymer”) has a cationic group and an alkyl group having 8 to 30 carbon atoms.
• the antibacterial polymer is also characterized in that the content of the structural unit having a cationic group is 10% by mass or more and less than 51% by mass, and the content of the structural unit having an alkyl group having 8 to 30 carbon atoms is 30% by mass or more and less than 90% by mass, relative to 100% by mass of the antibacterial polymer.
• the monomer mixture that is the raw material of the present polymer contains 10% by mass or more and less than 51% by mass of the monomer having the cationic group and 30% by mass or more and less than 90% by mass of the monomer having an alkyl group having 8 to 30 carbon atoms.
• antibacterial refers to the ability to bactericidal (kill microorganisms), bacteriostatic (suppress the growth of microorganisms), sterilization, disinfection, bacteriostatic, antibacterial, antiseptic, antifungal, etc.
• the target microorganisms are bacteria and fungi.
• the bacteria include gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, Salmonella, Moraxella, Legionella, etc.; and gram-positive bacteria such as Staphylococcus aureus and Clostridium bacteria.
• yeasts such as Candida, Rhodotorula, and baker's yeast
• molds such as red mold and black mold.
• the present polymer exhibits the above-mentioned effects is not entirely clear, but is presumed to be, for example, as follows.
• the cationic group e.g., quaternary ammonium salt
• the present polymer is adsorbed to the negatively charged surface of the microorganism.
• the hydrophobic group which is an alkyl group having 8 to 30 carbon atoms, of the present polymer exhibits affinity for the cell membrane portion and interacts with the cell membrane, destroying the interaction between lipids and the like that compose the cell membrane and/or inhibiting the function of proteins and the like bound to the membrane, thereby destroying the cell and/or inhibiting the physiological activity of the cell, and thus killing the microorganism.
• animal cells are larger than bacteria and are known to be highly resistant to physical external stimuli.
• this polymer does not have the destructive power to destroy animal cells, it can destroy bacteria without any problems and is thought to have the characteristic of being selective in destroying certain cell types. Therefore, this polymer is presumed to have the function of having excellent antibacterial properties as well as good blood compatibility.
• the present polymer has a cationic group in the polymer molecule. That is, the present polymer has a constituent unit having the cationic group.
• the constituent unit having the cationic group may be derived from a monomer having the cationic group, or may be a constituent unit derived from a monomer not having the cationic group, in which a functional group in the constituent unit is converted into a cationic group.
• the monomer having a cationic group may have at least one ethylenically unsaturated group and one cationic group, and examples thereof include (meth)acrylic acid esters having a cationic group, (meth)acrylamides having a cationic group, styrene-based monomers having a cationic group, and vinyl ester compounds having a cationic group. Of these, (meth)acrylic acid esters having a cationic group and (meth)acrylamides having a cationic group are preferred, and (meth)acrylic acid esters having a cationic group are more preferred.
• Examples of the cationic group include imidazolium salts, pyrrolidinium salts, pyridinium salts, piperidinium salts, morphonium salts, phosphonium salts, sulfonium salts, and ammonium salts, preferably ammonium salts, more preferably quaternary ammonium salts, and particularly preferably quaternary ammonium salts represented by the following general formula (1).
• the cationic group is a quaternary ammonium salt, it is less susceptible to the effects of external environments such as pH, and therefore a polymer with consistent antibacterial properties tends to be obtained regardless of the usage environment.
• R 5 to R 7 each independently represent a hydrocarbon group having 1 to 30 carbon atoms
• Y ⁇ represents an anion
• * represents a bond.
• the hydrocarbon group may be an alkyl group, an alkenyl group, an aryl group, or a combination thereof, and is preferably an alkyl group or an alkenyl group.
• the number of carbon atoms in the hydrocarbon group is preferably 1 to 22.
• alkyl group examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, n-octyl, isooctyl, 2-ethylhexyl, n-nonyl, isononyl, n-decyl, isodecyl, undecyl, lauryl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, n-stearyl, isostearyl, nonadecyl, eicosyl, henicosyl, and docosyl.
• Examples of the alkenyl group include a vinyl group, an allyl group, a propenyl group, an isopropenyl group, a 2-methyl-1-propenyl group, a 2-methylallyl group, and a 2-butenyl group.
• Examples of the aryl group include a phenyl group, a naphthyl group, and a pyrene group.
• Examples of the group consisting of a combination of the alkyl group, the alkenyl group, and the aryl group include a benzyl group, a phenylethyl group, a tolyl group, and a xylyl group.
• Examples of the Y ⁇ include halide ions such as chloride ion, bromide ion, and iodine ion; alkyl sulfate ions such as methyl sulfate ion; sulfonate ions such as methanesulfonate ion, trifluoromethanesulfonate ion, and p-toluenesulfonate ion; boron ions such as tetrahydroborate ion; nitrogen ions such as dicyanamide ion and bis(trifluoromethanesulfonyl)imide; phosphorus ions such as hexafluorophosphorus ion; and ions of organic acids such as acetate ion, formate ion, lactate ion, and fumaric acid.
• the Y ⁇ is not particularly limited as long as it is an anion, but is preferably a halide, an alkyl s
• the monomer having the quaternary ammonium salt may have at least one ethylenically unsaturated group and one quaternary ammonium salt, and examples thereof include (meth)acrylic acid ester having a quaternary ammonium salt, (meth)acrylamide having a quaternary ammonium salt, and styrene having a quaternary ammonium salt, and preferably (meth)acrylic acid ester having a quaternary ammonium salt, and (meth)acrylamide having a quaternary ammonium salt, and more preferably (meth)acrylic acid ester having a quaternary ammonium salt.
• Examples of the (meth)acrylic acid ester having a quaternary ammonium salt include monomers obtained by adding a quaternizing agent to N,N-dialkylamino group-containing (meth)acrylates such as N,N-dimethylaminoethyl (meth)acrylate, N,N-diethylaminoethyl (meth)acrylate, N,N-dimethylaminopropyl (meth)acrylate, and N,N-diethylaminopropyl (meth)acrylate.
• N,N-dialkylamino group-containing (meth)acrylates such as N,N-dimethylaminoethyl (meth)acrylate, N,N-diethylaminoethyl (meth)acrylate, N,N-dimethylaminopropyl (meth)acrylate, and N,N-diethylaminopropyl (meth)acrylate.
• AETAC [2-(acryloyloxy)ethyl]trimethylammonium chloride
• METAC [2-(methacryloyloxy)ethyl]trimethylammonium chloride
• DAEA-BQ [2-(methacryloyloxy)ethyl]-N-benzyl-N,N-dimethylammonium chloride
• Examples of (meth)acrylamides having a quaternary ammonium salt include monomers obtained by adding a quaternizing agent to N,N-dialkylamino group-containing (meth)acrylamides such as N,N-dimethylaminoethyl(meth)acrylamide, N,N-diethylaminoethyl(meth)acrylamide, N,N-dimethylaminopropyl(meth)acrylamide, and N,N-diethylaminopropyl(meth)acrylamide.
• N,N-dialkylamino group-containing (meth)acrylamides such as N,N-dimethylaminoethyl(meth)acrylamide, N,N-diethylaminoethyl(meth)acrylamide, N,N-dimethylaminopropyl(meth)acrylamide, and N,N-diethylaminopropyl(meth)acrylamide.
• DMAPAA-Q (3-acrylamidopropyl)trimethylammonium chloride
• DMAPAA-TSMQ (3-acrylamidopropyl)trimethyl methylammonium p-toluenesulfonate
• the addition method may be, for example, a method using a quaternizing agent, or a known method such as a method using a substitution reaction may be used.
• the monomer not having a quaternary ammonium salt is not particularly limited as long as it is a monomer having a functional group that can add a quaternary ammonium salt to the polymer molecule by any of the above methods, but is preferably (meth)acrylic acid esters, (meth)acrylamides, or styrenes having such functional groups, more preferably (meth)acrylic acid esters and (meth)acrylamides, and even more preferably (meth)acrylic acid esters.
• Examples of (meth)acrylic acid esters having a functional group to which a quaternary ammonium salt can be added include N,N-dialkylamino group-containing (meth)acrylates such as N,N-dimethylaminoethyl (meth)acrylate, N,N-diethylaminoethyl (meth)acrylate, N,N-dimethylaminopropyl (meth)acrylate, and N,N-diethylaminopropyl (meth)acrylate; and aliphatic heterocycle-containing (meth)acrylates such as glycidyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate glycidyl ether, (3-ethyloxetan-3-yl)methyl (meth)acrylate, 2-piperidineethyl (meth)acrylate, and 1,2,2,6,6-pentamethyl-4-piperidyl (meth)acrylate.
• Examples of (meth)acrylamides having a functional group to which a quaternary ammonium salt can be added include (meth)acrylamides containing N,N-dialkylamino groups, such as N,N-dimethylaminoethyl (meth)acrylamide, N,N-diethylaminoethyl (meth)acrylamide, N,N-dimethylaminopropyl (meth)acrylamide, and N,N-diethylaminopropyl (meth)acrylamide.
• styrenes having functional groups to which quaternary ammonium salts can be added include halogen-containing styrenes such as p-chloromethylstyrene.
• the quaternizing agent is not particularly limited as long as it is a known agent, but examples thereof include organic halogen compounds such as methyl chloride, ethyl chloride, benzyl chloride, methyl bromide, benzyl bromide, and methyl iodide; alkylating agents such as alkyl sulfates such as dimethyl sulfate, diethyl sulfate, and di-n-propyl sulfate; alkylating agents such as methyl methanesulfonate, methyl trifluoromethanesulfonate, and methyl p-toluenesulfonate; and tertiary amine compounds such as triethylamine, dimethylaminoethanol, and diethylaminoethanol.
• organic halogen compounds such as methyl chloride, ethyl chloride, benzyl chloride, methyl bromide, benzyl bromide, and methyl i
• the present polymer may contain one type of structural unit having a cationic group, or two or more types of structural units having a cationic group.
• the content of the structural unit having a cationic group relative to 100% by mass of the present polymer is from 10% by mass to less than 51% by mass, preferably from 10% by mass to 50% by mass, more preferably from 12% by mass to 48% by mass, and even more preferably from 15% by mass to 46% by mass.
• the content of the cationic group in the present polymer varies depending on the molecular weight of the cationic group, but is preferably 1.0 ⁇ 10 ⁇ 4 to 50 ⁇ 10 ⁇ 4 mol/g.
• the content of the quaternary ammonium salt in the polymer is preferably 5.2 ⁇ 10 -4 to 18.9 ⁇ 10 -4 mol/g, more preferably 5.5 ⁇ 10 -4 to 18.4 ⁇ 10 -4 mol/g, and even more preferably 6 ⁇ 10 -4 to 18 ⁇ 10 -4 mol/g.
• the content of the quaternary ammonium salt-containing structural unit or the quaternary ammonium salt is within the above range, a polymer that has both antibacterial properties and blood compatibility and is excellent in flexibility and conformability tends to be obtained.
• the present polymer has an alkyl group having 8 to 30 carbon atoms in the polymer molecule. That is, the present polymer has a structural unit having the alkyl group having 8 to 30 carbon atoms.
• the structural unit having an alkyl group having 8 to 30 carbon atoms is usually a structural unit derived from a monomer having the alkyl group having 8 to 30 carbon atoms.
• the alkyl group having 8 to 30 carbon atoms may, for example, be a linear alkyl group, a branched alkyl group, or a cyclic alkyl group, and specific examples thereof include n-octyl, iso-octyl, 2-ethylhexyl, n-nonyl, iso-nonyl, n-decyl, iso-decyl, undecyl, lauryl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, n-stearyl, iso-stearyl, nonadecyl, eicosyl, docosyl, isobornyl, and adamantyl.
• the number of carbon atoms in the hydrocarbon group is preferably 8 to 25, and more preferably 8 to 20.
• the monomer having an alkyl group with 8 to 30 carbon atoms may have at least one ethylenically unsaturated group and one alkyl group with 8 to 30 carbon atoms, and examples thereof include (meth)acrylic acid esters having an alkyl group with 8 to 30 carbon atoms, (meth)acrylamides having an alkyl group with 8 to 30 carbon atoms, styrene-based monomers having an alkyl group with 8 to 30 carbon atoms, and vinyl ester compounds having an alkyl group with 8 to 30 carbon atoms, and preferably (meth)acrylic acid esters having an alkyl group with 8 to 30 carbon atoms.
• Examples of (meth)acrylic acid esters having an alkyl group having 8 to 30 carbon atoms include n-octyl (meth)acrylate, iso-octyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, n-nonyl (meth)acrylate, iso-nonyl (meth)acrylate, n-decyl (meth)acrylate, n-nonyl (meth)acrylate, iso-nonyl (meth)acrylate, n-decyl (meth)acrylate, iso-decyl (meth)acrylate, lauryl (meth)acrylate, tridecyl (meth)acrylate, n-stearyl (meth)acrylate, iso-stearyl (meth)acrylate, doco Examples of such acrylates include silyl (meth)acrylate and isobornyl (meth)acrylate, and preferably n
• the present polymer may contain one type of structural unit having an alkyl group having 8 to 30 carbon atoms, or two or more types of structural units.
• the content of the structural units having an alkyl group having 8 to 30 carbon atoms relative to 100% by mass of the present polymer is 30% by mass or more and less than 90% by mass, preferably 35% by mass or more and 88% by mass or less, and more preferably 40% by mass or more and 85% by mass or less.
• the content of the structural units having an alkyl group having 8 to 30 carbon atoms or the alkyl group having 8 to 30 carbon atoms is within the above range, there is a tendency that both antibacterial properties and blood compatibility can be achieved, and elution of components into the living body can be suppressed.
• the present polymer may contain other structural units in addition to the structural unit having a cationic group and the structural unit having an alkyl group having 8 to 30 carbon atoms, as long as the effects of the present invention are not impaired.
• the monomer that provides the other structural unit is not particularly limited as long as it does not have a cationic group and does not have an alkyl group having 8 to 30 carbon atoms and can be copolymerized with the cationic group-containing monomer and the alkyl group-containing monomer having 8 to 30 carbon atoms.
• (meth)acrylic acid esters having an alkyl group having 1 to 7 or 31 or more carbon atoms such as methyl (meth)acrylate, ethyl (meth)acrylate, n-butyl (meth)acrylate, iso-butyl (meth)acrylate, tert-butyl (meth)acrylate, hexyl (meth)acrylate, cyclohexyl (meth)acrylate, and heptyl (meth)acrylate
• alkoxy group-containing (meth)acrylates such as methoxymethyl (meth)acrylate and 2-methoxyethyl (meth)acrylate; 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 4-hydroxypropyl (meth)acrylate, and the like.
• Hydroxyl group-containing (meth)acrylates such as dimethylaminoethyl (meth)acrylate and diethylaminoethyl (meth)acrylate; amino group-containing (meth)acrylates such as dimethylaminoethyl (meth)acrylate and diethylaminoethyl (meth)acrylate; carboxyl group-containing monomers such as acrylic acid, methacrylic acid, ⁇ -carboxyethyl (meth)acrylate, 5-carboxypentyl (meth)acrylate, succinic acid mono(meth)acryloyloxyethyl ester, ⁇ -carboxypolycaprolactone mono(meth)acrylate, crotonic acid, maleic acid, fumaric acid, itaconic acid, and citraconic acid; (meth)acrylamide; N-methyl(meth)acrylamide N-alkyl(meth)acrylamides such as N-ethyl(meth)acrylamide,
• the monomers include cyano group-containing monomers such as tacrylonitrile; styrene-based monomers having an alkyl group having 1 to 7 or 31 or more carbon atoms, such as styrene, ⁇ -methylstyrene, p-methylstyrene, p-chlorostyrene, p-chloromethylstyrene, p-methoxystyrene, p-tert-butoxystyrene, divinylbenzene, and indene; vinyl ester compounds having an alkyl group having 1 to 7 or 31 or more carbon atoms, such as vinyl acetate, vinyl propionate, vinyl butyrate, vinyl caproate, vinyl benzoate, and vinyl cinnamate; and heavy metal salts of unsaturated carboxylic acids, such as zinc acrylate, zinc methacrylate, and zinc ⁇ -allyloxyacrylate.
• cyano group-containing monomers such as tacrylonitrile
• examples of the monomer include macromonomers having a radical polymerizable vinyl group at the monomer end obtained by polymerizing a vinyl group (e.g., poly(meth)acrylic macromonomers, polyalkylene glycol macromonomers, fluorine-based macromonomers, silicon-containing macromonomers, etc.).
• macromonomers having a radical polymerizable vinyl group at the monomer end obtained by polymerizing a vinyl group e.g., poly(meth)acrylic macromonomers, polyalkylene glycol macromonomers, fluorine-based macromonomers, silicon-containing macromonomers, etc.
• the present polymer may contain one or more types of the other structural units described above, provided that the effects of the present invention are not impaired.
• the content of the other structural units relative to 100% by mass of the present polymer is 0.01 to 60% by mass, preferably 0.05 to 50% by mass, and more preferably 0.1 to 40% by mass.
• the present polymer can be synthesized by polymerizing the above-mentioned monomer mixture, and may be, for example, any of random polymer, alternating polymer, block polymer, and graft polymer, and can be synthesized by various polymerization methods.
• the polymerization method is not particularly limited, and examples thereof include solution polymerization, bulk polymerization, emulsion polymerization, and suspension polymerization. Among these, when using the mixture of copolymers obtained by polymerization to produce the present composition, it is preferable to polymerize by solution polymerization, from the viewpoint that the processing step is relatively simple and can be performed in a short time.
• a specific example of solution polymerization is a method in which a monomer mixture, a polymerization initiator, and, if necessary, other components such as a chain transfer agent and polymerization solvent are charged into a reaction vessel, the reaction initiation temperature is set to usually 20 to 100°C, preferably 30 to 80°C, and the reaction system is maintained at a temperature of usually 30 to 90°C, preferably 40 to 90°C, for 1 to 20 hours.
• the reaction is carried out, for example, in an inert gas atmosphere such as nitrogen gas.
• at least one selected from the monomer mixture, polymerization initiator, chain transfer agent, and polymerization solvent may be additionally added during the polymerization reaction.
• Examples of the polymerization initiator include an azo-based initiator and a peroxide-based polymerization initiator.
• Examples of the azo initiator include 2,2'-azobisisobutyronitrile, 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile), 2,2'-azobis(2-cyclopropylpropionitrile), 2,2'-azobis(2,4-dimethylvaleronitrile), 2,2'-azobis(2-methylbutyronitrile), 1,1'-azobis(cyclohexane-1-carbonitrile), 2-(carbamoylazo)isobutyronitrile, and 2-phenylazo-4-methoxy-2,4-dimethyl.
• azo compounds include valeronitrile, 2,2'-azobis(2-amidinopropane) dihydrochloride, 2,2'-azobis(N,N'-dimethyleneisobutylamidine), 2,2'-azobis[2-methyl-N-(2-hydroxyethyl)-propionamide], 2,2'-azobis(isobutylamide) dihydrate, 4,4'-azobis(4-cyanopentanoic acid), 2,2'-azobis(2-cyanopropanol), and dimethyl-2,2'-azobis(2-methylpropionate).
• peroxide polymerization initiators examples include tert-butyl hydroperoxide, cumene hydroperoxide, dicumyl peroxide, benzoyl peroxide, lauroyl peroxide, caproyl peroxide, di-i-propyl peroxydicarbonate, di-2-ethylhexyl peroxydicarbonate, tert-butyl peroxypivalate, 2,2-bis(4,4-di-tert-butylperoxycyclohexyl ) propane, 2,2-bis(4,4-di-tert-amylperoxycyclohexyl)propane, 2,2-bis(4,4-di-tert-octylperoxycyclohexyl)propane, 2,2-bis(4,4-di- ⁇ -cumylperoxycyclohexyl)propane, 2,2-bis(4,4-di-tert-butylperoxycyclohexyl)butane, and 2,2-
• the polymerization initiator may be used alone or in combination of two or more.
• the polymerization initiator may be added multiple times during the polymerization.
• the amount of the polymerization initiator used is preferably 0.001 to 5 parts by mass, more preferably 0.005 to 3 parts by mass, based on 100 parts by mass of the monomer mixture.
• polymerization solvents used in solution polymerization include aromatic hydrocarbons such as benzene, toluene, and xylene; aliphatic hydrocarbons such as n-pentane, n-hexane, n-heptane, and n-octane; alicyclic hydrocarbons such as cyclopentane, cyclohexane, cycloheptane, and cyclooctane; ethers such as diethyl ether, diisopropyl ether, 1,2-dimethoxyethane, dibutyl ether, tetrahydrofuran, dioxane, anisole, phenylethyl ether, and diphenyl ether; halogenated hydrocarbons such as chloroform, carbon tetrachloride, 1,2-dichloroethane, and chlorobenzene; esters such as ethyl acetate, propyl acetate,
• the present polymer is preferably a (meth)acrylic copolymer.
• the "(meth)acrylic (co)polymer” is a (co)polymer derived from a polymerizable monomer containing at least a (meth)acrylic acid ester. That is, it is preferable that one or more of the constitutional units of the present polymer are derived from a (meth)acrylic acid ester, and it is particularly preferable that all of the constitutional units of the present polymer are derived from a (meth)acrylic acid ester.
• the weight average molecular weight (Mw) of the present polymer measured by gel permeation chromatography (GPC) is preferably from 10,000 to 2,000,000, more preferably from 50,000 to 1,500,000, and even more preferably from 100,000 to 1,000,000.
• Mw is within the above range, a polymer having excellent mechanical strength tends to be easily formed.
• the glass transition temperature (Tg) of the present polymer is preferably 50°C or lower, more preferably from -80 to 40°C, and even more preferably from -60 to 20°C.
• the glass transition temperature (Tg) can be determined by measurement using an analytical instrument such as differential scanning calorimetry (DSC) or by calculation using the Fox equation.
• Tg is the glass transition temperature (unit: K) of the present polymer
• Tg1 , Tg2 , ..., Tgm are the glass transition temperatures (unit: K) of homopolymers formed from each monomer
• W1 , W2 , ..., Wm are the mass fractions of the constitutional units derived from each monomer in the present polymer.
• the mass fractions of the constitutional units derived from each monomer can be determined by the ratio of each monomer to the total monomers used in synthesizing the present polymer.
• the glass transition temperature of a homopolymer prepared from a monomer can be, for example, an actual measurement value by differential scanning calorimetry (DSC) or a value in a known document such as Polymer Handbook Fourth Edition (Wiley-Interscience, 2003).
• DSC differential scanning calorimetry
• Tg glass transition temperature
• the content of components insoluble in water at 25°C (water-insoluble components) relative to 100% by mass of the present polymer is preferably 90% by mass or more, more preferably 93% by mass, and even more preferably 95% by mass.
• the content of the water-insoluble components is specifically calculated by the method described in the examples below.
• the hemolysis rate of the present polymer is preferably 20% or less, more preferably 15% or less, and further preferably 10% or less. When the hemolysis rate is within the above range, destruction of living cells is suppressed when the polymer is applied to a living body.
• the hemolysis rate is a value calculated by performing a blood compatibility test in accordance with the method described in the following literature (Y. Kotsuchibashi et al., ACS Omega 2021, 6, 17531-17544). The blood compatibility test is specifically performed by the method described in the following examples.
• the antibacterial activity value R of this polymer against at least one bacterium selected from the group consisting of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa is 2.0 or more, preferably 2.3 or more, and more preferably 2.5 or more.
• Methicillin-resistant Staphylococcus aureus is classified as a gram-positive bacterium, and Pseudomonas aeruginosa is classified as a gram-negative bacterium, and it is preferable from the viewpoint of antibacterial properties that the antibacterial activity value R against both bacteria is within the above range.
• An antibacterial polymer composition according to one embodiment of the present invention (hereinafter also referred to as "the present composition") is characterized by containing the present polymer.
• the content of the present polymer in the present composition is preferably 50 to 99.98% by mass, and more preferably 70 to 99.95% by mass, based on 100% by mass of the present composition.
• the present composition may contain other components other than the present polymer, such as polymers other than the present polymer, alkali regulators, surfactants, stabilizers, thickeners, curing agents, thermal polymerization initiators, photopolymerization initiators, pigments, and fillers, within the scope of not impairing the effects of the present invention.
• the composition may further contain inorganic substances such as metal salts, metal oxides, metal hydroxides, and metal particles, and organic substances such as benzalkonium chloride.
• metals in the metal salts, metal oxides, and metal hydroxides heavy metals such as copper, zinc, and silver are preferred.
• Each of these other components may be used alone or in combination of two or more.
• the content of these other components is not particularly limited as long as it does not impair the effects of the present invention, but it is preferably 0.01 to 20 parts by mass per 100 parts by mass of the present polymer.
• the present composition can be produced, for example, by mixing the present polymer and, if necessary, the other components described above, by a known method using a stirring device or the like.
• the components may be mixed and stirred all at once or sequentially.
• the stirring conditions are not particularly limited, but from the standpoint of workability and productivity, stirring for about 10 to 120 minutes at room temperature is sufficient.
• the present polymer and composition are antibacterial and blood compatible, do not elute components into the living body, and have excellent flexibility and conformability, and therefore can be suitably used as a biological surface adhesive.
• the biological surface adhesive can be used, for example, in pharmaceutical, veterinary, surgical, and cosmetic applications.
• the biological surface adhesive can be used as a wound dressing used to cover a wound in order to treat the wound.
• the biological surface adhesive can be used by covering a catheter, an intravenous injection needle, or an inter-arterial injection needle and placing it on the biological surface in order to stabilize the catheter, an intravenous injection needle, or an inter-arterial injection needle that is at least partially inserted into a subject (for example, into a lumen of the subject).
• the biological surface adhesive can also be used to fix a medical device to a subject.
• the biological surface adhesive materials include transdermal drugs such as analgesics and anti-inflammatory agents (e.g., plasters and poultices), ischemic heart disease treatments, female hormone supplements, bronchodilators, cancer pain relievers, smoking cessation aids, cold patches, antipruritic patches, and keratin softeners; various tape applications such as first aid bandages (containing disinfectants), surgical dressings and surgical tapes, bandages, hemostatic tapes, tapes for human waste disposal devices (e.g., artificial anus fixation tapes), suture tapes, antibacterial tapes, fixation taping, self-adhesive bandages, oral mucosa adhesive tapes, sports tapes, and hair removal tapes; beauty (cosmetic) applications such as face packs, eye moisturizing sheets, keratin peeling packs, shampoos, rinses, lotions, milky lotions, creams, sunscreens, foundations, and eye makeup products; cooling sheets and heating pads.
• transdermal drugs such as analgesics and
• DSC differential scanning calorimeter
• ⁇ Blood compatibility> The polymers obtained in the Examples and Comparative Examples were dissolved in ethanol on a PET film, applied using a bar coater, and dried at 105°C for 5 minutes to prepare a resin layer with a dry thickness of 2 ⁇ m, which was then processed to a size of 1 ⁇ 1 cm2 to obtain a test film.
• a blood compatibility test was carried out according to the following procedure. (1) 1.5 mL of rabbit red blood cells (Cosmo Bio Co., Ltd.) were dispersed in 10 mL of phosphate buffered saline (PBS) and washed using a centrifuge (3000 rpm, 5 min).
• PBS phosphate buffered saline
• a test solution for positive control (P.C., hemolysis rate 100%) was prepared by dissolving 40 mg of Triton X (manufactured by Nacalai Tesque, Inc.) in 10 mL of PBS.
• P.C. hemolysis rate 100%
• One sheet of each test film was placed in a 15 mL centrifuge tube, and 400 ⁇ L of the dispersion obtained in (1) and 400 ⁇ L of PBS were dropped into the tube.
• ⁇ Antibacterial> The polymers obtained in the Examples and Comparative Examples were tested in accordance with JIS Z 2801 to calculate the antibacterial activity value R.
• the bacterial species used in the test were Methicillin-resistant Saphylococcus aureus (MRSA) JCM 8702 and Pseudomonas aeruginosa NBRC 3080.
• Example 1 A reaction apparatus equipped with a stirrer, a reflux condenser, a thermometer, and a nitrogen inlet tube was charged with 30.5 parts by mass of [2-(methacryloyloxy)ethyl]trimethylammonium chloride (METAC: product name "DQ-100 (NN)” manufactured by Kyoeisha Chemical Co., Ltd.), 69.5 parts by mass of lauryl methacrylate, and 100 parts by mass of ethanol (product name "Neocoal R7" manufactured by Japan Alcohol Sales Co., Ltd.) as a solvent, and the temperature was raised to 70°C while introducing nitrogen gas.
• METAC product name "DQ-100 (NN)” manufactured by Kyoeisha Chemical Co., Ltd.
• ethanol product name "Neocoal R7” manufactured by Japan Alcohol Sales Co., Ltd.
• Example 2 Comparative Examples 1 to 3
• Polymers were obtained in the same manner as in Example 1, except that the types and amounts of the monomers used were changed as shown in Table 1.
• Each of the obtained polymers was subjected to various evaluations according to the above-mentioned methods. The results are shown in Table 1.
• Example 3 Comparative Example 4
• Polymers were obtained in the same manner as in Example 1, except that the types and amounts of monomers used were changed as shown in Table 1, and the solvent was changed to propylene glycol monomethyl ether (product name "Glycol Ether PM", manufactured by Lyondell).
• Various evaluations were performed on each of the obtained polymers according to the above-mentioned methods. The results are shown in Table 1.
• METAC [2-(methacryloyloxy)ethyl]trimethylammonium chloride (Tg of homopolymer: 167° C.)
• AETAC [2-(acryloyloxy)ethyl]trimethylammonium chloride (Tg of homopolymer: 118° C.)
• LMA Lauryl methacrylate (Tg of homopolymer: -28°C) 2EHA: 2-ethylhexyl acrylate (Tg of homopolymer: -70°C)
• BA n-butyl acrylate (Tg of homopolymer: -56°C)
• MAA methacrylic acid (Tg of homopolymer: 185° C.)

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