JP7664607B2 - Virus inactivation structure - Google Patents

Description

Application of Article 30, Paragraph 2 of the Patent Act Posted on the website https://www.amed.go.jp/news/topics/covid19_06.html on December 24, 2020

Application of Article 30, Paragraph 2 of the Patent Act Posted on January 4, 2021, on the website https://www. tsuruoka-nct. ac. jp/wp-content/uploads/2020/12/20210104-r. pdf

Application of Article 30, Paragraph 2 of the Patent Act Published on the front page of Shonai Nippo, January 9, 2021, January 9, 2021

The present invention relates to a virus inactivation structure that has a high virus inactivation function and can maintain this high virus inactivation function for a long period of time.

Many viral diseases such as influenza, measles, and chickenpox are easily transmitted by viruses attached to everyday objects, droplet infection, droplet nuclei infection, etc. For this reason, measures against viral infections are a major issue in modern society. As an attempt to prevent viral infections, for example, Patent Document 1 proposes compounds that have virus inactivation properties.

On the other hand, the global spread of the novel coronavirus (COVID-19) has become a major issue that is forcing changes in social life, and from the perspective of quickly and stably calming the global spread of infectious diseases caused by viruses such as the novel coronavirus (COVID-19), there is a strong demand for materials that have high virus inactivation properties and can maintain this high virus inactivation property for the long term.

JP 2020-128342 A

The present invention was made in consideration of these circumstances, and its purpose is to provide a virus inactivation structure that has a high virus inactivation function and can maintain this high virus inactivation function for a long period of time.

As a result of intensive research conducted by the inventors to achieve the above object, they discovered that a polymer brush structure containing multiple polymer chains having functional groups selected from ionic groups, nonionic hydrophilic groups, and electron-donating groups has a high virus inactivation function, and furthermore, that this high virus inactivation function can be sustained for a long period of time, which led to the completion of the present invention.

That is, the present invention relates to the following.
[1] A virus inactivation structure having a virus inactivation function, which comprises a polymer brush structure including a plurality of polymer chains each having a functional group selected from an ionic group, a nonionic hydrophilic group, and an electron-donating group.
[2] The virus inactivating structure according to [1], wherein the plurality of polymer chains are water-soluble.
[3] The virus inactivating structure according to [1] or [2], wherein a plurality of the polymer chains are fixed onto a substrate by covalent bonds to form a polymer brush structure.
[4] The virus inactivating structure according to [3], wherein a ratio (T _b /L _p ) of a thickness T _b of the polymer brush structure to an average molecular chain length L _p of the polymer chains constituting the polymer brush structure is 0.001 to 0.6.
[5] The virus inactivation structure according to [3] or [4], wherein the substrate is a fiber, a monofilament, a twisted yarn, a woven fabric, a nonwoven fabric, a cut fiber, a hollow fiber, glass, a metal, or a processed product thereof.
[6] The virus inactivation structure according to [1] or [2], wherein at least one end of each of the multiple polymer chains is present in the base polymer and at least a portion of the polymer chains is exposed from the base polymer, thereby forming a polymer brush structure.
[7] The virus inactivating structure according to [1] or [2], wherein the plurality of polymer chains are polymer graft chains branched from a main polymer chain, thereby forming a bottle-brush-shaped polymer brush structure.
[8] The virus inactivating structure according to any one of [1] to [7], wherein the polymer brush structure has an ionic conductivity of 5.0×10 ⁻¹ S/m or less.
[9] The virus inactivating structure according to any one of [1] to [8], wherein a plurality of the polymer chains have ammonium groups.

The present invention provides a virus inactivation structure that has high virus inactivation function and can maintain this high virus inactivation function for a long period of time.

FIG. 1 is a diagram showing a virus inactivating structure according to a first embodiment of the present invention. FIG. 2 is a diagram showing a virus inactivating structure according to a second embodiment of the present invention. FIG. 3 is a diagram showing a virus inactivating structure according to a third embodiment of the present invention.

The virus inactivating structure of the present invention has a polymer brush structure containing a plurality of polymer chains having specific functional groups selected from ionic groups, nonionic hydrophilic groups, and electron-donating groups, and has a virus inactivating function.
The present inventors conducted extensive research and found that a polymer brush structure containing multiple polymer chains having specific functional groups selected from ionic groups, nonionic hydrophilic groups, and electron-donating groups has high virus inactivation properties and furthermore maintains this virus inactivation function for a long period of time, which led to the completion of the present invention. In particular, the present inventors were the first to discover that such an effect is unique to the polymer brush structure. Here, the polymer brush structure may be any structure that includes multiple polymer chains that are physically or chemically fixed to a substrate, and as long as it is such a structure, its shape, etc. are not particularly limited.

First Embodiment
First, a first embodiment of the present invention will be described.
Fig. 1 is a diagram showing a virus inactivation structure according to a first embodiment of the present invention. As shown in Fig. 1, the virus inactivation structure according to the first embodiment is composed of a substrate 10 and a polymer brush layer 20 formed on the substrate 10.

The substrate 10 is not particularly limited, and may be a wide variety of materials such as fibers, monofilaments, twisted yarns, woven fabrics, nonwoven fabrics, cut fibers, hollow fibers, glass, metals, or processed products thereof. It may also be particles such as silica or carbon black. In particular, according to the present invention, by using a substrate 10 of any material and having any shape and forming a polymer brush layer 20 on its surface, it is possible to impart the virus inactivation effect of the polymer brush layer 20 to any material of any shape.

The polymer brush layer 20 is a layer containing multiple polymer chains fixed by covalent bonds onto the substrate 10 as a base body, and in the present invention, the polymer brush layer 20 is formed from polymer chains having a specific functional group (hereinafter referred to as "specific functional group" as appropriate) selected from an ionic group, a nonionic hydrophilic group, and an electron-donating group.

In the present invention, the reason why the polymer brush layer 20 exhibits an inactivating effect on viruses is not necessarily clear, but the following reason is thought to be the reason. That is, when a virus adheres to the surface of the polymer brush layer 20, a thermodynamic micelle fusion phenomenon causes multiple polymer chains having specific functional groups that make up the polymer brush layer 20 to fuse with the envelope that makes up the virus (pseudo-infection), causing the envelope to cleave. The RNA inside the virus is then expelled to the outside by the high osmotic pressure of the polymer chains having specific functional groups, which is thought to inactivate the virus.

In the present invention, the polymer brush layer 20 is composed of multiple polymer chains having specific functional groups, and by having such specific functional groups, it is easily fused with the envelope that constitutes the virus, and furthermore, since it is composed of multiple polymer chains, it exhibits high osmotic pressure, which can be said to exhibit high virus inactivation function. In addition, since the polymer brush layer 20 has a structure composed of multiple polymer chains, it can stably exhibit such high virus inactivation function without accompanying structural changes, etc., and therefore it can be said that the high virus inactivation function can be sustained for a long period of time.

Therefore, according to the present invention, a high inactivation effect is achieved against various viruses, particularly against enveloped viruses. As described above, in the present invention, it is believed that the multiple polymer chains having specific functional groups that constitute the polymer brush layer 20 fuse with the envelope that constitutes the virus (pseudo-infection) and cleave the envelope, and the envelope that constitutes the virus is generally composed of a phospholipid bilayer membrane. In contrast, fungi such as bacteria have a cell membrane composed of polysaccharides, etc., and in this respect, viruses and fungi such as bacteria are completely different, and furthermore, their size and characteristics are completely different from those of viruses. In particular, while substances that exhibit bactericidal or antibacterial effects generally destroy cell membranes composed of polysaccharides, etc. (i.e., act on polysaccharides), in the present invention, it is believed that the substance fuses with and cleaves an envelope composed of a phospholipid bilayer membrane (i.e., act on the phospholipid bilayer membrane), and therefore its mechanism of action and required characteristics are thought to be different from those that exhibit bactericidal or antibacterial effects.

The multiple polymer chains that make up the polymer brush layer 20 have specific functional groups selected from ionic groups, nonionic hydrophilic groups, and electron-donating groups.

The ionic group is not particularly limited and may be either a cationic functional group or an anionic functional group, but examples include ammonium groups, sulfonic acid groups, sulfonimide groups, sulfate groups, phosphonic acid groups, phosphoric acid groups, carboxylic acid groups, acrylic acid groups, methacrylic acid groups, or salts thereof, as well as hydroxyl groups, thiol groups, and other salts.

In addition, when the ionic group is a cationic functional group, it usually forms a salt structure together with a counter anion, and when the ionic group is an anionic functional group, it usually forms a salt structure together with a counter cation. The counter anion is not particularly limited, but examples thereof include BF ₄ ^- , PF ₆ ^- , AsF ₆ ^- , SbF ₆ ^- , AlCl ₄ ^- , NbF ₆ ^- , HSO ₄ -, ClO ₄ ^- , CH ₃ SO ₃ ^- , CF ₃ SO ₃ ^{- ,} CF ₃ CO ₂ ^- , (CF ₃ SO ₂ ) ₂ N ^- , Cl ^- , Br ^- , and I ^- . The counter cation is not particularly limited, but examples thereof include alkali metal ions such as Na ⁺ , K ⁺ , and Li ⁺ ; alkaline earth metal ions such as Ca ²⁺ and Mg ²⁺ ; and organic cations such as ammonium ion and alkylammonium ion.

Nonionic hydrophilic groups include, but are not limited to, hydroxyl groups, amide groups, amino groups, ether bonds, thiol groups, etc.

The electron-donating group may be any group that exhibits electron-donating properties and does not fall under the category of the above-mentioned ionic groups or nonionic hydrophilic groups, and examples of such groups include groups containing a nitrogen atom, an oxygen atom, a sulfur atom, a silicon atom, a phosphorus atom, etc., and specific examples of such groups include a hydroxyl group, an amino group, a methoxy group, and a sulfide group.

Among the specific functional groups described above, from the viewpoint of having a higher affinity for the envelope constituting the virus and therefore exhibiting a higher virus inactivation function, ionic groups and nonionic hydrophilic groups are preferred, ionic groups are more preferred, cationic functional groups are even more preferred, and ammonium groups are even more preferred. Note that the multiple polymer chains constituting the polymer brush layer 20 may contain only one type of specific functional group, or may contain two or more types.

The multiple polymer chains constituting the polymer brush layer 20 are preferably composed of polymers that exhibit water solubility. In particular, when the polymer brush layer 20 contains a trace amount of moisture or is wet with water (a state in which the polymer brush layer 20 is a layer that retains water), from the viewpoint of high virus adhesion and therefore high efficiency inactivation of viruses, the multiple polymer chains constituting the polymer brush layer 20 are preferably composed of polymers that exhibit water solubility. In the present invention, a polymer may be judged to be water soluble if it exhibits water solubility in any of the pH ranges of 1 to 12 (for example, if the absorbance is 0.3 or less when 1 wt % of the polymer is dispersed in water).

The polymer brush layer 20 can be formed, for example, by fixing multiple polymer chains onto the substrate 10 through covalent bonds, and more specifically, by introducing polymer chains onto the surface of the substrate 10 through a surface-initiated living radical polymerization method.

The surface-initiated living radical polymerization method is a technique for forming polymer chains (polymer graft chains) by introducing a polymerization initiator group into the surface of the substrate 10, which is the starting point of the polymer chain, and performing living radical polymerization using the polymerization initiator group as the starting point. For example, the methods described in JP-A-2009-59659 and JP-A-2010-218984 can be used.

〔上記一般式（１）中、ｍは、１以上１０以下の整数を示す。ｎは、１以上５以下の整数を示す。Ｒ^１は、水素原子、または炭素数１～３のアルキル基を示す。Ｒ^２、Ｒ^３、Ｒ^４は、炭素数１～５のアルキル基を示す。Ｒ^２、Ｒ^３、Ｒ^４は、酸素原子、硫黄原子、フッ素原子から選ばれる１種以上のヘテロ原子を含んでいてもよく、Ｒ^２、Ｒ^３、Ｒ^４は、２つ以上が連結して環状構造であってもよい。また、Ｚ^－は一価のアニオンを示す。〕 The monomer for forming the polymer chain is not particularly limited, and at least one of the monomers having the specific functional group described above may be used. However, a monomer having an ammonium group as the specific functional group is preferable, and a monomer capable of introducing an ammonium group into the side chain of the polymer chain is more preferable (i.e., it is more preferable that the multiple polymer chains constituting the polymer brush layer 20 have an ammonium group in the side chain). For example, a compound represented by the following general formula (1) can be used as the monomer having the ammonium group as the specific functional group. The monomer having the specific functional group may be used alone or in combination of two or more types. Furthermore, a monomer copolymerizable with the monomer having the specific functional group (monomer not having the specific functional group) may be used as the monomer for forming the polymer chain.

[In the above general formula (1), m represents an integer of 1 or more and 10 or less. n represents an integer of 1 or more and 5 or less. R ¹ represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms. ^{R 2} , R ³ , and R ⁴ represent alkyl groups having 1 to 5 carbon atoms. R ² , R ³ , and R ⁴ may each contain one or more heteroatoms selected from an oxygen atom, a sulfur atom, and a fluorine atom, and two or more of R ² , R ³ , and R ⁴ may be linked to form a cyclic structure. In addition, Z ^- represents a monovalent anion.]

The monovalent anion ^Z- in the above general formula (1) is not particularly limited, ^and _anions such as _BF4- ^{, PF6-} , _{AsF6- , SbF6-} , ^AlCl4- , _{NbF6- ,} ^HSO4- , _ClO4- ^, _CH3SO3- ^{, CF3SO3-} , _{CF3CO2- , (} ^{CF3SO2 )} _2N- ^, _Cl- ^{, Br-} _, ^{and I-} can ^be used, with _BF4- ^{, PF6-} _{, ( CF3SO2 ) 2N- ,} ^CF3SO3- _{, or CF3CO2- being} ^preferred .

〔上記一般式（２）～（９）中、ｎ、ｍ、Ｒ^１、Ｒ^２、Ｚ^－は、上記一般式（１）と同様である。〕 Among the compounds represented by the above general formula (1), the compounds represented by the following general formulas (2) to (9) are particularly suitable for use from the viewpoint of their high virus inactivation effect. These compounds may be used alone or in combination of two or more.

(In the above general formulas (2) to (9), n, m, R ¹ , R ² and Z ⁻ are the same as those in the above general formula (1).)

As a monomer used to form a polymer chain, instead of the compound represented by the above general formula (1) or together with the compound represented by the above general formula (1), for example, a (meth)acrylic acid-based monomer, a styrene-based monomer, a monofunctional monomer having one addition-polymerizable double bond, a hydrophobic monomer, a hydrophilic monomer, a monomer having a carboxyl group or a group that can be easily converted to a carboxyl group in the side chain, etc. can be used.

Specific examples of the (meth)acrylic acid monomer include:
(meth)acrylic acid, methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, isopropyl (meth)acrylate, butyl (meth)acrylate, isobutyl (meth)acrylate, tert-butyl (meth)acrylate, pentyl (meth)acrylate, hexyl (meth)acrylate, cyclohexyl (meth)acrylate;
heptyl (meth)acrylate, octyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, nonyl (meth)acrylate, decyl (meth)acrylate, dodecyl (meth)acrylate, phenyl (meth)acrylate, toluyl (meth)acrylate, benzyl (meth)acrylate;
2-methoxyethyl (meth)acrylate, 3-methoxypropyl (meth)acrylate, 3-methoxybutyl (meth)acrylate, 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, stearyl (meth)acrylate, glycidyl (meth)acrylate, 3-ethyl-3-(meth)acryloyloxymethyloxetane;
2-(meth)acryloyloxyethyl isocyanate, (meth)acrylate-2-aminoethyl, 2-(2-bromopropionyloxy)ethyl (meth)acrylate, 2-(2-bromoisobutyryloxy)ethyl (meth)acrylate;
1-(meth)acryloxy-2-phenyl-2-(2,2,6,6-tetramethyl-1-piperidinyloxy)ethane, 1-(4-((4-(meth)acryloxy)ethoxyethyl)phenylethoxy)piperidine, γ-(methacryloyloxypropyl)trimethoxysilane;
3-(3,5,7,9,11,13,15-heptaethylpentacyclo[9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ]octasiloxan-1-yl)propyl(meth)acrylate, 3-(3,5,7,9,11,13,15-heptaisobutyl-pentacyclo[9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ]octasiloxan-1-yl)propyl(meth)acrylate, 3-(3,5,7,9,11,13,15-heptaisooctylpentacyclo[9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ]octasiloxan-1-yl)propyl(meth)acrylate;
3-(3,5,7,9,11,13,15-heptacyclopentyl pentacyclo [9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ] octasiloxan-1-yl) propyl (meth) acrylate, 3-(3,5,7,9,11,13,15-heptaphenyl pentacyclo [9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ] octasiloxan-1-yl) propyl (meth) acrylate, 3-[(3,5,7,9,11,13,15-heptaethyl pentacyclo [9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ] octasiloxan-1-yloxy) dimethylsilyl] propyl (meth) acrylate;
3-[(3,5,7,9,11,13,15-heptaisobutylpentacyclo[9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ]octasiloxan-1-yloxy)dimethylsilyl]propyl (meth)acrylate, 3-[(3,5,7,9,11,13,15-heptaisooctylpentacyclo[9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ]octasiloxan-1-yloxy)dimethylsilyl]propyl (meth)acrylate;
3-[(3,5,7,9,11,13,15-heptacyclopentyl pentacyclo [9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ] octasiloxan-1-yloxy) dimethylsilyl] propyl (meth) acrylate, 3-[(3,5,7,9,11,13,15-heptaphenyl pentacyclo [9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ] octasiloxan-1-yloxy) dimethylsilyl] propyl (meth) acrylate;
Ethylene oxide adduct of (meth)acrylic acid, trifluoromethylmethyl (meth)acrylate, 2-trifluoromethylethyl (meth)acrylate, 2-perfluoroethylethyl (meth)acrylate, 2-perfluoroethyl-2-perfluorobutylethyl (meth)acrylate, 2-perfluoroethyl (meth)acrylate, trifluoromethyl (meth)acrylate, diperfluoromethylmethyl (meth)acrylate;
2-perfluoromethyl-2-perfluoroethylethyl (meth)acrylate, 2-perfluorohexylethyl (meth)acrylate, 2-perfluorodecylethyl (meth)acrylate, 2-perfluorohexadecylethyl (meth)acrylate; and the like.

Specific examples of styrene monomers include:
Styrene, vinyltoluene, α-methylstyrene, p-chlorostyrene, p-chloromethylstyrene, m-chloromethylstyrene, o-aminostyrene, p-styrene chlorosulfonic acid, styrenesulfonic acid and its salts, vinylphenylmethyldithiocarbamate, 2-(2-bromopropionyloxy)styrene, 2-(2-bromoisobutyryloxy)styrene;
1-(2-((4-vinylphenyl)methoxy)-1-phenylethoxy)-2,2,6,6-tetramethylpiperidine, 1-(4-vinylphenyl)-3,5,7,9,11,13,15-heptaethylpentacyclo[9.5.1.1 ^3,9 . ^{1 5,15} . 1 ^7,13 ]octasiloxane, 1-(4-vinylphenyl)-3,5,7,9,11,13,15-heptaisobutylpentacyclo[9.5.1.1 ^3,9 . 1 ^5,15 . 1 ^7,13 ]octasiloxane;
1-(4-vinylphenyl)-3,5,7,9,11,13,15-heptaisooctylpentacyclo[9.5.1.1 ^3,9 . ^{1 5,15} . ^{1 7,13} ]octasiloxane, 1-(4-vinylphenyl)-3,5,7,9,11,13,15-heptacyclopentylpentacyclo[9.5.1.1 ^3,9 . 1 ^5,15 . 1 ^7,13 ]octasiloxane, 1-(4-vinylphenyl)-3,5,7,9,11,13,15-heptaphenylpentacyclo[9.5.1.1 ^3,9 . 1 ^5,15 . 1 ^7,13 ]octasiloxane;
3-(3,5,7,9,11,13,15-heptaethylpentacyclo[9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ]octasiloxan-1-yl)ethylstyrene, 3-(3,5,7,9,11,13,15-heptaisobutylpentacyclo[9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ]octasiloxan-1-yl)ethylstyrene, 3-(3,5,7,9,11,13,15-heptaisooctylpentacyclo[9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ]octasiloxan-1-yl)ethylstyrene;
3-(3,5,7,9,11,13,15-heptacyclopentylpentacyclo[9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ]octasiloxan-1-yl)ethylstyrene, 3-(3,5,7,9,11,13,15-heptaphenylpentacyclo[9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ]octasiloxan-1-yl)ethylstyrene, 3-(3,5,7,9,11,13,15-heptaethylpentacyclo[9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ]octasiloxan-1-yloxy)dimethylsilyl)ethylstyrene;
3-(3,5,7,9,11,13,15-heptaisobutylpentacyclo[9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ]octasiloxan-1-yloxy)dimethylsilyl)ethylstyrene, 3-(3,5,7,9,11,13,15-heptaisooctylpentacyclo[9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ]octasiloxan-1-yloxy)dimethylsilyl)ethylstyrene;
3-((3,5,7,9,11,13,15-heptacyclopentyl pentacyclo [9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ] octasiloxane-1-yloxy) dimethylsilyl) ethyl styrene, 3-((3,5,7,9,11,13,15-heptaphenyl pentacyclo [9.5.1.1 ^3,9 .1 ^5,15 .1 ^7,13 ] octasiloxane-1-yloxy) dimethylsilyl) ethyl styrene; and the like.

Specific examples of the monofunctional monomer having one addition-polymerizable double bond include:
Fluorine-containing vinyl monomers (perfluoroethylene, perfluoropropylene, vinylidene fluoride, etc.), silicon-containing vinyl monomers (vinyltrimethoxysilane, vinyltriethoxysilane, etc.), maleic anhydride, maleic acid, monoalkyl esters and dialkyl esters of maleic acid, fumaric acid, monoalkyl esters and dialkyl esters of fumaric acid;
Maleimide monomers (maleimide, methylmaleimide, ethylmaleimide, propylmaleimide, butylmaleimide, hexylmaleimide, octylmaleimide, dodecylmaleimide, stearylmaleimide, phenylmaleimide, cyclohexylmaleimide, etc.);
Nitrile group-containing monomers (such as acrylonitrile and methacrylonitrile), amide group-containing monomers (such as acrylamide and methacrylamide), vinyl ester monomers (such as vinyl acetate, vinyl propionate, vinyl pivalate, vinyl benzoate, and vinyl cinnamate);
Olefins (ethylene, propylene, etc.), conjugated diene monomers (butadiene, isoprene, etc.), vinyl halides (vinyl chloride, etc.), vinylidene halides (vinylidene chloride, etc.), allyl halides (allyl chloride, etc.);
Allyl alcohol, vinylpyrrolidone, vinylpyridine, N-vinylcarbazole, methyl vinyl ketone, vinyl isocyanate, and the like.
In addition, as the monofunctional monomer having one addition-polymerizable double bond, a macromonomer having one polymerizable double bond in one molecule and having a main chain derived from styrene, a (meth)acrylic acid ester, a siloxane, or the like can also be used.

Specific examples of hydrophobic monomers include:
acrylic acid esters (alkyl esters of acrylic acid such as methyl acrylate, ethyl acrylate, propyl acrylate, butyl acrylate, cyclohexyl acrylate, hexafluoroisopropyl acrylate, etc.; aryl acrylates such as phenyl acrylate; aryl alkyl acrylates such as benzyl acrylate; alkoxy alkyl acrylates such as methoxymethyl acrylate, etc.);
Methacrylic acid esters (alkyl esters of methacrylic acid such as methyl methacrylate, ethyl methacrylate, propyl methacrylate, butyl methacrylate, cyclohexyl methacrylate, hexafluoroisopropyl methacrylate, etc.; aryl methacrylates such as phenyl methacrylate; aryl alkyl methacrylates such as benzyl methacrylate; alkoxy alkyl methacrylates such as methoxymethyl methacrylate, etc.);
Fumarate esters (alkyl esters of fumaric acid, such as dimethyl fumarate, diethyl fumarate, and diallyl fumarate), maleate esters (alkyl esters of maleic acid, such as dimethyl maleate, diethyl maleate, and diallyl maleate);
Itaconic acid esters (such as alkyl esters of itaconic acid), crotonic acid esters (such as alkyl esters of crotonic acid), methyl vinyl ether, ethoxyethyl vinyl ether, vinyl acetate, vinyl propionate, vinyl benzoate, styrene;
Alkyl styrene, vinyl chloride, vinyl methyl ketone, vinyl stearate, vinyl alkyl ether; and the like.

Specific examples of hydrophilic monomers include:
Hydroxy-substituted alkyl acrylates (such as 2-hydroxyethyl acrylate, 2-hydroxypropyl acrylate, 2-hydroxypropyl acrylate, 2,3-dihydroxypropyl acrylate, polyethoxyethyl acrylate, polyethoxypropyl acrylate, etc.);
Hydroxy-substituted alkyl methacrylates (such as 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, 2-hydroxypropyl methacrylate, 2,3-dihydroxypropyl methacrylate, polyethoxyethyl methacrylate, and polyethoxypropyl methacrylate);
Acrylamide, N-alkylacrylamide (N-methylacrylamide, N,N-dimethylacrylamide, etc.), N-alkylmethacrylamide (N-methylmethacrylamide, etc.);
Polyethylene glycol monoacrylate, polyethylene glycol monomethacrylate, alkoxypolyethylene glycol acrylate, alkoxypolyethylene glycol methacrylate, phenoxypolyethylene glycol acrylate, phenoxypolyethylene glycol methacrylate, 2-glucosyloxyethyl methacrylate;
Examples of the monomer include acrylic acid, methacrylic acid, fumaric acid, maleic acid, itaconic acid, crotonic acid, methacrylamide, allyl alcohol, N-vinylpyrrolidone, and N,N-dimethylaminoethyl acrylate.

Specific examples of monomers having a carboxyl group or a group that can be easily converted to a carboxyl salt group on the side chain include:
1-methoxyethyl acrylate, 1-ethoxyethyl acrylate, 1-propoxyethyl acrylate, 1-(1-methylethoxy)ethyl acrylate, 1-butoxyethyl acrylate, 1-(2-methylpropoxy)ethyl acrylate, 1-(2-ethylhexoxy)ethyl acrylate;
Pyranyl acrylate, 1-methoxyethyl methcrete, 1-ethoxyethyl methcrete, 1-propoxyethyl methcrete, 1-(1-methylethoxy)ethyl methcrete, 1-butoxyethyl methcrete, 1-(2-methylpropoxy)ethyl methcrete, 1-(2-ethylhexoxy)ethyl methacrylate;
Pyranyl methacrylate, di-1-methoxyethyl malate, di-1-ethoxyethyl malate, di-1-propoxyethyl malate, di-1-(1-methylethoxy)ethyl malate, di-1-butoxyethyl malate, di-1-(2-methylpropoxy)ethyl malate, dipyranyl malate, and the like.

When polymerization is performed by the surface-initiated living radical polymerization method, the polymerization initiation group to be introduced onto the surface of the substrate 10 is not particularly limited as long as it can initiate polymerization, but halogenated alkyl groups, halogenated sulfonyl groups, etc. are preferred.

From the viewpoint of controllability of the graft density and the primary structure of the grafted polymer chain (molecular weight, molecular weight distribution, monomer arrangement pattern), it is preferable that the polymerization initiation group is physically or chemically bonded to the surface of the substrate 10.

Methods for introducing (binding) the polymerization initiating group to the surface of the substrate 10 include chemical adsorption and Langmuir-Blodgett (LB) methods.

For example, when a silicon wafer is used as the substrate 10, the chlorosulfonyl group (polymerization initiator group) can be fixed to the silicon wafer surface by chemical bonding using 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane, 2-(4-chlorosulfonylphenyl)ethyltrichlorosilane, or the like, by reacting it with the oxide layer on the silicon wafer surface.

When introducing a polymerization initiator group for surface-initiated living radical polymerization onto the surface of the substrate 10, it is preferable to use a polymerization initiator group-containing surface treatment agent that has a polymerization initiator group and a group that has binding ability to the substrate or a group that has affinity to the substrate. Such a polymerization initiator group-containing surface treatment agent may be a low molecular weight compound or a high molecular weight compound.

The polymerization initiator group-containing surface treatment agent is not particularly limited, but a compound having a group capable of bonding to the substrate 10 and a radical generating group is preferred. For example, the polymerization initiator group-containing surface treatment agents disclosed in JP-A-2010-218984, i.e., TEMPO-, ATRP-, RAFT-, and RTCP-based polymerization initiator group-containing surface treatment agents, can be used. Among these, TEMPO-, RAFT-, and RTCP-based polymerization initiator group-containing surface treatment agents are more preferred. Furthermore, among the TEMPO-based polymerization initiator group-containing surface treatment agents, DEPN-based polymerization initiator group-containing surface treatment agents are particularly preferred. Examples of the group capable of bonding to the substrate 10 include -SiCl ₃ , -Si(CH ₃ )Cl ₂ , -Si(CH ₃ ) ₂ Cl, and -Si(OR) ₃ (wherein R represents methyl, ethyl, propyl, or butyl). Alternatively, as the polymerization initiator group-containing surface treatment agent, (2-bromo-2-methyl)propionyloxyhexyltriethoxysilane (BHE), (2-bromo-2-methyl)propionyloxypropyltriethoxysilane (BPE), and the like, which are described in WO 2006/087839, can also be used.

In addition, in order to adjust the graft density, a silane coupling agent that does not contain a polymerization initiator group (for example, a commonly used alkyl silane coupling agent) may be used in combination with the above-mentioned surface treatment agent containing a polymerization initiator group.

The graft density can be freely changed by adjusting the ratio of the surface treatment agent containing a polymerization initiator group to the silane coupling agent not containing a polymerization initiator group. In addition, the LB method or the gas phase adsorption method can be used to introduce the polymerization initiator group onto the surface of the substrate 10, in terms of the uniformity of the polymerization initiator group introduced and the controllability of the graft density of the polymerization initiator group.

In the LB method, the membrane-forming material is first dissolved in a suitable solvent (e.g., chloroform, benzene, etc.). Next, a small amount of this solution is spread on a clean liquid surface, preferably the surface of pure water, and the solvent is then evaporated or diffused into an adjacent aqueous phase to form a low-density membrane of membrane-forming molecules on the water surface.

Then, the partition is typically mechanically swept across the water surface to compress the film and increase its density by reducing the surface area of the water surface on which the film-forming molecules are spread, resulting in a dense monolayer on the water surface.

Next, under appropriate conditions, while maintaining a constant surface density of the molecules that make up the monolayer on the water surface, the substrate on which the monolayer is to be deposited is immersed or pulled across the monolayer on the water surface, thereby transferring the monolayer on the water surface onto the substrate 10, and the monolayer is deposited on the substrate.

Details and specific examples of the LB method are described in "Kiyonari Fukuda et al., New Experimental Chemistry Lectures, Vol. 18 (Interfaces and Colloids), Chapter 6 (1977), Maruzen," "Kiyonari Fukuda, Michio Sugi, Hiroyuki Suzumebe eds., LB Films and Electronics (1986), CMC," and "Yoshio Ishii, Practical Techniques for Making Good LB Films (1989), Kyoritsu Shuppan," etc.

Then, a polymerization initiator group is introduced onto the surface of the substrate 10 using the polymerization initiator described above. The substrate 10 with the polymerization initiator group introduced therein is then immersed in a polymerization reaction solution containing the monomer described above and heated as necessary, thereby forming a polymer chain containing the monomer described above as a polymerization unit on the surface of the substrate 10. In addition to the monomer described above, the polymerization reaction solution can contain various radical initiators, solvents, and other components necessary for the polymerization reaction.

In the present invention, the polymer chains formed on the surface of the substrate 10 are preferably formed with a graft density such that the occupied area ratio (occupancy rate per polymer cross-sectional area) relative to the surface area of the substrate 10 is 0.1 to 50%, more preferably 10 to 45%, and even more preferably 20 to 40%. The graft density can be calculated from the absolute value of the number average molecular weight (Mn) of the polymer chain, the amount of grafted polymer, and the surface area of the substrate 10. The occupied area ratio in the polymer brush layer 20 can be calculated by multiplying the cross-sectional area by the graft density, which is calculated from the repeating unit length in the stretched form of the polymer and the bulk density of the polymer. The occupied area ratio means the ratio of the substrate 10 surface occupied by the graft point (the first monomer) (100% in close packing, no more than this can be grafted). By setting the ratio of the area of the polymer chains to the surface area of the substrate 10 within the above range, the virus inactivation function can be more appropriately improved; if the ratio of the area of the polymer chains is too low or too high, the virus inactivation function will decrease.

According to the findings of the present inventors, the state of the polymer chains in the polymer brush layer 20 does not necessarily need to be uniform, and may be a mixture of sparse and dense polymer chains when viewed microscopically. Even in such an embodiment, the virus inactivation function can be sufficiently exerted. Therefore, when measuring the above-mentioned exclusive area ratio, it is preferable that a relatively wide area range (specifically, an area range of 5 cm x 5 cm) of the surface of the substrate 10 is measured, and when the measurement is performed, the exclusive area ratio is within the above-mentioned range.

The graft density per unit area of the polymer chains is preferably 0.0005 to 0.4 chains/nm ² , more preferably 0.05 to 0.4 chains/nm ² , still more preferably 0.1 to 0.4 chains/nm ² _{, and} particularly preferably 0.12 to 0.25 chains/nm ² .

The graft density of the polymer chains can be measured, for example, according to the methods described in Macromolecules, 31, 5934-5936 (1998), Macromolecules, 33, 5608-5612 (2000), Macromolecules, 38, 2137-2142 (2005), etc. Specifically, the graft density (chains/nm ² ) can be calculated by measuring the graft amount (W) and the number average molecular weight (Mn) of the graft chains, according to the following formula:
Graft density (chains/ ^nm2 ) = W (g/ ^nm2 )/Mn x (Avogadro's number)
(In the formula, W represents the graft amount, and Mn represents the number average molecular weight.)

When the substrate 10 is a planar substrate, the graft amount (W) can be determined by measuring the dry film thickness, i.e., the thickness of the grafted polymer chain layer in a dry state, by ellipsometry, and calculating the graft amount per unit area using the density of the bulk film. Alternatively, when the substrate 10 is fibrous, the graft amount can be measured by infrared absorption spectroscopy (IR), thermogravimetric analysis (TG), elemental analysis, etc.

The number average molecular weight (Mn) of the polymer chains constituting the polymer brush layer 20 is preferably 500 to 10,000,000, more preferably 100,000 to 10,000,000. From the viewpoint of further enhancing the virus inactivation function, the molecular weight distribution (Mw/Mn) of the polymer chains constituting the polymer brush layer 20 is preferably close to 1, and is preferably 1.5 or less, more preferably 1.3 or less, even more preferably 1.25 or less, even more preferably 1.2 or less, and particularly preferably 1.15 or less. The number average molecular weight (Mn) and molecular weight distribution (Mw/Mn) of the polymer chains can be measured, for example, by cutting out the polymer chains from the substrate 10 by hydrofluoric acid treatment, and measuring the values in terms of polyethylene oxide by gel permeation chromatography using the cut out polymer chains. Alternatively, a method may be adopted in which the free polymer produced during polymerization is assumed to have the same molecular weight as the polymer chain introduced into the substrate 10, and the number average molecular weight (Mn) and molecular weight distribution (Mw/Mn) of the free polymer are measured in terms of polyethylene oxide using gel permeation chromatography, and the results are used as is.

Furthermore, the average molecular chain length _Lp (i.e., the polymer brush length) of the polymer chains constituting the polymer brush layer 20 is preferably 10 nm or more, and from a practical standpoint, is more preferably in the range of 10 to 1000 nm. If the average molecular chain length _Lp of the polymer chains is too short, the virus inactivation function may be insufficient. Furthermore, the average molecular chain length _Lp of the polymer chains can be adjusted, for example, by the type of monomer constituting the polymer chains, the polymerization conditions, etc.

The average molecular chain length _Lp of the polymer chain can be determined, for example, by measuring the number average molecular weight (Mn) and molecular weight distribution (Mw/Mn) of the polymer chain and determining the results of these measurements. The number average molecular weight (Mn) and molecular weight distribution (Mw/Mn) of the polymer chain can be measured, for example, by cutting out the polymer chain from the substrate 10 by hydrofluoric acid treatment and measuring the cut-out polymer chain by gel permeation chromatography. Alternatively, it is assumed that the free polymer generated during polymerization has a molecular weight equal to that of the polymer chain introduced into the substrate 10, and the number average molecular weight (Mn) and molecular weight distribution (Mw/Mn) of the free polymer are measured by gel permeation chromatography and used as is. The molecular weight distribution (Mw/Mn) of the polymer brush forming the first sliding surface is preferably close to 1, and is preferably 1.3 or less, more preferably 1.25 or less, even more preferably 1.2 or less, and particularly preferably 1.15 or less.

Furthermore, the ratio (T _b /L _p ) of the thickness T _b of the polymer brush layer 20 to the average molecular chain length L _p constituting the polymer brush layer 20 is preferably 0.001 to 0.6, more preferably 0.1 to 0.6, even more preferably 0.2 to 0.6, and particularly preferably 0.3 to 0.5. By setting the ratio (T _b /L _p ) of the thickness T _b of the polymer brush layer 20 to the average molecular chain length L _p in the above range, the virus inactivation function can be further improved.

The thickness T _b of the polymer brush layer 20 can be measured by spectroscopic ellipsometry after the polymer brush layer 20 is vacuum-dried at 25° C. for 1 hour and volatile components, mainly including moisture, are removed. That is, in the present invention, the ratio (T _b /L _p ) of the thickness T _b of the polymer brush layer 20 to the average molecular chain length L _p is the value in the state in which the volatile components are removed. Therefore, when the polymer brush layer 20 contains a volatile component such as moisture in its usage state, the polymer chains constituting the polymer brush layer 20 approach a fully extended state due to the inclusion of moisture, and the ratio (T _b /L _p ) may exceed the above range due to the influence of the contained moisture. Even in such a case, it is preferable that the ratio (T _b /L _p ) in the state in which the volatile components are removed is in the above range. Furthermore, for example, a polymer brush layer swollen with a non-volatile liquid such as a lubricating oil or an ionic liquid will remain swollen with the non-volatile liquid even after the volatile components are removed, and therefore will generally exhibit a large ratio (T _b /L _p ) of more than 0.6 even after the volatile components are removed.

The ionic conductivity of the polymer brush layer 20 is preferably 5.0×10 ^-1 S/m or less, more preferably 1.0×10 ^-1 S/m or less, and even more preferably 5.0×10 ^-2 S/m or less. Although there is no particular lower limit, the ionic conductivity is preferably 1.0×10 ^-4 S/m or more. That is, the polymer brush layer 20 does not substantially contain a liquid with a relatively high ionic conductivity (e.g., an ionic liquid, etc.), and therefore the ionic conductivity is low as in the above range. As a result, a state in which moisture can be contained or a state in which moisture is contained is preferable from the viewpoint of high virus adhesion and, by extension, from the viewpoint of achieving highly efficient virus inactivation. Note that the ionic conductivity of the polymer brush layer 20 is preferably in the above range either in a state in which a volatile component such as moisture is contained or in a state in which a volatile component such as moisture is not contained. The method for measuring the ionic conductivity of the polymer brush layer 20 is not particularly limited, but examples include a method for measuring conductivity by a four-terminal method (for example, measurement using a resistivity meter (Loresta, manufactured by Nitto Seiko Analytech Co., Ltd.)).

Second Embodiment
Next, a second embodiment of the present invention will be described.
FIG. 2(A) is a diagram showing a virus inactivating structure according to a second embodiment of the present invention, FIG. 2(B) is a diagram showing the detailed structure of part IIb in FIG. 2(A), and FIG. 2(C) is a diagram showing the detailed structure of part IIc in FIG. 2(A).

As shown in FIG. 2(B), the virus inactivation structure according to the second embodiment of the present invention is formed by dispersing a plurality of block copolymer chains 40 in a base polymer 30. The plurality of block copolymer chains 40 each include a polymer block (A) and a polymer block (B) that has a lower affinity for the base polymer 30 than the polymer block (A), and the block copolymer chain has the polymer block (A) in at least two locations.

In FIG. 2B, the polymer block (A) constituting the block copolymer chain 40 is shown by a dashed line, and the polymer block (B) is shown by a solid line. In FIG. 2B, an ABA type block copolymer chain consisting of polymer block (A)/polymer block (B)/polymer block (A) is shown as an example of the block copolymer chain 40, but the structure is not limited to this structure as long as the structure has polymer block (A) at at least two places. For example, the block copolymer chain may be an ABAB type block copolymer chain consisting of polymer block (A)/polymer block (B)/polymer block (A)/polymer block (B), or may be an ABABA type block copolymer chain consisting of polymer block (A)/polymer block (B)/polymer block (A)/polymer block (B)/polymer block (A).

As shown in FIG. 2(C), in the virus inactivation structure according to the second embodiment, at least some of the block copolymer chains 40 are present in a state in which the polymer block (A) is in the base polymer 30 and the polymer block (B) is exposed from the base polymer 30. That is, in the virus inactivation structure according to the second embodiment, the surface has a structure in which a plurality of loop structures formed in the polymer chain based on the block copolymer chain 40 are exposed. Specifically, the polymer block (A) is present in the base polymer 30, and a polymer brush structure is formed in which a plurality of polymer chains of the loop structure formed by the polymer block (B) are exposed. In the second embodiment, the polymer block (B) has a specific functional group selected from an ionic group, a nonionic hydrophilic group, and an electron donating group. As a result, the virus inactivation structure according to the second embodiment has a high virus inactivation function, similar to the polymer brush layer 20 in the first embodiment described above, and further, the high virus inactivation function can be sustained for a long period of time.

In the virus inactivation structure according to the second embodiment, a block copolymer chain 40 having a structure of polymer block (A)/polymer block (B)/polymer block (A) is used, in which polymer block (A) has a relatively high affinity for the base polymer 30, while polymer block (B) has a relatively low affinity for the base polymer 30. Therefore, while the polymer blocks (A) located on both sides of polymer block (B) remain in the base polymer 30, polymer block (B) is exposed from the base polymer 30, forming a loop structure of polymer block (B) as shown in FIG. 2(C).

In addition, in the virus inactivation structure according to the second embodiment, the base polymer 30 has a structure in which a plurality of block copolymer chains 40 that are not involved in the loop structure shown in FIG. 2(C) are dispersed (see, for example, FIG. 2(B)). Therefore, for example, when a defect occurs in a portion of the block copolymer chains 40 that are involved in the loop structure shown in FIG. 2(C), the block copolymer chains 40 located near the defective portion among the block copolymer chains 40 dispersed in the base polymer 30 change to one having the loop structure shown in FIG. 2(C), thereby having a self-repairing effect that can compensate for such a defect. Note that, for example, when a configuration is adopted in which a plurality of block copolymer chains 40 are brought into contact with the surface of the base polymer 30 to form a loop structure instead of the method of dispersing a plurality of block copolymer chains 40 in the base polymer 30, when such a defect occurs in the loop structure, a self-repairing effect that compensates for the defect cannot be expected.

The base polymer 30 is not particularly limited, and various resins and rubbers can be used without restrictions. The resin may be either a thermosetting resin or a thermoplastic resin. Examples of thermosetting resins include epoxy resin, phenol resin, amino resin, unsaturated polyester resin, polyurethane resin, urea resin, melamine resin, thermosetting polyimide resin, and diallyl phthalate resin.

Examples of thermoplastic resins include polyolefin-based resins such as polyethylene, polypropylene, polystyrene, and polycycloolefin; vinyl-based resins such as polystyrene, acrylic resin, polyvinyl chloride resin, and polyvinyl alcohol; fluorine-based resins such as polytetrafluoroethylene; polyester-based resins such as polyethylene terephthalate, polybutylene terephthalate, polytrimethylene terephthalate, and polyethylene naphthalate; and silicone resins such as polydimethylsiloxane.

Examples of rubber include diene-based rubbers such as butadiene rubber, styrene butadiene rubber, chloroprene rubber, isoprene rubber, natural rubber, nitrile rubber, and butyl rubber; and rubbers other than diene-based rubbers such as ethylene propylene rubber, acrylic rubber, polyether rubber, polyurethane rubber, fluororubber, and silicone rubber.

Among these resins or rubbers, polystyrene, acrylic resin, silicone resin, and styrene-butadiene rubber are preferred, and acrylic resin is preferred, and among acrylic resins, polybutyl methacrylate is particularly preferred.

The base polymer 30 preferably has a glass transition temperature (Tg) lower than the use temperature of the composite 10; specifically, it is preferable that the Tg is 50°C or less, and more preferably that the Tg is 20°C or less.

The block copolymer chain 40 is not particularly limited as long as it comprises a polymer block (A) and a polymer block (B) that has a lower affinity for the base polymer 30 than the polymer block (A), and has the polymer block (A) at at least two locations in the block copolymer chain. However, from the viewpoint of being able to form the loop structure shown in FIG. 2(C) in the process, it is preferable to use a polymer block (B) that is incompatible with the base polymer 30, and it is particularly preferable to use a polymer block (B) that is incompatible with the base polymer 30 and a polymer block (A) that is compatible with the base polymer 30.

Here, the polymer block (A) being compatible with the base polymer 30 refers to the following state. That is, when a polymer consisting of only the polymer block (A) is mixed with the base polymer 30 by hot melt mixing, co-solution mixing, or the like, and the resulting mixture is then solidified by cooling or evaporating and removing the solvent, or the like, and the glass transition temperature (Tg) of the obtained sample is measured. If a Tg different from the Tg of the polymer consisting of only the polymer block (A) and the Tg of the base polymer 30 is observed in the temperature range between these, it can be determined that the two are compatible.

Alternatively, the polymer block (B) being incompatible with the base polymer 30 refers to the following state. That is, when a polymer consisting of only the polymer block (B) is mixed with the base polymer 30 by hot melt mixing, co-solution mixing, or the like, and the resulting mixture is then solidified by cooling or evaporating and removing the solvent, or the like, and the glass transition temperature (Tg) of the resulting sample is measured. If no Tg other than the Tg of the polymer consisting of only the polymer block (B) and the Tg of the base polymer 30 is observed, it can be determined that the two are incompatible.

As the polymer block (A) and the polymer block (B), those having the above-mentioned compatibility with the base polymer 30 may be used, but from the viewpoint of being able to form the loop structure shown in Fig. 2(C) in the process, with regard to their SP values (solubility parameters), the difference between the SP value of the polymer block (A) and the SP value of the polymer block (B) is preferably 1.5 (MPa) ^1/2 or more, more preferably 3 (MPa) ^1/2 or more, and even more preferably 5 (MPa) ^1/2 or more. With regard to the SP value of the polymer block (A), the difference between the SP value of the polymer block (A) and the SP value of the base polymer is preferably 0.5 (MPa) ^1/2 or less, more preferably 0.3 (MPa) ^1/2 or less, and even more preferably 0.2 (MPa) ^1/2 or less. Furthermore, with regard to the SP value of the polymer block (B), the difference between the SP value of the polymer block (B) and the SP value of the base polymer is preferably 1.5 (MPa) ^1/2 or more, more preferably 3 (MPa) ^1/2 or more, and even more preferably 5 (MPa) ^1/2 or more.

The polymer block (A) is not particularly limited as long as it satisfies the above-mentioned characteristics, and may be selected in relation to the base polymer 30 used. Specific examples include those made of polymer segments that make up the resins or rubbers exemplified as the resins or rubbers that make up the base polymer 30 described above.

The molecular weight (weight average molecular weight (Mw)) of the polymer block (A) portion of the block copolymer chain 40 is not particularly limited, but is preferably 1,000 to 100,000, more preferably 1,000 to 50,000, and even more preferably 1,000 to 20,000, from the viewpoint of exhibiting sufficient interaction with the base polymer 30, thereby more appropriately supporting the loop structure formed by the polymer block (B), and thereby further enhancing durability. The most preferred is 2,000 to 20,000.

The polymer block (B) may be any one having a specific functional group selected from an ionic group, a nonionic hydrophilic group, and an electron donating group, and satisfying the above-mentioned characteristics. It is not particularly limited and may be selected in relation to the base polymer 30 used. However, it is preferable that the polymer block is a polymer block formed by polymerizing a monomer mixture containing a monomer having a specific functional group. As in the first embodiment described above, it is more preferable that the polymer block is a polymer block formed by polymerizing a monomer mixture containing a monomer having an ammonium group as the specific functional group (more preferably, a monomer that can introduce an ammonium group into the side chain of the polymer chain, particularly preferably a compound represented by the above general formula (1)). As the monomer having the specific functional group, one type may be used alone, or two or more types may be used in combination. In addition, as a monomer for forming a polymer chain, a monomer that can be copolymerized with the monomer having the specific functional group (monomer not having a specific functional group) may be used.

As in the first embodiment described above, instead of the compound represented by the above general formula (1), or together with the compound represented by the above general formula (1), for example, a (meth)acrylic acid-based monomer, a styrene-based monomer, a monofunctional monomer having one addition-polymerizable double bond, a hydrophobic monomer, a hydrophilic monomer, a monomer having a carboxyl group or a group that can be easily converted to a carboxyl group in the side chain, etc. may be used.

The molecular weight (weight average molecular weight (Mw)) of the polymer block (B) portion of the block copolymer chain 40 is not particularly limited, but the molecular weight of the polymer block (B) portion is closely related to the loop length (the length of the loop constituting the loop structure) formed. If the molecular weight of the polymer block (B) portion is large, the loop length formed on the surface of the composite 10 will also be large. In other words, the polymer loop layer (the layer consisting of the loop structure formed by the polymer block (B) portion) will be made thicker. On the other hand, if the molecular weight of the polymer block (B) portion is small, the polymer loop layer will be thin. Considering the phenomenon of the loop brush being destroyed by the unevenness of the sliding surface facing the loop brush layer, the molecular weight (weight average molecular weight (Mw)) of the polymer block (B) portion is preferably 1,000 to 200,000, more preferably 2,000 to 100,000, even more preferably 3,000 to 50,000, and particularly preferably 3,000 to 20,000.

The synthesis method of the block copolymer chain 40 is not particularly limited, but when the block copolymer chain 40 is an ABA type block copolymer chain consisting of polymer block (A)/polymer block (B)/polymer block (A), it can be synthesized by the following method. That is, a method of forming polymer block (A) on both sides of polymer block (B) by polymerizing a monomer that forms polymer block (A) in the presence of polymer block (B), a method of polymerizing a monomer that forms polymer block (B) in the presence of polymer block (A) and then further polymerizing a monomer that forms polymer block (A), etc. can be mentioned. As a method that allows control of the molecular weight of each block and obtains a block copolymer with a narrow molecular weight distribution, the living radical polymerization method can be used extremely preferably. Among them, the atom transfer radical polymerization method can be used particularly preferably.

The polymer block (A) and the polymer block (B) may be directly bonded to each other, or may be bonded to each other via a monomer other than the monomer forming the polymer block (A) and the monomer forming the polymer block (B) or an oligomer block composed of such a monomer. The multiple polymer blocks (A) contained in the block copolymer chain 40 may be substantially the same polymer block (i.e., a block composed of substantially the same monomer units) or may be different polymer blocks. Furthermore, even when multiple polymer blocks (B) are contained in the block copolymer chain 40, the multiple polymer blocks (B) may be substantially the same polymer block (i.e., a block composed of substantially the same monomer units) or may be different polymer blocks.

In the second embodiment, the ionic conductivity of the polymer brush layer formed by the plurality of block copolymer chains 40 is preferably 5.0×10 ⁻¹ S/m or less, more preferably 1.0×10 ⁻¹ S/m or less, and even more preferably 5.0×10 ⁻² S/m or less, and although there is no particular lower limit, is preferably 1.0×10 ⁻⁴ S/m or more. The ionic conductivity of the polymer brush layer can be measured by the same method as in the first embodiment described above.

According to the second embodiment, the polymer brush structure has multiple exposed polymer chains with a loop structure formed by the polymer block (B), and the polymer block (B) has a specific functional group selected from an ionic group, a nonionic hydrophilic group, and an electron donating group. Therefore, as in the first embodiment described above, the polymer brush structure made of the polymer block (B) exposed in a loop shape has a specific functional group, which makes it easy to fuse with the envelope that constitutes the virus, and furthermore, since it is composed of multiple polymer chains, it exhibits high osmotic pressure, and thus can exhibit high virus inactivation function. In addition, since the polymer brush structure made of the polymer block (B) is composed of a polymer brush structure made of multiple polymer blocks (B), it can stably exhibit such high virus inactivation function without accompanying structural changes, etc., and therefore it can be said that the high virus inactivation function can be sustained for a long period of time.

In the second embodiment, an ABA type block copolymer chain consisting of polymer block (A)/polymer block (B)/polymer block (A) is used as the block copolymer chain 40, and a structure having a polymer brush structure in which multiple polymer chains of a loop structure formed by polymer block (B) are exposed is exemplified. However, an AB block copolymer chain consisting of polymer block (A)/polymer block (B) may be used, and a structure in which polymer block (B) is exposed without forming a loop structure may also be used.

Third Embodiment
Next, a third embodiment of the present invention will be described.
Fig. 3 is a diagram showing a virus inactivating structure according to a third embodiment of the present invention. As shown in Fig. 3, the virus inactivating structure according to the third embodiment is a branched polymer 50. As shown in Fig. 3, the branched polymer 50 has a structure in which a plurality of polymer graft chains (side chains) 52 branch off from a linear main chain (a linear polymer chain that serves as the main chain) 51 as a substrate. The branched polymer 50 has a shape like a bottle brush (a cleaning brush for cleaning containers having a bottle structure).

The branched polymer 50 has a branched polymer structure in which multiple side chains 52 branch off from a linear main chain 51 as described above, and the main chain 51 and the side chains 52 are each composed of multiple linked repeating units each containing at least a carbon atom and a hydrogen atom. In the branched polymer 50, the side chains 52 have a specific functional group selected from an ionic group, a nonionic hydrophilic group, and an electron-donating group, and the branched polymer 50 has such side chains 52 and thus has a virus inactivation function.

The number average degree of polymerization of the main chain 51 is preferably 10 to 10,000, more preferably 10 to 1,000, and even more preferably 10 to 100. The number average degree of polymerization of the main chain 51 is not particularly limited, but can be determined by measuring the number average molecular weight of the main chain precursor before the introduction of the side chain 52, and dividing the measured number average molecular weight by the monomer unit molecular weight.

The side chain 52 may be linear or may have a branched or crosslinked structure. The number-average degree of polymerization of the side chain 52 is preferably 1 to 1.00, more preferably 1 to 50, and even more preferably 5 to 20. There is no particular limitation on the method for measuring the number-average degree of polymerization of the side chain. For example, in the synthesis process of the branched polymer 50, when a reaction is carried out to extend the side chain 52 from the main chain 51, a small amount of a low-molecular-weight initiator (e.g., an organic compound having a halogen-substituted carbon group) is added to the reaction system so that a free polymer having a repeating structure common to the polymer chain of the side chain 52 is simultaneously synthesized, and the number-average degree of polymerization measured for the free polymer can be used as the number-average degree of polymerization of the side chain 52.

The number average molecular weight (Mn) of the entire branched polymer 50, including the main chain 51 and the side chains 52, is preferably 1,000 to 10,000,000, more preferably 1,000 to 1,000,000, and even more preferably 5,000 to 500,000. The number average molecular weight of the entire branched polymer 50 can be measured in polystyrene equivalent value by gel permeation chromatography.

The density of side chains branching from the main chain is the number per nm of main chain path length (chains/nm), and is preferably 1 chain/nm or more, more preferably 2 chains/nm or more, and even more preferably 3 chains/nm or more. Here, the density of the side chains can be determined from the grafting efficiency.

The branched polymer 50 used in the third embodiment is not particularly limited as long as it has a structure in which a plurality of side chains 52 are branched from a linear main chain 51 as a base, as shown in FIG. 3, and the plurality of side chains 52 have a specific functional group selected from an ionic group, a nonionic hydrophilic group, and an electron donating group. The branched polymer 50 can be manufactured, for example, by graft polymerizing a monomer mixture containing a monomer having a specific functional group to a polymer for forming the main chain 51 by a known graft polymerization method. In addition, as in the first embodiment described above, the branched polymer 50 is preferably manufactured by graft polymerizing a monomer mixture containing a monomer having an ammonium group as a specific functional group (more preferably, a monomer that can introduce an ammonium group into the side chain of the polymer chain, particularly preferably a compound represented by the above general formula (1)). Note that the monomer having the specific functional group may be used alone, or two or more types may be used in combination. In addition, a monomer that can be copolymerized with the monomer having the specific functional group (a monomer that does not have a specific functional group) may be used as a monomer for forming the polymer chain.

As in the first embodiment described above, instead of the compound represented by the above general formula (1), or together with the compound represented by the above general formula (1), for example, a (meth)acrylic acid-based monomer, a styrene-based monomer, a monofunctional monomer having one addition-polymerizable double bond, a hydrophobic monomer, a hydrophilic monomer, a monomer having a carboxyl group or a group that can be easily converted to a carboxyl group in the side chain, etc. may be used.

In the third embodiment, the branched polymer 50 may be a polymer in which a plurality of branched polymers 50 form a crosslinked structure, or a plurality of branched polymers 50 bonded to each other by ionic bonds, hydrogen bonds, hydrophobic interactions, or the like. Alternatively, a substrate or a filler may be used, a polymerization initiator group may be introduced to the surface of the substrate or filler, and a polymerization reaction may be carried out on the substrate or in a state containing the filler, thereby forming the branched polymer 50 on the substrate or with the filler. When a plurality of branched polymers 50 are formed on the substrate, a polymer brush layer made of a plurality of branched polymers 50 can be formed on the substrate. In this case, the ionic conductivity of the polymer brush layer made of a plurality of branched polymers 50 is preferably 5.0×10 −1 S/m or less, more preferably 1.0×10 ⁻¹ S/m or less, and even more preferably 5.0×10 ⁻² S/m or less. The lower limit is not particularly limited, but is preferably 1.0 ^{×10 −4 S} /m or more. The ionic conductivity of the polymer brush layer can be measured by the same method as in the first embodiment described above.

The branched polymer 50, which is a virus inactivation structure according to the third embodiment, has a structure in which multiple polymer graft chains (side chains) 52 are branched from a main chain 51, and the side chains 52 have a specific functional group selected from an ionic group, a nonionic hydrophilic group, and an electron donating group. Therefore, as in the first embodiment described above, the specific functional group contained in the side chains 52 makes it easy to fuse with the envelope that constitutes the virus, and since it is composed of multiple polymer chains, it exhibits high osmotic pressure, which can be said to exhibit a high virus inactivation function. In addition, since the branched polymer 50 has a bottle brush-like structure with multiple side chains 52, it can stably exhibit such a high virus inactivation function without undergoing structural changes, etc., and therefore can be said to have a high virus inactivation function that can be sustained for a long period of time.

The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

Example 1
(Formation of polymer brush layer)
Surface-initiated atom transfer radical polymerization (ATRP) of N,N-diethyl-N-(2-methacryloylethyl)-N-methylammonium bis(trifluoromethylsulfonyl)imide (DEMM-TFSI) was carried out as follows.
That is, first, 26.0 mg (0.13 mmol) of 2,2'-bipyridine (Bipy), 1.96 g of N,N-diethyl-N-(2-methacryloylethyl)-N-methylammonium bis(trifluoromethylsulfonyl)imide (DEMM-TFSI), and 8.0 g of acetonitrile were placed in a flask, and the solution was degassed by bubbling with argon for 10 minutes. The flask was then transferred to a glove box purged with argon, and 5.2 mg (0.052 mmol) of Cu(I)Cl and 0.78 mg (0.0058 mmol) of Cu(II)Cl ₂ were added, and a three-way stopcock was attached to the flask. Thereafter, the stopper was closed to keep the flask sealed, and the flask was removed from the glove box, and the mixture was stirred in an oil bath at 60°C to completely dissolve copper and Bipy. The flask was then transferred to a glove box, and the solution was filtered with a membrane filter (pore size: 0.2 μm). A vacuum pump was then used to volatilize and remove acetonitrile. The reason for adding acetonitrile in the above procedure is to reduce the viscosity of the solution and promote the dissolution of copper and Bipy as a ligand. In addition, in order to suppress the precipitation of copper chloride during the polymerization process, the reaction was carried out using a 10% excess amount of ligand (Bipy) relative to the required molar amount in terms of the molar amount relative to copper. Next, 8.0 g (16.6 mmol) of DEMM-TFSI and 0.65 mg (0.0033 mmol) of ethyl 2-bromoisobutyrate (2-(EiB)Br) were placed in another Schlenk tube, and the mixture was degassed by bubbling with argon for 20 minutes. The obtained solution was placed in a Schlenk tube and a flask and mixed to prepare a non-volatile ATRP polymerization solution. The molar composition ratio of the resulting ATRP polymerization solution was [DEMM-TFSI] ₀ /[2-(EiB)Br] ₀ /[Cu(I)Cl] ₀ /[Cu(II)Cl ₂ ] ₀ /[Bipy] ₀ =5000/1/20/5/50.

Then, the ATRP polymerization solution thus obtained was filtered, and the filtered ATRP polymerization solution was centrifuged at 500×g for 10 minutes using a centrifuge installed in a glove box to perform a degassing operation. The filtration and degassing operations are performed to prevent undissolved solid components of copper chloride or air bubbles mixed in during the preparation of the solution from adhering to a substrate such as a silicon wafer or glass, which would prevent the formation of a polymer brush on that part.

Next, in a glove box, the ATRP polymerization solution, which had been subjected to a filtering operation and a degassing operation, was applied onto a silicon wafer on which an ATRP initiator group was fixed using (2-bromo-2-methyl)propionyloxypropyltriethoxysilane (BPE) as a fixing initiator. Then, an ATRP polymerization reaction was carried out in an incubator (installed in a glove box) set at a temperature of 70°C. The ATRP polymerization solution prepared above was prepared only with non-volatile components and had a relatively high viscosity, so that it was maintained as a liquid layer having a thin liquid film on the silicon wafer until the polymerization was completed. In this ATRP polymerization reaction system, the polymerization conversion rate of the monomer reached 99% after 70 hours, and a polymer brush layer having a plurality of polymer chains with a number average molecular weight of 1,826,000 and a molecular weight distribution (Mw/Mn) of 1.20 was formed on the silicon wafer. The resulting polymer brush layer had a dry film thickness T _b (film thickness after drying in a vacuum at 25° C. for 1 hour) of 515 nm as measured by spectroscopic ellipsometry, and the graft density and surface occupancy as calculated by the above-mentioned method were 0.15 chains/nm ² and 35%, respectively. The ratio of the thickness T _b of the polymer brush layer to the average molecular chain length L _p of the multiple polymer chains constituting the polymer brush layer (T _b /L _p ), calculated by the above-mentioned method, was 0.41, and the ionic conductivity of the polymer brush layer as measured by a four-terminal conductivity measurement (using a resistivity meter (Loresta, manufactured by Nitto Seiko Analytech Co., Ltd.)) was 1.60×10 ⁻² S/m. Separately, a DEMM-TFSI polymer was prepared and dispersed in water at 1 wt % at pH=7, and the absorbance was measured. The absorbance was 0.3 or less, indicating water solubility.

(Evaluation of viral inactivation)
After the above-obtained silicon wafer (1 cm x 1 cm) on which the polymer brush layer was formed was sterilized, 3 μL of virus liquid (bovine herpes virus liquid) was dropped onto the surface on which the polymer brush layer was formed, and the virus liquid was spread over the surface on which the polymer brush layer was formed, covered with a cover glass, and left to stand at room temperature for 5 minutes. After 5 minutes had elapsed, the silicon wafer on which the polymer brush layer was formed was placed in a test tube together with 500 μL of culture liquid (MEM), and stirred for 10 seconds with a vortex mixer to liberate the virus adhering to the surface of the polymer brush layer into the culture liquid. Next, a portion of the culture liquid was extracted, and the extracted culture liquid was inoculated into cells, and the number of detected plaques was counted to evaluate the virus inactivation effect.
In addition, the virus inactivation effect was evaluated by performing the same measurement as above on a glass plate not formed with a polymer brush layer and comparing the number of plaques counted. As a result, the number of plaques detected on the silicon wafer with the polymer brush layer (average: 11) was 7% of the number of plaques detected on the glass plate not formed with a polymer brush layer (average: 157). In other words, the number of viruses was reduced by 93%.

The same measurements were also performed, but the time was changed from 5 minutes to 30 minutes. As a result, the number of plaques detected on the silicon wafer with the polymer brush layer (average: 1.3) was 1.2% of the number of plaques detected on the glass plate without the polymer brush layer (average: 104.3). In other words, the number of viruses was reduced by 98.8%.

Furthermore, when the silicon wafer having the polymer brush layer formed thereon, which had been subjected to the above-mentioned evaluation of virus inactivation (left to stand for 30 minutes), was washed with distilled water and the above-mentioned evaluation of virus inactivation was performed again (left to stand for 30 minutes) (i.e., evaluation by reuse was performed), the number of plaques detected on the silicon wafer having the polymer brush layer formed thereon was less than 10% of the number of plaques detected on the glass plate having no polymer brush layer formed thereon, resulting in a reduction in the number of viruses by 90% or more.
When washing with a 70% aqueous ethanol solution instead of distilled water was performed and the evaluation was carried out in the same manner as above, the number of plaques detected on the silicon wafer with the polymer brush layer formed was similarly less than 10% of the number of plaques detected on the glass plate without the polymer brush layer formed, which resulted in a reduction in the number of viruses by 90% or more.

From the above, it can be confirmed that a polymer brush containing multiple polymer chains having specific functional groups selected from ionic groups, nonionic hydrophilic groups, and electron-donating groups can achieve high virus inactivation function, and furthermore, that such high virus inactivation function can be sustained over a long period of time.

Example 2
(Formation of polymer brush layer)
A polymer brush layer was formed on silica particles in the same manner as in Example 1, except that (2-bromo-2-methyl)propionyloxyhexyltriethoxysilane (BHE) was used instead of (2-bromo-2-methyl)propionyloxypropyltriethoxysilane (BPE) as the immobilization initiator, and silica particles were used instead of silicon wafers. The obtained polymer brush layer was quantified by thermogravimetric analysis, and the weight fraction of the polymer content was 8.9%. The graft density measured by the above-mentioned method was calculated to be 0.15 chains/nm ² and the surface occupancy rate was 34%. In addition, in Example 2, taking into account the production conditions, etc., it can be said that the number average molecular weight and molecular weight distribution (Mw/Mn) of the polymer chains constituting the polymer brush layer, the dry film thickness T _b of the polymer brush layer, the ratio of the thickness T _b of the polymer brush layer (T _b /L _p ), and the ionic conductivity of the polymer brush layer are almost the same as those in Example 1.

(Evaluation of viral inactivation)
1.0 g of the silica particles having the obtained polymer brush layer formed thereon was dispersed in 200 mL of a solvent in which an equal volume of a 0.5 M acetonitrile acetate solution and water was mixed, to obtain an acetic acid dispersion of the silica particles having the polymer brush layer formed thereon. Then, 0.925 mL of the acetic acid dispersion of the silica particles having the obtained polymer brush layer formed thereon, 100 μL of a virus solution (bovine herpes virus solution), and 1.475 mL of phosphate buffered saline (PBS) were placed in a test tube to prepare a test solution. Then, 25 μL of the obtained test solution (prepared sample) was collected, and a shaking operation was performed for 1 hour, and 25 μL of the test solution after shaking for 1 hour (1-hour shaking sample) was collected, and further, a shaking operation was performed for 1 hour, and 25 μL of the test solution after shaking for 1 hour (2-hour shaking sample) was collected. The collected post-preparation sample, 1-hour shake sample, and 2-hour shake sample were then diluted 10,000-fold with culture medium (MEM) and inoculated onto cells. After standing for 1 hour, the cells were overlaid with methylcellulose medium and cultured for 2 days, after which the virus inactivation effect was evaluated in the same manner as in Example 1. In Example 2, a sample using silica particles without a polymer brush layer was also prepared under the same conditions and used as a comparison subject. As a result, the same virus inactivation function as in Example 1 was confirmed in Example 2.

Claims (10)

A virus inactivating material having a virus inactivating function, comprising a polymer brush layer on a substrate , the polymer brush layer including a plurality of polymer chains each having a functional group selected from an ionic group, a nonionic hydrophilic group, and an electron donating group,
A virus inactivation material having a virus inactivation function , wherein the polymer chain is introduced onto a substrate by a surface-initiated living radical polymerization method using a monomer containing at least a compound represented by the following general formula (1) :

[In the above general formula (1), m represents an integer of 1 or more and 10 or less. n represents an integer of 1 or more and 5 or less. R ¹ represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms. R ² , R ³ , and R ⁴ represent alkyl groups having 1 to 5 carbon atoms. R ² , R ³ , and R ⁴ may each contain one or more heteroatoms selected from an oxygen atom, a sulfur atom, and a fluorine atom, and two or more of R ² , R ³ , and R ⁴ may be linked to form a cyclic structure. In addition, Z ^- represents a monovalent anion.] The virus inactivating material according to claim 1 , wherein the plurality of polymer chains are water-soluble. 3. The virus inactivating material according to claim 1, wherein a plurality of the polymer chains are fixed onto the substrate by covalent bonds to form a polymer brush layer . 4. The virus inactivating material according to claim 1, wherein a ratio (T _b /L _p ) of a thickness T _b of the polymer brush layer to an average molecular chain length L _p of the polymer chains constituting the polymer brush layer is 0.001 to 0.6. 5. The virus inactivating material according to claim 1 , wherein the substrate is a fiber, a single fiber, a twisted yarn, a woven fabric, a nonwoven fabric, a cut fiber, a hollow fiber, glass, a metal, or a processed product thereof. 6. The virus inactivating material according to any one of claims 1 to ⁵ , wherein the graft density per unit area of the polymer chains is 0.12 to 0.25 chains/nm2, and the occupied area ratio to the surface area of the substrate is 20 to 40% in terms of the occupancy rate per polymer cross-sectional area. 7. The virus inactivating material according to claim 1 , wherein the polymer brush layer has an ionic conductivity of 5.0×10 ⁻¹ S/m or less. 8. The virus inactivating material according to claim 1, wherein the polymer chain fuses with an envelope constituting a virus, causing the envelope to open, and thereby RNA inside the virus is expelled to the outside by the osmotic pressure of the polymer chain , thereby inactivating the virus. 9. The virus inactivating material according to any one of claims 1 to 8 , wherein the number average molecular weight (Mn) of the polymer chain is from 100,000 to 10,000,000 and the molecular weight distribution (Mw/Mn) is 1.25 or less. Use of the virus inactivation material according to any one of claims 1 to 9 for inactivating viruses.

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