JP7122043B2 - Isolated nanosheet and method for producing the same - Google Patents

Description

TECHNICAL FIELD The present invention relates to an isolated nanosheet having a plurality of pseudo-polyrotaxanes and/or polyrotaxanes and a method for producing the same.

In recent years, nanosheets with a thickness of 100 nm or less have been developed for application to medicines, catalysts, optical materials, electrodes, biomaterials, and the like. Materials such as titanium oxide, boron nitride, carbon nitride, and graphene have been conventionally used (see, for example, Non-Patent Documents 1 to 5), but these inorganic materials are easily contaminated with impurities and are difficult to purify. . In addition, there are problems with biosafety and compatibility, and application to drugs and biomaterials has been difficult.

Several methods of synthesizing nanosheets using biocompatible organic molecules have also been proposed. Examples thereof include polymer nanosheets formed using polylactic acid (PLA), polydimethylsiloxane (PDMS), or the like. These polymer nanosheets are obtained by preparing a polymer solution, spin-coating the solution onto a substrate, peeling the obtained sheet from the substrate, and pulverizing the obtained release sheet ( See, for example, Non-Patent Document 6). Nanosheets using the above organic molecules are expected to be applied to medicines and biomaterials, but the synthesis process and film forming process are complicated. In addition, there is a problem that the manufacturing cost is enormous.

It is difficult for nanosheets to exist stably in a nano-state, and there are problems such as irregular adhesion of sheets to objects or aggregation of sheets, and difficulty in modifying and modifying the surface to prevent such problems. There is a problem. Solutions to these problems are also desired.

Zhang, S.; Sunami et al., Nanomaterials-Basel 2017, 7 (9). Tan, C. L. et al., Chem Rev 2017, 117 (9), 6225-6331. Li, X. et al., Small 2017, 13 (5). Kong, X. K. et al., Chem Soc Rev 2017, 46 (8), 2127-2157. Yang, G. H. et al., Nanoscale 2015, 7 (34), 14217-14231. Okamura, Y. et al., Adv Mater 2013, 25 (4), 545-551.

Therefore, an object of the present invention is to provide an isolated nanosheet that is excellent in biosafety and compatibility, can be applied to drugs and biomaterials, and has a relatively simple synthesis process and film forming process.
An additional object of the present invention is, in addition to the above objects, to provide an isolated nanosheet that does not adhere irregularly to an object and that does not aggregate with each other.

Furthermore, another object of the present invention is to provide a material having the isolated nanosheet.
Another object of the present invention is to provide a method for producing the isolated nanosheet.

According to one aspect of the present invention, an isolated nanosheet comprising a plurality of pseudo-polyrotaxanes and/or polyrotaxanes in which the opening of the first cyclic molecule is skewered and clathrated by a linear molecule, An isolated nanosheet is provided, wherein the linear molecule has at or near both ends thereof a first linear molecule having non-ionizable groups that do not ionize under nanosheet-forming conditions.
According to another aspect of the present invention, a method for producing an isolated nanosheet comprising a plurality of pseudo-polyrotaxanes in which the opening of the first cyclic molecule is skewered and clathrated by a linear molecule, a) Step of preparing a linear molecule having a first linear molecule having non-ionized groups at both ends or near both ends that are not ionized under nanosheet forming conditions; b) Step of preparing a first cyclic molecule and c) mixing the linear molecule and the first cyclic molecule in water or an aqueous solution; thereby obtaining the isolated nanosheet.

According to yet another aspect of the present invention, the production of an isolated nanosheet comprising a plurality of pseudo-polyrotaxanes and/or polyrotaxanes in which the opening of the first cyclic molecule is skewered with linear molecules A method comprising: a′) providing a linear molecule; b) providing a first cyclic molecule; c′) combining said linear molecule and said first cyclic molecule in water or an aqueous solution. to obtain a pseudo-polyrotaxane; d) introducing a non-ionizing group that does not ionize preferably in water or an aqueous solution under nanosheet forming conditions to both ends of at least a portion of the linear molecule; a step of forming the first linear molecule; e) a step of introducing blocking groups to both ends of at least a portion of the linear molecule of the pseudopolyrotaxane and/or the first linear molecule; f) obtaining mixing the obtained pseudo-polyrotaxane and/or polyrotaxane in water or an aqueous solution; thereby obtaining the isolated nanosheet.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a nanosheet that is excellent in biosafety and compatibility, can be applied to drugs and biomaterials, has a relatively simple synthesis process and film forming process, and has a reduced cost. .
In addition to the effects described above, the present invention can provide an isolated nanosheet that does not adhere irregularly to an object and that does not aggregate with each other.

Furthermore, the present invention can provide a material having the isolated nanosheet.
Moreover, the present invention can provide a method for producing the isolated nanosheet.

FIG. 4 is a diagram schematically showing that a pseudo-polyrotaxane 31 is formed from a polymer 11 and a cyclic molecule 21, and a plurality of the pseudo-polyrotaxanes 31 aggregate to form an isolated nanosheet 41 of the present invention. FIG. 4 is a diagram schematically showing that the isolated nanosheet is formed in a state where the first linear molecules of the pseudo-polyrotaxane or polyrotaxane constituting the isolated nanosheet are folded in a U shape. The first linear molecule of the pseudopolyrotaxane or polyrotaxane that constitutes the isolated nanosheet has four branched chains, each chain of the four branched chains includes a cyclic molecule, and each chain of the four branched chains has " It is a figure which shows typically that a "cyclic molecule free area" exists. FIG. 4 is a diagram schematically showing the first cyclic molecule, and a diagram showing that the distance indicated by D is the "thickness of the first cyclic molecule in the central axis direction". 1 is a diagram showing the results of small-angle X-ray scattering measurement of isolated nanosheet X1 of Example 1. FIG. FIG. 10 shows the results of small-angle X-ray scattering measurement of isolated nanosheet X2 of Example 2. FIG. FIG. 10 shows the results of small-angle X-ray scattering measurement of isolated nanosheet X3 of Example 3. FIG. 4 is a diagram showing the results of structural analysis by small-angle X-ray scattering measurement of the solution prepared in Comparative Example 1. FIG. FIG. 10 shows the results of small-angle X-ray scattering measurement of isolated nanosheet X4 of Example 4. FIG. FIG. 10 is a scanning electron microscope image of isolated nanosheet X4 of Example 4. FIG. FIG. 10 is a scanning electron microscope image of Example 5 in which the isolated nanosheet X1 is observed to be adsorbed to the silicon substrate. FIG. 10 is a scanning electron microscope image of the multi-layered nanosheet X9 of Example 9. FIG. FIG. 10 shows the results of small-angle X-ray scattering measurement of the multi-layered nanosheet X9 of Example 9. FIG. FIG. 10 shows the results of small-angle X-ray scattering measurement of the solution prepared in Comparative Example 6; FIG. 10 is a scanning electron microscope image of block-shaped particles observed in the solution prepared in Comparative Example 6; FIG. 10 shows the results of small-angle X-ray scattering measurement of the solution prepared in Comparative Example 7; FIG. 10 is a scanning electron microscope image of block-shaped particles observed in the solution prepared in Comparative Example 7; FIG. 10 shows the results of small-angle X-ray scattering measurement of the solution prepared in Comparative Example 8; FIG. 10 is a scanning electron microscope image of block-shaped particles observed in the solution prepared in Comparative Example 8; FIG. 10 is a scanning electron microscope image of nanosheet X10 of Example 10. FIG. FIG. 10 is a scanning electron microscope image of nanosheet X11 of Example 11. FIG. FIG. 10 is a scanning electron microscope image of nanosheet X12 of Example 12. FIG. SEM images of (A) porous membrane, (B) pore-β-CD/EO ₇₅ PO ₃₀ EO ₇₅ (5 mL) and (C) pore-β-CD/EO ₇₅ PO ₃₀ EO ₇₅ (20 mL). Absorbance of the nanosheets of Example 14.

The invention described in the present application will be described in detail below.
The present application provides isolated nanosheets.
The isolated nanosheet of the present invention comprises a plurality of pseudo-polyrotaxanes and/or polyrotaxanes in which the openings of the first cyclic molecules are skewered and clathrated by linear molecules.
In the present application, "isolated" in "isolated nanosheets" means that they can exist independently without being aggregated in a solution. In addition, the “isolated nanosheet” is a nanosheet having a plurality of pseudo-polyrotaxanes and / or polyrotaxanes in which the opening of the first cyclic molecule is skewered by a linear molecule, that is, a single nanosheet. or the nanosheet may consist of multiple layers. The formation of isolated nanosheets can be confirmed by small-angle X-ray scattering measurement, phase-contrast optical microscope observation, atomic force microscope observation, and scanning electron microscope observation. In particular, small-angle X-ray scattering measurements revealed that the material was sheet-like due to the shape factor. Specifically, the shape factor showed fringes characteristic of a sheet structure, and no increase in scattering intensity due to aggregation was observed on the base angle side. It can sometimes be identified as an isolated nanosheet (see, for example, Principles and Applications of X-ray, Light, and Neutron Scattering (KS Kagaku Specialty Book)).

In the present application, "nano" in "isolated nanosheet" means that the thickness of the single layer of the isolated nanosheet is 100 nm or less, specifically 0.5 to 100 nm, preferably 3 to 50 nm, more preferably 5 nm. ~20 nm. When the isolated nanosheet consists of multiple layers, the thickness of the constituent single-layer nanosheet is 100 nm or less, specifically 0.5 to 100 nm, preferably 3 to 50 nm, more preferably 5 to 20 nm. Say things.
In the isolated nanosheet of the present application, the thickness direction of the single-layered nanosheet is preferably the longitudinal direction of the pseudopolyrotaxane and/or the polyrotaxane, in other words, the longitudinal direction of the linear molecule. The longitudinal direction of the pseudo-polyrotaxane and/or the polyrotaxane and the longitudinal direction of the linear molecules are preferably the thickness direction of the single-layer isolated nanosheet of the present application. Although there are special cases shown in FIGS. 2 and 3 to be described later, basically, the longitudinal direction of the linear molecule is the thickness direction of the single-layer isolated nanosheet of the present application. can do.
In the present application, the “single layer” of the isolated nanosheet means that it is observed to consist of one layer by small-angle X-ray scattering measurement, scanning electron microscope image, or the like.

Further, in the present application, "pseudo-polyrotaxane" is defined in comparison with "polyrotaxane". A "pseudopolyrotaxane" is defined as different in that it does not have such a "group having a blocking action (blocking group)". In short, in the present specification, the term “pseudopolyrotaxane” means that only one end of a linear molecule has a group (blocking group) having the above blocking action, or both ends of the linear molecule have the above blocking action. (blocking group).

The linear molecule of pseudo-polyrotaxane and/or polyrotaxane that forms the isolated nanosheet of the present application preferably has non-ionized groups that do not ionize in water or an aqueous solution at both ends or in the vicinity of the both ends, preferably in water or an aqueous solution. It has 1 linear molecule. The vicinity of the chain polymer generally refers to a range of 1 to 10 monomer units, more preferably 1 to 5 monomer units from the end of the chain polymer, excluding the end of the chain polymer.

The linear molecules of the pseudopolyrotaxane and/or polyrotaxane that make up the isolated nanosheet either have the first linear molecule, for example consist essentially of the first linear molecule, or It is preferable to consist only of linear molecules of In addition, "the linear molecule consists only of the first linear molecule" means that the linear molecule of the pseudo-polyrotaxane and/or the polyrotaxane constituting the isolated nanosheet is the linear molecule other than the first linear molecule. does not exist. Further, "the linear molecule consists essentially of the first linear molecule" means that the linear molecule of the pseudo-polyrotaxane and/or polyrotaxane constituting the isolated nanosheet is the first linear molecule. It means that the presence of non-like molecules does not adversely affect the formation of isolated nanosheets.

In the present application, the term “non-ionizing group” refers to a group that does not ionize preferably in water or an aqueous solution under nanosheet-forming conditions.
The non-ionizing group is not particularly limited as long as it satisfies the above definition. pentyl group, tert-pentyl group, cyclopentyl group, pentene group, hexyl group, hexene group, heptyl group, heptene group, octyl group, octene group, nonyl group, nonene group, decyl group, decene group, undecyl group, undecene group, dodecyl group, dodecene group, tridecyl group, tridecene group, tetradecyl group, tetradecene group, pentadecyl group, pentadecene group, hexadecyl group, hexadecene group, heptadecyl group, heptadecene group, octadecyl group, octadecene group, nonadecyl group, nonadecene group, eicosyl group , eicosene group, henicosyl group, henicosene group, tetracosyl group, tetracosene group, triacontyl group, triacontene group and their isomers, 4-isopropylbenzenesulfonyl group, 1-octanesulfonyl group, 4-biphenylsulfonyl group, 4-tert -butylbenzenesulfonyl group, 2-mesitylenesulfonyl group, methanesulfonyl group, 2-nitrobenzenesulfonyl group, 4-nitrobenzenesulfonyl group, pentafluorobenzenesulfonyl group, 2,4,6-triisopropylbenzenesulfonyl group, p-toluenesulfonyl group groups, non-ionized hydroxyl groups, heptafluorobutyroyl groups, pivaloyl groups, perfluorobenzoyl groups, non-ionized amino groups (—NH ₂ ), non-ionized carboxylic acid groups (—COOH), and isovaleryl groups. It is preferably at least one selected from the group consisting of:

The non-ionized group is preferably at least one selected from the group consisting of non-ionized hydroxyl group, heptafluorobutyroyl group, perfluorobenzoyl group and isovaleryl group, more preferably perfluorobenzoyl group and isovaleryl group. It is preferably at least one selected from the group consisting of groups.
In addition, "not ionized" in "non-ionized hydroxyl group", "non-ionized amino group", and "non-ionized carboxylic acid group" means, as described above, under nanosheet preparation conditions, preferably It means that it is not ionized in water or aqueous solution.

The first linear molecule constituting the pseudo-polyrotaxane and/or polyrotaxane forming the isolated nanosheet of the present application has first and second regions (hereinafter referred to as may simply be described as a “cyclic molecule-free region”). That is, the first region exists inside from one end of the first linear molecule, and the second region exists inside from the other end of the first linear molecule.
Also, the lengths of the first and second regions are each independently 0.5 to 100 nm, preferably 1 to 70 nm, and more preferably 1 to 50 nm.
Although not based on complete theory, it is believed that having a "cyclic molecule-free region" of the above length works favorably for the formation of isolated nanosheets.

Here, the lengths of the first and second regions can be obtained as follows.
The "monolayer" thickness of an isolated nanosheet can be determined by small-angle X-ray scattering or atomic force microscopy (thickness t). Also, the extended chain length (L) of the first linear molecule can be obtained by measuring the molecular weight by gel permeation chromatography, nuclear magnetic resonance, or the like. The isolated nanosheets that are formed have the shape shown in FIG. Here, FIG. 1 shows that the pseudo-polyrotaxane 31 is formed from the polymer 11 and the cyclic molecule 21, and the cyclic molecule 21 included in the adjacent pseudo-polyrotaxane 31 is adjacent to the cyclic molecule 21 included in the adjacent pseudo-polyrotaxane 31. FIG. 4 is a diagram schematically showing that an isolated nanosheet 41 of the present invention is formed by aggregating a plurality of pseudo-polyrotaxanes 31. FIG. The isolated nanosheet 41 has a first region 51 and a second region 52 where the cyclic molecules 21 are not present.

_Therefore , from the shape _shown in FIG. The sum (l ₁ +l ₂ ) with the length of the region (l ₂ ) of 2 is given as L−t, the length of the first region (l ₁ ) and the length of the second region (l ₂ ) are the same length, the average value of the length of the first region (l ₁ ) and the length of the second region (l ₂ ) is
l ₁ =l ₂ =(L ₁ -t)/2 (hereinafter referred to as "formula A")
can be obtained as

The approximate thickness (t′) of the isolated nanosheet can be obtained from the extended chain length (L ₁ ) of the linear molecule and the inclusion rate of the cyclic molecule. is approximately half the thickness t′, the isolated nanosheets are considered to be formed in the state shown in FIG. 2 instead of the state shown in FIG. Here, FIG. 2 shows that the cyclic molecule 22 is included in the first linear molecule 12 to form the pseudo-polyrotaxane or polyrotaxane 32, and the pseudo-polyrotaxane or polyrotaxane 32 constituting the isolated nanosheet is the first is a schematic diagram showing that an isolated nanosheet 42 is formed in a state in which the linear molecule 12 of is folded in a U shape (however, FIG. 2 shows a part of the isolated nanosheet 42 for the sake of explanation. shown as an excerpt). Also in FIG. 2, the isolated nanosheet 42 has a first region 53 and a second region 54 where the cyclic molecules 21 are not present.

Therefore, if the thickness t of the isolated nanosheet is about half the approximate thickness t′, then the length of the first region (l ₁ ) and the length of the second region (l ₂ ) can be obtained by the following formula B. That is, since the portion where the cyclic molecule is enclosed is twice the thickness t, the average value of the length (l ₁ ) of the first region and the length (l ₂ ) of the second region is ,
l ₁ =l ₂ =(L ₁ -2t)/4 (equation B)
can be obtained as

Furthermore, when the linear molecule constituting the isolated nanosheet has four branches, a cyclic molecule is included in each chain of the first linear molecule having four branches to form a pseudopolyrotaxane or polyrotaxane. It is considered that the isolated nanosheets are formed by the pseudo-polyrotaxanes or polyrotaxanes adjacent to each other in the state shown in FIG. In FIG. 3, a cyclic molecule 23 is included in each of the four branched chains of the first linear molecule 13 having four branched chains, and a pseudo-polyrotaxane or polyrotaxane (hereinafter sometimes abbreviated as “pseudo-polyrotaxane etc.”) ) 33 are formed. Further, FIG. 3 shows that the cyclic molecule 23a included in the pseudo-polyrotaxane or the like 33a is adjacent to the cyclic molecule 23b included in the adjacent pseudo-polyrotaxane or the like 33b, and the pseudo-polyrotaxane or the like 33a and 33b are aggregated to form the cyclic molecule of the present invention. An isolated nanosheet 43 is formed (however, FIG. 3 shows a part of the isolated nanosheet for explanation), and the isolated nanosheet 43 also has no cyclic molecules 23. , having one region 55 and a second region 56. FIG.

Therefore, if an isolated nanosheet is formed using a first linear molecule having n branches (where n is an integer greater than or equal to 3), the length of the first region (l ₁ ) and the length of the first The length (l ₂ ) of the area of 2 can be obtained as shown in the following formula C. That is, the extended chain length (L ₂ ) of each chain of a linear molecule having n branches can be obtained by measuring the molecular weight by gel permeation chromatography, nuclear magnetic resonance, static light scattering, or the like. Suppose each of the n chains contains a cyclic molecule, and a region of L ₂ ×n can be included in the cyclic molecule, of which only n times the thickness t is included. . Therefore, the average value of the length of the first region (l ₁ ) and the length of the second region (l ₂ ) is
l ₁ =l ₂ =(nL ₂ -nt)/2n=(L ₂ -t)/2 (equation C)
can be obtained as The formula C is the same as the formula A, and it can be seen that the formula A can be used even when having n branched chains.

Here, the extended chain length (L) of the first linear molecule can be obtained from the weight average or number average molecular weight of the linear molecule used. It can also be determined from the obtained isolated nanosheet. In order to obtain the extended chain length (L) of the first linear molecule from the obtained isolated nanosheet, the cyclic molecule is removed from the pseudo-polyrotaxane or polyrotaxane state of the obtained isolated nanosheet, and the first linear molecule is obtained. It can be obtained by obtaining a chain molecule and then determining the weight average or number average molecular weight of the obtained first linear molecule.

As described above, the non-ionizing group preferably "has""at or near both ends" of the first linear molecule. may be indirectly linked via a spacer.
The isolated nanosheet of the present invention “comprising a plurality of” “pseudo-polyrotaxanes and/or polyrotaxanes” means that when “comprising a plurality” of only “pseudo-polyrotaxanes”, only “polyrotaxanes” are “comprising a plurality of”. When "comprises", it comprises at least one "pseudo-polyrotaxane" and at least one "polyrotaxane", and when the sum of "pseudo-polyrotaxane" and "polyrotaxane" is "multiple" and "comprises" means

The first linear molecule may comprise at least two sites.
In the present application, the linear molecule and the first cyclic molecule are not particularly limited as long as they are molecules capable of adopting a form in which the opening of the first cyclic molecule is skewered and clathrated by the linear molecule.
A first linear molecule comprising at least two sites may have at least three sites. A first linear molecule comprising at least three sites is hereinafter specifically referred to as a second linear molecule. A linear molecule may consist essentially of, for example, a second linear molecule having at least three moieties, and for example, a linear molecule may consist of a second linear molecule having at least three moieties. may consist of only

A first linear molecule having at least two sites may be a block copolymer comprising at least two blocks.
Also, the second linear molecule having at least 3 moieties may be a block copolymer comprising at least 3 blocks.

Each block of the "block copolymer" preferably consists of only one repeating unit, but may have a first spacer group between one repeating unit and the next repeating unit.
It may also have a second spacer group between adjacent blocks of the "block copolymer" which may be the same or different than the first spacer group.

Examples of the first and/or second spacer group include linear or branched alkyl groups having 1 to 20 carbon atoms, such as methylene, ethylene, propylene, butylene, pentylene (partially phenyl, straight or branched chain ethers having 1 to 20 carbon atoms; straight or branched chain esters having 1 to 20 carbon atoms; aromatic rings having 6 to 24 carbon atoms groups such as, but not limited to, phenyl groups.

The first cyclic molecule may be included in one of the at least two moieties of the first linear molecule comprising at least two moieties. wherein the first linear molecule comprising at least two moieties comprises or consists essentially of a second linear molecule comprising at least three moieties, or When consisting only of the second linear molecule, the first cyclic molecule may be included in one of the at least three sites of the second linear molecule. When the linear molecule and/or the first and/or second linear molecule is a block copolymer, the first cyclic molecule may be enclosed in a certain "block". .

The site where the first cyclic molecule is included in the linear molecule, for example, one of the at least two sites of the first linear molecule and at least three sites of the second linear molecule One of the sites, a "block" of the block copolymer, should have a chain length greater than the thickness of the first cyclic molecule. Here, the thickness of the first cyclic molecule is, more precisely, the thickness of the first cyclic molecule in the central axis direction. Here, the "thickness of the first cyclic molecule in the central axis direction" will be described with reference to the drawings. FIG. 4 is a diagram schematically showing the first cyclic molecule. In FIG. 4, the distance indicated by D is the "thickness of the first cyclic molecule in the central axis direction".
The site where the first cyclic molecule is included in the linear molecule, for example, one of the at least two sites of the first linear molecule and at least three sites of the second linear molecule One of the moieties and/or a certain “block” of the block copolymer has a chain length of 2 times or more, preferably 5 times, more preferably 14 times the thickness of the first cyclic molecule in the central axis direction. Double is better.

In the present application, as described above, the linear molecule is not particularly limited as long as it is a linear molecule that can adopt a form in which the opening of the first cyclic molecule is skewered and clathrated by the linear molecule. .

As a skeleton of a linear molecule, for example, as a skeleton forming at least two or at least three sites, polyvinyl alcohol, polyvinylpyrrolidone, poly(meth)acrylic acid, cellulose resins (carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, etc.) ), polyacrylamide, polyethylene oxide, polyethylene glycol, polypropylene glycol, polyvinyl acetal resin, polyvinyl methyl ether, polyamine, polyethyleneimine, casein, gelatin, starch, etc. and/or their copolymers, polyethylene, polypropylene, and other olefins Polyolefin resins such as copolymer resins with system monomers, polyester resins, polyvinyl chloride resins, polystyrene resins such as polystyrene and acrylonitrile-styrene copolymer resins, polymethyl methacrylate and (meth)acrylic acid ester copolymers , acrylic resins such as acrylonitrile-methyl acrylate copolymer resins, polycarbonate resins, polyurethane resins, vinyl chloride-vinyl acetate copolymer resins, polyvinyl butyral resins, etc.; Acrylonitrile-butadiene-styrene copolymer (ABS resin), polyamides such as nylon, polyimides, polyisoprene, polydienes such as polybutadiene, polysiloxanes such as polydimethylsiloxane, polysulfones, polyimines, polyacetic anhydrides , polyureas, polysulfides, polyphosphazenes, polyketones, polyphenylenes, polyhaloolefins, and derivatives thereof. For example, it may be selected from the group consisting of polyethylene glycol, polyisoprene, polyisobutylene, polybutadiene, polypropylene glycol, polytetrahydrofuran, polydimethylsiloxane, polyethylene, polypropylene, polyvinyl alcohol and polyvinyl methyl ether. Particularly preferred are polyethylene glycol and polypropylene glycol. Linear molecules in the isolated nanosheet may be of one type, or may be of two or more types.

When the linear molecule has, for example, at least two or at least three sites, the linear molecule itself preferably has a weight average molecular weight of 500 to 500,000, preferably 1,000 to 20,000, and more preferably 6,000 to 16,000. . The weight average molecular weight of linear molecules can be measured by gel permeation chromatography (GPC). GPC measurement conditions depend on the type of linear molecule, but it is preferable to appropriately select the type of eluent and column, temperature, standard substance, and flow rate.

Also, the linear molecule is preferably a water-soluble linear molecule. The water-soluble linear molecule is not particularly limited as long as it is water-soluble, for example, 1 g can be dissolved in 1 L of water.

As the backbone of the water-soluble linear molecule, for example, as a backbone forming at least two or at least three sites, polyethylene glycol, polypropylene glycol, polyvinyl alcohol, polyethyleneimine, polyacrylic acid, polymethacrylic acid, polyacrylamide, pullulan, Non-limiting examples include water-soluble cellulose derivatives such as hydroxypropylcellulose, polyvinylpyrrolidone, polypeptides, and copolymers including polyethylene glycol.

That is, the water-soluble linear molecule is at least one selected from the group consisting of the polymer species listed above, preferably polyethylene glycol, polypropylene glycol, polyvinyl alcohol, polyethyleneimine, and a copolymer containing polyethylene glycol. At least one selected from the group, more preferably at least one selected from the group consisting of polyethylene glycol and polypropylene glycol.
Although the molecular weight (number average molecular weight or weight average molecular weight) of the water-soluble linear molecule is not particularly limited, it is preferably 500 to 500,000, preferably 1,000 to 50,000, and more preferably 2,000 to 20,000.

In the present application, the first cyclic molecule is a molecule that can adopt a form in which the opening of the first cyclic molecule is skewered by a linear molecule. a molecule that can take the form of inclusion in one of at least two sites of a linear molecule, one of at least three sites of a second linear molecule, a "block" of a block copolymer If so, it is not particularly limited.

Examples of the first cyclic molecule include α-cyclodextrin (hereinafter, “cyclodextrin” may be simply referred to as “CD” in this specification), β-cyclodextrin, γ-cyclodextrin, crown ether, Examples include, but are not limited to, pillararene, calixarene, cyclophane, cucurbituril, derivatives thereof, and the like. Examples of derivatives include methylated α-cyclodextrin, methylated β-cyclodextrin, methylated γ-cyclodextrin, hydroxypropylated α-cyclodextrin, hydroxypropylated β-cyclodextrin, and hydroxypropylated γ-cyclodextrin. can include but are not limited to. The number of first cyclic molecules in the isolated nanosheet may be one, or two or more.

<<Inclusion rate>>
In the present application, the inclusion ratio refers to the ratio of cyclic molecules contained in the pseudo-polyrotaxane and/or the polyrotaxane.
In addition, the specified inclusion ratio refers to the inclusion ratio arithmetically defined from the linear molecule and the first cyclic molecule used in the pseudopolyrotaxane and/or the polyrotaxane. Defined from the length of the molecule and the thickness of the first cyclic molecule described above.

The specified inclusion rate will be explained concretely.
Consider the case where polyethylene glycol is used as the linear molecule and α-CD is used as the cyclic molecule.
It is known from molecular model calculations that the thickness of two repeating units of polyethylene glycol is the same as the thickness of α-CD. Therefore, when the ratio of the moles of α-CD to the number of repeating units is 1:2, the defined inclusion rate is 100%.

The proportion of cyclic molecules contained in the resulting pseudo-polyrotaxane and/or polyrotaxane, that is, the clathrate, can be determined by small-angle X-ray scattering (SAXS) measurement of the resulting nanosheet dispersion.
Specifically, the one-dimensional SAXS profile of the resulting pseudo-polyrotaxane and/or polyrotaxane dispersion was fitted using an equation assuming a sheet-like structure. It can be obtained from the ratio of cut chain lengths.

By doing so, the clathrate of the pseudo-polyrotaxane and/or the polyrotaxane can be determined.
In the present application, the clathrate of the pseudo-polyrotaxane and/or the polyrotaxane is 1 to 100%, preferably 5 to 100%, more preferably 10 to 100%, most preferably 20, when the specified clathrate is 100%. It should be ~100%.

In the present application, the linear molecule is a copolymer having a structure represented by a site consisting of PEG-a site consisting of PPG-a site consisting of PEG, and the first cyclic molecule is β-cyclodextrin or γ-cyclodextrin. , preferably β-cyclodextrin.
Furthermore, in the present application, the linear molecule is a polymer consisting only of the structure represented by the site: consisting of PEG, the non-ionizable group is a carboxylic acid group or an amino group, and the first cyclic molecule is α-cyclodextrin. It is good to have

The isolated nanosheet of the present application contains a plurality of pseudo-polyrotaxanes and/or polyrotaxanes, but may contain components other than the above-mentioned "pseudo-polyrotaxane and/or polyrotaxane" as long as the structure of the isolated nanosheet can be maintained. good.

Such components include a second cyclic molecule that may be the same as or different from the first cyclic molecule, a first substance that can be included in the opening of the second cyclic molecule, and a first substance. A second substance that is different from the second cyclic molecule and cannot be in an inclusion state with the second cyclic molecule, a pseudo-polyrotaxane and / or a polyrotaxane other than the "specific" pseudo-polyrotaxane and / or polyrotaxane of the present invention. It can be, but is not limited to.

Components other than these "pseudopolyrotaxanes and/or polyrotaxanes" may be present in the isolated nanosheet as a single layer and/or in the isolated nanosheet as multiple layers. In addition, when it is present in the isolated nanosheet as a plurality of layers, it may be present in each single layer of the isolated nanosheet forming the plurality of layers, or may be present between the layers of the plurality of layers.

Examples of the second cyclic molecule include, but are not limited to, those exemplified as the first cyclic molecule.

The first substance depends on the application field and application field of the isolated nanosheet of the present invention. , anthracene, pyrene, polyphenylene vinylene, polyaniline, rhodamine, Nile red, and the like.

The second substance can be selected depending on the application field and application field of the isolated nanosheet of the present invention. Polymeric materials that do not form inclusion complexes with cyclic molecules such as polyvinyl alcohol, polyamide, polyester, polyimide, polybenzoxazole, polyvinyl chloride, polypropylene, polysilane, and polysiloxanes; biopolymers such as DNA, proteins, and polypeptides; Biomolecules; Inorganic nanomaterials such as silica nanoparticles, titanium oxide nanoparticles, and silicon nanoparticles; Carbon materials such as fullerenes, carbon nanotubes, graphene, graphite, and carbon quantum dots; Gold nanoparticles, perovskite quantum dots, CdSeS/ZnS quantum dots, metal nanomaterials such as iron oxide nanoparticles; and the like.

In addition, the isolated nanosheet of the present invention can be composed of highly biosafety and biocompatible molecules such as cyclodextrin and polyethylene glycol, and is therefore suitable for use in vivo.
The isolated nanosheet of the present invention can be used for drug delivery materials (e.g., drug delivery vehicles), bioimaging, surface modifiers, adhesives, wound site anti-adhesion agents, hair care materials, coating materials, mouthwashes, and the like. It can be used as, but not limited to, oral care materials, bases for supplements, aggregation control materials for cells and algae, oxygen barrier materials, moisturizing agents, UV protection materials, odor prevention materials, and the like.

The present invention also provides materials comprising the isolated nanosheets described above. Such materials depend on the application field and application field of the isolated nanosheet of the present invention. Examples include, but are not limited to, oral care materials, adhesives, bases for supplements, functional beverages, aggregation control materials, oxygen barrier materials, moisturizers, UV protection materials, odor control materials, and the like.

The present invention provides methods I and II for producing the isolated nanosheets described above.
<Manufacturing method I>
In the present application, the manufacturing method I is
a) providing a linear molecule having at or near both ends a first linear molecule having non-ionizable groups that do not ionize, preferably in water or an aqueous solution, under nanosheet-making conditions;
b) providing a first cyclic molecule; and c) mixing said linear molecule and said first cyclic molecule in water or an aqueous solution;
By having, it is possible to obtain an isolated nanosheet having a plurality of pseudopolyrotaxanes in which the opening of the first cyclic molecule is skewered and clathrated by the linear molecule.
The "first linear molecule", "non-ionizing group", and "first cyclic molecule" are as described above. For example, the "first linear molecule" may be "comprising at least two moieties", and the "second linear molecule comprising at least three moieties", etc. may be used as described above. As I did.

<Step a)>
Step a) is a step of providing a linear molecule having a first linear molecule having a non-ionizable group that does not ionize in water or an aqueous solution, preferably in water or an aqueous solution, at or near both ends under nanosheet-forming conditions.
Here, the linear molecule may be purchased commercially or prepared. In addition, as described above, a “linear molecule” that “includes at least two sites” may be used. When preparing a “linear molecule” “having at least two sites”, it can be obtained by the methods described in Documents 1 to 4 below.
Reference 1: Hillmyer, MA et al., Macromolecules 1996, 29 (22), 6994-7002.
Reference 2: Ding, JF et al., Eur Polym J 1991, 27 (9), 901-905.
Reference 3: Allgaier, J. et al., Macromolecules 2007, 40 (3), 518-525.
Reference 4: Malik, MI et al., Eur Polym J 2009, 45 (3), 899-910.

In addition, the ``first linear molecule having non-ionized groups at both ends or in the vicinity thereof, preferably not ionized in water or an aqueous solution under nanosheet-forming conditions,'' is similar to the above-mentioned ``linear molecule'', It may be purchased commercially or prepared.
When preparing, it is preferable to provide a step of introducing non-ionizable groups at both ends of the above-mentioned "straight-chain molecule" or in the vicinity thereof.

As the step of introducing a non-ionizing group, a conventionally known technique can be used, for example, DMT/MM(4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmol folinium chloride), DCC (N,N'-dicyclohexylcarbodiimide), EDC (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide), BOP (benzotriazol-1-yloxy-trisdimethylaminophosphonium salt), PyBOP ((benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate), HATU (O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium Examples include, but are not limited to, condensation reactions such as esterification and amidation using a condensing agent such as hexafluorophosphate), nucleophilic substitution reactions, and addition reactions.

<Step b)>
Step b) is the step of providing a first cyclic molecule.
For this step, commercially available cyclic molecules may be purchased or prepared. When preparing a derivative, for example, it can be obtained by the method described in Document 5: Khan, AR et al., Chem Rev 1998, 98 (5), 1977-1996.
Note that step b) may be provided before step c). That is, step b) need not be provided after step a) and can be performed separately from steps a) and b).

<Step c)>
Step c) is a step of mixing the linear molecule and the first cyclic molecule in water or an aqueous solution.
Water or an aqueous solution is not particularly limited as long as it dissolves at least one of the first cyclic molecule and the linear molecule.
Specific examples of the water or aqueous solution used in step c) include, but are not limited to, pure water, alcohol aqueous solution, acid aqueous solution, alkaline aqueous solution, buffer solution, culture solution, blood plasma, and the like.
By having the above steps a) to c), the above isolated nanosheet can be obtained.

Note that the above-described manufacturing method may include steps other than the above steps a) to c).
For example, as steps other than the above steps a) to c), a step of preparing the above-mentioned “comprising at least two sites” “linear molecule” provided before step a), an isolated nanosheet provided after step d) purification step, inclusion of a cyclic molecule and the first substance that may be provided before step a), and synthesis of pseudo-polyrotaxane or polyrotaxane, but are not limited to these.
Further, when the isolated nanosheet has the above-described second cyclic molecule, first substance, and second substance, the production method of the present invention includes the second cyclic molecule, the first substance, and the second substance. into the isolated nanosheet.

Furthermore, after the c) step, it is preferable to further include the step of g) modifying a part of the obtained isolated nanosheets with the pseudo-polyrotaxane.
The modifying step may be a step of introducing a first substituent into the first linear molecule, eg, at the end of the first linear molecule. As long as an isolated nanosheet can be obtained, the first substituent may be a blocking group that blocks the first cyclic molecule so that it does not detach. or a group having other actions. The first substituent may have any combination of those actions, or may have all of those actions.

For example, groups having blocking action and non-ionizing group action include adamantane group, neopentyl group, isopentyl group, sec-pentyl group, 3-pentyl group, tert-pentyl group, cyclopentyl group, pentene group, hexyl group, hexene group, heptyl group, heptene group, octyl group, octene group, nonyl group, nonene group, decyl group, decene group, undecyl group, undecene group, dodecyl group, dodecene group, tridecyl group, tridecene group, tetradecyl group , tetradecene group, pentadecyl group, pentadecene group, hexadecyl group, hexadecene group, heptadecyl group, heptadecene group, octadecyl group, octadecene group, nonadecyl group, nonadecene group, eicosyl group, eicosene group, henicosyl group, henicosene group, tetracosyl group, tetracosene may include, but are not limited to, groups, triacontyl groups, triacontene groups and their isomers.

As a group having the action of an ionizing group, groups derived from oligopeptides such as folic acid, biotin, fluorescein, RGD and GRGDS, and monoclonal antibodies such as rituximab, bevacizumab, tocilizumab and infliximab may be introduced. For example, when introducing a group derived from folic acid, the resulting isolated sheet and folic acid are combined with a condensing agent such as DMT/MM (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)- 4-methylmorpholinium chloride), DCC (N,N'-dicyclohexylcarbodiimide), EDC (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide), BOP (benzotriazol-1-yloxy-trisdimethylamino phosphonium salt), PyBOP ((benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate), HATU (O-(7-azabenzotriazol-1-yl)-N,N,N',N'- It can be carried out by reacting in the presence of tetramethyluronium hexafluorophosphate).

The modification step may be a step of introducing a second substituent into the first cyclic molecule as long as an isolated nanosheet is obtained.
Incidentally, the second substituent, -OR group, -O-R1-X group, -O-CO-NH-R2 group, -O-CO-R3 group, -O-Si-R4 group, and -O —substituted with a nonionic group selected from the group consisting of —CO—O—R groups,
R is a linear or branched alkyl group having 1 to 12 carbon atoms, a linear or branched alkyl group having 2 to 12 carbon atoms containing at least one ether group, and 3 to 12 carbon atoms. a cyclic alkyl group, a cyclic alkyl ether group having 2 to 12 carbon atoms, a cyclic alkylthioether group having 2 to 12 carbon atoms,
R1 is a group obtained by removing one hydrogen from a linear or branched alkyl group having 1 to 12 carbon atoms, or a linear or branched chain having 2 to 12 carbon atoms containing at least one ether group. A group obtained by removing one hydrogen from an alkyl group of, a group obtained by removing one hydrogen from a cyclic alkyl group having 3 to 12 carbon atoms, a group obtained by removing one hydrogen from a cyclic alkyl ether group having 2 to 12 carbon atoms or a group obtained by removing one hydrogen from a cyclic alkylthioether group having 2 to 12 carbon atoms, X is OH, NH or SH,
R2 is a linear or branched alkyl group having 1 to 12 carbon atoms, a linear or branched alkyl group having 2 to 12 carbon atoms containing at least one ether group, and 3 to 12 carbon atoms. is a cyclic alkyl group, a cyclic alkyl ether group having 2 to 12 carbon atoms, or a cyclic alkylthioether group having 2 to 12 carbon atoms,
R3 is a linear or branched alkyl group having 1 to 12 carbon atoms, a linear or branched alkyl group having 2 to 12 carbon atoms containing at least one ether group, and 3 to 12 carbon atoms. is a cyclic alkyl group, a cyclic alkyl ether group having 2 to 12 carbon atoms, or a cyclic alkylthioether group having 2 to 12 carbon atoms,
R4 is a linear or branched alkyl group having 1 to 12 carbon atoms, a linear or branched alkyl group having 2 to 12 carbon atoms containing at least one ether group, and 3 to 12 carbon atoms. is a cyclic alkyl group, a cyclic alkyl ether group having 2 to 12 carbon atoms, or a cyclic alkylthioether group having 2 to 12 carbon atoms,
R5 is a linear or branched alkyl group having 1 to 12 carbon atoms, a linear or branched alkyl group having 2 to 12 carbon atoms containing at least one ether group, and 3 to 12 carbon atoms. , a cyclic alkyl ether group having 2 to 12 carbon atoms, or a cyclic alkylthioether group having 2 to 12 carbon atoms, but are not limited thereto.

<Manufacturing method II>
The isolated nanosheet comprising a plurality of pseudo-polyrotaxanes and/or polyrotaxanes of the present application can be obtained by the following production method.
Namely
a′) providing a linear molecule;
b) providing a first cyclic molecule;
c′) mixing the linear molecule and the first cyclic molecule in water or an aqueous solution to obtain a pseudo-polyrotaxane;
d) a step of introducing a non-ionizable group, preferably not ionized in water or an aqueous solution, to both ends of at least a portion of the linear molecule under nanosheet-forming conditions to form a first linear molecule;
e) introducing blocking groups to both ends of at least a portion of the linear molecule of the pseudopolyrotaxane and/or the first linear molecule;
f) mixing the resulting pseudo-polyrotaxane and/or polyrotaxane in water or an aqueous solution;
By having the above, the isolated nanosheet can be obtained.

Here, step a′) can use the “linear molecule” described in step a) above.
Step b) The step is the same as the “step b)” described above.
Step c') is a step of mixing the linear molecule and the first cyclic molecule in water or an aqueous solution, as in step c) above, and thereby obtaining a pseudo-polyrotaxane.
As described in step c), the water or aqueous solution is not particularly limited as long as it dissolves at least one of the first cyclic molecule and the linear molecule.
Specific examples of the water or aqueous solution used in step c) include, but are not limited to, pure water, alcohol aqueous solution, acid aqueous solution, alkaline aqueous solution, buffer solution, culture solution, blood plasma, and the like.

Step d) is a step of introducing a non-ionizable group, preferably not ionized in water or an aqueous solution, to both ends of at least a portion of the linear molecule under nanosheet-forming conditions to form a first linear molecule. is.
Examples of the method for introducing a non-ionizing group include, but are not limited to, the method described in step a) above.

Step e) is a step of introducing a so-called blocking group, and is a step of converting at least part of the pseudo-polyrotaxane into a polyrotaxane by introducing the blocking group.
A conventionally known method can be used for the step, and examples thereof include the steps described in Harada et. al, Nature, 1992, 356, 325-327.
As for the blocking group, blocking groups that can be used for conventionally known polyrotaxanes can also be mentioned. For example, blocking groups described in M. Okada et. al, J Polym. Sci. A: Polym. Chem, 2000, 38, 4839-4849 can be mentioned.

The present invention can also adopt the following configuration.
<1> An isolated nanosheet comprising a plurality of pseudo-polyrotaxanes and/or polyrotaxanes in which the opening of the first cyclic molecule is skewered and clathrated by linear molecules,
The isolated nanosheet, wherein the linear molecule has at or near both ends thereof a first linear molecule having a non-ionizable group, preferably not ionized in water or an aqueous solution, under nanosheet-forming conditions.
<2> In <1> above, the first linear molecule has first and second regions in which the first cyclic molecule does not exist inside from both ends of the first linear molecule. , the length of the first and second regions is 0.5 to 100 nm, preferably 1 to 70 nm, more preferably 1 to 50 nm.

<3> In the above <1> or <2>, the isolated nanosheet has a plurality of pseudo-polyrotaxanes and/or polyrotaxanes in which the openings of the first cyclic molecules are clathrated in a skewered manner by linear molecules. or comprising a plurality of layers of said nanosheets.
<4> In any one of <1> to <3> above, the linear molecule consists essentially of the first linear molecule.

<5> In any one of <1> to <4> above, the non-ionizable group is isopropyl group, sec-butyl group, tert-butyl group, hexyl group, neopentyl group, isopentyl group, sec-pentyl group, 3- pentyl group, tert-pentyl group, cyclopentyl group, pentene group, hexyl group, hexene group, heptyl group, heptene group, octyl group, octene group, nonyl group, nonene group, decyl group, decene group, undecyl group, undecene group, dodecyl group, dodecene group, tridecyl group, tridecene group, tetradecyl group, tetradecene group, pentadecyl group, pentadecene group, hexadecyl group, hexadecene group, heptadecyl group, heptadecene group, octadecyl group, octadecene group, nonadecyl group, nonadecene group, eicosyl group , eicosene group, henicosyl group, henicosene group, tetracosyl group, tetracosene group, triacontyl group, triacontene group and their isomers, 4-isopropylbenzenesulfonyl group, 1-octanesulfonyl group, 4-biphenylsulfonyl group, 4-tert -butylbenzenesulfonyl group, 2-mesitylenesulfonyl group, methanesulfonyl group, 2-nitrobenzenesulfonyl group, 4-nitrobenzenesulfonyl group, pentafluorobenzenesulfonyl group, 2,4,6-triisopropylbenzenesulfonyl group, p-toluenesulfonyl group group, non-ionized hydroxyl group, heptafluorobutyroyl group, pivaloyl group, perfluorobenzoyl group, non-ionized amino group, non-ionized carboxylic acid group and isovaleryl group. It's good. The non-ionized group is preferably at least one selected from the group consisting of non-ionized hydroxyl group, heptafluorobutyroyl group, perfluorobenzoyl group and isovaleryl group, more preferably perfluorobenzoyl group and isovaleryl group. is at least one selected from the group consisting of groups;

<6> In any one of <1> to <5> above, the first linear molecule is a block copolymer comprising two blocks that are at least two sites.
<7> In any one of <1> to <5> above, the first linear molecule is a block copolymer comprising three blocks that are at least three sites.

<8> In <6> or <7> above, the first cyclic molecule is included in one of the at least two sites or one of the at least three sites. .
<9> In any one of <6> to <8> above, at least two moieties or at least three moieties are derived from block copolymers each comprising at least two blocks or at least three blocks.

<10> In <9> above, at least three blocks are formed from a site composed of polyethylene glycol (PEG) and a site composed of polypropylene glycol (PPG).
<11> In any one of <1> to <10> above, the isolated nanosheet further has a second cyclic molecule that is not included in the linear molecule.
<12> In <11> above, the second cyclic molecule clathrates the first substance in its opening.

<13> In any one of <1> to <12> above, the isolated nanosheet further has a second substance that is not clathrated by the second cyclic molecule.
<14> In <13> above, the isolated nanosheet is a nanosheet comprising a plurality of pseudo-polyrotaxanes and/or polyrotaxanes in which the opening of the first cyclic molecule is skewered and clathrated by a linear molecule. It has a plurality of layers, and further has the second substance between the nanosheets of the plurality of layers.

<15> In any one of <1> to <14> above, the first and second cyclic molecules are α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, crown ether, pillar allene, calixarene, cyclo selected from the group consisting of fan, cucurbituril, and derivatives thereof;
As derivatives, methylated α-cyclodextrin, methylated β-cyclodextrin, methylated γ-cyclodextrin, hydroxypropylated α-cyclodextrin, hydroxypropylated β-cyclodextrin, hydroxypropylated γ-cyclodextrin selected from a group of
<16> In any one of the above <1> to <15>, the linear molecule is preferably a copolymer having a structure represented by a site consisting of PEG-a site consisting of PPG-a site consisting of PEG. . Also, the first cyclic molecule is β-cyclodextrin.

<17> In any one of the above <1> to <15>, the linear molecule is a triblock copolymer consisting only of a structure represented by a site consisting of PEG-a site consisting of PPG-a site consisting of PEG. It's good. Also, the first cyclic molecule is β-cyclodextrin.
<18> In any one of the above <1> to <17>, the thickness of the single layer of the isolated nanosheet is 100 nm or less, specifically 0.5 to 100 nm, preferably 3 to 50 nm, more preferably 5 to 5 nm. It should be 20 nm. When the isolated nanosheet consists of multiple layers, the thickness of the constituent single-layer nanosheet is 100 nm or less, specifically 0.5 to 100 nm, preferably 3 to 50 nm, more preferably 5 to 20 nm. .

<19> The isolated nanosheet according to any one of <1> to <18> above exhibits adhesiveness.
<20> A drug delivery material comprising the isolated nanosheet of any one of the above <1> to <19>, bioimaging, surface modifier, adhesive, wound site adhesion preventive agent, hair care material, coating material, mouthwash oral care materials, bases for supplements, aggregation control materials such as cells and algae, oxygen barrier materials, moisturizing agents, UV protection materials, or odor control materials.
<21> Drug delivery materials, bioimaging, surface modifiers, adhesives, wound site anti-adhesion agents, hair care materials, coating materials, oral care materials such as mouthwash, bases for supplements, aggregation of cells, algae, etc. Use of the isolated nanosheet according to any one of <1> to <19> above in a control material, oxygen barrier material, moisturizing agent, UV protection material, or odor prevention material.
<22> A material having the isolated nanosheet according to any one of <1> to <19> above.
<23> The material is a structural material, an artificial living body substitute material, a packaging material, a rubber material, a hair care material, a coating material, a paint, an oral care material such as a mouthwash, an adhesive, a base for supplements, a high-performance beverage, an aggregation The material according to <22>, which is a control material, oxygen barrier material, moisturizing agent, UV protection material, or odor prevention material.
<24> A method for producing an isolated nanosheet comprising a plurality of pseudo-polyrotaxanes in which the opening of the first cyclic molecule is skewered and clathrated by the linear molecule,
a) providing a linear molecule having at or near both ends a first linear molecule having a non-ionizable group that does not ionize, preferably in water or an aqueous solution, under nanosheet-forming conditions;
b) providing a first cyclic molecule; and c) mixing said linear molecule and said first cyclic molecule in water or an aqueous solution;
to obtain the isolated nanosheet.
<25> In the above <24>, after the c) step, g) modifying a part of the obtained isolated nanosheet with the pseudo-polyrotaxane;

<26> A method for producing an isolated nanosheet comprising a plurality of pseudo-polyrotaxanes and/or polyrotaxanes in which the opening of the first cyclic molecule is skewered with linear molecules, comprising:
a′) providing a linear molecule;
b) providing a first cyclic molecule;
c′) mixing the linear molecule and the first cyclic molecule in water or an aqueous solution to obtain a pseudo-polyrotaxane;
d) a step of introducing a non-ionizable group, preferably not ionized in water or an aqueous solution, to both ends of at least a portion of the linear molecule under nanosheet-forming conditions to form a first linear molecule;
e) introducing blocking groups to both ends of at least a portion of the linear molecule of the pseudopolyrotaxane and/or the first linear molecule;
f) mixing the resulting pseudo-polyrotaxane and/or polyrotaxane in water or an aqueous solution;
to obtain the isolated nanosheet.

<27> In the above <26>, after the f) step, g) modifying a part of the obtained isolated nanosheet with the pseudo-polyrotaxane and/or the polyrotaxane;
<28> In any one of <24> to <27> above, the pseudo-polyrotaxane and/or the polyrotaxane are the first and second and the length of the first and second regions is 0.5 to 100 nm, preferably 1 to 70 nm, more preferably 1 to 50 nm.
<29> In any one of <24> to <28> above, the isolated nanosheet has a plurality of pseudo-polyrotaxanes in which the opening of the first cyclic molecule is skewered and clathrated by a linear molecule. or comprising a plurality of layers of said nanosheets.

<30> In any one of <24> to <29> above, the linear molecule consists essentially of the first linear molecule.
<31> In any one of the above <24> to <30>, the non-ionizing group is isopropyl group, sec-butyl group, tert-butyl group, neopentyl group, isopentyl group, sec-pentyl group, 3-pentyl group, tert-pentyl group, cyclopentyl group, pentene group, hexyl group, hexene group, heptyl group, heptene group, octyl group, octene group, nonyl group, nonene group, decyl group, decene group, undecyl group, undecene group, dodecyl group, dodecene group, tridecyl group, tridecene group, tetradecyl group, tetradecene group, pentadecyl group, pentadecene group, hexadecyl group, hexadecene group, heptadecyl group, heptadecene group, octadecyl group, octadecene group, nonadecyl group, nonadecene group, eicosyl group, eicosene group , henicosyl group, henicosene group, tetracosyl group, tetracosene group, triacontyl group, triacontene group and their isomers, 4-isopropylbenzenesulfonyl group, 1-octanesulfonyl group, 4-biphenylsulfonyl group, 4-tert-butylbenzene sulfonyl group, 2-mesitylenesulfonyl group, methanesulfonyl group, 2-nitrobenzenesulfonyl group, 4-nitrobenzenesulfonyl group, pentafluorobenzenesulfonyl group, 2,4,6-triisopropylbenzenesulfonyl group, p-toluenesulfonyl group, ionization at least one selected from the group consisting of unionized hydroxyl group, heptafluorobutyroyl group, pivaloyl group, perfluorobenzoyl group, non-ionized amino group, non-ionized carboxylic acid group and isovaleryl group. . The non-ionized group is preferably at least one selected from the group consisting of non-ionized hydroxyl group, heptafluorobutyroyl group, perfluorobenzoyl group and isovaleryl group, more preferably perfluorobenzoyl group and isovaleryl group. is at least one selected from the group consisting of groups;

<32> In step c) or step f) of any one of <24> to <31> above, the substance is further mixed, and the opening of the first cyclic molecule is skewered and clathrated by the linear molecule. The substance is contained in a single layer of nanosheets comprising a plurality of pseudo-polyrotaxanes and/or polyrotaxanes, or the substance is contained between a plurality of layers comprising a plurality of layers of the nanosheets.
<33> In any one of <24> to <32> above, the isolated nanosheet further has a second cyclic molecule that is not included in the linear molecule.
<34> In <32> or <33> above, the second cyclic molecule clathrates the substance in its opening.

<35> In any one of <25> and <27> to <34> above, the modifying step is a step of introducing a first substituent to the end of the first linear molecule.
<36> In <25> and <27> to <35> above, the modifying step is a step of introducing a second substituent into the first cyclic molecule.

EXAMPLES The present invention will be described in more detail below based on examples, but the present invention is not limited to these examples.
[Example 1: Preparation of isolated nanosheet X1 using α,ω-bis-hydroxypolyethylene glycol having a weight average molecular weight of 2 kDa and α-cyclodextrin]
First, 4.04 g of α-cyclodextrin was dissolved in 16.6 mL of water.
Next, 1.0 g of α,ω-bis-hydroxypolyethylene glycol having a weight average molecular weight of 2 kDa was dissolved in 16.6 mL of water. The α,ω-bis-hydroxypolyethylene glycol had terminal hydroxyl groups, which are non-ionizing groups. These aqueous solutions were mixed and stirred at room temperature for one week to obtain the desired isolated nanosheet X1.
The formation of isolated nanosheets was confirmed by small-angle X-ray scattering measurement, phase-contrast optical microscope observation, atomic force microscope observation, and scanning electron microscope observation. Measurement conditions are as follows.

Rigaku NANOPIX was used for small-angle X-ray scattering measurements. Hypix-3000 was used as a detector. The X-ray wavelength used for the measurement was 0.154 nm. The camera length was calibrated using the diffraction peak of silver behenate. All measurements were made at room temperature.

A Nikon ECLIPSE Ts2R was used for the phase-contrast microscope. A Nikon microscope digital camera DS-Fi3 was used as a camera. Measurements were made at room temperature.
Bruker Nano Multimode 8 was used for atomic force microscope observation. Antimony doped silicon cantilever tips (Bruker RTESPA-300) were used as needles for measurement. The resonance frequency was 300 kHz and the spring constant was 40 Nm ^-1 . The measurement mode was tapping mode, and all measurements were performed at room temperature.
A JEOL JSM-7800F was used for scanning electron microscopy. The acceleration voltage was 1.0 keV, and the measurement was performed at room temperature under vacuum. In the following examples and comparative examples, experiments were conducted under the same conditions.

FIG. 5 shows the results of small-angle X-ray scattering measurement of the isolated nanosheet X10. In FIG. 5, the form factor of the sheet structure was confirmed, and it was confirmed that it was an isolated nanosheet.
The inclusion rate of the isolated nanosheet X1 was 91%. The isolated nanosheet consisted of a single layer and its thickness was found to be 14.6 nm from small-angle X-ray scattering measurements (thickness t). The extended chain length (L) of the linear molecule was determined to be 16 nm from gel permeation chromatography. From the above equation A: l ₁ =l ₂ =(L−t)/2, the average length of the first and second regions was 0.7 nm.

[Example 2: Preparation of isolated nanosheet X2 using α,ω-bis-hydroxypolyethylene glycol having a weight average molecular weight of 4 kDa and α-cyclodextrin]
First, 4.04 g of α-cyclodextrin was dissolved in 16.6 mL of water.
Next, 1.0 g of α,ω-bis-hydroxypolyethylene glycol having a weight average molecular weight of 4 kDa was dissolved in 16.6 mL of water. The α,ω-bis-hydroxypolyethylene glycol had terminal hydroxyl groups, which are non-ionizing groups. These aqueous solutions were mixed and stirred at room temperature for one week to obtain the desired isolated nanosheet X2.

In the same manner as in Example 1, the formation of isolated nanosheets was confirmed by small-angle X-ray scattering measurement, phase-contrast optical microscope observation, atomic force microscope observation, and scanning electron microscope observation.
FIG. 6 shows the results of small-angle X-ray scattering measurement of the isolated nanosheet X2. In FIG. 6, the form factor of the sheet structure was confirmed, and it was confirmed that it was an isolated nanosheet.
The inclusion rate of the isolated nanosheet X2 was 91%. The isolated nanosheet consisted of a single layer and its thickness was found to be 29.0 nm from small-angle X-ray scattering measurements (thickness t). The extended chain length (L) of the axial molecule was determined to be 32 nm from gel permeation chromatography. From the above equation A: l ₁ =l ₂ =(L ₁ -t)/2, the average length of the first and second regions was 1.5 nm.

[Example 3: Preparation of isolated nanosheet X3 using α,ω-bis-hydroxypolyethylene glycol having a weight average molecular weight of 6 kDa and α-cyclodextrin]
First, 4.04 g of α-cyclodextrin was dissolved in 16.6 mL of water.
Next, 1.0 g of α,ω-bis-hydroxypolyethylene glycol having a weight average molecular weight of 6 kDa was dissolved in 16.6 mL of water. The α,ω-bis-hydroxypolyethylene glycol had terminal hydroxyl groups, which are non-ionizing groups. These aqueous solutions were mixed and stirred at room temperature for one week to obtain the desired isolated nanosheet X3.
In the same manner as in Example 1, the formation of isolated nanosheets was confirmed by small-angle X-ray scattering measurement, phase-contrast optical microscope observation, atomic force microscope observation, and scanning electron microscope observation.

FIG. 7 shows the results of small-angle X-ray scattering measurement of the isolated nanosheet X3. In FIG. 7, the form factor of the sheet structure was confirmed, and it was confirmed that it was an isolated nanosheet.
The inclusion rate of the isolated nanosheet X3 was 87%. The isolated nanosheets consisted of a single layer and were found to be 21 nm thick from small-angle X-ray scattering measurements (thickness t). The extended chain length (L) of the linear molecule was determined to be 48 nm from gel permeation chromatography. Although the clathrate is 87%, the thickness (t) of the isolated nanosheet is 21 nm, which is too short. As shown in FIG. It is considered that an isolated nanosheet is formed. In this case, by applying Equation B, as described above, the average length of the first and second regions was calculated to be 1.5 nm each.

[Comparative Example 1: Preparation of inclusion complex using α,ω-bis-hydroxypolyethylene glycol having a weight average molecular weight of 20 kDa and α-cyclodextrin]
First, 4.04 g of α-cyclodextrin was dissolved in 16.6 mL of water.
Next, 1.0 g of α,ω-bis-hydroxypolyethylene glycol having a weight average molecular weight of 20 kDa was dissolved in 16.6 mL of water. These aqueous solutions were mixed and stirred at room temperature for one week, but no isolated nanosheets were obtained.
Structural analysis of the prepared solution was performed by small-angle X-ray scattering measurements, and no fringes due to the isolated sheet structure were observed, as shown in FIG.

[Example 4: Preparation of isolated nanosheet X4 using four-branched hydroxyl group-terminated polyethylene glycol having a weight average molecular weight of 10 kDa and α-cyclodextrin]
First, 4.04 g of α-cyclodextrin was dissolved in 16.6 mL of water.
Next, 1.0 g of 4-branched hydroxyl-terminated polyethylene glycol having a weight average molecular weight of 10 kDa was dissolved in 16.6 mL of water. The four-branched hydroxyl group-terminated polyethylene glycol had terminal hydroxyl groups, which are non-ionizing groups. These aqueous solutions were mixed and stirred at room temperature for one week to obtain the desired isolated nanosheet X4. In the same manner as in Example 1, the formation of isolated nanosheets was confirmed by small-angle X-ray scattering measurement, phase-contrast optical microscope observation, atomic force microscope observation, and scanning electron microscope observation.

In FIG. 9, the form factor of the sheet structure was confirmed, and it was confirmed that it was an isolated nanosheet. Further, FIG. 10 shows an image obtained by observation with a scanning electron microscope. From FIG. 10, an isolated nanosheet was confirmed.
The inclusion rate of the isolated nanosheet X4 was 45%. The isolated nanosheet consisted of a single layer and was found to be 9 nm thick from small-angle X-ray scattering measurements (thickness t). Also, the extended chain length (L) of each of the 4-branched chains was determined to be 20 nm by gel permeation chromatography. Since this example uses a linear molecule with n branches, by applying Equation C above (which is the same as Equation A), the average length of the first and second regions The value was calculated as (20 nm - 9 nm)/2 = 5.5 nm

[Example 5: Solid surface adsorption experiment of isolated nanosheet X5 produced using linear molecules having hydroxyl groups]
A silicon substrate having hydroxyl groups on its surface was immersed for 3 seconds in an aqueous dispersion of isolated nanosheet X1 using α,ω-bis-hydroxypolyethylene glycol having a weight average molecular weight of 2 kDa and α-cyclodextrin prepared in Example 1, When the substrate surface after being pulled up was observed with a scanning electron microscope, it was observed that the nanosheet was adsorbed to the silicon substrate as shown in FIG.
From this observation, it was confirmed that the isolated nanosheet X1 has a hydroxyl group, which is a non-ionizable group, and that the hydroxyl group acts as an adhesive group on the silicon substrate surface.

[Synthesis Example 1: Synthesis of polyethylene glycol-α,ω-bis-heptafluorobutyrate (weight average molecular weight 2000)]
1 g of α,ω-bis-hydroxypolyethylene glycol (molecular weight 2000) was dissolved in 19 mL of methylene chloride, and 0.95 g (12 mmol) of triethylamine and heptafluorobutyl chloride (1.5 mL, 10 mmol) were added. After that, the mixture was stirred at room temperature for 7 hours. 50 mL of ion-exchanged water was added to stop the reaction, and extraction was performed using methylene chloride. After distilling off the methylene chloride under reduced pressure, recrystallization was performed from 250 mL of ethanol, resulting in a yield of 99% or more, resulting in polyethylene glycol-α having a heptafluorobutyroyl group, which is a non-ionizing group, at its end. , ω-bis-heptafluorobutyrate (weight average molecular weight 2000).

[Example 6: Preparation of isolated nanosheet X6 using polyethylene glycol-α,ω-bis-heptafluorobutyrate (weight average molecular weight 2000) and α-cyclodextrin]
First, 4.04 g of α-cyclodextrin was dissolved in 16.6 mL of water.
Next, 1.0 g of polyethylene glycol-α,ω-bis-heptafluorobutyrate (non-ionizing/adhesive functional group terminal, weight average molecular weight 2000) obtained in Synthesis Example 1 was dissolved in 16.6 mL of water. . These aqueous solutions were mixed and stirred at room temperature for one week to obtain the desired isolated nanosheet X6.

In the same manner as in Example 1, the formation of isolated nanosheets was confirmed by small-angle X-ray scattering measurement, phase-contrast optical microscope observation, atomic force microscope observation, and scanning electron microscope observation.
The inclusion rate of the isolated nanosheet X6 was 93%. The isolated nanosheet consisted of a single layer and was found to be 16 nm thick from small-angle X-ray scattering measurements (thickness t). The extended chain length (L) of the linear molecule was determined to be 17.2 nm from gel permeation chromatography. From the above equation A: l ₁ =l ₂ =(L−t)/2, the average length of the first and second regions was 0.6 nm.

[Synthesis Example 2: Synthesis of polyethylene glycol-α,ω-bis-heptafluorobutyrate (weight average molecular weight 6000)]
0.4 g of α,ω-bis-hydroxypolyethylene glycol (molecular weight 6000) was dissolved in 19 mL of methylene chloride, and 0.38 g (4.8 mmol) of triethylamine and heptafluorobutyl chloride (0.4 mL, 2.7 mmol) were added. . After that, the mixture was stirred at room temperature for 7 hours. 50 mL of ion-exchanged water was added to stop the reaction, and extraction was performed using methylene chloride. After distilling off the methylene chloride under reduced pressure, recrystallization was performed from 250 mL of ethanol, resulting in a yield of 99% or more, resulting in polyethylene glycol-α having a heptafluorobutyroyl group, which is a non-ionizing group, at its end. , ω-bis-heptafluorobutyrate (weight average molecular weight 6000).

[Example 7: Preparation of isolated nanosheet X7 using polyethylene glycol-α,ω-bis-heptafluorobutyrate (weight average molecular weight 6000) and α-cyclodextrin]
First, 4.04 g of α-cyclodextrin was dissolved in 16.6 mL of water.
Next, 1.0 g of polyethylene glycol-α,ω-bis-heptafluorobutyrate (non-ionizing/adhesive functional group terminal, weight average molecular weight 6000) obtained in Synthesis Example 2 was dissolved in 16.6 mL of water. . These aqueous solutions were mixed and stirred at room temperature for one week to obtain the desired isolated nanosheet X7.
In the same manner as in Example 1, the formation of isolated nanosheets was confirmed by small-angle X-ray scattering measurement, phase-contrast optical microscope observation, atomic force microscope observation, and scanning electron microscope observation.

The inclusion rate of the isolated nanosheet X7 was 85%. The isolated nanosheets consisted of a single layer and were found to be 21 nm thick from small-angle X-ray scattering measurements (thickness t). The extended chain length (L) of the linear molecule was determined to be 49.2 nm from gel permeation chromatography. Although the inclusion ratio is 85%, the thickness (t) of the isolated nanosheet is 21 nm, which is too short. As shown in FIG. It is considered that an isolated nanosheet is formed. In this case, by applying Equation B, as described above, the average length of the first and second regions was calculated to be 1.8 nm each.

[Synthesis Example 3: Synthesis of polyethylene glycol-α,ω-bis-pivalate (weight average molecular weight 2000)]
1 g of α,ω-bis-hydroxypolyethylene glycol (molecular weight 2000) was dissolved in 19 mL of methylene chloride, and 0.95 g (12 mmol) of triethylamine and pivaloyl chloride (1.2 mL, 10 mmol) were added. After that, the mixture was stirred at room temperature for 7 hours. 50 mL of ion-exchanged water was added to stop the reaction, and extraction was performed using methylene chloride. After distilling off the methylene chloride under reduced pressure, recrystallization was performed from 250 mL of ethanol, resulting in a yield of 99% or more, resulting in polyethylene glycol-α,ω-, the target product having a pivaloyl group, which is a non-ionizing group, at its end. A bis-pivalate (weight average molecular weight 2000) was obtained.

[Example 8: Preparation of isolated nanosheet X8 using polyethylene glycol-α,ω-bis-pivalate (weight average molecular weight 2000) and α-cyclodextrin]
First, 4.04 g of α-cyclodextrin was dissolved in 16.6 mL of water.
Next, 1.0 g of polyethylene glycol-α,ω-bis-pivalate (non-ionizing/adhesive functional group terminal, weight average molecular weight 2000) obtained in Synthesis Example 3 was dissolved in 16.6 mL of water. These aqueous solutions were mixed and stirred at room temperature for one week to obtain the desired isolated nanosheet X8.

In the same manner as in Example 1, the formation of isolated nanosheets was confirmed by small-angle X-ray scattering measurement, phase-contrast optical microscope observation, atomic force microscope observation, and scanning electron microscope observation.
The inclusion rate of the isolated nanosheet X8 was 54%. The isolated nanosheet consisted of a single layer and was found to be 9 nm thick from small-angle X-ray scattering measurements (thickness t). The extended chain length (L) of the linear molecule was determined to be 16.6 nm from gel permeation chromatography. As described above, by applying Equation A, the average length of the first and second regions was calculated to be 3.8 nm each.

[Comparative Synthesis Example 1: Synthesis of polyethylene glycol-α,ω-bis-propionate (weight average molecular weight 2000)]
1 g of α,ω-bis-hydroxypolyethylene glycol (molecular weight 2000) was dissolved in 19 mL of methylene chloride, and 0.95 g (12 mmol) of triethylamine and propionyl chloride (0.93 mL, 10 mmol) were added. After that, the mixture was stirred at room temperature for 7 hours. 50 mL of ion-exchanged water was added to stop the reaction, and extraction was performed using methylene chloride. After the methylene chloride was distilled off under reduced pressure, the desired product was obtained with a yield of 99% or more by recrystallization from 250 mL of ethanol.

[Comparative Example 2: Preparation of inclusion complex using polyethylene glycol-α,ω-bis-propionate (weight average molecular weight: 2000) and α-cyclodextrin]
First, 4.04 g of α-cyclodextrin was dissolved in 16.6 mL of water.
Next, 1.0 g of polyethylene glycol-α,ω-bis-propionate (weight average molecular weight: 2000) obtained in Comparative Synthesis Example 1 was dissolved in 16.6 mL of water. These aqueous solutions were mixed and stirred at room temperature for one week, but no isolated nanosheets were obtained.
Structural analysis of the prepared solution by small-angle X-ray scattering measurements revealed no fringes due to the isolated sheet structure.

[Comparative Synthesis Example 2: Synthesis of polyethylene glycol-α,ω-bis-n-butyrate (weight average molecular weight 2000)]
1 g of α,ω-bis-hydroxypolyethylene glycol (molecular weight 2000) was dissolved in 19 mL of methylene chloride, and 0.95 g (12 mmol) of triethylamine and n-butyl chloride (1.1 mL, 10 mmol) were added. After that, the mixture was stirred at room temperature for 7 hours. 50 mL of ion-exchanged water was added to stop the reaction, and extraction was performed using methylene chloride. After the methylene chloride was distilled off under reduced pressure, the desired product was obtained with a yield of 99% or more by recrystallization from 250 mL of ethanol.

[Comparative Example 3: Preparation of inclusion complex using polyethylene glycol-α,ω-bis-n-butyrate (weight average molecular weight: 2000) and α-cyclodextrin]
First, 4.04 g of α-cyclodextrin was dissolved in 16.6 mL of water.
Next, 1.0 g of polyethylene glycol-α,ω-bis-n-butyrate (weight average molecular weight: 2000) obtained in Comparative Synthesis Example 2 was dissolved in 16.6 mL of water. These aqueous solutions were mixed and stirred at room temperature for one week, but no isolated nanosheets were obtained.
Structural analysis of the prepared solution by small-angle X-ray scattering measurements revealed no fringes due to the isolated sheet structure.

[Comparative Synthesis Example 3: Synthesis of polyethylene glycol-α,ω-bis-n-valerate (non-ionizing/adhesive functional group terminal, weight average molecular weight 2000)]
1 g of α,ω-bis-hydroxypolyethylene glycol (molecular weight 2000) was dissolved in 19 mL of methylene chloride, and 0.95 g (12 mmol) of triethylamine and n-valeryl chloride (1.2 mL, 10 mmol) were added. After that, the mixture was stirred at room temperature for 7 hours. 50 mL of ion-exchanged water was added to stop the reaction, and extraction was performed using methylene chloride. After the methylene chloride was distilled off under reduced pressure, the desired product was obtained with a yield of 99% or more by recrystallization from 250 mL of ethanol.

[Comparative Example 4: Preparation of inclusion complex using polyethylene glycol-α,ω-bis-n-valerate (weight average molecular weight: 2000) and α-cyclodextrin]
First, 4.04 g of α-cyclodextrin was dissolved in 16.6 mL of water.
Next, 1.0 g of polyethylene glycol-α,ω-bis-n-valerate (weight average molecular weight: 2000) obtained in Comparative Synthesis Example 3 was dissolved in 16.6 mL of water. These aqueous solutions were mixed and stirred at room temperature for one week, but no isolated nanosheets were obtained.
Structural analysis of the prepared solution by small-angle X-ray scattering measurements revealed no fringes due to the isolated sheet structure.

[Comparative Synthesis Example 4: Synthesis of polyethylene glycol-α,ω-bis-methacrylate (weight average molecular weight 2000)]
1 g of α,ω-bis-hydroxypolyethylene glycol (molecular weight 2000) was dissolved in 19 mL of methylene chloride, and 0.95 g (12 mmol) of triethylamine and methacryloyl chloride (1.1 mL, 10 mmol) were added. After that, the mixture was stirred at room temperature for 7 hours. 50 mL of ion-exchanged water was added to stop the reaction, and extraction was performed using methylene chloride. After the methylene chloride was distilled off under reduced pressure, the desired product was obtained with a yield of 99% or more by recrystallization from 250 mL of ethanol.

[Comparative Example 5: Preparation of inclusion complex using polyethylene glycol-α,ω-bis-methacrylate (weight average molecular weight 2000) and α-cyclodextrin]
First, 4.04 g of α-cyclodextrin was dissolved in 16.6 mL of water.
Next, 1.0 g of polyethylene glycol-α,ω-bis-methacrylate (weight average molecular weight: 2000) obtained in Comparative Synthesis Example 4 was dissolved in 16.6 mL of water. These aqueous solutions were mixed and stirred at room temperature for one week, but no isolated nanosheets were obtained.
Structural analysis of the prepared solution by small-angle X-ray scattering measurements revealed no fringes due to the isolated sheet structure.

[Example 9: α,ω-bis-hydroxy polyethylene glycol-block-polypropylene glycol-block-polyethylene glycol (Pluronic® F68; PEO ₇₆ PPO ₂₉ PEO ₇₆ , M _w =8400 g/mol) and β-cyclo Preparation of multilayer nanosheet X9 using dextrin]
First, 0.45 g of β-cyclodextrin was dissolved in 25 mL of water.

Next, 0.1 g of the triblock copolymer PEO ₇₆ PPO ₂₉ PEO ₇₆ was added to the previously prepared β-cyclodextrin aqueous solution and stirred at room temperature for one week to obtain the intended multi-layered nanosheet X9.
The formation of isolated nanosheets was confirmed by scanning electron microscopy (FIG. 12) and small-angle X-ray scattering measurement (FIG. 13).
Scanning electron microscope observation (FIG. 12) confirmed that the nanosheet consisted of multiple layers from a real image. Furthermore, the small-angle X-ray scattering measurement (FIG. 13) also confirmed a structural factor based on the laminated structure of the nanosheets, confirming that the nanosheets consist of a plurality of layers. Also, by analyzing the peak positions, it was confirmed that the distance between the multilayer nanosheets was 36 nm.

[Comparative Example 6: α,ω-bis-hydroxy polyethylene glycol-block-polypropylene glycol-block-polyethylene glycol (Pluronic® L61; PEO ₂ PPO ₂₉ PEO ₂ , M _w =2000 g/mol) and β-cyclo Attempt to prepare nanosheets using dextrin]
Example 9 is different from Example 9 in that the PEO repeating unit of the triblock copolymer used is "76" in Example 6, but "2" in Comparative Example 6. In the same manner as in 9, an attempt was made to prepare a nanosheet.
That is, an aqueous β-cyclodextrin solution (0.45 g dissolved in 25 mL of water) was prepared, 0.1 g of the triblock copolymer was added thereto, and the mixture was stirred at room temperature for one week.
However, the desired nanosheet was not obtained.
Structural analysis of the solution containing 0.1 g of the triblock copolymer was performed by small-angle X-ray scattering measurement, and no fringes due to the sheet structure or structural factors due to the multi-layered sheet structure were observed (Fig. 14). Scanning electron microscopic observation revealed thick, large block-like particles, confirming that no nanosheet structure was formed (FIG. 15).

[Comparative Example 7: α,ω-bis-hydroxy polyethylene glycol-block-polypropylene glycol-block-polyethylene glycol (Pluronic® L62; PEO ₅ PPO ₂₉ PEO ₅ , M _w =2500 g/mol) and β-cyclo Attempt to prepare nanosheets using dextrin]
Example 9 is different from Example 9 in that the PEO repeating unit of the triblock copolymer used is "76" in Example 6, but "5" in Comparative Example 7. In the same manner as in 9, an attempt was made to prepare a nanosheet.
That is, an aqueous β-cyclodextrin solution (0.45 g dissolved in 25 mL of water) was prepared, 0.1 g of the triblock copolymer was added thereto, and the mixture was stirred at room temperature for one week.
However, almost no desired nanosheets were obtained.
Structural analysis of a solution containing 0.1 g of the triblock copolymer was performed by small-angle X-ray scattering measurement, and only slight fringes based on the sheet structure were observed (Fig. 16). Scanning electron microscopic observation revealed a large number of block-like particles, confirming that almost no nanosheet structure was formed (FIG. 17).

[Comparative Example 8: α,ω-bis-hydroxy polyethylene glycol-block-polypropylene glycol-block-polyethylene glycol (Pluronic® L64; PEO ₁₄ PPO ₂₉ PEO ₁₄ , M _w =2900 g/mol) and β-cyclo Attempt to prepare nanosheets using dextrin]
Example 9 is different from Example 9 in that the PEO repeating unit of the triblock copolymer used is "76" in Example 6, but "14" in Comparative Example 8. In the same manner as in 9, an attempt was made to prepare a nanosheet.
That is, an aqueous β-cyclodextrin solution (0.45 g dissolved in 25 mL of water) was prepared, 0.1 g of the triblock copolymer was added thereto, and the mixture was stirred at room temperature for one week.
However, almost no desired nanosheets were obtained.
Structural analysis of the solution containing 0.1 g of the triblock copolymer was performed by small-angle X-ray scattering measurement, and only slight fringes based on the sheet structure were observed (Fig. 18). Scanning electron microscopic observation confirmed that a large number of block-like particles were observed, indicating that almost no nanosheet structure was formed (FIG. 19).

[Example 10: α,ω-bis-hydroxy polyethylene glycol-block-polypropylene glycol-block-polyethylene glycol (Pluronic® F68; PEO ₇₆ PPO ₂₉ PEO ₇₆ , M _w =8400 g/mol) and γ-cyclo Preparation of nanosheet X10 using dextrin]
First, 4.04 g of γ-cyclodextrin was dissolved in 33.2 mL of water.
Next, 1.0 g of PEO ₇₆ PPO ₂₉ PEO ₇₆ was added to the previously prepared γ-cyclodextrin aqueous solution and stirred at room temperature for one week to obtain the desired nanosheet X10.
By scanning electron microscope observation, it was confirmed from a real image that a nanosheet was formed (FIG. 20).

Example 11: α,ω-bis-hydroxypolyethyleneglycol-block-polypropyleneglycol-block-polyethyleneglycol (Pluronic® F108; PEO ₁₄₀ PPO ₅₆ PEO ₁₄₀ , M _w =14600 g/mol and γ-cyclo Preparation of nanosheet X11 using dextrin]
First, 4.04 g of γ-cyclodextrin was dissolved in 33.2 mL of water.
Next, 1.0 g of PEO ₁₄₀ PPO ₅₆ PEO ₁₄₀ was added to the previously prepared γ-cyclodextrin aqueous solution and stirred at room temperature for one week to obtain the desired nanosheet X11.
By scanning electron microscope observation, it was confirmed from a real image that a nanosheet was formed (FIG. 21).
The inclusion rate of the isolated nanosheet X11 was 26%. The isolated nanosheet consisted of a single layer with a thickness of 31 nm, as determined by small-angle X-ray scattering measurements (thickness t). The extended chain length (L) of the linear molecule was determined to be 117.3 nm from gel permeation chromatography. As described above, by applying Equation A, the average length of the first and second regions was calculated to be 43.2 nm each.

[Example 12: Preparation of nanosheet X12 using α,ω-bis-hydroxypolyethylene glycol having a weight average molecular weight of 20 kDa and γ-cyclodextrin]
First, 4.04 g of γ-cyclodextrin was dissolved in 33.2 mL of water. The α,ω-bis-hydroxypolyethylene glycol had terminal hydroxyl groups, which are non-ionizable groups.
Next, 1.0 g of PEO ₁₄₀ PPO ₅₆ PEO ₁₄₀ was added to the previously prepared γ-cyclodextrin aqueous solution and stirred at room temperature for one week to obtain the intended nanosheet X12.
By scanning electron microscope observation, it was confirmed from a real image that a nanosheet was formed (FIG. 22).

[ Example 13: Gas barrier function of nanosheet coating ]
β-CD was purchased from Fujifilm Wako Pure Chemical Industries, Ltd. _{EO75PO30EO75 ( subscripts} are units) was purchased from Sigma Aldrich.
The preparation of sheet-like nanostructures is as follows. 18 mg of β-CD was dissolved in 1 mL of deionized water (pH about 7) at 23±1°C. 4 mg of EO ₇₅ PO ₃₀ EO ₇₅ was added to 1 mL of the prepared β-CD aqueous solution. The mixed solution was vortexed for 1 minute. The solution was then placed on a shaker and aged. In one week, the precipitate and the liquid layer were separated, and complex formation was almost completed. The sample is _{designated β} -CD/ _EO75PO30EO75 .
5 mL and 20 mL of the dispersion water of β-CD/EO ₇₅ PO ₃₀ EO ₇₅ were passed through a porous membrane (PMMA-milipore: TYPE JCWP 10.0 μm, hydrophilic, pore diameter about 10 μm) to obtain β-CD/EO ₇₅ PO ₃₀ EO. I attached ₇₅ . It was then air-dried at room temperature. These samples are designated as pore-β-CD/EO ₇₅ PO ₃₀ EO ₇₅ (5 mL) and pore-β-CD/EO ₇₅ PO ₃₀ EO ₇₅ (20 mL).
SEM images of the porous membrane, pore-β-CD/EO ₇₅ PO ₃₀ EO ₇₅ (5 mL) and pore-β-CD/EO ₇₅ PO ₃₀ EO ₇₅ (20 mL) are shown in FIGS. 23(C). In the case of pure-β-CD/EO ₇₅ PO ₃₀ EO ₇₅ (5 mL), β-CD/EO ₇₅ PO ₃₀ EO ₇₅ did not pass through the pores and remained in the membrane. I was able to confirm the situation. Pore-β-CD/EO ₇₅ PO ₃₀ EO ₇₅ (20 mL) was found to completely cover the pores.
Since it was confirmed that the pores were completely covered in pore-β-CD/EO ₇₅ PO ₃₀ EO ₇₅ (20 mL), a sample was then prepared for evaluating oxygen permeability. . The preparation method is as follows. Nitrile rubber was dissolved in an organic solvent at a concentration of 2 wt %, and pore-β-CD/EO ₇₅ PO ₃₀ EO ₇₅ (20 mL) was immersed therein. Thereafter, the sample was taken out and air-dried at room temperature to prepare a nitrile rubber film supporting pure-β-CD/EO ₇₅ PO ₃₀ EO ₇₅ (20 mL).
When the oxygen permeability of the nitrile rubber film carrying pore-β-CD/EO ₇₅ PO ₃₀ EO ₇₅ (20 mL) was measured, the oxygen permeability coefficient was 18.6 cc·mm/(m 2 ·day·atm). Since the oxygen permeability coefficient is suppressed to about 1/300 of the value of normal nitrile rubber film (18.6 cc・mm/(m2・day・atm)), β-CD/EO ₇₅ PO ₃₀ EO ₇₅ It was found to have oxygen barrier properties. The equipment and conditions for measuring the oxygen coefficient are as follows:
Measurement device: MOCON® Coulometric Oxygen Permeability Measurement Device (OX-TRAN® 2/22L)
Detector: Self-humidifying coulometric sensor Corresponding standard: JIS K7126-2 (Plastics - Film and sheet - Gas permeability test method - Part 2: Isobaric method)
(ISO 15105-2), ASTM D3985/F1927/F1307
Measurement temperature: 23℃
Relative Humidity: 0%
Effective Membrane Area: 1cm ^{^2}

[ Example 14 UV cut function of nanosheet ]
β-CD was purchased from Fujifilm Wako Pure Chemical Industries, Ltd. _{EO75PO30EO75 ( subscripts} are units) was purchased from Sigma Aldrich.
A sheet-like nanostructure was prepared in the same manner as in Example 13. The sample is _{designated β} -CD/ _EO75PO30EO75 .
The UV cut function of the dispersion water of β-CD/EO ₇₅ PO ₃₀ EO ₇₅ was evaluated using a UV-visible spectrophotometer (UV3150, Shimadzu Corporation). The wavelength of incident light was from 250 nm to 800 nm, and absorbance was measured.
FIG. 24 shows the measurement results. It was found that the transmittance was low in the UVA (315 to 400 nm) and UVB (290 to 320 nm) wavelength regions and the light was transmitted in the visible wavelength region (400 to 700 nm).

Claims (17)

An isolated nanosheet comprising a plurality of pseudo-polyrotaxanes and/or polyrotaxanes in which the opening of the first cyclic molecule is skewered and clathrated by a linear molecule,
The isolated nanosheet, wherein the linear molecule has a first linear molecule that has a non-ionizable group that does not ionize in water or an aqueous solution at both ends or in the range of 1 to 10 monomer units from both ends. The first linear molecule has first and second regions in which the first cyclic molecule does not exist inside from both ends of the first linear molecule, The isolated nanosheet according to claim 1, wherein the length of the region of is 0.5 to 100 nm. The isolated nanosheet consists of a single layer of a nanosheet having a plurality of pseudo-polyrotaxanes and/or polyrotaxanes in which the openings of the first cyclic molecules are skewered with linear molecules, or 3. The isolated nanosheet according to claim 1, comprising a plurality of nanosheet layers. 4. The isolated nanosheet according to any one of claims 1 to 3, wherein said linear molecule consists essentially of said first linear molecule. The non-ionizing group is isopropyl group, sec-butyl group, tert-butyl group, neopentyl group, isopentyl group, sec-pentyl group, 3-pentyl group, tert-pentyl group, cyclopentyl group, pentene group, hexyl group, hexene group, heptyl group, heptene group, octyl group, octene group, nonyl group, nonene group, decyl group, decene group, undecyl group, undecene group, dodecyl group, dodecene group, tridecyl group, tridecene group, tetradecyl group, tetradecene group, pentadecyl group, pentadecene group, hexadecyl group, hexadecene group, heptadecyl group, heptadecene group, octadecyl group, octadecene group, nonadecyl group, nonadecene group, eicosyl group, eicosene group, henicosyl group, henicosene group, tetracosyl group, tetracosene group, triacontyl group , triacontene group and their isomers, 4-isopropylbenzenesulfonyl group, 1-octanesulfonyl group, 4-biphenylsulfonyl group, 4-tert-butylbenzenesulfonyl group, 2-mesitylenesulfonyl group, methanesulfonyl group, 2- Nitrobenzenesulfonyl group, 4-nitrobenzenesulfonyl group, pentafluorobenzenesulfonyl group, 2,4,6-triisopropylbenzenesulfonyl group, p-toluenesulfonyl group, non-ionized hydroxyl group, heptafluorobutyroyl group, pivaloyl group, per The isolated nanosheet according to any one of claims 1 to 4, which is at least one selected from the group consisting of fluorobenzoyl groups, non-ionized amino groups, non-ionized carboxylic acid groups and isovaleryl groups. 6. The isolated nanosheet according to any one of claims 1 to 5, wherein the isolated nanosheet further has a second cyclic molecule that is not included in the linear molecule. 7. The isolated nanosheet according to claim 6, wherein the second cyclic molecule encloses the first substance in its opening. 8. The isolated nanosheet according to claim 7 , wherein the isolated nanosheet further comprises a second substance not enclosed by the second cyclic molecule. The isolated nanosheet has a plurality of layers of nanosheets each having a plurality of pseudo-polyrotaxanes and/or polyrotaxanes in which the opening of the first cyclic molecule is skewered with a linear molecule, 9. The isolated nanosheet of claim 8, further comprising said second material between nanosheets in layers. 1. The first cyclic molecule is selected from the group consisting of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, crown ether, pillar allene, calixarene, cyclophane, cucurbituril, and derivatives thereof. 10. The isolated nanosheet according to any one of claims 1-9. The isolated nanosheet according to any one of claims 1 to 10, wherein the thickness of a monolayer of the isolated nanosheet is 100 nm or less. The isolated nanosheet is an isolated nanosheet comprising a plurality of pseudopolyrotaxanes in which the opening of the first cyclic molecule is skewered and clathrated by a linear molecule,
A part of the isolated nanosheet is modified with a pseudopolyrotaxane,
The modification is introduction of a first substituent to the end of the first linear molecule, and the first substituent has the effect of blocking the first cyclic molecule so that it does not detach. 2. The isolated nanosheet according to claim 1, which is a group having the action of a blocking group or an ionizing group. The first cyclic molecule is an -OR group, -O-R1-X group, -O-CO-NH-R2 group, -O-CO-R3 group, -O-Si-R4 group, and -O- 2. The isolated nanosheet of claim 1, having a nonionic group selected from the group consisting of CO--O--R5 groups.
(In the formula,
R is a linear or branched alkyl group having 1 to 12 carbon atoms, a linear or branched alkyl group having 2 to 12 carbon atoms containing at least one ether group, and 3 to 12 carbon atoms. is a cyclic alkyl group, a cyclic alkyl ether group having 2 to 12 carbon atoms, or a cyclic alkylthioether group having 2 to 12 carbon atoms,
R1 is a group obtained by removing one hydrogen from a linear or branched alkyl group having 1 to 12 carbon atoms, or a linear or branched chain having 2 to 12 carbon atoms containing at least one ether group. A group obtained by removing one hydrogen from an alkyl group of, a group obtained by removing one hydrogen from a cyclic alkyl group having 3 to 12 carbon atoms, a group obtained by removing one hydrogen from a cyclic alkyl ether group having 2 to 12 carbon atoms or a group obtained by removing one hydrogen from a cyclic alkylthioether group having 2 to 12 carbon atoms, and X is OH, NH ₂ , or SH,
R2 is a linear or branched alkyl group having 1 to 12 carbon atoms, a linear or branched alkyl group having 2 to 12 carbon atoms containing at least one ether group, and 3 to 12 carbon atoms. is a cyclic alkyl group, a cyclic alkyl ether group having 2 to 12 carbon atoms, or a cyclic alkylthioether group having 2 to 12 carbon atoms,
R3 is a linear or branched alkyl group having 1 to 12 carbon atoms, a linear or branched alkyl group having 2 to 12 carbon atoms containing at least one ether group, and 3 to 12 carbon atoms. is a cyclic alkyl group, a cyclic alkyl ether group having 2 to 12 carbon atoms, or a cyclic alkylthioether group having 2 to 12 carbon atoms,
R4 is a linear or branched alkyl group having 1 to 12 carbon atoms, a linear or branched alkyl group having 2 to 12 carbon atoms containing at least one ether group, and 3 to 12 carbon atoms. is a cyclic alkyl group, a cyclic alkyl ether group having 2 to 12 carbon atoms, or a cyclic alkylthioether group having 2 to 12 carbon atoms,
R5 is a linear or branched alkyl group having 1 to 12 carbon atoms, a linear or branched alkyl group having 2 to 12 carbon atoms containing at least one ether group, and 3 to 12 carbon atoms. is a cyclic alkyl group, a cyclic alkyl ether group having 2 to 12 carbon atoms, or a cyclic alkylthioether group having 2 to 12 carbon atoms. ) A material comprising the isolated nanosheets according to any one of claims 1-13 . A product comprising the isolated nanosheet according to any one of claims 1 to 13,
Drug delivery materials, hair care materials, coating materials, oral care materials, coagulation control materials, oxygen barrier materials, UV protection materials, odor prevention materials, structural materials, artificial biosubstitute materials, packaging materials, rubber materials, surface modification Products that are agents, adhesives, wound anti-adhesion agents, supplement bases, moisturizers, or functional beverages . A method for producing an isolated nanosheet having a plurality of pseudo-polyrotaxanes in which the opening of the first cyclic molecule is skewered and clathrated by the linear molecule,
a) providing a linear molecule having a first linear molecule having a non-ionizable group that does not ionize in water or an aqueous solution at either end or in the range of 1 to 10 monomer units from both ends ;
b) providing a first cyclic molecule; and c) mixing said linear molecule and said first cyclic molecule in water or an aqueous solution;
to obtain the isolated nanosheet. 17. The method according to claim 16 , further comprising, after step c), the step of g) modifying a portion of the obtained isolated nanosheets with the pseudo-polyrotaxane.

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