JP5824688B2 - Method for producing pH-responsive polymer fine particles and dispersion thereof - Google Patents

Description

Detailed Description of the Invention

  The present invention relates to a novel polymer fine particle having a cationic and / or nonionic hydrophilic polymer chain on its surface and a method for producing the same, and in particular, the average particle size is reversible in accordance with a change in pH. The present invention relates to a simple method for producing pH-responsive polymer fine particles and dispersions thereof.

  A macromonomer having a radically polymerizable group at one end of a polymer can produce a graft copolymer with a clearly controlled structure. By copolymerizing a hydrophilic macromonomer and a hydrophobic monomer, Water-dispersible polymer fine particles having a hydrophilic polymer chain on the surface and composed of a hydrophobic polymer compound inside can be produced. For example, conventionally known polymer fine particles obtained by copolymerization of a hydrophilic macromonomer and a hydrophobic monomer include polymer fine particles obtained by copolymerization of a polyethylene glycol macromonomer and a hydrophobic monomer (Non-patent Document 1, Non-patent Document). 2), polymer fine particles obtained by copolymerizing an N-vinylamide macromonomer and a hydrophobic monomer, polymer fine particles obtained by saponifying the amide portion of the polymer fine particles to an amine (Patent Document 1), N-isopropylacrylamide macromonomer And polymer fine particles obtained by copolymerization of a hydrophobic monomer (Patent Document 2).

  The fine polymer particles obtained by copolymerizing N-isopropylacrylamide macromonomer and hydrophobic monomer have a particle diameter that varies with changes in temperature, but the variation range is 320 nm to 440 nm, and the variation range is very small (non-patent) Reference 3).

Polymer Journal, Vol. 17, 827, 1985 Macromolecules 2000, 33, 1759-1764 Journal of Polymer Chemistry, Vol. 34, 2213-2220 (1996) Japanese Patent Laid-Open No. 02-296808 Japanese Patent Laid-Open No. 08-183760

  An object of the present invention is to provide a novel polymer fine particle having a cationic and / or nonionic hydrophilic polymer chain on the surface and a method for producing a dispersion thereof, and an average depending on a change in pH. An object of the present invention is to provide a pH-responsive polymer fine particle whose particle diameter reversibly changes and a simple method for producing the fine particle dispersion.

  As a result of intensive research, the present inventors have found that hydrophilic polymer chains are localized on the surface of the fine particles, and the fine polymer particles in which the core of the fine particles is composed of a hydrophobic polymer and a pH-sensitive polymer are reversible. It has been found that responsiveness can be obtained, and furthermore, by dispersing a hydrophilic macromonomer, a hydrophobic monomer and a pH sensitive monomer, a dispersion of the pH responsive polymer fine particles can be easily obtained, The present invention has been completed.

  That is, the pH-responsive polymer fine particle of the present invention includes at least one selected from structural units represented by the following general formula (1):

[In Formula (1), Q ₁ represents a hydrogen atom, a methyl group or a cyano group, Q ₂ represents a hydrogen atom,

(R ₁ and R ₁ ′ are the same or different and each represents a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, a halogen atom or a halogenomethyl group, and R ₂ is a linear, branched or cyclic group having 1 to 18 carbon atoms. An alkyl group, a benzyl group or a hydroxypropyl group; R ₂ ′ represents a linear, branched or cyclic alkyl group or phenyl group having 1 to 18 carbon atoms; and R ₃ represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms. R ₄ represents an alkyl group having 1 to 10 carbon atoms (provided that R ₃ and R ₄ have 3 to 20 carbon atoms in total). ]

At least one selected from structural units represented by the following general formula (2) or at least one selected from structural units represented by the following general formula (2 ');

[In Formula (2), Q ₃ represents a hydrogen atom or a methyl group, and Q ₄ represents

(X ₁ represents COO (CH ₂ ) _n or CONH (CH ₂ ) _n (n represents an integer of 1 to 3), and R ₅ and R ₆ are the same or different and have a hydrogen atom or a carbon number of 1 to 4. A lower alkyl group or a benzyl group). ]

[In formula (2 ′), Q ₃ ′ represents a hydrogen atom or a methyl group, and Q ₄ ′ represents

(M represents a hydrogen atom, a light metal ion, or an ammonium ion). ]

Water-dispersible polymer fine particles comprising at least one selected from structural units represented by the following general formulas (3) and (4), and having an average particle diameter reversibly according to a change in pH Changes.

[In Formula (3), Q ₅ represents a hydrogen atom or a methyl group, and Q ₆ represents

(A ₁ represents an alkylene group having 1 to 10 carbon atoms), Q ₇ represents an oxygen atom or —NH—, Q ₈ represents an alkylene group having 1 to 10 carbon atoms, and Q ₉ represents an oxygen atom or Represents a sulfur atom, Y ₁ represents an oxygen atom or two hydrogen atoms, R ₇ represents a hydrogen atom or a methyl group, and X ₂ represents

(R ₈ , R ₉ and R ₁₀ are the same or different and represent a lower alkyl group having 1 to 4 carbon atoms or a benzyl group, R ₁₁ represents a hydrogen atom, a methyl group or an ethyl group, and R ₁₂ represents a hydrogen atom or a methyl group. Represents a group, Z ⁻ represents an anion), and l represents a number of 1 to 100. ]

[In Formula (4), Q ₁₀ and Q ₁₂ are the same or different and each represents a hydrogen atom or a methyl group, Q ₁₁ represents an oxygen atom or —NH—, and m represents a number of 1 to 100. ]

  Moreover, the method for producing the pH-responsive polymer fine particle dispersion of the present invention comprises at least one selected from monomers represented by the following general formula (5):

Wherein _{(5), Q 13} represents a hydrogen atom, a methyl group or a cyano _{group, Q 14} is a hydrogen atom,

(R ₁₃ and R ₁₃ ′ are the same or different and each represents a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, a halogen atom or a halogenomethyl group, and R ₁₄ is a linear, branched or cyclic group having 1 to 18 carbon atoms. An alkyl group, a benzyl group or a hydroxypropyl group, R ₁₄ ′ represents a linear, branched or cyclic alkyl group or phenyl group having 1 to 18 carbon atoms, and R ₁₅ represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms. R ₁₆ represents an alkyl group having 1 to 10 carbon atoms (however, the total carbon number of R ₁₅ and R ₁₆ is 3 to 20). ]

At least one selected from monomers represented by the following general formula (6) or at least one selected from structural units represented by the following general formula (6 ');

[In the formula (6), Q ₁₅ represents a hydrogen atom or a methyl group, and Q ₁₆ represents

(X ₃ represents COO (CH ₂ ) _n or CONH (CH ₂ ) _n (n represents an integer of 1 to 3), and R ₁₇ and R ₁₈ are the same or different and each represents a hydrogen atom or a carbon number of 1 to 4 A lower alkyl group or a benzyl group). ]

[In the formula (6 ′), Q ₁₅ ′ represents a hydrogen atom or a methyl group, and Q ₁₆ ′ represents

(M represents a hydrogen atom, a light metal ion, or an ammonium ion). ]

It is characterized by copolymerizing at least one selected from hydrophilic macromonomers represented by the following general formulas (7) and (8).

[In the formula (7), Q ₁₆ represents a hydrogen atom or a methyl group, and Q ₁₇ represents

(A ₂ represents an alkylene group having 1 to 10 carbon atoms), Q ₁₈ represents an oxygen atom or —NH—, Q ₁₉ represents an alkylene group having 1 to 10 carbon atoms, and Q ₂₀ represents an oxygen atom or Represents a sulfur atom, Y ₂ represents an oxygen atom or two hydrogen atoms, R ₁₉ represents a hydrogen atom or a methyl group, and X ₄ represents

(R ₂₀ , R ₂₁ and R ₂₂ are the same or different and represent a lower alkyl group having 1 to 4 carbon atoms or a benzyl group, R ₂₃ represents a hydrogen atom, a methyl group or an ethyl group, and R ₂₄ represents a hydrogen atom or a methyl group. Represents a group, Z ⁻ represents an anion), and l represents a number of 1 to 100. ]

Wherein _{(8), Q 22} and _{Q 24} are the same or different and each represents a hydrogen atom or a methyl _{group, Q 23} represents an oxygen atom or -NH-, m is a number of 1 to 100. ]

  According to the present invention, water-dispersible pH-responsive polymer particles having a cationic and / or nonionic hydrophilic polymer chain on the surface and composed of a hydrophobic polymer compound inside are aggregated. It can be easily produced as a dispersion without by-products.

  Hereinafter, the present invention will be described in detail.

  The pH-responsive fine particles of the present invention include a structural unit represented by the general formula (1) that forms the core of the fine particles, and a structural unit represented by the general formula (2) or (2 ′) that expresses the pH response performance. And a hydrophilic polymer chain represented by the general formula (3) and / or (4) localized on the surface of the fine particles.

  First, the general formula (1) constituting the pH-responsive polymer fine particles of the present invention will be described.

The lower alkyl group having 1 to 4 carbon atoms represented by R ₁ and R ₁ ′ represented by the formula (Q ₂ -1) of Q _{2 in} the structural unit represented by the general formula (1) is a methyl group, An ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, and the like can be mentioned. A halogen atom can include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom, and a halogenomethyl group can include chloromethyl. Group, bromomethyl group, iodomethyl group and the like. In the formula (1), the alkyl group having 1 to 18 carbon atoms represented by the formula _{Q 2 (Q} 2 -2) and _(Q 2 -3) _{R 2} and _{R 2} 'represented by a straight or branched Or a cyclic alkyl group, and specific examples thereof include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, t-butyl group, n-pentyl group, n-hexyl group, lauryl group, Stearyl group etc. are mentioned. Among these, R ₂ and R ₂ ′ are more preferably an alkyl group having 1 to 5 carbon atoms, and a methyl group, an ethyl group, and an isopropyl group are particularly preferable. In the formula (1), if either R ₃ and R ₄ is represented by the formula Q ₂ (Q 2 _-4) is a hydrogen atom and the other alkyl group, and both have the alkyl group However, the total carbon number of both is 3-20. For example, when R ₃ is a hydrogen atom, R ₄ is an alkyl group having 3 to 20 carbon atoms, and when R ₃ and R ₄ are alkyl groups, the total number of carbon atoms of the alkyl groups of R ₃ and R ₄ is 3 A combination of ˜20.

Q _{2 in} the structural unit of the general formula (1) may be one kind selected from the structures of the formulas (Q ₂ -1), (Q ₂ -2), (Q ₂ -3) and (Q ₂ -4) Well, two or more may be combined, but the following formula (1a)

Is more preferable. Furthermore, the following formula (1b)

(Wherein R ₁ is as defined above) is more preferred, and the case where R ₁ is a hydrogen atom is particularly preferred.

  Next, the general formulas (2) and (2 ') constituting the pH-responsive polymer fine particles of the present invention will be described.

In the structural unit represented by the general formula (2), Q ₄ , (CH ₂ ) _n represented by X ₁ in the formula (Q ₄ -1) is an alkylene group having 1 to 3 carbon atoms, Specific examples include a methylene group, an ethylene group, and a trimethylene group, with an ethylene group being preferred. Of _{Q 4} in the formula (2), the formula _{(Q 4 -1), (Q} 4 -2) and _(Q 4 -3) methyl group as the lower alkyl group represented by _{R 5} and _{R 6} in ethyl Group, n-propyl group, isopropyl group, butyl group and the like.

Q _{4 in} the structural unit of the general formula (2) may be one kind selected from (Q ₄ -1), (Q ₄ -2) and (Q ₄ -3), or a combination of two or more kinds. Is the following formula (2a)

(Wherein Q ₃ , R ₅ and R ₆ are the same as above)

Is more preferred, and the following formula (2b)

The structural unit represented by

The formula (2 ') _{Q 4} in the structural unit represented by', as the light metal ion represented by M in the formula _{(Q 4} '-1) and _{(Q 4'} -2), lithium-ion, Sodium ion, potassium ion, etc. are mentioned.

Q _{4 in} the structural unit of the general formula (2 ′) may be one type selected from the formulas (Q ₄ ′ -1) and (Q ₄ ′ -2), or a combination of two or more types. Equation (2'a)

(Wherein M is the same as above)

Is more preferable, and has the following formula (2'b)

The structural unit represented by

  Next, general formulas (3) and (4) constituting the pH-responsive polymer fine particles of the present invention will be described.

In the structural unit represented by the general formula (3), the alkylene group having 1 to 10 carbon atoms represented by A _{1 of} Q ₆ and Q ₈ is a linear or branched alkylene group having 1 to 10 carbon atoms. Specific examples include a methylene group, an ethylene group, a trimethylene group, a hexamethylene group, a (ethyl) ethylene group, and a (dimethyl) ethylene group. Among these, a linear or branched alkylene group having 1 to 5 carbon atoms is more preferable.

X _{8 in} the structural unit represented by the general formula (3), R ₈ in the formulas (X ₂ -1), (X ₂ -2), (X ₂ -3) and (X ₂ -4), Examples of the lower alkyl group represented by R ₉ and R ₁₀ include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, and a butyl group.

In formula of _{X 2} of the structural unit represented by (3), Formula _(X 2 -1) and _(X 2 -2) in the _{(CH 2) n} is an alkylene group having 1 to 3 carbon atoms, Specific examples include a methylene group, an ethylene group, and a trimethylene group, with an ethylene group being preferred.

X _{2 in} the structural unit represented by the general formula (3) is Z ⁻ in the formulas (X ₂ -1), (X ₂ -2), (X ₂ -3) and (X ₂ -4). Examples of the anions shown include fluorine ions, chlorine ions, bromine ions, iodine ions, and sulfate ions, and among them, chlorine ions are particularly preferable.

The repeating unit containing X ₂ in the structural unit represented by the general formula (3) includes (X ₂ -1), (X ₂ -2), (X ₂ -3), (X ₂ -4), ( X ₂ -5) and _(X 2 -6) may be a one selected from among, or in combination of two or more.

  In the structural unit of the general formula (3), the following formula (3a)

(Wherein, Q ₇ , Q ₈ , Q ₉ , Y ₁ , X ₂ , R ₇ and l are the same as described above) are more preferable, and further, the structural unit (3b)

(Wherein X ₂ , R ₇ and l are the same as defined above) are more preferred, and the formula (3c)

A structural unit represented by the formula (wherein Z and l are the same as above) is particularly preferred.

  In the structural unit of the general formula (4), the following formula (4a)

(Wherein Q ₁₁ and m are the same as those described above), and a structural unit represented by formula (4b)

A structural unit represented by (wherein m is the same as above) is particularly preferred.

  The structural unit forming the core of the fine particles may be selected from one or more structural units represented by the general formula (1). Moreover, the structural unit that expresses the pH response performance may be selected from one or more structural units represented by the general formula (2). In this case, the particle diameter increases as the pH changes from alkaline to acidic. The pH-responsive fine particles are increased. In addition, one or more structural units represented by the general formula (2 ') may be selected. In this case, environmentally responsive fine particles whose particle diameter increases as the pH changes from acidic to alkaline. The structural unit which is a hydrophilic polymer chain localized on the surface of the fine particle may be selected from one or more structural units represented by the general formula (3), or may be selected from the structural unit represented by the general formula (4). 1 type or 2 types or more may be selected, or 2 or more types may be selected from the group of the general formulas (3) and (4). A more preferred combination is one selected from the structural unit represented by the general formula (1), one selected from the structural unit represented by the general formula (2), and the general formula (3) or the general formula (4 Or a combination selected from the structural units represented by the general formula (1) and a structural unit represented by the general formula (2 ′) , A combination with one selected from structural units represented by general formula (3) or general formula (4).

  The structural unit represented by the general formula (1), the structural unit represented by the general formula (2) or (2 ′), the general formula (3) and / or (4) constituting the pH-responsive fine particles of the present invention. The ratio of the structural unit is not particularly limited, but from the viewpoint of pH responsiveness, the structural unit represented by the general formula (1), the structural unit represented by the general formula (2) or (2 ′), and the general formula ( The ratio of the structural unit represented by 3) and (4) to the repeating unit constituting the polymer chain localized on the surface of the polymer fine particle is in the range of 1 / 0.01 to 100 / 0.01 to 100. Is preferable, the range of 1 / 0.1 to 50 / 0.1 to 50 is more preferable, and 1 / 0.5 to 10 / 0.5 to 10 is particularly preferable.

  The pH-responsive polymer fine particle dispersion of the present invention includes at least one selected from the monomers represented by the general formula (5) that forms the core of the fine particles, and the general formula (6) that expresses pH response performance. And at least one selected from the monomers represented by the general formula (6 ′), and the general formula (7) and / or localized on the surface of the fine particles. Or it can manufacture by copolymerizing at least 1 sort (s) chosen from the hydrophilic macromonomer represented by (8).

  The manufacturing method will be described in detail below.

The lower alkyl group having 1 to 4 carbon atoms represented by the general formula (5) wherein the _{Q 14} of the monomer represented by _(Q 14 -1) _{R 13} and _{R 13} represented by 'a methyl group, ethyl Group, n-propyl group, isopropyl group, n-butyl group and the like. As the halogen atom, fluorine atom, chlorine atom, bromine atom and iodine atom can be mentioned. As halogenomethyl group, chloromethyl can be mentioned. Group, bromomethyl group, iodomethyl group and the like. Equation _(5), examples of the alkyl group having 1 to 18 carbon atoms represented by the formula of _{Q 14 (Q} 14 -2) and _(Q 14 -3) _{R 14} and _{R 14} represented by ', straight-chain or branched Or a cyclic alkyl group, and specific examples thereof include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, t-butyl group, n-pentyl group, n-hexyl group, lauryl group, Stearyl group etc. are mentioned. Among these, as R <_14> and R < ₁₄ '>, a C1-C5 alkyl group is more preferable, and a methyl group, an ethyl group, and an isopropyl group are especially preferable. In the formula _(5), if either one _{of R 15} and _{R 16} is represented by the formula _{Q 14 (Q} 14 -4) is a hydrogen atom and the other alkyl group, and both have the alkyl group However, the total carbon number of both is 3-20. For example, when R ₁₅ is a hydrogen atom, R ₁₆ is an alkyl group having 3 to 20 carbon atoms, and when R ₁₅ and R ₁₆ are alkyl groups, the total number of carbon atoms of the alkyl groups of R ₁₅ and R ₁₆ is 3 A combination of ˜20.

  As the monomer represented by the general formula (5), styrene, monomethylstyrene, dimethylstyrene, chlorostyrene, dichlorostyrene, chloromethylstyrene, ethyl acrylate, propyl acrylate, butyl acrylate, lauryl acrylate, stearyl acrylate, methyl methacrylate , Ethyl methacrylate, butyl methacrylate, lauryl methacrylate, stearyl methacrylate, benzyl methacrylate, hydroxypropyl methacrylate, vinyl acetate, vinyl propionate, vinyl caproate, vinyl laurate, vinyl cyclohexanecarboxylate, vinyl benzoate, N-butylacrylamide, acrylonitrile These monomers can be used alone or in appropriate combination, Styrene is particularly preferred.

Represented by _{X 3} represented by the general formula _{Q 16} of the monomer represented by (6) the formula _{(Q 16 -1) (CH 2} ) n is an alkylene group having 1 to 3 carbon atoms, specifically Examples include methylene group, ethylene group and trimethylene group, and ethylene group is preferred. In the formula _(6), the lower alkyl group represented by _{R 17} and _{R 18} of the formula of _{Q 16 (Q} 16 -1) and _(Q 16 -2) and _(Q 16 -3) methyl, ethyl Group, n-propyl group, isopropyl group, butyl group and the like.

Among the monomers represented by the general formula (6), the monomers in which Q ₁₆ is represented by the formula (Q ₁₆ -1) include dimethylaminomethyl (meth) acrylate, dimethylaminoethyl (meth) acrylate, dimethyl Aminopropyl (meth) acrylate, diethylaminoethyl (meth) acrylate, methylethylaminoethyl (meth) acrylate, dimethylaminomethyl (meth) acrylamide, dimethylaminoethyl (meth) acrylamide, dimethylaminopropyl (meth) acrylamide, diethylaminomethyl ( meth) acrylamide, diethylaminoethyl (meth) acrylamide, diethylaminopropyl (meth) _acrylamide, and examples of the _{monomer Q 16} is represented by the formula _(Q 16 -2), N- vinylformamide, N- bi Ruasetoamido and the _like, and the _{monomer Q 16} is represented by the formula _(Q 16 -3), vinyl benzylamine, N- methyl vinyl benzylamine, N- ethyl-vinyl benzyl amine, N, N- dimethyl vinyl Examples include benzylamine, N, N-diethylvinylbenzylamine, and dimethylaminoethyl methacrylate is more preferable.

The light metal ions represented by M of formula _{(Q 16} '-1) and _{(Q 16'} -2) of formula (6 ') _{Q 16} of the monomer represented by', a lithium ion, sodium Ions, potassium ions, and the like.

Among the monomers represented by the general formula (6 ′), examples of the monomer in which Q ₁₆ ′ is represented by the formula (Q ₁₆ ′ -1) include (meth) acrylic acid, sodium (meth) acrylate, ( meth) ammonium acrylate and the like, and the monomer Q _{16 'has} the formula (Q _16' represented by -2), (meth) acrylamide-methylpropanesulfonic acid, (meth) sodium acrylamido methyl propane sulfonic acid, Examples thereof include ammonium (meth) acrylamidomethylpropanesulfonate, and sodium acrylate is more preferable.

In the macromonomer represented by the general formula (7), the alkylene group having 1 to 10 carbon atoms represented by A _{2 of} Q ₁₈ and Q ₂₀ is a linear or branched alkylene group having 1 to 10 carbon atoms. Specific examples include a methylene group, an ethylene group, a trimethylene group, a hexamethylene group, a (ethyl) ethylene group, and a (dimethyl) ethylene group. Among these, a linear or branched alkylene group having 1 to 5 carbon atoms is more preferable.

Formula (7) expressed in _{X 4} in the macromonomer is in the formula _{(X 4} -1), (X 4 _{-2), (X} 4 -3) and _(X 4 -4) _{R 20} in, Examples of the lower alkyl group represented by R ₂₁ and R ₂₂ include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, and a butyl group.

(CH ₂ ) _n in the formula (X ₄ -1) and (X ₄ -2) of X _{4 in} the macromonomer represented by the general formula (7) is an alkylene group having 1 to 3 carbon atoms, Specific examples include a methylene group, an ethylene group, and a trimethylene group, with an ethylene group being preferred.

X _{4 in} the macromonomer represented by the general formula (7) is Z ⁻ in the formulas (X ₄ -1), (X ₄ -2), (X ₄ -3) and (X ₄ -4). Examples of the anions shown include fluorine ions, chlorine ions, bromine ions, iodine ions, and sulfate ions, and among them, chlorine ions are particularly preferable.

The repeating unit containing X ₄ in the macromonomer represented by the general formula (7) is (X ₄ -1), (X ₄ -2), (X ₄ -3), (X ₄ -4), ( X ₄ -5) and _(X 4 -6) may be a one selected from among, or in combination of two or more.

Among the hydrophilic macromonomers corresponding to the structural unit of the general formula (7), _{X 4} is formula of the repeating unit _{(X 4 -1), (X} 4 -2), (X 4 -3) and _{(X 4} - 6) The hydrophilic macromonomer represented by 6) is radical-polymerized in the presence of a chain transfer agent having an amino group, hydroxyl group or carboxyl group in the molecule, and the terminal is an amino group, hydroxyl group or carboxyl group. Can be produced by reacting with a vinyl monomer such as vinyl benzyl halide or methacrylic acid alkyl ester dioxide.

As a monomer corresponding to the repeating unit in the case where a hydrophilic macromonomer in which X ₄ of the structural unit of the general formula (7) is represented by the formula (X ₄ -1) is produced, (meth) acryloyloxyalkyltrialkyl is used. Specific examples include ammonium salts such as acryloyloxymethyltrimethylammonium chloride, acryloyloxyethyltrimethylammonium chloride, acryloyloxymethyltriethylammonium chloride, acryloyloxyethyltriethylammonium chloride, acryloyloxyethyldimethylbenzylammonium chloride, methacryloyloxymethyltrimethyl. Ammonium chloride, methacryloyloxyethyltrimethylammonium chloride, methacryloyloxymethyltriethyl Nmo chloride, methacryloyloxyethyl triethylammonium chloride, methacryloyloxyethyl dimethylbenzyl ammonium chloride.

In the case of producing a hydrophilic macromonomer in which X ₄ of the structural unit of the general formula (7) is represented by the formula (X ₄ -2), the monomer corresponding to the repeating unit is (meth) acryloylaminoalkyltrialkyl. Specific examples of the (meth) acryloylaminoalkyltrialkylammonium salt include acryloylaminomethyltrimethylammonium chloride, acryloylaminoethyltrimethylammonium chloride, acryloylaminomethyltriethylammonium chloride, and acryloylaminoethyltriethylammonium chloride. , Acryloylaminoethyldimethylbenzylammonium chloride, methacryloylaminomethyltrimethylammonium chloride, methacryloylaminoethyl Trimethyl ammonium chloride, methacryloyl aminomethyl triethylammonium chloride, methacryloyl aminoethyl triethylammonium chloride, methacryloyl aminoethyl dimethyl benzyl ammonium chloride.

In the case of producing a hydrophilic macromonomer in which X ₄ of the structural unit of the general formula (7) is represented by the formula (X ₄ -3), a monomer corresponding to the repeating unit is exemplified by vinylbenzyltrialkylammonium salt. Specific examples include vinylbenzyltrimethylammonium chloride, vinylbenzyltriethylammonium chloride, vinylbenzyltributylammonium chloride and the like.

When the hydrophilic macromonomer in which X ₄ of the structural unit of the general formula (7) is represented by the formula (X ₄ -6) is produced, examples of the monomer corresponding to the repeating unit include acrylamide, N-methylacrylamide, N -Ethylacrylamide, N, N-dimethylacrylamide, methacrylamide, N-methylmethacrylamide, N-ethylmethacrylamide, N, N-dimethylmethacrylamide and the like.

  These monomers can be used alone or in appropriate combination.

  Synthesis of a polymer or copolymer having an amino group, a hydroxyl group or a carboxyl group at the end is carried out in the presence of a monomer, a chain transfer agent, and a radical polymerization initiator corresponding to the desired repeating unit of the hydrophilic macromonomer. In this case, the solvent may or may not be present, but it is preferable that the solvent is present from the viewpoint of reaction control and operation. As the solvent, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, polar solvents such as dimethylformamide and water can be used, and mixed solvents such as alcohols / water or ketones / water can also be used.

  As the chain transfer agent, mercaptoalkylamines, mercaptoalkanols, ω-mercaptocarboxylic acids, alkylene glycols and the like can be used, but 2-mercaptoethylamine, 2-mercaptoethanol, mercaptoacetic acid, and β-mercaptopropionic acid. preferable. The preferred amount of chain transfer agent used depends on the number average molecular weight of the hydrophilic macromonomer to be obtained and the reaction conditions, but the preferred number average molecular weight of the hydrophilic macromonomer is 500 to 50,000, and the number average molecular weight is 500 to 50. In the case of obtaining 1,000,000 hydrophilic polymer chains, the amount of the chain transfer agent used is about 0.1 to 50 mol with respect to 100 mol of the monomer. A number average molecular weight of less than 500 is not preferred because it is difficult to obtain polymer fine particles in which hydrophilic macromonomers are accumulated on the surface. On the other hand, if the number average molecular weight exceeds 50,000, the polymerizability of the radical polymerizable group bonded to the end of the hydrophilic polymer is lowered, which is not preferable.

  As the radical polymerization initiator, ammonium persulfate, potassium persulfate, hydrogen peroxide, benzoyl peroxide, t-butyl hydroperoxide, azobisisobutyronitrile, azobis (2-aminodipropane) hydrochloride, etc. can be used. However, azobis (2-aminodipropane) hydrochloride is preferred. The preferred amount of polymerization initiator used is about 0.02 to 2 moles per 100 moles of monomer.

  The polymerization time varies depending on the type and amount of polymerization initiator used, the polymerization temperature, etc., but is usually from 30 minutes to 10 hours, and it is preferable to carry out the polymerization until the monomer is consumed by the polymerization.

  Polymerization may be carried out by dissolving the monomer and chain transfer agent in a polar solvent, raising the temperature, and then adding a polymerization initiator, or adding the monomer, chain transfer agent, and polymerization initiator in the heated polar solvent, respectively. You may add separately or in mixture. The polymerization temperature is preferably 50 ° C to 100 ° C.

  Reaction of a vinyl monomer with a polymer or copolymer having an amino group, hydroxyl group or carboxyl group at the end obtained as described above is easier than general acid amide reaction, etherification reaction or esterification reaction. Can be achieved. As the vinyl monomer, chloromethylstyrene and glycidyl methacrylate are preferable.

  For example, a polymer or copolymer having a functional group such as a hydroxyl group, an amino group, or a carboxyl group at the terminal is reacted with a vinylbenzyl halide such as chloromethylstyrene or an epoxy group-containing (meth) acrylate such as glycidyl methacrylate. A radical polymerizable group is introduced at the terminal. This reaction can be carried out in a polar medium such as dimethylformamide by maintaining a temperature of 10 ° C. to 80 ° C. in the presence of a base and a phase transfer catalyst.

  Bases include potassium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, or organic amines such as ethylenediamine, monoethanolamine, diethanolamine, triethanolamine, diethylenetriamine, triethylenetetramine, or trichloro Examples include alkali generators such as sodium acetate, but are not particularly limited. The amount of base used is 1 to 10 times the number of moles of chain transfer agent used when synthesizing a cationic hydrophilic polymer having a functional group such as a hydroxyl group, an amino group, or a carboxyl group at the terminal. Is preferred.

  Examples of the phase transfer catalyst include, but are not limited to, phosphonium salts such as tetrabutylphosphonium bromide, tetraethylphosphonium bromide, and tetrabutylphosphonium chloride, or ammonium salts such as tetrabutylammonium bromide, tetraethylammonium bromide, and tetrabutylammonium chloride. . The amount of phase transfer catalyst used is 0.05 to the number of moles of chain transfer agent used when synthesizing a cationic hydrophilic polymer having a functional group such as a hydroxyl group, an amino group, or a carboxyl group at the terminal. It is preferable to use 1 time.

  Examples of vinyl benzyl halides include chloromethyl styrene, bromomethyl styrene, and iodomethyl styrene. Epoxy group-containing (meth) acrylates include glycidyl methacrylate, glycidyl acrylate, 3,4-epoxycyclohexyl methacrylate, and the like. Methylstyrene is particularly preferred. The amount of vinylbenzyl halide or epoxy group-containing (meth) acrylate used is the mole of chain transfer agent used when synthesizing a cationic hydrophilic polymer having a functional group such as a hydroxyl group, amino group, or carboxyl group at the terminal. It is preferable to use 1 to 10 times the number.

  The time required for the reaction between the hydrophilic polymer having a functional group such as a hydroxyl group, an amino group, or a carboxyl group at the terminal and the vinylbenzyl halide or epoxy group-containing (meth) acrylate is the above-mentioned hydrophilic polymer and vinylbenzyl halide or epoxy. It varies depending on the amount of group-containing (meth) acrylate used, the type and amount of catalyst used, the reaction temperature, etc., but it is usually 10 to 100 hours, and a radical polymerizable group is introduced at the end of the hydrophilic polymer. It is preferable to carry out the reaction until.

  Polar solvents used in the reaction of a hydrophilic polymer having a functional group such as a hydroxyl group, an amino group or a carboxyl group with vinylbenzyl halide or an epoxy group-containing (meth) acrylate are alcohols such as methanol, ethanol and propanol. , Ketones such as acetone and methyl ethyl ketone, dimethylformamide, water and the like can be used, but a hydrophilic polymer having a high solubility in water and a vinylbenzyl halide or an epoxy group-containing (meth) acrylate having a low solubility in water In order to improve the familiarity, it is preferable to mix the above-mentioned alcohols, ketones or polar organic solvents such as dimethylformamide with water. In this case, the mixing ratio is preferably 5% to 50% by weight of the above-mentioned polar organic solvent such as alcohols, ketones or dimethylformamide with respect to water.

Among the hydrophilic macromonomers corresponding to the structural unit of the general formula (7), the hydrophilic macromonomer in which the repeating unit X ₄ is represented by the formulas (X ₄ -4) and (X ₄ -5) is N- At least one monomer selected from N-vinylamide monomers such as vinylformamide and N-vinylacetamide is radically polymerized in the presence of a chain transfer agent having an amino group, hydroxyl group or carboxyl group in the molecule, as described above. After synthesizing a polymer or copolymer having an amino group, a hydroxyl group or a carboxyl group at the terminal, it is reacted with a vinyl monomer such as vinyl benzyl halide or alkyl methacrylate ester methacrylate, and then in the presence of an acid such as hydrochloric acid. Hydrophilic macromonomers having primary amino groups by hydrolyzing amide groups in polar solvents such as alcohol or / and water Over it can be obtained. When the primary amino group is quaternized, halogen compounds such as alkyl halides such as methyl chloride and ethyl chloride (halogen atoms are chlorine, bromine or iodine atoms) and benzyl halides such as benzyl chloride are used. It is done. Quaternization is easily accomplished by various known methods.

  As the hydrophilic macromonomer represented by the general formula (7), the following formula (7a)

(Wherein Q ₁₉ , Q ₂₀ , Q ₂₁ , Y ₂ , X ₄ , R ₁₉ and l are the same as those described above) are more preferred, and further a formula (7b)

(Wherein X ₄ , R ₁₉ and l are the same as those described above), more preferably, a hydrophilic macromonomer represented by formula (7c)

A hydrophilic macromonomer represented by the formula (wherein Z and l are the same as described above) is more preferable, but the formula (7d)

A hydrophilic macromonomer represented by the formula (wherein l is the same as described above) is particularly preferred.

  As the hydrophilic macromonomer represented by the general formula (8),

A hydrophilic macromonomer represented by the formula (wherein Q ₂₃ and m are the same as described above) is more preferable, but the formula (8b)

A hydrophilic macromonomer represented by the formula (wherein m is the same as described above) is particularly preferred.

  As the hydrophilic macromonomer corresponding to the structural unit of the formula (8), a commercially available hydrophilic macromonomer can be used.

  At least one of the hydrophilic macromonomer corresponding to the structural unit of the general formula (7) and the hydrophilic macromonomer corresponding to the structural unit of the general formula (8) obtained as described above is represented by the general formula (5). And at least one monomer corresponding to the structural unit of general formula (6) or (6 ′), a polymerization initiator, and optionally a chain transfer agent The pH-responsive polymer fine particle dispersion of the present invention by copolymerization in alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, and polar solvents such as water in the presence of Can do.

  The polymerization temperature is preferably 50 ° C. to 100 ° C. As the solvent, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, dimethylformamide, water and the like can be used, and alcohols / water or ketones A mixed solvent such as water / water can also be used. Examples of the polymerization initiator include ammonium persulfate, potassium persulfate, hydrogen peroxide, benzoyl peroxide, t-butyl hydroperoxide, azobisisobutyronitrile, azobis (2-aminodipropane) hydrochloride, and the like. It is done. The preferable use amount of the polymerization initiator is about 0.02 to 2 mol with respect to 100 mol in total of the monomer represented by the general formula (5) and the monomer represented by the general formula (6). The polymerization time varies depending on the type and amount of polymerization initiator used, the polymerization temperature, etc., but is usually 30 minutes to 10 hours, and is a hydrophobic monomer represented by the general formula (5) that contributes to the formation of the core part of the fine particles, Until the monomer represented by the general formula (6) contributing to the pH responsive expression and the hydrophilic macromonomer represented by the general formula (7) or (8) having a radical polymerizable group at the terminal are consumed by polymerization. It is preferable to perform polymerization.

  Among the general formula (6), at least one monomer selected from N-vinylamide monomers such as N-vinylformamide and N-vinylacetamide is at least one monomer corresponding to the structural unit of the general formula (5). And, when copolymerized with at least one hydrophilic macromonomer corresponding to the structural unit of the general formula (7) and / or the general formula (8), it is then hydrolyzed by a known method, and further secondaryized or The dispersion of pH-responsive polymer fine particles of the present invention can be produced by tertiaryization.

  In the synthesis of the pH-responsive fine particles of the present invention, the monomer represented by the general formula (5), the monomer represented by the general formula (6) or (6 ′), the general formula (7) and / or (8) The ratio of the hydrophilic macromonomer represented by () is not particularly limited, but from the viewpoint of pH responsiveness, the monomer represented by the general formula (5) and the single monomer represented by the general formula (6) or (6 ′). The ratio of the monomer and the repeating unit constituting the polymer chain localized on the surface of the polymer fine particle in the hydrophilic macromonomer represented by the general formulas (7) and (8) is 1 / 0.01 to The range of 100 / 0.01 to 100 is preferable, the range of 1 / 0.1 to 50 / 0.1 to 50 is more preferable, and 1 / 0.5 to 10 / 0.5 to 10 is particularly preferable.

  The pH-responsive polymer fine particles of the present invention correspond to at least one hydrophobic monomer corresponding to the structural unit of the general formula (5) and the structural unit of the general formula (6) or (6 ′). Copolymerizing at least one monomer contributing to the expression of pH responsiveness and at least one hydrophilic macromonomer corresponding to the structural unit of the general formula (7) and / or the general formula (8); It is obtained by hydrolysis as necessary, and becomes a fine particle composed of a hydrophobic polymer in which hydrophilic macromonomers are localized on the surface and the inside has environmental responsiveness.

  FIG. 1 shows a typical polymer fine particle obtained when a cationic hydrophilic macromonomer having a radical polymerizable group at the terminal synthesized from styrene, dimethylaminoethyl methacrylate and methacryloyloxyethyltrimethylammonium chloride is used. This is a schematic representation of the mechanism. The terminal radical polymerizable group-containing cationic macromonomer 1 comprises a methacryloyloxyethyltrimethylammonium chloride unit 1a and a vinylbenzyl group 1b. First, the cationic macromonomer 1, the styrene monomer 2 and dimethylaminoethyl methacrylate 3 are mixed (step A), and the styrene monomer and dimethylaminoethyl methacrylate are polymerized to copolymerize the styrene monomer and dimethylaminoethyl methacrylate (step). B) occurs partly, but copolymerization with vinylbenzyl group 1b (step C) occurs simultaneously. As a result of the copolymerization, a polymer having a structure as if the cationic macromonomer is grafted to the styrene and dimethylaminoethyl methacrylate copolymer is obtained. Since the reaction is carried out in a polar medium, the hydrophobic styrene units are selectively accumulated on the inside and the cationic macromonomer 1 is selectively accumulated on the outside (Step D). When the polymerization is completed in this way, polymer fine particles 6 in which the cationic polymer chain 5 is located on the surface of the core portion 4 of the styrene / dimethylaminoethyl methacrylate unit are obtained (Step E).

  Since the fine particles have a hydrophilic surface, they are dispersed in an aqueous medium. However, by changing the pH of the medium, the hydrophobic polymer inside the fine particles becomes hydrophilic, so that the core part swells. The diameter is considered to change.

  The pH-responsive polymer fine particles of the present invention are expected to be applied to medical materials, chelating agents, adsorbents and the like.

Hereinafter, the features of the present invention will be made clearer by giving examples and comparative examples, but the present invention is not limited to the following examples. In addition, the weight average molecular weight of the polymer in a comparative manufacture example and a manufacture example was measured in accordance with the following method.
<Measurement of polymer weight average molecular weight and polymerization yield>
Shimadzu CTO-20A for the column thermostat, Shimadzu RID-10A for the detector, Shimadzu LC-20AD for the eluent flow path pump, Shimadzu DGU-20A for the degasser, autosampler Was measured by GPC method using SIL-20A manufactured by Shimadzu Corporation. The column used was a Tosoh water-based SEC column TSKgelG3000PWXL (exclusion limit molecular weight 2 × 10 ⁵ ), TSKgelG5000PWXL (exclusion limit molecular weight 2.5 × 10 ⁶ ), and TSKgelG6000PWXL (exclusion limit molecular weight 5 × 10 ⁷ ). The sample was prepared to a concentration of 2 g / 100 ml with an eluent and used for measurement. As an eluent, an aqueous solution adjusted to 0.5 mol / liter each of acetic acid and sodium acetate was used. The column temperature was 40 ° C. and the flow rate was 1.0 ml / min. A calibration curve was determined using nine types of polyethylene glycols having molecular weights of 1065, 5050, 24000, 50000, 107000, 140000, 250,000, 540000, and 920000 as standard samples, and the weight average molecular weight of the polymer was determined based on the calibration curve. . The particle diameter of the pH-responsive polymer fine particles according to the present invention was measured by a dynamic light scattering method (Malvern: Zetasizer Nano ZS). The following abbreviations mean the following compounds.
MATMAC: methacryloyloxyethyltrimethylammonium chloride DMAEMA: dimethylaminoethyl methacrylate DEAEMA: diethylaminoethyl methacrylate 2EHA: 2-ethylhexyl acrylate VAm: vinylamine VBTMAC: vinylbenzyltrimethylammonium chloride NVF: N-vinylformamide VBA: vinylbenzylamine AAc: acrylic acid ATBS: acrylamide tert-butyl sulfonic acid St: styrene

Synthesis example 1

Synthesis of pH-responsive polymer fine particle dispersion <1> in which MATMAC polymer chains are accumulated on the surface ( synthesis of MATMAC polymer)
In a reaction vessel equipped with a stirrer, a reflux condenser, two dropping funnels, a nitrogen gas inlet tube and a thermometer, 463.5 g of water was charged and heated to raise the temperature to 80 ° C. Under a nitrogen stream, a mixed solution of 500 g (1.93 mol) of an 80 wt% aqueous solution of methacryloyloxyethyltrimethylammonium chloride (MATMAC) and 20.3 g (0.22 mol) of mercaptoacetic acid and an aqueous 16 wt% solution of potassium persulfate 16 .2 g (0.003 mol) was added dropwise simultaneously over 2 hours. After completion of dropping, the mixture was kept at 80 ° C. for 3 hours to obtain a MATMAC polymer solution having a carboxyl group at the end (solid content concentration: 42.1%). After completion of the reaction, the MATMAC polymer was purified by reprecipitation with acetone several times. The obtained polymer had a weight average molecular weight of 12,000 and a number average molecular weight of 6,000, as determined from GPC (liquid chromatography).

(Introduction of radical polymerizable group to MATMAC polymer terminal)
Next, in a reaction vessel equipped with a stirrer, a reflux condenser, and a thermometer, 700.0 g of the above MATMAC polymer solution (solid concentration: 42.8%) [0.15 mol as a mercaptoacetic acid unit (obtained from pre-charging) In addition, 280.0 g of ethanol was added, 16.7 g (0.20 mol) of a 48 wt% aqueous solution of sodium hydroxide, 13.0 g (0.04 mol) of tetrabutylammonium bromide, and p-chloromethyl 30.2 g (0.20 mol) of styrene was added and reacted at 30 ° C. for 72 hours to obtain a terminal vinylbenzyl group-containing MATMAC polymer solution (solid content concentration 32.8%). After completion of the reaction, reprecipitation with acetone was performed to purify the terminal vinylbenzyl group-containing MATMAC polymer. As a result of ¹ H-NMR measurement, it was found that the introduction rate of vinylbenzyl group at the terminal was almost 100%. The number average molecular weight of the terminal vinylbenzyl group-containing MATMAC polymer measured by GPC (liquid chromatography) was 6,100.

(Synthesis of pH-responsive polymer fine particle dispersion <1> in which MATMAC polymer chains are accumulated on the surface)
Next, in a reaction vessel equipped with a stirrer, a reflux condenser, a nitrogen gas inlet tube and a thermometer, 330.6 g of the above-mentioned terminal vinylbenzyl group-containing MATMAC polymer solution [0.43 mol as a MATMAC repeating unit (obtained from pre-charging) )], DMAEMA 67.0 g (0.43 mol), styrene 44.4 g (0.43 mol), and water 476.9 g were charged, the pH was adjusted with hydrochloric acid, and the temperature was raised to 60 ° C. Under a nitrogen stream, 81.1 g (0.015 mol) of a 5% by weight aqueous solution of potassium persulfate was added and copolymerized for 6 hours to obtain a milky white dispersion (solid content concentration 23.8%).

  The pH-responsive polymer fine particles thus obtained had an average particle diameter at pH 5 of 530 nm. The reaction formula (9) for producing the polymer fine particles is

（ただし、ｈ、ｊ、ｊ、ｋは重合度を表す整数である。）により表されると考えられる。

(Where h, j, j, and k are integers representing the degree of polymerization).

Synthesis example 2

Synthesis of pH-responsive polymer fine particle dispersion <2> in which MATMAC polymer chains are accumulated on the surface In synthesis of pH-responsive polymer fine particle <1> in Synthesis Example 1 above, terminal vinylbenzyl group-containing MATMAC polymer solution 247 6.4 g [0.32 mol as MATMAC repeating unit (determined from the previous charge)], DMAEMA 100.4 g (0.64 mol), styrene 33.3 g (0.32 mol), and water except 537.6 g The reaction was carried out in the same manner as in Example 1 to obtain a milky white dispersion (solid content concentration 22.9%). The average particle diameter at pH 5 of the pH-responsive polymer fine particles thus obtained was 1170 nm.

Synthesis example 3

Synthesis of pH-responsive polymer fine particle dispersion <3> in which MATMAC polymer chains are accumulated on the surface In synthesis of pH-responsive polymer fine particle <1> in Synthesis Example 1 above, terminal vinylbenzyl group-containing MATMAC polymer solution 282 .3 g [0.36 mol as MATMAC repeating unit (determined from pre-charging)], DMAEMA 57.3 g (0.36 mol), 2EHA 67.1 g (0.36 mol), and water synthesis 512.2 g Reaction was carried out in the same manner as in 1 to obtain a milky white dispersion (solid content concentration 22.5%). The average particle diameter at pH 5 of the pH-responsive polymer fine particles thus obtained was 890 nm.

Synthesis example 4

Synthesis of pH-responsive polymer fine particle dispersion <4> having MATMAC polymer chains accumulated on the surface In the synthesis of pH-responsive polymer fine particle <1> in Synthesis Example 1 above, terminal vinylbenzyl group-containing MATMAC polymer solution 227 .2 g [0.29 mol as MATMAC repeating unit (determined from pre-charge)], DEAEMA 108.6 g (0.58 mol), styrene 30.5 g (0.29 mol), water 552.6 g The reaction was carried out in the same manner as in Example 1 to obtain a milky white dispersion (solid content concentration 23.0%). The average particle diameter at pH 5 of the pH-responsive polymer fine particles obtained in this manner was 980 nm.

Synthesis example 5

Synthesis of pH-responsive polymer fine particle dispersion <5> in which MATMAC polymer chains are accumulated on the surface In synthesis of pH-responsive polymer fine particle <1> in Synthesis Example 1 above, terminal vinylbenzyl group-containing MATMAC polymer solution 308 0.5 g [0.40 mol as a MATMAC repeating unit (determined from the previous charge)], 56.9 g (0.80 mol) of NVF, 41.7 g (0.40 mol) of styrene, 511.8 g of water, and Synthesis Example 1 After carrying out the reaction in the same manner, 203 g (2.00 mol) of hydrochloric acid (36% aqueous solution) was added and reacted at 80 ° C. for 48 hours. The acetamide group was converted to an amino group (VAm), and a milky white dispersion ( Solid content concentration 21.8%) was obtained. The average particle diameter at pH 5 of the pH-responsive polymer fine particles obtained in this manner was 790 nm.

Synthesis Example 6

Synthesis of pH-responsive polymer fine particle dispersion <6> in which MATMAC polymer chains are accumulated on the surface In synthesis of pH-responsive polymer fine particle <1> in Synthesis Example 1 above, terminal vinylbenzyl group-containing MATMAC polymer solution 246 .8 g [0.32 mol as MATMAC repeating unit (determined from the previous charge)], VBA 85.2 g (0.64 mol), styrene 33.3 g (0.32 mol), and synthesis except water 553.6 g The reaction was conducted in the same manner as in Example 1 to obtain a milky white dispersion (solid content concentration 21.5%). The average particle diameter at pH 5 of the pH-responsive polymer fine particles thus obtained was 715 nm.

Synthesis example 7

Synthesis of pH-responsive polymer fine particle dispersion <7> with VBTMA polymer chains accumulated on the surface ( synthesis of VBTMAC polymer)
In a reaction vessel equipped with a stirrer, a reflux condenser, two dropping funnels, a nitrogen gas inlet tube and a thermometer, 463.5 g of water was charged and heated to raise the temperature to 80 ° C. Under a nitrogen stream, a mixed solution of 500 g (1.89 mol) of an 80 wt% aqueous solution of vinylbenzyltrimethylammonium chloride (VBTMAC) and 20.3 g (0.22 mol) of mercaptoacetic acid and a 5 wt% aqueous solution of potassium persulfate 16. 2 g (0.003 mol) was added dropwise simultaneously over 2 hours. After completion of dropping, the mixture was kept at 80 ° C. for 3 hours to obtain a VBTMAC polymer solution having a carboxyl group at the end (solid content concentration 41.9%). After completion of the reaction, the VBTMAC polymer was purified by reprecipitation with acetone several times. The obtained polymer had a weight average molecular weight of 14,000 and a number average molecular weight of 7,000 determined by GPC (liquid chromatography).

(Introduction of radical polymerizable group to VBTMAC polymer terminal)
Next, in a reaction vessel equipped with a stirrer, a reflux condenser, and a thermometer, 700.0 g of the VBTMAC polymer solution (solid content concentration 41.9%) [0.15 mol as a mercaptoacetic acid unit (obtained from pre-charging) In addition, 280.0 g of ethanol was added, 16.7 g (0.20 mol) of a 48 wt% aqueous solution of sodium hydroxide, 13.0 g (0.04 mol) of tetrabutylammonium bromide, and p-chloromethyl 30.2 g (0.20 mol) of styrene was added and reacted at 30 ° C. for 72 hours to obtain a terminal vinylbenzyl group-containing MATMAC polymer solution (solid content concentration 32.2%). After completion of the reaction, reprecipitation was performed with acetone to purify the terminal vinylbenzyl group-containing VBTMAC polymer. As a result of ¹ H-NMR measurement, it was found that the introduction rate of vinylbenzyl group at the terminal was almost 100%. The number average molecular weight of the terminal vinylbenzyl group-containing MATMAC polymer measured by GPC (liquid chromatography) was 7,100.

(Synthesis of pH-responsive polymer fine particle dispersion <7> in which VBTMAC polymer chains are accumulated on the surface)
Next, in a reaction vessel equipped with a stirrer, a reflux condenser, a nitrogen gas inlet tube, and a thermometer, 338.1 g of the above-mentioned vinyl vinyl group-containing VBTMAC polymer solution [0.43 mol as a VBTMAC repeating unit (determined from the previous preparation) )], DMAEMA 67.0 g (0.43 mol), styrene 44.4 g (0.43 mol), and water 468.8 g were charged, the pH was adjusted with hydrochloric acid, and the temperature was raised to 60 ° C. Under a nitrogen stream, 81.1 g (0.015 mol) of a 5% by weight aqueous solution of potassium persulfate was added and copolymerized for 6 hours to obtain a milky white dispersion (solid content concentration 24.4%). The pH-responsive polymer fine particles thus obtained had an average particle diameter at pH 5 of 540 nm.

Synthesis Example 8

Synthesis of pH-responsive polymer fine particle dispersion <8> with NVF polymer chains accumulated on the surface ( synthesis of NVF polymer)
In a reaction vessel equipped with a stirrer, a reflux condenser, two dropping funnels, a nitrogen gas inlet tube and a thermometer, 463.5 g of water was charged and heated to raise the temperature to 80 ° C. Under a nitrogen stream, a mixed solution of 500 g (5.63 mol) of an 80% by weight aqueous solution of N-vinylformamide (NVF) and 20.3 g (0.22 mol) of mercaptoacetic acid and 16.2 g of a 5% by weight aqueous solution of potassium persulfate. (0.003 mol) was added dropwise simultaneously over 2 hours. After completion of dropping, the mixture was kept at 80 ° C. for 3 hours to obtain an NVF polymer solution having a carboxyl group at the end (solid content concentration 41.8%). After completion of the reaction, the NVF polymer was purified by reprecipitation with acetone several times. The weight average molecular weight of the obtained polymer obtained by GPC (liquid chromatography) was 28,000, and the number average molecular weight was 14,000.

(Introduction of radical polymerizable group to the terminal of NVF polymer)
Next, in a reaction vessel equipped with a stirrer, a reflux condenser, and a thermometer, 700.0 g of the above-mentioned NVF polymer solution (solid content concentration 41.8%) [0.15 mol as a mercaptoacetic acid unit (obtained from pre-charging) In addition, 280.0 g of ethanol was added, 16.7 g (0.20 mol) of a 48 wt% aqueous solution of sodium hydroxide, 13.0 g (0.04 mol) of tetrabutylammonium bromide, and p-chloromethyl 30.2 g (0.20 mol) of styrene was added and reacted at 30 ° C. for 72 hours to obtain a terminal vinylbenzyl group-containing NVF polymer solution (solid content concentration 31.5%). After completion of the reaction, reprecipitation with acetone was performed to purify the terminal vinylbenzyl group-containing MATMAC polymer. As a result of ¹ H-NMR measurement, it was found that the introduction rate of vinylbenzyl group at the terminal was almost 100%. The number average molecular weight of the terminal vinylbenzyl group-containing NVF polymer measured by GPC (liquid chromatography) was 14,100.

(Synthesis of pH-responsive polymer fine particle dispersion <8> with NVF polymer chains accumulated on the surface)
Next, in a reaction vessel equipped with a stirrer, a reflux condenser, a nitrogen gas inlet tube and a thermometer, 158.4 g of the above-mentioned terminal vinylbenzyl group-containing NVF polymer solution [0.60 mol as an NVF repeating unit (determined from pre-charging) )], 94.3 g (0.60 mol) of DMAEMA, 62.5 g (0.60 mol) of styrene, and 603.7 g of water were adjusted, the pH was adjusted with hydrochloric acid, and the temperature was raised to 60 ° C. Under a nitrogen stream, 81.1 g (0.015 mol) of a 5% by weight aqueous solution of potassium persulfate was added and copolymerized for 6 hours to obtain a milky white dispersion (solid content concentration 22.4%). The pH-responsive polymer fine particles thus obtained had an average particle size at pH 5 of 580 nm.

Synthesis Example 9

Synthesis of pH-responsive polymer fine particle dispersion <9> having PEG chains accumulated on the surface thereof In a reaction vessel equipped with a stirring device, a reflux condenser, a nitrogen gas introduction tube, and a thermometer, PEG macromonomer (Blemmer PME-1000 ) 50.4 g [1.14 mol as a repeating unit], DMAEMA 90.0 g (0.57 mol), styrene 59.6 g (0.57 mol), ethanol 100.0 g, water 618.9 g, and pH with hydrochloric acid After adjustment, the temperature was raised to 60 ° C. Under a nitrogen stream, 81.1 g (0.015 mol) of a 5% by weight aqueous solution of potassium persulfate was added and copolymerized for 6 hours to obtain a milky white dispersion (solid content concentration 22.0%). The average particle diameter at pH 5 of the pH-responsive polymer fine particles obtained in this manner was 1080 nm.

Synthesis Example 10

PEG macromonomer (Blemmer PME-1000) 71 in a reaction vessel equipped with a synthesis stirrer, reflux condenser, nitrogen gas inlet tube and thermometer for pH-responsive polymer fine particles <10> having PEG chains accumulated on the surface 1.9 g [1.63 mol as a repeating unit], 117.6 g (1.31 mol) of an 80 wt% aqueous solution of acrylic acid (AAc), 34.0 g (0.33 mol) of styrene, 100.0 g of ethanol, water 618 .9 g was charged, the pH was adjusted with sodium hydroxide, and the temperature was raised to 60 ° C. Under a nitrogen stream, 81.1 g (0.015 mol) of a 5% by weight aqueous solution of potassium persulfate was added and copolymerized for 6 hours to obtain a milky white dispersion (solid content concentration 22.5%). The average particle diameter at pH 7 of the pH-responsive polymer fine particles thus obtained was 670 nm.

Synthesis Example 11

Synthesis of pH-responsive polymer fine particle dispersion <11> having PEG chains accumulated on the surface thereof In a reaction vessel equipped with a stirring device, a reflux condenser, a nitrogen gas introduction tube and a thermometer, PEG macromonomer (Blemmer PME-1000 ) 37.8 g [0.86 mol as repeating unit], ATBS 143.0 g (0.69 mol), styrene 17.7 g (0.17 mol), ethanol 100.0 g, water 620.4 g, sodium hydroxide After adjusting the pH, the temperature was raised to 60 ° C. Under a nitrogen stream, 81.1 g (0.015 mol) of a 5% by weight aqueous solution of potassium persulfate was added and copolymerized for 6 hours to obtain a milky white dispersion (solid content concentration: 21.2%). The average particle diameter at pH 7 of the pH-responsive polymer fine particles thus obtained was 710 nm.

Comparative Synthesis Example 1

Synthesis of Polymer Fine Particle Dispersion with MATMAC Polymer Chains Accumulated on the Surface In the synthesis of pH-responsive polymer fine particles <1> in Synthesis Example 1 above, 532.0 g of a terminal vinylbenzyl group-containing MATMAC polymer solution [MATMAC repeat unit As 0.70 mol (obtained from the previous charge)], 67.9 g (0.65 mol) of styrene and 319.0 g of water, the reaction was carried out in the same manner as in Synthesis Example 1, and a milky white dispersion (solid content concentration 23.3%) was obtained. 8%). The average particle size at pH 5 of the polymer fine particles thus obtained was 100 nm.

Comparative Synthesis Example 2

Synthesis of Polymer Fine Particle Dispersion with PEG Chains Accumulated on the Surface In the synthesis of pH-responsive polymer fine particles <8> in Synthesis Example 8 above, 59.4 g of PEG macromonomer (Blemmer PME-1000) [1. 35 mol], 140.6 g (1.35 mol) of styrene, 100.0 g of ethanol, and 618.9 g of water, the reaction was conducted in the same manner as in Synthesis Example 8 to obtain a milky white dispersion (solid content concentration 21.6%). It was. The average particle size of the polymer fine particles thus obtained at pH 5 was 160 nm.

  Table 1 shows the constituent units of each pH-responsive polymer fine particle and the molar ratio of each constituent unit.

  The pH of a 0.2% dispersion of each fine particle was adjusted with hydrochloric acid or sodium hydroxide, and the particle diameter at each pH was measured. The relationship between pH and the average particle size of each fine particle is shown in Table 2 and FIGS.

  Further, 0.2% dispersion of pH-responsive polymer fine particles obtained in Synthesis Example 1, Synthesis Example 2, Synthesis Example 9, Comparative Synthesis Example 1 and Comparative Synthesis Example 2 was added to sodium hydroxide from pH 5 to pH 9 The average particle size was measured when the pH was changed to pH 5, and then hydrochloric acid was added from pH 9 to return to pH 5. The pH-responsive polymer fine particles obtained in Synthesis Example 10 were measured for the average particle size when the 0.2% dispersion was changed from pH 9 to hydrochloric acid to pH 5, and then sodium hydroxide was added from pH 5. Then, the average particle size when the pH was returned to 9 again was measured. The results are shown in FIGS.

  The particle size of the pH-responsive polymer fine particles of the present invention reversibly changed as the pH changed. On the other hand, in the method according to the comparative example, the particle diameter hardly changed even when the pH was changed.

It is the schematic showing the mechanism in which polymer microparticles are obtained. The relationship between pH and an average particle diameter in the synthesis examples 1-4 and the comparative synthesis example is shown. The relationship between pH and an average particle diameter in the synthesis examples 5-8 and the comparative synthesis example is shown. The relationship between pH and an average particle diameter in the synthesis examples 9-11 and the comparative synthesis example is shown. The relationship between pH and average particle diameter in Synthesis Example 1, Synthesis Example 2, and Comparative Synthesis Example 1 is shown. The relationship between pH and an average particle diameter in the synthesis example 9, the synthesis example 10, and the comparative synthesis example 2 is shown.

DESCRIPTION OF SYMBOLS 1 ... Terminal radical polymerizable group containing cationic polymer 1a ... methacryloyloxyethyltrimethylammonium chloride unit 1b ... vinylbenzyl group 2 ... styrene monomer 3 ... dimethylaminoethyl methacrylate 4 ... styrene unit Core part 5 ... cationic polymer chain 6 ... polymer fine particles

Claims (2)

At least one selected from structural units represented by the following general formula (1);

[In Formula (1), Q ₁ represents a hydrogen atom, a methyl group or a cyano group, Q ₂ represents a hydrogen atom,

(R ₁ and R ₁ ′ are the same or different and each represents a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, a halogen atom or a halogenomethyl group, and R ₂ is a linear, branched or cyclic group having 1 to 18 carbon atoms. An alkyl group, a benzyl group or a hydroxypropyl group; R ₂ ′ represents a linear, branched or cyclic alkyl group or phenyl group having 1 to 18 carbon atoms; and R ₃ represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms. R ₄ represents an alkyl group having 1 to 10 carbon atoms (provided that R ₃ and R ₄ have 3 to 20 carbon atoms in total). ]
At least one selected from structural units represented by the following general formula (2) or at least one selected from structural units represented by the following general formula (2 ′);

[In Formula (2), Q ₃ represents a hydrogen atom or a methyl group, and Q ₄ represents

(X ₁ represents COO (CH ₂ ) _n or CONH (CH ₂ ) _n (n represents an integer of 1 to 3), and R ₅ and R ₆ are the same or different and have a hydrogen atom or a carbon number of 1 to 4. A lower alkyl group or a benzyl group). ]

[In formula (2 ′), Q ₃ ′ represents a hydrogen atom or a methyl group, and Q ₄ ′ represents

(M represents a hydrogen atom, a light metal ion, or an ammonium ion). ]
Water-dispersible polymer fine particles comprising at least one selected from structural units represented by the following general formulas (3) and (4), wherein the general formulas (3) and (4) A hydrophilic polymer chain that is at least one selected from the structural units represented by the formula is localized, and the core of the fine particles is at least one selected from the structural units represented by the general formula (1) PH sensitivity which is at least one selected from a certain hydrophobic polymer and at least one selected from structural units represented by the general formula (2) or a structural unit represented by the general formula (2 ′) A pH-responsive polymer particle comprising polymer particles, wherein the average particle size reversibly changes in accordance with a change in pH.

[In Formula (3), Q ₅ represents a hydrogen atom or a methyl group, and Q ₆ represents

(A ₁ represents an alkylene group having 1 to 10 carbon atoms), Q ₇ represents an oxygen atom or —NH—, Q ₈ represents an alkylene group having 1 to 10 carbon atoms, and Q ₉ represents an oxygen atom or Represents a sulfur atom, Y ₁ represents an oxygen atom or two hydrogen atoms, R ₇ represents a hydrogen atom or a methyl group, and X ₂ represents

(R ₈ , R ₉ and R ₁₀ are the same or different and represent a lower alkyl group having 1 to 4 carbon atoms or a benzyl group, R ₁₁ represents a hydrogen atom, a methyl group or an ethyl group, and R ₁₂ represents a hydrogen atom or a methyl group. indicates group, Z ^- represents a represents an anion), l is a number of 1 to 100. ]

[In Formula (4), Q ₁₀ and Q ₁₂ are the same or different and each represents a hydrogen atom or a methyl group, Q ₁₁ represents an oxygen atom or —NH—, and m represents a number of 1 to 100. ]
At least one selected from monomers represented by the following general formula (5);

Wherein _{(5), Q 13} represents a hydrogen atom, a methyl group or a cyano _{group, Q 14} is a hydrogen atom,

(R ₁₃ and R ₁₃ ′ are the same or different and each represents a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, a halogen atom or a halogenomethyl group, and R ₁₄ is a linear, branched or cyclic group having 1 to 18 carbon atoms. An alkyl group, a benzyl group or a hydroxypropyl group, R ₁₄ ′ represents a linear, branched or cyclic alkyl group or phenyl group having 1 to 18 carbon atoms, and R ₁₅ represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms. R ₁₆ represents an alkyl group having 1 to 10 carbon atoms (however, the total carbon number of R ₁₅ and R ₁₆ is 3 to 20). ]
At least one selected from monomers represented by the following general formula (6), or at least one selected from structural units represented by the following general formula (6 ′);

[In the formula (6), Q ₁₅ represents a hydrogen atom or a methyl group, and Q ₁₆ represents

(X ₃ represents COO (CH ₂ ) _n or CONH (CH ₂ ) _n (n represents an integer of 1 to 3), and R ₁₇ and R ₁₈ are the same or different and each represents a hydrogen atom or a carbon number of 1 to 4 A lower alkyl group or a benzyl group). ]

[In the formula (6 ′), Q ₁₅ ′ represents a hydrogen atom or a methyl group, and Q ₁₆ ′ represents

(M represents a hydrogen atom, a light metal ion, or an ammonium ion). ]
The dispersion of pH-responsive polymer fine particles according to claim 1, wherein at least one selected from macromonomers represented by the following general formulas (7) and (8) is copolymerized: Manufacturing method.

[In Formula (7), Q ₁₇ represents a hydrogen atom or a methyl group, and Q ₁₈ represents

(A ₂ represents an alkylene group having 1 to 10 carbon atoms), Q ₁₉ represents an oxygen atom or —NH—, Q ₂₀ represents an alkylene group having 1 to 10 carbon atoms, and Q ₂₁ represents an oxygen atom or Represents a sulfur atom, Y ₂ represents an oxygen atom or two hydrogen atoms, R ₁₉ represents a hydrogen atom or a methyl group, and X ₄ represents

(R ₂₀ , R ₂₁ and R ₂₂ are the same or different and represent a lower alkyl group having 1 to 4 carbon atoms or a benzyl group, R ₂₃ represents a hydrogen atom, a methyl group or an ethyl group, and R ₂₄ represents a hydrogen atom or a methyl group. Represents a group, Z ⁻ represents an anion), and l represents a number of 1 to 100. ]

Wherein _{(8), Q 22} and _{Q 24} are the same or different and each represents a hydrogen atom or a methyl _{group, Q 23} represents an oxygen atom or -NH-, m is a number of 1 to 100. ]

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