JP4355806B2 - Magnetic hollow fine particles and method for producing the same - Google Patents

Description

  The present invention relates to separation and recovery of heavy metals in waste water, separation and recovery of physiologically active substances such as proteins and nucleic acids, magnetic hollow fine particles used as sustained release drug carriers for transporting drugs to target sites, and the like It relates to the manufacturing method.

  Conventionally known magnetic fine particles are solid fine particles containing a magnetic substance. Solid fine particles are used in such a method that a target substance is captured by adsorption to the surface or pores and is collected using magnetism. However, since it is solid, it cannot be used as a drug carrier.

In addition, in Patent Document 1, after manufacturing hollow fine particles, the hollow fine particles are impregnated with a liquid magnetic material, and then the magnetic material is changed to a magnetic material by heating, so that the micron size encapsulates the magnetic material. Discloses a method for producing the magnetic hollow fine particles. In this method, the amount of magnetic substance retained is larger than that of conventional magnetic fine particles. However, depending on the purpose of use, fine particles that retain a larger amount of magnetic substance may be required. Moreover, since the magnetic hollow fine particle of patent document 1 may have a magnetic body partly exposed on the fine particle surface, it requires caution when applied in vivo.
JP 2003-15171 A

  It is an object of the present invention to provide a magnetic hollow fine particle that holds a large amount of a magnetic material and a simple method for producing such a magnetic hollow fine particle.

The inventors of the present invention have made researches to solve the above problems, and have obtained the following knowledge.
(1) selected from the group consisting of (a) a crosslinkable monomer, or a crosslinkable monomer and a monofunctional monomer, (b) a carbonyl complex of iron, nickel and cobalt, an alkoxide, and a magnetic fluid in an aqueous dispersion stabilizer solution. At least one magnetic material, (c) a solvent that is poorly compatible with a polymer or copolymer obtained by polymerizing or copolymerizing the above monomers, and (d) an initiator. At least one selected from the group consisting of iron, nickel and cobalt carbonyl complexes and alkoxides is formed by dispersing the mixture and performing suspension polymerization to form hollow fine particles containing the magnetic material in the hollow portion. In this case, the hollow fine particles containing a large amount of the magnetic material can be produced by magnetically treating the hollow fine particles to produce a magnetic material from the magnetic material. Child can be obtained.
(2) In the above method, when a mixture containing the target substance in addition to (a) to (d) is dispersed in an aqueous dispersion stabilizer solution, a magnetic substance and fine particles enclosing the substance are obtained. It is done. The target substance is obtained by polymerizing or copolymerizing monomers with (c) a solvent and (e) an interfacial tension (γ ^s ) (mN / m) between a solution obtained by dissolving the target substance and water. Substances having a relationship of γ ^s ≧ γ ^y between the interfacial tension (γ ^y ) (mN / m) between the polymer and water are targeted.
(3) In the above method, in the aqueous solution of the dispersion stabilizer, in addition to (a) to (d), (f) low compatibility with the polymer obtained by polymerizing or copolymerizing the monomer, and Interfacial tension (γ ^z ) (mN / m) between the auxiliary polymer and water, and interfacial tension (γ ^y ) (mN / m) between the polymer obtained by polymerizing or copolymerizing the monomers and water In the same manner, when a mixture containing an auxiliary polymer having a relationship of γ ^z ≧ γ ^y is dispersed, hollow fine particles containing a large amount of a magnetic substance are obtained.

When the auxiliary polymer is used, any solvent can be used as long as it is a poorly water-soluble solvent. Further, an arbitrary target substance is further added to the mixed liquid dispersed in the dispersion stabilizer solution, whereby a magnetic substance and fine particles enclosing the substance can be obtained.
(4) In the fine particles obtained by the above methods (1) to (3), since the magnetic substance is present in the inner surface region of the shell of the fine particles, the magnetic substance is not exposed or hardly exposed on the surface of the fine particles.
(5) The method of the present invention uses a solvent that is poorly compatible with a polymer or copolymer obtained by polymerizing or copolymerizing the above monomers and is hardly soluble in water, and is liquid at room temperature or this solvent. The use of a specific magnetic material material that dissolves in the shell makes it possible to completely or almost completely enclose a large amount of magnetic material inside the shell.

  The present invention has been completed based on the above findings, and provides the following magnetic hollow fine particles and a method for producing the same.

  Item 1. A shell and a hollow part are provided, and the shell is composed of a polymer or copolymer of a crosslinkable monomer, or a copolymer of a crosslinkable monomer and a monofunctional monomer, and a magnetic substance is included in the hollow part. Magnetic hollow fine particles.

  Item 2. Item 2. The magnetic hollow fine particles according to Item 1, wherein the magnetic material is at least one selected from the group consisting of simple substances and compounds of iron, cobalt and nickel.

  Item 3. Item 3. The magnetic hollow fine particles according to Item 2, wherein the magnetic material is at least one selected from the group consisting of a simple substance of iron and a compound.

  Item 4. Item 4. The magnetic hollow fine particles according to any one of Items 1 to 3, wherein the magnetic material is contained in an amount of 0.1 to 50% by weight.

  Item 5. The magnetic hollow fine particles according to any one of claims 1 to 4, wherein a magnetic substance is contained in the shell inner surface region.

  Item 6. Item 6. The magnetic hollow microparticle according to any one of Items 1 to 5, wherein the shell is composed of a polymer or copolymer of a crosslinkable monomer.

  Item 7. Item 7. The magnetic hollow fine particles according to any one of Items 1 to 6, wherein the average particle size is 0.05 to 50 µm.

  Item 8. Item 8. The magnetic hollow microparticle according to any one of Items 1 to 7, wherein a target component is further encapsulated in the hollow portion.

Item 9. In an aqueous dispersion stabilizer solution, at least one selected from the group consisting of (a) a crosslinkable monomer, or a crosslinkable monomer and a monofunctional monomer, (b) a carbonyl complex of iron, nickel and cobalt, an alkoxide, and a magnetic fluid. (C) a mixture containing a solvent or a poorly water-soluble solvent having low compatibility with a polymer or copolymer obtained by polymerizing or copolymerizing the monomer, and (d) an initiator. Including the step of dispersing and performing suspension polymerization to form hollow microparticles enclosing the magnetic material in the hollow part,
When using at least one selected from the group consisting of iron, nickel and cobalt carbonyl complexes and alkoxides as the magnetic material, a step of generating a magnetic material by magnetizing the resulting hollow fine particles A method for producing a magnetic hollow fine particle.

  Item 10. Item 11. The method according to Item 10, wherein the magnetic material is at least one selected from the group consisting of iron carbonyl complexes, alkoxides, and oily magnetic fluids.

  Item 11. Item 11. The method according to Item 9 or 10, wherein the amount of the magnetic material used is such that the magnetic hollow particles obtained contain 0.1 to 50% by weight of the magnetic material.

  Item 12. Item 12. The method according to any one of Items 9 to 11, wherein a crosslinking monomer is used as the monomer.

Item 13. As the solvent, the interfacial tension (γ ^x ) (mN / m) between the solvent and water and the interfacial tension (γ ^y ) (mN / m) between the polymer obtained by polymerizing or copolymerizing the monomers and water. 13. The method according to any one of Items 9 to 12, wherein a solvent having a relationship of γ ^x ≧ γ ^y is used.

  Item 14. Item 14. The method according to any one of Items 9 to 13, wherein the solvent is a solvent having 12 to 16 carbon atoms that is liquid at room temperature.

Item 15. In addition to (a) to (d) above, (e) the target substance, and the interfacial tension (γ ^s ) between the solution obtained by dissolving it and water (mN) in an aqueous dispersion stabilizer solution / M) and a substance having a relationship of γ ^s ≧ γ ^y between the polymer obtained by polymerizing or copolymerizing monomers and the interfacial tension (γ ^y ) (mN / m) between water and Item 15. The method according to any one of Items 9 to 14, which is dispersed.

Item 16. In an aqueous dispersion stabilizer solution, at least one selected from the group consisting of (a) a crosslinkable monomer, or a crosslinkable monomer and a monofunctional monomer, (b) a carbonyl complex of iron, nickel and cobalt, an alkoxide, and a magnetic fluid. (C) a poorly water-soluble solvent, (d) an initiator, and (f) a low compatibility with the polymer obtained by polymerizing or copolymerizing the monomer, and the auxiliary polymer and water. gamma ^z ≧ between interfacial tension ^{(γ z) (mN / m} ) between, and the surface tension between the polymer and water obtained by monomer polymerization or copolymerization to ^{(γ y) (mN / m} ) a step of dispersing a mixture containing an auxiliary polymer having a relationship of γ ^y and performing suspension polymerization to form hollow fine particles enclosing a magnetic material in a hollow portion;
When using at least one selected from the group consisting of iron, nickel and cobalt carbonyl complexes and alkoxides as the magnetic material, a step of generating a magnetic material by magnetizing the resulting hollow fine particles A method for producing a magnetic hollow fine particle.

  Item 17. Item 17. The method according to Item 16, wherein the magnetic material is at least one selected from the group consisting of iron carbonyl complexes, alkoxides, and oily magnetic fluids.

  Item 18. Item 18. The method according to Item 16 or 17, wherein the amount of the magnetic material used is such that the magnetic hollow particles obtained contain 0.1 to 50% by weight of the magnetic material.

  Item 19. Item 19. The method according to any one of Items 16 to 18, wherein a crosslinking monomer is used as the monomer.

  Item 20. Item 20. The method according to any one of Items 16 to 19, wherein a mixture containing the target component in addition to (a) to (d) and (f) is dispersed in an aqueous dispersion stabilizer solution.

  According to the method of the present invention, fine particles holding a large amount of magnetic substance can be produced by a simple method of suspension polymerization and magnetizing treatment performed as necessary. Furthermore, fine particles encapsulating a target component such as a drug can be obtained together with a large amount of magnetic substance.

  The magnetic hollow fine particles of the present invention carry a much larger amount of magnetic material than conventional magnetic fine particles and exhibit strong magnetism, and therefore can be applied to a wide range of applications.

  Further, the magnetic hollow fine particles of the present invention can easily recover heavy metals and the like together with fine particles by using a magnet or centrifuging after attaching a target substance such as heavy metals.

  Similarly, the magnetic hollow fine particles of the present invention can adsorb proteins by adjusting the surface potential, introducing a functional group such as a thiol group, introducing a monoclonal antibody or a polyclonal antibody, and specific or non-specific. Nucleic acids can be hybridized by surface modification with simple oligonucleotides. Furthermore, proteins and nucleic acids can be easily separated and collected by using magnetism.

  The magnetic hollow microparticles of the present invention can be used as a drug carrier by encapsulating a drug in a hollow part, and the drug carrier can be transported to, for example, a diseased site in a living body using magnetism. Since the magnetic hollow microparticles of the present invention have a high porosity, when used as a drug carrier, a large amount of drug can be retained, and as a result, the drug can be released gradually over a long period of time.

  The magnetic hollow fine particles of the present invention are easy to apply in vivo because the magnetic material is not exposed or hardly exposed on the shell surface.

  The magnetic hollow fine particles of the present invention contain a magnetic substance, but are light because they are hollow, so that, for example, when used in a living body, adhesion to blood vessels and organs due to precipitation hardly occurs. Also, when used for recovering heavy metals, it can be easily dispersed in a liquid.

Hereinafter, the present invention will be described in detail. First, the production method will be described, and then the magnetic hollow fine particles obtained thereby will be described.
(I) Method for Producing First Magnetic Hollow Fine Particle The method for producing the first magnetic hollow fine particle of the present invention comprises:
In an aqueous dispersion stabilizer solution, at least one selected from the group consisting of (a) a crosslinkable monomer, or a crosslinkable monomer and a monofunctional monomer, (b) a carbonyl complex of iron, nickel and cobalt, an alkoxide, and a magnetic fluid. A mixture containing (c) a solvent having low compatibility with a polymer or copolymer obtained by polymerizing or copolymerizing the above monomers and a poorly water-soluble solvent, and (d) an initiator. Including the step of dispersing and performing suspension polymerization to form hollow microparticles enclosing the magnetic material in the hollow part,
When the magnetic material is at least one selected from the group consisting of iron, nickel and cobalt carbonyl complexes and alkoxides, a magnetic material is produced from the magnetic material by further magnetizing the resulting hollow fine particles Including the step of causing the reaction to occur.
As a dispersion stabilizer, a dispersion stabilizer having a function of preventing a liquid droplet formed by dispersing a uniform solution composed of a monomer, a magnetic material, a solvent and an initiator in water from being combined from a wide range. Can be used.

  For example, polymer dispersion stabilizers such as polyvinyl alcohol, methyl cellulose, ethyl cellulose, polyacrylic acid, polyacrylimide, polyethylene oxide, poly (hydroxystearic acid-g-methyl methacrylate-co-methacrylic acid) copolymer, nonion -Based surfactants, anionic surfactants, amphoteric surfactants and the like. Among these, polymer dispersion stabilizers such as polyvinyl alcohol are preferable.

  The amount of the dispersion stabilizer used can be selected from a wide range, but generally it is preferably about 0.001 to 10 parts by weight with respect to 1 part by weight of the homogeneous solution composed of the monomer, the magnetic material raw material, the solvent and the initiator. About 0.1 to 0.5 parts by weight is more preferable.

In addition, in the dispersion stabilizer aqueous solution, the concentration of the dispersion stabilizer may be appropriately selected so that the droplets do not coalesce. In general, the concentration of the aqueous dispersion stabilizer solution is preferably adjusted to a range of usually about 0.05 to 5% by weight, particularly about 0.1 to 1% by weight.
The monomer crosslinking monomer and monofunctional monomer are preferably hydrophobic, but this requirement is usually met.

  As the monomer, a crosslinkable monomer is used, or a crosslinkable monomer and a monofunctional monomer are used. When only a crosslinkable monomer is used as the monomer, the resulting magnetic hollow fine particles have extremely high strength.

  When the monomer component is a mixture of a crosslinkable monomer and a monofunctional monomer, the strength of the magnetic hollow fine particles obtained can be arbitrarily set by adjusting the mixing ratio of the two. The finer the particles, the higher the content of the crosslinkable monomer.

When the crosslinkable monomer and the monofunctional monomer are used in combination, the ratio of the crosslinkable monomer is 30% by weight or more, preferably 50% by weight or more, based on the total amount of the monofunctional monomer and the crosslinkable monomer. Preferably, it may be 60% by weight or more.
<Crosslinkable monomer>
A crosslinkable monomer can be used individually by 1 type or in combination of 2 or more types.
Examples of the crosslinkable monomer include polymerizable functional groups, particularly polyfunctional monomers having two or more polymerizable double bonds (particularly 2 to 4). In particular, a polyfunctional monomer having two or more polymerizable C═C double bonds (particularly 2 to 4) is preferred. Examples thereof include divinylbenzene, divinylbiphenyl, divinylnaphthalene, diallyl phthalate, triallyl cyanurate, ethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, and the like. In particular, divinylbenzene and ethylene glycol dimethacrylate are preferable, and divinylbenzene is more preferable in terms of high heat resistance of the polymer. When a carbonyl complex is used as the magnetic material, heat treatment is performed as a magnetizing treatment. Divinylbenzene is preferable because it is difficult to decompose even when heated at 150 to 250 ° C.
<Monofunctional monomer>
A monofunctional monomer can be used individually by 1 type or in combination of 2 or more types.
Examples of monofunctional monomers include monovinyl aromatic monomers, acrylic monomers, vinyl ester monomers, vinyl ether monomers, monoolefin monomers, halogenated olefin monomers, A diolefin etc. are mentioned.

  Examples of the monovinyl aromatic monomer include a monovinyl aromatic hydrocarbon represented by the following general formula (1), a vinylbiphenyl optionally substituted with a lower (1 to 4 carbon) alkyl group, and a lower (carbon number). 1-4) Vinyl naphthalene which may be substituted with an alkyl group.

[Wherein, R ¹ is a hydrogen atom, a lower (1 to 4 carbon atoms) alkyl group or a halogen atom, and R ² is a hydrogen atom, a lower (1 to 4 carbon atoms) alkyl group, a halogen atom, —SO 2 _{3 represents a} Na group, a lower (C1-4) alkoxy group, an amino group or a carboxyl group. ]
In the general formula (1), R ¹ is preferably a hydrogen atom, a methyl group or a chlorine atom, and R ² is preferably a hydrogen atom, a chlorine atom, a methyl group or a —SO ₃ Na group.

  Specific examples of the monovinyl aromatic hydrocarbon represented by the general formula (1) include styrene, α-methylstyrene, vinyltoluene, α-chlorostyrene, o-chlorostyrene, m-chlorostyrene, p-chlorostyrene, Examples thereof include sodium styrene sulfonate.

  Furthermore, vinyl biphenyl which may be substituted with a lower alkyl group, and vinyl naphthalene which may be substituted with a lower alkyl group include vinyl biphenyl substituted with a lower alkyl group such as vinyl biphenyl, methyl group and ethyl group. And vinylnaphthalene substituted with a lower alkyl group such as vinylnaphthalene, methyl group, and ethyl group. These monovinyl aromatic monomers can be used alone or in combination of two or more.

  Moreover, as said acrylic monomer, the acrylic monomer represented by following General formula (2) is mentioned.

Wherein, ^{R 3} represents a hydrogen atom or a lower (1-4 carbon atoms) alkyl group, ^{R 4} is a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, a phenyl group, a hydroxy 1 to 6 carbon atoms alkyl, lower (1-4 carbon atoms) amino alkyl group or a di _(C 1 -C ₄ alkyl) amino - _(C 1 -C ₄₎ an alkyl group. ]
In the general formula (2), R ³ is preferably a hydrogen atom or a methyl group, and R ⁴ is a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, a phenyl group, or lower (1 to 4 carbon atoms) hydroxy. An alkyl group and a lower (C1-4) aminoalkyl group are preferred.

  Specific examples of the acrylic monomer include acrylic acid, methacrylic acid, methyl acrylate, ethyl acrylate, butyl acrylate, 2-ethylexyl acrylate, cyclohexyl acrylate, phenyl acrylate, methyl methacrylate, and methacrylic acid. Hexyl, 2-ethylhexyl methacrylate, β-hydroxyethyl acrylate, γ-hydroxybutyl acrylate, δ-hydroxybutyl acrylate, β-hydroxyethyl methacrylate, γ-aminopropyl acrylate, γ-N, N acrylate -Diethylaminopropyl and the like.

  Examples of the vinyl ester monomer include those represented by the following general formula (3).

[Wherein, R ⁵ represents a hydrogen atom or a lower (1 to 4 carbon atoms) alkyl group. ]
Specific examples of the vinyl ester monomer include vinyl formate, vinyl acetate, vinyl propionate and the like.

  Examples of the vinyl ether monomer include vinyl ether monomers represented by the following general formula (4).

[R ⁶ represents an alkyl group having 1 to 12 carbon atoms, a phenyl group, or a cyclohexyl group. ]
Specific examples of the vinyl ether monomer include vinyl methyl ether, vinyl ethyl ether, vinyl n-butyl ether, vinyl phenyl ether, vinyl cyclohexyl ether and the like.

  Examples of the monoolefin monomer include those represented by the following general formula (5).

[In formula, R < ⁷ > and R < ⁸ > is a hydrogen atom or a lower (C1-C4) alkyl group, and may differ or may be the same respectively. ]
Specific examples of the monoolefin monomer include ethylene, propylene, butene-1, pentene-1, 4-methylpentene-1.

  Examples of the halogenated olefin monomer include vinyl chloride and vinylidene chloride.

  Furthermore, diolefins such as butadiene, isoprene and chloroprene can also be included in the monofunctional monomer. These can be used alone or in admixture of two or more.

  As the monofunctional monomer to be copolymerized with the crosslinkable monomer, a monovinyl aromatic monomer, an acrylic monomer, a vinyl ester monomer, a vinyl ether monomer, and the like are preferable, a monovinyl aromatic monomer, Acrylic monomers and vinyl ester monomers are more preferred. Particularly preferred are styrene, methyl methacrylate and butyl methacrylate.

In the case of using both a crosslinkable monomer and a monofunctional monomer, a suitable combination of both is ethylene glycol dimethacrylate, which is a crosslinkable monomer, and styrene, monoacrylate, methacrylic ester, monofunctional monomer. A single combination of styrene and acrylic acid ester, styrene and methacrylic acid ester, acrylic acid ester and methacrylic acid ester, styrene, acrylic acid ester and methacrylic acid ester, or the like.
As the solvent, a solvent having low compatibility with the above polymer or copolymer of the monomer and hardly soluble in water is used. More particularly, the interfacial tension ^{(γ x) (mN / m} ) between the solvent and water, interfacial tension between the polymer and water obtained by monomer polymerization or copolymerization to (γ ^y) (mN / A solvent having a relationship with m) such that γ ^x ≧ γ ^y may be used. As a result, when the monomer is polymerized and adsorbed at the interface with water, the polymer or copolymer is more easily adsorbed at the interface with water than the solvent, and as a result, the magnetic material is included. Hollow fine particles are obtained.

Specifically, a solvent having 12 to 16 carbon atoms that is liquid at normal temperature may be used. Such solvents include linear and branched aliphatic hydrocarbons such as dodecane (C ₁₂ ), tridecane (C ₁₃ ), tetradecane (C ₁₄ ), pentadecane (C ₁₅ ), and hexadecane (C ₁₆ ). Solvent: Aromatic hydrocarbon solvent such as cyclohexylbenzene (C ₁₂ ), 1,2-dimethylnaphthalene (C ₁₂ ), 1,3-dimethylnaphthalene (C ₁₂ ), 1,6-dimethylnaphthalene (C ₁₂ ) Ether solvents such as dibenzyl ether (C ₁₄ ); triethyl acetyl citrate (C ₁₄ ), isoamyl benzoate (C ₁₂ ), benzyl benzoate (C ₁₄ ), isoamyl salicylate (C ₁₂ ), benzyl salicylate ( C ₁₄ ), diamyl oxalate (C ₁₂ ), dibutyl tartrate (C ₁₂ ), diethyl phthalate (C Ester solvents such as _12); dioctylamine _{(C 16),} dicyclohexylamine _(C 12), N, N-dibutyl aniline _{(C 14),} triamylamine _{(C 15),} tri -n- butylamine _{(C 12} And nitrogen-containing solvents such as

  Of these, hydrocarbon solvents are preferred in that they have excellent phase separation power and do not adversely affect the magnetic retentivity by interacting with this substance when encapsulating the target substance described later, and are linear or branched. Of these, aliphatic hydrocarbon solvents are more preferred. A linear aliphatic hydrocarbon solvent is even more preferable because it is inexpensive and easily available.

  A particularly preferred aliphatic hydrocarbon solvent is hexadecane.

As a combination of a polymer or a copolymer and a solvent ^{satisfying the} above relationship of γ ^x ≧ γ ^y , for example, a combination of polydivinylbenzene and hexadecane, a combination of polydivinylbenzene and dodecane, a combination of polystyrene and hexadecane, A combination, a combination of polystyrene and dodecane, and the like can be given.

  In the present specification, the compatibility between the solvent and the polymer or copolymer is measured by the following method. That is, an initiator (2% by weight with respect to the monomer component) is added to a monomer solution containing the raw material monomer and solvent in an appropriate weight ratio, and the polymerization reaction of the monomer component is performed in a nitrogen gas atmosphere at 30 ° C. Wake up. This reaction is carried out in a quartz glass cell having an optical path length of 1 cm, and the light transmittance is measured over time when irradiated with light having a wavelength of 550 nm. As the concentration of the solvent is increased, the transmittance, which was about 100% at the beginning, rapidly decreases to near 0% as the polymerization time elapses due to phase separation of the polymer. In this case, when the compatibility between the solvent and the polymer is low, it decreases to near 0%, but when the compatibility between the solvent and the polymer is high, the transmittance hardly decreases. Further, the lower the compatibility between the solvent and the polymer, the shorter the time from the start of polymerization until the decrease in transmittance occurs.

  As a solvent having low compatibility with the polymer, when the transmittance is measured by the above method, the polymerization rate of the monomer is about 1 to 10%, preferably about 1 to 5%, and the transmittance is lowered. Is mentioned.

  In the present specification, the interfacial tension is a value measured by Dunui's platinum ring method as defined in ASTM-971-50.

Although the usage-amount of a solvent can be selected from a wide range, generally about 0.1-5 weight part is preferable with respect to 1 weight part of monomers, and about 0.5-2 weight part is more preferable. If the amount of the solvent is too small, it is difficult to form a hollow portion. Conversely, if the amount is too large, the shell layer is dented and the hollow portion is reduced or eliminated, but such a problem does not occur within the above range.
As the magnetic material , a material that dissolves in a liquid or the above solvent at room temperature and changes to a magnetic material by heat treatment is used. It is preferable to use a raw material such that the magnetic material obtained by the heat treatment becomes a compound containing a ferromagnetic material such as iron, nickel, or cobalt.

Specifically, carbonyl complexes such as pentacarbonyl iron (Fe (CO) ₅ ), tetracarbonyl nickel (Ni (CO) ₄ ), tetracarbonyl cobalt (Co ₂ (CO) ₈ ); iron alkoxide, magnetic fluid, etc. It can be illustrated. These may be used by diluting in an appropriate organic solvent. The magnetic fluid is obtained by dispersing a magnetic material such as ultrafine magnetite (Fe ₃ O ₄ ) in a medium at a high density. In the method of the present invention, any known magnetic fluid can be used without limitation as long as magnetic ultrafine particles containing iron, nickel, or cobalt are dispersed in an oily medium. Examples of such known magnetic fluid include those in which Fe ₃ O ₄ is dispersed in silicone oil, isoparaffin, hexane, kerosene, and the like. These can be purchased from Sigma High Chemical Co., Ferrotec Co., Ltd., Taiho Kogyo Co., etc.

If attention is paid to the ligand, a carbonyl complex is preferable in terms of good miscibility with the monomer and the solvent. If attention is paid to metals, iron complexes are preferred because they are non-toxic and low in cost. Most preferred is pentacarbonyliron (Fe (CO) ₅ ).

The amount of the magnetic material used is such that the content of the magnetic substance in the resulting fine particles is usually about 0.1 to 50% by weight, particularly about 10 to 50% by weight, more particularly about 20 to 50% by weight, and more particularly 30. It is preferable that the amount be about ˜50% by weight. If the amount of the magnetic material used is too small, practically sufficient fine particles cannot be obtained, and conversely if too large, it becomes difficult to form a hollow portion. Magnetic hollow fine particles having both characteristics and a hollow structure can be obtained.
Initiator The initiator used in the present invention is for initiating polymerization of the monomer in the droplet, and an oil-soluble polymerization initiator can be widely used. For example, azo compounds such as azobisisobutyronitrile which is a radical polymerization initiator, cumene hydroperoxide, t-butyl hydroperoxide, dicumyl peroxide, di-t-butyl peroxide, benzoyl peroxide, lauroyl peroxide, etc. Those soluble in monomers such as peroxides. Moreover, you may use the photoinitiator which starts superposition | polymerization by light, such as an ultraviolet-ray. Such a photopolymerization initiator is not particularly limited as long as it is oil-soluble, and those conventionally used can be used.

The amount of the initiator used is preferably about 0.005 to 0.1 parts by weight, particularly about 0.01 to 0.05 parts by weight, with respect to 1 part by weight of the monomer.
Target Component In the first method, in addition to (a) the monomer, (b) the magnetic material, (c) the solvent, and (d) the initiator, (e) a mixture containing the target component is added to the dispersion stabilizer aqueous solution. Can be dispersed.

As the target component, (c) a polymer obtained by polymerizing or copolymerizing monomers with an interfacial tension (γ ^s ) (mN / m) between a solution obtained by dissolving the target component in a solvent and water A substance having a relationship of γ ^s ≧ γ ^y can be used between the surface tension (γ ^y ) (mN / m) between water and water. As a result, at the time of suspension polymerization, when the monomer polymer or the like is adsorbed on the interface with water, it moves into the interior together with the solvent and is finally encapsulated in the shell made of the monomer polymer or the like. Become.

  Examples of the target component include adriamycin having a medicinal effect on cancer cells.

The amount of the target component used is usually about 0.1 to 1 part by weight, preferably about 0.2 to 0.5 part by weight, based on 1 part by weight of the monomer.
A mixture containing the monomer, the magnetic material raw material, the solvent and the initiator in the above ratio is dispersed in an aqueous solution of the suspension polymerization dispersion stabilizer. In this mixture, it is preferable that the magnetic material and the initiator are dissolved in a monomer and a solvent to form a uniform solution.

  This mixture is preferably used in an amount of about 1 to 200 parts by weight, particularly about 10 to 100 parts by weight per 100 parts by weight of the dispersion stabilizer aqueous solution, but is not particularly limited to this range. .

  As a dispersion method, various known methods such as a dispersion method using mechanical shearing force such as ultrasonic emulsification, a homogenizer, and a film emulsification method can be employed. Although the temperature condition in the case of dispersion | distribution will not be limited if it is below the temperature which influences decomposition | disassembly of the initiator to be used, Usually, about 0-30 degreeC is preferable.

  In the above dispersion method, the size of droplets formed by dispersing a mixture of a monomer, a magnetic material, a solvent, and an initiator is not monodispersed, and generally droplets having various different particle sizes are mixed. Become. Therefore, the finally obtained magnetic hollow fine particles are also an aggregate of fine particles having different particle sizes.

  On the other hand, by selecting a dispersion method, it is possible to make the size of the droplets uniform and obtain monodispersed droplets. As a method for obtaining such monodispersed droplets, for example, a method of producing monodispersed droplets by a membrane emulsification method using porous glass (SPG), a seed swelling method (JP-A-8-20604), or the like. Can be mentioned.

  When such monodispersed droplets having a uniform particle diameter are prepared, the finally obtained magnetic hollow fine particles are also monodispersed with a uniform particle diameter.

  In either case, the average particle size of the droplets may be determined as appropriate according to the desired average particle size of the magnetic hollow fine particles, but is generally about 0.05 to 50 μm, particularly about 0.1 to 20 μm. It is preferable to do this. By appropriately setting the viscosity of the mixture, the amount of the dispersion stabilizer used, the viscosity of the dispersion stabilizer aqueous solution, and the dispersion method / dispersion condition within the above ranges, the droplet average particle diameter in this range can be obtained.

  In order to subject the aqueous solution of the dispersion stabilizer in which the mixture thus obtained is dispersed to suspension polymerization, the aqueous solution may be heated while stirring.

  The heating temperature is not particularly limited as long as it is a temperature that allows the monomer to be polymerized by the initiator in the droplets of the above mixture, but is generally about 20 to 90 ° C, particularly about 30 to 70 ° C. .

  Suspension polymerization is performed until hollow microparticles enclosing a desired magnetic material are obtained. The time required for suspension polymerization varies depending on the magnetic material used, the monomer, the type of the initiator, and the like, but is generally about 3 to 96 hours.

  The suspension polymerization is preferably performed in an inert gas atmosphere such as nitrogen gas or argon gas.

By performing suspension polymerization in this way, the monomer is polymerized in the droplets of the mixture of the monomer, the magnetic material raw material, the solvent and the initiator. In the polymer or copolymer obtained by polymerization, phase separation is promoted by the presence of a solvent, and as a result, a shell having a single layer structure made of the polymer or copolymer is formed. On the other hand, the magnetic material is included in the hollow portion inside the shell.
Magnetic treatment was then subjected to a magnetic treatment in particles containing the magnetic material. When a magnetic material such as a magnetic fluid is used from the beginning as a magnetic material, no magnetic treatment is required.
<Heat treatment>
When a carbonyl complex is used as the magnetic material, the magnetic material can be magnetized by heat-treating the hollow fine particles enclosing the magnetic material.

  The heat treatment may be performed on the magnetic substance-encapsulated fine particles usually at about 150 to 300 ° C. for about 1 to 10 hours, preferably at about 180 to 260 ° C. for about 2 to 6 hours. The heat treatment can be performed in an air atmosphere or a nitrogen atmosphere. By this heat treatment, the carbonyl complex is oxidized or the like in the hollow portion of the fine particles, and a magnetic material is generated.

By adjusting the treatment temperature and / or the atmosphere, the composition of the obtained magnetic material can be specified as, for example, Fe ₃ O ₄ , FeO, Fe ₂ O ₃ or the like. Moreover, a simple substance can be obtained as a magnetic material by relatively increasing the treatment temperature in a nitrogen atmosphere.
<Hydrolysis treatment>
When alkoxide is used as the magnetic material, hollow fine particles enclosing the magnetic material are immersed in an acid aqueous solution or an alkali aqueous solution, and usually 5 to 50 in acid (pH 1 to 4) or alkaline conditions (pH 9 to 12). It can be carried out by stirring at about 10 ° C. for about 1-10 hours, preferably at about 10-40 ° C. for about 2-5 hours. In this case, the solvent in the hollow may be evaporated by performing a short-time steam treatment so that the acid or alkali penetrates into the hollow.

  By adjusting the treatment temperature, the composition of the obtained magnetic material can be adjusted.

In both the case where magnetic treatment is not performed and the case where magnetic treatment is performed, the magnetic substance is usually present in the shell inner surface region in the obtained magnetic hollow fine particles. Specifically, the magnetic body is mainly attached to the inner surface of the shell, and a part thereof is buried in the shell or may exist in a hollow portion away from the inner surface of the shell.
(II) Method for Producing Second Magnetic Hollow Fine Particle The method for producing the second magnetic hollow fine particle of the present invention comprises:
In an aqueous dispersion stabilizer solution, at least one selected from the group consisting of (a) a crosslinkable monomer, or a crosslinkable monomer and a monofunctional monomer, (b) a carbonyl complex of iron, nickel and cobalt, an alkoxide, and a magnetic fluid. (C) a poorly water-soluble solvent, (d) an initiator, and (f) a low compatibility with the polymer obtained by polymerizing or copolymerizing the monomer, and the auxiliary polymer and water. gamma ^z ≧ between interfacial tension ^{(γ z) (mN / m} ) between, and the surface tension between the polymer and water obtained by monomer polymerization or copolymerization to ^{(γ y) (mN / m} ) a step of dispersing a mixture containing an auxiliary polymer having a relationship of γ ^y and performing suspension polymerization to form hollow fine particles enclosing a magnetic material in a hollow portion;
When using at least one selected from the group consisting of iron, nickel and cobalt carbonyl complexes and alkoxides as the magnetic material, a step of generating a magnetic material by magnetizing the resulting hollow fine particles It is the method of including.
Auxiliary polymer The second method uses the specific auxiliary polymer described above.

  The compatibility between the auxiliary polymer and the polymer obtained by polymerization or copolymerization of the monomer is measured using the auxiliary polymer in place of the solvent in the method described for the compatibility between the solvent and the polymer. As an auxiliary polymer having low compatibility with the polymer, an auxiliary polymer in which the transmittance decreases when the polymerization rate of the monomer component is about 1 to 10% can be exemplified.

  Further, as described above, the interfacial tension is a value measured by Dunui's platinum ring method specified in ASTM-971-50.

  The auxiliary polymer is desirably soluble in the monomer, but this requirement is usually satisfied.

  The auxiliary polymer promotes phase separation between the monomer and a polymer obtained by polymerization or copolymerization thereof. Furthermore, in a homogeneous solution of monomer, magnetic material, solvent, auxiliary polymer, and initiator, the monomer is polymerized or copolymerized to form a polymer, and this polymer is adsorbed at the interface with water. This is more easily adsorbed at the interface with water than the auxiliary polymer, and as a result, fine particles in which the magnetic material and the solvent are encapsulated inside the shell made of the polymer are obtained.

Therefore, when the auxiliary polymer is used, the range of usable solvents is widened, and if it is poorly water-soluble, it can be used without limitation. Similarly to the first method, the target component can be further added to the above mixture to be dispersed in the dispersion stabilizer aqueous solution to obtain fine particles containing the magnetic material, the target component and the solvent. The range of various target components is widened.
As such an auxiliary polymer, for example, polystyrene, polymethyl methacrylate, polybutyl methacrylate and the like can be used.

  The combination of the monomer and the auxiliary polymer can be easily selected by the method described above, and examples thereof include the combinations shown in the following table.

Monomer Auxiliary polymer Ethylene glycol dimethacrylate Polystyrene Ethylene glycol dimethacrylate Polymethyl methacrylate
Or
Polybutyl methacrylate divinylbenzene Polystyrene Divinylbenzene Polybutyl methacrylate A particularly preferred combination is a combination of divinylbenzene as a monomer and polystyrene as an auxiliary polymer.

  In general, the amount of the auxiliary polymer used is preferably about 0.05 to 0.4 parts by weight, particularly preferably about 0.1 to 0.2 parts by weight with respect to 1 part by weight of the monomer component.

The molecular weight of the auxiliary polymer can usually be about several hundred thousand. The auxiliary polymer can be produced by a known method such as solution polymerization or bulk polymerization. For example, polystyrene having a molecular weight of about several hundred thousand can be obtained by solution polymerization in which 18 g of styrene as a monomer, 12 g of toluene as a solvent, and 54 mg of AIBN as an initiator are reacted at 60 ° C. for 24 hours.
Target component In the first method, the target component that can be used is limited to those in which the interfacial tension between the solvent solution and water is within a certain range. On the other hand, in the second method, since an auxiliary polymer is used, the target component is highly compatible with the monomer, that is, a hydrophobic substance that does not dissolve in water, particularly a hydrophobic organic compound that does not dissolve in water. If it is, it can be used without limitation. The target substance may be either liquid or solid at normal temperature.

  Specific examples of such target components include adriamycin.

The amount of the target component used is usually about 0.1 to 1 part by weight, preferably about 0.2 to 0.5 part by weight, based on 1 part by weight of the monomer.
Other types and amounts of the dispersion stabilizer, monomer, magnetic material, solvent, and initiator are as described above for the first method.

The operations such as suspension polymerization and magnetizing treatment and the conditions thereof are also as described above for the first method.
(II) Magnetic hollow fine particles The magnetic hollow fine particles of the present invention obtained as described above have a shell and a hollow portion, and the shell is a polymer or copolymer of a crosslinkable monomer, or a crosslinkable monomer and a monofunctional monomer. Are fine particles in which a magnetic material is encapsulated in a hollow portion.

The type of the magnetic material varies depending on the magnetic material used, but a simple substance or a compound (particularly an oxide) of iron, nickel, or cobalt is preferable. Examples of the iron oxide include triiron tetroxide (Fe ₃ O ₄ ), iron monoxide (FeO), and diiron trioxide (Fe ₂ O ₃ ). Examples of the nickel oxide include nickel oxide (NiO). Examples of the cobalt oxide include cobalt oxide (CoO), dicobalt trioxide (Co ₂ O ₃ ), dicobalt oxide (III) cobalt (II) (Co ₃ O ₄ ), and the like.

  In particular, iron alone or an iron compound is preferable, and iron oxide is more preferable because it does not cause toxicity and is low in cost.

  The magnetic substance is preferably contained in an amount of about 0.1 to 50% by weight, more preferably about 10 to 50% by weight, and further preferably about 20 to 50% by weight. More preferred. Even more preferably, it is contained in an amount of about 30 to 50% by weight.

  The polymer or copolymer constituting the shell is as described in the item of the method of the present invention.

  The average thickness of the shell of the magnetic hollow fine particles of the present invention is usually about 0.005 to 5 μm, particularly about 0.01 to 3 μm.

  Moreover, the volume ratio of the hollow part of the magnetic hollow fine particles of the present invention is about 10 to 80%, particularly about 10 to 60% on average.

  In the present specification, the “volume ratio of the hollow portion” A is calculated by the following equation.

A (%) = (rh / rp) ³ × 100
(In the formula, rh is the radius of the hollow portion of the magnetic hollow fine particle (1/2 of the inner diameter of the shell), and rp is the radius of the magnetic hollow fine particle (1/2 of the outer diameter of the shell).)
The average particle size of the magnetic hollow fine particles obtained by the method of the present invention is usually about 0.05 to 50 μm. In the production method described above, droplet particles of a mixture of monomer, magnetic material, solvent, and initiator (a mixture that may further contain a target component or / and an auxiliary polymer) dispersed in an aqueous dispersion stabilizer solution By adjusting the diameter, a magnetic hollow fine particle having a particle diameter according to the purpose may be obtained.

  When the average particle diameter is about 0.05 to 2 μm, it can be suitably used as a drug carrier, and when the average particle diameter is about 0.2 to 20 μm, it can be suitably used for metal recovery.

In the present invention, the shell thickness and the volume ratio of the hollow part are average values of particle diameters measured with an electron microscope or an optical microscope for 100 fine particles. The average particle diameter is a value measured using a DLS (Dynamic Light Scattering Analyzer) (DLS700; Otsuka Electronics Co., Ltd.).
Further, the magnetic hollow fine particles of the present invention may encapsulate the target component in the hollow portion. The kind of the target component is as described above for the method of the present invention. Since these fine particles release the target component, for example, fine particles having sustained medicinal effects and capable of being guided to a desired position using magnetism are obtained.
EXAMPLES Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.
Example 1
In an aqueous solution obtained by dissolving 50 mg of polyvinyl alcohol (polymerization degree 1700, saponification degree 88%) as a dispersion stabilizer in 15 g of water, 170 mg of divinylbenzene as a monomer, 170 mg of pentacarbonyl iron as a magnetic material, 170 g of hexadecane as a solvent, Then, a homogeneous solution in which 6 mg of 2,2′-azobis (4-methoxy-dimethylvaleronitrile) (manufactured by Wako Pure Chemical Industries, Ltd., V-70) was uniformly mixed as an initiator was added, and the mixture was mixed with an ultrasonic homogenizer at room temperature. O / W type suspension was obtained by suspending by sonication for minutes. The obtained suspension droplets had an average particle size of about 0.3 μm.

  Next, the suspension was heated at 30 ° C. for 72 hours with stirring in a nitrogen gas atmosphere to carry out polymerization.

The obtained pentacarbonyliron-containing hollow fine particles were heated with a hot stirrer at 250 ° C. for 4 hours to decompose pentacarbonyliron. The average particle diameter of the obtained magnetic hollow fine particles was 0.3 μm, the thickness of the shell was about 0.02 μm, and the volume ratio of the hollow portion was about 60%.
Test Example Transmission micrographs (a, b) of magnetic hollow microparticles and transmission micrographs (b, d) of the ultrathin sections are shown in FIG. In FIG. 1, a and c are photographs before the heat treatment, and b and d are photographs after the heat treatment. A black portion was observed on the inner surface of the fine particle shell. It was predicted that this black part was a magnetic material.

X-ray analysis of the magnetic material was performed using an X-ray diffractometer (RINT2100, Rigaku). The X-ray diffraction pattern of the fine particles obtained in Example 1 is shown in FIG. The right column of FIG. 2 shows the peak position and peak intensity in the X diffraction pattern of iron trioxide (Fe ₃ O ₄ ). Both peak positions and peak intensities almost coincided with each other, suggesting that iron trioxide (Fe ₃ O ₄ ) is retained in the fine particles.

  Further, it was observed that fine particles were attracted to the magnet by bringing a magnet having a magnetic flux density of 1650G closer.

Furthermore, the weight change at the time of heating the magnetic hollow microparticles obtained in Example 1 was measured using a thermogravimetric analyzer (TG-DTA6200; Seiko Instruments Inc.). The results are shown in FIG. In the graph of FIG. 3, the solid line shows the change in the weight loss rate of the fine particles, and the dotted line shows the change in the temperature. As is apparent from FIG. 3, at about 500 ° C., the weight of the microparticles is reduced to the initial about 27%. From this, it can be seen that the magnetic hollow microparticles obtained in Example 1 retained about 20% by weight of the total magnetic iron trioxide (Fe ₃ O ₄ ). At such a high temperature, it is considered that almost no polymer constituting the fine particle shell remains.
Example 2
In an aqueous solution obtained by dissolving 50 mg of polyvinyl alcohol (polymerization degree 1700, saponification degree 88%) as a dispersion stabilizer in 15 g of water, divinylbenzene 95 mg, ethylvinylbenzene 70 mg as a monomer, pentacarbonyliron 170 mg as a magnetic material, A uniform solution in which 6 g of hexadecane as a solvent and 6 mg of 2,2′-azobis (4-methoxy-dimethylvaleronitrile) (manufactured by Wako Pure Chemical Industries, Ltd., V-70) as an initiator was uniformly mixed was added at room temperature. By sonicating with an ultrasonic homogenizer for 5 minutes, the suspension was suspended to obtain an O / W type suspension. The obtained suspension droplets had an average particle size of about 0.3 μm.

  Next, the suspension was heated at 30 ° C. for 72 hours with stirring in a nitrogen gas atmosphere to carry out polymerization.

  The obtained pentacarbonyliron-containing hollow fine particles were heated with a hot stirrer at 250 ° C. for 4 hours to decompose pentacarbonyliron. The average particle diameter of the obtained magnetic hollow fine particles was 0.3 μm, the thickness of the shell was about 0.02 μm, and the volume ratio of the hollow portion was about 60%.

2 is a transmission electron micrograph (drawing substitute photograph) of an ultrathin section of magnetic hollow microparticles obtained in Example 1. FIG. It is a figure which shows the X-ray-diffraction pattern (A) of the magnetic hollow microparticles obtained by Example 1, and the X-ray-diffraction pattern (B) of iron oxide. FIG. 4 is a diagram showing the results of thermogravimetric analysis of the magnetic hollow fine particles obtained in Example 1.

Claims (17)

In an aqueous dispersion stabilizer solution, (a) a crosslinkable monomer, or at least one selected from the group consisting of a crosslinkable monomer and a monofunctional monomer, (b) a carbonyl complex of iron, nickel and cobalt, an alkoxide, and a magnetic fluid. of the magnetic material, liquid der in (c) room temperature, dispersing the mixture carbon atoms include linear or branched aliphatic hydrocarbon solvent is 12 to 16, and (d) is the initiator , Including a step of forming hollow fine particles enclosing the magnetic material in the hollow portion by performing suspension polymerization,
When using at least one selected from the group consisting of iron, nickel and cobalt carbonyl complexes and alkoxides as the magnetic material, a step of generating a magnetic material by magnetizing the resulting hollow fine particles A method for producing a magnetic hollow fine particle. The method according to claim 1, wherein the solvent having 12 to 16 carbon atoms that is liquid at room temperature is dodecane, tridecane, tetradecane, pentadecane, or hexadecane. The method according to claim 1 or 2 , wherein the solvent having 12 to 16 carbon atoms that is liquid at room temperature is dodecane or hexadecane. The solvent of 12 to 16 carbon atoms which is liquid at normal temperature, the method according to any one of claims 1 to 3, which is hexadecane. Crosslinking monomer, divinylbenzene, divinyl biphenyl, divinyl naphthalene, diallyl phthalate, triallyl cyanurate, is at least one selected from ethylene glycol dimethacrylate and the group consisting of tetraethylene glycol dimethacrylate, of claim 1-4 The method according to any one. The method according to any one of claims 1 to 5 , wherein the crosslinkable monomer is at least one selected from the group consisting of divinylbenzene and ethylene glycol dimethacrylate. Crosslinking monomer is divinylbenzene, the method according to any of claims 1-6. The method according to any one of claims 1 to 7 , wherein the magnetic material is at least one selected from the group consisting of an iron carbonyl complex, an alkoxide, and an oily magnetic fluid. The method according to any one of claims 1 to 8 , wherein the amount of the magnetic material used is such that the magnetic hollow particles obtained contain 0.1 to 50% by weight of the magnetic material. The method according to any one of claims 1 to 9, using a crosslinking monomer as a monomer. As the solvent, the interfacial tension (γ ^x ) (mN / m) between the solvent and water and the interfacial tension (γ ^y ) (mN / m) between the polymer obtained by polymerizing or copolymerizing the monomers and water. the method according to any one of claims 1 to 10 using the associated solvent γ ^x ≧ γ ^y between). In an aqueous dispersion stabilizer solution, in addition to the above (a) to (d), (e) the target substance, and the interfacial tension (γ ^s ) between the solution obtained by dissolving it and water (γ ^s ) (mN / m) and a substance having a relationship of γ ^s ≧ γ ^y between the polymer obtained by polymerizing or copolymerizing monomers and the interfacial tension (γ ^y ) (mN / m) between water and the method according to any one of claims 1 to 11 for dispersing. In an aqueous dispersion stabilizer solution, (a) a crosslinkable monomer, or at least one selected from the group consisting of a crosslinkable monomer and a monofunctional monomer, (b) a carbonyl complex of iron, nickel and cobalt, an alkoxide, and a magnetic fluid. of the magnetic material, I liquid der in (c) room temperature, linear or branched aliphatic hydrocarbon solvent having a carbon number is 12 to 16, (d) is the initiator, and (f) monomer 2% by weight of an initiator is added to a monomer solution containing a polymer obtained by polymerization or copolymerization and an auxiliary polymer, and the polymerization reaction of the monomer component is performed in a nitrogen gas atmosphere at 30 ° C. The reaction was carried out in a quartz glass cell with an optical path length of 1 cm, and when the light transmittance when irradiating light with a wavelength of 550 nm was measured over time, the monomer polymerization rate was 1 to 10%. Rate decline And an interfacial tension between the auxiliary polymer and water (γ ^z ) (mN / m) and an interfacial tension between the polymer obtained by polymerizing or copolymerizing the monomer and water (γ ^y ) (mN / m) and γ ^z ≧ γ ^y
Including a step of forming a hollow fine particle containing a magnetic material in a hollow portion by dispersing a mixture containing an auxiliary polymer having the relationship of
When using at least one selected from the group consisting of iron, nickel and cobalt carbonyl complexes and alkoxides as the magnetic material, a step of generating a magnetic material by magnetizing the resulting hollow fine particles A method for producing a magnetic hollow fine particle. The method according to claim 13 , wherein the magnetic material is at least one selected from the group consisting of an iron carbonyl complex, an alkoxide, and an oily magnetic fluid. The method according to claim 13 or 14 , wherein the amount of the magnetic material used is such that the magnetic hollow particles obtained contain 0.1 to 50% by weight of the magnetic material. The method according to any one of claims 13 to 15 , wherein a crosslinkable monomer is used as the monomer. The method according to any one of claims 13 to 16 , wherein a mixture containing the target component (e) in addition to the above (a) to (d) and (f) is dispersed in an aqueous dispersion stabilizer solution.

Images