JPH11191510A - Magnetic polymer particles, production method thereof and diagnostic agent - Google Patents

Abstract

(57) [Summary] [Purpose] Carriers for diagnostic agents, bacteria separation carriers, cell separation carriers,
A magnetic particle useful as a carrier for separating and purifying nucleic acid, a carrier for separating and purifying protein, an immobilized enzyme carrier, a drug delivery carrier, and a method for producing the same are obtained. The present invention relates to a magnetic polymer particle, wherein a particle of a magnetic metal or metal compound synthesized by a gas phase method is coated with a polymer, and a magnetic metal or metal compound having no surfactant on its surface. Magnetic polymer particles, characterized by being coated with a polymer, wherein the particles are made of a metal or metal compound having an active hydroxyl group on the surface and having magnetism. After reacting magnetic polymer particles, a metal or a metal compound having magnetism synthesized by a gas phase method, and a lipophilic treatment agent, the mixture is dispersed in a polymerizable monomer to form a monomer composition, and this monomer composition is placed in an aqueous medium. A method for producing magnetic polymer particles characterized by polymerizing a polymerizable monomer after dispersing to obtain a suspension, and a method for preparing magnetic polymer particles. Diagnostics.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a magnetic polymer particle and a method for producing the same, and more particularly, to a diagnostic drug carrier,
The present invention relates to a magnetic polymer particle useful as a bacterial separation carrier, a cell separation carrier, a nucleic acid separation and purification carrier, a protein purification carrier, an immobilized enzyme carrier, a drug delivery carrier, a magnetic toner, a magnetic ink, a magnetic paint and the like, and a method for producing the same.

[0002]

2. Description of the Related Art A magnetic polymer latex is an excellent carrier for use as a diagnostic agent carrier, a carrier for separating and purifying cells, proteins or nucleic acids, etc. because of its advantage that latex particles can be easily separated and recovered by utilizing magnetic force. It is expected to be easy to handle. Further, the magnetic polymer latex formed into a film by drying or heating is expected to be applied to uses such as magnetic toner, magnetic ink, and magnetic paint. As a method for synthesizing magnetic polymer particles constituting such a magnetic polymer latex, the following methods (1) to (3) are known as methods for obtaining particles of a type in which a magnetic substance is present inside the particles.

(1) A method in which a magnetic material subjected to a magnetization treatment and a lipophilic treatment is dispersed in a polymerizable monomer, and the polymerizable monomer is subjected to suspension polymerization to obtain magnetic polymer particles (JP-A-59-221302). Reference). (2) The magnetic substance subjected to the lipophilic treatment is dispersed in an organic phase containing a vinyl aromatic monomer, and the dispersion is uniformly dispersed in an aqueous phase using a homogenizer, and then polymerized. A method of obtaining magnetic polymer particles having a relatively small particle size (see Japanese Patent Publication No. 4-3088). (3) Precipitating an iron compound in the presence of the porous polymer particles having a specific functional group, and oxidizing the iron compound to introduce a magnetic substance into the inside of the porous polymer particles.
A method of obtaining magnetic polymer particles having a large particle diameter of at least μm and a uniform diameter (see Japanese Patent Publication No. 5-10808).

However, in the above method (1), since a magnetic substance synthesized by a wet method is used, even if a large amount of lipophilic treatment is used, the magnetic substance which is well dispersed in the polymerization reaction system (monomer) is used. However, there is a problem that the polymer particles are separated and agglomerated inside the polymer particles after polymerization or are precipitated on the surface of the polymer particles.

The magnetic polymer particles obtained by the method (2) have poor uniformity of the magnetic substance inside the particles, and the magnetic substance is localized on the particle surface. For this reason, iron ions elute from the magnetic polymer particles,
Under acidic conditions, there is a problem that the magnetic substance dissolves and flows out and the properties as magnetic polymer particles are impaired.

The method (3) has a problem in that the production process of the magnetic polymer particles is complicated, and since the magnetic substance is not encapsulated by the polymer, iron ions are eluted.

On the other hand, a method has been disclosed in which an iron compound is precipitated in a polymer particle emulsion to ferrite the surface of the polymer particles (Japanese Patent Laid-Open No. Hei 3 (1994)).
-1155862 and JP-A-5-13809. However, the magnetic polymer particles obtained by this method have a problem that the elution of iron ions occurs remarkably due to the presence of a magnetic substance on the particle surface. When the magnetic polymer particles obtained by the conventional synthesis method as described above are used, for example, as a diagnostic drug carrier, sufficient sensitivity cannot be obtained, or good practical performance cannot be obtained due to a nonspecific enzyme reaction. . The reason is that the magnetic material is partially exposed on the particle surface of the magnetic polymer particles,
Alternatively, it is considered that a micropass is formed between the particle surface and the magnetic substance existing inside the particle, so that iron ions are eluted to the outside and adversely affect practical performance.

In order to suppress the exposure of iron ions to the outside to some extent, magnetic polymer particles containing magnetic particles are obtained by polymerizing a hydrophobic crosslinking monomer in an aqueous phase using magnetic particles as a core material. Although a technique is disclosed (see JP-A-2-286729), the elution of iron ions cannot be sufficiently suppressed by this technique. Further, a technique of forming a coating layer made of a polymer not containing a magnetic substance on the surface of magnetic polymer particles has been disclosed (see Japanese Patent Application Laid-Open No. Hei 5-16164). Only the legal and spray-dry spray methods are shown and the scope of application is limited.

Further, a technique for synthesizing magnetic polymer particles by an emulsion polymerization method has been disclosed (Japanese Patent Publication No. 3-57 / 1990).
No. 921), it is difficult to synthesize particles having a large particle diameter by an emulsion polymerization method, and thus it has not been possible to obtain magnetic polymer particles having good magnetic sedimentation properties with good reproducibility.

[0010] As described above, the magnetic polymer particles obtained by the conventional synthesis method have a problem of elution of metal ions to the outside. Therefore, they are applied only to applications and fields which are not affected by the elution of metal ions. It is not possible at present. For this reason, development of magnetic polymer particles which are excellent in dispersibility of a magnetic substance, excellent in magnetic response, and do not elute metal ions to the outside is desired.

[0011]

The first object of the present invention is to provide novel magnetic polymer particles having excellent uniform dispersibility by subjecting a magnetic metal or metal compound synthesized by a gas phase method to lipophilic treatment. To provide. A second object of the present invention is to provide magnetic polymer particles which are excellent in magnetic responsiveness and in which metal ions derived from a magnetic substance are hardly eluted to the outside and can be widely applied to various uses and fields. It is in. A third object of the present invention is to provide a method capable of reliably producing magnetic polymer particles having the above excellent properties.

[0012]

SUMMARY OF THE INVENTION The present invention provides a magnetic polymer particle and a surface active agent, wherein a particle comprising a magnetic metal or metal compound synthesized by a gas phase method is coated with a polymer. Magnetic polymer particles characterized by being coated with a polymer and particles of a magnetic metal or metal compound having no magnetic particles, particles of a magnetic metal or metal compound having an active hydroxyl group on the surface and having a magnetic property with a polymer After reacting the magnetic polymer particles characterized by being coated, a metal or a metal compound having magnetism synthesized by a gas phase method and a lipophilic treatment agent, a polymer composition is dispersed in a polymerizable monomer to form a monomer composition, After producing a suspension by dispersing the monomer composition in an aqueous medium, a method for producing magnetic polymer particles characterized by polymerizing a polymerizable monomer, and It is to provide a gender diagnostic agents.

[0013] The method for producing magnetic polymer particles of the present invention comprises:
A polymer or a metal compound having magnetism synthesized by a gas phase method subjected to lipophilic treatment is dispersed in a polymerizable monomer to prepare a monomer composition, and the monomer composition is dispersed and suspended in an aqueous medium. A liquid is obtained, and the polymerizable monomer is polymerized in the suspension.

[0014]

(1) A magnetic metal or metal compound synthesized by a gas phase method subjected to a lipophilic treatment is uniformly dispersed in a polymer (specific polymer) to form magnetic polymer particles having a suitable particle size. Can be configured. (2) Magnetic polymer particles composed by dispersing a metal or metal compound having magnetism and synthesized by a gas phase method subjected to lipophilic treatment are less likely to cause agglomeration and fusion of dispersed particles during the synthesis. , Having a suitable particle size. Therefore, the magnetic polymer particles are unlikely to settle in the aqueous medium, and can exist in a uniform dispersed state in the aqueous medium. (3) Since the lipophilic magnetic metal compound is contained in the magnetic polymer particles of the present invention at a specific ratio, excellent magnetic responsiveness is exhibited, and the gas phase method magnetic metal / metal compound exhibits excellent magnetic responsiveness. Elution of the derived metal ions to the outside is prevented.

[Detailed description of the invention] <Magnetic polymer particles of the present invention> The magnetic polymer particles of the present invention are formed by dispersing (including) lipophilic magnetic metal compounds in polymer particles. I have.

<Magnetic Metal or Metal Compound Synthesized by Gas Phase Method> A magnetic metal or metal compound synthesized by a gas phase method to constitute the magnetic polymer particles of the present invention (hereinafter referred to as “gas phase magnetic compound”). "Metals and metal compounds"), such as triiron tetroxide (Fe ₃ O ₄ ), γ-iron sesquioxide (γ-Fe ₂ O ₃ ), various ferrites, iron, manganese, cobalt, nickel and chromium. Metals, alloys of iron, manganese, cobalt, nickel and the like can be mentioned, among which ferrite, nickel and nickel alloys are particularly preferred. Known methods can be used as the synthesis method by the gas phase method, and examples thereof include an inert gas evaporation method, a plasma evaporation method, a hydrogen plasma reaction method, and a gas phase chemical reaction method (CVD method). As an example of the synthesis method by the evaporation method in an inert gas, the inside of a benger is 10 ⁻³ Torr.
r, and then introduce an inert gas of several Torr to several tens Torr into the benger. After introducing the inert gas,
The metal particles are obtained by heating and evaporating the metal and cooling the metal vapor on the cooling plate. The shape of the metal particles obtained by the gas phase method varies depending on the control of the production conditions, and includes a spherical shape, a rod shape, and the like. The particle diameter of the primary particles of the vapor phase magnetic metal / metal compound constituting the magnetic polymer particles of the present invention is preferably 0.001 to 3 μm,
More preferably, the thickness is 0.002 to 0.5 μm.

<Treatment Agent for Making Lipophilic> In the present invention, the treatment agent for making the vapor-phase-process magnetic metal / metal compound lipophilic (hereinafter referred to as "lipophilic treatment agent") is metal or metal. A compound having a group capable of reacting with an active hydroxyl group on the surface of a metal compound is preferable. Metal alkoxides such as aluminum coupling agents, silane coupling agents, and titanium coupling agents, acid chlorides, carboxylic anhydrides, and isocyanate as a functional group Organic compounds containing a group can be exemplified. Specific examples of the lipophilic treatment agent include acetoalkoxyaluminum diisopropylate; vinyltrichlorosilane, vinyltrimethoxysilane, vinyltris (β-methoxyethoxy) silane, β
-(3,4-epoxychlorohexyl) ethyltrimethoxysilane, γ-glycidoxypropyltrimethoxysilane, γ-methacryloyloxypropyltrimethoxysilane, N-β (aminoethyl) γ-aminopropylmethyldimethoxysilane, N- β (aminoethyl) γ-aminopropyltrimethyldimethoxysilane; isopropyl triisostearoyl titanate, isopropyl tridodecylbenzenesulfonyl titanate, isopropyl tris (dioctylpyrophosphate) titanate;
Tetraisopropyl bis (dioctyl phosphite) titanate, tetraoctyl bis (ditridecyl phosphite) titanate, tetra (2,2-diallyloxymethyl-1-butyl) bis (di-tridecyl) phosphite titanate, bis (dioctyl pyrophosphate) )
Oxyacetate titanate, bis (dioctyl pyrophosphate) ethylene titanate; acryloyl chloride, isophthaloyl chloride, 3-chloropivaloyl chloride,
6-chloropiperoyl chloride, dimethylmalonyl chloride, stearoyl chloride, tetradecanoyl chloride, terephthaloyl chloride, dodecanoyl chloride, nonanoyl chloride, palmitoyl chloride, valeroyl chloride, β-phenylacryloyl chloride, 3-phenylpropenoyl chloride, n-butanoyl chloride, Trans-2-butenoyl chloride, myristoyl chloride, methallyl chloride, 2-methylpropanoyl chloride, lauroyl chloride; maleic anhydride, phthalic anhydride, itaconic anhydride, citraconic anhydride, n-decylsuccinic anhydride, n- Dodecyl succinic anhydride, n-tetradecyl succinic anhydride, n-hexadecyl succinic anhydride; phenyl isocyanate, naphthyl isocyanate, 2-methacryloyloxyethyl isocyanate, etc. It is below.

These lipophilic treatment agents preferably have a group copolymerizable with the polymerizable monomer. Since the lipophilic treatment agent has a group that can be copolymerized with the polymerizable monomer, polymerization of the polymerizable monomer occurs on and near the surface of the gas phase magnetic metal / metal compound,
The vapor phase magnetic metal / metal compound is more completely covered with the polymer. The polymer coverage is evaluated by observing magnetic polymer particles dyed with uranyl acetate using a transmission electron microscope. Preferred examples of the lipophilic treatment agent include γ-methacryloyloxypropyltrimethoxysilane, isopropyl isostearyl diacryl titanate, acryloyl chloride, methallyl chloride, 2-methacryloyloxyethyl isocyanate, and the like.

The lipophilic treatment agent used in the present invention is usually 1 to 3 parts by weight based on 100 parts by weight of the magnetic metal / metal compound by the gas phase method.
Use 0 parts by weight. When the use ratio of the lipophilic treatment agent is 1 part by weight or less, the gas phase method magnetic metal / metal compound cannot be sufficiently coated, and the dispersibility in the polymerizable monomer decreases,
Further, it becomes difficult to suppress the elution of metal ions from the obtained magnetic particles. On the other hand, the use ratio of the lipophilic treatment agent is 3
If it is 0 part by weight or more, another reaction occurs during the polymerization, and the polymerization becomes unstable. As a method for lipophilizing the vapor-phase magnetic metal / metal compound of the present invention, a lipophilic agent alone or a mixture of a polymerizable monomer or a solvent described below is added to the vapor-phase magnetic metal / metal compound. The dispersion is performed using a dispersion device such as an ultrasonic dispersion machine.

<Polymer> In the present invention, the polymer constituting the particles together with the vapor phase magnetic metal compound is a vinyl polymer, an olefin polymer, a polyester,
Examples include polyamides, polyamideimides, polyimides, polysiloxanes, polyacetals, polycarbonates, polysulfones, porsulfides, and these polymers may also contain functional groups. In the present invention, a particularly preferred polymer is a vinyl polymer or a vinyl polymer having a functional group.
In the present invention, styrene, α-methylstyrene, o-
Aromatic vinyl compounds such as vinyltoluene, m-vinyltoluene, p-vinyltoluene and divinylbenzene; unsaturated carboxylic acids such as (meth) acrylic acid and crotonic acid;
Methyl (meth) acrylate, ethyl (meth) acrylate, n-propyl (meth) acrylate, i-propyl (meth) acrylate, n-butyl (meth) acrylate, t-butyl (meth) acrylate, n-hexyl (meth) Acrylate, 2-ethylhexyl (meth) acrylate, (poly) ethylene glycol di (meth) acrylate, (poly) propylene glycol di (meth)
(Meth) acrylates such as acrylate and trimethylolpropane tri (meth) acrylate; vinyl cyanide compounds such as (meth) acrylonitrile and vinyldene cyanide; vinyl chloride, vinylidene chloride, vinyl fluoride;
Vinyl halide compounds such as vinylidene fluoride and tetrafluoroethylene; and the like. Among these vinyl monomers, aromatic vinyl compounds and (meth) acrylates are preferred. The vinyl monomers can be used alone or in combination of two or more.

The weight average molecular weight of the polymer constituting the magnetic polymer particles of the present invention in terms of polystyrene is usually 1
0000 or more, preferably 20,000 to 1,000
It is 0000.

The content of the vapor-phase magnetic metal / metal compound in the magnetic polymer particles of the present invention is determined based on 100 parts by weight of the vapor-phase magnetic metal / metal compound.
To 2000 parts by weight. When the proportion of the polymer is more than 2,000 parts by weight, the obtained particles cannot exhibit sufficient magnetic responsiveness.

The number average particle diameter of the magnetic particles of the present invention is usually 0.02 to 30 μm, preferably 0.1 to 20 μm.
m, more preferably 0.2 to 15 μm, particularly preferably 0.3 to 10 μm. Number average particle size is 0.02μ
If it is less than m, sufficient magnetic responsiveness cannot be exhibited. On the other hand, when the number average particle diameter exceeds 30 μm, the magnetic polymer particles are likely to settle in an aqueous medium, and the magnetic polymer particles have a small particle surface area, and are used as an adsorbent for a specific substance. When using, it is not possible to adsorb a sufficient amount of the target substance.

The magnetic polymer particles of the present invention preferably have, on the surface thereof, a layer (hereinafter also referred to as "surface coating layer") made of a polymer not containing a vapor phase magnetic metal / metal compound. . By configuring such a surface coating layer, the elution of metal ions from the magnetic polymer particles can be more reliably performed without impairing the excellent handling properties of the vapor-phase magnetic metal compound present inside the magnetic polymer particles. Can be prevented. Here, the thickness of the surface coating layer is preferably larger than the particle diameter of the vapor-phase-method magnetic metal / metal compound used, for example, 0.01 μm or more.

<Production Method> In the production method of the present invention, a gas phase method magnetic metal / metal compound subjected to lipophilic treatment is dispersed in a polymerizable monomer to prepare a monomer composition. The suspension is emulsified and dispersed (particulated into fine particles) in an aqueous medium to obtain a suspension which is an oil droplet dispersion, and the polymerizable monomer is polymerized in this suspension state.

In the production method of the present invention, a polymerizable monomer alone or a mixture of a polymerizable monomer and an organic solvent can be used as a dispersion medium of the lipophilic treated magnetic metal / metal compound. As the organic solvent used for the dispersion medium, alcohols, ketones, esters, and the like can be used. As a specific example, ethanol, isopropanol, butyl alcohol, dioxane, acetone, methyl ethyl ketone, or the like can be used alone or in combination. The ratio of the organic solvent used for the dispersion medium is 0 to 100 parts by weight of the polymerizable monomer.
100 parts by weight, preferably 50 parts by weight or less. 10
If the amount is more than 0 parts by weight, polymerization becomes unstable and particles cannot be obtained.

In the production of the present invention, as a method of dispersing the lipophilized magnetic metal or metal compound in the dispersion medium, a conventionally known dispersing apparatus such as an ultrasonic dispersing machine can be used. In the monomer composition thus obtained, coarse particles and the like are not generated by agglomeration of the lipophilic treated magnetic metal / metal compound, and therefore, the monomer composition is uniformly dispersed in an aqueous medium. It becomes possible to emulsify and disperse.

As a disperser used for emulsifying and dispersing the monomer composition in an aqueous medium, a conventionally known ultrasonic disperser, a high-pressure homogenizer, a disperser with a high shear rate and the like can be used. The type of the ultrasonic dispersing machine is not particularly limited. For example, a dispersing machine having a horn-type oscillator, a dispersing machine having a plate-type oscillator, and a continuous dispersing machine for flowing a liquid through an oscillating unit. And the like. Examples of the high shear rate disperser include a homomixer, a colloid mill, a jet homogenizer, a high-pressure homogenizer, and the like.These dispersers may be appropriately selected according to the target dispersed particle diameter. Can be. Furthermore, a membrane emulsification method in which the monomer composition is emulsified and dispersed in an aqueous medium by extruding the monomer composition into an aqueous medium through a porous membrane or a porous filter, or by applying pressure, vibration or high voltage from a nozzle, A nozzle method for discharging the monomer composition may be employed.

In the production method of the present invention, it is preferable to use water as the aqueous medium that is the dispersion medium of the monomer composition. The ratio of water is 500 to 2000 parts by weight of water based on 100 parts by weight of the monomer composition. If the amount is less than 500 parts by weight, droplets of the emulsified monomer composition coalesce and uniform magnetic polymer particles are not formed. Further, in the aqueous medium, a surfactant such as an anionic surfactant, a nonionic surfactant, a water-soluble polymer, or an inorganic suspension protectant, an emulsifier, or a suspension protectant may be added. .

In the method for producing magnetic polymer particles of the present invention, the polymerization initiator for polymerizing the polymerizable monomer is not particularly limited, and a conventionally known radical polymerization initiator, for example, an organic peroxide, Azo initiators, persulfate initiators, and the like can be used. Among these, it is preferable to use an oil-soluble polymerization initiator. In particular, when preparing a monomer composition by dispersing a lipophilic magnetic metal compound in a hydrophobic monomer, it is preferable to add an oil-soluble polymerization initiator, thereby not containing a lipophilic magnetic metal compound. Generation of polymer particles can be prevented. The ratio of the polymerization initiator is 100 polymerizable monomers.
The polymerizable initiator is 0.1 to 5 parts by weight based on part by weight.

In the present invention, the polymerization reaction of the polymerizable monomer is preferably performed in an oxygen-free atmosphere. The reaction temperature varies depending on the decomposition temperature of the polymerization initiator to be used. For example, when benzoyl peroxide is used, the polymerization reaction can suitably proceed at 75 to 85 ° C.

In the production method of the present invention, after preparing the magnetic polymer particles, the particles may be washed in order to remove the surfactant or suspension protective agent used in the polymerization. On this occasion,
It is preferable to use water or a water-soluble solvent such as alcohol or acetone, and it is also preferable to add a small amount of a surfactant to this. Further, if necessary, the polymerized magnetic polymer particles can be classified by means such as sedimentation separation, coagulation separation, centrifugation, or magnetic separation to adjust the particle diameter and the particle size distribution to the desired values.

[0033]

Hereinafter, embodiments of the present invention will be described.
The present invention is not limited to these examples.
In the following, “parts” means “parts by weight”.

Example 1 Fine powder of γ-Fe ₂ O ₃ having a primary particle diameter of 0.02 μm synthesized by a gas phase method “NanoTek”
[C-I Kasei Co., Ltd.] 7 parts of γ-methacryloyloxypropyltrimethoxysilane “A-174” (manufactured by Nippon Unicar Co., Ltd.) (lipophilic treatment agent) is added to 35 parts, and an ultrasonic disperser is sufficient. The lipophilic magnetic metal compound was obtained by dispersing well and allowing to react at room temperature for 30 minutes. 95 parts of cyclohexyl methacrylate, 5 parts of methacrylic acid and perloyl 355 were added to the lipophilic magnetic metal compound.
[Nippon Oil & Fats Co., Ltd.] (polymerization initiator) (2 parts) was added, and the system was mixed and stirred to uniformly disperse the lipophilic magnetic metal compound to prepare a monomer composition. On the other hand, an aqueous medium was prepared by dissolving 2 parts of polyoxyethylene nonylphenyl ether and 2 parts of dodecyl lauryl sulfate in 1300 parts of water. The monomer composition was added to the obtained aqueous medium (aqueous phase), and the system was preliminarily stirred with a homomixer, and then subjected to dispersion treatment with an ultrasonic disperser, whereby oil droplets (oil phase) were converted to the aqueous medium. A suspension (oil droplet dispersion) was prepared. Next, the obtained suspension was charged into a two-liter flask with a stirrer having a capacity of 2 liters, the system was heated to 75 ° C., and the monomers in the oil droplets were polymerized for 5 hours while stirring under a nitrogen atmosphere ( (Suspension polymerization) to prepare a dispersion (magnetic polymer latex) in which the magnetic polymer particles of the present invention are dispersed in an aqueous medium. The magnetic polymer particles of the present invention dispersed in the magnetic polymer latex can be easily suctioned and settled by a magnet and collected, and the collected magnetic polymer particles can be easily redispersed in water. there were.

Example 2 The lipophilic treatment agent was 2-methacryloyloxyethyl isocyanate "Karenz MOI"
A monomer composition and a suspension were prepared and subjected to suspension polymerization in the same manner as in Example 1 except for changing to [manufactured by Showa Denko KK]. (Magnetic polymer latex) was prepared.

Example 3 As a magnetic metal synthesized by a gas phase method, a nickel powder having a primary particle size of 0.02 μm “N
i (200) UFMP "(manufactured by Vacuum Metallurgy Co., Ltd.) except that the monomer composition and the suspension were prepared and suspension polymerization was carried out in the same manner as in Example 1 to obtain the magnetic material of the present invention. A dispersion (magnetic polymer latex) in which polymer particles were dispersed in an aqueous medium was prepared.

Comparative Example 1 Magnetite fine particles having a particle diameter of 0.3 μm “magnetite EPT500” synthesized by a wet method as a metal compound having magnetism [Toda Kogyo Co., Ltd.]
Except for using), by adjusting the monomer composition and suspension in the same manner as in the examples, and by performing suspension polymerization,
A dispersion (magnetic polymer latex) in which comparative magnetic polymer particles were dispersed in an aqueous medium was prepared.

Comparative Example 2 Magnetite fine particles having a particle diameter of 0.3 μm “magnetite EPT500” synthesized by a wet method as a metal compound having magnetism [Toda Kogyo Co., Ltd.]
Except that the lipophilic treatment was not performed, the monomer composition and the suspension were adjusted in the same manner as in the example, and the suspension was subjected to suspension polymerization, whereby magnetic polymer particles for comparison were prepared in an aqueous medium. A dispersion (magnetic polymer latex) thus dispersed was prepared.

With respect to each of the magnetic polymer latexes obtained in Examples 1 to 3 and Comparative Examples 1 and 2, the composition and the content of the metal / metal compound having magnetism were measured. Further, according to the evaluation method described below, polymerization stability, the dispersibility of the metal compound having magnetism in the magnetic polymer particles, to evaluate the magnetic responsiveness, according to the measurement method described below, the shape of the magnetic polymer particles, number average particle diameter and The coefficient of variation was measured. Table 1 shows the results.

[0040]

[Evaluation method] Evaluation of polymerization stability After the completion of the polymerization reaction, the reaction product was passed through a 200-mesh stainless steel wire mesh, and the amount of aggregates remaining on the wire mesh was 10%.
The case of less than 10% by weight was judged as "good" and the case of more than 10% by weight was judged as "poor".

Evaluation of Dispersibility of Magnetic Metal Compound After dyeing with uranyl acetate, the dispersion state of the magnetic metal compound in the magnetic polymer particles was observed by a transmission electron microscope, and the dispersion was uniformly dispersed throughout the polymer particles. Or, the case where the polymer particles were uniformly dispersed inside the polymer particles was determined as “good”, and the case where the polymer particles were localized in a part of the surface vicinity or in the entire vicinity of the surface was determined as “poor”.

Magnetic response time The magnetic polymer latex was diluted to a solid concentration of 0.1
The diluted solution was put into a 1 cm square plastic cell, and the magnetic flux density on the plastic cell wall was 3%.
A magnet that is 00 gauss is deposited. The transmitted light at 550 nm was measured using an absorptiometer, the time when the magnet was attached was T = 0, and the time when the transmittance was 98% was defined as the magnetic response time.

Metal ion elution amount 0.1 g of magnetic polymer particles were added to pure water 1 heated to 70 ° C.
After immersion in 00 ml for 2 hours, the metal content in the eluate is measured. When the metal content is 3 ppm or less, it can be determined that the magnetic polymer particles do not elute metal ions.

Measurement of Number Average Particle Diameter and Coefficient of Variation of Magnetic Polymer Particles After staining with uranyl acetate, an electron micrograph of the magnetic polymer particles was taken with a transmission electron microscope, and 500 magnetic polymer particles randomly selected were taken. The number average particle diameter and the coefficient of variation thereof were determined by measuring the particle diameter.

[0045]

[Table 1]

<Test Example 1> Carrier particles for immunodiagnostic agents (carriers for enzyme immunoassay) by carrying out the following tests.
Was evaluated. Each of the magnetic polymer latexes obtained in Examples 1 to 3 and Comparative Examples 1 and 2 was collected in an amount of 10 mg in terms of solid content, and magnetic polymer particles were magnetically separated from the collected magnetic polymer latex to obtain the magnetic polymer particles. It was dispersed in 1 ml of a phosphate buffered saline solution (pH 7.5).
Next, 200 μg of anti-human IgM antibody was added to the dispersion, and the mixture was gently shaken at room temperature for 1 hour to adsorb the antibody on the particle surface to sensitize the magnetic polymer particles. The magnetic polymer particles after the sensitization were magnetically separated, and whether or not the antibody remained in the separated supernatant was confirmed by measuring the absorbance at 280 nm. The presence of the antibody was not recognized, and thus it was confirmed that all the added antibodies were adsorbed on the magnetic polymer particles. Each of the magnetically separated magnetic polymer particles (anti-human IgM antibody-sensitized particles) was provided with 0.5% bovine serum albumin and 0.1%
% Polyethylene glycol and 1 ml of a phosphate buffered saline solution (pH 7.5) was added, and the mixture was vibrated and dispersed with a vibrator, and then gently shaken at room temperature for 30 minutes to prevent the antibody from being adsorbed. By subjecting the particle surface to a blocking treatment with albumin, diagnostic drug particles for such enzyme immunoassay (EIA method) were prepared. The following operation was performed using each of the diagnostic agent particles prepared as described above. 0 ng / ml, 50 ng / ml, 100 ng / ml
100 μl of a phosphate buffer solution containing human IgM antigen was prepared at a concentration of 500 μg / ml, and 20 μl of a dispersion containing particles of the diagnostic agent was added to each of the buffer solutions, and allowed to stand at room temperature for 30 minutes. Subsequently, 200 μl of a solution containing 100 μg of an anti-human IgM antibody in which acetylcholinesterase was bound to magnetically separated magnetic polymer particles was added, and the solution was vibrated and dispersed by a vibrator.
Let stand for hours. Then, 100 μl of “Ellman's reagent” (manufactured by Cayman), which is a substrate of acetylcholinesterase, was added, and the mixture was gently shaken at room temperature for 10 minutes to allow the enzyme reaction to develop color. Thereafter, the absorbance at 412 nm was measured. As a control test, 20 μl of a dispersion containing particles not sensitized was added to 100 μl of a phosphate buffered saline solution containing no human IgM antigen, and the same operation was performed to measure the absorbance. Table 2 shows the results.

[0047]

[Table 2]

[0048]

According to the magnetic polymer particles of the present invention,
It is characterized in that the magnetic substance dispersed in the particles is a metal or metal compound having magnetism synthesized by a gas phase method, and contains a metal and a metal compound having magnetism synthesized by a gas phase method. As a result, it is possible to obtain higher magnetic responsiveness than conventional magnetic polymer particles containing a magnetic substance. Also, the surface of the vapor phase magnetic metal / metal compound is more active and more reactive than the conventional magnetic substance, and the lipophilic treatment is easy. Further, according to the method of the present invention, it is possible to reliably produce a dispersion (magnetic polymer latex) in which the magnetic polymer particles of the present invention are dispersed in an aqueous medium. The magnetic polymer particles of the present invention can be widely applied to various uses and fields that require magnetic responsiveness due to the above excellent properties. For example,
By adsorbing antigens, antibodies, proteins, nucleic acids, and the like physically or chemically, they can be applied to a wide range as diagnostic agents. In addition, when used as a diagnostic agent for enzyme immunoassay, non-specific coloring caused by elution of iron ions from magnetic polymer particles is suppressed, so that the practicality and reliability as a diagnostic agent are further enhanced. I have.
Further, since the vapor phase magnetic metal compound is not exposed on the surface of the magnetic polymer particles, it is excellent in electrostatic properties and film forming properties, and is useful as a magnetic toner, a magnetic ink, and a magnetic paint.

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Claims (5)

[Claims] A magnetic polymer particle obtained by coating a particle made of a metal or a metal compound having magnetism synthesized by a gas phase method with a polymer. 2. A magnetic polymer particle obtained by coating a particle made of a metal or a metal compound having magnetism and having no surfactant on its surface with a polymer. 3. Magnetic polymer particles comprising particles of a metal or metal compound having an active hydroxyl group on the surface and having magnetism coated with a polymer. 4. After reacting a magnetic metal or metal compound synthesized by a gas phase method with a lipophilic treatment agent, the mixture is dispersed in a polymerizable monomer to form a monomer composition, and the monomer composition is dissolved in an aqueous medium. A method for producing magnetic polymer particles, comprising polymerizing a polymerizable monomer after obtaining a suspension by dispersing the polymerizable polymer in a suspension. 5. A diagnostic agent comprising the magnetic polymer particles according to claim 1.