JPH07316466A - Particle protected with polymer and its production - Google Patents

Abstract

PURPOSE:To enable the coating of particles and the simultaneous simple introduction of a spacer and reactivity by carrying out the formation of an adsorptive layer on the surface of a particle, the solubilization of a radical-polymerizable unsaturated monomer and the formation of a protective coating film in a specified manner. CONSTITUTION:This production process is one for producing a particle protected with a polymer comprising the steps of: mixing particles with a cationic surfactant having a radical-polymerizable unsaturation to form an adsorptive layer of the surfactant on the surface of each particle, adding a radical-polymerizable unsaturated monomer and a polymerization initiator to the system to form a complex salt of the surfactant with the initiator on the absorptive layer formed on the surface of the particle and solubilizing the radical-polymerizable unsaturated monomer within the absorptive layer, and copolymerizing the radical-polymerizable unsaturated monomer with the cationic surfactant to form a protective film on the particles.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to particles coated with a polymer and a method for producing the same, and more particularly, a medical diagnostic agent capable of controlling movement in a living body, a drug delivery system for moving a drug to a diseased part of a patient, Alternatively, the present invention relates to particles protectively coated with a polymer used for separation and purification of biological substances, antigen-antibody reaction and the like, and a method for producing the same.

[0002]

2. Description of the Related Art In recent years, it does not require a special device such as an ELISA method or a RIA method, and is excellent in its simplicity and sensitivity. It is an antigen antibody for the examination of tuberculosis, hepatitis, AIDS (acquired immune deficiency syndrome), etc. Medical diagnostic agents that utilize reactions are used.

In general, the agglutination reaction is a phenomenon in which suspended particles such as bacteria and red blood cells are bound to each other by the action of antibodies to form a large mass. Such agglomeration increases the density, and when this reaction occurs in a solution, it causes a precipitation reaction.

Therefore, a specific carrier for a specific aggregated molecule is attached to an appropriate carrier,
For example, many kits have been developed in which an antigen or an antibody is bound to react with the antibody or the antigen to be measured and then precipitated. These have the advantage that even IgM type antibodies, which are difficult to detect by the ELISA method, can be detected.

Usually, red blood cells are often used as the carrier. After chemically treating the surface of the erythrocyte, a protein serving as a specific aggregation molecule source is attached to the surface of the erythrocyte to cause an aggregation reaction with an antibody or an antigen as a desired measurement target and precipitate the protein. However, in recent years, a diagnostic agent in which inert particles such as bentonite and polystyrene latex are provided with an antigen or the like for the agglutination reaction has also been used.

However, since the bentonite and the like are inactive particles, in order to attach an antibody or the like, which is a source of aggregated molecules, to the inactive particles, a spacer or a reactive active group binding to the antibody is added to the inactive particles. It had to be introduced on the surface.

"Process for producing inorganic fine particles coated with epoxy group-containing polymer" in JP-A-5-310808
The inorganic fine particles coated with the epoxy group-containing polymer are obtained by dispersing the inorganic fine particles in an aqueous catalyst containing a specific cationic surfactant and a polymerization initiator, and then adding an epoxy group-containing polymer to polymerize the inorganic fine particles. A method of manufacturing is disclosed. On the surface of the inorganic fine particles produced by the above method,
It is described that, because of the presence of a reactive group called an epoxy group, it can be used as a functional composite fine particle such as an immobilized catalyst, various packing materials for chromatography, and medical materials. That is, it is suggested to use the epoxy group present on the surface of the inorganic fine particles as the spacer or the reaction active group.

In addition, one of the inventors of the present application, Nagai, and other collaborators are Polymer Preprints, Japan Vol.42, No.11.
(1993), a cationic surfactant adsorption layer was provided on the surface of silica (SiO ₂ ) particles, and a polymerization initiator potassium persulfate (KPS) was deposited in the adsorption layer, and the vinyl monomer described below was further added. It is disclosed that the reactive composite fine particles in which the functional groups of the vinyl monomer are present on the surface of the fine particles can be provided, while the surface of the fine silica particles is protected and coated by solubilizing the polymer and then polymerizing. Here, the disclosed vinyl monomer is acrylic acid of N-hydroxysuccinimide or methacrylic acid ester of N-hydroxysuccinimide having an active ester group. These are useful for immobilization of amino group-containing substances (eg protein enzymes).

[0009]

However, when the surface of the inorganic fine particles is coated by the method described in Japanese Unexamined Patent Publication (Kokai) No. 5-310808, the effect of a spacer is not obtained because the epoxy group has a small number of carbon atoms.

Also, the above Polymer Preprints, Japan Vol.
42, No. 11 (1993), N having an active ester group.
Since the monomer such as hydroxysuccinimide acrylic acid is generally a solid, it has been necessary to dissolve it in a solubilizing monomer such as styrene and then perform the polymerization. Further, the acrylic acid of N-hydroxysuccinimide having an active ester group has different solubility depending on the monomer to be solubilized. Further, even if the same solubilizing monomer is used, the solubility of the monomer having the active ester group is different if the type of the monomer having the active ester group is different. Therefore, the amount of the monomer having an active ester group is limited, and as a result, the amount of the active ester group as a reaction active group is limited, and there is a problem that an antibody or an antigen cannot be immobilized sufficiently. It was With this, the role as a carrier cannot be exerted.

There has been a method in which inorganic particles are coated with a silane coupling agent to give a reactive group, but the number of steps is large and complicated.

[0012]

[Chemical 6] The present invention has been made in view of the above-mentioned conventional problems, and an object thereof is to provide a particle coated with a polymer that simultaneously coats the particle and at the same time easily introduces a spacer and a reactive group and a method for producing the particle. That is.

[0013]

In order to achieve the above object, the particles protectively coated with the polymer according to the present invention have the following characteristics.

(1) The particles are protected by a coating layer formed by copolymerizing the following (a) and (b), and the following chemical formula 9 is formed on the surface of the coating layer.
The compound chain represented by the general formula is exposed and
The C-O bond or the C-S bond inside cleaves when at least either the antibody or the antigen is sensitized.

(A) Cationic surfactant having a radical-polymerizable unsaturated bond represented by the following general formula

[Chemical 7] (In the formula, R _{1 is} hydrogen or an alkyl group having 1 to 4 carbon atoms R ₂ : a bonding group having a heterocycle or a functional group having an aromatic carbocycle A: a functional group shown in Chemical formula 8 B ⁺ : sulfonium or phosphonium X ^- : Alkyl sulfate ion, halogen ion, perchlorate ion, hydrogen sulfate ion, p-toluenesulfonate ion n: 0 or an integer of 1 to 18
)

[Chemical 8]

Embedded image _{- (CH 2) n -A-} R 3 -B + X - ( wherein, R _3: a functional group having a functional group or an aromatic carbon having a heterocyclic A: functional groups shown in Chemical Formula 8 B ⁺ sulfonium, quaternary ammonium or phosphonium X ^-: alkyl sulfate ion, a halogen ion, perchlorate ion, hydrogen sulfate ion, p- toluenesulfonate ion n: 0 or 1 to 18 integer
) (B) Radical-polymerizable unsaturated monomer (2) In the particles protectively coated with the polymer described in (1) above, the particles are obtained by coating resin core particles with ferrite fine particles.

(3) In the particles protectively coated with the polymer described in (1) or (2) above, the radical-polymerizable unsaturated monomer as the component (b) is at least itaconic acid esters, fumaronitrile, maleonitrile, fumar. Includes acid esters or maleic acid esters.

In order to achieve the above object, (4) particles protected by a polymer are manufactured through the following steps (A), (B) and (C).

(A): The particles and the cationic surfactant having a radical polymerizable unsaturated bond as the component (a) are mixed to form an adsorption layer of the cationic surfactant on the surface of the particles. Adsorption layer forming step (B): The radical-polymerizable unsaturated monomer of the component (b) and the polymerization initiator are added in any order, and the adsorption layer formed on the surface of the particles is added with the component (a). Radical-polymerizable unsaturated monomer solubilization step (C) of forming a double salt of a cationic surfactant and a polymerization initiator, and further solubilizing the radical-polymerizable unsaturated monomer of the component (b) in the adsorption layer : Copolymerizing the radically polymerizable unsaturated monomer of the component (b) and the cationic surfactant of the component (a),
Protective coating forming step of forming a protective coating on the particles (5) In the method for producing particles protectively coated with a polymer according to the above (4), the particles are obtained by coating resin core particles with ferrite fine particles.

(6) In the method for producing particles protectively coated with the polymer as described in (4) or (5) above, the cationic surfactant having a radical-polymerizable unsaturated bond is a compound represented by the following general formula: Have.

[0020]

[Chemical 10] (In the formula, R _{1 is} hydrogen or an alkyl group having 1 to 4 carbon atoms R ₂ : a bonding group having a heterocycle or a functional group having an aromatic carbocycle A: a functional group shown in Chemical formula 11 B ⁺ : sulfonium or phosphonium X ^- : Alkyl sulfate ion, halogen ion, perchlorate ion, hydrogen sulfate ion, p-toluenesulfonate ion n: 0 or an integer of 1 to 18
)

[Chemical 11] (7) In the method for producing particles protectively coated with the polymer according to any one of (4), (5) and (6), the radically polymerizable unsaturated monomer is at least itaconic acid ester, fumaronitrile, maleonitrile. , Fumaric acid esters or maleic acid esters.

R ₃ in the cationic surfactant having a radical-polymerizable unsaturated bond of the component (a) is a heterocyclic ring-bonding group represented by the following chemical formulas 12 and 13 or a functional group having an aromatic carbon ring. It is at least one functional group selected from

[0022]

[Chemical 12]

[Chemical 13] In the method for producing particles protectively coated with the polymer, in the adsorption layer forming step (A), the particles are uniformly dispersed in the medium by the cationic surfactant of the component (a), and (a) ) Component is a step of forming an adsorption layer of a cationic surfactant. Usually, the particles 10 and the component (a) are added to the medium and mixed to form an adsorbed bilayer on the surface of the particles 10 as shown in FIG. Although various methods can be used for forming the adsorption layer, it is preferable to employ a method of shaking with a shaker after ultrasonic irradiation. Particularly, in the case of particles in which the surface of resin core particles described below is coated with ferrite fine particles, the surface of the particles is negatively charged. Therefore, the cationic group of the component (a) surfactant is electrically attracted to the surface of the particle 10, and the component (a) cationic surfactant is oriented with the unsaturated bond facing the outside of the particle 10. . On the other hand, by adjusting the addition amount of the cationic surfactant as the component (a), the interaction between the hydrophobic groups causes the cationic groups to be oriented outward. As a result, an adsorption layer which is an adsorption bilayer is formed.

Here, as the medium, water, methanol,
Acetone, N, N-dimethylformaldehyde, tetrahydrofuran, ethyl acetate, chloroform, benzene and the like are used, but ion-exchanged water is preferable. The amount of the medium added is 10 to 2,000 times the volume of the particles,
It is preferably 50 to 1,000 times.

Next, in the step (B) of solubilizing the radical-polymerizable unsaturated monomer, the radical-polymerizable unsaturated monomer of component (b) and the polymerization initiator are added to the adsorption layer formed in the step (A) of forming the adsorption layer. Is added to form a sparingly soluble double salt of the cationic surfactant (a) and the polymerization initiator in the adsorption layer, and the radically polymerizable unsaturated monomer (b) can be added in the adsorption layer. To dissolve. Here, in order to form a double salt of the cationic surfactant as the component (a) and the polymerization initiator on the particle surface, it is described in JP-A-61-247763 and JP-A-2-48038. Such an initiator deposition polymerization method can be applied. Further, the polymerization initiator may be added after adding the radically polymerizable unsaturated monomer as the component (b), or the radically polymerizable unsaturated monomer as the component (b) may be added after adding the polymerization initiator. Good. Moreover, you may add simultaneously.

Further, in the protective film forming step (C), the radically polymerizable unsaturated monomer of the component (b) solubilized in the adsorption layer and the cationic surfactant of the component (a) having an unsaturated bond. And are copolymerized to form a uniform protective coating on the surface of the particles 10. At that time, the polymerization temperature for copolymerization can be appropriately selected, but is preferably 30 ° C to 90 ° C.
More preferably, it is 50 ° C to 70 ° C. Further, it is preferable to carry out the polymerization in an inert gas (for example, nitrogen) atmosphere with constant stirring. After completion of the polymerization, the particles in the medium are separated by a method such as centrifugation or a magnet, the precipitate is filtered, washed with methanol or the like, and vacuum dried. This makes it possible to obtain particles that are protected and coated with the target polymer.

In the present invention, examples of the particles include particles obtained by coating resin core particles with ferrite fine particles, inorganic fine particles and organic polymer particles, resin particles containing ferrite fine particles, and the like.

Here, as the resin core particles or the organic polymer particles, polystyrene, poly (meth) acrylate, poly (meth) acrylate n-butyl, etc. having a particle size of 3 are used.
Particles having a diameter of 0 to 800 nm are used, and the shape may be spherical or modified, and may be appropriately used. The resin core particles may be used as they are, but for example, the resin core particles may be subjected to physical treatment such as plasma treatment, alkali treatment, or acid treatment. By performing these treatments, the wettability with respect to the aqueous solution is improved. Therefore, the surface of the resin core particles can be uniformly coated with the ferrite fine particles. Next, in order to coat the surface of the resin core particles with the fine ferrite particles, JP-A-3-237019 and JP-A-4-253455 are used.
The method can be carried out by the method described in Japanese Patent Application Laid-Open No. 2004-242242, and the core particles are dispersed in water or an aqueous solution, and the pH of this solution is set to 6 to 11,
An iron ion aqueous solution and an oxidant aqueous solution such as nitrite or hydrogen peroxide are added so as to be maintained within a predetermined pH-redox potential range, and the supply rate of the oxidant aqueous solution and the ferrous ion aqueous solution is 0. 1 to 15 × 10 ⁻³ . Thereby, the particle size of the ferrite fine particles is 4 to 50 nm, and the particle size ratio of the resin core particles to the ferrite fine particles is 8/1 to 80 /.
Ferrite-coated particles of 1 are obtained.

As the ferrous ion, ferric chloride,
Sulfate, acetate, etc. are used. When it contains only ferrous ions, magnetite (Fe ₃ O ₄ ) particles are formed and other metal ions such as Mn, Ni, Zn, Co,
When mixed metal oxides of Cu, Mg, Sn, Ca and / or Cd are used together, each mixed crystal ferrite particle is formed.

The ferrite-coated particle suspension obtained as described above can be freeze-dried and stored as dry particles.

The inorganic fine particles include Si, Al, Zr,
Fine particles of oxides such as Ti, phosphates, and their composites, and the particle size is, for example, 0.01 μm to 10 μm.
It is a degree. These particles preferably have a large specific surface area. For example, in the case of silica, the specific surface area is 10
˜1000 m ² / g. Further, the fine particles may be a hydrogel, and as the hydrogel, an alumina hydrogel, a silica alumina hydrogel, a silica hydrogel, a zirconium hydrogel or the like can be usually used, and further, these Co-gel can be used.

Further, resin fine particles containing ferrite fine particles in which an aggregate of a plurality of ferrite fine particles is coated with a resin may be used. The included particle size is 10 to 100
0 nm is preferable, and more preferably 100 to 500 n.
m. Moreover, the number of the encapsulated particles is preferably 1 to 10, and more preferably 1 to 3. As the resin to be coated, those obtained by polymerizing a polymerizable monomer such as styrene, (meth) acrylic acid and ethyl (meth) acrylate are preferable.

Examples of the radically polymerizable unsaturated monomer as the component (b) include aromatic vinyl compounds such as styrene, α-methylstyrene, chloromethylstyrene and divinylbenzene, acrylonitrile, (meth) acrylic acid, ( (Meth) acrylic acid ester such as methyl (meth) acrylate, ethyl (meth) acrylate, butyl (meth) acrylate, hydroxyethyl (meth) acrylate, ethylene glycol dimethacrylate, (meth) acrylamide, N, N-dimethylacrylamide, N-
(Meth) acrylamide compounds such as ethyl (meth) acrylamide, N-propyl acrylamide, n-butyl acrylamide, n-octyl achiryl amide,
Examples thereof include compounds having a conjugated double bond such as butadiene and chloroprene. Then, a homopolymer or a copolymer can be formed by using at least one kind or two kinds or more selected from compounds having these unsaturated bonds. A hydrophobic monomer such as styrene is preferable, and when the hydrophilicity of the monomer becomes high, it becomes difficult to solubilize the monomer in the adsorption layer of the surfactant.

Further, as the radically polymerizable unsaturated monomer as the component (b), maleic acid ester and fumaric acid ester represented by the following chemical formula 14 are also mentioned.

[0034]

[Chemical 14] (In the formula, R, R ₁ , an alkyl group having 1 to 8 carbon atoms or a phenyl group) In particular, the cationic surfactant having a radical-polymerizable unsaturated bond of the above component (a) and the above component (b). In the case of copolymerizing with the radical-polymerizable unsaturated monomer (1), it is preferable that the radical-polymerizable unsaturated monomer (b) contains a fumarate ester as an essential component.

That is, the cationic surfactant having a radical-polymerizable unsaturated bond as the component (a) has low polymerizability. On the other hand, the radical-polymerizable unsaturated monomer of the component (b) has a relatively high polymerization rate and high polymerizability. Therefore, the component (a) differs from the component (b) in the polymerization rate and the like, and therefore, in some cases, the component (a) and the component (b) are different from each other.
In some cases, the components cannot be sufficiently copolymerized. But,
When the component (a) and the other monomer of the component (b) are copolymerized with the fumarate ester interposed, the copolymerization can be easily performed and a sufficient protective coating can be formed on the particle surface. it can.

Here, the molar ratio of the cationic surfactant having a radical-polymerizable unsaturated bond as the component (a) and the fumaric acid ester is preferably 1: 0.5 or more, more preferably 1: 1 to 2 Is. If the molar ratio of the component (a) to the fumaric acid ester is less than 1: 0.5, unreacted monomer that does not polymerize is generated, and the polymer is less likely to precipitate.
Polymer coverage is reduced.

The addition amount of the cationic surfactant having a radical-polymerizable unsaturated bond of the component (a) to the above particles is 0.05 to 1000 wt. %,Preferably,
1.0-500 wt. %. The amount of the component (a) added to the particles is 1000 wt. When it exceeds%,
Micelle is formed in addition to the adsorption bilayer, while the addition amount of the component (a) to the above particles is 0.05 wt. If it is less than%, the adsorption bilayer cannot be formed.

The addition amount of the radically polymerizable unsaturated monomer of the component (b) to the above particles is 0.05 to 1,
000 wt. %, Preferably 0.1 to 500 wt. %. The component (b) is 0.05 wt. If it is less than%, the entire particle surface cannot be uniformly coated. on the other hand,
The component (b) is 1,000 wt. If it exceeds%, the particles tend to aggregate during the polymerization.

The polymerization initiator is a compound having a polymerization initiation ability to form a double salt with the cationic surfactant having a radical-polymerizable unsaturated bond of the component (a), and is an alkali metal or ammonium persulfate salt. Is mentioned. Preferably, di (4-dimethylsulfoniophenyl) persulfate is used.
10-undecylenic acid ester)

[Chemical 15] Such a double salt as described above is formed in the adsorption layer on the surface of the ferrite-coated particles, and serves as a polymerization initiator of the radically polymerizable unsaturated monomer.

The molar ratio of the polymerization initiator to the cationic surfactant having a radical-polymerizable unsaturated bond as the component (a) is 1: 0.5 or more, preferably 1: 2-10.
When the amount of the polymerization initiator is less than 0.5 mol with respect to the component (a), the formation of double salts of both of them on the particle surface is reduced.

That is, by forming the double salt, the initiator can be localized in the adsorption layer, and only the monomer solubilized in the adsorption layer can be selectively polymerized. Therefore, when the amount of double salt is small, unreacted polymer is likely to be generated and the polymer is less likely to be deposited, so that the polymer coating amount is reduced.

The addition amount of the polymerization initiator to the radically polymerizable unsaturated monomer of the component (b) is 0.01 to 2
0 wt. %, Preferably 1-10 wt. %.
The amount of the polymerization initiator added to the component (b) is 0.01 w
t. If it is less than 20% by weight, the polymerization rate is lowered and unreacted monomers remain. %, The production of a polymer having a low degree of polymerization is promoted. In both cases, the coverage of the particle surface with the polymer is reduced.

[0043]

According to the particles protectively coated with the polymer and the method for producing the same according to the present invention, the cationic surfactant having the radical polymerization unsaturated bond of the component (a) is electrically oriented on the surface of the particles. Further, by adjusting the addition amount of the cationic surfactant of the component (a), an adsorption bilayer of the cationic surfactant of the component (a) can be formed on the surface of the particles. This adsorption bilayer is called an adsorption layer. By this orientation, toward the outside of the particles, the [-(CH ₂ ) _n- ] portion corresponding to the spacer from the cationic surfactant of the component (a) of the second layer of the adsorption layer and the above-mentioned general portion corresponding to the reactive group are contacted. [A] in the chemical formula 7 and the cationic group are projected. On the other hand, the reactive monomer is solubilized in the adsorption layer, and the initiator forms a double salt with the cationic surfactant of the component (a) and deposits. Therefore, it is uniformly dispersed in the adsorption layer. Then, the cationic initiator of the component (a) and the reactive monomer are copolymerized by the polymerization initiator to coat the surface of the particle with a resin, and the spacer and the reactive group are projected and fixed on the surface of the particle. It is possible to

When a fumaric acid ester is contained as the radical-polymerizable unsaturated monomer of the component (b), a cationic surfactant having a radical-polymerizable unsaturated bond of the component (a) and having a different polymerization rate (b) is used. Component (2) can be sufficiently copolymerized with the other radically polymerizable unsaturated monomer, and a protective coating having good coatability can be formed on the particle surface.

[0045]

EXAMPLES Next, the present invention will be specifically described with reference to Examples and Comparative Examples.

Examples 1 to 18 and Comparative Examples 1 to 5 [Production Example 1] 0.1 g of ferrite-coated magnetic particles A in 50 ml of water and 4-dimethylsulfoniophenyl-10-undecylenate methyl ester represented by the following formula 16 Sulfate (hereinafter abbreviated as "UPDS") 0.008 mmol
Put it in, disperse with ultrasonic waves for 1 hour, stir for 6 hours, and then add 0.008 mmol of dibutyl fumarate and 0.03 of styrene.
g was added and the mixture was stirred at 25 ° C. for 20 hours. Next, 0.027 mmol of potassium persulfate (KPS) is added,
Polymerization was carried out at 60 ° C. for 24 hours with stirring. After the polymerization, it was centrifuged and the precipitate was filtered off, washed with methanol,
It was filtered off and vacuum dried. The precipitate was dried and weighed to be 0.117 g, and the coating polymer amount was 0.0
It was 17 g (yield 20.6%). The amount of the coating polymer was determined by the difference in weight. Here, the yield is the amount of the coating polymer with respect to the added amount (g) of the added monomer of the component (b) and the surfactant of the component (a).

[0047]

[Chemical 16] Method for producing ferrite-coated particles A 0.9 L of ion-exchanged water was charged into a reaction vessel, and polystyrene particles having a particle size of 300 nm (Nippon Paint Co., Ltd.) were used.
10 g of Nippe Microgel E-3101 manufactured by Ippen Co., Ltd., which was previously dispersed in ion-exchanged water, was added to the reactor. The pH of this dispersion was adjusted with 0.1N NaOH aqueous solution.
The temperature was adjusted to 8.0 and kept warm at 70 ° C. To this one,
FeCl ₂ .4H ₂ O was previously dissolved in ion-exchanged water to prepare 30 wt. % Ferrous ion aqueous solution 60 ml /
At a feed rate of 15 wt. % Sodium nitrite was fed at a feed rate of 0.3 ml / min. During this time, the pH was kept constant at 8.0. In addition, the sodium nitrite and the aqueous solution were first added so that the redox potential of this solution was kept constant at -550 mV.
The supply rate ratio of the iron ion aqueous solution was adjusted to 5 × 10 ⁻³ . The obtained ferrite-coated particles were alternately separated by filtration and washed to obtain ferrite-coated polystyrene particles. The particle size of ferrite fine particles is 20-10
was nm. Method for producing ferrite-coated particles B Instead of the ferrous ion aqueous solution in Example 1, 26.1 g of FeCl ₂ .4H ₂ O and MnCl ₂ .4H were previously prepared.
13.0 g of ₂ O was dissolved in 60.0 g of deionized water, and 30 wt. % Aqueous solution was prepared. Further, as an oxidizing agent aqueous solution, 20 wt. % Mn ferrite-coated polystyrene particles were obtained in the same manner as in the method for producing the ferrite-coated particles A, except that an aqueous solution of hydrogen peroxide was used. The particle size of the ferrite fine particles was 20-10 nm.

Manufacturing Method of Ferrite-Encapsulated Particles C 50 ml of water was charged with 0.12 mmol of cetyltrimethylammonium bromide and 0.1 g of ferrite particles having a particle size of 80 mm, followed by ultrasonic irradiation for 1 hour and stirring, and then 0.20 of styrene was added. And shaken at 25 ° C. for 20 hours.
Then, add 0.04 mmol of potassium persulfate, and add 60
Polymerization was performed under a nitrogen atmosphere while shaking at 24 ° C. for 24 hours.
After completion of the polymerization, separation by filtration and washing were alternately repeated to obtain ferrite-encapsulated particles.

Hereinafter, as shown in Table 1, the type of particles, the type of fumaric acid ester, the type of radical-polymerizable unsaturated monomer of component (b), and the addition amount of component (b) were changed. According to the manufacturing method, particles protectively coated with the polymers of Examples 2 to 15 were manufactured.

[Evaluation Method] (1) Evaluation of Coverability When the ferrite fine particles are used as the particles, the obtained protective coated particles are evaluated as 0 to confirm whether or not the ferrite fine particles are completely protected by the polymer. .0
It was placed in a 1 M oxalic acid solution and immersed at 20 ° C. for 70 minutes. Then, the resistance was examined by the change in color of the particles during the immersion. The results are shown in Table 1.

The above "resistance index" means a value when the resistance of the ferrite-coated particles not coated with the polymer is 1.

(2) Evaluation of capture ability of antibody or antigen

[Table 1]

[Table 2]

[Table 3] According to the present invention, a protective coating having good coatability in which elution of ferrite is suppressed under oxidizing conditions is formed on the surface of particles.
The ability to capture antibodies or antigens was also good.

Similar effects were obtained when inorganic particles were used instead of the ferrite-coated particles.

Further, the following embodiments can be mentioned as preferred embodiments of the present invention.

1. Particles protected and coated with a polymer protected by a coating layer obtained by copolymerizing the following (a) and (b).

(A) Cationic surfactant having a radical-polymerizable unsaturated bond represented by the following general formula (17)

[Chemical 17] (In the formula, R _{1 is} hydrogen or an alkyl group having 1 to 4 carbon atoms R ₂ : a functional group shown in Chemical formula 18 or 19; A: a functional group shown in Chemical formula 20 B ⁺ : sulfonium or phosphonium X ⁻ : alkyl sulfate ion, Halogen ion, perchlorate ion, hydrogen sulfate ion, p-toluenesulfonate ion n: 0 or an integer of 1 to 18
)

[Chemical 18]

[Chemical 19]

[Chemical 20] (B) Radical-polymerizable unsaturated monomer 2. The cationic surfactant having a radically polymerizable unsaturated bond of the component (a) is 4-dimethylsulfoniophenyl-10-undecylenic acid ester methylsulfate (UPDS).

3. The radically polymerizable unsaturated monomer of the component (b) is an aromatic vinyl compound such as styrene, α-methylstyrene, chloromethylstyrene, divinylbenzene, acrylonitrile, (meth) acrylic acid, (meth) acrylic acid. (Meth) acrylic acid ester such as methyl, ethyl (meth) acrylate, butyl (meth) acrylate, hydroxyethyl (meth) acrylate, ethylene glycol dimethacrylate, (meth) acrylamide, N, N-dimethylacrylamide , N-
(Meth) acrylamide compounds such as ethyl (meth) acrylamide, N-propyl acrylamide, n-butyl acrylamide, n-octyl achiryl amide,
It is at least one kind or two or more kinds selected from compounds having a conjugated double bond such as butadiene, chloroprene, fumaric acid esters, and maleic acid esters.

4. The radical-polymerizable unsaturated monomer of the component (b) is a combination of UPDS, styrene and dibutyl fumarate.

5. The particles are inorganic fine particles.

6. The particles are resin particles containing ferrite particles.

7. In the adsorption layer forming step (A), after the ultrasonic irradiation, the particles and the cationic surfactant of the component (a) are added to the medium by a method of shaking with a shaker, and (a) is added to the surface of the particles. It is a step of forming an adsorption layer of a cationic surfactant as a component.

8. As the medium, water, methanol, acetone, N, N-dimethylformaldehyde, tetrahydrofuran, ethyl acetate, chloroform, or benzene is used.

9. The medium is ion-exchanged water.

10. The amount of the medium added is 10 to 2,000 times, preferably 50 to 1,000 times, the volume of the particles.

11. An initiator deposition polymerization method is applied to the sparingly soluble double salt of the radically polymerizable unsaturated monomer as the component (b) formed in the radically polymerizable unsaturated monomer solubilization step (B).

12. In the step (B) of solubilizing the radically polymerizable unsaturated monomer, the polymerization initiator is added after adding the radically polymerizable unsaturated monomer of the component (b).

13. In the radical-polymerizable unsaturated monomer solubilization step (B), the radical-polymerizable unsaturated monomer of the component (b) is added after the polymerization initiator is added.

14. In the step (B) of solubilizing the radically polymerizable unsaturated monomer, the polymerization initiator and the radically polymerizable unsaturated monomer of the component (b) are added at the same time.

15. The polymerization temperature in the protective film forming step (C) is 30 ° C to 90 ° C. 16. The polymerization temperature in the protective film forming step (C) is 5
It is 0 ° C to 70 ° C. 17. The polymerization in the protective film forming step (C) is performed in a nitrogen atmosphere with constant stirring.

18. After completion of the polymerization in the protective film forming step (C), particles in the medium are separated by a method such as centrifugation.
The precipitate is filtered, washed with water or the like, and vacuum dried.

19. In the particles obtained by coating the resin core particles with ferrite fine particles, the resin core particles are particles having a particle size of 30 to 800 nm, such as polystyrene, poly (meth) acrylate n-butyl poly (meth) acrylate, and the like. .

20. The shape of the resin core particles is spherical or deformed.

21. The resin core particles are further subjected to plasma treatment, acrylic treatment, acid treatment or physical treatment.

22. In order to coat the surface of the resin core particles with the fine ferrite particles, the resin core particles are dispersed in water or an aqueous solution, the pH of the liquid is set to 6 to 11, and the aqueous ferrous ion solution, nitrite salt, or peroxide is used. An oxidant aqueous solution such as hydrogen is added so as to be maintained within a predetermined pH-redox potential range, and the supply rate of the oxidant aqueous solution and the ferrous iron aqueous solution is 0.1 to 15 × 10 ⁻³ . To do.

23. The particle size of the ferrite fine particles is 4 to
It is 50 nm.

24. The particle diameter ratio of the resin core particles and the ferrite fine particles is 8/1 to 80/1.

25. The ferrous iron is ferric chloride, sulfate, or acetate.

26. The inorganic fine particles are Si, Al, Z
Fine particles of oxides such as r and Ti, phosphates, and their composites.

27. The particle size of the inorganic fine particles is 0.01 μm
10 to 10 μm.

28. The specific surface area of the inorganic fine particles is 10 to 1
It is 000 m ² / g.

29. The inorganic fine particles are hydrogel.

30. The above hydrogel is alumina hydrogel, silica alumina hydrogel, silica hydrogel,
Zirconium hydrogel, alumina hydrogel, and Co-gel thereof.

31. The resin fine particles contained in the ferrite fine particles are particles obtained by coating an aggregate of a plurality of ferrite fine particles with a resin.

32. The particle size of the ferrite fine particles included in the resin particles is 10 to 1000 nm.

33. The number of ferrite fine particles included in the resin fine particles containing the ferrite fine particles is 1 to 10
Is.

34. The resin coating the ferrite fine particles contained therein is obtained by polymerizing a polymerizable monomer such as styrene, (meth) acrylic acid and methyl (meth) acrylate.

35. The molar ratio of the cationic surfactant having a radical-polymerizable unsaturated bond of the component (a) and the fumarate ester is 1: 0.5 or more.

36. The molar ratio of the cationic surfactant having a radical-polymerizable unsaturated bond as the component (a) and the fumarate ester is 1: 1 to 2.

37. The amount of the cationic surfactant having a radically polymerizable unsaturated bond of the component (a) added to the particles is 0.05 to 1000 wt. %.

38. The addition amount of the radically polymerizable unsaturated monomer of the component (b) to the particles is 0.05 to 1,000.
0 wt. %.

39. The addition amount of the radically polymerizable unsaturated monomer of the component (b) to the particles is 0.1 to 500 w.
t. %.

40. The polymerization initiator is an alkali metal or ammonium persulfate.

41. The polymerization initiator is persulfate di (4-dimethylsulfoniophenyl-10-undecyl ester).

[Chemical 21] Is.

42. The molar ratio of the polymerization initiator to the cationic surfactant having a radical-polymerizable unsaturated bond of the component (a) is 1: 0.5 or more.

43. The molar ratio of the polymerization initiator to the cationic surfactant having a radical-polymerizable unsaturated bond as the component (a) is 1: 2 to 10.

44. The addition amount of the polymerization initiator to the radically polymerizable unsaturated monomer of the component (b) is 0.01 to 2
0 wt. %.

45. The addition amount of the polymerization initiator to the radically polymerizable unsaturated monomer of the component (b) is 1 to 10 w.
t. %.

[0098]

INDUSTRIAL APPLICABILITY As described above, according to the particles protectively coated with the polymer and the method for producing the same according to the present invention, the cationic surfactant having the radical polymerization unsaturated bond of the component (a) is formed on the surface of the particles. The agent is electrically oriented, and by further adjusting the addition amount of the cationic surfactant of the component (a), an adsorption bimolecular layer of the cationic surfactant of the component (a) is formed on the surface of the particles. be able to. This adsorption bilayer is called an adsorption layer. Due to this orientation, the cationic surfactant, which is the component (a) of the second layer of the adsorption layer, hits the spacer toward the outside of the particle [-(CH ₂ ) _n- ].
, The [A] of the general formula of the above-mentioned component (a) corresponding to the reactive group, and the cationic group are projected. On the other hand, the reactive monomer is deposited in the adsorption layer, and the initiator forms a double salt with the cationic surfactant as the component (a). Therefore, it is uniformly dispersed in the adsorption layer. Then, the cationic initiator of the component (a) and the reactive monomer are copolymerized by the polymerization initiator to coat the surface of the particle with a resin, and the spacer and the reactive group are projected and fixed on the surface of the particle. It is possible to

As a result, it is possible to reduce the number of steps for producing the particles protectively coated with the polymer, which is economically superior.

When the fumaric acid ester is contained as the radical-polymerizable unsaturated monomer of the component (b), a cationic surfactant having a radical-polymerizable unsaturated bond of the component (a) and having a different polymerization rate (b) is used. Component (2) can be sufficiently copolymerized with the other radically polymerizable unsaturated monomer, and a protective coating having good coatability can be formed on the particle surface.

[Brief description of drawings]

FIG. 1 is a process chart illustrating a process for producing particles protectively coated with a polymer according to the present invention.

[Explanation of symbols]

 10 particles

Claims (7)

[Claims] 1. A particle is protected by a coating layer formed by copolymerizing (a) and (b) below, and a compound chain represented by the general formula of the following chemical formula 3 is exposed on the surface of the coating layer. Particles protected by a polymer, wherein the C—O bond or the C—S bond in A is cleaved when at least one of an antibody and an antigen is sensitized. (A) Cationic surfactant having a radical-polymerizable unsaturated bond represented by the following general formula (1): (In the formula, R _{1 is} hydrogen or an alkyl group having 1 to 4 carbon atoms R ₂ : a bonding group having a heterocycle or a functional group having an aromatic carbocycle A: a functional group shown in Chemical formula 2 B ⁺ : sulfonium or phosphonium X ^- : Alkyl sulfate ion, halogen ion, perchlorate ion, hydrogen sulfate ion, p-toluenesulfonate ion n: 0 or an integer of 1 to 18
) [Chemical 2] ## STR3 ## _{- (CH 2) n -A-} R 3 -B + X - ( wherein, R _3: a functional group having a functional group or a benzene ring having a heterocyclic ring A: functional groups shown in Chemical Formula 2 B ⁺ sulfonium, quaternary ammonium or Houhoniumu X ^-: alkyl sulfate ion, a halogen ion, perchlorate ion, hydrogen sulfate ion, p- toluenesulfonate ion n: 0 or 1 to 18 integer
) (B) Radical-polymerizable unsaturated monomer 2. The particles protectively coated with the polymer according to claim 1, wherein the particles are resin core particles coated with ferrite fine particles, and the particles are protectively coated with the polymer. 3. The particles protectively coated with the polymer according to claim 1, wherein the radically polymerizable unsaturated monomer as the component (b) is at least itaconic acid ester, fumaronitrile, maleonitrile, fumaric acid ester, or Particles protectively coated with a polymer, characterized in that it contains maleic acid esters. 4. A method for producing particles protective-coated with a polymer, which comprises producing the particles protective-coated with a polymer through the following steps (A), (B) and (C). (A) Adsorption layer forming step of mixing particles and a cationic surfactant having a radical polymerizable unsaturated bond to form an adsorption layer of the cationic surfactant on the surface of the particles (B) Radical polymerizable A saturated monomer and a polymerization initiator are added in any order to form a double salt of the cationic surfactant and the polymerization initiator in the adsorption layer formed on the surface of the particles, and radicals are further present in the adsorption layer. Radical Polymerizable Unsaturated Monomer Solubilizing Step for Solubilizing Polymerizable Unsaturated Monomer (C) Protective Coating Forming Protective Coating on Particles by Copolymerizing the Radical Polymerizable Unsaturated Monomer and Cationic Surfactant Forming process 5. The method for producing particles protectively coated with a polymer according to claim 4, wherein the particles are resin core particles coated with ferrite fine particles. Production method. 6. The method for producing particles protectively coated with the polymer according to claim 4 or 5, wherein the cationic surfactant having a radical-polymerizable unsaturated bond has a general formula of the following chemical formula 4. A process for producing particles protectively coated with a polymer. [Chemical 4] (In the formula, R _{1 is} hydrogen or an alkyl group having 1 to 4 carbon atoms R ₂ : a functional group having a heterocycle or a functional group having an aromatic carbocycle A: a functional group shown in Chemical formula 5 B ⁺ : sulfonium or phosphonium X ^- : Alkyl sulfate ion, halogen ion, perchlorate ion, hydrogen sulfate ion, p-toluenesulfonate ion n: 0 or an integer of 1 to 18
) [Chemical 5] 7. The method for producing particles protectively coated with the polymer according to claim 4, 5, or 6, wherein the radically polymerizable unsaturated monomer is at least an itaconic acid ester fumaronitrile, maleonitrile, or fumaric acid ester. Of a polymer or a maleic acid ester, and a method for producing particles protectively coated with a polymer.