JPH0661034A - Powdery polymer and manufacture thereof - Google Patents

Abstract

PURPOSE:To provide a magnetized powdery polymer by polymerizing specific vinyl compounds with magnetic metal oxide using a radical-generating catalyst. CONSTITUTION:A powdery polymer containing magnetized hydrophilic free radicals is prepared from a magnetic metal oxide and a copolymer expressed by the formula shown. In the formula, R is H, 1-4C alkyl, or phenyl; R1 is H or 1-4C alkyl; R2 and R3 are independently H, halogen, or 1-4C alkyl, or 1-4C alkoxy; R4 and R5 are independently 1-4C alkyl; X is alkyl sulfate ion, halogen ion, perchlorate ion, hydrogen sulfate ion, or p-toluenesulfonate ion; R6 and R7 are independently H, halogen or organic group. R and R1 to R7 may individually be different species; m and n are in mol.%, 0<m<20, 80<n<100, m+n=100.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a novel fine particle polymer and a method for producing the same. More specifically, it relates to a functionalized fine particle polymer which is magnetized and contains a hydrophilic reactive group, and a method for producing the same.

[0002]

2. Description of the Related Art In recent years, polymers, in particular, fine-particle polymers having a reactive group have been actively developed. Particularly in the field of testing and diagnostic agents, testing agents that utilize antigen-antibody reaction require accuracy and speed of testing. For example, Japanese Patent Laid-Open No. 61-167866 discloses a diagnostic agent in which a fine particle polymer is magnetized. It is disclosed. However, according to this disclosure, the reactive group for immobilizing the antigen or antibody is —OH group, —CHO group, —SH group or the like, and there is a problem that the reactive activity is weak or the reaction is complicated. .

[0003]

DETAILED DESCRIPTION OF THE INVENTION The present inventors have invented a fine particle polymer composed of Chemical Formula 5 and a magnetic metal oxide and a method for producing the same, as a result of intensive studies in view of the above situation, and will be disclosed here.

[Chemical 5] (However, R is hydrogen, a C _{1 to} C ₄ alkyl group, a phenyl group, R ₁ is hydrogen, a C _{1 to} C ₄ alkyl group, R ₂ , R
₃ independently represents any one of hydrogen, halogen, a C ₁ -C ₄ alkyl group, and a C ₁ -C ₄ alkoxy group, and R ₄ , R
₅ independently represents a C ₁ -C ₄ alkyl group. X is an alkyl sulfate ion, a halogen ion, a perchlorate ion,
Either hydrogen sulfate ion or p-toluenesulfonate ion, and R ₆ and R ₇ independently represent hydrogen, halogen, or an organic group. Then, different kinds of R and R _{1 to} R ₇ may exist at the same time. Further, m and n represent mole percentages, and 0 <m <20, 80 <n <100 and m + n = 100. )

The fine particle polymer of the chemical formula 5 and the magnetic metal oxide of the present invention is converted into one or more vinyl compounds represented by the chemical formula 6 in the presence of the magnetic metal oxide in water and / or an organic solvent. It is obtained by polymerizing at least one vinyl compound represented by the formula (1) with a radical-generating catalyst. This fine particle polymer, without using an emulsifier,
A magnetic metal oxide can be incorporated and polymerized.

[0005]

[Chemical 6] (However, R is hydrogen, a C ₁ -C ₄ alkyl group, a phenyl group, R ₁ is hydrogen, a C ₁ -C ₄ alkyl group, R ₂ , R
₃ independently represents any one of hydrogen, halogen, a C ₁ -C ₄ alkyl group, and a C ₁ -C ₄ alkoxy group, and R ₄ , R
₅ independently represents a C ₁ -C ₄ alkyl group. X represents an alkylsulfate ion, a halogen ion, a perchlorate ion, a hydrogensulfate ion, or p-toluenesulfonate ion. )

[Chemical 7] (However, R ₆ and R ₇ independently represent hydrogen, halogen, or an organic group.)

Examples of the acrylate compound represented by Chemical formula 6 are 4-dimethylsulfoniophenyl methacrylate methyl sulfate, 4-dimethylsulfoniophenyl acrylate methyl sulfate, 4-diethylsulfoniophenyl methacrylate ethyl sulfate, 4-diethylsulfoniophenyl methacrylate Dimethylsulfoniophenyl methacrylate perchlorate, 4-
Examples thereof include dimethylsulfoniophenyl methacrylate p-toluenesulfonate, 2-chloro-4-dimethylsulfonio-6-tert-butylphenylmethacrylate methylsulfate, 4-dimethylsulfoniophenylmethacrylate chloride and the like.

Examples of the vinyl compound represented by the chemical formula 7 include methyl acrylate, ethyl acrylate,
acrylate compounds such as n-butyl acrylate,
Examples thereof include compounds such as styrene, α-methylstyrene, vinyltoluene, acrylonitrile, vinyl chloride, and acrylamide, but are not limited thereto, and two or more monomers may be present at the same time. The magnetic metal oxide which is a component for magnetizing the fine particle polymer of the present invention is a magnetic substance other than paramagnetic. An example of the magnetic metal oxide is a compound represented by Chemical formula 8.

[0008]

[Chemical 8] (However, M represents a divalent metal atom of iron, cobalt, nickel, magnesium, copper, zinc, strontium, manganese, and calcium, and different kinds may be present at the same time. Further, q is 0 ≦ q ≦ 1.) In particular, q =
0 is γ-Fe ₂ O ₃ , and M = Fe and q = 1.
Is Fe ₃ O ₄ (magnetite), and magnetite is desirable for the present invention.

Examples of the radical-generating catalyst used for producing the fine particle polymer of the present invention include 2,2'-azobis (2-methylpropionamidine) dihydrochloride.
4,4'-azobis (4-cyanovaleric acid), 2,2'-
Azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride, 2,2′-azobis [2- (5-methyl-2-imidazolin-2-yl) propane] dihydrochloride,
2,2'-azobisisobutyramide dihydrate and the like can be mentioned. The polymerization temperature in the manufacturing process is 0 to 90 ° C.,
It is preferably 50 to 70 ° C. The polymerization time is
It is 0.5 to 50 hours, preferably 2 to 5 hours.

[0010]

The fine particle polymer of the present invention is a novel fine particle having a function of magnetizing and a function of containing a hydrophilic reactive group. Therefore, the dispersion state is stable in the medium and the latex state can be maintained without adding a third component such as a dispersant. Further, the enzyme, protein, etc. can be immobilized on the surface by easily reacting with the amino group of the enzyme, protein, etc. Further, it has a feature that the fine particles having the enzyme, protein, etc. immobilized thereon can be separated and collected by magnetism.

[0011]

EXAMPLES Examples of the present invention will be shown below, but the scope of the present invention is not limited thereto.

Example 1 A thermometer, a nitrogen blowing thin tube, a condenser and a stirrer are installed in a 100 ml four-necked Kolben. Magnetite TCM-4521 (magnetic fluid Fe ₃ manufactured by Toda Kogyo Co., Ltd.
Trade name of O ₄ ) 5 g, pure water 25 g, 4-dimethylsulfoniophenyl methacrylate methyl sulfate 0.5 g,
Charge 5 g of styrene. After replacing the inside of the system with nitrogen, the system is heated to 70 ° C. in a water bath and stirred. 10 minutes after the start of stirring,
2,2'-azobis (2-methylpropionamidine)
0.14 g of dihydrochloride was added, and the reaction was carried out for 5 hours under the initial setting conditions to obtain a light brown latex suspension. Since it was possible to separate the solid matter with a magnet, it was confirmed that the solid matter was magnetized. In addition, when the particle state was observed with a scanning electron microscope, the particles were spherical with a relatively uniform particle size of around 1.0 μm. Next, the membrane filter was separately washed, dried, and subjected to IR analysis. 2,920 cm
^-1, 1,495Cm ^-1, absorption of polystyrene 700 cm ^-1, also in 1,750Cm ^-1, absorption of C = O of 4 dimethylsulfoxide niobium phenyl methacrylate was observed. The sulfur content measured by the combustion flask method was 0.82%. The theoretical value is 0.9
1%. From this, it is shown that the charged magnetic substance and monomer were taken in almost quantitatively.

Example 2 A thermometer, a nitrogen blowing thin tube, a condenser and a stirrer are installed in a 100 ml four-necked Kolben. Magnetite TCM-4521 (magnetic fluid Fe ₃ manufactured by Toda Kogyo Co., Ltd.
5 g of O ₄ (trade name), 25 g of pure water, 0.5 g of 4-dimethylsulfoniophenyl acrylate methyl sulfate, and 5 g of styrene are charged. After replacing the inside of the system with nitrogen, the system is heated to 70 ° C. in a water bath and stirred. 10 minutes after the start of stirring, 2,
A light brown latex suspension was obtained by adding 0.07 g of 2'-azobis (2-methylpropionamidine) dihydrochloride and reacting for 5 hours under the initial setting conditions. It was possible to separate solids with a magnet. From this, it was confirmed that the solid matter was magnetized.
Further, as in Example 1, when observed with a scanning electron microscope, the particles were spherical with a particle size of about 1.0 μm and a relatively uniform particle size. Next, the membrane filter was separately washed, dried, and subjected to IR analysis. The spectrum is shown in FIG. 2,920cm ^-1, 1,495c
m ^-1, absorption of polystyrene 700 cm ^-1 is also a 1,750Cm ^-1, absorption of C = O of 4 dimethylsulfoxide niobium phenyl acrylate was observed. The sulfur content measured by the combustion flask method was 0.83%. The theoretical value is 0.95%. This indicates that the charged magnetic substance and the monomer were quantitatively incorporated.

Reference Example 1 5 g of the suspension obtained in Example 1 was placed in a 30 ml beaker, 0.189 g of N, N-dimethylethylenediamine was added, and the reaction was carried out at room temperature for 24 hours while shaking and stirring. The solid content of the suspension after the reaction could be separated by a magnet. After the reaction, the membrane was washed with a membrane filter and dried, and the measured sulfur content was 0.51%.

Reference Example 2 1 g of the suspension obtained in Example 2 was placed in a 30 ml beaker, 10 ml of a phosphate buffer (pH 7.2) was added, 500 mg of trypsin was added, and the mixture was stirred at room temperature for 24 hours.
Reacted for hours. After the reaction, the solid matter was separately washed with a membrane filter, the solid matter was suspended in a phosphate buffer (pH 7.6), and N-α-benzoyl-L-arginine ethyl ester was incubated at 25 ° C for 16 hours. The activity of trypsin was evaluated by measuring the absorbance of the reaction solution from which the solid content was removed. As a result, it was found that trypsin was bound at a reaction rate of 54%.

[0016]

INDUSTRIAL APPLICABILITY The fine particle polymer of the present invention can be obtained in a dispersion-stable latex state in water in the presence of a magnetic metal oxide without using an emulsifier. Since the fine particle polymer has a hydrophilic active reactive group and is magnetized, the enzyme for the fine particle polymer,
Immobilization by reaction of amino groups of proteins and the like, and further magnetic separation and collection can be easily performed.

Continuation of front page (51) Int.Cl. ⁵ Identification number Reference number within the agency FI Technical display location H01F 1/34 Z (72) Inventor Masaru Nagai 2-661 Shimohanazawa, Yonezawa City, Yamagata Prefecture

Claims (7)

[Claims] 1. A fine particle polymer comprising the copolymer shown in Chemical formula 1 and a magnetic metal oxide. (However, R is hydrogen, a C _{1 to} C ₄ alkyl group, a phenyl group, R ₁ is hydrogen, a C _{1 to} C ₄ alkyl group, R ₂ , R
₃ independently represents any one of hydrogen, halogen, a C ₁ -C ₄ alkyl group, and a C ₁ -C ₄ alkoxy group, and R ₄ , R
₅ independently represents a C ₁ -C ₄ alkyl group. X represents an alkylsulfate ion, halogen ion, perchlorate ion, hydrogensulfate ion or p-toluenesulfonate ion, and R ₆ and R ₇ independently represent hydrogen, halogen or an organic group. Then, different kinds of R and R _{1 to} R ₇ may simultaneously exist. Further, m and n represent mole percentages, and when 0 <m <20 and 80 <n <100, m and n
+ N = 100. ) 2. The fine particle polymer according to claim 1, wherein the chemical formula 1 is a copolymer of 4-dimethylsulfoniophenyl acrylate methyl sulfate and styrene. 3. The fine particle polymer according to claim 1, wherein the chemical formula 1 is a copolymer of 4-dimethylsulfoniophenyl methacrylate methylsulfate and styrene. 4. The fine particle polymer according to claim 1, wherein the magnetic metal oxide is represented by the chemical formula 2. (However, M represents a metal ion of iron, cobalt, nickel, magnesium, copper, zinc, strontium, manganese, and calcium, and different kinds may be present at the same time. Further, q is 0 ≦ q ≦ 1. It is.) 5. A magnetic metal oxide is 0.001 μm to 1 μm.
4. Fine particles having an average particle diameter in the range of m.
Fine particle polymer described 6. The polymer-coated magnetic fine particles according to claim 1.
Particulate polymer according to 3 7. A radical-generating catalyst for at least one vinyl compound represented by Chemical Formula 3 and at least one vinyl compound represented by Chemical Formula 4 in the presence of a magnetic metal oxide in water and / or an organic solvent. Polymerizing, characterized in that
Method for producing fine particle polymer described in the following (However, R is hydrogen, a C ₁ -C ₄ alkyl group, a phenyl group, R ₁ is hydrogen, a C ₁ -C ₄ alkyl group, R ₂ , R
₃ independently represents any one of hydrogen, halogen, a C ₁ -C ₄ alkyl group, and a C ₁ -C ₄ alkoxy group, and R ₄ , R
₅ independently represents a C ₁ -C ₄ alkyl group. X represents an alkylsulfate ion, a halogen ion, a perchlorate ion, a hydrogensulfate ion, or p-toluenesulfonate ion. ) [Chemical 4] (However, R ₆ R ₇ independently represents hydrogen, halogen or an organic group.)