JPH0616444B2 - Method for manufacturing magnetic microspheres - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing a magnetic microsphere in which ferromagnetic fine particles are contained in a polymeric microsphere. More specifically, it is suitable for use as a column packing material for separating and purifying useful substances in a solution by magnetism, or as a carrier for a test reagent for magnetically determining a diagnostic reagent. The present invention relates to a method for effectively producing magnetic microspheres having excellent chemical stability and magnetic responsiveness.

2. Description of the Related Art Conventionally, polymer microspheres produced from various natural polymers and synthetic polymers have been widely used as various fillers, colorants, spacers, toners, medical carriers, substance separation fillers, and the like.

In particular, various synthetic polymer microspheres such as polystyrene are excellent in chemical stability and dimensional stability, and therefore, for example, as a packing material for liquid chromatography, a separating and purifying agent for enzymes and proteins, a carrier for diagnostic reagents, etc.
The demand is growing rapidly.

Recently, CaCO ₃ , Fe ₃ O ₄ , and
Inorganic powders such as TiO ₂ , dyes, or composite microspheres that have been functionalized by blending various chemicals are attracting attention, such as conductive paints, electromagnetic wave shield paints, medical magnetic carriers,
Attempts have been made to apply it to magnetic fillers with improved separation function.

By the way, magnetic microspheres used as fillers for various columns and medical carriers have been produced by emulsion polymerization or suspension polymerization. For example, in emulsion polymerization, a method has been performed in which a surfactant-containing aqueous solution and a monomer are mixed, heated to a constant temperature while stirring, and an aqueous solution of a polymerization initiator is added to carry out polymerization to obtain microspheres. Microspheres produced by such a method are suitable as column packings and carriers for diagnostic reagents by changing the polymerization conditions,
Although the size is from 0.1 to 100 μm, when the magnetic powder is mixed with the ferromagnetic powder, the ferromagnetic powder is difficult to enter the inside of the microfiber during the polymerization process.

On the other hand, in suspension polymerization, a method is known in which a monomer in which a polymerization initiator is dissolved is mixed in an aqueous or non-aqueous solution in which a dispersant is dissolved, and the mixture is heated to a constant temperature while stirring to obtain a microsphere. In this case, the magnetic powder can be produced by hydrophobizing the ferromagnetic powder, dispersing it in a non-aqueous solution, adsorbing the monomer, and then polymerizing it, but the ferromagnetic powder is exposed on the surface of the microsphere. Therefore, there are problems such as poor chemical stability. Further, the size of the microspheres obtained by the aqueous suspension polymerization is from 03 to 1.5 mm, which is a drawback that it is too large as a carrier for diagnostic reagents.

As a method of producing magnetic microspheres by a method other than emulsion polymerization or suspension polymerization, for example, a magnetite colloid is dispersed in an aqueous solution of gelatin, pH is adjusted to microspheres, and further insolubilized by an aldehyde crosslinking agent. Method (JP-A-59-195161),
A method is known in which a magnetite colloid is mixed with a water-soluble polymer or a protein such as serum albumin, and then emulsified into microspheres, which is then insolubilized by heat treatment.However, when the coating polymer is hydrophilic in this way, it is used in an aqueous solution. At this point, swelling of microspheres occurs, and the magnetite contained inside comes into contact with the dispersion medium solution, so there is a problem in chemical stability. Further, when the magnetite colloid is directly coated with the polymer, there is a drawback that it is difficult to completely coat the magnetite particles.

Therefore, it has been desired to develop a magnetic microsphere having excellent chemical stability and dispersibility in various aqueous solutions and excellent magnetic response by completely enclosing the ferromagnetic powder in the microsphere.

DISCLOSURE OF THE INVENTION Problems to be Solved by the Invention The object of the present invention is to meet such a demand, the particle size of microspheres can be varied in the range of 0.1 to several tens of μm, and the particle size distribution is relatively narrow, and the dispersibility in various aqueous solutions and An object of the present invention is to provide a method for effectively producing a magnetic microsphere having excellent chemical stability and high magnetic response.

Means for Solving the Problems As a result of intensive studies, the present inventor has dispersed ferromagnetic fine particles that have been hydrophobized with a surfactant in a monomer,
After adding a polymerization initiator, by dispersing and suspending it in an aqueous solution containing a dispersion stabilizer to adjust the particle size of particles to be generated by performing low-frequency ultrasonic irradiation during heat polymerization. The inventors have found that the above objects can be achieved, and have completed the present invention based on this finding.

That is, the present invention is to add a polymerization initiator to a mixture of uniformly dispersed ferromagnetic fine particles that have been subjected to a hydrophobic treatment in a monomer, and disperse and suspend while stirring this in an aqueous solution containing a dispersion stabilizer. In heating and polymerizing, microparticles characterized by finely controlling the particle size of microspheres generated by performing low-frequency ultrasonic irradiation in the suspension process or both the suspension process and the polymerization process A method for producing magnetic microspheres having a diameter is provided.

The ferromagnetic fine particles used in the method of the present invention preferably have a particle size of about 150Å produced by the coprecipitation method. The fine particles are subjected to a hydrophobizing treatment so as to be uniformly dispersed in various monomers. This hydrophobizing treatment is carried out by adsorbing an unsaturated fatty acid such as oleic acid on the surface of the fine particles, or It is performed by further adsorbing a surfactant on the unsaturated fatty acid adsorption layer.

Regarding the polymerization initiator used in the method of the present invention,
There is no particular limitation as long as it is an oil-soluble radical polymerization initiator such as an organic peroxide such as benzoyl peroxide, an azo-based initiator such as azobisdimethylvaleronitrile or azobisisobutyronitrile. These polymerization initiators may be dissolved in the monomer in advance before dispersing the ferromagnetic fine particles, or may be dissolved in the monomer after the fine particles are dispersed in the monomer.

In the method of the present invention, a dispersant is used to disperse and suspend the monomer in which the ferromagnetic fine particles are dispersed in an aqueous solution. As the dispersant, polyvinyl alcohol used in ordinary suspension polymerization is used. Preferred examples thereof include water-soluble polymers such as carboxymethyl cellulose and gelatin.

The particle size of the magnetic microspheres produced by the method of the present invention varies from 0.1 μm to several μm depending on the amount of the dispersant added, the ratio of the monomer solution and the aqueous dispersion medium solution, and the method of dispersing the monomers in the suspension process and the polymerization process. It can be changed up to 10 μm.

In the method of the present invention, it is necessary to control the particle size of the microspheres to be formed by using ultrasonic radiation of low frequency in combination during stirring only in the suspension process or in both the suspension process and the polymerization process. is there. The size of microspheres generated under ultrasonic irradiation changes depending on the frequency of ultrasonic waves. Generally, in the case of ultrasonic waves in the low frequency region, for example, 100 KHz or less, fine microspheres with a particle size of 0.1 to several tens of μm. Is obtained. In this case, if the agitation is performed only by mechanical agitation without the combined use of ultrasonic radiation, large particles having a particle size exceeding 300 μm are generated.

In the method of the present invention, mechanical stirring is used in addition to ultrasonic radiation, and as the stirring speed at this time,
A range of 200-600 rpm is used.

Polymerization of the monomer is usually carried out at a temperature of 60 to 80 ° C.
It is performed by heating for 4 hours or more.

The magnetic microspheres thus obtained are insoluble in the polymer forming the microspheres, and after removing the unreacted monomer, the polymerization initiator and the excess dispersant by washing with a solvent that dissolves the monomer, It may be dispersed in water to give a suspension, or it may be dried and taken out as a powder. Further, in order to obtain microspheres having a uniform particle size, a normal classification operation by centrifugation or filtration using a mesh may be performed.

EFFECTS OF THE INVENTION According to the method of the present invention, since the ferromagnetic fine particles are made hydrophobic and dispersed in the monomer, the affinity between the fine particles and the polymer molecular chain is high, and as a result, the ferromagnetic fine particles inside the microsphere are dispersed. It is possible to manufacture a chemically stable magnetic microsphere that is not easily affected by the pH of the solvent.

In addition, by irradiating low-frequency ultrasonic waves in the process of suspending the monomer in the aqueous solution or in the process of polymerization, it was not possible to obtain by conventional suspension polymerization. Microspheres having a size of 0.1 to several tens of μm can be obtained.

The magnetic microspheres obtained by the method of the present invention have excellent dispersibility in various aqueous solutions, are chemically stable, and have excellent magnetic responsiveness, and their particle size is adjusted to a fine range of 0.1 to several tens of μm. Therefore, it is particularly useful as a magnetic filler for various columns and a magnetic carrier for diagnostic reagents.

EXAMPLES Next, the present invention will be described in more detail with reference to examples.

Comparative Example 30 g of styrene monomer purified by vacuum distillation was used to wash hydrophobic magnetite fine particles [Ferri colloid HC-50 (trade name, manufactured by Taiho Kogyo Co., Ltd.)] having a particle size of about 150Å with acetone, and then dried to obtain a powder. 1 g) was added and dispersed by ultrasonic waves for 1 hour. A monomer stock solution was prepared by dissolving 0.1 g of benzoyl peroxide in this solution.

On the other hand, in 70 g of distilled water, Poval PVA-117 (trade name,
Kuraray) 0.50g and Popal PVA-217 (trade name,
0.02 g (manufactured by Kuraray Co., Ltd.) was dissolved to obtain an aqueous dispersion medium solution.

The monomer stock solution and the aqueous dispersion medium solution thus obtained were placed in a reaction vessel and stirred at 400 rpm for 2 hours while blowing argon gas.

Next, while the reaction tank was kept at 80 ° C., the mixture was stirred at 400 rpm for 5 hours, and then gradually cooled to room temperature while continuing stirring. Next, about 600 ml of the resulting microsphere suspension
It was poured into methanol and left for a whole day and night while stirring gently. This solution was filtered with a filter paper, the recovered microspheres were dispersed in distilled water, and then classified using a stainless steel mesh to obtain the target magnetic microspheres.

Example 1 3 g of hydrophobized magnetite was added to 30 g of purified styrene monomer and dispersed for 1 hour by ultrasonic waves at 45 KHz. 0.3 g of azobis dimethyl valeronitrile was dissolved in this solution to make a stock solution of monomer, while 70 g of distilled water was added to Poval PV.
A-1170.5 g and Poval PVA-2170.02 g were dissolved to obtain a dispersion medium aqueous solution.

Put the dispersion medium aqueous solution thus obtained in the reaction tank,
The mixture was stirred at 400 rpm while radiating an ultrasonic wave of 45 KHz, the monomer stock solution was added to this solution, and the mixture was dispersed at room temperature for 2 hours while blowing an argon gas.

Then keep the reaction vessel at 65 ° C and continue to radiate ultrasonic waves.
The mixture was stirred at 400 rpm for 5 hours and then gradually cooled to room temperature. The obtained suspension of microspheres was poured into about 600 ml of methanol, and the mixture was allowed to stand overnight with agitation. This solution was filtered with a filter paper, the recovered microspheres were dispersed in distilled water, and then classified with a stainless steel mesh and a centrifuge to obtain the target magnetic microspheres.

Example 2 After treating as in Example 1 except that the magnetite / monomer charge was changed to 20%, the product was treated as in Example 1.
Washing and classification were carried out in the same manner as in 1. to obtain magnetic microspheres.

Example 3 After treating in the same manner as in Example 1 except that the magnetite / monomer charging rate was changed to 30%, the product was treated as in Example 1.
Washing and classification were carried out in the same manner as in 1. to obtain magnetic microspheres.

Example 4 In Example 1, the magnetite / monomer charge was set to 1.
The monomer stock solution was prepared by changing the amount to 5 g / 30, and the stirring speed in the aqueous dispersion medium solution was set to 200 rpm, and the dispersion was carried out for 1 hour while radiating an ultrasonic wave of 45 KHz. Then, stop the ultrasonic radiation, keep the reactor temperature at 65 ℃, 200rpm
After stirring for 5 hours, the mixture was gradually cooled to room temperature.

The obtained microspheres were washed and classified in the same manner as in Example 2 to obtain magnetic microspheres.

Example 5 0.1 g of azobisdimethylvaleronitrile was dissolved,
10 g of the purified styrene monomer was added to 90 g of an aqueous solution containing the dispersant having the same concentration as in Example 2, and the mixture was dispersed for 2 hours at a stirring speed of 400 rpm while radiating an ultrasonic wave of 45 KHz.

Then, the ultrasonic radiation was stopped, the temperature of the reaction vessel was kept at 65 ° C., the mixture was stirred at 400 rpm for 5 hours, and then gradually cooled to room temperature.

The obtained microspheres were washed and classified in the same manner as in Example 1 to obtain magnetic microspheres.

Example 6 Example 1 was repeated except that 20 KHz ultrasonic waves were used and the dispersion treatment time before polymerization was changed to 4 hours.
A magnetic microsphere was obtained in the same manner as in.

Example 7 In Example 1, except that the ultrasonic wave of 38 KHz is used,
A magnetic microsphere was obtained in the same manner as in Example 1.

The main properties of the magnetic microspheres thus obtained are shown in the attached table.

The content of magnetite in the particles was determined by iron analysis by atomic absorption. For magnetic sedimentation time, place a test tube with an inner diameter of 6 mm on a 1200 G magnet, inject a 5% magnetic microsphere suspension aqueous solution to a height of 5 cm, and measure the time until all microspheres settle. did. However, the value in the table is the spontaneous sedimentation time in the absence of magnetism.

Claims (1)

[Claims] 1. A polymerization initiator is added to a mixture in which ferromagnetic particles which have been subjected to a hydrophobic treatment are uniformly dispersed in a monomer,
This is a microsuspension which is generated by performing low-frequency ultrasonic irradiation in the suspension process or both in the suspension process and the polymerization process in dispersing and suspending it in an aqueous solution containing a dispersion stabilizer while heating and polymerizing it. A method for producing magnetic microspheres having a fine particle size, which comprises finely controlling the particle size of the fair.