JP4602814B2 - Vinyl polymer particles encapsulating a water-soluble fluorescent dye and a method for producing the same. - Google Patents

Description

  The present invention relates to vinyl polymer particles encapsulating a water-soluble fluorescent dye and a method for producing the same.

  Currently, fine particles that emit fluorescence are widely used in various fields. Among them, they play an important role as fluid tracer tracers, flow-site quality control standard particles, and immunodiagnostic drug carriers.

Conventionally, as a method for producing such fluorescent fine particles,
(1) A method of dyeing polymer particles by immersing them in a fluorescent dye bath,
(2) A method of forming a layer having a functional group that reacts with a fluorescent dye on the surface of the polymer particles, and then dyeing by immersing in a fluorescent dye bath (for example, US Pat. No. 4,774,189 (Patent Document 1)) US Pat. No. 5,194,300 (described in Patent Document 2))
(3) A method in which a fluorescent dye is infiltrated into the interior by swelling the polymer particle in a dye bath in which a hydrophobic fluorescent dye is dissolved in an organic solvent that swells but does not dissolve the polymer particle (for example, Japanese Patent Laid-Open No. 2001-520323) (Described in Patent Document 3),
(4) Method of forming phosphor (fluorescent dye) -containing resin particles by suspension polymerization in which a monomer composition in which a phosphor or fluorescent dye is added to a monomer is dispersed in a medium and polymerization is performed, and the phosphor and fluorescent pigment used And a surface treatment method for improving the dispersibility of the fluorescent dye in the monomer composition (for example, described in JP-A-9-176366 (Patent Document 4))
Etc. are known.

US Pat. No. 4,774,189 US Pat. No. 5,194,300 JP-T-2001-520323 JP-A-9-176366

However, the conventional methods as described above have the following problems.
That is, in the method (1), although the dyeing method is very simple, the fluorescent dye is merely physically adsorbed on the surface layer of the polymer particles, and the fixing of the fluorescent dye is difficult. In use, there is a problem that the fluorescent dye gradually deviates and fading occurs.
In the method (2), in addition to the production steps necessary for producing the polymer particles, a step of forming a layer having a functional group that reacts with the dye on the surface of the polymer particles, and then a fluorescent dye bath is used. A dyeing process is required, the manufacturing process is complicated, and the dye is used only for the surface layer. There is a problem that it deviates and fading occurs.
In the method (3), it is necessary to use hydrophobic fluorescent dyes that are few in kind and relatively weak in fluorescence, and further, it is necessary to use an organic solvent for dyeing, so that it must be recovered and disposed of. There's a problem.
Furthermore, since the production methods (1), (2) and (3) all require a fluorescent dye bath, the common problem with these is that the use efficiency of the fluorescent dye is very poor and unnecessary fluorescence is used. When washing off the dye, it is necessary to repeat washing, and the process is complicated and time consuming, and the addition to the environment in wastewater treatment and the like is very large.

  On the other hand, the present inventors tried to obtain vinyl polymer particles uniformly containing a water-soluble fluorescent dye by the method of (4). Specifically, Patent Document 4 (Japanese Patent Laid-Open No. 9-176366) described above. In accordance with the procedure described in Example 2 of the publication), the fluorescent white dye (Ciba Geigy, Ubitex OB, hydrophobic fluorescent dye) was replaced with rhodamine B, which is a water-soluble dye, and polymerization was attempted. Was hardly dissolved in a polymerizable composition comprising styrene as a polymerizable vinyl monomer and divinylbenzene as a crosslinking agent, and good water-soluble fluorescent dye-containing resin particles could not be obtained.

Further, as the method (4), as described in the text of Patent Document 4, the surface treatment is performed to improve the dispersibility of the fluorescent dye in the polysynthetic composition, and then the water treatment is performed in the same manner. In order to obtain vinyl polymer particles containing water-soluble fluorescent dye uniformly, it has polar groups or reactive groups necessary for surface treatment of water-soluble fluorescent dye. As the amount of the polymerizable monomer used increased, the solubility of the polymerizable monomer composition containing them in water increased.
Specifically, the fluorescent dye and the unreacted polymerizable monomer migrate into the aqueous dispersion medium, and uniform and fine oil droplets cannot be formed due to poor suspension, resulting in deformation of the particles. In addition, problems such as coarsening and inability to complete polymerization occurred. As a result, vinyl polymer particles in which the water-soluble fluorescent dye was uniformly encapsulated could not be obtained.

  The object of the present invention is that, for example, when used as a tracer for a fluid visualization device, a standard particle for flow site accuracy control, a carrier for an immunodiagnostic drug, or the like, a fading change due to deviation from a fluorescent dye hardly occurs. An object of the present invention is to produce vinyl polymer particles uniformly containing a water-soluble fluorescent dye that has a low environmental impact due to the outflow of dye and the use of an organic solvent.

  As a result of intensive studies by the present inventors to solve the above problems, a vinyl monomer having a certain solubility in water and having a reactive group that binds well to a water-soluble fluorescent dye is used. The vinyl monomer and the water-soluble fluorescent dye are sufficiently bonded to each other, and the water-soluble fluorescent dye can be present uniformly and stably in the polysynthetic monomer composition. It was. Furthermore, when the polymerizable monomer is subjected to suspension polymerization in an aqueous solvent dispersion medium, an acidic organic modified phosphoric acid compound is contained in the polymerizable monomer, thereby allowing a water-soluble fluorescent dye and It has been found that the vinyl monomer having a reactive group does not migrate into an aqueous dispersion medium, produces fine oil droplets of a stable polymerizable monomer composition, and does not inhibit polymerization.

That is, the present invention is 20 solubility in water 100ml at ℃ is less 50g and methacrylic acid 2 as a vinyl monomer consisting of acrylic acid or methacrylic acid derivative having at least one of a carboxyl group or a hydroxyl group -Containing at least one of hydroxybutyl and 2-methacryloyloxyethyl succinic acid, rhodamine dye as water-soluble fluorescent dye , and lauryl phosphate or caprolactone EO-modified phosphate dimethacrylate as acidic organic modified phosphate compound Preparation of vinyl polymer particles encapsulating a water-soluble fluorescent dye, wherein the polymerizable monomer composition is prepared, the polymerizable monomer composition is suspended in an aqueous dispersion medium and polymerized Provide a method.

According to the method for producing vinyl polymer particles according to the present invention, from acrylic acid or methacrylic acid derivative having a solubility in 100 ml of water at 20 ° C. of 50 g or less and having at least one of carboxyl group or hydroxyl group. By adopting at least one of 2-hydroxybutyl methacrylate or 2-methacryloyloxyethyl succinic acid as the vinyl monomer, a rhodamine dye is used as a water-soluble fluorescent dye in the vinyl monomer. It is possible to obtain fluorescent polymer particles in which a water-soluble fluorescent dye is firmly bonded in a polymer by suspension polymerization in an aqueous dispersion medium. In addition, when the polymerizable monomer composition is subjected to suspension polymerization in an aqueous dispersion medium, lauryl phosphoric acid or caprolactone EO-modified phosphate dimethacrylate is present as the acidic organic-modified phosphate compound in the polymerizable monomer composition. By doing so, it is possible to prevent the water-soluble fluorescent dye and the vinyl monomer from migrating into the aqueous dispersion medium without adversely affecting the polymerization of the monomer, and extremely close to a spherical shape. Fluorescent fine particles can be obtained.

In the production method according to the present invention, preferably the amount of an acidic organic modified phosphoric acid compound, relative to the vinyl monomer of 100 parts by weight, it shall be the 0.01 to 5 parts by weight.

Furthermore, in the production method according to the present invention, preferably, the vinyl monomer and the water-soluble fluorescent dye are uniformly mixed, and then styrene is further mixed as another vinyl monomer.

Further, the present invention is 20 solubility in water 100ml at ℃ is less 50g and methacrylic acid 2 as a vinyl monomer consisting of acrylic acid or methacrylic acid derivative having at least one of a carboxyl group or a hydroxyl group -Containing at least one of hydroxybutyl and 2-methacryloyloxyethyl succinic acid, rhodamine dye as water-soluble fluorescent dye , and lauryl phosphate or caprolactone EO-modified phosphate dimethacrylate as acidic organic modified phosphate compound A vinyl polymer particle containing a water-soluble fluorescent dye, wherein the polymerizable monomer composition is prepared, suspended in an aqueous dispersion medium and polymerized. I will provide a.

According to the present invention, there is no fading change due to the deviation of the water-soluble fluorescent dye, and there is little environmental load caused by the outflow of the water-soluble fluorescent dye and the use of an organic solvent during the production, and the vinyl that uniformly contains the water-soluble fluorescent dye. System polymer particles can be obtained.
Therefore, the present invention is extremely suitable for applications such as a fluid visualization device tracer, flow site accuracy control standard particles, and an immunodiagnostic drug carrier.

The present invention is a method for producing vinyl polymer particles uniformly containing a water-soluble fluorescent dye by suspension polymerization, wherein the solubility in 100 ml of water at 20 ° C. is 50 g or less, and among carboxyl groups or hydroxyl groups. A water-based dispersion of a polymerizable monomer composition containing a vinyl monomer comprising at least one of acrylic acid or methacrylic acid derivatives, a water-soluble fluorescent dye, and an acidic organically modified phosphoric acid compound It is suspended in a medium and polymerized.

Hereinafter, the present invention will be described in more detail.
The vinyl monomer used in the present invention has acrylic acid or methacrylic acid having a solubility in 100 ml of water at 20 ° C. (hereinafter simply referred to as solubility) of 50 g or less and having at least one of a carboxyl group or a hydroxyl group. A vinyl monomer composed of an acid derivative (hereinafter referred to as a reactive group-containing vinyl monomer). The acrylic acid or methacrylic acid derivative may have a glycidyl group in addition to the reactive group.
By using such a reactive group-containing vinyl monomer, the water-soluble fluorescent dye can be sufficiently bound, and the water-soluble fluorescent dye is present uniformly and stably in the polymerizable monomer composition. be able to.
If the solubility is larger than 50 g, the fluorescent dye and the unreacted polymerizable monomer are transferred to the aqueous dispersion medium, and it becomes difficult to form fine oil droplets with a uniform particle diameter due to poor suspension.

As the reactive group-containing vinyl monomer, at least one of 2-hydroxybutyl methacrylate [solubility 5.8 g] or 2-methacryloyloxyethyl succinic acid [1.9 g] is used. Further, the reactive group-containing vinyl monomer, things have preferable solubility is 0.5 to 20 g. Furthermore, as the reactive group-containing vinyl monomer, other acrylic acid or methacrylic acid derivatives can be used together with the above-mentioned substances. Examples of such acrylic acid or methacrylic acid derivatives include 2-hydroxypropyl methacrylate. [same 15.5 g], there may be mentioned acrylic acid or methacrylic acid derivatives such as main methacrylic acid glycidyl [the 2.6 g], may be used singly or in combination.

  Here, the solubility in 100 ml of water at 20 ° C. means that a constant amount of distilled water and a supersaturated amount of a reactive group-containing vinyl monomer are added to a separating funnel at 20 ° C. and shaken for 1 hour. The aqueous layer is separated and diluted, and the amount of the reactive group-containing vinyl monomer contained therein is calculated from the value measured by HPLC.

As the water-soluble fluorescent dye used in the present invention, a rhodamine dye is used. Of these, rhodamine B, rhodamine 6G and the like can be preferably used. Further, as the water-soluble fluorescent dye, other water-soluble fluorescent dyes that can be dissolved in the reaction group-containing vinyl monomer substantially uniformly and bonded well together with the above substances can be used. the water-soluble fluorescent dye, for example, stilbene-based dyes, methylene blue, fluorescein, Ru and the like can be illustrated fluorescein derivatives such as uranine or erythrosine.

  The amount of the water-soluble fluorescent dye used depends on the type of the water-soluble fluorescent dye used, but the water-soluble fluorescent dye is 0.005 per 100 parts by weight of the reactive group-containing vinyl monomer. -20 parts by weight is preferable, and 0.01-10 parts by weight is more preferable. If the amount of water-soluble fluorescent dye used is less than 0.005 parts by weight, the resulting polymer particles may not have a sufficient degree of coloration. The increased effect is not so much seen, there is a possibility that undissolved matter is precipitated, and a polymerizable monomer composition containing a reactive group-containing vinyl monomer and a water-soluble fluorescent dye (hereinafter, polymerizable monomer). This is not preferred because there is a risk of inhibiting the polymerization of the composition).

In addition, vinyl monomers other than the reactive group-containing vinyl monomers can be used in combination of one or more, as long as the effects of the present invention are not hindered.
The vinyl monomer other than the reactive group-containing vinyl monomer that can be used in the present invention is not particularly limited, and various commonly used vinyl monomers may be used. it can. For example, styrene, o-methylstyrene, m-methylstyrene, p-methylstyrene, p-ethylstyrene, 2,4-dimethylstyrene, pn-butylstyrene, p-tert-butylstyrene, pn-hexyl Styrene, pn-octyl styrene, pn-nonyl styrene, pn-decyl styrene, pn-dodecyl styrene, n-methoxy styrene, p-phenyl styrene, p-chloro styrene, 3,4-di Styrene and its derivatives such as chlorostyrene, vinyl halides such as vinyl chloride, vinylidene chloride, vinyl bromide and vinyl fluoride, vinyl esters such as vinyl acetate, vinyl propionate, vinyl benzoate and vinyl butyrate, acrylic acid Methyl, ethyl acrylate, n-butyl acrylate, isobutyl acrylate, acrylic Propyl, n-octyl acrylate, dodecyl acrylate, 2-ethylhexyl acrylate, stearyl acrylate, 2-chloroethyl acrylate, phenyl acrylate, methyl α-chloroacrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate , N-butyl methacrylate, isobutyl methacrylate, n-octyl methacrylate, dodecyl methacrylate, 2-ethylhexyl methacrylate, stearyl methacrylate, phenyl methacrylate, dimethylaminoethyl acrylate, dimethylaminoethyl methacrylate, diethylaminoacrylate Α-methylene aliphatic monocarboxylic acid esters such as ethyl, diethylaminoethyl methacrylate, acrylonitrile, methacrylonitrile, acrylamide, methacrylamide It can be used such as acrylic acid or methacrylic acid derivatives.

  Further, vinyl ethers such as vinyl methyl ether, vinyl ethyl ether, vinyl isobutyl ether, vinyl ketones such as vinyl methyl ketone, vinyl hexyl ketone, methyl isopropenyl ketone, N-vinyl pyrrole, N-vinyl carbazole, N-vinyl indole, N-vinyl compounds such as N-vinylpyrrolidone, vinyl naphthalene salts, and the like can be used alone or in combination of two or more in a range not impeding the effects of the present invention.

  A compound having two or more polymerizable double bonds may be added to the polymerizable monomer composition as a crosslinking agent. Examples of the crosslinking agent include aromatic divinyl compounds such as divinylbenzene, divinylnaphthalene and derivatives thereof, and diethylenic carboxylic acid esters such as ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol triacrylate, and trimethylolpropane triacrylate. , N, N-divinylaniline, divinyl ether, divinyl sulfite, and other divinyl compounds and compounds containing three or more vinyl groups can be used, and these can be used alone or in combination of two or more. .

  The polymerizable monomer composition may be polymerized in the presence of an inorganic pigment or the like to form pigment-containing resin particles. Inorganic pigments include titanium oxide, zinc oxide, zirconium oxide, magnesium oxide, silica, calcium carbonate, magnesium carbonate, barium sulfate, barium silicate, calcium silicate, magnesium silicate, calcium phosphate, hydroxyapatite, zeolite, alumina, talc , Mica, bentonite, kaolin, sericite and the like.

  In order to accelerate the polymerization of the vinyl monomer, a polymerization initiator may be used. As the polymerization initiator, a known polymerization initiator that is soluble in a vinyl monomer used for suspension polymerization of a vinyl monomer can be used. Examples of the polymerization initiator include benzoyl peroxide, lauroyl peroxide, octanoyl peroxide, orthochlorobenzoyl peroxide, orthomethoxybenzoyl peroxide, methyl ethyl ketone peroxide, diisopropyl peroxydicarbonate, cumene hydroperoxide, cyclohexanone peroxide. , Peroxide initiators such as t-butyl hydroperoxide and diisopropylbenzene hydroperoxide, 2,2′-azobisisobutyronitrile, 2,2′-azobis (2,4-dimethylvaleronitrile), 2,2'-azobis (2,3-dimethylbutyronitrile), 2,2'-azobis (2-methylbutyronitrile), 2,2'-azobis (2,3,3-trimethylbutyronitrile) 2,2′-azobis (2-isopro Rubutyronitrile), 1,1′-azobis (cyclohexane-1-carbonitrile), 2,2′-azobis (4-methoxy-2,4-dimethylvaleronitrile), 2- (carbamoylazo) isobutyronitrile, 4 4,4'-azobis (4-cyanovaleric acid), dimethyl-2,2'-azobisisobutyrate and the like. Among these, benzoyl peroxide, lauroyl peroxide, 2,2′-azobisisobutyronitrile, and 2,2′-azobis (2,4-dimethylvaleronitrile) are preferable. A polymerization initiator may be used independently and may be used in combination of 2 or more types. The use ratio is preferably about 0.01 to 2 parts by weight with respect to 100 parts by weight of the total amount of the reactive group-containing vinyl monomer and other vinyl monomers used together.

  In the present invention, suspension polymerization of the polymerizable monomer composition is performed in a state where the polymerizable monomer composition contains an acidic organic modified phosphoric acid compound. Transfer of water-soluble fluorescent dye and unreacted polymerizable monomer to aqueous dispersion medium when suspended in aqueous dispersion medium by including acidic organic modified phosphoric acid compound in polymerizable monomer composition In addition to prevention, fine oil droplets of a stable polymerizable monomer composition can be generated.

As such an acidic organic modified phosphoric acid compound, lauryl phosphoric acid or caprolactone EO modified phosphoric acid dimethacrylate is used. Further, as the acidic organic modified phosphoric acid compound, for example, phosphorous acid monoester or phosphorous acid diester, phosphoric acid monoester, and phosphoric acid diester can be used together with the above substances . These phosphorous acid monoester or phosphite diesters, phosphoric monoesters, although phosphodiester is not particularly limited, polyoxyethylene (1) lauryl ether phosphate, dipolyoxyethylene (2) alkyl ether phosphates, Jipori Oxyethylene (4) alkyl ether phosphoric acid, dipolyoxyethylene (6) alkyl ether phosphoric acid, dipolyoxyethylene (8) alkyl ether phosphoric acid, dipolyoxy ether (4) nonylphenyl ether phosphoric acid , 2 -methacrylic acid acryloyloxyethyl ethyl acid phosphate and the like Ru mentioned.

  Moreover, the addition amount of the acidic organic modified phosphoric acid compound is preferably 0.01 to 5 parts by weight, and 0.01 to 3 parts by weight with respect to 100 parts by weight of the reactive group-containing vinyl monomer. Is more preferable.

In suspension polymerization, a suspension stabilizer can be added to the aqueous dispersion medium in order to stabilize the suspended particles.
The suspension stabilizer is not limited as long as the desired resin particles can be obtained. For example, phosphates such as calcium phosphate, magnesium phosphate, aluminum phosphate and zinc phosphate, calcium pyrophosphate , Pyrophosphates such as magnesium pyrophosphate, aluminum pyrophosphate, zinc pyrophosphate, calcium carbonate, magnesium carbonate, calcium hydroxide, magnesium hydroxide, aluminum hydroxide, calcium metasilicate, calcium sulfate, barium sulfate, colloidal silica, etc. Examples thereof include a dispersion stabilizer of a water-soluble inorganic compound. Among them, it is preferable to use an inorganic compound that can be easily dissolved and removed by adjusting the pH of the system after the completion of polymerization. For example, it is preferable to use tribasic calcium phosphate, magnesium pyrophosphate, calcium pyrophosphate, or colloidal silica produced by a metathesis generation method, because target resin particles can be obtained more stably.

In addition, a surfactant such as an anionic surfactant, a cationic surfactant, an amphoteric surfactant, or a nonionic surfactant may be added to the aqueous dispersion medium.
Examples of anionic surfactants include fatty acid oils such as sodium oleate and castor oil potassium, alkyl sulfate salts such as sodium lauryl sulfate and ammonium lauryl sulfate, alkylbenzene sulfonates such as sodium dodecylbenzenesulfonate, and alkylnaphthalene sulfonates. , Alkane sulfonate, dialkyl sulfosuccinate, naphthalene sulfonic acid formalin condensate, polyoxyethylene alkyl phenyl ether sulfate, polyoxyethylene alkyl sulfate, and the like.

  The suspension stabilizer can be used by appropriately adjusting the composition and the amount of use so that the vinyl polymer particles obtained have a predetermined particle size. The amount of the suspension stabilizer used is usually preferably 0.1 to 30 parts by weight and more preferably 0.5 to 20 parts by weight with respect to 100 parts by weight of the polymerizable monomer composition. Moreover, 0.01-5 weight part is preferable with respect to 100 weight part of polymerizable monomer compositions, and, as for the said surfactant, 0.05-3 weight part is more preferable.

  The vinyl polymer particles encapsulating the water-soluble fluorescent dye of the present invention can be suitably used as a fluid visualization device tracer, a flow particle quality control standard particle, or an immunodiagnostic carrier, in which case, the average particle diameter Is preferably 1 to 100 μm, more preferably 3 to 20 μm.

Next, a preferred production procedure for the vinyl polymer particles according to the present invention will be described.
First, a water-soluble fluorescent dye is dissolved in a reactive group-containing vinyl monomer in advance, and after sufficiently binding, another vinyl monomer and a polymerization initiator are added and mixed as necessary. Then, an acidic organic modified phosphoric acid compound is mixed to prepare a hydrophobic polymerizable monomer composition (hereinafter also referred to as an oil phase). That is, before mixing other vinyl monomer, polymerization initiator, or acidic organic modified phosphoric acid compound, the water-soluble fluorescent dye and the reactive group-containing vinyl monomer are sufficiently stirred and mixed in advance. It is preferable. Thus, the water-soluble fluorescent dye can be sufficiently dissolved in the reactive group-containing vinyl monomer, and the water-soluble fluorescent dye and the reactive group of the vinyl monomer can be bonded.

  Furthermore, a suspension stabilizer, a surfactant and the like are preliminarily dispersed in an aqueous medium (for example, water, a mixture of water and a water-soluble alcohol) to form an aqueous phase, and then the oil phase and the aqueous phase are mixed. It is preferable that the composition containing the vinyl monomer is dispersed in the aqueous medium by stirring. The average particle diameter of the vinyl polymer particles can be appropriately adjusted by adjusting the mixing condition and stirring condition of the oil phase and the aqueous phase.

  In order to disperse the oil phase in the water phase with fine droplets, for example, a method using a stirring force such as a propeller blade, a method using a general homogenizer that is a disperser using a high shear force composed of a rotor and a stator. Examples thereof include a method using an ultrasonic disperser, a method using a high-pressure disperser utilizing a collision force against a machine wall such as a microfluidizer or a nanomizer, or a collision force between droplets. In order to make the average particle diameter of the polymer particles 1 to 100 μm, it is preferable to set the median diameter of the oil droplets to about 1 to 100 μm by the dispersion method.

  Next, the polymerization reaction can be started by mixing the oil phase and the aqueous phase and then raising the temperature while stirring. The stirring speed at this time should just be a grade which can prevent the floating of an oil drop and sedimentation of the particle | grains after superposition | polymerization. The water phase is used in an amount of 100 to 1000 parts by weight with respect to 100 parts by weight of the oil phase. The polymerization start temperature is preferably 40 to 90 ° C. And it is preferable to make it superpose | polymerize generally about 1 to 10 hours, hold | maintaining at this temperature. Thereafter, the polymerization temperature is preferably about 95 to 120 ° C., and the polymerization reaction is more preferably completed in about 0.1 to 5 hours. After completion of the polymerization reaction, the reaction mixture is cooled, and if necessary, filtered and dried to obtain vinyl polymer particles.

  The average particle diameter of the vinyl polymer particles can be adjusted by adjusting the mixing ratio of the oil phase and the aqueous phase, the addition amount of the suspension stabilizer, the stirring conditions, the dispersion conditions, and the like. The average particle diameter of the vinyl polymer particles is appropriately selected according to the use, but according to the production method of the present invention, polymer particles having an average particle diameter of about 1 to 100 μm can be easily obtained. If the average particle diameter of the polymer particles is 1 to 100 μm, for example, when used as a tracer for a fluid visualization device, the particles can be easily visualized, and the followability of the particles to the fluid becomes good. It becomes possible to visualize the fluid.

EXAMPLES Hereinafter, although this invention is demonstrated in detail based on an Example, this invention is not limited by these Examples.
In the following examples and comparative examples, the average particle size is a value measured with Multisizer II (Beckman Coulter, Inc.). The measuring method was measured according to Reference MANUAL FOR THE COULTER MULTISIZER (1987) published by Coulter Electronics Limited.

Example 1
After adding 3.0 g of rhodamine B which is a water-soluble fluorescent dye to 97 g of 2-methacryloyloxyethyl succinic acid (Kyoeisha, light ester HOMS solubility 1.9 g) which is a reactive group-containing vinyl monomer, a mechanical stirrer is used. And stirred for 5 hours. The resulting solution dissolved Rhodamine B uniformly, and no dissolution residue was observed.
To this solution, 1.0 g of azobisisobutyronitrile as a polymerization initiator and 1.5 g of caprolactone EO-modified phosphoric dimethacrylate (Nippon Kayaku Co., Ltd., KAYAMER PM-21) as an acidic organic modified phosphoric acid compound are added to form a polymerizable composition. A product was prepared.
Next, this polymerizable composition was put into 300 g of water in which 0.02% by weight of sodium dodecylbenzenesulfonate prepared in advance and 2.5% by weight of magnesium pyrophosphate were dispersed, and a homogenizer (manufactured by Kinematica Co., Ltd., Polytron). ) And finely dispersed by stirring at 10,000 rpm for 5 minutes. This finely dispersed suspension was added to a 500 mL autoclave and thoroughly purged with nitrogen. Then, the stirring speed was maintained at 300 rpm, and suspension polymerization was performed at 60 ° C. for 3 hours. The temperature was then raised to 100 ° C. and heated at 100 ° C. for 1 hour to complete the polymerization.
Subsequently, after the polymerization-completed suspension was cooled to room temperature, 10 ml of a 20% hydrochloric acid solution was added to dissolve magnesium pyrophosphate as a suspension stabilizer, and then solid-liquid separation and water washing were repeated.
At this time, coloring due to the elution of rhodamine B was not substantially observed in the separated hydrochloric acid acidic solution and the subsequent aqueous solution.
After solid-liquid separation, it was dried at 60 ° C. for 24 hours to obtain about 92 g of polymer particles of the present invention. The average particle diameter of the obtained polymer particles was 4.7 μm, and when observed with a transmission microscope, it was recognized that the particles were uniformly colored red, and no uncolored particles were observed.
Further, 2 g of the obtained polymer particles were placed in a 100 ml beaker, and again a solution dispersed in 50 g of water was irradiated with black light. As a result, the solution showed a fluorescent dark orange color.

(Example 2)
After adding 2.0 g of rhodamine B, which is a water-soluble fluorescent dye, to 48 g of 2-methacryloyloxyethyl succinic acid (Kyoeisha, Light Ester HOMS, solubility 1.9 g) which is a reactive group-containing vinyl monomer, a mechanical stirrer is added. The mixture was stirred for 5 hours. The resulting solution dissolved Rhodamine B uniformly, and no dissolution residue was observed.
In this solution, 30 g of styrene and 20 g of divinylbenzene as other vinyl monomers, 1.0 g of azobisisobutyronitrile as a polymerization initiator, caprolactone EO-modified phosphate dimethacrylate (Nippon Kayaku Co., Ltd.) as an acidic organic modified phosphate compound , KAYAMER PM-21) 1.0 g was added to prepare a polymerizable composition.
Next, the polymerizable composition was put into 300 g of water in which 0.02% by weight of sodium dodecylbenzenesulfonate and 2% by weight of magnesium pyrophosphate were dispersed in advance, and the homogenizer (manufactured by Kinematica, Polytron) was added. And then finely dispersed by stirring at 8,500 rpm for 5 minutes. This finely dispersed suspension was added to a 500 mL autoclave and thoroughly purged with nitrogen. Then, the stirring speed was maintained at 300 rpm, and suspension polymerization was performed at 60 ° C. for 3 hours. The temperature was then raised to 100 ° C. and heated at 100 ° C. for 1 hour to complete the polymerization.
Subsequently, after the polymerization-completed suspension was cooled to room temperature, 10 ml of a 20% hydrochloric acid solution was added to dissolve magnesium pyrophosphate as a suspension stabilizer, and then solid-liquid separation and water washing were repeated.
At this time, coloring due to the elution of rhodamine B was not substantially observed in the separated hydrochloric acid acidic solution and the subsequent aqueous solution.
After solid-liquid separation, it was dried at 60 ° C. for 24 hours to obtain about 90 g of polymer particles of the present invention. The average particle diameter of the obtained polymer particles was 6.9 μm, and as observed with a transmission microscope, the particles were uniformly colored in red, and no uncolored particles were observed. Further, 2 g of the obtained polymer particles were placed in a 100 ml beaker, and the solution dispersed in 50 g of water was again irradiated with black light, and the solution showed a fluorescent dark orange color.

(Example 3)
After adding 0.3 g of rhodamine B, which is a water-soluble fluorescent dye, to 19.7 g of 2-hydroxybutyl methacrylate (Kyoeisha, light ester HOB, solubility 5.8 g), which is a reactive group-containing vinyl monomer, a mechanical stirrer is used. And stirred for 5 hours. The resulting solution dissolved Rhodamine B uniformly, and no dissolution residue was observed. 5 g of this solution was collected, and further 51.8 g of styrene and 3.0 g of divinylbenzene as the other vinyl monomers, 40 g of barium sulfate as the inorganic pigment, 1.2 g of azobisisobutyronitrile as the polymerization initiator, acidic organic A polymerizable composition was prepared by adding 1.5 g of caprolactone EO-modified phosphate dimethacrylate (Nippon Kayaku Co., Ltd., KAYAMER PM-21) as a modified phosphate compound.
Next, the polymerizable composition was added to 300 g of water in which 0.02% sodium dodecylbenzenesulfonate and 2% magnesium pyrophosphate were dispersed in advance, and the mixture was stirred at 3,500 rpm for 5 minutes with a homogenizer. And finely dispersed. This finely dispersed suspension was added to a 500 mL autoclave and thoroughly purged with nitrogen. Then, the stirring speed was maintained at 300 rpm, and suspension polymerization was performed at 60 ° C. for 3 hours. The temperature was then raised to 100 ° C. and heated at 100 ° C. for 1 hour to complete the polymerization.
Subsequently, after the polymerization-completed suspension was cooled to room temperature, 10 ml of a 20% hydrochloric acid solution was added to dissolve magnesium pyrophosphate as a suspension stabilizer, and then solid-liquid separation and water washing were repeated.
At this time, coloring due to the elution of rhodamine B was not substantially observed in the separated hydrochloric acid acidic solution and the subsequent aqueous solution.
After solid-liquid separation, it was dried at 60 ° C. for 24 hours to obtain about 92 g of polymer particles of the present invention. The average particle diameter of the obtained polymer particles was 27.6 μm, and as observed with a transmission microscope, the particles were uniformly pink colored, and no uncolored particles were observed. Further, 2 g of the obtained polymer particles were taken in a 100 ml beaker, and again a solution dispersed in 50 g of water was irradiated with black light. As a result, the solution showed a fluorescent orange color.

Example 4
After adding 0.5 g of rhodamine 6G, which is a water-soluble fluorescent dye, to 49.5 g of 2-methacryloyloxyethylsuccinic acid (Kyoeisha, Light Ester HOMS, solubility 1.9 g), which is a reactive group-containing vinyl monomer, mechanical Stirring was performed for 5 hours using a stirrer. The obtained solution uniformly dissolved rhodamine 6G, and no dissolution residue was observed.
In this solution, 30 g of styrene and 20 g of divinylbenzene as other vinyl monomers, 1.0 g of azobisisobutyronitrile as a polymerization initiator, lauryl phosphoric acid as an acidic organic modified phosphate compound (Nikko Chemical Co., Phosten HLP) 1.2 g was added to prepare a polymerizable composition.
Next, the polymerizable composition was put into 300 g of water in which 0.02% by weight of sodium dodecylbenzenesulfonate and 2% by weight of magnesium pyrophosphate were dispersed in advance, and the homogenizer (manufactured by Kinematica, Polytron) was added. The mixture was finely dispersed by stirring at 6,500 rpm for 5 minutes. This finely dispersed suspension was added to a 500 mL autoclave and thoroughly purged with nitrogen. Then, the stirring speed was maintained at 300 rpm, and suspension polymerization was performed at 60 ° C. for 3 hours. The temperature was then raised to 100 ° C. and heated at 100 ° C. for 1 hour to complete the polymerization.
Subsequently, after the polymerization-completed suspension was cooled to room temperature, 10 ml of a 20% hydrochloric acid solution was added to dissolve magnesium pyrophosphate as a suspension stabilizer, and then solid-liquid separation and water washing were repeated.
At this time, coloring due to elution of rhodamine 6G was not substantially observed in the separated hydrochloric acid acidic solution and the subsequent aqueous solution.
After solid-liquid separation, it was dried at 60 ° C. for 24 hours to obtain about 88 g of polymer particles of the present invention. The average particle diameter of the obtained polymer particles was 13.2 μm. When observed with a transmission microscope, the particles were uniformly colored in red, and no uncolored particles were observed. Further, 2 g of the obtained polymer particles were taken in a 100 ml beaker, and again a solution dispersed in 50 g of water was irradiated with black light. As a result, the solution showed a fluorescent orange color.

(Comparative Example 1)
After adding 2.0 g of rhodamine B, which is a water-soluble fluorescent dye, to 48 g of methyl methacrylate, the mixture was stirred for 5 hours using a mechanical stirrer. Although the obtained solution dissolved Rhodamine B, a dissolution residue was observed.
Next, 30 g of styrene, 20 g of divinylbenzene, 1.0 g of azobisisobutyronitrile as a polymerization initiator, and caprolactone EO-modified phosphate dimethacrylate (as an acidic organic-modified phosphate compound) were added to the solution obtained by filtering and removing this dissolution residue. A polymerizable composition was prepared by adding 1.0 g of KAYAMER PM-21) manufactured by Nippon Kayaku Co., Ltd.
Next, this polymerizable composition was put into 300 g of water in which 0.02% by weight of sodium dodecylbenzenesulfonate and 2% by weight of magnesium pyrophosphate were dispersed in advance, and the mixture was homogenized at 8,500 rpm for 5 minutes. The mixture was finely dispersed by stirring. This finely dispersed suspension was added to a 500 mL autoclave and thoroughly purged with nitrogen. Then, the stirring speed was maintained at 300 rpm, and suspension polymerization was performed at 60 ° C. for 3 hours. The temperature was then raised to 100 ° C. and heated at 100 ° C. for 1 hour to complete the polymerization.
Subsequently, after the polymerization-completed suspension was cooled to room temperature, 10 ml of a 20% hydrochloric acid solution was added to dissolve magnesium pyrophosphate as a suspension stabilizer, and then solid-liquid separation and water washing were repeated.
At this time, the separated acidic hydrochloric acid solution and the subsequent aqueous solution had a red color due to coloring with rhodamine B.
After solid-liquid separation, it was dried at 60 ° C. for 24 hours to obtain about 85 g of polymer particles. The average particle diameter of the obtained polymer particles was 5.7 μm. Further, the coloring of the obtained polymer particles is light pink and very thin. Even when 2 g of the obtained polymer particles are taken in a 100 ml beaker and the solution dispersed in 50 g of water is irradiated again with black light. Almost no fluorescence was developed.

(Comparative Example 2)
A polymerizable composition was prepared in the same manner as in Example 1 except that caprolactone EO-modified phosphate dimethacrylate was not added as the acidic organically modified phosphate compound.
Next, this polymerizable composition was put into 300 g of water in which 0.02% by weight of sodium dodecylbenzenesulfonate and 2.5% by weight of magnesium pyrophosphate were dispersed, and the homogenizer was used at 10,000 rpm. Although fine dispersion was attempted by stirring for 5 minutes, fine oil droplets of a stable polymerizable monomer composition could not be formed, and therefore polymer particles were not obtained.

(Comparative Example 3)
A polymerizable composition was prepared in the same manner as in Example 2 except that methacrylic acid having a solubility of 100 g or more was used instead of 2-methacryloyloxyethyl succinic acid.
Next, this polymerizable composition was put into 300 parts by weight of water in which 0.02% by weight of sodium dodecylbenzenesulfonate and 2% by weight of magnesium pyrophosphate were dispersed in advance, and the homogenizer was used at 8,500 rpm. Although the fine dispersion was attempted by stirring for 5 minutes, fine oil droplets of a stable polymerizable monomer composition could not be generated, and therefore polymer particles were not obtained.

  The vinyl polymer particles encapsulating the water-soluble fluorescent dye of the present invention are particularly suitable for use in the fields of a fluid visualization device tracer, a flow site quality control standard particle, an immunodiagnostic drug carrier, and the like.

Claims (4)

20 solubility in water 100ml at ℃ is less 50g and methacrylate, 2-hydroxybutyl vinyl-based monomer consisting of acrylic acid or methacrylic acid derivative having at least one of a carboxyl group or hydroxyl group or a 2 A polymerizable monomer containing at least one of methacryloyloxyethyl succinic acid, a rhodamine dye as a water-soluble fluorescent dye , and lauryl phosphate or caprolactone EO-modified phosphate dimethacrylate as an acidic organic modified phosphate compound A method for producing vinyl polymer particles encapsulating a water-soluble fluorescent dye, comprising preparing a composition, suspending the polymerizable monomer composition in an aqueous dispersion medium and polymerizing the composition.   The water-soluble fluorescent dye according to claim 1, wherein the content of the acidic organic modified phosphoric acid compound is 0.01 to 5 parts by weight with respect to 100 parts by weight of the vinyl monomer. A method for producing encapsulated vinyl polymer particles. 3. The water-soluble fluorescent dye according to claim 1 , wherein after mixing the vinyl monomer and the water-soluble fluorescent dye, styrene is further mixed as another vinyl monomer. A method for producing encapsulated vinyl polymer particles. 2-Hydroxybutyl methacrylate or 2- A polymerizable monomer containing at least one of methacryloyloxyethyl succinic acid, a rhodamine dye as a water-soluble fluorescent dye, and lauryl phosphate or caprolactone EO-modified phosphate dimethacrylate as an acidic organic modified phosphate compound Vinyl polymer particles encapsulating a water-soluble fluorescent dye, wherein the composition is prepared, the polymerizable monomer composition is suspended in an aqueous dispersion medium and polymerized.