Method for producing polymer particles

Abstract

To provide a manufacturing method of a polymer particle capable of simultaneously realizing a smaller particle diameter of the polymer particle and a reduction of an environmental load in water treatment, at a high level.SOLUTION: A manufacturing method of a polymer particle utilizes a synthesis by emulsion polymerization using a surfactant. The manufacturing method includes: a step of preparing a raw material mixture liquid containing styrene and glycidyl methacrylate; a step of mixing a surfactant to the raw material mixture liquid to prepare a dispersion mixture liquid; and a step of mixing a polymerization initiator to the dispersion mixture liquid to prepare a reaction mixture liquid. The surfactant is a polyethylene glycol ester.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a method for producing polymer particles and polymer particles produced by the method for producing the polymer particles.

Background Art

[0002] In the fields of biosensors and bioseparation, polymer particles having high reactivity with a target substance are used. As such polymer particles, particles granulated from a styrene monomer and a glycidyl methacrylate (hereinafter also referred to as GMA) monomer (hereinafter also referred to as SG particles) are widely used.

[0003] In order to obtain high reactivity with a target substance, the polymer particles preferably have a small particle size.

[0004] In SG particles, the particle size can be easily controlled by changing the charged amount of the monomer during granulation. However, in order to produce particles having a small particle size, it is necessary to reduce the charged amount of the monomer, and there is a problem that the productivity is low and the production cost is high because the amount of particles that can be produced in one step is small. Furthermore, when the charged amount of the monomer is reduced, the number of times of repeating the steps required to produce a certain amount of particles increases, resulting in a problem that the environmental load due to water treatment increases.

[0005] On the other hand, as a method for granulating polymer particles having a small particle size, a method of performing emulsion polymerization in the presence of a surfactant is known. Patent Document 1 discloses a method for producing SG particles using a non-alkylphenol ethoxylate (APE)-based polyoxyethylene alkyl ether as a surfactant as a method for solving the above problems. Patent Document 1 discloses that polymer particles having a narrowly controlled particle size distribution can be obtained by using a non-APE-based polyoxyethylene alkyl ether.

Prior Art Documents

Patent Document

[0006]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0007] However, in the fields of biosensors and bioseparation, against the backdrop of the pursuit of further high reactivity with respect to target substances, in the production of polymer particles, the production of particles having an even smaller particle size and a further reduction in the environmental load in water treatment are required.

[0008] Therefore, an object of the present invention is to provide a method for producing polymer particles capable of achieving both a reduction in the particle size of polymer particles and a reduction in the environmental load in water treatment at a high level.

Means for Solving the Problems

[0009] As a result of intensive studies by the present inventors, it has been found that the above problems can be solved by the method for producing polymer particles according to the following present invention.

[0010] That is, the method for producing polymer particles according to one aspect of the present invention is a method for producing polymer particles using synthesis by emulsion polymerization using a surfactant, comprising a step of preparing a raw material mixture containing styrene and glycidyl methacrylate, a step of mixing a surfactant into the raw material mixture to prepare a dispersion mixture, and a step of mixing a polymerization initiator into the dispersion mixture to prepare a reaction mixture, characterized in that the surfactant is a polyethylene glycol ester. Further, the polymer particles according to another aspect of the present invention are polymer particles produced by the above method for producing polymer particles.

Advantages of the Invention

[0011] According to the present invention, there is provided a method for producing polymer particles capable of achieving both a reduction in the particle size of the polymer particles and a reduction in the environmental load in water treatment at a high level.

Embodiments for Carrying Out the Invention

[0012] Specific embodiments of the present invention will be described below, but the present invention is not limited to the following embodiments.

[0013] The method for producing polymer particles according to the present invention is a method for producing polymer particles using synthesis by emulsion polymerization using a surfactant, a step of preparing a raw material mixture containing styrene and glycidyl methacrylate, a step of mixing a surfactant with the raw material mixture to prepare a dispersion mixture, a step of mixing a polymerization initiator with the dispersion mixture to prepare a reaction mixture, and characterized in that the surfactant is a polyethylene glycol ester.

[0014] 1. Surfactant In the present invention, synthesis by emulsion polymerization using a surfactant is utilized. By utilizing synthesis by emulsion polymerization, polymer particles having a small particle size can be produced more efficiently than a method of controlling the particle size by changing the charged amount of the monomer. As a result, the environmental load due to water treatment can be effectively reduced.

[0015] In biosensors and bioseparation, polymer particles may be used together with antibodies. In the synthesis of polymer particles by emulsion polymerization, anionic surfactants or cationic surfactants are generally used. However, if these surfactants remain as residues in the polymer particles, they may denature the antibodies. An antibody with a changed three-dimensional structure due to denaturation may not be able to cause a specific reaction with the antigen, and as a result, the desired functions in biosensors and bioseparation may not be expressed.

[0016] Therefore, the inventors selected a nonionic surfactant that does not cause antibody denaturation from among nonionic surfactants used in emulsion polymerization. As a result, it was found that when the surfactant used in emulsion polymerization is a polyethylene glycol ester, the polymer particles produced can be effectively reduced in particle size.

[0017] The details of the mechanism by which the use of a polyethylene glycol ester as a surfactant in emulsion polymerization can effectively reduce the particle size of polymer particles are unclear, but it is thought as follows. Polyethylene glycol esters having an ester group have a high affinity due to structural similarity with glycidyl methacrylate, which also has an ester group. Specifically, it is considered that the interfacial adsorption of the ester group of the polyethylene glycol ester to the ester group of glycidyl methacrylate constituting the oil droplets is good. Therefore, it is considered that a high interfacial activity effect can be obtained by the polyethylene glycol ester, and further reduction in the particle size of the produced polymer particles becomes possible.

[0018] Also, in the present invention, the surfactant preferably has a high hydrophilicity and an HLB (Hydrophilic-Lipophilic Balance) of 18.6 or more and 20.0 or less. Here, the HLB refers to a value calculated according to the following formula from the base numbers determined for each functional group by the Davis method (for example, see "Color Materials", 77(10), 564-469(2004), written by Toshiyuki Suzuki). HLB = 7 + Σ (hydrophilic group base number) + Σ (lipophilic group base number)

[0019] If the HLB value of the surfactant is 18.6 or more, the dispersion stability of the surfactant in the aqueous system is high, and the targeted reduction in particle size can be stably achieved. In addition, its solubility in monomers such as styrene and glycidyl methacrylate is low, and it is difficult for the surfactant to remain in the polymer particles after the purification process. More preferably, the surfactant has an HLB of 19.0 or more and 20.0 or less.

[0020] Preferably, the surfactant is a compound represented by the following formula (1), a compound represented by the following formula (2), or a mixture of a compound represented by the following formula (1) and a compound represented by the following formula (2). R1COO(CH2CH2O) m H ··· Formula (1) R2COO(CH2CH2O) m COR3 ··· Formula (2) (In Formula (1) and Formula (2), R1, R2, and R3 each independently represent a hydrogen atom or an alkyl group, and m is an integer of 2 or more.) In Formula (1) and Formula (2), preferably, R1, R2, and R3 are each independently an alkyl group having 5 or more and 50 or less carbon atoms.

[0021] More preferably, the surfactant is polyethylene glycol monostearate, polyethylene glycol distearate, or a mixture of polyethylene glycol monostearate and polyethylene glycol distearate. Particularly preferably, the surfactant is polyethylene glycol monostearate.

[0022] Furthermore, more preferably, the surfactant is polyethylene glycol monostearate in which the degree of polymerization of the polyethylene glycol moiety is 100 or more and 300 or less. Even more preferably, it is polyethylene glycol monostearate in which the degree of polymerization of the polyethylene glycol moiety is 130 or more and 170 or less.

[0023] In particular, the surfactant is most preferably polyethylene glycol monostearate with a degree of polymerization of 150 in the polyethylene glycol moiety. Examples of polyethylene glycol monostearate with a degree of polymerization of 150 in the polyethylene glycol moiety include Emal 3199VB (manufactured by Kao Corporation, HLB: 19.4).

[0024] 2. Monomer In the present invention, the monomers used for synthesizing the polymer particles are styrene and GMA. When styrene is used as a monomer, the polymer particles obtained by synthesis have a high glass transition temperature and repeating units of styrene with excellent mechanical strength. Therefore, when purifying by methods such as centrifugation or ultrafiltration, the effect of suppressing damage such as cracking and chipping of the particles can be obtained. Also, when GMA is used as a monomer, non-specific adsorption is suppressed by the GMA arranged on the surface of the polymer particles obtained by synthesis. This is considered to be because non-specific adsorption is suppressed by a part of the glycidyl groups of GMA arranged on the surface of the polymer particles being ring-opened to exhibit glycol.

[0025] 3. Crosslinking agent The polymer particles may contain repeating units derived from radically polymerizable monomers having crosslinkability. Examples of the radically polymerizable monomers having crosslinkability include diethylene glycol diacrylate, triethylene glycol diacrylate, tetraethylene glycol diacrylate, polyethylene glycol diacrylate, 1,6 - hexanediol diacrylate, neopentyl glycol diacrylate, tripropylene glycol diacrylate, polypropylene glycol diacrylate, 2,2'-bis(4-(acryloxydiethoxy)phenyl)propane, trimethylolpropane triacrylate, pentaerythritol tetraacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, 1,3 - butylene glycol dimethacrylate, 1,6 - hexanediol dimethacrylate, neopentyl glycol dimethacrylate, polypropylene glycol dimethacrylate, 2,2'-bis(4-(methacryloxydiethoxy)phenyl)propane, 2,2'-bis(4-(methacryloxypolyethoxy)phenyl)propane, trimethylolpropane trimethacrylate, pentaerythritol tetramethacrylate, divinylbenzene, divinylnaphthalene, and divinyl ether. However, the present invention is not limited thereto as long as the object of the present invention can be achieved. In addition, two or more radically polymerizable monomers having crosslinkability may be used in combination.

[0026] When the total amount of styrene and glycidyl methacrylate is 100 parts by mass, the addition amount of the crosslinking agent is preferably in the range of 0.1 part by mass or more and 5 parts by mass or less. If the addition amount of the crosslinking agent is 0.1 part by mass or more with respect to 100 parts by mass of the total amount of styrene and glycidyl methacrylate, high particle strength and solvent resistance can be obtained. Further, if the addition amount of the crosslinking agent is 5 parts by mass or less with respect to 100 parts by mass of the total amount of styrene and glycidyl methacrylate, it is easy to maintain a desired particle size distribution and particle diameter.

[0027] 4. Polymerization initiator In this embodiment, the polymerization initiator used for the synthesis of polymer particles can be used without particular limitation as long as it can achieve the object of the present invention, as long as it is generally used for the synthesis of SG particles. Further, the polymerization initiator in this embodiment is preferably a water-soluble polymerization initiator.

[0028] As the water-soluble polymerization initiator, for example, peroxides such as ammonium persulfate (APS), potassium persulfate (KPS), hydrogen peroxide, and water-soluble azo polymerization initiators such as 2,2'-azobis(2-methylpropionamidine) dihydrochloride (V-50) can be preferably used.

[0029] The amount of the polymerization initiator used may be appropriately adjusted according to the reaction conditions. For example, the amount of the polymerization initiator used is preferably 0.1% by mass or more and 20% by mass or less, more preferably 5% by mass or more and 15% by mass or less, based on the total amount of the monomers for synthesizing the polymer particles.

[0030] The polymerization initiator, or its decomposition product, may remain in the water suspension containing the polymer particles as long as it does not impair the functions and properties of the produced polymer particles.

[0031] 5. Method for evaluating particle size The polymer particles according to the present invention are polymer particles produced by the method for producing polymer particles described above. The particle size of the polymer particles can be measured using a Zetasizer NS manufactured by Malvern based on the principle of dynamic light scattering (DLS). However, the particle size measurement is not limited to the above-described measurement method and measuring instrument as long as the purpose of the particle size measurement can be achieved.

[0032] As the measurement sample, a dispersion in which SG particles are dispersed in an ultrapure water solvent at a concentration of 0.005 wt% can be used. Further, in the measurement, the dispersion can be placed in a disposable plastic cell for measurement.

[0033] As analysis parameters, for example, the refractive index of the particles is 1.59 equivalent to latex, the particle absorbance is 0.01, the refractive index of the dispersion medium is 1.33 equivalent to water, the viscosity of the dispersion medium is 0.8872 [cP] equivalent to water, and the temperature is 25 [°C]. Also, the number of measurements is 3 times, and the average value is adopted. Also, the comparison of the particle size is made based on the Z-average particle size among the average particle sizes. However, the average particle size to be adopted is not limited to this, and the number-average particle size, volume-average particle size, etc. may also be used.

Example

[0034] Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited by the following examples.

[0035] [Example 1] To 69.74 mL of ultrapure water, 0.26 g of a nonionic polyethylene glycol ester “Emanon 3199VB” (manufactured by Kao Corporation) was added, and the mixture was stirred at 70 °C for 30 minutes at 200 rpm under the condition of a N2 flow of 200 mL / min to prepare a surfactant aqueous solution. On the other hand, to 40 mL of ultrapure water, 1.2 g of styrene, 1.8 g of GMA, and 0.04 g of divinylbenzene (hereinafter referred to as DVB) as a crosslinking agent were mixed to prepare a raw material mixture. To this raw material mixture, 70 mL of the surfactant aqueous solution prepared above was mixed, and the mixture was stirred at 70 °C for 30 minutes at 200 rpm to prepare a dispersion mixture. To this dispersion mixture, a polymerization initiator aqueous solution in which 0.06 g of polymerization initiator V-50 (water-soluble azo polymerization initiator, manufactured by Fuji Film Wako Pure Chemical Corporation) was dissolved in 10 mL of ultrapure water was mixed, and the mixture was stirred at 70 °C for 1 hour at 200 rpm to prepare a reaction mixture. The stirring was performed using a flask mixer LM200 (manufactured by Yamato Scientific Co., Ltd.). Thereafter, 0.33 g of GMA was added to this reaction mixture, and the mixture was stirred at 70 °C for 24 hours at 200 rpm. Subsequently, this reaction mixture was centrifuged to remove the supernatant, and a purification step of adding and redispersing the reduced amount of ultrapure water was performed 3 times to obtain an aqueous dispersion of polymer particles.

[0036] [Example 2] In Example 1, the type of surfactant used was changed to the nonionic polyethylene glycol ester "Emanon 3299RB" (manufactured by Kao Corporation). Otherwise, a dispersion of polymer particles was obtained in the same process as in Example 1.

[0037] [Example 3] In Example 1, the type of surfactant used was changed to the nonionic polyethylene glycol ester "Emanon 3299VB" (manufactured by Kao Corporation). Otherwise, a dispersion of polymer particles was obtained in the same process as in Example 1.

[0038] [Comparative Example 1] In Example 1, the type of surfactant used was changed to the non-alkylphenol ethoxylate-based polyoxyethylene alkyl ether surfactant "EMULGEN 1150S-60" (manufactured by Kao Corporation). Otherwise, a dispersion of polymer particles was obtained in the same process as in Example 1.

[0039] [Comparative Example 2] To 110 mL of ultrapure water, 1.2 g of styrene, 1.8 g of GMA, and 0.04 g of DVB were mixed and stirred under the conditions of 70 °C, 30 minutes, and 200 rpm to prepare a raw material mixture. To this raw material mixture, an aqueous polymerization initiator solution in which 0.06 g of a polymerization initiator (V-50) was dissolved in 10 mL of ultrapure water was mixed and stirred under the conditions of 70 °C, 1 hour, and 200 rpm to carry out the reaction. Thereafter, 0.33 g of GMA was added to this mixture, and the mixture was stirred under the conditions of 70 °C, 24 hours, and 200 rpm to further carry out the reaction. Thereafter, this reaction solution was centrifuged to remove the supernatant, and a purification step of adding and redispersing the reduced amount of ultrapure water was performed three times to obtain an aqueous dispersion of polymer particles.

[0040] [Comparative Example 3] In Example 1, the type of surfactant used was changed to the APE-based surfactant "NP-40" (manufactured by Nacalai Tesque). Otherwise, a dispersion of polymer particles was obtained in the same process as in Example 1.

[0041] [Comparative Example 4] In Example 1, the type of surfactant used was changed to the non-APE-based polysorbate surfactant "Tween 20" (manufactured by Nacalai Tesque). A dispersion of polymer particles was obtained in the same process as in Example 1 except for this change.

[0042] Regarding the polymer particles obtained in Examples 1 to 3 and Comparative Examples 1 to 3, the particle sizes were measured by the method described above. The results are shown in Table 1. The particle size is the average value of the values obtained by measuring 10 times. Also, regarding the polymer particles obtained in Comparative Example 4, since it was visually observed that they were aggregated in the dispersion, the particle size was not measured.

[0043]

Table 1

[0044] As shown in Table 1, compared with the polymer particles obtained in Comparative Examples 1 to 3, the polymer particles obtained in Examples 1 to 3 could be made into particles with a small particle size. In particular, the polymer particles granulated using the Emulon 3199VB surfactant in Example 1 could have a significantly small particle size (114 nm).

[0045] In particular, when the surfactant was used at the same concentration, in Examples 1 to 3, particles with a smaller particle size were obtained compared to Comparative Examples 1 and 3. From this, it can be seen that when manufacturing polymer particles having the same particle size, by using a polyethylene glycol ester as the surfactant, the amount of the surfactant used can be reduced. That is, it can be seen that by using a polyethylene glycol ester as the surfactant in the production of polymer particles, it is possible to reduce the load of surfactant removal in the production process.

Claims

1. A method for producing polymer particles using synthesis by emulsion polymerization with a surfactant, comprising a step of preparing a raw material mixture containing styrene and glycidyl methacrylate, a step of mixing a surfactant with the raw material mixture to prepare a dispersion mixture, and a step of mixing a polymerization initiator with the dispersion mixture to prepare a reaction mixture, wherein the surfactant is a polyethylene glycol ester. A method for producing polymer particles.

2. The production method according to claim 1, wherein the surfactant has an HLB value of 18.6 or more and 20.0 or less.

3. The method for producing polymer particles according to claim 1 or 2, wherein the surfactant is a compound represented by the following formula (1), a compound represented by the following formula (2), or a mixture of a compound represented by the following formula (1) and a compound represented by the following formula (2). R1COO(CH ２ CH ２ O) ｍ H... Formula (1) R2COO(CH ２ CH ２ O) ｍ COR3... Formula (2) (In Formula (1) and Formula (2), R1, R2, and R3 each independently represent a hydrogen atom or an alkyl group, and m is an integer of 2 or more.)

4. The method for producing polymer particles according to claim 3, wherein the surfactant is polyethylene glycol monostearate, polyethylene glycol distearate, or a mixture of polyethylene glycol monostearate and polyethylene glycol distearate.

5. The method for producing polymer particles according to claim 4, wherein the surfactant is polyethylene glycol monostearate.

6. The method for producing polymer particles according to claim 5, wherein the surfactant is polyethylene glycol monostearate having a degree of polymerization of 150 in the polyethylene glycol moiety. **Claim 7**: The method for producing polymer particles according to any one of claims 1 to 5, wherein the polymerization initiator is any one of ammonium persulfate (APS), potassium persulfate (KPS), hydrogen peroxide, and 2,2'-azobis(2-methylpropionamidine) dihydrochloride.

Images