JP2014094931A - Sustained release particles and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide sustained release particles excellent not only in sustained release property but also in dispersibility and storage stability, and a method for producing the same.SOLUTION: The sustained release particles are obtained by: preparing a hydrophobic solution by dissolving 3-iodo-2-propynyl butyl carbamate (IPBC) in a hydrophobic polymerizable vinyl monomer; preparing an aqueous emulsifier-polyvinyl alcohol solution by blending water, an emulsifier and polyvinyl alcohol; emulsifying the hydrophobic solution in the aqueous emulsifier-polyvinyl alcohol solution; and subjecting the polymerizable vinyl monomer of the emulsified hydrophobic solution to miniemulsion polymerization in the presence of a polymerization initiator; and producing a polymer including the IPBC and having an average particle size of 1 μm or lower. In the polymer obtained by the miniemulsion polymerization, a dipole-dipole force component δof a solubility parameter δ is 5.0-7.0 [(J/cm)], and a hydrogen bonding force component δof the solubility parameter δ is 8.0-10.0 [(J/cm)].

Description

  The present invention relates to sustained release particles and a method for producing the same, and more particularly to sustained release particles for gradually releasing 3-iodo-2-propynylbutylcarbamate and a method for producing the same.

  In recent years, sustained release particles containing 3-iodo-2-propynylbutylcarbamate have been proposed.

  As a method for producing such sustained release particles, the following method has been proposed (for example, see Patent Document 1).

  That is, in Patent Document 1, first, a polymerizable vinyl monomer such as 3-iodo-2-propynylbutylcarbamate (IPBC, antifungal agent), methyl methacrylate and dilauroyl peroxide (polymerization initiator) are blended, While preparing a hydrophobic solution, water and polyvinyl alcohol (dispersant) are mix | blended and aqueous solution is prepared.

  Thereafter, a suspension of IPBC-containing sustained-release particles is prepared by blending a hydrophobic solution and an aqueous solution to prepare a suspension, and then raising the temperature while stirring to perform suspension polymerization. Have gained.

JP 2011-79816 A

  However, since the sustained release particles proposed in Patent Document 1 are obtained by suspension polymerization, the median diameter is as large as 1 μm or more. Therefore, the sustained release particles may settle in the suspension and cause caking.

  Further, in the sustained release particles proposed in Patent Document 1, when the content ratio of IPBC in the sustained release particles is increased, IPBC precipitates as acicular crystals over time in the suspension, and storage stability May decrease.

  An object of the present invention is to provide sustained-release particles that are excellent in dispersibility and storage stability as well as sustained-release properties, and a method for producing the same.

  The present inventors diligently studied the above-mentioned sustained-release particles and the production method thereof. As a result, 3-iodo-2-propynylbutylcarbamate was dissolved in a hydrophobic polymerizable vinyl monomer to obtain a hydrophobic solution. Prepared, water, an emulsifier and polyvinyl alcohol (hereinafter abbreviated as PVA) to prepare an emulsifier-PVA aqueous solution, and the hydrophobic solution is emulsified in the emulsifier-PVA aqueous solution. We have found that by conducting miniemulsion polymerization of a polymerizable vinyl monomer in the presence of a polymerization initiator, it is possible to obtain sustained release particles that are excellent in dispersibility and storage stability, as well as sustained release properties. As a result of research, the present invention has been completed.

That is, the present invention
(1) A hydrophobic solution is prepared by dissolving 3-iodo-2-propynylbutylcarbamate with a hydrophobic polymerizable vinyl monomer, and an aqueous emulsifier-PVA solution is prepared by blending water, an emulsifier and PVA. The hydrophobic solution is emulsified in the emulsifier-PVA aqueous solution, and the polymerizable vinyl monomer is subjected to miniemulsion polymerization in the presence of a polymerization initiator to produce a polymer having an average particle diameter of less than 1 μm. The polymer obtained by miniemulsion polymerization is a dipole force term δ _{p, polymer} with a solubility parameter δ defined by Hansen and calculated by the van Krevelen and Hoftyzer method is 5.0. 7.0 a ^{[(J / cm 3) 1/2} ], hydrogen bonding term of the solubility parameter [delta] [delta] _{h, poly} wherein the _er is ^{8.0~10.0 [(J / cm 3)} 1/2], the controlled release particles,
(2) The sustained release particles according to (1) above, wherein the content of 3-iodo-2-propynylbutylcarbamate with respect to the sustained release particles is 10 to 50% by mass,
(3) The polymerizable vinyl monomer contains 50% by mass or more of the first monomer, and the first monomer is between dipoles of the solubility parameter δ of the monomer unit constituting the polymer obtained from the first monomer. The force term δ _{p, 1st monomer unit (s)} is 5.6 to 6.0 [(J / cm ³ ) ^1/2 ], and the hydrogen bonding force term δ _{h, 1 st monomer unit (s} ) of the solubility parameter δ ₎ Is contained in an amount of 9.2 to 9.9 [(J / cm ³ ) ^1/2 ] in an amount of 50% by mass or more, and is gradually reduced according to (1) or (2) above Release particles,
(4) The sustained-release particles according to (3), wherein the first monomer contains methyl methacrylate and / or ethylene glycol dimethacrylate,
(5) A step of preparing a hydrophobic solution by dissolving 3-iodo-2-propynylbutylcarbamate with a hydrophobic polymerizable vinyl monomer, and preparing an aqueous emulsifier-PVA solution by mixing water, an emulsifier and PVA. A step of emulsifying the hydrophobic solution in the emulsifier-PVA aqueous solution, and a miniemulsion polymerization of the polymerizable vinyl monomer of the emulsified hydrophobic solution in the presence of a polymerization initiator to obtain an average particle A method for producing sustained-release particles, comprising a step of producing a polymer having a diameter of less than 1 μm, wherein the polymer obtained by miniemulsion polymerization is defined by Hansen and is a solubility parameter calculated by the van Krevelen and Hoftyzer method polar term [delta] _{p, Polymer} of [delta] is ^{5.0~7.0 [(J / cm 3)} 1/2] There, wherein the solubility parameter hydrogen bonding term [delta] _{h, Polymer} of [delta] is ^{8.0~10.0 [(J / cm 3)} 1/2], a method of manufacturing a controlled release particles,
(6) In the step of preparing the hydrophobic solution, an oil-soluble polymerization initiator is blended in the hydrophobic solution, and in the step of miniemulsion polymerization of the polymerizable vinyl monomer, the water-soluble polymerization initiator is started after the start of the miniemulsion polymerization. The method for producing sustained-release particles as described in (5) above, further comprising:

  In the method for producing sustained-release particles of the present invention, a polymerizable vinyl monomer in a hydrophobic solution emulsified in an emulsifier-PVA aqueous solution prepared by blending water, an emulsifier and PVA is prepared in the presence of a polymerization initiator. In order to obtain the sustained release particles of the present invention by miniemulsion polymerization to produce a polymer having an average particle size of less than 1 μm containing 3-iodo-2-propynylbutylcarbamate, the sustained release particles are: Excellent dispersibility and storage stability.

Furthermore, in the sustained-release particles of the present invention, the polymer is defined by Hansen, and the dipole force term δ _{p, polymer of the} solubility parameter δ calculated by the van Krevelen and Hoftyzer method is 5.0 to 7.0. In [(J / cm ³ ) ^1/2 ], the hydrogen bonding force term δ _{h, polymer} of the solubility parameter δ is set to 8.0 to 10.0 [(J / cm ³ ) ^1/2 ]. The compatibility with 3-iodo-2-propynyl butyl carbamate is even more outstanding. As a result, the polymer contains 3-iodo-2-propynylbutylcarbamate so that 3-iodo-2-propynylbutylcarbamate is uniformly present in the polymer.

  Therefore, the sustained-release particles of the present invention can be used for various industrial products as sustained-release particles having excellent sustained-release properties, dispersibility, and storage stability.

  In addition, since 3-iodo-2-propynyl butyl carbamate can also be used as a hydrophobe in miniemulsion polymerization, it contains 3-iodo-2-propynyl butyl carbamate easily without any additional hydrophobe. A polymer having an average particle diameter of less than 1 μm can be produced.

FIG. 1 shows an image processing diagram of a TEM photograph of sustained-release particles of Example 2. FIG. 2 shows an image processing diagram of a TEM photograph of sustained-release particles of Example 2. FIG. 3 is an image processing diagram of an SEM photograph of sustained release particles of Comparative Example 15. FIG. 4 is an image processing diagram of an SEM photograph of sustained release particles of Comparative Example 16. FIG. 5 shows a graph of sustained release tests of Examples 1 to 4. FIG. 6 shows a graph of sustained release tests of Examples 5-7. FIG. 7 shows graphs of sustained release tests of Examples 8 to 11. FIG. 8 shows graphs of sustained release tests of Examples 12 to 14. FIG. 9 shows graphs of sustained release tests of Examples 15 to 17.

  The sustained-release particles of the present invention are prepared by dissolving 3-iodo-2-propynylbutylcarbamate (hereinafter sometimes simply referred to as IPBC) with a hydrophobic polymerizable vinyl monomer to prepare a hydrophobic solution, Separately, water, an emulsifier and PVA are blended to prepare an emulsifier-PVA aqueous solution. Subsequently, the hydrophobic solution is emulsified in the emulsifier-PVA aqueous solution, and then the polymerizable vinyl monomer is added in the presence of the polymerization initiator. It is obtained by mini-emulsion polymerization to produce a polymer containing IPBC.

  IPBC is an iodine-based antibiotic compound (for example, fungicides).

  IPBC acts as a hydrophobe (costabilizer) in miniemulsion polymerization, specifically, by preventing the Ostwald ripening by contributing to stabilization of the miniemulsion (described later) in miniemulsion polymerization, miniemulsion particles Suppresses the enlargement of particles (increase in particle diameter).

  IPBC is substantially hydrophobic and has, for example, extremely low solubility in water at room temperature (20 to 30 ° C., more specifically 25 ° C.). Specifically, the solubility at room temperature is based on mass. And 0.015 parts by mass / 100 parts by mass of water (150 ppm).

In addition, IPBC has a dipole force term δ _{p, IPBC of the} solubility parameter δ calculated by the Krevelen and Hoftyzer method of 3.23, and a hydrogen bond strength term δ _{h, IPBC of} the solubility parameter δ of 7. 83.

Incidentally, polar term [delta] _{p, IPBC} and hydrogen bonding term [delta] _{h, IPBC} solubility parameter [delta] is defined by Hansen, calculated in van Krevelen and Hoftyzer method, specifically, JP 2011-79816 Detailed in this publication.

The subscript IPBC of each term δ (δ _p and δ _h ) indicates IPBC, and the polymer, the monomer unit (monomer unit) of the first monomer, and the monomer unit (monomer unit) of the second monomer, which will be described later, It is the same.

The polymerizable vinyl monomer is, for example, a polymerizable monomer having at least one polymerizable carbon-carbon double bond in the molecule, and a dipole force term δ _{p, polymer} and hydrogen of _{the polymer} obtained by polymerization. The binding force term δ _{h, polymer} is selected to be in a desired range.

  Examples of the polymerizable vinyl monomer include a first monomer.

The first monomer has a dipole force term δ _{p, 1st monomer unit (s)} of a solubility parameter δ of a monomer unit (described later) constituting the polymer obtained therefrom, for example, 5.6 to 6.0 [( J / cm ³ ) ^1/2 ], preferably 5.7 to 6.0 [(J / cm ³ ) ^1/2 ], and the hydrogen bonding force term δ _{h, 1 st monomer unit (s )} Is, for example, 9.2 to 9.9 [(J / cm ³ ) ^1/2 ], preferably 9.2 to 9.8 [(J / cm ³ ) ^1/2 ].

It should be _{noted that} the dipole force term δ _{p, 1st monomer unit (s)} and hydrogen bond term δ _{h, 1st monomer unit (s)} of the solubility parameter δ of the monomer unit constituting the polymer obtained from the first monomer, Hereinafter, they may be simply referred to as “a dipole force term δ _{p, 1st monomer unit (s)} and a hydrogen bond force term δ _{h, 1st monomer unit (s)} ” of the monomer unit based on the first monomer ”. The monomer unit based on the first monomer will be described later.

  A 1st monomer is a main monomer contained as a main component in a polymerizable vinyl monomer, for example, the compatible monomer selected so that the compatibility with respect to IPBC of the polymer obtained may become high. Specific examples of the first monomer include methyl methacrylate (MMA), ethylene glycol dimethacrylate (EGDMA), and more preferably MMA.

  Specifically, the first monomer preferably contains at least MMA as an essential component.

  The first monomer can be used alone or in combination of two or more. Preferably, single use of MMA and combined use of MMA and EGDMA are mentioned, More preferably, combined use of MMA and EGDMA is mentioned.

  When only MMA and EGDMA are used in combination as the first monomer, the blending ratio of MMA is, for example, 50% by mass or more, preferably 60% by mass or more, and more preferably 70% by mass with respect to the first monomer. It is preferably at least 80% by mass, more preferably at least 80% by mass, at least 90% by mass, at least 95% by mass, at least 98% by mass, and it is also less than 100% by mass. Further, when only MMA and EGDMA are used in combination as the first monomer, the blending ratio of EGDMA is, for example, 50% by mass or less, preferably 40% by mass or less, more preferably, with respect to the first monomer. 30% by mass or less, more preferably 20% by mass or less, 10% by mass or less, 5% by mass or less, and 2% by mass or less, and more than 0% by mass.

  The ratio (surface area / volume) of the surface area (interface area) of the miniemulsion particles to the miniemulsion particle volume is inversely proportional to the average particle diameter, and the average particle diameter of the miniemulsion particles is less than 1 μm (described later). IPBC tends to leak into the aqueous phase. In particular, even when the polymer is in a compatible state with IPBC, when the polymer density in a unit volume is high due to crosslinking of the resulting polymer, the amount (ratio) with which IPBC is compatible with the polymer is In some cases, IPBC crystals may partially precipitate during cooling after miniemulsion polymerization or within several days to several months after cooling.

Next, for the monomer unit dipole force term δ _{p, 1st monomer unit (s)} and hydrogen bond strength term δ _{h, 1st monomer unit (s) based} on the first monomer, MMA is used alone as the first monomer. And MMA and EGDMA are used as the first monomer in combination.

1. Definition of Dipole Force Term δ _p and Hydrogen Bond Force Term δ _h Definitions of dipole force term δ _p and hydrogen bond force term δ _h are as described in Japanese Patent Application Laid-Open No. 2011-79816. Are represented by the following formulas (1) and (2), respectively.

(In the formula, F _p is a dipole force element of intermolecular force (polar component of the molar attraction function), and V is a molar volume.)

(Where E _h is an element of hydrogen bonding force of intermolecular force (contribution of the hydrogen bonding to the cohesive energy). energy), V is the molar volume.)
2. When MMA is used alone as the first monomer (1) Structural formula of polymethyl methacrylate (PMMA) PMMA which is a polymer of MMA is represented by the following formula (3).

(In the formula, n represents the degree of polymerization.)
(2) Dipole force term δ _{p, monomer unit} (= dipole force term δ _{p, MMA unit} )
In the monomer unit (—CH ₂ —C (CH ₃ ) COOCH ₃ —) of the above formula (3), F _p and V corresponding to each atomic group are described below.
^{_{-CH 3 F p: 0 (J}} 1/2 · cm 3/2 · mol -1)
V: 33.5 (cm ³ · mol)
^{_{-CH 2 - F p: 0 (}} J 1/2 · cm 3/2 · mol -1)
V: 16.1 (cm ³ · mol)
> C <F _p : 0 (J ^1/2 · cm ^3/2 · mol ^-1 )
V: -19.2 (cm ³ · mol)
^{_{-COO- F p: 490 (J 1/2}} · cm 3/2 · mol -1)
V: 18 (cm ³ · mol)
Accordingly, the dipole force term δ _{p, monomer unit} (dipole force term δ _{p, MMA unit} ) of the monomer unit is 5.98 [(J / cm ³ ) ^{1 as} shown in the following formula (4). ^{/ 2} ].

The above-mentioned dipole force term δ _{p, MMA unit} of the monomer unit is equivalent to the dipole force term δ _{p, PMMA of} polymethyl methacrylate which is a repeating structure of the monomer unit.
(3) Hydrogen bond strength term δ _{h, monomer unit} (hydrogen bond strength term δ _{h, MMA unit} )
In the monomer unit (—CH ₂ —C (CH ₃ ) COOCH ₃ —) of the above formula (3), E _h corresponding to each atomic group is described below.
—CH ₃ E _h : 0 (J · mol ⁻¹ )
—CH ₂ —E _h : 0 (J · mol ⁻¹ )
> C <E _h : 0 (J · mol ^-1 )
—COO—E _h : 7000 (J · mol ⁻¹ )
Therefore, the hydrogen bond strength term δ _{h, monomer unit} (hydrogen bond strength term δ _{h, MMA unit} ) of the monomer unit is 9.25 [(J / cm ³ ) ^{1/2 as} shown in the following formula (5). ] Is calculated.

The above hydrogen bond strength term δ _{h, MMA unit} of the monomer unit is equivalent to the hydrogen bond strength term δ _{h, PMMA} of the PMMA which is the repeating structure of the monomer unit.

3. When only MMA and EGDMA are used in combination as the first monomer When the first monomer is used in combination with a plurality of types of monomers, the dipole force term δ _{p, of} monomer units based on each monomer _{Multiplying the first monomer unit} by the mass ratio of each monomer and adding them together (arithmetic mean), the dipole force term δ _{p, of} the monomer units constituting the copolymer obtained from the entire first monomer Calculate _{1st monomer units} .

In addition, by multiplying the hydrogen bonding force term δ _{h, 1st} monomer unit of the monomer unit based on each monomer by the mass ratio of the monomers and adding them together (arithmetic mean), the copolymer weight obtained from the entire first monomer The hydrogen bond strength term δ _h, monomer units of the monomer unit constituting the coalescence is calculated.

Next, as an example of a copolymer, poly (methyl methacrylate-ethylene glycol dimethacrylate) (P (MMA-EGDMA)), which is a copolymer of a first monomer containing MMA and EGDMA at a mass ratio of 94: 6 ) And a method for calculating the dipole force term δ _{p, 1st monomer units} and the hydrogen bond force term δ _{h, 1st} monomer units of the solubility parameter δ of the monomer unit will be described.
(1) Force term between dipoles δ _{p, 1st monomer units}
The dipole force term δ _{p, MMA unit} of the monomer unit of _MMA is 5.98 [(J / cm ³ ) ^1/2 ] as calculated above.

Further, the dipole force term δ _{p, EDGMA unit} of the monomer unit of _EGDMA is 5.37 [(J / cm ³ ) ^1/2 ] by calculation in the same manner as described above.

Then, the dipole force term δ _{p, 1st} monomer units of the monomer unit based on these first monomers is calculated as in the following formula (6).
δ _{p, 1st monomer units} = (94/100) δ _{p, MMA unit} + (6/100) δ _{p, EGDMA unit}
= (94/100) x 5.98 + (6/100) x 5.37
= 5.95 [(J / cm ³ ) ^1/2 ] (6)
This value is equivalent to the dipole force term δ _{p, P (MMA-EGDMA) of} poly (methyl methacrylate-ethylene glycol dimethacrylate).
(2) Hydrogen bond strength term δ _{h, 1st monomer units}
The hydrogen bond term δ _{h, MMA unit} of the monomer unit of _MMA is 9.25 [(J / cm ³ ) ^1/2 ].

Further, the hydrogen bond term δ _h , EGDMA of the monomer unit of _EGDMA is 10.42 [(J / cm ³ ) ^1/2 ].

Then, the hydrogen bonding force term δ _{h, 1st monomer units} of the first monomer is calculated as in the following formula (7).
_{δh, 1st monomer units} = (94/100) _{δh, 1st monomer units} + (6/100) _{δh, EGDMA units}
= (94/100) x 9.25 + (6/100) x 10.42
= 9.32 [(J / cm ³ ) ^1/2 ] (7)
This value is the same as the hydrogen bond term _{δh, PMMA-EGDMA of} polymethyl methacrylate-ethylene glycol dimethacrylate, which is a copolymer.

In addition, the calculation method of the dipole force term δ _{p, 1st monomer unit (s)} and the hydrogen bond force term δ _{h, 1st monomer unit (s)} of the monomer unit based on the first monomer is disclosed in JP 2011-79816 A. Is described in detail.

From the above, the solubility parameter δ (dipole force term δ _{p, 2nd monomer units} and hydrogen bond strength term δ _{h, 2nd monomer units} ) of the first monomer is different from that of the first monomer when different types are used in combination. (That is, a value calculated as a mixture of different types).

  The blending ratio of the first monomer is, for example, 50% by mass or more, preferably 70% by mass or more, more preferably 75% by mass or more, and particularly preferably 80% by mass or more with respect to the polymerizable vinyl monomer. Furthermore, 85 mass% or more, 90 mass% or more, 95 mass% or more, 98 mass% or more is preferable, and it is also 100 mass parts or less.

  Moreover, the polymerizable vinyl monomer can also contain a second monomer.

The second monomer is a secondary monomer that is used together with the first monomer and is optionally contained in the polymerizable vinyl monomer. Specifically, the second monomer is copolymerizable with the first monomer, and is co-polymerized with the first monomer. The combined dipole force term δ _{p, polymer} and the hydrogen bond force term δ _{h, polymer} are selected to be in the desired ranges.

  The second monomer is a copolymerizable monomer that can be copolymerized with the first monomer, and includes, for example, a (meth) acrylic acid ester monomer, a (meth) acrylic acid monomer, and an aromatic vinyl monomer excluding MMA. , Vinyl ester monomers, maleic acid ester monomers, vinyl halides, vinylidene halides, nitrogen-containing vinyl monomers, crosslinkable monomers other than EGDMA, and polymerization reactive emulsifiers.

  In the case where the glass transition temperature of the copolymer produced by copolymerization with the first monomer is lowered by blending the second monomer with the polymerizable vinyl monomer, such a copolymer has a crosslinking density, Compared to a homopolymer produced by homopolymerization of the first monomer, it can be increased. That is, when the first monomer and the second monomer are used in combination, and the MMA and EGDMA of the first monomer are used in combination, the blending ratio of EGDMA with respect to the polymerizable vinyl monomer is, for example, 5% by mass or more, preferably 10% by mass or more, more preferably 20% by mass or more, particularly preferably 30% by mass or more, and for example, 60% by mass or less, preferably 50% by mass or less, More preferably, it is 40 mass% or less.

  Examples of (meth) acrylic acid ester monomers include methacrylic acid esters (excluding MMA) and / or acrylic acid esters, specifically, methyl acrylate, ethyl (meth) acrylate, and (meth) acrylic. N-propyl acid, iso-propyl (meth) acrylate, n-butyl (meth) acrylate, iso-butyl (meth) acrylate, tert-butyl (meth) acrylate, n-pentyl (meth) acrylate, N-hexyl (meth) acrylate, n-heptyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, n-octyl (meth) acrylate, iso-nonyl (meth) acrylate, (meth) acrylic acid n-dodecyl (lauryl), (meth) acrylic acid n-octadecyl (stearyl), (meth) acrylic acid (Meth) acrylic acid alkyl ester (excluding MMA) in which the alkyl portion such as hexyl has a linear, branched or cyclic alkyl portion having 1 to 20 carbon atoms, for example, 2-methoxyethyl (meth) acrylate (Meth) acrylic acid alkoxyalkyl esters such as, for example, (meth) acrylic acid hydroxyalkyl such as hydroxyethyl (meth) acrylate, for example, epoxy group-containing (meth) acrylic acid esters such as glycidyl (meth) acrylate, etc. Is mentioned. Preferably, (meth) acrylic acid alkyl ester (except MMA) is mentioned.

  As the (meth) acrylic acid alkyl ester, more preferably, an acrylic acid alkyl ester having an alkyl moiety having 2 or more carbon atoms, particularly preferably ethyl acrylate, n-propyl acrylate, iso-propyl acrylate, etc. Examples thereof include propyl acrylate, and butyl acrylate such as n-butyl acrylate (n-BA), iso-butyl acrylate, and tert-butyl acrylate. Further, as the methacrylic acid alkyl ester, more preferably, a methacrylic acid alkyl ester having an alkyl moiety having 4 or more carbon atoms, particularly preferably methacrylic acid such as n-butyl methacrylate, iso-butyl methacrylate, and tert-butyl methacrylate. Examples include butyl acid.

  In addition, the epoxy group-containing (meth) acrylic acid ester has a function of suppressing discoloration of IPBC due to heat or ultraviolet rays, and is blended in the second monomer as necessary to obtain this effect.

  Examples of the (meth) acrylic acid monomer include methacrylic acid (MAA), acrylic acid, itaconic acid, and the like. The (meth) acrylic acid monomer has a function of enhancing the colloidal stability of the emulsion formed by the copolymer with the first monomer, and is blended as necessary to obtain this effect.

  Examples of the aromatic vinyl monomer include styrene, p-methylstyrene, o-methylstyrene, and α-methylstyrene.

  Examples of vinyl ester monomers include vinyl acetate and vinyl propionate.

  Examples of maleate monomers include dimethyl maleate, diethyl maleate, and dibutyl maleate.

  Examples of the vinyl halide include vinyl chloride and vinyl fluoride.

  Examples of the vinylidene halide include vinylidene chloride and vinylidene fluoride.

  Examples of the nitrogen-containing vinyl monomer include (meth) acrylonitrile, N-phenylmaleimide, vinylpyridine, and the like.

  Examples of the crosslinkable monomer (excluding EGDMA) include mono- or polyethylene glycol di (meth) acrylate (excluding EGDMA) such as ethylene glycol diacrylate and diethylene glycol di (meth) acrylate, such as 1,3-propanediol diene. Alkanediol di (meth) acrylates such as (meth) acrylate, 1,4-butanediol di (meth) acrylate, 1,5-pentanediol di (meth) acrylate, for example, trimethylolpropane tri (meth) acrylate, penta Alkane polyol poly (meth) acrylates such as erythritol tetra (meth) acrylate (PETA / PETM), for example, allylic monomers such as allyl (meth) methacrylate and triallyl (iso) cyanurate , For example, divinyl monomers such as divinylbenzene.

The polymerization-reactive emulsifier is an emulsifier having a polymerizable carbon-carbon double bond in the molecule, and is also an emulsifier and a polymerizable monomer. The polymerization-reactive emulsifier has a hydrophilic group that exhibits an emulsifying function in the molecule. Examples of such a hydrophilic group include anionic hydrophilic groups such as a sulfonate group and a carboxylate group, for example, Nonionic hydrophilic groups such as polyoxyethylene groups can be mentioned. Preferred examples of the polymerization-reactive emulsifier include those containing both an anionic hydrophilic group and a nonionic hydrophilic group, those containing only an anionic hydrophilic group, and those containing only a nonionic hydrophilic group. Particularly preferable examples include those containing both an anionic hydrophilic group and a nonionic hydrophilic group. As those containing both such an anionic hydrophilic group and a nonionic hydrophilic group, specifically, CH ₂ ═C (CH ₃ ) —COO (AO) _n SO ₃ Na (wherein AO represents an alkylene oxide such as ethylene oxide or propylene oxide). As the reactive emulsifier, for example, a commercially available product may be used. A soap series (manufactured by ADEKA), an antox series (manufactured by Nippon Emulsifier Co., Ltd.), a blemmer series (manufactured by NOF Corporation) and the like are used.

  The second monomer is preferably a (meth) acrylic acid ester-based monomer excluding MMA, a (meth) acrylic acid-based monomer, or a polymerization-reactive emulsifier.

  When the second monomer contains a (meth) acrylic acid ester-based monomer (specifically, n-BA or the like) excluding MMA, the glass transition temperature of the copolymer can be lowered.

  When the second monomer contains a (meth) acrylic acid monomer, the carboxyl group and / or carboxylate group of the (meth) acrylic acid monomer is distributed on the surface of the sustained release particles, and the sustained release particles Colloidal stability in the emulsion can be improved.

  When the second monomer contains a polymerization-reactive emulsifier, colloidal stability can be maintained even in a dilute sustained-release particle emulsion, and even when mechanical shearing force is applied. Further, aggregation / destruction of sustained release particles can be prevented.

  As the second monomer, a (meth) acrylic acid ester monomer is more preferable.

The second monomer has a dipole force term δ _{p, 2nd monomer unit (s)} having a solubility parameter δ of, for example, 3.0 to 6.0 [(J / cm ³ ) ^1/2 ], preferably 3 5 to 6.0 [(J / cm ³ ) ^1/2 ], and the hydrogen bonding term δ _{h, 2nd monomer unit (s) of} the solubility parameter δ is, for example, 7.0 to 10.0 [( J / cm ³ ) ^1/2 ], preferably 7.2 to 9.5 [(J / cm ³ ) ^1/2 ].

It should be _{noted that} the solubility parameter δ of the second monomer (dipole force term δ _{p, 2nd monomer units} and hydrogen bond force term δ _{h, 2nd monomer units} ) is different from the second monomer as a whole ( That is, it is a value calculated as a mixture of different types). Such a calculation method is the same as that for the entire first monomer.

The blending ratio of the second monomer is such that the solubility parameter δ of _{the polymer} (dipole force term δ _{p, polymer} and hydrogen bonding force term δ _{h, polymer} ) is the solubility parameter δ of the first monomer, its blending ratio, Calculated from the solubility parameter δ of the monomer and the blending ratio thereof (see JP 2011-79816 A), set appropriately, specifically, for example, 50% by mass or less with respect to the polymerizable vinyl monomer, Preferably, it is 40% by mass or less, more preferably 38% by mass or less, and further 30% by mass or less, 25% by mass or less, 20% by mass or less, 15% by mass or less, 10% by mass or less, and 5% by mass or less. Preferably, for example, it exceeds 0% by mass, and preferably 2% by mass or more.

  When the blending ratio of the second monomer exceeds the above upper limit, the compatibility between the copolymer and IPBC may be reduced. In this case, during miniemulsion polymerization, during cooling after polymerization, or Some IPBC crystals may precipitate within several days to several months after cooling.

  In addition, the polymerizable vinyl monomer is mainly composed of, for example, a (meth) acrylic acid alkyl ester having 6 or less carbon atoms in the alkyl portion, and an arbitrary (meth) acrylic acid alkyl ester having 7 or more carbon atoms in the alkyl portion. It can also be contained as a component.

  The number of carbon atoms in the alkyl moiety in the (meth) acrylic acid alkyl ester having 6 or less carbon atoms in the alkyl moiety is, for example, 1 or more, preferably 4 or less, more preferably 3 or less, and still more preferably 2 It is as follows. When the number of carbon atoms in the alkyl portion is not more than the above upper limit, a decrease in polymerization rate is small, and a polymer compatible with IPBC can be easily obtained. The (meth) acrylic acid alkyl ester having 6 or less carbon atoms in the alkyl portion is a (meth) acrylic acid short-chain alkyl ester, which includes MMA as the first monomer described above, and further includes a part of the second monomer. Including. Examples of (meth) acrylic acid alkyl ester having 6 or less carbon atoms in the alkyl moiety include, for example, methyl (meth) acrylate, ethyl (meth) acrylate, n-propyl (meth) acrylate, iso- (meth) acrylate. Propyl, n-butyl (meth) acrylate, iso-butyl (meth) acrylate, tert-butyl (meth) acrylate, n-pentyl (meth) acrylate, n-hexyl (meth) acrylate, etc. . As the (meth) acrylic acid short chain alkyl ester, preferably, MMA which is the first monomer is used.

  The (meth) acrylic acid alkyl ester having 7 or more carbon atoms in the alkyl moiety is a (meth) acrylic acid long-chain alkyl ester. The (meth) acrylic acid alkyl ester having 7 or more carbon atoms in the alkyl portion is the remainder of the (meth) acrylic acid alkyl ester in the second monomer described above, for example, (meth) acrylic acid n-heptyl, (meth) Linear (meth) acrylic acid alkyl esters such as n-octyl acrylate, n-dodecyl (lauryl) (meth) acrylate, and n-octadecyl (stearyl) (meth) acrylate, such as (meth) acrylic acid Examples include branched (meth) acrylic acid alkyl esters such as 2-ethylhexyl and iso-nonyl (meth) acrylate. In addition, the (meth) acrylic acid alkyl ester having 10 or more carbon atoms in the alkyl portion exhibits an effect as a hydrophobe in miniemulsion polymerization, while the (meth) acrylic acid alkyl ester having 10 or more carbon atoms is incorporated into the mini portion. When preparing emulsions, higher mechanical shear forces are required to reach particle sizes below 1 μm and even below 500 nm.

  The blending ratio of the (meth) acrylic acid short chain alkyl ester is, for example, 75% by mass or more, preferably 80% by mass or more, more preferably 85% by mass or more, and further preferably, with respect to the total amount of the polymerizable vinyl monomer. Is 90% by mass or more. In other words, the blending ratio of the (meth) acrylic acid long chain alkyl ester is, for example, 25% by mass or less, preferably 20% by mass or less, and more preferably 15% by mass with respect to the total polymerizable vinyl monomer amount. Hereinafter, it is more preferably 10% by mass or less.

  When the blending ratio of the (meth) acrylic acid short chain alkyl ester is less than the above lower limit or the blending ratio of the (meth) acrylic acid long chain alkyl ester exceeds the above upper limit, the polymerization rate of the miniemulsion polymerization is lowered. In addition, the compatibility between IPBC and the polymerizable vinyl monomer is reduced, and IPBC is not sufficiently dissolved in the polymerizable vinyl monomer, or even if IPBC is dissolved in the polymerizable vinyl monomer, It leaks outside and forms needle-like crystals. That is, a uniform phase (described later) that is equal to the charged composition ratio of IPBC and polymer cannot be formed.

  The polymerizable vinyl monomer described above is substantially hydrophobic and has, for example, extremely low solubility in water at room temperature. Specifically, the solubility at room temperature is, for example, 8 parts by mass / 100 parts by mass or less of water, Preferably, it is 5 parts by mass / 100 parts by mass or less of water, more preferably 3 parts by mass / 100 parts by mass or less of water. The polymerizable vinyl monomer may be used in combination with different types (for example, when the first monomer and the second monomer are used in combination, for example, with different types of the first monomer in combination, or (meta ) When short-chain alkyl esters of acrylic acid and long-chain alkyl esters of (meth) acrylic acid are used together), the entire polymerizable vinyl monomer (ie, a mixture of different types of polymerizable vinyl monomers) is substantially hydrophobic. It is.

And regarding the polymer obtained by miniemulsion polymerization, the dipole force term δ _{p, polymer} of the solubility parameter δ is 5.0 to 7.0 [(J / cm ³ ) ^1/2 ], preferably 5 0.0 to 6.5 [(J / cm ³ ) ^1/2 ], and the hydrogen bonding term δ _{h, polymer of} the solubility parameter δ is 8.0 to 10.0 [(J / cm ³ ) ^{1 / 2} ], preferably 9.0 to 10.0 [(J / cm ³ ) ^1/2 ].

If the dipole force term δ _{p, polymer} and / or the hydrogen bond force term δ _{h, polymer} of _{the polymer} is less than the above range _{, the polymer} becomes excessively hydrophobic and has sufficient compatibility with IPBC. Even if compatibility can be obtained, IPBC leaks out of the sustained-release particles during the miniemulsion polymerization, making it difficult to synthesize sustained-release particles sufficiently containing IPBC. It may become.

On the other hand, when the polymer dipole force term δ _{p, polymer} and / or the hydrogen bond force term δ _{h, polymer} exceeds the above range, the hydrophilicity of the polymer becomes excessively high and sufficient compatibility with IPBC is achieved. Even if compatibility can be obtained, the free energy of the interface with the aqueous phase in the miniemulsion polymerization becomes low, and IPBC leaks out of the sustained release particles during the miniemulsion polymerization. Thus, it may be difficult to synthesize sustained release particles sufficiently encapsulating IPBC.

Further, in the solubility parameter δ, a value Δδ _p (= δ _{p, polymer} −−) obtained by subtracting the dipole force term δ _{p, IPBC} (= 3.23) of _IPBC from _{the polymer} dipole force term δ _{p, polymer of the polymer.} [delta] _{p, IPBC),} for ^{example, 0~3 [(J / cm 3} ) 1/2], ^{preferably, 1~3 [(J / cm 3} ) 1/2].

The hydrogen bonding term polymer [delta] _h, the hydrogen bonding term of IPBC from _{polymer δ h, IPBC (= 7.83} ) obtained by subtracting the value _{Δδ h (= δ h, polymer} -δ h, IPBC) is For example, 0 to 3 [(J / cm ³ ) ^1/2 ], preferably 1 to 3 [(J / cm ³ ) ^1/2 ].

If .DELTA..delta _p and .DELTA..delta _h is within the range shown above, to ensure excellent compatibility IPBC and polymers, it is possible to ensure excellent sustained release.

IPBC dipole force term δ _{p, IPBC} and hydrogen bond force term δ _{h, IPBC} are the values described above, and the dipole force term δ _{p, polymer} and hydrogen bond force term δ _{h, polymer} of _{the polymer} are Within the above range, IPBC is defined as being compatible with the polymer without leakage from the sustained release particles during miniemulsion polymerization. That is, the sustained release particles are composed of a uniform phase equal to the charged composition ratio of IPBC and polymer.

  Examples of the emulsifier include emulsifiers commonly used in miniemulsion polymerization. For example, sodium dialkyl sulfosuccinate such as sodium dioctyl sulfosuccinate, sodium dodecyl diphenyl ether disulfonate, sodium alkyl diphenyl ether sulfonate such as sodium nonyl diphenyl ether sulfonate, dodecylbenzene sulfone. Acid sodium, sodium lauryl sulfate, polyoxyethylene dodecyl ether sulfate sodium salt, polyoxyethylene nonyl phenyl ether sulfate sodium salt, polyoxyethylene styrenated phenyl ether sulfate ammonium salt, polyoxyethylene nonyl phenyl ether phosphate ammonium salt And anionic emulsifiers.

  Examples of the emulsifier include nonionic emulsifiers such as polyoxyalkylene alkyl ether, polyoxyalkylene alkyl aryl ether, polyoxyalkylene aralkyl aryl ether, polyoxyalkylene block copolymer, and polyoxyalkylene aryl ether.

  Examples of the polyoxyalkylene alkyl ether include polyoxyethylene alkyl ether.

  Examples of the polyoxyalkylene alkyl aryl ether include polyoxyethylene nonyl phenyl ether and polyoxyethylene octyl phenyl ether.

  Examples of the polyoxyalkylene aralkyl aryl ether include polyoxyethylene styrenated phenyl ether (for example, Neugen EA-177 (Daiichi Kogyo Seiyaku Co., Ltd.)).

  Examples of the polyoxyalkylene block copolymer include a polyoxyethylene-polyoxypropylene block copolymer.

  Examples of the polyoxyalkylene aryl ether include polyoxyethylene aryl ether.

  HLB of a nonionic emulsifier is 11-20, for example, Preferably, it is 12-19, More preferably, it is 13-18.

  The HLB is calculated by the Griffin equation shown by the following equation (1).

HLB = 20 × (sum of formula weight of hydrophilic part / molecular weight) (1)
As a nonionic emulsifier, Preferably, a polyoxyalkylene aralkyl aryl ether is mentioned.

  The emulsifiers can be used alone or in combination of two or more. Preferably, an anionic emulsifier is used alone, and more preferably, a sodium dialkylsulfosuccinate is used alone.

  When an anionic emulsifier and a nonionic emulsifier are used in combination, the blending ratio of the anionic emulsifier is, for example, 10 to 60% by mass, preferably 15 to 50% by mass with respect to the emulsifier. Is, for example, 40 to 90 mass%, preferably 50 to 85 mass% with respect to the emulsifier.

  In addition, an emulsifier can also be previously mixed and dissolved in water at an appropriate ratio to prepare an emulsifier-containing aqueous solution. The mixture ratio of the emulsifier in the emulsifier-containing aqueous solution is, for example, 10 to 90% by mass, preferably 20 to 80% by mass.

  PVA is a dispersant blended in an aqueous phase to form a protective colloid of a mini-emulsion, for example, a polyvinyl acetate system obtained by polymerizing a vinyl monomer containing vinyl acetate as a main component by an appropriate method. It can be obtained by saponifying the polymer.

  The degree of saponification of PVA is, for example, 70% or more, preferably 80% or more, and for example, 99% or less, preferably 90% or less.

  The average degree of polymerization of PVA is, for example, 300 or more, preferably 500 or more, and for example, 4000 or less, preferably 2500 or less.

  PVA has a 4% aqueous solution having a viscosity at 20 ° C. of, for example, 3 mPa · sec or more, preferably 5 mPa · sec or more, and for example, 100 mPa · sec or less, preferably 50 mPa · sec or less.

  The viscosity of PVA can be measured using a B-type viscometer with a 4% aqueous solution at 20 ° C.

  Examples of the polymerization initiator include polymerization initiators usually used in miniemulsion polymerization, and examples include oil-soluble polymerization initiators and water-soluble polymerization initiators.

  Examples of the oil-soluble polymerization initiator include dilauroyl peroxide, 1,1,3,3-tetramethylbutylperoxy-2-ethylhexanoate, t-hexylperoxy-2-ethylhexanoate, and diisopropyl. Oil-soluble organic peroxides such as peroxydicarbonate and benzoyl peroxide, such as 2,2′-azobisisobutyronitrile, 2,2′-azobis (2,4-dimethylvaleronitrile), 2,2 Examples thereof include oil-soluble azo compounds such as' -azobis (2-methylbutyronitrile).

  Examples of the water-soluble polymerization initiator include 2,2′-azobis (2-methylpropionamidine) disulfate, 2,2′-azobis (2-methylpropionamidine) dihydrochloride, and 2,2′-azobis. (2-amidinopropane) dihydrochloride, 2,2′-azobis [N- (2-carboxyethyl) -2-methylpropionamidine] hydrate, 2,2′-azobis (N, N′-dimethylene) Isobutylamidine), 2,2′-azobis {2- [1- (2-hydroxyethyl) -2-imidazolin-2-yl] propane} dihydrochloride, 2,2′-azobis (1-imino-1- Pyrrolidino-2-methylpropane) dihydrochloride, 2,2′-azobis {2-methyl-N- [1,1-bis (hydroxymethyl) -2-hydroxyethyl] propionamide}, 2,2′-azo [2-methyl-N- (2-hydroxyethyl) propionamide], 2,2′-azobis [2- (2-imidazolin-2-yl) propane], 2,2′-azobis [2- (2 -Imidazolin-2-yl) propane] dihydrochloride, 2,2′-azobis [2- (2-imidazolin-2-yl) propane] disulfate dihydrate, such as peroxy Persulfate compounds such as potassium sulfate, sodium persulfate (SPS), and ammonium persulfate, for example, water-soluble inorganic peroxides such as hydrogen peroxide, and water-soluble organic peroxides such as tert-butyl peroxide and cumene peroxide. An oxide etc. are mentioned. Further, as a water-soluble polymerization initiator, for example, a water-soluble polymerization initiator excluding a water-soluble azo compound, ascorbic acid, sodium bisulfite, sodium hyposulfite, sodium bisulfite, sodium sulfite, sodium bisulfite, hydroxymethanesulfine Examples also include redox-based water-soluble polymerization initiators in combination with water-soluble reducing agents such as sodium acid (Longalite), thiourea dioxide, sodium thiosulfate, divalent iron salt, monovalent copper salt, and amines.

  The polymerization initiators can be used alone or in combination of two or more.

  Preferably, an oil-soluble polymerization initiator is used, and more preferably, an oil-soluble organic peroxide is used.

  And in the manufacturing method of the sustained release particle | grains of this invention, a hydrophobic solution is first prepared by melt | dissolving IPBC with a hydrophobic polymerizable vinyl monomer.

  That is, by mixing IPBC and a polymerizable vinyl monomer and stirring them uniformly, a hydrophobic solution is obtained.

  The hydrophobic solution should contain, for example, a solvent capable of dissolving IPBC (hydrophobic organic solvent such as hexane, toluene and ethyl acetate) and / or hydrophobe (costabilizer such as cetyl alcohol and hexadecane). Prepared. Thereby, environmental load can be reduced.

  The blending ratio of IPBC to the polymerizable vinyl monomer is, for example, 0.01 or more, preferably 0.05 or more, more preferably, on a mass basis (that is, IPBC mass part / polymerizable vinyl monomer mass part). 0.1 or more, more preferably 0.2 or more, particularly preferably 0.3 or more, and for example, 1.5 or less, preferably 1.0 or less, more preferably 0.75 or less. More preferably, it is 0.5 or less.

  The hydrophobic solution may be prepared at room temperature, for example, or may be heated to increase the dissolution rate of IPBC in the polymerizable vinyl monomer.

  The heating temperature is, for example, 30 to 100 ° C, preferably 40 to 80 ° C.

  In the preparation of the hydrophobic solution, when an oil-soluble polymerization initiator is used as a polymerization initiator, an oil-soluble polymerization initiator is blended together with IPBC and a polymerizable vinyl monomer. The blending of the oil-soluble polymerization initiator is preferably carried out at room temperature. When IPBC and a polymerizable vinyl monomer are blended and heated to dissolve IPBC in the polymerizable vinyl monomer, the solution is cooled to room temperature, and then an oil-soluble polymerization initiator is blended.

  The blending ratio of the oil-soluble polymerization initiator is, for example, 0.01 parts by mass or more, preferably 0.1 parts by mass or more, for example, 5 parts by mass or less, preferably 100 parts by mass of the polymerizable vinyl monomer. Is also 3 parts by mass or less.

  When the blending ratio of the oil-soluble polymerization initiator exceeds the above upper limit, the molecular weight of the polymer may be excessively decreased, and when it does not satisfy the above lower limit, the conversion rate is not sufficiently improved and unreacted. In some cases, several% or more of the polymerizable vinyl monomer may remain.

  Moreover, in the manufacturing method of the sustained release particle | grains of this invention, water, an emulsifier, and PVA are mix | blended separately and an emulsifier-PVA aqueous solution is prepared.

  Specifically, an aqueous PVA solution is prepared in advance, water and an emulsifier are blended therein, and they are uniformly stirred to obtain an emulsifier-PVA aqueous solution.

  The amount of the emulsifier is sufficient for the emulsifier to be adsorbed on the entire surface of the hydrophobic solution emulsified droplets, and the presence of excess emulsifier causes the generation of emulsion polymerized particles of a new polymerizable vinyl monomer that does not contain IPBC. Is selected depending on the type of emulsifier, but for example, the active ingredient (AI: Active Ingredient) amount of the emulsifier is 0.1 to 20% by mass, preferably, It is 0.2-10 mass%.

  The blending ratio of PVA is selected in an amount sufficient for PVA to be adsorbed on the entire surface of the hydrophobic solution emulsified droplet, and varies depending on the type of PVA. As an amount, it is 0.5-10 mass%, for example, Preferably, it is 1-8 mass%.

  For the preparation of the PVA aqueous solution, for example, PVA is added to and dispersed in cold water at 25 ° C. or lower with stirring, and the temperature is raised to 60 to 90 ° C. and dissolved. After confirming that PVA is completely dissolved in water, it can be carried out by cooling to room temperature.

  Further, the emulsifier-PVA aqueous solution may contain a dispersant other than PVA.

  Examples of the dispersant include condensates of aromatic sulfonic acid and formaldehyde, polycarboxylic acid type oligomers, and preferably condensates of aromatic sulfonic acid and formaldehyde.

  Examples of the condensate of aromatic sulfonic acid and formaldehyde include sodium salt of β-naphthalene sulfonic acid formaldehyde condensate.

  These dispersants can be used alone or in combination of two or more.

  The blending ratio of the dispersant is, for example, 0.001% by mass or more, preferably 0.01% by mass or more, for example, 0.5% by mass or less, preferably, with respect to the hydrophobic solution. 0.3 mass% or less, and more preferably 0.2 mass% or less.

  In the preparation of the emulsifier-PVA aqueous solution, when a water-soluble polymerization initiator is used as the polymerization initiator, a water-soluble polymerization initiator is blended together with water, the emulsifier and the PVA aqueous solution. The blending of the water-soluble polymerization initiator is preferably carried out at room temperature.

  The mixing ratio of the water-soluble polymerization initiator is, for example, 0.01 parts by mass or more, preferably 0.1 parts by mass or more, for example, 5 parts by mass or less, preferably 3 parts with respect to 100 parts by mass of water. It is also below mass parts.

  When the blending ratio of the water-soluble polymerization initiator exceeds the above upper limit, the molecular weight of the polymer may be excessively reduced. When the blending ratio is less than the above lower limit, the conversion rate is not sufficiently improved and unreacted. In some cases, several% or more of the polymerizable vinyl monomer may remain.

  In the method for producing sustained-release particles of the present invention, the hydrophobic solution is then emulsified in an emulsifier-PVA aqueous solution.

  Specifically, a hydrophobic solution is blended in an emulsifier-PVA aqueous solution, and a high shear force is applied to them to emulsify the hydrophobic solution in the emulsifier-PVA aqueous solution to prepare a miniemulsion.

  In emulsification of the hydrophobic solution, for example, an emulsifier such as a homomixer (homogenizer), an ultrasonic homogenizer, a pressure homogenizer, a milder, or a porous membrane press emulsifier is used, and preferably a homomixer is used.

  The stirring conditions are set as appropriate, and when a homomixer is used, the number of rotations is set to, for example, 6000 rpm or more, preferably 8000 rpm or more, more preferably 10,000 rpm or more, for example, 30000 rpm or less.

  If the rotational speed is less than the lower limit, miniemulsion particles having a particle diameter of less than 1 μm may not be formed.

  The stirring time is, for example, 1 minute or longer, preferably 2 minutes or longer, and 1 hour or shorter.

  The miniemulsion can be prepared, for example, at room temperature or by heating. Preferably, the miniemulsion is prepared at room temperature.

  When preparing a miniemulsion by heating, the heating temperature is, for example, less than the temperature at which the polymerization initiator decomposes, specifically, for example, 30 ° C. or higher, preferably 35 ° C. or higher, For example, it is 50 ° C. or lower, preferably 40 ° C. or lower.

  The mixing ratio of the hydrophobic solution is, for example, 10 to 150 parts by mass, preferably 25 to 90 parts by mass with respect to 100 parts by mass of the emulsifier-PVA aqueous solution.

  A mini-emulsion of a hydrophobic solution is prepared by the method described above. In the hydrophobic emulsion miniemulsion, the emulsifier is adsorbed on the miniemulsion particles (hydrophobic solution emulsified droplets), and the hydrophobic emulsion miniemulsion particles with an average particle diameter of less than 1 μm are formed in the aqueous medium. Has been.

  The average particle diameter (median diameter, which will be described later) of the miniemulsion particles is adjusted to less than 1 μm, preferably 750 nm or less, more preferably 500 nm or less, particularly preferably 300 nm or less, and for example, 50 nm or more.

  Note that an emulsifier is adsorbed on the surface of the miniemulsion particles, thereby stabilizing the miniemulsion.

  Therefore, after the miniemulsion prepared by stirring is prepared and allowed to stand, it can be subjected to the next miniemulsion polymerization. In that case, the standing time may be 24 hours or longer, for example.

  The average particle size of the miniemulsion particles does not change substantially with time, or the rate of change is extremely small.

  Specifically, the ratio of the average particle size after the lapse of 24 hours (standing at room temperature) after the preparation to the average particle size after lapse of 20 minutes (standing at room temperature) from the preparation of the miniemulsion (from the preparation to 24 The average particle diameter after the lapse of time / the average particle diameter after the lapse of 20 minutes from the preparation) is, for example, 0.9 to 1.1, preferably 0.95 to 1.05.

  In the present invention, the polymerized vinyl monomer in the emulsified hydrophobic solution is then subjected to miniemulsion polymerization in the presence of a polymerization initiator to produce a polymer.

  This miniemulsion polymerization is an in situ polymerization because all of the polymerizable vinyl monomers as raw materials are only in the miniemulsion particles (hydrophobic liquid phase).

  That is, in the mini-emulsion polymerization, by heating the mini-emulsion while stirring, the polymerization vinyl monomer starts polymerization in the mini-emulsion particles as it is, and a polymer is generated.

  Agitation can be performed, for example, with a stirrer having a stirring blade, and stirring sufficient to control uniform heat conduction to the miniemulsion, sticking of the miniemulsion particles to the wall, and retention of the miniemulsion on the surface of the miniemulsion. As long as the effect can be realized, excessive stirring causes aggregation of the miniemulsion particles. As for the stirring speed, the peripheral speed of the stirring blade is, for example, 10 m / min or more, preferably 20 m / min or more, and 400 m / min or less, preferably 200 m / min or less.

  Under heating conditions, the heating temperature is, for example, not less than the melting point (60 ° C.) of IPBC, specifically 40 to 100 ° C., preferably 60 to 80 ° C. Since the miniemulsion polymerization proceeds in a state where the IPBC is compatible with the polymer, the heating temperature is at least the melting point of the IPBC, that is, 60 ° C. or more, at least from the end of the polymerization, preferably from the beginning of the polymerization. It is necessary. The heating time is, for example, 2 to 12 hours, preferably 3 to 8 hours. Furthermore, after heating to a predetermined temperature, the temperature can be maintained for a predetermined time, and then heating and temperature maintenance can be repeated to heat in stages.

  MMA is known to have a strong odor even in small amounts, and even if it remains slightly unreacted, it may damage the environment. Therefore, for example, in MMA, in accordance with Article 95-6 of the Occupational Safety and Health Regulations, those containing MMA with a mass of 0.1% or more shall be Submission is required. For this reason, in order to reduce the amount of the polymerizable vinyl monomer containing MMA remaining at the end of polymerization (residual monomer amount), for example, in the residual polymerizable vinyl monomer and the sustained-release particles that are saturated and dissolved in the aqueous phase In order to polymerize both of the remaining monomers, the above-mentioned water-soluble polymerization initiator is preferably added.

  Examples of the water-soluble polymerization initiator include the same water-soluble polymerization initiators as described above. Preferably, a persulfate compound is used.

  The mixing ratio of the water-soluble polymerization initiator is, for example, 0.01 to 0.5 parts by mass with respect to 100 parts by mass of the polymerizable vinyl monomer.

  As a result, the amount of residual monomer at the end of the polymerization is, for example, less than 0.1% by mass, preferably less than 0.08% by mass of the sustained-release particle emulsion.

  As described above, the miniemulsion polymerization is clearly different from emulsion polymerization in which the polymerization process is not in situ polymerization but polymerization is performed by mass transfer of a polymerizable vinyl monomer, in that the polymerization process is in situ polymerization. .

  Specifically, emulsion polymerization is carried out in the aqueous phase in the presence of an emulsifier, a polymerizable vinyl monomer, and a polymerization initiator (radical polymerization initiator), and is polymerized by radicals generated by decomposition of the radical polymerization initiator. To start. At this time, the polymerizable vinyl monomer exists in the following three states. That is, (1) a state solubilized in micelles of an emulsifier (state having an average particle diameter of less than several tens of nanometers), (2) a state dissolved in an aqueous phase, and (3) a state existing as oil droplets (particle diameter The polymerizable vinyl monomer exists in three states (several μm or more).

  The radicals generated by the decomposition of the radical polymerization initiator may collide and invade the three-state polymerizable vinyl monomer and add to the polymerizable vinyl monomer to start polymerization. 1) The micelle of the emulsifier solubilized with the polymerizable vinyl monomer has an overwhelmingly larger number of particles than the oil droplets of the above-described (3) polymerizable vinyl monomer, and therefore has a large surface area and a radical penetration probability. Since it is high, (1) Polymerization starts in the micelle of the emulsifier to form polymer particles. In addition, when a highly water-soluble polymerizable vinyl monomer is used as the polymerizable vinyl monomer, radical addition to the vinyl monomer dissolved in the above-described (2) aqueous phase also occurs, and the produced polymer is water. When it cannot be dissolved in the phase and is precipitated, it is stabilized by an emulsifier and polymer particles are produced. Such an initiation reaction is also observed in the emulsion polymerization process.

  When the emulsion polymerization starts, (3) the polymerizable vinyl monomer is dissolved in the water phase from the oil droplets of the polymerizable vinyl monomer, and then the polymerizable vinyl monomer moves to the polymer particles and the polymerization proceeds. That is, the polymerization field is polymer particles, and the oil droplets of the polymerizable vinyl monomer only serve as a supply source of the polymerizable vinyl monomer, and polymerization, that is, in situ polymerization does not occur on the spot. .

  In contrast, miniemulsion polymerization is highly sheared into oil droplets of polymerizable vinyl monomers in the aqueous phase by the presence of emulsifiers and hydrophobes (costabilizers), using homomixers, homogenizers, and ultrasonic irradiation. When the particle size is reduced to less than 1 μm, preferably less than 0.5 μm by applying force, and the polymerization initiator (radical polymerization initiator) is oil-soluble, the minute and stable polymerizable vinyl monomer In the oil droplets, polymerization is caused by radicals generated by decomposition of the polymerization initiator, or when the polymerization initiator is water-soluble, radicals enter the oil droplets from the aqueous phase, It is a polymerization method that starts and radical polymerization proceeds.

  Specifically, fine polymerizable vinyl monomer oil droplets having a particle diameter of less than 1 μm exist stably by employing, for example, an anionic emulsifier as an emulsifier. At the same time, oil droplets of minute polymerizable vinyl monomers having a particle diameter of less than 1 μm have a large total surface area and the molecular weight of the polymerizable vinyl monomers easily diffuses into the aqueous phase. By using a hydrophobe (costabilizer), Stable by controlling the bloating (Ostwald ripening) due to the transfer of polymerizable vinyl monomer from oil droplets of smaller (fine) polymerizable vinyl monomer to oil droplets of larger polymerizable vinyl monomer via the aqueous phase Exists.

  On the other hand, in the present invention, miniemulsion particles (fine oil droplets composed of IPBC and polymerizable vinyl monomer) produced by the reduction of the interfacial free energy by the emulsifier and a large mechanical shear force are colloidally stabilized by the emulsifier and PVA. At the same time, IPBC suppresses an increase in the particle diameter by the role of the hydrophobe and stabilizes the particles. Miniemulsion polymerization in which the polymerizable vinyl monomer is polymerized (radical polymerization) proceeds in the miniemulsion particles. During miniemulsion polymerization, the polymer of polymerizable vinyl monomer is preferably compatible with IPBC. That is, the polymer is dissolved in IPBC to form an IPBC solution of the polymer, and the IPBC solution particles are emulsified in water.

  The polymerizable vinyl monomer is preferably selected such that the polymer of the polymerizable vinyl monomer and the IPBC are compatible as described above at the polymerization temperature (heating temperature) during the above-described miniemulsion polymerization. Therefore, phase separation is prevented from occurring during miniemulsion polymerization, and the polymer (polymer in the middle of reaction) is dissolved in IPBC, or the polymer (polymer in the middle of reaction) is dissolved in IPBC. Then, the reaction proceeds in a swollen state, and sustained release particles in which a uniform phase is formed can be obtained.

  In addition, since the miniemulsion particles during polymerization form a stable hydrated layer by the protective colloid of PVA, aggregation due to collision between the particles hardly occurs, and is added to reduce the amount of residual monomers. The destabilization of the miniemulsion particles by the water-soluble polymerization initiator can be prevented. That is, the method for producing sustained release particles of the present invention is excellent in polymerization stability.

  In other words, in order to obtain stable particles of less than 1 μm by miniemulsion polymerization, it is necessary to be electrostatically stabilized with an emulsifier, but such electrostatically stabilized particles are Addition of electrolyte impairs stability. However, in the miniemulsion polymerization of the present invention, even when an electrolyte is added to the solution, the resulting particles are stabilized and the generation of aggregates can be extremely reduced.

  Thereafter, the emulsion after polymerization is cooled, for example, by cooling, and filtered through a 100th filter cloth or the like to obtain an emulsion of sustained release particles.

  The cooling temperature is, for example, room temperature (20 to 30 ° C., more specifically 25 ° C.).

  Since the melting point of IPBC is 60 ° C., the compatible state of the polymer of the polymerizable vinyl monomer and IPBC is frozen by cooling to form sustained-release particles as a uniform phase.

  When the sustained-release particles are formulated as a powder (described later) or a granule (described later), preferably at a room temperature, the hard-release glass is used to prevent the sustained-release particles from fusing together. As such, a polymerizable vinyl monomer is selected.

  In addition, when the mold-proof property is exhibited by adhering to the substrate to which mold-proof property is to be imparted, the polymerizable monomer is selected so as to be in a soft rubber state.

  The average particle size of the sustained-release particles (polymer) thus obtained is a median size of less than 1 μm, preferably 750 nm or less, more preferably 500 nm or less, and particularly preferably 300 nm or less. For example, it is 10 nm or more, preferably 50 nm or more.

  This median diameter can be measured as a volume-based median diameter by a dynamic light scattering method using a particle size analyzer (FPAR-1000, Otsuka Electronics Co., Ltd.).

  The content ratio of IPBC in the sustained release particles is, for example, 10% by mass or more, preferably 20% by mass or more, and for example, 50% by mass or less, preferably 40% by mass or less.

  Thereby, an emulsion in which sustained-release particles in which IPBC exists uniformly is finely dispersed can be obtained.

  The obtained emulsion can suppress the precipitation of IPBC needle crystals during storage of the emulsion by controlling the production and growth of IPBC needle crystals of PVA.

  In addition, this emulsion is suppressed in aggregation due to the protective colloid effect of PVA during the polymerization of the mini-emulsion, and the amount of residue on the filter cloth when filtered through the 100th filter cloth, which is an indicator of polymerization stability, is The amount is, for example, 0.2% by mass or less, preferably 0.1% by mass or less, with respect to the sustained release particles.

  Further, the content of sustained-release particles exceeding 1 μm (measurement method will be described later) is, for example, 30% by volume or less, preferably 10% by volume or less, more preferably 0 volume with respect to the total amount of the sustained-release particles. %.

  In addition, known additives such as other dispersants, thickeners, antifreeze agents, preservatives, microbial growth inhibitors, specific gravity regulators, and the like are appropriately blended into the emulsion containing sustained release particles as necessary. .

  The thus obtained sustained-release particles may be used as they are (emulsion), that is, as an emulsion, or aggregated by spray drying, freezing / thawing, salting out, or the like. After that, solid-liquid separation is performed by centrifugation, washing, drying, and the like, and for example, it may be formulated into a known dosage form such as powder or granule. In particular, (meth) acrylic acid alkyl ester as the second monomer (specifically, for example, acrylic acid alkyl ester having an alkyl moiety having 2 or more carbon atoms such as n-BA, for example, 2-ethylhexyl methacrylate, etc. The sustained-release particles containing a methacrylic acid alkyl ester having an alkyl moiety having 5 or more carbon atoms) have a low glass transition temperature, and therefore have a low minimum film-forming temperature (MFT). Therefore, it is excellent in film forming property, and therefore is suitably used for film forming applications.

  And the manufacturing method of the sustained release particle | grains of this invention makes the minimization of the polymerizable vinyl monomer of the hydrophobic solution emulsified in the emulsifier-PVA aqueous solution containing water, an emulsifier, and PVA in presence of a polymerization initiator. Since the sustained-release particles of the present invention are obtained by emulsion polymerization to produce a polymer having an average particle diameter of less than 1 μm containing IPBC, the sustained-release particles are excellent in dispersibility and storage stability.

Further, in this sustained-release particle, the polymer has a solubility parameter δ of the dipole force term δ _{p, polymer} of the solubility parameter δ of 5.0 to 7.0 [(J / cm ³ ) ^1/2 ]. since the hydrogen bonding term [delta] _{h, Polymer} of is set to ^{8.0~10.0 [(J / cm 3)} 1/2], compatibility with IPBC is superior to more remarkable. As a result, the polymer contains IPBC so that IPBC exists uniformly.

  Since the sustained release particles have an average particle diameter of less than 1 μm, sedimentation based on gravity hardly occurs, and the sustained release particles are uniformly dispersed in the emulsion due to Brownian motion of the sustained release particles. When the liquid is added to various aqueous media, it can be uniformly dispersed in the liquid.

  Therefore, the sustained-release particles of the present invention are uniformly (uniformly) dispersed with an average particle diameter of less than 1 μm (submicron size) in the added medium, so that excellent sustained-release properties, excellent dispersibility and As sustained release particles having excellent storage stability, they can be used in various applications.

  Specifically, the sustained-release particles can be applied to various industrial products, such as indoor and outdoor paints, rubber, fibers, resins, plastics, adhesives, joint agents, sealing agents, building materials, caulking agents. , Soil treatment agent, wood, white water in papermaking process, pigment, printing plate treatment liquid, cooling water, ink, cutting oil, cosmetics, non-woven fabric, spinning oil, leather, etc., antibiotic activity (specifically, prevention It can be added as an additive (an antifungal agent) that develops (mold). In addition, the addition amount of IPBC in the sustained release particles for these industrial products is, for example, 10 mg / kg to 100 g / kg (product mass).

  Moreover, this sustained release particle | grain can be suitably mix | blended with the water-based coating material in which the emulsifier common to the emulsifier-PVA aqueous solution is used. The water-based paint is a water-based paint used indoors and outdoors. Specifically, for example, acrylic, acrylic-styrene, styrene, vinyl acetate, vinyl acetate-acrylic, polyester, silicone, urethane Paints using vehicle, alkyd, and fluororesin emulsions or water-based resins and mixtures of these as vehicles. Among them, when blended with zero VOC paints, they are environmentally friendly and contain sustained release particles. The stability can be maintained well, and the sustainability of the effect can be further improved.

  In addition, since IPBC can also be used as a hydrophobe in miniemulsion polymerization, it is possible to easily produce sustained-release particles having an average particle diameter of less than 1 μm without separately adding a hydrophobe.

  Further, if the average particle diameter of the sustained-release particles is 750 nm or less and 100 nm or more, for example, when there is a difference of 0.2 or more between the refractive index of the sustained-release particles and the refractive index of the medium The reflection of light (visible light, wavelength 360 to 760 nm) is large at the interface between the sustained-release particles and the medium, and the sustained-release particles mixed in the medium appear white.

  Furthermore, if the average particle size of the sustained-release particles is less than 100 nm, the ratio of light (visible light, wavelength 360 to 760 nm) that permeates the sustained-release particles is high regardless of the medium, and the transparency is enhanced. .

  Therefore, the sustained-release particles of the present invention blended in an appropriate medium can be suitably used as an additive for paints because even when IPBC is substantially discolored, discoloration is suppressed by visual observation.

  Details of the raw materials or measurement methods used in each example and each comparative example are described below.

IPBC: Trade name “Fangitrol 400”, 3-iodo-2-propynylbutylcarbamate, molecular weight 281, melting point: 60 ° C., solubility in water: 150 ppm, dipole force term δ p, IPBC of solubility parameter δ: IPBC : 3 .23 [(J / cm 3 ) 1/2 ], hydrogen bond strength term δ h, IPBC of solubility parameter δ: 7.83 [(J / cm 3 ) 1/2 ], epoxy manufactured by International Specialty Products, Inc. Conazole: cis-1-[[3- (2-chlorophenyl) -2- (4-fluorophenyl) oxiranyl] methyl] -1H-1,2,4-triazole, molecular weight 330, melting point: 136-137 ° C. solubility in water: 6.6 ppm, polar term [delta] p of the solubility parameter [delta], epoxiconazole: 5.82 [(J / cm 3 ) 1 2], the solubility parameters [delta] of the hydrogen bonding term [delta] h, epoxiconazole: 7.1 [(J / cm 3 ) 1/2], LKT Laboratories, Inc. triticonazole: 5 - [(4-chlorophenyl) methylene ] -2,2-dimethyl-1- (1H-1,2,4-triazol-1-ylmethyl) cyclopentanol, molecular weight 318, melting point: 139-141 ° C., water solubility: 9.3 ppm, solubility parameter Dipole force term of δ δ p, triticonazole : 5.27 [(J / cm 3 ) 1/2 ], hydrogen bond term of solubility parameter δ δ h, triticonazole : 10.81 [(J / cm 3) 1/2], LKT Laboratories, Inc. MMA: methyl methacrylate, trade name "ACRYESTER M", the solubility in water: 1.6 wt%, dipole-dipole force solubility parameter δ δ p, 1st monomer unit: 5.98 [(J / cm 3) 1/2], hydrogen bonding term solubility parameter δ δ h, 1st monomer unit: 9.25 [(J / cm 3) 1/2 ], Manufactured by Mitsubishi Rayon Co., Ltd. n-BA: n-butyl acrylate, solubility in water: 0.2 mass%, dipole force term δ p, 2nd monomer unit of solubility parameter δ: 4.26 [(J / cm 3 ) 1/2 ], hydrogen bond strength term δ h, 2nd monomer unit of solubility parameter δ: 7.81 [(J / cm 3 ) 1/2 ], Nippon Shokubai Co., Ltd. EGDMA: ethylene glycol dimethacrylate, commodity the name "light ester EG", solubility in water: 5.37 ppm, polar term of a solubility parameter δ δ p, 1st monomer unit: 5.3 [(J / cm 3) 1/2 ], hydrogen bonding term solubility parameter δ δ h, 1st monomer unit: 10.42 [(J / cm 3) 1/2], Kyoeisha Chemical Co., Ltd. MAA: methacrylic acid Solubility in water: 8.9% by mass, dipole force term δ p, 2nd monomer unit of solubility parameter δ as monomer unit : 7.13 [(J / cm 3 ) 1/2 ], as monomer unit Hydrogen bond term of solubility parameter δ of δ h, 2nd monomer unit : 13.03 [(J / cm 3 ) 1/2 ], manufactured by Mitsubishi Rayon Co., Ltd. Stearyl acrylate: Dipole force of solubility parameter δ as a monomer unit Term δ p, 2nd monomer unit : 1.44 [(J / cm 3 ) 1/2 ], hydrogen with solubility parameter δ as a monomer unit Bonding force term δh, 2nd monomer unit : 4.54 [(J / cm 3 ) 1/2 ], Wako Pure Chemical Industries, Ltd., Eleminol RS-3000: trade name, methacryloyloxypolyoxypropylene sulfate sodium salt 50% Aqueous solution, polymerization reactive emulsifier (anionic emulsifier having nonionic hydrophilic group), Sanyo Kasei Kogyo Co., Ltd. PETA: pentaerythritol tetraacrylate, dipole force term δ p, 2 nd monomer unit of solubility parameter δ as a monomer unit : 3.79 (J / cm 3 ) 1/2 ], hydrogen bonding term δ h, 2nd monomer unit of solubility parameter δ as a monomer unit : 10.41 [(J / cm 3 ) 1/2 ], Aldrich PAROYLE L: Product name (“PAROYL” is a registered trademark) Uroyl peroxide, made by NOF Corporation Neocol SW-C: trade name, 70% by weight isopropanol solution of sodium dioctylsulfosuccinate (anionic emulsifier), Daiichi Kogyo Seiyaku Co., Ltd. Neugen EA-177: trade name, polyoxyethylene Styrenated phenyl ether (nonionic emulsifier, HLB: 15.6), manufactured by Daiichi Kogyo Seiyaku Co., Ltd. PVA205: trade name, polyvinyl alcohol, saponification degree: 87.0-89.0%, polymerization degree: 500, viscosity (4 % Aqueous solution, 20 ° C.): 5.0 to 6.0 mPa · sec, manufactured by Kuraray Co., Ltd. PVA217: trade name, polyvinyl alcohol, saponification degree: 87.0-89.0%, polymerization degree: 1700, viscosity (4% aqueous solution) 20 ° C.): 22.0 to 27.0 mPa · sec, manufactured by Kuraray Co., Ltd. PVA224: trade name, polyvinyl alcohol, Degree of saponification: 87.0-89.0%, Degree of polymerization: 2400, Viscosity (4% aqueous solution, 20 ° C.): 42.0-50.0 mPa · sec, Kuraray Co., Ltd. Demol NL: Trade name, β-naphthalene Sodium salt of sulfonic acid formaldehyde condensate, dispersant, manufactured by Kao Chemical Co., Ltd. Metroze 90SH-50: trade name, hydroxypropylmethylcellulose, viscosity (2% aqueous solution, 20 ° C.): 50 mPa · sec, manufactured by Shin-Etsu Chemical Co., Ltd. Metroze 90SH -100: Trade name, hydroxypropylmethylcellulose, viscosity (2% aqueous solution, 20 ° C.): 100 mPa · sec, manufactured by Shin-Etsu Chemical Co., Ltd. SPS: sodium persulfate (SPS), water-soluble polymerization initiator, Wako Pure Chemical Industries Note that “%” in Tables 1 to 6 indicates “% by mass” unless otherwise specified.

Example 1
(Manufacture of sustained release particles containing IPBC by miniemulsion polymerization)
In a 200 mL container, 25 g of IPBC, 70.5 g of MMA, 4.5 g of EGDMA, and 0.5 g of Parroyl L were charged and stirred at room temperature to prepare a uniform hydrophobic solution.

  Separately, in a 500 mL beaker, 106.3 g of deionized water, 1.0 g of Neocor SW-C, 40 g of PVA217 (10%) aqueous solution, and 0.24 g of Demol NL are stirred and stirred at room temperature to obtain a uniform emulsifier-PVA aqueous solution. Prepared.

  Next, the hydrophobic solution was added to the emulsifier-PVA aqueous solution in a 500 mL beaker. K. A hydrophobic emulsion was emulsified in an emulsifier-PVA aqueous solution by stirring with a homomixer MARK 2.5 type (manufactured by Primix) at a rotational speed of 14,000 rpm for 5 minutes to prepare a miniemulsion.

  Thereafter, the prepared mini-emulsion was transferred to a 300 mL four-necked flask equipped with a stirrer, a reflux condenser, a thermometer, and a nitrogen introduction tube, and the rotation speed was 125 rpm (circumferential speed 23. While stirring at 6 m / min), the temperature of the four-necked flask was raised with a water bath to carry out miniemulsion polymerization.

  The mini-emulsion polymerization was started at the time when the temperature reached 55 ° C., and then continuously carried out at 62 ± 2 ° C. for 3 hours and 70 ± 2 ° C. for 2 hours.

  Subsequently, the temperature of the water bath is raised so that the temperature of the reaction solution becomes 80 ± 2 ° C., and 2 g of SPS (5%) aqueous solution is supplied over 1 hour (addition of SPS), and at that temperature for 2 hours Aged.

  Thereafter, the reaction solution was cooled to 30 ° C. or lower to obtain an emulsion of sustained-release particles containing IPBC.

  Then, after filtering an emulsion with the filter cloth of 100th, when the median diameter of the sustained release particle | grains in a filtrate was measured, the result was 435 nm.

  This emulsion was a stable colloidal dispersion similar to ordinary polymer latex, and no tendency of sedimentation of sustained release particles or phase separation was observed during storage at room temperature.

Examples 2-17
Based on Tables 1 to 5, an emulsion of sustained-release particles was obtained in the same manner as in Example 1 except that the formulation and conditions of each component were changed.

  All the emulsions of Examples 2 to 17 were stable colloidal dispersions as in the case of ordinary polymer latex, and no tendency of particle sedimentation or phase separation was observed during storage at room temperature.

Comparative Examples 1-11 and Comparative Examples 15, 16
Based on Table 3, Table 4, and Table 6, it processed similarly to Example 1 except having changed the compounding prescription and conditions of each component, and obtained the emulsion of the sustained release particle | grains.

Comparative Example 12
(Manufacture of sustained-release particles containing IPBC by emulsion polymerization)
A 300 mL four-necked flask equipped with a stirrer, reflux condenser, thermometer and nitrogen inlet tube was charged with 50 g of deionized water, 0.1 g of Neocor SW-C, 4 g of PVA217 (10%) aqueous solution and 0.24 g of Demol NL. By stirring at room temperature, a uniform emulsifier-PVA aqueous solution was obtained.

  In a 200 mL container, 70.5 g of MMA and 4.5 g of EGDMA were charged and stirred at room temperature to prepare a uniform monomer mixture.

0.75 g of the monomer mixture was subdivided into 2 mL glass bottles with airtight stoppers. A uniform hydrophobic solution was prepared by adding 25 g of IPBC to the remaining monomer mixture and stirring at room temperature.
Separately, 36.66 g of deionized water, 0.9 g of Neocol SW-C, and 36 g of PVA217 (10%) aqueous solution were charged into a 500 mL beaker and stirred at room temperature to obtain a uniform emulsifier-PVA aqueous solution.

Next, the hydrophobic solution was added to the emulsifier-PVA aqueous solution in a 500 mL beaker. K. The hydrophobic solution was dispersed in water in an emulsifier-PVA aqueous solution by stirring for 5 minutes at 500 rpm with a homodisper 2.5 type (manufactured by Primics) to prepare an emulsion of an IPBC monomer mixture.
A 300 mL 4-necked flask equipped with an emulsifier-PVA aqueous solution 54.34 g, equipped with a stirrer, reflux condenser, thermometer, and nitrogen inlet tube was rotated at 125 rpm (circumferential speed 23.6 m / min) with a 6 cm diameter stirrer. The temperature was raised under a nitrogen stream while stirring. When the temperature reached 50 ° C., 0.75 g of the monomer mixture that had been subdivided was added. When the temperature reached 70 ° C., 0.1 g of sodium persulfate (SPS) was added to start the synthesis of emulsion polymerization seed particles.
After preparing seed particles at 70 ± 2 ° C. for 20 minutes, 4 grams of an IPBC monomer mixture emulsion (maintaining the emulsion state by continuing stirring) at the same temperature and 20 g of an SPS (2%) aqueous solution were added. Feeding was performed over time, and emulsion polymerization was performed. After the emulsion feed, the temperature was raised to 80 ° C. 2 g of an aqueous solution of sodium persulfate (SPS) (5%) was fed over 1 hour, and an aging reaction was performed at 80 ± 2 ° C. including the temperature rising time.

  . Agglomeration becomes remarkable from the time when the emulsion feed has progressed about 25%, and at the end of the emulsion feed, an okara-like (aggregate becomes agglomerated and non-uniformly highly viscous, highly concentrated pulp liquid) is produced. . Furthermore, the reaction product cooled to room temperature gelled.

Comparative Example 13
(Manufacture of sustained-release particles containing epoxiconazole by miniemulsion polymerization)
Based on Table 6, it tried to obtain the emulsion of sustained-release particle | grains by processing like Example 1 except having changed the formulation and conditions of each component.

  However, epoxiconazole was not compatible with MMA and EGDMA. That is, epoxiconazole did not dissolve in MMA and EGDMA.

  Therefore, a uniform hydrophobic solution could not be prepared and the subsequent steps were not performed.

Comparative Example 14
(Manufacture of sustained-release particles containing triticonazole by miniemulsion polymerization)
Based on Table 6, it tried to obtain the emulsion of sustained-release particle | grains by processing like Example 1 except having changed the formulation and conditions of each component.

  However, triticonazole was not compatible with MMA and EGDMA. That is, triticonazole did not dissolve in MMA and EGDMA.

  Therefore, a uniform hydrophobic solution could not be prepared and the subsequent steps were not performed.

(Composition and conditions)
Tables 1 to 6 show the formulation and conditions in Examples and Comparative Examples.

  The formulation and conditions of Example 5 are described in Table 6 in addition to Table 1.

(Evaluation)
1. Properties of emulsion (1) Measurement of particle size of sustained release particles Dynamic light using a particle size analyzer (FPAR-1000, Otsuka Electronics Co., Ltd.) for the filtrate obtained by filtering the emulsion with a 100th filter cloth. The volume-based median diameter was measured by a scattering method.

The results are shown in Tables 1-6.
(2) Content of sustained-release particles exceeding 1 μm The above-mentioned “(1) Measurement of particle diameter of sustained-release particles” is carried out, and at the same time, the obtained “scattering intensity distribution, frequency distribution table” shows the particle size. The cumulative frequency of 1 μm or less was defined as X%, and (100−X)% was defined as the content of sustained release particles exceeding 1 μm.

The results are shown in Tables 1-6.
(3) 100 mesh filter cloth remaining amount (polymerization stability)
The emulsion was filtered through a 100th filter cloth, and the amount (mass%) of the residue on the filter cloth which was air-dried was calculated based on the sustained release particles.

The results are shown in Tables 1-6.
(4) Residual monomer About the filtrate which filtered the emulsion with the filter cloth of 100th, the amount of residual monomers was measured on the following measuring conditions using the Shimadzu Corporation gas chromatography. First, a standard curve was prepared by preparing a standard solution for a standard curve using MMA as a standard, an internal standard as cyclohexanone, and methanol as a diluent solvent, and vaporizing the pyrolyzer at 220 ° C. for 20 seconds. An internal standard solution was added to 4 g of the emulsion sample, and the residual monomer was quantified in a sample solution made up to a total amount of 10 g with methanol under the same measurement conditions as the standard solution.

The results are shown in Tables 1-6.
2. Storage stability Storage stability was evaluated by the following measurement method.

  Predetermined emulsion was weighed into a glass bottle with a sealed stopper and allowed to stand in a constant temperature room at 40 ° C. After 1 day, 4 days, 20 days from the start of standing, after 2 months, filtration was performed with a 100-mesh filter cloth, and the amount (mass%) of the residue on the filter cloth was air-dried, based on the sustained-release particles, While calculating, the residue on the filter cloth was observed with an optical microscope.

  The case where no IPBC needle-like crystals were observed from the preparation of the emulsion until the lapse of 2 months was evaluated as ◎, and the sustained release particles were evaluated until the lapse of 2 months from the preparation of the emulsion. When the precipitation of IPBC needle crystals was not observed, it was evaluated as ◯, and the precipitation of IPBC needle crystals was observed after 2 months from the preparation of the emulsion. Was evaluated as x.

The results are shown in Tables 1-6.
3. TEM (Transmission Electron Microscope) Observation The emulsion of Example 2 was naturally dried, dispersed in a bisphenol liquid epoxy resin, and cured with an amine. A cross section was obtained by cutting this with an ultramicrotome, stained with ruthenium tetroxide, and cut into ultrathin sections with an ultramicrotome to prepare a sample. The prepared sample was observed with a transmission electron microscope (model number “H-7100”, manufactured by Hitachi, Ltd.) by TEM.

  Image processing diagrams of the TEM photograph of Example 2 are shown in FIGS.

As is clear from FIGS. 1 and 2, it can be seen that the inner layer (inside) of the sustained release particles has a uniform structure without phase separation.
4). SEM (Scanning Electron Microscope) Observation The emulsions obtained in Comparative Example 15 and Comparative Example 16 were air-dried and further subjected to metal coating (conductive treatment) to prepare a sample. The prepared sample was observed by SEM with a scanning electron microscope (model number “S-3000”, manufactured by Hitachi High-Technologies Corporation).

  The image processing diagrams of the SEM photographs of Comparative Example 15 and Comparative Example 16 are shown in FIGS. 4 and 5, respectively.

In both Comparative Example 15 and Comparative Example 16, IPBC needle crystals were observed. In particular, in Comparative Example 16, a large amount of acicular crystals was observed.
5. Sustained release particles containing IPBC (Example 1 to Example 17) and sustained release test of IPBC suspension as control Preparation of IPBC suspension (Control) Example 3 of JP 2007-204441 A IPBC 30 parts by mass, Metrolose 90SH-100 2 parts by mass, DK ester F-160 (sucrose fatty acid ester, manufactured by Daiichi Kogyo Seiyaku Co., Ltd.) 1.5 parts by mass, Plex SSL (sodium alkyldiphenyl ether sulfonate) 0.6 An IPBC suspension consisting of parts by mass and 65.9 parts by mass of ion-exchanged water was prepared.

  According to the following operation, the IPBC sustained release test was carried out using the IPBC suspension as a control for the sustained release particles of Examples 1 to 17 containing IPBC.

  That is, first, the emulsions of Examples 1 to 17 (IPBC concentration of 10% by mass) and the IPBC suspension (IPBC concentration of 30% by mass) as a control were respectively used in the sustained release test. Prepared as a sample.

  Next, the prepared sample was poured into three polypropylene 50 mL centrifuge tubes in an amount of 20 mg each as IPBC mass, and then an IPBC-containing liquid having an IPBC concentration of 0.05 mass% with deionized water to make a total amount of 40 g. Prepared.

  Next, shake the three centrifuge tubes on a shaker (TAITEC RECIPRO SHAKER SR-1 manufactured by Taitec Corporation) at 140 times / minute, stop shaking every predetermined time, and centrifuge the centrifuge tube Solid-liquid separation was performed at 15000 rpm for 5 minutes by using a machine (microcooled centrifuge 3740, manufactured by Kubota Seisakusho).

  The solid part was added with deionized water to a total amount of 40 g, re-dispersed with microspatel, and then shaken again with a shaker.

  On the other hand, the liquid part quantified IPBC using Shimadzu HPLC, and calculated the sustained release rate.

  The sustained release rate at each shaking time was calculated as an integrated value (that is, total sustained release rate).

  The result is shown in FIG.

  It was confirmed that the sustained release particles of Examples 1 to 17 obtained by miniemulsion polymerization have a slow release rate as compared with IPBC of the control IPBC suspension.

  The sustained-release particles of the present invention can be applied to various industrial products, such as indoor and outdoor paints, rubber, fibers, resins, plastics, adhesives, joint agents, sealing agents, building materials, caulking agents, soils. Additives that exhibit antibiotic activity (antifungal properties) in processing agents, wood, white water, pigments, printing plate processing liquid, cooling water, ink, cutting oil, cosmetics, non-woven fabric, spinning oil, leather, etc. It can be added as an agent.

Claims (3)

By dissolving 3-iodo-2-propynylbutylcarbamate with a hydrophobic polymerizable vinyl monomer, a hydrophobic solution is prepared, and water, an emulsifier and polyvinyl alcohol are blended to prepare an emulsifier-polyvinyl alcohol aqueous solution, The hydrophobic particles are emulsified in the emulsifier-polyvinyl alcohol aqueous solution, the polymerizable vinyl monomer is miniemulsion polymerized in the presence of a polymerization initiator, and average particles containing 3-iodo-2-propynylbutylcarbamate. Sustained-release particles obtained by producing a polymer having a diameter of less than 1 μm,
The polymer obtained by miniemulsion polymerization is defined by Hansen, and the dipole force term δ _{p, polymer of the} solubility parameter δ calculated by the van Krevelen and Hoftyzer method is 5.0 to 7.0 [(J / cm ³ ) ^1/2 ], and the hydrogen bonding term δ _{h, polymer of the} solubility parameter δ is 8.0 to 10.0 [(J / cm ³ ) ^1/2 ], Sustained release particles.   The sustained-release particles according to claim 1, wherein the content ratio of 3-iodo-2-propynylbutyl carbamate with respect to the sustained-release particles is 10 to 50% by mass. Preparing a hydrophobic solution by dissolving 3-iodo-2-propynylbutylcarbamate with a hydrophobic polymerizable vinyl monomer;
A step of blending water, an emulsifier and polyvinyl alcohol to prepare an emulsifier-polyvinyl alcohol aqueous solution,
Emulsifying the hydrophobic solution in the emulsifier-polyvinyl alcohol aqueous solution, and
The polymerizable vinyl monomer of the emulsified hydrophobic solution is subjected to miniemulsion polymerization in the presence of a polymerization initiator to produce a polymer having an average particle diameter of less than 1 μm and containing 3-iodo-2-propynylbutylcarbamate. A process for producing sustained-release particles, comprising the step of:
The polymer obtained by miniemulsion polymerization is defined by Hansen, and the dipole force term δ _{p, polymer of the} solubility parameter δ calculated by the van Krevelen and Hoftyzer method is 5.0 to 7.0 [(J / cm ³ ) ^1/2 ], and the hydrogen bonding term δ _{h, polymer of the} solubility parameter δ is 8.0 to 10.0 [(J / cm ³ ) ^1/2 ], A method for producing sustained-release particles.