JP5873714B2 - Method for producing sustained release particles - Google Patents

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.

  An object of the present invention is to provide sustained-release particles having excellent dispersibility 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. Prepare and mix water and emulsifier to prepare an aqueous emulsifier solution, emulsify the hydrophobic solution in the aqueous emulsifier solution, and then dissolve the polymerizable vinyl monomer in the emulsified hydrophobic solution in the presence of a polymerization initiator. As a result of finding out that sustained-release particles can be obtained by polymerization, sustained-release particles having excellent dispersibility can be obtained, and further studies have been made. As a result, 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 solution is prepared by blending water and an emulsifier. The sustained-release particles obtained by emulsifying the solution in the aqueous emulsifier solution and miniemulsion polymerization of the polymerizable vinyl monomer in the presence of a polymerization initiator to produce a polymer having an average particle size 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 Klevelen and Hoftyzer method is 5.0 to 6.0 [( J ^/ cm ^{3) 1/2],} wherein the solubility parameter hydrogen bonding term of [delta] [delta] _{h, Polymer} is from 9.0 to 9.9 [ Characterized in that J ^/ cm ^{3) 1/2]} is, the controlled release particles,
(2) 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 ₎ Containing 50 mass% or more of the first monomer of 9.2 to 9.9 [(J / cm ³ ) ^1/2 ], the sustained release particles according to (1) above,
(3) The sustained-release particles according to (2), wherein the first monomer contains methyl methacrylate and / or ethylene glycol dimethacrylate,
(4) A step of preparing a hydrophobic solution by dissolving 3-iodo-2-propynylbutylcarbamate with a hydrophobic polymerizable vinyl monomer, a step of preparing an aqueous emulsifier solution by blending water and an emulsifier, Emulsifying a hydrophobic solution in the aqueous emulsifier solution, and subjecting the polymerizable vinyl monomer of the emulsified hydrophobic solution to miniemulsion polymerization in the presence of a polymerization initiator to produce a polymer having an average particle size of less than 1 μm. A method for producing sustained-release particles, comprising a step of forming a coalescence, wherein the polymer obtained by miniemulsion polymerization is defined by Hansen and has a solubility parameter δ calculated by the van Klevelen and Hoftyzer method. force term [delta] _{p, Polymer} is ^{5.0~6.0 [(J / cm 3)} 1/2], wherein the solubility parameter Wherein the hydrogen bonding term [delta] _{h, Polymer} of over data [delta] is ^{9.0~9.9 [(J / cm 3)} 1/2], a method for producing controlled release particles.

  The method for producing sustained-release particles of the present invention comprises 3-iodo-2-propynylbutylcarbamate by subjecting a polymerizable vinyl monomer in an emulsified hydrophobic solution to miniemulsion polymerization in the presence of a polymerization initiator. Since the sustained release particles of the present invention are obtained by producing a polymer having an average particle diameter of less than 1 μm, the sustained release particles are excellent in dispersibility.

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 Klevelen and Hoftyzer method is 5.0 to 6.0. In [(J / cm ³ ) ^1/2 ], the hydrogen bonding force term δ _{h, polymer} of the solubility parameter δ is set to 9.0-9.9 [(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 in various industrial products as sustained release particles having excellent sustained release properties and excellent dispersibility.

  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 an SEM photograph of sustained-release particles of Example 2. FIG. 2 shows an image processing diagram of an SEM photograph of sustained-release particles of Example 2. FIG. 3 shows an image processing diagram of a TEM photograph of sustained-release particles of Example 2. FIG. 4 shows an image processing diagram of a TEM photograph of sustained-release particles of Example 2. FIG. 5 shows a graph of sustained release tests of Examples 1 and 2 and Comparative Example 3.

  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 and an emulsifier are blended to prepare an emulsifier aqueous solution, followed by emulsifying the hydrophobic solution in the emulsifier aqueous solution, and then polymerizing the polymerizable vinyl monomer in the presence of a polymerization initiator by miniemulsion polymerization. It is obtained by producing 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).

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

Incidentally, polar term [delta] _{p, IPBC} and hydrogen bonding term [delta] _{h, IPBC} solubility parameter [delta] is defined in Hansen, calculated in van Klevelen 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, MMA is used alone, or MMA and EGDMA are used in combination, and more preferably, MMA is used alone.

  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 partially precipitate during miniemulsion polymerization, during cooling after polymerization, or within several days after cooling.

  However, when only MMA and EGDMA are used in combination as the first monomer, the crosslink density is low if the blending ratio of MMA is equal to or more than the lower limit described above, so that the amount of IPBC compatible with the polymer ( Ratio) is sufficient. Therefore, it is possible to effectively prevent the above-described decrease in the compatible amount and effectively prevent the precipitation of IPBC.

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.

  Examples of the second monomer include (meth) acrylic acid ester monomers excluding MMA, (meth) acrylic acid monomers, aromatic vinyl monomers, vinyl ester monomers, maleic acid ester monomers, vinyl halides, halogens And vinylidene chloride, nitrogen-containing vinyl monomers, and crosslinkable monomers other than EGDMA.

  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.

  The (meth) acrylic acid ester monomer is also a compatible monomer because the copolymer with the first monomer described above has a relatively high compatibility with IPBC.

  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. Alkyl such as n-propyl acid, iso-propyl (meth) acrylate, n-butyl (meth) acrylate, iso-butyl (meth) acrylate, tert-butyl (meth) acrylate, cyclohexyl (meth) acrylate (Meth) acrylic acid alkyl ester having 1 to 20 carbon atoms (excluding MMA) or (meth) acrylic acid alkoxyalkyl ester such as 2-methoxyethyl (meth) acrylic acid, for example, (meth) acrylic And hydroxyalkyl (meth) acrylates such as hydroxyethyl acid . 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, iso-butyl acrylate, tert-butyl acrylate, and the like. 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.

  Examples of (meth) acrylic acid monomers include methacrylic acid and acrylic acid. 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, for example, allyl monomers such as allyl (meth) methacrylate, triallyl (iso) cyanurate, such as divinyl vinyl Such as divinyl monomers such as Zen and the like.

  The polymerizable vinyl monomer is preferably a (meth) acrylic acid ester monomer.

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, 40% by mass or less, more preferably 38% by mass or less, further 30% by mass or less, 25% by mass or less, 20% by mass, 15% by mass, 10% by mass or less, 5% by mass or less, 2 mass% or less is preferable, and exceeds 0 mass%.

  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 a few days after cooling.

  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 is polymerized when different types are used together (for example, when the first monomer and the second monomer are used together, for example, when different types of the first monomer are used together). The entire reactive vinyl monomer (ie, a mixture of different types of polymerizable vinyl monomers) is substantially hydrophobic.

The polymerizable vinyl monomer obtained by miniemulsion polymerization has a dipole force term δ _{p, polymer} with a solubility parameter δ of 5.0 to 6.0 [(J / cm ³ ) ^{1 / 2} ], preferably 5.1 to 6.0 [(J / cm ³ ) ^1/2 ], and the hydrogen bond term δ _{h, polymer of} the solubility parameter δ is 9.0 to 9.9 [( J / cm ³ ) ^1/2 ], preferably 9.0 to 9.8 [(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 can 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.

  Examples of the emulsifier include emulsifiers commonly used in miniemulsion polymerization, such as sodium dioctyl sulfosuccinate, sodium dodecylbenzene sulfonate, sodium lauryl sulfate, sodium dodecyl diphenyl ether disulfonate, sodium nonyl diphenyl ether sulfonate, naphthalene sulfonate formaldehyde condensate Anionic emulsifiers such as sodium salts are listed.

  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 and a nonionic emulsifier are used in combination, and more preferably, a dioctyl sodium sulfosuccinate and a polyoxyalkylene aralkyl aryl ether are used in combination.

  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.

  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) Water-soluble azo compounds such as isobutylamidine), 2,2′-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride, for example persulfuric acid such as potassium persulfate, sodium persulfate, ammonium persulfate Salt compounds, for example, water-soluble inorganic peroxides such as hydrogen peroxide, for example, water-soluble organic peroxides such as tert-butyl peroxide, cumene peroxide, etc. And the like. Furthermore, as a water-soluble polymerization initiator, for example, a redox-based water-soluble polymerization initiator in which a water-soluble polymerization initiator excluding a water-soluble azo compound and a water-soluble reducing agent such as sodium ascorbate and sodium hyposulfite are combined. Can be mentioned.

  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 to 1.5, preferably 0.05 to 1.1, in terms of mass (that is, IPBC mass part / polymerizable vinyl monomer mass part). 0.

  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. Of the polymerizable vinyl monomer may remain.

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

  Specifically, an aqueous emulsifier solution is obtained by blending water and an emulsifier and stirring them uniformly.

  The blending ratio of the emulsifier is an amount sufficient for the emulsifier to be adsorbed on the entire surface of the hydrophobic solution emulsified droplet, and the presence of excess emulsifier causes the generation of emulsion polymerized particles of a new polymerizable vinyl monomer that does not contain IPBC. The amount to be suppressed is selected and varies depending on the type of the emulsifier. For example, the effective amount of the emulsifier is 0.1 to 20% by mass, preferably 0.2 to 10% by mass with respect to the hydrophobic solution. It is.

  Preparation of the emulsifier aqueous solution may be performed, for example, at room temperature, or may be performed by heating as necessary.

  The heating temperature is, for example, 40 to 100 ° C, preferably 60 to 80 ° C.

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

  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. 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 aqueous emulsifier solution.

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

  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.

  In addition, it can also heat at the time of emulsification. The heating temperature is, for example, lower than the temperature at which the polymerization initiator decomposes, and specifically, 30 ° C. or higher and 50 ° C. or lower, preferably 35 ° C. or higher and 40 ° C. or lower.

  The blending ratio of the hydrophobic solution is, for example, 10 to 1500 parts by mass, preferably 25 to 90 parts by mass with respect to 100 parts by mass of the emulsifier aqueous solution.

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

  The average particle diameter (median diameter, described later) of the miniemulsion particles is adjusted to, for example, 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. The

  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. In addition, IPBC tends to color yellowish brown by heating, and the heating condition is 60 ° C. or higher when the conversion rate from the polymerizable vinyl monomer to the polymer is 98% or higher, preferably 99% or higher. In the temperature range, the temperature is preferably set as low as possible and in a short time.

  In order to reduce the polymerizable vinyl monomer remaining at the end of the polymerization, in order to polymerize the polymerizable vinyl monomer saturated and dissolved in the aqueous phase, a water-soluble polymerization initiator (excluding water-soluble azo compounds) and water-soluble A reducing agent can also be added.

  Examples of water-soluble polymerization initiators (excluding water-soluble azo compounds) include persulfate compounds such as potassium persulfate, ammonium persulfate, and sodium persulfate, such as organic compounds such as tertiary butyl peroxide and cumene hydroxy peroxide. Peroxides (water-soluble organic peroxides), for example, inorganic peroxides such as hydrogen peroxide.

  Examples of the water-soluble reducing agent include ascorbic acid, sodium bisulfite, sodium hyposulfite, sodium formaldehyde sulfoxylate, divalent iron salt, monovalent copper salt, amines and the like.

  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, and the mixing ratio of the water-soluble reducing agent is the start of water-soluble polymerization. It is 0.01-0.5 mass part with respect to 100 mass parts of agents.

  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.

  In detail, the oil droplets of a minute polymerizable vinyl monomer exist stably by adopting an anionic emulsifier as an emulsifier, for example. At the same time, oil droplets of small polymerizable vinyl monomers can be produced from oil droplets of smaller (fine) polymerizable vinyl monomers via the aqueous phase by using hydrophobes (costabilizers). It exists stably by controlling the enlargement (Ostwald ripening) due to the transfer of the polymerizable vinyl monomer to the oil droplets.

  On the other hand, in the present invention, miniemulsion polymerization in which a polymerizable vinyl monomer is polymerized (radical polymerization) proceeds in miniemulsion particles (fine oil droplets composed of IPBC and a polymerizable vinyl monomer). 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.

  On the other hand, since the average particle size of the miniemulsion particles is as small as less than 1 μm, the polymerizable vinyl monomer is likely to diffuse in the water phase. In the miniemulsion polymerization of the present invention, IPBC may act as a hydrophobe. Therefore, as a result of effectively preventing the molecular diffusion described above, Ostwald ripening can be prevented and enlargement of the miniemulsion particles (increase in particle diameter) can be suppressed.

  Thereafter, the emulsion after polymerization is cooled, for example, by standing to cool.

  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.

  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.

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

  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.

  And the manufacturing method of the sustained release particle | grains of this invention carries out miniemulsion polymerization of the polymerizable vinyl monomer of the emulsified hydrophobic solution in presence of a polymerization initiator, and the average particle diameter containing IPBC is less than 1 micrometer. Since the sustained-release particles of the present invention are obtained by producing a polymer, the sustained-release particles are excellent in dispersibility.

Furthermore, in this sustained release particle, the polymer has a dipole force term δ _{p, polymer} of the solubility parameter δ of 5.0 to 6.0 [(J / cm ³ ) ^1/2 ], and the solubility parameter δ since the hydrogen bonding term [delta] _{h, Polymer} of is set to ^{9.0~9.9 [(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.

  For this reason, 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, thereby providing excellent sustained-release properties and excellent dispersibility. The sustained-release particles having the above can be used for 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 an antifungal property. 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 aqueous coating material in which the emulsifier common with the emulsifier mix | blended with the emulsifier 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 durability 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 ], MMA manufactured by International Specialty Products : Methyl methacrylate, trade name “acrylic ester M”, solubility in water: 1.6 mass%, dipole force term δ _{p, 1st monomer unit of} solubility parameter δ: 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], three Rayon Co., Ltd. EGDMA: ethylene glycol dimethacrylate, trade name "Light Ester EG", solubility in water: insoluble, polar term of a solubility parameter _{δ δ p, 1st monomer unit:} 5.37 [(J / cm 3 ) ^1/2 ], hydrogen bond strength term δ _{h, 1st monomer unit of} solubility parameter δ: 10.42 [(J / cm ³ ) ^1/2 ], manufactured by Kyoeisha Chemical Co., Ltd. nBMA: n-butyl methacrylate, to water Solubility of 0.08% by mass, dipole force term δ _{p, 2nd monomer unit of} solubility parameter δ: 3.76 (J / cm ³ ) ^1/2 ], hydrogen bond strength term δ _{h of} solubility parameter δ _{, ^{2nd monomer unit: 7.33 [(J}} / cm 3) 1/2], manufactured by Mitsubishi Rayon Co., Ltd. MA: methyl acrylate, dissolved in water : 5.7 wt%, polar term of a solubility parameter _{δ δ p, 2nd monomer unit:} 7.36 [(J / cm 3) 1/2], hydrogen bonding term solubility parameter [delta] [delta] _{h, 2nd monomer unit} : 10.25 [(J / cm ³ ) ^1/2 ], manufactured by Nippon Shokubai Co., Ltd. EA: ethyl acrylate, solubility in water: 1.5 mass%, dipole force term δ _{p with} solubility parameter δ _{, 2nd monomer unit} : 5.93 [(J / cm ³ ) ^1/2 ], hydrogen bonding force term δ _{h of} solubility parameter δ _{, 2nd monomer unit} : 9.20 [(J / cm ³ ) ^1/2 ], Nippon Shokubai nBA: acrylate n- butyl, solubility in water: 0.2 wt%, solubility parameter polar term of _{δ δ p, 2nd monomer unit:} 4.26 [(J / c ^{3) 1/2],} the solubility parameters [delta] of the hydrogen bonding term _{δ h, 2nd monomer unit: 7.81} [(J / cm 3) 1/2], manufactured by Nippon Shokubai Co., Ltd. SM: Styrene, insoluble in water, solubility Dipole force term of parameter δ δ _{p, 2 nd monomer unit} : 1.27 [(J / cm ³ ) ^1/2 ], hydrogen bonding force term δ _{h, 2 nd monomer unit of} solubility parameter δ: 0.00 [( J / cm ³ ) ^1/2 ]
Parroyl L: trade name (“Parroyl” is a registered trademark), dilauroyl peroxide, manufactured by NOF Corporation Neocol SW-C: trade name, 70% by weight isopropanol solution of sodium dioctylsulfosuccinate (anionic emulsifier), Daiichi Kogyo Neugen EA-177 manufactured by Pharmaceutical Co., Ltd., trade name, polyoxyethylene styrenated phenyl ether (nonionic emulsifier, HLB: 15.6), manufactured by Daiichi Kogyo Seiyaku Co., Ltd. Average particle size: And evaluated.

Hydrophobic solution-dispersed particles and sustained-release particles of Examples 1 to 20 and Comparative Examples 4 to 6, and hydrophobic solution-dispersed particles of Comparative Examples 1 and 2:
Particle size analyzer (FPAR-1000, measurable average particle size of 3 nm to 7 μm, but in the region where the particle size exceeds several μm and the influence of gravity on the Brownian motion is greatly reduced, the measurement accuracy decreases significantly, Otsuka Electronics Co., Ltd.) Measured as volume-based median diameter by dynamic light scattering method using.

        For hydrophobic solution-dispersed particles, measure the miniemulsion after 20 minutes from the preparation.

        For sustained-release particles, the filtrate filtered through a 100th filter cloth was measured.

Sustained release particles of Comparative Example 3:
Laser diffraction scattering type particle size distribution measuring device LA-920 (measurable average particle size of 20 nm to 2000 μm, however, if the particle size is 1 μm or less, mu scattering is not angularly dependent and the measurement accuracy is significantly reduced. ), And the filtrate filtered through a 100th filter cloth is measured as a volume-based median diameter.

Example 1
(Manufacture of sustained release particles containing IPBC by miniemulsion polymerization)
A uniform hydrophobic solution was prepared by charging 25 g of IPBC, 75 g of MMA and 0.5 g of Parroyl L into a 200 mL container and stirring at room temperature.

  Separately, 125.5 g of deionized water, 4.0 g of Neocor SW-C, and 20 g of a 25% by weight aqueous solution of Neugen EA-177 were placed in a 500 mL beaker and stirred at room temperature to prepare a uniform aqueous emulsifier solution.

  Next, the hydrophobic solution was added to the emulsifier aqueous solution of the 500 mL beaker. K. By stirring for 5 minutes at a rotational speed of 12000 rpm with a homomixer MARK 2.5 type (manufactured by Primix), the hydrophobic solution was emulsified in an aqueous emulsifier solution to prepare a mini-emulsion.

  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 60 ± 2 ° C. for 1 hour and at 70 ± 2 ° C. for 3.5 hours.

  Subsequently, the temperature of the water bath was raised, the temperature of the reaction solution was raised to 78 ± 2 ° C., and the mixture was aged at that temperature for 2.5 hours.

  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 201 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, 3, 7-9, 13 and 17
Based on Table 1 and Table 2, except for changing the formulation of the polymerizable vinyl monomer, it was treated in the same manner as in Example 1 to obtain sustained-release particles.

  All the emulsions of Examples 2, 3, 7-9, 13 and 17 are stable colloidal dispersions similar to ordinary polymer latex, and the tendency of the particles to settle or phase separate during storage at room temperature. I was not able to admit.

Example 4
(Manufacture of sustained release particles containing IPBC by miniemulsion polymerization)
A uniform hydrophobic solution was prepared by charging 40 g of IPBC, 54 g of MMA, 6 g of EGDMA, and 0.5 g of Parroyl L in a 200 mL container and stirring at room temperature.

  Separately, 275.5 g of deionized water, 4.0 g of Neocor SW-C and 20 g of a 25% by weight aqueous solution of Neugen EA-177 were charged into a 1000 mL beaker and stirred at room temperature to prepare a uniform aqueous emulsifier solution.

  Next, the hydrophobic solution was added to the emulsifier aqueous solution in a 1000 mL beaker, and the T.P. K. By stirring for 5 minutes at a rotational speed of 12000 rpm with a homomixer MARK 2.5 type (manufactured by Primix), the hydrophobic solution was emulsified in an aqueous emulsifier solution to prepare a mini-emulsion.

  Thereafter, the prepared miniemulsion was transferred to a 500 mL four-necked flask equipped with a stirrer, a reflux condenser, a thermometer and a nitrogen introduction tube, and miniemulsion polymerization was carried out by the same procedure as in Example 1.

  Thereafter, the reaction solution was cooled to 30 ° C. or lower to obtain an emulsion of sustained-release particles containing IPBC. The emulsion was filtered through a 100th filter cloth, and the median diameter of the sustained-release particles in the filtrate was measured. The result was 238 nm.

  This emulsion was a stable colloidal dispersion similar to ordinary polymer latex, and no tendency for particle settling or phase separation during storage at room temperature was observed.

Examples 5, 6, 10-12, 14-16 and 18-20
Based on Table 1 and Table 2, except for changing the formulation of the polymerizable vinyl monomer, it was treated in the same manner as in Example 4 to obtain sustained-release particles.

  Each of the emulsions of Examples 5, 6, 10-12, 14-16 and 18-20 is a stable colloidal dispersion similar to ordinary polymer latex, and the particles settle and phase during storage at room temperature. There was no tendency for separation.

Comparative Example 1
(Preparation of aqueous dispersion without emulsifier)
In the preparation of the emulsifier aqueous solution, an aqueous dispersion of a hydrophobic solution was prepared in the same manner as in Example 1 except that Neocol SW-C and Neugen EA-177 (above, emulsifier) were not blended.

  However, oil droplets made of a hydrophobic solution were not formed as miniemulsion particles, and therefore, miniemulsion polymerization could not be carried out.

Comparative Example 2
(Preparation of water dispersion without IPBC)
An aqueous dispersion of a hydrophobic solution was prepared in the same manner as in Example 1 except that 25 g of IPBC and 75 g of MMA were replaced with 100 g of MMA in the preparation of the hydrophobic solution.

  However, oil droplets made of a hydrophobic solution were not formed into miniemulsion particles having an average particle size of less than 1 μm, and therefore miniemulsion polymerization could not be carried out.

Comparative Example 3
(Production of sustained-release particles containing IPBC by suspension polymerization)
In a 200 mL container, 25 g of IPBC, 67.5 g of MMA, 7.5 g of EGDMA and 0.5 g of Parroyl L were charged and stirred at room temperature to prepare a uniform hydrophobic solution.

  Separately, 109.3 g of deionized water, 40 g of a 10% by weight aqueous solution of PVA-217, and 200 mg of a 5% aqueous solution of DBN were placed in a 500 mL beaker and stirred at room temperature to prepare a uniform aqueous solution.

  The hydrophobic solution was then added to the 500 mL beaker. K. The suspension was prepared by dispersing the hydrophobic solution in the aqueous solution by stirring for 10 minutes at a rotational speed of 3000 rpm with a homomixer (manufactured by Primix).

  Thereafter, the suspension was transferred to a 300 mL four-necked flask equipped with a stirrer, reflux condenser, thermometer, and nitrogen introduction tube, and the four-necked flask was water bathed while stirring at 125 rpm with a stirrer under a nitrogen stream. Then, the temperature was raised and suspension polymerization was carried out.

  The suspension polymerization was initiated at the time when it reached 55 ° C., and then reacted continuously at 60 ± 2 ° C. for 1 hour, 70 ± 2 ° C. for 3 hours, and 80 ± 2 ° C. for 2 hours.

  Thereafter, the suspension after the reaction was cooled to 30 ° C. or lower to obtain a suspension of sustained-release particles containing IPBC.

  Thereafter, the median diameter of the suspension was measured, and the result was a median diameter of 10 μm.

  The obtained suspension was transferred from a four-necked flask to a translucent polyethylene container, and the state of the sustained-release particles when allowed to stand at room temperature for several hours was observed. Separation was confirmed.

  Subsequently, after 3 days at room temperature, a hard cake was formed in which the sedimented lower layer could not be redispersed even if shaken strongly.

Comparative Examples 4-6
Based on Table 3, except for changing the formulation of the polymerizable vinyl monomer, the same procedure as in Example 4 was performed to try to synthesize sustained release particles.

  However, the polymerization stability of the miniemulsion described later (see Table 3, remaining amount of 100-mesh filter cloth) is low, and a large amount of IPBC needle-like crystals precipitated and remained on the 100-mesh filter cloth during filtration. Therefore, miniemulsion polymerization which fully encapsulates IPBC could not be carried out.

(Combination prescription)
Tables 1 to 4 show the formulation of each example and each comparative example.

  In each table, the numerical values in the raw material blending prescription column indicate the number of grams blended unless a unit is specifically mentioned.

(Evaluation)
1. Stability of miniemulsion (1) Examples 1-20
When the mini-emulsions of Examples 1 to 20 were allowed to stand at room temperature for a predetermined time, the median diameter of the hydrophobic solution-dispersed particles (mini-emulsion particles) was measured. The results are shown below.
(1-1) Example 1
194 nm after 20 minutes from preparation
195 nm after 5 hours from preparation
192 nm after 24 hours from preparation
(1-2) Example 2
223 nm after 20 minutes from preparation
16 hours after preparation 223 nm
(1-3) Example 3
231m after 20 minutes from preparation
233 nm after 5 hours from preparation
233 nm after 24 hours from preparation
(1-4) Examples 4 to 20
The ratio of the median diameter after 20 minutes from the preparation to the median diameter after 5 hours from the preparation was in the range of 0.95 to 1.05.

The ratio of the median diameter after 20 minutes from the preparation to the median diameter after 24 hours from the preparation was also in the range of 0.95 to 1.05.
(2) Comparative Examples 1 and 2
When the aqueous dispersions of Comparative Examples 1 and 2 were allowed to stand at room temperature for a predetermined time, the state of the hydrophobic solution dispersed particles (oil droplets) was observed, or the median diameter was measured. The results are shown below.
(2-1) Comparative Example 1
1 hour after preparation Enlargement of oil droplets (ie coalescence of oil droplets, phase separation)
(2-2) Comparative Example 2
20 minutes after preparation 2.06 μm
2.54 μm after 5 hours of preparation
24 hours after preparation 3.31 μm
2. 100-mesh filter cloth remaining amount The reaction solution after standing for 16 hours after polymerization of the mini-emulsions of Examples 1 to 20 and Comparative Examples 4 to 6 was filtered with a 100-mesh filter cloth, and the needle-like IPBC remaining on the filter cloth The amount (mass) of crystals was measured.

The results are shown in Tables 1 and 2.
3. SEM (Scanning Electron Microscope) Observation The emulsion obtained in Example 2 was naturally dried, and further metal-coated (conductive treatment) to prepare a sample. The prepared sample was observed by SEM with a scanning electron microscope (model number “S-4800”, manufactured by Hitachi High-Technologies Corporation).

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

It can be confirmed that the sustained-release particles are particles corresponding to a measured median diameter of 230 nm.
4). 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.

The outer layer (surface) of the sustained-release particles is covered with an extremely thin emulsifier layer dyed with ruthenium tetroxide, and the inner layer (inner) of the sustained-release particles has a uniform structure without phase separation I understand.
5). Sustained release test of IPBC-containing sustained release particles (Examples 1 and 2 and Comparative Example 3) According to the following procedure, IPBC-containing sustained release particles of Examples 1 and 2 and Comparative Example 3 were subjected to IPBC. A sustained release test was conducted.

  That is, first, the emulsions of Examples 1 and 2 and Comparative Example 3 (IPBC concentration 10% by mass), and the IPBC suspension (IPBC concentration 30% by mass) in which IPBC was suspended in water as a blank, Were prepared as samples for sustained release tests. A blank sample was used as Comparative Example 7.

  Next, the prepared samples were put into 5 polypropylene centrifuge tubes of 50 mL each in an amount of 20 mg 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, the five centrifuge tubes were shaken 140 times / minute on a shaker (TAITEC RECIPRO SHAKER SR-1 manufactured by Taitec Corporation), and the centrifuge tube was centrifuged after stopping shaking at predetermined intervals. 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.

  The sustained-release particles of Examples 1 and 2 obtained by miniemulsion polymerization were obtained by suspension polymerization, while the slow-release rate was slower than the IPBC suspension IPBC suspension of Comparative Example 7 which was a blank. Compared to the IPBC prepared in Comparative Example 3, the sustained release rate was faster.

  Considering the above, since the sustained-release particles of Example 1 have an average particle diameter of 201 nm, the surface area is about 50 times the surface area of the sustained-release particles of Comparative Example 3 having an average particle diameter of 10 μm. In consideration of the wide range, the sustained release per unit surface area of the sustained release particles is superior to the sustained release particles of Comparative Example 3.

  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)

A hydrophobic solution is prepared by dissolving 3-iodo-2-propynylbutylcarbamate with a hydrophobic polymerizable vinyl monomer, and an aqueous emulsifier solution is prepared by mixing water and an emulsifier. In the emulsifier aqueous solution, the emulsion is mixed once and emulsified, and the polymerizable vinyl monomer is subjected to miniemulsion polymerization in the presence of a polymerization initiator, and the average particle diameter containing 3-iodo-2-propynylbutylcarbamate is less than 1 μm. Sustained release particles obtained by producing a polymer,
The polymer obtained by miniemulsion polymerization is defined by Hansen and has a dipole force term δ _{p, polymer of} a solubility parameter δ calculated by the van Klevelen and Hoftyzer method of 5.0 to 6.0 [(J / cm ^{3) 1/2],} wherein the solubility parameter hydrogen bonding term [delta] _{h, Polymer} of [delta] is ^{9.0~9.9 [(J / cm 3)} 1/2] der is,
Wherein the emulsifier is characterized Rukoto anionic emulsifiers and nonionic emulsifiers are used together, a process for producing a sustained-release particles. The polymerizable vinyl monomer contains 50% by mass or more of the first monomer,
The first monomer has a dipole force term δ _{p, 1st monomer unit (s) of the} solubility parameter δ of the monomer unit constituting the polymer obtained from the first monomer of 5.6 to 6.0 [( J / cm ³ ) ^1/2 ], and the hydrogen bonding force term δ _{h, 1st monomer unit (s) of the} solubility parameter δ is 9.2 to 9.9 [(J / cm ³ ) ^1/2 ]. The method for producing sustained-release particles according to claim 1, wherein the first monomer is contained in an amount of 50% by mass or more. The method for producing sustained-release particles according to claim 2, wherein the first monomer contains methyl methacrylate and / or ethylene glycol dimethacrylate.