JP2016052613A - Core-shell particle - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a core-shell particle in which a large amount of inclusions can be encapsulated, and which can achieve both inclusion encapsulation stability and sustained release ability.SOLUTION: Provided is a core-shell particle obtained by using a block polymer having a hydrophilic block and a hydrophobic block, and having a solid, liquid or gas therein in which a shell contains an organic matter different from the block polymer, and in which the organic matter and the block polymer are crosslinked.SELECTED DRAWING: None

Description

The present invention relates to a core-shell particle that can encapsulate a large amount of inclusions, and can achieve both the encapsulation stability and sustained release properties of the inclusions.

There are known micelle-like particles encapsulating a functional liquid or gas inside an assembly of amphiphilic substances such as surfactants. For example, Patent Document 1 discloses a hydrophilic block and a hydrophobic block. Polymeric micelles comprising a block polymer having a polynucleotide are described.
However, since such polymer micelles are only self-assembled with molecules, unintentional leakage of inclusions occurs and the inclusion stability of the inclusions is low.

On the other hand, a microcapsule obtained by polymerizing a shell by a precipitation phase separation method by radical polymerization is disclosed.
However, the microcapsules obtained by such a method have a problem that transparency cannot be obtained due to their large size. Further, the obtained microcapsules have a problem of poor dispersibility and inferior permeability to small gaps. Furthermore, since the thickness of the shell becomes large, there have been problems that the inclusion rate of the functional liquid or the like is lowered, or the release of the functional liquid or the like is deteriorated.

On the other hand, there is known a method of obtaining a microcapsule by forming a film by curing an epoxy resin at an interface between oil droplets and water by interfacial polymerization.
In such a method, the size of the microcapsules is reduced, but since the role of holding and releasing the inclusions is only played by the epoxy resin, the encapsulation stability decreases when the shell is thin, and the amount of inclusions when the shell is thick There was a problem that there were fewer. Furthermore, the obtained microcapsules have a problem that they cannot be stabilized in a state of a high encapsulation rate.

Special table 2011-520901 gazette

The present invention provides a core-shell particle that can encapsulate a large amount of inclusions while being nano-sized, and can achieve both encapsulation stability and sustained-release properties of the inclusions in view of the above-mentioned present situation. For the purpose.

The present invention is a core-shell particle obtained by using a block polymer having a hydrophilic block and a hydrophobic block, and has a solid, liquid, or gas inside, and the shell contains an organic substance different from the block polymer. The core-shell particles are characterized in that the organic substance and the block polymer are crosslinked.
Hereinafter, the present invention will be described in detail.

As a result of intensive studies, the present inventor has used a block polymer having a hydrophilic block and a hydrophobic block as a raw material for the core-shell particles, and the shell contains an organic substance different from the block polymer, and the organic substance A core-shell particle capable of encapsulating a large amount of inclusions and having both the encapsulation stability and sustained release properties of the inclusions by being cross-linked with the block polymer. And the present inventors have found that it is possible to obtain core-shell particles having excellent transparency and dispersibility, and have completed the present invention.

The core-shell particle of the present invention is obtained using a block polymer having a hydrophilic block and a hydrophobic block. By using the block polymer, it becomes possible to maintain a nano-size (size on the order of nanometers) state.
The block polymer may be nonionic, anionic, cationic or amphoteric, but is preferably nonionic.

As the hydrophilic block constituting the block polymer, for example, a polymer comprising a monomer of a linear, branched, or cyclic aliphatic or aromatic hydrocarbon compound containing at least one unsaturated bond and having a hydrophilic group Thing etc. are mentioned.
Examples of the hydrophilic group include an amino group, a hydroxyl group, a carboxyl group, an isocyanate group, an amide group, a sulfonic acid group, an ethyleneoxy group, a phosphoric acid group, a urea group, a thiol group, and a sulfuric acid group. Of these, an amino group, a hydroxyl group, a carboxyl group, an isocyanate group, and an amide group are preferable.

Specific examples of the hydrophilic block include (meth) acrylic acid, hydroxyethyl (meth) acrylate, hydroxypropyl (meth) acrylate, methoxypolyethylene glycol (meth) acrylate, (meth) acrylamide, N-isopropyl ( (Meth) acrylamide, N-cyclopropyl (meth) acrylamide, Nn-propyl (meth) acrylamide, N-ethoxyethyl (meth) acrylamide, N, N-dimethyl (meth) acrylamide, 2- (N, N-diethylamino) Polymers such as ethyl (meth) acrylate are exemplified. Of these, a polymer of dimethylaminoethyl methacrylate (PDMAEMA) is preferable. These may be used alone or in combination of two or more.

Examples of the hydrophobic block constituting the block polymer include a polymer of a monomer of a linear, branched, or cyclic aliphatic or aromatic hydrocarbon compound containing at least one unsaturated bond.
Examples of the polymer include aromatic vinyl resins, aliphatic vinyl resins, and acrylic ester resins. Specifically, for example, styrene, α-methylstyrene, vinyl acetate, (meth) acrylonitrile, butadiene, isoprene, male vinyl ether, vinyl chloride, vinylidene chloride, methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) Polymers such as acrylate and butyl (meth) acrylate are exemplified. Among these, a polymer of styrene is preferable. These may be used alone or in combination of two or more.

The weight ratio of the hydrophilic block to the hydrophobic block in the block polymer is preferably 10:90 to 90:10. By setting the weight ratio within the above-mentioned range, it is possible to obtain a high inclusion rate and retention with a smaller particle size. The weight ratio is more preferably 20:80 to 80:20.

The number average molecular weight of the block polymer is not particularly limited, but is preferably 2,000 to 100,000. By being within the above range, the size of the core-shell particles can be reduced, the encapsulation rate can be increased, and good dispersibility can be obtained. A more preferred number average molecular weight is 4,000 to 40,000.
The molecular weight distribution (weight average molecular weight / number average molecular weight) of the block polymer is preferably 1.00 to 2.00. By being in the said range, the uniformity of a size or an inclusion rate can be improved.

The core-shell particles of the present invention preferably have a form in which the block polymer is in the form of an aggregate (micelle). In particular, the core-shell particles are arranged radially with a hydrophobic block on the inside and a hydrophilic block on the outside. It is preferable. Thereby, the outstanding dispersibility is realizable.

The shell constituting the core-shell particle of the present invention contains an organic substance different from the block polymer, and has a structure in which the organic substance and the block polymer are crosslinked.
Examples of the organic substance include a compound having two or more functional groups reactive with the functional group of the block polymer (polyfunctional organic substance), a compound having hydrogen bonding properties with the functional group of the block polymer (hydrogen bonding compound) ) And the like.
Examples of the polyfunctional organic material include bis (haloalkoxy) alkanes such as 1,2-bis- (iodoethoxy) ethane (BIEE), thermosetting resins having a plurality of glycidyl groups such as epoxy resins, and adipic acid Examples thereof include compounds having a plurality of acid halide groups such as dichloride, compounds having a plurality of halogens such as 1,6-dichlorohexane, and polyamine compounds such as hexamethylenediamine.
Examples of the hydrogen bonding compound include water-soluble polymers such as polyvinyl alcohol, polyvinyl butyral, carboxymethylcellulose, and hydroxypropylmethylcellulose.

The shell contains an organic substance different from the block polymer and has a structure in which the organic substance and the block polymer are crosslinked. The cross-linking means a state where the organic substance and the block polymer are chemically bonded or hydrogen bonded. In particular, it is preferable that a chemical bond or a hydrogen bond is formed between the hydrophilic group of the hydrophilic block of the block polymer and the functional group of the organic substance. Thereby, since a strong cross-linked structure is formed between the hydrophilic blocks of the block polymer, the organic substance becomes a dense film, and as a result, high encapsulation stability can be obtained with a higher inclusion amount.
The presence or absence of chemical bonds or hydrogen bonds can be observed from IR, NMR, and the like.

Examples of the chemical bond between the block polymer and the organic substance include a chemical bond between the block polymer and a polyfunctional organic substance. Specifically, for example, an amide group of the block polymer and an organic substance such as a polyfunctional organic substance. It is preferable that a chemical bond is formed with the halogen-containing group of
In particular, by using bis (haloalkoxy) alkane or the like as the polyfunctional organic substance, a strong cross-linked structure is formed between the hydrophilic blocks of the block polymer, so that the organic substance becomes a dense film. High encapsulation stability can be obtained with a higher encapsulation amount.
Moreover, as a hydrogen bond of the said block polymer and organic substance, the hydrogen bond of the said block polymer and a hydrogen bonding compound etc. are preferable, for example.

The core-shell particles of the present invention preferably have an organic content of 1 to 50% by weight. By making content of the said organic substance in the said range, higher enclosure stability can be obtained with much inclusion amount. More preferably, it is 5 to 30% by weight.

The core-shell particles of the present invention have a solid, liquid or gas (hereinafter also referred to as an internal substance) inside.
The solid, liquid, or gas does not include liquid crystal that is in an intermediate state between the solid and the liquid.
The internal substance is different from the block polymer and the organic substance.

Examples of the solid include polymer fine particles, amines such as wax and imidazole, salts, inorganic powders such as silica, metal nanoparticles such as gold nanoparticles, metal complexes, and the like.
Examples of the polymer fine particles include fine particles composed of acrylic resin, polystyrene, polyester, polyurethane, epoxy resin, polyamide, olefin resin, and the like.
Examples of the wax include normal paraffins having 20 or more carbon atoms, such as animal waxes such as beeswax and spermaceti, plant waxes such as wood wax and rice bran wax, mineral waxes such as montan wax and ozokerite, paraffin wax and microcrystalline. Examples include petroleum wax such as wax, synthetic wax such as Fischer-Tropsch wax and polyethylene wax.
Examples of the amines include hydrazide compounds, aliphatic polyamine compounds, primary amine compounds, tertiary amine compounds, and imidazole compounds. More specifically, malonic acid dihydrazide, dicyandiamide, 2-methylimidazole, 1-cyanoethyl-2-undecylimidazole, 1-dodecyl-2-methyl-3-benzylimidazolium chloride, and adducts thereof Can be mentioned.
Examples of the salts include hydrochloride, sulfate, malonate, tartrate, maleate, phosphate, citrate, acetate, and the like.
Examples of the inorganic powder include silica (silicon dioxide), titania (titanium dioxide), alumina (aluminum oxide), zirconia (zirconium oxide), ceria (cerium oxide), magnesia (magnesium oxide), and ferrite (iron oxide). , Silicon carbide, silicon nitride, aluminum nitride, boron nitride, barium titanate, lead zirconate titanate and the like.
Examples of the metal nanoparticles include gold, silver, copper, nickel, iron, platinum, tungsten, and cobalt.
Examples of the metal complex include a diammine silver complex, a tetraammine copper complex, a hexacyanoiron complex, and a tetrachloride iron complex.

Examples of the liquid include aromatic hydrocarbons, aliphatic hydrocarbons, alicyclic hydrocarbons, aqueous solutions of salts, amines such as imidazole, and the like.
Examples of the aromatic hydrocarbon include toluene, xylene, benzene and the like. Examples of the aliphatic hydrocarbon include aliphatic hydrocarbons having 5 to 19 carbon atoms and isomers such as pentane, hexane, heptane, octane, and decane.
Examples of the alicyclic hydrocarbon include cyclohexane, cyclohexene, cycloheptane and the like.
Examples of the aqueous salt solution include sodium chloride, and examples of the amines include hydrazide compounds, aliphatic polyamine compounds, primary amine compounds, tertiary amine compounds, and imidazole compounds. More specifically, 1-benzyl-2-methylimidazole, 1,2-dimethylimidazole, 2-ethyl-4-methylimidazole, 1-benzyl-2-phenylimidazole, 1-cyanoethyl-2-methylimidazole, 1 -Cyanoethyl-2-ethyl-4-methylimidazole, adducts thereof and the like. Examples of the aqueous salt solution include an aqueous salt solution exemplified in the above solid.

Examples of the gas include air, nitrogen, low boiling point hydrocarbon gas, and the like. Examples of the low boiling point hydrocarbon gas include butane and propane, and aliphatic hydrocarbons having 4 or less carbon atoms.

The core-shell particles of the present invention preferably have a content of the internal substance of 5 to 90% by weight. By setting the content of the internal substance within the above range, the internal substance can be diffused at a high concentration and uniformly to the surroundings during use. More preferably, it is 10 to 80% by weight.

The core-shell particle of the present invention may have a shape having a solid, liquid, or gas inside the block polymer aggregate, and is a hollow particle obtained by removing a portion corresponding to a hydrophobic block from the block polymer aggregate. A shape having a solid, liquid, or gas inside may be used.

The core shell particles of the present invention have a preferred lower limit of the average particle diameter of 10 nm and a preferred upper limit of 100 nm. Within the above range, good transparency and dispersibility can be obtained. A more preferable lower limit of the average particle diameter is 20 nm, and a more preferable upper limit is 70 nm.

The average upper limit of the CV value of the average particle diameter of the core-shell particles of the present invention is 50%. When the CV value is in the above range, good transparency and dispersibility can be obtained. A more preferable upper limit of the CV value is 40%. The CV value is a numerical value indicated by a percentage (%) of a value obtained by dividing the standard deviation by the average particle diameter.

In the core-shell particles of the present invention, the preferred lower limit of the shell thickness is 1 nm, and the preferred upper limit is 30 nm. When the thickness is in the above range, higher encapsulation stability can be obtained with a large amount of inclusion. The more preferable lower limit of the thickness is 2 nm, and the more preferable upper limit is 20 nm. A more preferred lower limit is 3 nm, and a more preferred upper limit is 10 nm.

The core-shell particles of the present invention include drug delivery carrier, diagnostic agent carrier, bacteria or cell separation carrier, nucleic acid or protein separation / purification carrier, enzyme reaction carrier, cell culture carrier, X-ray contrast agent, adhesive curing control agent, rubber It can be suitably used as a vulcanization control agent, a catalyst reaction control agent, and the like.

Examples of the method for producing the core-shell particles of the present invention include a step of producing a block polymer having a hydrophilic block and a hydrophobic block, and an oil phase containing an internal substance is added to the aqueous phase containing the block polymer. And a method of forming a block polymer aggregate (emulsion) and a step of adding and reacting an organic substance different from the block polymer.
FIG. 1 is a diagram schematically showing a process for producing core-shell particles of the present invention. As shown in FIG. 1, by using the above production method, the core-shell particles of the present invention can be easily produced in a series of steps.

As a process for producing the block polymer having the hydrophilic block and the hydrophobic block, for example, living radical polymerization, living cation polymerization, living anion polymerization, and the like that are iniferter polymerization and living polymerization are possible. In particular, it is preferable to use living radical polymerization, and atom transfer radical polymerization (ATRP), reversible addition fragmentation chain transfer (RAFT) polymerization, polymerization using nitroxide (Nitroxide) -Mediated Polymerization: NMP), etc., may be prepared by polymerizing the monomer that forms the hydrophilic block and the monomer that forms the hydrophobic block.

By performing the step of adding the oil phase containing the internal substance to the aqueous phase containing the block polymer, an aggregate (emulsion) of the block polymer containing the internal substance can be formed (emulsified).
Specifically, it is preferable to use a phase inversion emulsification method, a D phase emulsification method, a gel emulsification method, a liquid crystal emulsification method, a solubilization method (aggregation method), a phase inversion emulsification method, or the like. In the phase inversion emulsification method, in particular, an oil phase containing an internal substance is added to an aqueous phase containing a block polymer, and the temperature is kept below the phase inversion temperature of the block polymer, and then heated to above the phase inversion temperature with stirring. The phase inversion temperature emulsification method by rapidly cooling to the phase inversion temperature or lower is preferable as a method for easily obtaining fine and uniform size particles.

Next, a step of adding and reacting an organic substance different from the block polymer is performed.
By performing such a process, the hydrophilic block of the block polymer forms a crosslinked structure via an organic substance, and therefore, particles having a core-shell structure can be obtained.

According to the present invention, it is possible to obtain core-shell particles that can encapsulate a large amount of inclusions and can achieve both the encapsulation stability and sustained release properties of the inclusions. The core-shell particles of the present invention can have a small particle size and excellent transparency and dispersibility.

It is the figure which showed typically the process of manufacturing the core-shell particle of this invention.

Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples.

(Example 1)
(1) Synthesis of block polymer DMAEMA (7.9 g), N, N, N ′, N ″, N ″ -pentamethyldiethylenetriamine (0.17 g) and methanol (2.0 mL) were added. Further, 2.0 mL of methanol and 2-hydroxyethyl-2-bromoisobutyrate were added to another container, and freeze deaeration of these two solutions was performed. To the solution to which DMAEMA was added, 0.050 g of copper (I) chloride was added under a nitrogen atmosphere, and then a 2-hydroxyethyl-2-bromoisobutyrate solution was added and reacted in a constant temperature water bath at 25 ° C. for 3 hours to give PDMAEMA. Was synthesized. After completion of the reaction, purification was performed by reprecipitation using n-hexane as a poor solvent through an alumina column.
Next, 0.34 g of synthesized PDMAEMA, 0.47 g of styrene, 0.010 g of N, N, N ′, N ″, N ″ -pentamethyldiethylenetriamine were added, and freeze deaeration was performed. Subsequently, 0.0030 g of copper (I) chloride was added under a nitrogen atmosphere, and the reaction was performed in a 110 ° C. oil bath for 2 hours. After completion of the reaction, purification was performed by reprecipitation using n-hexane through an alumina column.
The number average molecular weight and molecular weight distribution of the obtained block polymer were measured using gel permeation chromatography. The weight ratio of PDMAEMA (hydrophilic block) to polystyrene (hydrophobic block) was defined as “hydrophilic / hydrophobic ratio”.

(2) Synthesis of emulsion 0.030 g of the synthesized block polymer was dissolved in 0.030 g of toluene, and 6.0 g of ultrapure water was added. After stirring at 45 ° C. for 10 minutes, the mixture was quickly transferred to an ice bath and stirred for 10 minutes.

(3) Preparation of core-shell particles To 2.0 mL of the synthesized emulsion liquid, 2.2 μL of 1,2-bis (2-iodoethoxy) ethane was added and reacted for 3 days. And core-shell particles having a crosslinked organic substance in the shell.

(Example 2)
Core-shell particles having toluene inside and having a crosslinked organic substance in the shell were produced in the same manner as in Example 1 except that “(2) Synthesis of emulsion” in Example 1 was changed to the following method.

(2) Synthesis of emulsion 0.030 g of the block polymer synthesized in Example 1 was dissolved in 0.060 g of toluene, and 6.0 g of ultrapure water was added. After stirring at 45 ° C. for 10 minutes, the mixture was quickly transferred to an ice bath and stirred for 10 minutes.

(Example 3)
Core-shell particles having toluene in the interior and a crosslinked organic substance in the shell were produced in the same manner as in Example 1 except that “(1) Synthesis of block polymer” in Example 1 was changed to the following method.

(1) Synthesis of block polymer 15.7 g of DMAEMA, 0.47 g of 2,2′-bipyridine, and 4.0 mL of methanol were added. Further, 4.0 mL of methanol and 0.21 g of 2-hydroxyethyl-2-bromoisobutyrate were added to another container, and these two solutions were freeze-degassed. To the solution to which DMAEMA was added, 0.099 g of copper (I) chloride was added under a nitrogen atmosphere, and then a 2-hydroxyethyl-2-bromoisobutyrate solution was added, and the reaction was performed in a 25 ° C. constant temperature water bath for 6 hours. After completion of the reaction, purification was performed by reprecipitation using n-hexane through an alumina column.
Next, 1.4 g of synthesized PDMAEMA, 1.0 g of styrene, 0.092 g of tris [2- (dimethylamino) ethyl] amine, and 1.0 mL of N, N-dimethylformamide were added, and freeze deaeration was performed. Subsequently, 0.020 g of copper (I) chloride was added under a nitrogen atmosphere, and the reaction was performed in a 110 ° C. oil bath for 26 hours. After completion of the reaction, the mixture was passed through an alumina column, reprecipitated with n-hexane, and then purified by dialysis with toluene / methanol = 1/1 (v / v).
The number average molecular weight and molecular weight distribution of the obtained block polymer were measured using gel permeation chromatography.

Example 4
Core-shell particles having toluene inside and having a crosslinked organic substance in the shell were prepared in the same manner as in Example 3 except that “(2) Synthesis of emulsion” in Example 3 was changed to the following method.

(2) Synthesis of emulsion 0.030 g of the block polymer synthesized in Example 3 was dissolved in 0.060 g of toluene, and 6.0 g of ultrapure water was added. After stirring at 45 ° C. for 10 minutes, the mixture was quickly transferred to an ice bath and stirred for 10 minutes.

(Example 5)
The core-shell particles obtained in Example 1 were put into an aluminum cup and heated in a vacuum dryer at 50 ° C. for 24 hours to obtain hollow particles from which inclusions were removed.

(Example 6)
The core-shell particles obtained in Example 3 were put into an aluminum cup and heated in a vacuum dryer at 50 ° C. for 24 hours to obtain hollow particles from which inclusions were removed.

(Comparative Example 1)
To a solution of 1.0 g of sodium dodecyl sulfate (sulfate group as hydrophilic part, dodecyl group as hydrophobic part, molecular weight 288) dissolved in 200 g of water, 1 g of toluene is added and emulsified and dispersed with an ultrasonic homogenizer. Core / corona particles in which a dodecyl group was in contact with the core and the core, a sulfate group was spread on the aqueous phase side, and the shell was not crosslinked were obtained.

(Comparative Example 2)
1 g of toluene is added to a solution obtained by dissolving polyethylene glycol (PEG, hydroxyl group as a hydrophilic group) as a hydrophilic block and 1 g of polylactic acid (PLGA) as a hydrophobic block in 200 g of water, and emulsified and dispersed with an ultrasonic homogenizer. The core / corona particles in which the PLGA block was in contact with the core and the core with toluene, the PEG spread on the water phase side, and the shell was not crosslinked were obtained.

(Comparative Example 3)
Methyl methacrylate 0.9 g, ethylene glycol dimethacrylate 0.1 g, toluene 1.0 g, and azobisisobutyronitrile 0.1 g were dissolved to obtain an oil phase. 0.1 g of sodium dodecyl sulfate (sulfate group as hydrophilic part, dodecyl group as hydrophobic part, molecular weight 288) was dissolved in 10 g of water to obtain an aqueous phase. Add the oil phase to the aqueous phase, emulsify and disperse with an ultrasonic homogenizer, and heat at 70 ° C. for 8 hours with stirring to perform the polymerization reaction. Toluene is the core and the methyl methacrylate cross-linked polymer is the shell As a result, core-shell particles having sodium dodecyl sulfate attached to the shell surface were obtained.

(Comparative Example 4)
1.0 g of bis A type epoxy resin (JER828) manufactured by Japan Epoxy Resin Co., Ltd. and 1.0 g of toluene were dissolved to obtain an oil phase. 0.1 g of sodium dodecyl sulfate (sulfate group as hydrophilic part, dodecyl group as hydrophobic part, molecular weight 288) was dissolved in 10 g of water to obtain an aqueous phase. Add the oil phase to the water phase, emulsify and disperse with an ultrasonic homogenizer, add 0.02 g of 25 wt% ammonia aqueous solution over about 30 minutes using a syringe pump while stirring. Then, a core-shell particle was obtained in which a cross-linked epoxy resin was coated as a shell and sodium dodecyl sulfate was adhered to the shell surface.

(Comparative Example 5)
In Example 1, except that 2.2 μL of 1,2-bis (2-iodoethoxy) ethane was not added, toluene was the core, the polystyrene block was in contact with the core, and the water phase side Core / corona particles were obtained in which the poly DMAEMA was spread and the shell was not crosslinked.

<Evaluation>
The following evaluation was performed on the core-shell particles obtained in Examples and Comparative Examples. The results are shown in Table 1.

(1) Inclusion rate (hollow rate)
About 0.0003 g of core-shell particles were measured with a pyrolysis GC / MS (Q1000) manufactured by JEOL Ltd. at a pyrolysis temperature of 550 ° C. By comparing and analyzing the peak area of the inclusion (core) with a calibration curve prepared in advance with a compound corresponding to the inclusion (core), the amount of core contained in the core-shell particles was calculated and used as the inclusion rate.

(2) Average particle diameter Core-shell particles and water are adjusted in a 10 mL sample bottle so that they are about 0.05 g and about 6.0 g, shaken vigorously up and down for 30 seconds, and then dynamic light scattering manufactured by Otsuka Electronics Co., Ltd. Measurement was performed with an apparatus “LPA-3100”, and the obtained volume average particle diameter was defined as the average particle diameter.

(3) The sample was adjusted in a 10 mL sample bottle so that the transparent core-shell particles and water were about 0.05 g and about 6.0 g, shaken up and down for 30 seconds, and allowed to stand for 5 minutes. For the appearance of the liquid after standing, transparency was judged according to the following criteria.
◎: Transparent and clear beyond the liquid ○: Slightly transparent and the other side of the liquid is blurred △: White and cloudy and almost the other side of the liquid cannot be seen ×: White and cloudy and the other side of the liquid cannot be seen at all

(4) The dispersible core-shell particles and water were adjusted in a 10 mL sample bottle so as to be about 0.05 g and about 6.0 g, shaken up and down for 30 seconds and allowed to stand for 5 minutes. About the external appearance of the liquid after standing, dispersibility was judged according to the following criteria.
◎: Transparent and there is no lump that can be visually discerned ○: Slightly cloudy, but there is no lump that can be visually discerned Δ: Slightly lump that can be visually discerned is visible in the liquid ×: In the liquid You can see many lumps that can be identified visually

(5) Encapsulation stability (retainability)
(5-1) Encapsulation Retention Core shell particles and water are adjusted in a 10 mL sample bottle so as to be about 0.05 g and about 6.0 g, shaken vigorously up and down for 30 seconds, and then 50 ° C. in a vacuum drying oven. The powder was dried for 1 day and night to obtain water / heat-treated core-shell particle powder. About 0.0003 g of the obtained powder was measured with a pyrolysis GC / MS (Q1000) manufactured by JEOL Ltd. at a pyrolysis temperature of 550 ° C. By comparing and analyzing the peak area of the inclusion (core) with a calibration curve prepared in advance with a compound corresponding to the inclusion (core), the amount of core contained in the water-heat treated core-shell particles was calculated. The inclusion retention was determined by the inclusion rate Y, Y / X after the water / heat treatment relative to the inclusion rate X before the water / heat treatment (the inclusion rate obtained by “(1) inclusion rate (hollow rate)”).
◎: 0.8 or more ○: 0.3 or more Δ: 0.1 or more ×: less than 0.1 (5-2) Shape-retaining core-shell particles are dispersed on a sheet mesh, and excess powder is blown off. Observation was performed with a transmission electron microscope TEM. The number of particles that looked like a circle and the number of particles that looked like fragments such as cracks and crushing were counted, and the number of particles that looked like a circle out of 30 particles was judged.
◎: 27 or more in a circular shape ○: 25 or more in a circular shape Δ: 20 or more in a circular shape ×: 19 or less in a circular shape

According to the present invention, it is possible to provide core-shell particles that can encapsulate a large amount of inclusions and can achieve both the encapsulation stability and sustained release properties of the inclusions.

Claims (4)

Core-shell particles obtained using a block polymer having a hydrophilic block and a hydrophobic block,
Has a solid, liquid or gas inside,
A core-shell particle, wherein the shell contains an organic substance different from the block polymer, and the organic substance and the block polymer are crosslinked. The core-shell particle according to claim 1, wherein the block polymer and the organic substance are chemically bonded or hydrogen bonded. The hydrophilic group block is a hydrophilic group selected from the group consisting of an amino group, a hydroxyl group, a carboxyl group, an isocyanate group, an amide group, a sulfonic acid group, an ethyleneoxy group, a phosphoric acid group, a urea group, a thiol group, and a sulfuric acid group. The core-shell particles according to claim 1 or 2, wherein 4. The core-shell particle according to claim 1, 2 or 3, wherein an average particle diameter is 70 nm or less.

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