WO2024101250A1

WO2024101250A1 - Method for producing microgel, and method for producing decorative microgel aggregate

Info

Publication number: WO2024101250A1
Application number: PCT/JP2023/039495
Authority: WO
Inventors: 淳平山中; 彰子豊玉; 透奥薗; 綾音平井; 麻菜濱中; 智彦佐藤; 亮太中村
Original assignee: 公立大学法人名古屋市立大学; 株式会社ダイセル
Priority date: 2022-11-11
Filing date: 2023-11-01
Publication date: 2024-05-16

Abstract

Provided is a method for producing: a gel having a particle size that is small enough to be capable of exhibiting structural colors due to light interference when formed into an aggregate; and a decorative microgel aggregate that exhibits structural colors due to light interference.　A decorative microgel aggregate according to the present disclosure is obtained by mixing a W/O type emulsion in which a polymer aqueous solution has been emulsified with an emulsifier and a W/O type emulsion in which a polyvalent cation aqueous solution that can form the polymer aqueous solution into a gel has been emulsified with an emulsifier, and thereby forming a microgel dispersion (emulsion mixing step S1), and destroying the emulsion state by adding, to the microgel dispersion, an emulsion breaker which is a good solvent for the emulsifier and a poor solvent for the polymer (emulsion destruction step S2).

Description

Method for producing microgel and method for producing decorative microgel aggregate

This disclosure relates to a method for producing a microgel and a method for producing a decorative microgel aggregate.

It is known that a water-soluble polymer gels when an aqueous solution containing multivalent cations such as magnesium or calcium is added to the polymer (for example, adding "bittern" containing magnesium salt to soy milk causes the polymer to coagulate and become tofu). A method for producing polymer gel particles utilizing this phenomenon is also known. For example, Patent Document 1 describes that fish egg-shaped spherical particles can be obtained by dropping an aqueous solution of sodium alginate into an aqueous solution of calcium and coagulating the solution.
However, in the method of producing gel particles by dropping an aqueous polymer solution into an aqueous solution containing polyvalent cations, it is difficult to reduce the particle size to approximately the wavelength of visible light.

As a method for obtaining small-sized gel particles, Non-Patent Document 1 describes a method in which an aqueous solution of sodium alginate containing _CaCO3 is dispersed in an oil phase to form an emulsion, and acetic acid is added to dissolve the _CaCO3 and gel the alginic acid to form microparticles.
However, even if this method is used, the diameter of the alginate gel particles is 200 to 1000 μm, and it is difficult to obtain gel particles smaller than this. Therefore, even if the gel particles obtained by this method are collected into an aggregate, they will not exhibit structural color due to light interference.

JP 59-159759 A

The present invention was made in consideration of the above-mentioned conventional situation, and aims to provide a gel (hereinafter referred to as a "microgel") with a small enough diameter that, when assembled, it is capable of exhibiting structural color due to the interference of light, and to provide a decorative microgel assembly that exhibits structural color due to the interference of light.

The microgel manufacturing method of the present invention is characterized by mixing a first W/O type emulsion in which an aqueous polymer solution is emulsified with an emulsifier in an oil phase with a second W/O type emulsion in which an aqueous polyvalent cation solution capable of gelling the aqueous polymer solution is emulsified with an emulsifier in an oil phase to produce a microgel dispersion.

In the microgel manufacturing method of the present invention, a first W/O type emulsion in which an aqueous polymer solution is emulsified with an emulsifier in an oil phase is mixed with a second W/O type emulsion in which an aqueous polyvalent cation solution capable of gelling the aqueous polymer solution is emulsified with an emulsifier in an oil phase. This causes the microdroplets of the emulsified aqueous polymer solution to merge with the microdroplets of the emulsified aqueous polyvalent cation solution and gel, forming a dispersion of microgels with particle sizes comparable to or smaller than the wavelength of visible light.

The decorative microgel manufacturing method of the present invention is characterized by comprising an emulsion mixing step of mixing a first W/O type emulsion obtained by emulsifying a polymer aqueous solution in an oil phase with an emulsifier with a second W/O type emulsion obtained by emulsifying a polyvalent cation aqueous solution capable of gelling the polymer aqueous solution in an oil phase with an emulsifier to obtain a microgel dispersion, and an emulsion breaking step of adding an emulsion breaker, which is a good solvent for the emulsifier and a poor solvent for the polymer, to the microgel dispersion to break the emulsion state.

In the decorative microgel manufacturing method of the present invention, in the emulsion mixing step, the micro-droplets of the emulsified polymer aqueous solution in the first W/O type emulsion are united with the micro-droplets of the emulsified polyvalent cation aqueous solution in the second W/O type emulsion to gel, forming a dispersion of microgels made of polymers with a size equal to or smaller than the wavelength of visible light. Furthermore, in the emulsion breaking step, the dispersion of microgels made of polymers is a good solvent for the emulsifier, and the emulsion is broken by an emulsion breaker that is a poor solvent for the polymers to form an aggregate of microgels. The aggregate of microgels manufactured in this way is an aggregate of microgels with a particle size equal to or smaller than the wavelength of visible light, and therefore exhibits structural color due to the interference of light.

The average primary particle size of the microgel particles that make up the decorative microgel aggregate is preferably 10 nm or more and 1000 nm or less. This makes it possible to cause diffraction of visible light and produce structural colors through interference. More preferably, it is 20 nm or more and 830 nm or less, and most preferably, it is 100 nm or more and 500 nm or less. The lower limit of the wavelength range of visible light is said to be 360 to 400 nm, but since there are cases where microgel particles undergo secondary aggregation, even colloidal particles with an average particle size below the lower limit can cause diffraction of visible light.

By using a naturally derived water-soluble polymer as the polymer, the decorative microgel aggregate has excellent biocompatibility. Therefore, it can be used favorably in areas that come into direct contact with the skin, such as cosmetics. In addition, by using a naturally derived water-soluble polymer, it is possible to produce a decorative microgel aggregate with low environmental impact.

FIG. 1 is a process diagram of a microgel production method. FIG. 2 is a schematic diagram showing how emulsified particles of a W/O emulsion of an aqueous polymer solution and emulsified particles of a W/O emulsion of an aqueous polyvalent cation solution coalesce in the emulsion mixing step S1. FIG. 2 is a process diagram of a method for producing a decorative microgel assembly. 1A to 1C are schematic diagrams showing a manufacturing process of a decorative microgel assembly. 1 is an optical microscope photograph of the alginate microgel dispersion of Example 1. 1 is an optical microscope photograph of an alginate microgel particle aggregate of Example 1. 1 is a graph showing the measurement of the reflectance spectrum of the alginate microgel aggregate of Example 1. 1 is an optical microscope photograph of a gel particle aggregate of Comparative Example 1. FIG. 1 is a schematic diagram showing a method for producing gel particles of Comparative Examples 2-1 to 2-4 (excerpted from the product catalog of SPG Techno Co., Ltd.). 1 shows optical microscope photographs of Comparative Example 2-1 to Comparative Example 2-4 (in the figure, (a) shows a sample in an emulsion state, (b) shows gel particles before washing, and (c) shows gel particles after washing).

(Microgel Manufacturing Method)
Emulsion mixing step S1
FIG. 1 shows a process diagram of the microgel production method according to the embodiment.
The polymer aqueous solution and the emulsifier are added to the oil phase and mixed to obtain a W/O type emulsion 1 of the polymer aqueous solution. As the oil phase, any solvent that becomes an immiscible phase when mixed with the polymer aqueous solution can be used. For example, low polarity solvents such as hydrocarbon solvents such as hexane and octane, and aromatic solvents such as benzene and alkylbenzene can be used. Natural oils such as rapeseed oil can also be used. In addition, the type of polymer is not particularly limited as long as it is a polymer that gels with polyvalent cations. Examples of such polymers include acidic polymer polysaccharides having carboxy groups, such as alginic acid, pectinic acid, colominic acid, and glucuronic acid, and alkali metal salts thereof, and proteins such as glycinin. As the emulsifier, nonionic surfactants (e.g., Tween 20, Tween 40, Tween 80, etc.), anionic surfactants, cationic surfactants, betaine type surfactants, etc. can be used. As for the mixing method, mixing by a stirrer, mixing by ultrasonic waves, mixing by a homogenizer, mixing by using a fine channel, and mixing by using a combination of these can be performed.

Furthermore, another container is prepared, and the polyvalent cation aqueous solution and the low polarity solvent are mixed with the addition of an emulsifier to obtain a W/O type emulsion 2 of a polyvalent cation aqueous solution. Examples of polyvalent cations include calcium ions, magnesium ions, strontium ions, aluminum ions, iron ions, and copper ions. In addition, the oil phase can be any solvent that is an immiscible phase when mixed with the polymer aqueous solution. For example, low polarity solvents such as hydrocarbon solvents such as hexane and octane, and aromatic solvents such as benzene and alkylbenzene can be used. The oil phase can be the same as that used in the W/O type emulsion 1 of a polymer aqueous solution, or a different oil phase. In addition, the emulsifier can be the same as that used in the W/O type emulsion 1 of a polymer aqueous solution, or a different emulsifier. The type of emulsifier that can be used includes nonionic surfactants (e.g., Tween 20, Tween 40, Tween 80, etc.), anionic surfactants, cationic surfactants, betaine type surfactants, etc. Mixing methods include mixing with a stirrer, mixing with ultrasonic waves, mixing with a homogenizer, mixing using a microchannel, and a combination of these.

The thus prepared W/O type emulsion 1 of the aqueous polymer solution and the W/O type emulsion 2 of the aqueous polyvalent cation solution are mixed (emulsion mixing step S1). The mixing method can be agitator mixing, ultrasonic mixing, microchannel mixing, or a combination of these. By carrying out this emulsion mixing step S1, as shown in FIG. 2, emulsion particles 6 made of the aqueous polymer solution emulsified by emulsifier 5 in oil phase 4 and emulsion particles 9 made of the aqueous polyvalent cation solution emulsified by emulsifier 8 in oil phase 7 are united and gelled to form microgel particles 10. The particle diameter of the microgel particles 10 thus obtained can be approximately the same as or smaller than the wavelength of visible light.

(Method for producing decorative microgel aggregate)
Emulsion breaking step S2
An emulsion breaker, which is a good solvent for the emulsifier and a poor solvent for the polymer, is added to the microgel dispersion 3 obtained by carrying out the above-mentioned emulsion mixing step S1 to extract the emulsifier, thereby flocculating the microgel into a decorative microgel aggregate 11 (see FIG. 3). Examples of such emulsion breakers include alkyl alcohols such as ethanol and propanol. The decorative microgel aggregate can be separated by filtration, decantation, or precipitating the decorative microgel aggregate using a centrifuge.

Hereinafter, further specific examples of the present disclosure will be described.
Example 1
・Preparation of microgel dispersion (emulsion mixing step S1)
A microgel dispersion was prepared using an aqueous sodium alginate solution (a commercially available product (Wako Pure Chemical Industries, Ltd.) with a viscosity of 300 to 400 cps for a 1% aqueous solution) by the method shown in FIG. 4.
30 mL of hexane was placed in a 100 mL eggplant flask, 1 mL of SPAN80 (sorbitan monooleate) was added as a nonionic surfactant, and the mixture was stirred at 1500 rpm using a magnetic stirrer to obtain a hexane solution of the nonionic surfactant. Furthermore, 1.25 mL of a 2 wt% aqueous sodium alginate solution was added dropwise while continuing to stir. Stirring was continued overnight to obtain a W/O type emulsion of the aqueous sodium alginate solution (hereinafter referred to as "Liquid A").
30 mL of hexane was placed in a 100 mL beaker, 1 mL of SPAN80 was added, and dissolved using a magnetic stirrer. 1.25 mL of 0.2 M calcium chloride aqueous solution was then added, and the mixture was dispersed using ultrasonic treatment to obtain a W/O type emulsion of calcium chloride aqueous solution (hereinafter referred to as "liquid B").
While stirring Liquid B, Liquid A was added dropwise in small amounts. After the addition of Liquid A was completed, stirring was continued to obtain an alginate microgel dispersion. An optical microscope image of this alginate microgel dispersion is shown in Figure 5. As a result, it was observed that alginate microgel particles with a relatively uniform particle size of about 1 μm were uniformly dispersed.

Emulsion breaking step S2
0.1 mL of the alginate microgel dispersion obtained by the emulsion mixing step S1 was placed in a glass bottle, and 0.5 mL of ethanol was added as an emulsion breaker and mixed. The glass bottle was then heated with a dryer to volatilize hexane, which has a lower boiling point than ethanol. The ethanol phase was removed by centrifuging twice at 13,500 rpm for 10 minutes using a centrifuge to obtain a precipitate. When the precipitate was observed under an optical microscope, aggregates of orange and red alginate microgel particles were clearly observed, as shown in Figure 6.

The above results can be explained as follows.
Hexane and ethanol can be mixed in any ratio to form a homogeneous liquid, so the hexane in the alginate microgel dispersion is extracted into ethanol. Furthermore, since ethanol is a good solvent for SPAN80 (the solubility of SPAN80 in ethanol is approximately 5 wt%), SPAN80 is extracted into the ethanol-hexane phase. Furthermore, since ethanol is a poor solvent for sodium alginate, sodium alginate is not extracted into the ethanol-hexane phase. Furthermore, at least a part of the water migrates to the ethanol-hexane phase. As a result, the W/O emulsion is destroyed and aggregates of alginate microgel are precipitated.

When the reflectance spectrum of the alginate microgel aggregates was measured using microspectroscopy, a reflected light peak was observed in the orange to red region (see Figure 7). Furthermore, when the size distribution of the microgels in the alginate microgel aggregates was measured using dynamic light scattering, it was revealed that microgels with a diameter of approximately 350 nm were formed. These results demonstrated that the visible light observed in the alginate microgel aggregates is a structural color caused by light interference.

Example 2
In Example 2, 1-propanol was used as the solvent added in the emulsion breaking step S2. The rest of the process was the same as in Example 1, and the description will be omitted.
As a result, in Example 2 as well, as in Example 1, an alginate microgel aggregate emitting visible light was obtained.

(Comparative Example 1)
In Comparative Example 1, gel particles were prepared from an aqueous sodium alginate solution by a method described in the following literature, with some modifications:
A.Tachaprutinun, P.Pan-In, and S.Wanichwecharungruang, “Mucosa-plate for direct evaluation of mucoadhesion of drug carriers”, Int. J. Pharmaceutics 441,(2013)801-808.

Sodium alginate was used as a commercially available product (Wako Pure Chemical Industries, Ltd.) with a viscosity of 300-400 cps for a 1% aqueous solution. 15 mL of 2 wt% sodium alginate aqueous solution, 90 mL of rapeseed oil, 1.8 mL of ethanol, and 6 mL of nonionic surfactant Celmoris B044 (manufactured by Daicel Corporation) were placed in a 300 mL round-bottom flask and stirred at room temperature at 1500 rpm for 15 minutes using a magnetic stirrer to obtain a W/O type emulsion with the sodium alginate aqueous solution as the aqueous phase. Then, 75 mL of 0.05 M _CaCl2 aqueous solution was dropped into this W/O type emulsion and stirred for an additional 3.5 hours. After that, the mixture was placed in a separatory funnel and left to stand overnight, and the aqueous layer containing the gel particles was taken out. The aqueous layer was filtered using filter paper to obtain an aqueous dispersion of alginate gel.

The aqueous dispersion of alginic acid gel thus obtained was filtered through a 5 μm, 1 μm, 0.45 μm, and 0.2 μm membrane filter in this order using a glass suction filter, and the gel particles remaining on the filter were finally collected. These gel particles were dispersed again in water, and ion exchange resin was added, followed by shaking to desalt.
After purifying a 0.5 wt% aqueous solution of hydroxyethyl cellulose (SE900, Daicel Corporation) by adding an ion exchange resin, 200 μL was taken and mixed with 100 μL of desalted gel dispersion and 100 μL of water, and allowed to stand for 25 hours to obtain an aggregate. The gel particles formed an aggregate because the addition of hydroxyethyl cellulose caused a depletion attractive force between the gel particles.
When this aggregate was observed under an optical microscope, as shown in Figure 8, an aggregate of gel particles was observed, and the particle size of this aggregate was about 3 to 5 μm. However, no coloring was observed. From these results, it was found that even if a W/O type emulsion in which an aqueous sodium alginate solution is used as the water phase is contacted with an aqueous calcium chloride solution, it is not possible to obtain a microgel with a particle size small enough to show structural color due to light interference.

(Comparative Example 2-1 to Comparative Example 2-4)
In Comparative Examples 2-1 to 2-4, gel particles were prepared by a method in which the aqueous polymer solution was extruded through a filter and brought into contact with the aqueous gelling agent solution (see FIG. 9).
A sodium alginate solution (300-400 cps, Wako Pure Chemical Industries, Ltd.), NaCl (Wako Pure Chemical Industries, Ltd.), and calcium carbonate (CaCO3) (Wako Pure Chemical Industries, Ltd.) finely ground in a mortar were added to water and mixed to prepare a dispersion (however, calcium carbonate was not added in Comparative Examples 2-3 and 2-4).
In addition, a sorbitan monooleate solution was prepared by dissolving sorbitan monooleate (Span 80) (Wako Pure Chemical Industries, Ltd.) in n-hexane (Wako Pure Chemical Industries, Ltd.).

The dispersion was then filled into a syringe (Hamilton Gastight Syringe 5 mL (Hamilton Company Inc.)) and a porous glass filter (SPG membrane) (SPG Techno Co., Ltd.) with uniform micron-sized pores was attached to the injection port of the syringe (the pore size of the filter was 10 μm in Comparative Examples 2-1 and 2-2, and 1 μm in Comparative Examples 2-3 and 2-4). The filter part was then immersed in the sorbitan monooleate solution and the syringe was gradually pulled back to suck up the sorbitan monooleate solution, allowing the SPG membrane to be infiltrated with the sorbitan monooleate solution. The disk holder was then removed and the sucked up sorbitan monooleate solution was completely pushed out. After the dispersion was extruded, approximately 2 mL of the dispersion was sucked up, the disk holder was reconnected, and it was fixed to a microsyringe pump (AS ONE Corporation). The filter portion was then again immersed in the sorbitan monooleate solution, and while stirring at 300 rpm, the syringe was gradually lowered to extrude the dispersion into the sorbitan monooleate solution, forming a W/O type emulsion. After extruding approximately 1.5 mL of the dispersion in this way, the syringe was removed, and while stirring at 300 rpm, 4 μL of glacial acetic acid was added to gel the solution, yielding a gel particle dispersion. All water used in the experiments was obtained using a Milli-Q system (Millipore, MA, U.S.A.) (electrical conductivity 0.6 μS/cm or less).

Thirty minutes after the start of gelation, the same volume of 0.1 M calcium chloride (CaCl ₂ ) aqueous solution (Wako Pure Chemical Industries, Ltd.) as that of the sorbitan monooleate solution was added to form gel particles, which were then washed with 1% Tween 80 solution (Tokyo Chemical Industry Co., Ltd.) and Milli-Q water (Millipore, MA, USA) and stored in Milli-Q water.

The amount of each reagent and the preparation conditions for the gel particle dispersion are shown in Table 1. The concentrations of _CaCO3 and NaCl are shown with the total amount of the dispersion taken as 100%, and the concentration of sodium alginate is shown relative to the total weight of the dispersion.

The gel particles thus obtained and the emulsion before gelation were observed using an inverted optical microscope ECLIPSE Ti-S (Nikon Corporation). The objective lenses used were ×20 and ×40 (both Plan Fluor, Nikon Corporation).
As a result, the particle diameters of the gel particles were all 1 μm or more and varied greatly from particle to particle, as shown in Figure 10. In addition, no structural color due to light interference was observed ((a) in the figure shows the sample in an emulsion state, (b) shows the gel particles before washing, and (c) shows the gel particles after washing).

The decorative microgel aggregates disclosed herein exhibit structural colors due to the interference of light. Moreover, they can also be made into gel aggregates of naturally occurring water-soluble polymers. For this reason, they can be ideally used in cosmetics and the like.

1...W/O type emulsion of aqueous polymer solution,
2...W/O type emulsion of polyvalent cation aqueous solution, 3...Microgel dispersion,
4, 7: oil phase, 5, 8: emulsifier, 6, 9: emulsified particles, 10: microgel particles, 11: decorative microgel aggregates S1: emulsion mixing step, S2: emulsion breaking step

Claims

a first W/O type emulsion obtained by emulsifying an aqueous polymer solution in an oil phase with an emulsifier; and a second W/O type emulsion obtained by emulsifying an aqueous polyvalent cation solution capable of gelling the aqueous polymer solution in an oil phase with an emulsifier.
A method for producing a microgel, comprising: mixing the above components to obtain a microgel dispersion.
The method for producing a microgel according to claim 1, wherein the polymer is a naturally occurring water-soluble polymer.
The method for producing a microgel according to claim 1 or 2, wherein the polymer is either an acidic polymer polysaccharide having a carboxy group or an alkali metal salt thereof, or a protein.
The method for producing a microgel according to claim 3, wherein the polymer is any one of alginic acid, pectinic acid, colominic acid, glucuronic acid and their alkali metal salts, and glycinin.
The method for producing a microgel according to claim 1 or 2, wherein the polyvalent cation is at least one of calcium ions, magnesium ions, strontium ions, aluminum ions, iron ions, and copper ions.
a first W/O type emulsion obtained by emulsifying an aqueous polymer solution in an oil phase with an emulsifier; and a second W/O type emulsion obtained by emulsifying an aqueous polyvalent cation solution capable of gelling the aqueous polymer solution in an oil phase with an emulsifier.
an emulsion mixing step of mixing the above to obtain a microgel dispersion;
and an emulsion breaking step of adding an emulsion breaker, which is a good solvent for the emulsifier and a poor solvent for the polymer, to the microgel dispersion to break the emulsion state.
The method for producing a decorative microgel assembly according to claim 6, wherein the polymer is a naturally occurring water-soluble polymer.
The method for producing a decorative microgel assembly according to claim 6 or 7, wherein the polymer is either an acidic polymer polysaccharide having a carboxy group or an alkali metal salt thereof, or a protein.
The method for producing a decorative microgel aggregate according to claim 8, wherein the polymer is any one of alginic acid, pectinic acid, colominic acid, glucuronic acid and their alkali metal salts, and glycinin.
The method for producing a decorative microgel aggregate according to claim 6 or 7, wherein the polyvalent cation is at least one of calcium ions, magnesium ions, strontium ions, aluminum ions, iron ions, and copper ions.
A decorative microgel assembly produced by the method of claim 6 or 7.
The decorative microgel aggregate according to claim 11, wherein the average primary particle diameter of the microgel is 10 nm or more and 1000 nm or less.