Manufacturing method of cellulose nanofiber capsules

Abstract

This method for producing a cellulose nanofiber capsule comprises: a step for forming a Pickering emulsion by irradiating a mixture, which contains cellulose nanofibers, water and a carbon dioxide fluid, with ultrasonic waves within a closed container; and a step for promoting encapsulation of cellulose nanofibers from the Pickering emulsion by opening the closed container. The present invention enables, for example, encapsulation of cellulose nanofibers from a Pickering emulsion that does not contain an organic solvent; and the present invention is useful, for example, in the technological fields of pharmaceutical products, food and cosmetic products.

Description

[Technical Field]

[0001] The present invention relates to a method for producing cellulose nanofiber capsules, and more particularly to a method for producing cellulose nanofiber capsules that utilizes the formation of a Pickering emulsion. [Background technology]

[0002] Capsules using Pickering emulsions, which are emulsions stabilized by solid particles adsorbed at the liquid-liquid interface, have recently attracted attention as emulsifier-free emulsion capsules due to their potential applications in cosmetics, medical products, and pharmaceutical compositions, and various manufacturing methods have been proposed.

[0003] On the other hand, a technology has been proposed to encapsulate various substances in cellulose nanofibers using Pickering emulsions of cellulose nanofibers.

[0004] For example, Patent Document 1 discloses a method for producing capsules by forming an oil-in-water Pickering emulsion and filling this Pickering emulsion and a propellant into a pressure-resistant container, or filling this Pickering emulsion into a container other than the pressure-resistant container that generates foam when the Pickering emulsion is dispensed. However, while the method in Patent Document 1 makes it possible to produce cellulose nanofiber capsules using a Pickering emulsion, it uses harmful triglycerides in the process of preparing the liquid oil phase, making it difficult to apply, particularly to biological systems.

[0005] Patent Document 2 discloses a method for producing capsules by preparing cellulose nanocrystals and incorporating the cellulose nanocrystals into the aqueous phase of a composition to stabilize the emulsion. According to the method described in Patent Document 2, cellulose nanofiber capsules are produced by mixing the prepared cellulose nanocrystals in a 30:70 oil-water ratio and irradiating them with ultrasound. However, this method also uses hexadecane, which is harmful to the human body, in the oil phase, making it difficult to apply to biological systems.

[0006] Patent Document 3 discloses a method for preparing a Pickering emulsion by mixing an aqueous suspension of cellulose nanofibers, which has been prepared using a nano-fiber reduction method (such as the underwater counter-collision method) that uses only the flow energy of a fluid medium such as water as a driving force to disrupt only the interactions between fibers, with a water-insoluble organic solvent. According to the method in Patent Document 3, the cellulose nanofiber preparation method does not use an organic solvent, but the use of an organic solvent is essential for preparing the emulsion, making it difficult to apply to biological systems.

[0007] As described above, various methods for producing cellulose nanofiber capsules using Pickering emulsions have been reported, but all of them require the use of organic solvents. Meanwhile, for applications in cosmetics, medical products, or pharmaceutical compositions, there is a need to establish manufacturing technologies that do not use any organic solvents in the manufacturing process. For this reason, it cannot be said that technologies for producing cellulose nanofiber capsules using safe Pickering emulsions have been fully established, and further development is desired. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] Special Publication No. 2010-527332 [Patent Document 2] Special Publication No. 2013-534561 [Patent Document 3] International Publication No. 2015 / 076191 Summary of the Invention [Problem to be solved by the invention]

[0009] The present invention addresses the above-mentioned problems, and its objective is to provide a method for producing cellulose nanofibers that can be produced via the formation of a Pickering emulsion, and that can be applied to living organisms while avoiding the use of organic solvents. [Means for solving the problem]

[0010] The present invention provides a method for producing cellulose nanofiber capsules, A step of irradiating a mixture containing cellulose nanofibers, water, and carbon dioxide fluid with ultrasound in a closed container to form a Pickering emulsion; Opening the closed container to promote encapsulation of the Pickering emulsion by the cellulose nanofibers; The method includes:

[0011] In one embodiment, the cellulose nanofibers comprise cellulose nanofibers that have been physically defibrated from plant material.

[0012] In one embodiment, the mixture includes a core material.

[0013] In further embodiments, the core material is a hydrophilic material, a hydrophobic material, or a water-insoluble material.

[0014] In one embodiment, the mixture does not contain an organic solvent.

[0015] In one embodiment, the ultrasonic irradiation is carried out by directly irradiating the mixture with ultrasonic waves from an ultrasonic probe disposed within the closed container. [Effects of the Invention]

[0016] According to the present invention, cellulose nanofiber capsules can be efficiently produced using Pickering emulsions. The cellulose nanofibers obtained by the production method of the present invention can be produced without using organic solvents. This eliminates the possibility of organic solvents remaining in the resulting cellulose nanofiber capsules. Such cellulose nanofiber capsules can be provided with higher safety when used on the human body, such as in DDS (drug delivery systems). [Brief explanation of the drawings]

[0017] [Figure 1] FIG. 1 is a schematic diagram showing an example of a manufacturing apparatus for cellulose nanofiber capsules using the manufacturing method for cellulose nanofiber capsules of the present invention. [Figure 2] (a) is a photograph showing the cellulose nanofiber suspension before it was placed in the closable container used in Example 1, and (b) is a photograph of the cellulose nanofiber capsules obtained in Example 1, and a photograph of the liquid containing the capsules removed from the closable container after the experiment. [Figure 3] 1 is a graph showing the particle size distribution and particle concentration of particles contained in a liquid obtained after completely deflocculating the cellulose nanofiber capsules (cellulose nanofiber microparticles) produced in Example 1. [Figure 4] (a) is a photograph showing the cellulose nanofiber suspension containing brominated copper phthalocyanine before it was placed in the closable container used in Example 2, and (b) is a photograph of the cellulose nanofiber capsules encapsulating brominated copper phthalocyanine obtained in Example 2, and a photograph of the liquid containing the capsules removed from the closable container after the experiment. [Figure 5] 1 is a photograph obtained by observing the cellulose nanofiber capsules encapsulating brominated copper phthalocyanine produced in Example 2 using a 3D measuring laser microscope. [Figure 6]1 is a graph showing the particle size distribution and particle concentration of particles contained in a liquid obtained after completely deflocculating the cellulose nanofiber capsules (cellulose nanofiber microparticles) produced in Example 2. [Figure 7] (a) is a photograph showing the cellulose nanofiber suspension containing phycocyanin before it was placed in the closable container used in Example 3, and (b) is a photograph of the cellulose nanofiber capsules containing phycocyanin obtained in Example 3, and a photograph of the liquid containing the capsules removed from the closable container after the experiment. [Figure 8] 1 is a photograph obtained by observing the cellulose nanofiber capsules encapsulating phycocyanin prepared in Example 3 with a 3D measuring laser microscope. DETAILED DESCRIPTION OF THE INVENTION

[0018] The present invention will be described in detail below.

[0019] (Method of manufacturing cellulose nanofiber capsules) In the method for producing cellulose nanofiber capsules of the present invention, first, a mixture containing cellulose nanofibers, water, and carbon dioxide fluid is irradiated with ultrasound in a closed container.

[0020] In the present invention, "cellulose nanofibers" (hereinafter sometimes referred to as CNFs) refer to fibrous structures derived from plants. Many plants have cell walls as their extracellular matrix. The cell walls are composed of, for example, approximately 50% cellulose, 50% hemicellulose, 20% to 30% hemicellulose, and 20% to 30% lignin, based on mass. CNFs can be obtained by isolating cellulose from such plant materials by removing the hemicellulose and lignin, for example, through high-temperature treatment using steam in an alkaline solution, and then subjecting the cellulose to a predetermined chemical or physical treatment to break the bonds and entanglements between the cellulose molecules. In one embodiment, the CNFs are composed of cellulose fibers having a diameter of 1 nm to 100 nm and an aspect ratio of 100 or greater.

[0021] Plant materials that can be used as raw materials for CNFs include, for example, trees obtained from natural or industrial afforestation; wood obtained as industrial waste, wheat straw, rice straw, corn cobs and stems, and bagasse; and combinations of these.

[0022] These plant materials are processed into CNFs using various methods known to those skilled in the art. Examples of methods for obtaining CNFs from plant materials include the ACC (aqueous counter collision) method, in which the pulp of the plant material is placed in a tank equipped with a nozzle together with water, and the pulp and water are sprayed from the nozzle at high pressure to cause collisions between the cellulose molecules in the pulp, thereby pulverizing the plant material; a method in which the primary alcohol present at the C6 position of the cellulose molecules contained in the plant material is oxidized using a TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl) catalyst, thereby utilizing charge repulsion to pulverize the plant material; and a method in which the plant material is hydrolyzed using microorganisms derived from the genus Trichoderma or enzymes produced by these microorganisms. In the present invention, in order to form a CNF Pickering emulsion in the CNF capsule production process, it is preferable to use a material containing physically defibrated CNFs, as in the ACC method.

[0023] The amount of CNF added to the closed container can be determined appropriately depending on, for example, the type of plant material from which the CNF is derived, the particle size of the CNF capsules to be produced, and the production volume, but is preferably 0.5% (w / v) to 10% (w / v), more preferably 1% (w / v) to 3% (w / v), relative to the volume of the closed container. If the amount of CNF added is less than 0.5% (w / v), a Pickering emulsion may not be properly formed in the closed container, making it difficult to efficiently produce the desired CNF capsules. If the amount of CNF added is more than 10% (w / v), there may be too much CNF in the closed container, making it difficult to produce CNF capsules with a uniform particle size.

[0024] The water used is preferably purified in order to avoid contamination of the CNF capsules produced. The water can be purified by any suitable method known to those skilled in the art, such as reverse osmosis, deionization, distillation, filtration, ultrafiltration, etc. For example, ion-exchanged water, pure water, or ultrapure water can be used.

[0025] The amount of water charged into the closed container is not limited as long as it is an amount that can generate a water-carbon dioxide two-phase system with the high-pressure fluid carbon dioxide in the container and contain the produced CNF capsules, but is preferably 10% (w / v) to 40% (w / v), more preferably 15% (w / v) to 30% (w / v) of the volume of the closed container. By containing water in this range in the closed container, a Pickering emulsion of CNF can be properly formed within the container.

[0026] Carbon dioxide fluid refers to carbon dioxide in a state capable of forming an interface with water to produce a carbon dioxide-water two-phase separation system. In the present invention, carbon dioxide fluid can function as a substitute for organic solvents, thereby making it possible to avoid the use of organic solvents. Carbon dioxide fluid may be in a supercritical state, a subcritical state, or a liquid state, and these states can be changed by controlling the pressure or temperature.

[0027] The supercritical state refers to the state of a substance when placed under a temperature and pressure above the critical point of the substance, and has the diffusibility of a gas and the solubility of a liquid. Carbon dioxide fluid in a supercritical state is called supercritical carbon dioxide. Supercritical carbon dioxide refers to carbon dioxide at a temperature above its critical temperature (Tc: 31.1°C) and a pressure above its critical pressure (Pc: 7.38 MPa). A supercritical fluid is a high-density fluid that exceeds its critical point and critical pressure, and is preferably 200 kg / m 3 ~900kg / m 3 and preferably has a density of 10 -5 Pa·sec~10 -4 It has a viscosity of 10 Pa·sec, preferably 10 -8 m 2 / sec~10- 7 m 2 / sec and / or preferably 10 -3 W / m 2 K-10 -1 W / m 2 It is a fluid with a thermal conductivity of .K.

[0028] The subcritical state refers to the state of a substance in a region slightly lower than the critical point. A subcritical fluid is a fluid that is in a liquid state at a temperature range lower than the critical temperature and at a pressure higher than the vapor pressure curve, preferably 500 kg / m 3 ~1100kg / m 3 and preferably has a density of 10 -4 Pa·sec~10 -3 It has a viscosity of 10 Pa·sec, preferably 10 -10 m 2 / sec~10- 9 m 2 1 / sec and / or preferably a fluid with a thermal conductivity of 0.08 W / m·K to 0.10 W / m·K.

[0029] In contrast, when carbon dioxide fluid in a closed container is in a liquid state, it means that the pressure is higher than atmospheric pressure (0.1 MPa), higher than the vapor pressure curve, and at a temperature lower than the supercritical or subcritical state.

[0030] Since the supercritical state, subcritical state, or liquid state can be changed by controlling the temperature and pressure, the fluid in the closed container can be in a supercritical state, subcritical state, or liquid state during the manufacturing method of the present invention. Thus, for example, in this specification, when it is said that "supercritical carbon dioxide is used," it does not necessarily exclude a subcritical state or a liquid state (especially under high pressure).

[0031] In one embodiment of the present invention, the mixture may contain a core material. The core material is a substance intended to be encapsulated in the resulting CNF capsules (the encapsulated target substance). Examples of core materials include hydrophilic (e.g., water-soluble), hydrophobic (e.g., fat-soluble), and water-insoluble materials. Examples of core materials include active ingredients used in pharmaceuticals, food additives, nutritional supplements, cosmetics, and the like. Suitable hydrophilic materials for the core material include, but are not limited to, phenylalanine, phycocyanin, hyaluronic acid, xanthan gum, gelatin, aspartic acid, arginine, polyethylene glycol, and α-tocopherol, as well as combinations thereof. Suitable hydrophobic materials for the core material include, but are not limited to, phthalocyanine, mesalazine, levofloxacin, cyclodextrin, cyclosporine, carbamazepine, and phenytoin, as well as combinations thereof. Examples of water-insoluble substances suitable as the core material include, but are not limited to, silica particles, metal particles (e.g., metal particles such as iron nanoparticles, copper nanoparticles, and zinc nanoparticles), oils and fats (e.g., salad oil, soybean oil, sesame oil, cocoa butter, and lard), polymer particles (e.g., polymer particles such as polystyrene particles, latex particles, and PLGA (lactic acid-co-glycolic acid) nanoparticles), and pigments (e.g., graphite particles, titanium particles, cobalt particles, disazo yellow particles, and quinacridone red pigments), as well as combinations thereof.

[0032] The amount of core material charged into the closed container can be determined appropriately depending on, for example, the amount of CNF charged, the particle size of the CNF capsules to be produced, and the production volume, but is preferably 0.01 to 3 parts by mass, more preferably 0.1 to 1 part by mass, per 1 part by mass of CNF charged into the closed container. If the amount of core material is less than 0.01 part by mass, the amount of core material that can be encapsulated by the CNF relative to the CNF may be small, making it difficult for the resulting CNF capsules to fully exhibit the various functions possessed by the core material. If the amount of core material charged exceeds 3 parts by mass, the amount of core material may be too great relative to the CNF present in the closed container, and the core material may not be fully encapsulated by the CNF.

[0033] When the mixture is irradiated with ultrasonic waves, examples of the closed container that contains the mixture include an autoclave, a pressure-resistant cell, and a high-pressure cell of a supercritical device.

[0034] In the present invention, for example, when CNF, water, and optionally a core material are charged into a closed container (without adding carbon dioxide fluid), the CNF can be dispersed in water to form a CNF suspension. When carbon dioxide fluid is then added to the container, the CNF can be adsorbed at the interface between water and carbon dioxide in the water-carbon dioxide two-phase system. Then, by irradiating this mixture with ultrasound, the CNF can function as a surfactant in the water-carbon dioxide two-phase system, forming a Pickering emulsion.

[0035] Ultrasonic irradiation can be performed by operating an ultrasonic probe (e.g., an ultrasonic vibrator (horn)) placed in a closed container (e.g., a high-pressure cell of a supercritical device) that generates ultrasonic vibrations at a frequency of, for example, 15 to 400 kHz, preferably 20 kHz. For example, electrical energy amplified to 20 kHz by a solid-state power supply can be converted into longitudinal mechanical vibrations by a converter, and the converted mechanical vibrations can be transmitted to the probe (this is called ultrasonic vibration). The ultrasonic vibrations become pressure waves, causing cavitation. Cavitation can cause problems. Cavitation refers to the continuous formation and decay of countless extremely small bubbles due to a localized pressure drop in a solution (fluid). Ultrasonic irradiation is preferably performed using a horn-type vibrator attached to the inside of a high-pressure cell, but a Lajuvin-type vibrator attached to the outside of the high-pressure cell is also possible. When using an ultrasonic vibrator with a frequency of 20 kHz, 500 W, and an amplitude of 18.3 μm, the ultrasonic irradiation time is preferably 75 to 250 seconds, more preferably 150 to 200 seconds. By keeping the irradiation time within the above range, the efficiency of forming a Pickering emulsion of CNF can be improved.

[0036] Ultrasonic irradiation can be carried out while maintaining the temperature and pressure within the closed container at a level that allows carbon dioxide fluid to exist. The pressure that can be set within the closed container is, for example, 5.0 MPa to 12.0 MPa, preferably 7.0 MPa to 9.0 MPa. By keeping the pressure within this range, the CNF Pickering emulsion can be formed more efficiently. The temperature that can be set within the closed container is, for example, 10°C to 70°C, preferably 30°C to 50°C. By keeping the temperature within this range, the CNF Pickering emulsion can be formed more efficiently.

[0037] It should be noted that ultrasonic irradiation of the mixture does not particularly require the mixture to contain any organic solvent. Rather, considering that the resulting CNF capsules can be used in cosmetics, medical products, or pharmaceutical compositions, it is preferable that the mixture does not contain any organic solvent.

[0038] As described above, a mixture containing cellulose nanofibers, water, and carbon dioxide fluid, and optionally a core substance, is irradiated with ultrasound in a closed container to form a Pickering emulsion.

[0039] In the present invention, the closed vessel is then opened to facilitate encapsulation of the core material by CNF from the Pickering emulsion.

[0040] The closed container is opened by depressurizing the container. When the high-pressure carbon dioxide adjusted for the formation of the Pickering emulsion is released from the closed container, the CNF fibers of the CNF Pickering emulsion maintain a particulate structure in which they are intricately entangled. If a core substance is contained, the CNF capsules are encapsulated to form the core substance, and the CNF capsules are dispersed in the aqueous phase remaining in the closed container. These CNF capsules can be easily removed from the closed container together with the aqueous phase liquid under atmospheric pressure.

[0041] In this way, cellulose nanofiber (CNF) capsules can be produced.

[0042] (Cellulose nanofiber capsule manufacturing equipment) The method for producing CNF capsules of the present invention can be carried out, for example, by an apparatus designed to include a closable container containing a mixture, a means for supplying carbon dioxide fluid to the closable container, a means for irradiating ultrasonic waves into the closable container, and a means for discharging the carbon dioxide fluid from the closable container. For example, an apparatus used in conventional supercritical technology can be applied. A specific example of such an apparatus for producing CNF capsules will be described below.

[0043] FIG. 1 is a schematic diagram showing an example of an apparatus for producing cellulose nanofiber capsules using the method for producing cellulose nanofiber capsules of the present invention.

[0044] The apparatus 100 shown in Figure 1 is composed of a pressure-increasing section A1 for subjecting carbon dioxide to high pressure and a CNF capsule production section A2 for irradiating a mixture containing CNF with ultrasound in a closable container, and the pressure-increasing section A1 and the CNF production section A2 can be separated by a stop valve 142.

[0045] In the pressurization section A1, the carbon dioxide can be pressurized by a liquid carbon dioxide pressurization pump 105. A cylinder 101 is provided to supply carbon dioxide to the pressurization pump 105. A cylinder with a siphon filled with liquid carbon dioxide can be used as a supply source of liquid carbon dioxide.

[0046] A drying tube 102 filled with a desiccant is provided between the cylinder 101 and the boosting pump 105. When the liquid carbon dioxide from the cylinder 101 passes through this drying tube 102, the moisture in the liquid carbon dioxide is removed.

[0047] A cooling unit 103 is provided downstream of the drying tube 102. The cooling unit 103 is filled with, for example, ethylene glycol, and this ethylene glycol is cooled to approximately 260 K. The liquid carbon dioxide, from which moisture has been removed by the desiccant while passing through the drying tube 102, is cooled by the ethylene glycol in the cooling unit 103 and supplied to a boost pump 105.

[0048] A filter 104 is provided between the cooling unit 103 and the boost pump 105. The filter 104 removes impurities such as dust and can prevent impurities from entering the boost pump 105.

[0049] The carbon dioxide that has passed through the filter 104 is supplied to a boost pump 105. A cooler (not shown) can be attached to the head portion of the boost pump 105 to prevent evaporation of the liquid carbon dioxide.

[0050] The pressure increasing section A1 is provided with a pressure regulating valve 141. The pressure regulating valve 141 can set the pressure in the systems of the pressure increasing section A1 and the CNF capsule production section A2 to any desired pressure.

[0051] The pressure boosting section A1 is provided with a pressure gauge 106. The pressure inside the system of the pressure boosting section can be measured by the pressure gauge 106. The pressure gauge 106 is equipped with an upper limit contact output terminal, and can be set to turn off the power to the pressure boosting pump 105 at a specified pressure.

[0052] The supply of carbon dioxide to the CNF capsule production section can be adjusted by a stop valve 142 disposed between the pressure increasing section A1 and the CNF capsule production section A2.

[0053] In addition, a safety valve 107 may be provided between the pressure increasing section A1 and the CNF capsule production section A2 to ensure safety.

[0054] 1, the CNF capsule production unit A2 is installed in a constant temperature water bath 110. The water temperature in the constant temperature water bath 110 is controlled by a temperature controller (not shown) to within ±0.1°C, for example. A temperature measuring unit 116 may be provided to measure the temperature in the constant temperature water bath 110.

[0055] In the manufacturing apparatus 100 shown in FIG. 1, a closable container 111 is placed in a constant-temperature water bath 110. The closable container 111 is, for example, a high-pressure cell, and is preferably both heat-resistant and pressure-resistant. Ultrasonic irradiation is performed in the closable container 11 (closed container) containing CNF, a core material, carbon dioxide fluid, and water. An ultrasonic probe 112, such as an ultrasonic vibrator (horn), is installed inside the closable container 11. Electrical energy amplified to, for example, 20 kHz by an ultrasonic vibration power supply 113 is converted into longitudinal mechanical vibration by a converter (not shown), and this converted mechanical vibration is transmitted to the ultrasonic probe 112 (ultrasonic vibration). The ultrasonic vibration generated by the ultrasonic probe 112 becomes a pressure wave and can be irradiated onto the mixture in the container 111. Ultrasonic irradiation is performed in this manner in the closable container 111 while the container is closed, and a Pickering emulsion can be formed by the CNF adsorbed at the water-carbon dioxide interface.

[0056] Carbon dioxide fluid can be supplied to the closable container 111 as follows. Liquid carbon dioxide supplied from the stop valve 142 can be made into a fluid in the constant temperature water bath 110 before being supplied to the closable container 111. The liquid carbon dioxide supplied from the stop valve 142 is introduced into the closable container 111 via a heater 108, a check valve 109, and a stop valve 143, which are installed in the constant temperature water bath 110. The heater 108 can heat the liquid carbon dioxide to make it into a fluid. The check valve 109 is provided to prevent backflow of the fluid. The stop valve 143 can adjust the supply of carbon dioxide fluid to the closable container 111.

[0057] The closable container 111 is equipped with a pressure gauge 115, which can measure the pressure inside the closable container 111.

[0058] Furthermore, a safety valve 117 is installed downstream of the closable container 111, and the safety valve 117 can prevent an explosion due to a pressure increase inside the closable container 111.

[0059] In the CNF capsule production section A2, after ultrasonic irradiation, the Pickering emulsion formed by CNF adsorbed at the water-carbon dioxide interface is adjusted to atmospheric pressure by reducing the pressure inside the closable container 111 using the pressure control valve 141, and the CNF fibers become intricately entangled to maintain a particulate structure, and if a core substance is contained, the core substance is encapsulated to form CNF capsules, which remain dispersed in the aqueous phase remaining in the container. After reducing the pressure, the carbon dioxide fluid is discharged outside the closable container 111.

[0060] The CNF capsules obtained in this manner have a particle size of, for example, 10 μm to 500 μm, preferably 50 μm to 400 μm, and more preferably 100 μm to 300 μm, although this may depend on the type of CNF and the type of core substance (e.g., hydrophilic or hydrophobic substance). The particle size (particle size) of the CNF capsules can be measured, for example, by dynamic light scattering.

[0061] A filtration process or the like may be further carried out as necessary to adjust the particle size distribution of the CNF capsules to fall within the desired range and to remove impurities and perform sterilization.

[0062] Additionally, the solution containing the CNF capsules may be freeze-dried, which may result in the CNF capsules being in a form suitable for storage until use.

[0063] The manufacturing method of the present invention makes it possible to produce CNF capsules by forming a Pickering emulsion of CNF adsorbed at the water-carbon dioxide interface using only water and carbon dioxide, without using organic solvents that are harmful to living organisms, such as hexane. The CNF capsules obtained in this way do not come into contact with harmful organic solvents during the manufacturing process, so even when used on the human body, there is no risk of residual organic solvents being introduced into the human body. Therefore, CNF capsules using Pickering emulsions that are safe for the human body can be used for a variety of purposes. Furthermore, the present invention utilizes the extremely large interface generated by water and carbon dioxide upon ultrasonic irradiation as the Pickering emulsion formation site, making mass production possible.

[0064] The CNF capsules produced by the production method of the present invention can be used in various fields, such as pharmaceuticals, foods, cosmetics, etc. Such CNF capsules can be used in cosmetics, medical products, pharmaceutical compositions, etc. [Example]

[0065] The present invention will be described below with reference to examples, but the present invention is not limited to these examples. In these examples, a CNF capsule manufacturing apparatus 100 shown in Figure 1 was used.

[0066] (Example 1: Production of CNF microparticles (E1)) First, ultrapure water and a CNF suspension derived from coniferous trees (manufactured by Chuetsu Pulp Industries Co., Ltd.; purity 1.03%) were charged into a 150 mL closable container 111 in the CNF capsule manufacturing apparatus 100 shown in Figure 1. Next, with the temperature of the thermostatic water bath 110 set to a predetermined temperature, 89 g of carbon dioxide (ρ CO2 =0.742) was pumped into the container 111, which was then closed to create a high pressure state (6.8 MPa) inside the container 111. Ultrasonic waves were then irradiated from the ultrasonic probe 112 at a frequency of 20 kHz and an amplitude of 30% (18.3 μm) for 125 seconds. After a CNF Pickering emulsion was formed in the container 111, a pressure reduction operation was performed to open the container 111, and CNF microparticles, which are CNF capsules, were recovered from the container 111 together with the solution.

[0067] The above procedure was carried out using 27 mL of water, 3 mL of CNF suspension water, a temperature of 25°C, and five ultrasonic irradiations (25 seconds each), and it was confirmed that CNF microparticles (E1) were obtained in this manner. The CNF suspension water before being placed in the closable container and the liquid containing CNF microparticles (E1) removed from the closable container after the above production were photographed with a camera, and the particle sizes in the solution were measured with a laser analysis particle size distribution analyzer (SALD-2000, manufactured by Shimadzu Corporation).

[0068] As shown in Figure 2, the CNF suspension (Figure 2(a)) before being placed in the closable container was a liquid in which CNFs were uniformly dispersed, whereas the CNF capsule-containing suspension removed from the closable container after the experiment contained particles corresponding to CNF microparticles (E1) dispersed in a manner clearly different from that shown in Figure 2(a), indicating the presence of CNF capsules in the liquid. The average particle diameter of the CNF microparticles (E1) produced in this example was 180 μm.

[0069] Next, the dispersion containing the CNF microparticles (E1) was ultrasonicated for 5 minutes to completely disaggregate the particles (E1). The particle size distribution and particle concentration of the particles contained in the resulting liquid (E1b) were measured using dynamic light scattering (DLS) with a laser diffraction particle size analyzer (Shimadzu SALD-7500). The results are shown in Figure 3. The average particle diameter of the particles contained in this liquid (E1b) was 121 nm, and the particle concentration (cumulative) was 459 μg / mL.

[0070] As shown in Figure 3, the CNF capsules (CNF microparticles (E1)) produced in this example had an average particle diameter of 180 μm, but this was found to be composed of aggregates (secondary particles) of fine particles (primary particles) that were slightly larger than 100 nm (0.1 μm) and had a relatively narrow particle size distribution.

[0071] (Example 2: Production of CNF capsules (E2) containing hydrophobic particles) First, ultrapure water, a suspension of coniferous CNFs, and brominated copper phthalocyanine (hydrophobic particles) were charged into a 150 mL volume closable container 111 in the CNF capsule manufacturing apparatus 100. Next, with the temperature of the thermostatic water bath 110 set to a predetermined temperature, 89 g of carbon dioxide (ρ CO2=0.742) was pumped into the container 111, creating a high pressure state (6.8 MPa) inside the container 111. Then, ultrasonic waves were irradiated from the ultrasonic probe 112 at a frequency of 20 kHz and an amplitude of 30% (18.3 μm) for 125 seconds. After a Pickering emulsion of CNF was formed inside the container 111, the pressure was reduced to open the container 111, and the CNF capsules were recovered from the container 111 together with the solution.

[0072] The above procedure was carried out using 27 mL of water, 3 mL of CNF suspension, 0.01 g of brominated copper phthalocyanine, at a temperature of 25°C, with five ultrasonic irradiations (25 seconds per time). The obtained CNF capsules (E2) containing brominated copper phthalocyanine were confirmed. Images of the CNF suspension containing brominated copper phthalocyanine before being placed in a closable container and the liquid containing the brominated copper phthalocyanine-encapsulating CNF capsules removed from the container after the experiment were each taken with a camera, and the particle diameter in the solution was measured in the same manner as in Example 1. The morphology of the CNF capsules containing brominated copper phthalocyanine was also measured with a 3D measuring laser microscope (OLS4100, manufactured by Olympus Corporation).

[0073] As shown in Figure 4, the CNF suspension containing brominated copper phthalocyanine (Figure 4(a)) before being placed in the closable container was a liquid in which CNFs were uniformly dispersed (here, in Figure 4(a), brominated copper phthalocyanine, a hydrophobic particle, was placed on the liquid). However, in the CNF capsules containing brominated copper phthalocyanine removed from the closable container after the experiment, blue-green CNF capsules (E2) due to brominated copper phthalocyanine were dispersed in a manner clearly different from that shown in Figure 4(a), and CNF capsules were generated in the liquid (Figure 4(b)). The average particle diameter of the CNF microparticles (E2) produced in this example was 200 μm. Furthermore, as shown in Figure 5, when observed with a 3D measuring laser microscope, the CNF capsules (E2) produced in this example were fine particles of brominated copper phthalocyanine surrounded by CNF.

[0074] Next, the dispersion containing the CNF microparticles (E2) was ultrasonicated for 5 minutes to completely disaggregate the particles (E2). The particle size distribution and particle concentration of the particles contained in the resulting liquid (E2b) were measured using dynamic light scattering (DLS) with a laser diffraction particle size analyzer (Shimadzu SALD-7500). The results are shown in Figure 6. The average particle diameter of the particles contained in this liquid (E2b) was 144 nm, and the particle concentration (cumulative) was 549 μg / mL.

[0075] As shown in Figure 6, the CNF capsules (CNF microparticles (E2)) produced in this example had an average particle diameter of 200 μm, but this was found to be composed of aggregates (secondary particles) of fine particles (primary particles) that were slightly larger than 100 nm (0.1 μm) and had a relatively narrow particle size distribution.

[0076] (Example 3: Production of CNF capsules (E3) containing hydrophilic particles) First, ultrapure water, a CNF suspension derived from coniferous trees, and phycocyanin (hydrophilic particles) were charged into a 150 mL closable container 111 in the CNF capsule manufacturing apparatus 100. Next, with the temperature of the thermostatic water bath 110 set to a predetermined temperature, 89 g of carbon dioxide (ρ CO2 =0.742) was pumped into the container 111, creating a high pressure state (6.8 MPa) inside the container 111. Then, ultrasonic waves were irradiated from the ultrasonic probe 112 at a frequency of 20 kHz and an amplitude of 30% (18.3 μm) for 125 seconds. After a CNF Pickering emulsion was formed inside the container 111, the pressure was reduced to open the container 111, and the CNF capsules were recovered from the container 111 together with the solution.

[0077] The above procedure was carried out using 27 mL of water, 3 mL of CNF suspension, 0.01 g of phycocyanin, a temperature of 25°C, and five ultrasonic irradiations (25 seconds per irradiation). The resulting CNF capsules (E3) containing phycocyanin were confirmed. Images of the CNF suspension containing phycocyanin before being placed in a closable container and the liquid containing the phycocyanin-containing CNF capsules (E3) removed from the container after the experiment were taken with a camera, and the particle diameters in the solution were measured in the same manner as in Example 1. The morphology of the CNF capsules containing phycocyanin was also measured with a 3D measuring laser microscope (OLS4100, manufactured by Olympus Corporation).

[0078] As shown in Figure 7, the CNF suspension containing phycocyanin (Figure 7(a)) before being placed in the closable container was a light blue liquid in which CNF and phycocyanin were uniformly dispersed. However, in the CNF capsules containing phycocyanin removed from the closable container after the experiment, CNF capsules (E3) were dispersed in a manner clearly different from that shown in Figure 7(a), and CNF capsules were generated in the liquid (Figure 7(b)). The average particle diameter of the CNF microparticles (E3) produced in this example was 200 μm. Furthermore, as shown in Figure 8, when observed with a 3D measuring laser microscope, the CNF capsules (E3) produced in this example were composed of fine particles of phycocyanin surrounded by CNF. [Industrial Applicability]

[0079] The present invention is useful, for example, in the fields of pharmaceuticals, food and cosmetics. [Explanation of symbols]

[0080] 100 Manufacturing equipment 101 Cylinder 102 Drying tube 103 Cooling Unit 104 filters 105 Booster pump 105 106 Pressure Gauge 107 Safety valve 108 Heater 109 Check valve 110 Constant Temperature Water Bath 111 Closable containers 112 Ultrasound probe 115 Pressure Gauge 116 Temperature measuring unit 117 Safety valve 141 Pressure Regulating Valve 142,143 Stop valve

Claims

1. A method for producing cellulose nanofiber capsules, comprising: A step of irradiating a mixture containing cellulose nanofibers, water, and carbon dioxide fluid with ultrasound in a closed container to form a Pickering emulsion; Opening the closed container to promote encapsulation of the Pickering emulsion by the cellulose nanofibers; The method includes:

2. 10. The method of claim 1, wherein the cellulose nanofibers comprise cellulose nanofibers physically defibrated from plant material.

3. The method of claim 1 or 2, wherein the mixture further comprises a core material.

4. The method of claim 3 , wherein the core material is a hydrophilic material, a hydrophobic material, or a water-insoluble material.

5. 5. The method of claim 1, wherein the mixture does not contain an organic solvent.

6. The method according to any one of claims 1 to 5, wherein the ultrasonic irradiation is carried out by directly irradiating the mixture with ultrasonic waves from an ultrasonic probe disposed within the closed container.

Images