WO2011024959A1 - Method for preparing microcapsules - Google Patents

Method for preparing microcapsules Download PDF

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Publication number
WO2011024959A1
WO2011024959A1 PCT/JP2010/064619 JP2010064619W WO2011024959A1 WO 2011024959 A1 WO2011024959 A1 WO 2011024959A1 JP 2010064619 W JP2010064619 W JP 2010064619W WO 2011024959 A1 WO2011024959 A1 WO 2011024959A1
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WIPO (PCT)
Prior art keywords
fluid
mist
gas
liquid
microcapsule
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PCT/JP2010/064619
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French (fr)
Japanese (ja)
Inventor
紀彦 土本
正司 河守
正明 大川原
龍信 小山
Original Assignee
サッポロビール株式会社
大川原化工機株式会社
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Application filed by サッポロビール株式会社, 大川原化工機株式会社 filed Critical サッポロビール株式会社
Priority to JP2011528872A priority Critical patent/JP5501367B2/en
Publication of WO2011024959A1 publication Critical patent/WO2011024959A1/en

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
    • B01J13/02—Making microcapsules or microballoons
    • B01J13/04—Making microcapsules or microballoons by physical processes, e.g. drying, spraying
    • B01J13/046—Making microcapsules or microballoons by physical processes, e.g. drying, spraying combined with gelification or coagulation
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00—Shaping or working of foodstuffs characterised by the products
    • A23P10/30—Encapsulation of particles, e.g. foodstuff additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5015—Organic compounds, e.g. fats, sugars
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5089—Processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
    • B01J13/02—Making microcapsules or microballoons
    • B01J13/04—Making microcapsules or microballoons by physical processes, e.g. drying, spraying
    • B01J13/043—Drying and spraying

Definitions

  • the present invention relates to a method for producing microcapsules. More specifically, the present invention relates to a method for producing a microcapsule that can obtain a microcapsule having a sufficiently small average particle diameter and that has a high recovery rate in a small space.
  • a substance having physiological activity is ingested by taking fine particles (microcapsules) encapsulating a physiologically active substance (fat-soluble substance) with alginic acid. ing. And as a method of manufacturing this microcapsule, for example, an aqueous solution containing a physiologically active substance is sprayed in a conical shape from two nozzles, and the mist-like aqueous solution is brought into contact with each other to be gelled.
  • a physiologically active substance fat-soluble substance
  • alginic acid alginic acid
  • an aqueous solution containing a physiologically active substance is sprayed from one nozzle to obtain a mist-like first fluid containing droplets having a predetermined particle diameter, and an aqueous solution containing a gelling agent is supplied from the other nozzle.
  • the mist-like first fluid and the mist-like second fluid are A method for obtaining gelled microcapsules by bringing them into contact with each other is known (see, for example, Patent Document 2).
  • the present invention has been made to solve the above-described problems of the prior art, and it is possible to obtain a microcapsule having a sufficiently small particle diameter, and manufacturing a microcapsule having a small space and a high recovery rate.
  • a method is provided.
  • the present invention provides the following microcapsule production method.
  • a thin film-like first mist-like fluid containing a first droplet containing a gel-forming substance and a fat-soluble substance, and a thin-film second containing a second drop containing a gelling agent A method for producing a microcapsule, in which a mist fluid is caused to collide with each other so as to cross each other in a gas phase to obtain a microcapsule having an average particle size of 100 ⁇ m or less.
  • a first gas channel having a first gas supply port, a first liquid channel having a first liquid supply port, the first gas channel and the first liquid channel Are combined to form a first mist fluid passage forming a first injection port composed of an annular slit, a second gas flow path having a second gas supply port, and a second liquid supply
  • a microcapsule wherein the second injection port is a nozzle formed in a region surrounded by the first injection port, wherein the first injection From the mouth, either the first mist fluid or the second mist fluid is jetted and the second jet port The first mist fluid or the second mist fluid is jetted to cross the first mist fluid and the second mist fluid in the gas phase.
  • the method for producing a microcapsule of the present invention can obtain a microcapsule having a sufficiently small particle diameter, and has a high recovery rate in a small space (that is, a microcapsule in a small space (with a small facility (apparatus)).
  • the microcapsules can be manufactured and the microcapsule recovery rate is high).
  • FIG. 1 It is a perspective view which shows the nozzle of the manufacturing apparatus which can be used for the manufacturing method of the microcapsule of this invention. It is sectional drawing which shows the front-end
  • One embodiment of the method for producing a microcapsule of the present invention includes a first mist-like fluid in the form of a thin film including first droplets containing a gel-forming substance and a fat-soluble substance, and a second containing a gelling agent.
  • a first mist-like fluid in the form of a thin film including first droplets containing a gel-forming substance and a fat-soluble substance, and a second containing a gelling agent.
  • microcapsules having an average particle diameter of 100 ⁇ m or less are obtained by colliding with a thin film-like second mist-like fluid containing the above-mentioned droplets so as to cross each other in the gas phase.
  • the production method of the present invention is a method for obtaining “microcapsules having an average particle size of 100 ⁇ m or less”, and within the scope of the present invention, as long as microcapsules having an average particle size of 100 ⁇ m or less can be obtained by the above method. In practice, however, microcapsules having an average particle size of 10 to 100 ⁇ m can be obtained due to the convenience of the apparatus and the like. In this specification, the “average particle size” means “volume average particle size”.
  • the microcapsules are fine particles in which a fat-soluble substance such as tocopherol is encapsulated with a gel-forming substance such as alginic acid.
  • the “collision” in the present invention is to bring the first droplet and the second droplet into contact at a predetermined speed or more, specifically, 80 m / second or more, more preferably 100 m / second or more, More preferably, the first droplet and the second droplet are respectively ejected at a speed of 120 m / second or more and are brought into contact with each other while maintaining the speed.
  • the first droplet and the second droplet are temporarily maintained while maintaining the momentum of the collision. Are then mixed and then re-split by the momentum of the collision, so that it is possible to effectively prevent the average particle size from becoming large and to obtain microcapsules having a sufficiently small particle size.
  • the total mass A is the total mass of the solid content of “microcapsules with an average particle diameter of 100 ⁇ m or less” obtained by producing “microcapsules with an average particle diameter of 100 ⁇ m or less” for a predetermined time and drying.
  • the total mass B is the total mass of the solid content of the first droplet obtained by ejecting the first droplet for the same time as the predetermined time and then drying the ejected first droplet. .
  • either the first or second mist fluid is suspended in the space as in the conventional manufacturing method (see Patent Documents 1 and 2). Is no longer necessary. Since the space for floating is no longer necessary, the microcapsules can be manufactured in a small space (that is, the space required for manufacturing the microcapsules (specifically, the size of the equipment (device) is reduced)). .
  • the first mist fluid is a thin film containing a first droplet containing a gel-forming substance and a fat-soluble substance.
  • the first mist fluid is a mist fluid in which the first droplet is dispersed in a gas such as air, and is formed by being ejected so as to form a thin film.
  • the gel-forming substance contained in the first droplet is a compound that gels by reacting with a gelling agent such as an inorganic salt or an acid.
  • a gelling agent such as an inorganic salt or an acid.
  • the gel-forming substance include water-soluble alginic acid derivatives, Examples include low methoxyl pectin, gelatin, xanthan gum, deacylated gellan gum, carboxymethyl cellulose, water-soluble cellulose derivatives, ⁇ -carrageenan, ⁇ -carrageenan, nylon, and polyethylene glycol.
  • a water-soluble alginic acid derivative and low methoxyl pectin are preferable from the viewpoint that gelation can be performed instantaneously (formation of a gel).
  • water-soluble alginic acid derivatives include alginic acid, sodium alginate, potassium alginate, and ammonium alginate.
  • the viscosity of the gel-forming substance at 25 ° C. is preferably 5 to 1000 mPa ⁇ s, more preferably 10 to 500 mPa ⁇ s, and particularly preferably 20 to 300 mPa ⁇ s.
  • the viscosity of the gel-forming substance is less than 5 mPa ⁇ s, the formed gel is weak (that is, a gel with sufficient hardness cannot be obtained), and it may be difficult to obtain a microcapsule having a good shape. There is. On the other hand, if it exceeds 1000 mPa ⁇ s, it may be difficult to obtain microcapsules having a sufficiently small average particle diameter (100 ⁇ m or less).
  • Examples of the fat-soluble substance contained in the first droplet include substances having physiological activity when taken by oral administration, and specifically include coenzymes Q such as ubiquinone, retinol, retinoin.
  • Vitamin A such as acid, retinoid and carotene
  • vitamin D such as cholecalciferol and ergocalciferol
  • vitamin E such as tocopherol, tocopherol acetate, tocopherol succinate, tocopherol nicotinate and tocotrienol
  • vitamins such as phytonadione and menatetrenone
  • Examples include fats and oils such as Ks, DHA, and EPA, sterols such as phytosterols (plant sterols) and yeast sterols, astaxanthin, zeaxanthin, and fucoxanthin.
  • the microcapsule obtained by the method for producing a microcapsule of the present invention contains a fat-soluble substance (substance having physiological activity) in its small particles
  • the fat-soluble substance can be obtained by taking the microcapsule. Can be taken.
  • the first droplet can contain other components (1).
  • other component (1) an emulsifier, an absorption promoter, protein, saccharides, a fragrance
  • the emulsifier is not particularly limited as long as it is used for pharmaceuticals and foods.
  • monoglycerol fatty acid organic acid ester glycerol acetate fatty acid ester, glycerol lactate fatty acid ester, glycerol succinate fatty acid ester, glycerol diacetyl List tartaric acid fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sucrose acetate isobutyric acid ester, sorbitan fatty acid ester, polyglycerin condensed ricinoleic acid ester, propylene glycol fatty acid ester, calcium stearoyl lactate, sodium stearoyl lactate, lecithin, etc. Can do.
  • absorption promoters examples include vegetable oils such as sesame oil, soybean oil, camellia oil, olive oil, coconut oil, palm oil, rapeseed oil, fallen raw oil, cottonseed oil, safflower oil, fish oil, beef tallow, pork fat, etc. Animal fats and oils, fatty acid triglycerides and the like.
  • the content ratio of the fat-soluble substance in the first droplet is not particularly limited, but is preferably 0.5 to 50% by mass with respect to the total amount of the first droplet of 100% by mass.
  • the content is more preferably 0 to 40% by mass, and particularly preferably 1.5 to 30% by mass.
  • the content ratio of the fat-soluble substance is less than 0.5% by mass, the fat-soluble substance to be contained in the microcapsule may not be a sufficient amount.
  • the fat-soluble substance cannot be emulsified in the gel-forming substance (that is, if there are more fat-soluble substances than the gel-forming substance (water-soluble substance), the oil-in-water type (O / W) Since an emulsified state of the structure is not formed and a water-in-oil (W / O) structure is formed, the fat-soluble substance cannot be wrapped with a gel), and it may be difficult to form microcapsules.
  • the thickness of the thin film at the time of jetting the first mist fluid is preferably 5 to 45 ⁇ m, more preferably 6 to 40 ⁇ m, and particularly preferably 10 to 35 ⁇ m. If the thickness is less than 5 ⁇ m, the gas-liquid ratio, which will be described later, increases, so the chance of collision between the first mist fluid and the second mist fluid is reduced, and the microcapsule recovery rate is not sufficient. There is a fear. On the other hand, when it exceeds 45 ⁇ m, the gas-liquid ratio becomes low, so when the first mist fluid (first droplet) collides with the second mist fluid (second droplet), There is a possibility that the average particle diameter of the obtained microcapsules becomes large due to the aggregation with the adjacent droplets again.
  • thin film shape means that when the atomized fluid is cut on a plane orthogonal to the spraying direction of the atomized fluid, the thickness of the section of the atomized fluid is thin.
  • the shape is not particularly limited. For example, it may be flat (film-like) or cylindrical, such as cylindrical, rectangular, or megaphone (cylinder that gradually expands from one to the other).
  • the method for measuring the thickness of the thin film will be described below by taking the first mist fluid as an example.
  • the flow rate (thin film flow rate) of the first mist fluid injected from the injection port is 1/50 of the compressed gas flow rate.
  • the thin film flow velocity [m / s] of the first mist fluid in which the first droplet and the compressed air are mixed is calculated.
  • a value [m 2 / s] obtained by adding the circumferential length of the injection port to the calculated thin film flow velocity [m / s] is calculated, and the first droplet of the first droplet is calculated with this value [m 2 / s].
  • the thickness of the second mist fluid thin film is also measured by the same method as the thickness of the first mist fluid thin film.
  • the gas-liquid ratio of the first mist fluid is preferably 4.0 ⁇ 10 2 to 1.1 ⁇ 10 4 m 3 / m 3 , and 7.5 ⁇ 10 2 to 5.5 ⁇ 10 3 m. 3 / m 3 is more preferable, and 1.0 ⁇ 10 3 to 3.5 ⁇ 10 3 m 3 / m 3 is particularly preferable.
  • the gas-liquid ratio is less than 4.0 ⁇ 10 2 m 3 / m 3 , the first mist fluid (first droplet) and the second mist fluid (second droplet) are Before the collision, adjacent droplets may aggregate to increase the average particle size of the microcapsules.
  • the “gas-liquid ratio” means the volume ratio (gas (m 3 ) / liquid (m 3 )) of the gas constituting the first mist fluid and the first droplet.
  • the viscosity at 25 ° C. of an emulsion obtained by dispersing a fat-soluble substance in a gel-forming substance is preferably 5 to 1000 mPa ⁇ s, and 10 to 500 mPa ⁇ s. More preferably, it is particularly preferably 20 to 300 mPa ⁇ s.
  • the viscosity of the emulsion is less than 5 mPa ⁇ s, the gel formed is weak (that is, a gel with sufficient hardness cannot be obtained), and it may be difficult to obtain a microcapsule having a good shape. is there.
  • microcapsules having an extremely small average particle size for example, an average particle size of about 10 to 30 ⁇ m
  • the first mist fluid in the form of a thin film can be formed by appropriately adopting a conventionally known method.
  • an emulsion is supplied at a flow rate of 0.01 to 0.06 m 3 / hour and compressed. After the emulsion is atomized by injecting air at a flow rate of 25 to 100 m 3 / hour and a pressure of 0.05 to 0.5 MPa, it is slit-shaped with an opening width of 0.2 to 1.5 ⁇ m, which will be described later. It can be formed by being injected from an injection port.
  • the opening width of the injection port is preferably 0.2 to 1.5 mm, more preferably 0.3 to 1.0 mm, and particularly preferably 0.4 to 0.8 mm. By setting it as the said range, a thin film-like fluid can be obtained effectively. If the opening width is less than 0.2 mm, the fluid film becomes too thin, and the recovery rate may decrease. On the other hand, if it exceeds 1.5 mm, the fluid becomes too thick and the average particle size of the resulting microcapsules may be increased.
  • the symbol “a” illustrated in FIG. 2 indicates the opening width of the injection port (the opening width a of the first injection port).
  • the opening shape of the first mist-like fluid injection port is not particularly limited as long as a thin film fluid can be formed, and examples thereof include a substantially annular shape and a substantially rectangular shape.
  • the emulsion can be obtained by treating a mixture of a gel-forming substance and a fat-soluble substance with a homomixer, a homogenizer, a high-pressure homogenizer, a polytron or the like.
  • This emulsion contains emulsion particles composed of a mixture of a gel-forming substance and a fat-soluble substance, and the average particle size of the emulsion particles in the emulsion is preferably 20 ⁇ m or less, more preferably 10 ⁇ m or less, 5 ⁇ m or less is more preferable. If the average particle diameter of the emulsified particles is more than 20 ⁇ m, the average particle diameter of the resulting microcapsules may be increased (close to 100 ⁇ m). In the present specification, the average particle diameter of the emulsified particles is a volume average particle diameter measured using a laser diffraction / scattering particle size distribution meter.
  • the second mist fluid is a thin film containing second droplets containing a gelling agent. Similar to the first mist fluid described above, the second mist fluid is a mist fluid in which second droplets are dispersed in a gas such as air. It is formed by injecting fluid to form a thin film.
  • the gelling agent contained in the second droplet has an action of gelling the first droplet.
  • the gelling agent include inorganic salts and acids.
  • a water-soluble alginic acid derivative or low methoxyl pectin is used as the gel forming substance, it is preferable to use calcium chloride, magnesium chloride, barium chloride, calcium lactate, calcium sulfate, or the like. Among these, those containing calcium ions are preferable.
  • the solution containing calcium ions is preferably an aqueous calcium chloride solution, an aqueous calcium lactate solution, or an aqueous calcium sulfate solution from the viewpoint that gelation can be instantaneously performed. From the viewpoint that ions are easily released, an aqueous calcium chloride solution is preferred.
  • the concentration of calcium ions in the solution containing calcium ions is preferably 0.5 to 20% by mass, and more preferably 1 to 10% by mass. If the calcium ion concentration is less than 0.5% by mass, gelation tends to be difficult. On the other hand, if it exceeds 20% by mass, the cost tends to increase.
  • the second droplet can contain other component (2) in addition to the gelling agent.
  • other components include proteins, carbohydrates, dietary fibers, lipids, and fragrances.
  • the content ratio of the gelling agent in the aqueous solution containing the gelling agent is not particularly limited, but is 0.1% with respect to 100% by mass of the total amount of the aqueous solution. It is preferably from ⁇ 30 mass%, more preferably from 0.5 to 20 mass%, particularly preferably from 1 to 10 mass%.
  • aqueous solution is not particularly limited, but is 0.1% with respect to 100% by mass of the total amount of the aqueous solution. It is preferably from ⁇ 30 mass%, more preferably from 0.5 to 20 mass%, particularly preferably from 1 to 10 mass%.
  • the speed (curing) from immediately after the first droplet collides with the second droplet of the second mist-like fluid to gelation (Speed) becomes slow, and it may be difficult to obtain microcapsules having a good shape.
  • microcapsules having a very small average particle size for example, an average particle size of about 10 to 30 ⁇ m
  • the thickness of the thin film when the second mist fluid is jetted is preferably 5 to 45 ⁇ m, more preferably 6 to 40 ⁇ m, and particularly preferably 10 to 35 ⁇ m. If the thickness is less than 5 ⁇ m, the gas-liquid ratio increases, so the chance of collision between the first mist fluid and the second mist fluid is reduced, and the microcapsule recovery rate may not be sufficient. is there. On the other hand, when it exceeds 45 ⁇ m, the gas-liquid ratio becomes low, so when the first mist fluid (first droplet) collides with the second mist fluid (second droplet), There is a risk that the average particle diameter becomes large by aggregating again with adjacent droplets.
  • the gas-liquid ratio of the second mist fluid is preferably 4.0 ⁇ 10 2 to 1.1 ⁇ 10 4 m 3 / m 3 , and 7.5 ⁇ 10 2 to 5.5 ⁇ 10 3 m. 3 / m 3 is more preferable, and 1.0 ⁇ 10 3 to 3.5 ⁇ 10 3 m 3 / m 3 is particularly preferable. If the gas-liquid ratio is less than 4.0 ⁇ 10 2 m 3 / m 3 , the particle size of the microcapsules may increase. On the other hand, if it exceeds 1.1 ⁇ 10 4 m 3 / m 3 , the microcapsule recovery rate and production efficiency may not be sufficient.
  • the thin film-like second mist fluid can be formed by appropriately adopting a conventionally known method.
  • an aqueous solution containing a gelling agent is flowed at a flow rate of 0.01 to 0.06 m 3 / hour.
  • the aqueous solution was atomized by supplying and jetting compressed air at a flow rate of 25 to 100 m 3 / hour and a pressure of 0.05 to 0.5 MPa. It can be formed by spraying from a slit-shaped spray port of 2 to 1.5 mm.
  • the opening width of the injection port is preferably 0.2 to 1.5 mm, more preferably 0.3 to 1.0 mm, and particularly preferably 0.4 to 0.8 mm. By setting it as the said range, a thin film-like fluid can be obtained effectively. If the opening width is less than 0.2 mm, the fluid film becomes too thin, and the recovery rate may decrease. On the other hand, if it exceeds 1.5 mm, the thickness of the fluid becomes too thick, the possibility of colliding with the first mist fluid (first droplet) decreases, and the recovery rate may decrease.
  • the symbol “b” illustrated in FIG. 2 indicates the opening width of the injection port (opening width b of the second injection port).
  • the opening shape of the second mist fluid injection port is not particularly limited as long as a thin film fluid can be formed, and may be the same shape as the first mist fluid injection port described above. it can.
  • the first mist fluid and the second mist fluid are such that each first droplet constituting the first mist fluid is each second droplet constituting the second mist fluid. It is preferable to be injected so as to collide.
  • the gas phase for causing the first mist fluid and the second mist fluid to collide with each other is not particularly limited, and can be, for example, air, nitrogen, oxygen, carbon dioxide, helium, or the like.
  • the microcapsule manufacturing method of the present invention includes a first gas flow path having a first gas supply port, a first liquid flow path having a first liquid supply port, and a first gas flow path. And a first gas flow path having a first gas flow path formed by joining the first liquid flow path and forming a first injection port composed of an annular slit, and a second gas supply port And a second liquid channel having a second liquid supply port, a second gas channel, and a second liquid channel are joined together to form a second injection port composed of an annular slit A second mist fluid path, and a second injection port is formed in a region surrounded by the first injection port, from the first injection port to the first Either the mist-like fluid or the second mist-like fluid is injected, and the first mist-like fluid or the second mist-like flow is discharged from the second injection port.
  • microcapsule having an average particle size of 100 ⁇ m or less is obtained. It is preferable. According to such a method, since the microcapsule can be manufactured with only one nozzle, there is an advantage that the manufacturing of the microcapsule becomes easy (the space occupied by the manufacturing facility can be reduced). Further, since the first mist fluid and the second mist fluid can be efficiently collided, there is an advantage that the recovery rate of the microcapsules is improved. Furthermore, microcapsules can be produced with good production efficiency (g / hour).
  • the first gas channel 26 having the first gas supply port 51 and the first liquid channel having the first liquid supply port 52 are used as the nozzle.
  • the second gas channel 28 having the second gas supply port 53, the second liquid channel 29 having the second liquid supply port 54, the second gas channel 28 and the second gas channel 28 And a second mist-like fluid path 36 that is formed by joining the liquid flow path 29 and forms an annular slit-shaped second injection port 14b.
  • FIG. 1 is a perspective view showing a nozzle of a manufacturing apparatus that can be used in the method of manufacturing a microcapsule of the present invention
  • FIG. 2 is a cross-sectional view showing a tip portion of the nozzle of FIG. Specifically, FIG. 2 is a cross-sectional view of the tip when the nozzle of FIG. 1 is cut parallel to the central axis of the nozzle.
  • the nozzle 100 shown in FIG. 1 and FIG. 2 is inserted and arranged on a cylindrical outer cap 41 that forms an outer appearance, and an inner end surface of the outer cap 41, and between the inner end surface of the outer cap 41.
  • An annular ring is inserted between the outer core 42 forming the first slit-shaped gas flow path 26 a in the form of an annular slit and the inner side surface of the outer core 42.
  • An annular slit-shaped first is formed between the outer frame 43 forming the slit-shaped first slit-shaped liquid flow path 27a and the inner surface of the outer frame 43 at the front end inner surface.
  • An annular slit-shaped second core is formed between the inner core 44 forming the second slit-shaped liquid flow path 29a and the inner side surface of the inner core 44.
  • Slit gas flow path 28a An inner frame 45 which forms, with a, are those cylindrical as a whole, on one end face portion, the first injection port 14a and a second injection port 14b is formed.
  • the first slit-shaped gas flow path 26a is a part of the first gas flow path 26
  • the first slit-shaped liquid flow path 27a is a part of the first liquid flow path 27,
  • the slit-shaped gas flow path 28 a is a part of the second gas flow path 28, and the second slit-shaped liquid flow path 29 a is a part of the second liquid flow path 29.
  • Examples of such a nozzle 100 include model numbers “TJ-100”, model numbers “TJ-1000”, and model numbers “TJ-50” manufactured by Okawara Chemical Co., Ltd.
  • the fluid 31b is ejected. More specifically, an emulsified liquid 21 containing a gel-forming substance and a fat-soluble substance supplied from the first liquid channel 27, and a gas (first compressed air 23) supplied from the first gas channel 26 , The first mist fluid 31a is ejected from the first ejection port 14a as an annular thin film. At this time, the smooth surface 35a formed in the first mist-like fluid path 35 makes the first mist-like fluid 31a well in a thin film shape.
  • the aqueous solution 22 containing the gelling agent supplied from the second liquid channel 29 and the gas (second compressed air 24) supplied from the second gas channel 28 are gas-liquid mixed.
  • the second mist fluid 31b is ejected from the second ejection port 14b as an annular thin film. At this time, the second mist fluid 31b is favorably formed into a thin film by the smooth surface 36a formed in the second mist fluid passage 36.
  • first mist fluid 31a and the second mist fluid 31b are caused to collide with each other so as to cross each other in the gas phase. More specifically, the first mist fluid 31a injected from the first injection port 14a moves by the distance L1, and the second mist fluid 31b injected from the second injection port 14b is They have moved by L2 and collided so as to intersect at right angles at a collision position 60 in the atmosphere.
  • the first mist fluid 31a and the second mist fluid 31b join together after collision to form one fluid (synthetic fluid 32).
  • the synthetic fluid 32 proceeds in a direction (compositing direction) in which the traveling direction of the first mist fluid 31a and the traveling direction of the second mist fluid 31b are combined.
  • the synthetic fluid 32 large turbulence and vortices are generated, and the large turbulence and vortices cause the first droplet and the second mist fluid 31b included in the first mist fluid 31a.
  • the resulting second droplet collides, and microcapsules having an average particle diameter of 100 ⁇ m or less can be obtained.
  • the synthetic fluid 32 is formed in an umbrella shape from the tip of the nozzle. In other words, as shown in FIG.
  • the synthetic fluid 32 is formed in a square shape when cut in parallel to the central axis of the nozzle shown in FIG.
  • the direction in which the synthetic fluid 32 travels is determined by the difference in the amount of the first mist fluid 31a and the second mist fluid 31b.
  • collision so as to intersect is set such that the first mist fluid injection direction extension line and the second mist fluid injection direction extension line intersect each other, It means that the first droplet in the first mist fluid and the second droplet in the second mist fluid collide with each other when the formed thin film fluids intersect each other. .
  • the first mist fluid and the second mist fluid collide so that the predetermined row of the mist fluid and the predetermined row of the thin film-like second mist fluid intersect at a predetermined position. means. Therefore, for example, it does not mean that only a predetermined row (a predetermined row group) of the thin film-like first mist fluid intersects the thin film-like second mist fluid at a predetermined position.
  • volume average particle diameter ( ⁇ m) The volume average particle size was measured using a particle size distribution measuring device (“SALD-2200” manufactured by Shimadzu Corporation).
  • the first droplet was ejected at the same time as the predetermined time (the production time of the microcapsule), and the ejected first droplet was dried at 105 ° C. for 6 hours.
  • the total mass B of the solid content (dried product) was measured. Thereafter, the recovery rate (%) was calculated by the following formula.
  • Recovery rate (%) (total mass A / total mass B) ⁇ 100
  • Example 1 First, sodium alginate (“Duck Algin NSPM” manufactured by Food Chemifa Co., Ltd.) 1.5 kg as a gel-forming substance and vitamin E (“Emix-D” manufactured by Eisai Food Chemical Co., Ltd.) as a fat-soluble substance 0 kg and 1.2 kg of polyglycerester (Mitsubishi Chemical Foods, "Ryoto polyglycerester P-8D") as an emulsifier were charged into 144.3 kg of ion-exchanged water and homomixer (Micro Corporation) An emulsion was prepared by mixing using “Hiscotron” manufactured by Tech Nichion.
  • the emulsified liquid is supplied to the first liquid supply port of the nozzle (manufactured by Okawara Kako Co., Ltd., model number “TJ-100”), and the flow rate (“liquid flow rate (m 3 / Time) ”) was discharged from the first liquid channel at 0.0525 m 3 / hour.
  • compressed air from the first gas flow path has a flow rate (referred to as “air flow rate (m 3 / hour)” in Table 1), 27 m 3 / hour, pressure (referred to as “air pressure (MPa)” in Table 1). It was discharged at 0.05 MPa.
  • the gas-liquid ratio in the first atomized fluid at this time is 514 m 3 / m 3
  • the injection speed was 153.9m / s.
  • the injection speed is the speed at the first injection port. The injection speed was calculated by correcting the pressure of the flow meter and dividing by the area of the injection port.
  • the second liquid supply port of the nozzle by supplying the aqueous solution, (in Table 1, referred to as "liquid flow rate (m 3 / hour)”) flow rate 0.0545m 3 / time, the second Drained from the liquid flow path.
  • the compressed air from the second gas flow path has a flow rate (denoted as “air flow rate (m 3 / hour)” in Table 1) 27 m 3 / hour, pressure (in Table 1, “air pressure (MPa)”. It was discharged at 0.05 MPa. And these were gas-liquid mixed, and the thin film-like 2nd mist-like fluid was injected from the 2nd injection port of the said nozzle.
  • the gas-liquid ratio of the second atomized fluid at this time is 495m 3 / m 3, the injection speed was 153.9m / s.
  • the injection speed is the speed at the second injection port.
  • the microcapsule was manufactured by crossing the thin film-like first mist-like fluid ejected from the nozzle and the thin-film-like second mist-like fluid.
  • the spraying time was 20 minutes.
  • Example 2 A microcapsule was obtained in the same manner as in Example 1 except that the conditions shown in Table 1 were used using the substances shown in Table 1 (gel-forming substance, fat-soluble substance, and gelling agent). It was. Each evaluation mentioned above was performed about the obtained microcapsule. The evaluation results are shown in Table 1.
  • Example 7 An aqueous calcium chloride solution was prepared in the same manner as in Example 1. Then, this calcium chloride aqueous solution was adjusted to pH 4.0 with citric acid (Wako Pure Chemical Industries, Ltd.). A microcapsule was obtained in the same manner as in Example 1 except that the solution thus prepared was used as an aqueous solution. Each evaluation mentioned above was performed about the obtained microcapsule. The evaluation results are shown in Table 1. In Table 1, “UNIPECTINE LMSN325 CITRUS” manufactured by Unitech Foods Co., Ltd. was used as “low methoxyl pectin”, and “SATIAGEL KHG30T” manufactured by Unitech Foods Co., Ltd. was used as “ ⁇ -carrageenan”. .
  • the microcapsule production methods of Examples 1 to 9 can obtain microcapsules having a sufficiently small particle size, and can be obtained in a small space (with a small facility (equipment)). It was confirmed that the microcapsules were recovered at a high rate.
  • the method for producing microcapsules of the present invention is suitable as a method for producing microparticles (microcapsules) encapsulating a substance having physiological activity, for example.
  • 14a first injection port, 14b: second injection port, 21: emulsion, 22: aqueous solution, 23: first compressed air, 24: second compressed air, 26: first gas flow path, 26a: first slit-shaped gas flow path, 27: first liquid flow path, 27a: first slit-shaped liquid flow path, 28: second gas-flow path, 28a: second slit-shaped gas flow path , 29: second liquid flow path, 29a: second slit-shaped liquid flow path, 31a: first mist-like fluid, 31b: second mist-like fluid, 32: synthetic fluid, 35a: smooth surface, 35 : First mist fluid path, 36a: smooth surface, 36: second mist fluid path, 41: outer cap, 42: outer core, 43: outer frame, 44: inner core, 45: inner frame , 51: first gas supply port, 52: first liquid supply port, 53: second gas supply port, 54: second liquid Inlet, 60: collision position, 100: nozzle, L1, L2: length.

Abstract

Disclosed is a method for preparing microcapsules having a sufficiently small particle diameter at a high recovery rate in a small space. In the method, a first atomized fluid in a thin film state containing first droplets which include a gel-forming substance and a lipophilic substance, and a second atomized fluid in a thin film state containing second dropletes which include a gelling agent are collided so that they cross each other in a gas phase, and microcapsules having an average particle diameter of not more than 100 μm are formed.

Description

マイクロカプセルの製造方法Method for producing microcapsules
　本発明は、マイクロカプセルの製造方法に関する。更に詳しくは、平均粒子径が十分に小さいマイクロカプセルを得ることが可能であり、小スペースで回収率が高いマイクロカプセルの製造方法に関する。 The present invention relates to a method for producing microcapsules. More specifically, the present invention relates to a method for producing a microcapsule that can obtain a microcapsule having a sufficiently small average particle diameter and that has a high recovery rate in a small space.
　従来、医療分野や食品分野などでは、生理活性を有する物質（脂溶性物質）をアルギン酸等で内包した微粒子（マイクロカプセル）を服用することにより、上記生理活性を有する物質を摂取することが行われている。そして、このマイクロカプセルを製造する方法としては、例えば、生理活性を有する物質を含む水溶液を、２つのノズルから円錐状に噴霧して、霧状の上記水溶液を互いに接触させてゲル化させるという方法が知られている（例えば、特許文献１参照）。 2. Description of the Related Art Conventionally, in the medical field, food field, and the like, a substance having physiological activity is ingested by taking fine particles (microcapsules) encapsulating a physiologically active substance (fat-soluble substance) with alginic acid. ing. And as a method of manufacturing this microcapsule, for example, an aqueous solution containing a physiologically active substance is sprayed in a conical shape from two nozzles, and the mist-like aqueous solution is brought into contact with each other to be gelled. Is known (see, for example, Patent Document 1).
　また、一方のノズルから生理活性を有する物質を含む水溶液を噴霧して、所定の粒子径の液滴を含む霧状の第一の流体を得るとともに、他方のノズルからゲル化剤を含む水溶液を噴霧して、上記霧状の第一の流体よりも小さな粒子径の液滴を含む霧状の第二の流体を得た後、霧状の第一の流体と霧状の第二の流体を互いに接触させることによって、ゲル化したマイクロカプセルを得る方法が知られている（例えば、特許文献２参照）。 Also, an aqueous solution containing a physiologically active substance is sprayed from one nozzle to obtain a mist-like first fluid containing droplets having a predetermined particle diameter, and an aqueous solution containing a gelling agent is supplied from the other nozzle. After spraying to obtain a mist-like second fluid containing droplets having a particle size smaller than that of the mist-like first fluid, the mist-like first fluid and the mist-like second fluid are A method for obtaining gelled microcapsules by bringing them into contact with each other is known (see, for example, Patent Document 2).
特開２００４－３００４２６号公報Japanese Patent Laid-Open No. 2004-300396 特開２００７－２９０９９７号公報JP 2007-290997 A
　しかしながら、特許文献１及び２に記載のマイクロカプセルの製造方法は、粒子径が十分に小さいマイクロカプセルを得ることは困難であり、また、これらの従来の製造方法によると、第一の流体と第二の流体を接触させるための空間を広く確保する必要があり、小スペースでマイクロカプセルの回収率を高くすることができないという問題があった。そのため、粒子径が十分に小さく、小スペースで回収率が高いマイクロカプセルの製造方法の開発が切望されていた。 However, in the microcapsule production methods described in Patent Documents 1 and 2, it is difficult to obtain microcapsules having a sufficiently small particle diameter, and according to these conventional production methods, the first fluid and the first fluid It is necessary to secure a wide space for contacting the two fluids, and there is a problem that the microcapsule recovery rate cannot be increased in a small space. Therefore, development of a method for producing microcapsules having a sufficiently small particle size, a small space and a high recovery rate has been desired.
　本発明は、上述のような従来技術の課題を解決するためになされたものであり、粒子径が十分に小さいマイクロカプセルを得ることが可能であり、小スペースで回収率が高いマイクロカプセルの製造方法を提供するものである。 The present invention has been made to solve the above-described problems of the prior art, and it is possible to obtain a microcapsule having a sufficiently small particle diameter, and manufacturing a microcapsule having a small space and a high recovery rate. A method is provided.
　本発明により、以下のマイクロカプセルの製造方法が提供される。 The present invention provides the following microcapsule production method.
［１］ゲル形成物質及び脂溶性物質を含有する第一の液滴を含む薄膜状の第一の霧状流体と、ゲル化剤を含有する第二の液滴を含む薄膜状の第二の霧状流体とを、気相中で相互に交差するように衝突させて、平均粒子径が１００μｍ以下のマイクロカプセルを得るマイクロカプセルの製造方法。 [1] A thin film-like first mist-like fluid containing a first droplet containing a gel-forming substance and a fat-soluble substance, and a thin-film second containing a second drop containing a gelling agent A method for producing a microcapsule, in which a mist fluid is caused to collide with each other so as to cross each other in a gas phase to obtain a microcapsule having an average particle size of 100 μm or less.
［２］前記第一の霧状流体及び前記第二の霧状流体の気液比（気体／液体）が、それぞれ、４．０×１０２～１．１×１０４である前記［１］に記載のマイクロカプセルの製造方法。 [2] The [1], wherein the gas-liquid ratio (gas / liquid) of the first mist fluid and the second mist fluid is 4.0 × 10 2 to 1.1 × 10 4 , respectively. A method for producing the microcapsule according to 1.
［３］第一の気体供給口を有する第一の気体流路と、第一の液体供給口を有する第一の液体流路と、前記第一の気体流路及び前記第一の液体流路が合流して構成され、環状のスリットからなる第一の噴射口を形成する第一の霧状流体路と、第二の気体供給口を有する第二の気体流路と、第二の液体供給口を有する第二の液体流路と、前記第二の気体流路及び前記第二の液体流路が合流して構成され、環状のスリットからなる第二の噴射口を形成する第二の霧状流体路と、を備え、前記第二の噴射口が、前記第一の噴射口に囲まれた領域内に形成されているノズルを用いるマイクロカプセルの製造方法であって、前記第一の噴射口から、前記第一の霧状流体または前記第二の霧状流体のいずれか一方を噴射させるとともに、前記第二の噴射口から、前記第一の霧状流体または前記第二の霧状流体のいずれか他方を噴射させて、前記第一の霧状流体及び前記第二の霧状流体を、気相中で相互に交差するように衝突させて、平均粒子径が１００μｍ以下のマイクロカプセルを得る前記［１］または［２］に記載のマイクロカプセルの製造方法。 [3] A first gas channel having a first gas supply port, a first liquid channel having a first liquid supply port, the first gas channel and the first liquid channel Are combined to form a first mist fluid passage forming a first injection port composed of an annular slit, a second gas flow path having a second gas supply port, and a second liquid supply A second liquid channel having a mouth, a second mist that is formed by joining the second gas channel and the second liquid channel, and forms a second injection port composed of an annular slit. A microcapsule, wherein the second injection port is a nozzle formed in a region surrounded by the first injection port, wherein the first injection From the mouth, either the first mist fluid or the second mist fluid is jetted and the second jet port The first mist fluid or the second mist fluid is jetted to cross the first mist fluid and the second mist fluid in the gas phase. The method for producing microcapsules according to [1] or [2] above, wherein microcapsules having an average particle size of 100 μm or less are obtained by collision.
　本発明のマイクロカプセルの製造方法は、粒子径が十分に小さいマイクロカプセルを得ることが可能であり、小スペースで回収率が高い（即ち、小スペースで（小さな設備（装置）で）マイクロカプセルを製造することができ、かつ、マイクロカプセルの回収率が高い）という効果を奏するものである。 The method for producing a microcapsule of the present invention can obtain a microcapsule having a sufficiently small particle diameter, and has a high recovery rate in a small space (that is, a microcapsule in a small space (with a small facility (apparatus)). The microcapsules can be manufactured and the microcapsule recovery rate is high).
本発明のマイクロカプセルの製造方法に用いることができる製造装置のノズルを示す斜視図である。It is a perspective view which shows the nozzle of the manufacturing apparatus which can be used for the manufacturing method of the microcapsule of this invention. 図１のノズルの先端部を示す断面図である。It is sectional drawing which shows the front-end | tip part of the nozzle of FIG.
　以下、本発明を実施するための形態について説明するが、本発明は以下の実施の形態に限定されるものではない。即ち、本発明の趣旨を逸脱しない範囲で、当業者の通常の知識に基づいて、以下の実施の形態に対し適宜変更、改良等が加えられたものも本発明の範囲に属することが理解されるべきである。 Hereinafter, although the form for implementing this invention is demonstrated, this invention is not limited to the following embodiment. That is, it is understood that modifications and improvements as appropriate to the following embodiments are also within the scope of the present invention based on ordinary knowledge of those skilled in the art without departing from the spirit of the present invention. Should be.
［１］マイクロカプセルの製造方法：
　本発明のマイクロカプセルの製造方法の一実施形態は、ゲル形成物質及び脂溶性物質を含有する第一の液滴を含む薄膜状の第一の霧状流体と、ゲル化剤を含有する第二の液滴を含む薄膜状の第二の霧状流体とを、気相中で相互に交差するように衝突させて、平均粒子径が１００μｍ以下のマイクロカプセルを得る方法である。なお、本発明の製造方法は、「平均粒子径が１００μｍ以下のマイクロカプセル」を得る方法であり、上記方法により平均粒子径が１００μｍ以下のマイクロカプセルを得ることができる限り、本発明の範囲に属するが、実際には装置などの都合上、平均粒子径１０～１００μｍのマイクロカプセルを得ることができるものである。本明細書において「平均粒子径」とは、「体積平均粒子径」のことを意味する。また、マイクロカプセルは、トコフェロールなどの脂溶性物質をアルギン酸などのゲル形成物質で内包した微粒子である。 [1] Manufacturing method of microcapsule:
One embodiment of the method for producing a microcapsule of the present invention includes a first mist-like fluid in the form of a thin film including first droplets containing a gel-forming substance and a fat-soluble substance, and a second containing a gelling agent. In this method, microcapsules having an average particle diameter of 100 μm or less are obtained by colliding with a thin film-like second mist-like fluid containing the above-mentioned droplets so as to cross each other in the gas phase. The production method of the present invention is a method for obtaining “microcapsules having an average particle size of 100 μm or less”, and within the scope of the present invention, as long as microcapsules having an average particle size of 100 μm or less can be obtained by the above method. In practice, however, microcapsules having an average particle size of 10 to 100 μm can be obtained due to the convenience of the apparatus and the like. In this specification, the “average particle size” means “volume average particle size”. The microcapsules are fine particles in which a fat-soluble substance such as tocopherol is encapsulated with a gel-forming substance such as alginic acid.
　本発明における「衝突」とは、第一の液滴と第二の液滴とを所定速度以上で接触させることであり、具体的には、８０ｍ／秒以上、より好ましくは１００ｍ／秒以上、更に好ましくは１２０ｍ／秒以上の速度で第一の液滴及び第二の液滴をそれぞれ噴射して、上記速度を維持した状態で互いに接触させることである。 The “collision” in the present invention is to bring the first droplet and the second droplet into contact at a predetermined speed or more, specifically, 80 m / second or more, more preferably 100 m / second or more, More preferably, the first droplet and the second droplet are respectively ejected at a speed of 120 m / second or more and are brought into contact with each other while maintaining the speed.
　このような製造方法によると、第一の霧状流体と第二の霧状流体とを衝突させた際に、衝突の勢いを維持したまま、一旦、第一の液滴と第二の液滴が混ざり合い、その後、衝突の勢いにより再び***させることで、平均粒子径が大きくなることを効果的に防止し、粒子径が十分に小さいマイクロカプセルを得ることが可能である。 According to such a manufacturing method, when the first mist fluid and the second mist fluid are caused to collide, the first droplet and the second droplet are temporarily maintained while maintaining the momentum of the collision. Are then mixed and then re-split by the momentum of the collision, so that it is possible to effectively prevent the average particle size from becoming large and to obtain microcapsules having a sufficiently small particle size.
　また、薄膜状の霧状流体をそれぞれ衝突させるため、各霧状流体を効率的に衝突させることができ、高い回収率でマイクロカプセルを製造することができる。ここで、本明細書において「回収率」とは、式：回収率（％）＝（全質量Ａ／全質量Ｂ）×１００により算出される値である。但し、全質量Ａは、「平均粒子径が１００μｍ以下のマイクロカプセル」を所定時間製造した後、乾燥させて得られる「平均粒子径１００μｍ以下のマイクロカプセル」の固形分の全質量である。また、全質量Ｂは、第一の液滴を上記所定時間と同じ時間噴射した後、噴射された第一の液滴を乾燥させて得られる第一の液滴の固形分の全質量である。 Further, since the thin film-like mist fluids are caused to collide with each other, each mist fluid can be efficiently caused to collide, and the microcapsules can be manufactured with a high recovery rate. Here, the “recovery rate” in this specification is a value calculated by the formula: recovery rate (%) = (total mass A / total mass B) × 100. However, the total mass A is the total mass of the solid content of “microcapsules with an average particle diameter of 100 μm or less” obtained by producing “microcapsules with an average particle diameter of 100 μm or less” for a predetermined time and drying. Further, the total mass B is the total mass of the solid content of the first droplet obtained by ejecting the first droplet for the same time as the predetermined time and then drying the ejected first droplet. .
　更に、薄膜状の霧状流体を互いに衝突させるため、従来の製造方法（特許文献１，２参照）のように、第一または第二の霧状流体のいずれかを空間中に浮遊させておくことが不要となる。そして、浮遊させる空間が不要になったため、小スペースでマイクロカプセルを製造することができる（即ち、マイクロカプセルの製造に必要なスペース（具体的には設備（装置）の大きさ）が小さくなる）。 Furthermore, in order to cause the thin film-like mist fluids to collide with each other, either the first or second mist fluid is suspended in the space as in the conventional manufacturing method (see Patent Documents 1 and 2). Is no longer necessary. Since the space for floating is no longer necessary, the microcapsules can be manufactured in a small space (that is, the space required for manufacturing the microcapsules (specifically, the size of the equipment (device) is reduced)). .
［１－１］第一の霧状流体：
　第一の霧状流体は、ゲル形成物質及び脂溶性物質を含有する第一の液滴を含む薄膜状のものである。この第一の霧状流体は、空気などの気体中に上記第一の液滴が分散している霧状の流体であり、薄い膜状を形成するように噴射されることによって形成される。 [1-1] First mist fluid:
The first mist fluid is a thin film containing a first droplet containing a gel-forming substance and a fat-soluble substance. The first mist fluid is a mist fluid in which the first droplet is dispersed in a gas such as air, and is formed by being ejected so as to form a thin film.
　第一の液滴に含有されるゲル形成物質は、無機塩や酸などのゲル化剤と反応することによってゲル化する化合物のことであり、ゲル形成物質としては、例えば、水溶性アルギン酸誘導体、低メトキシルペクチン、ゼラチン、キサンタンガム、脱アシル型ジェランガム、カルボキシメチルセルロース、水溶性セルロース誘導体、κ－カラギーナン、ι－カラギーナン、ナイロン、ポリエチレングリコールなどを挙げることができる。これらの中でも、瞬時にゲル化させること（ゲルを形成すること）ができるという観点から、水溶性アルギン酸誘導体、低メトキシルペクチンが好ましい。 The gel-forming substance contained in the first droplet is a compound that gels by reacting with a gelling agent such as an inorganic salt or an acid. Examples of the gel-forming substance include water-soluble alginic acid derivatives, Examples include low methoxyl pectin, gelatin, xanthan gum, deacylated gellan gum, carboxymethyl cellulose, water-soluble cellulose derivatives, κ-carrageenan, ι-carrageenan, nylon, and polyethylene glycol. Among these, a water-soluble alginic acid derivative and low methoxyl pectin are preferable from the viewpoint that gelation can be performed instantaneously (formation of a gel).
　水溶性アルギン酸誘導体としては、例えば、アルギン酸、アルギン酸ナトリウム、アルギン酸カリウム、アルギン酸アンモニウムなどを挙げることができる。 Examples of water-soluble alginic acid derivatives include alginic acid, sodium alginate, potassium alginate, and ammonium alginate.
　ゲル形成物質の２５℃の粘度は、５～１０００ｍＰａ・ｓであることが好ましく、１０～５００ｍＰａ・ｓであることが更に好ましく、２０～３００ｍＰａ・ｓであることが特に好ましい。ゲル形成物質の上記粘度が５ｍＰａ・ｓ未満であると、形成されるゲルが弱く（即ち、十分な硬さのゲルが得られず）、良好な形状のマイクロカプセルを得ることが困難になるおそれがある。一方、１０００ｍＰａ・ｓ超であると、平均粒子径が十分に小さい（１００μｍ以下の）マイクロカプセルを得ることが困難になるおそれがある。 The viscosity of the gel-forming substance at 25 ° C. is preferably 5 to 1000 mPa · s, more preferably 10 to 500 mPa · s, and particularly preferably 20 to 300 mPa · s. When the viscosity of the gel-forming substance is less than 5 mPa · s, the formed gel is weak (that is, a gel with sufficient hardness cannot be obtained), and it may be difficult to obtain a microcapsule having a good shape. There is. On the other hand, if it exceeds 1000 mPa · s, it may be difficult to obtain microcapsules having a sufficiently small average particle diameter (100 μm or less).
　第一の液滴に含有される脂溶性物質としては、例えば、経口投与による摂取で生理活性を有する物質などを挙げることができ、具体的には、ユビキノンなどの補酵素Ｑ類、レチノール、レチノイン酸、レチノイド、カロチンなどのビタミンＡ類、コレカルシフェロール、エルゴカルシフェロールなどのビタミンＤ類、トコフェロール、酢酸トコフェロール、コハク酸トコフェロール、ニコチン酸トコフェロール、トコトリエノールなどのビタミンＥ類、フィトナジオン、メナテトレノン等のビタミンＫ類、ＤＨＡ，ＥＰＡなどの油脂類、ファイトステロール（植物ステロール）、酵母ステロール等のステロール類、アスタキサンチン、ゼアキサンチン、フコキサンチンなどを挙げることができる。 Examples of the fat-soluble substance contained in the first droplet include substances having physiological activity when taken by oral administration, and specifically include coenzymes Q such as ubiquinone, retinol, retinoin. Vitamin A such as acid, retinoid and carotene, vitamin D such as cholecalciferol and ergocalciferol, vitamin E such as tocopherol, tocopherol acetate, tocopherol succinate, tocopherol nicotinate and tocotrienol, vitamins such as phytonadione and menatetrenone Examples include fats and oils such as Ks, DHA, and EPA, sterols such as phytosterols (plant sterols) and yeast sterols, astaxanthin, zeaxanthin, and fucoxanthin.
　本発明のマイクロカプセルの製造方法によって得られるマイクロカプセルは、その小さな粒子中に脂溶性物質（生理活性を有する物質）が含有されているものであるため、上記マイクロカプセルを服用すれば脂溶性物質を摂取することが可能である。 Since the microcapsule obtained by the method for producing a microcapsule of the present invention contains a fat-soluble substance (substance having physiological activity) in its small particles, the fat-soluble substance can be obtained by taking the microcapsule. Can be taken.
　第一の液滴には、ゲル形成物質及び脂溶性物質以外に、その他の成分（１）を含有させることができる。その他の成分（１）としては、例えば、乳化剤、吸収促進剤、タンパク質、糖類、香料などを挙げることができる。乳化剤としては、医薬品、食品用途で使用されているものであれば特に制限はないが、例えば、モノグリセリン脂肪酸有機酸エステル、グリセリン酢酸脂肪酸エステル、グリセリン乳酸脂肪酸エステル、グリセリンコハク酸脂肪酸エステル、グリセリンジアセチル酒石酸脂肪酸エステル、ポリグリセリン脂肪酸エステル、ショ糖脂肪酸エステル、ショ糖酢酸イソ酪酸エステル、ソルビタン脂肪酸エステル、ポリグリセリン縮合リシノレイン酸エステル、プロピレングリコール脂肪酸エステル、ステアロイル乳酸カルシウム、ステアロイル乳酸ナトリウム、レシチンなどを挙げることができる。また、吸収促進剤としては、例えば、ごま油、大豆油、ツバキ油、オリーブ油、ヤシ油、パーム油、菜種油、落下生油、綿実油、サフラワー油などの植物油脂や、魚油、牛脂、豚脂などの動物油脂、脂肪酸トリグリセライドなどを挙げることができる。 In addition to the gel-forming substance and the fat-soluble substance, the first droplet can contain other components (1). As other component (1), an emulsifier, an absorption promoter, protein, saccharides, a fragrance | flavor, etc. can be mentioned, for example. The emulsifier is not particularly limited as long as it is used for pharmaceuticals and foods. For example, monoglycerol fatty acid organic acid ester, glycerol acetate fatty acid ester, glycerol lactate fatty acid ester, glycerol succinate fatty acid ester, glycerol diacetyl List tartaric acid fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sucrose acetate isobutyric acid ester, sorbitan fatty acid ester, polyglycerin condensed ricinoleic acid ester, propylene glycol fatty acid ester, calcium stearoyl lactate, sodium stearoyl lactate, lecithin, etc. Can do. Examples of absorption promoters include vegetable oils such as sesame oil, soybean oil, camellia oil, olive oil, coconut oil, palm oil, rapeseed oil, fallen raw oil, cottonseed oil, safflower oil, fish oil, beef tallow, pork fat, etc. Animal fats and oils, fatty acid triglycerides and the like.
　第一の液滴中の脂溶性物質の含有割合は、特に制限はないが、第一の液滴の総量１００質量％に対して、０．５～５０質量％であることが好ましく、１．０～４０質量％であることが更に好ましく、１．５～３０質量％であることが特に好ましい。上記脂溶性物質の含有割合が０．５質量％未満であると、マイクロカプセルに含有させる脂溶性物質としては十分量でない場合がある。一方、５０質量％超であると、ゲル形成物質内に脂溶性物質を乳化させることができず（即ち、ゲル形成物質（水溶性物質）より脂溶性物質が多いと、水中油型（Ｏ／Ｗ）構造の乳化状態が形成されずに油中水型（Ｗ／Ｏ）構造になるため、脂溶性物質をゲルで包み込めず）、マイクロカプセルを形成することが困難になるおそれがある。 The content ratio of the fat-soluble substance in the first droplet is not particularly limited, but is preferably 0.5 to 50% by mass with respect to the total amount of the first droplet of 100% by mass. The content is more preferably 0 to 40% by mass, and particularly preferably 1.5 to 30% by mass. When the content ratio of the fat-soluble substance is less than 0.5% by mass, the fat-soluble substance to be contained in the microcapsule may not be a sufficient amount. On the other hand, if it exceeds 50% by mass, the fat-soluble substance cannot be emulsified in the gel-forming substance (that is, if there are more fat-soluble substances than the gel-forming substance (water-soluble substance), the oil-in-water type (O / W) Since an emulsified state of the structure is not formed and a water-in-oil (W / O) structure is formed, the fat-soluble substance cannot be wrapped with a gel), and it may be difficult to form microcapsules.
　第一の霧状流体の噴射時の薄膜の厚さは、５～４５μｍであることが好ましく、６～４０μｍであることが更に好ましく、１０～３５μｍであることが特に好ましい。上記厚さが５μｍ未満であると、後述する気液比が高くなるため、第一の霧状流体と第二の霧状流体との衝突機会が低減し、マイクロカプセルの回収率が十分でなくなるおそれがある。一方、４５μｍ超であると、気液比が低くなるため、第一の霧状流体（第一の液滴）と第二の霧状流体（第二の液滴）とが衝突した際に、近接する液滴と再び凝集することに起因して、得られるマイクロカプセルの平均粒子径が大きくなってしまうおそれがある。本明細書において「薄膜状」とは、霧状流体の噴射方向と直交する面で霧状流体を切断した場合に、霧状流体の断面の厚みが薄いことを意味し、霧状流体は、このような薄膜状である限りその形状は特に制限はない。例えば、平らな（フィルム状の）ものであってもよいし、円筒状、角筒状、メガホン状（一方から他方に向かうに従って次第に広がる筒状）などの筒状のものであってもよい。 The thickness of the thin film at the time of jetting the first mist fluid is preferably 5 to 45 μm, more preferably 6 to 40 μm, and particularly preferably 10 to 35 μm. If the thickness is less than 5 μm, the gas-liquid ratio, which will be described later, increases, so the chance of collision between the first mist fluid and the second mist fluid is reduced, and the microcapsule recovery rate is not sufficient. There is a fear. On the other hand, when it exceeds 45 μm, the gas-liquid ratio becomes low, so when the first mist fluid (first droplet) collides with the second mist fluid (second droplet), There is a possibility that the average particle diameter of the obtained microcapsules becomes large due to the aggregation with the adjacent droplets again. In this specification, “thin film shape” means that when the atomized fluid is cut on a plane orthogonal to the spraying direction of the atomized fluid, the thickness of the section of the atomized fluid is thin. As long as it is such a thin film, the shape is not particularly limited. For example, it may be flat (film-like) or cylindrical, such as cylindrical, rectangular, or megaphone (cylinder that gradually expands from one to the other).
　ここで、本明細書において、薄膜の厚さ（膜厚［μｍ］）の測定方法について第一の霧状流体を例にして以下に示す。まず、噴射口（図２中の符号「１４ａ」で示す）から噴射される第一の霧状流体の流速（薄膜流速）が圧縮気体流速の１／５０と仮定し、実験時の圧縮気体の噴射流速［ｍ／ｓ］の値に１／５０を積算することによって、第一の液滴と圧縮空気が混合された第一の霧状流体の薄膜流速［ｍ／ｓ］を算出する。次に、算出した薄膜流速［ｍ／ｓ］に、噴射口の円周長さを積算した値［ｍ２／ｓ］を算出し、この値［ｍ２／ｓ］で第一の液滴の流量［ｍ３／ｓ］を割り、膜厚［μｍ］を算出する。なお、第二の霧状流体の薄膜の厚さについても第一の霧状流体の薄膜の厚さと同様の方法で測定する。 Here, in the present specification, the method for measuring the thickness of the thin film (film thickness [μm]) will be described below by taking the first mist fluid as an example. First, it is assumed that the flow rate (thin film flow rate) of the first mist fluid injected from the injection port (indicated by reference numeral “14a” in FIG. 2) is 1/50 of the compressed gas flow rate. By adding 1/50 to the value of the jet flow velocity [m / s], the thin film flow velocity [m / s] of the first mist fluid in which the first droplet and the compressed air are mixed is calculated. Next, a value [m 2 / s] obtained by adding the circumferential length of the injection port to the calculated thin film flow velocity [m / s] is calculated, and the first droplet of the first droplet is calculated with this value [m 2 / s]. Divide the flow rate [m 3 / s] to calculate the film thickness [μm]. The thickness of the second mist fluid thin film is also measured by the same method as the thickness of the first mist fluid thin film.
　第一の霧状流体の気液比は、４．０×１０２～１．１×１０４ｍ３／ｍ３であることが好ましく、７．５×１０２～５．５×１０３ｍ３／ｍ３であることが更に好ましく、１．０×１０３～３．５×１０３ｍ３／ｍ３であることが特に好ましい。上記気液比が４．０×１０２ｍ３／ｍ３未満であると、第一の霧状流体（第一の液滴）と第二の霧状流体（第二の液滴）とが衝突する前に、近接する液滴同士が凝集して、マイクロカプセルの平均粒子径が大きくなるおそれがある。一方、１．１×１０４ｍ３／ｍ３超であると、第一の霧状流体と第二の霧状流体との衝突機会が低減し、マイクロカプセルの回収率や製造効率（ｇ／時間）が十分でなくなるおそれがある。ここで、本明細書において「気液比」は、第一の霧状流体を構成する気体と第一の液滴との体積比（気体（ｍ３）／液体（ｍ３））を意味し、式：｛単位時間あたりの気体の供給量（ｍ３／時間）／単位時間あたりの液体の供給量（ｍ３／時間）｝によって算出される値である。 The gas-liquid ratio of the first mist fluid is preferably 4.0 × 10 2 to 1.1 × 10 4 m 3 / m 3 , and 7.5 × 10 2 to 5.5 × 10 3 m. 3 / m 3 is more preferable, and 1.0 × 10 3 to 3.5 × 10 3 m 3 / m 3 is particularly preferable. When the gas-liquid ratio is less than 4.0 × 10 2 m 3 / m 3 , the first mist fluid (first droplet) and the second mist fluid (second droplet) are Before the collision, adjacent droplets may aggregate to increase the average particle size of the microcapsules. On the other hand, if it exceeds 1.1 × 10 4 m 3 / m 3 , the chance of collision between the first mist fluid and the second mist fluid is reduced, and the microcapsule recovery rate and production efficiency (g / Time) may be insufficient. Here, in this specification, the “gas-liquid ratio” means the volume ratio (gas (m 3 ) / liquid (m 3 )) of the gas constituting the first mist fluid and the first droplet. , The formula: {amount of gas supply per unit time (m 3 / hour) / amount of liquid supply per unit time (m 3 / hour)}.
　ゲル形成物質に脂溶性物質を分散した乳化液（以下、単に「乳化液」と記す場合がある）の２５℃の粘度は、５～１０００ｍＰａ・ｓであることが好ましく、１０～５００ｍＰａ・ｓであることが更に好ましく、２０～３００ｍＰａ・ｓであることが特に好ましい。乳化液の上記粘度が５ｍＰａ・ｓ未満であると、形成されるゲルが弱く（即ち、十分な硬さのゲルが得られず）、良好な形状のマイクロカプセルを得ることが困難になるおそれがある。一方、１０００ｍＰａ・ｓ超であると、平均粒子径が非常に小さい（例えば平均粒子径１０～３０μｍ程度）マイクロカプセルを得ることができない場合がある。 The viscosity at 25 ° C. of an emulsion obtained by dispersing a fat-soluble substance in a gel-forming substance (hereinafter sometimes simply referred to as “emulsion”) is preferably 5 to 1000 mPa · s, and 10 to 500 mPa · s. More preferably, it is particularly preferably 20 to 300 mPa · s. When the viscosity of the emulsion is less than 5 mPa · s, the gel formed is weak (that is, a gel with sufficient hardness cannot be obtained), and it may be difficult to obtain a microcapsule having a good shape. is there. On the other hand, if it exceeds 1000 mPa · s, microcapsules having an extremely small average particle size (for example, an average particle size of about 10 to 30 μm) may not be obtained.
　薄膜状の第一の霧状流体は、従来公知の方法を適宜採用して形成することができるが、例えば、乳化液を、流量０．０１～０．０６ｍ３／時間で供給するとともに、圧縮空気を、流量２５～１００ｍ３／時間、圧力０．０５～０．５ＭＰａで噴射することによって、上記乳化液を霧状にした後、後述する開口幅０．２～１．５μｍのスリット状の噴射口から噴射させて形成することができる。 The first mist fluid in the form of a thin film can be formed by appropriately adopting a conventionally known method. For example, an emulsion is supplied at a flow rate of 0.01 to 0.06 m 3 / hour and compressed. After the emulsion is atomized by injecting air at a flow rate of 25 to 100 m 3 / hour and a pressure of 0.05 to 0.5 MPa, it is slit-shaped with an opening width of 0.2 to 1.5 μm, which will be described later. It can be formed by being injected from an injection port.
　更に、噴射口の開口幅は、０．２～１．５ｍｍであることが好ましく、０．３～１．０ｍｍであることが更に好ましく、０．４～０．８ｍｍであることが特に好ましい。上記範囲とすることによって、効果的に薄膜状の流体を得ることができる。上記開口幅が０．２ｍｍ未満であると、流体の膜が薄くなりすぎ、回収率が低下するおそれがある。一方、１．５ｍｍ超であると、流体の厚さが厚くなりすぎ、得られるマイクロカプセルの平均粒子径が大きくなってしまうおそれがある。例えば、図２に示す符号「ａ」は、噴射口の開口幅（第一の噴射口の開口幅ａ）を示している。 Furthermore, the opening width of the injection port is preferably 0.2 to 1.5 mm, more preferably 0.3 to 1.0 mm, and particularly preferably 0.4 to 0.8 mm. By setting it as the said range, a thin film-like fluid can be obtained effectively. If the opening width is less than 0.2 mm, the fluid film becomes too thin, and the recovery rate may decrease. On the other hand, if it exceeds 1.5 mm, the fluid becomes too thick and the average particle size of the resulting microcapsules may be increased. For example, the symbol “a” illustrated in FIG. 2 indicates the opening width of the injection port (the opening width a of the first injection port).
　上記第一の霧状流体の噴射口の開口形状は、薄膜状の流体を形成することができれば特に制限はなく、例えば、略環状、略矩形状などを挙げることができる。 The opening shape of the first mist-like fluid injection port is not particularly limited as long as a thin film fluid can be formed, and examples thereof include a substantially annular shape and a substantially rectangular shape.
　乳化液は、ゲル形成物質及び脂溶性物質の混合物を、ホモミキサー、ホモジナイザー、高圧ホモジナイザー、ポリトロンなどで処理して得ることができる。 The emulsion can be obtained by treating a mixture of a gel-forming substance and a fat-soluble substance with a homomixer, a homogenizer, a high-pressure homogenizer, a polytron or the like.
　この乳化液は、ゲル形成物質及び脂溶性物質の混合物からなる乳化粒子を含有しており、乳化液中の乳化粒子の平均粒子径は、２０μｍ以下であることが好ましく、１０μｍ以下がより好ましく、５μｍ以下が更に好ましい。乳化粒子の平均粒子径が２０μｍ超であると、得られるマイクロカプセルの平均粒子径が大きくなる（１００μｍに近くなる）おそれがある。本明細書において、乳化粒子の平均粒子径は、レーザー回析／散乱式粒度分布計を用いて測定される体積平均粒子径のことである。 This emulsion contains emulsion particles composed of a mixture of a gel-forming substance and a fat-soluble substance, and the average particle size of the emulsion particles in the emulsion is preferably 20 μm or less, more preferably 10 μm or less, 5 μm or less is more preferable. If the average particle diameter of the emulsified particles is more than 20 μm, the average particle diameter of the resulting microcapsules may be increased (close to 100 μm). In the present specification, the average particle diameter of the emulsified particles is a volume average particle diameter measured using a laser diffraction / scattering particle size distribution meter.
［１－２］第二の霧状流体：
　第二の霧状流体は、ゲル化剤を含有する第二の液滴を含む薄膜状のものである。このような第二の霧状流体は、上述した第一の霧状流体と同様に、空気などの気体中に第二の液滴が分散している霧状の流体であり、この霧状の流体が薄い膜状を形成するように噴射されることによって形成される。 [1-2] Second mist fluid:
The second mist fluid is a thin film containing second droplets containing a gelling agent. Similar to the first mist fluid described above, the second mist fluid is a mist fluid in which second droplets are dispersed in a gas such as air. It is formed by injecting fluid to form a thin film.
　第二の液滴に含有されるゲル化剤は、第一の液滴をゲル化させる作用を有するものである。ゲル化剤としては、例えば、無機塩、酸などを挙げることができる。なお、ゲル形成物質として水溶性アルギン酸誘導体や低メトキシルペクチンを使用した場合には、塩化カルシウム、塩化マグネシウム、塩化バリウム、乳酸カルシウム、硫酸カルシウムなどを用いることが好ましい。これらの中でも、カルシウムイオンを含むものが好ましい。 The gelling agent contained in the second droplet has an action of gelling the first droplet. Examples of the gelling agent include inorganic salts and acids. When a water-soluble alginic acid derivative or low methoxyl pectin is used as the gel forming substance, it is preferable to use calcium chloride, magnesium chloride, barium chloride, calcium lactate, calcium sulfate, or the like. Among these, those containing calcium ions are preferable.
　なお、カルシウムイオンを含有する溶液としては、瞬時にゲル化することができるという観点から、具体的には、塩化カルシウム水溶液、乳酸カルシウム水溶液または硫酸カルシウム水溶液であることが好ましく、これらの中でも、カルシウムイオンが容易に遊離するという観点から、塩化カルシウム水溶液であることが好ましい。 The solution containing calcium ions is preferably an aqueous calcium chloride solution, an aqueous calcium lactate solution, or an aqueous calcium sulfate solution from the viewpoint that gelation can be instantaneously performed. From the viewpoint that ions are easily released, an aqueous calcium chloride solution is preferred.
　カルシウムイオンを含有する溶液におけるカルシウムイオンの濃度は、０．５～２０質量％であることが好ましく、１～１０質量％であることが更に好ましい。カルシウムイオンの濃度が０．５質量％未満であると、ゲル化し難くなる傾向がある。一方、２０質量％を超えると、コストが増大する傾向がある。 The concentration of calcium ions in the solution containing calcium ions is preferably 0.5 to 20% by mass, and more preferably 1 to 10% by mass. If the calcium ion concentration is less than 0.5% by mass, gelation tends to be difficult. On the other hand, if it exceeds 20% by mass, the cost tends to increase.
　第二の液滴には、ゲル化剤以外にその他の成分（２）を含有させることができる。その他の成分としては、例えば、タンパク質、糖質、食物繊維、脂質、香料などを挙げることができる。 The second droplet can contain other component (2) in addition to the gelling agent. Examples of other components include proteins, carbohydrates, dietary fibers, lipids, and fragrances.
　ゲル化剤を含有する水溶液（以下、単に「水溶液」と記す場合がある）中のゲル化剤の含有割合は、特に制限はないが、上記水溶液の総量１００質量％に対して、０．１～３０質量％であることが好ましく、０．５～２０質量％であることが更に好ましく、１～１０質量％であることが特に好ましい。上記ゲル化剤の含有割合が０．１質量％未満であると、第一の液滴が第二の霧状流体の第二の液滴に衝突した直後からゲル化するまでの速さ（硬化速度）が遅くなり、良好な形状のマイクロカプセルを得ることが困難になるおそれがある。一方、３０質量％超であると、上記平均粒子径の液滴を得ることが困難になるおそれがあり、平均粒子径が非常に小さい（例えば平均粒子径１０～３０μｍ程度）マイクロカプセルを得ることができない場合がある。 The content ratio of the gelling agent in the aqueous solution containing the gelling agent (hereinafter sometimes simply referred to as “aqueous solution”) is not particularly limited, but is 0.1% with respect to 100% by mass of the total amount of the aqueous solution. It is preferably from ˜30 mass%, more preferably from 0.5 to 20 mass%, particularly preferably from 1 to 10 mass%. When the content of the gelling agent is less than 0.1% by mass, the speed (curing) from immediately after the first droplet collides with the second droplet of the second mist-like fluid to gelation (Speed) becomes slow, and it may be difficult to obtain microcapsules having a good shape. On the other hand, if it exceeds 30% by mass, it may be difficult to obtain droplets having the above average particle size, and microcapsules having a very small average particle size (for example, an average particle size of about 10 to 30 μm) can be obtained. May not be possible.
　第二の霧状流体の噴射時の薄膜の厚さは、５～４５μｍであることが好ましく、６～４０μｍであることが更に好ましく、１０～３５μｍであることが特に好ましい。上記厚さが５μｍ未満であると、気液比が高くなるため、第一の霧状流体と第二の霧状流体との衝突機会が低減し、マイクロカプセルの回収率が十分でなくなるおそれがある。一方、４５μｍ超であると、気液比が低くなるため、第一の霧状流体（第一の液滴）と第二の霧状流体（第二の液滴）とが衝突した際に、近接する液滴と再び凝集して平均粒子径が大きくなってしまうおそれがある。 The thickness of the thin film when the second mist fluid is jetted is preferably 5 to 45 μm, more preferably 6 to 40 μm, and particularly preferably 10 to 35 μm. If the thickness is less than 5 μm, the gas-liquid ratio increases, so the chance of collision between the first mist fluid and the second mist fluid is reduced, and the microcapsule recovery rate may not be sufficient. is there. On the other hand, when it exceeds 45 μm, the gas-liquid ratio becomes low, so when the first mist fluid (first droplet) collides with the second mist fluid (second droplet), There is a risk that the average particle diameter becomes large by aggregating again with adjacent droplets.
　第二の霧状流体の気液比は、４．０×１０２～１．１×１０４ｍ３／ｍ３であることが好ましく、７．５×１０２～５．５×１０３ｍ３／ｍ３であることが更に好ましく、１．０×１０３～３．５×１０３ｍ３／ｍ３であることが特に好ましい。上記気液比が４．０×１０２ｍ３／ｍ３未満であると、マイクロカプセルの粒子径が大きくなるおそれがある。一方、１．１×１０４ｍ３／ｍ３超であると、マイクロカプセルの回収率や製造効率が十分でなくなるおそれがある。 The gas-liquid ratio of the second mist fluid is preferably 4.0 × 10 2 to 1.1 × 10 4 m 3 / m 3 , and 7.5 × 10 2 to 5.5 × 10 3 m. 3 / m 3 is more preferable, and 1.0 × 10 3 to 3.5 × 10 3 m 3 / m 3 is particularly preferable. If the gas-liquid ratio is less than 4.0 × 10 2 m 3 / m 3 , the particle size of the microcapsules may increase. On the other hand, if it exceeds 1.1 × 10 4 m 3 / m 3 , the microcapsule recovery rate and production efficiency may not be sufficient.
　薄膜状の第二の霧状流体は、従来公知の方法を適宜採用して形成することができるが、例えば、ゲル化剤を含有する水溶液を、流量０．０１～０．０６ｍ３／時間で供給するとともに、圧縮空気を、流量２５～１００ｍ３／時間、圧力０．０５～０．５ＭＰａで噴射することによって、上記水溶液を霧状にした後、この霧状の水溶液を、開口幅０．２～１．５ｍｍのスリット状の噴射口から噴射させることによって形成することができる。 The thin film-like second mist fluid can be formed by appropriately adopting a conventionally known method. For example, an aqueous solution containing a gelling agent is flowed at a flow rate of 0.01 to 0.06 m 3 / hour. The aqueous solution was atomized by supplying and jetting compressed air at a flow rate of 25 to 100 m 3 / hour and a pressure of 0.05 to 0.5 MPa. It can be formed by spraying from a slit-shaped spray port of 2 to 1.5 mm.
　更に、噴射口の開口幅は、０．２～１．５ｍｍであることが好ましく、０．３～１．０ｍｍであることが更に好ましく、０．４～０．８ｍｍであることが特に好ましい。上記範囲とすることによって、効果的に薄膜状の流体を得ることができる。上記開口幅が０．２ｍｍ未満であると、流体の膜が薄くなりすぎ、回収率が低下するおそれがある。一方、１．５ｍｍ超であると、流体の厚さが厚くなりすぎ、第一の霧状流体（第一の液滴）と衝突する可能性が低下し、回収率が低下するおそれがある。例えば、図２に示す符号「ｂ」は、噴射口の開口幅（第二の噴射口の開口幅ｂ）を示している。 Furthermore, the opening width of the injection port is preferably 0.2 to 1.5 mm, more preferably 0.3 to 1.0 mm, and particularly preferably 0.4 to 0.8 mm. By setting it as the said range, a thin film-like fluid can be obtained effectively. If the opening width is less than 0.2 mm, the fluid film becomes too thin, and the recovery rate may decrease. On the other hand, if it exceeds 1.5 mm, the thickness of the fluid becomes too thick, the possibility of colliding with the first mist fluid (first droplet) decreases, and the recovery rate may decrease. For example, the symbol “b” illustrated in FIG. 2 indicates the opening width of the injection port (opening width b of the second injection port).
　上記第二の霧状流体の噴射口の開口形状は、薄膜状の流体を形成することができれば特に制限はなく、上述した第一の霧状流体の噴射口と同様の形状を例示することができる。また、第一の霧状流体と第二の霧状流体は、第一の霧状流体を構成する各第一の液滴が、第二の霧状流体を構成する各第二の液滴と衝突するように噴射されることが好ましい。 The opening shape of the second mist fluid injection port is not particularly limited as long as a thin film fluid can be formed, and may be the same shape as the first mist fluid injection port described above. it can. In addition, the first mist fluid and the second mist fluid are such that each first droplet constituting the first mist fluid is each second droplet constituting the second mist fluid. It is preferable to be injected so as to collide.
　第一の霧状流体と第二の霧状流体とを相互に衝突させるための気相としては、特に制限はなく、例えば、空気、窒素、酸素、二酸化炭素、ヘリウムなどとすることができる。 The gas phase for causing the first mist fluid and the second mist fluid to collide with each other is not particularly limited, and can be, for example, air, nitrogen, oxygen, carbon dioxide, helium, or the like.
　また、本発明のマイクロカプセルの製造方法は、第一の気体供給口を有する第一の気体流路と、第一の液体供給口を有する第一の液体流路と、第一の気体流路及び第一の液体流路が合流して構成され、環状のスリットからなる第一の噴射口を形成する第一の霧状流体路と、第二の気体供給口を有する第二の気体流路と、第二の液体供給口を有する第二の液体流路と、第二の気体流路及び第二の液体流路が合流して構成され、環状のスリットからなる第二の噴射口を形成する第二の霧状流体路と、を備え、第二の噴射口が、第一の噴射口に囲まれた領域内に形成されているノズルを用い、第一の噴射口から、第一の霧状流体または第二の霧状流体のいずれか一方を噴射させるとともに、第二の噴射口から、第一の霧状流体または第二の霧状流体のいずれか他方を噴射させて、第一の霧状流体及び第二の霧状流体を、気相中で相互に交差するように衝突させることによって、平均粒子径が１００μｍ以下のマイクロカプセルを得ることが好ましい。このような方法によると、一つのノズルのみでマイクロカプセルを製造することができるため、マイクロカプセルの製造が容易になる（製造設備が占めるスペースを小さくすることができる）という利点がある。また、第一の霧状流体と第二の霧状流体とを効率よく衝突させることができるため、マイクロカプセルの回収率が向上するという利点がある。更に、良好な製造効率（ｇ／時間）で、マイクロカプセルを製造することができる。 In addition, the microcapsule manufacturing method of the present invention includes a first gas flow path having a first gas supply port, a first liquid flow path having a first liquid supply port, and a first gas flow path. And a first gas flow path having a first gas flow path formed by joining the first liquid flow path and forming a first injection port composed of an annular slit, and a second gas supply port And a second liquid channel having a second liquid supply port, a second gas channel, and a second liquid channel are joined together to form a second injection port composed of an annular slit A second mist fluid path, and a second injection port is formed in a region surrounded by the first injection port, from the first injection port to the first Either the mist-like fluid or the second mist-like fluid is injected, and the first mist-like fluid or the second mist-like flow is discharged from the second injection port. By spraying one of the other and colliding the first mist fluid and the second mist fluid so as to cross each other in the gas phase, a microcapsule having an average particle size of 100 μm or less is obtained. It is preferable. According to such a method, since the microcapsule can be manufactured with only one nozzle, there is an advantage that the manufacturing of the microcapsule becomes easy (the space occupied by the manufacturing facility can be reduced). Further, since the first mist fluid and the second mist fluid can be efficiently collided, there is an advantage that the recovery rate of the microcapsules is improved. Furthermore, microcapsules can be produced with good production efficiency (g / hour).
　例えば、上記ノズルとしては、図１及び図２に示すノズル１００のように、第一の気体供給口５１を有する第一の気体流路２６と、第一の液体供給口５２を有する第一の液体流路２７と、第一の気体流路２６及び第一の液体流路２７が合流することによって構成され、円環スリット状の第一の噴射口１４ａを形成する第一の霧状流体路３５と、第二の気体供給口５３を有する第二の気体流路２８と、第二の液体供給口５４を有する第二の液体流路２９と、第二の気体流路２８及び第二の液体流路２９が合流することによって構成され、円環スリット状の第二の噴射口１４ｂを形成する第二の霧状流体路３６と、を備え、第一の噴射口１４ａと第二の噴射口１４ｂが同心円となるように配置されている（即ち、第二の噴射口１４ｂが、第一の噴射口１４ａに囲まれた領域内に形成されている）ものを用いることができる。なお、図１は、本発明のマイクロカプセルの製造方法に用いることができる製造装置のノズルを示す斜視図であり、図２は、図１のノズルの先端部を示す断面図である。具体的には、図２は、図１のノズルを、このノズルの中心軸に平行に切断した場合における先端部の断面図である。 For example, as the nozzle, as in the nozzle 100 shown in FIGS. 1 and 2, the first gas channel 26 having the first gas supply port 51 and the first liquid channel having the first liquid supply port 52 are used. The first mist-like fluid passage formed by the liquid passage 27, the first gas passage 26, and the first liquid passage 27 joining together to form the first injection port 14a having an annular slit shape. 35, the second gas channel 28 having the second gas supply port 53, the second liquid channel 29 having the second liquid supply port 54, the second gas channel 28 and the second gas channel 28 And a second mist-like fluid path 36 that is formed by joining the liquid flow path 29 and forms an annular slit-shaped second injection port 14b. The first injection port 14a and the second injection port It arrange | positions so that the opening 14b may become a concentric circle (namely, the 2nd injection opening 14b is 1st Iguchi is formed in a region surrounded by the 14a) that can be used. FIG. 1 is a perspective view showing a nozzle of a manufacturing apparatus that can be used in the method of manufacturing a microcapsule of the present invention, and FIG. 2 is a cross-sectional view showing a tip portion of the nozzle of FIG. Specifically, FIG. 2 is a cross-sectional view of the tip when the nozzle of FIG. 1 is cut parallel to the central axis of the nozzle.
　更に、図１及び図２に示すノズル１００は、外観を形成する円筒状のアウターキャップ４１と、このアウターキャップ４１の先端内側面に挿入・配置され、アウターキャップ４１の先端内側面との間に円環スリット状の第一のスリット状気体流路２６ａを形成している外側中子４２と、外側中子４２の内側に挿入・配置され、外側中子４２の内側面との間に円環スリット状の第一のスリット状液体流路２７ａを形成する外側フレーム４３と、外側フレーム４３の先端内側面に挿入・配置され、外側フレーム４３の先端内側面との間に円環スリット状の第二のスリット状液体流路２９ａを形成している内側中子４４と、内側中子４４の内側に挿入・配置され、内側中子４４の内側面との間に円環スリット状の第二のスリット状気体流路２８ａを形成している内側フレーム４５と、を備え、全体として円柱状のものであり、一方の端面部分に、第一の噴射口１４ａと第二の噴射口１４ｂが形成されている。なお、第一のスリット状気体流路２６ａは、第一の気体流路２６の一部であり、第一のスリット状液体流路２７ａは、第一の液体流路２７の一部であり、スリット状気体流路２８ａは、第二の気体流路２８の一部であり、第二のスリット状液体流路２９ａは、第二の液体流路２９の一部である。 Further, the nozzle 100 shown in FIG. 1 and FIG. 2 is inserted and arranged on a cylindrical outer cap 41 that forms an outer appearance, and an inner end surface of the outer cap 41, and between the inner end surface of the outer cap 41. An annular ring is inserted between the outer core 42 forming the first slit-shaped gas flow path 26 a in the form of an annular slit and the inner side surface of the outer core 42. An annular slit-shaped first is formed between the outer frame 43 forming the slit-shaped first slit-shaped liquid flow path 27a and the inner surface of the outer frame 43 at the front end inner surface. An annular slit-shaped second core is formed between the inner core 44 forming the second slit-shaped liquid flow path 29a and the inner side surface of the inner core 44. Slit gas flow path 28a An inner frame 45 which forms, with a, are those cylindrical as a whole, on one end face portion, the first injection port 14a and a second injection port 14b is formed. The first slit-shaped gas flow path 26a is a part of the first gas flow path 26, the first slit-shaped liquid flow path 27a is a part of the first liquid flow path 27, The slit-shaped gas flow path 28 a is a part of the second gas flow path 28, and the second slit-shaped liquid flow path 29 a is a part of the second liquid flow path 29.
　このようなノズル１００としては、例えば、大川原化工機社株式会社製の型番「ＴＪ－１００」、型番「ＴＪ－１０００」、型番「ＴＪ－５０」などを挙げることができる。 Examples of such a nozzle 100 include model numbers “TJ-100”, model numbers “TJ-1000”, and model numbers “TJ-50” manufactured by Okawara Chemical Co., Ltd.
　そして、ノズル１００を用いて、マイクロカプセルを製造する場合、まず、第一の噴射口１４ａから、第一の霧状流体３１ａを噴射させるとともに、第二の噴射口１４ｂから、第二の霧状流体３１ｂを噴射させる。より具体的には、第一の液体流路２７から供給するゲル形成物質及び脂溶性物質を含有する乳化液２１と、第一の気体流路２６から供給する気体（第一の圧縮空気２３）と、を気液混合することによって、第一の噴射口１４ａから第一の霧状流体３１ａを、円環状の薄膜として噴射させる。このとき、第一の霧状流体路３５に形成された平滑面３５ａによって第一の霧状流体３１ａが良好に薄膜状になる。また、第二の液体流路２９から供給するゲル化剤を含有する水溶液２２と、第二の気体流路２８から供給する気体（第二の圧縮空気２４）と、を気液混合することによって、第二の噴射口１４ｂから第二の霧状流体３１ｂを、円環状の薄膜として噴射させる。このとき、第二の霧状流体路３６に形成された平滑面３６ａによって第二の霧状流体３１ｂが良好に薄膜状になる。 And when manufacturing a microcapsule using the nozzle 100, first, while spraying the 1st mist-like fluid 31a from the 1st injection port 14a, from the 2nd injection port 14b, it is the 2nd mist shape. The fluid 31b is ejected. More specifically, an emulsified liquid 21 containing a gel-forming substance and a fat-soluble substance supplied from the first liquid channel 27, and a gas (first compressed air 23) supplied from the first gas channel 26 , The first mist fluid 31a is ejected from the first ejection port 14a as an annular thin film. At this time, the smooth surface 35a formed in the first mist-like fluid path 35 makes the first mist-like fluid 31a well in a thin film shape. In addition, the aqueous solution 22 containing the gelling agent supplied from the second liquid channel 29 and the gas (second compressed air 24) supplied from the second gas channel 28 are gas-liquid mixed. The second mist fluid 31b is ejected from the second ejection port 14b as an annular thin film. At this time, the second mist fluid 31b is favorably formed into a thin film by the smooth surface 36a formed in the second mist fluid passage 36.
　次に、第一の霧状流体３１ａ及び第二の霧状流体３１ｂを、気相中で相互に交差するように衝突させる。より具体的には、第一の噴射口１４ａから噴射した第一の霧状流体３１ａが、距離Ｌ１だけ移動するとともに、第二の噴射口１４ｂから噴射した第二の霧状流体３１ｂが、距離Ｌ２だけ移動して、大気中の衝突位置６０で相互に直角に交差するように衝突している。 Next, the first mist fluid 31a and the second mist fluid 31b are caused to collide with each other so as to cross each other in the gas phase. More specifically, the first mist fluid 31a injected from the first injection port 14a moves by the distance L1, and the second mist fluid 31b injected from the second injection port 14b is They have moved by L2 and collided so as to intersect at right angles at a collision position 60 in the atmosphere.
　そして、第一の霧状流体３１ａと第二の霧状流体３１ｂとは、衝突後、合流して１つの流体（合成流体３２）を形成する。この合成流体３２は、第一の霧状流体３１ａの進行方向と第二の霧状流体３１ｂの進行方向とを合成した方向（合成方向）に進む。このとき、合成流体３２においては、大きな乱れと渦が生じており、大きな乱れと渦によって第一の霧状流体３１ａに含まれていた第一の液滴と第二の霧状流体３１ｂに含まれていた第二の液滴とが衝突することになり、平均粒子径が１００μｍ以下のマイクロカプセルを得ることができる。合成流体３２は、ノズルの先端部から傘状に形成される。別言すれば、合成流体３２は、図２に示すように、図１に示すノズルの中心軸に平行に切断した場合においてハの字状に形成されている。なお、合成流体３２が進む方向は、第一の霧状流体３１ａと第二の霧状流体３１ｂとの量の違いによって決定される。 The first mist fluid 31a and the second mist fluid 31b join together after collision to form one fluid (synthetic fluid 32). The synthetic fluid 32 proceeds in a direction (compositing direction) in which the traveling direction of the first mist fluid 31a and the traveling direction of the second mist fluid 31b are combined. At this time, in the synthetic fluid 32, large turbulence and vortices are generated, and the large turbulence and vortices cause the first droplet and the second mist fluid 31b included in the first mist fluid 31a. The resulting second droplet collides, and microcapsules having an average particle diameter of 100 μm or less can be obtained. The synthetic fluid 32 is formed in an umbrella shape from the tip of the nozzle. In other words, as shown in FIG. 2, the synthetic fluid 32 is formed in a square shape when cut in parallel to the central axis of the nozzle shown in FIG. The direction in which the synthetic fluid 32 travels is determined by the difference in the amount of the first mist fluid 31a and the second mist fluid 31b.
　また、本明細書において「交差するように衝突」とは、第一の霧状流体の噴射方向延長線と第二の霧状流体の噴射方向延長線とがそれぞれ交差するように設定され、噴射された薄膜状の各流体が交差することによって、第一の霧状流体中の第一の液滴と第二の霧状流体中の第二の液滴とが、それぞれ衝突することを意味する。具体的には、薄膜状の第一の霧状流体と薄膜状の第二の霧状流体とをそれぞれ複数の行及び複数の列からなる複数のブロックに分けたときに、薄膜状の第一の霧状流体の所定の列と薄膜状の第二の霧状流体の所定の列とが所定の位置で交わるように第一の霧状流体と第二の霧状流体とが衝突することを意味する。従って、例えば薄膜状の第一の霧状流体の所定の列（所定の列群）のみが薄膜状の第二の霧状流体と所定の位置で交わることを意味するものではない。 Further, in the present specification, “collision so as to intersect” is set such that the first mist fluid injection direction extension line and the second mist fluid injection direction extension line intersect each other, It means that the first droplet in the first mist fluid and the second droplet in the second mist fluid collide with each other when the formed thin film fluids intersect each other. . Specifically, when the thin film-like first mist fluid and the thin film-like second mist fluid are divided into a plurality of blocks each having a plurality of rows and a plurality of columns, The first mist fluid and the second mist fluid collide so that the predetermined row of the mist fluid and the predetermined row of the thin film-like second mist fluid intersect at a predetermined position. means. Therefore, for example, it does not mean that only a predetermined row (a predetermined row group) of the thin film-like first mist fluid intersects the thin film-like second mist fluid at a predetermined position.
　以下、本発明を実施例及び比較例に基づいて具体的に説明するが、本発明はこれらの実施例及び比較例に限定されるものではない。 Hereinafter, the present invention will be specifically described based on Examples and Comparative Examples, but the present invention is not limited to these Examples and Comparative Examples.
［体積平均粒子径（μｍ）］
　体積平均粒子径は、粒度分布測定装置（株式会社島津製作所製、「ＳＡＬＤ－２２００」）を用いて測定した。 [Volume average particle diameter (μm)]
The volume average particle size was measured using a particle size distribution measuring device (“SALD-2200” manufactured by Shimadzu Corporation).
［回収率（％）］
　表１に示す条件にて所定時間（表１中の「噴霧時間（分）」参照）で「平均粒子径が１００μｍ以下のマイクロカプセル」を製造した（なお、全ての実施例において、製造したマイクロカプセルの平均粒子径は１００μｍ以下である）。製造した「平均粒子径が１００μｍ以下のマイクロカプセル」をイオン交換水で十分に洗浄した後（イオン交換水で第二の液滴の固形分を洗い落とした後）、１０５℃、６時間の条件で乾燥させ、乾燥した「平均粒子径１００μｍ以下のマイクロカプセル」の全質量Ａを測定する。一方、第一の液滴を上記所定時間（上記マイクロカプセルの製造時間）と同じ時間で噴射し、噴射された第一の液滴を、１０５℃、６時間の条件で乾燥させ、得られた固形分（乾燥物）の全質量Ｂを測定した。その後、下記式にて、回収率（％）を算出した。
式：回収率（％）＝（全質量Ａ／全質量Ｂ）×１００ [Recovery rate(%)]
“Microcapsules having an average particle size of 100 μm or less” were produced under the conditions shown in Table 1 for a predetermined time (see “spraying time (minutes)” in Table 1). The average particle diameter of the capsule is 100 μm or less). The produced “microcapsules with an average particle size of 100 μm or less” are thoroughly washed with ion-exchanged water (after the solid content of the second droplet is washed away with ion-exchanged water), and then at 105 ° C. for 6 hours. The total mass A of the dried “microcapsules with an average particle diameter of 100 μm or less” is measured. On the other hand, the first droplet was ejected at the same time as the predetermined time (the production time of the microcapsule), and the ejected first droplet was dried at 105 ° C. for 6 hours. The total mass B of the solid content (dried product) was measured. Thereafter, the recovery rate (%) was calculated by the following formula.
Formula: Recovery rate (%) = (total mass A / total mass B) × 100
［製造効率（ｇ／時間）］
　［回収率（％）］の評価と同様にして、表１に示す条件にて所定時間（表１中の「噴霧時間（分）」参照）で「平均粒子径が１００μｍ以下のマイクロカプセル」を製造した。製造した「平均粒子径が１００μｍ以下のマイクロカプセル」を、１０５℃、６時間の条件で乾燥させ、乾燥した「平均粒子径が１００μｍ以下のマイクロカプセル」の全質量を測定した後、１時間当りの製造量（ｇ）を算出して、製造効率（ｇ／時間）とした。 [Production efficiency (g / hour)]
Similarly to the evaluation of [Recovery rate (%)], “microcapsules having an average particle size of 100 μm or less” were obtained under the conditions shown in Table 1 for a predetermined time (see “Spraying time (minutes)” in Table 1). Manufactured. The produced “microcapsules with an average particle size of 100 μm or less” were dried at 105 ° C. for 6 hours, and the total mass of the dried “microcapsules with an average particle size of 100 μm or less” was measured. The production amount (g) was calculated as production efficiency (g / hour).
（実施例１）
　まず、ゲル形成物質としてアルギン酸ナトリウム（株式会社フードケミファ社製、「ダックアルギンＮＳＰＭ」）１．５ｋｇ、脂溶性物質としてビタミンＥ（エーザイフード・ケミカル株式会社製、「イーミックス－Ｄ」）３．０ｋｇ、及び、乳化剤としてポリグリエステル（三菱化学フーズ株式会社製、「リョートーポリグリエステルＰ－８Ｄ」）１．２ｋｇを、イオン交換水１４４．３ｋｇ中に投入して、ホモミキサー（株式会社マイクロテック・ニチオン社製の「ヒスコトロン」）を用いて混合して、乳化液を調製した。その後、ゲル化剤として塩化カルシウム（富田製薬株式会社製、「塩化カルシウムＨ」）８．７１５ｋｇを、イオン交換水１４１．２８５ｋｇ中に投入して、ホモミキサーを用いて混合して、水溶液（塩化カルシウム水溶液）を調製した。なお、調製した乳化液中の乳化粒子の体積平均粒子径は、０．７５５μｍであった。 Example 1
First, sodium alginate (“Duck Algin NSPM” manufactured by Food Chemifa Co., Ltd.) 1.5 kg as a gel-forming substance and vitamin E (“Emix-D” manufactured by Eisai Food Chemical Co., Ltd.) as a fat-soluble substance 0 kg and 1.2 kg of polyglycerester (Mitsubishi Chemical Foods, "Ryoto polyglycerester P-8D") as an emulsifier were charged into 144.3 kg of ion-exchanged water and homomixer (Micro Corporation) An emulsion was prepared by mixing using “Hiscotron” manufactured by Tech Nichion. Thereafter, 8.715 kg of calcium chloride (“Calcium Chloride H”, manufactured by Tomita Pharmaceutical Co., Ltd.) as a gelling agent is put into 141.285 kg of ion-exchanged water, mixed using a homomixer, and an aqueous solution (salt chloride). Calcium aqueous solution) was prepared. The volume average particle size of the emulsified particles in the prepared emulsion was 0.755 μm.
　次に、ノズル（大川原化工機社株式会社製、型番「ＴＪ－１００」）の第一の液体供給口に、上記乳化液を供給して、流量（表１中、「液流量（ｍ３／時間）」と記す）０．０５２５ｍ３／時間で、第一の液体流路から排出した。また、第一の気体流路から圧縮空気を、流量（表１中、「エア流量（ｍ３／時間）」と記す）２７ｍ３／時間、圧力（表１中、「エア圧力（ＭＰａ）」と記す）０．０５ＭＰａで排出した。そして、これらを気液混合することによって、上記ノズルの第一の噴射口から、薄膜状の第一の霧状流体を噴射した。なお、このときの第一の霧状流体の気液比は５１４ｍ３／ｍ３であり、噴射速度は１５３．９ｍ／ｓであった。なお、噴射速度は、第一の噴射口における速度である。噴射速度は流量計の値を圧力補正し、噴射口面積で割って算出した。 Next, the emulsified liquid is supplied to the first liquid supply port of the nozzle (manufactured by Okawara Kako Co., Ltd., model number “TJ-100”), and the flow rate (“liquid flow rate (m 3 / Time) ”) was discharged from the first liquid channel at 0.0525 m 3 / hour. In addition, compressed air from the first gas flow path has a flow rate (referred to as “air flow rate (m 3 / hour)” in Table 1), 27 m 3 / hour, pressure (referred to as “air pressure (MPa)” in Table 1). It was discharged at 0.05 MPa. And these were gas-liquid mixed, and the thin film-like 1st mist-like fluid was injected from the 1st injection port of the said nozzle. Incidentally, the gas-liquid ratio in the first atomized fluid at this time is 514 m 3 / m 3, the injection speed was 153.9m / s. The injection speed is the speed at the first injection port. The injection speed was calculated by correcting the pressure of the flow meter and dividing by the area of the injection port.
　更に、上記ノズルの第二の液体供給口に、上記水溶液を供給して、流量（表１中、「液流量（ｍ３／時間）」と記す）０．０５４５ｍ３／時間で、第二の液体流路から排出した。また、第二の気体流路から圧縮空気を、流量（表１中、「エア流量（ｍ３／時間）」と記す）２７ｍ３／時間、圧力（表１中、「エア圧力（ＭＰａ）」と記す）０．０５ＭＰａで排出した。そして、これらを気液混合することによって、上記ノズルの第二の噴射口から、薄膜状の第二の霧状流体を噴射した。なお、このときの第二の霧状流体の気液比は４９５ｍ３／ｍ３であり、噴射速度は１５３．９ｍ／ｓであった。噴射速度は、第二の噴射口における速度である。 Further, the second liquid supply port of the nozzle, by supplying the aqueous solution, (in Table 1, referred to as "liquid flow rate (m 3 / hour)") flow rate 0.0545m 3 / time, the second Drained from the liquid flow path. In addition, the compressed air from the second gas flow path has a flow rate (denoted as “air flow rate (m 3 / hour)” in Table 1) 27 m 3 / hour, pressure (in Table 1, “air pressure (MPa)”. It was discharged at 0.05 MPa. And these were gas-liquid mixed, and the thin film-like 2nd mist-like fluid was injected from the 2nd injection port of the said nozzle. Incidentally, the gas-liquid ratio of the second atomized fluid at this time is 495m 3 / m 3, the injection speed was 153.9m / s. The injection speed is the speed at the second injection port.
　そして、上記ノズルから噴射された薄膜状の第一の霧状流体と薄膜状の第二の霧状流体を相互に交差させることによって、マイクロカプセルを製造した。なお、噴霧時間は２０分とした。 Then, the microcapsule was manufactured by crossing the thin film-like first mist-like fluid ejected from the nozzle and the thin-film-like second mist-like fluid. The spraying time was 20 minutes.
　本実施例で製造したマイクロカプセルについて、上述した各評価を行った。評価結果は、体積平均粒子径は９７．１μｍであり、回収率は２０．３％であり、製造効率は５８７．６ｇ／時間であった。 Each evaluation mentioned above was performed about the microcapsule manufactured in the present Example. As a result of the evaluation, the volume average particle size was 97.1 μm, the recovery rate was 20.3%, and the production efficiency was 587.6 g / hour.
（実施例２～６）
　表１に示す物質（ゲル形成物質、脂溶性物質、及びゲル化剤）を用いて表１に示す条件とした以外は、実施例１と同様にしてマイクロカプセルの製造を行ってマイクロカプセルを得た。得られたマイクロカプセルについて、上述した各評価を行った。評価結果を表１に示す。 (Examples 2 to 6)
A microcapsule was obtained in the same manner as in Example 1 except that the conditions shown in Table 1 were used using the substances shown in Table 1 (gel-forming substance, fat-soluble substance, and gelling agent). It was. Each evaluation mentioned above was performed about the obtained microcapsule. The evaluation results are shown in Table 1.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
（実施例７～９）
　実施例１と同様にして塩化カルシウム水溶液を調製した。その後、この塩化カルシウム水溶液をクエン酸（和光純薬株式会社）でｐＨ４．０に調製した。このようにして調整したものを水溶液として用いたこと以外は実施例１と同様にしてマイクロカプセルを得た。得られたマイクロカプセルについて、上述した各評価を行った。評価結果を表１に示す。なお、表１中、「低メトキシルペクチン」としては、ユニテックフーズ株式会社製の「ＵＮＩＰＥＣＴＩＮＥ　ＬＭＳＮ３２５　ＣＩＴＲＵＳ」を使用し、「ι－カラギーナン」としては、ユニテックフーズ株式会社製の「ＳＡＴＩＡＧＥＬ　ＫＨＧ３０Ｔ」を使用した。 (Examples 7 to 9)
An aqueous calcium chloride solution was prepared in the same manner as in Example 1. Then, this calcium chloride aqueous solution was adjusted to pH 4.0 with citric acid (Wako Pure Chemical Industries, Ltd.). A microcapsule was obtained in the same manner as in Example 1 except that the solution thus prepared was used as an aqueous solution. Each evaluation mentioned above was performed about the obtained microcapsule. The evaluation results are shown in Table 1. In Table 1, “UNIPECTINE LMSN325 CITRUS” manufactured by Unitech Foods Co., Ltd. was used as “low methoxyl pectin”, and “SATIAGEL KHG30T” manufactured by Unitech Foods Co., Ltd. was used as “ι-carrageenan”. .
　表１から明らかなように、実施例１～９のマイクロカプセルの製造方法は、粒子径が十分に小さいマイクロカプセルを得ることが可能であり、小スペースで（小さな設備（装置）で）マイクロカプセルを製造することができ、かつ、マイクロカプセルの回収率が高いことが確認できた。 As is apparent from Table 1, the microcapsule production methods of Examples 1 to 9 can obtain microcapsules having a sufficiently small particle size, and can be obtained in a small space (with a small facility (equipment)). It was confirmed that the microcapsules were recovered at a high rate.
　本発明のマイクロカプセルの製造方法は、例えば、生理活性を有する物質が内包された微粒子（マイクロカプセル）を製造する方法として好適である。 The method for producing microcapsules of the present invention is suitable as a method for producing microparticles (microcapsules) encapsulating a substance having physiological activity, for example.
１４ａ：第一の噴射口、１４ｂ：第二の噴射口、２１：乳化液、２２：水溶液、２３：第一の圧縮空気、２４：第二の圧縮空気、２６：第一の気体流路、２６ａ：第一のスリット状気体流路、２７：第一の液体流路、２７ａ：第一のスリット状液体流路、２８：第二の気体流路、２８ａ：第二のスリット状気体流路、２９：第二の液体流路、２９ａ：第二のスリット状液体流路、３１ａ：第一の霧状流体、３１ｂ：第二の霧状流体、３２：合成流体、３５ａ：平滑面、３５：第一の霧状流体路、３６ａ：平滑面、３６：第二の霧状流体路、４１：アウターキャップ、４２：外側中子、４３：外側フレーム、４４：内側中子、４５：内側フレーム、５１：第一の気体供給口、５２：第一の液体供給口、５３：第二の気体供給口、５４：第二の液体供給口、６０：衝突位置、１００：ノズル、Ｌ１，Ｌ２：距離。 14a: first injection port, 14b: second injection port, 21: emulsion, 22: aqueous solution, 23: first compressed air, 24: second compressed air, 26: first gas flow path, 26a: first slit-shaped gas flow path, 27: first liquid flow path, 27a: first slit-shaped liquid flow path, 28: second gas-flow path, 28a: second slit-shaped gas flow path , 29: second liquid flow path, 29a: second slit-shaped liquid flow path, 31a: first mist-like fluid, 31b: second mist-like fluid, 32: synthetic fluid, 35a: smooth surface, 35 : First mist fluid path, 36a: smooth surface, 36: second mist fluid path, 41: outer cap, 42: outer core, 43: outer frame, 44: inner core, 45: inner frame , 51: first gas supply port, 52: first liquid supply port, 53: second gas supply port, 54: second liquid Inlet, 60: collision position, 100: nozzle, L1, L2: length.

Claims (3)

  1. 　ゲル形成物質及び脂溶性物質を含有する第一の液滴を含む薄膜状の第一の霧状流体と、ゲル化剤を含有する第二の液滴を含む薄膜状の第二の霧状流体とを、気相中で相互に交差するように衝突させて、平均粒子径が１００μｍ以下のマイクロカプセルを得るマイクロカプセルの製造方法。 A thin film-like first mist-like fluid containing a first droplet containing a gel-forming substance and a fat-soluble substance, and a thin-film-like second mist-like fluid containing a second drop containing a gelling agent Are collided so as to cross each other in the gas phase, thereby producing a microcapsule having an average particle diameter of 100 μm or less.
  2. 　前記第一の霧状流体及び前記第二の霧状流体の気液比（気体／液体）が、それぞれ、４．０×１０２～１．１×１０４である請求項１に記載のマイクロカプセルの製造方法。 2. The micro of claim 1, wherein a gas-liquid ratio (gas / liquid) of the first mist fluid and the second mist fluid is 4.0 × 10 2 to 1.1 × 10 4 , respectively. Capsule manufacturing method.
  3. 　第一の気体供給口を有する第一の気体流路と、第一の液体供給口を有する第一の液体流路と、前記第一の気体流路及び前記第一の液体流路が合流して構成され、環状のスリットからなる第一の噴射口を形成する第一の霧状流体路と、第二の気体供給口を有する第二の気体流路と、第二の液体供給口を有する第二の液体流路と、前記第二の気体流路及び前記第二の液体流路が合流して構成され、環状のスリットからなる第二の噴射口を形成する第二の霧状流体路と、を備え、前記第二の噴射口が、前記第一の噴射口に囲まれた領域内に形成されているノズルを用いるマイクロカプセルの製造方法であって、
    　前記第一の噴射口から、前記第一の霧状流体または前記第二の霧状流体のいずれか一方を噴射させるとともに、前記第二の噴射口から、前記第一の霧状流体または前記第二の霧状流体のいずれか他方を噴射させて、前記第一の霧状流体及び前記第二の霧状流体を、気相中で相互に交差するように衝突させて、平均粒子径が１００μｍ以下のマイクロカプセルを得る請求項１または２に記載のマイクロカプセルの製造方法。     The first gas channel having the first gas supply port, the first liquid channel having the first liquid supply port, the first gas channel and the first liquid channel are merged. A first mist fluid passage forming a first injection port composed of an annular slit, a second gas channel having a second gas supply port, and a second liquid supply port A second mist-like fluid passage formed by joining the second liquid passage, the second gas passage, and the second liquid passage to form a second injection port formed of an annular slit. And the second injection port is a method for manufacturing a microcapsule using a nozzle formed in a region surrounded by the first injection port,
    Either the first mist fluid or the second mist fluid is ejected from the first ejection port, and the first mist fluid or the second mist fluid is ejected from the second ejection port. Either one of the two mist fluids is jetted, and the first mist fluid and the second mist fluid are caused to collide with each other in the gas phase so that the average particle diameter is 100 μm. The manufacturing method of the microcapsule of Claim 1 or 2 which obtains the following microcapsules.
PCT/JP2010/064619 2009-08-28 2010-08-27 Method for preparing microcapsules WO2011024959A1 (en)

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KR20150031197A (en) * 2013-09-13 2015-03-23 주식회사 나노브릭 Method of producing micro capsule
KR20170051293A (en) * 2015-10-31 2017-05-11 주식회사 나노브릭 Color Nanocomposite and Manufacturing Method Thereof
KR101840260B1 (en) 2015-10-31 2018-03-20 주식회사 나노브릭 Microparticles Containing Color Nanocomposite and Manufacturing Method Thereof

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JP2003284938A (en) * 2002-02-05 2003-10-07 Degussa Ag Method for manufacturing finely divided, and stable solid dispersion
JP2008284514A (en) * 2007-05-21 2008-11-27 Kao Corp Manufacturing method of oil-in-water emulsion composition

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JP2003284938A (en) * 2002-02-05 2003-10-07 Degussa Ag Method for manufacturing finely divided, and stable solid dispersion
JP2008284514A (en) * 2007-05-21 2008-11-27 Kao Corp Manufacturing method of oil-in-water emulsion composition

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Publication number Priority date Publication date Assignee Title
KR20150031197A (en) * 2013-09-13 2015-03-23 주식회사 나노브릭 Method of producing micro capsule
KR101778198B1 (en) * 2013-09-13 2017-09-26 주식회사 나노브릭 Method of producing micro capsule
KR20170051293A (en) * 2015-10-31 2017-05-11 주식회사 나노브릭 Color Nanocomposite and Manufacturing Method Thereof
KR101840260B1 (en) 2015-10-31 2018-03-20 주식회사 나노브릭 Microparticles Containing Color Nanocomposite and Manufacturing Method Thereof
KR101880908B1 (en) 2015-10-31 2018-07-23 (주)나노브릭 Color Nanocomposite and Manufacturing Method Thereof

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