JP2013224314A - Method for producing ceramide dispersion composition, and ceramide dispersion composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a ceramide dispersion composition having high dispersion stability while containing a ceramide compound at high concentration, and to provide a method for producing the same.SOLUTION: A method for producing a ceramide dispersion composition includes: a process of dissolving an oil phase component, containing a ceramide compound represented by formula (1-11), for example, in an amount of ≥25.9 mass% relative to the total mass of the oil phase component, in a water-soluble organic solvent to prepare an oil phase; and a process of mixing the obtained oil phase and an aqueous phase together by counter-current collision after passing the oil phase and the aqueous phase separately through micro channels, in each of which a sectional area in the narrowest portion is from 1 μmto 1 mm, to obtain a ceramide dispersion composition wherein dispersed particles with a volume-average particle size of 1-200 nm are dispersed.

Description

  The present invention relates to a method for producing a ceramide dispersion composition and a ceramide dispersion composition.

Ceramides and ceramide derivatives belonging to sphingosines are well known as functional oily components that exhibit an emollient effect (moisturizing effect) that moisturizes and softens the skin. Cosmetics, foods and the like using the ceramide and ceramide derivatives are disclosed.
For example, Patent Document 1 discloses an emulsified composition comprising a specific glycosphingolipid group having a moisturizing action, a rough skin preventing action, and an emulsifying action.
In Patent Document 2, in order to provide a cosmetic product containing various ceramides and free of ceramide crystallizing with time, at least one of alkylyl lactic acid and its salt, glycerin and a polyglycerin fatty acid ester having a polymerization degree of 2 or more. A ceramide-containing cosmetic additive in which at least one of them is further combined is disclosed.
In Patent Document 3, a salt formed from sphingosines and a specific fatty acid, which has excellent dispersion stability and good usability even when the temperature changes drastically, is used as an emulsifier, and an oil-soluble antioxidant is specified. A water-in-oil emulsion composition added in proportions is disclosed.
Patent Document 4 discloses a method for producing a cosmetic additive in which a coarse dispersion of a glycosphingolipid is subjected to a micronization treatment using a predetermined jet flow in order to sufficiently exhibit the emollient effect of the glycosphingolipid. Has been.
Patent Document 5 discloses a method for producing a ceramide emulsion, in which sphingo and an acidic compound having a molecular weight of 200 or less that forms a salt with sphingo are mixed.
Patent Document 6 discloses a skin external preparation containing sphingosines.
However, none of these techniques is sufficient to incorporate ceramide or a ceramide derivative exhibiting an emollient effect without compromising dispersion stability while maintaining a high concentration of 10% by mass.

JP 2000-51676 A JP 2001-199872 A JP 2006-335692 A JP-A-11-310512 JP 2003-171229 A Japanese Patent No. 2964183

  An object of the present invention is to provide a method for producing a ceramide dispersion composition having excellent dispersion stability while containing a ceramide compound at a high concentration, and a ceramide dispersion composition.

Specific means for achieving the above object are as follows.
<1> Oil phase preparation for preparing an oil phase by dissolving an oil phase component containing 25.9% by mass or more of a ceramide compound represented by the following general formula 1 in a total amount of the oil phase component in a water-soluble organic solvent The process and the obtained oil phase and water phase are separately passed through a microchannel having a cross-sectional area of 1 μm ² to 1 mm ² at the narrowest portion, respectively, and then the oil phase and the water phase are subjected to counterflow collision. And a mixing step of mixing a water phase to obtain a ceramide dispersion composition in which dispersed particles having a volume average particle diameter of 1 nm to 200 nm are dispersed.

In General Formula 1, R ¹ and R ³ each independently represent an alkyl group or alkenyl group having 3 to 60 carbon atoms, or an aryl group having 6 to 60 carbon atoms. R ² represents a hydroxy group, an alkyl group or alkenyl group having 3 to 30 carbon atoms, an aryl group having 6 to 30 carbon atoms, or a phosphocholine group having the following partial structure.

  <2> The method for producing a ceramide dispersion composition according to <1>, wherein the oil phase component contains a ceramide compound in an amount of 40% by mass or more based on the total mass of the oil phase component.

<3> The oil phase preparation step of preparing the oil phase by dissolving the oil phase component containing the ceramide compound represented by the general formula 1 in a water-soluble organic solvent, and the obtained oil phase and water phase are the narrowest After passing through each of the microchannels having a cross-sectional area of 1 μm ² to 1 mm ² separately, the oil phase and the aqueous phase are mixed by countercurrent collision, so that the volume average particle diameter is 1 nm to A method for producing a ceramide dispersion composition comprising a mixing step of obtaining a ceramide dispersion composition in which dispersed particles of 200 nm are dispersed and a step of removing a water-soluble organic solvent.
<4> The method for producing a ceramide dispersion composition according to <3>, wherein the water-soluble organic solvent is ethanol.

  <5> A ceramide dispersion composition comprising an oil phase containing an oil phase component and containing 25.9% by mass or more of the ceramide compound represented by the general formula 1 with respect to the total mass of the oil phase component, and an aqueous phase. It is.

In General Formula 1, R ¹ and R ³ each independently represent an alkyl group or alkenyl group having 3 to 60 carbon atoms, or an aryl group having 6 to 60 carbon atoms. R ² is a hydroxy group, an alkyl group or an alkenyl group having 3 to 30 carbon atoms, an aryl group having 6 to 30 carbon atoms, or show a phosphocholine group the following partial structure.

<6> The ceramide dispersion composition according to <5>, wherein the oil phase contains a ceramide compound in an amount of 40% by mass or more based on the total mass of the oil phase component.
<7> The ceramide dispersion composition according to <5> or <6>, further including a compound represented by the following general formula 2 in the oil phase.

In the general formula 2, R ^{5 to} R ⁸ each independently represent a hydrogen atom or a methyl group. R ⁹ represents an alkyl group or alkenyl group having 3 to 30 carbon atoms, a carbonyl group, or an amide group.

  <8> The oil phase according to any one of <5> to <7>, wherein the oil phase includes at least one of a compound represented by the following general formula 3a and a compound represented by the following general formula 3b. It is a ceramide dispersion composition.

In the general formula 3a and the general formula 3b, R ^{10 to} R ¹³ each independently represent a hydrogen atom or a methyl group. R ¹⁴ represents an alkyl group or alkenyl group having 3 to 30 carbon atoms, a carbonyl group, or an amide group. In the general formula 3b, R represents an alkyl group or alkenyl group having 1 to 60 carbon atoms.

  <9> The ceramide dispersion composition according to any one of <5> to <8>, further including a compound represented by the following general formula 4 in the oil phase.

In the general formula 4, R ¹⁵ represents an alkyl group or alkenyl group having 3 to 60 carbon atoms, or an aryl group having 6 to 60 carbon atoms. R ¹⁶ represents an alkyl group or alkenyl group having 3 to 60 carbon atoms. R ¹⁷ represents a saccharide.

  <10> The ceramide dispersion composition according to any one of <5> to <9>, further including at least one compound represented by the following general formula 5 and the following general formula 6 in the oil phase: It is a thing.

In the general formula 5, R ¹⁸ represents an alkyl group or alkenyl group having 3 to 60 carbon atoms. X represents a single bond or a divalent linking group, and R ²¹ represents a hydrogen atom, an alkyl group or alkenyl group having 3 to 60 carbon atoms, or an aryl group having 6 to 60 carbon atoms.

In the general formula 6, R ¹⁹ represents an alkyl group having 3 to 60 carbon atoms. R ²⁰ represents a hydroxy group or an alkyl group having 3 to 60 carbon atoms. X represents a single bond or a divalent linking group,
R ²¹ represents a hydrogen atom, an alkyl group or alkenyl group having 3 to 60 carbon atoms, or an aryl group having 6 to 60 carbon atoms.

  <11> The ceramide dispersion composition according to any one of <5> to <10>, wherein the oil phase contains a functional material for cosmetics that is insoluble or hardly soluble in water.

  <12> The ceramide dispersion composition according to any one of <5> to <11>, wherein the oil phase contains a functional material for food that is insoluble or hardly soluble in water.

  <13> The ceramide dispersion composition according to any one of <5> to <12>, wherein the oil phase contains a functional material for pharmaceuticals that is insoluble or hardly soluble in water.

  ADVANTAGE OF THE INVENTION According to this invention, the manufacturing method and ceramide dispersion composition of a ceramide dispersion composition excellent in dispersion stability can be provided, containing a ceramide compound in high concentration.

It is a disassembled perspective view of the micro device as an example of a micro mixer. It is a schematic sectional drawing of the T-shaped microreactor which shows an example of the mixing mechanism by a T-shaped microreactor. It is a conceptual diagram of the T-shaped microreactor which shows another example of the mixing mechanism by a T-shaped microreactor.

<Method for producing ceramide dispersion composition>
The method for producing a ceramide dispersion composition of the present invention includes an oil phase preparation step of preparing an oil phase by dissolving an oil phase component containing at least a ceramide compound represented by the following general formula 1 in a water-soluble organic solvent. A mixing step of mixing the oil phase and the poor solvent phase of the ceramide compound.

In General Formula 1, R ¹ and R ³ each independently represent an alkyl group or alkenyl group having 3 to 60 carbon atoms, or an aryl group having 6 to 60 carbon atoms. R ² represents a hydroxy group, an alkyl group or alkenyl group having 3 to 30 carbon atoms, an aryl group having 6 to 30 carbon atoms, or a phosphocholine group having the following partial structure.

In the present invention, the ceramide compound is ceramide or a ceramide derivative, and more specifically refers to a compound represented by the general formula 1.
A dispersion of a ceramide compound obtained by mixing an oil phase containing at least the compound represented by the general formula 1 and a poor solvent phase of a ceramide compound is referred to as a ceramide dispersion composition. Here, since the ceramide compound is an oil component, the dispersion of the ceramide compound, that is, the dispersed particles, is present mainly in the dispersion composition as oil droplet particles.
Hereinafter, the poor solvent of the ceramide compound may be simply referred to as “poor solvent”.

  The ceramide compound in the oil phase component is dissolved in a water-soluble organic solvent to prepare an oil phase. Therefore, an oil phase containing a high concentration of ceramide compound can be obtained. By mixing the obtained oil phase and the poor solvent phase of the ceramide compound, a ceramide dispersion composition having excellent dispersion stability can be obtained.

Each component such as the ceramide dispersion composition, the water-soluble organic solvent, the oil phase component, and the poor solvent used in the method for producing the ceramide dispersion composition of the present invention will be described in detail later.
The method for producing a ceramide dispersion composition of the present invention includes the oil phase preparation step and the mixing step, but may further include a poor solvent phase preparation step of preparing a poor solvent phase of the ceramide compound.

The method for producing a ceramide dispersion composition of the present invention includes, for example, a) preparing a poor solvent phase using a poor solvent (such as water) of a ceramide compound as a poor solvent phase preparation step, and b) preparing an oil phase preparation step. Mix at least 10.0% by mass of a ceramide compound and a water-soluble organic solvent with respect to the total mass of the oil phase component, and further, if necessary, a stenone compound and other oil components (such as carotenoids) described later. An oil phase is prepared by mixing, and as the mixing step, c) a step of mixing the oil phase and the poor solvent phase and emulsifying and dispersing to obtain a ceramide dispersion composition (emulsion).
Moreover, it is preferable that pH of the prepared poor solvent phase and oil phase is 7 or less.

  When it is desired to obtain a ceramide dispersion composition in a powder state, by adding a step of drying the ceramide dispersion in an emulsion state obtained as described above by spray drying or the like, a ceramide dispersion composition in a powder state (powder dispersion) Can be obtained.

The ratio (volume%) between the oil phase and the poor solvent phase in the emulsification dispersion is not particularly limited, but is 0.1 / 99.9 to 50/50 as the oil phase / poor solvent phase ratio (volume%). 50 is preferable, 0.5 / 99.5 to 30/70 is more preferable, and 1/99 to 20/80 is still more preferable.
By setting the oil phase / poor solvent phase ratio to 0.1 / 99.9 or more, active ingredients such as a ceramide compound and a functional component do not decrease, so that a practical problem of the ceramide dispersion composition tends not to occur, which is preferable. . In addition, by setting the oil phase / poor solvent phase ratio to 50/50 or less, the concentration of the surfactant that can be contained in the oil phase can be increased, and the emulsion stability of the ceramide dispersion composition can be improved, which is preferable. .

  In the method for producing a ceramide dispersion composition of the present invention, the mixing step may be mixing by submerged jet. The mixing by the submerged jet in the present invention refers to a mixing method in which the oil phase is directly injected into the poor solvent phase without touching the external environment at a speed of 300 m / min or more. As such a mixing method, for example, a method described in JP-A-2005-103421 can be applied.

From the viewpoint of miniaturization of the dispersed particles of the ceramide dispersion composition, the mixing step includes a microchannel having an oil phase and a poor solvent phase of the ceramide compound having a cross-sectional area of 1 μm ² to 1 mm ² at the narrowest portion. It is preferable that the oil phase and the poor solvent phase are mixed and then obtained to obtain a ceramide dispersion composition in which dispersed particles having a volume average particle diameter of 1 nm to 200 nm are dispersed. .
By setting it as such a process, the dispersion stability of the dispersion particle contained in a ceramide dispersion composition can be improved more. Examples of the device having the microchannel include a micromixer.
Hereinafter, the micromixer which can be used for the manufacturing method of the ceramide dispersion composition of this invention is demonstrated.

[Micromixer]
In the method for producing a ceramide dispersion composition of the present invention, the oil phase and the poor solvent phase of the ceramide compound are separately passed through the microchannel having a cross-sectional area of 1 μm ² to 1 mm ² at the narrowest portion. Then, it is preferable to mix.
The mixing of the oil phase and the poor solvent phase is preferably mixing by counterflow collision from the viewpoint of obtaining finer dispersed particles.
The most suitable device for mixing by countercurrent collision is a countercurrent collision type micromixer. The micromixer mainly mixes two different liquids in a minute space, one liquid is an oil phase containing a ceramide compound, and the other is a poor solvent phase of the ceramide compound.
When a micromixer is applied to emulsion preparation with a small particle size, which is one of the microchemical processes, the heat generation is relatively low and the heat generation is small, and the particle size is uniform compared to the usual stirring emulsification dispersion method and high-pressure homogenizer emulsification dispersion. In addition, it is easy to obtain a good emulsion or dispersion having excellent storage stability. This is the most suitable method for emulsification including natural components that are susceptible to thermal degradation.

  The outline of the method of emulsifying or dispersing using a micromixer is to divide the poor solvent phase and the oil phase into fine spaces, and to contact or collide the fine spaces. This is clearly different from the membrane emulsification method and microchannel emulsification method, in which only one side is divided into microspaces and the other is bulky, and even if only one side is actually divided into microspaces, the present invention Such an effect cannot be obtained. Known micromixers have various structures. Focusing on the flow and mixing in the microchannel, there can be mentioned two types: a method of mixing while maintaining a laminar flow, and a method of mixing with a turbulent flow. In the method of mixing while maintaining the laminar flow, the size of the channel depth is made larger than the channel width, the boundary area between the two liquids is made as large as possible, and the thickness of both layers is made thin, thereby reducing the mixing efficiency. We are trying to make it. In addition, a method has been devised in which the inlet of the two liquids is divided into a large number and is made into a multilayer flow that flows alternately.

  On the other hand, in the method of mixing by turbulent flow, a method of dividing each liquid into narrow channels and flowing at a relatively high speed is common. There has also been devised a method of ejecting one liquid into the other liquid introduced into a micro space using an arrayed micro nozzle. Moreover, the mixing effect is particularly good in the method of forcibly contacting the liquids flowing at high speed using various means. The former method using laminar flow generally produces large particles but relatively uniform distribution, but the latter method using turbulent flow may give a very fine emulsion and is stable. In many cases, the method using turbulent flow is preferable from the viewpoint of stability and transparency. As a method using turbulent flow, a comb type and a collision type are typical. The comb-shaped micromixer has a structure in which two comb-shaped flow paths are arranged so as to face each other so as to face each other, as represented by IMM.

  A collision type micromixer represented by a KM mixer has a structure that uses kinetic energy to make forced contact. Specifically, the center collision disclosed by Nagasawa et al. (“H. Nagasawa et al, Chem. Eng. Technol, 28, No. 3, 324-330 (2005)”, JP 2005-288254 A). Type micromixer. In the method of causing the poor solvent phase and the oil phase to collide with each other, the mixing time is extremely short, and oil phase droplets are instantly formed. Therefore, it is easy to form a very fine emulsion or dispersion.

  In the present invention, when emulsifying by micromixing with a collision type micromixer, the temperature during emulsification (emulsification temperature) is the temperature of the other microspace of the micromixer from the viewpoint of particle size uniformity of the resulting emulsion (micro Micromixing is preferably performed at a temperature of the micromixing portion of the mixer of 80 ° C. or less, more preferably 0 ° C. to 80 ° C., and particularly preferably 5 ° C. to 75 ° C. By setting the emulsification temperature to 0 ° C. or higher, the main component of the dispersion medium is water. It is preferable that the heat retention temperature of the micro space of the micromixer is 100 ° C. or less. By setting the temperature to 100 ° C. or lower, the temperature control can be easily controlled, and the micro bumping phenomenon that adversely affects the emulsification performance can be eliminated. More preferably, the heat retention temperature is controlled at a temperature of 80 ° C. or lower.

  The oil phase, the poor solvent phase divided into the microspace of the micromixer, and the heat retention temperature of the microspace of the micromixer are different depending on the components contained in the poor solvent phase and the oil phase, but are independently 0 ° C. -50 ° C is preferable, and 5 ° C to 25 ° C is particularly preferable. Insulation temperature of the micro space of the micromixer, heat insulation temperature of the oil phase and the poor solvent phase divided into the micro space of the micro mixer, and the oil phase and the poor solvent phase before being divided into the micro space of the micro mixer The heat retention temperatures (that is, the heat retention temperatures of the oil phase and the poor solvent phase supply tank) may be different from each other, but the same temperature is preferable in terms of mixing stability.

  In the present invention, the antisolvent phase before and after being divided into the microspace of the micromixer, the oil phase, and the micromixer of the micromixer and the other microspace are kept at a temperature higher than room temperature and micromixed to emulsify. Thereafter, it is particularly preferable that the oil-in-water emulsion obtained by the micromixer is cooled to room temperature after being collected.

The cross-sectional area of the narrowest part of the micro space (flow path) of the micromixer in the present invention is 1 μm ^{2 to} 1 mm ² , and from the viewpoint of refining the emulsion particle size and sharpening the particle size distribution, 500 μm ² to 50 μm. 1,000 μm ² is preferred.
Sectional area of the narrowest part of the fine space of the micromixer used in the poor solvent phase in the present invention (the channel), from the viewpoint of mixing stability, 1,000μm ² ~50,000μm ² is particularly preferred.
Sectional area of the narrowest part of the fine space of the micromixer used in the oil phase (flow path), from the viewpoint of miniaturization and sharpness of the particle size distribution of the emulsion particle size, particularly preferably 500μm ² ~20,000μm ^2.
In addition, when emulsifying and dispersing with a micromixer, the flow rate of the oil phase and the poor solvent phase during emulsification dispersion varies depending on the micromixer used, but from the viewpoint of making the emulsion particle size fine and sharpening the particle size distribution, The flow rate of the poor solvent phase is preferably 1 mL / min to 1,000 mL / min, more preferably 20 mL / min to 350 mL / min, and particularly preferably 50 mL / min to 200 mL / min.
The flow rate of the oil phase is preferably 1 mL / min to 150 mL / min, more preferably 3 mL / min to 50 mL / min, and more preferably 5 mL / min from the viewpoint of refining the emulsion particle size and sharpening the particle size distribution. ˜50 mL / min is particularly preferred.

  The value obtained by dividing the flow rate of both phases by the cross-sectional area of the microchannel, that is, the flow rate ratio (Vo / Vw) of both phases, is in the range of 0.05 to 5 in terms of particle refinement and micromixer design. Is preferred. Where Vo is the flow rate of the oil phase containing the ceramide compound, and Vw is the flow rate of the poor solvent phase. In addition, the flow rate ratio (Vo / Vw) is 0.1 or more and 3 or less is the most preferable range from the viewpoint of further particle refinement.

Moreover, as the liquid feeding pressure of the poor solvent phase and the oil phase, the poor solvent phase and the oil phase are preferably 0.030 MPa to 5 MPa and 0.010 MPa to 3.0 MPa, and more preferably 0.1 MPa to 2 MPa and 0.2 MPa. ˜1.5 MPa is more preferable, and 0.2 MPa to 1 MPa and 0.04 MPa to 0.6 MPa are particularly preferable. By setting the liquid feeding pressure of the poor solvent phase to 0.030 MPa to 5 MPa, a stable liquid feeding flow rate tends to be maintained, and by setting the liquid feeding pressure of the oil phase to 0.010 MPa to 3.0 MPa, it is uniform. This is preferable because a good mixing property tends to be obtained.
In the present invention, a combination of preferable examples of the flow rate, the liquid supply pressure, and the heat retention temperature is more preferable.

Next, using the example of the microdevice (FIG. 1) as an example of the micromixer in the present invention, the path until the poor solvent phase and the oil phase are introduced into the micromixer and discharged as an oil-in-water emulsion. explain.
As shown in FIG. 1, the microdevice 100 includes a supply element 102, a merging element 104, and a discharge element 106 each having a cylindrical shape.
On the surface of the supply element 102 facing the confluence element 104, annular channels 108 and 110 having a rectangular cross section as a flow path of the oil phase or the poor solvent phase in the present invention are formed concentrically. The feed element 102 is formed with bores 112 and 114 that penetrate in the thickness (or height) direction to the respective annular channels.
The joining element 104 is formed with a bore 116 penetrating in the thickness direction. This bore 116 is such that when the elements are fastened to form the microdevice 100, the end 120 of the bore 116 located in the face of the confluence element 104 facing the supply element 102 opens into the annular channel 108. Yes. In the illustrated embodiment, four bores 116 are formed and are arranged at equal intervals in the circumferential direction of the annular channel 108.

A bore 118 is formed through the confluence element 104 in the same manner as the bore 116. As with the bore 116, the bore 118 is also formed to open to the annular channel 110. The bores 118 are also arranged at equal intervals in the circumferential direction of the annular channel 110, and the bores 116 and the bores 118 are arranged alternately.
Microchannels 124 and 126 are formed on the surface 122 of the confluence element 104 facing the discharge element 106. One end of the microchannel 124 or 126 is the opening of the bore 116 or 118, and the other end is the center 128 of the surface 122, and all microchannels extend from the bore toward the center 128; It meets at the center. The cross section of the microchannel may be rectangular, for example.

The discharge element 106 is formed with a bore 130 that passes through the center thereof and penetrates in the thickness direction. Therefore, this bore opens at the center 128 of the confluence element 104 at one end and opens outside the microdevice at the other end.
In the present microdevice 100, fluids A and B supplied from the outside of the microdevice 100 at the ends of the bores 112 and 114 flow into the annular channels 108 and 110 via the bores 112 and 114, respectively.

The annular channel 108 and the bore 116 communicate with each other, and the fluid A flowing into the annular channel 108 enters the microchannel 124 through the bore 116. In addition, the annular channel 110 and the bore 118 communicate with each other, and the fluid B flowing into the annular channel 110 enters the microchannel 126 via the bore 118. The fluids A and B flow into the microchannels 124 and 126, respectively, and then flow toward the center 128 and merge.
The merged fluid is discharged as a stream C to the outside of the micro device via the bore 130.

Such a micro device 100 can have the following specifications.
Cross-sectional shape of annular channel 108, width / depth / diameter: rectangular, 1.5 / 1.5 / 25mm
Cross-sectional shape, width, depth, diameter of the annular channel 110: rectangular, 1.5 / 1.5 / 20 mm
Diameter and length of bore 112: 1.5 / 10 mm (circular cross section)
Diameter and length of bore 114: 1.5 / 10 mm (circular cross section)
Diameter and length of bore 116: 0.5 / 4 mm (circular cross section)
Diameter and length of bore 118: 0.5 / 4 mm (circular cross section)
Microchannel 124 cross-sectional shape, width, depth, length: rectangle, cross-sectional area,
350 μm / 100 μm / 12.5 mm / 35000 μm ²
Microchannel 126 cross-sectional shape, width, depth, length: rectangle, cross-sectional area,
50 μm / 100 μm / 10 mm / 5000 μm ²
Diameter and length of bore 130: 500 μm, 10 mm (circular cross section)

  The dimensions of the microchannels (124 and 126 in FIG. 1) where the poor solvent phase and the oil phase collide define a preferable range in relation to the flow rate of the poor solvent phase and the oil phase.

In the present invention, a micromixer disclosed in JP-A-2004-33901 can also be used.
FIG. 2 is a schematic cross-sectional view of a T-shaped microreactor showing an example of a mixing mechanism using the T-shaped microreactor.
FIG. 2 shows a cross section of the T-shaped channel 200 of the T-shaped microreactor. In the T-shaped channel 200, the fluid that flows in from the inlet 202 a in the direction of arrow D and the fluid that flows in from the inlet 202 b in the direction of arrow E are in the center of the T-shaped channel 200 in the channel. Colliding and mixing to form fine fluid particles. The formed fine fluid particles flow out from the outlet 204 in the direction of arrow F. This T-shaped microreactor is useful for mixing when the volume of the flow path is small.

  FIG. 3 is a conceptual diagram of a T-shaped microreactor showing another example of a mixing mechanism using a T-shaped microreactor. In the fluid mixing mechanism (concept) 300 of another T-shaped microreactor shown in FIG. 3, the fluid mixing mechanism is configured such that the fluids flowing out from the two flow paths 302a and 302b collide and mix with each other to form a fine granular fluid. It becomes. That is, on the other hand, the fluid flows into the flow path 302a in the direction of arrow G and flows out in the direction of arrow H. On the other hand, it flows into the flow path 302b in the direction of arrow I and flows out in the direction of arrow J. The fluids flowing out from the flow paths 302a and 302b collide, mix, and scatter in a direction approximately perpendicular to the directions of arrows G to J. As described above, the fluid mixing mechanism shown in FIG. 3 collides and mixes the fluid diffused by a technique such as atomization. By this collision / mixing, the fluid becomes finer and a large contact surface can be obtained.

  In the production method of the present invention, the water-soluble organic solvent used is preferably removed after emulsification or dispersion through the microchannel. As a method for removing the solvent, an evaporation method using a rotary evaporator, a flash evaporator, an ultrasonic atomizer or the like, and a membrane separation method such as an ultrafiltration membrane or a reverse osmosis membrane are known, and an evaporator method is particularly preferable.

  Ultrafiltration (abbreviated as UF) is a method of pressurizing a stock solution (mixed aqueous solution of water, high molecular weight material, low molecular weight material, colloidal material, etc.) and injecting it into a UF device, thereby allowing the stock solution to pass through ( It is a device that can be separated into two systems of solution (low molecular weight material) and concentrated liquid (high molecular weight material, colloidal material) and taken out.

  The ultrafiltration membrane is a typical asymmetric membrane made by the Rob-Three Yang method. Examples of the polymer material used include polyacrylonitrile, polyvinyl chloride-polyacrylonitrile copolymer, polysulfone, polyether sulfone, vinylidene fluoride, aromatic polyamide, and cellulose acetate. Recently, ceramic films have been used. Unlike the reverse osmosis method and the like, the ultrafiltration method does not perform pretreatment, and therefore fouling in which a polymer or the like is deposited on the membrane surface occurs. For this reason, it is common to periodically wash the membrane with chemicals or warm water. For this reason, the membrane material is required to have resistance to chemicals and heat resistance. There are various types of membrane modules for ultrafiltration membranes: flat membrane type, tubular type, hollow fiber type, and spiral type. The performance index of the ultrafiltration membrane is a fractional molecular weight, and various membranes ranging from 1,000 to 300,000 are commercially available. Examples of commercially available membrane modules include, but are not limited to, Microzer UF (Asahi Kasei Chemicals Corporation), capillary element NTU-3306 (Nitto Denko Corporation), and the like.

For removing the solvent from the emulsion according to the present invention, the material of the membrane is particularly preferably polysulfone, polyethersulfone, or aromatic polyamide from the viewpoint of solvent resistance. As a form of the membrane module, a flat membrane is mainly used on a laboratory scale, but a hollow fiber type and a spiral type are industrially used, but a hollow fiber type is particularly preferable. The molecular weight cut off varies depending on the type of the active ingredient, but usually a molecular weight in the range of 5,000 to 100,000 is used.
The operating temperature can be from 0 ° C. to 80 ° C., but the range of 10 to 40 ° C. is particularly preferable in consideration of deterioration of the active ingredient.

  Lab-scale ultrafiltration devices include ADVANTEC-UHP (Advantech Co., Ltd.), flow type lab test unit RUM-2 (Nitto Denko Co., Ltd.), etc., using flat membrane modules. Industrially, a plant can be configured by arbitrarily combining the size and number of each membrane module according to the required capacity. As a bench scale unit, RUW-5A (Nitto Denko Corporation) and the like are commercially available.

  In the manufacturing method of this invention, you may add the process of concentrating the obtained emulsion following solvent removal. As a concentration method, the same method and apparatus as the solvent removal such as an evaporation method and a filtration membrane method can be used. In the case of concentration, the ultrafiltration membrane method is a preferred method. Although it is preferable if the same membrane as that used for solvent removal can be used, ultrafiltration membranes having different fractional molecular weights can be used if necessary. It is also possible to increase the concentration efficiency by operating at a temperature different from the solvent removal.

[Particle size]
In the mixing step in the method for producing a ceramide dispersion composition of the present invention, as described above, the oil phase containing the ceramide compound and the poor solvent phase are passed through a specific microchannel and mixed to obtain a volume. It is preferable to obtain dispersed particles having an average particle diameter of 1 nm to 200 nm.
The particle diameter of the dispersed particles is preferably 1 nm to 75 nm or less, more preferably 1 m to 50 nm or less, and most preferably 1 nm to 13 nm.
By setting the dispersed particle diameter of the ceramide dispersion composition to 200 nm or less, the transparency of pharmaceuticals, foods, cosmetics and the like produced using the ceramide dispersion composition of the present invention is hardly deteriorated, and the body, skin absorbability Is preferable in that it is difficult to decrease. Moreover, it is preferable at the point which can improve the skin absorbability of the said ceramide compound by making the dispersion particle diameter of a ceramide dispersion composition 1 nm or more.

The particle diameter of the dispersed particles dispersed in the ceramide dispersion composition of the present invention can be measured with a commercially available particle size distribution meter or the like. When the ceramide dispersion composition of the present invention is, for example, an emulsion, the particle size distribution measurement method of the emulsion includes optical microscopy, confocal laser microscopy, electron microscopy, atomic force microscopy, static light scattering, Laser diffraction methods, dynamic light scattering methods, centrifugal sedimentation methods, electric pulse measurement methods, chromatographic methods, ultrasonic attenuation methods, and the like are known, and devices corresponding to the respective principles are commercially available.
In view of the particle size range and ease of measurement in the present invention, the dynamic light scattering method is preferred for measuring the particle size of the dispersed particles. As a commercially available measuring device using dynamic light scattering, Nanotrac UPA (Nikkiso Co., Ltd.), dynamic light scattering type particle size distribution measuring device LB-550 (Horiba, Ltd.), a concentrated particle size analyzer FPAR-1000 (Otsuka Electronics Co., Ltd.) etc. are mentioned.
The particle diameter in the present invention is a value measured using the dynamic light scattering particle size distribution measuring device LB-550 (Horiba, Ltd.), and specifically, the value measured as follows is adopted. .
The particle diameter is measured by diluting with pure water so that the concentration of the oil phase component is 1% by mass and using a quartz cell. The particle diameter can be obtained as a median diameter when the sample refractive index is 1.600, the dispersion medium refractive index is 1.333 (pure water), and the viscosity of the pure water is set as the dispersion medium viscosity.

  The particle size of the ceramide dispersion composition is not limited to the components of the ceramide dispersion composition described above, but the stirring conditions (shearing force / temperature / pressure) and the use conditions of the micromixer in the mixing step of the method for producing the ceramide dispersion composition described above. It can be refined by factors such as the ratio of oil phase and poor solvent phase.

<Ceramide dispersion composition>
The ceramide dispersion composition of the present invention is a mixture of an oil phase obtained by dissolving an oil phase component containing a ceramide compound represented by the following general formula 1 in a water-soluble organic solvent and a poor solvent phase of the ceramide compound. And at least 10.0% by mass or more of the ceramide compound with respect to the total mass of the oil phase.

In General Formula 1, R ¹ and R ³ each independently represent an alkyl group or alkenyl group having 3 to 60 carbon atoms, or an aryl group having 6 to 60 carbon atoms. R ² represents a hydroxy group, an alkyl group or alkenyl group having 3 to 30 carbon atoms, an aryl group having 6 to 30 carbon atoms, or a phosphocholine group having the following partial structure.

  By making the ceramide dispersion composition of the present invention having the above-described configuration, it can be contained at least 10.0% by mass or more based on the total mass of the oil phase, and the dispersion stability of the dispersed particles dispersed in the ceramide dispersion composition is improved. can do. Therefore, when the ceramide dispersion composition of the present invention is used, for example, for cosmetics, the emollient effect that is an effect of ceramide can be sufficiently exhibited.

The form of the ceramide dispersion composition of the present invention may be an emulsion or a powder dispersion obtained by drying the emulsion. When the ceramide dispersion composition of the present invention is contained in a pharmaceutical, food, cosmetic or the like, it can be used in a form that is easy to contain.
Hereinafter, the present invention will be described in detail. In this specification, the ceramide dispersion composition in an emulsion state will be mainly described.

[Ceramide]
The ceramide dispersion composition of the present invention contains a ceramide compound represented by the following general formula 1 in an oil phase.

In General Formula 1, R ¹ and R ³ each independently represent an alkyl group or alkenyl group having 3 to 60 carbon atoms, or an aryl group having 6 to 60 carbon atoms. R ² represents a hydroxy group, an alkyl group or alkenyl group having 3 to 30 carbon atoms, an aryl group having 6 to 30 carbon atoms, or a phosphocholine group having the following partial structure.

The alkyl group or alkenyl group represented by R ¹ or R ³ in the general formula 1 may be linear, branched or cyclic. Furthermore, it may contain a divalent linking group and may have a substituent. The carbon number of the alkyl group or alkenyl group represented by R ¹ or R ³ in the general formula 1 is 3 to 60 carbon atoms. The number of carbons herein includes the number of carbon atoms of the divalent linking group and substituent that the alkyl group and alkenyl group may have.

Examples of the divalent linking group include a carbonyl group, —OCO—, —COO—, an ether group (oxygen atom), and the like. Examples of the divalent linking group for ^{R 1} or ^{R 3} in the formula 1, a carbonyl group, -OCO-, or COO- is preferred, -OCO-, or COO- is more preferable.

Examples of the substituent include an alkyl group, an alkenyl group, an aryl group, a heterocyclic group, a hydroxy group, an amino group, a carboxy group, a phosphate group, and a phosphate ester group.
The carbon number of the substituent can be used within the range of the carbon number of the alkyl group.
The heterocyclic group is not particularly limited as long as it is a cyclic group having a hetero atom, but has 4 to 6 members having at least one atom selected from the group consisting of a nitrogen atom, an oxygen atom, a sulfur atom and a phosphorus atom. A ring group is preferred, and among them, 2-pyronyl, 2-pyridyl, piperidino, oxacyclohexyl and oxacyclopentyl are preferred, and oxacyclohexyl and piperidino are more preferred.
The phosphate ester group may further have a hydrophilic group.
Examples of the hydrophilic group include an ionic group having a quaternary amine structure, an amide group, and a carboxyl group.

The alkyl group or alkenyl group represented by R ¹ and R ³ in the general formula 1 is preferably linear.
The number of carbon atoms of the alkyl group represented by R ¹ is preferably 6 to 55, more preferably 15 to 50, from the viewpoint of dispersion stability. On the other hand, the number of carbon atoms of the alkyl group represented by R ³ is preferably 6 to 30 and more preferably 9 to 20 from the viewpoint of dispersion stability.

The number of carbon atoms of the alkenyl group represented by R ¹ is preferably 6 to 55, more preferably 15 to 50, from the viewpoint of dispersion stability, while the alkenyl group represented by R ³ The number of carbon atoms in the group is preferably 6 to 30, and more preferably 9 to 20, from the viewpoint of dispersion stability. In the alkenyl group represented as R ¹ or R ³ , the number of unsaturated double bonds is not limited, and two or more may be contained. The number of unsaturated double bonds in the alkenyl group is preferably 2 or 3 from the viewpoint of improving the solubility in a water-soluble organic solvent.

The aryl group represented as R ¹ or R ³ in the general formula 1 has 6 to 60 carbon atoms, and may further have a substituent. The number of carbon atoms of the aryl group includes the number of carbon atoms of the substituent that the aryl group may have.
Here, examples of the substituent that can be included in the aryl group include the substituents mentioned in the description of the alkyl group or alkenyl group, and these substituents are used within the range of the carbon number of the aryl group. Can do.

The number of carbon atoms of the aryl group represented by R ¹ in the general formula 1, from the viewpoint of dispersion stability, preferably from 9-55, more preferably from 15 to 50, whereas, in the general formula 1 The number of carbon atoms of the aryl group represented by R ³ is preferably 9-30, and more preferably 12-20.

In the general formula 1, R ² represents a hydroxy group, an alkyl or alkenyl group having 3 to 30 carbon atoms, an aryl group having 6 to 30 carbon atoms, or a phosphocholine group having the following partial structure (hereinafter simply referred to as “phosphocholine group”). The alkenyl and alkenyl group represented by R ² may further have a substituent and may further contain a divalent linking group.

The alkyl group or alkenyl group represented by R ² may be linear, branched or cyclic. The carbon number of the alkyl group or alkenyl group represented by R ² and the carbon number of the aryl group include the carbon number of the substituent that the alkyl group, alkenyl group, or aryl group may have, respectively.
Here, examples of the substituent and divalent linking group that may be included in the alkyl group, alkenyl group, or aryl group represented by R ² include the substituents exemplified in the description of the alkyl group represented by R ¹ and include a divalent linking group, these substituents and the divalent linking group, it can be used within the scope of the carbon atoms of the alkyl group represented by R ^2.
In General Formula 1, the number of carbon atoms of the aryl group represented by R ² is preferably 6 to 15 from the viewpoint of dispersion stability.
Among the above, R ² is preferably a phosphocholine group from the viewpoint of a structure similar to a natural ceramide compound present in an animal cell membrane and the functionality of the ceramide compound. Specific examples (1-10) described later are given as specific examples in which R ² in General Formula 1 is represented by a phosphocholine group.

  Specific examples of the ceramide compound represented by the general formula 1 as described above include the following, but the present invention is not limited thereto.

  Among the above compounds, (1-1) is ceramide 1, (1-2) is ceramide 9, (1-3) is ceramide 4, (1-4) is ceramide 2, (1-5) is ceramide 3, (1-6) is ceramide 5, (1-7) is ceramide 6, (1-8) is ceramide 7, (1-9) is ceramide 8, (1-11) is a compound known as ceramide 3B It is.

  The content of the ceramide compound may be at least 10.0% by mass relative to the total mass of the oil phase component of the ceramide dispersion composition of the present invention, and is preferably 10% by mass from the viewpoint of dispersion stability. -75 mass%, More preferably, it can be 40 mass%-60 mass%. By setting the content of the ceramide compound to 75% by mass or less, it is possible to prevent poor dispersion.

Here, in the present invention, the “oil phase component” refers to a component in the oil phase excluding a poor solvent typified by water, a water-soluble organic solvent, and a pH adjuster.
In the present invention, the “oil component” refers to a functional oil component such as the ceramide compound, a compound represented by formulas 2 to 6 described later, fats and oils, and vitamins, and includes a surfactant. Absent.

The ceramide dispersion composition of the present invention may contain only one kind or a plurality of kinds of the ceramide compound, but a plurality of ceramides are present in the skin. Therefore, it is preferable to use the ceramide compound in combination.
The ceramide compound can be obtained by synthesis or as a commercial product. For example, the specific example (1-5) is available as “ceramide 3” (trade name), and the specific example (1-7) is available as “ceramide 6” (trade name).

[Water-soluble organic solvent]
The oil phase in the ceramide dispersion composition of the present invention is prepared by dissolving the oil phase component in a water-soluble organic solvent.
By preparing an oil phase containing a ceramide compound using the water-soluble organic solvent, the oil phase and the poor solvent phase can be easily mixed. When the ceramide dispersion composition of the present invention contains a natural product such as a green alga Hematococcus, this aqueous organic solvent can also be used as a main component of an extract for extracting the natural product. That is, the natural product is used for mixing with the poor solvent phase in a state where it is extracted into an extract containing a water-soluble organic solvent as a main component.
The water-soluble organic solvent used in the present invention refers to an organic solvent having a solubility in water at 25 ° C. of 10% by mass or more. The solubility in water is preferably 30% by mass or more, more preferably 50% by mass or more from the viewpoint of the stability of the finished emulsion or dispersion.
The water-soluble organic solvent may be used alone or a mixed solvent of a plurality of water-soluble organic solvents. Moreover, you may use as a mixture with water. When a mixture with water is used, the water-soluble organic solvent is preferably contained at least 50% by volume, more preferably 70% by volume or more.

  Examples of such water-soluble organic solvents include methanol, ethanol, 1-propanol, 2-propanol, 2-butanol, acetone, tetrahydrofuran, acetonitrile, methyl ethyl ketone, dipropylene glycol monomethyl ether, methyl acetate, methyl acetoacetate, N -Methylpyrrolidone, dimethyl sulfoxide, ethylene glycol, 1,3-butanediol, 1,4-butanediol, propylene glycol, diethylene glycol, triethylene glycol and the like and mixtures thereof. Among these, when limited to food applications, ethanol, propylene glycol, or acetone is preferable, and ethanol or a mixed solution of ethanol and water is particularly preferable.

(Stenone, sterol)
The ceramide dispersion composition of the present invention preferably further contains a compound represented by the following general formula 2 in the oil phase, and is also represented by a compound represented by the following general formula 3a and the following general formula 3b. It is preferable to include at least one of the compounds. Here, the compound represented by General Formula 2 and the compound represented by General Formula 3a or General Formula 3b may be used in combination, or only one of them may be used. Moreover, you may use the compound represented by General formula 3a, and the compound represented by General formula 3b simultaneously. Thus, when the ceramide dispersion composition of the present invention contains the compound represented by the general formula 2, the general formula 3a, or the general formula 3b, the dispersion stability of the dispersed particles in the ceramide dispersion composition of the present invention is improved. Can be higher.

In the general formula 2, R ^{5 to} R ⁸ each independently represent a hydrogen atom or a methyl group. R ⁹ represents an alkyl group or alkenyl group having 3 to 30 carbon atoms, a carbonyl group, or an amide group.
In the general formula 3a and the general formula 3b, R ^{10 to} R ¹³ each independently represent a hydrogen atom or a methyl group. R ¹⁴ represents an alkyl group or alkenyl group having 3 to 30 carbon atoms, a carbonyl group, or an amide group. In the general formula 3b, R represents an alkyl group or alkenyl group having 1 to 60 carbon atoms.

  A compound having a skeleton represented by the general formula 2 is generally referred to as stenone. In the present specification, the compound represented by the general formula 2 is appropriately referred to as a “specific stenone compound”. A compound having a skeleton represented by the above general formula 3a is generally called a sterol. In the present specification, the compound represented by the general formula 3a is appropriately referred to as “specific sterol compound”.

R ⁹ in the general formula 2, R ¹⁴ in the general formula 3a and the general formula 3b, and an alkyl group and an alkenyl group represented by R in the general formula 3b are all linear or branched structures. Alternatively, it may be a cyclic structure, and may further have a substituent. The alkyl group and alkenyl group represented by R ⁹ , R ¹⁴ , and R have the same meanings as the alkyl group and alkenyl group in the description of R ¹ and R ^{3 in} the general formula 1, respectively.

The substituents that can be introduced into the alkyl group or alkenyl group represented by R ⁹ , R ¹⁴ , and R are the same as those described in the description of the substituents for R ¹ and R ³ in General Formula 1. And may have a substituent within the range of the carbon number of R ⁹ , R ¹⁴ , and R.

The number of carbon atoms of the alkyl group and alkenyl group represented by R ⁹ and the alkyl group and alkenyl group represented by R ¹⁴ is preferably 6 to 30 from the viewpoint of dispersion stability, More preferably, it is 20.
Moreover, it is preferable that the carbon number of the alkyl group or alkenyl group represented as R in the said General formula 3b is 6-30 from a viewpoint of dispersion stability.

Among the above, R ^{5 to} R ⁸ are preferably hydrogen atoms, and R ⁹ is preferably a 4-ethyl-1,5-dimethylhexyl group or a 1,4,5-trimethylhexyl group.

R ¹⁰ is preferably a methyl group, R ¹¹ is preferably a hydrogen atom, R ¹² is preferably a hydrogen atom, R ¹³ is preferably a methyl group, and R ¹⁴ Is 4-ethyl-1,5-dimethylhexyl group, 1,4,5-trimethylhexyl group, 4-ethyl-1,5-dimethyl-hex-2-en-1-yl group, or 1,4 , 5-trimethyl-hex-2-en-1-yl group is preferred.

A preferable combination of R ^{5 to} R ^{9 and} a preferable combination of R ^{10 to} R ¹⁴ are combinations in the above preferable range.
In general formula 3b, R is preferably an alkyl group or alkenyl group having 3 to 20 carbon atoms from the viewpoint of dispersion stability.

  Specific examples of the compound represented by the general formula 2 include the following.

  Next, specific examples of the compound represented by the general formula 3a include the following.

  Specific examples of the compound represented by the general formula 3b include the following.

The specific stenone compound, the specific sterol compound and the compound represented by the general formula 3b may be used singly or in combination.
The content of the specific stenone compound, when used alone, is 30% by mass to 70% by mass from the viewpoint of dispersion stability with respect to the total mass of the oil phase component of the ceramide dispersion composition of the present invention. Preferably, it is 40 mass%-60 mass%.
When each of the specific sterol compound or the compound represented by the general formula 3b is used alone, it is 20% by mass from the viewpoint of dispersion stability with respect to the total mass of the oil phase component of the ceramide dispersion composition of the present invention. It is preferable that it is -80 mass%, and it is more preferable that it is 30 mass%-70 mass%.
When the specific stenone compound, the specific sterol compound, and the compound represented by the general formula 3b are used in combination, the total content of the combined compounds is the oil phase component of the ceramide dispersion composition of the present invention. From the viewpoint of dispersion stability, the content is preferably 30% by mass to 70% by mass, and more preferably 40% by mass to 60% by mass.

  The specific stenone compound, the sterol compound, and the compound represented by the general formula 3b can be obtained by synthesis or as a commercial product.

(Ceramide containing sugars)
The ceramide dispersion composition of the present invention preferably further contains a compound represented by the following general formula 4 in the oil phase. The compound represented by the following general formula 4 corresponds to a ceramide compound containing a saccharide in the molecule. Dispersion particles of the ceramide dispersion composition of the present invention by containing a compound represented by the following general formula 4 (hereinafter also referred to as “specific sugar ceramide compound”) in the oil phase of the ceramide dispersion composition of the present invention. The dispersion stability of can be further improved.

In the general formula 4, R ¹⁵ represents an alkyl group or alkenyl group having 3 to 60 carbon atoms, or an aryl group having 6 to 60 carbon atoms. R ¹⁶ represents an alkyl group or alkenyl group having 3 to 60 carbon atoms. R ¹⁷ represents a saccharide.

The alkyl group or alkenyl group represented by R ¹⁵ or R ¹⁶ in the general formula 4 may be linear, branched, or cyclic. Furthermore, it may contain a divalent linking group and may have a substituent. Number of carbon atoms in the alkyl group or alkenyl group represented as R ¹⁵ or R ¹⁶ in the general formula 4, a divalent linking group and substituent of the alkyl group or alkenyl group represented as R ¹⁵ or R ¹⁶ may have The number of carbon atoms is included.
Here, as the divalent linking group and substituent that may be contained in the alkyl group or alkenyl group represented by R ¹⁵ or R ¹⁶ , the alkyl group or alkenyl represented by R ¹ or R ³ in the above general formula 1 Examples thereof include the divalent linking groups and substituents mentioned in the description of the groups, and these groups can be used within the range of the carbon number of the alkyl group or alkenyl group represented by R ¹⁵ or R ¹⁶ .

From the viewpoint of dispersion stability, the number of carbon atoms of the alkyl group or alkenyl group represented by R ¹⁵ in the general formula 4 is preferably 6 to 55, and more preferably 15 to 50.

The number of carbon atoms of the alkyl group represented by R ¹⁶ in the general formula 4 is preferably 6-30, more preferably 9-20, from the viewpoint of dispersion stability.
From the viewpoint of dispersion stability, the number of carbon atoms of the alkenyl group represented by R ¹⁶ in the general formula 4 is preferably 6 to 55, and more preferably 15 to 50.

The aryl group represented by R ¹⁵ in the general formula 4 has 3 to 60 carbon atoms, and may further have a substituent. The number of carbon atoms of the aryl group includes the number of carbon atoms of the substituent that the aryl group may have.
Here, examples of the substituent that can be included in the aryl group represented by R ¹⁵ include the substituents exemplified in the description of the alkyl group represented by R ¹ or R ³ in the general formula 1, and these substitutions based on, it can be used within the scope of the number of carbon atoms of the aryl group represented by R ^15.

In the general formula 4, the number of carbon atoms of the aryl group represented by R ¹⁵ is preferably 6 to 55, more preferably 15 to 50, from the viewpoint of dispersion stability.

The saccharide represented as R ¹⁷ in the general formula 4 refers to a saccharide having 1 to 100,000 saccharide units, such as monosaccharides such as glucose and galactose, disaccharides such as lactose and maltose, and And oligosaccharides and polysaccharides obtained by polymerizing these monosaccharides and disaccharides by glucoside bonds. Further, the sugar unit may be a sugar derivative in which the hydroxyl group is replaced with another group. For example, there are glucosamine, cururonic acid, N-acetylglucosamine and the like.
Among these, from the viewpoint of dispersion stability, saccharides having 1 to 5 saccharide units are preferable. Specifically, glucose and lactose are preferable, and glucose is more preferable.
A preferred combination of R ^{15 to} R ^{17 is} a combination in the above preferred range.

  Specific examples of the compound represented by the general formula 4 (specific sugar ceramide compound) include the following.

The specific sugar ceramide compounds may be used alone or in combination of two or more.
The content of the specific sugar ceramide compound with respect to the total mass of the oil phase component of the ceramide dispersion composition of the present invention is preferably 10% by mass to 70% by mass from the viewpoint of dispersion stability. More preferably, it is 50 mass%.
Further, the ratio (mass ratio) of the specific sugar ceramide compound to the ceramide compound is preferably 20% by mass or more, and more preferably 30% by mass or more.

  The specific sugar ceramide compound can be obtained by synthesis or as a commercial product. For example, the specific example (4-1) can be obtained as “comesfingo glycolipid” (trade name).

(General Formula 5, General Formula 6)
The ceramide dispersion composition of the present invention preferably further contains at least one compound represented by the following general formula 5 and the following general formula 6 in the oil phase.
The compound represented by the following general formula 5 or the following general formula 6 (generally called “phytosphingosine”) can stabilize the dispersion of the ceramide compound, and as a result, the oil of the ceramide dispersion composition of the present invention. By containing it in the phase, the stability of the dispersed particles can be enhanced.

In the general formula 5, R ¹⁸ represents an alkyl group or alkenyl group having 3 to 60 carbon atoms. X represents a single bond or a divalent linking group, and R ²¹ represents a hydrogen atom, an alkyl group or alkenyl group having 3 to 60 carbon atoms, or an aryl group having 6 to 60 carbon atoms.

In the general formula 6, R ¹⁹ represents an alkyl group having 3 to 60 carbon atoms. R ²⁰ represents a hydroxy group or an alkyl group having 3 to 60 carbon atoms. X represents a single bond or a divalent linking group,
R ²¹ represents a hydrogen atom, an alkyl group or alkenyl group having 3 to 60 carbon atoms, or an aryl group having 6 to 60 carbon atoms.

The alkyl group or alkenyl group represented by R ¹⁸ or the alkyl group represented by R ¹⁹ may be linear, branched or cyclic. Furthermore, it may contain a divalent linking group and may have a substituent. Alkyl or alkenyl group represented as the R ^18, or the number of carbon atoms in the alkyl group represented by the R ¹⁹ is alkyl, expressed as the alkyl group or alkenyl group represented as R ¹⁸ or said R ^19, The divalent linking group that the group may have and the number of carbon atoms of the substituent are included.
Here, as the divalent linking group and substituent that may be included in the alkyl group or alkenyl group represented by R ¹⁸ or the alkyl group represented by R ¹⁹ , R ¹ or R in General Formula ¹ may be used. ^And divalent linking groups and substituents mentioned in the description of the alkyl group or alkenyl group represented as ³ , and these groups as the alkyl group or alkenyl group represented as R ¹⁸ or R ¹⁹ It can be used within the range of the carbon number of the alkyl group represented.

The alkyl group or alkenyl group represented by R ¹⁸ or R ¹⁹ is preferably a straight chain. Among these, from the viewpoint of dispersion stability, the alkyl group or alkenyl group represented by R ¹⁸ or R ¹⁹ preferably has 6 to 55 carbon atoms, and more preferably 6 to 12 carbon atoms.

The divalent linking group represented by X has the same meaning as the divalent linking group in the description of R ¹ and R ^{3 in} the general formula 1. The divalent linking group represented by X is preferably a carbonyl group, —OCO—, or COO—, and more preferably a carbonyl group.

The aryl group represented by R ²¹ may be a monocyclic group such as a phenyl group, a bicyclic group such as a naphthyl group, or a polycyclic group, and may further have a substituent. .
The number of carbon atoms of the aryl group represented by ²¹ is preferably 6-30, more preferably 9-20, from the viewpoint of dispersion stability.
Note that the range of the carbon number of the aryl group represented by R ²¹ does not include the carbon number of the substituent. The number of carbon atoms of the substituent that the aryl group represented by R ²¹ may have is preferably 1 to 10.

Specific examples of the aryl group represented by R ²¹ include a phenyl group, a naphthyl group, and a tolyl group. A tolyl group is preferable, and an o-tolyl group is more preferable.

A preferable combination of R ¹⁸ , X, and R ²¹ in the general formula 5 and a preferable combination of R ¹⁹ , R ²⁰ , X, and R ^{21 in} the general formula 6 are combinations in the above preferable range.

  Specific examples of the compound represented by the general formula 5 or the general formula 6 include the following.

The compound represented by the general formula 5 and the compound represented by the general formula 6 may each be a single species or a plurality of species, or both of them may be used in combination.
Content of the compound represented by the general formula 5 and the compound represented by the general formula 6 (when the compound represented by the general formula 5 and the compound represented by the general formula 6 are used in combination, the total content) Is preferably 10% by mass to 90% by mass and more preferably 30% by mass to 90% by mass with respect to the total mass of the oil phase component of the ceramide dispersion composition of the present invention from the viewpoint of dispersion stability. Is more preferable.

  The compound represented by the general formula 5 and the compound represented by the general formula 6 can be obtained by synthesis or as a commercial product. For example, the specific example (5-5) is available as “phytosphingosine” (trade name).

[Other oily ingredients]
The ceramide dispersion composition of the present invention can contain other oil components in the oil phase in addition to the compounds represented by the general formulas 1 to 6.
For example, when the ceramide dispersion composition of the present invention is used for cosmetics, foods, or pharmaceuticals, it is a functional material for cosmetics, a functional material for foods, or a pharmaceutical that is insoluble or hardly soluble in an aqueous medium, particularly water. The functional material for use is preferably contained as an oil component. The ceramide dispersion composition of the present invention contains a functional oil component such as astaxanthin, which will be described later, so that when the ceramide dispersion composition of the present invention is used for cosmetics, for example, an ingredient having an emollient effect and aging Cosmetics containing simultaneously the component which has an inhibitory effect and an antioxidant effect can be obtained.
The oily component that can be used in the present invention is not particularly limited as long as it is a component that is insoluble or hardly soluble in water and dissolves in the oily medium, but oils such as carotenoids and tocopherols. Radical scavengers containing soluble vitamins and fats and oils such as coconut oil are preferably used.
The term “insoluble in an aqueous medium” means that the solubility in 100 mL of the aqueous medium is 0.01 g at 25 ° C., and the term “insoluble in an aqueous medium means that the solubility in 100 mL of the aqueous medium is 0. It means exceeding 01 g and 0.1 g or less.

(Carotenoids)
As the oil component, carotenoids containing natural pigments can be preferably used.
The carotenoids that may be contained in the ceramide dispersion composition of the present invention are pigments of yellow to red terpenoids, and include natural products such as plants, algae, and bacteria.
Moreover, it is not limited to the thing of natural origin, Any thing will be contained in the said carotenoid if it can be obtained in accordance with a conventional method. For example, many of the carotenoids described below are produced by synthesis, and many commercially available β-carotene is produced by synthesis.

Examples of carotenoids include hydrocarbons (carotenes) and oxidized alcohol derivatives thereof (xanthophylls).
Examples of carotenoids include actinioerythrol, astaxanthin, bixin, canthaxanthin, capsanthin, capsorbin, β-8′-apo-carotenal (apocarotenal), β-12′-apo-carotenal, α-carotene, β-carotene, “Carotene” (mixture of α- and β-carotenes), γ-carotene, β-cryptoxanthin, lutein, lycopene, biorelythrin, zeaxanthin, and esters of those containing hydroxyl or carboxyl.

Many of the carotenoids occur naturally in the form of cis and trans isomers, but the composites are often racemic mixtures.
Carotenoids can generally be extracted from plant materials. These carotenoids have a variety of functions, for example, lutein extracted from marigold petals is widely used as an ingredient in poultry food and colors poultry skin and fat and eggs produced by poultry There is a function.

  In the present invention, carotenoids that are particularly preferably used include astaxanthin and astaxanthin, which are known as colorants in the yellow to red range, which have an antioxidant effect, an anti-inflammatory effect, a skin aging preventive effect, a whitening effect, and the like. It is at least one of derivatives such as esters (hereinafter collectively referred to as “astaxanthins”).

Examples of the natural product include red yeast Phaffia, green alga Hematococcus, marine bacteria, krill, and the like. Moreover, the extract from the culture etc. can be mentioned.
The astaxanthin may be contained in the emulsion composition of the present invention as an astaxanthin-containing oil separated and extracted (and appropriately purified as necessary) from other natural products containing the astaxanthins.

At least one of the astaxanthin and its ester (astaxanthins) may be contained in the ceramide dispersion composition of the present invention as an astaxanthin-containing oil separated and extracted from a natural product containing at least one of astaxanthin and its ester. . Examples of such astaxanthin-containing oils include red yeast paffia, green algae hematococcus, marine bacteria, and the like, and extracts from the cultures, extracts from Antarctic krill, and the like.
It is known that the Haematococcus alga extract (haematococcus alga-derived pigment) differs from the krill-derived pigment and the synthesized astaxanthin in terms of the type of ester and its content.

Astaxanthins that can be used in the present invention may be the above-mentioned extract, or a product obtained by appropriately purifying the extract as necessary, or a synthetic product.
As the astaxanthins, those extracted from Haematococcus alga (also referred to as Haematococcus alga extract) are particularly preferred from the viewpoint of quality and productivity.

  Specific examples of the haematococcus alga extract that can be used in the present invention include Haematococcus pluviaris, Haematococcus lacustris, Examples thereof include Haematococcus droebakensis, Haematococcus zimbabiensis, and the like.

  In addition, in the present invention, commercially available Haematococcus alga extract can be used. For example, ASTOTS-S, -2.5 O, -5 O, and -10 manufactured by Takeda Shiki Co., Ltd. O, etc., Fuji Chemical Industry Co., Ltd. Asteril Oil 50F, 5F, etc., Toyo Enzyme Chemical Co., Ltd. BioAstin SCE7 etc. are available.

The content of astaxanthin as a pure pigment content in the Haematococcus alga extract that can be used in the present invention is preferably 0.001 to 50% by mass, more preferably from the viewpoint of handling during the production of the ceramide dispersion composition. Is 0.01 to 25% by mass.
The Haematococcus alga extract that can be used in the present invention contains astaxanthin or an ester thereof as the pure pigment as in the pigment described in JP-A-2-49091, but the ester is generally 50 mol%. As mentioned above, it contains 75 mol% or more, more preferably 90% mol or more.
For more detailed explanation, see “Astaxanthin Chemistry”, 2005, Internet <URL: http: // www. astaxanthin. co. jp / chemical / basic. htm>.

(Oils and fats)
Examples of the fats and oils in the oil component include liquid fats and oils (fatty oils) and solid fats and oils (fats) at room temperature.
Examples of the liquid oil include olive oil, camellia oil, macadamia nut oil, castor oil, avocado oil, evening primrose oil, turtle oil, corn oil, mink oil, rapeseed oil, egg yolk oil, sesame oil, persic oil, wheat germ oil, and sasanca Oil, flaxseed oil, safflower oil, cottonseed oil, eno oil, soybean oil, peanut oil, tea seed oil, kaya oil, rice bran oil, cinnagari oil, Japanese kiri oil, jojoba oil, germ oil, triglycerin, glycerin trioctanoate, Examples include glycerin triisopalmitate, salad oil, safflower oil (safflower oil), palm oil, coconut oil, peanut oil, almond oil, hazelnut oil, walnut oil, and grape seed oil.
Moreover, as the solid fats and oils, beef tallow, hardened beef tallow, beef leg fat, beef bone fat, mink oil, egg yolk oil, pork tallow, horse fat, sheep fat, hardened oil, cocoa butter, palm oil, hardened palm oil, Palm oil, palm hardened oil, owl, owl kernel oil, hardened castor oil and the like can be mentioned.
Among these, coconut oil, which is a medium chain fatty acid triglyceride, is preferably used from the viewpoint of the dispersed particle size and stability of the ceramide dispersion composition.

  In the present invention, commercially available products can be used as the fats and oils. Moreover, in this invention, the said fats and oils may be used individually by 1 type, or may be mixed and used.

  Examples of the compound having phenolic OH include polyphenols (for example, catechin), guaiac fat, nordihydroguaiaretic acid (NDGA), gallic acid esters, BHT (butylhydroxytoluene), BHA (butylhydroxyanisole), vitamins E, bisphenols, etc. are mentioned. Examples of gallic acid esters include propyl gallate, butyl gallate, and octyl gallate.

  Examples of the amine compound include phenylenediamine, diphenyl-p-phenylenediamine, and 4-amino-p-diphenylamine, and diphenyl-p-phenylenediamine and 4-amino-p-diphenylamine are more preferable.

  Examples of oil-solubilized derivatives of ascorbic acid and erythorbic acid include stearic acid L-ascorbyl ester, tetraisopalmitic acid L-ascorbyl ester, palmitic acid L-ascorbyl ester, palmitic acid erythorbyl ester, tetraisopalmitic acid erythorbyl ester, etc. Is mentioned.

Among these, vitamin E is particularly preferably used from the viewpoint of excellent safety and antioxidant function.
Vitamin E is not specifically limited, For example, what is chosen from the compound group which consists of tocopherol and its derivative (s), and the compound group which consists of tocotrienol and its derivative (s) can be mentioned. These may be used alone or in combination. Moreover, you may use combining the compound group which consists of a tocophenol and its derivative, and each selected from the compound group which consists of a tocotrienol and its derivative, respectively.

The compound group consisting of tocopherol and its derivatives includes dl-α-tocopherol, dl-β-tocopherol, dl-γ-tocopherol, dl-δ-tocopherol, dl-α-tocopherol acetate, nicotinic acid-dl-α-tocopherol Linoleic acid-dl-α-tocopherol, succinic acid dl-α-tocopherol and the like. Among these, dl-α-tocopherol, dl-β-tocopherol, dl-γ-tocopherol, dl-δ-tocopherol, and a mixture thereof (mixed tocopherol) are more preferable. In addition, as the tocopherol derivative, these acetates are preferably used.
The compound group consisting of tocotrienol and derivatives thereof includes α-tocotrienol, β-tocotrienol, γ-tocotrienol, δ-tocotrienol and the like. In addition, as the tocotrienol derivative, these acetates are preferably used. Tocotrienol is a tocopherol-like compound contained in wheat, rice bran, palm oil, and the like, and has three double bonds in the side chain portion of tocopherol and has excellent antioxidant performance.

  It is preferable that these vitamin Es are contained in the ceramide dispersion composition as an oil-soluble antioxidant, particularly in the oil phase, because the antioxidant function of the oil component can be effectively exhibited. Among the above vitamin E, it is more preferable to contain at least one selected from the group of compounds consisting of tocotrienol and derivatives thereof from the viewpoint of the antioxidant effect.

The content of the oil component in the ceramide dispersion composition of the present invention is the oil phase component of the ceramide dispersion composition from the viewpoint of application to pharmaceuticals, foods and cosmetics, and from the viewpoint of dispersion particle size and emulsion stability. Preferably they are 0.1 mass%-50 mass% with respect to the total mass, More preferably, they are 0.2 mass%-25 mass%, More preferably, they are 0.5 mass%-10 mass%.
When the content of the oil component is 0.1% by mass or more, the efficacy of an active ingredient such as a ceramide compound can be sufficiently exerted, so that the emulsion composition can be easily applied to pharmaceuticals, foods, and cosmetics. On the other hand, when it is 50% by mass or less, it is difficult to increase the dispersed particle size and to deteriorate the emulsion stability.

[Surfactant]
The ceramide dispersion composition of the present invention may contain a surfactant in the oil phase.
As described above, the emulsification stability of the dispersed particles can be improved by containing the specific stenone compound or the specific sterol compound in the ceramide dispersion composition of the present invention. In place of the specific sterol compound, or in addition to the specific stenone compound or the specific sterol compound, even when a surfactant is used, the emulsion stability and dispersion stability of the dispersed particles can be improved.

The surfactant in the present invention is preferable in that the interfacial tension between the oil phase and the poor solvent phase in the ceramide dispersion composition can be greatly reduced, and as a result, the particle diameter can be reduced.
The surfactant in the present invention is preferably an HLB of 8 or more, more preferably 10 or more, and particularly preferably 12 or more, from the viewpoint of emulsion stability. Moreover, although the upper limit of an HLB value is not specifically limited, Generally, it is 20 or less, and 18 or less is preferable.

  Here, HLB is a hydrophilic-hydrophobic balance that is usually used in the field of surfactants, and a commonly used calculation formula such as the Kawakami formula can be used. In the present invention, the following Kawakami equation is adopted.

HLB = 7 + 11.7 log (M _w / M ₀ )
Here, the molecular weight M _w of the hydrophilic group, M ₀ is the molecular weight of the hydrophobic group.

Moreover, you may use the numerical value of HLB described in the catalog etc.
Further, as can be seen from the above formula, a surfactant having an arbitrary HLB value can be obtained by utilizing the additivity of HLB.

  Examples of the surfactant that can be used in the present invention include cationic, anionic, amphoteric, and nonionic surfactants, and there is no particular limitation, but nonionic surfactants are preferred. . Examples of nonionic surfactants include glycerin fatty acid ester, organic acid monoglyceride, polyglycerin fatty acid ester, propylene glycol fatty acid ester, polyglycerin condensed ricinoleic acid ester, sorbitan fatty acid ester, sucrose fatty acid ester, polyoxyethylene sorbitan Examples include fatty acid esters. More preferred are polyglycerin fatty acid ester, sorbitan fatty acid ester, sucrose fatty acid ester, and polyoxyethylene sorbitan fatty acid ester. In addition, the surfactant described above is not necessarily highly purified by distillation or the like, and may be a reaction mixture.

The polyglycerin fatty acid ester used in the present invention has an average degree of polymerization of 2 or more, preferably 6 to 15, more preferably 8 to 10 and fatty acid having 8 to 18 carbon atoms, such as caprylic acid and caprin. Esters with acids, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, and linoleic acid. Preferred examples of polyglycerol fatty acid esters include hexaglycerol monooleate, hexaglycerol monostearate, hexaglycerol monopalmitate, hexaglycerol monomyristate, hexaglycerol monolaurate, decaglycerol monooleate , Decaglycerin monostearic acid ester, decaglycerin monopalmitic acid ester, decaglycerin monomyristic acid ester, decaglycerin monolauric acid ester and the like.
Among these, more preferably, decaglycerol monooleate (HLB = 12), decaglycerol monostearate (HLB = 12), decaglycerol monopalmitate (HLB = 13), decaglycerol monomyristate (HLB = 14), decaglycerin monolaurate (HLB = 16), and the like.
These polyglycerin fatty acid esters can be used alone or in combination.
Examples of commercially available products include Nikko Chemicals, Inc., NIKKOL DGMS, NIKKOL DGMO-CV, NIKKOL DGMO-90V, NIKKOL DGDO, NIKKOL DGMIS, NIKKOL DGTI, NIKKOL DGTI, NIKKOL DGTI Tetraglyn 3-S, NIKKOL Tetraglyn 5-S, NIKKOL Tetraglyn 5-O, NIKKOL Hexaglyn 1-L, NIKKOL Hexaglyn 1-M, NIKKOL Hexaglyn 1-SV, NIKKOL Hexaglyn 1-O, NIKKOL Hexaglyn 3-S, NIKKOL Hexaglyn 4 -B, NIKKOL Hexaglyn 5-S, IKKOL Hexaglyn 5-O, NIKKOL Hexaglyn PR-15, NIKKOL Decaglyn 1-L, NIKKOL Decaglyn 1-M, NIKKOL Decaglyn 1-SV, NIKKOL Decaglyn 1-50SV, NIKKOL Decaglyn 1-ISV, NIKKOL Decaglyn 1-O, NIKKOL Decaglyn 1-OV, NIKKOL Decaglyn 1-LN, NIKKOL Decaglyn 2-SV, NIKKOL Decaglyn 2-ISV, NIKKOL Decaglyn 3-SV, NIKKOL Decaglyn 3-OV, NIKKOL Decaglyn 5-SV, NIKKOL Decaglyn 5-HS, NIKKOL Decaglyn 5- I , NIKKOL Decaglyn 5-OV, NIKKOL Decaglyn 5-O-R, NIKKOL Decaglyn 7-S, NIKKOL Decaglyn 7-O, NIKKOL Decaglyn 10-SV, NIKKOL Decaglyn 10-IS, NIKKOL Decaglyn 10-OV, NIKKOL Decaglyn 10-MAC , NIKKOL Decaglyn PR-20, Ryoto polyglycerase manufactured by Mitsubishi Chemical Foods, Inc., L-7D, L-10D, M-10D, P-8D, SWA-10D, SWA-15D, SWA-20D, S- 24D, S-28D, O-15D, O-50D, B-70D, B-100D, ER-60D, LOP-120DP, DS13W, DS3, HS11, HS9, TS4, S2, DL15, DO13, Sunsoft Q-17UL, Sunsoft Q-14S, Sunsoft A-141C, Riken Vitamin Co., Ltd. Poem DO-100, Poem J-0021, etc. It is done.
Among these, preferably, NIKKOL Decaglyn 1-L, NIKKOL Decaglyn 1-M, NIKKOL Decaglyn 1-SV, NIKKOL Decaglyn 1-50SV, NIKKOL Decaglyn 1-ISV, NIKKOL Decaglyn 1-O, NIKKOL Decaglyn 1-OV, NIKKOL Decaglyn 1-LN, Ryoto-polyglycerester L-7D, L-10D, M-10D, P-8D, SWA-10D, SWA-15D, SWA-20D, S-24D, S-28D, O-15D, O -50D, B-70D, B-100D, ER-60D, LOP-120DP.

The sorbitan fatty acid ester used in the present invention preferably has a fatty acid having 8 or more carbon atoms, more preferably 12 or more. Preferred examples of the sorbitan fatty acid ester include sorbitan monocaprylate, sorbitan monolaurate, sorbitan monostearate, sorbitan sesquitite, sorbitan tristearate, sorbitan isostearate, sorbitan sesquiisostearate, sorbitan oleate, sorbitan sesquioleate, And sorbitan trioleate.
These sorbitan fatty acid esters can be used alone or in combination.
As a commercial item, Nikko Chemicals Co., Ltd. make, NIKKOL SL-10, SP-10V, SS-10V, SS-10MV, SS-15V, SS-30V, SI-10RV, SI-15RV, SO-15 10V, SO-15MV, SO-15V, SO-30V, SO-10R, SO-15R, SO-30R, SO-15EX, manufactured by Daiichi Kogyo Seiyaku Co., Ltd., Sorgen 30V, 40V, 50V, 90, 110, manufactured by Kao Corporation, Rheodor AS-10V, AO-10V, AO-15V, SP-L10, SP-P10, SP-S10V, SP-S30V, SP-O10V, SP-O30V and the like. .

The sucrose fatty acid ester used in the present invention preferably has a fatty acid having 12 or more carbon atoms, more preferably 12-20.
Preferred examples of sucrose fatty acid esters include sucrose dioleate, sucrose distearate, sucrose dipalmitate, sucrose dimyristic ester, sucrose dilaurate, sucrose monooleate, sucrose Examples include sugar monostearate, sucrose monopalmitate, sucrose monomyristic ester, and sucrose monolaurate. Among these, sucrose monooleate, sucrose monostearate, sucrose Monopalmitate, sucrose monomyristate, and sucrose monolaurate are more preferable.
In the present invention, these sucrose fatty acid esters can be used alone or in combination.
Examples of commercially available products include Ryoto Sugar Esters S-070, S-170, S-270, S-370, S-370F, S-570, S-770, and S-970 manufactured by Mitsubishi Chemical Foods Corporation. , S-1170, S-1170F, S-1570, S-1670, P-070, P-170, P-1570, P-1670, M-1695, O-170, O-1570, OWA-1570, L -195, L-595, L-1695, LWA-1570, B-370, B-370F, ER-190, ER-290, POS-135, DK ester SS manufactured by Daiichi Kogyo Seiyaku Co., Ltd., F160, F140, F110, F90, F70, F50, F-A50, F-20W, F-10, F-A10E, Cosmelike B-30, S-10, S-50, S-70, S -110, S-160, S-190, SA-10, SA-50, P-10, P-160, M-160, L-10, L-50, L-160, L-150A, L-160A , R-10, R-20, O-10, O-150 and the like.
Among the above, preferably Leutou Sugar Esters S-1170, S-1170F, S-1570, S-1670, P-1570, P-1670, M-1695, O-1570, L-1695, DK Esters SS, F160, F140, F110, cosmetics S-110, S-160, S-190, P-160, M-160, L-160, L-150A, L-160A, O-150.

The polyoxyethylene sorbitan fatty acid ester used in the present invention preferably has a fatty acid having 8 or more carbon atoms, more preferably 12 or more. Moreover, as length (addition mole number) of the ethylene oxide of polyoxyethylene, 2-100 are preferable and 4-50 are more preferable.
Preferable examples of polyoxyethylene sorbitan fatty acid ester include sorbitan polyoxyethylene monocaprylate, sorbitan polyoxyethylene monolaurate, sorbitan polyoxyethylene monostearate, sorbitan polyoxyethylene sesquistearate, sorbitan polyoxyethylene tristearate Sorbitan polyoxyethylene isostearate, sorbitan polyoxyethylene sesquiisostearate, sorbitan polyoxyethylene oleate, sorbitan polyoxyethylene sesquioleate, sorbitan polyoxyethylene trioleate, and the like.
These polyoxyethylene sorbitan fatty acid esters can be used alone or in combination.
As a commercial item, Nikko Chemicals Co., Ltd. make, NIKKOL TL-10, NIKKOL TP-10V, NIKKOL TS-10V, NIKKOL TS-10MV, NIKKOL TS-106V, NIKKOL TS-30V, NIKKOL TS-30V, NIKOL TS-30V NIKKOL TO-10V, NIKKOL TO-10MV, NIKKOL TO-106V, NIKKOL TO-30V, manufactured by Kao Corporation, Rheodor TW-L106, TW-L120, TW-P120, TW-S106V, TW-S120V, TW -S320V, TW-O106V, TW-O120V, TW-O320V, TW-IS399C, Rheodor Super SP-L10, TW-L120, manufactured by Daiichi Kogyo Seiyaku Co., Ltd., Sorgen TW-20, TW-60V, TW 80V, and the like.

In the present invention, lecithin can be used in combination with the water-soluble nonionic surfactant. The lecithin used in the present invention comprises a glycerin skeleton, a fatty acid residue and a phosphate residue as essential components, and a base, a polyhydric alcohol and the like bound thereto, and is also referred to as a phospholipid.
Since lecithin has a hydrophilic group and a hydrophobic group in the molecule, it has been widely used as an emulsifier in the food, pharmaceutical and cosmetic fields.

  Industrially, lecithin having a purity of 60% or more is used as lecithin and can be used in the present invention. However, from the viewpoint of formation of fine oil droplet size and stability of functional oily components, it is generally high. This is called purity lecithin, which has a lecithin purity of 80% or more, more preferably 90% or more.

Examples of lecithin include various conventionally known ones extracted and separated from plants, animals and microorganisms.
Specific examples of such lecithin include various lecithins derived from plants such as soybean, corn, peanut, rapeseed and wheat, animals such as egg yolk and cattle, and microorganisms such as Escherichia coli.
Examples of such lecithins by their compound names include phosphatidic acid, phosphatidylglycerin, phosphatidylinositol, phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylcholine, phosphatidylserine, bisphosphatidic acid, diphosphatidylglycerin (cardiolipin) and the like; sphingomyelin And the like can be mentioned.
In the present invention, hydrogenated lecithin, enzymatically decomposed lecithin, enzymatically decomposed hydrogenated lecithin, hydroxylecithin, and the like can be used in addition to the high-purity lecithin described above. These lecithins that can be used in the present invention can be used alone or in the form of a mixture of plural kinds.

The amount of the surfactant in the ceramide dispersion composition of the present invention exceeds 0.5 times on a mass basis with respect to the total mass of the oil component, and 5 times on a mass basis with respect to the amount of phospholipid. An amount exceeding is preferred. By making the amount of the surfactant 0.5 times or more with respect to the total mass of the oil component, an emulsion having a fine particle diameter can be obtained, and more than 5 times with respect to the amount of phospholipid. Thus, it is possible to make it difficult to impair the emulsion stability. Such an amount of the surfactant can make the emulsion stability remarkably good especially when ascorbic acid, citric acid, or a salt thereof and the like are simultaneously present in the composition.
In order to obtain a fine particle size, the surfactant amount relative to the total mass of the oil component is preferably more than 0.5 times by mass, more preferably 2 times or less, and more preferably 1.5 times or less. Is more preferable, and an amount of 1 times or less is particularly preferable. By making the amount of the surfactant 2 times or less, it is preferable in that the problem that foaming becomes severe tends to be eliminated.
In order to improve the emulsion stability, the surfactant amount relative to the phospholipid amount is preferably more than 5 times, more preferably 50 times or less, and even more preferably 30 times or less on a mass basis. The amount is preferably 15 times or less. When the amount of the surfactant is 50 times or less, the particle size can be reduced to an appropriate amount for emulsification stability, and the tendency to suppress the occurrence of problems such as foaming of the composition can be suppressed. It is preferable.

0.5-30 mass% is preferable with respect to a ceramide dispersion composition, and, as for the addition amount of the said surfactant, 1-20 mass% is more preferable, and 2-15 mass% is still more preferable.
By setting the surfactant amount (addition amount to the ceramide dispersion composition) to 0.5% by mass or more, the interfacial tension between the oil phase and the poor solvent phase can be easily lowered, and by setting it to 30% by mass or less, It is preferable in that it does not cause an excessive amount of the ceramide dispersion composition to cause problems such as excessive foaming.

[Polyhydric alcohol]
The ceramide dispersion composition of the present invention preferably contains a polyhydric alcohol from the viewpoints of particle diameter, stability, and antiseptic properties.
The polyhydric alcohol has a moisturizing function and a viscosity adjusting function. The polyhydric alcohol also has a function of reducing the interfacial tension between water and an oil and fat component, facilitating the widening of the interface, and facilitating the formation of fine and stable fine particles.
From the above, the fact that the ceramide dispersion composition contains a polyhydric alcohol can make the dispersed particle size of the ceramide dispersion composition finer, and the particle size is stable over a long period of time in a fine particle size state. It is preferable from the viewpoint that it can be held.
Moreover, the addition of a polyhydric alcohol can reduce the water activity of the ceramide dispersion composition and suppress the growth of microorganisms.

The polyhydric alcohol that can be used in the present invention is not particularly limited as long as it is a dihydric or higher alcohol.
Examples of the polyhydric alcohol include glycerin, diglycerin, triglycerin, polyglycerin, 3-methyl-1,3-butanediol, 1,3-butylene glycol, isoprene glycol, polyethylene glycol, and 1,2-pentanediol. 1,2-hexanediol, propylene glycol, dipropylene glycol, polypropylene glycol, ethylene glycol, diethylene glycol, pentaerythritol, neopentyl glycol, maltitol, reduced starch syrup, sucrose, lactitol, palatinit, erythritol, sorbitol, mannitol, xylitol, Xylose, glucose, lactose, mannose, maltose, galactose, fructose, inositol, pentaerythritol, maltoto Orth, sorbitan, trehalose, starch degradation sugars, starch decomposing sugar reduced alcohol and the like, can be used in the form of a single or a plurality of kinds of mixtures.

  As the polyhydric alcohol, it is preferable to use a polyhydric alcohol having 3 or more hydroxyl groups in one molecule. Thereby, the interfacial tension between the aqueous solvent and the oil and fat component can be reduced more effectively, and finer and more stable fine particles can be formed. As a result, intestinal absorbability can be increased for food applications, and skin absorbability can be increased for transdermal pharmaceutical applications and cosmetic applications.

  Among the polyhydric alcohols that satisfy the above-described conditions, particularly when glycerin is used, the oil droplet particle size of the ceramide dispersion composition becomes smaller, and the particle size is kept small and stable for a long period of time. Therefore, it is preferable.

The content of the polyhydric alcohol is preferably 10 to 60% by mass with respect to the ceramide dispersion composition, more preferably from the viewpoint of the viscosity of the ceramide dispersion composition in addition to the particle size, stability and antiseptic properties described above. Is 20-55 mass%, More preferably, it is 30-50 mass%.
It is preferable that the content of the polyhydric alcohol is 10% by mass or more from the viewpoint that sufficient storage stability is easily obtained depending on the type and content of the fat and oil component. On the other hand, when the content of the polyhydric alcohol is 60% by mass or less, the maximum effect is obtained, and this is preferable because it is easy to suppress an increase in the viscosity of the ceramide dispersion composition.

  Other additives can be added to the ceramide dispersion composition of the present invention as necessary.

[Poor solvent phase]
The poor solvent in the present invention refers to a solvent in which the ceramide compound is poorly soluble, that is, the ceramide compound is difficult to dissolve or does not dissolve, and water is preferably used. Further, it is possible to further add a water-soluble functional component such as a water-soluble antioxidant to the poor solvent phase as long as the effects of the present invention are not impaired. An aqueous solution of an organic component can be used as the poor solvent phase.

[PH adjuster]
In order to adjust the pH of the poor solvent phase and the oil phase, a pH adjusting agent may be added to the poor solvent phase and the oil phase.
As said pH adjuster, various inorganic salts, such as an acid and an alkali, buffers, such as lactic acid-sodium lactate, a citric acid-sodium citrate, a succinic acid-sodium succinate, etc. can be used.

<Application>
The ceramide dispersion composition of the present invention is a fine emulsion or powder dispersion containing a ceramide compound exhibiting an emollient effect. For this reason, it is preferably used for various uses according to the function of the ceramide compound.
As such an application, it can be widely used for pharmaceuticals, foods, cosmetics, and the like. Here, as pharmaceuticals, tablets, capsules, granule oral preparations, injections, suppositories, parenteral preparations such as coating agents (skin external preparations), foods such as beverages, frozen desserts, and cosmetics Skin cosmetics (skin lotion, cosmetic liquid, milky lotion, cream, etc.), lipsticks, sunscreen cosmetics, makeup cosmetics and the like can be mentioned, but are not limited thereto.
Moreover, although the ceramide dispersion composition of the said this invention is contained in the said pharmaceutical, foodstuff, or cosmetics of this invention, the component which can be added to a pharmaceutical, foodstuffs, or cosmetics can be added suitably as needed.

The amount of the ceramide dispersion composition of the present invention used for pharmaceuticals, foods, cosmetics and the like varies depending on the type and purpose of the product and cannot be specified unconditionally, but is 0.01 to 10% by mass with respect to the product. Preferably, it can be used in the range of 0.05 to 5% by mass.
When the addition amount is too small, the desired effect may not be achieved, and when it is too large, the excessively added ceramide dispersion composition may not contribute to the effect.
The ceramide dispersion composition of the present invention is applied to beverages (in the case of foods), lotions, cosmetic liquids, emulsions, cream packs / masks, packs, hair washing cosmetics, fragrance cosmetics, liquid body cleaning agents, UV care cosmetics, deodorant cosmetics, and the like. When used in aqueous products such as oral care cosmetics (in the case of cosmetics), a transparent product is obtained, and precipitation and precipitation of insoluble substances under severe conditions such as long-term storage or sterilization Or generation | occurrence | production of inconvenient phenomena, such as a neck ring, can be suppressed.

  EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to the following examples unless it exceeds the gist thereof.

Example 1
The following oil phase components were dissolved in 80 g of ethanol [water-soluble organic solvent] and stirred at room temperature for 1 hour to prepare an oil phase solution A.
Ceramide 2 [Ceramide Compound, Specific Example 1-4] 0.14 g
Ceramide 3B [ceramide compound, specific example 1-11] 0.54 g
Ceramide 6 [Ceramide Compound, Specific Example 1-7] 0.67 g
Phytosphingosine 0.5g
Lactic acid 0.15g

The obtained oil phase liquid A (oil phase) and water (poor solvent phase) were micromixed at a ratio of 1: 7 (volume ratio) using a counter-flow collision type KM micromixer. The emulsion (ceramide dispersion composition) of Example 1 was obtained.
The conditions for using the micromixer are as follows.
-Microchannel-
Oil phase side microchannel Cross-sectional shape / width / depth / length = rectangle / 70 μm / 100 μm / 10 mm
Poor solvent phase side microchannel Cross-sectional shape / width / depth / length = rectangle / 490 μm / 100 μm / 10 mm
-Flow rate-
A poor solvent phase was added to the outer ring at 21.0 mL / min. The oil phase was introduced into the inner ring at a flow rate of 3.0 mL / min. Were introduced at a flow rate of 5 μm and micromixed.

(Examples 2 to 5 and Examples 8 to 11)
In the preparation of the oil phase liquid A of Example 1, the oil phase component was changed to the component having the composition shown in Table 1 below, and hydrochloric acid was added if necessary. The emulsions of Examples 2 to 5 and Examples 8 to 11 were prepared.
In addition, hydrochloric acid (1 N) used in Example 2 and Example 8 was added to the oil phase liquid so that the liquid property of each emulsion [ceramide dispersion composition] was pH 7 or less.

The details of the oil phase component used in each example are as follows.
・ Ceramide 3
Ceramide compound (specific example I-5)
・ PEO-sterol "Polyoxyethylene phytosterol" [specific sterol compound]
-1: 1 mixture (mass ratio) of phytostenone Sitostenone [specific stenone compound] and Campestenone [specific stenone compound]
Glycosphingolipid Comomesphingoglycolipid having the structure represented by the specific example (4-1) Phytosphingosine Compound represented by the specific example (5-5)

(Example 6)
In the preparation of the oil phase liquid A of Example 1, the oil phase component was changed to a component having the composition shown in Table 1 below to prepare an oil phase liquid B, and the oil phase liquid and the poor solvent phase (water) by the KM mixer were prepared. The mixing was performed in the same manner as in Example 1 except that the mixing was changed to mixing by German IMM (IMM, comb-tooth type SSIMM-SS-Ni25) in which a 5 μm sintered metal filter was installed in each flow path. The emulsion of Example 6 was prepared.

-IMM usage conditions-
The IMM micromixer, water, and oil phase liquid B were all placed in a 25 ° C. environment, and the water flow rate was 21.0 mL / min. The flow rate of the oil phase liquid B is 3.0 mL / min. Then, a precision metering pump was set up so that water and oil phase liquid B were introduced into an IMM micromixer and micromixed.

(Example 7)
In the preparation of the oil phase liquid A of Example 1, the oil phase component was changed to a component having the composition shown in Table 1 below to prepare an oil phase liquid C, and the oil phase liquid and the poor solvent phase (water) by the KM mixer were prepared. The emulsion of Example 7 was prepared in the same manner as in Example 1 except that the mixing with was changed to the following submerged jet conditions.

-Jet condition in liquid-
50 ml of oil phase liquid C was supplied at a flow rate of 75 ml / min (378 m / min) from a supply port having a supply diameter of 0.5 mm into 350 ml of water stirred at 500 rpm by a three-one motor. The oil phase liquid C was supplied into water using a syringe pump.

(Comparative Example 1)
The following oil phase components were stirred at 90 ° C. for 1 hour to prepare an oil phase liquid D.
Ceramide 3B [ceramide compound, specific example 1-11] 0.2 g
Glycosphingolipid 0.2g
Coconut MT [Oil component (oils and fats)] 50g
Glycerin [polyhydric alcohol] 50g

  The obtained oil phase liquid D (oil phase) and 400 g of water (poor solvent phase) were mixed with a stirrer and immediately stirred at 10,000 rpm for 5 minutes with a stirring homogenizer (manufactured by Nippon Seiki Co., Ltd.). And an emulsion was obtained. The obtained emulsion was subjected to high-pressure emulsification at 200 MPa using an optimizer HJP-25005 (manufactured by Sugino Machine Co., Ltd.) to obtain an emulsion (ceramide dispersion composition) of Comparative Example 1.

(Comparative Example 2)
An emulsion of Comparative Example 2 was prepared in the same manner as Comparative Example 1 except that the oil phase component was changed to a component having the composition shown in Table 1 below in the preparation of the oil phase liquid D of Comparative Example 1.

(Comparative Example 3, Comparative Example 4)
In the preparation of the oil phase liquid A of Example 1, the oil phase component was changed to a component having the composition shown in Table 1 below, and the oil phase component was stirred at 90 ° C. for 1 hour without using ethanol. Emulsions of Comparative Examples 3 and 4 were prepared in the same manner as Comparative Example 1 except that the phase liquid was prepared.

(Comparative Example 5)
In the preparation of the oil phase liquid D of Comparative Example 1, the oil phase component was changed to a component having the composition shown in Table 1 below to prepare an oil phase liquid E, and the mixing of the oil phase liquid and water by high pressure emulsification was performed. An emulsion of Comparative Example 5 was prepared in the same manner as Comparative Example 1 except that the stirring and mixing with a stirring bar (10 minutes at 30 rpm / min) was changed.
In addition, 0.2 g of phosphoric acid was added during the mixing of the oil phase liquid and water.

-Concentration, desolvation-
About each emulsion of the Example obtained by making it above, and a comparative example, the density | concentration of the oil phase component with respect to the emulsion total mass after a process is used using the Ogawara Seisakusho Co., Ltd. (CEP-lab). The following evaluation was performed after concentration and desolvation until the concentration of ethanol with respect to the total mass of the emulsion after treatment was 0.1 mass% or less.

<Evaluation>
1. The particle diameter of the dispersed particles The particle diameter of the dispersed particles immediately after the preparation of each of the emulsions of Examples 1 to 11 and Comparative Examples 1 to 5, using a concentrated particle size analyzer FPAR-1000 (Otsuka Electronics Co., Ltd.) Measured at 50 ° C.
In addition, while maintaining the above emulsions at 50 ° C., the dispersion particle size of each emulsion after 7 days from the measurement of the particle size was measured using a concentrated particle size analyzer FPAR-1000 (Otsuka Electronics Co., Ltd.). And measured at 50 ° C.
The measurement results are shown in Table 1.

2. Dispersion Stability Each of the emulsions of Examples 1 to 11 and Comparative Examples 1 to 5 was visually checked for a dispersion state immediately after the emulsion preparation and a dispersion state after 7 days from immediately after the emulsion preparation.

  In Table 1, the numerical value in the “total ceramide” column indicates the total content of the ceramide compound relative to the total mass of the oil phase component.

As can be seen from Table 1, the emulsions of Examples 1 to 11 are each prepared by dissolving an oil phase component in a water-soluble organic solvent (ethanol). Therefore, the concentration of the ceramide compound in the oil phase was high. Moreover, the particle diameter of the dispersed particles was 200 nm or less, and particularly 60 nm or less.
In Examples 1 to 11, a transparent emulsion was obtained immediately after the preparation of the emulsion (ceramide dispersion composition). Moreover, even after 7 days passed immediately after the preparation of the emulsion, it was found that the emulsion was transparent, and the emulsions of Examples 1 to 11 had good dispersion stability.
As can be seen from Examples 6 and 7, even when the method of mixing (emulsifying) the oil phase and the poor solvent phase is different, according to the present invention, the ceramide compound is contained in the oil phase at a high concentration, and An emulsion having good dispersion stability could be obtained.

On the other hand, in the emulsions of Comparative Examples 1 to 5, the oil phase component was dissolved in a water-soluble organic solvent (ethanol) and the oil phase was not obtained, so that a high-concentration ceramide compound could not be contained in the oil phase. . As in Comparative Example 3, when the concentration of the ceramide compound was increased, the dispersion was poor, and the dispersion stability was not excellent. The emulsion of Comparative Example 5 was whitish. The emulsion of Comparative Example 3 was cloudy immediately after preparation of the emulsion and was poorly dispersed. The emulsion of Comparative Example 4 was transparent.

  Therefore, according to the present invention, a ceramide dispersion composition having excellent dispersion stability while containing a ceramide compound at a high concentration can be obtained.

100 Micro device 102 Supply element 104 Merge element 106 Discharge element 124 Micro channel 126 Micro channel 128 Center 200 T-shaped channel 202 Inlet 204 Outlet 300 Fluid mixing mechanism 302 Channel

Claims (13)

An oil phase preparation step of preparing an oil phase by dissolving an oil phase component containing 25.9% by mass or more of a ceramide compound represented by the following general formula 1 with respect to the total mass of the oil phase component in a water-soluble organic solvent; The obtained oil phase and aqueous phase are separately passed through microchannels having a cross-sectional area of 1 μm ² to 1 mm ² at the narrowest portion, and then the oil phase and the water phase are separated by counterflow collision. And a mixing step of obtaining a ceramide dispersion composition in which dispersed particles having a volume average particle diameter of 1 nm to 200 nm are dispersed.


[In General Formula 1, R ¹ and R ³ each independently represents an alkyl group or alkenyl group having 3 to 60 carbon atoms, or an aryl group having 6 to 60 carbon atoms. R ² is a hydroxy group, an alkyl group or an alkenyl group having 3 to 30 carbon atoms, an aryl group having 6 to 30 carbon atoms, or show a phosphocholine group the following partial structure. ]

  The method for producing a ceramide dispersion composition according to claim 1, wherein the oil phase component contains a ceramide compound in an amount of 40% by mass or more based on the total mass of the oil phase component. An oil phase preparation step of preparing an oil phase by dissolving an oil phase component containing a ceramide compound represented by the following general formula 1 in a water-soluble organic solvent, and dividing the obtained oil phase and aqueous phase into the narrowest part After individually passing through the microchannels having an area of 1 μm ² to 1 mm ² , the oil phase and the aqueous phase are mixed by countercurrent collision to disperse the volume average particle diameter of 1 nm to 200 nm. A method for producing a ceramide dispersion composition, comprising: a mixing step of obtaining a ceramide dispersion composition in which particles are dispersed; and a step of removing a water-soluble organic solvent.


[In General Formula 1, R ¹ and R ³ each independently represents an alkyl group or alkenyl group having 3 to 60 carbon atoms, or an aryl group having 6 to 60 carbon atoms. R ² is a hydroxy group, an alkyl group or an alkenyl group having 3 to 30 carbon atoms, an aryl group having 6 to 30 carbon atoms, or show a phosphocholine group the following partial structure. ]

  The method for producing a ceramide dispersion composition according to claim 3, wherein the water-soluble organic solvent is ethanol. A ceramide dispersion composition comprising an oil phase containing an oil phase component and containing 25.9% by mass or more of a ceramide compound represented by the following general formula 1 with respect to the total mass of the oil phase component, and an aqueous phase.


[In General Formula 1, R ¹ and R ³ each independently represents an alkyl group or alkenyl group having 3 to 60 carbon atoms, or an aryl group having 6 to 60 carbon atoms. R ² is a hydroxy group, an alkyl group or an alkenyl group having 3 to 30 carbon atoms, an aryl group having 6 to 30 carbon atoms, or show a phosphocholine group the following partial structure. ]

  The ceramide dispersion composition according to claim 5, wherein the oil phase contains a ceramide compound in an amount of 40% by mass or more based on the total mass of the oil phase component. The ceramide dispersion composition according to claim 5 or 6, further comprising a compound represented by the following general formula 2 in the oil phase.


[In General Formula 2, R ^{5 to} R ⁸ each independently represent a hydrogen atom or a methyl group. R ⁹ represents an alkyl group or alkenyl group having 3 to 30 carbon atoms, a carbonyl group, or an amide group. ] The ceramide dispersion composition according to any one of claims 5 to 7, wherein the oil phase contains at least one of a compound represented by the following general formula 3a and a compound represented by the following general formula 3b.




[In said general formula 3a and said general formula 3b, R < ¹⁰ > -R < ¹³ > shows a hydrogen atom or a methyl group each independently. R ¹⁴ represents an alkyl group or alkenyl group having 3 to 30 carbon atoms, a carbonyl group, or an amide group. In the general formula 3b, R represents an alkyl group or alkenyl group having 1 to 60 carbon atoms. ] The ceramide dispersion composition according to any one of claims 5 to 8, further comprising a compound represented by the following general formula 4 in the oil phase.


[In General Formula 4, R ¹⁵ represents an alkyl group or alkenyl group having 3 to 60 carbon atoms, or an aryl group having 6 to 60 carbon atoms. R ¹⁶ represents an alkyl group or alkenyl group having 3 to 60 carbon atoms. R ¹⁷ represents a saccharide. ] The ceramide dispersion composition according to any one of claims 5 to 9, further comprising at least one compound represented by the following general formula 5 and the following general formula 6 in the oil phase.


[In General Formula 5, R ¹⁸ represents an alkyl group or alkenyl group having 3 to 60 carbon atoms. X represents a single bond or a divalent linking group, and R ²¹ represents a hydrogen atom, an alkyl group or alkenyl group having 3 to 60 carbon atoms, or an aryl group having 6 to 60 carbon atoms. ]


[In General Formula 6, R ¹⁹ represents an alkyl group having 3 to 60 carbon atoms. R ²⁰ represents a hydroxy group or an alkyl group having 3 to 60 carbon atoms. X represents a single bond or a divalent linking group,
R ²¹ represents a hydrogen atom, an alkyl group or alkenyl group having 3 to 60 carbon atoms, or an aryl group having 6 to 60 carbon atoms. ]   The ceramide dispersion composition according to any one of claims 5 to 10, wherein the oil phase contains a functional material for cosmetics that is insoluble or hardly soluble in water.   The ceramide dispersion composition according to any one of claims 5 to 11, wherein the oil phase contains a functional material for food that is insoluble or hardly soluble in water.   The ceramide dispersion composition according to any one of claims 5 to 12, wherein the oil phase contains a functional material for pharmaceuticals that is insoluble or hardly soluble in water.