JP4567341B2 - Production method of monodispersed solid particles - Google Patents

Description

  The present invention relates to monodispersed solid fine particles containing a sphingolipid structural substance, a dispersion containing the monodispersed solid fine particles, and methods for producing them. More specifically, for example, the present invention relates to monodispersed solid fine particles containing a sphingolipid structural material that can be suitably used for pharmaceuticals, cosmetics, foods, and the like, dispersions containing the monodispersed solid fine particles, and methods for producing them.

  The sphingolipid structural material is suitably used for pharmaceuticals, cosmetics, foods, etc., but the product form is a dispersion liquid in which solid fine particles containing the sphingolipid structural material are dispersed in a continuous phase. preferable.

  As a method for producing solid fine particles, (a) a method in which an oily component dissolved by heating is added to a heated continuous phase, and is atomized by applying mechanical shearing force with a homogenizer, a colloid mill or the like, and then solidified by cooling. And (b) a method in which an oily component dissolved by heating is dropped into a continuous phase cooled to a solidification temperature or lower using a vibrating nozzle or the like.

  However, in the method (a), since the shearing force applied to the particles is not uniform, the particle size distribution of the particles obtained is wide. Moreover, the average particle diameter of the fine particles obtained is several μm or less, and when the product is in a form in which the particles are dispersed in a transparent liquid such as an aqueous gel, the liquid feels cloudy.

  Further, in the method (b), although particles having a certain degree of monodispersity can be obtained, only those having a large average particle size of several hundreds of μm or more can be obtained, so that its application is limited. (For example, refer to Patent Document 1).

  On the other hand, a method using a microporous glass film is known as a method for producing solid fine particles (Patent Document 2). The average particle size of particles obtained by this method is as small as 0.3 to 0.6 μm, and is water-based. When the product is in such a form that particles are dispersed in a transparent liquid such as a gel, the liquid gives a cloudy feeling.

  Further, the solid fine particles exemplified in Patent Document 2 have a content of the sphingolipid structural material in the total emulsion composition of only 0.2% by weight, and the content of the sphingolipid structural material in the oil phase component is also 1% by weight. The content of the sphingolipid structural substance is dilute. For this reason, in order to fully demonstrate the effect of a sphingolipid structure substance, it is necessary to use a lot of emulsion compositions etc.

  As a method of obtaining monodisperse high melting point solid lipid fine particles of several tens of μm, a dispersed phase composed of high melting point oils and fats liquefied by heating is dispersed in a continuous phase through microchannels, and the emulsion is cooled. There is known a method for producing monodispersed solid oil microspheres in a suspension (see, for example, Patent Document 3).

However, when solid particles having a high content of sphingolipid structural material are prepared according to this method, in order to improve the stable formation and monodispersity of the solid particles in the continuous phase, sodium carboxylate or alkyl is used as a surfactant. When a low molecular surfactant such as sodium taurine is used, the dispersion becomes cloudy or emulsified and the continuous phase becomes cloudy, and the appearance is not transparent, resulting in a reduction in commercial value.
JP 2002-58990 A JP 2002-302414 A JP 2000-273188 A

  The present invention relates to a dispersion that does not generate turbidity even if it contains solid fine particles containing a large amount of sphingolipid structural material, a monodispersed solid having an average particle diameter of 10 to 100 μm and containing a large amount of sphingolipid structural material It is an object of the present invention to provide fine particles and a method for producing them.

The present invention
[1] (1) Step of obtaining a liquid composition by heating and liquefying an oil component containing a sphingolipid structural substance [hereinafter referred to as step (1)],
(2) A step of pressurizing the liquid composition obtained in (1) and dispersing the liquid composition in a continuous phase containing a polymer compound through a microchannel to obtain an emulsion [hereinafter, step ( 2)], and (3) a step of cooling the emulsion obtained in (2) below the melting point of the liquid composition to obtain a dispersion of solid fine particles (hereinafter referred to as step (3)).
A process for producing a dispersion containing monodispersed solid fine particles having an average particle diameter of 10 to 100 μm, comprising a step comprising
[2] A dispersion obtained by the production method according to [1],
[3] (1) a step of liquefying and mixing an oil component containing a sphingolipid structural substance to obtain a liquid composition;
(2) Pressurizing the liquid composition obtained in (1) and dispersing the liquid composition in a continuous phase containing a polymer compound through a microchannel to obtain an emulsion; and (3) Production of monodispersed solid fine particles having an average particle size of 10 to 100 μm, comprising the step of cooling the emulsion obtained in (2) below the melting point of the liquid composition to obtain a dispersion of solid fine particles. And [4] monodispersed solid fine particles obtained by the production method described in [3] above.

  According to the present invention, it is possible to obtain monodispersed solid fine particles having an average particle diameter of 10 to 100 μm and containing a sphingolipid structural substance in a high concentration, and a dispersion containing the solid fine particles. Moreover, this dispersion liquid has high transparency and produces the effect of not generating turbidity.

  Below, the manufacturing method of the monodispersed solid fine particle and dispersion liquid of this invention is demonstrated based on the flowchart shown in FIG.

  Step (1) is a step of obtaining a liquid composition by heat-liquefying and mixing an oil component containing a sphingolipid structural substance.

The sphingolipid structural substance refers to a substance having a sphingolipid structure, and includes, for example, ceramide derivatives such as ceramides I to VI, sphingosine, phytosphingosine, and ceramide-related substances such as lipid precursors. Specific examples of the sphingolipid structural substance include N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethyl hexadecanamide. These can be used alone or in admixture of two or more.

  The content of the sphingolipid structural substance in the liquid composition obtained in the step (1) (hereinafter simply referred to as the liquid composition) is based on the viewpoint of improving the feel when the particles are stretched with a finger and the strength stability of the particles. From the viewpoint of improvement, 5 to 70% by weight is preferable, and when applied to cosmetics, 20 to 70% by weight is more preferable. When the content of the sphingolipid structural substance in the liquid composition is as described above, it is possible to obtain solid fine particles in which the content of the sphingolipid structural substance in the solid fine particles is preferably 5 to 70% by weight. The solid fine particles in which the content of the sphingolipid structural substance in the solid fine particles is more preferably 20 to 70% by weight can be obtained.

  The liquid composition contains a sphingolipid structural material, but may contain other oily components (hereinafter referred to as other oily components) other than the sphingolipid structural material in order to improve feel and stability. . Examples of other oily components include esters and hydrocarbons. Examples of esters and hydrocarbons include squalane, liquid paraffin, isononyl isononanoate, isotridecyl isononanoate, octyl palmitate, isostearyl myristate, neopentyl glycol dioctanoate, neopentyl glycol dicaprate, diheptyl adipate Decyl, trioctanoin, tri (capryl / capric acid) glyceryl, pentaerythrityl tetraoctanoate, polyglyceryl tetraisostearate, octyldodecyl lactate, diisostearyl malate, polyglyceryl monoisostearate, polyglyceryl diisostearate, polyglyceryl triisostearate , Dipentaerythritol fatty acid esters and the like, and these may be used alone or in combination of two or more. It can be.

  The content of the esters and / or hydrocarbons in the liquid composition is preferably 30 to 80% by weight from the viewpoint of improving the feel when stretched with a finger and the strength stability of the particles.

  The heating temperature of the liquid composition may be a temperature at which the sphingolipid structural substance and other oily components are uniformly melted. From the viewpoint of imparting fluidity to the liquid composition and facilitating passage through the microchannel, the heating temperature may be adjusted according to the viscosity of the liquid composition. The upper limit of the heating temperature is preferably less than the boiling point of the liquid constituting the continuous phase from the viewpoint of the stability of the continuous phase used in step (2). For example, when water is used for the continuous phase, It is preferable that the temperature is less than ° C.

  Step (2) is a step of pressurizing the liquid composition obtained in the step (1) and dispersing the liquid composition in a continuous phase through a microchannel to obtain an emulsion.

  As the continuous phase, water is preferred. In the present invention, a polymer compound is added as a dispersant in order to improve the stable formation and monodispersity of solid fine particles in the continuous phase. By adding a polymer compound to the continuous phase, solid fine particles can be stably formed, and even when a high concentration of sphingolipid structural material is contained in the solid fine particles, the occurrence of turbidity in the dispersion liquid can be prevented. Can do.

  The polymer compound is preferably an amphiphilic polymer compound from the viewpoint of obtaining a stable dispersion state. Among them, a polymer compound obtained by copolymerizing a monomer containing a hydrophilic group and a monomer containing a hydrophobic group (partially crosslinked) May be used). The hydrophilic group is preferably a hydroxyl group, a carboxyl group or a carboxy anion. Moreover, as a hydrophobic group, an alkyl group is preferable and a C10-C30 alkyl group is more preferable.

  Examples of such polymer compounds include acrylic acid / alkyl methacrylate copolymers, polyvinyl alcohol and modified products thereof, polyacrylic acid amides and derivatives thereof, ethylene / vinyl acetate copolymers, styrene / maleic anhydride copolymers. Examples include polymers, ethylene / maleic anhydride copolymers, isobutylene / maleic anhydride copolymers, polyvinylpyrrolidone, ethylene / acrylic acid copolymers, vinyl acetate / acrylic acid copolymers, and the like. These can be used alone or in admixture of two or more. Of these, acrylic acid / alkyl methacrylate copolymers are particularly preferred.

  The content of the polymer compound in the continuous phase is preferably 0.001% by weight or more, and more preferably 0.01% by weight or more for stabilizing the fine particles. On the other hand, the content of the polymer compound in the continuous phase is preferably 0.5% by weight or less from the viewpoint that the viscosity of the continuous phase is not too high and the productivity in forming fine particles through the microchannel is good. More preferably, it is 1% by weight or less. Therefore, the content of the polymer compound in the continuous phase is preferably 0.001 to 0.5% by weight, and more preferably 0.01 to 0.1% by weight.

  The ratio of the liquid composition to the total liquid phase (the total of the continuous phase and the liquid composition) is preferably 50% by weight or less, more preferably 30% by weight or less, and more preferably 20% by weight or less from the viewpoint of uniform particle formation. Is more preferable.

  The heating temperature of the continuous phase when the liquid composition is dispersed in the continuous phase may be a temperature at which the sphingolipid structural substance and other oily components are uniformly melted. The heating temperature of the continuous phase may be adjusted according to the viscosity of the liquid composition from the viewpoint of imparting fluidity to the liquid composition and facilitating passage through the microchannel. The upper limit of the heating temperature is preferably less than the boiling point of the liquid constituting the continuous phase from the viewpoint of the stability of the continuous phase used in step (2). For example, when water is used for the continuous phase, It is preferable that the temperature is less than.

  The pressure at which the liquid composition is pressurized in order to disperse the liquid composition in the continuous phase is not particularly limited, and may be set as appropriate according to the type of the liquid composition and the continuous phase. Usually, when the pressure at the time of pressurizing the liquid composition is low, it becomes difficult for the liquid composition to enter the continuous phase. On the other hand, when the pressure at the time of pressurizing the liquid composition is too high, There is a tendency that the liquid composition is connected immediately after the liquid composition is extruded therein, and droplets are not formed. Therefore, in consideration of such circumstances, the pressure when pressurizing the liquid composition is preferably 0.5 to 25 kPa, and more preferably 1.0 to 20 kPa.

  The microchannel means a gap having a certain shape in which a liquid composition can be dispersed in a continuous phase to form a dispersed phase.

  The microchannel is preferably configured by integrating a large number of gaps (flow paths) having the same size and the same shape from the viewpoint of improving monodispersibility and productivity.

  The cross-sectional shape of the microchannel is not particularly limited. The cross-sectional shape is preferably rectangular or trapezoidal.

  When the equivalent diameter of the cross section of the microchannel (flow path) is small, the pressure loss when the liquid composition passes through the flow path increases, and conversely, when the equivalent diameter of the cross section is large, droplets are normally formed. Since the range of pressure that can be applied is remarkably narrowed, the equivalent diameter of the cross section shown below is preferably 2.5 to 50 μm, and more preferably 2.5 to 35 μm.

Here, the equivalent diameter (μm) (D) of the cross section of the microchannel (flow path) is expressed by the formula (I):
D = 4A / L (I)
[In the formula, A represents the cross-sectional area (μm ² ) of the microchannel (flow channel), and L represents the wet side length (circumferential length) (μm) of the microchannel (flow channel) cross section]
This means the diameter required by.

  An apparatus used when the liquid composition is dispersed in a continuous phase to produce an emulsion is not particularly limited, and for example, an apparatus described in JP-A-2000-273188 can be used.

  By dispersing the liquid composition in the continuous phase through the microchannel, an emulsion composed of particles having a high monodispersity of the average particle size distribution can be obtained. The resulting emulsion is then subjected to step (3).

  Step (3) is a step of cooling the emulsion obtained in step (2) to obtain a dispersion of solid fine particles.

  The cooling temperature of the emulsion is a temperature below the melting point of the liquid composition from the viewpoint of solidifying the sphingolipid structural substance.

  Thus, a monodispersed solid fine particle having an average particle diameter of 10 to 100 μm, a good monodispersibility, and including a sphingolipid structure substance in the solid fine particle, and a dispersion containing the monodispersed solid fine particle Obtainable. The monodispersed solid fine particles can be separated from the dispersion by an appropriate method (for example, filtration) and used alone or in combination with other components.

The monodispersity of the particles can be represented by a CV value. The CV value is calculated from the formula (II):
[CV value]
= [Standard deviation of average particle diameter (μm)] / [Average particle diameter (μm)] × 100 (II)
Sought by.

  The average particle size and standard deviation of the solid fine particles can be measured by analyzing an image of 300 particles photographed by a microscopic video system using image analysis software “Win ROOF” [Mitani Corporation].

  According to the present invention, solid fine particles having a CV value of 15 or less can be easily obtained, and solid fine particles having a CV value of 10 or less can be obtained by changing the temperature and / or pressure.

  Below, one embodiment of the apparatus used when manufacturing an emulsion in the manufacturing method of this invention is demonstrated based on FIGS.

  2 is a schematic cross-sectional view of the emulsion generating apparatus, FIG. 3 is a schematic enlarged view of a main part of the emulsion generating apparatus shown in FIG. 2, and FIG. 4A is a plan view of a substrate in the emulsion generating apparatus. 4 (b) is a bottom view of the substrate in the emulsion generating apparatus, and FIG. 5 is a schematic enlarged view of the microchannel portion.

  The emulsion production | generation apparatus connects the main body 1 to the thermostat 2, and makes it possible to control the temperature of the main body 1 to predetermined | prescribed temperature. Then, a plate 3 made of a glass plate or the like is fitted into one opening of the main body 1, a lid body 4 is fitted into the other opening, and a liquid composition (O) supply port 5 is formed at the center of the lid body 4. The continuous-phase (W) supply port 6 is formed at a location off the center of the lid 4 (upper in the figure), and the emulsion (E) is at a location off the center of the lid 4 (lower in the figure). An outlet 7 is formed.

  A liquid composition reservoir 8 is connected to the supply port 5 of the liquid composition (O) via a pipe, a heater 9 is provided around the pipe, and the supply port 6 of the continuous phase (W) is connected to the supply port 6 via a pipe. The continuous phase reservoir 10 is connected, and the recovery pipe 11 is connected to the outlet 7 for the emulsion (E). Here, the liquid composition reservoir 8 and the continuous phase reservoir 10 can be adjusted in the vertical position, and the pressure acting on the liquid composition (O) and the pressure can be adjusted according to the water level difference. The pressure acting on the continuous phase (W) can be adjusted.

  A substrate 12 is disposed in the space between the plate 3 and the lid 4. An opening 13 is formed in the center of the substrate 12, and a protrusion 14 is formed on the front side of the substrate 12 facing the plate 3 so as to surround the opening 13 in a rectangular shape, and the upper surface of the protrusion 14 is flat. The projections 16 are formed on the terrace 15 at regular intervals, and the microchannels 17 are formed between the projections 16 and 16. The size of the microchannel 17 is, for example, a width of 16 μm, a height of 7 μm, and a terrace length of 30 μm. In addition, wet etching or dry etching is suitable as a method for forming the protrusion 14 including the microchannel 17.

  Further, a partition member 18 such as an O-ring is interposed between the substrate 12 and the lid 4, and the convex portion 16 is brought into contact with the inside of the plate 3 by the elastic force of the partition member 18. The liquid composition (O) supply port 5 is opened in the inner region surrounded by the partition wall member 18, and the continuous phase (W) supply port 6 and the emulsion (E) outlet are formed in the outer region. 7 is open.

  A camera 19 connected to the video system is disposed outside the plate 3.

  An apparatus for producing a monodispersed emulsion is not limited to the above-described configuration. For example, in the example shown in FIGS. 2 to 5, the plate 3, the lid body 4, and the substrate 12 are arranged in the vertical direction, but these may be arranged in the horizontal direction. As another device, a substrate is placed in a case, a continuous phase flow path is formed between the substrate and the plate, and a microchannel that opens in a direction intersecting the flow path is formed in the substrate. It is good also as a cross flow type which forms and supplies a liquid composition from the direction which cross | intersects with respect to the continuous phase in a fluid state. In addition to this, a through hole is formed in the substrate, a substrate that can be used as a microchannel is disposed in the case, and the liquid composition is supplied and dispersed in the continuous phase through the substrate. It may be a penetration type.

Example 1
The apparatus shown in FIGS. The microchannel 17 had a width of 16 μm, a height of 7 μm, and a terrace length of 30 μm. The equivalent diameter obtained based on the formula (I) was 7.9 μm.

  N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide (Kao Co., Ltd. sphingolipid E: melting point about 75 ° C.) 55 parts by weight and dipentaerythritol fatty acid ester 15 parts by weight (Cosmol 168AR manufactured by Nisshin Oilio Co., Ltd.) and 30 parts by weight of polyglyceryl diisostearate (Cosmol 42 manufactured by Nisshin Oilio Co., Ltd.) are respectively weighed, heated to 80 ° C., dissolved and mixed. Thus, a liquid composition was prepared.

  As a continuous phase, 100 parts by weight of ion-exchanged water, 0.03 part by weight of acrylic acid / alkyl methacrylate copolymer (trade name: PEMULEN (TR-1), manufactured by Nikko Chemicals Co., Ltd.) and 1N aqueous sodium hydroxide solution ( 0.175 parts by weight of Wako Pure Chemical Industries, Ltd. reagent special grade) was added and dissolved.

  The liquid composition is placed in a reservoir, the temperature of the liquid composition in the reservoir and the temperature of the continuous phase are adjusted to 80 ° C., and the liquid composition is pressurized to a rate of 1.7 g / H into the continuous phase through the microchannel. An emulsion was formed by extruding and dispersing at. At this time, the supply pressure of the liquid composition was adjusted to 1.5 to 8.9 kPa. Moreover, the supply rate of the continuous phase at this time was 10 g / H. That is, the ratio of the liquid composition to the total liquid phase (the total of the continuous phase and the liquid composition) was 14.5% by weight.

  The produced emulsion was collected, cooled to 25 ° C. and solidified to obtain a dispersion of monodispersed solid fine particles. The average particle size and standard deviation of the obtained monodispersed solid fine particles are obtained by analyzing an image of 300 particles photographed by a microscopic video system using image analysis software “Win ROOF” (manufactured by Mitani Corporation). As a result, the average particle diameter was 31.2 μm, and the standard deviation was 3.10 μm. Since the CV value obtained based on the formula (II) is 9.9, it can be seen that the obtained monodispersed solid fine particles have good monodispersity.

  When the obtained solid fine particles were crushed with a finger, they disintegrated smoothly and showed a good feel. Further, the obtained dispersion was stored at 25 ° C. for 24 hours and then filtered through a filter paper (TOYO No. 5A). The filtrate was put into a quartz cell having an optical path length of 10 mm, and the transmittance at a wavelength of 660 nm was measured (the blank was It was 85%. Therefore, it turns out that the transparency of a filtrate is favorable.

Example 2
The same apparatus as used in Example 1 was used. 25 parts by weight of N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide (Kao Co., Ltd. sphingolipid E: melting point about 75 ° C.) and dipentaerythritol fatty acid ester 30 parts by weight (Cosmol 168AR manufactured by Nisshin Oilio Co., Ltd.) and 45 parts by weight of polyglyceryl diisostearate (Cosmol 42 manufactured by Nisshin Oilio Co., Ltd.) are respectively weighed, heated to 80 ° C., dissolved and mixed. Thus, a liquid composition was prepared.

  As a continuous phase, 100 parts by weight of ion-exchanged water, 0.03 part by weight of acrylic acid / alkyl methacrylate copolymer (trade name: PEMULEN (TR-1), manufactured by Nikko Chemicals Co., Ltd.) and 1N aqueous sodium hydroxide solution ( 0.175 parts by weight of Wako Pure Chemical Industries, Ltd. reagent special grade) was added and dissolved.

  By placing the liquid composition in a reservoir, adjusting the temperature of the liquid composition in the reservoir and the continuous phase to 78 ° C., respectively, and pressurizing and dispersing the liquid composition through the microchannel into the continuous phase; An emulsion was formed. At this time, the supply pressure of the liquid composition was adjusted to 1.5 to 9.0 kPa.

  The produced emulsion was collected, cooled to 25 ° C. and solidified to obtain a dispersion of monodispersed solid fine particles. The obtained monodispersed solid fine particles were measured by the same method as in Example 1. As a result, the average particle size was 30.4 μm, and the standard deviation was 2.84 μm. Since the CV value calculated | required based on Formula (II) is 9.3, it turns out that the obtained monodispersed solid fine particle has favorable monodispersibility.

  When the obtained solid fine particles were crushed with a finger, they disintegrated smoothly and showed a good feel. Furthermore, the obtained dispersion was stored at 25 ° C. for 24 hours and then filtered with a filter paper (TOYO No. 5A). The filtrate was put into a quartz cell having an optical path length of 10 mm, and the transmittance at a wavelength of 660 nm was measured (the blank was As a continuous phase), it was 84%. Therefore, it turns out that the transparency of a filtrate is favorable.

Comparative Example 1
The same apparatus as used in Example 1 was used. N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide (Kao Co., Ltd. sphingolipid E: melting point about 75 ° C.) 55 parts by weight and dipentaerythritol fatty acid ester 15 parts by weight (Cosmol 168AR manufactured by Nisshin Oilio Co., Ltd.) and 30 parts by weight of polyglyceryl diisostearate (Cosmol 42 manufactured by Nisshin Oilio Co., Ltd.) are respectively weighed, heated to 80 ° C., dissolved and mixed. Thus, a liquid composition was prepared.

  As a continuous phase, a solution obtained by adding 0.10 parts by weight of 30% N-cocoylmethyltaurine aqueous solution (trade name: Nikkor CMT-30, manufactured by Nikko Chemicals Co., Ltd.) to 100 parts by weight of ion-exchanged water was used. .

  The liquid composition was placed in a reservoir, the temperature of the liquid composition in the reservoir and the temperature of the continuous phase were adjusted to 80 ° C., and the liquid composition was pressurized and extruded through the microchannel into the continuous phase. The liquid composition droplets coalesced at the outlet and did not form an emulsion. The results were the same even when the supply pressure of the liquid composition was changed variously.

Comparative Example 2
The same apparatus as used in Example 1 was used. N- (2-hydroxy-3-hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamide (Kao Co., Ltd. sphingolipid E: melting point about 75 ° C.) 55 parts by weight and dipentaerythritol fatty acid ester 15 parts by weight (Cosmol 168AR manufactured by Nisshin Oilio Co., Ltd.) and 30 parts by weight of polyglyceryl diisostearate (Cosmol 42 manufactured by Nisshin Oilio Co., Ltd.) are respectively weighed, heated to 80 ° C., dissolved and mixed. Thus, a liquid composition was prepared.

  As a continuous phase, a solution obtained by adding 1.70 parts by weight of 30% N-cocoylmethyl taurine aqueous solution (trade name: Nikkor CMT-30, manufactured by Nikko Chemicals Co., Ltd.) to 100 parts by weight of ion-exchanged water was used. .

  The liquid composition is placed in a reservoir, the temperature of the liquid composition in the reservoir and the temperature of the continuous phase are adjusted to 80 ° C., respectively, and the liquid composition is pressurized and extruded through the microchannel and dispersed in the continuous phase, An emulsion was formed. At this time, the supply pressure of the liquid composition was adjusted to 1.5 to 5.9 kPa.

  The produced emulsion was collected, cooled to 25 ° C. and solidified to obtain a dispersion of monodispersed solid fine particles. The obtained monodispersed solid fine particles were measured by the same method as in Example 1. As a result, the average particle diameter was 29.1 μm, and the standard deviation was 2.46 μm. Since the CV value obtained based on the formula (II) was 8.4, it was shown that the obtained monodispersed solid fine particles have good monodispersity.

  The obtained dispersion was stored at 25 ° C. for 24 hours and then filtered through a filter paper (TOYO No. 5A). The filtrate was put into a quartz cell having an optical path length of 10 mm, and the transmittance at a wavelength of 660 nm was measured (the blank is a continuous phase). However, it was 2%. Visually, the filtrate was milky white and the transparency was poor.

  From the above results, the monodispersed solid fine particles obtained in Examples 1 and 2 have high monodispersibility, and disintegrate smoothly by crushing with a finger, exhibiting a good feel, and at the same time in the state of an aqueous dispersion. It turns out that a continuous phase does not become cloudy and shows favorable transparency.

  The monodispersed solid fine particles or dispersions thereof obtained by the present invention are used for, for example, pharmaceuticals, cosmetics, foods and the like.

FIG. 1 is a flowchart of each step in the production method of the present invention. FIG. 2 is a schematic cross-sectional view of the emulsion generator. FIG. 3 is a schematic enlarged view of a main part of the emulsion generating apparatus shown in FIG. FIG. 4A is a plan view of a substrate in the emulsion generating apparatus, and FIG. 4B is a bottom view of the substrate in the emulsion generating apparatus. FIG. 5 is a schematic enlarged view of the microchannel portion.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Main body 2 Constant temperature bath 3 Plate 4 Lid 5 Supply port 6 Supply port 7 Collection pipe 8 Liquid composition reservoir 9 Heater 10 Continuous phase reservoir 11 Collection pipe 12 Substrate 13 Opening 14 Projection 15 Terrace 16 Protrusion 17 Microchannel 18 Bulkhead member 19 Camera

Claims (5)

(1) A step of liquefying and mixing an oily component containing a sphingolipid structural substance to obtain a liquid composition,
(2) Pressurizing the liquid composition obtained in (1) above, and dispersing the liquid composition in a continuous phase containing 0.001 to 0.1% by weight of a polymer compound via a microchannel And (3) cooling the emulsion obtained in (2) below the melting point of the liquid composition to obtain a dispersion of solid fine particles. What 10~100μm der, 5 to 70% by weight content of sphingolipids structure material, and production method of the dispersion CV value contains monodisperse solid fine particles Ru der 15 below. Preparation of the dispersion of claim 1 Symbol placement polymer compound is an amphiphilic polymeric compound. The manufacturing method of the dispersion liquid of Claim 1 or 2 which pressurizes a liquid composition with the pressure of 0.5-25 kPa. (1) A step of liquefying and mixing an oily component containing a sphingolipid structural substance to obtain a liquid composition,
(2) Pressurizing the liquid composition obtained in (1) above, and dispersing the liquid composition in a continuous phase containing 0.001 to 0.1% by weight of a polymer compound via a microchannel And (3) cooling the emulsion obtained in (2) below the melting point of the liquid composition to obtain a dispersion of solid fine particles. What 10~100μm der, a content of sphingolipids structure material 5 to 70 wt%, and preparation of monodisperse solid fine particles CV value Ru der 15 below. The method for producing monodispersed solid fine particles according to claim 4, wherein the liquid composition is pressurized at a pressure of 0.5 to 25 kPa.

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