Method for producing lipid membrane structure-containing composition

Abstract

Provided is a method whereby the particle diameter of a lipid membrane structure can be controlled by a simple method when the lipid membrane structure is produced. The present disclosure pertains to a method for producing a composition containing a lipid membrane structure, the method including a dispersion step of mixing (A) a hydrogenated phospholipid having an acid value of 5 mgKOH / g or more, (B) a compound represented by formula 1, and (C) water to obtain a dispersion in which a lipid membrane structure having a particle diameter of 10-200 nm is spontaneously formed, the dispersion step includes a treatment for determining the concentration of the component (A) with respect to the dispersion liquid on the basis of the target particle diameter of the lipid membrane structure contained in the lipid membrane structure-containing composition.

Description

Technical Field

[0001] The present invention relates to a method for producing a lipid-containing membrane structure composition. Background Art

[0002] Lipid membrane structures such as liposomes or bicelles have skin care effects such as moisturizing and can encapsulate active ingredients, so they are useful in cosmetic applications and skin topical preparations. As the raw materials of the lipid membrane structures in the above-mentioned applications, phospholipids of natural origin and high safety are mainly used. Among them, hydrogenated phospholipids to which hydrogen atoms are added to the unsaturated carbon bonds of phospholipids are not easily degraded by oxidation, so they are preferably used.

[0003] So far, the technology of forming lipid membrane structures with hydrogenated phospholipids has been studied. For example, Japanese Patent Publication No. 2011-32230 records a technical solution of preparing a composition mixed with ceramides, branched alcohols, etc. in hydrogenated phospholipids and dispersing it in a large amount of excess water to obtain a liposome with high softness and storage stability of the lipid membrane. Japanese Patent Publication No. 2012-504620 (corresponding to WO2010 / 039490 specification) records a technical solution of mixing an oil-soluble composition and a water-soluble composition containing hydrogenated phospholipids, diol compounds, and fat-soluble compounds to form multilayer liposomes, and then using a conversion process to obtain fine single-layer liposomes. Summary of the invention

[0004] Problem that the invention aims to solve

[0005] In cosmetic applications and external skin preparation applications, requirements are put forward for fine (e.g., particle size below 200 nm) lipid membrane structures from the viewpoints of permeability to the skin and the effect of the encapsulated active ingredient, storage stability, etc. However, compared with phospholipids without hydrogenation, hydrogenated phospholipids have a high phase transition temperature and are difficult to form fine lipid membrane structures. In fact, in the technology of forming lipid membrane structures with hydrogenated phospholipids recorded in Japanese Patent Publication No. 2011-32230 and Japanese Patent Table No. 2012-504620 (corresponding to WO2010 / 039490 specification), in order to form fine (e.g., particle size below 200 nm) lipid membrane structures, it is necessary to use a refinement method such as a microfluidizer.

[0006] In addition, the lipid membrane structure preferably adjusts the particle size according to its use. For example, the smaller the particle size, the lighter the touch when applying the lipid membrane structure composition, the better the penetration to the skin, and the closer the appearance is to transparency, while the larger the particle size, the heavier the touch when applying the lipid membrane structure composition, the smoother the penetration to the skin, and the appearance is close to white turbidity from translucent. Therefore, it is required to design the particle size according to the touch and appearance as the target. In addition, for the purpose of giving the appearance a high-grade sense, in the case of making the appearance translucent, the degree of translucency varies depending on the particle size, and thus the technology that can appropriately adjust the particle size is also needed in quality management. With regard to the refinement methods used in industry such as microfluidizers, it is difficult to control the particle size, and it is necessary to explore the complicated conditions such as pressure and the number of passes. In the case where the composition research of the formula and the condition exploration of the device are not properly combined, the tendency of obtaining a widely distributed lipid membrane structure will be generated in terms of the dispersion uniformity of the particle size. Furthermore, even in the case of small-scale production, the refinement methods (e.g., ultrasonic treatment and extrusion) used have the problem of difficulty in controlling the particle size, or the particle size can be controlled but the operation is complicated. Therefore, it is difficult to easily obtain liposomes with a certain specific particle size.

[0007] Therefore, an object of the present invention is to provide a method for controlling the particle size of a lipid membrane structure by a simple method when producing the lipid membrane structure.

[0008] Solutions to the problem

[0009] In view of the above problems, the present inventors have conducted intensive research. As a result, it was found that in a method for producing a lipid membrane structure composition containing (A) a hydrogenated phospholipid having an acid value of 5 mgKOH / g or more, (B) a compound represented by the following formula 1, and (C) water,

[0010] Formula 1

[0011]

[0012] (In the above formula 1, R is a substituted or unsubstituted alkyl group having 2 to 6 carbon atoms, or a substituted or unsubstituted cycloalkyl group having 3 to 6 carbon atoms, X is -O-, -C(=O)O- or -OC(=O)-, and n is 0 or 1) The concentration of the component (A) in the dispersion obtained by mixing these components and the particle size of the lipid membrane structure contained in the lipid membrane structure-containing composition produced by the production method show a strong positive correlation (when the above concentration is increased, the particle size increases accordingly, and hereinafter, this correlation is referred to as "the relationship of the present invention"). Furthermore, based on this knowledge, it was found that when obtaining the above dispersion, the concentration of the component (A) in the dispersion can be controlled according to the target particle size of the lipid membrane structure, thereby completing the present invention.

[0013] That is, one embodiment of the present invention is a method for producing a lipid membrane structure-containing composition, which is a method for producing a lipid membrane structure-containing composition containing the (A) component, the (B) component and the (C) component, wherein the method comprises a dispersion step of mixing the (A) component, the (B) component and the (C) component to obtain a dispersion liquid in which a lipid membrane structure having a particle size of 10 nm or more and 200 nm or less is spontaneously formed, and the dispersion step comprises a process of determining the concentration of the (A) component relative to the dispersion liquid based on the target particle size of the lipid membrane structure contained in the lipid membrane structure-containing composition.

[0014] Brief description of the attached figure

[0015] Figure 1 This is an image of the lipid membrane structure of the example taken by cryo-electron microscopy (Cryo-TEM). DETAILED DESCRIPTION

[0016] The present invention is described in detail below. In addition, the present invention is not limited to the following embodiments, and various modifications can be made within the scope of the claims. In addition, the embodiments described in this specification can be arbitrarily combined to obtain other embodiments.

[0017] Throughout the specification, unless otherwise specified, expressions in the singular should be understood to include concepts in the plural form. Therefore, unless otherwise specified, articles in the singular (e.g., "a", "an", "the", etc. in English) should be understood to include concepts in the plural form. Also, unless otherwise specified, the terms used in this specification should be understood to be used with the meanings commonly used in the art. Therefore, unless otherwise defined, all technical terms and scientific and technical terms used in this specification have the same meanings as those commonly understood by those of ordinary skill in the art to which the invention belongs. In the event of a conflict, this specification (including definitions) shall take precedence.

[0018] In addition, in this specification, "X to Y" is used to mean that the numerical values ​​(X and Y) recorded before and after it are included as lower limits and upper limits, and means "above X and below Y". Furthermore, unless otherwise specified, concentration and % represent mass concentration and mass %, respectively, and unless otherwise specified, ratio refers to mass ratio. Furthermore, unless otherwise specified, operations and measurements of physical properties are carried out under conditions of room temperature (20 to 25°C) / relative humidity 40 to 50% RH. Furthermore, "A and / or B" means including A, B individually and their combinations.

[0019] One embodiment of the present invention is a method for producing a lipid membrane structure-containing composition, the method comprising: a method for producing a lipid membrane structure-containing composition containing (A) a hydrogenated phospholipid having an acid value of 5 mgKOH / g or more, (B) a compound represented by the following formula 1, and (C) water.

[0020] Formula 1

[0021]

[0022] (In the above formula 1, R is a substituted or unsubstituted alkyl group having 2 to 6 carbon atoms, or a substituted or unsubstituted cycloalkyl group having 3 to 6 carbon atoms, X is -O-, -C(=O)O- or -OC(=O)-, and n is 0 or 1) wherein the step of dispersing the component (A), the component (B) and the component (C) to obtain a dispersion liquid in which a lipid membrane structure having a particle size of 10 nm to 200 nm is spontaneously formed is included, and the dispersing step includes a treatment for determining the concentration of the component (A) relative to the dispersion liquid based on the target particle size of the lipid membrane structure contained in the lipid membrane structure-containing composition. According to this production method of the present invention, when producing a lipid membrane structure, the particle size of the lipid membrane structure can be controlled by a simple method.

[0023] According to the lipid membrane structure-containing composition of the present invention, a fine lipid membrane structure having a target particle size (specifically, a particle size of 10 nm to 200 nm) can be formed without requiring a refinement method such as a microfluidizer.

[0024] As mentioned above, lipid membrane structures such as liposomes and bicellular bodies are useful in cosmetic applications and skin external preparation applications. In the above-mentioned applications, from the perspectives of permeability to the skin, the effect of the encapsulated active ingredient, storage stability, etc., requirements are put forward for fine (e.g., particle size below 200nm) lipid membrane structures. In addition, depending on which of the above-mentioned viewpoints is used as the purpose, the appropriate particle size of the lipid membrane structure will be different, so it is required to control the particle size according to the application.

[0025] As the raw material of the lipid membrane structure in the above-mentioned use, phospholipids of natural origin and high safety are mainly used. Among them, hydrogenated phospholipids are not easily degraded by oxidation, so they are preferably used. However, compared with the phospholipids that are not hydrogenated, the phase transition temperature of hydrogenated phospholipids is high, and the physical properties of the two are very different. Therefore, with respect to the technology recorded in Japanese Patent Publication No. 2011-32230 and Japanese Patent Table No. 2012-504620 (corresponding to WO2010 / 039490 specification), it is difficult to easily manufacture a fine lipid membrane structure (for example, a particle size of less than 200nm) with hydrogenated phospholipids with a high phase transition temperature, and a lipid membrane structure with a target particle size cannot be obtained.

[0026] In view of this, the present inventors have conducted intensive research on a method for simply forming a fine lipid membrane structure using hydrogenated phospholipids. As a result, surprisingly, it was found that in the process of preparing a lipid membrane structure-containing composition, in which (A) a hydrogenated phospholipid having an acid value of 5 mgKOH / g or more, (B) a compound represented by the above formula 1 (hereinafter, also referred to as a "polyol compound") and (C) water are mixed to obtain a dispersion, by changing the concentration of the (A) component in the dispersion according to the target particle size of the lipid membrane structure, a lipid membrane structure of a fine target particle size (specifically, a particle size of 10 nm or more and 200 nm or less) can be formed without a refinement method (i.e., the relationship of the present invention exists). In the present invention, the target particle size of the lipid membrane structure is in the range of 10 nm or more and 200 nm or less.

[0027] <Method for producing lipid membrane structure-containing composition>

[0028] A method for producing a lipid membrane structure-containing composition according to one embodiment of the present invention comprises a dispersing step of mixing (A) a hydrogenated phospholipid having an acid value of 5 mgKOH / g or more, (B) a compound represented by the following formula 1, and (C) water to obtain a dispersion liquid in which a lipid membrane structure having a particle size of 10 nm or more and 200 nm or less is spontaneously formed,

[0029] Formula 1

[0030]

[0031] (In the above formula 1, R is a substituted or unsubstituted alkyl group having 2 to 6 carbon atoms, or a substituted or unsubstituted cycloalkyl group having 3 to 6 carbon atoms, X is -O-, -C(=O)O- or -OC(=O)-, and n is 0 or 1) The dispersion step also includes determining the concentration of component (A) relative to the dispersion liquid based on the target particle size of the lipid membrane structure contained in the lipid membrane structure-containing composition.

[0032] That is, in the method for producing a lipid membrane structure-containing composition according to one embodiment of the present invention, the desired particle size of the lipid membrane structure to be produced is determined, and the concentration of the component (A) in the dispersion prepared in the dispersion step is determined by comparing the desired particle size with the relationship of the present invention. The lipid membrane structure produced in the production method of the present invention has a particle size of 10 nm to 200 nm.

[0033] Hereinafter, before describing the production method of the present invention, the lipid membrane structure will be described first.

[0034] [Lipid membrane structure]

[0035] As long as the lipid molecules have a lamellar structure (lipid bilayer membrane) in which the hydrophilic groups are aligned to the outside and the hydrophobic groups are aligned to the inside, there is no particular limitation on the form of the lipid membrane structure, and examples thereof include liposomes, bilayers, α-gels, etc. The lipid membrane structure may be a single-layer lamellar structure called a unilamellar or single-layer structure, a multi-layer lamellar structure called an oligo-lamellar structure having several layers (2 to 10 layers), or a multi-layer lamellar structure having a greater number of layers, and these may be mixed.

[0036] Whether the lipid membrane structure is a single-layer lamellar structure (hereinafter also referred to as "monolayer") or a multi-layer lamellar structure (hereinafter also referred to as "multilayer") can be confirmed by, for example, cryo-electron microscopy (Cryo-TEM).

[0037] In one embodiment of the present invention, the lipid membrane structure is preferably a single-layer lamellar liposome. The single-layer lamellar liposome has a fine particle size and a high internal water phase volume, so it is a single-layer lamellar structure with excellent encapsulation efficiency and permeability of water-soluble compounds. Therefore, it is useful in cosmetics and skin topical preparations mixed with water-soluble beauty ingredients. In addition, in one embodiment of the present invention, the lipid membrane structure is preferably a bilayer. The bilayer is a fine disc-shaped single-layer lamellar structure with a thickness of 3 to 10 nm and a diameter of 15 to 100 nm, and has excellent encapsulation efficiency and permeability of fat-soluble components. Therefore, it is useful in cosmetics and skin topical preparations mixed with fat-soluble beauty ingredients.

[0038] In one embodiment of the present invention, the lipid membrane structure is preferably a multilamellar liposome. The multilamellar liposome has a fine particle size and a high volume of the lamellae, and can encapsulate fat-soluble compounds in the lamellae, so the encapsulation efficiency and permeability of the fat-soluble compounds are excellent. Therefore, it is useful in cosmetics and skin external preparations blended with fat-soluble cosmetic ingredients.

[0039] The lipid membrane structure-containing composition of the present invention may contain only one of unilamellar liposomes, bilayers or multilamellar liposomes, or may contain a mixture of two or more selected from the group consisting of multilamellar liposomes, unilamellar liposomes and bilayers.

[0040] In the present invention, the particle size of the lipid membrane structure is more than 10nm and less than 200nm. The particle size of the lipid membrane structure is preferably more than 20nm and less than 190nm, more preferably more than 30nm and less than 180nm, and further preferably more than 40nm and less than 170nm, particularly preferably more than 50nm and less than 160nm, and most preferably more than 50nm and less than 150nm. From the perspective of dispersibility, storage stability and permeability to the skin, there is no special limitation on the upper limit of the particle size of the lipid membrane structure, for example, less than 200nm, less than 190nm, less than 180nm, less than 170nm, less than 160nm, less than 150nm, less than 140nm, less than 135nm or less than 130nm. There is no special limitation on the lower limit of the particle size of the lipid membrane structure, but from the perspective of the formation efficiency of the lipid membrane structure, for example, more than 10nm, more than 20nm, more than 30nm, more than 40nm or more than 50nm.

[0041] From the viewpoint of dispersibility and storage stability, permeability to skin, the upper limit of the polydispersity index (PDI) of the lipid membrane structure is not particularly limited, for example, 0.80 or less, 0.70 or less, 0.60 or less, 0.50 or less, 0.40 or less, 0.30 or less, 0.25 or less, or 0.20 or less. The lower limit of the polydispersity index (PDI) of the lipid membrane structure is not particularly limited, for example, 0.01 or more.

[0042] In this specification, the particle size of the lipid membrane structure refers to the average hydrodynamic diameter. In addition, the particle size (average hydrodynamic diameter) and polydispersity index (PDI) of the lipid membrane structure are measured using a dynamic light scattering measuring device (Malvern Instruments, Zetasizer Nano ZSP), using a tuned average diameter (Z-Average) and polydispersity index (PDI) based on the scattered light intensity standard of cumulative analysis. In addition, the definitions of the particle size and polydispersity index used here follow the records in "JIS Z8828: 2019 Particle Size Analysis-Dynamic Light Scattering Method".

[0043] The lipid membrane structure-containing composition of the present invention contains the above-mentioned lipid membrane structure. In this specification, if the particle size of the lipid membrane structure-containing composition can be measured using a dynamic light scattering measurement device, more specifically, Zetasizer NanoZSP (manufactured by Malvern Instruments), it is considered that a lipid membrane structure is formed.

[0044] The lipid membrane structure contained in the lipid membrane structure-containing composition of the present invention is formed by dispersing the components forming the lipid membrane structure in the (C) component (water). In the present invention, in the dispersion step, the components forming the lipid membrane structure are dispersed in the (C) component to form the lipid membrane structure. Therefore, the dispersion obtained by the dispersion step is a solution in which the lipid membrane structure is formed. Specifically, in the present invention, the dispersion obtained by the dispersion step is a dispersion in which a lipid membrane structure having a particle size of 10 nm or more and 200 nm or less is spontaneously formed.

[0045] Here, the lipid membrane structure-containing composition of the present invention includes i) a state of a dispersion obtained by a dispersion step, and ii) a state in which the dispersion obtained by a dispersion step is further adjusted in concentration with component (C). Therefore, in the case of i), the dispersion of the present invention directly constitutes a lipid membrane structure-containing composition. And, in the case of ii), the dispersion of the present invention further constitutes a lipid membrane structure-containing composition after adjusting the concentration with component (C). Therefore, in the case of i), a lipid membrane structure-containing composition is obtained by a dispersion step, and in the case of ii), the dispersion is subjected to a concentration adjustment step described later to obtain a lipid membrane structure-containing composition. In addition, component (C) in which components forming a lipid membrane structure are dispersed can be used together with components other than component (C), for example, it can be used together with components (D) to (F) described later and components described in [Other components] described later, or a mixture of these components mixed in advance can be used. In addition, there is also a case where component (C) in a system where a lipid membrane structure exists (i.e., component (C-2) and component (C-3) described later) are referred to as "aqueous phase". For example, the component (C-2) and the component (C-3) in which the components forming the lipid membrane structure are dispersed constitute the "aqueous phase" relative to the components forming the lipid membrane structure.

[0046] In the method for producing a lipid membrane structure-containing composition of the present invention, in addition to the dispersion step, the (C) component is also used as an added component in the mixing step and the concentration adjustment step described later. Therefore, hereinafter, the (C) component for mixing added in the mixing step is referred to as "(C-1) component" or "water (for forming agent)", the (C) component for dispersion added in the dispersion step is referred to as "(C-2) component" or "water (for dispersion)", and the (C) component for concentration adjustment added in the concentration adjustment step is referred to as "(C-3) component" or "water (for concentration adjustment)". The (C) component contained in the lipid membrane structure-containing composition is the total amount of the (C-1) component for mixing added in the mixing step, the (C-2) component for dispersion added in the dispersion step, and the (C-3) component for concentration adjustment added in the concentration adjustment step described later. In addition, in the method for producing a lipid membrane structure-containing composition of the present invention, the mixing step and the concentration adjustment step are steps implemented as needed.

[0047] Hereinafter, a preferred embodiment of a production method according to one embodiment of the present invention will be described.

[0048] [Dispersion process]

[0049] The dispersion process is a process of mixing the (A) component, the (B) component and the (C-2) component to obtain a dispersion liquid in which a lipid membrane structure having a particle size of more than 10 nm and less than 200 nm is spontaneously formed. At this time, in the dispersion process, the concentration of the (A) component relative to the dispersion liquid is determined based on the relationship of the present invention and is determined according to the target particle size of the lipid membrane structure contained in the lipid membrane structure-containing composition. Specifically, if a lipid membrane structure having a larger particle size is to be manufactured, it is only necessary to further increase the concentration of the (A) component relative to the dispersion liquid. In addition, the manufacturing method of this embodiment can also include obtaining a correlation (relationship of the present invention) between the concentration of the above-mentioned (A) component in the dispersion liquid and the particle size of the lipid membrane structure contained in the lipid membrane structure-containing composition. With regard to this correlation, a preliminary experiment can be performed to obtain a lipid membrane structure-containing composition having various particle sizes by changing the concentration of the (A) component in the dispersion liquid for the composition of the desired lipid membrane structure-containing composition, and the result can be obtained by a known regression analysis method such as the least squares method (OLS). Here, there is no particular limitation on the specific expression form of the "relationship of the present invention" obtained by the known regression analysis method, for example, it can be an approximate straight line (linear regression) or an approximate curve (polynomial approximation). Furthermore, there is no particular limitation on the order of the approximate curve (polynomial approximation), but it is preferably 2 to 5 times, and more preferably 3 to 4 times. Regarding these approximate straight lines and approximate curves, the "straight line approximation" and "polynomial approximation" functions in the "approximate curve format setting" of Microsoft Excel (made by Microsoft Corporation) can be obtained. In addition, in the case where the "relationship of the present invention" obtained by this method can be obtained separately, these can also be used to implement the manufacturing method of this embodiment. At this time, the manufacturing method of this embodiment does not include obtaining the "relationship of the present invention". The target particle size of the lipid membrane structure can be appropriately set from the range of particle sizes described in the [lipid membrane structure] column. For example, the target particle size of the lipid membrane structure is above 10nm and below 200nm.

[0050] After determining the target particle size of the lipid membrane structure, the concentration of the component (A) relative to the dispersion is then determined based on the particle size (reference "Relationship of the present invention"). For example, the concentration of the component (A) determined based on the target particle size of the lipid membrane structure is preferably 0.01 to 15% by mass, more preferably 0.05 to 15% by mass, further preferably 0.1 to 12% by mass, further preferably 0.2 to 10% by mass, particularly preferably 0.3 to 7.5% by mass, and most preferably 0.5 to 5% by mass, relative to the dispersion (total mass 100% by mass). For example, the lower limit of the concentration of component (A) determined by the target particle size of the lipid membrane structure relative to the dispersion (total mass 100 mass %) is 0.01 mass % or more, 0.02 mass % or more, 0.1 mass % or more, 0.2 mass % or more, 0.3 mass % or more, 0.4 mass % or more, 0.5 mass % or more, 0.6 mass % or more, 0.7 mass % or more, 0.8 mass % or more, 0.9 mass % or more, 1.0 mass % or more, 1.1 mass % or more, 1.2 mass % or more, 1.3 mass % or more, 1.4 mass % or more, 1.5 mass % or more, 1.6 mass % or more, 1.7 mass % or more, 1.8 mass % or more, 1.9 mass % or more, or 2.0 mass % or more. And, as the upper limit of the concentration of (A) component at this time, relative to dispersion liquid (total mass 100 mass %), be 15 mass % or less, 14 mass % or less, 13 mass % or less, 12 mass % or less, 11 mass % or less, 10 mass % or less, 9.5 mass % or less, 9.0 mass % or less, 8.5 mass % or less, 8.0 mass % or less, 7.5 mass % or less, 7.0 mass % or less, 6.5 mass % or less, 6.0 mass % or less, 5.5 mass % or less or 5.0 mass % or less. In one embodiment, relative to dispersion liquid, the concentration of (A) component determined according to the target particle size of lipid membrane structure is 0.05 mass % or more and less than 4.5 mass %. By controlling the concentration of (A) component within the above range, the particle size of the lipid membrane structure obtained can be controlled. That is, the present inventors have found that when a lipid membrane structure-containing composition is produced by setting the concentration of component (A) within the above range, the particle size of the lipid membrane structure contained in the lipid membrane structure-containing composition can be controlled, thereby completing the present invention.

[0051] That is, when producing a lipid membrane structure-containing composition, the concentration of component (A) in the dispersion obtained in the dispersion step is changed according to the target particle size of the lipid membrane structure (this is compared with the relationship of the present invention). Thus, a lipid membrane structure of the target particle size is formed in the finally obtained lipid membrane structure-containing composition. According to this mode, the particle size of the lipid membrane structure can be controlled in the lipid membrane structure-containing composition, and there is an advantage that the particle size can be set according to the purpose.

[0052] Here, the inventors have found that according to the manufacturing method of one embodiment of the present invention, the structure of the lipid membrane structure contained in the lipid membrane structure composition can also be controlled. In the embodiment, when the concentration of the (A) component in the dispersion process of the lipid membrane structure composition is 2% by mass or less relative to the dispersion liquid (total mass 100% by mass), a lipid membrane structure having a structure of a single-layer lamellar liposome is confirmed (Examples 1-1, 1-2, etc.). On the other hand, when the concentration of the (A) component in the dispersion process of the lipid membrane structure composition is 3% by mass or more relative to the dispersion liquid (total mass 100% by mass), a lipid membrane structure having a structure of a multi-layer lamellar liposome is confirmed (Examples 1-3 to 1-5, etc.). That is, the inventors have also found that according to the manufacturing method of the present invention, by adjusting the concentration of the (A) component in accordance with the relationship of the present invention, the structure of the lipid membrane structure can be controlled.

[0053] In addition, in the manufacturing method of one embodiment of the present invention, when forming a lipid membrane structure, it is preferred that after forming a lipid membrane structure at a concentration higher than the concentration of the component (A) in the target lipid membrane structure composition, the component (C-3) is added until the concentration of the target component (A) is reached, thereby obtaining a lipid membrane structure composition. That is, as one embodiment of the present invention, after the dispersion process, there may also be a concentration adjustment process of mixing the dispersion liquid with the component (C-3) (water). According to this embodiment, by forming a lipid membrane structure in a state where the concentration of the component (A) is high and then performing a dilution process, even if the composition (the content of each component, especially the concentration of the component (A)) in the lipid membrane structure composition is the same, the particle size of the lipid membrane structure in the lipid membrane structure composition can be made different. That is, in the lipid membrane structure composition containing the same composition, the particle size of the lipid membrane structure can be controlled, and thus there is an advantage that the particle size can be set according to the purpose.

[0054] The dispersion obtained by the dispersion step contains component (A), component (B) and component (C) (component (C-2)), and may contain components (D) to (F) and components described in [other components] described later as needed. These components constituting the dispersion are described below. In addition, even in the case where the dispersion contains components other than components (A) to (C-2), the relationship of the present invention still exists according to its composition. Therefore, even in this case, the manufacturing method of this embodiment can be implemented by the same method as above and utilizing the relationship of the present invention.

[0055] [(A) ingredient]

[0056] The dispersion of the present invention contains a hydrogenated phospholipid having an acid value of 5 mgKOH / g or more as component (A). Component (A) may be one or two or more hydrogenated phospholipids having an acid value of 5 mgKOH / g or more, or may be a combination of one or more hydrogenated phospholipids having an acid value of less than 5 mgKOH / g and one or more hydrogenated phospholipids having an acid value of 5 mgKOH / g or more to achieve an acid value of 5 mgKOH / g or more.

[0057] Hydrogenated phospholipids can be obtained by adding hydrogen atoms to the unsaturated carbon bonds of phospholipids by existing known methods. There is no particular limitation on the source of phospholipids, but lecithin is a natural source and can be applied to cosmetics and skin topical preparations, and is therefore particularly preferred. Therefore, in one embodiment of the present invention, component (A) is hydrogenated lecithin. In addition, lecithin can be derived from soybeans, egg yolks, rapeseed, sunflowers, corn, etc., preferably from plants such as soybeans, rapeseed, sunflowers, corn, and is more preferably derived from soybeans from the viewpoint of easy availability and quality stability.

[0058] The acid value of component (A) is 5 mgKOH / g or more. When using a hydrogenated phospholipid having an acid value lower than 5 mgKOH / g, even if combined with component (B), a fine lipid membrane structure cannot be formed. From the viewpoint of obtaining a finer lipid membrane structure and from the viewpoint of obtaining a structure, the acid value of component (A) is preferably 12 mgKOH / g or more, more preferably 15 mgKOH / g or more, further preferably 17 mgKOH / g or more, further preferably 20 mgKOH / g or more, and particularly preferably 22 mgKOH / g or more. The acid value of the component (A) is, for example, 6 mgKOH / g or more, 7 mgKOH / g or more, 8 mgKOH / g or more, 9 mgKOH / g or more, 10 mgKOH / g or more, 11 mgKOH / g or more, 12 mgKOH / g or more, 13 mgKOH / g or more, 14 mgKOH / g or more, 15 mgKOH / g or more, 16 mgKOH / g or more, 17 mgKOH / g or more, 18 mgKOH / g or more, 19 mgKOH / g or more, 20 mgKOH / g or more, 21 mgKOH / g or more, 22 mgKOH / g or more, 23 mgKOH / g or more, 24 mgKOH / g or more, 25 mgKOH / g or more, 26 mgKOH / g or more, or 27 mgKOH / g or more. In addition, although there is no particular limitation on the acid value of component (A), for example, it is less than 70 mgKOH / g, less than 60 mgKOH / g, less than 50 mgKOH / g or less than 40 mgKOH / g. By appropriately selecting the type of phospholipid, a hydrogenated phospholipid with a desired acid value can be obtained. In addition, the acid value of component (A) is the value measured according to "General Test Method 28. Acid Value Determination Method for Quasi-drug Raw Materials Specifications 2021".

[0059] As component (A), any of synthetic products and commercial products can be used. Examples of commercial products include EMALEX (registered trademark) SLP manufactured by Japan Emulsion Co., Ltd. and SLP-white H manufactured by Tsuji Oil Manufacturing Co., Ltd. These can be used alone or in combination of two or more.

[0060] The content of the component (A) in the dispersion of the present invention is the above-mentioned “concentration of the component (A) determined according to the target particle size of the lipid membrane structure.” Therefore, the above-mentioned concentration of the component (A) determined according to the target particle size of the lipid membrane structure is applied.

[0061] [(B) ingredient]

[0062] The dispersion of the present invention contains, as the component (B), a compound represented by the following formula 1. The component (B) may be one kind or two or more kinds.

[0063] Formula 1

[0064]

[0065] In the above formula 1, R is a substituted or unsubstituted alkyl group having 2 to 6 carbon atoms, or a substituted or unsubstituted cycloalkyl group having 3 to 6 carbon atoms.

[0066] The alkyl group having 2 to 6 carbon atoms may be any of a straight chain or a branched chain. Examples of the alkyl group having 2 to 6 carbon atoms include ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, tert-pentyl, neopentyl, n-hexyl, 3-methylpentane-2-yl, 3-methylpentane-3-yl, 4-methylpentyl, 4-methylpentane-2-yl, 1,3-dimethylbutyl, 3,3-dimethylbutyl, 3,3-dimethylbutane-2-yl, etc. The alkyl group having 2 to 6 carbon atoms is preferably a straight chain. That is, the alkyl group having 2 to 6 carbon atoms is preferably a group selected from the group consisting of ethyl, n-propyl, n-butyl, n-pentyl and n-hexyl.

[0067] Examples of the cycloalkyl group having 3 to 6 carbon atoms include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, and cyclohexyl is preferred.

[0068] As long as the effects of the present invention can be exerted, there is no particular limitation on the substituents that may be present on the alkyl group having 2 to 6 carbon atoms and the cycloalkyl group having 3 to 6 carbon atoms. Examples of the substituents include halogen atoms, acyl groups, alkyl groups, aryl groups, alkoxy groups, nitro groups, amino groups, cyano groups, etc. Among them, the alkyl group having 2 to 6 carbon atoms will not be substituted by an alkyl group.

[0069] In the above formula 1, X is -O-, -C(=O)O- or -OC(=O)-, preferably -O-. In the above formula 1, n is 0 or 1. In the above formula 1, when X is -O- and n is 1, the carbon number of the alkyl group as R is preferably 4 or more.

[0070] As the component (B), for example, at least one selected from the group consisting of 1,2-pentanediol, 1,2-hexanediol, 1,2-heptanediol, 1,2-octanediol, cyclohexylglycerol, and hexylglycerol is preferred.

[0071] In particular, when 1,2-hexanediol, 1,2-heptanediol, and hexylglycerol are used as component (B), an extremely fine lipid membrane structure can be formed. At this time, it can be considered that the lipid membrane structure forms a bilayer. The bilayer is a disc-shaped single-layer structure, and has excellent permeability to the stratum corneum compared to liposomes of the same particle size. Therefore, from the perspective of obtaining a lipid membrane structure with high permeability of fat-soluble components, it is preferred to use at least one selected from the group consisting of 1,2-hexanediol, 1,2-heptanediol, and hexylglycerol as component (B).

[0072] The component (B) may be a synthetic product or a commercially available product.

[0073] The content of the component (B) in the dispersion of the present invention is preferably more than 0.01% by mass and less than 24% by mass, more preferably 0.02% by mass to less than 23% by mass, further preferably 0.05% by mass to less than 20% by mass, particularly preferably 0.1% by mass to less than 18% by mass, and most preferably 0.2% by mass to less than 15% by mass. For example, the lower limit of the content of the component (B) in the dispersion is preferably more than 0.01% by mass, relative to the dispersion (total mass 100% by mass). The lower limit of the content of the component (B) in the dispersion is preferably 0.011% by mass or more, 0.02% by mass or more, 0.05% by mass or more, 0.1% by mass or more, 0.2% by mass or more, 0.3% by mass or more, 0.4% by mass or more, 0.5% by mass or more, 0.6% by mass or more, 0.7% by mass or more, 0.8% by mass or more, 0.9% by mass or more, 1.0% by mass or more, 1.1% by mass or more, 1.2% by mass or more, 1.3% by mass or more, 1.4% by mass or more, 1.5% by mass or more, 1.6% by mass or more, 1.7% by mass or more, 1.8% by mass or more, 1.9% by mass or more, or 2.0% by mass or more relative to the dispersion (total mass 100% by mass). The upper limit of the content of the component (B) in the dispersion is preferably 24% by mass or less relative to the dispersion (total mass 100% by mass). The upper limit of the content of the component (B) in the dispersion is 23% by mass or less, 22% by mass or less, 21% by mass or less, 20% by mass or less, 19% by mass or less, 18% by mass or less, 17% by mass or less, 16% by mass or less, 15% by mass or less, 14% by mass or less, 13% by mass or less, 12% by mass or less, 11% by mass or less, 10% by mass or less, 9.5% by mass or less, 9.0% by mass or less, 8.5% by mass or less, 8.0% by mass or less, 7.5% by mass or less, 7.0% by mass or less, 6.5% by mass or less, 6.0% by mass or less, 5.5% by mass or less, 5.0% by mass or less, or 4.5% by mass or less.

[0074] In the dispersion of the present invention, the content of component (B) is preferably more than 100 parts by mass, more preferably 110 parts by mass to 2000 parts by mass, further preferably 120 parts by mass to 1800 parts by mass, further preferably 130 parts by mass to 1500 parts by mass, particularly preferably 140 parts by mass to 1200 parts by mass, and most preferably 150 parts by mass to 1000 parts by mass. When the content of component (B) is within the above range, component (A) is easy to form a lipid membrane structure more effectively in the dispersion, and a lipid membrane structure with excellent dispersibility can be formed. Furthermore, from the viewpoint of obtaining a finer lipid membrane structure, the content of the component (B) is, for example, 160 parts by mass or more, 170 parts by mass or more, 180 parts by mass or more, 190 parts by mass or more, 200 parts by mass or more, 210 parts by mass or more, 220 parts by mass or more, 230 parts by mass or more, 240 parts by mass or more, 250 parts by mass or more, 260 parts by mass or more, 270 parts by mass or more, 280 parts by mass or more, 290 parts by mass or more, 300 parts by mass or more, 310 parts by mass or more, 320 parts by mass or more, 330 parts by mass or more, 340 parts by mass or more, 350 parts by mass or more, 360 parts by mass or more, 370 parts by mass or more, 380 parts by mass or more, 390 parts by mass or more, or 400 parts by mass or more, relative to 100 parts by mass of the component (A). On the other hand, there is no special limit for the upper limit of the content of (B) component relative to 100 parts by mass of (A) component, but exceeding 2000 parts by mass will not affect the solubility or dispersibility of (A) component in the dispersion, which will only lead to waste. Therefore, relative to 100 parts by mass of (A) component, for example, the content of (B) component is less than 2000 parts by mass, less than 1900 parts by mass, less than 1800 parts by mass, less than 1700 parts by mass, less than 1600 parts by mass, less than 1500 parts by mass, less than 1400 parts by mass, less than 1300 parts by mass, less than 1200 parts by mass, less than 1100 parts by mass, less than 1000 parts by mass, less than 900 parts by mass, less than 800 parts by mass, less than 700 parts by mass, less than 600 parts by mass or less than 500 parts by mass. Therefore, according to a preferred embodiment of the present invention, relative to 100 parts by mass of (A) component, the content of (B) component is preferably less than 2000 parts by mass from 110 parts by mass.

[0075] [(C-2) component)]

[0076] The dispersion of the present invention contains water as component (C-2). Component (C-2) serves as a medium for dispersing components that form lipid membrane structures and is a main component that forms an aqueous phase in the dispersion. In addition, component (C-2) serves to help blend the following component (D) (basic compound) and component (E) (acidic compound) into the dispersion. Specifically, by pre-dissolving component (D) and / or component (E) in component (C-2) and then mixing them in component (A) and component (B), component (D) and / or component (E) can be easily blended into the dispersion.

[0077] As the component (C-2), water with few impurities is preferred, for example, water such as purified water, which is water purified from ordinary water by a system such as ion exchange, distillation, reverse osmosis or ultrafiltration alone or in combination, is preferred.

[0078] The content of the component (C-2) in the dispersion of the present invention is preferably 50% by mass or more and 99.97% by mass or less, more preferably 60% by mass or more and 99.9% by mass or less, further preferably 60% by mass or more and 99.8% by mass or less, particularly preferably 65% ​​by mass or more and 99.7% by mass or less, and most preferably 70% by mass or more and 99.6% by mass or less, relative to the dispersion (total mass 100% by mass). For example, the lower limit of the content of the component (C-2) in the dispersion is 50% by mass or more, 55% by mass or more, 60% by mass or more, 65% by mass or more, 70% by mass or more, 75% by mass or more, 80% by mass or more, 85% by mass or more, or 90% by mass or more. For example, the upper limit of the content of the component (C-2) in the dispersion is 99.97 mass % or less, 99.9 mass % or less, 99.8 mass % or less, 99.7 mass % or less, or 99.6 mass % or less relative to the dispersion (total mass 100 mass %).

[0079] In the dispersion of the present invention, the lower limit of the mass ratio of the component (B) to the component (C-2) ("component (B) : component (C-2)") is preferably greater than 0.01:99.99, and is 0.01:99.9 or more, 1:99 or more, 2:98 or more, or 3:97 or more. In the dispersion, the upper limit of the mass ratio of the component (B) to the component (C-2) is preferably less than 25:75, and is 24:76 or less, 20:80 or less, 16:84 or less, 12.5:87.5 or less, or 10:90 or less.

[0080] In the present invention, a mixture that spontaneously forms a lipid membrane structure having a particle size of 10 nm to 200 nm when the components (A), (B) and (C-2) (i.e., component (C)) are mixed is referred to as a "dispersion liquid", and a step that spontaneously forms a lipid membrane structure having a particle size of 10 nm to 200 nm when the components (A), (B) and (C-2) are mixed is referred to as a "dispersion step". Therefore, for example, in the mixing step described later, components (A), (B) and (C-1) (i.e., component (C)) may be mixed, but even if component (C-1) (i.e., component (C)) is present, "a lipid membrane structure having a particle size of 10 nm to 200 nm" will not be spontaneously formed in the mixing step. The lipid membrane-forming agent obtained in the mixing step does not have a lipid membrane structure having a particle size of 10 nm to 200 nm. That is, whether it is the dispersion of the present invention (for example, whether it is a dispersion or a lipid membrane-forming agent) can be identified by measuring the particle size to confirm whether a "lipid membrane structure with a particle size of 10 nm to 200 nm" is formed.

[0081] For example, one method of controlling "spontaneous formation of a lipid membrane structure having a particle size of 10 nm or more and 200 nm or less" is to control the (B) component and the (C-2) component in the dispersion to a specified ratio. Specifically, when the mass ratio of the (B) component to the (C-2) component in the dispersion ("(B) component: (C-2) component") exceeds 0.01:99.98 and is less than 25:75, a lipid membrane structure having a particle size of 10 nm or more and 200 nm or less is spontaneously formed by mixing the (A) component, the (B) component and the (C-2) component, thereby obtaining a dispersion.

[0082] [(D) ingredient]

[0083] In addition to the above-mentioned components (A), (B) and (C-2), the dispersion of the present invention may further contain a basic compound as a component (D). When a component (A) having a high acid value is used, a dispersion having a lipid membrane structure with better dispersibility can be obtained by containing the component (D). The component (D) may be only one or two or more.

[0084] Examples of the component (D) include inorganic bases such as sodium hydroxide, potassium hydroxide, and ammonia, basic amino acids such as arginine, lysine, and histidine, and amine compounds such as ethanolamine, diethanolamine, triethanolamine, 2-amino-2-methyl-1,3-propanediol (AMPD), and 2-amino-2-hydroxymethyl-1,3-propanediol (tromethamine). Among them, arginine is preferred.

[0085] As the component (D), either a synthetic product or a commercially available product may be used.

[0086] Relative to the dispersion (total mass 100 mass%), the content of the component (D) in the dispersion of the present invention is preferably 0.000005 mass% or more and 1.5 mass% or less, more preferably 0.00001 mass% or more and 1.5 mass% or less, further preferably 0.0001 mass% or more and 1.0 mass% or less, particularly preferably 0.001 mass% or more and 1.0 mass% or less, and most preferably 0.01 mass% or more and 1.0 mass% or less. Relative to the dispersion (total mass 100 mass%), the lower limit of the content of the component (D) in the dispersion is 0.000005 mass% or more, 0.00001 mass% or more, 0.0001 mass% or more, 0.001 mass% or more, 0.01 mass% or more, or 0.02 mass% or more. Relative to the dispersion (total mass 100 mass%), the upper limit of the content of the component (D) in the dispersion is preferably 1.5 mass% or less, more preferably 1.0 mass% or less.

[0087] In the dispersion of the present invention, the lower limit of the content of the component (D) is preferably 0.05 parts by mass or more, more preferably 0.1 parts by mass or more, and the upper limit is preferably 10 parts by mass or less, more preferably 5 parts by mass or less, relative to 100 parts by mass of the component (A).

[0088] [(E) ingredient]

[0089] In addition to the above-mentioned components (A), (B) and (C-2), the dispersion of the present invention may further contain an acidic compound as component (E). By containing component (E), the dispersibility of the lipid membrane structure in the aqueous phase can be improved. Component (E) may be only one or more.

[0090] Examples of the component (E) include inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, and carbonic acid, and organic acids such as acetic acid, formic acid, propionic acid, butyric acid, citric acid, lactic acid, succinic acid, malic acid, tartaric acid, pyrrolidonecarboxylic acid (PCA), gluconic acid, benzoic acid, ethylenediaminetetraacetic acid (EDTA), oxalic acid, glutaric acid, and phytic acid. Among them, organic acids are preferred from the viewpoint of obtaining a dispersion having a more excellent dispersibility of the lipid membrane structure.

[0091] Among them, from the viewpoint of being easy to form lipid membrane structure more effectively and being able to obtain a dispersion liquid with better dispersibility, and from the viewpoint of improving the storage stability of the dispersion liquid and the lipid membrane structure composition containing the dispersion liquid, (E) component preferably has an organic acid with chelation. As the main component forming the lipid membrane structure, the (A) component sometimes has the property of being easy to combine with metal ions. At this time, by adding an organic acid with chelation as the (E) component, the metal ions in the dispersion liquid are captured, and it is easy to form the lipid membrane structure more effectively, and a dispersion liquid with better dispersibility of the lipid membrane structure can be obtained, and the storage stability of the lipid membrane structure composition containing the dispersion liquid can be improved at the same time. That is, it can be inferred that a lipid membrane structure with excellent dispersibility and storage stability in the aqueous phase can be formed in the dispersion liquid. As an organic acid with chelation, for example, preferably citric acid, ethylenediaminetetraacetic acid (EDTA), oxalic acid, glutaric acid, more preferably ethylenediaminetetraacetic acid (EDTA).

[0092] As the component (E), either a synthetic product or a commercially available product may be used.

[0093] In the dispersion of the present invention, the lower limit of the content of the component (E) (calculated as free acid) is preferably 0.00001% by mass or more, 0.0001% by mass or more, 0.001% by mass or more, 0.01% by mass or more, 0.02% by mass or more, or 0.04% by mass or more, relative to the dispersion (total mass 100% by mass). The upper limit of the content of the component (E) (calculated as free acid) is preferably 3.0% by mass or less, 2.5% by mass or less, 2.0% by mass or less, 1.5% by mass or less, or 1.0% by mass or less, relative to the dispersion (total mass 100% by mass).

[0094] In the dispersion of the present invention, the lower limit of the content of the component (E) (calculated as free acid) is preferably 0.1 parts by mass or more, and more preferably 0.2 parts by mass or more, relative to 100 parts by mass of the component (A). The upper limit of the content of the component (E) (calculated as free acid) is more preferably 20 parts by mass or less, and further preferably 10 parts by mass or less, relative to 100 parts by mass of the component (A).

[0095] The dispersion of the present invention preferably contains both the components (D) and (E) from the viewpoint of improving the solubility of the components (D) and (E) in the dispersion and controlling the pH of the dispersion within a specified range. Such a dispersion can be obtained by adding the components (D) and (E) separately or by adding salts of the components (D) and (E).

[0096] There are no particular limitations on the salts of component (D) and component (E). Examples include lysine hydrochloride, sodium citrate salts such as trisodium citrate, sodium phosphate salts such as disodium hydrogen phosphate, sodium benzoate, sodium salts of ethylenediaminetetraacetic acid such as trisodium ethylenediaminetetraacetate (EDTA-3Na), sodium salts of diethylenetriaminepentaacetic acid such as pentasodium diethylenetriaminepentaacetate (5Na glutarate), and the like.

[0097] When the dispersion contains component (D) and component (E), the mass ratio (D) / (E) of component (D) to component (E) is 0.2 to 10. The lower limit of the range of the mass ratio (D) / (E) may be 0.3, 0.4 or 0.5. Furthermore, the upper limit of the range of the mass ratio (D) / (E) may be 10, 9, 8, 7, 6 or 5. The range of the mass ratio (D) / (E) is preferably, for example, 0.5 to 5.

[0098] In the dispersion of the present invention, the lower limit of the total content of components (D) and (E) is preferably 0.05% by mass or more, more preferably 0.1% by mass or more. The upper limit of the total content of components (D) and (E) is preferably 4.5% by mass or less, more preferably 2% by mass or less.

[0099] [(F)INGREDIENT]

[0100] In addition to the above-mentioned (A) component, (B) component and (C-2) component, the dispersion of the present invention may also contain a fat-soluble compound as the (F) component. When using the (A) component with a high acid value, by using the (B) component and the (F) component in combination, it is easy to form a lipid membrane structure in which the (A) component and the (F) component are oriented, and a lipid membrane structure with high storage stability can be formed. Furthermore, by using the (F) component in combination with the above-mentioned (D) component and / or (E) component, a more refined lipid membrane structure can be formed. The (F) component may be only one or more than two.

[0101] Examples of the component (F) include sterols such as phytosterol, cholesterol, di(phytosteryl / octyldodecyl) lauroyl glutamate, phytosteryl oleate, and phytosteryl glucoside; triterpenoids such as γ-oryzanol, glycyrrhizic acid, ursolic acid, and Centella asiatica extract (a mixture of asiatic acid, madecassic acid, and asiaticoside); fat-soluble vitamins such as retinol, hydrogenated retinol, cholecalciferol, tocopherol, and ascorbic acid esters; carotenoids such as astaxanthin and β-carotene; coenzymes such as ubiquinone; hydrocarbon compounds such as limonene, vaseline, and squalane; ceramides such as ceramide EOS, ceramide NG (ceramide 2), ceramide NP (ceramide 3), ceramide AP (ceramide 6II), ceramide EOP (ceramide 1), dihydroxylignoceryl phytosphingosine, cerebrosides, glycosphingolipids, and cetyl PG hydroxyethyl palmitamide; and polyphenols such as tetrahydrodiferuloyl methane and pterostilbene. Among them, from the viewpoint that when the component (F) is combined with the component (A) and the component (B), a lipid membrane structure in which the components (A) and (F) are oriented can be easily formed, and a dispersion with good storage stability can be obtained, and from the viewpoint of improving the storage stability of the lipid membrane structure-containing composition using the dispersion, the component (F) is preferably at least one selected from the group consisting of phytosterols, cholesterol, γ-oryzanol, glycyrrhizic acid, ursolic acid, Centella asiatica extract (a mixture of asiatic acid, madecassic acid and asiaticoside), hydrogenated retinol, tocopherol, astaxanthin, ubiquinone, ceramide NG, ceramide NP, ceramide AP, ceramide EOP, tetrahydrodiferuloylmethane and pterostilbene.

[0102] (F) component can use any of synthetic products and commercial products. As commercial products, for example, plant sterol-SKP manufactured by Tama Biochemical Co., Ltd., TECA manufactured by Bayer AG, dl-α-tocopherol manufactured by DSM Co., Ltd., NIKKOL (registered trademark) retinol H10, NIKKOL (registered trademark) VC-IP, squalane manufactured by Nikko Chemical Co., Ltd., astaxanthin-20C, γ-oryzanol manufactured by Oryza Oil Chemical Co., Ltd., Kaneka-coenzyme Q10 manufactured by KANEKA Co., Ltd., CERAMIDE2 manufactured by Croda Japan Co., Ltd., 90% ursolic acid, SabiWhite, pTeroWhite manufactured by Sabinsa Japan Co., Ltd., etc.

[0103] The content of the component (F) in the dispersion of the present invention is, for example, 0.0000005% by mass or more, 0.000001% by mass or more, 0.00001% by mass or more, 0.0001% by mass or more, 0.001% by mass or more, 0.01% by mass or more, or 0.1% by mass or more, relative to the dispersion (total mass 100% by mass). The upper limit of the content of the component (F) is 9% by mass or less, 8% by mass or less, 7% by mass or less, 6% by mass or less, 5% by mass or less, 4% by mass or less, 3% by mass or less, 2% by mass or less, or 1% by mass or less, relative to the dispersion (total mass 100% by mass).

[0104] Furthermore, in the dispersion of the present invention, the lower limit of the content of the component (F) is preferably 0.005 parts by mass or more, more preferably 0.05 parts by mass or more, further preferably 0.5 parts by mass or more, and particularly preferably 5 parts by mass or more, relative to 100 parts by mass of the component (A). The upper limit is preferably 60 parts by mass or less, more preferably 50 parts by mass or less, further preferably 40 parts by mass or less, and particularly preferably 30 parts by mass or less.

[0105] [Other ingredients]

[0106] The dispersion of the present invention may also contain ingredients (other ingredients) other than the above-mentioned (A) to (F) components. There is no particular limitation on other ingredients, and polyol compounds, oils, surfactants, moisturizers, whitening agents, pigments, alcohols, amino acids, sugars, vitamins, viscosity modifiers, polymers, colorants, powders, ultraviolet absorbers, preservatives, antibacterial agents, antioxidants, fragrances, beauty ingredients, electrolytes, fibers, plant extracts, etc. other than (B) components can be listed. One of these can be used alone, or two or more can be used in combination. For example, by blending beauty ingredients such as moisturizers and whitening agents in the dispersion, a lipid membrane structure encapsulating the beauty ingredients can be formed. In addition, when forming a lipid membrane structure encapsulating the beauty ingredients, there is no particular limitation on the timing of blending the beauty ingredients. The particle size and structure (single layer or multilayer) of the lipid membrane structure change until the concentration of the (A) component determined by the target particle size in the dispersion is reached, that is, the lipid membrane structure is in a reconstructible state. At this time, it can be considered that the beauty ingredients present in the dispersion are taken in and encapsulated in the reconstructed lipid membrane structure. Therefore, by appropriately designing the concentration of the component (A) in the dispersion, the cosmetic ingredient to be enhanced in penetration and the cosmetic ingredient to be enhanced in sustained release by suppressing penetration can be encapsulated in the lipid membrane structure that is most suitable from the viewpoint of the particle size and structure (monolayer or multilayer) of the lipid membrane structure. Thus, a variety of lipid membrane structures designed with the most suitable penetration and sustained release for various cosmetic ingredients can be easily and differently prepared, and by combining these, a product group with high functionality that meets the needs of various consumers can be easily and differently prepared.

[0107] [Dispersion method in dispersion step]

[0108] In the dispersion process, as long as the dispersion spontaneously forms a lipid membrane structure of more than 10nm and less than 200nm, there is no special limitation on the mixing method of component (A), component (B) and component (C-2). For example, in the dispersion process, the components can be mixed at one time or sequentially. In the case of sequentially mixing the components, there is no special limitation on the order. For example, after the components (A) and (B) are mixed, the component (C-2) can be added to mix, or after the components (A) and (C-2) are mixed, the component (B) can be added to mix, or the components (B) and (C) can be added to the component (A) at the same time (for example, a mixed solvent of the components (B) and (C-2) is added) to mix. And, for example, in addition to the above-mentioned components (A), (B) and (C-2), components (D) and / or (E) are further used to prepare the dispersion, components (D) and / or (E) can be added separately, or they can be pre-mixed and then added to the mixture. Furthermore, for example, in the case where a dispersion is prepared by further using component (D) and / or component (E) in addition to the above-mentioned component (A), component (B), component (C-2) and component (F), there is no particular limitation on the order of addition of component (F). For example, after mixing component (A), component (B), component (C-2) and component (F), component (C-2), component (D) and / or component (E) may be added simultaneously or sequentially. Alternatively, in addition to component (A), component (B) and component (C-2), component (D) and / or component (E) may be mixed simultaneously or sequentially, and component (F) may be added last. Furthermore, when a dispersion is prepared by further using the components described in the above-mentioned [other components], there is no particular limitation on the order of addition of the components described in the above-mentioned [other components], and for example, it may be appropriately selected according to solubility. For example, if it is fat-soluble, it may be added together with component (F) or added last. Alternatively, if it is water-soluble, it may be added together with the addition of the component (D) and / or the component (E), or may be added last.

[0109] In the dispersion process, it is preferred to mix component (A), component (B) and component (C-2) above the phase transition temperature of component (A). At this time, the formation efficiency of the lipid membrane structure is further improved, and a dispersion having better dispersion stability is formed. As the mixing temperature in the dispersion process, for example, the upper limit is 120°C or less, 110°C or less, 100°C or less, 95°C or less, or 90°C or less, and the lower limit is 40°C or more, 45°C or more, 50°C or more, 55°C or more, 60°C or more, 65°C or more, 70°C or more, 75°C or more, 80°C or more, or 85°C or more. As for the mixing temperature in the dispersion process, for example, it is 40 to 120°C, preferably 40 to 100°C, and more preferably 60 to 90°C. As a water-soluble component, for example, when mixing component (D), component (E) and / or other cosmetic ingredients, these water-soluble components can be uniformly dissolved in component (C-2) in advance and then mixed. The dissolution temperature of the water-soluble component at this time is not limited to the above-mentioned mixing temperature, and the water-soluble component can also be heated and dissolved at a temperature suitable for the dissolution of the water-soluble component. Thus, when mixing after uniformly dissolving the water-soluble component with component (C-2), mixing can be performed at any time and temperature. For example, in the case of mixing all the components in one container, first heat and dissolve the water-soluble component with component (C-2), and then add component (A) and component (B) thereto and mix. Alternatively, after heating and dissolving the water-soluble component with component (C-2) in other containers, it can be mixed with component (A) and component (B), and can be mixed at any time and any temperature. In addition, there is no special limitation on the mixing time, and it is preferably 10 to 180 minutes.

[0110] As for the dispersion obtained by mixing the components (A), (B) and (C-2), the lipid membrane structure will spontaneously form a fine lipid membrane structure without substantial mechanical shearing force, so it is sufficient to stir these components with a stirring force that is uniformly mixed. Specifically, the mixed solution obtained by mixing the components (A) and (B) can be added to the component (C-2) in an unstirred state, and then mixed with a stirring force that is uniformly mixed with these components, or it can be added while stirring the component (C-2). At this time, there is no particular limitation on the stirring conditions, for example, it can be carried out at a rotation speed of 10 to 300 rpm using a known stirring device. In addition, the mixed solution of the components (A) and (B) can be added all at once, can be added in multiple times, and can also be added sequentially at any addition speed using a known dropwise addition method. There is no particular limitation on the stirring method, and it can be carried out using a known stirring device such as a magnetic stirrer (for example, a hot stirrer, etc.), a paddle stirrer, a propeller stirrer, a planetary stirrer, etc., and these methods do not require a high degree of mechanical shearing force.

[0111] In the present invention, as one embodiment, the dispersing step may be a step of heating the mixed solution obtained by mixing the (A) component and the (B) component to a temperature higher than the phase transition temperature of the (A) component (e.g., 80°C, in which case the mixed solution is not equivalent to the lipid film forming agent), and then mixing with the (C-2) component heated to a temperature higher than the phase transition temperature of the (A) component (e.g., 80°C) to obtain a dispersion. In another embodiment, the dispersing step may be a step of mixing the (A) component, the (B) component, and the (C-2) component while heating to a temperature higher than the phase transition temperature of the (A) component (e.g., 80°C) to obtain a dispersion.

[0112] Here, the particle size of the lipid membrane structure in the dispersion obtained in the dispersing step is the same as that of the lipid membrane structure-containing composition described above. This is because in the present invention, the particle size of the lipid membrane structure contained in the dispersion is determined in the dispersing step.

[0113] From the viewpoint of obtaining a finer lipid membrane structure, the pH of the dispersion is preferably above 4.0, more preferably above 5.0, further preferably above 7.0, and further preferably above 8.0. On the other hand, from the viewpoint of obtaining a lipid membrane structure with uniform particle size (i.e., a dispersion with high uniformity), the pH of the dispersion is preferably below 10.0, more preferably below 9.5, and further preferably below 9.0. Therefore, the pH of the dispersion of a preferred embodiment of the present invention is 4.0 to 10.0. Here, the "pH of the dispersion" is the pH of the dispersion at 25°C measured using a pH meter based on the glass electrode method (HM-25R manufactured by DKK East Asia Co., Ltd.).

[0114] [Mixing process]

[0115] In the method for producing the lipid membrane structure composition of the present invention, a mixing step is performed before the dispersion step as needed. That is, in the method for producing the lipid membrane structure composition of the present invention, a mixing step is included in one embodiment. The mixing step is a step in which the components (A) and (B) are heated and uniformly mixed before the dispersion step to obtain a lipid film forming agent. That is, the mixing step is a step in which the components forming the lipid membrane structure are preheated and uniformly mixed to form a lipid film forming agent in a mixed state in which the components are uniformly mixed. Here, with respect to the difference between the mixing in the dispersion step and the mixing step, it can be distinguished by whether a uniform mixed state can be formed without containing the component (C-2). For example, when the lipid film forming agent that has undergone the mixing step is heated and dissolved above the phase transition temperature of the component (A) (for example, above 80°C), it is in a uniform and transparent liquid state, and then even if it is left for a certain period of time or cooled, it can maintain a uniform state, and there will be no precipitation, separation, or precipitation of a part of the components contained. For example, in the dispersion process, components (A) and (B) are heated to a temperature above the phase transition temperature of component (A) (e.g., 80° C.), and if undissolved components still exist or the mixture is in an uneven turbid state, the mixture can be distinguished by the precipitation, separation, or settling of a portion of the components when the mixture is subsequently left to stand for a certain period of time or cooled.

[0116] Therefore, the lipid film-forming agent obtained by the mixing step forms a uniform transparent solution when the phase transition temperature of component (A) is reached or above. When a solution containing components (A) and (B), or a solution containing components (A), (B) and (C-1) (i.e., component (C)) undergoes a transparent uniform solution stage, the solution is a lipid film-forming agent, and the step of obtaining the solution is regarded as a "mixing step".

[0117] In the case of an embodiment including a mixing step, the dispersing step is a step of mixing the lipid film-forming agent obtained in the mixing step with the component (C-2) to obtain a dispersion liquid that spontaneously forms a lipid film structure having a particle size of 10 nm or more and 200 nm or less. That is, the dispersing step in this case is a step of mixing the lipid film-forming agent containing the components (A) and (B) with the component (C-2) to obtain a dispersion liquid that spontaneously forms a lipid film structure having a particle size of 10 nm or more and 200 nm or less.

[0118] In addition to component (A) and component (B), the lipid film forming agent obtained in the mixing step may also contain component (C-1), components (D) to (F), and components described in the [Other components] section as needed. The preferred content of each component in the lipid film forming agent is described below, but the preferred forms of each component other than the content are as described above. In one embodiment, the mixing step is a step of mixing component (A), component (B), and one or more components selected from the group consisting of component (C-1), component (D), component (E), and component (F) as needed to obtain a lipid film forming agent.

[0119] There is no particular limitation on the content of component (A) in the lipid film forming agent of the present invention. For example, relative to the lipid film forming agent (total mass 100 mass%), the lower limit is 5 mass% or more, 6 mass% or more, 7 mass% or more, 8 mass% or more, 9 mass% or more, 10 mass% or more, 11 mass% or more, 12 mass% or more, 13 mass% or more, 14 mass% or more, 15 mass% or more, 16 mass% or more, 17 mass% or more, 18 mass% or more or 19 mass% or more. Relative to the lipid film forming agent (total mass 100 mass%), the upper limit of the content of component (A) in the lipid film forming agent is 40 mass% or less, 35 mass% or less, 30 mass% or less, 25 mass% or less or 20 mass% or less. The content of component (A) in the lipid film forming agent is preferably 5 to 40 mass%, more preferably 10 to 20 mass%.

[0120] There is no particular limitation on the content of component (B) in the lipid film forming agent of the present invention. For example, relative to the lipid film forming agent (total mass 100 mass%), the lower limit is 15 mass% or more, 20 mass% or more, 25 mass% or more, 30 mass% or more, 35 mass% or more, 40 mass% or more, 45 mass% or more or 50 mass% or more. Relative to the lipid film forming agent (total mass 100 mass%), the upper limit of the content of component (B) in the lipid film forming agent is 95 mass% or less, 90 mass% or less, 85 mass% or less, 80 mass% or less, 75 mass% or less, 70 mass% or less, 65 mass% or less, 60 mass% or less or 55 mass% or less. The content of component (B) in the lipid film forming agent is preferably 30 to 90 mass%, more preferably 40 to 80 mass%, and further preferably 50 to 70 mass%.

[0121] In the lipid film forming agent of the present invention, relative to 100 parts by mass of component (A), the content of component (B) exceeds 100 parts by mass. When the content of component (B) is less than 100 parts by mass relative to 100 parts by mass of component (A), a fine lipid film structure cannot be formed. Furthermore, relative to 100 parts by mass of component (A), the content of component (B) is more than 110 parts by mass, more than 120 parts by mass, more than 130 parts by mass, more than 140 parts by mass or more than 150 parts by mass. In the case of more than 150 parts by mass, component (A) is easy to be more evenly mixed in the lipid film forming agent. By using this lipid film forming agent, a lipid film structure with excellent dispersibility in an aqueous phase can be formed. Furthermore, from the viewpoint of obtaining a finer lipid membrane structure, the content of the component (B) is, for example, 160 parts by mass or more, 170 parts by mass or more, 180 parts by mass or more, 190 parts by mass or more, 200 parts by mass or more, 210 parts by mass or more, 220 parts by mass or more, 230 parts by mass or more, 240 parts by mass or more, 250 parts by mass or more, 260 parts by mass or more, 270 parts by mass or more, 280 parts by mass or more, 290 parts by mass or more, 300 parts by mass or more, 310 parts by mass or more, 320 parts by mass or more, 330 parts by mass or more, 340 parts by mass or more, 350 parts by mass or more, 360 parts by mass or more, 370 parts by mass or more, 380 parts by mass or more, 390 parts by mass or more, or 400 parts by mass or more, relative to 100 parts by mass of the component (A). On the other hand, there is no particular limitation on the upper limit of the content of (B) component relative to 100 parts by mass of (A) component, but when exceeding 2000 parts by mass, the solubility or dispersibility of (A) component in lipid film forming agent will not be affected, which will only lead to waste. Therefore, relative to 100 parts by mass of (A) component, for example, the content of (B) component is less than 2000 parts by mass, less than 1900 parts by mass, less than 1800 parts by mass, less than 1700 parts by mass, less than 1600 parts by mass, less than 1500 parts by mass, less than 1400 parts by mass, less than 1300 parts by mass, less than 1200 parts by mass, less than 1100 parts by mass, less than 1000 parts by mass, less than 900 parts by mass, less than 800 parts by mass, less than 700 parts by mass, less than 600 parts by mass or less than 500 parts by mass. Therefore, according to a preferred embodiment of the present invention, relative to 100 parts by mass of (A) component, the content of (B) component is preferably 110 to 2000 parts by mass.

[0122] In the lipid film-forming agent of the present invention, the component (C-1) is added as needed, and the lower limit of the content thereof is not particularly limited, but relative to the lipid film-forming agent (total mass 100 mass %), for example, the lower limit of the content of the component (C-1) in the lipid film-forming agent is 0.5 mass % or more, 1 mass % or more, 2 mass % or more, 3 mass % or more, 4 mass % or more, 5 mass % or more, 6 mass % or more, 7 mass % or more, 8 mass % or more, 9 mass % or more, 10 mass % or more, 11 mass % or more, 12 mass % or more, 13 mass % or more, 14 mass % or more, 15 mass % or more, 16 mass % or more, 17 mass % or more, 18 mass % or more, 19 mass % or more, 20 mass % or more, 21 mass % or more, 22 mass % or more, 23 mass % or more, 24 mass % or more, or 25 mass % or more. Relative to the lipid film forming agent (total mass 100 mass%), the upper limit of the content of the component (C-1) in the lipid film forming agent is 75 mass% or less, 70 mass% or less, 65 mass% or less, 60 mass% or less, 55 mass% or less, 50 mass% or less, 45 mass% or less, 40 mass% or less, 35 mass% or less or 30 mass% or less. The content of the component (C-1) in the lipid film forming agent relative to the lipid film forming agent (total mass 100 mass%) is preferably 0.5 to 70 mass%, more preferably 5 to 60 mass%, further preferably 15 to 50 mass%, and particularly preferably 20 to 40 mass%.

[0123] In addition, in the lipid film-forming agent of the present invention, the mass ratio of the component (B) to the component (C-1) ("component (B) : component (C-1)") is, for example, 25:75 or more, 30:70 or more, 35:65 or more, 40:60 or more, 45:55 or more, or 50:50 or more. In addition, in the lipid film-forming agent, the component (C-1) is added as needed, and there is no particular limitation on the lower limit of its content. Therefore, there is no particular limitation on the upper limit of the mass ratio of the component (B) to the component (C-1) ("component (B) : component (C-1)"), but the upper limit of the mass ratio of the component (B) to the component (C-1) is, for example, 99:1 or less, 90:10 or less, or 80:20 or less. The mass ratio of the component (B) to the component (C-1) is preferably 25:75 to 99:1, more preferably 30:70 to 90:10, and even more preferably 35:65 to 80:20.

[0124] In the lipid film forming agent of the present invention, component (D) is added as needed, and there is no particular limitation on the lower limit of its content, but as for the content of component (D) in the plasma membrane forming agent relative to the lipid film forming agent (total mass 100 mass%), for example, the lower limit is 0.01 mass% or more or 0.02 mass% or more, and the upper limit is 2 mass% or less or 1 mass% or less. The content of component (D) in the lipid film forming agent is preferably 0.01 to 2 mass%, more preferably 0.02 to 1 mass%.

[0125] In the lipid film forming agent of the present invention, component (D) is added as needed, and there is no particular limitation on the lower limit of its content, but as the content of component (D) in the lipid film forming agent relative to 100 parts by mass of component (A), for example, the lower limit is 0.05 parts by mass or more or 0.1 parts by mass or more, and the upper limit is 10% by mass or less, 9% by mass or less, 8% by mass or less, 7% by mass or less, 6% by mass or less, or 5% by mass or less. In the lipid film forming agent, the content of component (D) relative to 100 parts by mass of component (A) is preferably 0.05 to 10 parts by mass, and more preferably 0.1 to 5 parts by mass.

[0126] In the lipid film forming agent of the present invention, component (E) is added as needed, and there is no particular limitation on the lower limit of its content, but the content (converted as free acid) of component (E) in the lipid film forming agent relative to the lipid film forming agent (total mass 100 mass%), for example, the lower limit is 0.02 mass% or more or 0.04 mass% or more, and the upper limit is 4 mass% or less, 3 mass% or less, or 2 mass% or less. In the lipid film forming agent, the content (converted as free acid) of component (E) relative to the lipid film forming agent (total mass 100 mass%) is preferably 0.02 to 4 mass%, more preferably 0.04 to 2 mass%.

[0127] In the lipid film forming agent of the present invention, component (E) is added as needed, and there is no particular limitation on the lower limit of its content, but as the content (converted as free acid) of component (E) in the lipid film forming agent relative to 100 parts by mass of component (A), for example, the lower limit is 0.1 parts by mass or more or 0.2 parts by mass, and the upper limit is 20 parts by mass or less, 19 parts by mass or less, 18 parts by mass or less, 17 parts by mass or less, 16 parts by mass or less, 15 parts by mass or less, 14 parts by mass or less, 13 parts by mass or less, 12 parts by mass or less, 11 parts by mass or less or 10 parts by mass or less. In the lipid film forming agent, the content (converted as free acid) of component (E) relative to 100 parts by mass of component (A) is preferably 0.1 to 20 parts by mass, and more preferably 0.2 to 10 parts by mass.

[0128] When the lipid film-forming agent of the present invention contains component (D) and component (E), the mass ratio (D) / (E) of component (D) to component (E) is, for example, 0.2 to 10. The lower limit of the mass ratio (D) / (E) is, for example, 0.2, 0.3, 0.4 or 0.5, and the upper limit is 10, 9, 8, 7, 6 or 5. The range of the mass ratio (D) / (E) is, for example, preferably 0.5 to 5.

[0129] When the lipid film forming agent of the present invention contains component (D) and component (E), the total content of component (D) and component (E) relative to the lipid film forming agent (total mass 100 mass%) is, for example, 0.05 mass% or more or 0.1 mass% or more at the lower limit, and 4.5 mass% or less, 4.0 mass% or less, 3.5 mass% or less, 3.0 mass% or less, 2.5 mass% or less or 2 mass% or less at the upper limit. In the lipid film forming agent, the total content of component (D) and component (E) is preferably 0.05 to 4 mass%, more preferably 0.1 to 2 mass%, relative to the lipid film forming agent (total mass 100 mass%).

[0130] In the lipid film forming agent of the present invention, component (F) is added as needed, and there is no particular limitation on the lower limit of its content, but as the content of component (F) in the lipid film forming agent relative to the lipid film forming agent (total mass 100 mass%), for example, the lower limit is 0.00025 mass% or more, 0.001 mass% or more, 0.01 mass% or more, 0.1 mass% or more, or 1 mass% or more, and the upper limit is 12 mass% or less, 11 mass% or less, 10 mass% or less, 9 mass% or less, 8 mass% or less, 7 mass% or less, or 6 mass% or less. The content of component (F) in the lipid film forming agent is preferably 0.001 to 12 mass%, more preferably 0.01 to 10 mass%, further preferably 0.1 to 8 mass%, and particularly preferably 1 to 6 mass% relative to the lipid film forming agent (total mass 100 mass%).

[0131] In addition, in the lipid film forming agent of the present invention, component (F) is added as needed, and there is no particular limitation on the lower limit of its content, but as the content of component (F) in the lipid film forming agent relative to 100 parts by mass of component (A), for example, the lower limit is 0.005 parts by mass or more, 0.05 parts by mass or more, 0.5 parts by mass or more, or 5 parts by mass or more, and the upper limit is 60 parts by mass or less, 50 parts by mass or less, 40 parts by mass or less, or 30 parts by mass or less. In the lipid film forming agent, the content of component (F) relative to 100 parts by mass of component (A) is preferably 0.005 to 60 parts by mass, more preferably 0.05 to 50 parts by mass, further preferably 0.5 to 40 parts by mass, and particularly preferably 5 to 30 parts by mass.

[0132] In the mixing process, each component can be mixed at one time or sequentially. In the case of sequentially mixing each component, there is no particular limitation on the order. For example, after mixing component (A) and component (B), component (C-1) can be added to mix, or component (A) and component (C-1) can be mixed, and then component (B) can be added to mix, or component (B) and component (C-1) can be added to component (A) at the same time (for example, a mixture of component (B) and component (C-1) is added) to mix. And, for example, in addition to component (A), component (B) and component (C-1), component (D) and / or component (E) are further used to prepare a lipid film-forming agent, component (D) and / or component (E) can be added separately, or they can be mixed with component (C-1) in advance, and then the mixture is added to the mixture of component (A) and component (B). Furthermore, for example, in the case where a lipid film forming agent is produced by further using component (D) and / or component (E) in addition to component (A), component (B), component (C-1) and component (F), there is no particular limitation on the order of addition of component (F). For example, component (A), component (B) and component (F) may be mixed, and then component (C-1), component (D) and / or component (E) may be added simultaneously or sequentially. Alternatively, in addition to component (A) and component (B), component (C-1), component (D) and / or component (E) may be mixed simultaneously or sequentially, and then component (F) may be added last. Furthermore, in the case where a lipid film forming agent is produced by further using the components described in the above-mentioned [other components], there is no particular limitation on the order of addition of the components described in the above-mentioned [other components], and for example, it may be appropriately selected according to solubility. For example, if it is fat-soluble, it may be added together with component (F) or added last. Alternatively, if it is water-soluble, it may be added together with the addition of the component (C-1), the component (D) and / or the component (E), or may be added last.

[0133] In the mixing process, there is no particular limitation on the mixing temperature, but it is preferred to mix the (A) component and the (B) component at a temperature above the phase transition temperature of the (A) component. At this time, the miscibility of the (A) component and the (B) component is improved, and a lipid film-forming agent having excellent dispersibility in the (C-2) component constituting the aqueous phase can be obtained. For example, the upper limit can be 120°C or less, 110°C or less, 100°C or less, 95°C or less, or 90°C or less, and the lower limit can be 40°C or more, 45°C or more, 50°C or more, 55°C or more, 60°C or more, 65°C or more, 70°C or more, 75°C or more, 80°C or more, or 85°C or more. It is preferably 25 to 120°C, more preferably 40 to 100°C, and further preferably 60 to 90°C. In addition, there is no particular limitation on the mixing time, and it is preferably 10 to 180 minutes. There is no particular limitation on the mixing method, and the mixing may be carried out by any known mixing method using a magnetic stirrer (eg, a thermal stirrer), a paddle stirrer, a propeller stirrer, a planetary stirrer, or the like, which does not require a high degree of mechanical shearing force.

[0134] [Concentration adjustment process]

[0135] In addition to the above-mentioned dispersion step, the method for producing a lipid membrane structure-containing composition of the present invention may further include a step of adjusting the concentration after further mixing the above-mentioned dispersion and component (C-3) (hereinafter referred to as "concentration adjustment step"). In the case where the production method of the present invention includes a concentration adjustment step, a lipid membrane structure-containing composition can be obtained through the concentration adjustment step.

[0136] In the method for producing a lipid membrane structure-containing composition of the present invention, the concentration adjustment step is performed after the dispersion step as needed. That is, in the method for producing a lipid membrane structure-containing composition of the present invention, a concentration adjustment step is included in one embodiment. The concentration adjustment step is a step in which, after the dispersion step, component (C-3) is further added to the dispersion obtained in the dispersion step to achieve the target concentration of component (A) contained in the lipid membrane structure-containing composition. That is, the concentration adjustment step is a step in which the dispersion obtained in the dispersion step is mixed with the amount of component (C-3) required to achieve the target concentration of component (A) contained in the lipid membrane structure-containing composition, thereby obtaining a lipid membrane structure-containing composition.

[0137] In the case where the mixing step is not performed, the amount of the component (C-3) mixed with the dispersion in the concentration adjustment step is the amount obtained by subtracting the amount of the component (C-2) used in the dispersion step from the amount of the component (C) contained in the target lipid membrane structure-containing composition. In the case where the mixing step is performed, the amount of the component (C-3) is the amount obtained by subtracting the amount of the component (C-1) used in the mixing step and the amount of the component (C-2) used in the dispersion step from the amount of the component (C) contained in the target lipid membrane structure-containing composition. Alternatively, the amount of the component (C-3) used to dilute the concentration of the component (A) in the dispersion to the concentration of the component (A) in the target lipid membrane structure-containing composition can also be calculated.

[0138] There is no particular limitation on the method for mixing the dispersion and the component (C-3) in the concentration adjustment step. It may be a method of adding the component (C-3) to the dispersion, or a method of adding the above dispersion to the component (C-3). From the viewpoint of improving the dispersibility of the lipid membrane structure, the latter method is preferred. Therefore, the method for producing a lipid membrane structure-containing composition according to one embodiment of the present invention comprises adding the above dispersion to the component (C-3).

[0139] Considering that there may be a case where the concentration adjustment step is not performed, the upper limit of the content (concentration) of the components (A) to (C) in the lipid membrane structure-containing composition is the same as the content of each component in the above-mentioned dispersion, and is therefore omitted here. The lower limits of the components (A) and (B) are not particularly limited because the dispersion is diluted in the concentration adjustment step, but can be calculated based on the content of each component in the above-mentioned dispersion as a value diluted according to the concentration adjustment step.

[0140] Here, the particle size of the lipid membrane structure in the lipid membrane structure-containing composition obtained by the concentration adjustment step is the same as the particle size of the lipid membrane structure in the above-mentioned dispersion liquid. This is because, in the present invention, the particle size of the lipid membrane structure contained in the dispersion liquid is determined in the dispersion step, and the particle size can be maintained even when it is diluted in the concentration adjustment step.

[0141] In the concentration adjustment process, there is no particular limitation on the mixing temperature, and the mixing process can be carried out at a temperature above the phase transition temperature of component (A) or below the phase transition temperature of component (A). If it is the former, for example, the lower limit is above 40°C, above 45°C, above 50°C, above 55°C, above 60°C or above 65°C, and the upper limit is below 100°C, below 95°C or below 90°C. If it is the latter, for example, the upper limit is below 40°C, below 35°C, below 30°C, below 25°C, below 20°C, below 15°C or below 10°C, and the lower limit is above -10°C, above -5°C, above 0°C or above 5°C. In addition, there is no particular limitation on the mixing time, for example, it is 10 to 60 minutes.

[0142] The dispersion and component (C-3) can be mixed without stirring the aqueous phase (adding the dispersion to component (C-3)), or while stirring component (C-3), or by adding component (C-3) to the dispersion. In this case, there is no particular limitation on the stirring conditions of component (C-3) and / or the dispersion. For example, the stirring can be carried out using a known stirring device at a rotation speed of 10 to 300 rpm. Furthermore, the dispersion and / or component (C-3) can be added all at once, or in portions, or can be added sequentially using a known dropwise addition method at an arbitrary addition speed.

[0143] In the concentration adjustment process, there is no particular limitation on the temperature of the dispersion and the (C-3) component, and the temperature may be above the phase transition temperature of the (A) component or below the phase transition temperature of the (A) component. In the former case, for example, the lower limit is above 40°C, above 45°C, above 50°C, above 55°C, above 60°C or above 65°C, and the upper limit is below 100°C, below 95°C or below 90°C. In the latter case, for example, the upper limit is below 40°C, below 35°C, below 30°C, below 25°C, below 20°C, below 15°C or below 10°C, and the lower limit is above -10°C, above -5°C, above 0°C or above 5°C. Furthermore, the temperatures of the two may be the same or different. For example, the dispersion or the (C-3) component may be above the phase transition temperature of the (A) component, and the other (C-3) component or the dispersion may be below the phase transition temperature of the (A) component.

[0144] Here, in addition to component (C-3), component (D), component (E) and / or component (F) may be mixed with the dispersion in the concentration adjustment step. In this case, component (D), component (E) and / or component (F) may be added separately, or the mixture may be added after premixing. Furthermore, when the lipid membrane structure-containing composition is further prepared using the components described in the above-mentioned [other components], there is no particular limitation on the order of adding the components described in the above-mentioned [other components], and for example, the order may be appropriately selected according to the solubility. For example, if it is fat-soluble, it may be added together with the addition of component (F) or it may be added last. Alternatively, if it is water-soluble, it may be added together with the addition of component (D) and / or component (E) or it may be added last. Considering that there may be a situation where the concentration adjustment step is not performed, the upper limit of the content of these components (D) to (F) and the components described in the above-mentioned [other components] is the same as the content of each component in the dispersion. Since the dispersion liquid is diluted in the concentration adjusting step, the lower limit is not particularly limited, but can be calculated based on the content of each component in the above-mentioned dispersion liquid as a value diluted in the concentration adjusting step.

[0145] Here, as long as the lipid membrane structure can be formed, other components can be further added in the concentration adjustment process. As such components, for example, polyol compounds, oils, surfactants, humectants, whitening agents, pigments, alcohols, amino acids, sugars, vitamins, viscosity modifiers, polymers, colorants, powders, ultraviolet light absorbers, preservatives, antibacterial agents, antioxidants, spices, beauty ingredients, electrolytes, fibers, plant extracts, etc. other than (B) component can be listed. There is no special restriction on the order of addition of these other components, for example, it can be suitably selected according to solubility. In addition, the particle size of the lipid membrane structure obtained is determined by the concentration of (A) component in the dispersion obtained in the dispersion process, and thus as mentioned above, even if other components are further mixed in the concentration adjustment process except (C-3) component, the particle size of the lipid membrane structure will not be affected by the addition of other components in the concentration adjustment process.

[0146] In the method for producing the lipid membrane structure-containing composition of the present invention, in addition to the above-mentioned dispersion step, mixing step and concentration adjustment step, other steps such as purification (eg, filtration, etc.), cooling, and storage may be further performed.

[0147] <Uses of lipid membrane structure composition>

[0148] The lipid membrane structure composition of the present invention can be used directly, or the lipid membrane structure composition of the present invention can be further used in a dispersion medium. There is no particular limitation on the dispersion medium at this time, and for example, water, a polyol compound, or a mixture thereof can be cited. As the polyol compound, for example, a polyol compound represented by formula (1) can be included, and 1,3-butanediol, dipropylene glycol, tripropylene glycol, glycerol, diglycerol, propylene glycol, and 1,2-pentanediol can be cited.

[0149] According to the lipid membrane structure composition of the present invention, a fine lipid membrane structure can be spontaneously formed without substantial mechanical shearing force, and in this case, water-soluble components and fat-soluble components can be encapsulated. Thus, not only can the manufacturing cost of the manufacturing plant be reduced, but also a system of cosmetics and skin external preparations can be formed, that is, in a cosmetics specialty store, etc., cosmetics and skin external preparations mixed with a lipid membrane structure composition encapsulating any water-soluble or fat-soluble beauty component can be prepared at any time based on consultation using the system, and further, the lipid membrane structure can be expected to be more widely used.

[0150] In addition to using it as a cosmetic and a skin preparation for external use, the lipid membrane structure-containing composition of the present invention can impart skin care effects such as moisturizing by blending the lipid membrane structure-containing composition into cosmetics and skin preparations for external use. Therefore, one embodiment of the present invention is a cosmetic blended with the above-mentioned lipid membrane structure-containing composition. And, one embodiment of the present invention is a skin preparation for external use blended with the lipid membrane structure-containing composition. Therefore, according to the present invention, a method for producing a cosmetic is provided, the method comprising producing a lipid membrane structure-containing composition using the above-described method for producing. And, according to the present invention, a method for producing a skin preparation for external use is provided, the method comprising producing a lipid membrane structure-containing composition using the above-described method for producing.

[0151] There is no particular limitation on the form of the cosmetics and skin external preparations of the present invention, as long as the lipid membrane structure can be stably incorporated, and examples thereof include milky, gel-like, emulsion-like, cream-like, shampoo-like, facial cleanser-like, etc. From the viewpoint of taking advantage of the transparency of the appearance, the penetration feeling during application, and the high stability produced when the fine (e.g., particle size of 200 nm or less) lipid membrane structure of the present invention is contained, it is preferred to incorporate it in a low-viscosity emulsion in which the lipid membrane structure is difficult to incorporate.

[0152] In addition to the lipid-containing membrane structure composition, the cosmetic or skin preparation of the present invention may further contain ingredients commonly used in cosmetics or skin preparations, within the scope of not impairing the effects of the present invention. Such ingredients include, but are not limited to, polyol compounds other than component (B), oils, surfactants, moisturizers, whitening agents, pigments, alcohols, amino acids, vitamins, viscosity modifiers, polymers, colorants, powders, ultraviolet absorbers, preservatives, antibacterial agents, antioxidants, fragrances, cosmetic ingredients, electrolytes, pH adjusters, fibers, water, plant extracts, and the like.

[0153] From the viewpoint of obtaining the skin care effect brought about by the lipid membrane structure, the concentration of the lipid membrane structure in the cosmetics and skin external preparations blended with the lipid membrane structure-containing composition of the present invention is preferably 0.0001% by mass or more, more preferably 0.01% by mass or more, and further preferably 1% by mass or more. On the other hand, there is no particular limitation on the upper limit of the concentration, for example, it is less than 5% by mass.

[0154] The embodiments of the present invention have been described in detail above, but these are illustrative and exemplary and have no limiting effect. The scope of the present invention should obviously be interpreted according to the scope of the appended claims.

[0155] The present invention includes the following forms and embodiments.

[0156] 1. A method for producing a lipid membrane structure-containing composition, wherein the lipid membrane structure-containing composition comprises (A) a hydrogenated phospholipid having an acid value of 5 mgKOH / g or more, (B) a compound represented by the following formula 1, and (C) water.

[0157] Formula 1

[0158]

[0159] In the above formula 1, R is a substituted or unsubstituted alkyl group having 2 to 6 carbon atoms, or a substituted or unsubstituted cycloalkyl group having 3 to 6 carbon atoms, X is -O-, -C(=O)O- or -OC(=O)-, and n is 0 or 1, characterized in that:

[0160] The method comprises the step of mixing the component (A), the component (B) and the component (C) to obtain a dispersion liquid in which a lipid membrane structure having a particle size of 10 nm to 200 nm is spontaneously formed,

[0161] The method further includes determining the concentration of the component (A) relative to the dispersion liquid according to the target particle size of the lipid membrane structure contained in the lipid membrane structure-containing composition.

[0162] 2. The method for producing a lipid membrane structure-containing composition according to 1 above, wherein the content of the component (B) exceeds 100 parts by mass based on 100 parts by mass of the component (A).

[0163] 3. The method for producing a lipid membrane structure-containing composition according to 1 or 2 above, wherein the concentration of the component (A) relative to the dispersion is 0.01 to 15% by mass.

[0164] 4. The method for producing a lipid membrane structure-containing composition according to any one of 1 to 3 above, further comprising a concentration adjustment step of mixing the dispersion and the component (C) to obtain the lipid membrane structure-containing composition.

[0165] 5. The method for producing a lipid membrane structure-containing composition according to any one of 1 to 4 above, wherein in the dispersing step, mixing is performed at a temperature not lower than the phase transition temperature of the component (A).

[0166] 6. A method for producing a cosmetic, characterized in that it comprises the step of producing a lipid membrane structure-containing composition using the production method described in any one of 1 to 5 above.

[0167] 7. A method for producing an external skin preparation, comprising the step of producing a lipid membrane structure-containing composition using the production method described in any one of 1 to 5 above.

[0168] Example

[0169] The effects of the present invention are described below using examples and comparative examples, but the technical scope of the present invention is not limited to the following examples. In addition, in the following examples, the operation is carried out at room temperature (20 to 25° C.) unless otherwise specified. Also, “%” and “parts” refer to “mass %” and “mass parts”, respectively, unless otherwise specified.

[0170] <Preparation of lipid membrane structure-containing composition>

[0171] The lipid membrane structure composition was prepared by the following method. In addition, hydrogenated lecithin was prepared by purchasing a plurality of commercially available soybean-derived hydrogenated lecithins (acid value 0.3 to 30.8 mgKOH / g) with different acid values ​​and mixing them in a ratio to achieve the desired acid value. In addition, the phase transition temperature of the hydrogenated lecithin of the component (A) or the component (A') used in the Examples and Comparative Examples was 40 to 50°C.

[0172] [Examples 1-0 and 1-1, Examples 2-0 and 2-1, and Comparative Examples 1-0 and 1-1, Comparative Examples 2-0 and 2-1]

[0173] In a 100 mL beaker, 0.1 or 1 part by mass of hydrogenated lecithin (acid value 6.1 mgKOH / g, 13.9 or 17.3 mgKOH / g) as component (A) or hydrogenated lecithin (acid value 0.3 mgKOH / g) as component (A') and 0.4 or 4 parts by mass of 1,2-pentanediol (referred to as "pentanediol" in Tables 1 and 2) as component (B) or propylene glycol as component (B') were added, and stirred at 80°C for 20 minutes using a hot stirrer to prepare a lipid film forming agent. Next, 99.5 or 95 mL of purified water (referred to as "water (for dispersion)" in Tables 1 or 2) as component (C-2) was added to a 200 mL beaker to prepare an aqueous phase. The aqueous phase was heated to 80°C, and the lipid film forming agent prepared at 80°C was added while stirring at 100 rpm. After the addition was completed, the mixture was stirred at 80° C. for 2 minutes to prepare a dispersion liquid. This dispersion liquid was used as a lipid membrane structure composition in Examples 1-0 and 1-1, Examples 2-0 and 2-1, and Comparative Examples 1-0 and 1-1, and Comparative Examples 2-0 and 2-1.

[0174] [Examples 3-0 and 3-1]

[0175] In a 100 mL beaker, 0.1 or 1 part by mass of hydrogenated lecithin (acid value: 23.1 mgKOH / g) as the component (A), 0.4 or 4 parts by mass of 1,2-pentanediol as the component (B), and 0.013 or 0.13 parts by mass of phytosterol as the component (F) were added, and stirred at 80° C. for 20 minutes using a thermostitrator. Then, 0.15 or 1.49 parts by mass of purified water (described as “water (forming agent)” in Table 1) heated to 80° C. as the component (C-1), 0.003 or 0.03 parts by mass of arginine as the component (D), and 0.001 or 0.01 parts by mass of citric acid as the component (E) were added, and stirred at 80° C. for 5 minutes using a thermostitrator to prepare a lipid film-forming agent. Next, 99.33 mL or 93.34 mL of purified water (recorded as "water (for dispersion)" in Table 1) as component (C-2) was added to a 200 mL beaker to prepare an aqueous phase. The aqueous phase was heated to 80°C, and the lipid film forming agent prepared at 80°C was added while stirring at 100 rpm. After the addition was completed, the mixture was stirred at 80°C for 2 minutes to prepare a dispersion. This dispersion was used as a lipid membrane structure-containing composition in Examples 3-0 and 3-1.

[0176] [Comparative Examples 3-0 and 3-1]

[0177] In a 100 mL beaker, 0.1 or 1 part by mass of hydrogenated lecithin (acid value 13.9 mgKOH / g) as component (A), 0.45 or 4.5 parts by mass of propylene glycol as component (B'), and 0.45 or 4.5 parts by mass of glycerol as component (B') were added, and stirred at 80°C for 20 minutes using a hot stirrer to prepare a lipid film-forming agent. Next, 99 mL or 90 mL of purified water (represented as "water (for dispersion)" in Table 2) as component (C-2) was added to a 200 mL beaker to prepare an aqueous phase. The aqueous phase was heated to 80°C, and the lipid film-forming agent prepared at 80°C was added while stirring at 100 rpm. After the addition was completed, the dispersion was prepared by stirring at 80°C for 2 minutes. In Comparative Examples 3-0 and 3-1, the dispersion was used as a lipid membrane structure-containing composition.

[0178] [Examples 1-2 to 1-5 and Examples 2-2 to 2-5 and Comparative Examples 1-2 to 1-5 and Comparative Examples 2-2 to 2-5]

[0179] In a 100 mL beaker, 1 part by mass of hydrogenated lecithin as component (A) or component (A') having an acid value (unit: mgKOH / g) as described in Table 1 or Table 2, and 4 parts by mass of 1,2-pentanediol as component (B) or component (B') of propylene glycol were added, and stirred at 80°C for 20 minutes with a hot stirrer to prepare a lipid film forming agent. Next, purified water (the amount recorded as "water (for dispersion)" in Table 1 or Table 2) as component (C-2) heated to 80°C was added to the lipid film forming agent, and stirred at 80°C for 5 minutes with a hot stirrer to prepare a dispersion. Subsequently, purified water (the amount recorded as "water (for concentration adjustment)" in Table 1 or Table 2) as component (C-3) was added to a 200 mL beaker to prepare an aqueous phase. The aqueous phase was heated to 80° C., and the dispersion prepared at 80° C. was added while stirring at 100 rpm. After the addition, the mixture was stirred at 80° C. for 2 minutes to prepare a lipid membrane structure-containing composition.

[0180] [Examples 3-2 to 3-5]

[0181] In a 100 mL beaker, 1 part by mass of hydrogenated lecithin as component (A) having an acid value (unit: mgKOH / g) as component (B), 4 parts by mass of 1,2-pentanediol as component (B), and 0.13 parts by mass of phytosterol as component (F) were added, and stirred at 80° C. for 20 minutes with a hot stirrer. Then, 1.49 parts by mass of purified water as component (C-1) (described as "water (forming agent)" in Table 1), 0.03 parts by mass of arginine as component (D), and 0.01 parts by mass of citric acid as component (E) heated to 80° C. were added, and stirred at 80° C. for 5 minutes with a hot stirrer to prepare a lipid film-forming agent. Next, purified water as component (C-2) heated to 80° C. (the amount described as "water (dispersion)" in Table 1) was added, and stirred at 80° C. for 5 minutes with a hot stirrer to prepare a dispersion. Subsequently, purified water (the amount recorded as "water (for concentration adjustment)" in Table 1) as component (C-3) was added to a 200 mL beaker to prepare an aqueous phase. The aqueous phase was heated to 80°C, and the dispersion prepared at 80°C was added while stirring at 100 rpm. After the addition was completed, the mixture was stirred at 80°C for 2 minutes to prepare a lipid membrane structure composition.

[0182] [Comparative Examples 3-2 to 3-5]

[0183] In a 100 mL beaker, 1 part by mass of hydrogenated lecithin (acid value 13.9 mgKOH / g) as component (A), 4.5 parts by mass of propylene glycol as component (B'), and 4.5 parts by mass of glycerol as component (B') were added, and stirred at 80°C for 20 minutes with a hot stirrer to prepare a lipid film forming agent. Next, purified water (the amount recorded as "water (for dispersion)" in Table 2) as component (C-2) was added to a 200 mL beaker to prepare an aqueous phase. The aqueous phase was heated to 80°C, and the lipid film forming agent prepared at 80°C was added while stirring at 100 rpm. After the addition was completed, the dispersion was prepared by stirring at 80°C for 2 minutes. Subsequently, purified water (the amount recorded as "water (for concentration adjustment)" in Table 2) as component (C-3) was added to a 200 mL beaker to prepare an aqueous phase. The aqueous phase was heated to 80° C., and the dispersion prepared at 80° C. was added while stirring at 100 rpm. After the addition, the mixture was stirred at 80° C. for 2 minutes to prepare a lipid membrane structure-containing composition.

[0184] In Tables 1 and 2, blank means that the reagent is not contained.

[0185] <Evaluation method>

[0186] [Particle size, polydispersity index]

[0187] For the lipid membrane structure-containing composition prepared as described above, the particle size (scattered light intensity standard) and polydispersity index (PDI) of the lipid membrane structure were measured by dynamic light scattering measurement apparatus (Zetasizer Nano ZSP manufactured by Malvern Instruments) and cumulative amount analysis. The measurement results of the particle size and polydispersity index of the lipid membrane structure-containing composition are shown in Tables 1 and 2. In addition, in the lipid membrane structure-containing composition having a concentration adjustment step, the result of measuring the particle size of the lipid membrane structure of the dispersion obtained by the dispersion step confirmed that the particle size and polydispersity index of the lipid membrane structure of the dispersion were the same as the particle size and polydispersity index of the lipid membrane structure of the lipid membrane structure-containing composition after the concentration adjustment step.

[0188] [Cryo-TEM observation]

[0189] The lipid-containing membrane structure compositions prepared in Examples 1-0 to 1-5, 2-0 to 2-5, and 3-0 to 3-5 were observed by cryo-TEM using a transmission electron microscope (H-7650 manufactured by Hitachi High-Technologies Corporation). The observation photographs obtained by cryo-TEM observation of the lipid-containing membrane structure compositions prepared in Examples 3-1 and 3-3 are shown in FIG. Figure 1 (a), (b). Figure 1 In the observation photograph shown in (a), the ring-shaped image represents a monolamellar liposome structure, and the rod-shaped image represents a bilamellar structure, thereby confirming the formation of a monolamellar lipid membrane structure. Figure 1 In the observation photograph shown in (b), the multi-layered ring-shaped images represent multi-lamellar liposome structures, and the formation of a multi-lamellar lipid membrane structure was confirmed.

[0190] The particle size, polydispersity index, and Cryo-TEM observation results of the lipid membrane structure are shown in Tables 1 and 2 below. In addition, the particle size of the lipid membrane structure-containing compositions of Comparative Examples 1-0 to 1-5 could not be measured due to poor dispersion. In addition, in the column "Membrane structure of lipid membrane structure" in Table 1, when a single-layer lamellar structure was confirmed, it was marked as "single-layer", and when a multi-layer lamellar structure was confirmed, it was marked as "multi-layer". In addition, for the lipid membrane structure-containing compositions prepared in the comparative examples, the particle size exceeded 200 nm, so Cryo-TEM observation was not performed.

[0191]

[0192]

[0193] As shown in Table 1, it can be seen that in the dispersion step, when the concentration of the component (A) in the dispersion liquid is increased according to the target particle size of the lipid membrane structure contained in the lipid membrane structure-containing composition, the particle size of the obtained lipid membrane structure becomes larger. On the other hand, as shown in Table 2, when the acid value of the hydrogenated phospholipid in the lipid membrane structure-containing composition is less than 5 mgKOH / g or when propylene glycol or glycerol is contained instead of the component (B), even if the concentration of the dispersion liquid in the dispersion step is changed, the particle size of the obtained lipid membrane structure does not show the consistency of the relationship of the present invention or the dispersion liquid cannot be prepared (poor dispersion, aggregation occurs).

[0194] In addition, for each series of Examples 1-0 to 1-5, Examples 2-0 to 2-5, and Examples 3-0 to 3-5, the concentration (%) of the component (A) in the dispersion obtained in the dispersion step was set as the explanatory variable (x), and the particle size [nm] of the lipid membrane structure contained in the finally obtained lipid membrane structure-containing composition was set as the dependent variable (y). Furthermore, the approximate curve (third-order polynomial) and its determination coefficient (R) obtained using the "polynomial approximation (third-order)" function in the "approximate curve format setting" of Microsoft Excel (manufactured by Microsoft Corporation) were calculated. 2 ) are shown in the following Table 3.

[0195] Table 3

[0196] Approximate curve (3rd degree polynomial) <![CDATA[Coefficient of determination R 2 > Example 1 series <h2 style=";text-align:left;direction:ltr"><![CDATA[y=-186470x <h2 style=";text-align:left;direction:ltr"> 3 <h2 style=";text-align:left;direction:ltr"> +26536x<h2 style=";text-align:left;direction:ltr"> 2 <h2 style=";text-align:left;direction:ltr"> +101.74x+80.77]]><h2 style=";text-align:left;direction:ltr"> 0.9998 Example 2 Series <![CDATA[y=-13263x 3 +16590x 2 +126.93x+81.926]]> 0.9999 Example 3 series <h2 style=";text-align:left;direction:ltr"><![CDATA[y=846175x <h2 style=";text-align:left;direction:ltr"> 3 <h2 style=";text-align:left;direction:ltr"> -27979x<h2 style=";text-align:left;direction:ltr"> 2 <h2 style=";text-align:left;direction:ltr"> +474.32x+87.483]]><h2 style=";text-align:left;direction:ltr"> 0.9998

[0197] From the above, it can be seen that by combining a hydrogenated phospholipid having an acid value of 5 mgKOH / g or more with a polyol compound having a specific structure, and determining the concentration of component (A) in the dispersion according to the target particle size of the lipid membrane structure contained in the lipid membrane structure-containing composition during the dispersion step, the particle size of the obtained lipid membrane structure can be controlled.

[0198] This application is based on Japanese patent application No. 2022-140891 filed on September 5, 2022, the disclosure of which is incorporated herein by reference in its entirety.

Claims

1. A method for producing a lipid membrane structure-containing composition, the method comprising: (A) a hydrogenated phospholipid having an acid value of 5 mgKOH / g or more, (B) a compound represented by the following formula 1, and (C) water. Formula 1 In the above formula 1, R is a substituted or unsubstituted alkyl group having 2 to 6 carbon atoms, or a substituted or unsubstituted cycloalkyl group having 3 to 6 carbon atoms, X is -O-, -C(=O)O- or -OC(=O)-, and n is 0 or 1, characterized in that: The method comprises the step of mixing the component (A), the component (B) and the component (C) to obtain a dispersion liquid in which a lipid membrane structure having a particle size of 10 nm to 200 nm is spontaneously formed, The dispersing step includes a process of determining the concentration of the component (A) relative to the dispersion liquid according to the target particle size of the lipid membrane structure contained in the lipid membrane structure-containing composition.

2. The method for producing a lipid-containing membrane structure composition according to claim 1, wherein: The content of the component (B) in the dispersion exceeds 100 parts by mass based on 100 parts by mass of the component (A).

3. The method for producing a lipid membrane structure composition according to claim 1 or 2, wherein: The concentration of the component (A) relative to the dispersion is 0.01 to 15% by mass.

4. The method for producing a lipid membrane structure composition according to claim 1 or 2, wherein: The method further includes a concentration adjustment step of mixing the dispersion and the component (C) to obtain the lipid membrane structure-containing composition.

5. The method for producing a lipid membrane structure composition according to claim 1 or 2, wherein: In the dispersing step, the component (A), the component (B), and the component (C) are mixed at a temperature not lower than the phase transition temperature of the component (A).

6. A method for producing cosmetics, characterized in that: The method comprises the step of producing a lipid membrane structure-containing composition by using the production method according to claim 1 or 2.

7. A method for producing a skin external preparation, characterized in that: The method comprises the step of producing a lipid membrane structure-containing composition by using the production method according to claim 1 or 2.

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