JPWO2020175703A1 - Aqueous dispersion for cosmetics, cosmetic composition, and method for producing cosmetics - Google Patents

Abstract

An aqueous dispersion for cosmetics containing curcuminoid particles having an average particle size of 200 nm or less, and when the aqueous dispersion for cosmetics is stored at 4 ° C. for one year, the average particle size of the curcuminoid particles after storage An aqueous dispersion having a rate of change of 15% or less and a polydisperse index of 60% or less.

Description

The present disclosure relates to an aqueous dispersion for cosmetics, a cosmetic composition, and a method for producing a cosmetic.

Curcuminoids contained in turmeric extract are known as substances that regulate intracellular signal transduction that control cancer cell growth, inflammation, etc., and are expected to be applied as pharmaceuticals. Research is underway (Non-Patent Documents 1 and 2).

Yan Chen et al. , Molecules, 2012, vol. 17, pp. 5972-5987 Hamid Reza Rahimi et al. , Avicenna Journal of Dytomedicine, 2015, Vol. 6, No. 4, pp. 383-398

From the above characteristics, application of curcuminoid to cosmetics is expected. However, according to the diligent study by the present inventor, there is room for studying the compoundability or skin permeability of the aqueous dispersion of curcuminoid when used as a cosmetic. Further, since the dispersion of Patent Document 1 uses liposomes containing a large amount of phospholipids, the degree of freedom in selecting the lipids to be blended when producing cosmetics is low.

The present disclosure has been made in view of such circumstances, and is an aqueous dispersion for cosmetics having excellent storage stability when blended in cosmetics, and a cosmetic composition containing the aqueous dispersion for cosmetics. The purpose is to provide. Another object of the present disclosure is to provide a method for producing a cosmetic using such an aqueous dispersion for cosmetics.

The aqueous dispersion for cosmetics of the present disclosure contains particles of curcuminoid having an average particle diameter of 200 nm or less, and when the aqueous dispersion for cosmetics is stored at 4 ° C. for one year, the average particles of the curcuminoid particles after storage are contained. The rate of change in diameter is within 15%, and the rate of change in the polydispersity index is within 60%. In the aqueous dispersion for cosmetics, the content of phospholipid with respect to the total amount of curcuminoid and phospholipid may be 95% by mass or less.

Further, the aqueous dispersion for cosmetics of the present disclosure contains particles of curcuminoid having an average particle diameter of 200 nm or less, and the content of phospholipid with respect to the total amount of curcuminoid and phospholipid in the aqueous dispersion for cosmetics is 95. It may be mass% or less.

The aqueous dispersion for cosmetics further contains a nonionic surfactant, and the mass ratio of curcumin to the nonionic surfactant in the aqueous dispersion is preferably 55 or more.

The aqueous dispersion for cosmetics preferably further contains 1 to 50% by mass of a nonionic surfactant with respect to the total amount of the aqueous dispersion.

The aqueous dispersion for cosmetics preferably contains an ester of a monohydric or divalent alcohol and a fatty acid.

The aqueous dispersion for cosmetics preferably contains a monofatty acid ester or a difatty acid ester.

The cosmetic composition of the present disclosure contains the above-mentioned aqueous dispersion for cosmetics.

The method for producing a cosmetic of the present disclosure includes a step of blending the above-mentioned aqueous dispersion for cosmetics with other raw materials.

According to the present disclosure, it is possible to provide an aqueous dispersion for cosmetics and a cosmetic composition containing the aqueous dispersion for cosmetics, which are excellent in storage stability when blended in cosmetics.

The aqueous dispersion of the present embodiment contains particles of curcuminoid having an average particle size of 200 nm or less. In the aqueous dispersion of the present embodiment, when the aqueous dispersion is stored at 4 ° C. for one year, the rate of change in the average particle size of the curcuminoid particles after storage is within 15%, and the rate of change in the polydispersity index is high. At least one of the condition that it is within 60% and the condition that the content of phospholipid with respect to the total amount of curcuminoid and phospholipid in the aqueous dispersion for cosmetics is 95% by mass or less is satisfied.
When such an aqueous dispersion is blended in cosmetics, it has good compatibility with various additives blended in cosmetics, can suppress the generation of aggregates in various cosmetic formulations, and has a wide pH. , The generation of agglomerates can be suppressed even in the range of temperature and the like. Therefore, the aqueous dispersion of the present embodiment is excellent in storage stability, compoundability, appearance of the aqueous dispersion, and the like. In addition, in various cosmetic formulations, the aqueous dispersion of the present embodiment is excellent in that stability, formulation and appearance can be improved during the cosmetic formulation. Further, the aqueous dispersion of the present embodiment tends to be able to suppress a decrease in antioxidant activity in a wide range of pH, temperature and the like. In addition, the aqueous dispersion of the present embodiment tends to be excellent in antioxidant activity and skin permeability.
As described above, the aqueous dispersion of the present embodiment is excellent as an ingredient to be blended in cosmetics, and can be used as an aqueous dispersion for cosmetics. Further, as described later, since the aqueous dispersion of the present embodiment has an effect of suppressing the production of IL6, IL8, or MMP1, it can also be used as an IL6 production inhibitor, an IL8 production inhibitor, or an MMP1 production inhibitor. Further, as described later, since the aqueous dispersion of the present embodiment has an action of promoting the production of type I procollagen or hyaluronic acid, it is preferably I as a type I procollagen production promoter or hyaluronic acid production promoter. It can also be used as a type procollagen production promoter. The use as a promoter or inhibitor for the production of these specific substances may be a combination of two or more uses.

The average particle size of the curcuminoid particles is 200 nm or less, preferably 170 nm or less, more preferably 150 nm or less, further preferably 120 nm or less, and even more preferably 100 nm or less, from the viewpoint of further enhancing storage stability. It is particularly preferable to have it. The lower limit of the average particle size of the particles is not particularly limited, but may be 5 nm or more from the viewpoint of storage stability. The average particle size of the particles can be measured by a dynamic light scattering method, and specific devices include Zetasizer Nano (manufactured by Malvern) and the like. The average particle size of the particles may be a particle size (d50) that is a cumulative 50% of the cumulative particle size distribution on a number basis. Similarly, the polydispersity index of curcuminoids in particles can be measured by the dynamic light scattering method.
When the aqueous dispersion of the present embodiment is stored at 4 ° C. for 1 year, the rate of change in the average particle size of the curcuminoid particles after storage may be within 15%, and the rate of change in the polydispersity index after storage. May be within 60%. As the storage condition, it may be left still in a dark place or a place where there is no vibration.
The rate of change in the average particle size of curcuminoid particles after storage is the absolute value of the difference between the average particle size at the end of storage and the average particle size at the start of storage divided by the average particle size at the start of storage. Is.
Similarly, the rate of change of the polydispersity index of curcuminoid particles after storage is the absolute value of the difference between the polydispersity index at the end of storage and the polydispersity index at the start of storage, and the polydispersity index at the start of storage. It is divided by.
The term "within" refers to a range from 0 to a predetermined upper limit. The rate of change in the average particle size after storage may be substantially 0%, may be larger than 0%, and may be 0.1% or more. Further, the rate of change of the polydispersity index after storage may be substantially 0%, may be larger than 0%, or may be 0.1% or more.
The storage start time may be immediately after the production of the aqueous dispersion, or may be any time after the production. The end point of storage is one year from the start of storage, and may be one year and two months, or one year and five months.
The rate of change in the average particle size of the curcuminoid particles after storage at 4 ° C. for 1 year may be within 13%. The rate of change in the average particle size of the curcuminoid particles after storage at 4 ° C. for 1 year may be within 58%.
The storage is carried out in an environment where the evaporation of water of the aqueous dispersion can be prevented, and for example, it is preferable to store the aqueous dispersion in a closed container.
The polydispersity index of the curcuminoid particles in the aqueous dispersion may be 0.5 or less, and may be 0.4 or less.

The particle size (d90), which is 90% of the cumulative particle size distribution based on the number of particles of the curcuminoid, is preferably 400 nm or less, more preferably 350 nm or less, and further preferably 300 nm or less.

Examples of curcuminoids include curcumin or curcumin analogs, and curcumin analogs include demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin, and the like, which are expected to have antioxidant activity or wrinkle improving effect. preferable. The particles may contain one or more of curcumin or curcumin analogs.

The particles of curcuminoid may contain components other than curcuminoid. The content of curcuminoid in the particles of curcuminoid is preferably 70% by mass or more, more preferably 80% by mass or more, based on the total amount of the particles of curcuminoid. The upper limit of the content of curcuminoid in the particles of curcuminoid is not particularly limited, and may be substantially 100% by mass or 95% by mass with respect to the total amount of particles of curcuminoid.

The particles may or may not contain phospholipids. The content of phospholipid in the above particles is the content of phospholipid with respect to the total amount of curcuminoid and phospholipid in the aqueous dispersion from the viewpoint of ensuring the freedom of selection of the lipid to be added when producing the cosmetic composition. The amount may be 95% by mass or less, 90% by mass or less, 85% by mass or less, 80% by mass or less, 70% by mass or less, and 50% by mass. % Or less, 30% by mass or less, and 10% by mass or less. When the aqueous dispersion contains a phospholipid, the content of the phospholipid is preferably 1% by mass or more, and more preferably 5% by mass or more.

The phospholipid has a phosphate ester structure in the molecule, and examples thereof include soybean phospholipid, hydrogenated soybean phospholipid, egg yolk phospholipid, and hydrogenated egg yolk phospholipid.

The aqueous dispersion may contain a surfactant. The surfactant is not particularly limited, and anionic surfactants, cationic surfactants, amphoteric surfactants, and nonionic surfactants generally used in cosmetics can be used.
Anionic surfactants include alkyl sulfates, polyoxyethylene alkyl sulfates, polyethylene glycol (PEG) fatty acid amide monoethanolamide (MEA) sulfates, alkylmethyl taurine salts, olefin sulfonates, alkyl sulfosuccinates, Examples thereof include alkyl phosphate ester salts, fatty acid salts, acyl amino acid salts, alkyl lactates, and alkyl ISEthionates.
Cationic surfactants include lauryltrimethylammonium chloride, cetyltrimethylammonium chloride, stearyltrimethylammonium chloride, behenyltrimethylammonium chloride, cetyltrimethylammonium bromide, stearyltrimethylammonium bromide, dipolyoxyethylene oleylmethylammonium chloride, chloride. Polyoxyethylene behenylyl methyleneammonium, behenyltrimethylammonium methylsulfate, stearylhydroxypropyltrimethylammonium chloride, dicocoyldimethylammonium chloride, dialkyl (C12-18) dimethylammonium, disetyldimethylammonium chloride, distearyldimethylammonium chloride, ethyl Lanolin Sulfate Fatty Acid Aminopropyl dimethylammonium, Dicocoyl Ethylhydroxyethylammonium Methyl Sulfate, Palm Oil Alkylpropylene Glycol (PG) Dimonium Chloridric Acid, Linolate Amidopropylpropylene Glycol (PG) Dimonium Chloridric Acid, Stearamidpropyl Methyl Examples thereof include amines, dimethyl stearamines, and polyethylene oxide (POE) coconut oil alkylamines.
Examples of the amphoteric surfactant include an alkylbetaine-type amphoteric surfactant such as betaine lauryldimethylaminoacetate, an amidobetaine-type amphoteric surfactant such as amidopropylbetaine laurate, and a carbo such as hydroxyalkyl (C12-14) hydroxyethylsarcosine. Ishibetaine-type amphoteric surfactant, amide sulfobetaine-type amphoteric surfactant such as amidopropyl hydroxysulfobetaine laurate, imidazolinium betaine-type amphoteric surfactant such as sodium cocoamphodiacate, sodium lauraminopropionate, etc. Propionic acid type amphoteric surfactant, amine oxide type amphoteric surfactant such as lauryldimethylamine oxide, N- [3-alkyl (12,14) oxy-2-hydroxypropyl] -L-arginine hydrochloride, etc. Amino acid-type surfactants and the like can be mentioned.
Nonionic surfactants include monoglycerin fatty acid ester type nonionic surfactants, polyglycerin fatty acid ester type nonionic surfactants, sorbitan and polyoxyethylene sorbitan type nonionic surfactants ( For example, polyoxyethylene sorbitan fatty acid ester), polyoxyethylene sorbit type nonionic surfactant, polyoxyethylene hydrogenated castor oil type nonionic surfactant, pyrrolidone carboxylic acid (PCA) polyisostearate. Oxyethylene hydrogenated castor oil type nonionic surfactant, polyoxyethylene fatty acid type nonionic surfactant, polyoxyethylene fatty acid glycerin type nonionic surfactant, polyoxyethylene alkyl ether type nonionic Sexual surfactant, polyoxyethylene / polyoxypropylene alkyl ether type nonionic surfactant, polyoxyethylene / polyoxypropylene block polymer type nonionic surfactant, alkanolamide type nonionic surfactant Examples thereof include sucrose ester-type nonionic surfactants, alkylglycoside-type nonionic surfactants, polyethylene glycol distearate (PEG) -type nonionic surfactants, and the like.
These may be used alone or in combination of two or more. The content of the surfactant in the aqueous dispersion is preferably 0.01 to 80% by mass, preferably 0.1 to 80% by mass, based on the total amount of the aqueous dispersion from the viewpoint of skin irritation and compoundability. It is more preferably about 50% by mass, and even more preferably 0.5 to 40% by mass. When the aqueous dispersion contains a nonionic surfactant, the content of the nonionic surfactant is the total amount of the aqueous dispersion from the viewpoint of skin irritation and compoundability in cosmetic formulation. It is preferably 1 to 50% by mass, preferably 10 to 50% by mass, and more preferably 15 to 40% by mass.
When the aqueous dispersion contains a nonionic surfactant, the mass ratio of curcumin to the nonionic surfactant in the aqueous dispersion is 55 from the viewpoint of skin irritation and compoundability in cosmetic formulation. The above is preferable. The nonionic surfactant may contain a polyoxyethylene sorbitan fatty acid ester, and the mass ratio of curcumin to the polyoxyethylene sorbitan fatty acid ester may be 55 or more. Examples of the polyoxyethylene sorbitan fatty acid ester include tween 20 (polyoxyethylene sorbitan monolaurate) and tween 80 (polyoxyethylene sorbitan monooleate).

The aqueous dispersion may contain a solubilizer. The solubilizer may be an ester of a monohydric or divalent alcohol and a fatty acid. Examples of the monohydric or divalent alcohol include alcohols having 2 to 6 carbon atoms, and specific examples thereof include ethylene glycol, 1,3-propylene glycol, and 1,2-propylene glycol. As the fatty acid, a fatty acid having 4 to 20 carbon atoms is preferable, a fatty acid having 6 to 18 carbon atoms is more preferable, and caprylic acid is specifically mentioned. The ester of the monohydric or divalent alcohol and the fatty acid is preferably a diester of the divalent alcohol and the fatty acid.
Further, the solubilizer may be a monofatty acid ester or a difatty acid ester. As the fatty acid contained in the monofatty acid ester or the difatty acid ester, a fatty acid having 4 to 20 carbon atoms is preferable, a fatty acid having 6 to 18 carbon atoms is more preferable, and caprylic acid is specifically mentioned. The monofatty acid ester or difatty acid ester may be an ester of a fatty acid and a monovalent or divalent alcohol, or a monoglyceride or diglyceride.
Specific examples of the solubilizer include propylene glycol dicaprylate. The content of the solubilizer may be 0.01 to 5% by mass, or 0.1 to 1% by mass, based on the total amount of the aqueous dispersion.

The content of the curcuminoid particles in the aqueous dispersion is preferably 0.01 to 50% by mass, more preferably 0.05 to 30% by mass, based on the total amount of the aqueous dispersion from the viewpoint of compoundability and the like. It is preferably 0.1 to 10% by mass, and more preferably 0.1 to 10% by mass.

The lower limit of the curcumin content in the curcuminoid particles is not particularly limited, but is preferably 70% by mass and 80% by mass with respect to the total amount of curcuminoid particles from the viewpoint of imparting physiological functions such as antioxidants. Is more preferable. The upper limit of the curcumin content in the curcuminoid particles is not particularly limited, but the curcuminoid particles may be composed of curcumin, and the curcuminoid particles may contain 99.5% by mass or less of curcumin. good.

The aqueous dispersion contains the particles of the curcuminoid as well as an aqueous medium that is a continuous phase. The aqueous medium may be water itself, but may contain other components such as an organic solvent and additives together with water. The additive may contain an antioxidant, a preservative, or the like. Examples of the antioxidant include ascorbic acid and the like. Examples of the preservative include paraoxybenzoic acid ester, 1,2hexanediol, citric acid, phenoxyethanol and the like.

The aqueous dispersion of the present embodiment can be produced by dispersing a raw material containing curcuminoid in an aqueous medium using a microfluidic device or the like. The raw material containing curcuminoid may be curcuminoid itself, or may be a raw material containing curcuminoid such as turmeric extract. For example, Euro. J. Pharm. Biopharm. 117, 286 to 291 (2017) and the method described in Euro. J. Pharm. Biopharm. A method for preparing an aqueous dispersion using the microfluidic device described in 63, 128-133 (2006) is available.

The aqueous dispersion of the present embodiment has an antioxidant power of 50% of the antioxidant power of an aqueous solution of gallic acid containing 21% by mass of gallic acid when the antioxidant power of the aqueous dispersion is measured by the FRAP method. The concentration of gallic acid in the body is preferably 95 μmol / l or less. That is, since the aqueous dispersion of the present embodiment has excellent antioxidant power, gallic acid is contained even when the concentration of curcuminoid particles (that is, curcuminoid) contained in the aqueous dispersion is relatively small, 95 μmol / l or less. It has an antioxidant power of about 50% of the antioxidant power of an aqueous solution containing 21 parts by mass ppm. In the present specification, the molar concentration of curcuminoid in the aqueous dispersion is the molar amount of the aqueous dispersion with respect to the total volume of the aqueous dispersion.

The antioxidant power referred to in the present specification is measured by the FRAP method. In the FRAP method, the antioxidant contained in the sample reduces ^{Fe 3+} contained in the test reagent to produce ^{Fe 2+.} The reaction of the resulting Fe ²⁺ with the colorimetric probe forms a detectable dark blue product at wavelengths between 540 and 600 nm. ^{The reduced Fe 3+} can be quantified by measuring the absorbance at 540 to 600 nm, and this can be used as an index of antioxidant power. Colorimetric probes include 2,4,6-tris (2-pyridyl) -1,3,5-triazine.

In addition, gallic acid can be used as an index for evaluating the antioxidant power. The evaluation criteria for the antioxidant power of the aqueous dispersion is to measure the gallic acid aqueous solution containing 21% by mass of gallic acid by the FRAP method, and set the antioxidant power equal to 50% of the antioxidant power of the aqueous solution. be able to. In addition, the maximum antioxidant power of the gallic acid aqueous solution that can be measured by the test reagent of the FRAP method used can be used as a reference. In this case, a plurality of concentrations of gallic acid aqueous solution are prepared in advance, the FRAP method is measured under the same conditions, the antioxidant power with respect to the concentration of gallic acid in the aqueous solution is plotted, and a calibration curve is prepared. When the concentration of galvanic acid in the aqueous solution exceeds the measurable amount of the test reagent used, the measured antioxidant power becomes constant. That is, the concentration at which the slope of the calibration curve changes from positive to 0) is obtained, and such a concentration is set as the maximum antioxidant power of the carious acid aqueous solution. Then, an antioxidant power equal to 50% of the maximum antioxidant power can be used as an evaluation standard for the antioxidant power of the aqueous dispersion. The antioxidant power of the aqueous dispersion of the present embodiment is more preferably when any of the above evaluation criteria is satisfied at a concentration of 100 μmol / l or less, and further when any of the above criteria is satisfied at a concentration of 90 μmol / l or less. preferable. As an evaluation criterion of the antioxidant power of the aqueous dispersion, the antioxidant power equal to 50% of the antioxidant power of the gallic acid aqueous solution containing 10.6 mass ppm may be used.

Further, in the aqueous dispersion of the present embodiment, when a reaction solution containing the aqueous dispersion was added to L929 cells and an intracellular antioxidant activity assay was performed, a reaction containing quercetin at a concentration of 1000 μmol / l as a comparison target. It is preferable that the concentration of curcuminoid in the aqueous dispersion showing an antioxidant activity value of 50% of the antioxidant activity value when the solution is added and the intracellular antioxidant activity assay is performed is 100 μmol / l or less. That is, since the aqueous dispersion of the present embodiment has excellent antioxidant power, the concentrations of quercetinoids are compared when an intracellular antioxidant activity assay was performed on L929 cells using the aqueous dispersion of the present embodiment. Even if it is a small value of 100 μmol / l or less, it tends to show an antioxidant activity value of 50% of the antioxidant activity value of the reaction solution containing quercetin at a concentration of 1000 μmol / l.

In this embodiment, the antioxidant activity value is determined by the following intracellular antioxidant activity assay.
First, a reaction solution containing the aqueous dispersion (sample) and a fluorescent probe is added to L929 cells, and a measurement sample in which the sample and the fluorescent probe are incorporated into the cells is prepared. As the fluorescent probe, a fluorescent probe having high cell permeability (2', 7'-dichlorofluoresin diacetate (DCFH-DA), etc.) is used. Then, in order to generate reactive oxygen species in the cells, a free radical initiator solution is added, and the fluorescence intensity of the measurement sample is measured at 3-minute intervals for a total of 60 minutes. Calculate the sum of the fluorescence intensity at each time divided by the fluorescence intensity at the start of measurement (0 minute), and correspond to the area where the area under the curve that plots the fluorescence intensity with respect to AUC (area under curve) is integrated. ) Is obtained, and this is used as the antioxidant activity value. Similarly, the AUC is obtained using the measurement sample in which the sample concentration is changed, and a calibration curve is prepared.
As a comparison target, the AUC is similarly calculated for a measurement sample in which a reaction solution containing quercetin at a concentration of 1000 μmol / l instead of the above sample is added to L929 cells. Then, using the above calibration curve, the sample concentration corresponding to the antioxidant activity value of 50% (which is used as the evaluation standard of the antioxidant activity value) of the antioxidant activity value of the measurement sample to be compared is determined.
Examples of commercially available kits for performing such measurements include OxiSelect Cellular Antioxidant Activity Assay Kit (Green Fluorescence) (manufactured by Cell Biolab).

The antioxidant activity value of the aqueous dispersion of the present embodiment is more preferably 90 μmol / l or less satisfying the above-mentioned evaluation criteria, and further preferably 80 μmol / l or less satisfying the above-mentioned evaluation criteria.

Since the aqueous dispersion of the present embodiment tends to have excellent skin permeability of curcuminoids, excellent results also tend to be obtained in the evaluation of antioxidant power using a three-dimensional skin model including the epidermis layer and the dermis layer. be. More specifically, the aqueous dispersion of the present embodiment is prepared in a medium after culturing a three-dimensional skin model containing the epidermis layer and the dermal layer, respectively, under the following conditions (A) and (B). When the content of interleukin 6 was measured by the sandwich ELISA method using a monoclonal antibody against interleukin 6, the content of interleukin 6 contained in the medium of condition (B) with respect to the medium of condition (A) was 90. It is preferably less than%.
(A) A 0.4 mass% ascorbic acid aqueous solution was added onto the epidermis layer of the three-dimensional skin model in an amount of 1 ^{mL per 1 cm 2 of the} three-dimensional skin model, and oxidative stress was applied in an atmosphere of 37 ° C. and a carbon dioxide concentration of 5% by volume. After that, it is cultured for 24 hours.
(B) After adding the aqueous dispersion on the epidermis layer of the three-dimensional skin model at the same concentration and amount as the ascorbic acid aqueous solution and applying oxidative stress in an atmosphere of 37 ° C. and a carbon dioxide concentration of 5% by volume. , Incubate for 24 hours.
In the condition (A), instead of the above ascorbic acid aqueous solution, potassium chloride 0.02 w / v%, potassium dihydrogen phosphate 0.02 w / v%, sodium chloride 0.8 w / v%, dihydrogen phosphate dihydrate. A phosphate buffer containing 0.115 w / v% sodium may be used.
The content of interleukin 6 in the medium of condition (B) with respect to the medium of condition (A) is more preferably 87% or less. When oxidative stress is applied by UVA irradiation, the content of interleukin 6 in the medium of condition (B) is preferably 30% or less, and is preferably 15% or less. More preferably, it is more preferably 10% or less, and particularly preferably 6% or less.

The content of matrix metalloproteinase 1 in the medium of the condition (B) with respect to the medium of the above-mentioned post-culture condition (A) is preferably 60% or less, more preferably 55% or less, and more preferably 50% or less. Is even more preferable. In this embodiment, the content of matrix metalloproteinase 1 in the medium is measured by the sandwich ELISA method using a monoclonal antibody against matrix metalloproteinase 1.

Since the aqueous dispersion of the present embodiment tends to have excellent skin permeability of curcuminoids, it is excellent in the amount of extracellular matrix produced using a three-dimensional skin model including the epidermis layer and the dermis layer after oxidative stress is applied. There is a tendency. The content of type I procollagen in the medium of the condition (B) with respect to the medium of the above-mentioned post-culture condition (A) is preferably 150% or more, more preferably 200% or more, and more preferably 250% or more. Is even more preferable. In this embodiment, the content of type I procollagen in the medium is measured by the sandwich ELISA method using a monoclonal antibody against type I procollagen.

The content of hyaluronic acid in the medium under the condition (B) under the above-mentioned post-culture condition (A) is preferably 120% or more, more preferably 150% or more, and more preferably 180% or more. Is even more preferable. In this embodiment, the content of hyaluronic acid in the medium is measured by the sandwich ELISA method using a monoclonal antibody against hyaluronic acid.

The content of interleukin 8 in the medium under the condition (B) under the condition (A) after culturing described above is preferably 90% or less, more preferably 85% or less, and more preferably 80% or less. More preferred. In this embodiment, the content of interleukin 8 in the medium is measured by the sandwich ELISA method using a monoclonal antibody against interleukin 8.

Interleukin 6 and interleukin 8 are substances involved in the inflammatory reaction, and their amounts increase when inflammation occurs due to reactive oxygen species generated by oxidative stress applied to the three-dimensional skin model. Therefore, it is often detected in the culture medium in which the inflamed three-dimensional skin model is cultured. Matrix metalloproteinase 1 is an enzyme that decomposes extracellular matrix such as collagen at the site of inflammation, and when the amount of interleukin 6 or interleukin 8 increases, the amount produced increases. When the oxidative stressed three-dimensional skin model in which the aqueous dispersion of the present embodiment was added onto the epidermis layer was cultured, the oxidative stressed three-dimensional skin model in which a phosphate buffer was added onto the epidermis layer was applied. Inflammation tends to be suppressed by suppressing the generation of active oxygen species due to oxidative stress in the three-dimensional skin model, and increases when inflammation occurs. Interleukin 6, interleukin 8, And matrix metalloproase 1 tends to decrease. In addition, since the amount of type I procollagen, which is a precursor of collagen, also increases, the amount of collagen produced tends to increase.

Examples of the oxidative stress include UVA irradiation, UVB irradiation and the like, and UVA irradiation may be used. In the case of UVA irradiation, the total irradiation amount is ^{preferably 300 mJ / cm 2} or more. In the case of UVB irradiation, the total irradiation amount is ^{preferably 120 mJ / cm 2} or more. Culture after UVA or UVB irradiation may be carried out for 24 hours or more.

As described above, since the aqueous dispersion of the present embodiment tends to effectively suppress skin aging due to oxidative stress, particularly photoaging, it can also be used as a wrinkle improving agent or the like.

Since the aqueous dispersion of the present embodiment tends to have excellent skin permeability of curcuminoids, a three-dimensional skin model including the epidermis layer and the dermis layer when no intentional oxidative stress such as UV irradiation is applied was used. Excellent results also tend to be obtained in the evaluation of the amount of extracellular matrix produced. More specifically, the aqueous dispersion of the present embodiment is prepared by culturing a three-dimensional skin model including a skin layer and a dermis layer under the following conditions (C) and (D), and then I in a medium. When the content of type procollagen was measured by the sandwich ELISA method using a monoclonal antibody against the content of type I procollagen, type I procollagen contained in the medium of condition (D) with respect to the medium of condition (C). The content of is preferably 120% or more.
(C) Add 1 mL of 0.4 mass% ascorbic acid aqueous solution on the epidermis layer of the three-dimensional skin model ^{per 1 cm 2 of the} three-dimensional skin model, and incubate in an atmosphere of 37 ° C. and a carbon dioxide concentration of 5% by volume for 48 hours.
(D) The aqueous dispersion is added onto the epidermis layer of the three-dimensional skin model at the same concentration and amount as the ascorbic acid aqueous solution, and cultured for 48 hours in an atmosphere of 37 ° C. and a carbon dioxide concentration of 5% by volume.
In the condition (C), instead of the above-mentioned ascorbic acid aqueous solution, potassium chloride 0.02 w / v%, potassium dihydrogen phosphate 0.02 w / v%, sodium chloride 0.8 w / v%, dihydrogen phosphate dihydrogen phosphate. A phosphate buffer containing 0.115 w / v% sodium may be used.
The content of type I procollagen in the medium of the condition (D) with respect to the medium of the condition (C) is more preferably 150% or more, and further preferably 170% or more.

The content of hyaluronic acid in the medium under the condition (D) under the condition (C) after culturing described above is preferably 120% or more, more preferably 150% or more, and further preferably 170% or more. preferable. In this embodiment, the content of hyaluronic acid in the medium is measured by the sandwich ELISA method using a monoclonal antibody against hyaluronic acid.

As described above, since the aqueous dispersion of the present embodiment tends to promote an increase in the amount of extracellular matrix produced, it can also be used as a wrinkle preventive agent or the like.

If desired, the aqueous dispersion of the present embodiment may appropriately contain particles other than curcuminoid particles (referred to as “other particles”). The other particles may contain one or more types, for example, vitamin E particles having an average particle size of 50 nm or less, gold particles having an average particle size of 200 nm or less, and ceramides having an average particle size of 200 nm or less. It may contain at least one of the particles. The vitamin E particles may contain components other than vitamin E, and preferably contain 70% by mass or more of vitamin E with respect to the total amount of the vitamin E particles. The gold particles may contain components other than gold, and preferably contain 70% by mass or more of gold with respect to the total amount of gold particles. The ceramide particles may contain components other than the ceramides, and it is preferable that the ceramides are contained in an amount of 70% by mass or more based on the total amount of the ceramide particles.

<Cosmetic composition>
The aqueous dispersion of the present embodiment can be made into a cosmetic composition by blending an ingredient (additive for cosmetics) that is usually blended in cosmetics. The content of the curcuminoid particles in the cosmetic composition is preferably 0.001% by mass or more, more preferably 0.01% by mass, from the viewpoint of further enhancing the storage stability of the curcuminoid particles in the cosmetic composition. The above is more preferably 0.05% by mass or more. Further, from the viewpoint of ensuring the performance as a cosmetic, it is preferably 50% by mass or less. Examples of the various components include those described below.

Examples of the cosmetic additives include oily components, powder components, oil gelling agents, aqueous components, water-soluble polymers, ultraviolet absorbers, antioxidants, beauty components, preservatives, and the like. Additives can be appropriately blended in order to impart various effects. In addition, a surfactant can be added to the cosmetic composition. Examples of the surfactant that may be added to the cosmetic composition include the same surfactants that may be blended in the above-mentioned aqueous dispersion, and a nonionic surfactant is preferable, and a polyglycerin fatty acid ester is preferable. Type nonionic surfactants are more preferred.

The oily components include hydrocarbons, fats and oils, waxes, ester oils, and hydrogenated oils, regardless of the origin of animal oils, vegetable oils, synthetic oils, etc., and the properties of solid, semi-solid oils, liquid oils, volatile oils, etc. Examples thereof include oils, fatty acids, higher alcohols, silicone oils, lanolin derivatives, oily gelling agents and the like. Specifically, hydrocarbons such as paraffin wax, ceresin wax, microcrystallin wax, montan wax, fishertroph wax, liquid paraffin, squalane, vaseline, mokurou, mink oil, olive oil, avocado oil, castor oil, macadamian nuts. Oils, fats and oils such as meadowfoam oil, waxes such as beeswax, carnauba wax, candelilla wax, gay wax, pentaerythric acid rosinate, jojoba oil, glyceryl tri-2-ethylhexanoate, isotridecyl isononanoate, 2- Cetyl ethylhexanoate, isopropyl myristate, isopropyl palmitate, octyldodecyl myristate, glyceryl trioctarate, polyglyceryl diisostearate, glyceryl triisostearate, diglyceryl triisostearate, polyglyceryl triisostearate, diisostearyl malate, diethylhexane Esters such as neopentyl glycol acid, fatty acids such as oleic acid, isostearic acid, stearic acid, lauric acid, myristic acid and behenic acid, higher alcohols such as stearyl alcohol, cetyl alcohol, lauryl alcohol, behenyl alcohol and oleyl alcohol, Methylpolysiloxane, dimethylpolysiloxane (dimethicone), methylphenylpolysiloxane, trimethylsirocylic acid, crosslinked polyether-modified methylpolysiloxane, methacryl-modified methylpolysiloxane, oleyl-modified methylpolysiloxane, polyvinylpyrrolidone-modified methylpolysiloxane, poly Examples thereof include silicone oils such as ether-modified polysiloxane, lanolin derivatives such as lanolin, lanolin acetate, lanolin fatty acid isopropyl, and lanolin alcohol, and oil-based gelling agents such as aluminum isostearate, calcium stearate, and 12-hydroxystearic acid. , One or more of these can be used. Among these, low molecular weight ester oils such as glyceryl tri-2-ethylcaproate, isononyl isononanoate, and neopentyl glycol diethylhexanoate are preferable from the viewpoint of spreading and adhesion. The oily component may be contained, for example, in an amount of 0.1 to 20% by mass based on the total amount of the cosmetic composition.

The powder component is not particularly limited by the shape such as spherical, plate-like, needle-like, particle size such as fumes, fine particles, pigment grade, and particle structure such as porous and non-porous, and inorganic powders. , Glittering powders, organic powders, dye powders, metal powders, composite powders and the like. Specifically, white inorganic pigments such as titanium oxide, zinc oxide, cerium oxide, and barium sulfate, colored inorganic pigments such as iron oxide, carbon black, chromium oxide, chromium hydroxide, dark blue, and ultramarine, talc, white mica, and gold. Mica, red mica, black mica, synthetic mica, silk mica (serisite), synthetic sericite, kaolin, silicon carbide, bentonite, smectite, aluminum oxide, magnesium oxide, zirconium oxide, antimony oxide, clay silicate, aluminum silicate , White constitution powder such as aluminum magnesium metasilicate, calcium silicate, barium silicate, magnesium silicate, calcium carbonate, magnesium carbonate, hydroxyapatite, boron nitride, silica, titanium dioxide coated mica, titanium dioxide coated bismuth chloride, Titanium oxide-coated mica, iron oxide mica, dark blue-treated mica titanium, carmine-treated mica titanium, bismuth oxychloride, bright powder such as fish scale foil, polyamide-based resin, polyethylene-based resin, polyacrylic resin, polyester-based resin, Fluorine-based resin, cellulose-based resin, polystyrene-based resin, copolymer resin such as styrene-acrylic copolymer, organic polymer resin powder such as polypropylene-based resin, silicone resin, urethane resin, zinc stearate, N-acylidine, etc. Natural organic powders such as organic low molecular weight powder, starch, silk powder, cellulose powder, red 201, red 202, red 205, red 226, red 228, orange 203, orange 204, blue Organic pigment powders such as No. 404 and No. 401, red No. 3, red No. 104, red No. 106, orange 205, yellow No. 4, yellow No. 5, green No. 3, blue No. 1 and the like zirconium, barium or Organic pigment powder such as aluminum lake or metal powder such as aluminum powder, gold powder, silver powder, fine particle titanium oxide coated mica titanium, fine particle zinc oxide coated mica titanium, barium sulfate coated mica titanium, titanium oxide silicon dioxide, zinc zinc oxide Composite powders such as silicon, polyethylene terephthalate / aluminum / epoxy laminated powder, polyethylene terephthalate / polyolefin laminated film powder, polyethylene terephthalate / polymethylmethacrylate laminated film powder powder, lame agent, tar dye, natural dye, etc. are mentioned. Can be used alone or in combination of two or more, and a composite thereof may be used. These powder components include fluorine-based compounds, silicone-based compounds, metal soaps, lecithin, hydrogenated lecithin, collagen, hydrocarbons, higher fatty acids, higher alcohols, esters, wax qualans, waxes, surfactants, and the like. Surface treatment may be performed using seeds or two or more kinds.

Examples of the oil gelling agent include dextrin fatty acid ester, sucrose fatty acid ester, starch fatty acid ester, hydroxystearic acid, calcium stearate, hydrophobic fuming silica, organically modified bentonite, and the like, and one or more of these are used. You may.

The aqueous component may be water or any component soluble in water, and in addition to water, for example, glycols such as propylene glycol, 1,3-butylene glycol, dipropylene glycol, polyethylene glycol, glycerin, and the like. Examples thereof include glycerols such as diglycerin and polyglycerin, and plant extracts such as aloe vera, witch hazel, hamamelis, cucumber, lemon, lavender, and rose.

Examples of the water-soluble polymer include natural polymers such as guar gum, sodium chondroitin sulfate, hyaluronic acid, arabic gum, sodium alginate, carrageenan, mucopolysaccharide, collagen, elastin, keratin, and xanthan gum, and methyl cellulose, hydroxyethyl cellulose, and carboxymethyl cellulose. Examples thereof include semi-synthetic ones and synthetic ones such as carboxyvinyl polymer, polyvinyl alcohol, polyvinylpyrrolidone and sodium polyacrylate. The water-soluble polymer may be contained, for example, in an amount of 1 to 30% by mass based on the total amount of the cosmetic composition.

Examples of the ultraviolet absorber include benzophenone-based, PABA-based, cinnamic acid-based, salicylic acid-based, 4-tert-butyl-4'-methoxydibenzoylmethane, oxybenzone and the like.

Examples of the antioxidant include vitamin E such as tocopherol and ascorbic acid.

Examples of cosmetological ingredients include vitamins, proteins, anti-inflammatory agents, crude drugs and the like.

Examples of the preservative include paraoxybenzoic acid ester, phenoxyethanol and the like.

In addition, various components other than the above include, for example, moisturizers, film-forming agents, anti-fading agents, defoamers, fragrances, perfluoropolyethers, perfluorodecalins, perfluorooctanes and other fluorine-based oils; polyhydric alcohols. , Sugars, amino acids, various polymers, ethanol, thickeners, pH adjusters, blood circulation promoters, cold sensitizers, bactericides, skin activators and the like can also be blended within the range not impairing the effects of the present disclosure.

Further, the cosmetic composition of the present embodiment is not particularly limited in its dosage form and product form, and is in the form of a water-in-oil type, an oil-in-water type, a water-dispersed type, a press form, a solid agent, a powder or the like. As a product form (cosmetics), skin cosmetics such as face wash foam cream, cleansing, massage cream, pack, lotion, milky lotion, cream, beauty liquid, makeup base, sunscreen, etc. Finishing cosmetics such as foundation, water powder, eye shadow, eye liner, mascara, eyebrow, concealer, lipstick, lip cream, hair mist, shampoo, rinse, treatment, hair tonic, hair cream, pomade, tic, liquid hair styling product, Examples thereof include hair cosmetics such as set lotions, hair sprays and hair dyes, and antiperspirants such as powder sprays and roll-ons. Among these, solid formulations such as foundations and face powders are cosmetics in which the effects of the present disclosure are likely to be exhibited.

The cosmetic composition or the method for producing the cosmetic is not particularly limited, and the aqueous dispersion of the present embodiment is blended with another raw material (additive for cosmetic, etc.) for producing the cosmetic. It suffices as long as it includes the step of performing.

Hereinafter, the present invention will be described in more detail based on Examples, but the present invention is not limited to the following Examples.

[Example 1]
<Preparation of curcumin aqueous dispersion>
Curcumin was dispersed in an aqueous solution containing a surfactant by a method for preparing an aqueous dispersion using a known microfluidic device to obtain a transparent aqueous dispersion containing curcumin particles. When the obtained aqueous dispersion was measured using a dynamic light scattering measuring device (trade name: Zethasizer Nano, manufactured by Malvern), the average particle size (number basis) of the curcumin particles was 95.8 nm. The polydispersity index was 0.374. The measurement by the dynamic light scattering method is an experimental condition at room temperature (25 ° C.), where the refractive index of the dispersion medium is 1.33, the refractive index of the sample is 1.46, and the viscosity (cP) of the sample is 0.89. I went there.
The blending amount of each component in the aqueous dispersion of curcumin was 0.3% by mass of curcumin (derived from a natural product), 25% by mass of polyoxyethylene sorbitan monooleate (nonionic surfactant, Tween 80), 0. 0.05% by weight citric acid (preservative), 0.35% by weight propylene glycol dicaprylate (solubilizer), and the balance of water.

<Curcumin particle stability test>
The stability of the aqueous dispersion was confirmed under the conditions shown in Table 1. The evaluation criteria in Table 1 are "A" if the aqueous dispersion is exposed to each condition of the stability test shown in Table 1 and then stored for 5 days, and the aqueous dispersion can maintain visual transparency. If a precipitate is visually confirmed, it is rated as "B".

<Curcumin aqueous dispersion test for stability over time>
The curcumin aqueous dispersion was stored in a refrigerator at 4 ° C. for 1 year and 5 months, and then the average particle size and the polydispersity index were measured by the same method as described above. The inside of the refrigerator is a dark place, and vibration was avoided as much as possible during storage. The average particle size (number basis) of the particles was 107.4 nm, and the polydispersity index was 0.584. In addition, the curcumin aqueous dispersion maintained its transparency even after storage. The average number of particles of curcumin particles and the rate of change of the polydispersity index after storage were 12.1% and 56.1%, respectively.

[Example 2]
<Evaluation of antioxidant activity by FRAP method>
A kit for evaluating antioxidant activity by the FRAP (Ferric Reducing Antioxidant Power) method (manufactured by Cell Biolabs, trade name "OxiSec Ferric Reducing Antioxidant Power (FRAP) Assay valence to iron with iron)) The antioxidant activity was evaluated as an index. The following curcumin aqueous dispersion and curcumin mixture were prepared and used for the evaluation of antioxidant activity.

Curcumin Aqueous Dispersion An aqueous dispersion containing curcumin particles was prepared in the same manner as in Example 1 above.

Preparation of curcumin mixture Curcumin (manufactured by Nakaraitesk Co., Ltd.) and ultrapure water were mixed and stirred with a magnetic stirrer for 5 minutes to prepare a 0.28% by mass curcumin mixture. The curcumin mixture was a turbid liquid in which curcumin was present as particles considerably larger than 200 nm, and was an unstable system in which curcumin aggregated and separated from water after a while after stirring. The curcumin mixture was used for evaluation immediately after stirring.

The curcumin aqueous dispersion prepared as described above and the curcumin mixture were diluted with ultrapure water to prepare each sample diluent having the concentrations shown in Tables 2 and 3.

In addition, an aqueous solution of gallic acid (manufactured by Nacalai Tesque, Inc.) having the following concentration was prepared as a comparison target of antioxidant activity.

Using the sample diluent and the gallic acid aqueous solution, the antioxidant activity was evaluated using the evaluation kit according to the attached protocol. More specifically, first, the antioxidant power of each of the gallic acid aqueous solutions was measured with the evaluation kit, a calibration curve was prepared, and the concentration immediately before the antioxidant power was saturated was obtained from the calibration curve. It was 0.6 mass ppm (21.9 μmol / l). Next, the antioxidant power of the sample diluent was measured with the evaluation kit, and a calibration curve was prepared for each of the curcumin aqueous dispersion and the curcumin mixture, and 50% of the 10.6 mass ppm gallic acid aqueous solution was prepared. The concentration showing the antioxidant power corresponding to the antioxidant power was calculated. The results are shown in Table 4 below. The surfactant used in the production of the curcumin aqueous dispersion does not show antioxidant activity.

From Table 4, it was found that the antioxidant activity was improved by dispersing curcumin as particles having an average particle size of 200 nm or less.

[Example 3]
<Assessment of intracellular antioxidant activity>
L929 cells were purchased from KAC. D-MEM (high) to which a final concentration of 10 (v / v)% fetal bovine serum (FBS) (DS Pharma Biomedical Co., Ltd.) and a final concentration of 2 mmol / l glutamine solution (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) were added. L929 cells were cultured using glucose) ((manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) (serum-added D-MEM medium) so that the L929 cells had a concentration of 5.0 × 10 ³ cells / cm ^2. The cells were seeded in a 100 mm cell culture dish (manufactured by BD Falcon) and _{cultured under the conditions of 37 ° C. and 5% by volume CO 2.} L929 cells cultured in a 100 mm cell culture dish to a state of 80% confluence were 0.25. After treatment with a mass% trypsin / 50 mmol / l EDTA solution, the same serum-added D-MEM medium as described above was added to stop the trypsin reaction to obtain a suspended cell suspension of L929 cells. The number of viable cells in the suspension of L929 cells was measured using a 4 (w / v)% tripan blue solution (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), and 5.0 × 10 ³ cells / cm. ^The cells were sown on a multi-well cell culture plate 96well (manufactured by BD Falcon, made of polystyrene) so as to have a value of 2.
After culturing L929 cells until they reach 90 to 100% confluence under the conditions of 37 ° C. and 5% by volume CO ₂ , use the sample additive solution having the following composition to use the OxiSelect Cellular Antioxidant Activity Assay Kit (Green Fluorescence) (Cell Biolab). Intracellular antioxidant activity was measured using (manufactured by). The measurement was carried out according to the protocol attached to the OxiSelect Cellular Antioxidant Assay Kit (Green Fluorescence) (manufactured by Cell Biolab).

(Sample additive)
Using the curcumin aqueous dispersion or curcumin mixture described in Example 1 and the serum-added D-MEM medium, each sample additive solution having the following concentration was prepared, and a calibration curve was prepared.
・ 73.3 μmol / l curcumin aqueous dispersion ・ 7.3 μmol / l curcumin aqueous dispersion ・ 73.3 μmol / l curcumin mixture ・ 7.3 μmol / l curcumin mixture

OxiSelect Cellular Antioxidant Activity Assay Kit (Green Fluorescence) (manufactured by Cell Biolab) The antioxidant activity of each sample is calculated according to the attached protocol, and the antioxidant activity of each sample is calculated according to the attached protocol. When the antioxidant activity value of the reaction solution containing the product quercetin at a concentration of 1000 μmol / l was set to 100%, the concentration of the curcumin aqueous dispersion showing an antioxidant activity value of 50% was 15 μmol / l.
On the other hand, no antioxidant activity was detected in the curcumin mixture.

[Example 4]
Preparation of Ascorbic Acid Aqueous Solution (Comparison Target) Ascorbic acid (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) and ultrapure water were mixed to prepare a 0.4 mass% ascorbic acid aqueous solution.

<Evaluation of antioxidant activity using a three-dimensional skin model>
The antioxidant activity of the curcumin aqueous dispersion was evaluated using T-skin (manufactured by Nicoderm Research Co., Ltd.), which is a human skin full-thickness model. T-skin Culture Medium (manufactured by Nicoderm Research) was added to 6-well Multiwell Cell Culture Plate (manufactured by CORNING) at 2 mL / well. T-skin delivered from Nicoderm Research Co., Ltd. was transferred to 6-well Multiwell Cell Cell Culture Plate supplemented with T-skin Culture Medium, and _{cultured at 37 ° C. under 5% by volume CO 2} conditions for 24 hours. After 24 h incubation, on the surface layer of T-skin of each well, 1.13 mL / well and such that (1 cm ² per 1mL of T-skin), phosphate-buffered saline (D-PBS (-), Fujifilm Wako Pure Chemical Industries, Ltd.), ascorbic acid aqueous solution, curcumin nanodisperse and curcumin aqueous solution were added, respectively, and the mixture was _{cultured at 37 ° C. under 5% by volume CO 2} conditions for 24 hours. ^{After 24 hours of culturing, UVB (irradiation amount: 120 mJ / cm 2} ) or UVA (irradiation amount: 120 mJ / cm 2) or UVA (irradiation amount: 120 mJ / cm 2) or UVA (irradiation amount: 120 mJ / cm 2) or UVA (irradiation amount: 120 mJ / cm 2) or UVA (irradiation amount: 120 mJ / cm 2) or UVA (irradiation amount: 120 mJ / cm 2) or UVA (irradiation amount: 120 mJ / cm 2) or UVA (irradiation amount: 120 mJ / cm 2) or UVA (irradiation amount: 120 mJ / cm 2) or UVA (irradiation amount: 120 mJ / cm 2) or UVA (irradiation amount: 120 mJ / cm 2) or UVA (irradiation amount: 120 mJ / cm 2) from above T-skin using a UVB lamp (GL15 sterilization lamp 15w: Toshiba) or a UVA lamp (TL20W / 12RS: manufactured by Philips). Amount: 300 mJ / cm ² ) was irradiated. After UV irradiation, the cells were cultured for 24 hours under the conditions of 37 ° C. and 5% by volume CO _{2, and the medium was collected and subjected to each analysis.} The medium was changed at 24-hour intervals.
Quantification of interleukin 6 (IL6) in the medium was carried out using IL6 ELISA Kit, Human (manufactured by ProteinTech) according to the protocol disclosed by the manufacturer. The quantification of matrix metalloproteinase 1 (MMP1) in the medium was carried out using MMP-1, Human, and ELISA Kit (manufactured by RayBiotech) according to the protocol disclosed by the manufacturer. Interleukin 8 (IL8) in the medium was carried out using IL8 ELISA Kit, Human (manufactured by ProeinTech) according to the protocol disclosed by the manufacturer. The quantification of type I procollagen in the ground was carried out using Procollagen Type IC-peptide EIA Kit (manufactured by Takara Bio Inc.) according to the protocol disclosed by the manufacturer. The quantification of hyaluronic acid in the medium was carried out using Hyaluronan Quantikine ELISA Kit (manufactured by R & D Systems) according to the protocol disclosed by the manufacturer.
When the content of IL6, MMP1, IL8 and type I procollagen in each medium is 100% and the content of IL6, MMP1, IL8 and type I procollagen in the medium to which D-PBS (-) buffer is added is 100%. The relative values of are shown in Tables 5 and 6, respectively.
In addition, the contents of type I procollagen and hyaluronic acid when irradiated with UVB are relative values when the content of type I procollagen and hyaluronic acid in the medium to which ascorbic acid is added is 100%, respectively. Shown in.

Since it was confirmed that the amount of IL6, IL8, and MMP1 produced decreased when the curcumin aqueous dispersion was used, the effect of improving the skin permeability by the nano-treatment and reducing the oxidative stress caused by UV irradiation. Is thought to have been promoted. In addition, an increase in the amount of type I procollagen produced was confirmed when the curcumin aqueous dispersion was used, indicating that the nano-treatment improves skin permeability and increases extracellular matrix production. ..

[Example 5]
<Evaluation of extracellular matrix generation using a three-dimensional skin model>
The extracellular matrix production amount of the curcumin aqueous dispersion was evaluated using T-skin (manufactured by Nicoderm Research Co., Ltd.), which is a human skin full-thickness model. T-skin Culture Medium (manufactured by Nicoderm Research) was added to 6-well Multiwell Cell Culture Plate (manufactured by CORNING) at 2 mL / well. The delivered T-skin was transferred to a 6-well Multiwell Cell Culture Plate supplemented with T-skin Culture Medium and _{cultured at 37 ° C. under 5% by volume CO 2} conditions for 24 hours. After culturing for 24 hours, D-PBS (-) (Fujifilm Wako Junyaku Co., Ltd.) was applied on the epidermis layer of T-skin of each well in ^{an amount of 1.13 mL / well (1 mL per 1 cm 2 of T-skin).} , Ascorbic acid aqueous solution, and curcumin aqueous dispersion were added, and the cells were _{cultured at 37 ° C. under 5% by volume CO 2} conditions for 48 hours to quantify the amount of type I procollagen and the amount of hyaluronic acid in the medium. .. The medium was changed at 24-hour intervals.
The quantification of type I procollagen in the medium was carried out using Procollagen Type IC-peptide EIA Kit (manufactured by Takara Bio Inc.) according to the protocol disclosed by the manufacturer. The quantification of hyaluronic acid in the medium was carried out using Hyaluronan Quantikine ELISA Kit (manufactured by R & D Systems) according to the protocol disclosed by the manufacturer.
Table 8 shows the relative values of type I procollagen and hyaluronic acid in each medium as relative values when the content of type I procollagen and hyaluronic acid in the medium to which D-PBS (-) buffer was added is 100%. Shown in.

Since the amount of type I procollagen and hyaluronic acid produced was improved when the curcumin aqueous dispersion was used, it was found that the nano-treatment improved the skin permeability and increased the production of extracellular matrix. rice field.

<Preparation of emulsion containing curcumin aqueous dispersion>
A milky lotion containing an aqueous curcumin dispersion having the composition shown in Table 9 was prepared.

<Evaluation of antioxidant activity of curcumin aqueous dispersion-containing emulsion using a three-dimensional skin model>
Using T-skin (manufactured by Nicoderm Research Co., Ltd.), which is a human skin full-thickness model, the antioxidant activity of the emulsion prepared above (hereinafter, also simply referred to as emulsion) was evaluated. T-skin Culture Medium (manufactured by Nicoderm Research) was added to 6-well Multiwell Cell Culture Plate (manufactured by CORNING) at 2 mL / well. T-skin delivered from Nicoderm Research Co., Ltd. was transferred to 6-well Multiwell Cell Cell Culture Plate supplemented with T-skin Culture Medium, and _{cultured at 37 ° C. under 5% by volume CO 2} conditions for 24 hours. After culturing for 24 hours, phosphate buffered saline (D-PBS (-), 1 mL ^{/ well (1 mL per 1 cm 2 of} T-skin) on the epidermis layer of T-skin of each well Fujifilm Wako Pure Chemical Industries, Ltd.), an aqueous ascorbic acid solution (ascorbic acid concentration: 4000 mass ppm), or the emulsion prepared above were added, and the mixture was cultured for 24 hours under the conditions of _{37 ° C. and 5% by volume CO 2.} .. After 24 hours of culturing, each sample added on the epidermis was removed, the epidermis was washed 3 times with D-PBS (-), and then above the T-skin using a UVA lamp (TL20W / 12RS: manufactured by Philips). UVA (irradiation amount: 1.5 mJ / cm ² ) was irradiated from. After UVA irradiation, each new sample was added onto the epidermis at 1.13 mL / well ( ^{1 mL per 1 cm 2 of} T-skin) and cultured at 37 ° C. under 5% by volume CO ₂ conditions for 24 hours. After culturing for 24 hours, the medium was collected and subjected to each analysis. The medium was changed at 24-hour intervals.
Quantification of interleukin 8 (IL8) in the medium was carried out using IL8 ELISA Kit, Human (manufactured by ProeinTech) according to the protocol disclosed by the manufacturer. The quantification of matrix metalloproteinase 1 (MMP1) in the medium was carried out using MMP-1, Human, and ELISA Kit (manufactured by RayBiotech) according to the protocol disclosed by the manufacturer.
The contents of IL8 and MMP1 in each medium are shown in Table 10 as relative values when the content of IL8 and MMP1 in the medium to which the D-PBS (-) buffer is added is 100%.

In an experiment using a milky lotion containing an aqueous dispersion of curcumin, it was confirmed that the amounts of IL8 and MMP1 produced were reduced. Therefore, it is considered that the curcumin particles were stably retained even during cosmetic formulation and exhibited antioxidant activity.

Claims (10)

Aqueous dispersion for cosmetics
Contains curcuminoid particles with an average particle size of 200 nm or less.
When the aqueous dispersion for cosmetics is stored at 4 ° C. for one year, the rate of change in the average particle size of the curcuminoid particles after storage is within 15%, and the rate of change in the polydispersity index is within 60%. , Aqueous dispersion. The aqueous dispersion according to claim 1, wherein the content of the phospholipid with respect to the total amount of the curcuminoid and the phospholipid in the aqueous dispersion for cosmetics is 95% by mass or less. Aqueous dispersion for cosmetics
An aqueous dispersion containing particles of curcuminoid having an average particle diameter of 200 nm or less and having a phospholipid content of 95% by mass or less based on the total amount of curcuminoid and phospholipid in the aqueous cosmetic dispersion. Further containing nonionic surfactant,
The aqueous dispersion according to any one of claims 1 to 3, wherein the mass ratio of curcumin to the nonionic surfactant in the aqueous dispersion is 55 or more. The aqueous dispersion according to any one of claims 1 to 4, further comprising 1 to 50% by mass of a nonionic surfactant with respect to the total amount of the aqueous dispersion. The aqueous dispersion according to any one of claims 1 to 5, further comprising an ester of a monohydric or divalent alcohol and a fatty acid. The aqueous dispersion according to any one of claims 1 to 6, further comprising a mono fatty acid ester or a di fatty acid ester. The aqueous dispersion according to any one of claims 1 to 7, which is a type I collagen production promoter. A cosmetic composition comprising the aqueous dispersion according to any one of claims 1 to 8. A method for producing a cosmetic, which comprises a step of blending the aqueous dispersion according to any one of claims 1 to 8 with another raw material.