JP7250899B2 - Aqueous dispersion for cosmetics, cosmetic composition, and method for producing cosmetic - Google Patents

Description

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

Curcuminoid contained in turmeric extract is known as a substance that regulates intracellular signaling that controls cancer cell growth, inflammation, etc., and is expected to be applied as a pharmaceutical. Research is in progress (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 Dhytomedicine, 2015, Vol. 6, no. 4, pp. 383-398

Due to the above properties, application of curcuminoids to cosmetics is expected. However, according to the results of intensive studies by the present inventors, there is room for further investigation of the blendability or skin permeability when using curcuminoid aqueous dispersions as cosmetics. In addition, since the dispersion of Patent Document 1 uses liposomes containing a large amount of phospholipids, there is a low degree of freedom in selecting lipids to be blended when producing cosmetics.

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

The aqueous dispersion for cosmetics of the present disclosure contains curcuminoid particles having an average particle size of 200 nm or less. The rate of change in diameter is within 15%, and the rate of change in polydispersity index is within 60%. The content of phospholipids in the aqueous dispersion for cosmetics may be 95% by mass or less with respect to the total amount of curcuminoids and phospholipids.

In addition, the aqueous dispersion for cosmetics of the present disclosure contains curcuminoid particles having an average particle size of 200 nm or less, and the content of phospholipids with respect to the total amount of curcuminoids and phospholipids in the aqueous dispersion for cosmetics is 95. % by mass or less.

Preferably, 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 55 or more.

The cosmetic aqueous dispersion preferably further contains a nonionic surfactant in an amount of 1 to 50% by mass relative to the total amount of the aqueous dispersion.

The cosmetic aqueous dispersion preferably contains an ester of a monohydric or dihydric alcohol and a fatty acid.

The aqueous dispersion for cosmetics preferably contains a mono-fatty acid ester or a di-fatty acid ester.

The cosmetic composition of the present disclosure includes the cosmetic aqueous dispersion.

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

According to the present disclosure, it is possible to provide an aqueous dispersion for cosmetics that exhibits excellent storage stability when incorporated into cosmetics, and a cosmetic composition containing the aqueous dispersion for cosmetics.

The aqueous dispersion of the present embodiment contains curcuminoid particles 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 1 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 At least one of the condition that the content is within 60% and the condition that the content of phospholipids relative to the total amount of curcuminoids and phospholipids in the cosmetic aqueous dispersion is 95% by mass or less is satisfied.
Such an aqueous dispersion, when blended in cosmetics, has good compatibility with various additives blended in cosmetics, can suppress the generation of aggregates in various cosmetic formulations, and has a wide pH range. , the generation of agglomerates can be suppressed even within the range of temperature, etc. Therefore, the aqueous dispersion of the present embodiment is excellent in storage stability, blendability, 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 it can improve stability, blendability and appearance in cosmetic formulations. Moreover, the aqueous dispersion of the present embodiment tends to be able to suppress a decrease in antioxidant activity over a wide range of pH, temperature, and the like. Moreover, 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 a component to be blended in cosmetics, and can be used as an aqueous dispersion for cosmetics. In addition, as will be described later, the aqueous dispersion of the present embodiment has the effect of suppressing the production of IL6, IL8, or MMP1, so it can also be used as an IL6 production inhibitor, an IL8 production inhibitor, or an MMP1 production inhibitor. Furthermore, as will be described later, the aqueous dispersion of the present embodiment has the effect of promoting the production of type I procollagen or hyaluronic acid. It can also be used as a type procollagen production promoter. Use as enhancers or inhibitors for the production of these particular substances may be a combination of two or more uses.

The average particle size of the curcuminoid particles is 200 nm or less, and from the viewpoint of further improving storage stability, it is preferably 170 nm or less, more preferably 150 nm or less, even more preferably 120 nm or less, and 100 nm or less. It is especially preferable to have Although the lower limit of the average particle size of the particles is not particularly limited, it can be 5 nm or more from the viewpoint of storage stability. The average particle size of particles can be measured by a dynamic light scattering method, and a specific device includes Zetasizer Nano (manufactured by Malvern). The average particle size of the particles may be a particle size (d50) at 50% of the cumulative particle size distribution based on number. Similarly, the polydispersity index of the curcuminoids of the particles can also be measured by dynamic light scattering.
When the aqueous dispersion of the present embodiment is stored at 4° C. for one 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 storage conditions, it may be left still in a dark place and in a place without 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 in 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. is divided by
Note that "within" refers to a range from 0 to a predetermined upper limit. The rate of change in average particle size after storage may be substantially 0%, but may be greater than 0% and may be 0.1% or more. Also, the rate of change in polydispersity index after storage may be substantially 0%, but may be greater than 0%, or may be 0.1% or more.
Storage may be started immediately after the production of the aqueous dispersion, or at any time after production. The end of storage may be one year from the start of storage, may be one year and two months, or may be one year and five months.
The average particle size change of the curcuminoid particles after storage at 4° C. for 1 year may be within 13%. The change in average particle size of curcuminoid particles after storage at 4° C. for 1 year may be within 58%.
The storage is performed in an environment that can prevent evaporation of the water content of the aqueous dispersion. For example, it is preferable to store the aqueous dispersion in a sealed 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.

In addition, the particle diameter (d90) at which cumulative 90% in the cumulative particle size distribution based on the number of curcuminoid particles is preferably 400 nm or less, more preferably 350 nm or less, and even more preferably 300 nm or less.

Curcuminoids include curcumin and curcumin analogues, and curcumin analogues include demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin, etc. Curcumin is expected to have antioxidant activity or wrinkle-improving effect. preferable. The particles may contain one or more curcumin or analogues of curcumin.

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

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

Some phospholipids have a phosphate ester structure in the molecule, and examples thereof include soybean phospholipids, hydrogenated soybean phospholipids, egg yolk phospholipids, and hydrogenated egg yolk phospholipids.

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, alkyl methyl taurate salts, olefin sulfonates, alkyl sulfosuccinates, Alkyl phosphate salts, fatty acid salts, acyl amino acid salts, alkyl lactates, alkyl isethionates and the like can be mentioned.
Cationic surfactants include lauryltrimethylammonium chloride, cetyltrimethylammonium chloride, stearyltrimethylammonium chloride, behenyltrimethylammonium chloride, cetyltrimethylammonium bromide, stearyltrimethylammonium bromide, dipolyoxyethylene oleylmethylammonium chloride, chloride Polyoxyethylenebehenyllylmethylene ammonium, behenyltrimethylammonium methylsulfate, stearylhydroxypropyltrimethylammonium chloride, dicocoyldimethylammonium chloride, dialkyl (C12-18) dimethylammonium chloride, dicetyldimethylammonium chloride, distearyldimethylammonium chloride, ethyl Lanolin fatty acid aminopropyldimethylammonium sulfate, dicocoylethyl hydroxyethylammonium methylsulfate, coconut oil alkyl propylene glycol (PG) dimonium chloride phosphate, linoleate amidopropyl propylene glycol (PG) dimonium chloride phosphate, stearamidopropyl methyl amines, dimethylstearamine, polyethylene oxide (POE) coconut oil alkylamines, and the like.
Amphoteric surfactants include alkylbetaine type amphoteric surfactants such as lauryldimethylaminoacetic acid betaine, amidobetaine type amphoteric surfactants such as lauramidopropyl betaine, carbohydrates such as hydroxyalkyl (C12-14) hydroxyethyl sarcosine. isibetaine-type amphoteric surfactants, amidosulfobetaine-type amphoteric surfactants such as lauramidopropyl hydroxysulfobetaine, imidazolinium betaine-type amphoteric surfactants such as sodium cocoamphodiacetate, sodium lauraminopropionate, etc. propionic acid-type amphoteric surfactants, amine oxide-type amphoteric surfactants such as lauryldimethylamine oxide, N-[3-alkyl (12,14)oxy-2-hydroxypropyl]-L-arginine hydrochloride, etc. and amino acid-type surfactants.
Examples of 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), tetraoleic acid polyoxyethylene sorbite type nonionic surfactant, polyoxyethylene hydrogenated castor oil type nonionic surfactant, pyrrolidone carboxylic acid (PCA) isostearic acid poly Oxyethylene hydrogenated castor oil type nonionic surfactant, polyoxyethylene fatty acid type nonionic surfactant, polyoxyethylene fatty acid glycerol type nonionic surfactant, polyoxyethylene alkyl ether type nonionic surfactant surfactant, polyoxyethylene/polyoxypropylene alkyl ether type nonionic surfactant, polyoxyethylene/polyoxypropylene block polymer type nonionic surfactant, alkanolamide type nonionic surfactant sucrose ester-type nonionic surfactants, alkyl glycoside-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 with respect to the total amount of the aqueous dispersion, from the viewpoint of skin irritation and blendability, and 0.1 It is more preferably up to 50% by mass, and even more preferably 0.5 to 40% by mass. In addition, when the aqueous dispersion contains a nonionic surfactant, from the viewpoint of skin irritation and blendability in cosmetic formulations, the content of the nonionic surfactant is less than the total amount of the aqueous dispersion. It is preferably 1 to 50% by mass, preferably 10 to 50% by mass, 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 should be 55 from the viewpoint of skin irritation and blendability in cosmetic formulations. It is preferable in it being above. The nonionic surfactant may contain polyoxyethylene sorbitan fatty acid ester and may have a mass ratio of curcumin to polyoxyethylene sorbitan fatty acid ester of 55 or more. Examples of polyoxyethylene sorbitan fatty acid esters 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 dihydric alcohol and a fatty acid. Examples of monohydric or dihydric alcohols include alcohols having 2 to 6 carbon atoms, and specific examples include ethylene glycol, 1,3-propylene glycol, 1,2-propylene glycol and the like. The fatty acid preferably has 4 to 20 carbon atoms, more preferably 6 to 18 carbon atoms, and specifically includes caprylic acid. The ester of monohydric or dihydric alcohol and fatty acid is preferably a diester of dihydric alcohol and fatty acid.
The solubilizer may also be a mono-fatty acid ester or a di-fatty acid ester. The fatty acid contained in the mono-fatty acid ester or di-fatty acid ester is preferably a fatty acid having 4 to 20 carbon atoms, more preferably a fatty acid having 6 to 18 carbon atoms, and specifically includes caprylic acid. Mono- or di-fatty acid esters may be esters of fatty acids with monohydric or dihydric alcohols, or monoglycerides or diglycerides.
Specific examples of solubilizers include propylene glycol dicaprylate. The content of the solubilizer may be 0.01 to 5% by weight, or 0.1 to 1% by weight, relative to 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 compatibility and the like. Preferably, it is more preferably 0.1 to 10% by mass.

The lower limit of the content of curcumin in the curcuminoid particles is not particularly limited, but from the viewpoint of imparting physiological functions such as antioxidant, it is preferably 70% by mass, preferably 80% by mass, based on the total amount of curcuminoid particles. is more preferable. The upper limit of the content of curcumin in the curcuminoid particles is not particularly limited, but the curcuminoid particles may consist of curcumin, and the curcuminoid particles may contain 99.5% by mass or less of curcumin. good.

Aqueous dispersions comprise an aqueous medium, which is the continuous phase, together with the curcuminoid particles. The aqueous medium may be water itself, or may contain other components such as organic solvents and additives together with water. The additives may include antioxidants, preservatives, and the like. Antioxidants include, for example, ascorbic acid. Examples of preservatives include paraoxybenzoic acid ester, 1,2-hexanediol, citric acid, phenoxyethanol and the like.

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

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

The antioxidant power referred to in this specification is measured by the FRAP method. In the FRAP method, antioxidants contained in the sample reduce Fe ³⁺ contained in the test reagent to produce Fe ²⁺ . The resulting Fe ²⁺ reacts with the colorimetric probe to form a dark blue product detectable at wavelengths between 540-600 nm. Reduced Fe ³⁺ can be quantified by measuring absorbance at 540 to 600 nm, and this can be used as an index of antioxidative 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 antioxidative power. The evaluation criteria for the antioxidant power of the aqueous dispersion are the gallic acid aqueous solution containing 21 ppm by mass of gallic acid, which is measured by the FRAP method, and the antioxidant power equal to 50% of the antioxidant power of the aqueous solution. be able to. Alternatively, the maximum antioxidative power of the gallic acid aqueous solution measurable with the test reagent of the FRAP method used can be used as the standard. In this case, gallic acid aqueous solutions with different concentrations are prepared in advance, the FRAP method is measured under the same conditions, and the antioxidative power is plotted against the concentration of gallic acid in the aqueous solution to create a calibration curve. When the concentration of gallic acid in the aqueous solution exceeds the measurable amount of the test reagent used, the measured antioxidant power becomes constant, so the concentration of gallic acid immediately before the antioxidant power becomes constant in the calibration curve ( That is, the concentration at which the slope of the calibration curve changes from positive to 0) is obtained, and this concentration is defined as the maximum antioxidative power of the gallic acid aqueous solution. Then, the antioxidative power equal to 50% of the maximum antioxidative power can be used as the evaluation criterion for the antioxidative power of the aqueous dispersion. The antioxidant power of the aqueous dispersion of the present embodiment more preferably satisfies any of the above evaluation criteria at a concentration of 100 μmol/l or less, and further satisfies any of the above criteria at a concentration of 90 μmol/l or less. preferable. As an evaluation criterion for the antioxidant power of the aqueous dispersion, the antioxidant power equivalent to 50% of the antioxidant power of the gallic acid aqueous solution containing 10.6 ppm by mass may be used.

In addition, the aqueous dispersion of the present embodiment was added to L929 cells to perform an intracellular antioxidant activity assay. It is preferable that the curcuminoid concentration in the aqueous dispersion exhibiting 50% of the antioxidant activity value when the intracellular antioxidant activity assay is performed by adding the liquid is 100 μmol/l or less. That is, since the aqueous dispersion of the present embodiment has excellent antioxidant power, when the intracellular antioxidant activity assay was performed on L929 cells using the aqueous dispersion of the present embodiment, the concentration of curcuminoids was compared. Even at a concentration of 100 μmol/l or less, which is relatively small, the antioxidant activity value tends to be 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 the fluorescent probe is added to L929 cells to prepare a measurement sample in which the sample and the fluorescent probe are incorporated into the cells. As the fluorescent probe, a highly cell-permeable fluorescent probe (2',7'-dichlorofluorescin diacetate (DCFH-DA), etc.) is used. After that, a free radical initiator solution is added to generate reactive oxygen species in the cells, and the fluorescence intensity of the measurement sample is measured at intervals of 3 minutes for a total of 60 minutes. Calculate the sum of the fluorescence intensity at each time point divided by the fluorescence intensity at the start of measurement (0 minute time point), AUC (area under curve, corresponding to the integrated area under the curve plotting the fluorescence intensity against time) ), and this is taken as the antioxidant activity value. Using a measurement sample with a different sample concentration, AUC is determined in the same manner to create a calibration curve.
For comparison, AUC is similarly calculated for a measurement sample in which a reaction solution containing quercetin at a concentration of 1000 μmol/l is added to L929 cells instead of the above sample. Then, using the calibration curve, the concentration of the sample corresponding to the antioxidant activity value of 50% of the antioxidant activity value of the measurement sample to be compared (which is used as the evaluation criterion for the antioxidant activity value) is determined.
Commercially available kits for such measurements include OxiSelect Cellular Antioxidant Activity Assay Kit (Green Fluorescence) (manufactured by Cell Biolabs).

The antioxidant activity value of the aqueous dispersion of the present embodiment more preferably satisfies the above evaluation criteria at a concentration of 90 μmol/l or less, and more preferably satisfies the above evaluation criteria at a concentration of 80 μmol/l or less.

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

The content of matrix metalloproteinase 1 in the medium under condition (B) relative to the medium under condition (A) after culture is preferably 60% or less, more preferably 55% or less, and 50% or less. and more preferred. In this embodiment, the content of matrix metalloprotease-1 in the medium is measured by a sandwich ELISA method using a monoclonal antibody against matrix metalloprotease-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 containing the epidermal layer and dermal layer after oxidative stress is applied. There is a tendency. The content of type I procollagen in the medium of condition (B) with respect to the medium of condition (A) after the culture is preferably 150% or more, more preferably 200% or more, and 250% or more. and more preferred. In this embodiment, the content of type I procollagen in the medium is measured by a sandwich ELISA method using a monoclonal antibody against type I procollagen.

In addition, the content of hyaluronic acid in the medium of condition (B) with respect to the medium of condition (A) after the culture is preferably 120% or more, more preferably 150% or more, and 180% or more. and more preferred. In this embodiment, the content of hyaluronic acid in the medium is measured by a sandwich ELISA method using a monoclonal antibody against hyaluronic acid.

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

Interleukin-6 and interleukin-8 are substances involved in inflammatory reactions, 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 a medium in which an inflamed three-dimensional skin model is cultured. Matrix metalloprotease 1 is an enzyme that degrades extracellular matrices such as collagen at an inflammatory site, and the amount of production increases as the amount of interleukin 6 and interleukin 8 increases. When a three-dimensional skin model subjected to oxidative stress in which the aqueous dispersion of the present embodiment is added on the epidermis layer is cultured, a three-dimensional skin model subjected to oxidative stress in which a phosphate buffer solution is added on the epidermis layer is cultured. Compared to the case of culturing, inflammation tends to be suppressed by suppressing the generation of reactive oxygen species due to oxidative stress in the three-dimensional skin model, and interleukin 6, interleukin 8, which increase when inflammation occurs. and matrix metalloproteinase 1 tend to decrease. In addition, since the amount of type I procollagen, which is a collagen precursor, also increases, the amount of collagen production tends to increase.

Oxidative stress includes UVA irradiation, UVB irradiation, and the like, and may be UVA irradiation. In the case of UVA irradiation, the total irradiation dose is preferably 300 mJ/cm ² or more. In the case of UVB irradiation, the total dose is preferably 120 mJ/cm ² or more. Cultivation after UVA or UVB irradiation may be performed for 24 hours or longer.

As described above, the aqueous dispersion of the present embodiment tends to effectively suppress skin aging due to oxidative stress, particularly photoaging, and thus can be used as a wrinkle reducing 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 intentional oxidative stress such as UV irradiation was not applied was used. Excellent results also tend to be obtained for evaluation of the amount of extracellular matrix produced. More specifically, the aqueous dispersion of the present embodiment is obtained by culturing a three-dimensional skin model containing an epidermal layer and a dermal layer under the following conditions (C) and (D), and then adding I in the medium. When the content of type I procollagen was measured by a sandwich ELISA method using a monoclonal antibody against the content of type I procollagen, the type I procollagen contained in the medium of condition (D) versus the medium of condition (C) is preferably 120% or more.
(C) Add 1 mL of 0.4 mass % ascorbic acid aqueous solution per 1 cm ² of the three-dimensional skin model onto the epidermal layer of the three-dimensional skin model, and culture for 48 hours at 37° C. in an atmosphere with a carbon dioxide concentration of 5% by volume.
(D) The aqueous dispersion is added to the epidermal layer of the three-dimensional skin model at the same concentration and amount as the ascorbic acid aqueous solution, and cultured at 37° C. for 48 hours in an atmosphere with a carbon dioxide concentration of 5% by volume.
In condition (C), instead of the aqueous ascorbic acid solution, potassium chloride 0.02 w/v%, potassium dihydrogen phosphate 0.02 w/v%, sodium chloride 0.8 w/v%, dihydrogen phosphate A phosphate buffer containing 0.115 w/v % sodium may be used.
The content of type I procollagen in the medium of condition (D) with respect to the medium of condition (C) is more preferably 150% or more, and even more preferably 170% or more.

The content of hyaluronic acid in the medium of condition (D) with respect to the medium of condition (C) after the culture is preferably 120% or more, more preferably 150% or more, and furthermore 170% or more. preferable. In this embodiment, the content of hyaluronic acid in the medium is measured by a sandwich ELISA method using a monoclonal antibody against hyaluronic acid.

As described above, the aqueous dispersion of the present embodiment tends to promote an increase in the amount of extracellular matrix produced, so it can also be used as an anti-wrinkle agent.

The aqueous dispersion of the present embodiment may optionally contain particles other than curcuminoid particles (referred to as "other particles"). Other particles may contain one or more kinds, for example vitamin E particles with an average particle size of 50 nm or less, gold particles with an average particle size of 200 nm or less, and ceramides with 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 the gold particles. The ceramide particles may contain components other than the ceramides, and preferably contain 70% by mass or more of the ceramides relative to 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 components (cosmetic additives) that are 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. Above, more preferably 0.05% by mass or more. Moreover, from the viewpoint of ensuring performance as a cosmetic, the content is preferably 50% by mass or less. Various components include those described below.

Examples of the above cosmetic additives include oily components, powder components, oil gelling agents, water-based components, water-soluble polymers, ultraviolet absorbers, antioxidants, beauty ingredients, preservatives, and the like. The additives in (1) can be appropriately blended in order to impart various effects. A surfactant may also be added to the cosmetic composition. Examples of surfactants that may be added to the cosmetic composition include the same surfactants that may be added to the above-described aqueous dispersion, preferably nonionic surfactants, and polyglycerin fatty acid esters. More preferred are nonionic surfactants of the type

Oily ingredients include hydrocarbons, oils and fats, waxes, ester oils, hardened Oils, fatty acids, higher alcohols, silicone oils, lanolin derivatives, oily gelling agents and the like. Specifically, hydrocarbons such as paraffin wax, ceresin wax, microcrystalline wax, montan wax, Fischer-Tropsch wax, liquid paraffin, squalane, petrolatum, Japanese wax, mink oil, olive oil, avocado oil, castor oil, macadamia nuts Oil, oils and fats such as meadowfoam oil, waxes such as beeswax, carnauba wax, candelilla wax, gei wax, pentaerythrityl ester of rosin acid, jojoba oil, glyceryl tri-2-ethylhexanoate, isotridecyl isononanoate, 2- Cetyl ethylhexanoate, isopropyl myristate, isopropyl palmitate, octyldodecyl myristate, glyceryl trioctanoate, polyglyceryl diisostearate, glyceryl triisostearate, diglyceryl triisostearate, polyglyceryl triisostearate, diisostearyl malate, diethylhexane esters such as acid neopentyl glycol; 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, trimethylsiloxysilicate, crosslinked polyether-modified methylpolysiloxane, methacryl-modified methylpolysiloxane, oleyl-modified methylpolysiloxane, polyvinylpyrrolidone-modified methylpolysiloxane, poly silicone oils such as ether-modified polysiloxane; lanolin derivatives such as lanolin, lanolin acetate, isopropyl lanolin fatty acid, and lanolin alcohol; and oily 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-ethylhexanoate, isononyl isononanoate, and neopentyl glycol diethylhexanoate are preferred from the viewpoint of spreadability and adhesion. The oily component may be contained, for example, in an amount of 0.1-20% by mass relative to the total amount of the cosmetic composition.

The powder component is not particularly limited depending on the shape such as spherical, plate-like, or needle-like, particle size such as aerosol, fine particle, or pigment grade, and particle structure such as porous or non-porous, and inorganic powders. , glitter powders, organic powders, pigment 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, Prussian blue, and ultramarine blue; talc, muscovite, and gold. Mica, red mica, biotite, synthetic mica, sericite, synthetic sericite, kaolin, silicon carbide, bentonite, smectite, aluminum oxide, magnesium oxide, zirconium oxide, antimony oxide, diatomaceous earth, aluminum silicate , magnesium aluminum metasilicate, calcium silicate, barium silicate, magnesium silicate, calcium carbonate, magnesium carbonate, hydroxyapatite, boron nitride, white solid powder such as silica, titanium dioxide-coated mica, titanium dioxide-coated bismuth oxychloride, Titanium oxide-coated mica, iron oxide mica, titanium blue-treated mica, titanium mica treated with carmine, bismuth oxychloride, bright powder such as fish scale foil, polyamide resin, polyethylene resin, polyacrylic resin, polyester resin, Fluorine resin, cellulose resin, polystyrene resin, copolymer resin such as styrene-acrylic copolymer, polypropylene resin, silicone resin, organic polymer resin powder such as urethane resin, zinc stearate, N-acyl lysine, etc. Natural organic powders such as organic low-molecular-weight powders, starches, silk powders, cellulose powders, Red No. 201, Red No. 202, Red No. 205, Red No. 226, Red No. 228, Orange No. 203, Orange No. 204, Blue 404, yellow No. 401 organic pigment powders, red No. 3, red No. 104, red No. 106, orange No. 205, yellow No. 4, yellow No. 5, green No. 3, blue No. 1, etc. 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 dioxide silicon oxide, zinc oxide Composite powders such as silicon, polyethylene terephthalate/aluminum/epoxy laminated powder, polyethylene terephthalate/polyolefin laminated film powder, polyethylene terephthalate/polymethyl methacrylate laminated film powder lame agents, tar pigments, natural pigments, etc., and these powders can be used alone or in combination of two or more thereof, and may be used in combination. In addition, 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.

Examples of oil gelling agents include dextrin fatty acid esters, sucrose fatty acid esters, starch fatty acid esters, hydroxystearic acid, calcium stearate, hydrophobic fumed silica, and organically modified bentonite. may

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

Water-soluble polymers include natural ones such as guar gum, sodium chondroitin sulfate, hyaluronic acid, gum arabic, sodium alginate, carrageenan, mucopolysaccharide, collagen, elastin, keratin, and xanthan gum; Examples include semisynthetic 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 1-30% by mass relative to the total amount of the cosmetic composition.

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

Examples of antioxidants include vitamin E such as tocopherol, ascorbic acid, and the like.

Examples of cosmetic ingredients include vitamins, proteins, antiphlogistic agents, herbal medicines, and the like.

Examples of preservatives include paraoxybenzoic acid esters and phenoxyethanol.

In addition, various components other than the above include, for example, moisturizing agents, film-forming agents, anti-fading agents, defoaming agents, fragrances, perfluoropolyethers, perfluorodecalin, perfluorooctane, and other fluorine-based oils; polyhydric alcohols. , saccharides, amino acids, various polymers, ethanol, thickeners, pH adjusters, blood circulation promoters, cooling agents, bactericides, skin activators, etc., can also be blended within a range that does not impair the effects of the present disclosure.

In addition, the cosmetic composition of the present embodiment is not particularly limited in its dosage form or product form. As the product form (cosmetics), skin cosmetics such as facial cleansing foam / cream, cleansing, massage cream, pack, lotion, milky lotion, cream, serum, makeup base, sunscreen, etc. Finishing cosmetics such as foundation, water powder, eyeshadow, eyeliner, mascara, eyebrow, concealer, lipstick, lip balm, hair mist, shampoo, rinse, treatment, hair tonic, hair cream, pomade, tick, liquid hair dressing, Hair cosmetics such as setting lotions, hair sprays, and hair dyes, powder sprays, and antiperspirants such as roll-ons can be exemplified. 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 method for producing the cosmetic composition or the cosmetic is not particularly limited, and the aqueous dispersion of the present embodiment is blended with other raw materials (additives for cosmetics, etc.) for producing the cosmetic. Any method may be used as long as it includes the step of

EXAMPLES The present invention will be described in more detail below 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 known method for preparing an aqueous dispersion using a microfluidic device to obtain a transparent aqueous dispersion containing curcumin particles. When the obtained aqueous dispersion was measured using a dynamic light scattering measurement device (trade name: Zetasizer Nano, manufactured by Malvern), the average particle size (number basis) of curcumin particles was 95.8 nm. The polydispersity index was 0.374. In addition, the measurement by the dynamic light scattering method was performed at room temperature (25 ° C.) under the experimental conditions of refractive index of the dispersion medium = 1.33, refractive index of the sample = 1.46, and viscosity (cP) of the sample = 0.89. I went with
The amount of each component in the curcumin aqueous dispersion is 0.3% by mass of curcumin (derived from 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 water.

<Stability test of curcumin particles>
The stability of the above aqueous dispersion was confirmed under the conditions shown in Table 1. The evaluation criteria in Table 1 are, after exposing the aqueous dispersion to each condition of the stability test described in Table 1, storing for 5 days, and if the aqueous dispersion can maintain visual transparency, "A", If deposits are visually observed, it is rated as "B".

<Temporal stability test of curcumin aqueous dispersion>
After storing the curcumin aqueous dispersion in a refrigerator at 4° C. for 1 year and 5 months, the average particle size and polydispersity index were measured in the same manner as above. The inside of the refrigerator is a dark place, and vibration was avoided as much as possible during storage. The particles had an average particle diameter (number basis) of 107.4 nm and a polydispersity index of 0.584. In addition, the curcumin aqueous dispersion maintained its transparency even after storage. The percentage changes in mean particle number and polydispersity index after storage of curcumin particles were 12.1% and 56.1%, respectively.

[Example 2]
<Antioxidant activity evaluation by FRAP method>
Using a kit for evaluating antioxidant activity by the FRAP (Ferric Reducing Antioxidant Power) method (manufactured by Cell Biolabs, trade name "OxiSelect Ferric Reducing Antioxidant Power (FRAP) Assay Kit"), the reducing power for trivalent iron ions was evaluated. Antioxidant activity was evaluated as an index. For evaluation of antioxidant activity, the following curcumin aqueous dispersion and curcumin mixed solution were prepared and used.

Curcumin Aqueous Dispersion Similar to Example 1 above, an aqueous dispersion containing particles of curcumin was prepared.

Preparation of Curcumin Mixture Curcumin (manufactured by Nacalai Tesque, Inc.) 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 mixed solution 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 mixed solution were diluted with ultrapure water to prepare sample diluted solutions having the concentrations shown in Tables 2 and 3.

In addition, gallic acid (manufactured by Nacalai Tesque Co., Ltd.) aqueous solutions having the following concentrations were prepared for comparison of antioxidant activity.

Antioxidant activity evaluation using the evaluation kit was performed according to the attached protocol, using the sample diluent and the gallic acid aqueous solution. More specifically, first, the antioxidative power of each gallic acid aqueous solution was measured using the evaluation kit, a calibration curve was prepared, and the concentration immediately before the antioxidative power was saturated was obtained from the calibration curve. .6 mass ppm (21.9 μmol/l). Next, the antioxidant power of the diluted sample solution was measured using the evaluation kit, and a calibration curve was prepared for each of the curcumin aqueous dispersion and the curcumin mixed solution. Concentrations showing antioxidant power equivalent to antioxidant power were calculated. The results are shown in Table 4 below. The surfactant used in the preparation of the curcumin aqueous dispersion does not exhibit antioxidant activity.

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

[Example 3]
<Evaluation of intracellular antioxidant activity>
L929 cells were purchased from KAC. D-MEM (high Glucose) ((manufactured by Fujifilm Wako Pure Chemical Industries ^, Ltd.) (serum-added D-MEM medium) was used to culture L929 cells ^. 2, seeded on a 100 mm cell culture dish (manufactured by BD Falcon) and cultured at 37 ° C., 5 vol% CO _2. L929 cells cultured in a 100 mm cell culture dish to 80% confluence were added at 0.25 After treatment with a trypsin/50 mmol/l EDTA solution of mass %, the same serum-supplemented D-MEM medium as above was added to stop the trypsin reaction to obtain a suspension cell suspension of L929 cells. A 4 (w/v)% trypan blue solution (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) was used to measure the number of viable cells in the suspension cell suspension of L929 cells, and the number was 5.0 × 10 ³ cells/cm. ² , and seeded on a 96-well multiwell cell culture plate (manufactured by BD Falcon, polystyrene).
After culturing L929 cells to 90 to 100% confluence under conditions of 37° C. and 5 vol% CO ₂ , OxiSelect Cellular Antioxidant Activity Assay Kit (Green Fluorescence) (Cell Biolabs) using a sample addition solution having the following composition: (manufactured) was used to measure intracellular antioxidant activity. The measurement was carried out according to the protocol attached to OxiSelect Cellular Antioxidant Activity Assay Kit (Green Fluorescence) (manufactured by Cell Biolabs).

(Sample addition liquid)
Using the curcumin aqueous dispersion or curcumin mixed solution described in Example 1 and the above serum-added D-MEM medium, each sample addition solution having the following concentrations was prepared, and a calibration curve was drawn.
・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 was calculated according to the attached protocol, and the OxiSelect Cellular Antioxidant Activity Assay Kit (manufactured by Green Cell) (attached to BioFlucuren Cell) When the antioxidant activity value of the reaction solution containing the product quercetin at a concentration of 1000 μmol/l is taken as 100%, the concentration of the aqueous dispersion of curcumin exhibiting 50% antioxidant activity 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) Ascorbic acid (manufactured by Fuji Film Wako Pure Chemical Industries, Ltd.) and ultrapure water were mixed to prepare a 0.4% by mass ascorbic acid aqueous solution.

<Evaluation of antioxidant activity using a three-dimensional skin model>
Using T-skin (manufactured by Nicoderm Research), which is a human skin full-thickness model, the antioxidant activity of curcumin aqueous dispersion was evaluated. T-skin Culture Medium (manufactured by Nikoderm Research) was added at 2 mL/well to a 6-well Multiwell Cell Culture Plate (manufactured by CORNING). T-skins supplied by Nicoderm Research were transferred to a 6-well Multiwell Cell Culture Plate supplemented with T-skin Culture Medium, and cultured for 24 hours at 37° C. and 5 vol % CO ₂ . After culturing for 24 hours ^, phosphate-buffered saline (D-PBS(-), FUJIFILM Wako Pure Chemical Industries, Ltd.), ascorbic acid aqueous solution, curcumin nanodispersion and curcumin aqueous solution were added, respectively, and cultured at 37° C. and 5 vol % CO ₂ for 24 hours. After 24 hours of culture, UVB (irradiation dose: 120 mJ/cm ² ) or UVA (irradiation dose: 300 mJ/cm ² ). After UV irradiation, the cells were cultured for 24 hours under conditions of 37° C. and 5 vol % CO ₂ , and the medium was collected and used for each analysis. In addition, medium exchange was performed at intervals of 24 hours.
Interleukin 6 (IL6) in the medium was quantified using IL6 ELISA Kit, Human (manufactured by ProteinTech) according to the protocol disclosed by the manufacturer. Matrix metalloproteinase 1 (MMP1) in the medium was quantified using MMP-1, Human, ELISA Kit (manufactured by RayBiotech) according to the protocol disclosed by the manufacturer. Interleukin 8 (IL8) in the medium was measured using IL8 ELISA Kit, Human (manufactured by ProeinTech) according to the protocol disclosed by the manufacturer. Quantification of type I procollagen in the soil was performed using Procollagen Type I C-peptide EIA Kit (manufactured by Takara Bio Inc.) according to the protocol disclosed by the manufacturer. Hyaluronic acid in the medium was quantified 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%, the content of IL6, MMP1, IL8 and type I procollagen in the medium supplemented with D-PBS(-) buffer is taken as 100%. are shown in Tables 5 and 6 as relative values.
In addition, the contents of type I procollagen and hyaluronic acid when irradiated with UVB irradiation are shown in Table 7 as relative values when the contents of type I procollagen and hyaluronic acid in the medium supplemented with ascorbic acid are taken as 100%. shown.

It was confirmed that the amount of IL6, IL8, and MMP1 produced decreased when the curcumin aqueous dispersion was used, suggesting that the nano-processing improves skin permeability and reduces oxidative stress caused by UV irradiation. is thought to have been promoted. In addition, when the aqueous dispersion of curcumin was used, an increase in the amount of type I procollagen produced was confirmed, suggesting that nanoization treatment improves skin permeability and increases the production of extracellular matrix. .

[Example 5]
<Evaluation of extracellular matrix production using three-dimensional skin model>
Using T-skin (manufactured by Nikoderm Research), which is a human skin full-thickness model, the amount of extracellular matrix produced by the curcumin aqueous dispersion was evaluated. T-skin Culture Medium (manufactured by Nikoderm Research) was added at 2 mL/well to a 6-well Multiwell Cell Culture Plate (manufactured by CORNING). The delivered T-skin was transferred to a 6-well Multiwell Cell Culture Plate supplemented with T-skin Culture Medium and cultured for 24 hours at 37° C. under 5 vol % CO ₂ conditions. After culturing for 24 hours, D-PBS (-) (Fujifilm Wako Pure Chemical Industries ^, Ltd. ), an aqueous solution of ascorbic acid, and an aqueous dispersion of curcumin, respectively, and cultured for 48 hours under conditions of 37° C. and 5% by volume of CO ₂ , and the amounts of type I procollagen and hyaluronic acid in the medium were quantified. . In addition, medium exchange was performed at intervals of 24 hours.
Type I procollagen in the medium was quantified using Procollagen Type I C-peptide EIA Kit (manufactured by Takara Bio Inc.) according to the protocol disclosed by the manufacturer. Hyaluronic acid in the medium was quantified using Hyaluronan Quantikine ELISA Kit (manufactured by R&D Systems) according to the protocol disclosed by the manufacturer.
The content of type I procollagen and hyaluronic acid in each medium is expressed as a relative value when the content of type I procollagen and hyaluronic acid in the medium supplemented with D-PBS(-) buffer is 100% Table 8 shown in

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

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

<Evaluation of Antioxidant Activity of Milky Lotion Containing Curcumin Aqueous Dispersion Using Three-Dimensional Skin Model>
Using T-skin (manufactured by Nicoderm Research), which is a human skin full-thickness model, the antioxidant activity of the emulsion prepared above (hereinafter simply referred to as emulsion) was evaluated. T-skin Culture Medium (manufactured by Nikoderm Research) was added at 2 mL/well to a 6-well Multiwell Cell Culture Plate (manufactured by CORNING). T-skins supplied by Nicoderm Research were transferred to a 6-well Multiwell Cell Culture Plate supplemented with T-skin Culture Medium, and cultured for 24 hours at 37° C. and 5 vol % CO ₂ . After culturing for 24 hours ^, phosphate-buffered saline (D-PBS(-), FUJIFILM Wako Pure Chemical Industries, Ltd.) and ascorbic acid aqueous solution (ascorbic acid concentration: 4000 ppm by mass), or the emulsion prepared above were added, respectively, and cultured at 37 ° C. and 5 vol% CO ₂ for 24 hours. . Remove each sample added on the epidermis after 24 hours of culture, wash the epidermis three times with D-PBS (-), and then use a UVA lamp (TL20W/12RS: manufactured by Philips) above the T-skin. was irradiated with UVA (irradiation amount: 1.5 mJ/cm ² ). After UVA irradiation, each new sample was applied onto the epidermis at 1.13 mL/well (1 mL per 1 cm ² of T-skin) and cultured for 24 hours under conditions of 37° C. and 5 vol % CO ₂ . After culturing for 24 hours, the medium was collected and used for each analysis. In addition, medium exchange was performed at intervals of 24 hours.
Interleukin 8 (IL8) in the medium was quantified using IL8 ELISA Kit, Human (manufactured by ProteinTech) according to the protocol disclosed by the manufacturer. Matrix metalloproteinase 1 (MMP1) in the medium was quantified using MMP-1, Human, 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 contents of IL8 and MMP1 in the medium supplemented with D-PBS(-) buffer are defined as 100%.

Experiments using curcumin aqueous dispersion-containing milky lotions confirmed a decrease in the amount of IL8 and MMP1 produced, suggesting that curcumin particles were stably retained even in cosmetic formulations and exhibited antioxidant activity.

Claims (9)

An aqueous dispersion for cosmetics,
Curcuminoid particles having an average particle size of 200 nm or less , a nonionic surfactant, and a mono- or di-fatty acid ester ,
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%. , an aqueous dispersion. The aqueous dispersion according to claim 1, wherein the content of phospholipids relative to the total amount of curcuminoids and phospholipids in the aqueous dispersion for cosmetics is 95% by mass or less. An aqueous dispersion for cosmetics,
Curcuminoid particles having an average particle size of 200 nm or less, a nonionic surfactant, and a mono-fatty acid ester or di-fatty acid ester , wherein the ratio of phospholipids to the total amount of curcuminoids and phospholipids in the cosmetic aqueous dispersion is An aqueous dispersion having a content of 95% by mass or less. The aqueous dispersion according to any one of claims 1 to 3 , wherein the curcuminoid content in the curcuminoid particles is 70% by mass or more relative to the total amount of the curcuminoid particles. The aqueous dispersion according to any one of claims 1 to 4 , wherein the content of the surfactant containing the nonionic surfactant is 0.01 to 80% by mass with respect to the total amount of the aqueous dispersion. dispersion. The aqueous dispersion according to any one of claims 1 to 5 , comprising 1 to 50% by weight of said nonionic surfactant relative to the total amount of the aqueous dispersion. The aqueous dispersion according to any one of claims 1 to 6, which is a type I collagen production promoter. A cosmetic composition comprising the aqueous dispersion according to any one of claims 1-7. A method for producing a cosmetic, comprising the step of blending the aqueous dispersion according to any one of claims 1 to 7 with other raw materials.