JP7291928B2 - An external or internal skin preparation containing an extract of safflower cultivated by irradiating it with light having a specific wavelength range - Google Patents

Description

TECHNICAL FIELD The present invention relates to a novel external or internal preparation for skin, which is excellent in antioxidant effect, filaggrin production promoting effect, ceramide production promoting effect, and the like.

The skin is located in the outermost layer of the living body, is an organ that is likely to generate active oxygen under the influence of ultraviolet rays, etc., and is constantly exposed to the oxygen stress. On the other hand, active oxygen scavenging enzymes are present in skin cells, and protect skin cells from injury by active oxygen unless the amount of active oxygen exceeding its capacity is generated. However, it is known that the activity of active oxygen scavenging enzymes in skin cells decreases with age. It is thought that it will continue. In addition, when organs other than the skin are exposed to active oxygen that exceeds their ability to scavenge active oxygen, it is thought that functional deterioration occurs and aging occurs, and various lifestyle-related diseases such as cancer and myocardial infarction develop. Therefore, active oxygen scavenging agents and antioxidants have been studied for the purpose of protecting against damage caused by active oxygen, and active oxygen scavenging enzymes such as SOD and catalase, and active oxygen scavenging agents and antioxidants such as SOD-like active substances are included. Foods, cosmetics, quasi-drugs, pharmaceuticals, etc. that have been developed have been developed (see Patent Documents 1 and 2).

It has long been known that natural moisturizing factor (NMF) plays an important role in moisturizing the stratum corneum, and NMF components have been applied to the development of moisturizing agents. A decrease in NMF in the stratum corneum reduces its moisturizing properties and leads to dryness. As a result, dry itching is caused. In recent years, it has become clear that the amino acids that constitute the main component of NMF are produced by the degradation of a protein called filaggrin, which is the main component of keratohyalin granules (Non-Patent Document 1). That is, profilaggrin synthesized in the epidermal granular layer is accumulated in keratohyalin granules and then dephosphorylated and hydrolyzed into filaggrin in the process from the upper granular layer to the stratum corneum. Furthermore, filaggrin is decomposed into amino acids in the process of reaching the upper stratum corneum and becomes the main component of NMF. On the other hand, research on filaggrin and pathological conditions of dry skin is progressing, and it is known that amino acids are reduced in the stratum corneum of dry skin such as xeroderma senile and atopic dermatitis. (Non-Patent Document 2). Therefore, in order to increase the production of NMF for the purpose of maintaining the moisturizing properties of the stratum corneum, it is considered important to promote the production of filaggrin or profilaggrin in keratinocytes. Filaggrin or profilaggrin production promoters have been reported.

Ceramide is a kind of sphingolipid and is a general term for a group of compounds in which sphingosine and fatty acid are amide bonded. Ceramides are known to be present at high concentrations in cell membranes. Also, ceramide is one of the components of intercorneocyte lipids, is secreted extracellularly in the process of keratinization, and plays an important role in the barrier function and water retention capacity of the skin. Furthermore, ceramide is known to regulate cell proliferation, differentiation, apoptosis, etc. as a signal transducing substance. Based on these findings, substances that promote ceramide production are expected to have effects such as cell growth suppression, differentiation induction, and apoptosis induction, and are expected to have therapeutic effects against diseases caused by these abnormalities.
Skin diseases highly associated with ceramide include, for example, squamous cell carcinoma, psoriasis and atopic dermatitis. From these facts, it is possible to treat and prevent skin diseases such as squamous cell carcinoma, psoriasis and atopic dermatitis by promoting the production of ceramide in the skin.

It has been confirmed that there are seven types of ceramides in human skin, and it is ideal to supplement the stratum corneum with all types of ceramides. Conventionally, ceramides have been blended into various external preparations for skin as cosmetics effective in preventing and improving such rough skin and dry skin. was technically difficult. Therefore, it is considered important to promote ceramide production in vivo. Patent document 5 and patent document 6 are reported as a ceramide production promoter.

A safflower extract was known to be used as a cell activator (Patent Document 7).

On the other hand, as a method for enhancing the medicinal efficacy of plants by plant cultivation methods, methods for characteristically increasing functional substances such as vitamins, polyphenols and rutin in plants have already been reported in patent documents. Patent Document 8 discloses a method for increasing the amount of vitamin A and vitamin E contained by irradiating soybean sprouts with light having a wavelength in the near-ultraviolet to blue region. A cultivation method for increasing α-tocopherol and vitamin C, which are functional substances, by performing artificial ultraviolet irradiation for 5 minutes a day is disclosed, and Patent Document 10 discloses blue light, red light and far-red light of artificial light sources A method for increasing vitamin C and vitamin A in Japanese mustard spinach and lettuce is disclosed by adjusting the strength of .

JP-A-9-118630 JP-A-9-208484 Japanese Patent Application Laid-Open No. 2001-261568 Japanese Patent Application Laid-Open No. 2002-201125 JP-A-8-217658 Japanese Patent Application Laid-Open No. 2001-220345 JP-A-2002-356435 JP-A-11-103680 Japanese Patent Application Laid-Open No. 2004-305040 JP-A-8-205677

Scott I. R. , Biochem Biophys Acta, Vol. 719, pp 110-117, 1982 Seguchi T. , Arch Dermatol Res, Vol. 288, pp442-446, 1996

An object of the present invention is to provide a novel skin external preparation or internal preparation that is excellent in antioxidant effect, filaggrin production-promoting effect, ceramide production-promoting effect, and the like.

The inventors of the present invention have conducted intensive studies to solve this problem, and found that the safflower extract has an excellent filaggrin production-promoting effect and can be irradiated with two types of light having a specific wavelength range. The inventors have discovered that the extract of safflower cultivated by the method has excellent antioxidant effect, filaggrin production-promoting effect and ceramide production-promoting effect, and have completed the present invention.

That is, the present invention consists of the following (1) to (6).

(1) Safflower cultivated by irradiating light with a photosynthetic photon flux density (PPFD) ratio of 4:1 to 1:1 in the wavelength range of 570 to 730 nm and 400 to 515 nm, or the water of the safflower, lower alcohol and An external preparation for skin characterized by containing an extract with one or more solvents selected from liquid polyhydric alcohols.
(2) The topical preparation for skin according to (1), wherein the ratio of photosynthetic photon flux density (PPFD) between wavelengths of 570-730 nm and 400-515 nm is 4:1-2:1.
(3) Safflower cultivated under fluorescent light or sunlight by irradiating with light having a photosynthetic photon flux density (PPFD) ratio of 4:1 to 1:1 in the wavelength range of 570 to 730 nm and 400 to 515 nm. A safflower characterized by enhancing one or more effects selected from an antioxidant effect, a filaggrin production promoting effect and a ceramide production promoting effect, as compared with a safflower.
(4) Safflower cultivated under fluorescent light or sunlight by irradiating with light having a photosynthetic photon flux density (PPFD) ratio of 4:1 to 1:1 in the wavelength range of 570 to 730 nm and 400 to 515 nm. compared with safflower, which enhances one or more effects selected from antioxidant effect, filaggrin production promoting effect and ceramide production promoting effect, or selected from water, lower alcohol and liquid polyhydric alcohol of the safflower A medicinal product characterized by containing an extract with one or more solvents.
(5) Safflower cultivated under fluorescent light or sunlight by irradiating with light having a photosynthetic photon flux density (PPFD) ratio of 4:1 to 1:1 in the wavelength range of 570 to 730 nm and 400 to 515 nm. compared with safflower, which enhances one or more effects selected from antioxidant effect, filaggrin production promoting effect and ceramide production promoting effect, or selected from water, lower alcohol and liquid polyhydric alcohol of the safflower A food product characterized by containing an extract with one or more solvents.
(6) A filaggrin production promoter characterized by containing a safflower extract.

The safflower or its extract of the present invention has excellent antioxidant effect, filaggrin production-promoting effect and ceramide production-promoting effect, and can contribute to the fields of pharmaceuticals, quasi-drugs, cosmetics, and foods. .

The present invention will be described in detail below.

The safflower extract used in the present invention is one extracted from a part or the whole plant such as flowers, fruits, seeds, stems, leaves, roots, etc. of safflower (scientific name: Carthamus tinctorius) belonging to the genus Safflower of the family Asteraceae. be. The extraction method is not particularly limited, and for example, extraction by heating, normal temperature extraction, or low temperature extraction may be used. In addition, in the present invention, instead of the extract, the plant body can be used as it is, or it can be used as it is, or it can be used as it is dried, and it can be used properly depending on the purpose. Furthermore, an extract and a plant body can also be used together.

As a cultivation method, cultivation using soil or hydroponics can be performed. In the case of hydroponics, seeds can be used for hydroponics in a rooted state after sowing, and commercially available seedlings can also be used. Cultivation is preferably performed in a facility where temperature, light and carbon dioxide concentration are controlled. The cultivation temperature is 15-30°C, preferably 20-25°C. Cultivation period varies depending on irradiation conditions, but can be harvested in about 10 to 40 days, and can be cultivated for less or longer periods.

As the light source, a light source or the like used in plant cultivation facilities can be used, and optical semiconductor elements such as light emitting diodes (LEDs) and laser diodes can be used. If there is, it is not limited to an optical semiconductor element.

In the cultivation of safflower, the irradiation wavelength is preferably red light with a wavelength range of 570 to 730 nm and blue light with a wavelength range of 400 to 515 nm, and more preferably red light with a wavelength range of 630 to 680 nm and blue light with a wavelength range of 430 to 460 nm. . It is most preferable to irradiate these lights simultaneously. The wavelength at this time refers to the maximum wavelength (peak wavelength) of the irradiation spectrum. As long as it is a light source having such a wavelength peak, it is possible to use a light source produced independently or a commercially available light source. Also, an optical filter may be used to selectively irradiate the above wavelengths. In addition to the above two ranges of light, light sources such as sunlight and fluorescent lamps can also be used.

The amount of irradiated light is expressed as photosynthetic photon flux density (PPFD). In the case of irradiating with a combination of two light emitters, it means the total amount of light. The amount of light after germination is preferably 10 to 300 μmol·m ⁻² s ⁻¹ , more preferably 50 to 200 μmol·m ⁻² s ⁻¹ . If the light intensity is out of this range, growth failure or poor growth may occur. Irradiation is preferably performed from a position 10 to 50 cm above the safflower. The irradiation time can be appropriately changed according to the characteristics and purpose of the plant, but is preferably 6 hours or longer, more preferably 12 to 24 hours.

The light amount ratio of red and blue means the ratio of each PPFD, and can be selected according to the purpose such as yield and effectiveness.

Above all, in order to increase the yield of plants, the light quantity ratio of red and blue is preferably 4:1 to 1:1, more preferably 4:1 to 3:1.

In order to enhance the action of scavenging active oxygen (action of scavenging and removing free radicals), any combination in which the light amount ratio of red and blue is 4:1 to 1:1 is preferable, and 4:1 to 2:1 is more preferable.

In order to enhance the filaggrin production-promoting action, the light amount ratio of red to blue is preferably 4:1 to 1:1, more preferably 4:1 to 2:1. Among them, 4:1 to 3:1 is most preferred.

In order to enhance the effect of promoting ceramide production, the light amount ratio of red to blue is preferably 4:1 to 1:1, more preferably 4:1 to 2:1. Among them, 4:1 to 3:1 is most preferred.

Generally speaking, the light amount ratio between red and blue is preferably 4:1 to 1:1, more preferably 4:1 to 2:1, and most preferably 4:1 to 3:1.

Examples of extraction solvents include water, lower alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol), liquid polyhydric alcohols (1,3-butylene glycol, propylene glycol, glycerin, etc.). ), ketones (acetone, methyl ethyl ketone, etc.), acetonitrile, esters (ethyl acetate, butyl acetate, etc.), hydrocarbons (hexane, heptane, liquid paraffin, etc.), ethers (ethyl ether, tetrahydrofuran, propyl ether, etc.) mentioned. Polar solvents such as water, lower alcohols and liquid polyhydric alcohols are preferred, and water, ethanol, 1,3-butylene glycol and propylene glycol are particularly preferred. These solvents may be used singly or in combination of two or more.

The extract may be used as an extracted solution, or may be used after concentration, dilution, filtration treatment, decolorization with activated charcoal or the like, deodorization treatment, etc., if necessary. Furthermore, the extracted solution may be subjected to a treatment such as concentration to dryness, spray drying, freeze drying, etc., and used as a dried product. It can also be eaten raw in salads and the like.

The preparation for external use or preparation for internal use of the present invention also includes foods, and the above-mentioned plant bodies and/or extracts may be used as they are. Oils and fats, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, metallic soaps, pH adjusters, preservatives, perfumes, moisturizing agents, etc. Ingredients such as agents, powders, ultraviolet absorbers, thickeners, pigments, antioxidants, whitening agents, chelating agents, excipients, film-forming agents, sweeteners, acidulants and the like can also be contained.

The dosage forms of the present invention include, for example, lotions, creams, massage creams, milky lotions, gels, aerosols, packs, cleansers, bath agents, foundations, dusting powders, lipsticks, ointments, poultices, pastes, Plasters, essences, powders, pills, tablets, injections, suppositories, emulsions, capsules, granules, liquids (including tinctures, liquid extracts, spirits, suspensions, limonades, etc.), tablets confectionery, beverages, tea bags, spices, and the like.

In the case of external use, the content of the extract used in the present invention is preferably 0.0001% by weight or more, more preferably 0.001 to 10% by weight in terms of solids, based on the total amount. Furthermore, 0.01 to 5% by weight is most preferred. If it is less than 0.0001% by weight, it is difficult to expect a sufficient effect. If the content exceeds 10% by weight, the enhancement of the effect is difficult to be recognized, which is uneconomical. On the other hand, in the case of internal use, the dosage varies depending on age, body weight, symptoms, therapeutic effect, administration method, treatment time, etc., but usually the daily dosage per adult is preferably 5 mg or more, and 10 mg to 5 g. is more preferred. Furthermore, 100 mg to 1 g is most preferred.

Next, in order to describe the present invention in detail, examples of cultivation of safflower used in the present invention, production examples of safflower extracts, experimental examples, and formulation examples will be given, but the present invention is not limited to these. . % shown in the examples means % by weight. In addition, the mixed extract or mixed dried product shown in the formulation examples is obtained by mixing equal amounts of each extract or mixed dried product.

(1) Experimental materials and growth conditions Safflower seeds are sown in vermiculite containing moisture, germinated in a dark place at a temperature of 22-24°C, wrapped in a sponge, and exposed to white fluorescent light for 12 hours at 22-24°C. Cultivated and raised seedlings. After that, using a hydroponic cultivation apparatus, a red LED (peak wavelength 660 nm) and a blue LED (peak wavelength 450 nm) were simultaneously irradiated from a position of 30 cm directly above the plant at a room temperature of 21 to 23 ° C. for 12 hours. Cultivation was carried out with a light amount ratio of red and blue of 4:1 to 1:1 so that the total photosynthetic photon flux density of the blue LEDs was 100 μmol·m ⁻² s ⁻¹ . In Comparative Cultivation Example 1, cultivation was performed under a white fluorescent lamp so that the photosynthetic photon flux density was 100 μmol·m ⁻² s ⁻¹ , and in Comparative Cultivation Example 2, cultivation was performed under sunlight. The light intensity ratio was not changed during cultivation. After cultivation for 4 weeks, the plants were harvested to obtain raw safflower. This was dried with hot air at about 60°C to obtain a dried safflower (Table 1).

(2) Extraction
Production Example 1A Hot water extract
200 mL of purified water was added to 10 g of the dried product of Cultivation Example 1, extracted at 95 to 100° C. for 2 hours, filtered, and the filtrate was concentrated and freeze-dried to obtain a hot water extract (Table 2).

Production Example 1B 25% ethanol extract 200 mL of 25% ethanol was added to 10 g of the dried product of Cultivation Example 1, extracted at room temperature for 7 days, filtered, and the filtrate was concentrated to dryness to obtain a 25% ethanol extract. (Table 2).

Production Example 1C Ethanol Extract 200 mL of ethanol was added to 10 g of the dried product of Cultivation Example 1, extracted at room temperature for 7 days, filtered, and the filtrate was concentrated to dryness to obtain an ethanol extract (Table 2).

Using the safflower of Cultivation Examples 2 to 4 and Comparative Cultivation Examples 1 and 2, extraction was performed in the same manner as in Production Examples 1A to 1C above to obtain Production Examples 2A to 4C and Comparative Production Examples 1A to 2C (Table 2).

Experimental Example 1 Active oxygen scavenging action For each sample of safflower cultivated under various light irradiation conditions, α,α-diphenyl-β-picrylhydrazyl (hereinafter referred to as DPPH), which is a kind of free radical, was used to remove DPPH radicals. The scavenging action was measured.
0.4 mL of absolute ethanol and 0.2 mL of absolute ethanol solution of 0.5 mM DPPH were added to 0.4 mL of 0.1 M acetate buffer (pH 5.5) to which each sample was added so that the final concentration was 100 μg/mL. liquid. In the case of an oil-soluble sample, the sample was added to 0.4 mL of absolute ethanol to prepare a reaction solution. After that, reaction was carried out at 37° C. for 30 minutes, and absorbance (A) at a wavelength of 517 nm was measured using water as a control. Also, as a blank, purified water was used in place of the sample to measure the absorbance (B). The DPPH radical scavenging rate was calculated from the following formula.
DPPH radical scavenging rate (%) = (1-A/B) x 100

These test results are shown in Table 3. It was confirmed that the extract of the present invention has a stable and excellent DPPH radical scavenging action at any light intensity ratio of red and blue. In particular, a high effect was observed when the light quantity ratio of red and blue was 4:1 to 2:1.

Experimental Example 2 Filaggrin Production Promotion Test The influence of NMF on filaggrin production, which is a precursor of NMF, was evaluated using the mRNA expression level of the filaggrin gene (FLG) as an index. That is, 1×10 ⁵ keratinocyte-derived HaCaT cells were seeded in a 6-cm petri dish and cultured in a DMEM culture medium containing 10% FBS under conditions of 37° C. and 5% CO ₂ for 4 days. Next, after culturing for 24 hours in a DMEM culture medium to which each sample (final concentration: 100 μg/mL) was added, total RNA was extracted. Total RNA was extracted from the cells using RNAiso Plus (Takara Bio), and the amount of total RNA was determined by absorbance at 260 nm using a spectrophotometer (NanoDrop). The mRNA expression level was measured by real-time RT-PCR method based on the total RNA extracted from the cells. For the real-time RT-PCR method, PrimeScript RT Master Mix (Takara Bio) and SYBR Select Master Mix (Life Technologies) were used. That is, after reverse transcription of 500 ng of total RNA, PCR reaction (95°C: 15 seconds, 60°C: 30 seconds, 40 cycles) was performed. Other operations were carried out according to the prescribed method, and the expression level of FLG mRNA was determined as a ratio to the expression level of GAPDH mRNA, which is an internal standard. The FLG expression level was calculated as the ratio of the FLG mRNA expression level of the sample addition group to the FLG mRNA expression level of the control. The following FLG primers were used.

Primer set GGCACTGAAAGGCAAAAGG for FLG (SEQ ID NO: 1)
AAACCCGGATTCACCATAATCA (SEQ ID NO: 2)
Primer set TGCACCACCAACTGCTTAGC for GAPDH (SEQ ID NO: 3)
TCTTCTGGGTGGCAGTGATG (SEQ ID NO: 4)

These test results are shown in Table 4. As a result, the extract of the present invention was found to have a filaggrin production promoting effect.

Experimental Example 3 Ceramide Production Promotion Test The mRNA expression level of serine palmitoyltransferase long chain base subunit 1 (SPTLC1), which is the rate-limiting enzyme gene in ceramide synthesis, was evaluated as an indicator. That is, 1×10 ⁵ keratinocyte-derived HaCaT cells were seeded in a 6-cm petri dish and cultured in a DMEM culture medium containing 10% FBS under conditions of 37° C. and 5% CO ₂ for 4 days. Next, after culturing for 24 hours in a DMEM culture medium to which each sample (final concentration: 10 μg/mL) was added, total RNA was extracted. Total RNA was extracted from the cells using RNAiso Plus (Takara Bio), and the amount of total RNA was determined by absorbance at 260 nm using a spectrophotometer (NanoDrop). The mRNA expression level was measured by real-time RT-PCR method based on the total RNA extracted from the cells. For the real-time RT-PCR method, PrimeScript RT Master Mix (Takara Bio) and SYBR Select Master Mix (Life Technologies) were used. That is, after reverse transcription of 500 ng of total RNA, PCR reaction (95°C: 15 seconds, 60°C: 30 seconds, 40 cycles) was performed. Other operations were performed according to the prescribed method, and the expression level of SPTLC1 mRNA was determined as a ratio to the expression level of GAPDH mRNA, which is an internal standard. The SPTLC1 expression level was calculated as the ratio of the SPTLC1 mRNA expression level in the sample addition group to the SPTLC1 mRNA expression level in the control. The primers used for measuring the expression level of each gene are as follows.

Primer set TGGTCACGGTGGAACAAACA for SPTLC1 (SEQ ID NO: 5)
GCCTGGGCTACCCTCCTTGA (SEQ ID NO: 6)
Primer set TGCACCACCAACTGCTTAGC for GAPDH (SEQ ID NO: 3)
TCTTCTGGGTGGCAGTGATG (SEQ ID NO: 4)

These test results are shown in Table 5. As a result, the extract of the present invention was found to have a ceramide production promoting effect.

Prescription example 1 Lotion Prescription Content (%)
1. Extract of Preparation Example 2B 1.0
2.1,3-butylene glycol 8.0
3. Glycerin 2.0
4. Xanthan gum 0.02
5. Citric acid 0.01
6. Sodium citrate 0.1
7. Ethanol 5.0
8. Methyl paraoxybenzoate 0.1
9. Polyoxyethylene hydrogenated castor oil (40E.O.) 0.1
10. Fragrance Appropriate amount 11. Adjust the total amount to 100 with purified water [Manufacturing method] Components 1 to 6 and 11 and components 7 to 10 are uniformly dissolved, mixed and filtered to obtain a product.

Formulation Example 2 Cream Formulation Content (%)
1. Extract of Preparation Example 1B 0.5
2. Squalane 5.5
3. Olive oil 3.0
4. stearic acid 2.0
5. Beeswax 2.0
6. Octyldodecyl myristate 3.5
7. Polyoxyethylene cetyl ether (20 E.O.) 3.0
8. behenyl alcohol 1.5
9. Glyceryl monostearate 2.5
10. Perfume 0.1
11. Methyl paraoxybenzoate 0.25
12.1,3-butylene glycol 8.5
13. The total amount is adjusted to 100 with purified water [Manufacturing method] Components 2 to 9 are dissolved by heating, mixed, and maintained at 70°C to form an oil phase. Ingredients 1 and 11 to 13 are dissolved by heating and mixed, and kept at 75° C. to form an aqueous phase. Add the water phase to the oil phase to emulsify, cool while stirring, add component 10 at 45°C, and further cool to 30°C to obtain the product.

Formulation Examples 3, 4 and 5 were obtained by replacing the extract of Production Example 1B with the extract of Production Example 1A, the extract of Production Example 2A and the extract of Production Example 3A in Formulation Example 2.

Formulation Example 6 Milky lotion Formulation Content (%)
1. Mixed extract of Preparation Examples 1A, 2A and 3A 1.0
2. Squalane 5.0
3. Olive oil 5.0
4. Jojoba oil 5.0
5. Cetanol 1.5
6. Glyceryl monostearate 2.0
7. Polyoxyethylene cetyl ether (20 E.O.) 3.0
8. Polyoxyethylene sorbitan monooleate (20E.O.) 2.0
9. Perfume 0.1
10. Propylene glycol 1.0
11. Glycerin 2.0
12. Methyl paraoxybenzoate 0.2
13. The total amount is adjusted to 100 with purified water [Manufacturing method] Components 2 to 8 are dissolved by heating, mixed, and maintained at 70°C to form an oil phase. Ingredients 1 and 10 to 13 are dissolved by heating and mixed, and the mixture is kept at 75°C to form an aqueous phase. Add the water phase to the oil phase to emulsify, cool while stirring, add component 9 at 45°C, and further cool to 30°C to obtain the product.

Formulation Example 7 Gel Formulation Content (%)
1. Mixed extract of Production Examples 1C and 2C 0.01
2. Ethanol 5.0
3. Methyl paraoxybenzoate 0.1
4. Polyoxyethylene hydrogenated castor oil (60E.O.) 0.1
5. Perfume Appropriate amount 6.1,3-butylene glycol 5.0
7. Glycerin 5.0
8. Xanthan gum 0.1
9. Carboxy vinyl polymer 0.2
10. Potassium hydroxide 0.2
11. The total amount is adjusted to 100 with purified water [Manufacturing method] Components 1 to 5 and components 6 to 11 are uniformly dissolved, and the two are mixed to obtain a product.

Prescription Example 8 Pack Prescription Content (%)
1. Extract of Preparation Example 2A 0.1
2. Extract of Preparation Example 2B 0.1
3. Polyvinyl alcohol 12.0
4. Ethanol 5.0
5.1,3-butylene glycol 8.0
6. Methyl paraoxybenzoate 0.2
7. Polyoxyethylene hydrogenated castor oil (20E.O.) 0.5
8. Citric acid 0.1
9. Sodium citrate 0.3
10. Fragrance Appropriate amount 11. Adjust the total amount to 100 with purified water [Manufacturing method] Components 1 to 11 are uniformly dissolved to obtain a product.

Prescription Example 9 Foundation Prescription Content (%)
1. Extract of Preparation Example 2A 1.0
2. stearic acid 2.4
3. Polyoxyethylene sorbitan monostearate (20E.O.) 1.0
4. Polyoxyethylene cetyl ether (20 E.O.) 2.0
5. Cetanol 1.0
6. Liquid Lanolin 2.0
7. Liquid paraffin 3.0
8. Isopropyl myristate 6.5
9. Carboxymethylcellulose sodium 0.1
10. Bentonite 0.5
11. Propylene glycol 4.0
12. Triethanolamine 1.1
13. Methyl paraoxybenzoate 0.2
14. Titanium dioxide 8.0
15. Talc 4.0
16. Bengara 1.0
17. Yellow iron oxide 2.0
18. Perfume Appropriate amount 19. The total amount is adjusted to 100 with purified water [Manufacturing method] Components 2 to 8 are dissolved by heating and maintained at 80°C to form an oil phase. Ingredient 19 is sufficiently swelled with ingredient 9, then ingredients 1 and 10 to 13 are added and mixed uniformly. Ingredients 14 to 17 pulverized and mixed with a pulverizer are added to this, stirred with a homomixer and kept at 75° C. to form an aqueous phase. The water phase is added to the oil phase with stirring to emulsify. After cooling, add component 18 at 45°C and cool to 30°C with stirring to obtain the product.

Formulation Example 10 Bath agent 1
Prescription content (%)
1. Extract of Preparation Example 2A 5.0
2. Extract of Preparation Example 2B 1.0
3. Sodium bicarbonate 50.0
4. Yellow No. 202 (1) Appropriate amount 5. Perfume appropriate amount 6. The total amount is adjusted to 100 with sodium sulfate [Manufacturing method] Components 1 to 6 are uniformly mixed to obtain a product.

Formulation Example 11 Ointment Formulation Content (%)
1. Mixed extract of Production Examples 1B and 2B 0.5
2. Polyoxyethylene cetyl ether (30 E.O.) 2.0
3. Glyceryl monostearate 10.0
4. Liquid paraffin 5.0
5. Cetanol 6.0
6. Methyl paraoxybenzoate 0.1
7. Propylene glycol 10.0
8. The total amount is adjusted to 100 with purified water [Manufacturing method] Components 2 to 5 are dissolved by heating, mixed, and maintained at 70°C to form an oil phase. Ingredients 1 and 6 to 8 are dissolved by heating, mixed, and maintained at 75°C to form an aqueous phase. The water phase is added to the oil phase to emulsify, and the mixture is cooled to 30°C while stirring to obtain a product.

Formulation Example 12 Powder Formulation Content (%)
1. Mixed extract of Production Examples 1A and 2A 20.0
2. Dry cornstarch 30.0
3. Microcrystalline cellulose 50.0
[Manufacturing method] Components 1 to 3 are mixed to form a powder.

Formulation Example 13 Tablet Formulation Content (%)
1. Extract of Preparation 2A 3.0
2. Dry cornstarch 27.0
3. Carboxymethylcellulose calcium 20.0
4. Microcrystalline cellulose 40.0
5. polyvinylpyrrolidone 7.0
6. Talc 3.0
[Manufacturing method] Components 1 to 4 are mixed, and then an aqueous solution of component 5 is added as a binder to form granules. Ingredient 6 is added to the molded granules and pressed into tablets. One tablet is 0.52 g.

Prescription Example 14 Tablet Confectionery Prescription Content (%)
1. Mixed extract of Production Examples 1A, 2A and 3A 0.5
2. Dry cornstarch 50.0
3. Erythritol 40.0
4. Citric acid 5.0
5. Sucrose fatty acid ester 3.0
6. Perfume Appropriate amount 7. The total amount is adjusted to 100 with purified water [Manufacturing method] Components 1 to 4 and 7 are mixed and granulated. Ingredients 5 and 6 are added to the molded granules and compressed into tablets. 1 grain is 1.0 g.

Formulation Example 15 Beverage Formulation Content (%)
1. Extract of Preparation Example 2A 2.0
2. Fructose glucose liquid sugar 12.5
3. Citric acid 0.1
4. Perfume 0.05
5. The total amount is adjusted to 100 with purified water [Manufacturing method] Components 1 to 5 are mixed to prepare a beverage.

Formulation Example 16 Powdered drink Formulation Content (%)
1. Mixed extract of Production Examples 1A and 2A 10.0
2. powdered sugar 65.0
3. Powdered peach juice 15.0
4. L-ascorbic acid 8.0
5. Crystalline citric acid 1.2
6. Sodium citrate 0.75
7. Aspartame 0.02
8. Powdered peach fragrance 0.03
[Manufacturing method] Ingredients 1 to 8 are mixed to prepare a powdered beverage.

Prescription Example 17 Herbal tea Prescription Content (%)
1. Mixed dried product of Cultivation Examples 1 and 2 50.0
2. Peppermint 25.0
3. Rosehip 25.0
[Manufacturing method] Mix ingredients 1 to 3 and seal 2 g of the mixture in a tea bag to make herbal tea.

Formulation Example 18 Bath agent 2
Prescription content (%)
1. 42-mesh sieve product of dried pulverized product of Cultivation Example 2 1.0
2. Sodium bicarbonate 50.0
3. Yellow No. 202 (1) Appropriate amount 4. Perfume Appropriate amount 5. [Manufacturing method] Components 1 to 5 are uniformly mixed to obtain a product.

From the above, the extract of safflower is excellent in filaggrin production promotion effect and ceramide production promotion effect, and furthermore, safflower cultivated by irradiating light having a specific wavelength range and its extract are excellent antioxidants. Effect, filaggrin production-promoting effect and ceramide production-promoting effect, and skin external preparations or internal preparations containing these are particularly effective.

Claims (2)

Selected from water of safflower cultivated by irradiating light with a photosynthetic photon flux density (PPFD) ratio of 4:1 to 2:1 in the wavelength range of 570 to 730 nm and 400 to 515 nm, lower alcohol and liquid polyhydric alcohol An external skin preparation for promoting filaggrin production, characterized by containing an extract with one or more solvents. It contains an ethanol extract of safflower cultivated under irradiation with light having a photosynthetic photon flux density (PPFD) ratio of 4:1 to 2:1 in the wavelength range of 570 to 730 nm and 400 to 515 nm. Antioxidant external skin preparation.