JP2022163643A - External preparation for skin - Google Patents

Abstract

To provide an external preparation for skin that contains novel active ingredients, is excellent in biological safety and effectiveness, and exhibits the effects of improving the skin barrier function, preventing and improving the dry skin, and preventing and improving the thinned skin.SOLUTION: An external preparation for skin contains niacin amide, and extract from fruits of Ziziphus jujuba (Ziziphus, Rhamnaceae) as active ingredients.SELECTED DRAWING: Figure 1

Description

TECHNICAL FIELD The present invention relates to a combination of active ingredients to be blended in an external preparation for skin.

Conventionally, with aging, inactivation of cell proliferation and differentiation, decrease in hormone secretion, quantitative decrease in extracellular matrix components (collagen, laminin, etc.) that make up the skin, and muscle strength decrease due to decrease in muscle fibers, etc. It is known that skin aging phenomena (wrinkles, sagging, etc.) or skin disorders (dryness, roughness) occur for the following reasons.

Various active ingredients have been proposed for the purpose of preventing and ameliorating unhealthy cells and aging, and cosmetics, foods and drinks, and pharmaceuticals containing these active ingredients have been put on the market. Examples thereof include cell activating components such as α-hydroxycarboxylic acid; extracellular matrix components such as collagen, elastin, hyaluronic acid or salts thereof; moisturizing agents such as urea; Furthermore, plant-derived antioxidants and moisturizing agents have also been proposed, but they are insufficient in terms of the effect of preventing and improving cell unhealthiness and aging.
Japanese Patent Application Laid-Open No. 51-123836 Japanese Patent Application Laid-Open No. 05-500230 Japanese Patent Application Laid-Open No. 09-194383 JP 2019-119713

In order to solve the above-mentioned problems of the prior art, the present applicant has developed hypoxia-induced factors ( Focusing on HIF-1α), the purpose is to find a combination of active ingredients that prevent and improve dry skin and thinning of the skin.

The present invention provides an HIF-1α transcription activity promoter containing niacinamide and an extract of jujube fruit of the genus Jujube of the family Buckthornaceae as active ingredients.
The present invention is an external preparation for skin containing an HIF-1α transcriptional activation enhancer containing niacinamide and an extract of jujube fruit of the genus Jujube of the family Buckthornaceae as active ingredients.

According to the present invention, the active ingredient of the present invention can provide an external preparation for skin that exerts the effects of preventing and improving dryness of the skin, preventing and improving thinning of the skin, and improving the skin barrier function.

FIG. 2 shows the HIF-1α transcriptional activation promoting effect of the composition according to the present invention.

Preferred embodiments of the present invention are described in detail below.
Niacinamide (also known as nicotinic acid amide), which is an active ingredient of the present invention, is one of water-soluble vitamins and is an amide compound of niacin (nicotinic acid).

The jujube, which is the active ingredient of the present invention, is a jujube (Ziziphus jujuba) belonging to the genus Jujube of the family Buckthorn family, and the dried fruit (large jujube) is known as a crude drug. In the present invention, jujube fruit is preferably used.

The jujube extract, which is one of the active ingredients of the present invention, can be prepared by first washing the jujube to be extracted, if necessary, in advance to remove foreign matter, and then drying it as it is or drying it. After cutting or pulverizing, it can be brought into contact with an extraction solvent according to a conventional method such as immersion method, countercurrent extraction method, steam distillation method, or the like. Moreover, in the present invention, a supercritical extraction method may be employed.

Extraction solvents used for extract treatment include water; lower alcohols such as methanol, ethanol and propanol; polyhydric alcohols such as ethylene glycol, propylene glycol, 1,3-butylene glycol and glycerin; ethyl acetate and butyl acetate. , esters such as methyl propionate; ketones such as acetone and methyl ethyl ketone; ethers such as ethyl ether and isopropyl ether; Two or more kinds are mixed and used.

In preparation of the extract, there is no particular limitation on the pH of the extract, but it is generally preferred to be in the range of pH 3-9. The pH is adjusted by adding an alkalinity adjuster such as sodium hydroxide, sodium carbonate, or potassium hydroxide, or an acidity adjuster such as citric acid, hydrochloric acid, phosphoric acid, or sulfuric acid to the extraction solvent. be able to.

Extraction conditions such as extraction temperature and time vary depending on the type and pH of the solvent used, or the size of the plant material. , the extraction temperature is in the range of 0 to 80°C. The extraction time is preferably in the range of 1 hour to 7 days in the case of cold extraction at 4°C, and in the range of 1 hour to 3 days in the case of medium temperature extraction around 40°C. In the case of high temperature extraction at 80° C., the time should be in the range of 1 hour to 24 hours. In the case of the immersion method, the bath ratio is generally 1 to 200 times, preferably 1 to 100 times, the weight of the raw material (jujube).

The jujube extract prepared as described above is further subjected to any one or two of activated carbon treatment, ion exchange resin treatment, synthetic adsorbent, silica gel, and recrystallization treatment in order to enhance stability and effectiveness. It is preferred to combine more than one species to prepare the extract. Activated charcoal can be made from plant materials such as pine, bamboo, coconut shells, walnut shells, etc., as well as coal, petroleum, etc., and high-temperature carbonization using gases such as steam, carbon dioxide, and air for these raw materials. Activated carbon can be obtained by a physical method such as a chemical method such as a method using a chemical such as zinc chloride, and then heated to make it porous. Examples of ion exchange resins include weakly basic anion exchange resins, strongly acidic cation exchange resins, strongly basic ion exchange resins, and weakly acidic cation exchange resins. Examples of synthetic adsorbents include nonionic resins such as chelate resins, strongly acidic cation-adsorbing resins, styrene/divinylbenzene copolymers, and methacrylic acid ester polymers.

In the present invention, external preparations for skin include cosmetics, quasi-drugs, and pharmaceuticals for external use. , white powder, facial cleanser, body shampoo, slimming agent, shampoo for hair, soap, etc., and bath agents, etc., but are of course not limited to these.

In addition to the combination of niacinamide and jujube extract, external preparations for skin include ingredients used in external preparations for skin, such as oily ingredients, surfactants (synthetic and natural products), moisturizers, thickeners, preservatives, and antiseptic agents. - Bactericidal agents, powder components, ultraviolet absorbers, antioxidants, pigments, fragrances, etc. can be appropriately blended as necessary. In addition, as long as the effectiveness and characteristics of the extract, hydrolyzate, or fermented product according to the present invention are not impaired, other physiologically active ingredients may be used in combination.

When the combination of niacinamide and jujube extract according to the present invention is used for external preparations for skin, ingredients that can be incorporated therein include, for example, oily ingredients, surfactants (synthetic and natural products), emulsifiers, moisturizing agents, Thickeners, antiseptic/bactericidal agents, antifoaming agents, powder components, antioxidants, chelating agents, pH adjusters, pigments, perfumes, etc. can be appropriately blended as needed. Moreover, as long as the effectiveness and characteristics of the fermented product according to the present invention are not impaired, it may be blended in combination with other physiologically active ingredients.

Examples of oily components include lotus oil, olive oil, jojoba oil, castor oil, soybean oil, rice oil, rice bran oil, rice germ oil, coconut oil, chamomile oil, palm oil, cacao oil, meadowfoam oil, Bergamot oil, rosehip oil, Arabic coffee tree seed oil, lavender oil, shea butter, tea tree oil, avocado oil, macadamia nut oil, vanilla oil, plant-derived oils such as squalane; mink oil, turtle oil, etc. Animal-derived oils and fats; Waxes such as beeswax, carnauba wax, rice wax, and lanolin; Hydrocarbons such as liquid paraffin, petrolatum, paraffin wax, and squalane; Myristic acid, palmitic acid, stearic acid, oleic acid, isostearic acid, eicosene Fatty acids such as acids; Higher alcohols such as lauryl alcohol, cetanol, and stearyl alcohol; ) and synthetic triglycerides.

Examples of surfactants include polyoxyethylene alkyl ethers, polyoxyethylene fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyethylene glycol fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, polyoxyethylene glycerin fatty acid esters, poly Nonionic surfactants such as oxyethylene hydrogenated castor oil and polyoxyethylene sorbitol fatty acid ester; Anionic surfactants such as ethylene alkylphenyl ether sulfates, polyoxyethylene alkyl ether phosphates, α-sulfonated fatty acid alkyl ester salts, polyoxyethylene alkylphenyl ether phosphates; quaternary ammonium salts, primary to secondary Tertiary fatty amine salts, trialkylbenzylammonium salts, alkylpyridinium salts, 2-alkyl-1-alkyl-1-hydroxyethylimidazolinium salts, N,N-dialkylmorphonium salts, polyethylenepolyamine fatty acid amide salts, etc. Cationic surfactant; N,N-dimethyl-N-alkyl-N-carboxymethylammoniobetaine, N,N,N-trialkyl-N-alkyleneammoniocarboxybetaine, N-acylamidopropyl-N',N Amphoteric surfactants such as '-dimethyl-N'-β-hydroxypropylammoniosulfobetaine can be used.

Examples of emulsifiers or emulsifying aids include stevia derivatives such as enzyme-treated stevia, saponin or its derivatives, casein or its salts (sodium, etc.), sugar-protein complexes, sucrose or its esters, lactose, soybean-derived Water-soluble polysaccharide, complex of soybean-derived protein and polysaccharide, lanolin or its derivative, cholesterol, stevia derivative (stevia enzyme fermented product, etc.), silicate (aluminum, magnesium, etc.), carbonate (calcium, sodium, etc.), saponin and derivatives thereof, lecithin and its derivatives (hydrogenated lecithin, etc.), lactic acid bacteria fermented rice, lactic acid bacteria fermented germinated rice, lactic acid bacteria fermented grains (barley, beans, cereals, etc.) and the like can also be blended.

Examples of moisturizing agents include glycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol, polyethylene glycol, sorbitol, xylitol, sodium pyrrolidone carboxylate, and 2-methacryloyloxyethylphosphorylcholine/butyl methacrylate copolymer liquid. etc., and further sugars such as trehalose, mucopolysaccharides (e.g., hyaluronic acid and its derivatives, chondroitin and its derivatives, heparin and its derivatives, etc.), tuberose polysaccharides, elastin and its derivatives, collagen and its derivatives, NMF-related Substances, hydrolyzed conchiolin, hydrolyzed silk, sphingomonas culture, glycosphingolipid, ceramide, lactic acid, urea, higher fatty acid octyldodecyl, seaweed extract, sylvatica root extract, various amino acids and their derivatives mentioned.

Examples of thickeners include alginic acid, agar, carrageenan, fucoidan, and other brown algae, green algae, or red algae-derived components; Birlan root (white) extract; pectin, locust bean gum, aloe polysaccharide, and Alcaligenes-producing polysaccharide. Polysaccharides such as polysaccharides; Gums such as xanthan gum, tragacanth gum, roasted bean gum, guar gum; Cellulose derivatives such as carboxymethyl cellulose and hydroxyethyl cellulose; Synthetic polymers such as conjugates; hyaluronic acid and its derivatives; polyglutamic acid and its derivatives;

Examples of antiseptic/bactericidal agents include urea; paraoxybenzoic acid esters such as methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, and butyl parahydroxybenzoate; phenoxyethanol, dichlorophen, hexachlorophene, and chlorhexidine hydrochloride. , benzalkonium chloride, salicylic acid, ethanol, undecylenic acid, phenols, jamal (imidazodenyl urea), polyphosphoric acid, propanediol, 1,2-pentanediol, various essential oils, dry distillation of bark, fermented radish, sugar cane plant-derived ethanol or 1,3-butylene glycol.

Examples of powder components include sericite, titanium oxide, talc, kaolin, bentonite, zinc oxide, magnesium carbonate, magnesium oxide, zirconium oxide, barium sulfate, silicic anhydride, mica, nylon powder, polyethylene powder, and silk. There are powders, cellulose-based powders, powders of grains (rice, wheat, corn, millet, etc.), and powders of beans (soybeans, adzuki beans, etc.).

Examples of UV absorbers include ethyl para-aminobenzoate, ethylhexyl paradimethylaminobenzoate, amyl salicylate and derivatives thereof, 2-ethylhexyl para-methoxycinnamate, octyl cinnamate, oxybenzone, 2,4-dihydroxybenzophenone, 2- Hydroxy-4-methoxybenzophenone-5-sulfonate, 4-tert-butyl-4-methoxybenzoylmethane, 2-(2-hydroxy-5-methylphenyl)benzotriazole, urocanic acid, ethyl urocanate, aloe extract etc.

Antifoaming agents include, for example, ethanol, isopropanol, disiloxane, dimethylpolycyclosan, silica dimethicone silicate, trisiloxane, silica silylate, dimethicone, trimethylsiloxysilicate, and DPG isobornyl ether.

Antioxidants include, for example, butylhydroxyanisole, butylhydroxytoluene, propyl gallate, purslane extract, sycamore root extract, peony extract, vitamin E and derivatives thereof (e.g., vitamin E nicotinate, vitamin E linoleate, etc.).

Examples of chelating agents include trisodium ethylenediaminehydroxyethyltriacetate, edetic acid or salts thereof, gluconic acid, phytic acid, sodium polyphosphate, sodium metaphosphate, tetrasodium hydroxyethanediphosphonate, and the like.

Examples of pH adjusters include citric acid or salts thereof, lactic acid or salts thereof, glycolic acid, succinic acid, hydrochloric acid, monoethanolamine, diethanolamine, triethanolamine, sodium hydroxide and potassium hydroxide.

As whitening agents, t-cycloamino acid derivatives, kojic acid and its derivatives, ascorbic acid and its derivatives, hydroquinone and its derivatives, ellagic acid and its derivatives, nicotinic acid and its derivatives, resorcinol derivatives, tranexamic acid and its derivatives , 4-methoxysalicylic acid potassium salt, magnolignan (5,5'-dipropyl-biphenyl-2,2'-diol), hydroxybenzoic acid and its derivatives, vitamin E and its derivatives, α-hydroxy acid, AMP (adenosine mono phosphate, adenosine monophosphate), and these may be blended singly or in combination.

Examples of the above kojic acid derivatives include kojic acid esters such as kojic acid monobutyrate, kojic acid monocaprate, kojic acid monopalmitate and kojic acid dibutyrate; kojic acid sugars such as kojic acid ethers and kojic acid glucoside; Ascorbic acid derivatives such as L-ascorbic acid-2-phosphate sodium, L-ascorbic acid-2-phosphate magnesium, L-ascorbic acid-2-sulfate sodium, L-ascorbic acid -Ascorbic acid ester salts such as 2-sulfate magnesium, L-ascorbic acid-2-glucoside, L-ascorbic acid-5-glucoside, ascorbyl tocopheryl maleate, ascorbyl tocopheryl potassium phosphate, myristyl 3-glyceryl ascorbate , ascorbic acid sugar derivatives such as caprylyl 2-glyceryl ascorbic acid, 6-position acylated products of these ascorbic acid sugar derivatives (acyl group is hexanoyl group, octanoyl group, decanoyl group, etc.), L-ascorbic acid tetraisopalmitate, L-ascorbic acid tetra-fatty acid esters such as L-ascorbic acid tetralaurate, 3-O-ethylascorbic acid, L-ascorbic acid-2-phosphate-6-O-palmitate sodium, glyceryl ascorbic acid or its Acylated derivatives, ascorbic acid glycerol derivatives such as bisglyceryl ascorbic acid, aminopropyl L-ascorbate phosphate, hyaluronic acid derivatives of L-ascorbic acid, 3-OD lactose-L-ascorbic acid, isostearyl ascorbyl phosphate Salts, hydroquinone derivatives such as arbutin (hydroquinone-β-D-glucopyranoside), α-arbutin (hydroquinone-α-D-glucopyranoside), etc., and tranexamic acid derivatives such as tranexamic acid esters (eg, lauryl tranexamic acid) ester, tranexamic acid hexadecyl ester, tranexamic acid cetyl ester or a salt thereof), amides of tranexamic acid (e.g., tranexamic acid methylamide), etc., and resorcinol derivatives include, for example, 4-n-butylresorcinol, 4- isoamylresorcinol and the like, and 2,5-dihydroxybenzoic acid derivatives such as 2,5-diacetoxybenzoic acid, 2-acetoxy-5-hydroxybenzoic acid, 2-hydroxy-5-propio nyloxybenzoic acid and the like; nicotinic acid derivatives such as nicotinamide and benzyl nicotinate; and α-hydroxy acids such as lactic acid, malic acid, succinic acid, citric acid and α-hydroxyoctanoic acid. .

Examples of physiologically active ingredients include placenta extract, saxifrage extract, saxifrage extract, perilla extract, rice bran extract or its hydrolyzate, white mustard extract or its hydrolyzate, and fermented white mustard. , peony extract or its hydrolyzate, murasaki kibu extract, lotus seed extract or its hydrolyzate, lotus seed fermented product, pearl barley hydrolyzate, pearl barley seed fermented product, royal jelly fermented product, sake lees extract or contained therein Ceramide, chamomile extract, coral grass extract, rice leaf extract or its hydrolyzate, eggplant (water eggplant, long eggplant, Kamo eggplant, rice eggplant, etc.) extract or its hydrolyzate, apricot extract seaweed extracts such as kelp, sea lettuce, or cattle mushroom extracts, extracts of marine flowering plants such as eelgrass, fermented soymilk, jellyfish water, rice extracts or their hydrolysates, fermented rice extracts, germinated rice extracts or its hydrolyzate, germinated rice fermented product, black soybean extract or its hydrolysate, brown sugar extract or its fermented product, damask rose flower extract, ylang ylang flower extract, bamboo shoot skin extract, linole Acids and their derivatives or processed products (for example, liposomal linoleic acid, etc.), animal- or fish-derived collagen and its derivatives, elastin and its derivatives, glycyrrhizic acid and its derivatives (dipotassium salt, etc.), t-cycloamino acid derivatives, vitamin A and derivatives thereof, allantoin, diisopropylamine dichloroacetate, γ-amino-β-hydroxybutyric acid, gentian extract, licorice extract, carrot extract, Panax ginseng extract or its fermented product, camellia extract, red ginseng extract, loofah extract, peach extract, plum extract, peach kernel extract, kiwi extract, sunflower extract, pau d'arco bark extract, daily lily extract or fermented product, hibiscus flower extract or fermented product, wormwood extract , cherimoya extract, mango extract, mangosteen extract, funori extract, oolong tea extract, red fuki extract, sycamore extract, sweet potato extract, Japanese pepper pericarp or seed coat extract or hydrolyzate, safflower flower extract , Casablanca extract, sweet potato extract or its fermented product, guava leaf extract, olive leaf extract, horse chestnut extract, ginger extract, vanilla extract, houttuynia cordata extract, banpeiyuzu extract, aloe extract, Aloe vera extract, fig flower extract, apple extract, white asparagus extract, etc.

Next, the present invention will be described in more detail with production examples, formulation examples and test examples, but the present invention is not limited thereto. In the following, all parts mean parts by weight, and all percentages mean weight %.

Production example 1. Preparation of jujube extract (1)
Jujube fruits were dried, and 20 kg of purified water was added to 2 kg of the dried fruit and immersed at 40°C. This was filtered to obtain 18 kg of a transparent brown jujube fruit water extract (solid concentration: 5.0%). Here, in order to further enhance the stability, a styrene-divinylbenzene-based synthetic adsorbent was used to concentrate the water extract of jujube fruit. Further, after the resulting concentrate was mixed with purified water and 1,3-butylene glycol, insoluble matter was filtered to obtain a light brown and transparent jujube fruit extract. In addition, 5.0 kg of light brown and transparent jujube fruit extract (solid concentration: 1.1%) was used in the evaluation test described later.

Production example 2. Preparation of jujube extract (2)
Instead of the preparation method of Production Example 1, a jujube fruit extract may be prepared by the following method.
Jujube fruits belonging to the genus Jujube of the family Buckthornaceae were dried, and 20 kg of a 30% 1,3-butylene glycol aqueous solution was added to 2 kg of the dried fruit and immersed at 40°C. After filtering this, it was diluted with purified water to give 5.0 kg of pale brown and transparent jujube fruit extract (solid concentration: 1.1%).

In the present invention, instead of the styrene-divinylbenzene synthetic adsorbent used in the concentration step of Production Example 1, other synthetic adsorbents, ion exchange resins or activated carbon may be used. In Production Example 1, the concentrate of the jujube fruit aqueous extract was mixed with purified water and 1,3-butylene glycol to obtain a pale brown and transparent jujube fruit extract. - Instead of butylene glycol, jujube fruit water extract and 1,3-butylene glycol prepared separately may be used.

In the present embodiment, focusing on HIF-1α (Seikagaku, Vol. 85, No. 3, pp187-195, 2013), which is involved in homeostatic mechanisms such as maintenance of stem cells and control of inflammation, The effect of promoting HIF-1α transcription activity by the active ingredient of the present invention was evaluated.

Test example 1. HIF-1α Transcriptional Activity Evaluation Test (1) Sample Preparation First, niacinamide was dissolved in purified water to a final concentration of 2 mM, which was used in the following evaluation test. A composition comprising this niacinamide and the extract of Production Example 1 was used as Sample 1 of the present invention in the following evaluation tests. On the other hand, for comparison purposes, comparative sample 1 consisting only of the extract of product 1 and comparative sample 2 consisting only of niacinamide (final concentration 2 mM) were also prepared.
(2) Evaluation Test Method Normal human epidermal cells were adjusted to 1×10 ⁵ cells/mL using Humedia-KG2 containing a growth additive [manufactured by Kurabo Industries], 100 μL of which was seeded in a 96-well microplate, and 5% CO2 was applied. _2. Cultured at 37°C under saturated steam. After culturing for 24 hours, a firefly luciferase reporter vector containing a nucleotide sequence (HRE) that binds to HIF-1α and a vector containing Renilla luciferase as an internal standard (Cignal HIF Pathway Reporter Assay Kit) [manufactured by QIAGEN] were added to the cells. was transfected using ViaFect transfection reagent (Promega). After 24 hours, the present invention sample 1, the comparative sample 1, or the comparative sample 2 were added as sample solutions to separate culture media to set the test group 1 and the comparative test groups 1 and 2, respectively. The concentration of the extract of Production Example 1 in Invention Sample 1 and Comparative Sample 1 was adjusted to a final concentration of 2.0% with respect to the total amount of the medium, and the concentration of niacinamide in Invention Sample 1 and Comparative Sample 2 was A final concentration of 2 mM was prepared. Twenty-four hours after the addition of each sample, the cell contents were extracted, and the luciferase activity of the cell extract was measured using a luciferase assay system (Promega) with a luminometer (Promega GloMax-Multi+Detection System). The HIF-1α transcription activity per cell was calculated by dividing the firefly luciferase measurement value (HRE transcription amount) by the Renilla luciferase measurement value (cell amount). Furthermore, the HIF-1α transcriptional activity of a group (control group) to which only medium was added instead of the sample solution was similarly tested and calculated. The HIF-1α transcription activity of Sample 1 of the present invention and Comparative Samples 1 and 2 was calculated relative to the value of the control group as 100.

It is shown in FIG. 1 of Test Example 1.
As shown in FIG. 1, Comparative Sample 1 (only the extract of Production Example 1) did not show the HIF-1α transcription activity promoting effect, while Sample 1 of the present invention (niacinamide and the extract of Production Example 1) combination) showed a remarkable effect of promoting HIF-1α transcriptional activity compared to Comparative sample 2 (niacinamide only). It was confirmed that a synergistic effect of promoting activity was exhibited.

HIF-1α is a factor involved in homeostatic mechanisms such as maintenance of stem cells and control of inflammation. It is suggested that the effect of improving and improving the barrier function of the skin is obtained.

Formulation example 1. Lotion [Ingredients] Part Eucalyptus oil 0.2
Polyoxyethylene (5.5) cetyl alcohol 5.0
Tocopherol acetate 0.02
Dipotassium glycyrrhizinate 0.5
Monoammonium glycyrrhizinate 0.5
Stearyl glycyrrhizinate 0.05
Isopropylmethylphenol 0.1
Align in 0.1
D- pantothenyl alcohol 0.1
Salicylic acid 0.5
Urea 5.0
l-menthol 0.9
dl-menthol 0.2
1,3-butylene glycol 5.0
Sodium citrate 0.2
Methylparaben 0.1
Hinokitiol 0.003
Photosensitive element No. 201 0.002
Niacinamide 5.0
Extract of Production Example 1 2.0
Purified water Amount that makes the total amount 100 parts

Formulation example 2. Lotion [Ingredients] Part Glyceryl caprylate 3.0
Polyglyceryl-10 Laurate 3.0
Cetanol 2.0
behenyl alcohol 2.0
Methylparaben 0.1
D- pantothenyl alcohol 0.1
Yeast hydrolyzate 2.0
Ascorbic acid 3.0
Glycyrrhizic acid 0.5
β-glycyrrhetinic acid 0.05
Tocopherol nicotinate 0.1
Resorcinol 0.1
Zinc oxide 2.0
dl-camphor 0.5
Glycerin 2.0
1,3-butylene glycol 5.0
Potassium hydroxide 0.5
Niacinamide 3.0
Extract of Production Example 1 2.0
Purified water Amount that makes the total amount 100 parts

Formulation example 3. Emulsion [Ingredients] Part Liquid paraffin 6.0
Hexalane 4.0
Jojoba oil 1.0
Polyoxyethylene (20) sorbitan monostearate 1.0
Lipophilic glyceryl stearate 1.0
Soy lecithin 1.5
L-ascorbic acid-2-glucoside 2.0
Potassium hydroxide 0.5
Glycerin 3.0
1,3-butylene glycol 2.0
Carboxymethyl cellulose 0.3
Sodium hyaluronate 0.01
Niacinamide 5.0
Extract of Production Example 1 2.0
Fragrance Appropriate amount Purified water Amount to make the total amount 100 parts

Formulation example 4. Milky lotion A milky lotion is obtained in the same manner as in Formulation Example 3, except that 2.0 parts of L-ascorbic acid-2-glucoside and 3.0 parts of arbutin are used in place of 0.5 parts of potassium hydroxide. rice field.

Formulation example 5. Milky lotion A milky lotion is prepared in the same manner as in Formulation Example 3, except that 2.0 parts of L-ascorbic acid-2-glucoside and 2.0 parts of tranexamic acid are used in place of 0.5 parts of potassium hydroxide. Obtained.

Formulation example 6. Milky Lotion A milky lotion was obtained in the same manner as in Formulation Example 3, except that the extract of Production Example 2 was used in place of 2.0 parts of the extract of Production Example 1.

Formulation example 7. Lotion [Ingredients] part ethanol 10.0
Glycerin 3.0
1,3-butylene glycol 2.0
Methylparaben 0.2
Citric acid 0.1
Sodium citrate 0.3
Carboxyvinyl polymer 0.1
Xanthan gum 0.1
Niacinamide 1.0
Extract of Production Example 1 2.0
Eggplant extract 1.0
Fragrance Appropriate amount Potassium hydroxide Appropriate amount Purified water Amount to make the total amount 100 parts

Formulation example 8. Essence [ingredient] part ethanol 2.0
Glycerin 5.0
1,3-butylene glycol 5.0
Methylparaben 0.1
Ceramide 1.0
Hyaluronic acid 0.1
Citric acid 0.3
Sodium citrate 0.6
Niacinamide 2.0
Extract of Production Example 1 2.0
Purified water Amount that makes the total amount 100 parts

Formulation example 9. Cream [Ingredients] Part Olive oil 5.0
Jojoba oil 5.0
Squalane 5.0
Hexyldecyl isostearate 5.0
Di(octyldodecyl/phytosteryl/behenyl) lauroyl glutamate 5.0
Glyceryl caprylate 1.0
Glyceryl stearate 1.0
isostearyl glyceryl 3.0
γ-oryzanol 0.1
behenyl alcohol 2.0
Palmitic acid 2.5
D-pantothenyl alcohol 3.0
Allantoin 0.1
Riboflavin 0.01
Resorcinol 0.1
Benzalkonium chloride 0.05
Urea 3.0
β-glycyrrhetinic acid 0.3
Stearyl glycyrrhetinate 0.3
Ammonium glycyrrhizinate 0.3
Lactic acid bacteria fermented rice 2.0
Hydrogenated lecithin 0.5
Hydrogenated lysolecithin 0.5
Water-soluble collagen 1.0
Hydrolyzed collagen 1.0
Xanthan gum 1.0
Zinc oxide 0.5
dl-camphor 0.3
l-menthol 0.5
Niacinamide 5.0
Extract of Production Example 1 2.0
Purified water Amount that makes the total amount 100 parts

Formulation example 10. Essence [ingredients] part ethanol 2.0
Glycerin 5.0
1,3-butylene glycol 5.0
Methylparaben 0.1
Hyaluronic acid hydrolyzate 1.0
Hyaluronic acid sodium salt 1.0
Kelp extract 1.0
Ulva extract 1.0
Catamen Eucheuma Extract 1.0
Citric acid 0.3
Sodium citrate 0.6
Niacinamide 5.0
Extract of Production Example 1 2.0
Purified water Amount that makes the total amount 100 parts

Formulation example 11. Pack dipropylene glycol 5.0
Polyoxyethylene (60) hydrogenated castor oil 5.0
Cetanol 3.0
behenyl alcohol 3.0
Allantoin 0.1
Dipotassium glycyrrhizinate 0.3
Ammonium glycyrrhizinate 0.3
β-glycyrrhetinic acid 0.3
Stearyl glycyrrhetinate 0.3
Salicylic acid 0.1
Tocopherol acetate 0.5
Tocopherol nicotinate 0.1
D- pantothenyl alcohol 0.3
Resorcinol 0.1
Sulfur 2.0
Estradiol 0.002
Yeast hydrolyzate 3.0
Water-soluble collagen 1.0
Xanthan gum 2.0
Polyglyceryl-6 myristate 1.0
Potassium cocoyl glutamate 1.0
Hydrogenated lecithin 3.0
Hydroxylated lecithin 3.0
Niacinamide 3.0
Extract of Production Example 1 2.0
Purified water Amount that makes the total amount 100 parts

Formulation example 12. Sheet mask A sheet mask is obtained by impregnating a nonwoven fabric with the following ingredients.
[Ingredients] Part glycerin 3.0
1,3-butylene glycol 2.0
L-ascorbic acid 2-glucoside 2.0
Methylparaben 0.2
Citric acid 0.1
Sodium citrate 0.3
Xanthan gum 1.0
Water-soluble collagen 1.0
Sodium hyaluronate 1.0
Niacinamide 3.0
Extract of Production Example 1 2.0
Potassium hydroxide Appropriate amount Purified water Amount to make the total amount 100 parts

Formulation example 13. Cleansing cosmetics [Ingredients] Part Potassium cocoylglycine 5.0
Glycerin 10.0
Glyceryl caprylate 1.0
Sodium lauroyl aspartate 10.0
Water-soluble collagen 5.0
Cetanol 3.0
Myristyl alcohol 3.0
Hatomugi seed fermented product 2.0
Isopropyl methyl alcohol 0.1
Allantoin 0.1
Sulfur 0.5
Glycyrrhizic acid 0.3
Dipotassium glycyrrhizinate 0.3
Monoammonium glycyrrhizinate 0.3
β-glycyrrhetinic acid 0.1
Stearyl glycyrrhetinate 0.1
Salicylic acid 0.2
Tocopherol acetate 0.2
Triclosan 0.1
Trichlorocarbanide 0.5
Trichlorohydroxydiphenyl ether 0.2
Concentrated benzalkonium chloride solution 50 0.2
Benzalkonium chloride 0.1
Niacinamide 5.0
Extract of Product 1 2.0
Purified water Amount that makes the total amount 100 parts

Formulation example 14. Body Shampoo [Ingredients] Part N-lauroylmethylalanine sodium 25.0
Coconut fatty acid potassium liquid (40%) 26.0
Coconut fatty acid diethanolamide 3.0
Methylparaben 0.1
1,3-butylene glycol 2.0
Niacinamide 2.0
Extract of Production Example 1 5.0
Purified water Amount that makes the total amount 100 parts

Formulation example 15. Hair Shampoo [Ingredient] Part Sodium N-coconut oil fatty acid methyl taurate 10.0
Sodium polyoxyethylene (3) alkyl ether sulfate 20.0
Lauryldimethylaminoacetate betaine 10.0
Coconut fatty acid diethanolamide 4.0
Methylparaben 0.1
Citric acid 0.1
Niacinamide 4.0
Extract of Production Example 1 2.0
Purified water Amount that makes the total amount 100 parts

Example 16. Hair conditioner [Ingredients] Part polyoxyethylene (10) hydrogenated castor oil 1.0
Distearyldimethylammonium chloride 1.5
Stearyltrimethylammonium chloride 2.0
Glyceryl 2-ethylhexanoate 1.0
Cetanol 3.2
Stearyl alcohol 1.0
Methylparaben 0.1
1,3-butylene glycol 5.0
Niacinamide 3.0
Extract of Production Example 1 2.0
Purified water Amount that makes the total amount 100 parts

Example 17. Liquid foundation [ingredients] part stearic acid 2.4
Propylene glycol monostearate 2.0
Cetostearyl alcohol 0.2
Liquid Lanolin 2.0
Liquid paraffin 3.0
Isopropyl myristate 8.5
Propylparaben 0.05
Carboxymethylcellulose sodium 0.2
Bentonite 0.5
Propylene glycol 4.0
Triethanolamine 1.1
Methylparaben 0.1
Titanium oxide 8.0
Talc 4.0
Niacinamide 1.0
Extract of Production Example 1 2.0
Color pigment Appropriate amount Purified water Amount to make the total amount 100 parts

Claims (2)

An HIF-1α transcription activity promoter containing niacinamide and an extract of jujube fruit belonging to the genus Jujube of the family Buckthornaceae as active ingredients. An external preparation for skin containing the HIF-1α transcriptional activation promoter according to claim 1.

Images