JP4612180B2 - Skin preparation - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an external preparation for skin, and more specifically, by containing a fermented product obtained by allowing microorganisms to act on a bean extract and vitamin A and / or a derivative thereof, the skin roughening can be prevented and improved, and the skin The present invention relates to a skin external preparation capable of preventing aging of the skin.
[0002]
[Prior art]
In aging skin, the stratum corneum turnover speed decreases, hyaluronic acid decreases in the skin, and it becomes easy to dry, rough skin, roughness, wrinkles, sagging, etc., the skin thickness decreases, It is known that phenomena such as disappearance of the beam (decrease in elasticity) are observed. As these causes, in addition to aging, external factors, that is, a decrease in function of epidermal cells and dermal fibroblasts due to exposure to ultraviolet rays, drying, oxidation, etc., degradation of hyaluronic acid, and the like are considered.
[0003]
As a method for improving aging skin in this way, cosmetics containing raw materials extracted from natural products such as herbal medicines, chemically synthesized raw materials, etc. are used, and physicochemical effects such as moisturizing effect, film formation, etc. The skin was moisturized and softened (JP-A-6-279227, JP-A-8-310934). However, although skin surface drying was improved, it was transient and an essential improvement effect could not be obtained.
[0004]
Therefore, attempts have been made to improve the skin metabolism of the skin itself and increase the production of hyaluronic acid. For example, retinoic acid, which is a metabolite of vitamin A, is one of the biologically active forms of vitamin A, and promotes proliferation of epidermal cells and fibroblasts (Tong PS et al., J. Invest. Dermatol. 94 , 126-131, 1990, Varani J et al., J. Investig. Dermatol. Symp. Proc. Three 57-60, 1998), hyaluronic acid production enhancing action (Tammi R et al., J. Invest. Dermatol. 92 326-332, 1989), keratinization improving effect (Wanner R et al., Arch. Dermatol. Res. 291 , 346-353, 1999), anti-psoriatic action (Orfanos CE et al., Br. J. Dermatol. 88 167-182, 1973), anti-acne action (Chalker DK et al., J. Am. Acad. Dermatol. 17 , 251-254,1987), anti-wrinkle action (Weiss JS et al., JAMA 259 , 527-535, 1988, Tadaki T et al., Tohoku J. Exp. Med. 169 131-139, 1993), photoaging skin improvement effect (Kligman AM et al., J. Am. Acad. Dermatol. 15 , 836-859, 1986) and the like. Therefore, already in the United States, retinoic acid combination preparations are used as photoaging skin improving agents and wrinkle improving agents.
[0005]
However, since retinoic acid has a problem that it is highly irritating, attempts have been made to use retinol, which is less irritating and less physiological. In order to enhance the physiological action of this retinol, the combined use with various compounds has been attempted. The combined use of retinol and a fatty acid amide (Japanese Patent Laid-Open No. 08-301748), or dimethylimidazoline (Japanese Patent Laid-Open No. 9-1001001). ) Is known to synergistically activate epidermal cells.
[0006]
However, it has been difficult to say that the conventional compounding of vitamin A such as retinol or retinoic acid or a derivative thereof has sufficient effect of activating epidermal cells and enhancing hyaluronic acid production.
[0007]
On the other hand, cosmetics using a bean extract such as soy milk are known and reported to have a moisturizing effect and a cleaning effect (Japanese Patent Laid-Open No. 62-36304). Further, a product obtained by allowing Rhizopus microorganisms to act on soy milk (Japanese Patent Laid-Open No. 1-102011), a product obtained by acting lactic acid bacteria (Japanese Patent Laid-Open No. 3-127713), and a microorganism belonging to the genus Bifidobacterium It is known to use so-called fermented beans such as products (Japanese Patent Laid-Open No. 10-287540) for cosmetics and the like. However, it has not been known at all about the activation of epidermal cells and the enhancement of hyaluronic acid production in combination with other components.
[0008]
[Problems to be solved by the invention]
The purpose of the present invention is to activate skin cells and enhance hyaluronic acid production, thereby having actions such as preventing and improving rough skin, improving keratin, moisturizing effect, preventing and improving wrinkle loss and wrinkles. An object of the present invention is to provide an external preparation for skin that is effective in preventing skin aging.
[0009]
[Means for Solving the Problems]
In view of such circumstances, the present inventors have conducted intensive research on means for enhancing the epidermal cell activation action and hyaluronic acid production enhancement action of vitamin A or its derivatives. As a result, microorganisms were allowed to act on the above components and legume extract. The combined use of the fermented product obtained in this way further enhances the cell activation of vitamin A and its derivatives, and also significantly promotes the production of hyaluronic acid in the skin tissue. Has found that skin dryness, rough skin, wrinkles and disappearance of a beam can be improved and skin aging can be prevented, and the present invention has been completed.
[0010]
That is, this invention provides the skin external preparation containing the fermentation product obtained by making microorganisms act on a bean extract, and 1 type, or 2 or more types of vitamin A and / or its derivative (s).
[0011]
DETAILED DESCRIPTION OF THE INVENTION
Fermentation products obtained by allowing microorganisms to act on bean extracts (hereinafter referred to as “fermented bean products”) used in the present invention are generally called fermented soy milk and are used as food materials. Is.
[0012]
Although it does not specifically limit as microorganisms used in order to manufacture said bean fermented material, In a bean extract culture medium, it is at least 1x10. ⁷ It is desirable that the microorganism has such a property that the concentration of acetic acid in the medium is 70 mM or less when cultured to cells / ml. Examples of such microorganisms include lactic acid-producing bacteria such as Lactobacillus, Streptococcus, Lactococcus, Pediococcus, and Leuconostoc, and Bifidobacterium, particularly Bifidobacterium. Microorganisms are preferred. Specific examples of the microorganism include Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Bifidobacterium addresscentis, Bifidobacterium bifidum, Bifidobacterium -Angular tam, Bifidobacterium catenatum tam etc. are mentioned. The fermentation of the bean extract may be mixed fermentation in which a plurality of strains are combined, or continuous fermentation in which a plurality of strains are combined. In that case, microorganisms other than the above include bacteria such as Bacillus genus, Acetobacter genus, Gluconobacter genus, or Saccharomyces genus, Candida genus, Rhodotorula genus, Pichia genus, Schizosaccharomyces genus, Torula genus, Tigo Examples include yeasts such as Saccharomyces, and filamentous fungi such as Aspergillus, Eurothium, Monascus, Mucor, Neurospora, Penicillium, and Rhizopus.
[0013]
Further, the bean extract used for obtaining the fermented bean product is not particularly limited as long as it can act on the above microorganisms. For example, soy beans, black beans, empty beans, red beans, kidney beans, peas Bean extracts such as beans and chickpeas can be mentioned, and soybean extract is particularly preferable. The shape of the beans used as the raw material of the bean extract is not particularly limited, but beans containing fats and oils, molted beans, flake beans, and the like are preferable, and molted beans are particularly preferable. Further, the bean extract may be produced by any method. For example, after the bean as a raw material is soaked in water, it contains hot water or 0.5 to 1.0% by mass of sodium carbonate. It is preferable to use what was manufactured by adding hot water and grinding, removing okara and further sterilizing by heating. Usually, the beans extract having a solid content of about 10% by mass is used.
[0014]
In addition, in the bean extract, if necessary, prior to fermentation treatment, saccharides used in foods such as sucrose, glucose, fructose, invert sugar, etc., growth of microorganisms such as meat extract, peptone, yeast extract, peptide, etc. You may add the nutrient etc. which are required for. In addition, in order to adjust the liquidity of the bean extract to the optimum pH of the microorganism, an acid used in foods such as citric acid, malic acid, ascorbic acid, lactic acid, and acetic acid may be added.
[0015]
The method for allowing the microorganism to act on the bean extract thus prepared is not particularly limited. For example, after inoculating the bean extract with a liquid solution of a microorganism cultured in advance, the temperature, time, and stirring suitable for the microorganism are performed. If it is an anaerobic bacterium, conditions such as anaerobicity may be appropriately determined and fermentation may be performed. Fermentation can also be performed under conditions suitable for culture, such as stationary culture, agitation culture, shaking culture, and aeration culture.
[0016]
The fermentation product thus obtained may be used after adding a lower alcohol such as ethanol or a polyhydric alcohol such as 1,3-butylene glycol and removing the polymer substance by centrifugation, filtration or the like. More preferred. Deodorization treatment, pH adjustment, etc. may be performed as necessary.
[0017]
The blending amount of the fermented legume product of the present invention to the external preparation for skin is not particularly limited, and may be an amount usually used for an external preparation for skin. 50%, preferably 0.01 to 20%, particularly preferably 0.5 to 10%.
[0018]
On the other hand, vitamin A used in the present invention is a general vitamin contained in many foods, and vitamin A derivatives are derived from the above vitamin A, and are both included in foods. It is highly probable. Vitamin A and / or derivatives thereof used in the present invention are not particularly limited, and various fatty acid esters such as β-carotene and / or derivatives thereof, retinol, retinol palmitate, stearate, acetate, etc. , Various organic acid esters such as lactic acid ester and glycolic acid ester of retinol, and various inorganic acid diester complexes such as phosphoric acid, pyrophosphoric acid and sulfuric acid of retinol can be used, and all-trans-retinol and its isomer, all- Preferred examples include trans-retinoic acid and its isomer, all-trans-retinal and its isomer, their 3 dehydro and 3,4 didehydro isomers. Of these, particularly preferred is retinol palmitate, which is widely commercially available and has relatively good stability. These vitamin A and / or derivatives thereof may be obtained by synthesis, may be obtained from natural extracts, or may be purified.
[0019]
The amount of vitamin A and / or its derivative used in the present invention is not particularly limited as long as it is a commonly used amount. For example, it is 0.0001 to 10% for retinol and retinoic acid. For example, 0.0001 to 10% is preferable, and about 0.0001 to 10% is preferable for retinol palmitate. In particular, retinol palmitate is preferably used at 0.01 to 1%.
[0020]
In producing the skin external preparation of the present invention, raw materials usually used in pharmaceuticals, quasi-drugs, cosmetics, bath preparations, foods and drinks, for example, surfactants, oils, alcohols, humectants, Thickeners, water-soluble polymers, antiseptics, antioxidants, chelating agents, pH adjusters, foaming agents, fragrances, dyes, pigments, UV absorbers / scattering agents, powders, vitamins, amino acids, antibacterial agents, Plant extracts, animal-derived components, seaweed extracts, various drugs, additives, water, and the like can be blended.
[0021]
Among these, sorbitan monolaurate, sorbitan monopalmitate, sorbitan sesquioleate, sorbitan trioleate, polyoxyethylene sorbitan monolaurate, polyoxetylene sorbitan monostearate, polyethylene glycol monooleate, polyethylene glycol Non-ionic surfactant such as alkylate, polyoxyethylene alkyl ether, polyglycol diether, lauroyl diethanolamide, fatty acid isopropanol amide, maltitol hydroxy fatty acid ether, alkylated polysaccharide, alkyl glucoside, sugar ester, lipophilic glycerin Monostearate, self-emulsifying glycerin monostearate, polyglycerin monostearate, polyglycerin alkyle Sorbitan monooleate, polyethylene glycol monostearate, polyoxyethylene sorbitan monooleate, polyoxyethylene cetyl ether, polyoxyethylenated sterol, polyoxyethylenated lanolin, polyoxyethylenated beeswax, polyoxyethylene hydrogenated castor oil Nonionic surfactant such as sodium stearate, potassium palmitate, sodium cetyl sulfate, sodium lauryl phosphate, sodium polyoxyethylene lauryl sulfate, triethanolamine palmitate, sodium polyoxyethylene lauryl phosphate, N-acyl glutamic acid Anionic surfactants such as sodium, stearyldimethylbenzylammonium chloride, stearyltrimethylammonium chloride, benzalkonium chloride Cationic surfactants such as lauryl amine oxide, hydrochloric alkylamino ethyl glycine solution, can be exemplified amphoteric surfactants such as lecithin.
[0022]
Oils include vegetable oils such as macadamia nut oil, castor oil, olive oil, cacao oil, coconut oil, palm oil, tree wax, jojoba oil, grape seed oil, avocado oil, animal oils such as mink oil and egg yolk oil, honey Waxes such as wax, whale wax, lanolin, carnauba wax and candelilla wax, hydrocarbons such as liquid paraffin, squalane, microcrystalline wax, ceresin wax, paraffin wax, petrolatum, lauric acid, myristic acid, stearic acid, oleic acid , Natural and synthetic fatty acids such as isostearic acid, behenic acid, palmitic acid, capric acid, lanolin fatty acid, linoleic acid, linolenic acid, cetanol, stearyl alcohol, hexyldecanol, octyldodecanol, lauryl alcohol, capryl alcohol, myristylua Call, natural and synthetic higher alcohols such as cetyl alcohol, cholesterol, phytosterol, may isopropyl myristate, isopropyl palmitate, octyldodecyl myristate, octyldodecyl oleate, be exemplified by esters such as cholesterol oleate.
[0023]
Examples of humectants include glycerin, erythritol, xylitol, maltitol, propylene glycol, 1,3-butylene glycol, sorbitol, polyglycerin, polyethylene glycol, dipropylene glycol, 1,2-pentanediol, and other pentylene glycols, isoprene. Polyhydric alcohols such as glycol, natural moisturizing ingredients (NMF) such as amino acids, sodium lactate, sodium pyrrolidone carboxylate, xyloglucan, quince seed, carrageenan, pectin, mannan, curdlan, galactan, dermatan sulfate, glycogen, keratan sulfate , Chondroitin, mucoitin sulfate, keratosulfate, locust bean gum, succinoglucan, caronic acid, heparan sulfate, sodium hyaluronate, hyaluronic acid, coller Emissions can be exemplified mucopolysaccharide, water-soluble polymer such as chondroitin sulfate.
[0024]
Thickeners include sodium alginate, xanthan gum, aluminum oxalate, quince seed extract, tragacanth gum, starch, gum arabic, hydroxyethyl guar gum, carboxymethyl guar gum, guar gum, dextran, chitin, chitosan, carboxymethyl chitin, agar, etc. Natural polymer materials, semi-synthetic polymer materials such as methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, soluble starch, and cationized cellulose, synthetic polymer materials such as carboxyvinyl polymer, polyvinyl alcohol, and alkyl methacrylate methacrylate copolymer It can be illustrated.
[0025]
Examples of preservatives include benzoate, salicylate, sorbate, dehydroacetate, p-hydroxybenzoate, 2,4,4′-trichloro-2′-hydroxydiphenyl ether, 3,4,4′-trichlorocarbani Lido, benzalkonium chloride, hinokitiol, resorcin, ethanol and the like can be exemplified.
[0026]
As an antioxidant, dibutylhydroxytoluene, butylhydroxyanisole, propyl gallate, ascorbic acid, etc., and as a chelating agent, edetate, pyrophosphate, hexametaphosphate, citric acid, tartaric acid, gluconic acid, etc. Examples of the pH adjuster include sodium hydroxide, triethanolamine, citric acid, sodium citrate, boric acid, borax, and potassium hydrogen phosphate.
[0027]
Examples of UV absorbers / scatterers include p-aminobenzoic acid UV absorbers, anthranilic acid UV absorbers, salicylic acid UV absorbers, cinnamic acid UV absorbers, benzophenone UV absorbers, sugar UV absorbers, 3- (4′-methylbenzylidene) -d-camphor, 3-benzylidene-d, 1-camphor, urocanic acid, urocanic acid ethyl ester, 2-phenyl-5-methylbenzoxazole, 2- (2′-hydroxy-5) '-T-octylphenyl) benzotriazole, 2- (2'-hydroxy-5'-methylphenyl) benzotriazole, dibenzalazine, dianisoylmethane, 4-methoxy-4'-t-butyldibenzoylmethane, 5- ( 3,3-dimethyl-2-norbornylidene) -3-pentan-2-one, 2-hydroxy-4 Methoxybenzophenone, octyl dimethyl para amino benzoate, can be exemplified ethylhexyl p-methoxycinnamate, titanium oxide, kaolin, talc and the like.
[0028]
As vitamins, vitamin B ₆ Hydrochloride, vitamin B ₆ Tripalmitate, Vitamin B ₆ Dioctanoate, vitamin B ₂ And its derivatives, vitamin B ₁₂ , Vitamin B ₁₅ And vitamin B such as derivatives thereof, ascorbic acid, ascorbic acid sulfate and salts thereof, ascorbic acid phosphate and salts thereof, ascorbic acid dipalmitate, ascorbic acid glucoside, acylascorbic acid glucoside, ascorbic acid tetraisopalmitate and the like Vitamin Cs, vitamin D, α-tocopherol, β-tocopherol, γ-tocopherol, vitamin E such as vitamin E acetate, vitamin F, vitamin K, pantothenic acid, pantethine, vitamin H, vitamin P, vitamin U, carnitine, Examples include ferulic acid, γ-oryzanol, α-lipoic acid, orotic acid, and derivatives thereof.
[0029]
As amino acids, glycine, alanine, valine, leucine, isoleucine, serine, threonine, phenylalanine, tyrosine, asparagine, glutamine, taurine, tryptophan, cystine, cysteine, methionine, proline, hydroxyproline, aspartic acid, glutamic acid, arginine, histidine And lysine and derivatives thereof.
[0030]
Examples of the antibacterial agent include benzoic acid, salicylic acid, sorbic acid, p-hydroxybenzoic acid ester, hexachlorophene and the like.
[0031]
As plant extracts, borage, clara, corn, orange, sage, yarrow, mallow, embellished, thyme, cypress, spruce, birch, horsetail, loofah, maroonie, yukinoshita, arnica, lily, mugwort, peonies, aloe, gardenia, Examples include extracts from Sawara, Bukkur, Sanshi, Ogon, licorice, Chinese mugwort, Kujin, Yokuinin, Nindo, Peonies, Sakuhakuhi, Hawthorn, Buttonpi, Cephalanthin and the like.
[0032]
As seaweed extracts, brown algae such as kombu, macombu, wakame, pheasant, ascophyllum, hibamata, mozuku, Okinawa mozuku, and Himantaria, red algae such as Proboscis, coral, palmaria, tunomata and green, green algae such as Aosa, Anaaosa, An extract from cyanobacteria can be exemplified.
[0033]
Various drugs include nicotinamide, benzyl nicotinate, γ-oryzanol, allantoin, glycyrrhizic acid and its salts, glycyrrhetinic acid and its derivatives, hinokitiol, bisabolol, eucarptone, thymol, inositol, saikosaponin, carrot saponin, and loof Examples thereof include saponins such as saponin and muclodisaponin, pantothenyl ethyl ether, ethinyl estradiol, tranexamic acid, arbutin, and placenta extract.
[0034]
The skin external preparation of the present invention can be of various dosage forms. Examples of the dosage form include cosmetics, pharmaceuticals, quasi drugs, and the like, and these can be produced by conventional methods. Specific examples of product forms include lotions, emulsions, moisturizing creams, cleansing creams, massage creams, patching agents, facial cleansing creams, packs, serums, ointments, foundations, lipsticks, mascaras, eye shadows, etc. Finished cosmetics, shampoos, rinses, treatments, hair tonics, hair liquids, hair creams, hair milk and other cosmetics for hair, after-shave lotions, body soaps, bath preparations and the like.
[0035]
【Example】
Hereinafter, the present invention will be described in more detail with reference to production examples, test examples, and examples, but the present invention is not limited thereto.
[0036]
Manufacturing example 1
Production of fermentation product (1):
Soybeans were washed with water and immersed in water overnight to allow sufficient water absorption. Four times the amount of water was added to the soybean and pulverized into a paste with a mixer. This was heated at 100 ° C. for 30 minutes and cooled, and the filtered product was steam sterilized at 100 ° C. for 90 minutes to produce soy milk (solid content concentration of about 10% by mass).
[0037]
After inoculating the pre-cultured Bifidobacterium breve YIT 4065 (FERM BP-6223) solution to 0.5% of the total amount of soymilk, it is left to stand at 37 ° C for 24 hours for fermentation. Soy milk was obtained. The number of viable bacteria in the obtained fermented soymilk is 1.3X10 ⁹ cells / ml. An equal amount of ethanol was added to this fermented soymilk and filtered with a filter paper to produce a fermentation product (hereinafter sometimes abbreviated as “SB”) 1.
[0038]
Manufacturing example 2
Production of fermentation product (2):
A soymilk produced in the same manner as in Production Example 1 was inoculated with a pre-cultured Bifidobacterium breve YIT 4065 (FERM BP-6223) solution to 1.0% of the total amount of soymilk, and then a nitrogen atmosphere. The solution was cultured at 30 ° C. until pH 5.5, adjusted to pH 4.5 by adding lactic acid, and then stirred and cultured at 37 ° C. for 26 hours in a nitrogen atmosphere. The number of viable bacteria in the obtained fermented soymilk is 4.2 × 10 ⁸ cells / ml. After culturing, 3-fold amount of 1,3-butylene glycol was added to this fermented soymilk and filtered through filter paper to produce fermentation product 2.
[0039]
Test example 1
Measurement of cell activation effect by cell culture (1):
(Cell culture)
As test cells, human epidermis cells (manufactured by Kurabo Industries) were used by Yasumoto et al. (Shigeru Yasumoto, cultured cell experiment method for molecular biology research, Toshio Kuroki et al., Yodosha, 1995, pp191-200) According to the above, immortalized cells obtained by transformation with SV40 virus T antigen were used. The cells are seeded in a 96 well plate (4 × 10 4 ³ Per ml / 0.1 ml / well) in a serum-free liquid medium for growth (Humdia-KG2: Kurabo Industries) at 37 ° C., CO ₂ Culturing was performed under conditions of a concentration of 5%. After 1 day of culture, a culture medium supplemented with fermentation product 1 produced in Production Example 1 above and all-trans-retinol (manufactured by Sigma: hereinafter sometimes abbreviated as “ROH”) as vitamin A and / or a derivative thereof. The culture was continued for another 2 days. For comparison, culture was performed in the same manner using a medium with each added alone and a medium without any as a control.
[0040]
(Measurement method of cell activation effect)
After 3 days of culturing, 10 μl of a reducing coloring reagent (WST-1: manufactured by Dojindo) was added to each well, followed by CO 2 at 37 ° C. ₂ Incubation was performed for 2 hours under the condition of 5% concentration, and absorbance at 450 nm to 660 nm was measured. The metabolic activity of the cells was calculated from the obtained absorbance, and the cell activation effect was evaluated from the rate of increase of metabolic activity relative to the control. The results are shown in FIG.
[0041]
From FIG. 1, 0.5% fermentation product 1 and 5 × 10 5, which are concentrations that do not affect metabolic activity alone. ^-9 When M all-trans-retinol was allowed to act simultaneously (SB + ROH), there was a significant increase in the metabolic activity of human epidermal cells compared to those added individually (SB, ROH). Was found to synergistically show cell activation.
[0042]
Test example 2
Measurement of cell activation effect by cell culture (2):
The effect of the combined use of fermentation product 1 and all-trans-retinoic acid (manufactured by Sigma: hereinafter sometimes abbreviated as “RA”) on the metabolic activity of human epidermal cells is the same as vitamin A and / or test example 1 Examination was conducted in the same manner as in Test Example 1 except that the derivative was all-trans-retinoic acid. The result is shown in FIG.
[0043]
According to FIG. 2, the fermentation product 1 of 0.5%, which is a concentration that alone does not affect the metabolic activity, and 5 × 10 ^-10 When M all-trans-retinoic acid was allowed to act simultaneously (SB + RA), there was a significant increase in the metabolic activity of human epidermis cells relative to those added individually (SB, RA). Was found to synergistically show cell activation.
[0044]
Test example 3
Measurement of hyaluronic acid production effect by cell culture (1):
Cells were cultured in the same manner as in Test Example 1, and the culture supernatant after 3 days of culture was collected and an ELISA-like method using biotin-labeled hyaluronic acid binding protein (Seikagaku Corporation) (Fosang AJ et al., Matrix). Ten , 306-313, 1990), and hyaluronic acid was quantified. The relative value (%) of hyaluronic acid when the quantitative value of the control to which no sample was added was 100 was set to 0.5% fermentation product 1 and 5 × 10. ^-9 The amount of fermentation product 1 and all-trans-retinol on the production of hyaluronic acid in human epidermal cells was determined from the quantitative value when M all-trans-retinol was allowed to act simultaneously and the quantitative value of each added individually. The effect of the combined use was examined. The result is shown in FIG.
[0045]
From the results of FIG. 3, it was revealed that fermentation product 1 and all-trans-retinol additively enhance hyaluronic acid production of human epidermal cells.
[0046]
Test example 4
Measurement of hyaluronic acid production effect by cell culture (2):
The effect of the combined use of fermentation product 1 and all-trans-retinoic acid on hyaluronic acid production in human epidermal cells was determined by comparing vitamin A and / or its derivative of Test Example 3 with 5 × 10 5. ^-10 Examination was conducted in the same manner as in Test Example 3 except that M was all-trans-retinoic acid. The results are shown in FIG.
[0047]
From the results of FIG. 4, it was revealed that fermentation product 1 and all-trans-retinoic acid additively enhance hyaluronic acid production of human epidermal cells.
[0048]
Test example 5
Wrinkle improvement test:
On the faces of five wrinkled women, a cosmetic solution having the following composition containing fermentation product 2 and retinol palmitate was externally applied for 3 months. The quantitative evaluation of wrinkles was performed by improving Hayashi's method (Hayashi Shoji, Fragrance Journal, 11, 55-61, 1992). That is, before and after the external application period, cheek skin replicas were made using opaque quick-drying silicone rubber (Sylflo: Flexico Developments), and image analysis using an image analysis device (ASPECT: Mitani Corporation) The maximum wrinkle depth was measured by the method, and the relative value when the maximum wrinkle depth before use was taken as 100% was determined. The results are shown in FIG.
[0049]
(Component) (mass%)
Ethanol 10.0
Fermentation product 2 ^* 5.0
1,3-butylene glycol 3.0
Trimethylglycine 1.0
Purified water balance
Carboxyvinyl polymer 0.1
Carrageenan 0.1
Glycerin 5.0
Squalane 1.0
Methylphenyl polysiloxane 1.0
Polymethacryloyloxyethyl phosphorylcholine solution 2.0
Behenyl alcohol 0.1
Polyoxyethylene sorbitan monostearate 0.2
Glycerol monostearate 0.1
Retinol palmitate 0.01
Stearyl glycyrrhizinate 0.1
Methylparaben 0.1
Fragrance 0.1
Sodium hydroxide appropriate amount
* Produced in Production Example 2.
[0050]
From the results shown in FIG. 5, the maximum depth of wrinkles on the human face was reduced by about 35% by external application for 3 months, and the wrinkle improving action was recognized in the fermented product and the retinol palmitate-containing cosmetic liquid.
[0051]
Test example 6
Skin elasticity improvement test:
Ten healthy women were allowed to apply the cosmetic solution of Test Example 4 to their face for 3 months. According to the method of Takema et al. (Takema Y et al., Br. J. Dermatol. 131: 641-648, 1994) before and after the external application period, a load of 300 mbar was applied for 1 second, and the facial skin elasticity 1 second after release of the load The property (R2 value) was measured with a cute meter SEM575 (Courage and Khazaka Co., Ltd.) having a probe diameter of 2 mm, and indicated as a relative value with the value before external use being 100%. The result is shown in FIG.
[0052]
As shown in FIG. 6, the skin elasticity of the human face increased by about 15% by applying the fermented product and the serum containing retinol palmitate for 3 months. This serum has been shown to improve skin elasticity (Takema Y et al., Br. J. Dermatol. 131, 641-648, 1994), which is known to decrease with age.
[0053]
Test example 7
Measurement of stratum corneum moisture content:
Ten healthy women were allowed to apply the cosmetic solution of Test Example 4 to their face for 3 months. Before and after the external use period, the horny layer moisture content (conductance) of the face before and after the external use period was measured according to a conventional method using a conductance meter (SKICON 200: manufactured by IBS Inc.). The result is shown in FIG.
[0054]
As shown in FIG. 7, the three-month topical application of the fermented product and retinol palmitate acid serum increased the horny layer moisture content (conductance) of the human face approximately twice. Therefore, it was revealed that this serum has a moisturizing action.
[0055]
Example 1
Lotion:
A lotion having the following composition was produced by a conventional method.
(Component) (mass%)
Fermentation product 1 ^* 10.0
Retinol palmitate 0.01
Ethanol 5.0
1,3-butylene glycol 2.0
Polyoxyethylene hydrogenated castor oil (50E.O.) 0.05
Methyl balaoxybenzoate 0.1
Fragrance 0.1
Purified water balance
* Produced in Production Example 1.
[0056]
The obtained lotion was excellent in preventing and improving skin roughness and had a refreshing feeling of use. Also, the storage stability was good.
[0057]
Example 2
Latex:
An emulsion having the following composition was produced by a conventional method.
(Component) (mass%)
Fermentation product 2 ^* 10.0
Retinol palmitate 0.02
Stearic acid 2.0
Liquid paraffin 6.0
Squalane 2.0
Sorbitan monostearate 1.5
Polyoxyethylene sorbitan monostearate (20E.O.) 2.0
Methyl paraoxybenzoate 0.05
Glycerin 1.0
Fragrance 0.15
Purified water balance
* Produced in Production Example 2.
[0058]
The obtained emulsion was excellent in keratin improving effect, skin elasticity improving effect and moisturizing effect, and had a moist use feeling. In addition, the storage stability was excellent.
[0059]
Example 3
cream:
A cream having the following composition was produced by a conventional method.
(Component) (mass%)
Fermentation product 2 ^* 10.0
Retinol palmitate 0.05
Liquid paraffin 23.0
Vaseline 7.0
Behenyl alcohol 1.0
Stearic acid 2.0
Beeswax 2.0
Solpitan monostearate 1.5
Polyoxyethylene sorbitan monostearate (20E.O.) 2.5
Butyl paraoxybenzoate 0.05
Glycerin 2.0
Methyl paraoxybenzoate 0.1
Fragrance 0.15
Purified water balance
* Produced in Production Example 2.
[0060]
The obtained cream was excellent in preventing and improving rough skin, improving wrinkles, and having a good feeling in use. In addition, the storage stability was excellent.
[0061]
Example 4
An ointment having the following composition was produced by a conventional method.
(Component) (mass%)
Fermentation product 2 ^* 10.0
Retinol palmitate 0.05
Japanese Pharmacopoeia Hydrophilic Ointment 89.95
* Produced in Production Example 2.
[0062]
This ointment was applied to the skin twice a day (5 mg / cm ² ), Excellent skin roughness prevention / improvement action, wrinkle improvement action were observed, and storage stability was also good.
[0063]
【The invention's effect】
In the external preparation for skin of the present invention, fermented beans synergistically enhance the activating action of epidermal cells possessed by vitamin A and its derivatives, and the same action possessed by the fermented beans is combined with the hyaluronic acid enhancement promoting action of the above compound. Excellent skin roughening prevention / improvement effect, keratin improvement effect, moisturizing effect, disappearance of wrinkles, wrinkle prevention effect. Is.
[0064]
In addition, the external preparation for skin of the present invention is not limited to the above, for example, as a medicine, for improving diseases caused by a decrease in the amount of hyaluronic acid in tissues such as rheumatoid arthritis and traumatic arthritis, suppressing pain, It can also be used as a therapeutic agent for promoting granulation tissue growth in the initial stage, an acne treatment agent, a psoriasis treatment agent, a wrinkle treatment agent, or a photoaging skin treatment agent.
[Brief description of the drawings]
BRIEF DESCRIPTION OF DRAWINGS FIG. 1 shows the effect of combined use of fermentation product 1 (SB) and all-trans-retinol (ROH) on the metabolic activity of cultured human epidermal cells.
FIG. 2 shows the effect of the combined use of fermentation product 1 (SB) and all-trans-retinoic acid (RA) on the metabolic activity of cultured human epidermal cells.
FIG. 3 shows the effect of the combined use of fermentation product 1 (SB) and all-trans-retinol (ROH) on hyaluronic acid production of cultured human epidermal cells.
FIG. 4 shows the effect of the combined use of fermentation product 1 (SB) and all-trans-retinoic acid (RA) on hyaluronic acid production of cultured human epidermal cells.
FIG. 5 is a drawing showing the effect of a serum containing a fermentation product 2 and retinol palmitate on wrinkles on a human face.
FIG. 6 is a drawing showing the effect of a serum containing a fermented product 2 and retinol palmitate on the skin elasticity of a human face.
FIG. 7 is a drawing showing the effect of a cosmetic liquid containing fermentation product 2 and retinol palmitate on the stratum corneum moisture content of the human face.
more than

Claims (8)

A fermented product obtained by bifidobacteria is allowed to act on the bean milk soy, retinol, retinoic acid, beta-carotene, stearic acid esters of retinol, acetate of retinol, lactic esters of retinol, retinol glycol Acid ester, retinol phosphate diester, retinol pyrophosphate diester, retinol sulfate diester, all-trans-retinol, all-trans-retinoic acid, all-trans-retinal, all-trans-retinol 3 dehydro, all 3,4-didehydro form of trans-retinol, 3-dehydro form of all-trans-retinoic acid, 3,4-didehydro form of all-trans-retinoic acid, 3-dehydro form of all-trans-retinoic acid The dermatological agent characterized by containing a vitamin A and / or one or two or more of its derivatives selected from 3,4-didehydro body and retinol palmitate of all -trans- retinal. Vitamin A and / or derivatives thereof are all-trans-retinol, all-trans-retinoic acid, all-trans-retinal, all-trans-retinol 3-dehydro, all-trans-retinol 3,4-didehydro, All-trans-retinoic acid 3-dehydro, all-trans-retinoic acid 3,4-didehydro, all-trans-retinal 3-dehydro, all-trans-retinal 3,4-didehydro or retinol palmitate The topical skin preparation according to claim 1. The skin external preparation according to claim 1 or 2, wherein the vitamin A and / or a derivative thereof is all-trans-retinol, all-trans-retinoic acid or retinol palmitate . The external preparation for skin according to any one of claims 1 to 3 , wherein the microorganism of the genus Bifidobacterium is Bifidobacterium breve YIT 4065 (FERM BP-6223) . Fermentation products obtained by allowing Bifidobacterium microorganisms to act on soy milk of soybeans are obtained by adding a lower alcohol or a polyhydric alcohol to the fermentation products and removing a high molecular substance by centrifugation or filtration. The external preparation for skin according to any one of claims 1 to 4. The skin external preparation according to claim 5 , wherein the lower alcohol or polyhydric alcohol is ethanol or 1,3-butylene glycol . The external preparation for skin according to any one of claims 1 to 6, which is for increasing the metabolic activity of human epidermal cells. The skin external preparation according to any one of claims 1 to 7, which is a cosmetic.

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