Skin viscoelasticity enhancer

Abstract

To provide a novel skin visco-elasticity improver.SOLUTION: The invention for solving above mentioned problems provides: 1. a skin pure elasticity improver including as an active ingredient, a tomato seed extract; 2. a skin net elasticity improver including as an active ingredient, a tomato seed extract; 3. a skin return rate improver including as active ingredient, a tomato seed extract; 4. a skin visco-elasticity improver being described in any of 1-3; 5. a skin visco-elasticity improver including as an active ingredient, a tomato seed extract; 6. an AGE production restrainer including as an active ingredient, a tomato seed extract; 7. the tomato seed extract in the above 1. to 6. includes lycoperoside; and 8. the lycoperoside in the agent in the above 7 is the lycoperoside H.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a novel skin viscoelasticity improver. The present invention is widely used in foods, pharmaceuticals, cosmetics, and the like.

Background Art

[0002] The health state of the skin is evaluated using various indices. For example, the presence or absence of the "firmness" feeling of the skin is regarded as one of the evaluation indices for the health state and the degree of aging. "Firmness" is divided into two types: firmness derived from the stratum corneum and epidermis, and firmness derived from the dermis. In particular, the firmness derived from the dermis has elasticity such that when the skin is pressed with a finger, it rebounds, and when the finger is released, it quickly returns to its original state, and physically it is also referred to as viscoelasticity. And this viscoelasticity exhibited by the skin also decreases due to age, ultraviolet exposure, skin exposure to chemical substances, and the like. Therefore, the firmness of the skin can also be an index of skin aging. Regarding the skin as an elastic body, methods and measuring devices have been developed to measure the viscoelastic modulus of the skin and use it in place of the sensory evaluation method of "firmness". As a typical skin viscoelasticity measuring device, there is CUTOMETER (trade name) (manufactured by Courage & Khazaka). This device draws the skin surface into the probe opening in a negative pressure state, measures the skin length drawn into the opening with a prism, then releases the suction, and similarly measures the displacement length (return) when the suction is released, and obtains the viscoelastic modulus using this measurement result as a parameter (see Non-Patent Document 1). Using the viscoelastic modulus measured by this device as an index, the evaluation of the degree of skin aging and the evaluation of the effects of cosmetics have become widespread in the cosmetics industry and the beauty-related medical field. Patent Document 1 describes using a cutometer as a means for evaluating the effects when performing a beauty treatment to improve skin sagging. Non-Patent Document 2 describes evaluating the effect of a glucosylceramide-containing beet extract on skin elasticity using a cutometer. Thus, skin viscoelasticity is recognized as an important parameter for evaluating the health state of the skin.

[0003] Furthermore, various ingredients and compositions have been proposed to improve the viscoelasticity of the skin. Patent Document 2 describes that fucoidan derived from kelp improves the reduced elasticity of the skin. Patent Document 3 describes that astaxanthin improves the elasticity of the skin (Patent Document 4).

[0004] Furthermore, it has become clear that the glycation of proteins in the body through the Maillard reaction is involved in various symptoms and diseases and leads to the aging process. For example, the accumulation of AGEs (Advanced Glycation End Products) in the body, produced by the Maillard reaction, can be one of the causes of various diseases such as diabetic complications, arteriosclerosis, osteoporosis, ossification of the posterior longitudinal ligament, muscle atrophy, rheumatoid arthritis, age-related macular degeneration, non-alcoholic steatohepatitis, insulin resistance, periodontal disease, Alzheimer's disease, neurodegenerative diseases, and skin diseases. Furthermore, when collagen, which makes up the dermis of the skin, is glycated by the Maillard reaction, the collagen that maintains the elasticity and firmness of the skin is broken down. As a result, the skin loses its elasticity, contributing to a decrease in firmness and the formation of wrinkles and sagging. Furthermore, when collagen, which makes up bone tissue, is glycated by the Maillard reaction, the bone loses its flexibility. When bone flexibility is lost, bone strength decreases even if bone density is normal. Therefore, the Maillard reaction to collagen in the body also affects the deterioration of bone flexibility (bone quality), which is one of the indicators of bone strength (Patent Document 5).

[0005] On the other hand, tomatoes (Solanum lycopersicum) are a plant that is consumed daily around the world and are sold as juices and supplements because they are rich in components such as vitamin C, lycopene, and GABA. Tomatoes have been reported to have functional effects such as lowering blood pressure and cholesterol. Furthermore, in 2004, novel saponins called esculeosides were identified from tomatoes (Non-Patent Documents 5 and 6), and esculeoside A, in particular, has been found to improve hyperlipidemia and arteriosclerosis in mice (Non-Patent Document 7). However, all of these findings are from tomato fruits, and there are few reports specifically focused on tomato seeds.

[0006] Furthermore, research focusing on tomato seeds has revealed that the main component of the seeds is the saponin compound lycoperoside H, and that tomato seed extract and lycoperoside H promote the production of collagen and elastin in human dermal fibroblasts (Non-Patent Literature 2). In addition, oral administration of tomato seed extract and lycoperoside H to atopic dermatitis model mice has been shown to alleviate skin inflammation symptoms accompanied by an improvement in transepidermal water loss (Non-Patent Literature 3).

[0007] [Patent Document 1] Japanese Patent Publication No. 2010-51717 [Patent Document 2] Japanese Patent Publication No. 2003-313131 [Patent Document 3] Japanese Patent Publication No. 2005-27589 [Patent Document 4] Japanese Patent Publication No. 2016-216436 [Patent Document 5] Japanese Patent Publication No. 2017-171638 [Non-Patent Document 1] Integral Co., Ltd. Cutometer dual MPA580 Instruction Manual (Cuto dual 07 / 2014 EN JA). 2014. [Non-Patent Document 2] Mio Hori, Yoshikazu Yonei et al., Anti-Aging Medicine, 7

[11] 129-142, 2010 [Non-Patent Document 2] Shogo Takeda, Wakana Yamada, Masahiro Nakamura, et al. Effects of tomato seed extract and its saponins on the extracellular matrix of skin cells. Abstracts of the 2019 Annual Meeting of the Japanese Society for Bioscience, Biotechnology, and Agrochemistry. 2019;242. [Non-Patent Document 3] Oryza Oil & Fat Chemical Co., Ltd. Tomato Seed Extract Catalog. Updated September 24, 2019. [Non-Patent Document 4] Ohshima H, Kinoshita S, Oyobikawa M, et al. Use of Cutometer area parameters in evaluating age-related changes in the skin elasticity of the cheek. Ski Res Technol. 2013;19(1):1-2. [Non-Patent Document 5] Fujiwara S. et al., Tetrahedron, 60, 4915-4920 (2004). [Non-Patent Document 6] Ono M. et al., Chem. Pharm. Bull., 54(2), 237-239 (2006). [Non-Patent Document 7] Nohara T., J. Trad. Med., 27, 217-224 (2010). [Disclosure of the Invention] [Problems that the invention aims to solve]

[0008] Against this background, the inventors discovered that tomato seed extract, particularly tomato seed extract containing lycoperosides, has the effect of improving the viscoelasticity of the skin and inhibiting AGE production, and thus completed the present invention. In other words, the present invention aims to provide a skin viscoelasticity enhancer and an AGE production inhibitor that contains a novel component as an active ingredient. [Means for solving the problem]

[0009] The features of the present invention for solving the above problems are as follows. 1. A pure skin elasticity enhancer containing tomato seed extract as an active ingredient. 2. A skin net elasticity enhancer containing tomato seed extract as an active ingredient. 3. A skin recovery agent containing tomato seed extract as an active ingredient. 4. A skin viscoelasticity improving agent as described in any of items 1 to 3 above. 5. A skin viscoelasticity improver containing tomato seed extract as an active ingredient. 6. An AGE production inhibitor containing tomato seed extract as an active ingredient. 7. The agent according to any one of 1. to 6. above, characterized in that the tomato seed extract contains lycoperosides. 8. The agent according to 7. above, characterized in that the lycoperosides are lycoperoside H.

Brief Description of the Drawings

[0010] [Figure 1] It is a chart measuring the deformation of the skin obtained when operating a cutometer. [Figure 2] It is a graph showing the effect of tomato seed extract - P intake on skin viscoelasticity. [Figure 3] It is a graph showing the effect of tomato seed extract - P intake on the amount of pentosidine in the blood.

Modes for Carrying Out the Invention

[0011] Hereinafter, the present invention will be described in detail. The present invention is characterized by using tomato seed extract as an active ingredient. Also, it is preferable that the tomato seed extract contains lycoperosides. This is because a more excellent skin viscoelasticity improver can be obtained. The lycoperosides are not particularly limited, but it is particularly preferable to contain lycoperoside H. Incidentally, lycoperoside H is a saponin represented by the following chemical formula (1).

[0012]

Chemical Formula

[0013] As extraction solvents for obtaining the above-mentioned tomato seed extract, polar solvents such as water, methanol, ethanol, isopropyl alcohol, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, and ethyl acetate can be used. Two or more of these solvents may also be mixed. Preferably, using water, ethanol, or aqueous ethanol (a mixture thereof) as the extraction solvent allows for efficient extraction of the active ingredient.

[0014] When using water as the extraction solvent, the type of water is not particularly limited, and tap water, distilled water, mineral water, alkaline ionized water, deep-sea water, etc., can be used.

[0015] When using aqueous ethanol as the extraction solvent, the ethanol concentration is not particularly limited, but it is preferable that the ethanol concentration be 10-90% (wt / wt), preferably 20-80% (wt / wt). The reason for limiting the ethanol concentration to 90% (wt / wt) or less is that if the ethanol concentration is too high, it becomes difficult to obtain a tomato seed extract containing high concentrations of lycoperosides.

[0016] The extraction temperature should ideally be between 20 and 80°C, preferably around 40 to 50°C. If the extraction temperature is too low, the active ingredients will not be easily extracted, and if the extraction temperature is too high, the active ingredients will decompose, reducing their physiological activity (health benefits).

[0017] Any extraction method can be employed, including stirring extraction, continuous extraction, immersion extraction, countercurrent extraction, and supercritical extraction, and any apparatus can be used at room temperature or under reflux heating.

[0018] To illustrate the specific extraction method, the raw material (tomato seeds) is placed in a processing tank filled with extraction solvent, and the active ingredients are dissolved while stirring. For example, when using aqueous ethanol as the extraction solvent, approximately 2 to 100 times the amount of extraction solvent (by weight) of the raw material is used, and the extraction is carried out for 30 minutes to 2 hours. After the active ingredients have been dissolved in the solvent, the extract is obtained by filtering to remove the extraction residue.

[0019] Subsequently, the extract is subjected to dilution, concentration, purification, drying, and other treatments according to conventional methods to obtain the agent according to the present invention. For purification, it is recommended to pass the extract through a synthetic adsorption resin, gel filtration resin, etc., to adsorb the active ingredients, and then concentrate the extract by eluting it with methanol, ethanol, etc.

[0020] Furthermore, the tomato seed extract mentioned above may be a commercially available product; for example, "Tomato Seed Extract-P" manufactured by Oryza Oil & Fat Chemical Co., Ltd. can be used. The above-mentioned "Tomato Seed Extract-P" is a water-soluble powder of aqueous ethanol extract from tomato seeds, and contains 0.5% or more of lycoperosides.

[0021] The skin viscoelasticity improving agent of the present invention can be used as an ingredient in various foods and beverages. Examples of foods and beverages include general foods such as confectionery (gum, candy, caramel, chocolate, cookies, snacks, jelly, gummies, tablets, etc.), noodles (soba, udon, ramen, etc.), dairy products (milk, ice cream, yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, and beverages (juice, coffee, tea, carbonated drinks, sports drinks, etc.), as well as health foods (tablets, capsules, etc.) and nutritional supplements (nutritional drinks, etc.). The agent of the present invention can be appropriately incorporated into these foods and beverages.

[0022] These foods and beverages can be formulated with various ingredients depending on their type. For example, they can contain food ingredients such as glucose, fructose, sucrose, maltose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, gum arabic, carrageenan, casein, gelatin, pectin, agar, B vitamins, nicotinamide, calcium pantothenate, amino acids, calcium salts, colorants, flavorings, and preservatives.

[0023] Specifically, the agent of the present invention can be spray-dried or freeze-dried together with powdered cellulose, and this can be easily incorporated into food and beverages (such as instant foods) by processing it into a powder, granules, tablets, or solution. Furthermore, the agent of the present invention can be dissolved in, for example, oils and fats, ethanol, glycerin, or mixtures thereof to form a liquid, which can then be added to beverages or solid foods. If necessary, it can also be mixed with a binder such as gum arabic or dextrin to form a powder or granules, which can then be added to beverages or solid foods.

[0024] When applying the agent of the present invention to food and beverages, the amount added is preferably such that the total content of the active ingredient relative to the food and beverage is 1 to 20 wt%, since the main purpose is disease prevention and health maintenance.

[0025] The skin viscoelasticity improving agent of the present invention may be used as a material for pharmaceuticals (including pharmaceuticals and quasi-drugs). It can be manufactured by appropriately blending the agent of the present invention with raw materials for pharmaceutical formulations. Examples of formulation ingredients that can be incorporated into the agent of the present invention include excipients (glucose, lactose, sucrose, sodium chloride, starch, calcium carbonate, kaolin, crystalline cellulose, cocoa butter, hydrogenated vegetable oil, kaolin, talc, etc.), binders (distilled water, physiological saline, ethanol water, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrants (sodium alginate, agar, sodium bicarbonate, calcium carbonate, sodium lauryl sulfate, monoglyceride stearate, starch, lactose, acacia powder, gelatin, ethanol, etc.), disintegration inhibitors (sucrose, stearin, cocoa butter, hydrogenated oil, etc.), absorption enhancers (quaternary ammonium base, sodium lauryl sulfate, etc.), adsorbents (glycerin, starch, lactose, kaolin, bentonite, silicic acid, etc.), and lubricants (purified talc, stearate, polyethylene glycol, etc.).

[0026] The present invention provides a method for administering the skin viscoelasticity improving agent by oral administration in the form of tablets, pills, soft or hard capsules, granules, powders, granules, or liquids, but it may also be administered parenterally. When administered parenterally, it can be administered in solution form or with the addition of dispersants, suspensions, stabilizers, etc., by local tissue administration, intradermal, subcutaneous, intramuscular, or intravenous injection. It may also be administered in the form of suppositories, etc. Furthermore, it can be administered as eye drops.

[0027] The dosage may vary depending on the method of administration, the patient's condition, and the patient's age, but typically, adults can be administered 0.5 to 5000 mg of the active ingredient per day, and children can be administered 0.5 to 3000 mg per day. Furthermore, it is preferable that the product contains 0.01 to 100 mg, preferably 0.1 to 10 mg, of lycoperoside H. The ratio of the skin viscoelasticity enhancer can be adjusted as appropriate depending on the dosage form, but generally, it should be around 0.3 to 15.0 wt% when administered orally or via mucosal absorption, and around 0.01 to 10 wt% when administered parenterally. Note that the dosage will vary depending on various conditions, so a smaller amount than the above may be sufficient in some cases, and it may also be necessary to administer a larger amount than the above range.

[0028] The skin viscoelasticity improving agent of the present invention can also be expected to improve the viscoelasticity of the skin when used as a topical skin preparation (including cosmetics, pharmaceuticals, and quasi-drugs). Examples of external skin preparations that may contain the skin viscoelasticity improving agent of the present invention include lotions, soaps, facial cleansers, bath additives, creams, lotions, toners, colognes, shaving creams, shaving lotions, cosmetic oils, sunscreens, face powders, foundations, perfumes, face masks, nail creams, nail polish, nail polish removers, eyebrow pencils, blushes, eye creams, eyeshadows, mascaras, eyeliners, lipsticks, lip balms, shampoos, conditioners, hair dyes, dispersions, and cleansing agents. Examples of pharmaceuticals or quasi-drugs that may contain the skin viscoelasticity improving agent of the present invention include ointments, creams, and topical solutions.

[0029] In addition to the skin viscoelasticity improving agent according to the present invention, the above-described form of topical skin preparation may contain ingredients commonly used in cosmetics, quasi-drugs, and other topical skin preparations, such as oils, higher alcohols, fatty acids, UV absorbers, powders, pigments, surfactants, polyhydric alcohols / sugars, polymers, physiologically active ingredients, solvents, antioxidants, fragrances, preservatives, etc., to the extent that they do not impair the skin viscoelasticity improving effect. Examples are listed below, but the present invention is not limited to these examples.

[0030] (1) Examples of oil content Ester-based oil phase components: Glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isocetyl isostearate, butyl stearate, butyl myristate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, diethyl adipate Sopropyl, Isoarachil Neopentanoate, Caprylic / Capric Triglyceride, Trimethylolpropane Tri-2-ethylhexanoate, Trimethylolpropane Triisostearate, Pentaerythritol Tetra-2-ethylhexanoate, Cetyl Caprylate, Decyl Laurate, Hexyl Laurate, Decyl Myristate, Myristyl Myristate, Cetyl Myristate, Stearyl Stearate, Decyl Oleate, Cetyl Ricinoleate, Isostearyl Laurate, Isotridecyl Myristate, Isocetyl Myristate, Iso Tearyl, Isocetyl Palmitate, Isostearyl Palmitate, Octyl Stearate, Isocetyl Stearate, Isodecyl Oleate, Octyldodecyl Oleate, Octyldodecyl Linoleate, Isopropyl Isostearate, Cetostearyl 2-Ethylhexanoate, Stearyl 2-Ethylhexanoate, Hexyl Isostearate, Ethylene Glycol Dioctanoate, Ethylene Glycol Dioleate, Propylene Glycol Dicaprate, Di(Capryl / Capric Acid)Propylene Glycol, Propylene Glycol Dicaprylate, Dicaprin Neopentyl glycol acid, neopentyl glycol dioctanoate, glyceryl tricaprylate, glyceryl triundecylate, glyceryl triisopalmitate, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate, octyl isononanoate, hexyldecyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, polyglycerin oleate, polyglycerin isostearate, dipropyl carbonate,Dialkyl (C12-18) carbonate, triisocetyl citrate, triisoarachil citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyldecyl lactate, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearate, di-2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate Examples include ropil, dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, dihydrocholesteryl oleate, phytosteryl isostearate, phytosteryl oleate, isocetyl 12-stearoylhydroxystearate, stearyl 12-stearoylhydroxystearate, and isostearyl 12-stearoylhydroxystearate. Hydrocarbon-based oil phase components include squalane, liquid paraffin, α-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, petrolatum, etc. Animal and vegetable oils and their hydrogenated oils, and naturally derived waxes: animal oils and their hydrogenated oils such as beef tallow, hydrogenated beef tallow, pork tallow, hydrogenated pork tallow, horse oil, hydrogenated horse oil, mink oil, orange roughy oil, fish oil, hydrogenated fish oil, egg yolk oil, avocado oil, almond oil, olive oil, cocoa butter, kiwi seed oil, apricot kernel oil, kukui nut oil, sesame oil, wheat germ oil, rice germ oil, rice bran oil, safflower oil, shea butter, soybean oil, evening primrose oil, perilla oil, tea seed oil, camellia oil, corn oil, rapeseed oil, Examples include hydrogenated rapeseed oil, palm kernel oil, hydrogenated palm kernel oil, palm oil, hydrogenated palm oil, peanut oil, hydrogenated peanut oil, castor oil, hydrogenated castor oil, sunflower oil, grape seed oil, jojoba oil, hydrogenated jojoba oil, macadamia nut oil, meadowfoam oil, cottonseed oil, hydrogenated cottonseed oil, coconut oil, hydrogenated coconut oil, and other vegetable oils and their hydrogenated oils, beeswax, high-acid value beeswax, lanolin, reduced lanolin, hydrogenated lanolin, liquid lanolin, carnauba wax, montan wax, and other waxes. Silicone-based oil phase components include dimethylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, methylhydrogenpolysiloxane, polyether-modified organopolysiloxane, dimethylsiloxane-methylcetyloxysiloxane copolymer, dimethylsiloxane-methylstearoxane copolymer, alkyl-modified organopolysiloxane, terminal-modified organopolysiloxane, amino-modified silicone oil, amino-modified organopolysiloxane, dimethiconol, silicone gel, acrylic silicone, trimethylsiloxysilicate, silicone RTV rubber, etc. Examples of fluorine-based oil phase components include perfluoropolyethers, fluorine-modified organopolysiloxanes, fluorinated pitch, fluorocarbons, fluoroalcohols, and fluoroalkyl / polyoxyalkylene copolymerized organopolysiloxanes.

[0031] (2) Examples of higher alcohols Examples include lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, behenyl alcohol, 2-ethylhexanol, hexadecyl alcohol, and octyldodecanol.

[0032] (3) Examples of fatty acids Examples include caprylic acid, capric acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid, arachidic acid, arachidonic acid, behenic acid, erucic acid, and 2-ethylhexanoic acid.

[0033] (4) Examples of UV absorbers Para-aminobenzoic acid, amyl para-aminobenzoate, ethyl dihydroxypropyl para-aminobenzoate, glyceryl para-aminobenzoate, ethyl para-aminobenzoate, octyl para-aminobenzoate, octyl dimethyl para-aminobenzoate, ethylene glycol salicylate, octyl salicylate, triethanolamine salicylate, phenyl salicylate, butylphenyl salicylate, benzyl salicylate, homomenthyl salicylate, benzyl cinnamate, octyl para-methoxycinnamate, 2-ethylhexyl para-methoxycinnamate, glyceryl mono-2-ethylhexanoate dipara-methoxycinnamate, isopropyl para-methoxycinnamate, diethanolamine para-methoxyhydrocinnamate salt, diisopropyl / diisopropyl cinnamic acid ester mixture, urocanic acid, ethyl urocanic acid, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and its salts, di Examples include hydroxymethoxybenzophenone, sodium dihydroxymethoxybenzophenone disulfonate, dihydroxybenzophenone, dihydroxydimethoxybenzophenone, hydroxyoctoxybenzophenone, tetrahydroxybenzophenone, butylmethoxydibenzoylmethane, 2,4,6-trianilino-p-(carbo-2-ethylhexyl-1-oxy)-1,3,5-triazine, 2-(2-hydroxy-5-methylphenyl)benzotriazole, methyl-O-aminobenzoate, 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate, phenylbenzimidazole sulfate, 3-(4-methylbenzylidene)camphor, isopropyldibenzoylmethane, 4-(3,4-dimethoxyphenylmethylene)-2,5-dioxo-1-imidazolidinepropionate 2-ethylhexyl, and their polymer derivatives and silane derivatives.

[0034] (5) Examples of powders and pigments Dyes such as Red No. 104, Red No. 201, Yellow No. 4, Blue No. 1, Black No. 401, lake dyes such as Yellow No. 4 AL Lake, Yellow No. 203 BA Lake, nylon powder, silk powder, urethane powder, Teflon (registered trademark) powder, silicone powder, polymethyl methacrylate powder, cellulose powder, starch, silicone elastomer spherical powder, polymers such as polyethylene powder, yellow iron oxide, red iron oxide, black iron oxide, chromium oxide, carbon black, ultramarine, Prussian blue, zinc oxide, titanium dioxide, acid Examples include white pigments such as cerium oxide, extender pigments such as talc, mica, sericite, kaolin, and plate-like barium sulfate, pearl pigments such as titanium mica, metal salts such as barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate, and magnesium silicate, inorganic powders such as silica and alumina, metal soaps such as aluminum stearate, magnesium stearate, zinc palmitate, zinc myristate, magnesium myristate, zinc laurate, and zinc undecylenate, bentonite, smectite, and boron nitride. There are no particular restrictions on the shape (spherical, rod-shaped, needle-shaped, plate-shaped, irregular shape, flake-shaped, spindle-shaped, etc.) and particle size of these powders. These powders may or may not have been pre-treated by conventional surface treatments such as fluorine compound treatment, silicone treatment, silicone resin treatment, pendant treatment, silane coupling agent treatment, titanium coupling agent treatment, oil treatment, N-acylated lysine treatment, polyacrylic acid treatment, metal soap treatment, amino acid treatment, lecithin treatment, inorganic compound treatment, plasma treatment, mechanochemical treatment, etc.

[0035] (6) Examples of surfactants Anionic surfactants include fatty acid soaps, α-acyl sulfonates, alkyl sulfonates, alkylallyl sulfonates, alkylnaphthalene sulfonates, alkyl sulfates, POE alkyl ether sulfates, alkylamide sulfates, alkyl phosphates, POE alkyl phosphates, alkylamide phosphates, alkylylalkyl taurates, N-acyl amino acid salts, POE alkyl ether carboxylates, alkyl sulfosuccinates, alkyl sulfoacetate sodium, acylated hydrolyzed collagen peptides, perfluoroalkyl phosphates, and the like. Cationic surfactants include alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, benzalkonium chloride, beheninamidepropyldimethylhydroxypropylammonium chloride, diethylaminoethylamide stearate, dimethylaminopropylamide stearate, quaternary ammonium salts of lanolin derivatives, and the like. Amphoteric surfactants include carboxybetaine type, amidebetaine type, sulfobetaine type, hydroxysulfobetaine type, amidesulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, and amideamine type. Nonionic surfactants include propylene glycol fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, POE sorbitan fatty acid esters, POE sorbitan fatty acid esters, POE glycerin fatty acid esters, POE alkyl ethers, POE fatty acid esters, POE hydrogenated castor oil, POE castor oil, POE-POP copolymers, POE-POP alkyl ethers, polyether-modified silicone lauric acid alkanolamides, alkylamine oxides, hydrogenated soybean phospholipids, and the like. Examples of natural surfactants include lecithin, saponin, and sugar-based surfactants.

[0036] (7) Examples of polyhydric alcohols and sugars Examples include ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, 3-methyl-1,3-butanediol, 1,3-butylene glycol, sorbitol, mannitol, raffinose, erythritol, glucose, sucrose, fructose, xylitol, lactose, maltose, maltitol, trehalose, alkylated trehalose, mixed isomerized sugars, sulfated trehalose, pullulan, etc. Chemically modified versions of these can also be used.

[0037] (8) Examples of polymers Acrylic acid ester / methacrylic acid ester copolymer (Plussize, manufactured by Go-O Chemical Co., Ltd.), vinyl acetate / crotonic acid copolymer (Resin 28-1310, manufactured by NSC Corporation), vinyl acetate / crotonic acid / vinyl neodecanate copolymer (28-2930, manufactured by NSC Corporation), methyl vinyl ether maleate half ester (Gantlets ES, manufactured by ISP Corporation), T-butyl acrylate / ethyl acrylate / methacrylic acid copolymer (Rubymer, manufactured by BASF Corporation), vinylpyrrolidone / vinyl acetate / vinyl propionate copolymer (Rubiscol VAP, manufactured by BASF Corporation), vinyl acetate β / crotonic acid copolymer (Rubicet CA, BASF), vinyl acetate / crotonic acid / vinylpyrrolidone copolymer (Rubicet CAP, BASF), vinylpyrrolidone / acrylate copolymer (Rubiflex, BASF), acrylate / acrylamide copolymer (Ultrahold, BASF), vinyl acetate / butyl maleate / isobornyl acrylate copolymer (Advantage, ISP), carboxyvinyl polymer (Carbopol, BFGoodrich), acrylic acid / alkyl methacrylate copolymer (Pemulene, BF Examples include anionic polymer compounds such as those manufactured by Goodrich, amphoteric polymer compounds such as the amphoteric acetate of dialkylaminoethyl methacrylate polymer (Yukaformer, manufactured by Mitsubishi Chemical Corporation), octylacrylamide acrylate / hydroxypropyl acrylate / butylaminoethyl methacrylate copolymer (AMPHOMER, manufactured by NSC), cationic polymer compounds such as the quaternary compound of vinylpyrrolidone / dimethylaminoethyl methacrylate (GAFQUAT, manufactured by ISP), methylvinylimidazolium chloride / vinylpyrrolidone copolymer (Rubicort, manufactured by BASF), and nonionic polymer compounds such as polyvinylpyrrolidone (Rubiscol K, manufactured by BASF), vinylpyrrolidone / vinyl acetate copolymer (Rubiscol VA, manufactured by BASF), vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (Copolymer 937, manufactured by ISP), and vinylcaprolactam / vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (Copolymer VC713, manufactured by ISP).Furthermore, naturally derived polymer compounds such as cellulose or its derivatives, keratin and collagen or their derivatives, calcium alginate, pullulan, agar, gelatin, tamarind seed polysaccharides, xanthan gum, carrageenan, high methoxyl pectin, low methoxyl pectin, guar gum, acacia gum, crystalline cellulose, arabinogalactan, karaya gum, tragacanth gum, alginic acid, albumin, casein, curdlan, gellan gum, and dextran can also be suitably used.

[0038] (9) Examples of bioactive ingredients Bioactive ingredients include substances that provide some kind of bioactivity to the skin when applied to the skin. Examples include whitening ingredients, immune stimulants, anti-aging agents, UV protection agents, slimming agents, skin tightening agents, antioxidants, hair growth agents, hair tonics, moisturizers, blood circulation promoters, antibacterial agents, disinfectants, drying agents, cooling agents, warming agents, vitamins, amino acids, wound healing promoters, irritation relievers, analgesics, cell activators, enzyme components, etc. Examples of suitable ingredients include Angelica keiskei extract, avocado extract, Hydrangea macrophylla extract, Althaea officinalis extract, Arnica montana extract, Aloe vera extract, apricot extract, apricot kernel extract, Ginkgo biloba extract, Fennel extract, Turmeric extract, Oolong tea extract, Rosa multiflora extract, Echinacea japonica leaf extract, Scutellaria baicalensis extract, Phellodendron amurense extract, Coptis japonica extract, Barley extract, Hypericum perforatum extract, Lamium album extract, Nasturtium officinale extract, Orange extract, Dried seawater, seaweed extract, hydrolyzed elastin, hydrolyzed wheat powder, hydrolyzed silk, chamomile extract, carrot extract, Artemisia capillaris extract, licorice extract, carrot extract, Arctium moniliforme extract, cinchona extract, cucumber extract, guanosine, gardenia extract, bamboo grass extract, Sophora flavescens extract, walnut extract, grapefruit extract, clematis extract, chlorella extract, mulberry extract, gentian extract, black tea extract, yeast extract, burdock extract, corn Rice bran fermentation extract, rice germ oil, comfrey extract, collagen, lingonberry extract, asarum extract, bupleurum extract, umbilical cord extract, salvia extract, soapwort extract, bamboo extract, hawthorn extract, sansho extract, shiitake mushroom extract, rehmannia extract, lithospermum extract, perilla extract, linden extract, meadowsweet extract, peony extract, calamus root extract, birch extract, horsetail extract, ivy extract, hawthorn extract, ce Elderflower extract, yarrow extract, peppermint extract, sage extract, mallow extract, Cnidium officinale extract, Swertia japonica extract, soybean extract, jujube extract, thyme extract, tea extract, clove extract, cogongrass extract, citrus peel extract, angelica extract, calendula extract, peach kernel extract, spruce extract, Houttuynia cordata extract, tomato extract, natto extract, carrot extract, garlic extract, wild rose extract, hibiscus extract,Examples of extracts include Ophiopogon japonicus extract, parsley extract, honey, witch hazel extract, Parietaria trifolia extract, Isodon japonicus extract, bisabolol, loquat extract, coltsfoot extract, butterbur extract, Poria cocos extract, butcher's broom extract, grape extract, propolis, loofah extract, safflower extract, peppermint extract, linden extract, peony extract, hop extract, pine extract, horse chestnut extract, skunk cabbage extract, soapberry extract, lemon balm extract, peach extract, cornflower extract, eucalyptus extract, saxifrage extract, coix seed extract, mugwort extract, lavender extract, apple extract, lettuce extract, lemon extract, astragalus extract, rose extract, rosemary extract, Roman chamomile extract, royal jelly extract, etc. Furthermore, it contains biopolymers such as deoxyribonucleic acid, mucopolysaccharides, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, and hydrolyzed eggshell membrane; moisturizing ingredients such as amino acids, hydrolyzed peptides, sodium lactate, urea, sodium pyrrolidone carboxylate, betaine, whey, and trimethylglycine; oily ingredients such as sphingolipids, ceramides, phytosphingosine, cholesterol, cholesterol derivatives, and phospholipids; immunostimulants such as ε-aminocaproic acid, glycyrrhizic acid, β-glycyrrhetinic acid, lysozyme chloride, guaiazulene, and hydrocholtisone; vitamins such as vitamin A, vitamin B2, vitamin B6, vitamin C, vitamin D, vitamin E, calcium pantothenate, biotin, nicotinamide, and vitamin C ester; allantoin and diisopropyl alcohol. Active ingredients such as mindichloroacetate and 4-aminomethylcyclohexanecarboxylic acid; antioxidants such as tocopherol, carotenoids, flavonoids, tannins, lignans, and saponins; cell activators such as α-hydroxy acids and β-hydroxy acids; blood circulation promoters such as γ-oryzanol and vitamin E derivatives; wound healing agents such as retinol and retinol derivatives; whitening agents such as arbutin, kojic acid, placenta extract, sulfur, ellagic acid, linoleic acid, tranexamic acid, and glutathione; cepharanthine, licorice extract, capsicum tincture, hinokitiol, garlic iodide extract, pyridoxine hydrochloride, DL-α-tocopherol, DL-α-tocopherol acetate, nicotinic acid, nicotinic acid derivatives, calcium pantothenate, and D-pantothenyl Examples of hair growth agents include alcohol, acetyl pantothenyl ethyl ether, biotin, allantoin, isopropylmethylphenol, estradiol, ethinylestradiol, capronium chloride, benzalkonium chloride, diphenhydramine hydrochloride, tacanal, camphor, salicylic acid, vanillyl nonyl acid, vanillyl nonanoate, piroctone olamine, glyceryl pentadecanoate, L-menthol, mononitroguaiacol, resorcinol, gamma-aminobutyric acid, benzethonium chloride, mexiletine hydrochloride, auxin, female hormones, cantharis tincture, cyclosporine, zinc pyrithione, hydrocoltisone, minoxidil, polyoxyethylene sorbitan monostearate, peppermint oil, and Sasanishiki extract.

[0039] (10) Examples of antioxidants Examples include sodium bisulfite, sodium sulfite, erythorbic acid, sodium erythorbate, dilauryl thiodipropionate, tocopherol, tol biguanide, nordihydroguaiaretinic acid, parahydroxyanisole, butylhydroxyanisole, dibutylhydroxytoluene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, carotenoids, flavonoids, tannins, lignans, saponins, and plant extracts with antioxidant effects such as apple extract and clove extract.

[0040] (11) Example of Be Examples include purified water, ethanol, lower alcohols, ethers, LPG, fluorocarbons, N-methylpyrrolidone, fluoroalcohols, volatile linear silicones, and next-generation chlorofluorocarbons (CFCs).

[0041] Furthermore, the AGE production inhibitor of the present invention is characterized by containing tomato seed extract as an active ingredient. The above-mentioned AGE production inhibitor can use tomato seed extract, similar to the skin viscoelasticity enhancer described above. [Examples]

[0042] The following describes examples of the present invention. These examples are provided to confirm the various actions and effects of the agent obtained by the present invention, and the scope of the present invention is not limited to these products and manufacturing methods.

[0043] Test example: Evaluation of the viscoelasticity and AGE (blood pentosidine level) inhibitory effects of tomato seed extract on skin. <Exam Overview> Study design: Randomized, double-blind, placebo-controlled, parallel-group comparative trial Target audience: Healthy adult women who are concerned about the elasticity of their facial skin. Test product: Oral ingestion of 200 mg / day of tomato seed extract-P (manufactured by Oryza Oil & Fat Chemical Co., Ltd.: total lycoperoside content 0.5% or more) (1 mg / day as lycoperoside H). Placebo: Starch hydrolysate 200 mg / day Duration of intake: 8 weeks Measurement points: Before intake, 4 weeks after intake, and 8 weeks after intake. Measurement items: Skin viscoelasticity measured by a cutometer (cheeks and upper arms), blood pentosidine levels. The results are shown in Figure 2 (viscoelasticity of the skin) and Figure 3 (blood pentosidine levels).

[0044] The viscoelasticity of the skin was measured using a cutometer as follows: The displacement of the deformed skin is analyzed after applying suction with a suction diameter of 6 mm and a suction pressure of 300 mb for 10 seconds, and then releasing the suction. The return elasticity ratio (pure elasticity) (Ur / Uf), which is obtained by analyzing the displacement of the skin deformed at a constant suction pressure and time, is the primary parameter used to evaluate the skin viscoelasticity value that can be obtained with a cutometer. A typical chart of the time-series measurement of skin displacement using a cutometer is shown in Figure 1. In Figure 1, Uf: maximum skin elongation during suction, Ur: immediate contraction, and Ue: immediate (instantaneous: 0.1 seconds) skin elongation due to suction. The parameters used as indicators of skin viscoelasticity are: R2: the rate at which the skin returns to its original height when suction is released relative to the maximum length stretched during suction = pure elasticity (R2 = Ur / Uf), R5: the value at which the skin returns to its original height relative to the length stretched instantaneously = net elasticity (R5 = Uf / Ue), and R7: the immediate (instantaneous) rate of contraction relative to the length stretched during suction = return rate (R7 = Ur / Ue). R2 represents net elasticity over measurement time, R5 represents net elasticity during suction, and R7 represents the magnitude of recovery relative to the maximum penetration depth. In all cases, a value closer to 1 indicates higher skin elasticity. A study investigating the relationship of each R parameter to the skin of Japanese women aged 29-55 using a Cutemeter confirmed that R2, R5, and R7 show a negative correlation with age, and R7 in particular was suggested to be an indicator that reflects age-related changes in the skin (Non-Patent Literature 4).

[0045] Results and Effects of the Examples The test results showed significant effects of tomato seed extract intake on elasticity parameters, specifically the ratio of the skin's ability to return to its original state to its maximum amplitude (R2), the ratio of the elastic recovery portion to the entire curve (R7), and the ratio of the elastic portion in the suction phase to the elastic portion in the relaxed phase of the cheek (R5) (Figure 2). Of these, a significant effect on R2 was observed after 4 weeks of intake, and significant effects on R5 and R7 were observed at both 4 and 8 weeks after intake. This confirms that tomato seed extract is useful as a pure elasticity enhancer, a net skin elasticity enhancer, and a skin recovery rate enhancer, and thus as a skin viscoelasticity enhancer. Furthermore, a significant decrease in blood pentosidine levels, a biomarker of glycation stress and one of the AGEs, was observed after 8 weeks of tomato seed extract intake (Figure 3). This confirmed that tomato seed extract is useful as an inhibitor of AGE production in the blood. Based on the above, it was confirmed that the tomato seed extract of this embodiment has the effect of maintaining skin elasticity, which decreases with age, when taken orally.

[0046] The following are examples of formulations for the skin viscoelasticity enhancer (lycoperoside H-containing tomato seed extract) of the present invention. Note that the following formulation examples are not limiting to the present invention. Furthermore, AGE production inhibitors can also be used in the same formulation examples as the skin viscoelasticity enhancer described above. Example formulation 1: Chewing gum Sugar 53.0 wt% Gum base 20.0 Glucose 10.0 Starch syrup 16.0 Fragrance 0.5 Skin viscoelasticity enhancer 0.5 100.0 wt%

[0047] Example formulation 2: Gummy Reduced starch syrup 40.0 wt% Granulated sugar 20.0 Glucose 20.0 Gelatin 4.7 Wednesday 9.68 Yuzu juice 4.0 Yuzu flavor 0.6 Dye 0.02 Skin viscoelasticity enhancer 1.0 100.0 wt%

[0048] Formula example 3: Candy Sugar 50.0 wt% Starch syrup 33.0 Wednesday 14.4 organic acid 2.0 Fragrance 0.2 Skin viscoelasticity enhancer 0.4 100.0 wt%

[0049] Example of formulation 4: Yogurt (hard / soft) Milk 41.5 wt% Skim milk powder 5.8 Sugar 8.0 Agar 0.15 Gelatin 0.1 Lactic acid bacteria 0.005 Skin viscoelasticity enhancer 0.4 fragrance trace amount water residue 100.0 wt%

[0050] Formulation example 5: Soft drink Fructose-glucose liquid sugar 30.0 wt% Emulsifier 0.5 Skin viscoelasticity enhancer 0.3 Fragrance (appropriate amount) Purified water remainder 100.0 wt%

[0051] Formulation example 6: Tablet confectionery Sugar 76.4 wt% Glucose 19.0 Sucrose fatty acid ester 0.2 Skin viscoelasticity enhancer 0.5 Purified water 3.9 100.0 wt%

[0052] Formulation Example 7: Soft Capsules Brown rice germ oil 47.0 wt% Yuzu seed oil 40.0 Emulsifier 12.0 Skin viscoelasticity enhancer 1.0 100.0 wt%

[0053] Formulation example 8: Tablets Lactose 54.0wt% Crystalline cellulose 30.0 Starch decomposition product 10.0 Glycerin fatty acid ester 5.0 Skin viscoelasticity enhancer 1.0 100.0 wt%

[0054] Example formulation 9: Cosmetic cream Squalane 20.0 wt% Beeswax 5.0 Refined jojoba oil 5.0 Glycerin 5.0 Glycerin monostearate 2.0 Polyoxyethylene (20) sorbitan Monosterate 2.0 Skin viscoelasticity enhancer 2.0 Preservative (appropriate amount) Fragrance (appropriate amount) Purified water remainder 100.0 wt%

[0055] Formula example 10: Lotion Ethanol 5.0 wt% Glycerin 2.0 1,3-Butylene glycol 2.0 Polyethylene oleyl ether 0.5 Sodium citrate 0.1 Citric acid 0.1 Skin viscoelasticity enhancer 0.1 Purified water remainder 100.0 wt%

[0056] Formula Example 11: Body Gel Macadamia nut oil 2.0 wt% Octyldodecyl myristate 10.0 Methylphenylpolysiloxane 5.0 Behenyl alcohol 3.0 Stearic acid 3.0 Batyl alcohol 1.0 Glyceryl monostearate 1.0 Polyoxyethylene sorbitol tetraoleate 2.0 Hydrogenated soybean phospholipid 1.0 Ceramide 0.1 Retinyl palmitate 0.1 Preservative (appropriate amount) Centella asiatica extract 1.0 Skin viscoelasticity enhancer 1.0 1,3-Butylene glycol 5.0 Purified water remainder 100.0 wt%

[0057] Formulation example 12: Emulsion Squalane 4.0 wt% Vaseline 2.5 Cetanol 2.0 Glycerin 2.0 Lipophilic glyceryl monostearate 1.0 Stearic acid 1.0 L-arginine 1.0 Skin viscoelasticity enhancer 0.5 Potassium hydroxide 0.1 fragrance trace amount Purified water remainder 100.0 wt%

[0058] Example of formulation 13: Bath additive (liquid) Propylene glycol 50.0 wt% Ethanol 20.0 Sodium sulfate 5.0 Skin viscoelasticity enhancer 0.5 Lanolin 0.5 Avocado oil 0.5 Dye 1.5 Fragrance 22.0 100.0 wt% [Industrial applicability]

[0059] Based on the above, the present invention can provide a novel skin viscoelasticity improving agent and an AGE production inhibitor.

Claims

1. An AGE production inhibitor containing aqueous ethanol extract from tomato seeds as the active ingredient.

2. The agent according to claim 1, characterized in that the above-mentioned aqueous ethanol extract of tomato seeds contains lycoperosides.

3. The agent according to claim 2, characterized in that the above-mentioned lycoperosides are lycoperoside H.

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