JP7735025B2 - Skin viscoelasticity improver - Google Patents

Description

The present invention relates to a novel skin viscoelasticity improver. This invention can be widely used in foods, pharmaceuticals, cosmetics, etc.

The health of skin is evaluated using a variety of indices. For example, the presence or absence of a feeling of "firmness" in the skin is considered one of the indicators for assessing health and the degree of aging. "Firmness" can be divided into two types: firmness derived from the stratum corneum/epidermis, and firmness derived from the dermis. Dermal firmness, in particular, has the elasticity to push back when pressed with a finger, and quickly returns to its original state when the finger is removed; in physical terms, this is also called viscoelasticity. The viscoelasticity of the skin decreases with age, exposure to ultraviolet rays, and exposure to chemicals. For this reason, skin firmness can also be used as an indicator of skin aging.
Methods and devices have been developed to measure the viscoelastic modulus of skin by treating the skin as a single elastic body, replacing the sensory evaluation method of "firmness." A representative skin viscoelasticity measuring device is the CUTOMETER (product name) (manufactured by Courage & Khazaka). This device draws the skin surface into a probe opening under negative pressure, measures the length of the skin drawn into the opening with a prism, then releases the suction and similarly measures the displacement length (return) upon release, and uses these measurement results as parameters to determine the viscoelastic modulus (see Non-Patent Document 1). Using the viscoelastic modulus measured with this device as an index to evaluate the degree of skin aging and the effectiveness of cosmetics has become widespread in the cosmetics industry and in the field of aesthetic medicine.
Patent Document 1 describes the use of a cutometer as a means for evaluating the effect of cosmetic treatments for improving sagging skin.
Non-Patent Document 2 describes the evaluation of the effect of 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.

A variety of ingredients and compositions that improve skin viscoelasticity have also been proposed. Patent Document 2 describes how fucoidan derived from kelp improves reduced skin elasticity. Patent Document 3 describes how astaxanthin improves skin elasticity (Patent Document 4).

It has also 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 phenomenon.
For example, the accumulation of AGEs produced by the Maillard reaction in the body can be one of the causes of the onset 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 that makes up the dermis of the skin is glycated by the Maillard reaction, the collagen that maintains the skin's elasticity and firmness is broken down, causing the skin to lose its elasticity and contributing to the formation of wrinkles and sagging skin.
Furthermore, when collagen, which constitutes bone tissue, is glycated by the Maillard reaction, bone flexibility is lost. When bone flexibility is lost, bone strength decreases even if bone density is normal. Therefore, the Maillard reaction of 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).

On the other hand, tomatoes (Solanum lycopersicum) are a plant commonly eaten around the world, and are sold as juice and supplements due to their rich content of vitamin C, lycopene, GABA, and other ingredients. Tomatoes have been reported to have functions such as lowering blood pressure and cholesterol. Furthermore, in 2004, new saponins called esculeosides were identified from tomatoes (Non-Patent Documents 5 and 6), and esculeoside A was found to have the effect of improving hyperlipidemia and arteriosclerosis in mice (Non-Patent Document 7). However, these findings are all based on tomato fruit, and there are few reports specifically focused on tomato seeds.

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 collagen and elastin production in human skin fibroblasts (Non-Patent Document 2). Furthermore, oral administration of tomato seed extract and lycoperoside H to a mouse model of atopic dermatitis has been shown to alleviate skin inflammation symptoms, along with an improvement in transepidermal water loss (Non-Patent Document 3).

JP 2010-51717 A Japanese Patent Application Laid-Open No. 2003-313131 Japanese Patent Application Laid-Open No. 2005-27589 Japanese Patent Application Laid-Open No. 2016-216436 Japanese Patent Application Laid-Open No. 2017-171638 Integral Corporation. Cutometer dual MPA580 Instruction Manual (Cuto dual 07/2014 EN JA). 2014. Mio Hori, Yoshikazu Yonei et al., Anti-Aging Medicine, 7[11]129-142, 2010 Takeda S, Yamada W, Nakamura S, et al. Effects of tomato seed extract and its saponin on skin extracellular matrix. Abstracts of the 2019 Annual Meeting of the Agricultural Chemical Society of Japan. 2019;242. Oryza Oil & Fat Chemical Co., Ltd. Tomato Seed Extract Catalog Updated September 24, 2019 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. Fujiwara S. et al., Tetrahedron, 60, 4915-4920 (2004). Ono M. et al., Chem. Pharm. Bull., 54(2), 237-239 (2006). Nohara T., J. Trad. Med., 27, 217-224 (2010).

Under these circumstances, the present inventors discovered that tomato seed extract, particularly tomato seed extract containing lycoperosides, has the effect of improving skin viscoelasticity and inhibiting AGE production, and thus completed the present invention.
That is, an object of the present invention is to provide a skin viscoelasticity improver and an AGE production inhibitor that contain a novel active ingredient.

The features of the present invention for solving the above problems are as follows.
1. A skin elasticity improver containing tomato seed extract as the active ingredient.
2. A skin net elasticity improver containing tomato seed extract as the active ingredient.
3. A skin recovery agent containing tomato seed extract as an active ingredient.
4. The skin viscoelasticity improver according to any one of 1. to 3. above.
5. A skin viscoelasticity improver containing tomato seed extract as an active ingredient.
6. An AGE production inhibitor with tomato seed extract as the active ingredient.
7. The agent according to any one of 1. to 6. above, wherein the tomato seed extract contains lycoperosides.
8. The agent according to 7. above, wherein the lycoperoside is lycoperoside H.

1 is a chart measuring the deformation of the skin obtained when operating the Cutometer. 1 is a graph showing the effect of tomato seed extract-P intake on skin viscoelasticity. 1 is a graph showing the effect of tomato seed extract-P intake on blood pentosidine levels.

The present invention will be described in detail below.
The present invention is characterized by using tomato seed extract as an active ingredient.
Furthermore, the tomato seed extract preferably contains lycoperosides, as this allows for the production of a more excellent skin viscoelasticity improver.
The lycoperosides are not particularly limited, but it is particularly preferred that they contain lycoperoside H.
Lycoperoside H is a saponin represented by the following chemical formula (1).

As the extraction solvent for obtaining the tomato seed extract, polar solvents such as water, methanol, ethanol, isopropyl alcohol, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, ethyl acetate, etc. Two or more of these solvents may be mixed.
Preferably, water, ethanol or a mixture thereof, such as aqueous ethanol, is used as the extraction solvent, which allows for efficient extraction of the active ingredients.

When water is used as the extraction solvent, there are no particular limitations on the type of water, and tap water, distilled water, mineral water, alkaline ionized water, deep sea water, etc. can be used.

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

The extraction temperature should be between 20 and 80°C, preferably around 40 to 50°C. If the extraction temperature is too low, the active ingredients will be difficult to extract, and if the extraction temperature is too high, the active ingredients will decompose, reducing their physiological activity (health functionality).

Any extraction method can be used, including stirring extraction, continuous extraction, immersion extraction, countercurrent extraction, and supercritical extraction, and any equipment can be used at room temperature or under reflux heating.

Specific extraction methods involve placing the raw material (tomato seeds) in a processing tank filled with an extraction solvent and stirring to dissolve the active ingredients. For example, if aqueous ethanol is used as the extraction solvent, approximately 2 to 100 times the amount (by weight) of the extraction solvent compared to the raw material is used, and extraction is carried out for approximately 30 minutes to 2 hours. After the active ingredients have dissolved into the solvent, the extract is obtained by filtering to remove the extraction residue.

Thereafter, the extract is subjected to treatments such as dilution, concentration, purification, and drying according to conventional methods to obtain the agent according to the present invention.
The purification method may be such that the extract is passed through a synthetic adsorption resin, a gel filtration resin, or the like to adsorb the active ingredient, and then the active ingredient is eluted with methanol, ethanol, or the like to concentrate it.

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

The skin viscoelasticity improver 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 confectioneries (gum, candy, caramel, chocolate, cookies, snacks, jelly, gummies, candy tablets, etc.), noodles (soba, udon, ramen, etc.), dairy products (milk, ice cream, yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, black tea, green tea, carbonated drinks, sports drinks, etc.), as well as health foods (tablets, capsules, etc.) and nutritional supplements (nutrition drinks, etc.). The agent of the present invention can be appropriately blended into these foods and beverages.

These foods and beverages can contain a variety of ingredients depending on their type, including, for example, 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 esters, polyglycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, gum arabic, carrageenan, casein, gelatin, pectin, agar, B vitamins, nicotinamide, calcium pantothenate, amino acids, calcium salts, colorings, flavorings, and preservatives.

Specific manufacturing methods include spray-drying or freeze-drying the agent of the present invention together with powdered cellulose, and then forming this into a powder, granules, tablets, or solution, which can be easily incorporated into foods and beverages (instant foods, etc.). The agent of the present invention can also be dissolved in, for example, fats and oils, ethanol, glycerin, or a mixture of these 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.

When the agent of the present invention is applied to food and beverages, the amount of active ingredient added is preferably 1 to 20 wt% in total, since the main purpose is to prevent disease and maintain health.

The skin viscoelasticity improver of the present invention may be used as a material for pharmaceuticals (including pharmaceuticals and quasi-drugs). Pharmaceutical preparations can be produced by appropriately blending the agent of the present invention with raw materials for pharmaceutical preparations. Examples of pharmaceutical 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, hardened vegetable oil, kaolin, talc, etc.), binders (distilled water, 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, stearate monoglyceride, starch, lactose, gum arabic, 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, stearates, polyethylene glycol, etc.).

The skin viscoelasticity enhancer of the present invention can generally be administered orally in the form of tablets, pills, soft or hard capsules, fine granules, powders, granules, liquids, etc., but can also be administered parenterally. When administered parenterally, it can be administered in the form of a solution or with the addition of a dispersing agent, suspending agent, stabilizer, etc., by local tissue administration, intradermal, subcutaneous, intramuscular, or intravenous injection. It may also be in the form of a suppository, etc. Furthermore, it can be administered as eye drops.

The dosage may vary depending on the administration method, the condition, the age of the patient, etc., but typically, adults are administered 0.5 to 5,000 mg of the active ingredient per day, and children are administered 0.5 to 3,000 mg. Furthermore, it is preferable that the dosage contains 0.01 to 100 mg, preferably 0.1 to 10 mg, of lycoperoside H.
The compounding ratio of the skin viscoelasticity enhancer can be changed as appropriate depending on the dosage form, but is usually about 0.3 to 15.0 wt% when administered orally or via mucosal absorption, and about 0.01 to 10 wt% when administered parenterally. Note that the dosage varies depending on various conditions, so in some cases a smaller dosage than the above-mentioned dosage is sufficient, and in other cases it may be necessary to administer an amount exceeding the range.

The skin viscoelasticity improver of the present invention can be expected to have an effect of improving skin viscoelasticity even when used as an external skin preparation (including cosmetics, pharmaceuticals and quasi-drugs).
Examples of the form of external skin preparations that can be blended with the skin viscoelasticity improver of the present invention include emulsions, soaps, facial cleansers, bath additives, creams, emulsions, lotions, colognes, shaving creams, shaving lotions, cosmetic oils, suntan/sunscreen lotions, face powders, foundations, perfumes, packs, nail creams, enamel, enamel removers, eyebrow pencils, blushers, eye creams, eye shadows, mascara, eyeliners, lipsticks, lip balms, shampoos, rinses, hair dyes, dispersions, cleansers, etc. Examples of the form of pharmaceuticals or quasi-drugs that can be blended with the skin viscoelasticity improver of the present invention include ointments, creams, external liquids, etc.

In addition to the skin viscoelasticity enhancer of the present invention, the above-mentioned topical skin preparations can contain ingredients that are typically incorporated into topical skin preparations such as cosmetics and quasi-drugs, as long as the skin viscoelasticity-enhancing effect is not impaired, such as oils, higher alcohols, fatty acids, UV absorbers, powders, pigments, surfactants, polyhydric alcohols/sugars, polymers, physiologically active ingredients, solvents, antioxidants, fragrances, and preservatives. Examples are listed below, but the present invention is not limited to these examples.

(1) Examples of oils: 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, diisopropyl adipate, isoarachidyl neopentanoate, caprylic/capric triglyceride, trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, tetra-2-ethylhexanoate Pentaerythritol phosphate, cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinoleate, isostearyl laurate, isotridecyl myristate, isocetyl myristate, isostearyl myristate, 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 Water, propylene glycol dicaprylate/dicaprate, propylene glycol dicaprylate, neopentyl glycol dicaprate, 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 carbonate (C12-18), triisocetyl citrate, triisoarachyl citrate, triisooctyl citrate, milk Examples of suitable hydroxystearic acid surfactants include lauryl lactate, myristyl lactate, cetyl lactate, octyldecyl lactate, triethyl citrate, acetyltriethyl citrate, acetyltributyl citrate, trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearate, di-2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, 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: 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: beef tallow, hydrogenated beef tallow, lard, hydrogenated lard, horse oil, hydrogenated horse oil, mink oil, orange roughy oil, fish oil, hydrogenated fish oil, egg yolk oil, and other animal oils and their hydrogenated oils, 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 of suitable oils include vegetable oils and their hydrogenated oils such as 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, medlar oil, cottonseed oil, hydrogenated cottonseed oil, coconut oil, and hydrogenated coconut oil; and waxes such as beeswax, high acid value beeswax, lanolin, reduced lanolin, hydrogenated lanolin, liquid lanolin, carnauba wax, and montan wax.
Silicone-based oil phase components: dimethylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, methylhydrogenpolysiloxane, polyether-modified organopolysiloxane, dimethylsiloxane-methylcetyloxysiloxane copolymer, dimethylsiloxane-methylstearoxysiloxane copolymer, alkyl-modified organopolysiloxane, terminal-modified organopolysiloxane, amino-modified silicone oil, amino-modified organopolysiloxane, dimethiconol, silicone gel, acrylic silicone, trimethylsiloxysilicate, silicone RTV rubber, and the like.
Fluorine-based oil phase components: perfluoropolyether, fluorine-modified organopolysiloxane, fluorinated pitch, fluorocarbon, fluoroalcohol, fluoroalkyl-polyoxyalkylene-co-modified organopolysiloxane, etc.

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

(3) Examples of fatty acids 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.

(4) Examples of ultraviolet absorbers: para-aminobenzoic acid, amyl para-aminobenzoate, dihydroxypropyl ethyl para-aminobenzoate, glyceryl para-aminobenzoate, ethyl para-aminobenzoate, octyl para-aminobenzoate, octyldimethyl 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 di-para-methoxycinnamate mono-2-ethylhexanoate, isopropyl para-methoxycinnamate, diethanolamine salt of para-methoxyhydrocinnamate, diisopropyl-diisopropylcinnamate mixture, urocanic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and its salts, di Examples of the hydroxymethoxybenzophenone include 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-diphenylacrylate, phenylbenzimidazole sulfate, 3-(4-methylbenzylidene)camphor, isopropyldibenzoylmethane, 2-ethylhexyl 4-(3,4-dimethoxyphenylmethylene)-2,5-dioxo-1-imidazolidinepropionate, and polymer derivatives and silane derivatives thereof.

(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 and 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, colored pigments such as ultramarine and Prussian blue, zinc oxide, titanium oxide, acid Examples include white pigments such as cerium chloride, extender pigments such as talc, mica, sericite, kaolin, and plate-like barium sulfate, pearl pigments such as mica titanium dioxide, 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, boron nitride, etc. There are no particular limitations on the shape (spherical, rod-like, needle-like, plate-like, irregular, flaky, spindle-like, etc.) and particle size of these powders. These powders may or may not have been previously surface-treated by conventionally known 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.

(6) Examples of surfactants Anionic surfactants: fatty acid soaps, α-acylsulfonates, alkylsulfonates, alkylarylsulfonates, alkylnaphthalenesulfonates, alkyl sulfates, POE alkyl ether sulfates, alkylamide sulfates, alkyl phosphates, POE alkyl phosphates, alkylamide phosphates, alkyloylalkyl taurine salts, N-acylamino acid salts, POE alkyl ether carboxylates, alkyl sulfosuccinates, sodium alkylsulfoacetates, acylated hydrolyzed collagen peptide salts, perfluoroalkyl phosphate esters, etc.
Cationic surfactants: alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, benzalkonium chloride, behenic acid amidopropyldimethylhydroxypropylammonium chloride, stearic acid diethylaminoethylamide, stearic acid dimethylaminopropylamide, lanolin derivative quaternary ammonium salts, etc.
Amphoteric surfactants: Examples of amphoteric surfactants include carboxybetaine type, amidobetaine type, sulfobetaine type, hydroxysulfobetaine type, amidosulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, and amidoamine type.
Nonionic surfactants: 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 acyl ethers, POE fatty acid esters, POE hydrogenated castor oil, POE castor oil, POE-POP copolymers, POE-POP alkyl ethers, polyether-modified silicone lauric acid alkanolamide, alkylamine oxide, hydrogenated soybean phospholipid, etc.
Natural surfactants: Examples include lecithin, saponin, sugar-based surfactants, etc.

(7) Examples of polyhydric alcohols and sugars 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 may also be used.

(8) Examples of polymers: acrylic acid ester/methacrylic acid ester copolymer (Plussize, manufactured by GOO Chemical Co., Ltd.), vinyl acetate/crotonic acid copolymer (Resin 28-1310, manufactured by NSC Co., Ltd.), vinyl acetate/crotonic acid/vinyl neodecanoate copolymer (28-2930, manufactured by NSC Co., Ltd.), methyl vinyl ether maleic acid half ester (Gantrez ES, manufactured by ISP Co., Ltd.), t-butyl acrylate/ethyl acrylate/methacrylic acid copolymer (Lubimer, manufactured by BASF Co., Ltd.), vinylpyrrolidone/vinyl acetate/vinyl propionate copolymer (Luviscol VAP, manufactured by BASF Co., Ltd.), vinyl Acetate/crotonic acid copolymer (Rubyset CA, BASF), vinyl acetate/crotonic acid/vinyl pyrrolidone copolymer (Rubyset CAP, BASF), vinyl pyrrolidone/acrylate copolymer (Rubyflex, BASF), acrylate/acrylamide copolymer (Ultrahold, BASF), vinyl acetate/butyl maleate/isobornyl acrylate copolymer (Advantage, ISP), carboxyvinyl polymer (Carbopol, BFGoodrich), acrylic acid/alkyl methacrylate copolymer (Pemulen, BF Examples of such polymers include anionic polymers such as dialkylaminoethyl methacrylate polymer acetate amphoteric salts (Yukaformer, Mitsubishi Chemical) and octylacrylamide acrylate/hydroxypropyl acrylate/butylaminoethyl methacrylate copolymers (AMPHOMER, NSC); cationic polymers such as vinylpyrrolidone/dimethylaminoethyl methacrylate quaternary salts (GAFQUAT, ISP) and methylvinylimidazolium chloride/vinylpyrrolidone copolymers (Rubycoat, BASF); and nonionic polymers such as polyvinylpyrrolidone (Ruviscol K, BASF), vinylpyrrolidone/vinyl acetate copolymers (Ruviscol VA, BASF), vinylpyrrolidone/dimethylaminoethyl methacrylate copolymers (Copolymer 937, ISP), and vinylcaprolactam/vinylpyrrolidone/dimethylaminoethyl methacrylate copolymers (Copolymer VC713, ISP). Also suitable for use are naturally occurring polymeric compounds such as cellulose or derivatives thereof, keratin and collagen or derivatives thereof, calcium alginate, pullulan, agar, gelatin, tamarind seed polysaccharides, xanthan gum, carrageenan, high methoxyl pectin, low methoxyl pectin, guar gum, gum arabic, crystalline cellulose, arabinogalactan, karaya gum, tragacanth gum, alginic acid, albumin, casein, curdlan, gellan gum, and dextran.

(9) Examples of physiologically active ingredients: Physiologically active ingredients include substances that impart some kind of physiological activity to the skin when applied to the skin. Examples include whitening ingredients, immunostimulants, anti-aging agents, UV protection agents, slimming agents, tightening agents, antioxidants, hair growth agents, hair restoration agents, moisturizing agents, blood circulation promoters, antibacterial agents, disinfectants, drying agents, cooling agents, warming agents, vitamins, amino acids, wound healing promoters, irritation soothing agents, analgesics, cell activators, and enzyme components. Suitable examples of these ingredients include angelica extract, avocado extract, hydrangea extract, althaea extract, arnica extract, aloe extract, apricot extract, apricot kernel extract, ginkgo extract, fennel extract, turmeric extract, oolong tea extract, angelica tree extract, echinacea leaf extract, Scutellaria root extract, Phellodendron bark extract, Coptis japonica extract, barley extract, St. John's wort extract, white dead nettle extract, watercress extract, orange extract, dried seawater, seaweed extract, hydrolyzed elastin, hydrolyzed wheat powder, hydrolyzed silk, chamomile extract, carrot extract, artemisia capillaris extract, licorice extract, kalkade extract, and kakyokueki extract. Cinchona extract, cucumber extract, guanosine, gardenia extract, kumazasa extract, sophora arvensis extract, walnut extract, grapefruit extract, clematis extract, chlorella extract, mulberry extract, gentian extract, black tea extract, yeast extract, burdock extract, fermented rice bran extract, rice germ oil, comfrey extract, collagen, bilberry extract, Chinese rhizome extract, Bupleurum extract, umbilical cord extract, salvia extract, soapwort extract, bamboo extract, hawthorn extract, Japanese pepper extract, shiitake mushroom extract, rehmannia root extract, lithospermum root extract, perilla extract, linden extract, meadowsweet extract, peony extract, calamus root extract, white flies Kiss, horsetail extract, ivy extract, hawthorn extract, elderberry extract, yarrow extract, peppermint extract, sage extract, mallow extract, cnidium extract, Swertia japonica extract, soybean extract, Chinese laurel extract, thyme extract, tea extract, clove extract, Imperata cylindrica extract, tangerine 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, burdock extract, parsley extract, honey, witch hazel extract, parietaria extract, burdock extract, bisabo Examples of such an extract include roll, loquat extract, coltsfoot extract, butterbur extract, poria 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, melissa 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, and royal jelly extract.
In addition, 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, ε-aminocaproic acid, glycyrrhizic acid, β-glycyrrhetinic acid, lysozyme chloride, guaiazulene, and hydrolyzed eggshell membrane. Immune stimulants such as cortisone, vitamins such as vitamin A, vitamin B2, vitamin B6, vitamin C, vitamin D, vitamin E, calcium pantothenate, biotin, nicotinamide, vitamin C ester, active ingredients such as allantoin, diisopropylamine dichloroacetate, 4-aminomethylcyclohexanecarboxylic acid, antioxidants such as tocopherol, carotenoids, flavonoids, tannins, lignans, saponins, cell activators such as alpha-hydroxy acids and beta-hydroxy acids, blood circulation promoters such as gamma-oryzanol and vitamin E derivatives, retinol, wound healing agents such as arbutin, kojic acid, placenta extract, sulfur, ellagic acid, linoleic acid, tranexamic acid, whitening agents such as glutathione, cepharanthine, licorice extract, capsicum tincture, hinokitiol, iodized garlic extract, pyridoxine hydrochloride, DL-α-tocopherol, DL-α-tocopherol acetate, nicotinic acid, nicotinic acid derivatives, calcium pantothenate, D-pantothenyl alcohol, acetyl pantothenyl ethyl ether, biotin, allantoin, isopropyl methylphenol, estradiol, ethinyl estradiol, Examples of hair growth agents include capronium chloride, benzalkonium chloride, diphenhydramine hydrochloride, takanal, camphor, salicylic acid, nonylic acid vanillylamide, nonanoic acid vanillylamide, piroctone olamine, glyceryl pentadecanoate, L-menthol, mononitroguaiacol, resorcinol, γ-aminobutyric acid, benzethonium chloride, mexiletine hydrochloride, auxin, female hormones, cantharides tincture, cyclosporine, zinc pyrithione, hydrocortisone, minoxidil, polyoxyethylene sorbitan monostearate, peppermint oil, and Sasanishiki extract.

(10) Examples of antioxidants include sodium bisulfite, sodium sulfite, erythorbic acid, sodium erythorbate, dilauryl thiodipropionate, tocopherol, tolylbiguanide, nordihydroguaiaretic acid, parahydroxyanisole, butylhydroxyanisole, dibutylhydroxytoluene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, carotenoids, flavonoids, tannins, lignans, saponins, and plant extracts that are recognized to have antioxidant effects, such as apple extract and clove extract.

(11) Examples of solvents include purified water, ethanol, lower alcohols, ethers, LPG, fluorocarbons, N-methylpyrrolidone, fluoroalcohols, volatile linear silicones, and next-generation chlorofluorocarbons.

Furthermore, the AGE production inhibitor of the present invention is characterized by containing tomato seed extract as an active ingredient.
The AGE production inhibitor can be the same tomato seed extract as the skin viscoelasticity improver described above.

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

Test example: Evaluation of the skin viscoelasticity and AGE (blood pentosidine level) inhibitory effect of tomato seed extract <Test overview>
Study design: Randomized, double-blind, placebo-controlled, parallel-group comparative study. Subjects: Healthy adult women with concerns about facial skin elasticity. Test product: Tomato seed extract, Tomato Seed Extract-P (Oryza Oil & Fat Chemical Co., Ltd.: total lycoperoside content 0.5% or more), 200 mg/day (1 mg/day as lycoperoside H). Placebo product: Starch hydrolysate 200 mg/day. Intake period: 8 weeks. Measurement points: Before intake, 4 weeks after intake, and 8 weeks after intake. Measurement items: Skin viscoelasticity (cheeks and upper arms) and blood pentosidine levels measured by a Cutometer. The results are shown in Figure 2 (skin viscoelasticity) and Figure 3 (blood pentosidine levels).

Measurement of skin viscoelasticity using a Cutometer was carried out as follows.
Suction is applied for 10 seconds with a suction diameter of 6 mm at a suction pressure of 300 mb, and then released, and the displacement of the deformed skin is analyzed. The return elasticity ratio (pure elasticity) (Ur/Uf), obtained by analyzing the skin displacement at a constant suction pressure and time, is the measurement parameter for skin viscoelasticity obtained with the Cutometer, and is primarily used for evaluation. A typical chart of the time-dependent measurement of skin displacement using the Cutometer is shown in Figure 1. In Figure 1, Uf is the maximum skin stretch during suction, Ur is the instantaneous contraction, and Ue is the instantaneous (instantaneous: 0.1 seconds) skin stretch due to suction.
The parameters used as skin viscoelasticity indexes are: R2: skin return rate when suction is released relative to the maximum length stretched during suction = pure elasticity (R2 = Ur/Uf); R5: non-net elasticity (R5 = Uf/Ue) of the value at which the skin returns to its original height relative to the length stretched instantaneously; R7: instantaneous (instantaneous) contraction rate of the skin relative to the length stretched during suction = return rate (R7 = Ur/Ue).
R2 indicates net elasticity throughout the measurement time, R5 indicates net elasticity during suction, and R7 indicates the magnitude of recovery relative to the maximum penetration depth; the closer each value is to 1, the higher the skin elasticity. In a study using a Cutometer to investigate the relationship between each R parameter and the skin of Japanese women aged 29 to 55, it was confirmed that R2, R5, and R7 show a negative correlation with age, and it was suggested that R7 in particular is an index that reflects age-related changes in the skin (Non-Patent Document 4).

Results and Effects of Examples: The test results confirmed significant effects of tomato seed extract intake on elasticity parameters: 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 relaxation phase of the cheek (R5) (Figure 2). Of these, a significant effect was confirmed for R2 after 4 weeks of intake, and for R5 and R7 after both 4 and 8 weeks of intake. This confirmed that tomato seed extract is useful as a net elasticity improver, a net skin elasticity improver, and a skin return rate improver, and therefore as a skin viscoelasticity improver.
Furthermore, a significant decrease in blood pentosidine levels, a biomarker of glycative stress and one of the AGEs, was confirmed after 8 weeks of intake of tomato seed extract (Figure 3).
This confirmed that tomato seed extract is useful as an inhibitor of AGE production in the blood.
From the above, it was confirmed that the tomato seed extract of this example has the effect of maintaining skin elasticity, which decreases with age, when taken orally.

Formulation examples of the skin viscoelasticity improver (lycoperoside H-containing tomato seed extract) of the present invention are shown below. Note that the following formulation examples do not limit the present invention. AGE production inhibitors can also be used as formulation examples similar to those of the skin viscoelasticity improver described above.
Formulation example 1: Chewing gum
Sugar 53.0 wt%
Gum base 20.0
Glucose 10.0
Starch syrup 16.0
Fragrance 0.5
Skin viscoelasticity improver 0.5
100.0 wt%

Mixing example 2: Gummies
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
Pigment 0.02
Skin viscoelasticity improver 1.0
100.0 wt%

Mixing example 3: Candy
Sugar 50.0 wt%
Starch syrup 33.0
Water 14.4
Organic acid 2.0
Fragrance 0.2
Skin viscoelasticity improver 0.4
100.0 wt%

Blend example 4: Yogurt (hard/soft)
Milk 41.5wt%
Skim milk powder 5.8
Sugar 8.0
Agar 0.15
Gelatin 0.1
Lactic acid bacteria 0.005
Skin viscoelasticity improver 0.4
fragrance trace amount
water residue
100.0 wt%

Formulation example 5: Soft drink
High fructose corn syrup 30.0 wt%
Emulsifier 0.5
Skin viscoelasticity improver 0.3
Fragrance (appropriate amount)
Purified water remainder
100.0 wt%

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

Formulation example 7: Soft capsule
Brown rice germ oil 47.0 wt%
Yuzu seed oil 40.0
Emulsifier 12.0
Skin viscoelasticity improver 1.0
100.0 wt%

Formulation Example 8: Tablets
Lactose 54.0wt%
Microcrystalline cellulose 30.0
Starch decomposition product 10.0
Glycerin fatty acid ester 5.0
Skin viscoelasticity improver 1.0
100.0 wt%

Formulation Example 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
Monostearate 2.0
Skin Viscoelasticity Improver 2.0
Preservatives: appropriate amount Flavoring: appropriate amount
Purified water remainder
100.0 wt%

Formulation 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 improver 0.1
Purified water remainder
100.0 wt%

Formulation 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 2.0 tetraoleate
Hydrogenated soybean phospholipid 1.0
Ceramide 0.1
Retinol palmitate 0.1
Preservatives: Appropriate amount Centella asiatica extract: 1.0
Skin viscoelasticity improver 1.0
1,3-butylene glycol 5.0
Purified water remainder
100.0 wt%

Formulation example 12: Emulsion squalane 4.0 wt%
Vaseline 2.5
Cetanol 2.0
Glycerin 2.0
Lipophilic glycerin monostearate 1.0
Stearic acid 1.0
L-arginine 1.0
Skin viscoelasticity improver 0.5
Potassium hydroxide 0.1
fragrance trace amount
Purified water remainder
100.0 wt%

Formulation Example 13: Bath additive (liquid)
Propylene glycol 50.0 wt%
Ethanol 20.0
Sodium sulfate 5.0
Skin viscoelasticity improver 0.5
Lanolin 0.5
Avocado oil 0.5
Pigment 1.5
Fragrance 22.0
100.0 wt%

As a result, the present invention can provide a novel skin viscoelasticity improver and AGE production inhibitor.

Claims (4)

An oral skin elasticity improver containing hydroethanolic extract of tomato seeds as the active ingredient. An oral skin elasticity improver containing a hydroethanolic extract of tomato seeds as the active ingredient. An oral skin regeneration agent containing hydroethanolic extract of tomato seeds as the active ingredient. An oral skin viscoelasticity improver containing hydroethanolic extract of tomato seeds as the active ingredient.