JP6799114B2 - ECM cycle normalizing agent - Google Patents

Description

The present invention relates to an agent for normalizing the production and uptake cycle of extracellular matrix components. The present invention is widely used in foods, chemicals, external preparations for skin and the like.

Tomato (Solanum lycopersicum) is a plant that is eaten daily all over the world and is sold as a juice or supplement because it is rich in vitamin C, lycopene, GABA and other ingredients. As the functionality of tomatoes, blood pressure lowering action and cholesterol lowering action have been reported. In 2004, esculeosides, which are novel saponins, were identified from tomatoes (Non-Patent Documents 1 and 2), and esculeoside A was found to have an improving effect on hyperlipidemia and arteriosclerosis in mice. (Non-Patent Document 3). However, these are all findings in tomato fruits, and there are few reports limited to tomato seeds.

Collagen, on the other hand, is a major component of the extracellular matrix in the skin and plays an important role in maintaining the elasticity and firmness of the skin. Elastin is a major constituent of the extracellular matrix other than collagen, and like collagen, elastin is also an important factor in maintaining the elasticity of the skin. It is known that collagen and elastin are produced by fibroblasts, and their degradation products are absorbed again by fibroblasts. However, it has been found that abnormalities occur in this cycle, and the accumulation of degradation products causes alteration of cell morphology and increased oxidative stress in the skin. Therefore, maintaining a normal production / degradation cycle of collagen and elastin, which constitute the extracellular matrix, is considered to be very important for maintaining normal skin condition.

Therefore, in order to maintain the normal production / degradation cycle of collagen and elastin constituting the extracellular matrix, lysosomes are organelles having an action of absorbing the degradation products into fibroblasts again (Patent Document 1).
Lysosomes are one of the organelles of eukaryotes and are the intracellular digestive sites with hydrolases inside. Biopolymers taken into the membrane by endocytosis or autophagy are degraded in lysosomes, useful ones are absorbed into the cytoplasm and reused, and unnecessary ones are discarded extracellularly by exocytosis. Or remain intracellular as lysosomes.

The activity of lysosomes is known to be involved in various diseases. Lysosomal storage disease is known as a typical disease. Lysosomal storage disease is often caused by the deficiency or mutation of a hydrolase that acts in the lysosome, which causes the substrate of the enzyme to accumulate in cells as a deposit without being degraded. Lysosomal storage diseases have widespread clinical heterogeneity and biodiversity and include lipid storage disease, mucopolysaccharidosis, mucolipidosis, and glycoprotein storage disease (see Patent Documents 2 and 3). ..

On the other hand, it is known that a whitening effect can be obtained by improving lysosomal activity in keratinocytes and promoting degradation of melanosome proteins (Patent Document 4, Non-Patent Documents 4 and 5).

In addition, cathepsins B1 and D, which are enzymes in lysosomes, decompose collagen (Non-Patent Document 6), hyaluronic acid is taken up and decomposed in lysosomes (Non-Patent Document 7), and compared with the skin of young people. It is known that the amount of fragmented collagen is significantly large in the skin of elderly people (Non-Patent Document 8).
Lysosomes are composed of more than 100 types of lysosomal membrane proteins, many of which are highly sugar-modified toward the lumen. These sugar chain modifications are believed to be important to escape the action of hydrolases. Major lysosomal membrane proteins include LAMP-1, LAMP-2, and LIMP-2, which account for 50% or more of the total amount of lysosomal membrane proteins (Non-Patent Document 9).
Therefore, the amount of intracellular lysosomes can be determined by evaluating the amount of these lysosomal membrane proteins in the cell. Thereby, the amount of LAMP-1 in the cell becomes an index of the amount of lysosome.

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). FUJIFILM Corporation, "Demonstrated the phenomenon that melanin pigments that cause age spots are decomposed in epidermal cells. Confirmed the effect of promoting melanin pigment decomposition in the whitening useful ingredient" AMA "", [online], November 2013 March 28, [Search on March 24, 2016], Internet <URL: http://www.fujifilm.co.jp/corporate/news/articleffnr_0831.html> FUJIFILM Corporation discovers that "proteolytic enzyme" cathepsin V "is involved in the decomposition of melanosomes containing melanin pigment that causes stains." Oryzanol "contained in rice bran lipid promotes the decomposition of melanosomes. Confirmation ”, [online], November 5, 2015, [Search on March 24, 2016], Internet <URL: http://www.fujifilm.co.jp/corporate/news/articleffnr_1020.html> Biochem. J. (1974) 137, 387-398 Matrix Biol. 2002 Jan; 21 (1): 15-23. The Journal of Investigative Dermatology vol. 120, No. 5 may 2003. Paul Saftig, Judith Klumperman Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function. Nat. Rev. Mol. Cell Biol .: 2009, 10 (9); 623-35 JP-A-2017-206468 Special Table 2014-517015 Gazette Special Table 2014-523881 Japanese Unexamined Patent Publication No. 2015-10071

However, little research has been done on the cycle of extracellular matrix component (ECM) production, degradation, and uptake such as collagen and elastin.
Against the above background, the present inventor relates to the gene related to the production of collagen and elastin, which are the main components of ECM, and the intracellular uptake of degraded collagen and elastin in the tomato seed extract and the saponin contained therein. It has been found that it has a function of promoting the expression of both genes.
In addition, as a result of promoting collagen production in skin fibroblasts and evaluating the amount of lysosomes in skin fibroblasts using LAMP-1 as an index, it was found that it has an action of increasing lysosomes in skin fibroblasts. ..
As a result, it was found that it has an action of normalizing the cycle of ECM production and uptake (hereinafter referred to as "ECM cycle") and finally maintaining the homeostasis of the extracellular matrix, and completed the present invention.
That is, an object of the present invention is to provide a novel ECM cycle normalizing agent.

The technical features of the present invention for solving the above problems are as follows.
1. 1. A smad gene expression promoter in skin fibroblasts containing lycoperoside A as an active ingredient.
2. 2. An endo180 gene expression promoter in skin fibroblasts containing lycoperoside A as an active ingredient.
3. 3. An endo180 gene expression promoter in skin fibroblasts containing tomato seed extract as an active ingredient.
4. Above 1. ~ Above 3. An agent for normalizing the collagen production / uptake cycle in skin fibroblasts containing the agent according to any one of the above as an active ingredient.
5. A fiblin gene expression promoter in skin fibroblasts containing lycoperoside A as an active ingredient.
6. A neuraminidase-1 gene expression promoter in skin fibroblasts containing lycoperoside A as an active ingredient.
7. 5. Above. Or the above 6. An agent for normalizing the elastin production / uptake cycle in skin fibroblasts containing the above agent as an active ingredient.
8. A collagen production promoter in skin fibroblasts containing tomato seed extract as an active ingredient.
9. A lysosome-increasing agent in skin fibroblasts containing tomato seed extract as an active ingredient.
10. A lysosome-increasing agent in skin fibroblasts containing lycoperoside A as an active ingredient.
11. A lysosome-increasing agent in skin fibroblasts containing lycoperoside H as an active ingredient.
12. Above 1. ~ Above 11. An ECM cycle normalizing agent in skin fibroblasts containing any one of the agents selected from the above as an active ingredient.
13. An ECM cycle normalizing agent in skin fibroblasts containing lycoperoside A as an active ingredient.
14. An ECM cycle normalizing agent in skin fibroblasts containing tomato seed extract as an active ingredient.

The smad gene expression promoter of the present invention is unique to tomato seeds because lycoperoside A, which is a saponin contained only in tomato seeds and is not contained in the pulp, promotes the expression of the smad gene involved in collagen production. Lycoperoside A, which is a component of, has the effect of promoting collagen production.
In addition, the endo180 gene expression promoter of the present invention promotes the expression of the endo180 gene, which is involved in the uptake of degraded collagen into cells by lycoperoside A, so that lycoperoside A is degraded into cells. It has the effect of promoting uptake.
As a result, lycoperoside A normalizes the collagen production / uptake cycle by promoting both the smad gene involved in collagen production and the endo180 gene involved in the intracellular uptake of degraded collagen. Has an action. Therefore, lycoperoside A has an excellent effect as a collagen production / uptake cycle normalizing agent.
Further, in the fiblin gene expression promoter of the present invention, lycoperoside A promotes the expression of the fiblin gene involved in the production of elastin, so that lycoperoside A, which is a component peculiar to tomato seeds, promotes the production of elastin. Have.
Then, the neuraminidase-1 gene expression promoter of the present invention promotes the expression of the neuraminidase-1 gene involved in the intracellular uptake of degraded elastin by lycoperoside A, so that lycoperoside A-degraded elastin It has the effect of promoting the uptake into cells.
As a result, lycoperoside A promotes both the fiblin gene involved in elastin production and the neuraminidase-1 gene involved in the intracellular uptake of degraded elastin, thus normalizing the elastin production and uptake cycle. Has the effect of elastinizing. Therefore, lycoperoside A has an excellent effect as an elastin production / uptake cycle normalizing agent.
Further, in the present invention, lycoperoside A and tomato seed extract have an excellent effect as a collagen production promoter.
In addition, lycoperoside A, lycoperoside H and tomato seed extracts have the effect of increasing LAMP-1, which is one of the membrane proteins constituting lysosomes, in dermal skin fibroblasts. As a result, lycoperoside A, lycoperoside H and tomato seed extracts have the effect of increasing lysosomes in dermal and cutaneous fibroblasts.
This has the effect of promoting the uptake of intracellular matrix components.
As described above, lycoperoside A has an action of normalizing the production / uptake cycle of both collagen and elastin, and therefore has an action of normalizing the production and uptake of extracellular matrix components, thereby serving as an ECM cycle normalizing agent. Has an excellent effect.

It is a graph which shows the effect on the collagen production amount of the tomato seed extract and saponin of this Example. It is a graph which shows the effect on the smad gene expression level of the tomato seed extract and saponin of this Example. It is a graph which shows the effect which the tomato seed extract and saponin of this Example have on the expression level of the endo180 gene. It is a graph which shows the effect on the fiblin-4 gene expression level of the tomato seed extract and saponin of this Example. It is a graph which shows the effect on the neuraminidase-1 gene expression level of the tomato seed extract and saponin of this Example. It is a photograph showing the effect of tomato seed extract and seed saponin on the amount of LAMP-1 in skin fibroblasts. White indicates LAMP-1. It is a fluorescence immunostaining image (3D image) of the extracellular matrix decomposition product accumulated in the cell sheet. Cylindrical and rounded shapes are cell nuclei, and those that look like haze between them are extracellular matrix degradation products. It is a graph which shows the effect on the endo180 gene expression in the cell sheet of tomato seed extract and lycoperosides. It is a graph which shows the effect on the neuraminidase-1 gene expression in the cell sheet of tomato seed extract and lycoperosides.

The present invention will be described in detail below.
The ECM cycle normalizing agent of the present invention is characterized by containing lycoperoside A as an active ingredient.
lycoperoside A is a saponin represented by the following chemical formula (1).

The method for obtaining lycoperoside A is not particularly limited, but a method of extracting and purifying from a plant is particularly preferable.
When lycoperoside A is extracted from a plant, the raw material thereof is not particularly limited, but it is particularly preferable to use tomato. This is because it contains a high concentration of lycoperoside A.
When lycoperoside A is obtained from tomato, tomato seeds are used as the site. This is because lycoperoside A is not contained in the pulp and skin of tomatoes, but is contained only in tomato seeds.

When solvent extraction is performed as an extraction method, the extraction solvent for obtaining the extract is, for example, water, lower monovalent alcohol (methyl alcohol, ethyl alcohol, 1-propanol, 2-propanol, 1-butanol, 2- Butanol, etc.), liquid polyhydric alcohols (glycerin, propylene glycol, 1,3-butylene glycol, etc.), lower esters (ethyl acetate, etc.), hydrocarbons (benzene, hexane, pentane, etc.), ketones (acetone, methyl ethyl ketone, etc.) , Ethers (diethyl ether, tetrahydrofuran, dipropyl ether, etc.), acetonitrile and the like, and one or more of them can be used.

As an example of a preferable extraction method, a method of using hydrous ethanol or hydrous methanol having a concentration of 0 to 100% (v / v), extracting at room temperature or heating for 1 to 10 hours, and then filtering is used. Can be mentioned.

As a purification method, the tomato seed extract obtained by the above method is sequentially subjected to partition extraction with ethyl acetate and n-butanol, and then silica gel chromatography, column chromatography and the like are performed to perform lycoperoside A (ECM cycle). Normalizing agent) can be obtained.

As a specific method for obtaining lycoperoside A from tomato seeds, the method according to the examples of the present specification is preferable.

In addition, the collagen production promoter of the present invention is characterized by containing tomato seed extract or lycoperoside A as an active ingredient.
The above can be produced by the method described above.

The ECM cycle normalizing agent of the present invention can be used as a material for various food and drink compositions. Foods and drinks include, for example, confectionery (gum, candy, caramel, chocolate, cookies, snacks, jelly, gummy, tablet confectionery, etc.), noodles (soba, udon, ramen, etc.), dairy products (milk, ice cream, yogurt, etc.) Etc.), seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, tea, tea, carbonated beverages, sports beverages, etc.) and other general foods, health foods (tablets, capsules, etc.), nutrition Supplementary foods (nutrient drinks, etc.) Functional foods, foods for specified health use can be mentioned. The ECM cycle normalizing agent of the present invention may be appropriately added to these foods and drinks.

Various components can be blended in these food and drink compositions depending on the type, for example, glucose, fructose, sucrose, maltose, sorbitol, stebioside, corn syrup, lactose, citric acid, tartrate, and malic acid. 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, Food materials such as arabic gum, carrageenan, casein, gelatin, pectin, agar, vitamin Bs, nicotinic acid amide, calcium pantothenate, amino acids, calcium salts, pigments, fragrances and preservatives can be used.

As a specific manufacturing method, the ECM cycle normalizing agent is spray-dried or freeze-dried together with powdered cellulose, and this is easily contained in foods and drinks (instant foods, etc.) by making it into powder, granules, tableting or solution. Can be done. Further, the ECM cycle normalizing agent can be dissolved in, for example, fats and oils, ethanol, glycerin or a mixture thereof to make a liquid, and added to a beverage or added to a solid food. If necessary, it can be mixed with a binder such as gum arabic or dextrin to form a powder or granules, and can be added to a beverage or a solid food.

When the ECM cycle normalizing agent of the present invention is applied to foods and drinks, the amount of the active ingredient added to foods and drinks is 1 to 20 wt% or less in total because the main purpose is to maintain health and beauty. It is preferable to have it.

The ECM cycle normalizing agent of the present invention may be used as a material for pharmaceutical compositions (including pharmaceuticals and quasi-drugs). It can be produced by appropriately blending the ECM cycle normalizing agent of the present invention with a raw material for chemical preparation. Examples of the preparation raw materials that can be blended in the ECM cycle normalizing agent of the present invention include excipients (glucose, lactose, sucrose, sodium chloride, starch, calcium carbonate, kaolin, crystalline cellulose, cacao butter, hardened vegetable oil, kaolin, etc. Tarku, etc.), binders (distilled water, physiological saline, ethanol water, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrants (sodium alginate, canten, carbonic acid, etc.) Sodium hydrogen hydrogen, calcium carbonate, sodium lauryl sulfate, stearic acid monoglyceride, starch, lactose, gum arabic powder, gelatin, ethanol, etc.), disintegration inhibitor (sucrose, stear, cacao butter, hydrogenated oil, etc.), absorption enhancer (No. 1) Tertiary ammonium bases, sodium lauryl sulfate, etc.), excipients (glycerin, starch, lactose, kaolin, bentonite, silicic acid, etc.), lubricants (purified talc, stearate, polyethylene glycol, etc.) and the like.

The method for administering the ECM cycle normalizing agent of the present invention can generally be orally administered in the form of tablets, pills, soft / hard capsules, fine granules, powders, granules, liquids and the like. , May be parenteral administration. When administered as a parenteral agent, it may be administered as a solution, or with the addition of dispersants, suspensions, stabilizers, etc., by local tissue administration, intradermal, subcutaneous, intramuscular or intravenous injection. it can. It may also be in the form of a suppository or the like.

The dose may vary depending on the administration method, medical condition, age of the patient, etc., but for adults, the active ingredient is usually 0.5 to 5000 mg per day, and for children, about 0.5 to 3000 mg is usually administered.
The compounding ratio of the ECM cycle normalizing agent can be appropriately changed depending on the dosage form, but is usually about 0.3 to 15.0 wt% when administered orally or by mucosal absorption, and when administered parenterally. Is preferably about 0.01 to 10 wt%. Since the dose varies depending on various conditions, a dose smaller than the above dose may be sufficient, or it may be necessary to administer beyond the range.

The ECM cycle normalizing agent of the present invention can be expected to have an ECM cycle normalizing effect even when used as an external preparation for skin (including cosmetics, pharmaceuticals and quasi-drugs).
Examples of the form of the external skin preparation that can contain the ECM cycle normalizing agent of the present invention include milky lotion, soap, washing pigment, bathing agent, cream, milky lotion, lotion, odecolon, shaving cream, and shaving lotion. , Toner, sunshade / sunscreen lotion, white powder, foundation, perfume, pack, nail cream, enamel, enamel remover, eyebrow, blush, eye cream, eye shadow, mascara, eyeliner, lipstick, lip balm, shampoo, Examples include rinsing, hair dye, dispersion, and cleaning agent. In addition, examples of the drug or quasi-drug to which the ECM cycle normalizing agent of the present invention can be added include ointments, creams, and external liquids.

In addition to the ECM cycle normalizing agent according to the present invention, the above-mentioned form of skin external preparation includes components and oils to be added to skin external preparations such as cosmetics and quasi-drugs as long as the ECM cycle normalizing action is not impaired. , Higher alcohols, fatty acids, ultraviolet absorbers, powders, pigments, surfactants, polyhydric alcohols / sugars, polymers, physiologically active ingredients, solvents, antioxidants, fragrances, preservatives and the like can be blended. Examples are listed below, but the present invention is not limited to these examples.

(1) Examples of oils Ester-based oil phase components: glyceryl tri2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isostearic acid Isocetyl, butyl stearate, butyl myristate, ethyl linate, isopropyl linoleate, ethyl oleate, isosetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isosetyl isostearate, diethyl sebacate, adipine Diisopropyl acid, isoaraquil neopentanoate, glyceryl tri (capryl capric acid), trimethylolpropane tri2-ethylhexanoate, trimethylrolpropane triisostearate, pentaerythritol tetra2-ethylhexanoate, cetyl caprylate, decyl laurate, Hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinoleate, isostearyl laurate, isotolideyl myristate, isosetyl myristate, isostearyl myristate, isosetyl palmitate, Isostearyl palmitate, octyl stearate, isosetyl stearate, isodecyl oleate, octyldodecyl oleate, octyldodecyl linoleate, isopropyl isostearate, cetostearyl 2-ethylhexanoate, stearyl 2-ethylhexarate, hexyl isostearate, Ethylene glycol dioctarate, ethylene glycol diocaneate, propylene glycol dicaprate, propylene glycol di (capryl capric acid), propylene glycol dicaprylate, neopentyl glycol dicaprate, neopentyl glycol dioctarate, glyceryl tricaprylate, glyceryl triundecylate, Glyceryl triisopalmitate, glyceryl triisostearate, octyldodecyl neopentaneate, isostearyl octanoate, octyl isononanoate, hexyldecyl neodecanoate, octyldodecyl neodecanoate, isosetyl isostearate, isostearyl isostearate, octyldecyl isostearate, poly Glycerin oleic acid ester, polyglycerin isostearic acid ester, charcoal Dipropyl acid, dialkyl carbonate (C12-18), triisocetyl citrate, triisoaraquil citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyldecyl lactate, triethyl citrate, acetyltriethyl citrate, citrate Acetyltributyl acid, trioctyl citrate, diisostearyl citrate, 2-ethylhexyl hydroxystearate, di2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, dioctyl sevacinate, cholesteryl stearate, cholesteryl isostearate, hydroxysteare Examples thereof include cholesteryl acid, cholesteryl oleate, dihydrocholesteryl oleate, phytosteryl isostearate, phytosteryl oleate, isocetyl 12-stearoyl hydroxystearate, stearyl 12-stearoyl hydroxystearate, isostearyl 12-stearoyl hydroxystearate.
Hydrocarbon-based oil phase components: squalane, liquid paraffin, α-olefin oligomer, isoparaffin, selecin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, petrolatum and the like.
Animal and vegetable oils and their hydrogenated oils, and naturally occurring waxes: animal oils such as beef fat, hardened beef fat, pork fat, hardened pork fat, horse oil, hardened horse oil, mink oil, orange raffy oil, fish oil, hardened fish oil, egg yolk oil and Its hydrogenated oil, avocado oil, almond oil, olive oil, cacao butter, kiwi seed oil, apricot 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, brown seed oil, camellia oil, corn oil, rapeseed oil, hydrogenated rapeseed oil, palm kernel oil, hardened palm kernel oil, palm oil, hardened palm oil, peanut oil, hardened peanut oil, castor oil, hardened castor oil , Sunflower oil, grape seed oil, jojoba oil, hydrogenated jojoba oil, macadamia nut oil, medhome oil, cotton seed oil, hardened cotton seed oil, coconut oil, hardened coconut oil and other vegetable oils and their hardened oils, beeswax, high acidity beeswax, lanolin, reduction Examples thereof include waxes such as lanolin, hydrogenated lanolin, liquid lanolin, carnauba wax and monttan wax.
Silicone-based oil phase components: dimethylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, methylhydrogenpolysiloxane, polyether-modified organopolysiloxane, dimethyl Siloxane / methylcetyloxysiloxane copolymer, dimethylsiloxane / methylstealoxysiloxane copolymer, alkyl-modified organopolysiloxane, terminal-modified organopolysiloxane, amino-modified silicone oil, amino-modified organopolysiloxane, dimethiconol, silicone gel, acrylic Examples thereof include silicone, trimethylsiloxysilicic acid, and silicone RTV rubber.
Fluorine-based oil phase components: perfluoropolyether, fluorine-modified organopolysiloxane, fluoride pitch, fluorocarbon, fluoroalcohol, fluoroalkyl-polyoxyalkylene co-modified organopolysiloxane and the like can be mentioned.

(2) Examples of higher alcohols 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 Caprylic acid, capric acid, undecylene acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, arachidonic acid, behenic acid , Elcaic acid, 2-ethylhexanoic acid and the like.

(4) Examples of UV absorbers Paraaminobenzoic acid, amyl paraaminobenzoate, ethyldihydroxypropyl paraaminobenzoate, glyceryl paraaminobenzoate, ethyl paraaminobenzoate, octyl paraaminobenzoate, octyldimethyl paraaminobenzoate, ethylene glycol salicylate, salicylate Octyl, triethanolamine salicylate, phenyl salicylate, butylphenyl salicylate, benzyl salicylate, homomentyl salicylate, benzyl silicate, octyl paramethoxysilicate, 2-ethylhexyl paramethoxysilicate, mono 2-ethylhexyl silicate. Glyceryl ethylhexanoate, isopropyl paramethoxysilicate, diethanolamine paramethoxyhydrosilicate, diisopropyl / diisopropylsilicate ester mixture, urocanic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and its salts, Dihydroxymethoxybenzophenone, dihydroxymethoxybenzophenone sodium disulfonate, dihydroxybenzophenone, dihydroxydimethoxybenzophenone, hydroxyoctoxybenzophenone, tetrahydroxybenzophenone, butylmethoxydibenzoylmethane, 2,4,6-trianilinino-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, Phenylbenzoimidazole sulfate, 3- (4-methylbenzylidene) camphor, isopropyldibenzoylmethane, 4- (3,4-dimethoxyphenylmethylene) -2, 5-dioxo-1-imidazolidine propionate 2-ethylhexyl, etc., and Examples thereof include these polymer derivatives and silane derivatives.

(5) Examples of powders and pigments Red 104, Red 201, Yellow 4, Blue 1, Black 401, etc., Yellow No. 4 AL Lake, Yellow 203 BA Lake, etc., 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 Colored pigments such as iron oxide, chromium oxide, carbon black, ultramarine blue and dark blue, white pigments such as zinc oxide, titanium oxide and cerium oxide, extender pigments such as talc, mica, sericite, kaolin and barium plate sulfate, mica titanium Pearl pigments such as barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate, metal salts such as magnesium silicate, inorganic powders such as silica and alumina, aluminum stearate, magnesium stearate, zinc palmitate, zinc myristine, myristin Examples thereof include metal pigments such as magnesium acid, zinc laurate, and zinc undecylene, bentonite, smectite, and boron nitride. The shape (spherical shape, rod shape, needle shape, plate shape, indefinite shape, flaky shape, spindle shape, etc.) and particle size of these powders are not particularly limited. These powders are treated with 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 agent treatment, N-acylated lysine treatment, and the like. It may or may not be surface-treated in advance by polyacrylic acid treatment, metal silane treatment, amino acid treatment, lysine treatment, inorganic compound treatment, plasma treatment, mechanochemical treatment, or the like.

(6) Examples of surfactants Anionic surfactants: fatty acid sulpene, α-acyl sulfonate, alkyl sulfonate, alkyl allyl sulfonate, alkylnaphthalene sulfonate, alkyl sulfate, POE alkyl ether sulfate , Alkylamide Sulfate, Alkyl Phosphate, POE Alkyl Phosphate, Alkylamide Phosphate, Alkyril Alkyl Taurine Salt, N-Acyl Amino Acid Salt, POE Alkyl Ether Carbate, Alkyl Sulfosuccinate, Alkyl Sulfoacetate Examples thereof include sodium, an acylated hydrolyzed collagen peptide salt, and a perfluoroalkyl phosphate ester.
Cationic surfactants: alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, benzalconium chloride , Behenic acid amidopropyldimethylhydroxypropylammonium chloride, diethylaminoethylamide stearate, dimethylaminopropylamide stearate, quaternary ammonium salt of lanolin derivative and the like.
Amphoteric tensides: carboxybetaine type, amide betaine type, sulfobetaine type, hydroxysulfobetaine type, amide sulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, amidoamine type and the like.
Nonionic surfactants: propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE sorbit fatty acid ester, POE glycerin fatty acid ester, POE acrylic ether, POE fatty acid ester, POE hardened sunflower Examples thereof include oil, POE castor oil, POE / POP copolymer, POE / POP alkyl ether, polyether-modified silicone lauric acid alkanolamide, alkylamine oxide, hydrogenated soybean phospholipid and the like.
Natural surfactants: Lecithin, saponin, sugar-based surfactants and the like can be mentioned.

(7) Examples of polyhydric alcohols and sugars Ethethylene 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, martitol, trehalose, alkylated trehalose, mixed isomerized sugar, sulfated trehalose, purulan and the like. Further, these chemically modified products and the like can also be used.

(8) Examples of polymers Acrylic acid ester / methacrylic acid ester copolymer (plus size, manufactured by Reciprocal Chemical Co., Ltd.), vinyl acetate / crotonic acid copolymer (resin 28-1310, manufactured by NSC), vinyl acetate / croton Acid / vinyl neodecaneate copolymer (28-2930, manufactured by NSC), methyl vinyl ether maleic acid half ester (Gantrez ES, manufactured by ISP), T-butyl acrylate / ethyl acrylate / methacrylic acid copolymer (rubimer) , BASF), Vinylpyrrolidone / Vinylacetate / Vinylpropionate copolymer (Rubiscol VAP, BASF), Vinylacetate / Crotonic acid copolymer (Rubiset CA, BASF), Vinylacetate / Croton Acid / vinyl pyroridone copolymer (Rubiset CAP, manufactured by BASF), vinyl pyrrolidone / acrylate copolymer (Rubiflex, manufactured by BASF), acrylate / acrylamide copolymer (Ultrahold, manufactured by BASF), vinyl acetate / Butylmalate / isobornylacryllate copolymer (Advantage, manufactured by ISP), carboxyvinyl polymer (Carbopol, manufactured by BFGoodrich), acrylate / alkyl methacrylate copolymer (Pemuren, manufactured by BF Goodrich), etc. Anionic polymer compounds, dialkylaminoethyl methacrylate polymer acetate amphoteric (Yukaformer, manufactured by Mitsubishi Chemical Corporation), octylacrylamide acrylate / hydroxypropyl acrylate / butylaminoethyl methacrylate copolymer (AMPHOMER, NSC) (Manufactured by) and other amphoteric polymer compounds, vinylpyrrolidone / dimethylaminoethyl methacrylate quaternized product (GAFQUAT, manufactured by ISP), methylvinylimidazolium chloride / vinylpyrrolidone copolymer (rubicoat, manufactured by BASF), etc. Polymer compound, polyvinylpyrrolidone (Rubiscol K, manufactured by BASF), vinylpyrrolidone / vinyl acetate copolymer (rubiscol VA, manufactured by BASF), vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (copolymer 937, manufactured by ISP) , Vinyl caprolactam / vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (copolymer VC713, manufactured by ISP) and other nonionic polymer compounds. In addition, cellulose or its derivatives, keratin and collagen or its derivatives, calcium alginate, pullulan, agar, gelatin, tamarind seed polysaccharide, xanthan gum, carrageenan, high methoxyl pectin, low methoxyl pectin, guar gum, arabic rubber, crystalline cellulose, arabino Naturally-derived high molecular compounds such as galactan, carrageenan, tragacant gum, alginic acid, albumin, casein, curdlan, gellan gum, and dextran can also be preferably used.

(9) Examples of bioactive ingredients Examples of the bioactive ingredients include substances that give some bioactivity to the skin when applied to the skin. For example, whitening ingredients, immunostimulators, anti-aging agents, UV protection agents, slimming agents, tightening agents, antioxidants, hair growth agents, hair growth agents, moisturizers, blood circulation promoters, antibacterial agents, bactericides, desiccants, Examples thereof include cold sensitizers, warm sensitizers, vitamins, amino acids, wound healing promoters, stimulant relievers, analgesics, cell activators, enzyme components and the like. Examples of these suitable compounding ingredients include, for example, Ashitaba extract, Avocado extract, Amacha extract, Artea extract, Arnica extract, Aloe extract, Apricot extract, Apricot kernel extract, Ginkgo extract, Wikyo extract, Ukon extract, Oolong tea extract, Ages. Extract, Echinashi leaf extract, Ogon extract, Oubaku extract, Ouren extract, Omugi extract, Otogirisou extract, Odorikosou extract, Dutch mustard extract, Orange extract, Dried seawater, Seaweed extract, Hydrolyzed elastin, Hydrolyzed wheat powder, Hydrolyzed silk , Chamomile extract, carrot extract, kawarayomogi extract, licorice extract, calcade extract, kakyoku extract, kina extract, cucumber extract, guanosine, cutinashi extract, kumazasa extract, clara extract, walnut extract, grapefruit extract, clematis extract, chlorella extract, quail extract, Gentiana extract, tea extract, yeast extract, gobo extract, fermented rice bran extract, rice germ oil, comfrey extract, collagen, moss peach extract, saishin extract, psycho extract, saitai extract, salvia extract, sabonsou extract, sasa extract, sanzashi extract , Sansho extract, Shiitake extract, Jio extract, Shikon extract, Shiso extract, Shinanoki extract, Shimotsukesou extract, Shakuyaku extract, Shobu root extract, Shirakaba extract, Sugina extract, Seiyoukizuta extract, Seiyousanzashi extract, Seiyouniwatoko extract, Seiyounokogirisou extract, Seiyo Hakka extract, sage extract, Zeniaoi extract, Senkyu extract, Senburi extract, Soybean extract, Taisou extract, Thyme extract, Tea extract, Chouji extract, Chigaya extract, Chimpi extract, Touki extract, Tokinsenka extract, Tounin extract, Tohi extract, Dokudami extract, Tomato Extract, Natto extract, Carrot extract, Carrot extract, Novara extract, Hibiscus extract, Bakumondou extract, Parsley extract, Honey, Hamamelis extract, Parietaria extract, Hikiokoshi extract, Bisaborol, Biwa extract, Fukitanpopo extract, Fukinoto extract, Bukuryo extract, Butcher Bloom extract, grape extract, propolis, hechima extract, benibana extract, peppermint extract, bodaiju extract, button extract, hop extract, pine extract, marronnier extract, mizubasho U extract, Mukuroji extract, Melissa extract, Peach extract, Yagurumagiku extract, Eucalyptus extract, Yukinoshita extract, Yokuinin extract, Yomogi extract, Lavender extract, Apple extract, Lettuce extract, Lemon extract, Rengesou extract, Rose extract, Rosemary extract, Roman chamomile extract , Royal jelly extract and the like.
In addition, biopolymers such as deoxyribonucleic acid, mucopolysaccharide, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, hydrolyzed eggshell membrane, amino acids, hydrolyzed peptides, sodium lactate, urea, sodium pyrrolidone carboxylate. , Moisturizing ingredients such as betaine, whey, trimethylglycine, oily ingredients such as phytosphingosin, cholesterol, cholesterol derivatives, phospholipids, ε-aminocaproic acid, glycyrrhizinic acid, β-glycyrrhetinic acid, lysozyme chloride, guaiazulene, Immunostimulators such as hydrocortisone, vitamins such as vitamin A, vitamin B2, vitamin B6, vitamin C, vitamin D, vitamin E, calcium pantothenate, biotin, nicotinic acid amide, vitamin C ester, allantin, diisopropylamine dichloro Active ingredients such as acetate, 4-aminomethylcyclohexanecarboxylic acid, antioxidants such as tocopherols, carotenoids, flavonoids, tannins, lignans, saponins, cell activators such as α-hydroxyic acid and β-hydroxyic acid, γ-orizanol, Blood circulation promoters such as vitamin E derivatives, wound healing agents such as retinol and retinol derivatives, whitening agents such as arbutine, kodiic acid, placenta extract, sulfur, ellagic acid, linoleic acid, tranexamic acid, glutathione, cepharanthin, can elephant extract, Togarashi tincture, hinokithiol, garlic iodide extract, pyridoxin hydrochloride, DL-α-tocopherol, DL-α-tocopherol acetate, nicotinic acid, nicotinic acid derivative, calcium pantothenate, D-pantothenyl alcohol, acetylpantothenyl ethyl ether, biotin , Allantin, isopropylmethylphenol, estradiol, ethynyl estradiol, capronium chloride, benzalkonium chloride, diphenhydramine hydrochloride, takanal, camphor, salicylic acid, nonyl acid vanillylamide, nonanoic acid vanillylamide, pyrocton olamine, glyceryl pentadecanoate, L-menthol, Mononitroguayacol, resorcin, γ-aminobutyric acid, benzethonium chloride, mexiretin hydrochloride, auxin, female hormone, cantalistinki, cyclosporin, zincpyritione, hydrocortisone, minoxidil, polyoxyethylene sorbitan monostearate, peppermint oil, sasani Hair growth agents such as shiki extract can be mentioned.

(10) Examples of Antioxidants Sodium hydrogen sulfite, sodium sulfite, erythorbic acid, sodium erythorbic acid, dilauryl thiodipropionate, tocopherol, trirubiguanoid, nordihydroguayaletinic acid, parahydroxyanisole, butylhydroxyanisole, dibutylhydroxy Examples thereof include plant extracts having an antioxidant effect such as toluene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, carotenoid, flavonoid, tannin, lignan, saponin, apple extract and chowdi extract.

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

The collagen production promoter of the present invention can be used as a raw material for food and drink compositions, drug compositions, and external preparations for skin.
As the raw materials for preparations that can be blended with these, the same raw materials as those used for the above-mentioned ECM cycle normalizing agent can be used, and the same manufacturing method and administration method as those used for the ECM cycle normalizing agent can be used. it can.

Hereinafter, the present invention will be described based on examples.
Example 1: Preparation of tomato seed extract, and isolation and identification of saponin component from tomato seeds 367.7 g of dried tomato seeds were extracted with methanol (70 ° C., 2 hours) to obtain a methanol extract. The obtained methanol extract was dispersed in water, and sequentially partitioned and extracted with ethyl acetate and n-butanol. Ethyl acetate-soluble part (ethyl acetate fraction) 0.63 g, n-butanol-soluble part (butanol fraction) 2.41 g and 5.05 g of water-soluble part (moisture image) were obtained. Then, among these, the butanol fraction was used as the tomato seed extract of this example. Then, the butanol fraction was subjected to silica gel chromatography (chloroform: methanol = 9: 1 → 7: 3 → chloroform: methanol: water = 6: 4: 1 → methanol) to obtain Fr. 1 to 6. Fr. 3 (1.1 g) was subjected to reverse phase ODS column chromatography (methanol concentration 20% → 50% → 80% → 100%) to obtain Fr.3-1 to Fr.3-4. The saponin compounds lycoperoside A (chemical formula (1) above) (7.0 mg) and H (chemical formula (2) below) by reverse phase HPLC fractionation (Inertsil ODS-SP, 70% methanol) from Fr.3-3 (mg). ) (7.5 mg) was isolated. Each compound was identified by comparing 1H-NMR (600 MHz) and 13C-NMR (150 MHz) spectra with literature values.

Test Example 1-1: Effect of tomato seed extract and saponin on collagen production Human skin fibroblasts (TIG-103) were seeded on a 24-well plate at a cell concentration of 1.0 × 10 ⁴ cells / well and cultured for 2 days. did. Butanol fractions (1, 3 and 10 μg / mL), lycoperoside A and H (0.1, 0.3 and 1.0 μg / mL) of tomato seed extract methanol extract were added to the cultured cells and cultured for 1 day. After the addition culture, the cells from which the medium had been removed were homogenized with PBS, and the amount of collagen in the cell layer was measured using the obtained cell suspension using the Collagen assay kit (Cosmo Bio Co., Ltd.). Toxicity evaluation by MTT assay was also performed. The result is shown in FIG.

Results and Effects of Examples in Test Example 1-1 As shown in FIG. 1, significantly collagen production in cells supplemented with butanol fraction (3 μg / mL) and lycoperoside A (0.3 and 1 μg / mL). Was found to be increasing. In addition, no cytotoxicity was observed due to the addition of the sample. This confirmed that tomato seed extract and lycoperoside A are useful as collagen production promoters.

Test Example 1-2: Effect of tomato seed extract and seed saponin on intracellular lysosomal amount Human skin fibroblasts (TIG-103) were seeded on a 48-well plate at a cell concentration of 1.0 × 10 ⁵ cells / well, and 1 Incubated for days. The n-butanol fraction (3 μg / mL), lycoperoside A and H (10 μM) of the tomato seed extract methanol extract were added to the cultured cells and cultured for 2 days. After the addition culture, the cells from which the medium had been removed were fixed with 4% paraformaldehyde / PBS, and the localization and abundance of LAMP-1 in the cells were confirmed under a microscope by fluorescent immunostaining.

Results and effects on Test Example 1-2 As a result, LAMP-in cells by the addition of n-butanol fraction (3 μg / mL), lycoperoside A and H (10 μM) compared to the control without sample addition. It was found that the amount of 1 was increased (Fig. 6). In particular, the increase due to the addition of lycoperoside A was remarkable.
From this result, it was confirmed that tomato seed extract and lycoperoside A and H contained therein increase the amount of lysosomes responsible for the uptake and decomposition of waste products in the extracellular matrix of the skin dermis.

Results and Effects of Examples for Test Examples 1-1 and 1-2 Based on the above, tomato seed extract and lycoperoside A promote collagen production and lysosomes responsible for the uptake and degradation of waste products in the extracellular matrix of the skin dermis. It was found that increasing the amount of collagen normalizes the ECM cycle and keeps the extracellular matrix normal at all times.

Test Example 2: Effect of tomato seed extract and saponin on extracellular matrix homeostasis Human skin fibroblasts (TIG-103) were seeded on a 12-well plate at a cell concentration of 1.0 × 10 ⁵ cells / well for 1 day. It was cultured. Butanol fractions (1, 3 and 10 μg / mL) of tomato seed extract methanol extract, lycoperoside A and H (1, 3 and 10 μM) were added to the cells after culturing, and the cells were cultured for 2 days. RNA was extracted from the cultured cells, and the expression level of each gene (smad gene, endo180 gene, fiblin gene, neuraminidase-1 gene) was evaluated by real-time RT-PCR.
The results are shown in FIG. 2 (smad gene), FIG. 3 (endo180 gene), FIG. 4 (fiblin-4 gene) and FIG. 5 (neuraminidase-1 gene).

Results and Effects of Examples in Test Example 2 As shown in FIG. 2, the expression of the smad gene involved in collagen production was significantly increased by the addition of lycoperoside A (3 and 10 μM), and is shown in FIG. As described above, it was confirmed that the expression of the endo180 gene involved in the uptake of degraded collagen was significantly increased by the addition of the butanol fraction (1 μg / mL) and the addition of lycoperoside A (3 μM). From this, it was confirmed that lycoperoside A is useful as a smad gene expression promoter and an endo180 gene expression promoter, and as a collagen production and uptake cycle normalizing agent.
In addition, as shown in FIG. 4, the expression of the fiblin gene involved in the production of elastin was significantly increased by the addition of lycoperoside A (10 μM). As shown in FIG. 5, the expression of the neuraminidase-1 gene involved in the uptake of elastin degradation products was significantly increased by the addition of lycoperoside A (3 μM). From this, it was confirmed that lycoperoside A is useful as a fiblin gene expression promoter and a neuraminidase-1 gene expression promoter, and is useful as an elastin production and uptake cycle normalizing agent.

Test Example 3: Evaluation of ECM cycle normalizing effect of tomato seed extract and seed saponin in a state where extracellular matrix is formed Human skin fibroblasts (TIG-103) are used as a temperature-responsive cell culture device (UpCell) for collecting cell sheets. : Seed in a registered trademark (manufactured by Cellseed Co., Ltd.) and cultured for 2 weeks until the cells adhered to each other to form a sheet. After cell sheet formation, collagen tripeptide (H-Gly-Pro-Hyp-OH) was added as an extracellular matrix degradation product at a final concentration of 200 μM. At the same time, the n-butanol fraction (1, 3 and 10 μg / mL), lycoperoside A and H (0.1, 0.3 and 1.0 μM) of the tomato seed extract methanol extract were added and cultured for 2 days. After the addition culture, the cell sheet was collected, and the amount of collagen degradation products accumulated in the cell sheet was examined by fluorescent immunostaining. In addition, RNA in the cell sheet was extracted, and the expression levels of genes involved in the uptake of collagen degradation products and elastin degradation products were evaluated by real-time RT-PCR.

Results and effects of Examples in Test Example 3 From the immunostaining images obtained as a result, extracellular matrix degradation products accumulated in the cell sheet were added with butanol fraction (10 μg / mL) and seed saponin (1.0 μM). It was found that it decreased due to (Fig. 7). In addition, as a result of gene expression analysis, tomato seed extract (10 μg / mL), lycoperoside A (1, 3 μM) and lycoperoside H ( It was significantly increased by 1 μM) (Fig. 8). Similarly, the expression of the Neuraminidase-1 gene involved in the uptake of elastin degradation products was significantly increased by tomato seed extract (10 μg / mL), lycoperoside A (1, 3, 10 μM) and lycoperoside H (10 μM) (Fig. 9). ..
From the above results, tomato seed extract and seed saponin promote the expression of genes involved in the uptake of extracellular matrix degradation products and increase the uptake ability of the degradation products even in cells that actually formed the extracellular matrix. I understood.

Effects of Examples From the above results, among the saponins contained in tomato seed extract and tomato, lycoperoside A is useful as an ECM cycle normalizing agent by promoting the production and decomposition of collagen and elastin, and therefore cells. It was found that it has the effect of maintaining the homeostasis of the extracellular matrix.

Examples of the formulation of the ECM cycle normalizing agent of the present invention will be given below, but the following formulation examples do not limit the present invention.
Formulation Example 1: Chewing gum
Sugar 52.0 wt%
Gum base 20.0
Glucose 10.0
Syrup 16.0
Fragrance 0.5
Cherry blossom extract 0.5
Glucosylceramide 0.5
ECM cycle normalizing agent 0.5
100.0 wt%

Formulation example 2: Gummies
Reduced starch syrup 38.0 wt%
Granulated sugar 20.0
Glucose 20.0
Gelatin 4.7
Water 9.68
Kiwi juice 4.0
Kiwi flavor 0.6
Dye 0.02
Cherry blossom extract 1.0
Glucosylceramide 1.0
ECM cycle normalizing agent 1.0
100.0 wt%

Formulation example 3: Candy
Sugar 50.0 wt%
Syrup 33.0
Water 14.2
Organic acid 2.0
Fragrance 0.2
Cherry blossom extract 0.1
Glucosylceramide 0.1
ECM cycle normalizing agent 0.4
100.0 wt%

Formulation example 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
Cherry blossom extract 0.1
Glucosylceramide 0.1
ECM cycle normalizing agent 0.4
Fragrance trace amount
Water residue
100.0 wt%

Formulation example 5: Soft drink
Fructose-glucose liquid sugar 30.0 wt%
Emulsifier 0.5
Strawberry seed extract 0.05
Glucosylceramide 0.05
ECM cycle normalizing agent 0.05
Appropriate amount of fragrance
Purified water residue
100.0 wt%

Formulation example 6: Soft capsule
Rice germ oil 86.0 wt%
Cherry blossom extract 0.5
Glucosylceramide 0.5
Emulsifier 12.0
ECM cycle normalizing agent 1.0
100.0 wt%

Formulation Example 7: Tablets
Lactose 53.0 wt%
Crystalline cellulose 30.0
Starch decomposition product 10.0
Cherry blossom extract 0.5
Glucosylceramide 0.5
Glycerin fatty acid ester 5.0
ECM cycle normalizing agent 1.0
100.0 wt%

Formulation example 8: Oral granules (pharmaceutical products)
ECM cycle normalizing agent 1.0 wt%
Strawberry seed extract 0.5
Glucosylceramide 0.5
Lactose 30.0
Cornstarch 60.0
Crystalline cellulose 7.0
Polyvinyl pyrrolidone 1.0
100.0 wt%

Formulation example 9: Tablet confectionery
Sugar 75.4 wt%
Glucose 19.0
Sucrose fatty acid ester 0.2
Strawberry seed extract 0.5
Glucosylceramide 0.5
ECM cycle normalizing agent 0.5
Purified water 3.9
100.0 wt%

Formulation example 10: Cat food
Corn 33.0 wt%
Flour 35.0
Meat meal 15.0
Beef tallow 8.9
Salt 1.0
Skipjack extract 4.0
Strawberry seed extract 0.5
Glucosylceramide 0.5
ECM cycle normalizing agent 1.0
Taurine 0.1
Vitamins 0.5
Minerals 0.5
100.0 wt%

Formulation example 11: Dog food
Corn 30.0 wt%
Meat (chicken) 15.0
Solvented soybeans 10.0
Flour 24.0
Rice bran 5.0
Cherry blossom extract 0.5
Glucosylceramide 0.5
ECM cycle normalizing agent 5.0
Animal fats and oils 8.9
Oligosaccharide 0.1
Vitamin 0.5
Mineral 0.5
100.0 wt%

Formulation example 12: 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
ECM cycle normalizing agent 2.0
Preservatives Appropriate amount Fragrances Appropriate amount
Purified water residue
100.0 wt%

Formulation example 13: Toner 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
ECM cycle normalizing agent 0.1
Purified water residue
100.0 wt%

Formulation Example 14: Body Gel Macademia Nut Oil 2.0 wt%
Octyldodecyl myristate 10.0
Methylphenyl polysiloxane 5.0
Behenyl alcohol 3.0
Stearic acid 3.0
Bacil 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 of Centella asiatica extract 1.0
ECM cycle normalizing agent 1.0
1,3-butylene glycol 5.0
Purified water residue
100.0 wt%

Formulation example 15: 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
ECM cycle normalizing agent 0.5
Potassium hydroxide 0.1
Fragrance trace amount
Purified water residue
100.0 wt%

Formulation Example 16: Bathing agent (liquid)
Propylene glycol 50.0 wt%
Ethanol 20.0
Sodium sulphate 5.0
ECM cycle normalizing agent 0.5
Lanolin 0.5
Avocado oil 0.5
Dye 1.5
Fragrance 22.0
100.0 wt%

As described above, the present invention can provide a novel ECM cycle normalizing agent.

Claims (7)

A smad gene expression promoter in skin fibroblasts containing lycoperoside A as an active ingredient. An endo180 gene expression promoter in skin fibroblasts containing lycoperoside A as an active ingredient. A collagen production / uptake cycle normalizing agent in skin fibroblasts containing the agent according to claim 1 or 2 as an active ingredient. A fiblin gene expression promoter in skin fibroblasts containing lycoperoside A as an active ingredient. A neuraminidase-1 gene expression promoter in skin fibroblasts containing lycoperoside A as an active ingredient. An agent for normalizing the elastin production / uptake cycle in skin fibroblasts containing the agent according to claim 4 or 5 as an active ingredient. An ECM cycle normalizing agent in skin fibroblasts containing lycoperoside A as an active ingredient.