Age production inhibitor

Abstract

To provide AGE production inhibitors and AGE decomposition accelerators that contain novel ingredients as active ingredients.SOLUTION: The features of the present invention for solving the above problems are as follows: an AGE production inhibitor containing as active ingredients Camellia sasanqua extract, Chrysanthemum extract, Prunus extract, and at least one of Aristotella chilensis extract, Camellia sinensis extract, Juglans extract, Oenothera tetraptera extract, Pomegranate flower extract, Trapa japonica extract, Vaccinium vitis-idaea extract, Litchi chinensis extract, Garcinia mangostana extract, and Ampelopsis grossedentata extract; and an AGE decomposition accelerator containing as an active ingredient at least one of Prunus blossom extract, Litchi chinensis extract, Cafe oil glucose, Camellia sinensis extract, quercetin glucoside, 1,2-di-Galloyl-4,6-Hexahydroxydiphenoyl-β-D-Glucose, Oenothera tetraptera extract, Trapa japonica extract, Aristotella chilensis extract, Ampelopsis grossedentata extract, and delphinidin-3,5-glucoside.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a novel AGE production inhibitor. The present invention is widely used in foods, pharmaceuticals, cosmetics, etc.

Background Art

[0002] Regarding the production process of AGE (Advanced Glycation End-product), there are still many unclear points, but it is considered that the non-enzymatic glycation reaction is the main body. That is, AGE is formed by the non-enzymatic reaction (Glycation) between the amino group present in the protein and the aldehyde group of reducing sugars such as glucose in the initial reaction, and an Amadori rearrangement product is formed via a Schiff base, and it is considered that this is formed through complex cleavage and condensation over a long time in the late-stage reaction.

[0003] Diabetic complications include retinopathy, nephropathy, neuropathy, ischemic heart disease, cerebrovascular disorders, etc., and it has been confirmed that AGE generated in the living body in a hyperglycemic state is involved in one of the causes of these diseases (for example, see Non-Patent Document 1). Diabetic nephropathy is a renal microvascular disorder caused by diabetes, and thickening of the glomerular basement membrane and expansion of the mesangial region are the basic pathological changes. In recent years, with the increase in the number of diabetic patients, the number of patients who develop end-stage renal failure due to diabetic nephropathy and require dialysis treatment has been increasing. AGE formed by the persistence of a hyperglycemic state is considered to be involved in the onset of nephropathy through 1) enhanced vascular permeability; 2) promotion of deposition of proteins and lipoproteins; 3) inactivation of nitric oxide (NO); 4) promotion of extracellular matrix production; etc. (for example, see Non-Patent Document 2).

[0004] For the purpose of preventing and improving diabetic complications, various AGE production inhibitors aimed at inhibiting the production of such AGE are known.

[0005] Examples of such AGE production inhibitors include novel AGE production inhibitory compositions that inhibit the production of AGEs, which are the causes of diabetic complications such as nephropathy and retinopathy (see, for example, Patent Document 1), and drugs that inhibit AGE formation (see, for example, Patent Document 2). However, pharmaceuticals such as AGE production inhibitors are still in the development stage, and conventionally, such synthetic compounds often have unexpected side effects. In recent years, research on components or food ingredients with functions that can prevent, suppress, improve, and treat diseases through diet has attracted more attention than treatment with synthetic pharmaceuticals.

[0006] On the other hand, under such circumstances, a final glycation product (AGE) production inhibitory composition characterized by containing an extract of a plant that can be used as a food (see, for example, Patent Documents 3 to 5) has also been disclosed.

[0007] However, the inhibitory activity of the AGE inhibitory active ingredients present in such plant extracts is generally extremely low compared to synthetic compounds, and the content of the active ingredients in the extracts is also generally extremely low.

[0008] In the prevention or treatment of diabetic complications, since it is necessary to continue for a long period of time, an AGE production inhibitor that can achieve both effective suppression of AGE production and avoidance of side effects is eagerly desired.

[0009]

Non-Patent Document 1

Non-Patent Document 2

Patent Document 1

Patent Document 2

Patent Document 3

[0010] In recent years, it has become clear that, apart from diabetes, AGE is also closely related to skin aging. Although AGE increases with aging, when the Maillard reaction occurs in the collagen part of skin proteins, the amino group of lysine residues or the guanidyl group of arginine residues in the protein reacts non-enzymatically with the carbonyl group of sugar, resulting in the generation of AGEs, which crosslink collagen parts with each other. When a crosslinked structure is formed, the molecule becomes hard and the original elasticity of the skin is lost. Also, the crosslinked product is judged as a foreign substance, and the secretion amount of degrading enzymes (collagenase, elastase) increases. Due to these reasons, the firmness and elasticity of the skin are lost, the skin becomes fragile, and furthermore, it leads to the occurrence of wrinkles, sagging, and dullness.

[0011] Thus, not only from the perspective of AGE as a trigger for diabetic complications, but also from the anti-aging perspective, the AGE generation mechanism has come to be attracting attention. [Summary of the Invention] [Problems to be Solved by the Invention]

[0012] The present invention aims to solve the above problems, and its object is to provide an AGE production inhibitor that can more effectively inhibit AGE production and has improved safety for living organisms, as well as a method for producing the same. Another object is to provide an agent that promotes the decomposition of newly produced AGE. [Means for Solving the Problems]

[0013] The features of the present invention for solving the above problems are as follows. 1. An AGE production inhibitor containing at least one of extracts of Camellia sasanqua, extracts of chrysanthemum, extracts of cherry blossoms, extracts of aronia berries, extracts of purple tea, extracts of walnuts, extracts of evening primrose, extracts of pomegranate, extracts of buckwheat, extracts of lingonberry, extracts of lychee, extracts of mangosteen, and extracts of rattan tea as an active ingredient. 2. An AGE degradation promoter containing at least one of extracts of cherry blossoms, extracts of lychee, caffeoyl glucose, extracts of purple tea, quercetin glucoside, 1,2-di-Galloyl-4,6-Hexahydroxydiphenoyl-β-D-Glucose (GHG), extracts of evening primrose, extracts of buckwheat, extracts of aronia berries, extracts of rattan tea, and delphinidin-3,5-O-diglucoside as an active ingredient.

Mode for Carrying Out the Invention

[0014] Hereinafter, the present invention will be described in detail. The AGE production inhibitor of the present invention is characterized by containing at least one of extracts of Camellia sasanqua, extracts of chrysanthemum, extracts of rattan tea, extracts of cherry blossoms, extracts of aronia berries, extracts of purple tea, extracts of walnuts, extracts of evening primrose, extracts of pomegranate, extracts of buckwheat, extracts of lingonberry, extracts of lychee, and extracts of mangosteen as an active ingredient.

[0015] Camellia sasanqua, which is the raw material of the Camellia sasanqua extract used in the present invention, is an evergreen broad-leaved tree of the genus Camellia in the family Theaceae.

[0016] The part of Camellia sasanqua used as the raw material of the present invention is not particularly limited, and examples include leaves, stems, trunks, flowers, roots, fruits, etc. However, it is preferable to use leaves or flowers, and further preferably flowers.

[0017] Here, when performing extraction with a polar solvent, the polar solvent to be used is not particularly limited. For example, water, methanol, ethanol, isopropanol, acetone, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, acetic acid, ethyl acetate, ether, hexane, etc. may be mentioned. Among these, water, methanol, and ethanol are preferred because the active ingredient can be extracted efficiently. Note that these may be used alone or in combination of two or more.

[0018] When using water as the extraction solvent, the extraction is preferably carried out at an extraction temperature of 20 to 100°C, more preferably about 40 to 70°C. This is because if the extraction temperature is too low, the active ingredient is difficult to extract, and if the extraction temperature is too high, the active ingredient is likely to decompose, which is not preferable. The type of water for extraction is not particularly limited, and tap water, distilled water, mineral water, alkaline ion water, etc. can be used.

[0019] When using a hydrous alcohol as the extraction solvent, the alcohol concentration is preferably 20 wt% or more, more preferably 25 to 50 wt%. This is because it is difficult to obtain a high extraction amount of the active ingredient when the alcohol concentration is less than 20 wt%. Also, when the alcohol concentration is 30 wt% or more, the extraction is preferably carried out at an extraction temperature of 0 to 95°C, more preferably about 0 to 50°C. Note that the extraction with hydrous ethanol may be repeated at various concentrations to improve the content rate of the active ingredient.

[0020] Also, when performing extraction with a polar solvent, the extraction method is not particularly limited. For example, any method such as continuous extraction, immersion extraction, countercurrent extraction, etc. can be adopted, and any apparatus can be used at room temperature or under reflux heating. Note that when performing extraction by the above-mentioned methods, only one of these may be carried out, or these methods may be combined. Also, these extractions may be carried out only once or two or more times.

[0021] Furthermore, when extraction is performed by supercritical extraction, the supercritical fluid used at this time is not particularly limited, and examples thereof include carbon dioxide and nitrogen. Note that only one of these may be used, or two or more of them may be used in combination. Among these, carbon dioxide is particularly preferable. This is because the active ingredient can be extracted more easily. Also, the extraction method at this time may be performed by a known method.

[0022] The chrysanthemum (scientific name: Chrysanthemum morifolium), which is the raw material of the chrysanthemum extract used in the present invention, is a short-day plant of the genus Chrysanthemum in the Asteraceae family. The above chrysanthemum grows wild in Japan and is easily available. The flower part of the chrysanthemum has been used medicinally in China since ancient times, and is also drunk as tea or sake in Japan, and furthermore, is used in cooking as food, and is said to be effective against dizziness, headache, eye fatigue, etc. The above chrysanthemum flower may include flower buds. Here, "including flower buds" means that a mixture of flower buds and flowers may be used, or only flower buds or only flowers may be used. Also, the part of the above chrysanthemum is not particularly limited, and examples include leaves, stems, trunks, flowers, roots, fruits, etc., but it is preferable to use leaves or flowers, and furthermore, flowers.

[0023] When using flowers as the part of the chrysanthemum extract, the extraction method is not particularly limited, and examples thereof include polar solvent extraction, supercritical extraction, etc. Note that only one of these may be performed, or both of these may be performed. In this specification, the one using flowers as the part of the chrysanthemum extract is referred to as "chrysanthemum flower extract". Also, as the chrysanthemum flower extract, commercially available products can be used. For example, chrysanthemum flower extract-P manufactured by Oriza Oil Co., Ltd. can be used.

[0024] Also, cherry blossoms are a general term for plants of the genus Prunus in the Rosaceae family, excluding ume, peach, apricot, etc., and generally refer to those belonging to the subgenus Cerasus.

[0025] The cherry species used in the present invention is not particularly limited. For example, cherries belonging to groups such as the Prunus jamasakura group, Prunus incisa group, Prunus mume group, Prunus campanulata group, Prunus grayana group, Prunus serrulata group, etc. can be used, and it is not further limited to these groups.

[0026] The part of the cherry used as the raw material of the present invention is not particularly limited, and examples include leaves, stems, trunks, flowers, roots, fruits, etc. However, it is preferable to use leaves or flowers. In this specification, the one using flowers as the part among the cherry extracts is referred to as "cherry flower extract". When extracting the active ingredient from the above-mentioned cherry, it can be carried out in the same manner as the camellia extract. Also, commercially available products can be used as the cherry extract. For example, Cherry Flower Extract-P manufactured by Oris Oyuka Co., Ltd. can be used.

[0027] The maqui berry (Aristotelia chilensis), which is the raw material of the maqui berry extract used in the present invention, is a berry-like plant native to southern Chile in South America and is known to have a very high antioxidant effect. Moreover, it is known to be rich in delphinidin-3,5-O-diglucoside and delphinidin-3-sambubioside-5-glucoside, which are not contained in other berries such as bilberries and blackcurrants. In the present invention, when extracting the active ingredient from the maqui berry, the part is not particularly limited. For example, fruits, seeds, flowers, leaves, roots, stems, etc. can be used, and it is particularly preferable to use fruits. This is because the active ingredient can be extracted at a high concentration. When extracting the active ingredient from the above-mentioned maqui berry, it can be carried out in the same manner as the camellia extract. Also, commercially available products can be used as the maqui berry extract. For example, Maqui Berry Extract-P35 manufactured by Oris Oyuka Co., Ltd. can be used.

[0028] The purple tea, which is the raw material of the purple tea extract used in the present invention, is a Camellia sinensis developed by cross-breeding by the Kenyan government and is named cultivar TRFK306. Since the tea leaves of purple tea contain anthocyanins and thus are purple, it is commonly called "purple tea". In addition to TRFK306, there are also known varieties such as Sanrouge developed by the National Agriculture and Food Research Organization. Purple tea contains a high concentration of 1,2-di-Galloyl-4,6-Hexahydroxydiphenoyl-β-D-Glucose (GHG), a specific component that does not exist in other purple teas.

[0029] The part of purple tea is not particularly limited, and leaves, stems, roots, flowers, seeds, etc. can be used, and it is particularly preferable to use leaves. This is because higher concentrations of GHG can be obtained. When extracting the active ingredient from the above purple tea, it can be carried out in the same manner as the camellia extract. In addition, commercially available products of purple tea extract can be used. For example, Purple Tea Extract-P manufactured by Oriza Oil & Fat Co., Ltd. can be used.

[0030] The walnut used as the raw material of the walnut extract used in the present invention is not particularly limited as long as it is a walnut of the genus Juglans (Juglans) of the family Juglandaceae. For example, Juglans regia, J. aulantifolia, J. ailantifolia var. cordiformis, J. regia var. orientis, etc. can be mentioned. As for the part of the walnut used as the raw material, the whole fruit can be used, but it is preferably the seed with the outer and inner pericarp removed. More preferably, only the seed coat is peeled off from the seed and the kernel is removed. This is because the active ingredient, polyphenol, is not contained in the kernel at all, and the polyphenol content of the seed coat is extremely high. When extracting the active ingredient from the above walnut, it can be carried out in the same manner as the camellia extract. In addition, commercially available products of walnut extract can be used. For example, Walnut Polyphenol-P manufactured by Oriza Oil & Fat Co., Ltd. can be used.

[0031] The evening primrose, which is the raw material of the evening primrose extract used in the present invention, is an annual, biennial, or perennial herb of the genus Oenothera. Rarely, the stem may lignify and form a shrub shape. The following four species are representative species. (1) Oenothera laciniata (2) Oenothera striata (3) Oenothera biennis (4) Oenothera erythrosepala In the present invention, the type of evening primrose is not limited, and any type can be used. Also, the part of the evening primrose is not particularly limited, and for example, leaves, stems, roots, flowers, seeds, etc. can be used, and it is particularly preferable to use seeds. When obtaining an evening primrose extract by extracting the active ingredient from the above evening primrose, it can be carried out in the same manner as the above camellia extract. Also, commercially available products can be used as the evening primrose extract, and for example, Evening Primrose Extract-P, Evening Primrose Extract-WSPS, etc. manufactured by Oris Oil Co., Ltd. can be used.

[0032] The pomegranate, which is the raw material of the pomegranate extract used in the present invention, is a plant of the genus Punica in the family Lythraceae. Preferably, it is Punica granatum (scientific name). The part of the plant can be any part, and for example, one or more parts such as the whole plant, leaves, trunk, stem, branches, branch leaves, pericarp, fruit, bark, sap, seeds, rhizome, roots, terminal flower, flowers, etc. can be used. Preferably, it is the flower of the pomegranate. In this specification, the one using the flower as the part among the pomegranate extracts is referred to as "pomegranate flower extract". When obtaining a pomegranate flower extract by extracting the active ingredient from the above pomegranate flower, it can be carried out in the same manner as the above camellia extract. Also, commercially available products can be used as the pomegranate flower extract, and for example, Pomegranate Flower Extract Powder manufactured by Koei Kogyo Co., Ltd. can be used.

[0033] As the water chestnut which is the raw material of the water chestnut extract used in the present invention, plants of the Trapaceae family: water chestnut (Trapa bispinosa Roxb. var. iinumai Nakano (=T. natans var. iinumai Makino, T. japonica Flerov.) (English name: Water Chestnut) (pharmacognosy name: water chestnut fruit, water chestnut seed, water chestnut, Trapa japonica) and the variety "T. natans var. bispinosa (Roxb.) Makino (English name: Singara Nut)" are mainly used. In addition, other plants of the same genus such as Trapa bicornus Osbeck (pharmacognosy name: black water chestnut), Trapa incisa Sieb. et Zucc. (=T. bispinosa var. incisa (Sieb. et Zucc.) Makino, T. natans L. var. incisa (Sieb.) et Zucc.), Trapa natans L. (=T. natans var. quadrispinosa (Roxb.) Makino, T. natans L. var. japonica Nakai) (English name: Europian Water Chestnut, Water Caltrops, Horn Chestnut), T. pseudoincisa Nakai (pharmacognosy name: Trapa pseudoincisa), Trapa bispinosa Roxb. var. makinoi Nakai, Trapa natans L. var. rubeola Makino, etc. can be used.

[0034] The water chestnut extract used in the present invention is obtained by directly using various parts of the plant body (stem, leaf, stalk, branch, seed, fruit, flower, rhizome, root, bark, aerial part, etc., preferably the fruit) or squeezing after pulverization. Or it is obtained by directly using or pulverizing and then extracting with a solvent. Also, commercially available products can be used as the water chestnut extract. For example, the water chestnut extract manufactured by Hayashi Ken Sangyo Co., Ltd. can be used.

[0035] The cowberry (lingonberry, scientific name: Vaccinium vitis-idaea L.), which is the raw material of the cowberry extract used in the present invention, is an evergreen dwarf shrub of the genus Rhododendron in the Ericaceae family, and its fruit is edible. At this time, the part is not particularly limited. For example, the skin, pulp, seeds, etc. of the cowberry can be used. In particular, it is preferable to use the pulp of the cowberry. This is because the arbutin and other active ingredients contained in the pulp can be obtained in a higher concentration. As the above-mentioned cowberry extract, those extracted with a solvent may be used, but cowberry juice may also be used. Furthermore, commercially available products can be used as this cowberry extract. For example, cowberry extract-J manufactured by Oris Oil Co., Ltd. can be used.

[0036] Lychee, which is the raw material of the lychee extract used in the present invention, is the fruit of the plant Litchi chinensis Sonn. of the family Sapindaceae. The seeds of this fruit are called lychee seeds. Lychee is called lychee, litchi or litchi for the fruit and is consumed all over the world. The part of the plant can be any part. For example, one or more parts such as the whole plant, leaves, trunk, stem, branches, branch leaves, pericarp, fruit, bark, sap, seeds, rhizome, roots, head flowers, flowers, etc. can be used. Among these, it is preferable to use the seeds. In this specification, the one using the seeds as the part among the lychee extracts is referred to as "lychee seed extract". The above-mentioned lychee seed extract is obtained by directly pressing the seeds of the above-mentioned lychee or pressing after grinding. Or, it is obtained by extracting with a solvent after directly using or grinding. In addition, commercially available products can be used as the above-mentioned lychee extract. For example, "Lychee Seed Extract-P" manufactured by Oris Oil Co., Ltd. can be used.

[0037] Mangosteen (scientific name: Garcinia mangostana), which is the raw material of the mangosteen extract used in the present invention, is a plant of the genus Garcinia in the Clusiaceae family. The part to be used for extraction is not particularly limited. For example, flowers, flower spikes, pericarp, fruits, pulp, stems, leaves, branches, branch and leaves, trunks, barks, rhizomes, root barks, roots, seeds, insects, heartwoods, aerial parts, underground parts or whole herbs can be used. Among them, the pericarp of mangosteen is preferred. When extracting the active ingredient from the above mangosteen to obtain a mangosteen extract, it can be carried out in the same manner as the above camellia extract. Also, commercially available products can be used as the mangosteen extract. For example, "Mangosteen Aqua" manufactured by Nippon Shinyaku Co., Ltd. can be used.

[0038] The tengcha used as the raw material of the tengcha extract used in the present invention is a grape family plant with the scientific name Ampelopsis grossedentata (Hand.-Mazz.) W.T.Wang CV, which is a perennial vine growing wild in a wide area from central to southern China, and is also cultivated in Taiwan.

[0039] In China, there are places where the leaves of this plant have been used as a beverage since ancient times. In addition, the roots or whole herbs have been used as folk medicines for the treatment of icteric hepatitis, colds, sore throats, acute conjunctivitis, etc. However, little is known about the active ingredients and pharmacological effects in these uses.

[0040] There is also a report (Chinese Pharmaceutical Journal, vol. 31, 458-461, 1996) that a flavonoid called ampelopsin was isolated from the leaves of tengcha.

[0041] The part of the above tengcha used in the present invention is not particularly limited, and various parts (trunks, leaves, stems, branches, seeds, fruits, flowers, rhizomes, roots, barks, aerial parts, etc., preferably fruits) can be used. In particular, it is preferable to use branches and leaves because higher concentrations of active ingredients can be extracted.

[0042] When extracting the active ingredient from the above-mentioned Ampelopsis grossedentata to obtain an Ampelopsis grossedentata extract, it can be carried out in the same manner as the camellia extract. Also, commercially available products can be used as the above-mentioned Ampelopsis grossedentata extract. For example, "Ampelopsis grossedentata extract powder" manufactured by Saito Trading Co., Ltd. can also be used.

[0043] In addition, for the camellia (Camellia sasanqua) extract, chrysanthemum extract, cherry extract, aronia berry extract, purple tea extract, walnut extract, evening primrose extract, pomegranate extract, buckwheat extract, lingonberry extract, Ampelopsis grossedentata extract, lychee extract, and mangosteen extract, only one kind can be used, or two or more kinds can be used in combination.

[0044] The AGE degradation promoter of the present invention contains at least one of cherry extract, lychee extract, purple tea extract, evening primrose extract, buckwheat extract, aronia berry extract, Ampelopsis grossedentata extract, caffeoyl glucose, quercetin glucoside, 1,2-di-Galloyl-4,6-Hexahydroxydiphenoyl-β-D-Glucose (GHG), and delphinidin-3,5-O-diglucoside as an active ingredient. In particular, it is preferably contained with Ampelopsis grossedentata extract, purple tea extract, GHG, buckwheat extract, aronia berry extract, and delphinidin-3,5-O-diglucoside. This is because a more excellent AGE degradation promoter can be obtained. In addition, only one kind of these can be used, or two or more kinds can be used in combination.

[0045] The cherry extract used as the AGE degradation promoter of the present invention can be the same as the above-mentioned AGE production inhibitor.

[0046] The above-mentioned caffeoyl glucose is a unique active ingredient contained in the above-mentioned cherry flower extract and is a compound represented by the following chemical formula (1).

[0047]

Chemical formula

[0048] Quercetin glucoside is a unique active ingredient contained in the above-mentioned cherry blossom extract and is a compound represented by the following chemical formula (2).

[0049]

Chem.

[0050] The method for obtaining the above-mentioned caffeoyl glucose and quercetin glucoside is not particularly limited. For example, it can be isolated from the above-mentioned cherry blossom extract by the method of the examples in this specification.

[0051] As the lychee extract used as the AGE degradation promoter of the present invention, the same one as the above-mentioned AGE production inhibitor can be used.

[0052] As the purple tea extract used as the AGE degradation promoter of the present invention, the same one as the above-mentioned AGE production inhibitor can be used.

[0053] 1,2-di-Galloyl-4,6-Hexahydroxydiphenoyl-β-D-Glucose (GHG) is a unique component richly contained in the above-mentioned purple tea extract and is a compound represented by the following chemical formula (3).

[0054]

Chem.

[0055] As a method for producing 1,2-di-Galloyl-4,6-Hexahydroxydiphenoyl-β-D-Glucose (GHG), for example, it is preferable to fractionate and purify the purple tea extract obtained as described above by ion exchange, size exclusion column chromatography, HPLC method, gel filtration, membrane separation, etc., using known GHG as an index. Of course, 1,2-di-Galloyl-4,6-Hexahydroxydiphenoyl-β-D-Glucose (GHG) may be extracted and purified from raw materials other than purple tea, or an organic synthesis method may be appropriately applied.

[0056] The evening primrose extract used as the AGE decomposition promoter of the present invention can be the same as the above-described AGE production inhibitor.

[0057] The buckwheat extract used as the AGE decomposition promoter of the present invention can be the same as the above-described AGE production inhibitor.

[0058] The maqui berry extract used as the AGE decomposition promoter of the present invention can be the same as the above-described AGE production inhibitor.

[0059] Delphinidin-3,5-O-diglucoside is a component contained in the above maqui berry extract and is a compound represented by the following chemical formula (4).

[0060]

Chemical formula

[0061] The method for obtaining the above delphinidin-3,5-O-diglucoside is not particularly limited, but it can be obtained by isolating and purifying from the above maqui berry extract by the method of the following examples.

[0062] The ampelopsis grossedentata extract used as the AGE decomposition promoter of the present invention can be the same as the above-described AGE production inhibitor.

[0063] The AGE production inhibitor and AGE degradation promoter of the present invention can be used as materials for various foods and drinks. Examples of the foods and drinks include general foods such as edible oils (salad oil), confectioneries (gum, candy, caramel, chocolate, cookie, snack, jelly, gummy, tablet confectionery, etc.), noodles (buckwheat noodles, udon noodles, ramen, etc.), dairy products (milk, ice cream, yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, black tea, tea, carbonated beverage, sports drink, etc.), health foods (tablets, capsules, etc.), and dietary supplements (nutritional drinks, etc.). The AGE production inhibitor of the present invention may be appropriately blended into these foods and drinks.

[0064] These food and beverage products can be formulated with various ingredients depending on their type. 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 ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, gum arabic, carrageenan, casein, gelatin, pectin, agar, vitamin Bs, nicotinamide, calcium pantothenate, amino acids, calcium salts, pigments, flavors, preservatives and other food materials can be used. Furthermore, in this AGE production inhibitor with health maintenance function, other antioxidant substances and health food materials, such as reduced ascorbic acid (vitamin C), vitamin E, reduced glutathione, tocotrienol, vitamin A derivative, lycopene, β-cryptoxanthin, astaxanthin, zeaxanthin, fucoxanthin, uric acid, ubiquinone, coenzyme Q10, folic acid, garlic extract, allicin, sesamin, lignans, catechin, isoflavone, chalcone, tannins, flavonoids, coumarin, isocoumarins, blueberry extract, health food materials) V. (vitamin) A, V.B1, V.B2, V.B6, V.B12, V.C, V.D, V.E, V.P, choline, niacin, pantothenic acid, calcium folate, EPA, oligosaccharide, dietary fiber, squalene, soy lecithin, taurine, dunaliella, protein, octacosanol, DHA, egg yolk lecithin, linoleic acid, lactoferrin, magnesium, zinc, chromium, selenium, potassium, heme iron, oyster meat extract, chitosan, chitooligosaccharide, collagen, chondroitin, elastin, turmeric, licorice, kudzu, cinnamon, Japanese quince, ginger, Ganoderma lucidum, clam extract, suppon, licorice, kudzu, cinnamon, Western, Japanese quince, ginger, Ganoderma lucidum, mulberry, chamomile, camomile, dandelion, hibiscus, honey, boren, royal jelly, lime, lavender, rose hip, rosemary, sage, bifidobacterium, faecalibacterium, lactris, wheat germ oil, sesame oil, perilla oil, soybean oil, medium-chain fatty acids, agaricus, ginkgo leaf extract,Chondroitin, germinated brown rice extract, jujube, onion, DHA, EPA, DPA, sweet tea, Cordyceps sinensis, garlic, bee pupa, papaya, propolis, magnolia officinalis, Grifola frondosa, royal jelly, coconut, hyaluronic acid, GABA, harp seal oil, shark cartilage, glucosamine, lecithin, phosphatidylserine, Panax japonicus Torr., mulberry leaves, soybean extract, Echinacea purpurea, Aralia elata, barley extract, olive leaves, olive fruits, Gymnema sylvestre, banaba, Salacia oblonga, Garcinia cambogia, chitosan, St. John's wort, Chinese date, carrot, passionflower, broccoli, placenta, coix seed, grape seeds, peanut skins, bilberry, black cohosh, Saussurea medusa, laurel, sage, rosemary, Rhaponticum uniflorum, black vinegar, bitter melon, maca, safflower, flax, oolong tea, Flos Carthami, caffeine, capsaicin, xylo-oligosaccharide, glucosamine, buckwheat, citrus, dietary fiber, protein, prune, spirulina, young barley leaves, nucleic acid, yeast, shiitake mushroom, ume flesh, amino acid, deep-sea shark extract, noni, oyster meat, loach, champignon, burdock, Acerola, pineapple, banana, peach, apricot, melon, strawberry, raspberry, orange, fucoidan, Ganoderma lucidum, cranberry, zinc, iron, silk peptide, glycine, niacin, chestnut tree, ceramide, L-cysteine, red wine juice, millet, horsetail, biotin, Centella asiatica, blueberry, picnogenol, sea mustard, rhubarb, clove, propolis, citric acid, brewer's yeast, melilot, black ginger, ginger, Curcuma longa, nattokinase, Monascus purpureus Went., tocotrienol, lactoferrin, buckwheat noodles, cocoa, Houttuynia cordata Thunb., kiwi, Actinidia polygama, lotus leaf, Poria cocos, star fruit, etc. can also be formulated.

[0065] As a specific manufacturing method, the above-mentioned active ingredients can be spray-dried or freeze-dried together with powdered cellulose, and can be easily incorporated into food and drink products (such as instant foods) by making them into powders, granules, tablets or solutions. In addition, the above-mentioned active ingredient can be dissolved in, for example, fats and oils, ethanol, glycerin or a mixture thereof to make it liquid, and added to beverages or solid foods. If necessary, it can be mixed with binders such as gum arabic and dextrin to make it powdery or granular, and then added to beverages or solid foods.

[0066] When applying the AGE production inhibitor and AGE decomposition accelerator of the present invention to food and beverages, the addition amount is preferably such that the total content of the active ingredient is 1 to 20 wt% or less with respect to the food and beverages, since the main purposes are disease prevention and health maintenance.

[0067] The AGE production inhibitor and AGE decomposition accelerator of the present invention may be used as a raw material for drugs (including pharmaceuticals and quasi-drugs). The AGE production inhibitor and AGE decomposition accelerator of the present invention can be appropriately formulated with raw materials for drug preparations for production. Examples of formulation raw materials that can be formulated with the AGE production inhibitor and AGE decomposition accelerator of the present invention include excipients (such as glucose, lactose, sucrose, sodium chloride, starch, calcium carbonate, kaolin, crystalline cellulose, cacao butter, hardened vegetable oil, kaolin, talc, etc.), binders (such as distilled water, physiological saline, ethanol water, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrants (such as sodium alginate, agar, sodium hydrogen carbonate, calcium carbonate, sodium lauryl sulfate, monoglyceride stearate, starch, lactose, powdered gum arabic, gelatin, ethanol, etc.), disintegration inhibitors (such as sucrose, stearin, cacao butter, hydrogenated oil, etc.), absorption promoters (such as quaternary ammonium base, sodium lauryl sulfate, etc.), adsorbents (such as glycerin, starch, lactose, kaolin, bentonite, silicic acid, etc.), lubricants (such as purified talc, stearate, polyethylene glycol, etc.).

[0068] The administration method of the AGE production inhibitor and AGE degradation promoter according to the present invention can generally be orally administered in the form of tablets, pills, soft and hard capsules, fine granules, powders, granules, liquid preparations, etc., but parenteral administration may also be possible. When administered as a parenteral preparation, it can be applied in dosage forms such as suppositories, lotions, ointments, tinctures, creams, etc. in a solution state or with the addition of dispersants, suspending agents, stabilizers, etc.

[0069] The dosage can vary depending on the administration method, disease condition, patient's age, etc. In adults, usually 1 to 1000 mg as the active ingredient per day can be administered, and in children, usually about 0.5 to 500 mg can be administered. The mixing ratio of the AGE production inhibitor and AGE degradation promoter can be appropriately changed depending on the dosage form. Usually, when administered orally or by mucosal absorption, it is about 0.3 to 15.0 wt%, and when administered parenterally, it is preferably about 0.01 to 10 wt%. Note that since the dosage varies under various conditions, there may be cases where an amount less than the above dosage is sufficient, and there may also be cases where it is necessary to administer beyond the range.

[0070] Examples of the forms of the external skin preparations containing the AGE production inhibitor and AGE degradation promoter of the present invention include emulsions, soaps, facial cleansers, bath agents, creams, emulsions, lotions, colognes, beard shaving creams, beard shaving lotions, makeup oils, sunburn and sunblock lotions, face powders, foundations, perfumes, packs, nail creams, enamels, enamel removers, eyebrow pencils, blushes, eye creams, eye shadows, mascaras, eyeliners, lipsticks, lip creams, shampoos, rinses, treatments, hair dyes, dispersions, cleaning agents, etc. Also, examples of the forms of the pharmaceuticals or quasi-drugs containing the AGE production inhibitor and AGE degradation promoter of the present invention include ointments, creams, external liquid preparations, etc.

[0071] In addition to the AGE production inhibitor and AGE degradation promoter according to the present invention, the skin preparation for external use of the above form may contain components, oils, higher alcohols, fatty acids, ultraviolet absorbers, powders, pigments, surfactants, polyhydric alcohols / sugars, polymers, physiologically active components, solvents, antioxidants, fragrances, preservatives, etc. that are formulated in skin preparations for external use such as cosmetics and quasi-drugs as long as their AGE production inhibitory effect and AGE degradation promoting effect are not impaired. 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, isoaralkyl neopentanoate, glyceryl tri(caprylic / capric acid), trimethylolpropane tri(2-ethylhexanoate), trimethylolpropane triisostearate, pentaerythritol tetra(2-ethylhexanoate), cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinoleate, isostearyl laurate, isotridecyl myristate, isocetyl myristate, 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, propylene glycol di(caprylic / capric acid), propylene glycol dicaprylate, neopentyl glycol dicaprylate, 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, octyldodecyl isostearate, polyglyceryl oleate, polyglyceryl isostearate, dipropyl carbonate,Dialkyl (C12-18) carbonates, tricisocetyl citrate, triisoarachidyl citrate, triisooctyl citrate, 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, isostearyl 12-stearoylhydroxystearate, etc. Hydrocarbon-based oil phase component : 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 waxes of natural origin: Animal oils such as beef tallow, hydrogenated beef tallow, lard, hydrogenated lard, horse oil, hydrogenated horse oil, mink oil, orange raffia oil, fish oil, hydrogenated fish oil, egg yolk oil and their hydrogenated oils, vegetable oils such as avocado oil, almond oil, olive oil, cocoa butter, 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, hydrogenated rapeseed oil, palm kernel oil, hydrogenated palm kernel oil, palm oil, hydrogenated palm oil, peanut oil, hydrogenated peanut oil, castor oil, hydrogenated castor oil, sunflower oil, grape seed oil, jojoba oil, hydrogenated jojoba oil, macadamia nut oil, meadowfoam oil, cottonseed oil, hydrogenated cottonseed oil, coconut oil, hydrogenated coconut oil and their hydrogenated oils, waxes such as beeswax, high acid value beeswax, lanolin, reduced lanolin, hydrogenated lanolin, liquid lanolin, carnauba wax, montan wax, etc. Silicone-based oil phase component: Dimethylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, methylhydrogenpolysiloxane, polyether-modified organopolysiloxane, dimethylsiloxane·methyl cetyloxysiloxane copolymer, dimethylsiloxane·methyl stearoxysiloxane copolymer, alkyl-modified organopolysiloxane, end-modified organopolysiloxane, amino-modified silicone oil, amino-modified organopolysiloxane, dimethiconol, silicone gel, acrylic silicone, trimethylsiloxysilicic acid, silicone RTV rubber, etc. Fluorine-based oil phase components: Perfluoropolyether, fluorine-modified organopolysiloxane, fluorinated pitch, fluorocarbon, fluoroalcohol, fluoroalkyl·polyoxyalkylene copolymer-modified organopolysiloxane, etc. (2) Examples of higher alcohols Lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, behenyl alcohol, 2-ethylhexanol, hexadecyl alcohol, octyldodecanol, etc. (3) Examples of fatty acids 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, 2-ethylhexanoic acid, etc. (4) Examples of ultraviolet absorbers Para - aminobenzoic acid, amyl para - aminobenzoate, ethyl dihydroxypropyl 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 paramethoxycinnamate, 2 - ethylhexyl paramethoxycinnamate, glyceryl diparamethoxycinnamate mono - 2 - ethylhexanoate, isopropyl paramethoxycinnamate, diethanolamine salt of paramethoxyhydroxycinnamic acid, diisopropyl · diisopropyl cinnamate ester mixture, urocanic acid, ethyl urocanic acid, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and its salts, dihydroxymethoxybenzophenone, 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 sulfonic acid, 3 - (4 - methylbenzylidene) camphor, isopropyldibenzoylmethane, 2 - ethylhexyl 4 - (3,4 - dimethoxyphenylmethylene) - 2,5 - dioxo - 1 - imidazolidinepropionate, and the like, and their polymer derivatives, silane derivatives, etc. (5) Examples of powders and pigments Dyes such as Red No. 104, Red No. 201, Yellow No. 4, Blue No. 1, Black No. 401, etc., Lake dyes such as Yellow No. 4 AL Lake, Yellow No. 203 BA Lake, etc., Nylon powder, Silk powder, Urethane powder, Teflon (registered trademark) powder, Silicone powder, Methyl polymethacrylate powder, Cellulose powder, Starch, Spherical powder of silicone elastomer, Polymers such as polyethylene powder, Colored pigments such as Yellow iron oxide, Red iron oxide, Black iron oxide, Chromium oxide, Carbon black, Ultramarine, Prussian blue, etc., White pigments such as Zinc oxide, Titanium oxide, Cerium oxide, etc., Extender pigments such as Talc, Mica, Sericite, Kaolin, Plate-shaped barium sulfate, etc., Pearl pigments such as Mica titanium, Metal salts such as Barium sulfate, Calcium carbonate, Magnesium carbonate, Aluminum silicate, Magnesium silicate, etc., Inorganic powders such as Silica, Alumina, etc., Metal soaps such as Aluminum stearate, Magnesium stearate, Zinc palmitate, Zinc myristate, Magnesium myristate, Zinc laurate, Zinc undecylenate, etc., Bentonite, Smeetite, Boron nitride, etc. There are no particular restrictions on the shape (spherical, rod-shaped, needle-shaped, plate-shaped, irregular shape, flaky, spindle-shaped, etc.) and particle diameter 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-acylation 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 surfactant : Fatty acid soaps, α-acyl sulfonates, Alkyl sulfonates, Alkyl allyl sulfonates, Alkyl naphthalene sulfonates, Alkyl sulfates, POE alkyl ether sulfates, Alkyl amide sulfates, Alkyl phosphates, POE alkyl phosphates, Alkyl amide phosphates, Alkyloyl alkyl taurates, N-acyl amino acid salts, POE alkyl ether carboxylates, Alkyl sulfosuccinates, Sodium alkyl sulfacetate, Acylated hydrolyzed collagen peptide salts, Perfluoroalkyl phosphate esters, etc. Cationic surfactant : Examples include alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, benzalkonium chloride, behenamidopropyldimethylhydroxypropylammonium chloride, diethylaminoethylamide stearate, dimethylaminopropylamide stearate, lanolin derivative quaternary ammonium salts, etc. Amphoteric surfactant : Examples include carboxybetaine type, amidobetaine type, sulfobetaine type, hydroxysulfobetaine type, amidosulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, amidoamine type, etc. Nonionic surfactant : Examples include 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 alkyl ether, POE fatty acid ester, POE hydrogenated castor oil, POE castor oil, POE·POP copolymer, POE·POP alkyl ether, polyether-modified silicone, alkanolamide laurate, alkylamine oxide, hydrogenated soy phospholipid, etc. Natural surfactant : Examples include lecithin, saponin, sugar-based surfactants, etc. (7) Examples of polyhydric alcohols and sugars Examples include ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, 3-methyl-1,3-butanediol, 1,3-butylene glycol, sorbitol, mannitol, raffinose, erythritol, glucose, sucrose, fructose, xylitol, lactose, maltose, maltitol, trehalose, alkylated trehalose, mixed isomerized sugars, sulfated trehalose, pullulan, etc. Further, chemical modified products thereof and the like can also be used. (8) Examples of polymers Acrylic acid ester / methacrylic acid ester copolymer (plus size, manufactured by Gohsei Chemical Industry Co., Ltd.), vinyl acetate / crotonic acid copolymer (Resin 28-1310, manufactured by NSC), vinyl acetate / crotonic acid / vinyl neodecanoate 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 (Lubimer, manufactured by BASF), vinyl pyrrolidone / vinyl acetate / vinyl propionate copolymer (Lubrisol VAP, manufactured by BASF), vinyl acetate / crotonic acid copolymer (Lubset CA, manufactured by BASF), vinyl acetate / crotonic acid / vinyl pyrrolidone copolymer (Lubset CAP, manufactured by BASF), vinyl pyrrolidone / acrylate copolymer (Lubiflex, manufactured by BASF), acrylate / acrylic amide copolymer (Ultrahold, manufactured by BASF), vinyl acetate / butyl maleate / isobornyl acrylate copolymer (Advantage, manufactured by ISP), anionic polymer compounds such as carboxyvinyl polymer (Carbopol, manufactured by BFGoodrich), acrylic acid / methacrylic acid alkyl copolymer (Pemulen, manufactured by BFGoodrich), etc., amphoteric polymer compounds such as amphoteric acetate of dialkylaminoethyl methacrylate polymer (Yukafoamer, manufactured by Mitsubishi Chemical), octyl acrylamide / acrylic acid / hydroxypropyl methacrylate / butylaminoethyl methacrylate copolymer (AMPHOMER, manufactured by NSC), etc., cationic polymer compounds such as quaternized product of vinyl pyrrolidone / dimethylaminoethyl methacrylate (GAFQUAT, manufactured by ISP), methyl vinyl imidazolium chloride / vinyl pyrrolidone copolymer (Lubricote, manufactured by BASF), etc., nonionic polymer compounds such as polyvinyl pyrrolidone (Lubrisol K, manufactured by BASF), vinyl pyrrolidone / vinyl acetate copolymer (Lubrisol VA, manufactured by BASF), vinyl pyrrolidone / dimethylaminoethyl methacrylate copolymer (Copolymer 937, manufactured by ISP), vinyl caprolactam / vinyl pyrrolidone / dimethylaminoethyl methacrylate copolymer (Copolymer VC713, manufactured by ISP), etc.In addition, natural polymer compounds such as cellulose or its derivatives, keratin, collagen or its derivatives, calcium alginate, pullulan, agar, gelatin, tamarind seed polysaccharide, 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, dextran, etc. can also be preferably used. (9) Examples of physiologically active ingredients Examples of physiologically active ingredients include substances that impart some physiological activity to the skin when applied thereto. For example, whitening agents, anti-inflammatory agents, anti-aging agents, UV protectants, slimming agents, tightening agents, antioxidants, hair growth stimulants, hair tonics, moisturizers, blood circulation promoters, antibacterial agents, germicides, desiccants, cooling agents, warming agents, vitamins, amino acids, wound healing promoters, irritation relievers, analgesics, cell activators, enzyme components, and the like. Examples of these preferred compounding ingredients include, for example, ashitaba extract, avocado extract, amacha extract, hollyhock extract, arnica extract, aloe extract, apricot extract, apricot kernel extract, ginkgo extract, perilla extract, turmeric extract, oolong tea extract, polygonatum extract, etinashi leaf extract, saffron extract, peony extract, cinnamon extract, barley extract, speedwell extract, chinese speedwell extract, horseradish extract, orange extract, seawater dried product, seaweed extract, hydrolyzed elastin, hydrolyzed wheat flour, hydrolyzed silk, chamomile extract, carrot extract, mugwort extract, licorice extract, calceolaria extract, kakyo extract, kiwi extract, quinine extract, cucurbit extract, guanosine, gardenia extract, kumasasa extract, clara extract, walnut extract, grapefruit extract, clematis extract, chlorella extract, mulberry extract, gentiana extract, black tea extract, yeast extract, burdock extract, rice bran fermented extract, rice germ oil, comfrey extract, collagen, loquat extract, saikosaponin extract, cyperus extract, sage extract, sasa extract, japanese medlar extract, sansho extract, shiitake extract, rhubarb extract, shikon extract, perilla extract, cinnamomum extract, meadowsweet extract, safflower extract, licorice root extract, white birch extract, japanese pimpernel extract, chinese gentian extract, schizonepeta extract, glycyrrhiza glabra extract, acanthopanax extract, thyme extract, mugwort extract, tea extract, clove extract, chigaya extract, chimpi extract, ligusticum extract, lilium lancifolium extract, torreya nucifera extract, houttuynia cordata extract, tomato extract, natto extract, carrot extract, garlic extract, rosa multiflora extract, hibiscus extract,Examples include Bacopa monnieri extract, parsley extract, honey, witch hazel extract, Parietaria judaica extract, Hordeum vulgare extract, bisabolol, loquat extract, Sonchus oleraceus extract, Petasites japonicus extract, Buchloe dactyloides extract, Butcher's broom extract, grape extract, propolis, Luffa cylindrica extract, safflower extract, peppermint extract, Ficus carica extract, button extract, hop extract, pine extract, elm extract, Peltiphyllum peltatum extract, Diospyros kaki extract, Melissa officinalis extract, peach extract, Tagetes patula extract, eucalyptus extract, Saxifraga stolonifera extract, Cnidium officinale extract, mugwort extract, lavender extract, apple extract, lettuce extract, lemon extract, Aster ageratoides extract, rose extract, rosemary extract, Roman chamomile extract, royal jelly extract, strawberry extract, Stellaria media extract, lotus leaf extract, papaya extract, star fruit extract, etc. In addition, biopolymers such as deoxyribonucleic acid, mucopolysaccharides, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, hydrolyzed eggshell membrane, amino acids, hydrolyzed peptides, moisturizing components such as sodium lactate, urea, sodium pyrrolidonecarboxylate, betaine, whey, trimethylglycine, oily components such as sphingolipids, ceramides, phytosphingosine, cholesterol, cholesterol derivatives, phospholipids, anti-inflammatory agents such as ε-aminocaproic acid, glycyrrhizic acid, β-glycyrrhetinic acid, lysozyme chloride, guaiazulene, hydrocortisone, 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, carotenoid, flavonoid, tannin, lignan, saponin, cell activators such as α-hydroxy acid, β-hydroxy acid, blood circulation promoters such as γ-oryzanol, vitamin E derivatives, wound healing agents such as retinol, retinol derivatives, whitening agents such as arbutin, kojic acid, placenta extract, sulfur, ellagic acid, linoleic acid, tranexamic acid, glutathione, cepharanthine, licorice extract, capsicum tincture, hinokitiol, garlic iodide extract, pyridoxine hydrochloride, DL-α-tocopherol, DL-α-tocopherol acetate, nicotinic acid, nicotinic acid derivatives, calcium pantothenate, D-pantothenyl alcohol, acetylpantothenyl ethyl ether, biotin, allantoin, isopropylmethylphenol, estradiol, ethinyl estradiol, capronium chloride, benzalkonium chloride, diphenhydramine hydrochloride, takanal, camphor, salicylic acid, nonyl vanillylamide, nonanoic acid vanillylamide, piroctone olamine, glyceryl pentadecanoate, L-menthol, mononitroguaiacol, resorcinol, γ-aminobutyric acid, benzethonium chloride, mexiletine hydrochloride, auxin, female hormones, cantharis tincture, cyclosporine, zinc pyrithione, hydrocortisone, minoxidil, polyoxyethylene sorbitan monostearate, peppermint oil,Examples of hair growth agents include Sasanishiki extract and the like. (10) Examples of antioxidants Sodium bisulfite, sodium sulfite, erythorbic acid, sodium erythorbate, dilauryl thiodipropionate, tocopherol, tolbiguanide, nordihydroguaiaretic acid, para-hydroxyanisole, butylhydroxyanisole, dibutylhydroxytoluene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, carotenoids, flavonoids, tannins, lignans, saponins, and plant extracts such as apple extract and clove extract that exhibit antioxidant effects. (11) Examples of solvents Purified water, ethanol, lower alcohols, ethers, LPG, fluorocarbons, N-methylpyrrolidone, fluoroalcohols, volatile linear silicones, next-generation chlorofluorocarbons, etc.

Examples

[0072] Hereinafter, examples of the present invention will be described. The examples shown below are for confirming the AGE production inhibitory action and the like of the composition obtained by the present invention, and the scope of the present invention is not limited to these products and manufacturing methods.

[0073] Examples 1. Production of camellia extract The dried camellia flowers were crushed with a mill and then immersed in 100 times the amount (v / w) of water, stirred at room temperature (20 - 30 °C) for 15 hours for extraction. Then, suction filtration was performed, and the filtrate was concentrated under reduced pressure (dried to dryness) using a rotary evaporator to obtain a camellia extract.

[0074] 2. Production of chrysanthemum flower extract The flowers of Chrysanthemum morifolium (scientific name: Chrysanthemum morifolium) were extracted with 75 wt% aqueous ethanol, and resin column chromatography was used on this extract to obtain fractions of 30 wt%, 75 wt%, and 100 wt% ethanol. Spray drying was performed on each fraction, and then each fraction powder was obtained. Then, the fraction powders were mixed so that the luteolin content became 20 wt%, and the chrysanthemum flower extract of this example was obtained.

[0075] 3. Production of cherry blossom extract The flower parts of Prunus lannesiana Wils. cv. Sekiyama were extracted with 30% (W / W) aqueous ethanol for 1 hour (60 °C). Then, filtration and concentration were performed to obtain a cherry blossom extract.

[0076] 4. Isolation of caffeoylglucose and quercetin glucoside from cherry blossom extract The above-mentioned cherry blossom extract (90.10 g) was subjected to HP-20 (manufactured by Mitsubishi Chemical Corporation) column chromatography, and an elution part with water (H2O) (62.16 g, 68.99%), an elution part with methanol (MeOH) (28.21 g, 31.31%), and an elution part with acetone (Acetone) (0.60 g, 0.67%) were obtained. The obtained elution part with methanol (MeOH) (26.00 g) was repeatedly separated and purified using normal-phase silica gel chromatography, reverse-phase ODS column chromatography, and HPLC to isolate caffeoylglucose (8.73 g, 9.6%) and quercetin glucoside (86.0 mg, 0.0954%). These known compounds were identified by comparing 1H-NMR, 13C-NMR, MS spectral data, and specific rotation values with literature values.

[0077] 5. Production of purple tea extract 50 g of purple tea was immersed in 500 mL of 50% ethanol aqueous solution, and extracted by heating under reflux at 40 °C for 2 hours while stirring. Then, 400 mL of the extract was obtained by suction filtration. After that, the extract was concentrated and dried to obtain 16.6 g of purple tea extract.

[0078] 6. Isolation of 1,2-di-Galloyl-4,6-Hexahydroxydiphenoyl-β-D-Glucose (GHG) from Purple Tea Extract When HPLC analysis was performed on the purple tea extract under the following conditions, a peak of a specific component unique to the purple tea extract that is not contained in common teas such as green tea, oolong tea, and black tea was confirmed at the 27.5 min mark. Sample preparation: 350 mg of purple tea extract was dissolved in 30% methanol aqueous solution and made up to 20 mL in a volumetric flask. The solution was diluted 2-fold, and after filter filtration, HPLC analysis was performed. The analysis conditions for HPLC are as follows. HPLC Analysis Conditions Flow rate: 0.7 mL / min Mobile phase A: 0.3% TFA aqueous solution Mobile phase B: Acetonitrile Gradient: As shown in Table 1 below Column: SunFire C18, 4.6×150 mm (Waters) or equivalent Column temperature: 30 °C Sample injection volume: 10 μL Detection wavelength: 280 nm

[0079]

Table 1

[0080] The above-mentioned specific component was separated and purified and subjected to NMR analysis. As a result, it was identified as GHG. 7. Production of Walnut Extract The seed coat of walnut was extracted by stirring with 50% ethanol (50 °C, 1 hour). Then, filtration was performed, and the obtained extract was concentrated and dried to obtain a powder of walnut extract. 8. Production of Lychee Seed Extract The lychee seeds were subjected to stirring extraction with 40% ethanol (75 °C, 4 hours). Subsequently, the obtained extract was concentrated and dried to obtain a powder of the lychee seed extract.

[0081] 9. Preparation of delphinidin-3,5-O-diglucoside Delphinidin-3,5-O-diglucoside was isolated and purified from the Vaccinium macrocarpon extract-P35 manufactured by Oriza Oils & Fats Co., Ltd. The method of isolation and purification was as follows: Vaccinium macrocarpon extract-P35 (0.25 g / 5 ml) was filtered through a cotton plug and then passed through an ODS Sep-Pak (manufactured by Waters). Then, isolation and purification were carried out by preparative HPLC. The conditions were as follows. Mobile phase: 25% MeOH 0.3% TFA UV: 520 nm Flow rate: 9.0 ml / min Column: Inertsil PREP-ODS 20×250 mm

[0082] As a result of isolating and purifying the components of Vaccinium macrocarpon extract-P35, 6.3 mg of delphinidin-3,5-O-diglucoside (Fr.2) could be isolated. Its purity was 95% or higher.

[0083] 10. Manufacture of Ampelopsis grossedentata extract 500 g of the coarsely ground product of dried Ampelopsis grossedentata branches and leaves was put into 5 liters of water and extracted under reflux heating for 4 hours. Subsequently, the obtained extract was filtered and concentrated under reduced pressure to obtain a paste-like substance, which was freeze-dried to obtain 97 g of a powdered extract.

[0084] 11. Regarding other extracts In this example, as the goji berry extract, Goji Berry Extract-P35 manufactured by Oriza Oil & Fat Co., Ltd. was used. Also, as the lingonberry extract, Lingonberry Extract-J manufactured by Oriza Oil & Fat Co., Ltd. was used. Furthermore, as the evening primrose extract (1), Evening Primrose Extract-P manufactured by Oriza Oil & Fat Co., Ltd. was used, and as the evening primrose extract (2), Evening Primrose Extract-WSPS manufactured by Oriza Oil & Fat Co., Ltd. was used. Also, as the pomegranate flower extract, pomegranate flower extract powder manufactured by Koei Kogyo Co., Ltd. was used, and as the water chestnut extract, water chestnut extract manufactured by Hayashi Kankosan Co., Ltd. was used. As the mangosteen extract, Mangostin Aqua manufactured by Nippon Shinyaku Co., Ltd. was used.

[0085] Test Example 1: Evaluation (screening) of the AGE production inhibitory effect in the extracts of the examples To a phosphate buffer solution (pH: 7.4, 900 μL) containing D-glucose (10%) and bovine serum albumin (fraction 5, 1%), a sample solution (100 μL) was added and allowed to stand at 60 °C for 2 days. The reaction solution was diluted with purified water so that the fluorescence intensity was around 500, and the fluorescence intensity (measurement wavelength: 360 nm, excitation wavelength: 460 nm) was measured. Note that the sample was dissolved in DMSO and diluted with a phosphate buffer solution so that the final DMSO concentration was 1% before use. Also, for the purpose of screening the AGE production inhibitory effect of each specimen, the evaluation concentration of the specimen was set to only "300 μg / mL". The results are shown in Table 1 below. Note that aminoguanidine hydrochloride (Fuji Film Wako Chemical Co., Ltd.), which is known to have an AGEs production inhibitory effect, was used in the control group.

[0086]

Table 2

[0087] Results and effects of the examples in Test Example 1 As shown in Table 2, the chrysanthemum flower extract, camellia flower extract, purple tea extract, walnut extract, maqui berry extract, evening primrose extract (2), pomegranate flower extract, and buckwheat extract showed higher activity than aminoguanidine hydrochloride in the control group. Therefore, it was confirmed that these have an effect as AGE production inhibitors. Also, the maqui berry extract, pomegranate flower extract, buckwheat extract, and purple tea extract were highly active in that order. Furthermore, the cherry blossom extract and lingonberry extract had an activity about 80% of that of aminoguanidine hydrochloride, and it was confirmed that these can also be used as AGE production inhibitors.

[0088] Test Example 2: Evaluation of the AGE production inhibitory effect when changing the concentration in the extract of the example A sample solution (100 μL) was added to a phosphate buffer (pH: 7.4, 900 μL) containing D-glucose (10%) and bovine serum albumin (fraction 5, 1%), and the mixture was allowed to stand at 60°C for 2 days. The reaction solution was diluted with purified water so that the fluorescence intensity was around 500, and the fluorescence intensity (measurement wavelength: 360 nm, excitation wavelength: 460 nm) was measured. The sample solution was dissolved in DMSO and then diluted with a phosphate buffer so that the final DMSO concentration was 1% before use. In addition, for the control group, a similar test was conducted using aminoguanidine hydrochloride (FUJIFILM Wako Pure Chemical Corporation). The results are shown in Table 2 and Table 3.

[0089]

Table 3

[0090]

Table 4

[0091] Results and effects of the examples in Test Example 2 As shown in Table 3 above, the camellia extract exhibited concentration-dependent inhibitory activity, and at all concentrations of "3 to 300 μg / mL", its activity was as high as that of aminoguanidine hydrochloride, which was the control group. Thereby, it was confirmed that the camellia extract is useful as an AGE production inhibitor. Also, as shown in Table 4 above, the cherry flower extract and the ampelopsis grossedentata extract showed concentration-dependent inhibitory activity at "3 to 300 μg / mL", and in the low concentration range of "3 to 100 μg / mL", their activity was higher than that of aminoguanidine hydrochloride in the control group. The chrysanthemum flower extract showed concentration-dependent inhibitory activity at "10 to 300 μg / mL", and its activity was higher than that of aminoguanidine hydrochloride. The maqui berry extract showed concentration-dependent inhibitory activity, and in the high concentration range of "100 to 300 μg / mL", its activity was higher than that of aminoguanidine hydrochloride. The purple tea extract, the yam extract, and the mangostin extract also had concentration-dependent inhibitory activity. From the above, it was confirmed that these extracts are useful as AGE production inhibitors.

[0092] Test Example 3: Evaluation of AGE degradation promoting effect (1) Test method Since N-phenacylthiazolium bromide (PTB) has been reported as a compound that decomposes the cross-linked structure of AGE, PTB was used as the positive reaction target. For the measurement of the AGE degradation effect, the sample solution or 10 mM PTB, 10 mM PPD, and 0.2 mol / L phosphate buffer (PH = 7.4) were mixed at a ratio of 5:1:4 and reacted at 37°C for 48 hours (n = 3). After the reaction was completed, 200 μl of 2M hydrochloric acid was added to stop the reaction. After the reaction, centrifugation was performed at 10,000 rpm for 2 minutes, and benzoic acid in the supernatant was analyzed by reverse-phase HPLC. The amount of benzoic acid in the reaction solution was determined by subtracting the amount of benzoic acid in the separately measured sample. Since 1 mol of PPD produces 1 mol of benzoic acid, the cross-link cleavage rate was calculated by the following formula. The relative value of cross-link cleavage was determined when the cross-link cleavage rate of PTB was set to 100. · Crosslinking cleavage rate (%) = {(A - B) / C} * 100 (A: Amount of benzoic acid during reaction, B: Amount of benzoic acid in sample, C: Amount of PPD used in reaction) · Mobile phase: 0.2% acetic acid: acetonitrile + EDTA (2 mM) = 70:30 · Flow rate: 1 ml / min · Column temperature: 40 °C · Detection wavelength: 270 nm · Sample injection volume: 20 μl The results are shown in Table 4 below.

[0093]

Table 5

[0094] (2) Results and effects of the examples in Test Example 3 As shown in Table 5 above, in the plant extract group, it was confirmed that Ampelopsis grossedentata extract, cherry blossom extract, litchi seed extract, purple tea extract, evening primrose extract (1), buckwheat extract, and blackcurrant extract have an AGE degradation promoting effect. In particular, it was confirmed that the groups added with Ampelopsis grossedentata extract, purple tea extract, and buckwheat extract have a stronger AGE degradation promoting effect than PTB, which is the positive control, in a concentration-dependent manner. Also, in the group of compounds contained in these, it was confirmed that the groups added with 1,2-di-Galloyl-4,6-Hexahydroxydiphenoyl-β-D-Glucose (GHG), delphinidin-3,5-O-diglucoside, caffeoyl glucose, and quercetin glucoside have an AGE degradation promoting effect. In particular, it was confirmed that the groups added with GHG and delphinidin-3,5-O-diglucoside have a stronger AGE degradation promoting effect than PTB, which is the positive control. Therefore, it was confirmed that these are useful as AGE degradation promoters.

[0095] Formulation examples of the AGE production inhibitor according to the present invention are shown. Note that in the following formulation examples, an AGE degradation promoter may be formulated instead of the AGE production inhibitor. Formulation example 1: Chewing gum Sugar 53.0 wt% Gum base 20.0 Glucose 10.0 Maltose 16.0 Flavor 0.5 AGE production inhibitor 0.5 100.0 wt%

[0096] Formulation Example 2: Gummy Candy Reduced maltose 40.0 wt% Granulated sugar 20.0 Glucose 20.0 Gelatin 4.7 Water 9.68 Yuzu juice 4.0 Yuzu flavor 0.6 Dye 0.02 AGE production inhibitor 1.0 100.0 wt%

[0097] Formulation Example 3: Candy Sugar 50.0 wt% Maltose 33.0 Water 14.4 Organic acid 2.0 Flavor 0.2 AGE production inhibitor 0.4 100.0 wt%

[0098] 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 AGE production inhibitor 0.4 Flavor trace Water remainder 100.0 wt%

[0099] Formulation Example 5: Soft Drink Fructose - glucose liquid sugar 30.0 wt% Emulsifier 0.5 AGE production inhibitor 0.3 Fragrance appropriate amount Purified water remainder 100.0wt%

[0100] Formulation Example 6: Tablet confectionery Sugar 76.4wt% Glucose 19.0 Sucrose fatty acid ester 0.2 AGE production inhibitor 0.5 Purified water 3.9 100.0wt%

[0101] Formulation Example 7: Soft capsule Brown rice germ oil 47.0wt% Yuzu seed oil 40.0 Emulsifier 12.0 AGE production inhibitor 1.0 100.0wt%

[0102] Formulation Example 8: Tablet Lactose 54.0wt% Crystalline cellulose 30.0 Starch hydrolyzate 10.0 Glycerin fatty acid ester 5.0 AGE production inhibitor 1.0 100.0wt%

[0103] Formulation Example 9: Cosmetic cream Squalane 20.0wt% Beeswax 5.0 Refined jojoba oil 5.0 Glycerin 5.0 Glycerin monostearate 2.0 Polyoxyethylene (20) sorbitan· Monostearate 2.0 AGE production inhibitor 2.0 Preservative appropriate amount Fragrance appropriate amount Purified water remainder 100.0wt%

[0104] 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 AGE Production Inhibitor 0.1 Purified water remainder 100.0 wt%

[0105] 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 Tetraoleate 2.0 Hydrogenated Soybean Phospholipid 1.0 Ceramide 0.1 Retinol Palmitate 0.1 Preservative Appropriate amount Tsubokusa Extract 1.0 AGE Production Inhibitor 1.0 1,3-Butylene Glycol 5.0 Purified water remainder 100.0 wt%

[0106] Formulation Example 12: Emulsion Squalane 4.0 wt% Petrolatum 2.5 Cetanol 2.0 Glycerin 2.0 Lipophilic Glyceryl Monostearate 1.0 Stearic Acid 1.0 L-Arginine 1.0 AGE production inhibitor 0.5 Potassium hydroxide 0.1 Fragrance trace Purified water remainder 100.0wt%

[0107] Formulation Example 13: Bath agent (liquid) Propylene glycol 50.0wt% Ethanol 20.0 Sodium sulfate 5.0 AGE production inhibitor 0.5 Lanolin 0.5 Avocado oil 0.5 Dye 1.5 Fragrance 22.0 100.0wt%

Industrial Applicability

[0108] As described above, the present invention can provide a novel AGE production inhibitor and an AGE degradation accelerator.

Claims

1. An AGE production inhibitor comprising at least one of a cherry extract, a bilberry extract, a purple tea extract, a walnut extract, an evening primrose extract, a pomegranate extract, a buckwheat extract, a lingonberry extract, a lychee extract, a mangosteen extract, and a rattan tea extract as an active ingredient.

2. An AGE degradation promoter comprising at least one of a cherry extract, a lychee extract, caffeoyl glucose, a purple tea extract, quercetin glucoside, 1,2-di-Galloyl-4,6-Hexahydroxydiphenoyl-β-D-Glucose (GHG), an evening primrose extract, a buckwheat extract, a bilberry extract, a rattan tea extract, and delphinidin-3,5-glucoside as an active ingredient.

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