JP7357360B2 - anti aging agent - Google Patents

Description

The present invention relates to an anti-aging agent that contains a natural product-derived material or a processed product of the natural product-derived material as an active ingredient and has the effect of inhibiting the binding between advanced glycation products and receptors for advanced glycation products.
The present invention also relates to a composition with improved taste that contains Terminalia and barley grass or Chomei grass among the above-mentioned naturally derived materials.

The reaction in which amino compounds such as amino acids, peptides, and proteins react with reducing sugars to produce brown substances (melanoidins) is called the Maillard reaction, and the substances produced as the final products of this Maillard reaction are called advanced glycation products (Advanced Glycation Products). AGEs).

Specific examples of final glycation products include imidazolone, Nε-carboxymethyllysine, pentosidine, pyrarine, crosslin, Nε-carboxyethyllysine, methylglyoxallysine dimer, glyoxallysine dimer, and the like.

Accumulation of final glycation products in the body causes various adverse effects, such as skin diseases such as age spots, wrinkles, and dullness, myocardial infarction, cerebral infarction, osteoporosis, Alzheimer's disease, rheumatoid arthritis, diabetic angiopathy, and aging such as cataracts. bring about symptoms. As a product derived from a natural product that has the effect of suppressing the production of AGEs, a pericarp extract of Diarium indum of the Fabaceae family is known (see Patent Document 1).

Japanese Patent Application Publication No. 2010-111615

However, as described in Patent Document 1, there are only a limited number of natural product-derived materials or processed products of natural product-derived materials known so far that have the effect of suppressing the production of final glycation products. Furthermore, although the pericarp extract described in Patent Document 1 can suppress the production of final glycation products in vivo, it is difficult to prevent the adverse effects of the generated final glycation products in vivo and prevent aging symptoms. .

Therefore, an object of the present invention is to provide an anti-aging agent containing a natural product-derived material that can prevent the adverse effects of final glycation products in the living body.

In addition, Terminaria, which is one of the above-mentioned natural-derived materials, has a unique bitterness and astringency, and its ingestion form is limited to tablets and other forms that have a hard taste. Therefore, the problem to be solved by the present invention is to improve the taste of Terminaria and provide foods containing Terminalia in various forms. Furthermore, the problem to be solved by the invention is to provide food for preventing obesity, which has become a social problem in modern times.

As a result of extensive research into the above-mentioned problem, the present inventors have focused on the receptor for advanced glycation end products (RAGE), which binds to advanced glycation end products. They then came up with the idea that if they could inhibit the binding between advanced glycation end products and receptors for advanced glycation end products, it would be possible to prevent the harmful effects of advanced glycation end products in the body and obtain anti-aging effects. Based on this idea, as a result of trial and error in order to find out from various natural product-derived materials those that exhibit binding inhibitory effects between advanced glycation end products and end glycation end product receptors, we have found certain natural product-derived materials and Since processed products derived from natural materials exhibit antagonistic and inhibitory effects on receptors for advanced glycation end products, containing these as active ingredients has the effect of inhibiting the binding between end glycation products and receptors for advanced glycation end products. We succeeded in creating an anti-aging agent that exhibits The present invention has been completed based on this successful example.

Furthermore, as a result of extensive research, the present inventors came up with the idea of combining Terminaria with other natural-derived materials. As a result of trial and error to find a combination of Terminaria and various natural-derived materials that exhibits a good taste, we found that a composition that combines Terminaria and barley grass, or Terminaria and Chomeiso grass exhibits a good taste. I discovered that. Furthermore, the present inventors have discovered that a combination of Terminalia and barley grass suppresses weight gain when ingested in combination, thereby completing the present invention.

Therefore, according to the present invention, at least one active ingredient selected from the group consisting of pine bark, kogomi, terminaria, kohaze, kudzu flower, mulberry leaf, sweet potato, mugwort, black ginger, long life grass, and barley grass. Provided is an anti-aging agent that inhibits the binding between advanced glycation end products and end glycation end product receptors.

According to another aspect of the present invention, at least one active ingredient selected from the group consisting of pine bark, kogomi, terminaria, amber, kudzu flower, mulberry leaf, sweet potato, mugwort, black ginger, long life grass, and barley grass. Provided is an anti-aging agent containing the ingredient, which inhibits activation of receptors for advanced glycation end products.

According to another aspect of the present invention, at least one active ingredient selected from the group consisting of pine bark, kogomi, terminaria, amber, kudzu flower, mulberry leaf, sweet potato, mugwort, black ginger, long life grass, and barley grass. Provided is an anti-aging agent containing the ingredient, which has an effect of inhibiting the expression of receptors for advanced glycation end products.

According to another aspect of the present invention, at least one active ingredient selected from the group consisting of pine bark, kogomi, terminaria, amber, kudzu flower, mulberry leaf, sweet potato, mugwort, black ginger, long life grass, and barley grass. A method (excluding medical treatment for humans) of inhibiting the binding of an advanced glycation end product to a receptor for advanced glycation end products is provided, the method comprising using a component or a composition containing the same.

According to another aspect of the present invention, there is provided a composition characterized by containing Terminalia and grass barley or long grass.

According to another aspect of the present invention, there is provided a powdered beverage composition characterized by containing Terminalia and barley grass or Chomei grass.

According to another aspect of the present invention, there is provided a composition characterized by containing Terminalia, barley grass, and long-term grass.

According to another aspect of the present invention, there is provided a powdered beverage composition characterized by containing Terminaria, barley grass, and Chomeiso.

According to the present invention, by using a specific natural product-derived material or a processed product of a specific natural product-derived material, the binding between the receptor for advanced glycation end products and the receptor for advanced glycation end products is inhibited, and the end glycation end product It is possible to prevent the adverse effects caused by this in vivo. Therefore, according to the present invention, aging symptoms such as skin diseases such as age spots, wrinkles, and dullness, myocardial infarction, cerebral infarction, osteoporosis, Alzheimer's disease, rheumatoid arthritis, diabetic angiopathy, and cataracts can be alleviated, improved, suppressed, and prevented. It can be expected to provide treatment and treatment.

Furthermore, according to the present invention, it is possible to ingest Terminalia, which has a unique bitterness and astringency, with good taste. Therefore, according to the present invention, it is possible to provide health foods and drinks containing Terminaria in various forms such as drinks, confectionery, and seasonings. Furthermore, by combining Terminalia and barley grass, it is possible to provide a health food for preventing obesity.

FIG. 3 is a diagram showing the results of the AGE-RAGE binding inhibition evaluation described in Examples.

The details of the present invention will be explained below.
The anti-aging agent of the present invention includes any one of pine bark, Kogomi, Terminalia, Kohaze, Kudzu flower, Mulberry leaf, sweet potato, mugwort, black ginger, Chomeiso, and Barley grass, or two of them in combination; Contains 3, 4, 5, 6, 7, 8, 9, 10, or all types of active ingredients (hereinafter these may be collectively referred to as active ingredients).

The pine bark is not particularly limited as long as it is a natural pine bark. Examples of pine bark include those of plants belonging to the order Pinus, such as French maritime pine, Japanese larch, Japanese black pine, Japanese red pine, Japanese pine, Japanese pine, Korean pine, Japanese pine, Japanese pine, Japanese pine, white pine, Aneda in the Quebec region of Canada, etc. These include, but are not limited to, bark. Among these, the bark of the French maritime pine ( Pinus maritima ), which is a marine pine that grows on the Atlantic coast of southern France, is preferred because it has been confirmed to be safe for human consumption.

The kogomi is not particularly limited as long as it is a young bud of a plant belonging to the family Sternidae, which is a type of perennial fern, or a matteuccia struthiopteris , which is a plant belonging to the family Mesidae.

Terminalia is not particularly limited as long as it is a plant of the genus Terminalia, for example, Terminalia bellirica , Terminalia bellerica , Terminalia catappa , Terminalia tomentosa , Terminalia nalia citrina , Terminalia phellocarpa , Terminalia coplandii , Terminalia brassi , Terminalia ivorensis , Terminalia supe rba , Terminalia arjuna , Examples include Terminalia chebula . In the present invention, Terminalia bellirica is preferably used. The whole terminaria may be used or any part thereof may be used, but the part excluding the seeds is preferably used, and the part of the fruit excluding the seeds (the pericarp and pulp part) is more preferably used.

Kohaze is a plant of the Ericaceae family, Vaccinium genus, and is not particularly limited as long as it is also called Natsuhaze. The whole or any part of the fruit can be used, but the part of the fruit excluding the seeds (the pericarp and pulp part) is preferably used.

The kudzu flower is not particularly limited as long as it is the flower part of the kudzu plant. The kudzu plant, as it is commonly known, is a climbing perennial plant of the genus Kudzu of the Fabaceae family, and is known to be distributed in Japan, China, Taiwan, Southeast Asia, etc. The type of kudzu plant is not particularly limited, and examples include Pueraria thomsonii , Pueraria lobata , and Pueraria thunbergiana , which are said to be used as raw materials for food and drinks. From this point of view, Pueraria thomsonii is preferred. Kudzu flowers may be collected at any stage of flowering, but from the viewpoint of abundant presence of tectorigenins, it is preferable to use kudzu flowers collected at the bud stage before full bloom. .

The mulberry leaves are not particularly limited as long as they are leaves of plants belonging to the Moraceae family, and mulberry leaves that have been plucked and then treated under anaerobic conditions are preferred (see JP-A-9-135671).

Sweet potato refers to a plant belonging to the Convolvulaceae family, and is not particularly limited as long as it is generally called a sweet potato. The variety of sweet potato is not particularly limited. Examples include varieties such as Suio, Joy White, Scarlet Goose, White Yutaka, Satsumastarch, and Ayamurasaki. Among these, watermelon with a high polyphenol content is preferred. The whole sweet potato can be used or any part of the sweet potato can be used, but the stalks and leaves are preferred, the tips of the stalks and leaves (young stalks and leaves) are more preferred, and the young stalks and leaves that retain their yellowish green color are even more preferred. preferable.

Mugwort is not particularly limited as long as it belongs to the genus Artemisia of the family Asteraceae, and examples include mugwort, mugwort, tarragon, nitrofu mugwort, mugwort, mugwort, mugwort, mugwort, mugwort, mugwort, Japanese ginseng, mugwort, mugwort, Japanese mugwort, Ezo Yomogi, Samani mugwort, Takane mugwort, Hahako mugwort, Shikotan mugwort, White mugwort, Iwa mugwort, Japanese mugwort, Cotton mugwort, Kesho mugwort, Hitotsuba mugwort, Chishima mugwort, Hirohauraji white mugwort, Hirohaya mugwort, Snow mugwort, Yabu mugwort, Great mugwort, Nishi mugwort, Asagiri Varieties such as cormorant, Kitadake mugwort, etc. Can be mentioned. The whole mugwort may be used or any part thereof may be used; for example, flowers, spikes, stems, leaves, branches, foliage, rhizomes, roots, seeds, etc. may be used.

Black ginger ( Kaempferia parviflora ) is not particularly limited as long as it is a plant of the Zingiberaceae genus, which is known to grow naturally in Southeast Asia. The part of black ginger used is not particularly limited as long as it contains components that contribute to the desired pharmacological action, and examples include the whole, root, leaf, stem, flower, branch, rhizome, etc., but preferably. It is a rhizome that contains a large amount of polymethoxyflavonoids (PMF) such as 5,7-dimethoxyflavone (57DMF).

The scientific name of Chomeisou is Peucedanum japonicum or Peucedanum japonicum Thunb. It is not particularly limited as long as it is, and depending on the region, it is called Botanbofuu, Chomeisou, Chomeigusa, Chomyfusa, Bofu, Sakuna, Upbaasafuna, Chomygusa, Peonyfusa, etc. The entire Chomeiso can be used or any part thereof can be used, such as leaves, flowers, roots, etc., but leaves are preferably used.

Barley ( Hordeum vulgare L. ) is said to be native to Central Asia, is an annual or perennial herb belonging to the Poaceae family, and is not particularly limited as long as it is broadly classified into two-rowed barley, six-rowed barley, etc. according to the ear shape. The barley grass only needs to contain barley leaves, and may contain other parts such as stems and roots in addition to barley leaves. The barley grass used in the present invention is not particularly limited as long as it is normally available, and any barley grass such as two-rowed barley or six-rowed barley may be used. Moreover, young barley leaves of any variety may be used.

It is preferable that the natural product-derived material serving as the active ingredient is immediately harvested or processed immediately after harvest. When processing requires time, it is preferable to store the natural product by storage means commonly used by those skilled in the art, such as low-temperature storage, in order to prevent deterioration of the natural product.

The natural product-derived material may be a processed product of a natural product-derived material. Processed products of natural product-derived materials include, for example, dried powder of natural product-derived materials, fragmented products of natural product-derived materials and their dry powder, squeezed juice of natural product-derived materials and their dried powder, and natural product-derived materials. Examples include, but are not limited to, extracts and dry powders thereof. However, from the viewpoint of ease of processing, storage, transportation, etc. and versatility in usage, dry powders of natural product-derived materials and dry powders of extracts of natural product-derived materials are preferred. For example, mulberry leaves, sweet potato, mugwort, kogomi, terminaria, kohaze, long life grass, and barley grass are dried powder of mulberry leaves, dry powder of young sweet potato leaves, dry powder of mugwort leaves, and kogomi (young shoots), respectively. It is preferable to use a dry powder, a dry powder of the pericarp and pulp of Terminaria, a dry powder of the pericarp and pulp of Kohaze, a dry powder of the leaves of Chomeisou, and a dry powder of young barley leaves. Moreover, pine bark, kudzu flower, and black ginger are preferably pine bark extract and dry powder thereof, kudzu flower extract and dry powder thereof, and black ginger extract and dry powder thereof, respectively.

For example, a conventionally known method can be used to dry and powder a natural product-derived material. As such a method, a method that combines drying treatment and pulverization treatment for natural product-derived materials can be used. Although either the drying treatment or the pulverization treatment may be performed first, it is preferable to perform the drying treatment first. For dry powderization, this method may be further combined with one or more treatments selected from treatments such as blanching treatment and sterilization treatment, if necessary. Further, the number of times the pulverization treatment is performed may be one time or a combination of two or more treatments, but it is preferable to perform a coarse pulverization treatment and then a pulverization treatment in which the material is finely pulverized.

Blanching treatment is a treatment for keeping the green color of naturally derived materials vivid, and examples of blanching treatment methods include hot water treatment and steaming treatment.

The sterilization treatment is not particularly limited as long as it is a treatment commonly known to those skilled in the art, but for example, it may be a treatment that physically or chemically kills microorganisms using temperature, pressure, electromagnetic waves, chemicals, etc. can. When blanching is performed in addition to drying and pulverization, the blanching is preferably performed before the drying. Further, when sterilization treatment is performed in addition to drying treatment and pulverization treatment, it is preferable that sterilization treatment is performed after drying treatment, before or after pulverization treatment.

The drying process is not particularly limited, but includes, for example, a process of drying the natural product-derived material so that the water content is 10% or less, preferably 5% or less. The drying process may be performed by any method known to those skilled in the art, such as hot air drying, high pressure steam drying, electromagnetic wave drying, freeze drying, and the like. Drying by heating can be carried out, for example, at 40° C. to 140° C., preferably 80° C. to 130° C., at a temperature and time such that the natural product-derived material does not discolor due to heating.

The pulverization process is not particularly limited, but includes, for example, a process in which the plant body is pulverized by any method commonly used by those skilled in the art using a pulverization device or tool such as a crusher, mill, blender, or stone mill. The pulverized natural product-derived material is passed through a sieve, for example, if necessary, and it is preferable to use the material that passes through a mesh of 30 to 250 as the powder of the natural product-derived material. By setting the particle size to 250 mesh or less, it becomes easier to handle the powder of natural product-derived materials during further processing, and by setting the particle size to 30 mesh or more, powder of natural product-derived materials and other It becomes easier to mix uniformly with other materials.

As a specific dry powdering method, for example, after cutting the natural product-derived material, blanching treatment is performed, and then drying so that the moisture content is 10% by mass or less, preferably 5% by mass or less, A method of pulverizing the material after that is mentioned. Other methods include, for example, cutting the natural product-derived material, subjecting it to blanching, then rolling, then drying and pulverizing; Examples include a method of heating in the above manner and further pulverizing.

The method for cutting the natural product-derived material into pieces is not particularly limited, and for example, methods commonly used by those skilled in the art to cut plant bodies into pieces, such as slicing, crushing, and shredding, can be used. As an example of fragmentation, it may be made into a slurry. Slurrying is performed by applying the natural product-derived material to a mixer, juicer, blender, mass colloider, etc., and turning the natural product-derived material into a thick gruel (a suspension of liquid and solid).

The method of squeezing the natural product-derived material is not particularly limited, but examples include a method of squeezing the natural product-derived material or its fragmented product, a method of centrifuging or filtering the fragmented product of the natural product-derived material, etc. can. As an example of a specific juice extraction method, juice is extracted by mechanical crushing means such as a mixer or juicer, and if necessary, crude solids are removed by means such as sieving or filtration to obtain squeezed liquid. There are several methods.

The method for obtaining an extract of a natural product-derived material is not particularly limited, but for example, adding an extraction solvent commonly used by those skilled in the art, such as ethanol, water, or aqueous ethanol, to a natural product-derived material or its fragments, Examples include a method of extraction by stirring or heating, if necessary.
The extract may be concentrated if necessary.

Examples of the extraction solvent used when obtaining an extract of a natural product-derived material include, but are not limited to, water, organic solvents, and water-containing organic solvents (hydrous alcohols such as hydrous ethanol). When water is used as a solvent, warm water or hot water may be used. As the organic solvent used for extraction, organic solvents that are generally acceptable for extracting natural product components are used, such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, butane, Acetone, hexane, cyclohexane, propylene glycol, aqueous ethanol, aqueous propylene glycol, ethyl methyl ketone, glycerin, methyl acetate, ethyl acetate, diethyl ether, dichloromethane, edible fat, 1,1,1,2-tetrafluoroethane, 1, Examples include 1,2-trichloroethene. These solvents may be used alone or in combination of two or more. Among these solvents, hot water, hydrous ethanol, and hydrous propylene glycol are preferably used.

The method for extracting materials derived from natural products is not particularly limited as long as it is normally an acceptable method for extracting natural product components; for example, solid-liquid extraction methods such as heating extraction method and supercritical fluid extraction method may be used. Can be mentioned.

The heating extraction method is, for example, a method in which a test substance and a solvent are brought into contact and treated at a temperature below the boiling point of the solvent to extract components contained in the test substance into the solvent. A reflux extraction method may also be used.

The supercritical fluid extraction method is a method of performing extraction using, for example, a supercritical fluid that is a fluid that exceeds the critical point (critical temperature, critical pressure) of gas and liquid of a substance. Examples of the supercritical fluid include carbon dioxide, ethylene, propane, nitrous oxide (laughing gas), and carbon dioxide is preferred.

The supercritical fluid extraction method includes an extraction step in which a target component is extracted using a supercritical fluid, and a separation step in which the target component and the supercritical fluid are separated. In the separation step, any of extraction separation by pressure change, extraction separation by temperature change, and extraction separation using adsorbent/absorbent may be performed.

Supercritical fluid extraction may be performed using an entrainer addition method. In this method, for example, ethanol, propanol, n-hexane, acetone, toluene, other aliphatic lower alcohols, aliphatic hydrocarbons, aromatic hydrocarbons, ketones are added to the extraction fluid at 2 to 20 W/V. This is an efficient method that dramatically increases the solubility of the target extract in the extraction solvent or enhances the selectivity of separation by performing supercritical fluid extraction using this fluid. It is possible to obtain extracts of materials derived from natural products.

Supercritical fluid extraction has the advantage that it can be operated at relatively low temperatures, so it can be applied to substances that change or decompose at high temperatures. It also has the advantage that no extraction fluid remains, and because it allows the circulation of the solvent, it can be used for desolvation. It has the advantage that steps can be omitted and the process becomes simple.

In addition to the above-mentioned extraction methods, the natural product-derived material may be extracted by a liquid carbon dioxide batch method, a liquid carbon dioxide reflux method, a supercritical carbon dioxide reflux method, or the like. Moreover, a plurality of extraction methods may be combined. By combining multiple extraction methods, it is possible to obtain extracts of natural product-derived materials with various compositions.

The extract of natural product-derived materials obtained through extraction can be purified by ultrafiltration, column methods using adsorbent carriers (Diaion HP-20, Sephadex-LH20, chitin, etc.), batch methods, etc. Preferable from the standpoint of safety.

In the present invention, commercially available natural product-derived materials and processed products of natural product-derived materials used as active ingredients may be used, and examples thereof include those described in the Examples described below.

By containing the above-mentioned active ingredients, the anti-aging agent of the present invention exhibits an inhibitory effect on the binding between advanced glycation end products and end glycation end product receptors, thereby providing an anti-aging effect. It can be effective. The active ingredient contained in the anti-aging agent of the present invention exhibits a competitive inhibitory effect on receptors for advanced glycation end products.

Advanced glycation end product receptors are known as pattern recognition receptors that belong to the immunoglobulin superfamily of cell surface molecules. When advanced glycation end products are recognized by the variable region at the N-terminus of the end glycation end product receptor, reactive oxygen species (ROS) are generated, MAP kinase is activated, and transcription factors (NF-κB) are translocated to the nucleus. As a result, cellular responses such as increased oxidative stress and induction of inflammatory reactions are triggered (see, for example, J Kanazawa Med Univ 37:141-161, 201).

In addition, expression of advanced glycation end product receptor protein has been confirmed in a wide range of tissues such as vascular endothelial cells, vascular smooth muscle cells, nerve cells, macrophages, and adipocytes, but the expression level in these cells is lower than that in lung cells. Except, very low. However, it is known that as the pathology in a living body worsens, the expression level in each cell increases.

For example, in rheumatoid arthritis, the expression of advanced glycation end product receptors is increased on vascular endothelial cells and synovial surface macrophages in the synovium and joint cavity, where inflammatory cytokines and ligands for advanced glycation end product receptors are abundant. It recognized. A positive feedback mechanism exists between the advanced glycation end product receptor system and inflammatory cytokines, and the binding between advanced glycation end products and the receptor for advanced glycation end products promotes the inflammatory process in rheumatoid arthritis. (For example, see Okayama Medical Society Journal, Vol. 119, January 2008, pp. 223-227).

As another example, it is known that in chronic hyperglycemic conditions, advanced glycation end products are formed and accumulated in circulating blood and tissues. When advanced glycation end products are recognized by receptors for advanced glycation end products, oxidative stress and inflammatory reactions are induced, which is said to be involved in the onset and progression of diabetic vascular disorders such as early diabetic retinopathy. Furthermore, it has been revealed that in the retina, receptors for advanced glycation end products are expressed at various sites such as the retinal pigment epithelium. Furthermore, when advanced glycation end products act on retinal pigment epithelial cells, expression of advanced glycation end product receptors increases. It is known that inflammatory changes and angiogenesis play an important role in the pathology of age-related macular degeneration, but these are caused by retinal pigment epithelial cells expressing advanced glycation end product receptors. This may be caused by continuous contact with drusen rich in advanced glycation end products (see, for example, Anti-Aging Medicine 7(10):112-119, 2010).

As another example, we investigated 250 men and women with no history of chronic inflammatory disease, renal failure, ischemic heart disease, or stroke, and measured serum levels of advanced glycation end product receptors and adiponectin, as well as blood pressure and waist circumference. The serum advanced glycation end product receptor value, which was compared with the relevant status of metabolic components, was found to be similar to adiponectin HMWR (high molecular weight adiponectin/total adiponectin), as well as metabolic components (BMI, waist circumference, blood pressure, uric acid, triglycerides). (For example, see Tokyo Women's Medical University Journal, 84:E135-E140, 2014).

As described above, the binding between advanced glycation end products and receptors for advanced glycation end products can cause cellular responses that have adverse effects on living organisms, such as increased oxidative stress and induction of inflammatory reactions. Therefore, the anti-aging agent of the present invention inhibits the binding between advanced glycation end products and end glycation end product receptors, thereby preventing the induction or enhancement of cellular responses such as increased oxidative stress and induction of inflammatory reactions. Alleviates, improves, suppresses, and prevents diseases and conditions caused by aging, such as skin diseases such as age spots, wrinkles, and dullness, and aging symptoms such as myocardial infarction, cerebral infarction, osteoporosis, Alzheimer's disease, rheumatoid arthritis, diabetic vascular disease, and cataracts. and can be expected to be treated. In addition, the anti-aging agent of the present invention not only improves aging symptoms that have already occurred, but also prevents aging symptoms by acting on sites where receptors for advanced glycation end products are likely to be expressed. There is a probability.

Furthermore, since the anti-aging agent of the present invention contains an active ingredient, it can exhibit an effect of inhibiting the activation of the receptor for advanced glycation end products and an effect of suppressing the expression of the receptor for advanced glycation end products. Another embodiment of the anti-aging agent is at least one active ingredient selected from the group consisting of pine bark, Japanese kogomi, terminaria, amber, kudzu flower, mulberry leaf, sweet potato, mugwort, black ginger, long life grass, and barley grass. It may take the form of an anti-aging agent that has an effect of inhibiting activation of a receptor for advanced glycation end products or an anti-aging agent that has an effect of inhibiting expression of a receptor for advanced glycation end products. In this specification, the effect of inhibiting the binding between advanced glycation end products and the end glycation end product receptor, the action of inhibiting activation of end glycation end product receptor, and the action of inhibiting expression of end glycation end product receptor may be collectively referred to as specific actions. .

The content of the active ingredient in the anti-aging agent of the present invention may consist only of the active ingredient, as long as it is an effective amount that can exhibit at least a specific action.

The content of the active ingredient is set so that the lower limit of the daily usage amount is, for example, 100 mg/kg or more, preferably 300 mg/kg or more, and more preferably 500 mg/kg or more in terms of dry mass of the active ingredient. can do. In addition, the upper limit for the daily usage amount should be, for example, 2,000 mg/kg or less, preferably 1,500 mg/kg or less, and more preferably 1,000 mg/kg or less, based on the dry mass of the active ingredient. Can be set.

Specifically, the content of the active ingredient is 100 to 5,000 mg, preferably 500 to 2,000 mg, in terms of dry mass of the active ingredient per day. However, if the anti-aging agent of the present invention contains other substances having specific effects, the content of the active ingredient can be adjusted accordingly, such as by reducing the content.

The anti-aging agent of the present invention may contain other appropriately selected ingredients in addition to the active ingredient. Other ingredients include, for example, various excipients, binders, lubricants, stabilizers, diluents, fillers, thickeners, emulsifiers, colorants, fragrances, additives, cosmetic raw materials, pharmaceutical raw materials, etc. can be mentioned. The content of other components can be appropriately selected depending on the usage form of the anti-aging agent of the present invention.

The anti-aging agent of the present invention can be used in various forms for the purpose of alleviating, improving, suppressing, preventing and treating aging symptoms, for example, it can be used in oral or parenteral forms. can. The anti-aging agent of the present invention may be used orally or parenterally as it is, or dissolved in a solvent for dissolving the active ingredient and used orally or parenterally, depending on its form. You may.

The form of the anti-aging agent of the present invention is not particularly limited, and can be in any form. Examples of the form of the anti-aging agent for oral use include forms suitable for oral use, specifically, granules, powders, tablets, chewables, capsules, liquids, syrups, etc. .

Examples of the parenteral anti-aging agent include forms suitable for parenteral use, specifically, lotions, creams, liquids, foundations, mist, emulsions, sprays, Examples include mousse, gel, etc.

The packaging form of the anti-aging agent of the present invention is not particularly limited and can be appropriately selected depending on the dosage form, etc., but for example, blister packs such as PTP; strip packaging; heat sealing; aluminum pouches; plastics, synthetic resins, etc. are used. Examples include film packaging; glass containers such as vials; and plastic containers such as ampoules.

Although the anti-aging agent of the present invention is suitably applied to humans, there is no particular limitation as long as the expected effects are achieved, and it can be applied to animals other than humans. The user of the anti-aging agent of the present invention is not particularly limited, and may be, for example, a healthy person, but is preferably a person who is expected to alleviate, improve, suppress, prevent, and treat aging symptoms. , people with aging symptoms, people who ingest products containing advanced glycation end products, people who highly express receptors for advanced glycation end products, people with oxidative stress, inflammatory reactions, and diseases caused by these, middle-aged people over 40 years old. is more preferred, and those who ingest products containing final glycation products and middle-aged and elderly people are even more preferred. Those with aging symptoms and middle-aged and elderly people include those who actually have aging symptoms, those who have had aging symptoms in the past, and those who are at risk of developing aging symptoms due to genetics, occupation, etc. The frequency of use of the anti-aging agent of the present invention is not particularly limited, and is, for example, once or more per week, preferably twice or more per week.

The blending amount of the active ingredient in the anti-aging agent of the present invention can be appropriately determined depending on its administration form, dosage form, etc., and is not particularly limited. For example, the amount of the active ingredient is set to 100 parts by mass, and the lower limit of the active ingredient is set to 0.001 part by mass or more, 0.01 part by mass or more, preferably 0.1 part by mass or more in terms of dry mass. The upper limit of the active ingredient can be set to, for example, 100 parts by mass or less, preferably 50 parts by mass or less, and more preferably 10 parts by mass or less in terms of dry mass.

The anti-aging agent of the present invention can contain, in addition to the active ingredient, a second physiologically active ingredient that provides an anti-aging effect. Such a second physiologically active ingredient is not particularly limited as long as it is a physiologically active ingredient that has a commonly known anti-aging effect. By containing an active ingredient and a second physiologically active ingredient, the anti-aging agent of the present invention can be a composition that exhibits a synergistic anti-aging effect. The second physiologically active ingredient can be one or more ingredients. The blending amount of the second physiologically active ingredient is not particularly limited as long as it does not impede the solving of the problems of the present invention, and may be adjusted as appropriate.

The method for producing the anti-aging agent of the present invention is not particularly limited, and may be produced according to general production methods known to those skilled in the art depending on the usage mode. For example, for granular or solid products, the active ingredient may be mixed as is or mixed with the other ingredients and second physiologically active ingredients mentioned above simultaneously or in several stages, using fluidized bed granulation, agitation granulation, etc. It can be granulated into granules according to a granulation method such as a granulation method or an extrusion granulation method, and then compressed into a tablet shape using a tablet machine or the like according to a conventional method.

Another aspect of the present invention is at least one active ingredient selected from the group consisting of pine bark, kogomi, terminaria, kohaze, kudzu flower, mulberry leaf, sweet potato, mugwort, black ginger, long life grass, and barley grass, or A method for inhibiting the binding between advanced glycation end products and receptors for advanced glycation end products, which comprises using a composition containing the active ingredient. However, the method of the present invention excludes medical treatment for humans.

The blending amount in a composition containing Terminalia of the present invention and barley grass or Chomei grass can be appropriately determined depending on the administration form, dosage form, etc., and is not particularly limited. For example, the blending amount of barley grass can be set to 50 parts by mass to 2000 parts by mass, preferably 150 parts by mass to 1000 parts by mass, and more preferably 300 parts by mass to 700 parts by mass, based on 100 parts by mass of Terminalia. . Further, the amount of Chomeiso can be set to 1 part by mass to 200 parts by mass, preferably 5 parts to 100 parts by mass, and more preferably 10 parts to 50 parts by mass, based on 100 parts by mass of Terminalia. .

Further, the amount of the composition containing Terminaria, barley grass, and Chomeiso is not particularly limited, and can be appropriately determined depending on the administration form, dosage form, etc. For example, the total amount of barley grass and Chomeiso is 50 parts by mass to 2000 parts by mass, preferably 150 parts to 1000 parts by mass, and more preferably 300 parts to 800 parts by mass, based on 100 parts by mass of Terminalia. Can be set.

Hereinafter, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples, and the present invention can take various embodiments as long as the problems of the present invention can be solved. .

[Test example 1]
(AGE-RAGE binding inhibition test)
(1) Test sample Test substances include Flavangenol (registered trademark) (Toyo Shinyakusha), which is a French maritime pine bark extract, Kogomi (commercial product), Terminaria berylica (commercial product), Kohaze (commercial product), Kudzu flowers (Toyo Shinyakusha; kudzu flower extract powder), mulberry leaves (Toyo Shinyakusha; mulberry young leaf powder), sweet potato ("sweet potato young leaf powder"; Toyo Shinyakusha), mugwort ("mugwort powder"; Toyo Shinyakusha) ), black ginger (Toyo Shinyaku Co., Ltd.; 60% ethanol extract), Chomeiso ("Chomeisosame"; Toyo Shinyaku Co., Ltd.), and barley grass ("Barley Wakaba Powder"; Toyo Shinyaku Co., Ltd.) were used.

Each test substance was dissolved in distilled water at a concentration of 100 mg/mL in an Eppendorf tube, and stirred for 1 hour using a vortex to obtain a suspension. The resulting suspension was centrifuged at 15,000 rpm for 3 minutes, and only the supernatant was carefully transferred to another Eppendorf tube to avoid any residue, and this was used as the stock solution of the test sample.

Four series with final concentrations of 5, 1, 0.33, and 0.11 mg/mL were prepared for flavangenol, Kogomi, Terminaria, Kohaze, Kuzunoha, and Mulberry leaf. On the other hand, three series with final concentrations of 5, 1, and 0.33 mg/mL were prepared for sweet potato, mugwort, black ginger, long life grass, and barley grass powder.

Using the stock solution of each test sample, each test substance was prepared with distilled water to a concentration 20 times the final concentration, and used as a test sample.

(2) Evaluation of AGE-RAGE binding inhibition The AGE-RAGE binding inhibition activity of the test sample was measured using CircuLex AGE-RAGE in vitro Binding Assay Kit (Cyclex) according to the manufacturer's instructions. That is, to each well of the AGE2-BSA coated Microplate or BSA coated Microplate in the kit, add 5 μL of the test sample prepared to a concentration 20 times the final concentration, 85 μL of Reaction Buffer, and His-Tagged sRAGE Soluti. on (50ng/mL) 10 μL each was dispensed.

Moreover, as a positive control (inhibitor control; Inh. Cont.), 20× Inhibitor Control Compound in the above kit was added instead of the test sample. Further, as a standard sample (STD), 100 μL of His-Tagged sRAGE prepared at 3.125 to 100 ng/mL was dispensed.

After dispensing, the Microplate was left standing at room temperature for 1 hour. Next, after removing the solution in each well, each well was washed four times using Wash Buffer. Next, 100 μL of HRP-conjugated Anti-His-tag monoclonal Antibody was added to each well and left at room temperature for 1 hour.

Then, after removing the solution from each well, the wells were washed four times using Wash Buffer. Next, 100 μL of Substrate Reagent (TBM: substrate solution) was added to each well, and the wells were allowed to stand at room temperature for 15 minutes. Next, Stop Solution (1N H ₂ SO ₄ : stop solution) was added, and the absorbance of each well was measured using a plate reader (450 nm).

Data analysis of the measured absorbance was performed as follows. That is, for the absorbance of the corresponding well, the value of the BSA plate was subtracted from the value of the AGE2-BSA plate (1). Next, from each value of STD, a sigmoid curve type calibration curve was created using image j (2) Next, the amount of RAGE bound to AGE when each test substance was added was calculated using the calibration curve created in (2). Calculated from (3). Next, the value in (3) above was subtracted from the amount of sRAGE added (50 ng/mL) to calculate the amount of RAGE whose binding was inhibited (4). Next, the inhibition rate was calculated using the following formula.
Inhibition rate (%) = [value of (4)] / [amount of sRAGE added] x 100

(3) Evaluation Results The measurement results of each test sample with a final concentration of 5 mg/mL are shown in FIG. As shown in Figure 1, surprisingly, flavangenol, Kogomi, Terminalia, Kohaze, Kudzu flower, Mulberry leaf, Sweet potato, Mugwort, Black ginger, Chomeiso and Barley grass were more AGE- than the positive control. It was confirmed that it has a RAGE binding inhibitory effect. Similarly, when the final concentration was 1 mg/mL, flavangenol, Kogomi, Terminaria, Kohaze, Kuzu flower, Mulberry leaf, Sweet Potato, Mugwort, and Black Ginger inhibited AGE-RAGE binding more than the positive control. It was confirmed that it has an effect. Furthermore, when the final concentration was 0.33 mg/mL, flavangenol, Kogomi, Terminalia, Kohaze, Kuzu flower, Mulberry leaf, Sweet Potato, and Mugwort had a stronger AGE-RAGE binding inhibitory effect than the positive control. It was confirmed that it has. Furthermore, when the final concentration was 0.11 mg/mL, it was confirmed that flavangenol, Kogomi, Terminaria, Kohaze, and Kudzu flower had a stronger AGE-RAGE binding inhibitory effect than the positive control.

[Test example 2]
(Sensory test 1 of powdered beverage containing Terminalia)
(1) Test sample Terminaria beryrica (commercially available), barley grass ("Barley grass end"; Toyo Shinyakusha), and Chomeisou ("Chomei grass end"; Toyo Shinyakusha) were used as test substances.

A powdered drink having the formulation shown in Table 1 below was prepared. A total of six samples, Comparative Examples 1 to 3 and Examples 1 to 3 shown in Table 1, were used in the sensory test.

(2) Sensory evaluation of powdered beverages containing Terminalia The above six samples were transferred to plastic cups, 100 mL of water was poured into each, and the mixture was thoroughly stirred. A total of five men and women ingested these six powdered beverages, and evaluated the aroma, mellowness, richness, astringency, bitterness, flavor intensity, texture, down the throat, aftertaste, and overall evaluation. The items were evaluated. The evaluation method was based on "3 points" for the Terminaria standalone powdered drink of Comparative Example 1 in all items, and each item was evaluated relatively on a scale of 1 to 10 (the higher the score, the better the evaluation). expensive).

(3) Evaluation results The results of the sensory test are shown in Table 2. The numbers in the table are the average scores of the five subjects.

From the results in Table 2, it can be seen that Example 1, in which Terminaria and barley grass were blended, and Example 2, in which Terminaria and Chomeiso were blended, compared to Comparative Examples 1 to 3, in which each material was used alone, in all items. It can be seen that the evaluation is higher than that of

Furthermore, Example 3, in which Terminaria, barley grass, and Chomeisou were all blended, was evaluated even higher than Examples 1 and 2 in all items.

From the above results, the combination of Terminaria and barley grass or Chomeisou improves the aroma, mellowness, richness, astringency, bitterness, depth of taste, texture, throat feel, and It was revealed that the aftertaste was improved compared to when each material was used alone, and it was possible to provide a drink with a more pleasant taste. Furthermore, it has been revealed that by blending all of Terminalia, barley grass, and long-term grass, it is possible to provide a beverage with an even more pleasant taste.

Based on the above results, the inventors conducted further research and conducted the following test to confirm the ratio of Terminaria, barley grass, and Chomeiso to create a drink with a more desirable taste. .

[Test example 3]
(Sensory test 2 of powdered beverage containing Terminalia)
(1) Test sample Terminaria beryrica (commercially available), barley grass ("Barley grass end"; Toyo Shinyakusha), and Chomeisou ("Chomei grass end"; Toyo Shinyakusha) were used as test substances.

A powdered drink having the formulation shown in Table 3 below was prepared. A total of five samples, Comparative Example 4 and Examples 4 to 7 shown in Table 3, were used in the sensory test.

(2) Sensory evaluation of powdered beverages containing Terminaria 3g of each of the above five samples was transferred to plastic cups, 100mL of water was poured into each, and the mixture was thoroughly stirred. A total of five men and women ingested these five powdered beverages, and evaluated the aroma, mellowness, richness, astringency, bitterness, flavor intensity, texture, down the throat, aftertaste, and overall evaluation. The items were evaluated. The evaluation method was to use the powdered beverage of Comparative Example 4 as a standard score of "3 points" for all items, and to evaluate each item relatively on a scale of 1 to 10 (the higher the score, the higher the evaluation).

(3) Evaluation Results The results of the sensory test are shown in Table 4. The numbers in the table are the average scores of the five subjects.

From the results in Table 4, Example 5, which contained 1.5 g of Terminaria, 8.2 g of young barley leaves, and 0.3 g of Chomeiso, received the highest evaluation in all items, and the amount of Terminaria combined was higher. There was a tendency for the evaluation to decrease as the number decreased or increased.

[Test example 4]
(Mouse weight gain suppression test)
(1) Test sample Terminaria beryrica (commercial product), barley grass ("Barley grass powder"; Toyo Shinyaku Co., Ltd.), and MF powder feed (commercial product) were used as test substances.

A test feed having the formulation shown in Table 5 below was prepared. A total of four samples, Comparative Examples 5 to 7 and Example 8 shown in Table 5, were used in the weight gain suppression test.

(2) Evaluation of suppression of weight gain in mice Male KK-Ay mice aged 8 to 15 weeks were divided into 4 groups after an acclimatization period or a rest period of 2 days or more so that their body weights were uniform. Thereafter, each test group was allowed to freely consume the test feed shown in Table 5 for 4 days. The weight of each mouse was measured using an electronic balance at the time of grouping (test day 0) and on the test day 4, and the amount of weight gain was measured.

(3) Evaluation results The results of the weight gain suppression test are shown in Table 6. The numbers in the table relatively indicate the average weight gain of the mice in each test group, when the average weight gain of the mice in the group that ingested the feed of Comparative Example 5 was set to 1.

From the results in Table 6, the group that ingested the feed of Comparative Example 5 containing only MF powder feed, compared to the group that ingested the feed of Comparative Example 5 containing only MF powder feed, and the group of Comparative Example 6 in which Terminaria was added alone to the MF powder feed, and the group in which barley grass was added to the MF powder feed alone. In the group that ingested the feed of Comparative Example 7, no effect of suppressing weight gain was observed, but rather a tendency for weight gain to be promoted was observed. However, surprisingly, in the group that ingested the feed of Example 8 in which Terminaria and barley grass were added to the MF powder feed, weight gain was suppressed.

From the above results, it was revealed that Terminaria and barley grass, when taken in combination, have the effect of suppressing weight gain in animals, which does not occur when each is taken alone.

According to the present invention, an anti-aging agent containing a natural product-derived material or a processed product of the natural product-derived material, which has the effect of inhibiting the binding between the final glycation product and the receptor for the final glycation product, is obtained. Pharmaceuticals useful for those who expect to alleviate, improve, suppress, prevent, and treat aging symptoms such as skin diseases such as dull skin, myocardial infarction, cerebral infarction, osteoporosis, Alzheimer's disease, rheumatoid arthritis, diabetic vascular disease, and cataracts. Cosmetics, quasi-drugs, general foods and drinks, foods and drinks for specified health uses, foods and drinks with nutritional functions, foods and drinks with health functions, foods and drinks for special purposes, nutritional supplements, health supplements, supplements, beauty foods and drinks, and other health products Can be used as food and drink.

Furthermore, according to the present invention, it is possible to improve the taste of Terminaria and provide foods containing Terminalia in various forms. In addition, by combining it with barley grass, it is possible to provide healthy foods and drinks that are useful for those who expect to alleviate, improve, suppress, prevent, and treat obesity.

Claims (1)

A composition for inhibiting binding between advanced glycation products and receptors for advanced glycation products , which contains dry powder of Chomeisou.