Oral composition

Abstract

To provide an oral composition that inhibits expression of SREBF1 or promotes expression of PPARα, HO-1 or NOS3 and thus may contribute to inhibiting increase or promoting decrease of neutral fat or cholesterol, improving brain functions, reducing and / or mitigating melancholic states such as depression due to stress, enhancing stress tolerance, improving the blood flow, relieving physical fatigue, or remedying erectile dysfunction.SOLUTION: The oral composition comprises gallic acid, and further comprises at least one selected from pomegranate, Shilajit, hibiscus, mastic, lonicerae flos and mango.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to oral compositions. [Background technology]

[0002] In recent years, there has been an increasing demand for natural ingredients to improve physical condition and function. For example, Sterol Regulatory Element Binding Transcription Factor 1 (hereinafter referred to as "SREBF1") is known as a protein that enhances the biosynthesis of neutral fats and cholesterol in the liver, etc. (Non-Patent Document 1). In addition, Peroxisome Proliferator-Activated Receptor α (hereinafter also referred to as "PPARα") is known as a protein that promotes the reduction of cholesterol and neutral fats in the blood, etc. (Non-Patent Document 1 and section 2.2 of Non-Patent Document 2). Therefore, if there were a composition that suppresses the expression of SREBF1 or enhances the expression of PPARα, it would be useful in suppressing an increase in or promoting a decrease in cholesterol and neutral fats in the blood, etc.

[0003] Oxidative stress and mitochondrial dysfunction are thought to be contributing factors to the decline in brain function (Non-Patent Document 3). It is believed that various stresses can cause mitochondrial dysfunction, which in turn induces neuronal damage, and that this is one of the causes of depression. It is also known that oxidative stress accumulates under depression (Non-Patent Document 4). Heme oxygenase 1 (hereinafter also referred to as "HO-1") is known to have a mitochondrial protective effect under oxidative stress (Non-Patent Document 5). For this reason, compositions that enhance HO-1 gene expression are thought to be useful for improving brain function and resistance to various stresses.

[0004] Furthermore, nitric oxide synthase 3 (hereinafter also referred to as "NOS3") is known to improve blood flow (Non-Patent Document 6), which is known to promote the supply of nutrients to muscles and reduce physical fatigue. Furthermore, it is known that decreased activity of NOS3 is related to erectile dysfunction (ED) (Non-Patent Document 7).

[0005] On the other hand, gallic acid, also known as 3,4,5-trihydroxybenzoic acid, is known to have antioxidant properties. Gallic acid has been known to have, for example, an α-glucosidase inhibitory effect (Patent Document 1).

[0006] On the other hand, various effects are also known from pomegranate, shilajit, hibiscus, mastic, goldenrod, and mango (Patent Documents 2 to 7). [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Japanese Patent Application Publication No. 2020-068671 [Patent Document 2] Re-tabled publication 2019 / 146669 [Patent Document 3] Japanese Patent Publication No. 2020-073552 [Patent Document 4] Japanese Patent Application Publication No. 2018-008903 [Patent Document 5] Japanese Patent Application Laid-Open No. 2002-238496 [Patent Document 6] Japanese Patent Application Publication No. 2019-055924 [Patent Document 7] Japanese Patent Application Publication No. 2019-001725 [Non-patent literature]

[0008] [Non-Patent Document 1] Chemistry and Biology, Vol.42, No.5, 2004, p300-308 [Non-patent document 2] Atherosclerosis, 205, (2005) p1-8 [Non-patent document 3] Biomed.Pharmacother.,74(2015),p101-110 [Non-patent document 4] Curr.Neuropharmacol.2016,14(6),p610-618 [Non-Patent Document 5] Mol.Pharmacol.2015,Sep.,88(3),p437-449 [Non-patent document 6] Proceedings of the 120th Japanese Medical Association Symposium, p. 68-73, http: / / jams.med.or.jp / symposium / full / 120068.pdf, retrieved March 31, 2021 [Non-Patent Document 7] Int.J.Impot.Res.,2007,19(2),p129-138 Summary of the Invention [Problem to be solved by the invention]

[0009] As described above, there is a demand for oral compositions that can suppress the expression of SREBF1 or promote the expression of PPARα, HO-1, or NOS3, thereby contributing to suppressing or promoting the decrease of triglyceride or cholesterol elevation, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, or improving erectile dysfunction. However, conventional oral compositions have not been sufficient in terms of solving these problems. [Means for solving the problem]

[0010] The present invention provides the following configurations. <1> Gallic acid is contained, and further, An oral composition comprising at least one selected from pomegranate, shilajit, hibiscus, mastic, goldenrod, and mango.

[0011] <2> The content of gallic acid is 0.1% by mass or more. <1> The oral composition according to claim 1.

[0012] <3> The total content of pomegranate, shilajit, hibiscus, mastic, goldenrod, and mango is 5% by mass or more and 40% by mass or less. <1> or <2> The oral composition according to claim 1.

[0013] <4> For inhibiting and / or reducing cholesterol elevation, <1> ~ <3> An oral composition according to any one of the above.

[0014] <5> For suppressing and / or reducing neutral fat elevation, <1> ~ <3> An oral composition according to any one of the above.

[0015] <6> It is for improving brain function. <1> ~ <3> An oral composition according to any one of the above.

[0016] <7> For reducing and / or alleviating depressive states such as depression caused by stress, or for improving stress tolerance, <1> ~ <3> An oral composition according to any one of the above.

[0017] <8> For improving blood flow, reducing physical fatigue, or improving erectile dysfunction. <1> ~ <3> An oral composition according to any one of the above. [Effects of the Invention]

[0018] According to the present invention, an oral composition can be provided that can suppress the expression of SREBF1 or promote the expression of PPARα, HO-1, or NOS3, thereby contributing to suppressing or promoting the decrease of neutral fat or cholesterol levels, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, or improving erectile dysfunction. DETAILED DESCRIPTION OF THE INVENTION

[0019] The oral composition of the present invention will be described in more detail below by way of preferred embodiments, but the present invention is not limited thereto.

[0020] The oral composition of the present invention comprises gallic acid and further comprises: It contains at least one selected from pomegranate, shilajit, hibiscus, mastic, goldenrod, and mango.

[0021] (Gallic Acid) Gallic acid, also known as 3,4,5-trihydroxybenzoic acid, has the following chemical formula:

[0022] [ka]

[0023] The present invention preferably contains gallic acid that is not derived from pomegranate, shilajit, hibiscus, mastic, marigold, or mango. Examples of gallic acid that can be used in the present invention include plant-derived gallic acid, gallic acid obtained by extracting or refining such gallic acid, and gallic acid obtained by synthesis. When plant-derived gallic acid is used, gallic acid derived from a plant other than pomegranate, shilajit, hibiscus, mastic, marigold, or mango is preferred. Furthermore, the gallic acid used in the present invention may be anhydrous or a hydrate such as a monohydrate.

[0024] The present inventors have surprisingly found that by combining the above-mentioned gallic acid with at least one selected from pomegranate, shilajit, hibiscus, mastic, marigold, and mango, it is possible to suppress the expression of SREBF1, which is involved in lipid metabolism, and promote the expression of PPARα, and further promote the expression of HO-1, thereby improving brain function and stress resistance, and further promote the expression of NOS3, thereby promoting blood flow, alleviating fatigue, and improving erectile dysfunction, etc.

[0025] (Pomegranate) Pomegranate is a plant of the genus Punica in the family Lythraceae, and its scientific name is Punica granatum. It is also called pomegranate, pomegranate, or young pomegranate. In the present invention, various parts of the pomegranate, such as flowers, leaves, fruits, peels, and seeds, can be used. However, it is preferable to use the peel from the viewpoints of suppressing or promoting the decrease of neutral fat or cholesterol levels, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, and improving erectile dysfunction.

[0026] In the present invention, harvested pomegranates can be processed and used. Examples of processed pomegranate products include chips, crushed products, squeezed products, extracts, and dried powders thereof. In consideration of formulation, the pomegranate used in the present invention is preferably crushed, squeezed, extract, or dried powder thereof, and more preferably an extract or dried powder thereof from the viewpoints of inhibiting or promoting cholesterol elevation, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, and improving erectile dysfunction. The processed pomegranate product may be produced by a method commonly known to those skilled in the art, or may be a product available on the market.

[0027] Examples of pomegranate extracts include extracts extracted using a solvent and extracts extracted using supercritical extraction methods such as carbon dioxide. The term "extract" used herein refers to an extract liquid, a diluted or concentrated liquid thereof, or a dried or powdered form thereof. While pomegranate extracts may be in liquid form, powder form is preferred in terms of ease of use when made into a solid formulation, suppression or promotion of reduction of neutral fat or cholesterol levels, improvement of brain function, reduction and / or alleviation of depressive states such as depression caused by stress, improvement of stress resistance, improvement of blood flow, improvement of physical fatigue, and improvement of erectile dysfunction.

[0028] When the pomegranate extract is a solvent extract, the solvent used can be one or more selected from the group consisting of water, lower alcohols such as methanol, ethanol, isopropanol, and butanol, ketones such as acetone, methyl ethyl ketone, and methyl butyl ketone, esters such as methyl acetate and ethyl acetate, glycols such as ethylene glycol and propylene glycol, glycerin, tetrahydrofuran, acetonitrile, organic acids such as acetic acid and propionic acid, amides such as acetamide and dimethylformamide, and dimethyl sulfoxide. In the present invention, water, lower alcohols, esters, glycols, organic acids, and mixed solvents of organic solvents and water can be suitably used. Examples of mixed solvents that can be used include mixed solvents of methanol, ethanol, isopropanol, butanol, ethyl acetate, methyl acetate, and acetone with water. From the viewpoints of inhibiting or promoting the decrease of cholesterol elevation, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, or improving erectile dysfunction, preferred examples include an acetone / water (2 / 8 to 8 / 2, volume ratio) mixture, ethanol, and an ethanol / water (2 / 9 to 9 / 2, volume ratio) mixture, with ethanol being particularly preferred. The temperature of the extraction solvent can be appropriately set between room temperature and the boiling point depending on the solvent used. In this specification, lower alcohol refers to an alcohol having 5 or fewer carbon atoms.

[0029] (Shilajit) Shilajit is commonly known as mineral pitch and its scientific name is Asphaltum, Asphaltum puniabiunum or Asphaltum Punjabinum.

[0030] Shilajit is a mixture of natural humus and plant organic matter collected at altitudes of 1,000 to 5,000 meters in the Himalayas. It contains fulvic acid, humic substances, and over 40 minerals. The shilajit used in the present invention, whether in the form of raw shilajit or an extract, preferably contains 5% or more by weight of fulvic acid, more preferably 10% or more by weight, and particularly preferably 20% or more by weight. Commercially available products can be used in the present invention. The form is not particularly limited, but powder is preferred. The amount of fulvic acid in shilajit is measured, for example, by gravimetric analysis.

[0031] In the present invention, shilajit may be raw shilajit, its chips, its pulverized product, or an extract thereof. However, the use of an extract is preferred in terms of suppressing or promoting the decrease of triglyceride or cholesterol levels, improving brain function, reducing and / or alleviating depressive states such as stress-induced depression, improving stress resistance, improving blood flow, improving physical fatigue, and improving erectile dysfunction. Examples of extracts include extracts extracted using a solvent and extracts extracted using a supercritical extraction method using carbon dioxide or the like. In the case of solvent extraction, the extraction solvent may be the same as that described for pomegranate. However, water, lower alcohols, or mixtures thereof are preferred in terms of safety and simplicity. Water is preferred in terms of safety, simplicity, and in terms of suppressing or promoting the decrease of triglyceride or cholesterol levels, improving brain function, reducing and / or alleviating depressive states such as stress-induced depression, improving stress resistance, improving blood flow, improving physical fatigue, and improving erectile dysfunction.

[0032] (hibiscus) Hibiscus is a plant of the genus Hibiscus in the family Malvaceae, and its scientific name is Hibiscus sabdariffa, and it is also known as roselle. In the present invention, various parts of the plant can be used, such as flowers, leaves, bark, roots, and seeds. However, it is preferable to use flowers from the viewpoints of suppressing or promoting the decrease of neutral fat or cholesterol levels, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, and improving erectile dysfunction. The flowers may include not only petals but also calyxes, etc.

[0033] In the present invention, harvested hibiscus can be processed and used, and examples of processed hibiscus products include chips, crushed products, squeezed products, extracts, and dried powders thereof. Considering formulation feasibility, the hibiscus used in the present invention is preferably crushed, squeezed, extract, or dried powder thereof, and more preferably an extract or dried powder thereof from the viewpoints of inhibiting or promoting cholesterol elevation, improving brain function, reducing and / or alleviating depressive states such as stress-induced depression, improving stress resistance, improving blood flow, improving physical fatigue, and improving erectile dysfunction. The processed hibiscus product may be one produced by a method commonly known to those skilled in the art, or may be one that is commercially available. The extraction method, etc. is the same as for pomegranate. When a solvent is used, water, a lower alcohol, or a mixture thereof is preferred as the solvent from the viewpoints of safety, inhibiting or promoting the decrease of neutral fat or cholesterol elevation, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, or improving erectile dysfunction. A mixture of water and a lower alcohol is particularly preferred, and a mixture of water and a lower alcohol having a lower alcohol concentration of 10 to 90% by mass, particularly 20 to 80% by mass, is most preferred.

[0034] (Mastic) Mastic (mastiha) belongs to the genus Pistacia (local name: Schinos, scientific name: Pistacia Lentiscus) of the Anacardiaceae family, and is found growing wild and cultivated only on the Greek island of Chios. Mastic is primarily separated into its sap, dried sap (sometimes called "mastic resin"), mastic oil obtained by diluting the sap or resin with vegetable oil or a polyhydric alcohol fatty acid ester, mastic essential oil obtained by steam distillation of the sap or resin, and the water-soluble component (mastic water) produced during the distillation process for producing the essential oil. Using sap or its dried form is preferred for its potential to inhibit or promote the reduction of triglyceride or cholesterol levels, improve brain function, reduce and / or alleviate depressive states such as stress-induced depression, improve stress resistance, improve blood flow, alleviate physical fatigue, and improve erectile dysfunction. Dried sap is even more preferred.

[0035] (Golden jasmine) Honeysuckle (Lonicera japonica Thunberg., also known as honeysuckle) is an evergreen, climbing woody plant belonging to the genus Honeysuckle in the family Caprifoliaceae. It grows naturally throughout Japan and East Asia and is easily available from these regions. Parts that can be used as raw materials for extraction include, for example, leaves, stems, flowers, buds, fruit, peel, stalk, aboveground parts, the whole plant, and mixtures thereof. The leaves, stems, flowers, and buds are preferred.

[0036] In the present invention, harvested monarch can be processed and used, and examples of processed monarch products include chips, pulverized products, squeezed products, extracts, and dried powders thereof. Considering formulation feasibility, the monarch used in the present invention is preferably pulverized, squeezed, extract, or dried powder thereof, and more preferably an extract or dried powder thereof from the viewpoints of inhibiting or promoting the decrease of neutral fat or cholesterol elevation, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, or improving erectile dysfunction. The processed monarch may be produced by a method commonly known to those skilled in the art, or may be a product available on the market. The extraction method, etc. is the same as for pomegranate, and when a solvent is used, water, lower alcohols, or mixtures thereof are preferred as the solvent from the viewpoints of safety, suppressing or promoting the decrease of neutral fat or cholesterol levels, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, or improving erectile dysfunction, and water is particularly preferred.

[0037] (mango) Mango is a plant of the genus Mangifera in the family Anacardiaceae, and its scientific name is Mangifera indica. Various parts of mango, such as the flowers, leaves, bark, roots, and seeds, are known to be used orally, but in the present invention, it is preferable to use the leaves from the viewpoints of inhibiting or promoting the decrease of neutral fat or cholesterol levels, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, and improving erectile dysfunction.

[0038] In the present invention, harvested mangoes can be processed and used. Examples of processed mango products include chips, crushed mangoes, squeezed mangoes, extracts, and dried powders thereof. Considering ease of formulation, crushed mangoes, squeezed mangoes, extracts, and dried powders thereof are preferred for use in the present invention, and extracts and dried powders thereof are more preferred from the viewpoint of efficacy. Processed mango products may be produced by methods commonly known to those skilled in the art or may be commercially available products. The extraction method is similar to that for pomegranates. When a solvent is used, water, lower alcohols, or mixtures thereof are preferred in terms of safety, suppression or promotion of reduction of neutral fat or cholesterol levels, improvement of brain function, reduction and / or alleviation of depressive states such as stress-induced depression, improvement of stress resistance, improvement of blood flow, improvement of physical fatigue, and improvement of erectile dysfunction. A mixture of water and lower alcohols is particularly preferred.

[0039] The composition of the present invention preferably has a gallic acid content of 0.001% by mass or more based on the solid content, from the viewpoints of suppressing SREBF1 expression or promoting the expression of PPARα, HO-1, or NOS3, suppressing or promoting a decrease in triglyceride or cholesterol levels, improving brain function, reducing and / or alleviating depressive states such as stress-induced depression, improving stress resistance, improving blood flow, improving physical fatigue, or improving erectile dysfunction; a content of 0.01% by mass or more is more preferred, and a content of 0.1% by mass or more is particularly preferred. Furthermore, the composition of the present invention preferably has a gallic acid content of 40% by mass or less based on the solid content, from the viewpoints of suppressing SREBF1 expression or promoting the expression of PPARα, HO-1, or NOS3, suppressing or promoting a decrease in triglyceride or cholesterol levels, improving brain function, reducing and / or alleviating depressive states such as stress-induced depression, improving stress resistance, improving blood flow, improving physical fatigue, or improving erectile dysfunction; a content of 35% by mass or less is more preferred. In the present invention, when gallic acid is a hydrate, the amount of gallic acid referred to in this specification is calculated as an anhydrous amount. In addition, in this specification, the solid content refers to the content in the composition when the composition is solid, and refers to the total amount of all components in the composition excluding water when the composition is liquid or fluid.

[0040] In the composition of the present invention, it is preferable that the total amount of pomegranate, shilajit, hibiscus, mastic, goldenrod, and mango be 0.01% by mass or more of the solid content, from the viewpoints of suppressing SREBF1 gene expression or easily promoting PPARα, HO-1, or NOS3 gene expression, thereby suppressing or promoting the decrease of triglyceride or cholesterol levels, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, or improving erectile dysfunction. It is more preferable that the total amount of pomegranate, shilajit, hibiscus, mastic, goldenrod, and mango be 0.01% by mass or more, particularly preferably 1% by mass or more, and most preferably 5% by mass or more. On the other hand, in terms of suppressing the expression of the SREBF1 gene or promoting the expression of the PPARα, HO-1 or NOS3 gene, thereby suppressing or promoting the decrease of increases in triglycerides or cholesterol, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, or improving erectile dysfunction, the upper limit of the total amount of pomegranate, shilajit, hibiscus, mastic, goldenrod, and mango in the solid content of the composition of the present invention is preferably 60% by mass or less, more preferably 50% by mass or less, and particularly preferably 40% by mass or less.

[0041] When the composition of the present invention contains pomegranate, the proportion of pomegranate in the composition is preferably 0.01% by mass or more and 60% by mass or less, more preferably 0.1% by mass or more and 50% by mass or less, particularly preferably 1% by mass or more and 40% by mass or less, and most preferably 5% by mass or more and 40% by mass or less, based on the solid content. When the composition of the present invention contains shilajit, the proportion of shilajit in the composition is preferably 0.01% by mass or more and 60% by mass or less, more preferably 0.1% by mass or more and 50% by mass or less, particularly preferably 1% by mass or more and 40% by mass or less, and most preferably 5% by mass or more and 40% by mass or less, based on the solid content. When the composition of the present invention contains hibiscus, the proportion of hibiscus in the composition is preferably 0.01% by mass or more and 60% by mass or less, more preferably 0.1% by mass or more and 50% by mass or less, particularly preferably 1% by mass or more and 40% by mass or less, and most preferably 5% by mass or more and 40% by mass or less, based on the solid content. When the composition of the present invention contains mastic, the proportion of mastic in the composition is preferably from 0.01% by mass to 60% by mass, more preferably from 0.1% by mass to 50% by mass, particularly preferably from 1% by mass to 40% by mass, and most preferably from 5% by mass to 40% by mass, based on the solid content. When the composition of the present invention contains goldenrod, the proportion of goldenrod in the composition is preferably 0.01% by mass or more and 60% by mass or less, more preferably 0.1% by mass or more and 50% by mass or less, particularly preferably 1% by mass or more and 40% by mass or less, and most preferably 5% by mass or more and 40% by mass or less, based on the solid content. When the composition of the present invention contains mango, the proportion of mango in the composition is preferably from 0.01% by mass to 60% by mass, more preferably from 0.1% by mass to 50% by mass, particularly preferably from 1% by mass to 40% by mass, and most preferably from 5% by mass to 40% by mass, based on the solid content.

[0042] In the composition of the present invention, the ratio of the total amount of gallic acid to pomegranate, shilajit, hibiscus, mastic, marigold, and mango is preferably a ratio of the dry mass of the former to the latter of 100:0.1 or more and 70,000 or less, from the standpoint of suppressing the expression of the SREBF1 gene or easily promoting the expression of the PPARα, HO-1, or NOS3 gene, suppressing or promoting the decrease of triglyceride or cholesterol levels, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, or improving erectile dysfunction. A ratio of 1 or more and 50,000 or less is more preferable, and a ratio of 10 or more and 40,000 or less is particularly preferable.

[0043] When the composition of the present invention contains pomegranate, the ratio of gallic acid to pomegranate, as the dry mass ratio of the former to the latter, is preferably 100:0.1 or more and 70,000 or less, from the viewpoints of inhibiting or promoting the decrease of neutral fat or cholesterol levels, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, or improving erectile dysfunction. It is more preferably 1 or more and 50,000 or less, and particularly preferably 10 or more and 40,000 or less. When the composition of the present invention contains shilajit, the ratio of gallic acid to shilajit, as measured by dry mass, is preferably 100:0.1 or more and 70,000 or less, from the viewpoints of inhibiting or promoting a decrease in neutral fat or cholesterol, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, or improving erectile dysfunction. The ratio is more preferably 1 or more and 50,000 or less, and particularly preferably 10 or more and 40,000 or less. When the composition of the present invention contains hibiscus, the ratio of gallic acid to hibiscus, as measured by dry mass, is preferably 100:0.1 or more and 70,000 or less, from the viewpoints of inhibiting or promoting a decrease in neutral fat or cholesterol, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, or improving erectile dysfunction. A ratio of 1 or more and 50,000 or less is more preferable, and a ratio of 10 or more and 40,000 or less is particularly preferable. When the composition of the present invention contains mastic, the ratio of gallic acid to mastic, as measured by dry mass, is preferably 100:0.1 or more and 70,000 or less, from the viewpoints of inhibiting or promoting a decrease in neutral fat or cholesterol, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, or improving erectile dysfunction. A ratio of 1 or more and 50,000 or less is more preferable, and a ratio of 10 or more and 40,000 or less is particularly preferable. When the composition of the present invention contains goldenrod, the ratio of gallic acid to goldenrod, or the dry mass ratio of the former to the latter, is preferably 100:0.1 or more and 70,000 or less, from the standpoint of inhibiting or promoting a decrease in triglyceride or cholesterol levels, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, or improving erectile dysfunction; it is more preferably 1 or more and 50,000 or less, and particularly preferably 10 or more and 40,000 or less. When the composition of the present invention contains mango, the ratio of gallic acid to mango, the dry mass ratio of the former to the latter, is preferably 100:0.1 or more and 70,000 or less, from the viewpoints of inhibiting or promoting a decrease in neutral fat or cholesterol, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, or improving erectile dysfunction. A ratio of 1 or more and 50,000 or less is more preferable, and a ratio of 10 or more and 40,000 or less is particularly preferable.

[0044] The oral composition of the present invention can be used, for example, as a pharmaceutical product (including quasi-drugs) or a so-called health food such as a functional food whose efficacy has been approved by a designated organization, such as a food for specified health uses, a food with nutrient function claims, or a food with functional claims.

[0045] As shown in the Examples below, the oral composition of the present invention can effectively suppress the expression of SREBF1 and can also effectively promote the expression of PPARα, HO-1, and NOS3.

[0046] As described in Non-Patent Document 1, SREBF1 is a transcription factor that regulates the biosynthesis and uptake of cholesterol in cells such as the liver. Increased expression of SREBF1 in the liver increases the expression of ATP citrate lyase. ATP citrate lyase is an enzyme that synthesizes acetyl-CoA from citrate. Cholesterol is formed from acetyl-CoA through the action of multiple enzymes, resulting in increased cholesterol in the liver. SREBF1 is also a fatty acid synthesis-related gene that increases the expression of various enzymes (called ribogenic enzymes) involved in fatty acid synthesis and triglyceride synthesis, thereby converting energy acquired through ingestion into fatty acids and triglycerides for active storage. Therefore, suppressing SREBF1 expression in hepatocytes can suppress increases in cholesterol and triglycerides in the blood and liver, or promote their reduction.

[0047] As described in Non-Patent Document 1, PPARα enhances the expression of genes involved in the beta-oxidation of fatty acids in the liver, thereby controlling fatty acid breakdown. Fatty acids derived from adipocytes and taken up from the blood undergo beta-oxidation in liver cells and are used for energy production. Gene expression of the enzymes responsible for this beta-oxidation is regulated by PPARα, and enhanced PPARα expression is known to promote fatty acid beta-oxidation. Furthermore, as described in Non-Patent Document 2, enhanced PPARα expression in the liver is known to promote an increase in HDL in blood vessels by regulating the expression of apolipoprotein in the liver. HDL is said to have the role of collecting excess cholesterol in the blood and transporting it to the liver for processing. Therefore, promoting PPARα expression in liver cells can suppress or promote the reduction of cholesterol and triglycerides in the blood and liver.

[0048] Furthermore, heme oxygenase 1 (HO-1, sometimes referred to as "HMOX1") is an enzyme that decomposes heme into biliverdin, carbon monoxide (CO), and free iron (Fe). HO cleaves the porphyrin ring of heme and adds oxygen molecules (oxygenase). Increased expression of HO-1 is thought to be one of the major mechanisms protecting cells from oxidative stress. Furthermore, as described in Non-Patent Document 3, oxidative stress such as reactive oxygen species and mitochondrial dysfunction are thought to be contributing factors to the decline in brain function. As described in Non-Patent Document 4, various physical, psychological, and physiological stresses imposed on individuals can cause mitochondrial dysfunction in neurons, leading to neuronal damage, which is one of the causes of depression, and it is known that depression increases oxidative stress in the brain (Non-Patent Document 4). Oxidative stress damages mitochondrial DNA in neurons and neuron-like cells, resulting in reduced expression of proteins important for ATP production, thereby reducing ATP production, which is important for brain function. As described in Non-Patent Document 5, HO-1 is known to have a mitochondrial protective effect under oxidative stress in neuronal cells. For these reasons, promoting the expression of HO-1 in neuronal cells, neuronal cells, etc. can prevent mitochondrial damage in neuronal cells and neuronal cells in the brain and improve brain function, as well as improve stress resistance, such as reducing or alleviating depression caused by various physical, psychological (psychosocial), and physiological stresses.

[0049] In this specification, improvement of brain function includes alleviating or reducing neurological disorders, depressive states such as depression, neuropathic pain, eye damage, decline in cognitive function, decline in memory, decline in judgment ability, etc., by protecting brain neurons or neuron-like cells from oxidative stress. In addition, in this specification, improving stress resistance includes not only suppressing or alleviating the above-mentioned depressive state caused by physical, physiological, or psychosocial stress, but also preventing neurological disorders, neuropathic pain, eye damage, decline in cognitive function, decline in memory, and decline in judgment ability by protecting nerve cells or nerve-like cells.

[0050] Nitric oxide synthase 3 (NOS3), also known as endothelial nitric oxide synthase (eNOS), is primarily responsible for the production of NO in the vascular endothelium. The vascular endothelium consists of a single layer of flattened cells lining the inner surface of blood vessels, forming the interface between the blood circulating in the lumen and the rest of the vascular wall. NO produced by NOS3 in the vascular endothelium plays an important role in regulating vascular tone, cell proliferation, leukocyte adhesion, and platelet aggregation. Activation of NOS3 is known to dilate capillaries and improve blood flow (Non-Patent Document 6), which is known to promote nutrient supply to muscles and reduce physical fatigue. Therefore, enhancing NOS3 expression is thought to improve blood flow and alleviate physical fatigue. Furthermore, it has been suggested that decreased NOS3 activity may inhibit smooth muscle relaxation and cause erectile dysfunction (ED) (Non-Patent Document 7), and enhancing NOS3 expression is thought to improve erectile dysfunction. In this specification, physical fatigue includes lethargy, fatigue, tiredness, physical exhaustion, and decreased physical function due to poor circulation. Furthermore, erectile dysfunction is also called erectile dysfunction and includes decreased erectile function.

[0051] The present invention is not particularly limited as long as the product is distinguishable from other products in that it contains gallic acid and further contains at least one selected from pomegranate, shilajit, hibiscus, mastic, goldenrod, and mango, and is used to suppress the increase or elevation of cholesterol, suppress cholesterol production, lower or promote the decrease of cholesterol, suppress the increase or elevation of triglycerides, lower or promote the decrease of triglycerides, improve brain function, suppress the decline of brain function, improve stress resistance, reduce or alleviate depressive states such as depression caused by stress, improve blood flow, reduce physical fatigue, and improve erectile dysfunction. For example, the present invention includes within its scope products that display these functions on the product itself, packaging, instructions, or promotional materials (advertising media). The oral composition of the present invention is not limited to those that display the plant material of the present invention as an active ingredient on the product packaging or the like. For example, the active ingredient may not be specified. Furthermore, even general foods that are manufactured and sold with a suggested use in mind are also included within the scope of the present invention.

[0052] Specifically, examples of so-called health foods include those labeled with claims such as "suppressing the increase of cholesterol," "suppressing the rise of cholesterol," "suppressing the production of cholesterol," "promoting the decrease of cholesterol," "promoting the decrease of cholesterol," "for those concerned about cholesterol," "suppressing the absorption of cholesterol," "for those with high cholesterol," "suppressing the increase of triglycerides," "suppressing the increase of triglycerides," "promoting the decrease of triglycerides," "promoting the decrease of triglycerides," "for those concerned about triglycerides," "suppressing fat absorption," "for those with high triglycerides," "improving brain function," "suppressing the decline of brain function," "for those concerned about memory decline," "preventing memory decline," "improving stress tolerance," "reducing mental fatigue," "relieving anxiety," "for persistent fatigue," "for daily fatigue," "supporting high physical and mental performance," "improving fatigue," "for those who tire easily," "improving blood flow," "reducing physical fatigue," "preventing physical fatigue," "improving erectile dysfunction," "improving male sexual function," "suppressing the decline of male sexual function," "supporting the maintenance of male sexual function," "for those concerned about the decline of male sexual function," and "improving men's QOL."

[0053] Examples of the form of the oral composition of the present invention include tablets, capsules, powders, granules, liquids, particles, rods, plates, blocks, solids, rounds, pastes, creams, caplets, gels, chewable tablets, sticks, etc. Among these, tablets, capsules, powders, granules, rounds, and chewable tablets are preferred, and tablets, capsules, rounds, and chewable tablets are more preferred.

[0054] When the oral composition of the present invention is made into a tablet, pill, or chewable tablet, it is preferable to add one or more of an excipient, a lubricant, and a fluidizing agent, because this improves moldability and improves the storage stability of the resulting tablet, pill, or chewable tablet. In particular, the use of an excipient and a lubricant can further improve storage stability.

[0055] An excipient is added to improve the handling or molding of a composition or to make it easier to take. The excipients that can be used in the present invention are not particularly limited, and examples thereof include starch or its derivatives such as starch, pregelatinized starch, partially pregelatinized starch, dextrin, and other starch hydrolysates, crystalline cellulose, sugar alcohol, lactose, brewer's yeast, low-substituted hydroxypropyl cellulose, hydroxypropyl cellulose, refined sucrose, light anhydrous silicic acid, calcium silicate, titanium oxide, precipitated calcium carbonate, etc. These may be used alone or in combination of two or more.

[0056] Lubricants are used to reduce friction between the tablet press punches and dies and the tablet when compressing powder for tablets, and to prevent tableting problems such as sticking. Lubricants that can be used in the present invention are not particularly limited as long as they are components that can achieve the above-mentioned purpose, and examples include stearic acid or salts thereof such as stearic acid, calcium stearate, and magnesium stearate, sodium stearyl fumarate, sucrose fatty acid esters, talc, polyethylene glycol, vegetable oils and fats, and hydrogenated oils. These may be used alone or in combination of two or more.

[0057] A fluidizer is used to improve the fluidity of mixed powders or granules. There are no particular limitations on the fluidizers that can be used in the present invention, and examples include silicon dioxide, aluminum silicate, magnesium aluminosilicate, calcium phosphate, magnesium carbonate, magnesium oxide, etc. These may be used alone or in combination of two or more. In the present invention, commercially available excipients, lubricants, and fluidizers can all be used.

[0058] Although there is no particular limitation on the amount of intake of the oral composition of the present invention, in order to further enhance its effect, the intake amount of gallic acid, pomegranate, shilajit, hibiscus, mastic, marigold, and mango of the present invention per day for an adult is preferably 1 mg or more, more preferably 10 mg or more, and even more preferably 50 mg or more, in dry mass. The upper limit is, for example, 10,000 mg, preferably 7,000 mg, and more preferably 5,000 mg.

[0059] The oral composition of the present invention may be appropriately designed so that the daily intake is the above-mentioned intake amount, and may be taken in one dose or in multiple doses. For example, in the case of tablets, capsules, pills, or chewable tablets, the number of doses may be 1 to 4 per day, and the total amount may be the above-mentioned intake amount. In the case of beverages, the above-mentioned intake amount may be blended into the daily intake amount. The oral composition of the present invention may be stored as a daily amount in a single container or divided into, for example, 2 to 3 containers so that the daily intake is the above-mentioned intake amount.

[0060] The oral compositions of the present invention can be prepared by known methods, if necessary, by adding other ingredients other than the plant material of the present invention. Examples of other ingredients include water-soluble vitamins (vitamins B1, B2, B3, B5, B6, B12, B13, B15, B17, biotin, choline, folic acid, inositol, PABA, vitamin C, and vitamin P) and oil-soluble vitamins (vitamins A, D, E, and K), minerals (magnesium, phosphorus, zinc, and iron), sulfur-containing compounds (e.g., found in taurine and garlic), flavanoids (e.g., hesperidin and quercetin), proteins (e.g., collagen), peptides, amino acids, animal fats and oils, vegetable fats and oils, and ground products or extracts of animals and plants. [Example]

[0061] The present invention will be described in more detail below with reference to examples. However, the scope of the present invention is not limited to these examples. Hereinafter, unless otherwise specified, "%" means % by mass and "parts" means parts by mass. In the examples, gallic acid that was used was not derived from pomegranate, shilajit, hibiscus, mastic, marigold, or mango.

[0062] In the following Examples, Comparative Examples and Production Examples, the following components were used as shown in the following tables. Gallic acid was used as a gallic acid reagent (anhydrous, powdery, purity approximately 100% by mass). For pomegranate, a powdered extract (pomegranate peel extract) was used, which was made by drying an ethanol extract of pomegranate peel.

[0063] The shilajit used was a dried powder of a water extract of shilajit ore. Specifically, the extract of shilajit ore was extracted with water, filtered, and then dried to obtain a powdered extract (shilajit extract). The amount of fulvic acid in the extract was 20% by mass.

[0064] The hibiscus used was a hydroethanol extract (dried powder) of hibiscus (scientific name: Hibiscus sabdariffa L.) flowers. Specifically, hibiscus flowers were extracted with 50% hydroethanol by mass, and the resulting extract was concentrated and then dried to form a powder (hibiscus flower extract).

[0065] The mastic used was made by drying the sap of the shrub mastic (scientific name: Pistacia lentiscus L.), which belongs to the Anacardiaceae family, and grinding it into powder (mastic powder).

[0066] The honeysuckle used was a dried powder of the water extract of the buds of honeysuckle (scientific name: Lonicera japonica Thunberg) of the Caprifoliaceae family (Lonicera japonica bud extract).

[0067] For the mango, dried powder of hydroethanolic extract of mango (scientific name: Mangifera indica) leaves (mango leaf extract) was used.

[0068] Commercially available dextrin was used.

[0069] [Examples 1-1 to 1-12, Comparative Examples 1-1 to 1-7] The components shown in Table 1 were mixed in the composition shown in Table 1.

[0070] (Test 1: Triglycerides, Cholesterol) Human hepatoma-derived cells (HepG2, RIKEN) were cultured in 10% FBS-DMEM and then plated on a collagen-coated 96-well plate at 2 × 10 4 The cells were seeded at 100 μL / well, and pre-cultured for 24 hours in a 37°C, 5% by volume CO 2 incubator. After removing the medium from each well, 100 μL / well of medium containing the test substance and 1.5 mM sodium oleate (Nacalai Tesque) as a fatty acid load was added. The medium used was 0.5% by volume DMSO, 2% by volume BSA-DMEM. The proportions (mass %) of each component in the test substance are shown in Tables 1 and 2. The concentration of the test substance in the medium was 25 μg / mL. The main culture was carried out for 24 hours in an incubator at 37°C and 5% by volume CO2. After removing the medium from each well, the wells were washed once with PBS, and RNA was recovered using an RNeasy Mini Kit (QIAGEN). cDNA was synthesized using ReverTra Ace® qPCR RT Master Mix (TOYOBO). Using the resulting cDNA as a template, quantitative real-time PCR was performed using a Rotor-Gene SYBR Green PCR Kit (QIAGEN) with a PPARα primer (QIAGEN, trade name: Hs_PPARA_1_SG QuantiTect Primer Assay (QT00017451)) and an SREBF1 primer (QIAGEN, trade name: Hs_SREBF1_1_SG QuantiTect Primer Assay (QT00036897)) to measure gene expression levels of PPARα and SREBF1. As an endogenous control, ACTB primer (QIAGEN, trade name: Hs_ACTB_1_SG QuantiTect primer assay (QT00095431)) was used to measure gene expression levels of ACTB. The values ​​of PPARα gene expression level / ACTB gene expression level and SREBF1 gene expression level / ACTB gene expression level were calculated relative to each other, with Comparative Example 1-1 set as 1. The results are shown in Tables 1 and 2.

[0071] [Table 1]

[0072] [Table 2]

[0073] HepG2 cells are commonly used as a liver model cell. As shown in Tables 1 and 2, the composition of the present invention contains gallic acid and at least one selected from pomegranate peel extract, shilajit extract, hibiscus flower extract, mastic powder, goldfish bud extract, and mango leaf extract, thereby effectively suppressing the expression of SREBF1 and promoting the expression of PPARα, thereby achieving effects for inhibiting and / or reducing elevated cholesterol and neutral fat levels.

[0074] [Examples 2-1 to 2-12, Comparative Examples 2-1 to 2-7] (Test 2: Brain Function) Rat adrenal pheochromocytoma cells (PC12, JCRB Cell Bank) were cultured in 10% FBS-RPMI 1640 medium and plated at 4 × 10 cells / well on a collagen-coated 96-well plate. 4 The cells were seeded at 100 μL / well so that the cells were present at 100 μL / well, and the cells were pre-cultured for 24 hours in a 37°C, 5% by volume CO 2 incubator. After the pre-incubation, 100 μL / well of medium containing the test substance was added to the medium already in the wells, and the cells were cultured for 24 hours in a 37°C, 5% CO2 incubator. The medium used was 0.5% DMSO (volume %), 10% FBS (volume %), and RPMI 1640 medium. The proportions (mass %) of each component in the test substance are shown in Tables 3 and 4. The concentration of the test substance in the medium was 1.25 μg / mL. After 24 hours of incubation, hydrogen peroxide was diluted to 2.2 mM with 10% FBS-RPMI 1640 and added at 20 μL / well (final concentration: 200 μM) onto the medium already in the wells. The cells were incubated at 37°C in a 5% CO incubator for 2 hours. After removing the medium from each well, RNA was collected using an RNeasy Mini Kit (QIAGEN), and cDNA was synthesized using ReverTra Ace® qPCR RT Master Mix (TOYOBO). Using the obtained cDNA as a template, quantitative real-time PCR was performed with a Rotor-Gene SYBR Green PCR Kit (QIAGEN) using a primer for the HO-1 gene (Hmox1) (manufactured by QIAGEN, trade name: Rn_Hmox1_1_SG QuantiTect Primer Assay (QT00175994)) to measure the expression level of the HO-1 gene (Hmox1). As an endogenous control, a primer for GAPDH (manufactured by QIAGEN, trade name: Rn_Gapd_1_SG QuantiTect Primer Assay (QT00199633)) was used to measure the expression level of the GAPDH gene. Relative values ​​were calculated, with Comparative Example 2-1 set to 1.

[0075] [Table 3]

[0076] [Table 4]

[0077] As shown in Tables 3 and 4, the composition of the present invention contains gallic acid and further contains at least one selected from pomegranate peel extract, shilajit extract, hibiscus flower extract, mastic powder, marigold bud extract, and mango leaf extract, thereby effectively promoting the expression of HO-1 (HMOX1) in neuron-like cells and providing effects for improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, and improving stress resistance.

[0078] [Examples 3-1 to 3-12, Comparative Examples 3-1 to 3-7] (3) Blood flow Human umbilical vein endothelial cells (HUVEC, Lonza) were cultured in EGM-2 medium (Lonza). 1 × 10 cells were plated onto a collagen-coated 96-well plate. 4 The cells were seeded at 100 μL / well so that the cells were 100 cells / well, and pre-cultured for 24 hours in a 37°C, 5% by volume CO 2 incubator. After removing the medium from each well, 100 μL / well of medium containing the test substance was added. 0.5% by volume DMSO-EGM-2 medium was used. The proportions (mass %) of each component in the test substance are shown in Tables 5 and 6. The concentration of the test substance in the medium was 6.25 μg / mL. After removing the medium from each well, the wells were washed once with PBS, and RNA was recovered using an RNeasy Mini Kit (QIAGEN). cDNA was synthesized using ReverTra Ace® qPCR RT Master Mix (TOYOBO). Using the resulting cDNA as a template, quantitative real-time PCR was performed using NOS3 (eNOS) primers (Takara, trade name: sense (5'-CCAGCTAGCCAAAGTCACCAT-3') (JP33538048), anti-sense (5'-GTCTCGGAGCCATACAGGATT-3') (JP33538049)) with a Rotor-Gene SYBR Green PCR Kit (QIAGEN) to measure the gene expression level of NOS3 (eNOS). As an endogenous control, ACTB primers (QIAGEN, trade name: Hs_ACTB_1_SG QuantiTect primer assay (QT00095431)) were used to measure the gene expression level of ACTB. Relative values ​​were calculated, with Comparative Example 3-1 set to 1. The results are shown in Tables 5 and 6 below.

[0079] [Table 5]

[0080] [Table 6]

[0081] As shown in Tables 5 and 6, the composition of the present invention contains gallic acid and further contains at least one selected from pomegranate peel extract, shilajit extract, hibiscus flower extract, mastic powder, goldfish bud extract, and mango leaf extract, thereby effectively promoting the expression of NOS3 in vascular endothelial cells and being effective for improving blood flow, reducing physical fatigue, or improving erectile dysfunction.

[0082] Granules containing the following ingredients were prepared (Production Examples 1 to 6). Taking the resulting granules, 3 g per dose, 1 to 3 times a day, suspended in water as needed, provides excellent effects such as suppressing or promoting the reduction of neutral fat or cholesterol elevation, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, and improving erectile dysfunction. The amounts of ingredients in the tables below are in mass %.

[0083] [Table 7]

[0084] Tablets (200 mg per tablet) consisting of the following ingredients were produced (Production Examples 7 to 12). Taking one to three tablets of the resulting tablets one to three times daily provides excellent results, such as suppressing or promoting the reduction of neutral fat or cholesterol elevation, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, and improving erectile dysfunction. The amounts of ingredients in the tables below are in mass %.

[0085] [Table 8]

[0086] Granules containing the following ingredients were prepared and encapsulated in hard capsules to produce capsules (Production Examples 13 to 18). Each capsule contains 200 mg of granules. Taking one to three capsules of the resulting capsules one to three times daily provides excellent results, including suppressing or promoting the reduction of neutral fat or cholesterol elevation, improving brain function, reducing and / or alleviating depressive states such as stress-induced depression, improving stress resistance, improving blood flow, improving physical fatigue, and improving erectile dysfunction. The amounts of ingredients in the tables below are in mass %.

[0087] [Table 9] [Industrial Applicability]

[0088] The present invention provides an oral composition that can contribute to suppressing or promoting the decrease of triglyceride or cholesterol elevation, improving brain function, reducing and / or alleviating depressive states such as depression caused by stress, improving stress resistance, improving blood flow, improving physical fatigue, or improving erectile dysfunction by suppressing the expression of SREBF1 or promoting the expression of PPARα, HO-1, or NOS3.

Claims

1. Gallic acid is contained, and further, An oral composition comprising at least one selected from pomegranate, shilajit, hibiscus, mastic, goldenrod, and mango.

2. The oral composition according to claim 1, wherein the content of gallic acid is 0.1% by mass or more.

3. 3. The oral composition according to claim 1, wherein the total content of pomegranate, shilajit, hibiscus, mastic, marigold and mango is 5% by mass or more and 40% by mass or less.

4. The oral composition according to any one of claims 1 to 3, which is for suppressing and / or reducing cholesterol elevation.

5. The oral composition according to any one of claims 1 to 3, which is used to suppress and / or reduce an increase in neutral fat.

6. The oral composition according to any one of claims 1 to 3, which is for improving brain function.

7. The oral composition according to any one of claims 1 to 3, which is used to reduce and / or alleviate stress-induced depression or to improve stress resistance.

8. The oral composition according to any one of claims 1 to 3, which is used for improving blood flow, reducing physical fatigue, or improving erectile dysfunction.

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