Composition for mitochondrial activation

Abstract

To provide a technique that enables metabolic activation.SOLUTION: A composition for mitochondrial activation contains specific components.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present disclosure relates to compositions for activating mitochondria, etc. [Background technology]

[0002] It is known that various factors (e.g., high glucose load) enhance oxidative stress in cells and cause metabolic abnormalities. In particular, it is believed that high glucose load causes metabolic abnormalities in diabetic patients and prediabetic subjects, resulting in various symptoms. These symptoms may include symptoms in the oral cavity.

[0003] For example, it has been reported that the metabolic function of periodontal tissues is impaired in a diabetic state, and that activating the metabolic function of the gingiva of diabetic rats suppresses alveolar bone resorption. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] J Clin Periodontol 2017; 44: 463-471. IADR / PER General Session 2018; Presentation ID 1622 Summary of the Invention [Problem to be solved by the invention]

[0005] The present inventors have explored possible means for activating metabolism. [Means for solving the problem]

[0006] For example, even if oxidative stress in cells is increased, it is expected that metabolic disorders will be less likely to occur if metabolism can be activated. For this reason, a means capable of activating metabolism is considered to be useful.

[0007] The present inventors have focused on the function of mitochondria, which plays a major role in intracellular metabolism, and in particular on the ability of cells to consume oxygen. They have searched for materials that can improve the oxygen consumption rate, found that the use of specific materials can improve the ability of cells to consume oxygen, and have made further improvements.

[0008] The present disclosure includes, for example, the subject matter described in the following sections:

[0009] Section 1. Contains at least one selected from the group consisting of components listed in the table below: A composition for activating mitochondria.

[0010] [Table 1a]

[0011] Section 2. The composition according to item 1, wherein the mitochondria are mitochondria in periodontal ligament cells.

[0012] Section 3. Item 3. The composition according to item 1 or 2, wherein the mitochondrial activation is an increase in oxygen consumption in mitochondria. Effect of the Invention

[0013] It is possible to activate mitochondria and improve metabolic functions related to mitochondria (particularly, improve the oxygen consumption ability of mitochondria). For example, even if oxidative stress in cells is increased, the occurrence of metabolic abnormalities can be suppressed by improving metabolic functions.

[0014] Furthermore, by improving the mitochondrial metabolism of cells in the oral cavity (e.g., gingival cells and periodontal ligament cells), it is possible to activate the metabolic function of cells in the oral cavity or suppress a decline in their metabolic function, which is expected to make it possible to keep the oral cavity healthy (e.g., prevent periodontal disease). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] Each embodiment included in the present disclosure will be described in more detail below. The present disclosure preferably includes a composition for mitochondrial activation, but is not limited thereto, and the present disclosure includes all that is disclosed in the present specification and that can be recognized by a person skilled in the art.

[0016] The composition for mitochondrial activation included in the present disclosure contains the specific components listed in the following table, either singly or in combination of two or more. The composition for mitochondrial activation included in the present disclosure may be referred to as the composition of the present disclosure. These specific components may also be referred to as the components of the present disclosure.

[0017] [Table 1b] TIFF2025030881000003.tif49170

[0018] Among these ingredients, the ingredients listed in the upper rows are more preferable. For example, soybean extract and ingredients listed in the upper rows are preferable, pantothenic acid and ingredients listed in the upper rows are more preferable, methionine and ingredients listed in the upper rows are even more preferable, and oat extract and ingredients listed in the upper rows are even more preferable.

[0019] These ingredients can be purchased commercially. The extract is preferably an extract made of water, alcohol, or hydroalcohol. The alcohol is preferably ethanol and / or butylene glycol. The extract may be in the form of a dry product or a liquid.

[0020] The components of the present disclosure can be broadly divided into compounds and extracts of living organisms (eg, whole or part of animals or plants).

[0021] Examples of the compound include inositol, reduced palatinose, isoleucine, cholecalciferol, glycyrrhizic acid or its salt, allantoin, alanine, protamine or its salt, cinnamaldhyde, paramylon, cyclodextrin (particularly γ-cyclodextrin), arginine, ceramide, methionine, glutamic acid or its salt, etc. As the salt of glycyrrhizic acid, an alkali metal salt is preferable, and a sodium salt or a potassium salt is more preferable. More specifically, dipotassium glycyrrhizinate and trisodium glycyrrhizinate are preferable. As the salt of protamine, a hydrochloride salt, a sulfate salt, etc. are preferable, and a sulfate salt is more preferable. As the salt of glutamic acid, an alkali metal salt is preferable, and a sodium salt or a potassium salt is more preferable.

[0022] As the extract of an organism, it is preferable to use an extract from a part that is usually used as an extract for external use or as food.

[0023] The chamomile extract is not particularly limited as long as it is an extract of chamomile. For example, extracts obtained from the stems, leaves, or flowers can be used. Among them, extracted oils (e.g., essential oils) can be particularly preferably used.

[0024] As the Cistanche salicina extract, an extract of the fleshy stem of Cistanche salicina is preferred. Cistanche salicina is a parasitic plant of the Orobanchaceae family, and its extract is used as a herbal medicine.

[0025] Olive leaf extract is an extract of olive leaves and is an ingredient used in supplements and topical agents.

[0026] As the eucommia extract, an extract of eucommia leaves is particularly preferable. The extract of eucommia leaves is widely used as a supplement and the like.

[0027] Arnica flower extract is an extract obtained from the flowers (and roots) of Arnica montana, and is an ingredient used as an external preparation, etc. Arnica is a plant of the Asteraceae family.

[0028] Honeysuckle leaf extract is an extract of honeysuckle leaves. Peony root extract is an extract of peony roots. Ginseng root extract is an extract of ginseng roots.

[0029] The ginger extract is preferably a ginger rhizome extract, which can be used in external preparations and foods to promote blood circulation.

[0030] Placenta extract is an extract obtained from the placenta of mammals (especially cows, pigs, horses, etc.) and is used in cosmetics and other products.

[0031] Lamium extract is an extract of the whole plant and / or flowers of Lamium, a plant of the Lamiaceae family, and is used in cosmetics and the like.

[0032] Melioba oleracea extract is an extract of the whole plant of Melioba oleracea (also called melilot), a legume plant, and is used in foods, etc.

[0033] Willow extract is an extract of the bark and / or shoots of the willow tree, and is used in supplements, etc.

[0034] Wild grape extract is an extract of wild grape (mainly fruit (especially seeds), stems, leaves, etc.) and is used in food and other applications.

[0035] Valeriana root extract is an extract of the root of Valeriana officinalis L. and is used in supplements, etc.

[0036] Fennel extract is an extract of the fruit of the fennel plant, which belongs to the Umbelliferae family, and is used in cosmetics and other products.

[0037] Devil's claw extract is an extract of the root (tuber) of devil's claw and is used in supplements, etc.

[0038] Hypericum extract is an extract of the flowers, stems, or leaves of Hypericum perforatum, and is used in external preparations, etc.

[0039] Senega extract is an extract of the root of the senega plant and is used as a cough suppressant and expectorant.

[0040] Rice bran extract is an extract of rice bran.

[0041] Fermented black garlic extract is an extract of fermented black garlic obtained by fermenting garlic (bulbs) for a certain period of time, and is used in supplements, etc.

[0042] Purple brown rice extract is an extract of ancient red-purple brown rice such as red rice and black rice, and is used in supplements, etc.

[0043] Wild thyme extract is an extract of the whole plant of wild thyme (especially the leaves and stems) and is used in external preparations, etc.

[0044] Turmeric rhizome extract is an extract of the rhizome of turmeric.

[0045] Panax notoginseng extract is an extract of Panax notoginseng (root) and is used in supplements, etc.

[0046] Among the components of the present disclosure, the components described in the following table are particularly preferred.

[0047] [Table 2]

[0048] The content of the components of the present disclosure in the composition of the present disclosure is not particularly limited as long as the effects are not impaired, and may be, for example, about 0.01 to 99.99% by mass.

[0049] The intake form of the composition of the present disclosure is not particularly limited, but is preferably oral intake or topical application to the oral mucosa. That is, the composition of the present disclosure is preferably an oral composition or an oral composition. By orally ingesting the composition of the present disclosure, mitochondria can be activated in cells (particularly cells in the oral cavity) and metabolic functions related to mitochondria can be improved (particularly, the oxygen consumption ability of mitochondria can be improved). The composition of the present disclosure is preferably, for example, an oral pharmaceutical composition, a food composition (including a beverage composition and a food additive composition), or an oral composition.

[0050] The composition of the present disclosure includes the above-mentioned components and may further include other components. The other components may be appropriately selected depending on the field in which the composition is used. For example, a medicamentically or food hygienically acceptable carrier may be used.

[0051] When used as a pharmaceutical composition, other components include pharma- ceutically acceptable bases, carriers, and / or additives (e.g., solvents, dispersants, emulsifiers, buffers, stabilizers, excipients, binders, disintegrants, lubricants, etc.), etc. The form of the pharmaceutical composition is not particularly limited, and examples thereof include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, creams, and poultices.

[0052] When used as a food composition, other ingredients include bases, carriers, additives that are acceptable from the viewpoint of food hygiene, and other ingredients and materials that can be used as foods. The form of the food composition is not particularly limited, and examples thereof include processed foods, health foods (nutritional supplements, nutritional functional foods, foods for the sick, foods for specified health uses, functional products, etc.), supplements, foods for the sick (hospital food, sick food, nursing food, etc.). These can be prepared by conventional methods. In particular, when preparing a food composition as a health food (nutritional supplements, nutritional functional foods, foods for the sick, foods for specified health uses, functional products, etc.) or supplements, it is preferable to prepare it in the form of, for example, granules, capsules, tablets (including chewable agents, etc.), beverages (drink powders, drinks, smoothies, etc.) so that it is easy to take continuously, and among them, the forms of capsules, tablets, tablets, drink powders, drinks, jellies, and gummies are preferable from the viewpoint of ease of intake, but are not particularly limited thereto. When the food composition is used as a food additive composition, the food composition may be in the form of, for example, liquid, powder, flake, granule, or paste.

[0053] When used as an oral composition, it can be in the form (dosage form) of, for example, an ointment, paste, gel, liquid, spray, mouthwash, liquid dentifrice, toothpaste, gum, etc.

[0054] As other components, components that are known to be blended in oral compositions can be used.

[0055] For example, the surfactant may be a nonionic surfactant, an anionic surfactant, or an amphoteric surfactant.Specifically, for example, nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid esters, maltose fatty acid esters, and lactose fatty acid esters; fatty acid alkanolamides; glycerin fatty acid esters; sorbitan fatty acid esters; fatty acid monoglycerides; polyoxyethylene alkyl ethers with a polyoxyethylene addition coefficient of 8 to 10 and an alkyl group with 13 to 15 carbon atoms; polyoxyethylene alkylphenyl ethers with a polyoxyethylene addition coefficient of 10 to 18 and an alkyl group with 9 carbon atoms; diethyl sebacate; polyoxyethylene hydrogenated castor oil; fatty acid polyoxyethylene sorbitan; etc. Examples of anionic surfactants include sulfate ester salts such as sodium lauryl sulfate and polyoxyethylene lauryl ether sodium sulfate; sulfosuccinates such as sodium lauryl sulfosuccinate and polyoxyethylene lauryl ether sodium sulfosuccinate; acylamino acid salts such as sodium cocoyl sarcosine and sodium lauroyl methyl alanine; and sodium cocoyl methyl taurine. Examples of amphoteric surfactants include acetate betaine type surfactants such as lauryl dimethylamino acetate betaine and coconut oil fatty acid amidopropyl dimethylamino acetate betaine; imidazoline type surfactants such as N-cocoyl-N-carboxymethyl-N-hydroxyethyl ethylenediamine sodium; and amino acid type surfactants such as N-lauryl diaminoethyl glycine. These surfactants can be blended alone or in combination of two or more. The blending amount is usually 0.1 to 5% by mass based on the total amount of the composition.

[0056] In addition, as the flavoring agent, for example, menthol, carboxylic acid, anethole, eugenol, methyl salicylate, limonene, ocimene, n-decyl alcohol, citronellol, α-terpineol, methyl acetate, citronenyl acetate, methyl eugenol, cineole, linalool, ethyl linalool, thymol, spearmint oil, peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, perilla oil, wintergreen oil, clove oil, eucalyptus oil, pimento oil, d-camphor, d-borneol, fennel oil, cinnamon oil, peppermint oil, vanillin, etc. can be used. These can be blended alone or in combination of two or more kinds, for example, at 0.001 to 1.5% by mass with respect to the total amount of the composition.

[0057] In addition, examples of sweeteners that can be used include saccharin sodium, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, perillartine, thaumatin, aspartyl phenylalanyl methyl ester, p-methoxycinnamic aldehyde, etc. These can be blended in an amount of, for example, 0.01 to 1% by mass based on the total amount of the composition.

[0058] Furthermore, as a wetting agent, sorbitol, ethylene glycol, propylene glycol, glycerin, 1,3-butylene glycol, polypropylene glycol, xylitol, maltitol, lactitol, polyoxyethylene glycol, etc. can be blended alone or in combination of two or more kinds.

[0059] As preservatives, parabens such as methylparaben, ethylparaben, propylparaben, and butylparaben, sodium benzoate, phenoxyethanol, alkyldiaminoethylglycine hydrochloride, and the like can be added.

[0060] As coloring agents, legal pigments such as Blue No. 1, Yellow No. 4, Red No. 202, Green No. 3, mineral pigments such as ultramarine, enhanced ultramarine, and Prussian blue, titanium oxide, etc. may be blended.

[0061] As a pH adjuster, citric acid, phosphoric acid, malic acid, pyrophosphoric acid, lactic acid, tartaric acid, glycerophosphoric acid, acetic acid, nitric acid, or chemically possible salts thereof, sodium hydroxide, etc. may be blended. These may be blended alone or in combination of two or more kinds so that the pH of the composition is in the range of 4 to 8, preferably 5 to 7. The blending amount of the pH adjuster may be, for example, 0.01 to 2% by weight.

[0062] Medicinal ingredients include vitamin E such as dl-α-tocopherol acetate, tocopherol succinate, or tocopherol nicotinate, amphoteric bactericides such as dodecyldiaminoethylglycine, non-ionic bactericides such as triclosan, isopropylmethylphenol, and hinokitiol, anionic bactericides such as sodium lauroyl sarcosine, cationic bactericides such as cetylpyridinium chloride, chlorhexidine hydrochloride, benzalkonium chloride, and benzethonium chloride, dextranase, amylase, protease, mutanase, lysozyme, and lytic enzymes (Retech Enzyme). and the like, alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate, fluorides such as sodium fluoride and stannous fluoride, tranexamic acid, epsilon aminocaproic acid, aluminum chlorohydroxyl allantoin, dihydrocholesterol, glycyrrhetinic acid, copper chlorophyllin sodium, glycerophosphate, chlorophyll, sodium chloride, callopeptide, carbazochrome, hinokitiol, potassium nitrate, palatinit, and the like can be blended alone or in combination of two or more kinds.

[0063] Furthermore, it is also possible to add, as a base, alcohols, silicone, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane, plastibase, and the like.

[0064] The composition of the present disclosure can be preferably used for activating mitochondria in cells. More specifically, the composition of the present disclosure can preferably improve the decrease in oxygen consumption rate caused by, for example, high glucose or oxidative stress load. Therefore, it can also be preferably used to improve metabolic abnormalities in cells derived from diabetic patients or humans at risk of diabetes. For example, the metabolic function of periodontal tissues is impaired in a diabetic state, which is thought to promote the progression of periodontal disease in diabetic patients, and therefore it can be preferably used to improve metabolic abnormalities in cells (e.g., periodontal ligament cells) in periodontal tissues in particular, and thus to inhibit and / or improve the progression of periodontal disease. In addition, it is possible to not only improve the metabolism of mitochondria in cells in the oral cavity (e.g., gingival cells and periodontal ligament cells), but also to activate the metabolic function of various cells or inhibit the decline in metabolic function, and therefore the composition of the present disclosure can be used not only to inhibit and / or improve the progression of periodontal disease, but also to improve the metabolic function of other tissues that are impaired, for example, in a diabetic or prediabetic state, or due to aging. For example, it can be used to inhibit and / or improve obesity, renal dysfunction, retinopathy, neuropathy, cardiovascular disease, cerebral dysfunction, dementia, frailty, muscle weakness, and osteoporosis.

[0065] The subject of ingestion or application of the composition of the present disclosure is not particularly limited, and for example, it can be preferably ingested or applied to healthy individuals. In addition, from the viewpoint that the effect can be preferably achieved, subjects with metabolic abnormalities (particularly, subjects with reduced mitochondrial metabolism due to, for example, enhanced oxidative stress in cells) are preferred, and more specifically, subjects with metabolic abnormalities due to, for example, high glucose load are more preferred. In addition, as described above, by improving the mitochondrial metabolism of cells in the oral cavity (for example, gingival cells and periodontal ligament cells), it is possible to activate the metabolic function of cells in the oral cavity or suppress the decline in metabolic function, and it is expected that it is possible to keep the oral cavity healthy (for example, prevent periodontal disease), so subjects with gingival inflammation or periodontal disease are also preferred.

[0066] The timing of taking or applying the composition of the present disclosure is not particularly limited, but it can be taken or applied, for example, before or after taking a meal. The meal preferably contains carbohydrates (particularly carbohydrates that can become glucose when absorbed into the body) and lipids. It can also be preferably used, for example, during or after periodontal disease treatment to prevent recurrence.

[0067] Furthermore, although not particularly limited, the cells in which metabolic abnormalities can be suppressed by ingestion or application of the composition of the present disclosure are preferably cells in the oral cavity, and among them, gingival cells and periodontal ligament cells (particularly gingival fibroblasts and periodontal ligament fibroblasts) are preferred. Periodontal ligament cells are known to be strongly involved in immune responses, inflammatory responses, and alveolar bone resorption in periodontal disease, and are therefore most preferred.

[0068] In addition, in this specification, the term "comprising" includes "consisting essentially of" and "consisting of." In addition, the present disclosure includes any combination of the constituent elements described in this specification.

[0069] In addition, the various characteristics (properties, structures, functions, etc.) described in each embodiment of the present disclosure above may be combined in any way to specify the subject matter included in the present disclosure. In other words, the present disclosure includes all subject matter consisting of all combinations of each combinable characteristic described in this specification. EXAMPLES

[0070] Hereinafter, the embodiments of the present disclosure will be described more specifically with reference to examples, but the embodiments of the present disclosure are not limited to the following examples.

[0071] The oxygen consumption rate (OCR) of human periodontal ligament fibroblasts (HPDLF) was measured after applying the test sample to the cells. More specifically, the procedure was as follows.

[0072] Measurement of oxygen consumption rate (OCR) in periodontal ligament fibroblasts OCR was measured using an extracellular OCR plate assay kit (E297, DOJINDO). Human periodontal ligament fibroblasts (HPDLF) were cultured at 2 × 10 5 The cells were seeded in a 96-well plate at a density of 100 μL / well and cultured overnight, after which they were treated with each test substance (sample: final concentration 1 μg / mL) for 24 hours.

[0073] OCR was measured as follows. 100 μL of oxygen probe reaction solution, which has the property of increasing phosphorescence intensity when the oxygen concentration in the culture medium decreases, was added to each well. Then, a drop of mineral oil was added to each well to prevent the inflow of oxygen from the air. Phosphorescence intensity was measured using a Cytation 5 plate reader (BioTek Instruments), and the OCR of the cells was calculated using the Stern-Volmer equation. The OCR value (relative value) of each test substance is shown as a numerical value when the steady OCR value without administration is set to 1. In other words, since the steady OCR value without administration is set to 1, if the OCR value doubles due to administration of the test substance, the OCR value is 2.

[0074] The type and amount of each sample, as well as the results obtained, are shown in Table 3.

[0075] [Table 3] TIFF2025030881000006.tif69170

Claims

1. Contains at least one selected from the group consisting of components listed in the table below: A composition for activating mitochondria. 【Table 1】

2. The composition according to claim 1 , wherein the mitochondria are mitochondria in periodontal ligament cells.

3. The composition according to claim 1 or 2, wherein the mitochondrial activation is an increase in oxygen consumption in mitochondria.

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