Anti-aging components
A composition of NMN, pine bark, and fulvic acid effectively addresses the inadequacies of existing anti-aging solutions by promoting SIRT1 gene expression, offering enhanced anti-aging benefits.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2025-12-23
- Publication Date
- 2026-03-17
AI Technical Summary
Existing anti-aging solutions, such as resveratrol and Euglena, do not provide sufficient anti-aging effects, and there is a need for a composition that can be safely used over a long period with enhanced anti-aging properties.
A composition containing nicotinamide mononucleotide (NMN) combined with pine bark, banaba, and fulvic acid, which promotes sirtuin gene expression and enhances anti-aging effects.
The combination of NMN with pine bark, banaba, and fulvic acid significantly increases SIRT1 gene expression, demonstrating superior anti-aging effects compared to individual components and resveratrol.
Smart Images

Figure 2026048953000001_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to an anti-aging composition characterized by containing nicotinamide mononucleotide and at least one selected from the group consisting of pine bark, banaba, and fulvic acid.
Background Art
[0002] In Japan, due to the development of medical technology, people's lifespan itself has been extended. However, on the other hand, there are problems such as difficulties in daily life due to the decline of physical and mental functions associated with aging, and suffering from various diseases. The decline in functions that occurs with aging is generally called aging, and examples include the decline in eyesight, hearing, memory, motor ability, immune function, organ function, etc. Therefore, suppressing aging is desirable from the perspective of improving the quality of life, and it is considered important to prevent it with foods and cosmetics that can be safely used over a long period of time. Thus, the development of foods and cosmetics having such effects is expected.
[0003] As foods and cosmetics for suppressing aging, for example, resveratrol (Non-Patent Document 1) and Euglena (Patent Document 1) are known. However, according to the investigation by the present inventors, the anti-aging effects of resveratrol and Euglena are not sufficient.
Prior Art Documents
Patent Documents
[0004]
Patent Document 1
Non-Patent Documents
[0005]
Non-Patent Document 1
[0006] The object of this invention is to provide a composition that can be used safely for a long period of time and exhibits excellent anti-aging effects.
[0007] The inventors of this invention, after diligently conducting research to solve the above problems, surprisingly discovered that combining nicotinamide mononucleotide with at least one selected from the group consisting of pine bark, banaba, and fulvic acid exhibits excellent anti-aging effects. This invention is a completed invention based on this finding.
[0008] The outline of this invention is as follows: [1] An anti-aging composition characterized by containing nicotinamide mononucleotide and at least one selected from the group consisting of pine bark, banaba, and fulvic acid. [2] A composition for promoting sirtuin gene expression, characterized by containing nicotinamide mononucleotide and at least one selected from the group consisting of pine bark, banaba, and fulvic acid. [3] An anti-aging composition containing nicotinamide mononucleotide as an active ingredient, further characterized by containing at least one selected from the group consisting of pine bark, banaba, and fulvic acid. [4] An oral composition characterized by containing nicotinamide mononucleotide and at least one selected from the group consisting of pine bark, banaba, and fulvic acid. [5] A topical composition characterized by containing nicotinamide mononucleotide and at least one selected from the group consisting of pine bark, banaba, and fulvic acid. [6] A topical composition for skin and / or hair characterized by containing nicotinamide mononucleotide and at least one selected from the group consisting of pine bark, banaba, and fulvic acid. [Effects of the Invention]
[0009] According to the present invention, a composition with excellent anti-aging properties can be provided by containing nicotinamide mononucleotide and at least one selected from the group consisting of pine bark, banaba, and fulvic acid. [Brief explanation of the drawing]
[0010] [Figure 1] Figure 1 shows the expression levels of the SIRT1 gene in the examples and comparative examples. [Modes for carrying out the invention]
[0011] The present invention will be described in detail below. However, the present invention is not limited to the embodiments described below.
[0012] The composition of the present invention is characterized by containing nicotinamide mononucleotide along with at least one selected from pine bark, banaba, and fulvic acid. The component selected from pine bark, banaba, and fulvic acid used together with nicotinamide mononucleotide may be used alone, or in combination of two or three types. However, from the viewpoint of anti-aging effects, it is preferable to use two or three types in combination, and particularly preferable to use three types in combination.
[0013] The following describes each component included in the composition of the present invention. [Nicotinamide mononucleotide] This invention uses nicotinamide mononucleotide (hereinafter also referred to as "NMN") as an essential component. Nicotinamide mononucleotide (chemical formula: C11H15N2O8P) is a nucleotide derived from ribose and nicotinamide, and is known as an intermediate metabolite involved in the biosynthesis of NAD+ (nicotinamide adenine dinucleotide). In this invention, NMN can be produced by fermentation using yeast or chemically synthesized, and is not particularly limited, but from the viewpoint of anti-aging effect and safety in long-term use, it is preferable to use NMN produced by fermentation using yeast.
[0014] In the present invention, the type of optical isomer of NMN is not limited; for example, α-isomers and β-isomers can be used. However, from the viewpoint of anti-aging effects, it is preferable to use the β-isomer (β-nicotinamide mononucleotide).
[0015] There are no particular restrictions on the proportion of NMN incorporated into the composition of the present invention, and the proportion can be appropriately set over a wide range depending on various conditions such as purpose, shape, and target of use. For example, when the composition of the present invention is an oral and solid preparation (powder, granules, tablets, capsules, chewables, etc.), the proportion of NMN in the composition of the present invention is preferably 0.001 to 70% by mass, more preferably 0.01 to 60% by mass, and particularly preferably 0.1 to 50% by mass, from the viewpoint of anti-aging effect. When the composition of the present invention is an oral and liquid preparation (liquid, gel, paste, etc.), the proportion of NMN in the composition of the present invention is preferably 0.0001 to 30% by mass, more preferably 0.001 to 20% by mass, and particularly preferably 0.01 to 10% by mass. When the composition of the present invention is a topical preparation, the proportion of NMN in the composition of the present invention is preferably 0.000001 to 20% by mass, more preferably 0.00001 to 10% by mass, and particularly preferably 0.0001 to 5% by mass.
[0016] [Pine bark] The present invention allows the use of pine bark together with NMN. Examples of pine trees used as raw materials for the pine bark in the present invention include, but are not limited to, French maritime pine (Pinus maritima), larch, Japanese black pine, Japanese red pine, Japanese white pine, Korean pine, Japanese stone pine, Ryukyu pine, Japanese white pine, longleaf pine, and Japanese white pine. Among these, French maritime pine is preferred in terms of its anti-aging effect and safety for long-term use.
[0017] In the present invention, pine bark can be processed and used. Examples of processed pine bark include chip-like substances, crushed materials, squeezed juices, extracts, and their dry powders. Considering the pharmaceutical properties, the pine bark used in the present invention is preferably a crushed material, squeezed juice, extract, or their dry powder because it is easy to apply. From the perspective of anti-aging effects, it is more preferably an extract or its dry powder. The processed pine bark may be produced by methods commonly known to those skilled in the art or may be commercially available. For example, the pine bark extract manufactured by Toyo Pharmaceutical Co., Ltd. can be used.
[0018] Examples of the extraction solvent used to obtain the pine bark extract include water, organic solvents, and water-containing organic solvents (water-containing alcohols such as water-containing ethanol). Examples of organic solvents include methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, butane, acetone, hexane, cyclohexane, propylene glycol, water-containing ethanol, water-containing propylene glycol, ethyl methyl ketone, glycerin, methyl acetate, ethyl acetate, diethyl ether, dichloromethane, edible oils and fats, 1,1,1,2-tetrafluoroethane, and 1,1,2-trichloroethene. These water and organic solvents may be used alone or in combination. However, from the perspective of anti-aging effects, water is preferably used as the extraction solvent. Note that the temperature of the solvent during extraction is not limited as long as it is below the boiling point of the solvent used.
[0019] There is no particular limitation on the method for obtaining the pine bark extract. For example, methods such as heating extraction method, supercritical fluid extraction method, liquid carbon dioxide batch method, liquid carbon dioxide reflux method, and supercritical carbon dioxide reflux method can be mentioned. Also, a plurality of extraction methods may be combined. By combining a plurality of extraction methods, it becomes possible to obtain pine bark extracts with various compositions.
[0020] Supercritical fluid extraction is a method of extraction using a supercritical fluid, which is a fluid in a state exceeding the critical points (critical temperature, critical pressure) of the gas and liquid of a substance. As the supercritical fluid, carbon dioxide, ethylene, propane, nitrous oxide (laughing gas), etc. are used, but carbon dioxide is preferably used.
[0021] In the supercritical fluid extraction method, an extraction step of extracting the target component with a supercritical fluid and a separation step of separating the target component and the supercritical fluid are performed. In the separation step, any of extraction separation by pressure change, extraction separation by temperature change, and extraction separation using an adsorbent or an absorbent may be performed.
[0022] Also, supercritical fluid extraction by the entrainer addition method may be performed. This method involves adding, for example, ethanol, propanol, n - hexane, acetone, toluene, and other lower aliphatic alcohols, aliphatic hydrocarbons, aromatic hydrocarbons, and ketones to the extraction fluid at about 2 - 20 W / V%, and performing supercritical fluid extraction using this fluid, thereby dramatically increasing the solubility of the target extract such as OPC (Oligomeric proanthocyanidin) and catechins in the extraction solvent, or enhancing the selectivity of separation. It is a method for obtaining an efficient pine bark extract.
[0023] The supercritical fluid extraction method has the advantages that it can be operated at a relatively low temperature, so it can be applied to substances that deteriorate and decompose at high temperatures, there is no residue of the extraction fluid, and since the solvent can be recycled, the solvent removal process and the like can be omitted, and the process becomes simple.
[0024] From the perspective of safety, it is preferable to purify the pine bark extract obtained by the above extraction by a column method or a batch method. Examples of the column method include purification methods using adsorbent carriers such as Diaion HP - 20, Sephadex - LH20, and chitin.
[0025] The pine bark extract used in the present invention contains proanthocyanidins as one of its main components. Proanthocyanidins are a group of compounds consisting of condensed polymers with a degree of polymerization of 2 or more, with flavan-3-ol and / or flavan-3,4-diol as constituent units.
[0026] The pine bark extract used in the present invention preferably contains a condensed polymer with a degree of polymerization of 2 or more as a proanthocyanidin. In particular, proanthocyanidins containing a large amount of condensed polymers with a low degree of polymerization are preferred. Examples of condensed polymers with a low degree of polymerization include condensed polymers with a degree of polymerization of 2 to 30 (2 to 30-mers), and from the viewpoint of anti-aging effect, condensed polymers with a degree of polymerization of 2 to 10 (2 to 10-mers) are preferred, and condensed polymers with a degree of polymerization of 2 to 4 (2 to 4-mers) are particularly preferred. In this specification, polymers with a degree of polymerization of 2 to 4 are referred to as OPC (oligomeric proanthocyanidin).
[0027] There are no particular restrictions on the proportion of pine bark to be incorporated into the composition of the present invention, and the proportion can be appropriately set over a wide range depending on various conditions such as purpose, shape, and target of use. For example, when the composition of the present invention is an oral preparation and a solid preparation (powder, granules, tablets, capsules, chewables, etc.), the proportion of pine bark in the composition of the present invention is preferably 0.001 to 50% by mass, more preferably 0.01 to 40% by mass, and particularly preferably 0.1 to 30% by mass, from the viewpoint of anti-aging effect. When the composition of the present invention is an oral preparation and a liquid preparation (liquid, gel, paste, etc.), the proportion of pine bark in the composition of the present invention is preferably 0.0001 to 30% by mass, more preferably 0.001 to 20% by mass, and particularly preferably 0.01 to 10% by mass. When the composition of the present invention is an external preparation, the proportion of pine bark in the composition of the present invention is preferably 0.000001 to 20% by mass, more preferably 0.00001 to 10% by mass, and particularly preferably 0.0001 to 5% by mass.
[0028] [Banaba] This invention allows the use of banaba in combination with NMN. Banaba (Lagerstroemia speciosa) is a plant belonging to the genus Lagerstroemia in the family Lythraceae, and is commonly known as "large-flowered crape myrtle." It is widely grown in Southeast Asia, including the Philippines, India, Malaysia, and southern China, as well as Australia. In this invention, the flowers, leaves, bark, roots, or seeds of banaba can be used, but it is preferable to use the leaves from the viewpoint of anti-aging effects and safety in long-term use. Banaba leaves may also include stems. Since banaba leaves are easily decayed, it is preferable to dry them immediately after harvesting to obtain a dried product. Drying of fresh leaves can be done by natural drying or air drying, but it is preferable to forcibly dry them by air drying. The dried product preferably has a moisture content of 20% by mass or less, and more preferably 10% by mass or less, from the viewpoint of preventing decay by microorganisms and stably retaining the components in the banaba leaves.
[0029] Examples of banaba used in the present invention include dried chips, pulverized products, juices, extracts, or dried powders thereof. From the viewpoint of anti-aging effects, the banaba used in the present invention is preferably pulverized products, juices, extracts, or dried powders thereof, and more preferably extracts or dried powders thereof. The banaba may be manufactured by methods commonly known to those skilled in the art, or it may be commercially available. The banaba preferably contains 1% by mass or more of corosolic acid, a component of banaba, more preferably 5% by mass or more, and even more preferably 7% by mass or more, from the viewpoint of anti-aging effects.
[0030] The method for obtaining the banaba pulverized product is not particularly limited, but for example, after washing and drying using the sun or a dryer, the processed product obtained either as is or cut into an appropriate shape and size can be pulverized using a pulverizing device. Commonly used pulverizing devices can be widely used, but for example, a pulverizing device consisting of a raw material hopper, pulverizer, classifier, and product holder can be used.
[0031] The method for obtaining banaba juice is not particularly limited, but examples include pressing banaba or its fragments, or centrifuging or filtering the fragments of banaba. Specific examples of methods for producing the juice include extracting the juice using mechanical crushing means such as a mixer or juicer, and, if necessary, removing the coarse solids by means of sieving or filtration to obtain the juice. The juice may be concentrated as needed, or it may be subjected to freeze-drying, hot-air drying, or spray-drying to obtain a dry powder.
[0032] The method for obtaining banaba extract is not particularly limited, but examples include extracts obtained by extracting components contained in banaba leaves with a solvent according to conventional methods, diluted or concentrated extracts thereof, or dried or powdered versions thereof.
[0033] Examples of solvents used for extraction include water; lower alcohols such as methanol, ethanol, isopropanol, and butanol; lower esters such as ethyl acetate and methyl acetate; acetone; and mixed solvents of these with water. In the present invention, a mixed solvent of an organic solvent and water can be used. Examples of such mixed solvents include methanol, ethanol, isopropanol, butanol, ethyl acetate, methyl acetate, acetone, and water. Preferably, an acetone / water (2 / 8 to 8 / 2 by volume) mixture or an ethanol / water (2 / 8 to 8 / 2 by volume) mixture is used. The temperature of the extraction solvent can be appropriately set from room temperature to below the boiling point depending on the solvent used.
[0034] Extraction methods include, for example, adding 1 to 20 times the mass, preferably 3 to 15 times the mass, more preferably 5 to 10 times the mass, of water and ethanol to the banaba, and performing extraction at room temperature or above, preferably 50°C or above, more preferably in the range of about 50 to 85°C, for several minutes to several tens of hours, preferably 30 minutes to about 2 hours, under any conditions such as standing, shaking, stirring, or reflux. When extracting at high temperatures, the organic solvent (e.g., ethanol) may evaporate, which may reduce the extraction efficiency, so it is preferable to perform extraction by heating and reflux. After the extraction, it is preferable to perform solid-liquid separation operations such as filtration and centrifugation to remove insoluble solids. By performing operations such as dilution and concentration as needed, an extract can be obtained. Furthermore, the same operation may be repeated to extract the insoluble matter, and this extract may be used together with the previous extract. These extracts may be further purified by purification methods commonly used by those skilled in the art before use.
[0035] The method for obtaining a dried product from the extract is not particularly limited. For example, the extract or its concentrate may be subjected to drying processes commonly used by those skilled in the art, such as spray drying, freeze-drying, vacuum drying, or fluidized bed drying. Furthermore, the dried product thus obtained can be powdered and used by methods known to those skilled in the art. For example, a banaba extract can be obtained according to the method described in Japanese Patent Publication No. 2005-263650. According to this method, a banaba extract can be obtained by subjecting banaba leaves to (a) an extraction step with an aqueous ethanol solution, (b) a treatment step with activated carbon, and (c) a concentration step to recover the precipitate.
[0036] There are no particular restrictions on the proportion of banaba incorporated into the composition of the present invention, and the proportion can be appropriately set over a wide range depending on various conditions such as purpose, shape, and target of use. For example, when the composition of the present invention is an oral and solid preparation (powder, granules, tablets, capsules, chewables, etc.), the proportion of banaba in the composition of the present invention is preferably 0.001 to 50% by mass, more preferably 0.01 to 40% by mass, and particularly preferably 0.1 to 30% by mass, from the viewpoint of anti-aging effect. When the composition of the present invention is an oral and liquid preparation (liquid, gel, paste, etc.), the proportion of banaba in the composition of the present invention is preferably 0.0001 to 30% by mass, more preferably 0.001 to 20% by mass, and particularly preferably 0.01 to 10% by mass. When the composition of the present invention is a topical preparation, the proportion of banaba in the composition of the present invention is preferably 0.000001 to 20% by mass, more preferably 0.00001 to 10% by mass, and particularly preferably 0.0001 to 5% by mass.
[0037] [Fulvic acid] This invention allows the use of fulvic acid together with NMN. Fulvic acid is an amorphous high-molecular-weight organic acid that is soluble in alkalis and acids, and is a substance found in humus. In this invention, fulvic acid can be extracted from humus or synthesized, and is not particularly limited, but it is preferable to use fulvic acid extracted from humus from the viewpoint of anti-aging effect and safety in long-term use.
[0038] The humic material used as a raw material for fulvic acid is not particularly limited, but examples include humic shale obtained from ancient plant deposits (shale layers) in Emery County, Utah, USA, shilajit collected at altitudes of 1,000 to 5,000 meters in the Himalayas, mature marine soil, and peat. Humic shale or shilajit are preferred in terms of their anti-aging properties, and shilajit is particularly preferred.
[0039] There are no particular limitations on the method for extracting fulvic acid from humus, and various known methods can be used. Examples of extraction methods include solid-liquid extraction, liquid-liquid extraction, immersion, leaching, decoction, reflux extraction, supercritical fluid extraction, microwave extraction, and mixing and stirring. The extraction method can be carried out individually or in combination of two or more methods.
[0040] Examples of solvents used for extraction include water; lower alcohols such as methanol, ethanol, isopropanol, and butanol; lower esters such as ethyl acetate and methyl acetate; acetone; and mixed solvents of these with water. While not particularly limited, water is preferred from the viewpoint of anti-aging effects. The temperature of the extraction solvent can be appropriately set between room temperature and below the boiling point, depending on the solvent used.
[0041] The humic extract may be filtered to remove unwanted substances and disinfect. The means of filtration are not particularly limited and can be carried out by conventional methods.
[0042] Humic acid extracts can be further processed to isolate or purify fulvic acid. Such isolation or purification processes include, for example, concentration, vacuum concentration, distillation, fractional distillation, transfusion, solvent extraction, crystallization, recrystallization, and chromatography. These methods can be performed individually or in combination of two or more.
[0043] There are no particular restrictions on the proportion of fulvic acid to be incorporated into the composition of the present invention, and the proportion can be appropriately set over a wide range depending on various conditions such as purpose, shape, and target of use. For example, when the composition of the present invention is an oral preparation and a solid preparation (powder, granules, tablets, capsules, chewables, etc.), the proportion of fulvic acid in the composition of the present invention is preferably 0.0001 to 30% by mass, more preferably 0.001 to 20% by mass, and particularly preferably 0.01 to 10% by mass, from the viewpoint of anti-aging effect. When the composition of the present invention is an oral preparation and a liquid preparation (liquid, gel, paste, etc.), the proportion of fulvic acid in the composition of the present invention is preferably 0.00001 to 10% by mass, more preferably 0.0001 to 5% by mass, and particularly preferably 0.001 to 1% by mass. When the composition of the present invention is a topical preparation, the blending ratio of fulvic acid in the composition of the present invention is preferably 0.000001 to 20% by mass, more preferably 0.00001 to 10% by mass, and particularly preferably 0.0001 to 5% by mass.
[0044] There are no particular restrictions on the total blending ratio of NMN, pine bark, banaba, and fulvic acid in the composition of the present invention, and the blending ratio can be appropriately set over a wide range depending on various conditions such as purpose, shape, and target of use. For example, when the composition of the present invention is an oral and solid preparation (powder, granules, tablets, capsules, chewables, etc.), the total blending ratio of NMN, pine bark, banaba, and fulvic acid in the composition of the present invention is preferably 0.02 to 100% by mass, more preferably 0.1 to 80% by mass, and particularly preferably 1.0 to 60% by mass, from the viewpoint of anti-aging effect. When the composition of the present invention is an oral preparation or a liquid preparation (liquid, gel, paste, etc.), the total blending ratio of NMN, pine bark, banaba, and fulvic acid in the composition of the present invention is preferably 0.0001 to 30% by mass, more preferably 0.001 to 20% by mass, and particularly preferably 0.01 to 10% by mass, from the viewpoint of anti-aging effect. When the composition of the present invention is a topical preparation, the total blending ratio of NMN, pine bark, banaba, and fulvic acid in the composition of the present invention is preferably 0.000001 to 50% by mass, more preferably 0.00001 to 30% by mass, and particularly preferably 0.0001 to 10% by mass, from the viewpoint of anti-aging effect.
[0045] In the composition of the present invention, the ratio of pine bark to NMN is not particularly limited, but from the viewpoint of anti-aging effect, the ratio of pine bark to NMN is preferably 0.0001 to 100 times, more preferably 0.001 to 30 times, and particularly preferably 0.01 to 10 times, per 1 mass of NMN.
[0046] In the composition of the present invention, the ratio of banaba to NMN is not particularly limited, but from the viewpoint of anti-aging effect, the ratio of banaba to NMN is preferably 0.0001 to 100 times, more preferably 0.001 to 30 times, and particularly preferably 0.01 to 10 times, per 1 mass of NMN.
[0047] In the composition of the present invention, the content ratio of fulvic acid to NMN is not particularly limited, but from the viewpoint of anti-aging effect, the content ratio of fulvic acid to NMN is preferably 0.000001 to 30 times, more preferably 0.00001 to 10 times, and particularly preferably 0.0001 to 1 time per 1 mass of NMN.
[0048] In the composition of the present invention, the total amount of pine bark, banaba, and fulvic acid relative to NMN is not particularly limited, but from the viewpoint of anti-aging effect, the total amount of pine bark, banaba, and fulvic acid relative to NMN is preferably 0.000001 to 230 times, more preferably 0.00001 to 70 times, and particularly preferably 0.0001 to 21 times, based on 1 mass of NMN.
[0049] When the composition of the present invention is an oral preparation, the daily intake amount of the composition of the present invention per unit of body weight is not particularly limited and can be appropriately set according to the manner of use and the user's usage. For example, when the composition of the present invention is a solid preparation (powder, granules, tablets, capsules, chewables, etc.), the amount is preferably 1 to 1000 mg / kg, more preferably 3 to 200 mg / kg, and particularly preferably 5 to 100 mg / kg, based on the user's body weight, with a strong anti-aging effect. Also, for example, when the composition of the present invention is a liquid preparation (liquid, gel, paste, etc.), the amount is preferably 200 to 20000 mg / kg, more preferably 600 to 15000 mg / kg, based on the user's body weight, and particularly preferably 1000 to 10000 mg / kg, with a strong anti-aging effect.
[0050] If the composition of the present invention is an oral preparation, the single dose per body weight of the composition of the present invention is also not particularly limited. For example, if the composition of the present invention is a solid preparation (powder, granules, tablets, capsules, chewables, etc.), the dose is preferably 0.3 to 1000 mg / kg, more preferably 1.0 to 200 mg / kg, and particularly preferably 1.6 to 100 mg / kg, based on the user's body weight, and particularly preferably 1.6 to 100 mg / kg, from the viewpoint of anti-aging effects. Also, for example, if the composition of the present invention is a liquid preparation (liquid, gel, paste, etc.), the dose is preferably 66 to 20000 mg / kg, more preferably 200 to 15000 mg / kg, based on the user's body weight, and particularly preferably 333 to 10000 mg / kg, from the viewpoint of anti-aging effects.
[0051] When the composition of the present invention is an oral preparation, the daily intake of the composition of the present invention is not particularly limited. For example, if the composition of the present invention is a solid preparation (powder, granules, tablets, capsules, chewables, etc.), the daily intake is preferably 0.01 to 50 g, more preferably 0.05 to 30 g, and particularly preferably 0.1 to 10 g from the viewpoint of anti-aging effects. Also, for example, if the composition of the present invention is a liquid preparation (liquid, gel, paste, etc.), the daily intake is preferably 10 to 1000 g, more preferably 30 to 750 g, and particularly preferably 50 to 500 g from the viewpoint of anti-aging effects.
[0052] When the composition of the present invention is an oral preparation, the single dose of the composition of the present invention is not particularly limited. For example, if the composition of the present invention is a solid preparation (powder, granules, tablets, capsules, chewables, etc.), the dose is preferably 0.003 to 50 g, more preferably 0.01 to 30 g, and particularly preferably 0.03 to 10 g from the viewpoint of anti-aging effects. Also, for example, if the composition of the present invention is a liquid preparation (liquid, gel, paste, etc.), the dose is preferably 3.3 to 1000 g, more preferably 10 to 750 g, and particularly preferably 16 to 500 g from the viewpoint of anti-aging effects.
[0053] When the composition of the present invention is an oral preparation, it may be taken before meals, between meals, after meals, or at the same time as a meal. However, from the viewpoint of anti-aging effects, it is preferable to take it before meals, after meals, or at the same time as a meal, and more preferably after meals.
[0054] When the composition of the present invention is a topical preparation, the amount used is not particularly limited and can be appropriately selected considering various factors such as the age, weight, constitution, and application site of the individual being treated.
[0055] When the composition of the present invention is a topical preparation, there are no particular limitations on the frequency of application to the subject, but from the viewpoint of anti-aging effect, 1 to 5 times / day is preferred, and 1 to 3 times / day is more preferred.
[0056] The composition of the present invention may contain only components selected from the group consisting of NMN, pine bark, banaba, and fulvic acid, or it may contain other components in addition to these. When the composition of the present invention is an oral preparation, the other components may include, for example, protein, dietary fiber such as water-soluble dietary fiber and insoluble dietary fiber, vitamins other than NMN, minerals, plants or plant products other than pine bark and banaba, algae, microorganisms such as lactic acid bacteria, etc. Furthermore, if necessary, ingredients commonly used in the food industry may be included, such as dextrin, sugars such as starch, oligosaccharides, sweeteners, acidulants, colorants, thickeners, glazing agents, excipients, nutritional supplements, binders, lubricants, stabilizers, diluents, bulking agents, emulsifiers, food additives, and seasonings.
[0057] When the composition of the present invention is a topical preparation, the other components include various pharmacoactive ingredients (such as reactive oxygen species scavengers, antioxidants, anti-inflammatory agents, cell activators, vitamins other than NMN, hormones, and extracts from plants and animals other than pine bark and banaba that have these effects), other oils (such as unsaturated fatty acids and their derivatives, such as linoleic acid, linolenic acid, palmitic acid, DHA, EPA, flaxseed oil, coconut oil, jojoba oil, olive oil, squalane, squalene, horse oil, rice bran oil, castor oil, and other oils and their derivatives extracted from plants and animals), and moisturizers (such as collagen or so Examples of ingredients include decomposition products of soybeans, soy peptides, amino acids, mucopolysaccharides such as hyaluronic acid, amino sugars such as chondroitin, sugars such as trehalose, seaweed, etc.), thickeners (alginic acid or its salts, cellulose derivatives, acrylic acid polymers or their derivatives, glucomannan, pectin, etc.), gelling agents, surfactants (lecithin, betaine, fatty acid esters, amino acid derivatives; anionic surfactants, cationic surfactants, nonionic surfactants, amphoteric surfactants, etc.), UV absorbers, UV scattering agents (zinc oxide, titanium dioxide, etc.), pigments, and the like.
[0058] The composition of the present invention can be used as an oral preparation or as a topical preparation applied to the skin or scalp, and is preferably used as an oral preparation from the viewpoint of its anti-aging effect.
[0059] The composition of the present invention is not particularly limited as long as it can be distinguished from other products in terms of its use for anti-aging. For example, any product in which the main body, packaging, instruction manual, or promotional materials of the present invention indicate that it has an anti-aging function is included within the scope of the present invention. Examples include so-called health foods such as pharmaceuticals (including quasi-drugs), functional foods whose efficacy has been approved by a designated institution, such as Foods for Specified Health Uses, Foods with Nutrient Function Claims, and Foods with Function Claims, as well as cosmetics. Examples of so-called health foods include those that display phrases such as "prevent aging," "prevent age-related decline," "stay youthful," "maintain youthfulness," "for those who want to stay youthful," "aging care," and "anti-aging."
[0060] The form of the composition of the present invention is not particularly limited and can be any form. When the composition of the present invention is an oral preparation, examples of forms include powder, granules, tablets, liquid, gel, paste, capsules such as hard capsules and soft capsules, caplets, tablets, gels, jellies, gummies, wafers, biscuits, cookies, cakes, chewables, syrups, and sticks. From the viewpoint of anti-aging effects, the composition of the present invention is preferably in the form of granules, tablets, capsules, or liquid, and more preferably in the form of granules, tablets, or capsules. Here, "granules" refers to a composition obtained by granulating powder, which may be taken directly or dissolved in a liquid such as water before taking. "Gel" refers to a composition containing water and a thickener or gelling agent, and having viscosity or elasticity.
[0061] When the composition of the present invention is a topical preparation, its form may include, for example, a lotion, emulsion, gel, cream, ointment, powder, granules, etc. Specifically, examples include lotions, cosmetic creams, emulsions, creams, packs, hair tonics, hair creams, shampoos, hair rinses, treatments, body washes, facial cleansers, soaps, foundations, face powders, lipsticks, lip glosses, blushes, eyeshadows, hair styling products, hair growth products, aqueous ointments, oily ointments, eye drops, eye washes, patches, gels, and the like.
[0062] The packaging form of the composition of the present invention is not particularly limited and can be appropriately selected depending on the dosage form, etc., but examples include blister packs such as PTP, strip packaging, heat seals, aluminum pouches, film packaging using plastic or synthetic resin, glass containers such as vials, and plastic containers such as ampoules. [Examples]
[0063] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples, and can take various forms as long as it can solve the problems of the present invention.
[0064] <Test: Evaluation of anti-aging effect> This study evaluated the expression level of the SIRT1 gene. The SIRT1 gene is a sirtuin gene that functions as an NAD+-dependent histone deacetylase (HDAC) and is known to have anti-aging effects through various pathways, including the activation of antioxidant enzymes and the regulation of the cell cycle and apoptosis. It is thought that promoting the expression of the SIRT1 gene leads to anti-aging effects. Therefore, evaluating the expression level of the SIRT1 gene allows for the assessment of anti-aging effects.
[0065] (1) Test substance As NMN, β-NMN produced by fermentation using yeast was used; as pine bark, a hot water extract of French maritime pine bark containing OPC (proanthocyanidins with a degree of polymerization of 2-4) was used; as banaba, an aqueous ethanol extract of banaba leaves containing 9.6% corosolic acid was used; and as fulvic acid, an aqueous extract of shilajit ore containing 20% fulvic acid was used. Resveratrol was also used as a food ingredient known to have anti-aging effects. NMN, pine bark, banaba, fulvic acid, and resveratrol were all commercially available. These were prepared using EGM-2 medium (manufactured by Lonza) in the proportions shown in Table 1, and culture media containing the test substances for the examples and comparative examples were prepared.
[0066] [Table 1]
[0067] (2)Cell culture Human umbilical vein endothelial cells (Lonza) were cultured in EGM-2 medium (Lonza). The cells were placed in 1 × 10⁶ wells of a collagen-coated 96-well plate. 4 Cells were seeded at a concentration of 100 μL / well to achieve a cell / well ratio, and pre-cultured for 24 hours in a 37°C, 5V %CO2 incubator. After removing the culture medium from each well, 100 μL / well of the culture medium containing the test substance shown in Table 1 was added, and the cells were cultured for 24 hours.
[0068] (3) Measurement of SIRT1 gene expression level After removing the culture medium from each well, RNA was recovered using the CellAmp Direct RNA Prep Kit for RT-PCR (Takara). Real-time PCR was performed on the obtained RNA using the One Step TB Green® PrimeScript RT-PCR Kit II (Takara). SIRT1 gene expression levels were measured using SIRT1 gene primers (QIAGEN). As an endogenous control, GAPDH gene expression levels were measured using GAPDH primers (QIAGEN).
[0069] (4) Evaluation of SIRT1 gene expression levels The relative expression levels of the SIRT1 gene were calculated, with the expression level of the control group (those not administered the test substance) set to 1. The results are shown in Figure 1.
[0070] In the groups administered NMN and at least one substance selected from the group consisting of pine bark, banaba, and fulvic acid (Examples 1-3), an increase in SIRT1 gene expression was observed in all cases compared to the group administered NMN alone (Comparative Example 1). In the groups administered pine bark alone (Comparative Example 2), banaba alone (Comparative Example 3), and fulvic acid alone (Comparative Example 4), no increase in SIRT1 gene expression was observed. Therefore, it was found that combining NMN with at least one substance selected from the group consisting of pine bark, banaba, and fulvic acid exhibits a SIRT1 gene expression promoting effect. From this, it was found that the composition of the present invention exhibits excellent anti-aging effects by containing NMN and at least one substance selected from the group consisting of pine bark, banaba, and fulvic acid. On the other hand, while the group administered only resveratrol (Comparative Example 5), which is known to have anti-aging effects, showed an increase in SIRT1 gene expression compared to the control group, the group administered NMN and resveratrol (Comparative Example 6) did not show an increase in SIRT1 gene expression compared to the group administered only NMN (Comparative Example 1). This indicates that the combination of NMN and resveratrol is not superior in terms of anti-aging effects.
[0071] (Manufacturing example) Based on the results of the examples, a manufacturing example of the present invention is shown below.
[0072] [Manufacturing Examples 1-4: Granules] As shown in Table 2, NMN, at least one selected from the group consisting of pine bark, banaba, and fulvic acid, and other raw materials were mixed, and then fluid bed granulation was performed using a granulator to produce the granules described in Production Examples 1-4. The granules described in Production Examples 1-4 only need to be taken at a dose of 3 g per day, and may be taken dissolved in 100 ml of water or other solvent, or taken as is without dissolving. All of the granules in Production Examples 1-4 can be taken orally continuously and safely over a long period of time and are effective for anti-aging.
[0073] [Table 2]
[0074] [Manufacturing Example 5-8: Tablets] As shown in Table 3, NMN was mixed with at least one ingredient selected from the group consisting of pine bark, banaba, and fulvic acid, along with other raw materials. The mixture was then compressed using a rotary tablet press to produce tablets of Production Example 5-8. The tablets were manufactured with a diameter of 8 mmφ, a thickness of 4.5 mm, a weight of 250 mg, and a hardness of 5 kgf or more. One to two tablets of Production Example 5-8 should be taken per day and can be taken with 100 ml of water or other liquid. All tablets of Production Example 5-8 can be safely and continuously taken orally over a long period and are effective for anti-aging.
[0075] [Table 3]
[0076] [Manufacturing Example 9-12: Hard Capsules] As shown in Table 4, hard capsules were manufactured by mixing NMN with at least one ingredient selected from the group consisting of pine bark, banaba, and fulvic acid, and other raw materials, and then encapsulating the mixture with a gelatin or hydroxypropyl cellulose-containing coating. Each hard capsule was manufactured to contain 300 mg. One to two capsules should be taken per day, and they can be taken with 100 ml of water or other liquid. Furthermore, all of the hard capsules in manufacturing examples 9-12 can be safely and continuously taken orally over a long period of time and are effective for anti-aging.
[0077] [Table 4]
[0078] [Manufacturing example 13-16: PET beverage] As shown in Table 5, a liquid formulation was prepared by mixing NMN with at least one ingredient selected from the group consisting of pine bark, banaba, and fulvic acid, and other raw materials. This mixture was then packaged in PET containers to produce PET beverages. Each PET beverage was produced in 500ml bottles. One bottle per day is sufficient. Furthermore, all of the PET beverages in production examples 13-16 can be safely and continuously ingested orally over a long period and are effective for anti-aging.
[0079] [Table 5]
[0080] [Manufacturing Example 17-20: Lotion] As shown in Table 6, lotions were prepared by combining NMN with at least one ingredient selected from the group consisting of pine bark, banaba, and fulvic acid, along with other raw materials. An appropriate amount should be applied topically three times a day. All of the lotions in Production Examples 17-21 can be used continuously and safely over a long period and are effective for anti-aging.
[0081] [Table 6]
[0082] [Manufacturing Examples 21-24: Cream] As shown in Table 7, creams were prepared by combining NMN with at least one ingredient selected from the group consisting of pine bark, banaba, and fulvic acid, along with other raw materials. An appropriate amount should be applied topically twice a day. All of the creams in Production Examples 21-24 can be used continuously and safely for a long period of time and are effective in anti-aging.
[0083] [Table 7]
[0084] [Manufacturing Example 25-28: Emulsion] As shown in Table 8, an emulsion was prepared by combining NMN with at least one ingredient selected from the group consisting of pine bark, banaba, and fulvic acid, along with other raw materials. An appropriate amount should be applied topically once a day. All of the emulsions in Production Examples 21-24 can be used continuously and safely for a long period of time and are effective in anti-aging.
[0085] [Table 8] [Industrial applicability]
[0086] The composition of the present invention exhibits excellent anti-aging effects, and therefore has high industrial utility.
Claims
1. An anti-aging composition characterized by containing nicotinamide mononucleotide and at least one selected from the group consisting of fulvic acid and banaba.
2. An oral composition characterized by containing nicotinamide mononucleotide and at least one selected from the group consisting of fulvic acid and banaba.
Citation Information
Patent Citations
Sirtuin expression level enhancer
JP2020127398A
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