Hyaluronic acid production promoter

Abstract

To discover, from among safe compositions of natural origin, the one having hyaluronic acid production promoting action, and provide a hyaluronic acid production promoter containing the discovered composition as an active ingredient.SOLUTION: A hyaluronic acid production promoter contains one or more kinds selected from Angelica keiskei extract, Prunus persica extract, and loquat extract as an active ingredient.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a hyaluronic acid production promoter. [Background technology]

[0002] The dermis and epidermis of the skin are composed of epidermal cells, fibroblasts, and the dermal extracellular matrix, etc. Hyaluronic acid, together with collagen, elastin, etc., constitutes the dermal extracellular matrix and is located outside cells such as epidermal cells and fibroblasts, supporting the skin structure. In young skin, the interaction of these skin tissues maintains homeostasis, ensuring moisture retention, flexibility, elasticity, etc., and the skin appears firm, glossy, and maintained in a fresh state.

[0003] However, under the influence of certain external factors such as ultraviolet radiation, extremely dry air, excessive skin washing, or with aging, the production of hyaluronic acid, one of the main components of the extracellular matrix, decreases, and hyaluronic acid decomposes and changes in quality.In addition, the influence of external factors and the decrease in the proliferation rate of fibroblasts associated with aging also lead to a decrease in the production of hyaluronic acid, a natural moisturizing factor.As a result, the skin's elasticity and moisturizing function decrease, keratin peeling occurs abnormally, the skin loses firmness and luster, and aging symptoms such as roughness, wrinkles, and dullness appear.

[0004] The decrease and degeneration of hyaluronic acid are involved in the following skin aging problems: roughness, wrinkles, dullness, loss of texture, loss of elasticity and loss of moisturizing function.Recently, ultraviolet rays etc. are considered to be the factor that induces this change, and are considered to be the major cause of skin wrinkle formation etc.Therefore, promoting the production of hyaluronic acid is important for preventing and improving skin aging.

[0005] Among these extracellular matrices, hyaluronic acid is a type of mucopolysaccharide that has the function of retaining cells by filling the intercellular spaces, and also has many other functions, such as retaining moisture in the intercellular spaces, imparting lubricity and flexibility to tissues, and resisting external forces such as mechanical damage.If the production of hyaluronic acid can be promoted, it is thought that it will be possible to prevent, treat, or improve skin aging symptoms such as rough skin, wrinkles, dullness, loss of texture, loss of elasticity, and loss of moisturizing function.

[0006] Hyaluronic acid is also present in the scalp, and it has been reported that it acts on keratinocytes and hair papilla cells, promoting their proliferation and ultimately enhancing the formation of hair follicles (see Non-Patent Document 1). Therefore, increasing the amount of hyaluronic acid in the scalp is thought to lead to the prevention of a decrease in the formation of hair follicles and scalp problems.

[0007] Hyaluronic acid is also present in connective tissues such as cartilage, synovial fluid, umbilical cord, vitreous body, and other tissues, in addition to skin tissue. Hyaluronic acid in synovial fluid coats the surface of articular cartilage, contributing to the smooth functioning of joints through its lubricating and cartilage-covering / protecting functions. Meanwhile, it is known that the concentration of hyaluronic acid in synovial fluid decreases in cases of arthritis, such as rheumatoid arthritis. Therefore, promoting hyaluronic acid production is believed to be effective in preventing or treating arthritis, including rheumatoid arthritis, osteoarthritis, septic arthritis, gouty arthritis, traumatic arthritis, and osteoarthritis. Furthermore, granulation tissue is formed during the healing process of wounds or burns, and it is known that hyaluronic acid significantly increases in the granulation tissue. Therefore, promoting hyaluronic acid production is believed to promote wound or burn healing.

[0008] Conventionally, substances known to have the effect of promoting hyaluronic acid production include extracts of Tremella fuciformis fruiting bodies (see Patent Document 1), eggshell membranes (see Patent Document 2), black raspberry extracts, and Himalayan raspberry extracts (see Patent Document 3). [Prior art documents] [Patent documents]

[0009] [Patent Document 1] Japanese Patent Application Publication No. 2019-099530 [Patent Document 2] Japanese Patent Application Laid-Open No. 2014-040402 [Patent Document 3] Japanese Patent Application Laid-Open No. 2013-018734 [Non-patent literature]

[0010] [Non-Patent Document 1] E. Kalabusheva, V. Terskikh, E. Vorotelyak, Stem Cells Int., 2017(1):1-14 Summary of the Invention [Problem to be solved by the invention]

[0011] The present invention aims to find a highly safe composition derived from natural products that has the effect of promoting hyaluronic acid production, and to provide a hyaluronic acid production promoter that uses it as an active ingredient. [Means for solving the problem]

[0012] In order to solve such problems, the present invention provides a hyaluronic acid production promoter containing one or more active ingredients selected from the group consisting of extracts of angelica tree, extracts of peach, and extracts of loquat. [Effects of the Invention]

[0013] According to the present invention, it is possible to find a highly safe composition derived from natural products that has the effect of promoting hyaluronic acid production, and to provide a hyaluronic acid production promoter that uses this as an active ingredient. DETAILED DESCRIPTION OF THE INVENTION

[0014] An embodiment of the present invention will be described. The hyaluronic acid production promoter according to this embodiment contains, as an active ingredient, one or more selected from an extract of Angelica keiskei, an extract of peach, and an extract of loquat.

[0015] The extract raw materials used to obtain the active ingredient in this embodiment are angelica tree (scientific name: Angelica keiskei), peach (scientific name: Prunus persica Batsch), and loquat (scientific name: Eriobotrya japonica Lindley).

[0016] Angelica keiskei is a perennial plant of the Apiaceae family, Angelica genus, that grows naturally in the Boso Peninsula, Izu Peninsula, and other areas, and can be easily obtained from these areas. Components of Angelica keiskei that can be used as the raw material for extraction include, for example, leaves, stems, flowers, buds, fruits, peels, pits, roots, and mixtures thereof, with leaves or stems being preferred.

[0017] Peach (Prunus persica Batsch) is a deciduous tree of the genus Prunus in the family Rosaceae. It has been cultivated in China and Japan for a long time and is easily available in these regions. Peach parts that can be used as the raw material for extraction include, for example, leaves, trunks, branches, flowers, buds, fruit, peel, pit, seeds, aboveground parts, and mixtures thereof, with leaves being preferred.

[0018] Loquat (Eriobotrya japonica Lindley) is an evergreen tall tree belonging to the genus Loquat in the family Rosaceae, native to southwestern China, cultivated in Nagasaki, Chiba, Kagoshima, etc., and can be easily obtained from these areas. The parts of the loquat that can be used as the extraction raw material can be appropriately selected depending on the purpose, and examples include leaves, trunks, branches, flowers, buds, fruits, peels, pits, seeds, roots, and mixtures thereof, with leaves being preferred.

[0019] Although the details of the substance that has the effect of promoting hyaluronic acid production contained in the extract from the above-mentioned extraction raw material are unknown, by the extraction method that is generally used for the extraction of plants, etc., the extract that has the effect of promoting hyaluronic acid production can be obtained from the above-mentioned extraction raw material.In addition, extract includes the extract obtained from the extraction raw material by extraction treatment, the diluted solution or concentrated solution of the extract, the dried product obtained by drying the extract, or any of these roughly purified products or purified products.

[0020] The extract can be obtained by drying the raw material, either directly or after crushing using a crusher, and then subjecting it to extraction with an extraction solvent. Drying can be performed in the sun or using a commonly used dryer. The raw material can also be used after pretreatment, such as degreasing, using a nonpolar solvent such as hexane. Pretreatment, such as degreasing, allows for efficient extraction of plants with a polar solvent.

[0021] The solvent that can be used for extraction can be water, hydrophilic organic solvent or their mixture, and preferably used at room temperature or the temperature below the boiling point of solvent.The component that contains in each extraction raw material and has the effect of promoting hyaluronic acid production can be easily extracted by using polar solvent as extraction solvent.

[0022] Examples of water that can be used as an extraction solvent include pure water, tap water, well water, mineral water, hot spring water, spring water, fresh water, and water that has undergone various treatments. Treatments that can be applied to water include purification, heating, sterilization, filtration, ion exchange, adjustment of osmotic pressure, buffering, etc. Therefore, water that can be used as an extraction solvent in the present invention also includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate-buffered physiological saline, etc.

[0023] Examples of hydrophilic organic solvents that can be used as extraction solvents include lower aliphatic alcohols having 1 to 5 carbon atoms, such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; lower aliphatic ketones, such as acetone and methyl ethyl ketone; and polyhydric alcohols having 2 to 5 carbon atoms, such as 1,3-butylene glycol, propylene glycol, and glycerin.

[0024] When a mixture of two or more polar solvents is used as the extraction solvent, the mixing ratio can be adjusted appropriately. For example, when using a mixture of water and a lower aliphatic alcohol, it is preferable to mix 10 parts by volume of water with 1 to 90 parts by volume of the lower aliphatic alcohol. When using a mixture of water and an aliphatic ketone, it is preferable to mix 10 parts by volume of water with 1 to 40 parts by volume of the lower aliphatic ketone. When using a mixture of water and a polyhydric alcohol, it is preferable to mix 10 parts by volume of water with 1 to 90 parts by volume of the polyhydric alcohol.

[0025] The extraction process does not require a special extraction method as long as the soluble components contained in the raw material can be dissolved into the extraction solvent. Extraction can be performed at room temperature or under reflux heating. For example, the raw materials are placed in a treatment tank filled with the extraction solvent, stirred as needed, and left to stand for 30 minutes to 4 hours to dissolve the soluble components. The extract can then be obtained by filtering and removing solids. Distilling the extraction solvent from the resulting extract yields a paste-like concentrate, which can then be further dried to obtain a dried product. When water is used as the extraction solvent, the extraction conditions are 50 to 95°C for approximately 1 to 4 hours. When a mixture of water and ethanol is used as the extraction solvent, the extraction conditions are 40 to 80°C for approximately 30 minutes to 4 hours.

[0026] The extract obtained as described above may be subjected to treatments such as dilution, concentration, drying, purification, etc. according to conventional methods to obtain a diluted or concentrated solution of the extract, a dried product of the extract, or a crude or purified product thereof.

[0027] The obtained extract can be used as it is as a hyaluronic acid production promoter, but it is more preferable to use it as a concentrated liquid or dried product.When obtaining a dried product, a carrier such as dextrin or cyclodextrin may be added to improve hygroscopicity.

[0028] Furthermore, because each extract material has a unique odor and taste, it is possible to purify it for the purpose of bleaching, deodorizing, etc., to the extent that this does not result in a decrease in its physiological activity, but since it is not used in large quantities when added to cosmetics, there is no practical problem in using it unpurified. Purification can be carried out, for example, by activated carbon treatment, adsorption resin treatment, ion exchange resin treatment, etc.

[0029] The extracts of angelica tree, peach, and loquat obtained in the manner described above have the effect of promoting hyaluronic acid production, and therefore can be used as active ingredients of hyaluronic acid production promoters by utilizing this effect.

[0030] In addition, in the hyaluronic acid production promoter of the present embodiment, any one of Angelica keiskei extract, peach extract and loquat extract can be used as above-mentioned active ingredient, or two or more of them can be mixed and used as above-mentioned active ingredient.When two or more of Angelica keiskei extract, peach extract and loquat extract are mixed and used as above-mentioned active ingredient, their compounding ratio can be suitably determined according to the degree of their effect.

[0031] The hyaluronic acid production promoter according to this embodiment may be a formulation of one or more selected from an extract of Angelica keiskei, an extract of peach, and an extract of loquat.

[0032] The above-mentioned extract can be formulated into any dosage form such as powder, granule, liquid, etc. according to conventional methods using pharmaceutically acceptable carriers such as dextrin, cyclodextrin, and other optional auxiliary agents.In this case, as auxiliary agents, for example, excipients, stabilizers, odorants, etc. can be used.The form of the hyaluronic acid production promoter that is formulated from the above-mentioned extract can be, for example, ointment, external liquid, etc.

[0033] The hyaluronic acid production promoter according to this embodiment can promote the production of hyaluronic acid in hair papilla cells, for example, through the hyaluronic acid production promoting action of Angelica keiskei extract, peach extract, and loquat extract, and can therefore be used for various purposes (for example, for preventing and improving a decrease in hair follicle formation ability and scalp troubles, etc.) Furthermore, through the hyaluronic acid production promoting action of Angelica keiskei extract, peach extract, and loquat extract, the hyaluronic acid production promoter can prevent, treat, or improve skin aging symptoms, such as the formation of wrinkles, loss of elasticity, and loss of moisturizing function. Furthermore, the above Angelica extract, peach extract, and loquat extract can be used as an active ingredient in a preventive, therapeutic or ameliorating agent for diseases and symptoms caused by a decrease in the production of hyaluronic acid (for example, a preventive, therapeutic or ameliorating agent for arthritis such as rheumatoid arthritis, osteoarthritis, septic arthritis, gouty arthritis, traumatic arthritis, osteoarthritis, etc.; a promoter for healing wounds or burns, etc.) by utilizing their hyaluronic acid production promoting effect. However, the hyaluronic acid production promoter according to this embodiment can be used for all other purposes where it is significant to exert the hyaluronic acid production promoting effect.

[0034] The method of administering the hyaluronic acid production promoter according to this embodiment to a patient may include subcutaneous administration, intramuscular administration, intravenous administration, oral administration, transdermal administration, etc., and a method suitable for the prevention, treatment, etc. may be appropriately selected depending on the type of disease. Furthermore, the dosage of the hyaluronic acid production promoter according to this embodiment may be appropriately increased or decreased depending on the type of disease, severity, individual differences in patients, administration method, administration period, etc.

[0035] In addition, the hyaluronic acid production promoter of this embodiment, or one or more selected from angelica extract, peach extract, and loquat extract, has excellent hyaluronic acid production promoting activity, and is therefore suitable for incorporation into cosmetics such as skin cosmetics, scalp cosmetics, and hair cosmetics, as well as foods and beverages.

[0036] Cosmetics that can contain one or more selected from Angelica keiskei extract, peach extract, and loquat extract, or the above-mentioned hyaluronic acid production promoter, include, for example, ointments, creams, emulsions, lotions, packs, foundations, hair tonics, hair lotions, shampoos, rinses, soaps, etc. When the above-mentioned extracts or hyaluronic acid production promoters are contained in cosmetics, the amount of each can be adjusted appropriately depending on the type of cosmetic, but a suitable blending ratio is about 0.0001 to 10% by mass, calculated as the standard extract, and a particularly suitable blending ratio is about 0.001 to 1% by mass, calculated as the standard extract. As long as the cosmetic preparation does not interfere with the hyaluronic acid production-promoting activity of the extract, it can be used in combination with the main ingredients, auxiliary agents, and other ingredients typically used in the manufacture of cosmetics, such as astringents, germicides / antibacterial agents, whitening agents, UV absorbers, moisturizers, cell activators, anti-inflammatory / anti-allergic agents, antioxidants / active oxygen scavengers, oils and fats, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, fragrances, etc. Such combinations can result in more general-purpose products, and the synergistic effect with the other active ingredients used in combination can sometimes bring about better effects than would normally be expected.

[0037] Food and drink products refer to those that are unlikely to be harmful to human health and are taken orally or by gastrointestinal administration in normal social life, and are not limited to administrative classifications such as food, medicine, or quasi-drug. Therefore, the "food and drink products" according to this embodiment broadly include compositions that constitute orally ingested general foods, health foods (functional food and drink products), health functional foods (foods for specified health uses, foods with nutrient functions, foods with functional claims), quasi-drugs, medicines, etc. The food and drink products according to this embodiment may be those that display the hyaluronic acid production-promoting effect of the extract on the food and drink products or their packaging, or may be health functional foods (foods for specified health uses, foods with functional claims, foods with nutrient functions), quasi-drugs, or medicines.

[0038] When the above-mentioned extract or the hyaluronic acid production promoter prepared from the above-mentioned extract is incorporated into food and drink, the amount of active ingredient contained therein can be appropriately changed considering the purpose of use, symptoms, sex, etc., but considering the general intake of the food and drink to be added, it is preferable that the amount of extract to be taken by an adult per day is about 1-1000mg.In addition, when the food and drink to be added is in the form of granule, tablet or capsule, the amount of the above-mentioned extract or the hyaluronic acid production promoter prepared from the above-mentioned extract is generally 0.1-100% by mass, preferably 5-100% by mass relative to the food and drink to be added.

[0039] There are no particular limitations on the foods and beverages that can contain the above-mentioned mixture of extracts or the hyaluronic acid production promoting agent formulated from the above-mentioned mixture of extracts. Specific examples include beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit drinks, and lactic acid drinks (including concentrated concentrates and powders for adjusting these beverages); frozen desserts such as ice cream, ice sorbet, and shaved ice; noodles such as soba, udon, vermicelli, gyoza wrappers, shumai wrappers, Chinese noodles, and instant noodles; candies, chewing gum, candies, chewing gum, chocolate, tablet sweets, snacks, biscuits, jellies, jams, creams, baked goods, etc. These include confectionery such as sweets; processed seafood and livestock foods such as kamaboko, ham, and sausage; dairy products such as processed milk and fermented milk; oils and fats and oil-processed foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressing; seasonings such as sauces and dressings; soups, stews, salads, side dishes, and pickles; and various other forms of health and nutritional supplements; tablets, capsules, and drinks.When these foods and beverages are formulated with the above-mentioned extract mixtures or hyaluronic acid production-promoting agents, commonly used auxiliary ingredients and additives can also be used in combination.

[0040] Although the hyaluronic acid production promoter according to this embodiment is preferably applied to humans, it can also be applied to animals other than humans as long as it has the effect of promoting hyaluronic acid production. [Example]

[0041] The present invention will be explained in more detail below by showing test examples, but the present invention is not limited to the following test examples.

[0042] [Production Example 1] Production of Angelica keiskei extract 1500 mL of a 70% by volume aqueous solution of butylene glycol was added to 100 g of dried leaves and stems of Angelica keiskei, followed by extraction by heating at 80 to 90°C for 2 hours and hot filtration. The resulting extract was dried to obtain Angelica keiskei extract (15 g).

[0043] [Production Example 2] Production of peach extract 1500 mL of a 30% by volume aqueous solution of butylene glycol was added to 100 g of dried peach leaves, followed by extraction with heating at 80 to 90°C for 2 hours and hot filtration. The resulting extract was dried to obtain peach leaf extract (24 g).

[0044] [Production Example 3] Production of loquat extract 1500 ml of 80% ethanol solution was added to 100 g of dried loquat leaves, and the mixture was refluxed for 2 hours and filtered while hot. The resulting extract was dried to obtain 14 g of loquat leaf extract.

[0045] [Test Example] Hyaluronic acid production promotion test The Angelica keiskei extract, peach extract, and loquat extract obtained in Production Examples 1 to 3 above were tested for their hyaluronic acid production promoting activity by the following method.

[0046] Normal human hair dermal papilla cells were cultured in a dermal papilla cell growth medium (manufactured by Takara Bio Inc.) containing a growth additive, and then the cells were harvested by trypsinization. The harvested cells were diluted to 1.6 x 10 in Dulbecco's MEM containing 0.25% FBS. 5 After dilution to a cell density of 1000 cells / mL, 100 μL of the cells were seeded into each well of a 96-well plate and cultured overnight. After the culture was completed, the medium was removed, and 100 μL of the test sample dissolved in Dulbecco's MEM containing 0.25% FBS was added to each well and cultured for 3 days.

[0047] To evaluate the hyaluronic acid production promotion effect, the amount of hyaluronic acid in the medium of each well after the culture was completed was measured by the sandwich method using hyaluronic acid binding protein (HABP).From the measurement results, the hyaluronic acid production promotion rate (%) was calculated using the following formula.

[0048] Hyaluronic acid production promotion rate (%) = A / B x 100 In the formula, "A" represents the amount of hyaluronic acid in cells to which a test sample was added, and "B" represents the amount of hyaluronic acid in cells to which no test sample was added.

[0049] The results of the above tests are shown in Tables 1 to 3. In the above formula, the promotion rate of hyaluronic acid production without addition of the test sample is 100%.

[0050] [Table 1]

[0051] [Table 2]

[0052] [Table 3]

[0053] As shown in Tables 1 to 3, Angelica keiskei extract, peach extract, and loquat extract all showed high hyaluronic acid production promotion rates. These results confirmed that these extracts have excellent hyaluronic acid production promotion effects. [Industrial Applicability]

[0054] The hyaluronic acid production promoter of the present invention has an excellent hyaluronic acid production promoting effect, and therefore can be suitably used as a component of cosmetics, foods and beverages, etc., and further as a research reagent.

Claims

1. A hyaluronic acid production promoter for preventing or improving a decrease in hair follicle formation ability, comprising as an active ingredient a water extract from the leaves and stems of Angelica keiskei and / or a hydrophilic organic solvent extract from the leaves and stems of Angelica keiskei.

2. The hyaluronic acid production promoter according to claim 1, wherein the hydrophilic organic solvent extract is a butylene glycol extract.

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