Hyaluronic acid production promoter

Abstract

To discover, from among highly safe compositions of natural origin, a composition 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, as an active ingredient, a water extract from peach leaves and / or a hydrophilic organic solvent extract from peach leaves.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to an agent for promoting hyaluronic acid production.

Background Art

[0002] The dermis and epidermis of the skin are composed of epidermal cells, fibroblasts, and extracellular matrix of dermal cells. Hyaluronic acid, together with collagen, elastin, etc., constitutes the extracellular matrix of the dermis, is outside cells such as epidermal cells and fibroblasts, and supports the skin structure. In young skin, due to the maintenance of homeostasis in the interaction of these skin tissues, water retention, flexibility, elasticity, etc. are ensured, and the skin has a firm and glossy appearance and a moist state is maintained.

[0003] However, when affected by certain external factors such as ultraviolet irradiation, significant air drying, excessive skin cleansing, or with advancing age, the production amount of hyaluronic acid, which is one of the main components of the extracellular matrix, decreases, and the decomposition and alteration of hyaluronic acid occur. In addition, the decrease in the proliferation rate of fibroblasts due to the influence of external factors and aging also leads to a decrease in the production amount of hyaluronic acid, which is a natural moisturizing factor. As a result, the elasticity and moisturizing function of the skin decrease, the keratin causes abnormal exfoliation, the skin loses firmness and gloss, and shows aging symptoms such as roughness, wrinkles, and dullness.

[0004] The decrease and denaturation of hyaluronic acid are involved in the roughness, wrinkles, dullness, disappearance of texture, decrease in elasticity, and decrease in moisturizing function associated with such skin aging. In recent years, ultraviolet rays and the like have been regarded as factors inducing this change and are considered to be major factors in skin wrinkle formation. 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. By filling the spaces between cells, it has the function of retaining cells. Additionally, it has numerous functions such as retaining moisture in the intercellular spaces, imparting lubricity and flexibility to tissues, and providing resistance to external forces such as mechanical damage. If the production of hyaluronic acid can be promoted, it is considered possible to prevent, treat, or improve skin aging symptoms such as rough skin, wrinkles, dullness, loss of texture, decreased elasticity, and decreased moisturizing function.

[0006] Furthermore, hyaluronic acid is also present in the scalp and has been reported to act on keratinocytes and dermal papilla cells to promote their proliferation, and as a result, enhance the hair follicle formation ability (see Non-Patent Document 1). Therefore, increasing the amount of hyaluronic acid in the scalp is considered to lead to the prevention of reduced hair follicle formation ability and scalp problems.

[0007] Moreover, hyaluronic acid is present not only in skin tissue but also in cartilage, synovial fluid, umbilical cord, vitreous humor, and other connective tissues. Among these, the hyaluronic acid contained in synovial fluid covers the surface of articular cartilage and contributes to the smooth operation of joints due to the lubricating function and the coating and protective functions of hyaluronic acid on cartilage. On the other hand, it is known that the concentration of hyaluronic acid in synovial fluid decreases in arthritis such as rheumatoid arthritis. Therefore, it is considered possible to prevent or treat arthritis such as rheumatoid arthritis, osteoarthritis, septic arthritis, gouty arthritis, traumatic arthritis, or osteoarthritis by promoting the production of hyaluronic acid. Furthermore, during the healing process of wounds or burns, granulation (tissue) is formed, and it is known that the amount of hyaluronic acid significantly increases in the granulation. Therefore, it is considered possible to promote the healing of wounds or burns by promoting the production of hyaluronic acid.

[0008] Conventionally, as substances having an effect of promoting hyaluronic acid production, extracts of jellyfish (see Patent Document 1), eggshell membranes (see Patent Document 2), strawberry extracts, or Himalayan raspberry extracts (see Patent Document 3), etc. are known.

Prior Art Documents

Patent Documents

[0009]

Patent Document 1

Patent Document 2

Patent Document 3

Non-Patent Documents

[0010]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0011] An object of the present invention is to find a composition derived from a highly safe natural product that has an effect of promoting hyaluronic acid production, and to provide a hyaluronic acid production promoter containing the same as an active ingredient.

Means for Solving the Problems

[0012] In order to solve such problems, the present invention provides a hyaluronic acid production promoter containing an aqueous extract from the leaves of a peach and / or a hydrophilic organic solvent extract from the leaves of a peach as an active ingredient.

Effects of the Invention

[0013] According to the present invention, it is possible to find a composition derived from a highly safe natural product that has an effect of promoting hyaluronic acid production, and to provide a hyaluronic acid production promoter containing the same as an active ingredient.

Modes for Carrying Out the Invention

[0014] Embodiments 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 the extracts of Angelica keiskei, peach, and loquat.

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

[0016] Angelica keiskei is a perennial herb belonging to the genus Angelica of the Apiaceae family, growing wild in the Boso Peninsula, Izu Peninsula, etc., and can be easily obtained from these regions. The constituent parts of Angelica keiskei that can be used as extraction raw materials include, for example, leaf parts, stem parts, flower parts, bud parts, fruit parts, pericarp parts, fruit stone parts, root parts, or mixtures thereof, etc., but preferably leaf parts or stem parts.

[0017] Prunus persica Batsch is a deciduous small tree belonging to the genus Prunus of the Rosaceae family, and has been cultivated in China and Japan since ancient times, and can be easily obtained from these regions. The constituent parts of Prunus persica Batsch that can be used as extraction raw materials include, for example, leaf parts, trunk parts, branch parts, flower parts, bud parts, fruit parts, pericarp parts, fruit stone parts, seed parts, above-ground parts, or mixtures thereof, etc., but preferably leaf parts.

[0018] Eriobotrya japonica Lindley is an evergreen tall tree belonging to the genus Eriobotrya of the Rosaceae family, native to southwestern China, and is cultivated in Nagasaki, Chiba, Kagoshima, etc., and can be easily obtained from these regions. The constituent parts of Eriobotrya japonica Lindley that can be used as extraction raw materials can be appropriately selected according to the purpose, and include, for example, leaf parts, trunk parts, branch parts, flower parts, bud parts, fruit parts, pericarp parts, fruit stone parts, seed parts, root parts, or mixtures thereof, etc., but preferably leaf parts.

[0019] Although the details of the substance having the effect of promoting hyaluronic acid production contained in the extract from the above extraction raw material are unknown, an extract having the effect of promoting hyaluronic acid production can be obtained from the above extraction raw material by an extraction method generally used for plant extraction or the like. The extract includes any of an extract obtained from the extraction raw material by an extraction treatment, a diluted solution or a concentrated solution of the extract, a dried product obtained by drying the extract, or a crude purified product or a purified product thereof.

[0020] The above extract can be obtained by drying the extraction raw material and then subjecting it as it is or pulverized using a crusher to extraction with an extraction solvent. The drying may be carried out in the open air or using a commonly used dryer. Further, a pretreatment such as degreasing may be performed with a non-polar solvent such as hexane and then used as an extraction raw material. By performing a pretreatment such as degreasing, the extraction treatment of the plant with a polar solvent can be efficiently carried out.

[0021] Examples of the solvent used for extraction include water, a hydrophilic organic solvent, or a mixture thereof, and it is preferably used at room temperature or a temperature below the boiling point of the solvent. The component having the effect of promoting hyaluronic acid production contained in each extraction raw material can be easily extracted by an extraction treatment using a polar solvent as the extraction solvent.

[0022] Examples of the water that can be used as the extraction solvent include, for example, pure water, tap water, well water, mineral water, mineral water, hot spring water, spring water, fresh water, etc., and those obtained by subjecting these to various treatments. Examples of the treatment applied to water include, for example, purification, heating, sterilization, filtration, ion exchange, adjustment of osmotic pressure, buffering, etc. Therefore, the water that can be used as the extraction solvent in the present invention also includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer solution, phosphate buffered 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; polyhydric alcohols having 2 to 5 carbon atoms such as 1,3-butylene glycol, propylene glycol, and glycerin, and the like.

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

[0025] For the extraction treatment, there is no need to adopt a special extraction method as long as the soluble components contained in the extraction raw material can be eluted into the extraction solvent, and the extraction can be carried out at room temperature or under reflux heating. For example, each extraction raw material is put into a treatment tank filled with the extraction solvent, and after standing for 30 minutes to 4 hours with stirring as necessary to elute the soluble components, the extract can be obtained by filtering to remove the solid matter. When the extraction solvent is distilled off from the obtained extract, a paste-like concentrate is obtained, and a dried product is obtained by further drying this concentrate. The extraction conditions are about 1 to 4 hours at 50 to 95°C when water is used as the extraction solvent. Also, when a mixed solvent of water and ethanol is used as the extraction solvent, it is about 30 minutes to 4 hours at 40 to 80°C.

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

[0027] Incidentally, the obtained extract can be used as it is as a hyaluronic acid production promoter, but it is preferably in the form of a concentrated solution or a dried product. When obtaining the dried product, carriers such as dextrin and cyclodextrin may be added to improve hygroscopicity.

[0028] In addition, since each extraction raw material has a unique smell and taste, it is possible to perform purification for the purpose of decolorization, deodorization, etc. within a range that does not cause a decrease in its physiological activity. However, when added to cosmetics, it is not used in large quantities, so there is no practical problem even if it remains unpurified. Purification can be carried out, for example, by activated carbon treatment, adsorption resin treatment, ion exchange resin treatment, etc.

[0029] The extracts of Japanese butterbur, peach, and loquat obtained as described above have a hyaluronic acid production promoting effect, and thus can be used as an active ingredient of a hyaluronic acid production promoter by utilizing this effect.

[0030] Incidentally, in the hyaluronic acid production promoter according to this embodiment, any one of the extracts of Japanese butterbur, peach, and loquat may be used as the above-mentioned active ingredient, or two or more of them may be mixed and used as the above-mentioned active ingredient. When two or more of the extracts of Japanese butterbur, peach, and loquat are mixed and used as the above-mentioned active ingredient, the blending ratio may be appropriately determined according to the degree of their actions.

[0031] The hyaluronic acid production promoter according to this embodiment may be a formulation of one or two or more selected from the extracts of Japanese butterbur, peach, and loquat.

[0032] The above 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 adjuvants. At this time, as the adjuvant, for example, excipients, stabilizers, odor correctors, etc. can be used. Examples of the form of the hyaluronic acid production promoter formulated from the above extract include ointments, external liquids, etc.

[0033] The hyaluronic acid production promoter according to this embodiment can promote the production of hyaluronic acid in, for example, dermal papilla cells through the hyaluronic acid production promoting action of the extracts of Japanese butterbur, peach, and loquat, and can be used for various applications (for example, prevention and improvement applications such as reduced hair follicle formation ability and scalp troubles). Further, the above hyaluronic acid production promoter can prevent, treat or improve skin aging symptoms such as the formation of skin wrinkles, reduction of elasticity, and reduction of moisturizing function through the hyaluronic acid production promoting action of the extracts of Japanese butterbur, peach, and loquat. Furthermore, the extracts of Japanese butterbur, peach, and loquat can be used as active ingredients of preventive, therapeutic or improving agents for diseases and symptoms caused by a decrease in the production amount of hyaluronic acid (for example, preventive, therapeutic or improving agents for arthritis such as rheumatoid arthritis, osteoarthritis, septic arthritis, gouty arthritis, traumatic arthritis, osteoarthritis; accelerators for promoting the healing of wounds or burns, etc.). However, the hyaluronic acid production promoter according to this embodiment can be used for all applications with significance in exerting the hyaluronic acid production promoting action other than this application.

[0034] Examples of the administration method of the hyaluronic acid production promoter according to this embodiment to patients include subcutaneous administration, intramuscular administration, intravenous administration, oral administration, transdermal administration, etc. However, according to the type of disease, a method suitable for its prevention, treatment, etc. may be appropriately selected. Also, 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 of the patient, administration method, administration period, etc.

[0035] In addition, since the hyaluronic acid production promoter according to the present embodiment, or one or more selected from the extracts of Japanese butterbur, peach, and loquat have an excellent hyaluronic acid production promoting effect, they are suitable for being formulated in cosmetics such as skin cosmetics, scalp cosmetics, hair cosmetics, and also in food and drink products, etc.

[0036] Examples of cosmetics that can contain one or more selected from the extracts of Japanese butterbur, peach, and loquat, and 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 formulating the above-mentioned extracts or hyaluronic acid production promoter in cosmetics, the blending amount can be appropriately adjusted according to the type of cosmetics. However, a suitable blending ratio is about 0.0001 to 10% by mass in terms of a standard extract, and a particularly suitable blending ratio is about 0.001 to 1% by mass in terms of a standard extract. Cosmetics can be used in combination with main agents, auxiliaries, or other components used in the production of ordinary cosmetics, such as astringents, bactericidal and antibacterial agents, whitening agents, ultraviolet absorbers, moisturizing agents, cell activators, anti-inflammatory and anti-allergy agents, antioxidants and active oxygen scavengers, oils, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, fragrances, etc., as long as they do not interfere with the hyaluronic acid production promoting effect of the above-mentioned extracts. By combining in this way, a more general product can be obtained, and there may be an excellent effect beyond the synergistic effect usually expected between the combined other active ingredients.

[0037] Food and drink products refer to those with little risk of harming human health and are usually ingested orally or through gastrointestinal administration in normal social life, not restricted by classifications such as food, pharmaceuticals, quasi-drugs, etc. in administrative classification. Therefore, the "food and drink products" according to this embodiment broadly include compositions constituting general foods, health foods (functional food and drink products), health function foods (foods for specified health use, nutritional function foods, foods with function claims), quasi-drugs, pharmaceuticals, etc. that are ingested orally. The food and drink products in this embodiment may display the hyaluronic acid production promoting effect of the above extract on the food and drink product or its packaging, or the food and drink product may be a health function food (foods for specified health use, foods with function claims, nutritional function foods), a quasi-drug, or a pharmaceutical.

[0038] When the above extract or a hyaluronic acid production promoter formulated from the above extract is blended into a food and drink product, the blending amount of the active ingredient in them can be appropriately changed considering the purpose of use, symptoms, gender, etc. However, considering the general intake amount of the food and drink product to which it is added, it is preferable that the extract intake amount per adult per day is about 1 to 1000 mg. When the food and drink product to which it is added is in the form of granules, tablets, or capsules, the addition amount of the above extract or a hyaluronic acid production promoter formulated from the above extract is usually 0.1 to 100% by mass, preferably 5 to 100% by mass, based on the food and drink product to which it is added.

[0039] Food and drink products that can contain the mixture of the above extracts or an agent for promoting hyaluronic acid production formulated from the mixture of the above extracts are not particularly limited. Specific examples thereof include beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks (including concentrated stock solutions and powder for adjustment of these beverages); frozen confections such as ice cream, ice sherbet, and shaved ice; noodles such as buckwheat noodles, udon noodles, glass noodles, wrappers for gyoza dumplings, wrappers for shumai dumplings, Chinese noodles, and instant noodles; confectionery such as candies, chewing gums, candies, gums, chocolates, tablet confections, snack foods, biscuits, jellies, jams, creams, and baked confections; processed fishery and livestock products such as kamaboko (fish cake), ham, and sausage; dairy products such as processed milk and fermented milk; fats and oils and processed fat and oil foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressings; seasonings such as sauces and condiments; soups, stews, salads, side dishes, and pickles; various other forms of health and nutritional supplements; tablets, capsules, and drink preparations. When formulating the mixture of the above extracts or the agent for promoting hyaluronic acid production in these food and drink products, auxiliary raw materials and additives commonly used can be used in combination.

[0040] Note that the hyaluronic acid production promoter according to the present embodiment is preferably applicable to humans, but it can also be applied to animals other than humans as long as the effect of promoting hyaluronic acid production is achieved.

Examples

[0041] Hereinafter, the present invention will be described more specifically by showing test examples and the like, but the present invention is not limited to the following test examples and the like.

[0042] 〔Production Example 1〕Production of Houttuynia cordata extract 1500 mL of a 70% by volume aqueous solution of butylene glycol was added to 100 g of the dried product of the leaves and stems of Houttuynia cordata, and heat extraction was performed at 80 to 90 °C for 2 hours, followed by filtration while hot. The obtained extract was dried to obtain a Houttuynia cordata extract (15 g).

[0043] 〔Production Example 2〕Production of peach extract To 100 g of the dried momo leaf, 1500 mL of a 30% by volume aqueous butylene glycol solution was added, and heat extraction was performed at 80 - 90 °C for 2 hours followed by hot filtration. The obtained extract was dried to obtain a momo leaf extract (24 g).

[0044] [Production Example 3] Production of loquat extract To 100 g of the dried loquat leaf, 1500 ml of an 80% by volume ethanol aqueous solution was added, and reflux extraction was performed for 2 hours followed by hot filtration. The obtained extract was dried to obtain a loquat leaf extract (14 g).

[0045] [Test Example] Test for hyaluronic acid production promoting effect For the ashitaba extract, momo extract, and loquat extract obtained in Production Examples 1 - 3 above, a test for hyaluronic acid production promoting effect was carried out by the following method.

[0046] Normal human hair papilla cells were cultured using a papilla cell growth medium (manufactured by Takara Bio Inc.) containing a growth additive, and then the cells were collected by trypsin treatment. The collected cells were diluted using Dulbecco's MEM containing 0.25% FBS to a cell density of 1.6×10 5 cells / mL, and then seeded at 100 μL per well in 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] The hyaluronic acid production promoting effect was measured by a sandwich method using hyaluronic acid - binding protein (HABP) for the amount of hyaluronic acid in the medium of each well after the culture was completed. From the measurement results, the hyaluronic acid production promotion rate (%) was calculated by the following formula.

[0048] Hyaluronic acid production promotion rate (%) = A / B × 100 In the formula, "A" represents the amount of hyaluronic acid in the cells to which the test sample was added, and "B" represents the amount of hyaluronic acid in the cells without the test sample added.

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

[0050]

Table 1

[0051]

Table 2

[0052]

Table 3

[0053] As shown in Tables 1 to 3, the extracts of Houttuynia cordata, peach, and loquat all showed a high hyaluronic acid production promotion rate. From these results, it was confirmed that these extracts have an excellent hyaluronic acid production promotion effect.

Industrial Applicability

[0054] Since the hyaluronic acid production promoter of the present invention has an excellent hyaluronic acid production promotion effect, it can be suitably used as a component of cosmetics, foods and drinks, etc., and further as a reagent for research.

Claims

【Claim 1】 A hyaluronic acid production promoter containing, as an active ingredient, a water extract from the leaf part of peach and / or a hydrophilic organic solvent extract from the leaf part of peach.

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