JP5512067B2 - Skin cosmetics - Google Patents

Description

  The present invention relates to an anti-inflammatory agent, a whitening agent, a tyrosinase inhibitor, an anti-aging agent, a slimming agent, a cyclic AMP phosphodiesterase inhibitor, a skin cosmetic, and a cosmetic food and drink.

  There are various causes and onset mechanisms of inflammatory diseases such as contact dermatitis (rash), psoriasis, pemphigus vulgaris, and various other skin diseases associated with rough skin, including hyaluronidase, histamine, and hexosa. The thing by minidase etc. is known.

  Hyaluronate that maintains affinity for living tissue is decomposed by ultraviolet rays, enzymes, and the like in a water-containing system, and the water retention effect decreases with a decrease in molecular weight. Hyaluronic acid is present in intercellular tissues and is also involved in vascular permeability. Furthermore, the activated hyaluronidase salt present in mast cells is said to be involved in degranulation from mast cells. Therefore, by inhibiting the activity of hyaluronidase, which is a hydrolase of hyaluronic acid, it can stabilize hyaluronic acid and prevent the release of various chemical mediators from mast cells. It is considered to be effective in preventing, treating or improving various inflammatory diseases such as dermatitis (rash), psoriasis, pemphigus vulgaris, and various other skin diseases associated with rough skin.

  Based on such an idea, as a substance having a hyaluronidase inhibitory action, for example, an extract of a plant belonging to the genus Osbecchia (see Patent Document 1), a wisteria tea extract (see Patent Document 2), rosemary, thyme and melissa Extracts (see Patent Document 3) and the like are known.

  Histamine is present in the mast cell, and the substance released by the degranulation reaction acts as a flammable substance. Since histamine in the cells is released and hexosaminidase is released at the same time, histamine release inhibitory action can be evaluated using hexosaminidase release as an index. Therefore, by inhibiting the release of hexosaminidase, it is also possible to inhibit the release of histamine at the same time, thereby causing various skin diseases such as contact dermatitis (rash), psoriasis, pemphigus vulgaris, and other rough skin. It is considered effective for prevention, treatment or improvement of inflammatory diseases.

  Based on such an idea, for example, red snow tea extract (see Patent Document 4) is known as one having a hexosaminidase release inhibitory action.

  Melanin also plays a role in protecting the body from ultraviolet rays in the skin, but overproduction and uneven accumulation cause skin darkening and spots. In general, melanin is converted from tyrosine to dopa and from dopa to dopaquinone by the action of the enzyme tyrosinase biosynthesized in pigment cells, and then formed through intermediates such as 5,6-dihydroxyindophenol. ing. Therefore, in order to prevent, treat or improve skin darkness (skin pigmentation), spots, buckwheat, etc., it is conceivable to inhibit the activity of tyrosinase involved in the production of melanin.

  Conventionally, for the prevention, treatment or improvement of skin pigmentation, stains, buckwheat, etc., a treatment using a whitening agent containing a chemically synthesized product such as hydroquinone as an active ingredient has been performed. However, chemically synthesized products such as hydroquinone may cause side effects such as skin irritation and allergies. Therefore, it is desired to develop a whitening agent containing a highly safe natural raw material as an active ingredient. Examples of those having a tyrosinase inhibitory action include wisteria tea extract (see Patent Document 5), willow extract (patent Reference 6) is known.

  One cause of skin aging with aging is a decrease in the secretion of estrogen, a female hormone. In other words, estrogen is deeply involved in maintaining the health of adult women, and its lack of secretion leads to various medical illnesses, as well as causes of unfavorable skin changes such as skin hypersensitivity, reduced elasticity, reduced moisture, etc. It is known that

  Therefore, a drug containing a substance having the same action as estrogen is transdermally or orally administered to women after menopause, whose estrogen secretion declines. As such an estrogen-like action, for example, an extract from the leaves of quince (see Patent Document 7) is known.

  The epidermis and dermis of the skin are composed of epidermal cells, fibroblasts, and an extracellular matrix such as collagen that is outside these cells and supports the skin structure. In young skin, the proliferation of fibroblasts is active, and moisture is retained in the skin by the interaction of skin tissues such as fibroblasts and collagen, and the flexibility and elasticity of the skin are secured. It is maintained in a fresh state with its tension and gloss.

  However, the growth of fibroblasts slows down due to the influence of certain external factors such as ultraviolet rays, drastic drying of air, excessive skin washing, etc., and aging progresses, and the moisture retention function and elasticity of the skin decrease. To do. And the skin loses its tension and gloss, and exhibits aging symptoms such as roughness and wrinkles. Therefore, it is considered that aging of the skin can be prevented or improved by promoting the proliferation of fibroblasts. Based on such an idea, as a substance having a fibroblast proliferation promoting action, for example, Kusunohagashi extract (see Patent Document 8) is known.

  In recent years, body fat has increased due to lifestyle habits such as satiety and lack of exercise, and obesity has increased. Such an increase in obesity is seen not only in humans but also in pets and livestock. Obesity is a cause of adult diseases such as hyperlipidemia and arteriosclerosis, which is not only a cosmetic problem but also a major problem in health.

In order to break down fat in the living body, the role of cyclic AMP is important. Cyclic AMP activates lipase present in the living body, and fat is decomposed into fatty acid and glycerol by the activated lipase. However, when cyclic AMP phosphodiesterase is activated, degradation of cyclic AMP is induced and lipase activation is inhibited. Therefore, it is considered that by inhibiting the activity of cyclic AMP phosphodiesterase, the amount of cyclic AMP in the cell can be increased and the decomposition of fat can be promoted. Based on such an idea, for example, a peanut astringent skin extract (see Patent Document 9) is known as one having a cyclic AMP phosphodiesterase inhibitory action.
Japanese Patent Laid-Open No. 2003-55242 JP 2003-12532 A JP-A-8-333267 JP 2003-212789 A JP 2002-370962 A JP 2004-83488 A JP 2002-226323 A JP 2003-146837 A JP 2004-26719 A

  A first object of the present invention is to find a highly safe natural product having a hyaluronidase inhibitory action and / or a hexosaminidase release inhibitory action, and to provide an anti-inflammatory agent comprising the active ingredient as an active ingredient. And

  The second object of the present invention is to find a natural product having a tyrosinase inhibitory action among highly safe natural products, and to provide a whitening agent or a tyrosinase inhibitor containing the same as an active ingredient.

  Thirdly, the present invention finds one having at least one action selected from the group consisting of an elastase inhibitory action, an estrogen-like action and a fibroblast proliferation promoting action among highly safe natural products, It aims at providing the anti-aging agent which uses it as an active ingredient.

  A fourth object of the present invention is to find a highly safe natural product having a cyclic AMP phosphodiesterase inhibitory action, and to provide a slimming agent or a cyclic AMP phosphodiesterase inhibitor containing the same as an active ingredient. To do.

  Fifth, among the highly safe natural products, the present invention includes hyaluronidase inhibitory action, hexosaminidase release inhibitory action, tyrosinase inhibitory action, elastase inhibitory action, estrogen-like action, fibroblast proliferation promoting action and cyclic An object of the present invention is to find one having at least one action selected from the group consisting of AMP phosphodiesterase inhibitory action, and to provide a skin cosmetic or cosmetic food or drink containing the same.

  In order to solve the above-mentioned problems, the anti-inflammatory agent, whitening agent, tyrosinase inhibitor, anti-aging agent, slimming agent and cyclic AMP phosphodiesterase inhibitor of the present invention contain an extract from tenninka as an active ingredient. In addition, the skin cosmetics and beauty foods and beverages of the present invention are characterized by blending an extract from tenninka.

  In the anti-inflammatory agent of the present invention, the extract preferably has a hyaluronidase inhibitory action and / or hexosaminidase release inhibitory action. In the anti-aging agent of the invention, the extract has an elastase inhibitory action. It preferably has one or more actions selected from the group consisting of an estrogen-like action and a fibroblast proliferation promoting action.

  According to the present invention, an anti-inflammatory agent, a whitening agent, a tyrosinase inhibitor, an anti-aging agent, a slimming agent, cyclic AMP phosphodiesterase inhibition, which contains an extract from natural tenninka as an active ingredient and is excellent in safety. An agent, skin cosmetic, or beauty food or drink can be provided.

The present invention will be described below.
[Anti-inflammatory agent, whitening agent, tyrosinase inhibitor, anti-aging agent, slimming agent, cyclic AMP phosphodiesterase inhibitor]
The anti-inflammatory agent, whitening agent, tyrosinase inhibitor, anti-aging agent, slimming agent or cyclic AMP phosphodiesterase inhibitor of the present invention contains an extract from tenninka as an active ingredient.

  Here, “slimming” means a slimming action. As the slimming action, for example, the action of promoting the degradation of fat cells accumulated in the living body or the accumulation of fat cells in the living body are suppressed. Although an effect etc. are mentioned, it is not limited to these actions. Therefore, in the present specification, the “slimming agent” means an anti-obesity agent that can prevent, treat or ameliorate obesity, and the slimming agent includes, for example, slimming agents, lipolysis promoters, fat accumulation inhibitors. Etc. are included.

  In the present invention, the “extract from Tenninka” includes an extract obtained from Tenninka as an extraction raw material, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, or these Either a crude product or a purified product is included.

The extraction raw material used in the present invention is tenninka (scientific name: Rhodomyrtus tomentosa (Ait.) Hassk.).
Tenninka (Rhodomyrtus tomentosa (Ait.) Hassk.) Is an evergreen shrub belonging to the family Myrtaceae distributed in the tropical and subtropical regions of Southeast Asia. In Japan, it grows naturally in Okinawa, etc. It can be easily obtained. Tenninka fruit is used as raw material for juice and jam in addition to being eaten raw. In China, it is called Momokin daughter, and the fruit is privately used as anemia and hemostatic agent for pregnant women, and the leaves and roots are privately used for the treatment of headache and abdominal pain.

  Examples of the constituent parts of the tenninka that can be used as the raw material for extraction include above-ground parts such as leaves, branches, barks, trunks, stems, fruits, and flower parts, roots, or mixtures of these parts. Is preferably the above-ground part, root part or fruit part, or a mixture of these parts.

  Of hyaluronidase inhibitory action, hexosaminidase release inhibitory action, tyrosinase inhibitory action, elastase inhibitory action, estrogen-like action, fibroblast proliferation promoting action or cyclic AMP phosphodiesterase inhibitory action contained in extracts from Tenninka Although details are unknown, extracts having these actions can be obtained from tenninka by an extraction method generally used for plant extraction.

  For example, after drying the above plant, it is pulverized as it is or using a crusher, and subjected to extraction with an extraction solvent, thereby inhibiting hyaluronidase inhibitory action, hexosaminidase release inhibitory action, tyrosinase inhibitory action, elastase inhibitory action, estrogen An extract having an action, a fibroblast proliferation promoting action or a cyclic AMP phosphodiesterase inhibitory action can be obtained. Drying may be performed in the sun or using a commonly used dryer. Moreover, after performing pretreatment, such as degreasing, with a nonpolar solvent such as hexane, it may be used as an extraction raw material. By performing pretreatment such as degreasing, extraction with a polar solvent of tenninka can be performed efficiently.

  As the extraction solvent, it is preferable to use a polar solvent, and examples thereof include water and hydrophilic organic solvents. These may be used alone or in combination of two or more at room temperature or a temperature below the boiling point of the solvent. Is preferred.

  Examples of water that can be used as the extraction solvent include pure water, tap water, well water, mineral spring water, mineral water, hot spring water, spring water, fresh water, and the like, and those subjected to various treatments. Examples of the treatment applied to water include purification, heating, sterilization, filtration, ion exchange, osmotic pressure adjustment, buffering, and the like. Therefore, the water that can be used as the extraction solvent in the present invention includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline, and the like.

  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; 1,3-butylene. Examples thereof include polyhydric alcohols having 2 to 5 carbon atoms such as glycol, propylene glycol and glycerin.

  When using the liquid mixture of 2 or more types of polar solvents as an extraction solvent, the mixing ratio can be adjusted suitably. For example, when using a liquid mixture of water and a lower aliphatic alcohol, it is preferable to mix 1 to 90 parts by weight of a lower aliphatic alcohol with respect to 10 parts by weight of water. When using a mixed solution, it is preferable to mix 1 to 40 parts by mass of a lower aliphatic ketone with 10 parts by mass of water, and when using a mixed solution of water and a polyhydric alcohol, water 10 It is preferable to mix 10 to 90 parts by mass of polyhydric alcohol with respect to parts by mass.

  The extraction treatment is not particularly limited as long as the soluble component contained in the extraction raw material can be eluted in the extraction solvent, and can be performed according to a conventional method. For example, the extraction raw material is immersed in an extraction solvent 5 to 15 times (mass ratio) of the extraction raw material, the soluble components are extracted at room temperature or under reflux, and then filtered to remove the extraction residue. A liquid can be obtained. The obtained extract is diluted, concentrated, dried, purified, etc. according to a conventional method in order to obtain a diluted or concentrated solution of the extract, a dried product of the extract, or a crude purified product or a purified product thereof. Processing may be performed.

  Purification can be performed by, for example, activated carbon treatment, adsorption resin treatment, ion exchange resin treatment, or the like. The obtained extract can be used as an active ingredient of an anti-inflammatory agent, a whitening agent, a tyrosinase inhibitor, an anti-aging agent, a slimming agent or a cyclic AMP phosphodiesterase inhibitor as it is, but it is a concentrated solution or a dried product. Things are easier to use.

  Since the extract from Tenninka has a unique odor, it can be purified for the purpose of decolorization, deodorization, etc. within the range that does not cause a decrease in its physiological activity. Since it is not used in large quantities when blended in food and drink, there is no practical problem even if it is not purified.

  The extract from tenninka obtained as described above has an anti-inflammatory action, a whitening action, a tyrosinase inhibitory action, an anti-aging action, a slimming action, or a cyclic AMP phosphodiesterase inhibitory action. Thus, it can be used as an active ingredient of an anti-inflammatory agent, whitening agent, tyrosinase inhibitor, anti-aging agent, slimming agent or cyclic AMP phosphodiesterase inhibitor.

  Here, the anti-inflammatory action of the extract from Tenninka is exhibited based on, for example, a hyaluronidase inhibitory action and / or a hexosaminidase release inhibitory action. However, the anti-inflammatory action which the extract from Tenninka has is not limited to the anti-inflammatory action exhibited based on the above action. In addition, since the extract from Tenninka has a hyaluronidase inhibitory action or a hexosaminidase release inhibitory action, it should be used as an active ingredient of a hyaluronidase inhibitor or a hexosaminidase release inhibitor. Can do.

  Moreover, the whitening action which the extract from Tenninka has is exhibited based on the tyrosinase inhibitory action, for example. However, the whitening action of the extract from tenninka is not limited to the whitening action exhibited based on the above action.

  Furthermore, the anti-aging effect of the extract from Tenninka is exhibited based on, for example, one or more actions selected from the group consisting of an elastase inhibitory action, an estrogen-like action, and a fibroblast proliferation promoting action. . However, the anti-aging action of the extract from Tenninka is not limited to the anti-aging action exhibited based on the above action. In addition, since the extract from Tenninka has an elastase inhibitory action, an estrogen-like action, or a fibroblast proliferation promoting action, the elastase inhibitor, an estrogen-like action agent, or a fibroblast proliferation promoting agent is utilized using those actions. It can be used as an active ingredient.

  Furthermore, the slimming action of the extract from Tenninka is exhibited based on, for example, a cyclic AMP phosphodiesterase inhibitory action. However, the slimming action of the extract from tenninka is not limited to the slimming action exhibited based on the above action.

  The anti-inflammatory agent, whitening agent, tyrosinase inhibitor, anti-aging agent, slimming agent or cyclic AMP phosphodiesterase inhibitor of the present invention may consist of only an extract from Tenninka, It may be converted into one.

  Extract from Tenninka is prepared into any dosage form such as powder, granule, tablet, liquid, etc. according to conventional methods using pharmaceutically acceptable carriers such as dextrin and cyclodextrin. It can be formulated. In this case, as an auxiliary agent, for example, an excipient, a binder, a disintegrant, a lubricant, a stabilizer, a flavoring / flavoring agent, and the like can be used. Extracts from Tenninka can be used by blending with other compositions (for example, skin cosmetics and cosmetic foods and beverages described later), and also used as ointments, external liquids, patches, etc. Can do.

  In addition, the anti-inflammatory agent, whitening agent, tyrosinase inhibitor, anti-aging agent, slimming agent or cyclic AMP phosphodiesterase inhibitor of the present invention may have an anti-inflammatory action, a hyaluronidase inhibitory action, or a hexosaminidase release inhibitor as necessary. Active ingredient with other natural extracts having action, whitening action, tyrosinase inhibitory action, anti-aging action, elastase inhibitory action, estrogen-like action, fibroblast proliferation promoting action, slimming action or cyclic AMP phosphodiesterase inhibitory action Can be used as

  The anti-inflammatory agent of the present invention has various inflammatory diseases such as contact dermatitis (rash), psoriasis and pemphigus vulgaris through hyaluronidase inhibitory action and / or hexosaminidase release inhibitory action of the extract from Tenninka. Can be prevented, treated or ameliorated. However, the anti-inflammatory agent of the present invention can be used for all purposes other than these uses, which are meaningful for exerting a hyaluronidase inhibitory action and / or a hexosaminidase release inhibitory action.

  The whitening agent of the present invention can prevent, treat or ameliorate skin pigmentation, blemishes, buckwheat etc. through the tyrosinase inhibitory action of the extract from Tenninka. However, the whitening agent of the present invention can be used for all purposes other than these uses, which are meaningful for exerting a tyrosinase inhibitory action.

  The tyrosinase inhibitor of the present invention can prevent, treat or ameliorate skin pigmentation, stains, buckwheat etc. through the tyrosinase inhibitory action of the extract from Tenninka. However, the tyrosinase inhibitor of the present invention can be used for all purposes that are meaningful for exerting a tyrosinase inhibitory action in addition to these uses.

  The anti-aging agent of the present invention is a skin wrinkle formation through one or more actions selected from the group consisting of an elastase inhibitory action, an estrogen-like action and a fibroblast proliferation promoting action possessed by an extract from Tenninka. It is possible to prevent, treat or improve an aging phenomenon such as a decrease in elasticity. However, the anti-aging agent of the present invention is significant in that it exhibits one or more actions selected from the group consisting of an elastase inhibitory action, an estrogen-like action and a fibroblast proliferation promoting action in addition to these uses. Can be used for all applications.

  The slimming agent of the present invention can prevent, treat or ameliorate obesity through the cyclic AMP phosphodiesterase inhibitory action of the extract from Tenninka. However, the slimming agent of this invention can be used for all the uses meaningful in exhibiting a cyclic AMP phosphodiesterase inhibitory effect besides these uses.

  The cyclic AMP phosphodiesterase inhibitor of the present invention can prevent, treat or ameliorate obesity through the cyclic AMP phosphodiesterase inhibitory action of the extract from Tenninka. However, the cyclic AMP phosphodiesterase inhibitor of the present invention can be used for all purposes other than these uses that are meaningful for exerting a cyclic AMP phosphodiesterase inhibitory action.

[Skin cosmetic]
Extract from Tenninka has hyaluronidase inhibitory action, hexosaminidase release inhibitory action, tyrosinase inhibitory action, elastase inhibitory action, estrogen-like action, fibroblast proliferation promoting action or cyclic AMP phosphodiesterase inhibitory action, Since it is excellent in usability and safety when applied to the skin, it is suitable for blending into skin cosmetics. In this case, the skin cosmetic may contain an extract from tenninka, or an anti-inflammatory agent, whitening agent, tyrosinase inhibitor, anti-aging agent, slimming agent, or cypress formulated from an extract from tenninka. A click AMP phosphodiesterase inhibitor may be added. By blending an extract from Tenninka, the anti-inflammatory agent, the whitening agent, the tyrosinase inhibitor, the anti-aging agent, the slimming agent or the cyclic AMP phosphodiesterase inhibitor into the skin cosmetic, Hyaluronidase inhibitory action, hexosaminidase release inhibitory action, tyrosinase inhibitory action, elastase inhibitory action, estrogen-like action, fibroblast proliferation promoting action or cyclic AMP phosphodiesterase inhibitory action can be imparted.

  The types of skin cosmetics that can be blended with the extract from Tenninka are not particularly limited, and examples thereof include ointments, creams, emulsions, lotions, packs, jellies, foundations, lip balms, lipsticks, bathing agents, and the like. It is done.

  When the extract from Tenninka is blended into the skin cosmetic, the blending amount can be adjusted as appropriate according to the type of skin cosmetic, but the preferred blending rate is converted to a standard extract. About 0.0001 to 10% by mass, and a particularly suitable blending ratio is about 0.001 to 1% by mass in terms of a standard extract.

  The skin cosmetic composition of the present invention comprises a hyaluronidase inhibitory action, hexosaminidase release inhibitory action, tyrosinase inhibitory action, elastase inhibitory action, estrogen-like action, fibroblast proliferation promoting action or cyclic AMP phosphodiesterase possessed by an extract from Tenninka As long as the inhibitory action is not hindered, main agents, auxiliaries or other components used in the production of ordinary skin cosmetics, such as astringents, bactericides / antibacterial agents, whitening agents, UV absorbers, humectants, cell activators, Anti-inflammatory / antiallergic agents, antioxidant / active oxygen scavengers, fats and oils, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, fragrances and the like can be used in combination. By using in this way, it becomes a more general product, and a synergistic action with the above-mentioned components used in combination may bring about an excellent effect that is usually expected.

[Beauty food and drink]
Extract from Tenninka has hyaluronidase inhibitory action, hexosaminidase release inhibitory action, tyrosinase inhibitory action, elastase inhibitory action, estrogen-like action, fibroblast proliferation promoting action or cyclic AMP phosphodiesterase inhibitory action, It has been confirmed that it is not digested in the digestive tract, and is excellent in safety, so it is suitable for blending into cosmetic foods and drinks. In this case, an extract from Tenninka may be added as it is, or an anti-inflammatory agent, whitening agent, tyrosinase inhibitor, anti-aging agent, slimming agent, or cyclic AMP phosphodiesterase inhibition formulated from an extract from Tenninka An agent may be blended.

  Here, “beauty food and drink” refers to food and drink intended for beautifying the skin, or food and drink intended to prevent and improve rough skin, aging of the skin and various skin diseases associated therewith. Means.

  When an extract from the above tenninka or an anti-inflammatory agent, whitening agent, tyrosinase inhibitor, anti-aging agent, slimming agent, or cyclic AMP phosphodiesterase inhibitor formulated therefrom is incorporated into a cosmetic food or drink, the active ingredient in them The amount of extract can be appropriately changed in consideration of the purpose of use, symptoms, gender, etc., but the amount of extract per day for adults is approximately It is preferable to be 1 to 1000 mg.

  The cosmetic food and drink of the present invention may be an extract from tenninka blended with any food or drink that does not impede its activity, or a dietary supplement mainly composed of an extract from tenninka It may be.

  When producing the cosmetic food and drink of the present invention, for example, sugars such as dextrin and starch; proteins such as gelatin, soybean protein and corn protein; amino acids such as alanine, glutamine and isoleucine; cellulose and gum arabic Polysaccharides: Foods and drinks of any shape can be obtained by adding any auxiliary agent such as oils and fats such as soybean oil and medium chain fatty acid triglycerides.

  Beauty foods and drinks that can be blended with extracts from Tenninka are not particularly limited, but specific examples thereof include beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit drinks, and lactic acid drinks (concentrated concentrates of these drinks and Including ice cream, ice sherbet, shaved ice, etc .; noodles such as buckwheat, udon, harusame, gyoza skin, cucumber skin, Chinese noodles, instant noodles; rice cake, chewing gum, candy, gum, chocolate , Tablet confectionery, snack confectionery, biscuits, jelly, jam, cream, baked confectionery, etc .; fish and shellfish processed foods such as kamaboko, ham, sausage; dairy products such as processed milk, fermented milk; salad oil, tempura oil, margarine , Mayonnaise, shortening, whipped cream, dressing and other fats and oils processed foods; sauces, sauces, etc. Soups, stews, salads, prepared dishes, pickles; other various forms of health and nutritional supplements; tablets, capsules, drinks, etc. In addition, commonly used auxiliary raw materials and additives can be used in combination.

  In addition, the anti-inflammatory agent, whitening agent, tyrosinase inhibitor, anti-aging agent, slimming agent, cyclic AMP phosphodiesterase inhibitor, skin cosmetic or cosmetic food or drink of the present invention is suitably applied to humans. However, it can be applied to animals other than humans as long as the respective effects are exhibited.

  Hereinafter, although a manufacture example, a test example, and a compounding example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to each following example at all.

[Production Example 1] Production of above-ground extract of Tenninka 2000 mL of extraction solvent was added to 200 g of the dried above-ground portion of Tenninka, and the mixture was heated and extracted at 80 ° C for 2 hours with a reflux extractor and filtered while hot. The same extraction process was further performed on the residue. The obtained extracts were combined, concentrated under reduced pressure, and dried to obtain an above-ground extract of a tenninka. As the extraction solvent, water, 50% by mass ethanol (mass ratio of water and ethanol = 1: 1), 80% by mass ethanol (mass ratio of water and ethanol = 1: 4) The yield is shown in Table 1.

[Table 1]
Sample extraction solvent extract yield (%)
1 water 6.8
2 50% ethanol 9.6
3 80% ethanol 7.8

[Production Example 2] Production of Tenninka Root Extract Extract 2000 ml of extraction solvent was added to 200 g of dried garlic root extract, and the mixture was heated and extracted at 80 ° C for 2 hours with a reflux extractor and filtered while hot. The same extraction process was further performed on the residue. The obtained extracts were combined, concentrated under reduced pressure, and dried to obtain a Tenninka root extract. As the extraction solvent, water, 50% by mass ethanol (mass ratio of water and ethanol = 1: 1), 80% by mass ethanol (mass ratio of water and ethanol = 1: 4) The yield is shown in Table 2.

[Table 2]
Sample extraction solvent extract yield (%)
4 Water 4.3
5 50% ethanol 5.7
6 80% ethanol 4.7

[Production Example 3] Production of Tenninka fruit part extract To 200 g of dried fruit of Tenninka fruit part, 2000 mL of extraction solvent was added, and the mixture was heated and extracted at 80 ° C for 2 hours with a reflux extractor and filtered while hot. The same extraction process was further performed on the residue. The obtained extracts were combined, concentrated under reduced pressure, and dried to obtain a Tenninka fruit part extract. As the extraction solvent, water, 50% by mass ethanol (mass ratio of water and ethanol = 1: 1), 80% by mass ethanol (mass ratio of water and ethanol = 1: 4) The yield is shown in Table 3.

[Table 3]
Sample extraction solvent extract yield (%)
7 Water 4.6
8 50% ethanol 5.8
9 80% ethanol 4.6

[Test Example 1] Hyaluronidase Inhibitory Action Test According to Tenninka ground extract (Samples 1 to 3) obtained in Production Example 1, Tenninka root extract (Samples 4 to 6) obtained in Production Example 2 and Production Example 3 About the obtained Tenninka fruit part extract (samples 7-9), the hyaluronidase inhibitory effect was tested as follows.

  0.2 mL of a sample solution prepared by dissolving each sample (samples 1 to 9) in 0.1 mol / L acetate buffer (pH 3.5) and a hyaluronidase solution (Type IV-S (from bovine testis), manufactured by SIGMA) 400 units / mL) and 0.1 mL were mixed and reacted at 37 ° C. for 20 minutes. Further, 0.2 mL of 2.5 mmol / L calcium chloride was added as an activator and reacted at 37 ° C. for 20 minutes to activate the enzyme. Thereafter, 0.5 mL of 0.4 mg / mL potassium hyaluronate solution (from rooster comb) was added and reacted at 37 ° C. for 40 minutes, and 0.2 mL of 0.4 mol / L sodium hydroxide solution was added and cooled with ice. The reaction was stopped.

  0.2 mL of boric acid solution was added to each reaction solution, heated in a boiling water bath for 3 minutes, and then ice-cooled for 10 minutes. Next, 6 mL of p-DABA reagent (10 g of p-dimethylaminobenzaldehyde dissolved in 12.5 mL of 10N hydrochloric acid and 87.5 mL of acetic acid and diluted 10-fold with acetic acid) was added, and the mixture was added at 37 ° C. for 20 minutes. Reacted. Thereafter, the absorbance at a wavelength of 585 nm was measured. A blank test was performed and corrected in the same manner. From the obtained results, the hyaluronidase inhibition rate (%) was calculated from the following formula.

Hyaluronidase inhibition rate (%) = {1− (St−Sb) / (Ct−Cb)} × 100
In the formula, St represents the absorbance of the sample solution at a wavelength of 585 nm, Sb represents the absorbance of the sample solution blank at a wavelength of 585 nm, Ct represents the absorbance of the control solution at a wavelength of 585 nm, and Cb represents the absorbance of the control solution blank at a wavelength of 585 nm. Represents.

The sample concentration was decreased stepwise to measure the hyaluronidase inhibition rate (%), and the sample concentration IC ₅₀ (μg / mL; ppm) that inhibited the hyaluronidase activity by 50% was determined by interpolation.
Table 4 shows the results of the above test.

[Table 4]
Sample IC ₅₀ (μg / mL)
1> 400
2 269.1
3> 400
4 248.3
5 224.5
6 268.1
7> 400
8 383.5
9> 400

  As shown in Table 4, it was confirmed that the extracts from the above-ground part, root part, and fruit part of Tenninka have an excellent hyaluronidase inhibitory action. It was also confirmed that the degree of hyaluronidase inhibitory action can be adjusted by the concentration of the extract.

[Test Example 2] Hexosaminidase release inhibitory action test Tenninka ground extract (Samples 1 to 3) obtained in Production Example 1, Tenninka root extract (Samples 4 to 6) obtained in Production Example 2 and About the Tenninka fruit part extract (samples 7-9) obtained by manufacture example 3, the hexosaminidase release inhibitory effect was tested as follows.

Rat basophil leukemia cells (RBL-2H3) were cultured in S-MEM medium containing 15% FBS, and then cells were collected by trypsin treatment. The collected cells are diluted to a cell density of 4.0 × 10 ⁵ cells / mL, and after adding DNP-specific IgE so that the final concentration of DNP-specific IgE is 0.5 μg / mL, 96 100 μL per well was seeded on a well plate and cultured overnight. After completion of the culture, the medium was removed and washing was performed twice with 500 μL of Silaganian buffer.

Next, 30 μL of the Siraganian buffer and 10 μL of the sample solution dissolved in the same buffer were added, and the mixture was allowed to stand at 37 ° C. for 10 minutes. Thereafter, 10 μL of a 100 ng / mL DNP-BSA solution was added, and the mixture was allowed to stand at 37 ° C. for 15 minutes to release hexosaminidase. Thereafter, the release of hexosaminidase was stopped by allowing the 96-well plate to stand on ice. 10 μL of cell supernatant in each well and 10 μL of 1 mmol / L p-nitrophenyl-N-acetyl-α-D-glucosaminide (p-NAG) solution were added to a new 96-well plate and reacted at 37 ° C. for 1 hour. I let you. After completion of the reaction, 250 μL of 0.1 mol / L Na ₂ CO ₃ / NaHCO ₃ was added to each well, and the absorbance at a wavelength of 415 nm was measured. Similarly, the absorbance of a mixed solution of 10 μL of cell supernatant and 250 μL of 0.1 mol / L Na ₂ CO ₃ / NaHCO ₃ was measured without adding a sample. Similarly, the sample was added and the absorbance was measured without adding p-NAG. From the obtained results, the hexosaminidase release inhibition rate (%) was calculated by the following formula.

Inhibition rate of hexosaminidase release (%) = {1− (B−C) / A} × 100
In the formula, A represents the absorbance when the sample was not added, B represents the absorbance when the sample was added, and C represents the absorbance when the sample was added and p-NAG was not added.

The concentration of the sample solution is decreased stepwise to calculate the hexosaminidase release inhibition rate (%), and the sample concentration IC ₅₀ (μg / mL; ppm) at which the hexosaminidase release inhibition rate is 50%. Was calculated by interpolation.
The results of the above test are shown in Table 5.

[Table 5]
Sample IC ₅₀ (μg / mL)
1 348
2 136
3 105
4 95.5
5 73.1
6 80.0
7 335
8 79.7
9 43.8

  As shown in Table 5, it was confirmed that the extracts from the above-ground part, root part, and fruit part of Tenninka have an excellent hexosaminidase release inhibitory action. Moreover, it was confirmed that the degree of hexosaminidase release inhibitory action can be adjusted by the concentration of the extract.

[Test Example 3] Tyrosinase inhibitory action test Tenninka ground extract (Samples 1 to 3) obtained in Production Example 1, Tenninka root extract (Samples 4 to 6) obtained in Production Example 2 and Production Example 3 About the obtained tenninka fruit part extract (samples 7-9), the tyrosinase inhibitory effect was tested as follows.

  In a 48-well plate, 0.2 mL of Mcllvaine buffer (pH 6.8), 0.06 mL of 0.3 mg / mL tyrosine solution and 0.18 mL of 25% DMSO solution of the sample (sample concentration of samples 1 to 6: 200 μg / mL) Sample concentration of Samples 7 and 8: 400 μg / mL, Sample concentration of Sample 9: 100 μg / mL) was added and allowed to stand at 37 ° C. for 10 minutes. To this, 0.02 mL of 2500 unit / mL tyrosinase solution was added, followed by reaction at 37 ° C. for 15 minutes. After completion of the reaction, the absorbance at a wavelength of 475 nm was measured. A blank test was performed and corrected in the same manner. From the obtained results, the tyrosinase inhibition rate (%) was calculated by the following formula.

Tyrosinase inhibition rate (%) = {1− (St−Sb) / (Ct−Cb)} × 100
In the formula, St represents the absorbance of the sample solution at a wavelength of 475 nm, Sb represents the absorbance of the sample solution blank at a wavelength of 475 nm, Ct represents the absorbance of the control solution at a wavelength of 475 nm, and Cb represents the absorbance of the control solution blank at a wavelength of 475 nm. Represents.
The results of the above test are shown in Table 6.

[Table 6]
Sample tyrosinase inhibition rate (%)
1 11.2
2 10.4
3 9.3
4 25.0
5 30.7
6 26.7
7 17.6
8 6.9
9 1.9

  As shown in Table 6, it was confirmed that the extracts from the above-ground part, root part, and fruit part of Tenninka have an excellent tyrosinase inhibitory action.

[Test Example 4] Elastase inhibitory action test Tenninka ground extract (Samples 1 to 3) obtained in Production Example 1, Tenninka root extract (Samples 4 to 6) obtained in Production Example 2 and Production Example 3 About the obtained tenninka fruit part extract (samples 7-9), the elastase inhibitory effect was tested as follows.

  In a 96-well plate, 50 μL of a sample solution prepared with 0.2 mol / L Tris-HCl buffer (pH 8.0) and 50 μL of 20 μg / mL elastase type III solution were mixed. Thereafter, 100 μL of 0.4514 mg / mL N-succinyl-Ala-Ala-Ala-p-nitroanilide prepared in the above buffer solution was added and reacted at 25 ° C. for 15 minutes. After completion of the reaction, absorbance at a wavelength of 415 nm was measured. A blank test was performed and corrected in the same manner. From the obtained results, the elastase inhibition rate (%) was calculated by the following formula.

Elastase inhibition rate (%) = {1- (C−D) / (A−B)} × 100
In the formula, A represents the absorbance at a wavelength of 415 nm when no sample was added and the enzyme was added, B represents the absorbance at a wavelength of 415 nm when no sample was added and the enzyme was not added, and C was at a wavelength of 415 nm when the sample was added and the enzyme was not added. Absorbance is represented, and D represents absorbance at a wavelength of 415 nm when a sample is added and no enzyme is added.

The elastase inhibition rate (%) was measured by gradually reducing the sample concentration, and the sample concentration IC ₅₀ (μg / mL; ppm) that inhibits the elastase activity by 50% was determined by interpolation.
Table 7 shows the results of the above test.

[Table 7]
Sample IC ₅₀ (μg / mL)
1 230.0
2 77.1
3 72.8
4 39.0
5 29.9
6 23.5
7> 400
8 80.3
9 246

  As shown in Table 7, it was confirmed that the extracts from the above-ground part, root part, and fruit part of Tenninka have an excellent elastase inhibitory action. It was also confirmed that the degree of elastase inhibitory action can be adjusted by the concentration of the extract.

[Test Example 5] Estrogen-like action test Tenninka ground extract (Samples 1 to 3) obtained in Production Example 1, Tenninka root extract (Samples 4 to 6) obtained in Production Example 2 and Production Example 3 About the obtained tenninka fruit part extract (samples 7-9), the estrogen-like action was tested as follows.

Human breast cancer-derived cells (MCF-7) were cultured in a MEM medium containing 10% FBS, 1% NEAA and 1 mmol / L sodium pyruvate, and then cells were collected by trypsin treatment. The recovered cells were treated with activated carbon-treated 10% FBS, 1% NEAA, and 1 mmol / L sodium pyruvate and no phenol red, and 3.0 × 10 ⁴ cells using MEM medium (T-MEM medium). After adjusting to a cell density of / mL, the cells were seeded in a 48-well plate at 450 μL per well and cultured to establish the cells. Six hours later (day 0), 50 μL of a sample solution (sample concentration: 12.5 μg / mL) adjusted to 10 times the final concentration in T-MEM medium was added to each well, and the culture was continued. On the third day, the medium was removed, 0.5 mL of the sample solution adjusted to the final concentration with T-MEM medium was added to each well, and the culture was further continued.

Estrogen-like effects were measured using the MTT assay. After completion of the culture, the medium was removed, and 200 μL of MTT dissolved in a final concentration of 0.4 mg / mL in MEM medium containing 1% NEAA and 1 mmol / L sodium pyruvate was added to each well. After culturing for 2 hours, blue formazan produced in the cells was extracted with 200 μL of 2-propanol. After extraction, the absorbance at a wavelength of 570 nm was measured. At the same time, the absorbance at a wavelength of 650 nm was measured as turbidity, and the difference between the two was used as the amount of blue formazan produced. As a positive control, 1 × 10 ⁻⁹ M estradiol was used. From the obtained results, the estrogen-like action rate (%) at the time of adding the sample solution was calculated by the following formula.

Estrogen-like action rate (%) = A / B × 100
In the formula, A represents the absorbance when the sample solution was added, and B represents the absorbance when no sample solution was added.
The results of the above test are shown in Table 8.

[Table 8]
Sample Estrogen-like action rate (%)
1 119.8
2 131.0
3 126.5
4 123.8
5 126.3
6 123.8
7 109.4
8 120.3
9 115.8

  As shown in Table 8, it was confirmed that extracts from the above-ground part, root part and fruit part of Tenninka have an excellent estrogenic action.

[Test Example 6] Fibroblast proliferation promoting action test Tenninka ground extract (Samples 1 to 3) obtained in Production Example 1, Tennin root extract (Samples 4 to 6) obtained in Production Example 2 and production About the Tenninka fruit part extract (samples 7-9) obtained in Example 3, the fibroblast proliferation promoting effect was tested as follows.

Human normal skin fibroblasts (NB1RGB) were cultured using α-MEM containing 10% FBS, and then cells were collected by trypsin treatment. The collected cells were diluted with α-MEM containing 5% FBS to a concentration of 7.0 × 10 ⁴ cells / mL, then seeded at 100 μL per well in a 96-well plate, and cultured overnight. After completion of the culture, a sample solution dissolved in α-MEM containing 5% FBS (sample concentration of samples 1 to 3: 50 μg / mL, sample concentration of samples 4 to 6: 400 μg / mL, sample concentration of sample 7: 200 μg / mL) , Sample concentration of sample 8: 100 μg / mL, sample concentration of sample 9: 50 μg / mL) was added to each well, and cultured for 3 days. Fibroblast proliferation was measured using the MTT assay. After completion of the culture, 100 μL of the medium was removed from each well, and 20 μL of MTT dissolved in PBS (−) at a final concentration of 5 mg / mL was added to each well. After culturing for 4.5 hours, 100 μL of a 0.01 mol / L hydrochloric acid solution in which 10% SDS was dissolved was added to each well and incubated overnight, and then the absorbance at a wavelength of 570 nm was measured. At the same time, the absorbance at a wavelength of 650 nm was measured as turbidity, and the difference between the two was used as the amount of blue formazan produced. In addition, a blank test was performed and corrected in the same manner. From the obtained results, the fibroblast proliferation promotion rate (%) was calculated by the following formula.

Fibroblast proliferation promotion rate (%) = (St−Sb) / (Ct−Cb) × 100
In the formula, St represents the absorbance in the cells to which the sample was added, Sb represents the absorbance in the blank test to which the sample was added, Ct represents the absorbance in the cells to which no sample was added, and Cb represents the blank test in which the sample was not added. Represents the absorbance.
Table 9 shows the results of the above test.

[Table 9]
Sample Fibroblast proliferation promotion rate (%)
1 103.6
2 111.7
3 126.0
4 110.3
5 126.4
6 129.6
7 103.4
8 129.5
9 133.6

  As shown in Table 9, it was confirmed that the extracts from the above-ground part, root part, and fruit part of Tenninka have an excellent fibroblast proliferation promoting action.

[Test Example 7] Cyclic AMP phosphodiesterase inhibitory action test Tenninka ground extract (Samples 1 to 3) obtained in Production Example 1, Tenninka root extract (Samples 4 to 6) obtained in Production Example 2 and production For the Tenninka fruit part extract (samples 7 to 9) obtained in Example 3, the cyclic AMP phosphodiesterase inhibitory action was tested as follows.

  To 0.2 mL of 50 mmol / L Tris-HCl buffer (pH 7.5) containing 5 mmol / L magnesium chloride, 0.1 mL of a 2.5 mg / mL bovine serum albumin solution, 0.1 mg / mL phosphodiesterase solution 0 .1 mL and 0.05 mL of the sample solution were added and pre-reacted at 37 ° C. for 5 minutes. To this reaction solution, 0.05 mL of a 0.5 mg / mL cyclic AMP solution was added and reacted at 37 ° C. for 60 minutes. The reaction was stopped by boiling on a boiling water bath for 3 minutes, this was centrifuged (3500 rpm, 4 ° C.), and the reaction substrate 5′-AMP in the supernatant was subjected to high performance liquid chromatography under the following conditions. And analyzed. In addition, a blank test was performed in the same manner without adding the sample solution.

<High performance liquid chromatography conditions>
Product name: Chromatocorder 12 (manufactured by SYSTEM INSTRUMENTS)
Stationary phase: Wakosil 5C ₁₈ (Wako Pure Chemical Industries, Ltd.)
Column diameter: 4.6 mm
Column length: 250mm
Mobile phase: 1 mM TBAP in 25 mM KH ₂ PO ₄ : CH ₃ CN = 90:10
Mobile phase flow rate: 1.0 mL / min
Detection: UV, 260nm

  The cyclic AMP phosphodiesterase inhibition rate (%) was calculated from the following formula using the cyclic AMP peak area, which is the analysis result of the liquid chromatography.

Inhibition rate (%) = (1−A / B) × 100
In the formula, A represents the peak area of cyclic AMP at the time of addition of the sample solution, and B represents the peak area of control cyclic AMP.

The concentration of the sample solution is decreased stepwise to calculate the cyclic AMP phosphodiesterase inhibition rate (%), and the value of the sample concentration IC ₅₀ (μg / mL; ppm) at which the cyclic AMP phosphodiesterase inhibition rate becomes 50%. Was calculated by interpolation.
The results of the above test are shown in Table 10.

[Table 10]
Sample IC ₅₀ (μg / mL)
1 195
2 57.6
3 75.5
4 45.1
5 20.5
6 185
7> 200
8 55.2
9 47.6

  As shown in Table 10, it was confirmed that the extracts from the aerial part, root part and fruit part of Tenninka have an excellent cyclic AMP phosphodiesterase inhibitory action. It was also confirmed that the degree of cyclic AMP phosphodiesterase inhibitory action can be adjusted by the concentration of the extract.

[Formulation Example 1]
An emulsion having the following composition was produced by a conventional method.
Tenninka Root Water Extract (Production Example 2) 0.01 g
Jojoba oil 4.0g
Placenta extract 0.1g
Chamomile extract 0.1g
Olive oil 2.0g
Squalane 2.0g
Cetanol 2.0g
Glyceryl monostearate 2.0g
Polyoxyethylene cetyl ether (20E.O.) 2.5g
Oleic acid polyoxyethylene sorbitan (20E.O.) 2.0g
1,3-butylene glycol 3.0 g
Hinokitiol 0.15g
Fragrance 0.05g
Purified water remainder (total amount is 100 g)

[Formulation Example 2]
A cream having the following composition was produced by a conventional method.
Tenninka above ground 50% ethanol extract (Production Example 1) 0.1 g
Carrot extract 0.1g
Walnut extract 0.1g
Liquid paraffin 5.0g
Salami beeswax 4.0g
Cetanol 3.0g
Squalane 10.0g
Lanolin 2.0g
Stearic acid 1.0g
Oleic acid polyoxyethylene sorbitan (20E.O.) 1.5g
3.0 g glyceryl monostearate
1,3-butylene glycol 6.0 g
1.5 g of methyl paraoxybenzoate
Fragrance 0.1g
Purified water remainder (total amount is 100 g)

[Composition Example 3]
A pack having the following composition was produced by a conventional method.
Tenninka above ground water extract (Production Example 1) 0.05 g
Aloe extract 0.1g
Hydrolyzed conchiolin 0.1g
Polyvinyl alcohol 15g
Polyethylene glycol 3g
7g of propylene glycol
Ethanol 10g
0.05 g ethyl paraoxybenzoate
Fragrance 0.05g
Purified water remainder (total amount is 100 g)

[Formulation Example 4]
A lotion having the following composition was produced by a conventional method.
Tenninka fruit part 80% ethanol extract (Production Example 3) 0.05 g
0.1g dipotassium glycyrrhizinate
Oil soluble licorice extract 0.1g
Glycerin 5.0g
Propylene glycol 5.0g
Polyethylene glycol 2.0g
Polyoxyethylene cetyl ether 2.0g
7.0g ethanol
Potassium hydroxide 0.01g
Fragrance 0.01g
Butyl paraoxybenzoate 0.05g
Water-soluble pigment 0.2g
Purified water remainder (total amount is 100 g)

The anti-inflammatory agent of the present invention is used for the prevention, treatment or improvement of various inflammatory diseases, and the whitening agent or tyrosinase inhibitor of the present invention is used for the prevention, treatment or improvement of skin pigmentation, stains, etc. The aging agent can greatly contribute to the prevention, treatment or improvement of skin aging, and the slimming agent or cyclic AMP phosphodiesterase inhibitor of the present invention can greatly contribute to the prevention, treatment or improvement of obesity.

Claims (3)

A slimming agent characterized by containing, as an active ingredient, an extract from tenninka extracted with water, a hydrophilic organic solvent or a mixture thereof . A cyclic AMP phosphodiesterase inhibitor comprising, as an active ingredient, an extract from tenninka extracted with water, a hydrophilic organic solvent or a mixture thereof . A slimming skin cosmetic characterized by containing an extract from Tenninka extracted with water, a hydrophilic organic solvent or a mixture thereof .