JP5859180B2 - TNF-α production inhibitor, cyclic AMP phosphodiesterase inhibitor, cyclooxygenase-2 (COX-2) inhibitor, elastase activity inhibitor, estrogen-like agent, type I collagen production promoter, and type IV collagen production promoter - Google Patents

Description

  The present invention relates to an anti-inflammatory agent and an anti-aging agent containing at least one of an extract of Murasaki mokuwang, an extract of phyllisocinka, and an extract of akabanazoshinka, and an external preparation for skin.

Inflammation is a complex reaction that exhibits symptoms such as redness, edema, fever, pain, and dysfunction. Microscopically, it consists of common reactions such as blood vessel reaction that causes plasma leakage, leukocyte infiltration, tissue destruction by inflammatory cells, and systemic reactions involving the central nervous system such as fever and hyperalgesia. There is also. Prostaglandins play an important role in such individual reactions of inflammation, and it has become clear that cyclooxygenase-2, an inducible cyclooxygenase, is mainly involved in the production of prostaglandins during this inflammation. Yes.
For this reason, many cyclooxygenase inhibitors represented by aspirin are used for the purpose of preventing and preventing inflammatory reactions (see Non-Patent Document 1). As plant-derived cyclooxygenase inhibitors, α-mangostin and γ-mangostin in mangosteen peel extract are known (see Patent Document 1). Further, as a compound having an inhibitory action on cyclooxygenase-2, 2-phenyl-1,2-benzisoselenazol-3 (2H) -one, a salt thereof, or a hydrate thereof is known (Patent Literature). 2).

TNF-α was found as a factor that necrotizes tumors, but is recently considered to be a cytokine that plays a mediator role not only for tumors but also for regulating the function of normal cells. TNF-α plays an important role in the process from the onset to the end of inflammation, but its continuous and excessive production causes damage to tissues including the skin, and causes systemic fever and cachexia. And cause worsening of inflammation. As such inflammation, for example, chronic inflammatory diseases such as rheumatoid arthritis and osteoarthritis are representative. Therefore, it is important to suppress excessive production of TNF-α in pathological inflammation.
Various proposals have been made for TNF-α production inhibitors for that purpose, such as perilla extract (see Non-Patent Document 2), Amaryllidaceae alkaloids ricolin and ricolicidinol (see Non-Patent Document 3).

In addition, 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. One known is platelet aggregation by cyclic AMP phosphodiesterase.
The platelet aggregation is related to the concentration of cyclic AMP in the platelet. When the cyclic AMP is degraded by the cyclic AMP phosphodiesterase, which is a degradation enzyme of the cyclic AMP, and the concentration decreases, the platelet aggregates. It becomes easy to do. For this reason, it is considered that platelet aggregation can be prevented by suppressing the action of cyclic AMP phosphodiesterase and preventing the decrease of cyclic AMP. As such an anti-inflammatory agent having a cyclic AMP phosphodiesterase inhibitory action, for example, pigmented rice or its koji extract (see Patent Document 3), monopod extract, Kora kaki extract, psycho An extract (see Patent Document 4) and the like have been reported.

  On the other hand, the skin is composed of the stratum corneum, epidermis, basement membrane and dermis. The dermis of the skin is composed of fibroblasts and extracellular matrices such as type I collagen and elastin that support the skin structure outside the cells. The basement membrane is present at the boundary between the epidermis and the dermis and plays an important role in maintaining the skin function as well as connecting the epidermis and the dermis (see Non-Patent Document 4). The main skeleton of the basement membrane has a network structure made of type IV collagen. Various glycoproteins mainly composed of laminin 5 exist at the boundary between the basement membrane and the epidermis and connect the basement membrane and the epidermis. In young skin, the retention of moisture, flexibility, elasticity, etc. is ensured by maintaining the constant interaction of these skin tissues, and the skin is maintained in a fresh state with a firm and glossy appearance. .

  However, the production of type I collagen, which is a major component of the extracellular matrix, decreases when affected by certain external factors such as ultraviolet rays, significant drying of the air, and excessive skin cleansing. At the same time, the elasticity decreases due to cross-linking, and type IV collagen and laminin 5 which are main components of the basement membrane are decomposed or altered, and the basement membrane structure is destroyed. As a result, the skin's moisturizing function and elasticity are lowered, and the keratin begins to exfoliate abnormally, so the skin loses its tension and gloss, and exhibits aging symptoms such as roughness and wrinkles. As described above, changes accompanying skin aging, ie, wrinkles, dullness, disappearance of texture, decreased elasticity, etc., decrease and degeneration of dermis matrix components such as type I collagen, hyaluronic acid, elastin, etc. and basement membrane Is associated with a decrease in type IV collagen, which is a major component of the structure, and structural changes in the basement membrane.

Recent studies have pointed out the involvement of matrix metalloproteinases (MMPs) as factors that induce this change. Among these MMPs, enzymes belonging to the gelatinase group, MMP-2 and MMP-9, are known as enzymes that degrade type IV collagen and laminin 5, which are the main components of the basement membrane. Is significantly increased by irradiation with ultraviolet rays, causing a decrease in basement membrane components and structural changes of the basement membrane due to ultraviolet rays, and it has been clarified that it becomes a major factor in the formation of wrinkles and sagging in the skin (non-patent literature). 5).
Furthermore, one cause of skin aging accompanying aging is a decrease in secretion of estrogen, a type of 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 the cause of unfavorable skin changes such as skin irritability, reduced elasticity, reduced moisture, etc. It is known to be.
Therefore, it is considered that aging of the skin can be prevented and improved by promoting the production of type I collagen in dermal fibroblasts. In addition, by promoting the production of type IV collagen in dermal fibroblasts, the remodeling of the basement membrane structure is induced, and by inhibiting the activity of MMPs, the decrease in basement membrane components and the structural change of the basement membrane are suppressed, Development of substances that improve skin function is desired. On the other hand, a substance (estrogen-like agent) having the same action as estrogen is transdermally or orally administered to women after menopause where estrogen secretion declines.

Known plant extracts having an action of promoting type I collagen production include, for example, licorice leaf extract (see Patent Document 5), lotus germ extract (see Patent Document 6), pentacot extract (see Patent Document 7), and the like. It has been.
Examples of the type IV collagen production-promoting action include flavonoids or glycosides derived from black azuki bean (see Patent Document 8), hydrolyzed casein, pre-extract, beech bud extract, erythrina extract, soluble eggshell membrane Cakkon extract and Western kizuta extract (see Patent Document 9), saponin or sapogenol (see Patent Document 10), and the like are known.
Moreover, as what has a matrix metalloprotease inhibitory effect, for example, the black reishi extract (refer patent document 11), the extract from chestnut astringent skin fermented product (refer patent document 12), etc. are known.
As the estrogen-like agent, for example, steroidal estrogens, nonsteroidal estrogens, flavone compounds and the like are used (see Patent Document 7, 13-14, etc.).

  However, it is excellent in safety and productivity, can be used on a daily basis, and is inexpensive, but has excellent cyclooxygenase-2 (COX-2) inhibitory action, TNF-α production inhibitory action, and cyclic AMP phosphodiesterase inhibitory action A natural anti-inflammatory agent having a type I collagen production promoting action, a type IV collagen production promoting action, an elastase activity inhibiting action, and an estrogen-like action, and the anti-inflammatory agent and the anti-inflammatory agent The demand of the consumer for the external preparation for skin containing at least one of the aging agents is very strong, and there is not yet a satisfactory one yet.

JP 2002-47180 A JP 2000-16935 A JP 2001-163796 A JP 2003-261457 A JP 2000-191498 A JP 2002-29980 A JP 2002-226323 A JP 2007-223918 A JP 2004-18471 A JP 2002-516837 A JP 2005-298391 A JP 2004-352634 A JP 2001-316240 A JP 2003-55245 A Pharmacology Atlas (P184), translated by Takehiko Fukuhara, Bunkodo "Inflammation" 1993, Vol. 13, No. 4, p.337-340 “Pharmaceutical Journal” 2001, Vol.121, No.2, p.167-171 Marinkovich MP et al., “J. Cell. Biol.”, 1992, Vol. 199, p.695-703 Gary J. Fisher et al., “Nature”, 1996, 379, 25, p.335

  An object of the present invention is to solve the conventional problems and achieve the following objects. That is, the present invention provides an anti-inflammatory agent having at least one of an excellent cyclooxygenase-2 (COX-2) inhibitory action, TNF-α production inhibitory action, and cyclic AMP phosphodiesterase inhibitory action, and excellent type I collagen production An anti-aging agent having at least one of a promoting action, a type IV collagen production promoting action, an elastase activity inhibiting action, and an estrogen-like action, and a skin external preparation containing at least one of the anti-inflammatory agent and the anti-aging agent The purpose is to provide.

The present inventors have for solving the above problems has conducted extensive studies, extracts of purple Mok Wan Ju (Bauhinia purpurea), extract of Fuirisoshinka (Bauhinia variegata), and from extracts of saffron Seo sinkers (Bauhinia blakeana) At least one selected has at least one of excellent cyclooxygenase-2 (COX-2) inhibitory action, TNF-α production inhibitory action, and cyclic AMP phosphodiesterase inhibitory action, and is effective as an anti-inflammatory agent I found out.
Further, extract of purple Mok Wan Ju (Bauhinia purpurea), extract of Fuirisoshinka (Bauhinia variegata), and at least one selected from extracts of saffron Seo sinkers (Bauhinia blakeana) has excellent type I collagen production promotion It has been found to be effective as an anti-aging agent, having at least one of an action, a type IV collagen production promoting action, an elastase activity inhibiting action, and an estrogen-like action.
And it discovered that the skin external preparation containing at least any one of the said anti-inflammatory agent and the said anti-aging agent has the outstanding anti-inflammatory effect and anti-aging effect of skin.

The present invention is based on the above findings by the present inventors, and means for solving the above problems are as follows. That is,
<1> extract of purple Mok Wan Ju (Bauhinia purpurea), characterized in that it contains at least one member selected from extracts of Fuirisoshinka extract (Bauhinia variegata), and rosacea source sinkers (Bauhinia blakeana) It is an anti-inflammatory agent.
<2> The anti-inflammatory agent according to <1>, which has at least one of a cyclooxygenase-2 (COX-2) inhibitory action, a TNF-α production inhibitory action, and a cyclic AMP phosphodiesterase inhibitory action.
<3> extract of purple Mok Wan Ju (Bauhinia purpurea), characterized in that it contains at least one member selected from extracts of Fuirisoshinka extract (Bauhinia variegata), and rosacea source sinkers (Bauhinia blakeana) It is an anti-aging agent.
<4> The anti-aging agent according to <3>, wherein the anti-aging agent has at least one selected from a type I collagen production promoting action, a type IV collagen production promoting action, an elastase activity inhibiting action, and an estrogen-like action.
<5> The anti-inflammatory agent according to any one of <1> to <2>, and the anti-aging agent according to any one of <3> to <4>. It is a skin external preparation.

  ADVANTAGE OF THE INVENTION According to this invention, the conventional problems can be solved, and it has at least one of excellent cyclooxygenase-2 (COX-2) inhibitory action, TNF-α production inhibitory action, and cyclic AMP phosphodiesterase inhibitory action. Inflammatory agent, and excellent anti-aging agent having at least one of type I collagen production promoting action, type IV collagen production promoting action, elastase activity inhibiting action, and estrogen-like action, and the anti-inflammatory agent and the anti-aging agent An external preparation for skin containing at least one of them can be provided.

(Anti-inflammatory agent and anti-aging agent)
Anti-inflammatory agents and anti-aging agent of the present invention, at least one selected extracts of purple Mok Wan Ju (Bauhinia purpurea), extract of Fuirisoshinka (Bauhinia variegata), and from extracts of saffron Seo sinkers (Bauhinia blakeana) It contains seeds and further contains other components as required.
The anti-inflammatory agent has at least one of a cyclooxygenase-2 (COX-2) inhibitory action, a TNF-α production inhibitory action, and a cyclic AMP phosphodiesterase inhibitory action as an anti-inflammatory action.
The anti-aging agent has at least one selected from a type I collagen production promoting action, a type IV collagen production promoting action, an elastase activity inhibiting action, and an estrogen-like action as an anti-aging action.
The details of the substance having at least one of an anti-inflammatory action and an anti-aging action in the extract of Murasaki Mokuwanju, the extract of Phyrisosinka, and the extract of Akabanasoshinka are unknown, but the Murasaki Mokuwan To date, it has been completely unknown that the extract of Juju, the extract of Phyrrhiosinka, and the extract of Akabanassoshinka have these excellent effects and are useful as anti-inflammatory agents and anti-aging agents. However, these are new findings from the inventors' diligent research.

The blossom purple ( Bauhinia purpurea ) is an evergreen sub-tree that belongs to the leguminous family native to Southeast Asia, and is also known as the purple purple flower (Shikaika). In the tropics, it is cultivated as a flowering tree in gardens, parks, streets, etc. In India, the inflorescence is used for curry dishes or pickled. The young leaves cure coughs, and the bark is used as a cleaning agent for burns and pus.
The phyllisocinka ( Bauhinia variegata ) is a deciduous shrub of the leguminous family, and the leaves are approximately the same in length and width, and are attached to the central part. The flowers are plain and large and reddish purple. You can eat young leaves, persimmons, etc., and take gum, tannins, and dyes from trunks.
The above-mentioned Akabanassoshinka ( Bauhinia blackeana ) is a leguminous plant, has a height of about 3 m, has a leaf that is slightly thick and deeply split, and the tip of the fragment is round. Several flowers that grow laterally are five-petal flowers with a diameter of 7 to 8 cm and are deep purple-red, and the petals are conspicuous.

  The Murasaki Mikuwanju extract, the Phyrisosinka extract, and the Akabanasoshinka extract can be easily obtained by a method generally used for plant extraction. In addition, the extract of Murasaki Mokuwange, the extract of Phyrisosinka, and the extract of Akabanasoshinka include the extract of Murasaki Mikuwanju, Phyrisosinka, and Akabanasoshinka, and a diluted solution of the extract. A dry product obtained by drying, or a crude product or a purified product thereof is included.

  As an extraction raw material of the purple mulberry, the phyllisocinka, and the red crow shinka, for example, ground parts such as leaves, bark, and branches, root parts, flower parts, fruit parts, and the like can be used. Among these, the flower part is particularly preferable.

  The raw materials for extraction, Murasaki Mikuwanju, Phyrrisocinka, and Akabanazoshinka can be obtained by drying or pulverizing them using a crusher and subjecting them to solvent extraction. Drying may be performed in the sun or using a commonly used dryer. In addition, you may use the said Murasaki mokuwanju, the said phyllosocinka, and the said akabanazoshinka as an extraction raw material, after performing pretreatments, such as degreasing, with nonpolar solvents, such as hexane and benzene. In addition, the extraction process by a polar solvent can be performed efficiently by performing pretreatments, such as degreasing.

As the solvent used for the extraction, it is preferable to use water, a hydrophilic organic solvent, or a mixture thereof at room temperature or a temperature not higher than the boiling point of the solvent.
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, as well as water that has been subjected to various treatments. Examples of the treatment applied to water include purification, heating, sterilization, filtration, ion exchange, adjustment of osmotic pressure, 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 the hydrophilic organic solvent include lower 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 glycol, propylene glycol, Examples thereof include polyhydric alcohols having 2 to 5 carbon atoms such as glycerin, and a mixed solvent of these hydrophilic organic solvents and water can be used.
In addition, when using the mixed solvent of the said water and a hydrophilic organic solvent, 1 mass-90 mass parts with respect to 10 mass parts of water in the case of a lower alcohol, and 10 mass parts of water in the case of a lower aliphatic ketone. It is preferable to add 1 part by mass to 40 parts by mass relative to the mass. In the case of polyhydric alcohol, it is preferable to add 1 part by mass to 90 parts by mass with respect to 10 parts by mass of water.

In the present invention, it is not necessary to employ a special extraction method for extracting the anti-inflammatory substance or anti-aging substance from the extraction raw materials Murasaki Mikuwanju, Phyrrhosinka, and Akabanasoshinka. It can extract using the apparatus of.
Specifically, murasakimokuwanju, phyllisocinka, and akabanazoshinka as raw materials for extraction are placed in a treatment tank filled with the extraction solvent, and further allowed to stand for 30 minutes to 2 hours with occasional stirring as necessary. After eluting soluble components, the solid matter is removed by filtration, and the extract is obtained by evaporating the extraction solvent from the resulting extract and drying. The amount of the extraction solvent is usually 5 to 15 times (mass ratio) of the extraction raw material. The extraction conditions are usually about 1 to 4 hours at 50 to 95 ° C. when water is used as the extraction solvent. Moreover, when the mixed solvent of water and ethanol is used as an extraction solvent, it is about 30 minutes-4 hours at 40 to 80 degreeC normally. In addition, the extract obtained by extracting with a solvent can be used as an anti-inflammatory agent or an anti-aging agent of the present invention as long as the extraction solvent is highly safe. The dried product is easier to use.

The obtained extract of Murasaki Mokuwanju, the extract of Phyrrhiosinka, and the extract of Akabanasoshinka are diluted or concentrated solution of the extract, dried product of the extract, or a crudely purified product or purified product thereof. In order to obtain a product, it may be subjected to treatments such as dilution, concentration, drying and purification according to a conventional method.
The obtained Murasaki Mikuwanju extract, Phyrisosinka extract and Akabanasoshinka extract can be used as an anti-inflammatory agent or anti-aging agent as they are, but the concentrated solution or its dried product It is easier to use. In obtaining a dried extract, a carrier such as dextrin or cyclodextrin may be added to improve hygroscopicity. In addition, the purple mulberry, phyllisocinka, and akabanazoshinka have unique odors, and therefore it is possible to carry out purification for the purpose of decolorization, deodorization, etc. within a range that does not cause a decrease in their physiological activity. However, when it is added to a skin external preparation or the like, it is not used in a large amount, so there is no practical problem even if it is not purified. Specifically, purification can be performed by activated carbon treatment, adsorption resin treatment, ion exchange resin treatment, or the like.

  The anti-inflammatory agent and anti-aging agent of the present invention have extremely high anti-inflammatory and anti-aging effects, and in particular, cyclooxygenase-2 (COX-2) inhibitory action, TNF-α production inhibitory action, cyclic AMP It can effectively achieve at least one of phosphodiesterase inhibitory action, type I collagen production promotion action, type IV collagen production promotion action, elastase activity inhibition action, and estrogen-like action, and also has high safety. And it can use suitably for the following skin external preparations of this invention.

(Skin external preparation)
The external preparation for skin of the present invention contains at least one of the anti-inflammatory agent and anti-aging agent of the present invention, and further contains other components appropriately selected as necessary.

Here, the skin external preparation means various drugs applied to the skin, and includes, for example, cosmetics, quasi drugs, pharmaceuticals, and the like.
The use of the external preparation for skin is not particularly limited and can be appropriately selected from various uses. For example, ointment, cream, emulsion, lotion, pack, jelly, lip balm, lipstick, bath preparation, tonic, rinse, Examples include shampoo and astringent.

  The blending amount of the anti-inflammatory agent or anti-aging agent with respect to the entire external preparation for skin can be adjusted as appropriate depending on the type of external preparation for skin and the physiological activity of the extract, etc. It is preferably 0.001% by mass to 10% by mass in terms of an extract of phyllisocinka or an extract of the above-mentioned akabanassocinka.

  For the anti-inflammatory agent and the anti-aging agent, various main ingredients and auxiliaries usually used in the production of the external preparation for skin are used as necessary, as long as the effects of the present invention are not impaired. Can do.

-Other ingredients-
The other components are not particularly limited as long as they do not hinder the anti-inflammatory action or anti-aging action, and include ingredients appropriately selected according to the purpose. For example, whitening agents, astringents, bactericidal / antibacterial agents, Examples include ultraviolet absorbers, humectants, cell activators, antioxidant / active oxygen scavengers, fats and oils, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, perfumes, and the like. These components may act synergistically when used in combination with the above-mentioned Murasaki Mokuwanju, Phyrrhiosinka, and Akabanazoshinka extract, resulting in a superior use effect than normally expected.

  Examples of the whitening agent include ascorbic acid or a derivative thereof, sulfur, placental hydrolyzate, ellagic acid or a derivative thereof, kojic acid or a derivative thereof, glucosamine or a derivative thereof, arbutin or a derivative thereof, hydroxycinnamic acid or a derivative thereof, Glutathione, Arnica extract, Ogon extract, Sakuhakhi extract, Psycho extract, Bowfu extract, Mannencho mycelium culture or its extract, Linden extract, Peach leaf extract, Ages extract, Kujin extract, Jiyu extract, Toki extract, Yakuinin extract, Oyster leaf extract , Dianthus extract, Buttonpi extract, Camelis extract, Maronnier extract, Hypericum extract, Oil-soluble Licorice extract (Liquorice flavone, Grabrizine, Grabrene, Lycochalcone A), etc. The may be used alone or in combination of two or more thereof. Among these, from the viewpoint of improving the whitening effect, it is preferable to use at least one selected from ascorbic acid or a derivative thereof, placenta extract, chamomile extract, arbutin, ellagic acid, lucinol and kojic acid.

  Examples of the astringent include, for example, citric acid or salts thereof, tartaric acid or salts thereof, lactic acid or salts thereof, aluminum chloride, aluminum sulfate / potassium, allantoinchlorohydroxyaluminum, allantoindihydroxyaluminum, zinc paraphenolsulfonate, zinc sulfate, Gyuyu extract, Ages extract, Hamamelis extract, Geno pepper extract, Chacatechins, Odrianthus extract, Hypericum extract, Daio extract, Cornflower extract, Kizuta extract, Cucumber extract, Maronier extract, Salvia extract, Melissa extract, etc. You may use individually and may use 2 or more types together.

  Examples of the bactericidal / antibacterial agent include benzoic acid, sodium benzoate, paraoxybenzoic acid ester, distearylmethylammonium chloride, benzethonium chloride, chlorhexidine hydrochloride, photosensitizer 101, photosensitizer 201, salicylic acid, sodium salicylate, sorbine Acid, halocarban, resorcinol, parachlorophenol, phenoxyethanol, bisabolol, hinokitiol, menthol, chitosan, chitosan degradation product, diyu extract, cucumber extract, enamel extract, loquat extract, yucca extract, aloe extract, cinnamon extract, gadget extract, etc. These may be used alone or in combination of two or more.

  Examples of the ultraviolet absorber include β-isopropylfuranone derivatives, urocanic acid, ethyl urocanate, oxybenzone, oxybenzonesulfonic acid, tetrahydroxybenzophenone, dihydroxydimethoxybenzophenone, dihydroxybenzophenone, synoxate, methyl diisopropylcinnamate, octyl methoxycinnamate Glyceryl paraaminobenzoate, amyl paradimethylaminobenzoate, octyl paradimethylbenzoate, paraaminobenzoic acid, ethyl paraaminobenzoate, titanium oxide, β-carotene, γ-oryzanol, rice bran extract, aloe extract, birch extract, birch extract, Chamomile extract, henna extract, butterfly extract, ginkgo biloba extract, chamomile extract, hawthorn extract, Soluble licorice extract, and the like, which may be used alone or in combination of two or more thereof.

  Examples of the humectant include serine, glycine, threonine, alanine, collagen, hydrolyzed collagen, hydronectin, fibronectin, keratin, elastin, royal jelly, chondroitin sulfate heparin, glycerophospholipid, glyceroglycolipid, sphingophospholipid, sphingosaccharide Lipids, linoleic acid or esters thereof, eicosapentaenoic acid or esters thereof, pectin, bifidobacteria fermentation product, lactic acid fermentation product, yeast extract, litchi mycelium culture or extract thereof, wheat germ oil, avocado oil, rice Germ oil, jojoba oil, soybean phospholipid, γ-oryzanol, bellows oyster extract, yokuinin extract, sage extract, taisou extract, diatomaceous earth extract, kidachi aloe extract, burdock extract, mannen wax extract, arnica extract, small Bran, and the like, which may be used alone or in combination of two or more thereof.

  Examples of the cell activator include riboflavin or derivatives thereof, pyridoxine or derivatives thereof, nicotinic acid or derivatives thereof, pantothenic acid or derivatives thereof, α-tocopherol or derivatives thereof, arnica extract, carrot extract, rapeseed extract, loofah extract (Saponin), shikon extract, buckwheat extract, button pea extract, peony extract, mugwort extract, safflower extract, ashitaba extract, loquat leaf extract, shrimp extract, saxifrage extract, jaundice extract, salvia extract, garlic extract, mannen wax extract, etc. These may be used alone or in combination of two or more.

  Examples of the antioxidant / active oxygen scavenger include, for example, dibutylhydroxytoluene, butylhydroxyanisole, propyl gallate, baicalin, baicalein, superoxide dismutase, catalase, rosemary extract, melissa extract, orgon extract, age extract, Loquat leaf extract, hop extract, clam extract, peony extract, sage extract, kina extract, chamomile extract, eucalyptus extract, perilla extract, ginkgo biloba extract, thyme extract, cardamom extract, caraway extract, nutmeg extract, mace extract, laurel extract, clove extract , Turmeric extract, willow extract, and the like. These may be used individually by 1 type and may use 2 or more types together.

  Examples of the oils and fats include soybean oil, linseed oil, sesame oil, nutka oil, cottonseed oil, rapeseed oil, safflower oil, corn oil, olive oil, camellia oil, almond oil, castor oil, peanut oil, cacao oil, palm kernel Oil, beef tallow, mink oil, jojoba oil, evening primrose oil, horse oil, and the like. These may be used individually by 1 type and may use 2 or more types together.

  Examples of the waxes include carnauba wax, candelilla wax, beeswax, white beeswax, whale wax, cerax, lanolins, and the like. These may be used individually by 1 type and may use 2 or more types together.

  Examples of the hydrocarbons include liquid paraffin, petrolatum, microlistin wax, ceresin, squalane, polyethylene powder, and the like. These may be used individually by 1 type and may use 2 or more types together.

  Examples of the fatty acids include stearic acid, linoleic acid, lauric acid, myristic acid, palmitic acid, hebenic acid, lanolinic acid, oleic acid, undecylenic acid, and isostearic acid. These may be used individually by 1 type and may use 2 or more types together.

  Examples of the alcohols include lauryl alcohol, cetyl alcohol, stearyl alcohol, lanolin alcohol, hydrogenated lanolin alcohol, oleyl alcohol, hexadecyl alcohol, 2-octyldodecanol, glycerin, sorbitol, propylene glycol, and 1,3-butylene. Examples include glycol, ethylene glycol or a polymer thereof, glucose, sucrose, cholesterol, phytosterol, cetostearyl alcohol, and the like. These may be used individually by 1 type and may use 2 or more types together.

  Examples of the esters include decyl oleate, butyl stearate, myristyl myristate, hexyl laurate, isopropyl palmitate, isopropyl myristate, octyldodecyl myristate, hexyl decyl dimethyloctanoate, propylene glycol dioleate, phthalic acid Examples include diethyl, glyceryl monostearate, glyceryl trimyristate, and cetyl lactate. These may be used individually by 1 type and may use 2 or more types together.

  As the surfactant, for example, a nonionic surfactant, an anionic surfactant, a cationic surfactant, an amphoteric surfactant, and the like can be used. Alternatively, surfactants listed in minor cosmetic raw material standards are preferable, for example, soybean lecithin, egg yolk lecithin, saponin, oligoglycoside, phospholipid biosurfactant, acyl peptide biosurfactant, polyoxyethylene polyoxypropylene glycol , Polyoxyethylene polyoxypropylene cetyl ether, polyoxyethylene polyoxypropylene butyl ether, polyoxyethylene coconut oil fatty acid monoethanolamide, polyoxyethylene lauryl ether, polyoxyethylene lauryl ether sulfate triethanol Amine, sodium polyoxyethylene lauryl ether sulfate, polyoxyethylene lauryl ether phosphate, polyoxyethylene lauryl ether sodium phosphate, polyoxyethylene lanolin, polyoxyethylene lanolin alcohol, polyoxypropylene butyl ether, polyvinyl alcohol, polyvinyl pyrrolidone, polyphosphorus Acid sodium, sorbitan monooleate, polyethylene glycol monooleate, polyoxyethylene sorbitan monooleate, ethylene glycol monostearate, sorbitan monostearate, propylene glycol monostearate, polyethylene glycol monostearate, polyoxystearate Ethylene glycerol, polyoxyethylene sorbitan monostearate, Sorbitan palmitate, monopalmitate polyoxyethylene sorbitan, sorbitan monolaurate, polyethylene glycol monolaurate, polyoxyethylene sorbitan monolaurate, polyoxyethylene monolaurate sorbitol, coconut oil fatty acid diethanol amide, a surfactant such as. These may be used individually by 1 type and may use 2 or more types together.

  Examples of the perfume include menthol, carvone, eugenol, anethole, mint oil, spearmint oil, peppermint oil, eucalyptus oil, anise oil, and the like. These may be used individually by 1 type and may use 2 or more types together.

  The external preparation for skin of the present invention has high safety when used on the skin, has extremely high anti-inflammatory action and anti-aging action, in particular, cyclooxygenase-2 (COX-2) inhibitory action, TNF It is possible to effectively achieve at least one of α-inhibition action, cyclic AMP phosphodiesterase inhibition action, type I collagen production promotion action, type IV collagen production promotion action, elastase activity inhibition action, and estrogen-like action. it can.

  The anti-inflammatory agent, anti-aging agent, and external preparation for skin of the present invention are preferably applied to humans, but are not particularly limited as long as their respective effects are exhibited. It can also be applied to animals.

  Examples of the present invention will be described below, but the present invention is not limited to these examples.

(Production Example 1)
-Production of water extract of each plant-
To the pulverized product of each plant shown in Table 1 below, 10 times the amount of water was added by mass ratio, heated at 80 ° C. for 2 hours with a reflux extractor, and filtered while hot. The same amount of water was added to the residue, heated at 80 ° C. for 2 hours, and filtered. The obtained filtrates were combined, concentrated, and lyophilized to obtain an aqueous extract of each plant.
The “extraction rate” of the water extract of each plant obtained is shown in Table 1.

(Production Example 2)
-Production of 50 mass% ethanol extract of each plant-
To the pulverized product of each plant shown in Table 2 below, a 10-fold amount of 50% by mass ethanol was added, heated at 80 ° C. for 2 hours, and filtered. The same amount of 50% by mass ethanol was added to the residue, heated at 80 ° C. for 2 hours, and filtered. The obtained filtrates were combined, concentrated, and lyophilized to obtain a 50% by mass ethanol extract of each plant.
Table 2 shows the “extraction rate” of the 50% by mass ethanol extract of each plant obtained.

(Production Example 3)
-Production of ethanol extract of each plant-
To the pulverized product of each plant shown in Table 3 below, 10 times the amount of ethanol was added by mass ratio, heated at 80 ° C. for 2 hours, and filtered. The same amount of 80% by mass ethanol was added to the residue, heated at 80 ° C. for 2 hours, and filtered. The obtained filtrates were combined, concentrated, and lyophilized to obtain an ethanol extract of each plant.
The “extraction rate” of the ethanol extract of each plant obtained is shown in Table 3.

Example 1
<Inhibition of PGE ₂ production via cyclooxygenase (COX-2)>
Hwang, B.H. -Y. The method (Planta Medica 67 (2001) 406-410) was modified with some modifications. That is, after pre-culturing mouse-derived macrophage-like cells (RAW264.7), the cells were collected, adjusted to 1 × 10 ⁵ cells / mL, seeded in 100 μL each in a 96-well plate, at 37 ° C. and 5% CO ₂ . Cultured for 18 hours. After culturing, in order to acetylate and inactivate COX-1 already present and COX-2 expressed in a small amount, the medium was replaced with a 500 μmol / L aspirin-containing medium and cultured for 4 hours. The cells were washed 3 times with PBS (−) and lysed in a medium containing 1 μg / mL LPS. 200 μL of each of the extract solutions 1 to 9 was added and cultured for 18 hours. After culturing, PGE ₂ in the supernatant was quantified using PGE ₂ EIA Kit (Cayman, Chemical, Ann Arbor, MI, USA). The inhibition rate of PGE ₂ production was calculated with the value when each of the extracts 1 to 9 was not added as 100%.
Next, no. The concentration of each of the extract solutions 1 to 9 was gradually reduced to measure the inhibition rate of PGE ₂ production via COX-2, and the concentration IC _{50 at} which the inhibition rate was 50% was determined by interpolation. (The smaller this IC ₅₀ value is, the stronger the action of inhibiting PGE ₂ production via COX-2). The results are shown in Table 4.

表４の結果から、Ｎｏ．１〜９の各抽出物がＣＯＸ−２を介したＰＧＥ_２産生抑制作用を有することが確認された。

From the results in Table 4, No. It was confirmed that each of the extracts 1 to 9 has a PGE ₂ production inhibitory action via COX-2.

(Example 2)
<TNF-α production inhibitory action test>
No. About each extract of 1-9, the TNF- (alpha) production inhibitory effect was tested with the following test method.
Mouse macrophage cells (RAW264.7 cells, manufactured by Dainippon Pharmaceutical Co., Ltd.) were pre-cultured in a 10% FBS-containing Dulbecco MEM (Nissui Pharmaceutical Co., Ltd.) medium, and the cells were collected from a cell scraper. Cells were seeded in a 96-well microplate at a density of × 10 ⁵ / cells / 100 μL, and pre-cultured at 37 ° C. under 5% CO ₂ for 4 hours. Next, the medium in the 96-well plate was discarded and No. 1 previously dissolved in a culture solution containing 1% DMSO. After adding 100 μL of each of the extracts 1 to 9, 100 μL of lipopolysaccharide (LPS, final concentration 1 μg / mL, E. coli 0111; B4, manufactured by DIFCO Laboratories) was added to stimulate the cells. Thereafter, the amount of TNF-α produced by culturing for 24 hours under conditions of 37 ° C. and 5% CO ₂ was measured using the following sandwich ELISA method.
Rat anti-mouse TNF-α monoclonal antibody (manufactured by Endogen Inc.), which is the primary antibody, was dissolved in 50 mM sodium carbonate buffer (pH 9.6) to 2.5 μg / mL, and 100 μL of the solution was dissolved in a 96-well microplate. And coated overnight at 4 ° C. Next, each well was washed with a washing solution (phosphate buffer containing 0.05% Tween 20) and then blocked with a phosphate buffer containing 1% BSA.
After washing each well with a washing solution, the culture supernatant was diluted with a test medium, and 100 μL thereof was added to each well and incubated at 37 ° C. for 120 minutes. After washing each well, 100 μL of a rabbit anti-mouse TNF-α polyclonal antibody (Endogen Inc.) dissolved in a phosphate buffer containing 0.3% BSA at a concentration of 2.5 μg / mL as a secondary antibody. Was added, incubated at 37 ° C. for 60 minutes, and then washed.
Next, 100 μL of 1000-fold diluted alkaline phosphatase-labeled anti-rabbit IgG antibody (manufactured by CHEMICON Inc.) was added and incubated at 37 ° C. for 60 minutes. After washing each well, 150 μL of a substrate solution prepared by dissolving 50 mg of p-nitrophenyl phosphate in 100 mL of a color-development buffer (20 mM magnesium sulfate-containing Tris-HCl buffer, pH 8.0) was added to the well, and the mixture was incubated at 37 ° C. The color was developed by performing an enzyme reaction for 20 to 30 minutes, and the absorbance at 405 nm was measured. From a standard curve prepared from a standard solution of recombinant mouse TNF-α (manufactured by Endogen Inc.), TNF-α in the culture supernatant was used. The amount (pg / mL) was determined. The TNF-α production inhibition rate of the test sample was calculated based on the following formula.
TNF-α production inhibition rate (%) = {(B−A) / B} × 100
In the above formula, “A” represents “a TNF-α amount when a sample is added”, and “B” represents a “a TNF-α amount when a sample is not added”.
The TNF-α production inhibition rate is a value calculated when a sample concentration of 12.5 μg / mL is added. The results are shown in Table 5.

表５の結果から、Ｎｏ．１〜９の各抽出物には、優れたＴＮＦ−α産生抑制作用が認められた。

From the results of Table 5, In each of the extracts 1 to 9, excellent TNF-α production inhibitory action was observed.

(Example 3)
<Cyclic AMP phosphodiesterase inhibitory action test>
No. Each extract of 1 to 9 was tested for cyclic AMP phosphodiesterase inhibitory action as follows.
0.1 mL of a 2.5 mg / mL bovine serum albumin solution, 0.1 mg / mL cyclic AMP phosphodiesterase solution in 0.2 mL of 50 mM Tris-HCl buffer (pH 7.5) containing 5 mM magnesium chloride No. 1 dissolved in 1 mL and 50% DMSO. 0.05 mL of each extract of 1 to 9 was added and incubated 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 incubated at 37 ° C. for 60 minutes. The reaction was stopped by boiling on a boiling water bath for 3 minutes, this was centrifuged (2260 × g, 10 minutes, 4 ° C.), and cyclic AMP, which is a reaction substrate in the supernatant, was subjected to a high-speed liquid under the following conditions. Analyzed using chromatography. 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 (manufactured by Wako Pure Chemical Industries)
Column diameter: 4.6 mm
-Column length: 250 mm
・ 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
Next, the peak area (A) of the cyclic AMP standard product, the peak area (B1) of the supernatant of the reaction solution of the cyclic AMP standard product and cyclic AMP phosphodiesterase when no sample is added, and the cyclic when the sample is added The peak area (B2) of the supernatant of the reaction solution of AMP standard product and cyclic AMP phosphodiesterase was determined. From the obtained results, the decomposition rate (C) of the cyclic AMP standard product when no sample was added and the decomposition rate (D) of the cyclic AMP standard product when the sample was added were calculated according to the following equations.
Standard product decomposition rate when no sample is added (C,%) = (1−B1 / A) × 100
Decomposition rate of standard product at the time of sample addition (D,%) = (1−B2 / A) × 100
Thereafter, the cyclic AMP phosphodiesterase inhibition rate (%) was calculated by the following formula based on the respective degradation rates (C, D) calculated by the above formula.
Cyclic AMP phosphodiesterase inhibition rate (%) = (1-D / C) × 100
The cyclic AMP phosphodiesterase inhibition rate was calculated by gradually reducing the concentration of the sample solution, and the sample concentration IC ₅₀ (μg / mL) at which the cyclic AMP phosphodiesterase inhibition rate was 50% was determined by interpolation. . The results are shown in Table 6.

表６の結果から、Ｎｏ．１〜９の各抽出物が、サイクリックＡＭＰホスホジエステラーゼ活性阻害作用を有することが確認された。

From the results of Table 6, It was confirmed that each extract of 1 to 9 has a cyclic AMP phosphodiesterase activity inhibitory action.

Example 4
<Type I collagen production promoting action test>
No. About each extract of 1-9, the type I collagen production promotion effect was tested by the following method.
Human normal fibroblasts (NB1RGB) were cultured using Dulbecco's MEM (Nissui Pharmaceutical Co., Ltd.) medium containing 10% FBS, and then cells were collected by trypsin treatment. The collected cells were diluted with the above medium to a concentration of 1.6 × 10 ⁵ cells / mL, then seeded at 100 μL per well in a 96-well microplate, and cultured overnight. After completion of the culture, the medium was removed and No. 2 dissolved in Dulbecco's MEM medium containing 0.25% FBS. After adding 200 μL of each extract of 1 to 9 to each well (sample concentration: 100 μg / mL) for 3 days, 90 μL of the supernatant was transferred to an ELISA plate and adsorbed on the plate at 4 ° C. overnight. Thereafter, the solution was discarded and washed with a phosphate physiological buffer solution (PBS-T) containing 0.05% Tween-20. Thereafter, a blocking operation was performed with a phosphate physiological buffer containing 1% bovine serum albumin. The solution was discarded, washed with a phosphate physiological buffer solution (PBS-T) containing 0.05% Tween-20, and reacted with an anti-human collagen type I antibody (rabbit IgG; manufactured by Chemicon). Discard the solution, wash with phosphate physiological buffer solution (PBS-T) containing 0.05% Tween-20, react with HRP-labeled anti-rabbit IgG antibody, and then perform the same washing procedure to develop color. Reaction was performed.
The rate of type I collagen production promotion was calculated by performing the above ELISA using a standard product, creating a calibration curve, and setting the amount of type I collagen production when no sample was added as 100%. Table 7 shows the type I collagen production promotion rate (%) of each sample.
The type I collagen production promotion rate was calculated with the amount of type I collagen production when no sample was added as 100%. The calculation method of the type I collagen production promotion rate is as follows.
Type I collagen production promotion rate (%) = A / B × 100
However, A represents the amount of type I collagen when the test sample is added, and B represents the amount of type I collagen when no test sample is added.

表７の結果から、Ｎｏ．１〜９の各抽出物が、ヒトの線維芽細胞のＩ型コラーゲン産生促進作用を有することが確認できた。

From the results in Table 7, no. It was confirmed that each of the extracts 1 to 9 has an action to promote type I collagen production of human fibroblasts.

(Example 5)
<Type IV collagen production promotion test>
No. About each extract of 1-9, the type IV collagen production promotion effect was tested by the following method.
Human fibroblasts were seeded in a 96-well plate and subjected to No. 5 under conditions of 37 ° C. and 5% CO ₂ -95% air. After culturing for 72 hours in a medium supplemented with each extract of 1 to 9 (sample concentration: 25 μg / mL), 100 μL of the supernatant was transferred to an ELISA plate and adsorbed on the plate overnight at 4 ° C., then the solution was discarded. Washing was performed with a phosphate physiological buffer solution (PBS-T) containing 0.05% Tween-20. Thereafter, a blocking operation was performed with a phosphate physiological buffer containing 1% bovine serum albumin. The solution was discarded, washed with a phosphate physiological buffer solution (PBS-T) containing 0.05% Tween-20, and reacted with an anti-human collagen type IV antibody (rabbit IgG, manufactured by Novotech). Discard the solution, wash with phosphate physiological buffer (PBS-T) containing 0.05% Tween-20, and react with HRP-labeled anti-rabbit IgG antibody. Reaction was performed.
The type IV collagen production promotion rate (%) was calculated by conducting the above ELISA using a standard product, creating a calibration curve, and assuming that the amount of type IV collagen produced when no sample was added was 100%. Table 8 shows the type IV collagen production promotion rate (%) of each sample.

表８の結果から、Ｎｏ．１〜９の各抽出物が、ヒトの線維芽細胞のＩＶ型コラーゲン産生促進作用を有することが確認できた。

From the results in Table 8, No. It was confirmed that each of the extracts 1 to 9 has an action of promoting type IV collagen production in human fibroblasts.

(Example 6)
<Elastase activity inhibition test>
No. About each extract of 1-9, the elastase activity inhibitory effect was tested by the following method.
In a 96-well plate, No. 2 prepared with 0.2 mol / L Tris-HCl buffer (pH 8.0) was prepared. 50 μL of each of the extracts 1 to 9 (sample concentration 400 μg / mL) was mixed with 50 μL of elastase type III solution. Thereafter, 100 μL of 4.514 mg / mL N-succinyl-Ala-Ala-Ala-p-nitroanilide prepared in the above buffer 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 activity inhibition rate (%) was calculated based on the following formula. The results are shown in Table 9.
Elastase activity inhibition rate (%) = {1− (C−D) / (A−B)} × 100
In the above formula, A represents “absorbance at a wavelength of 415 nm when no sample is added / enzyme added”, B represents “absorbance at a wavelength of 415 nm when no sample is added / enzyme is added”, and C is “sample added” -Represents "absorbance at a wavelength of 415 nm when an enzyme is added", and D represents "absorbance at a wavelength of 415 nm when a sample is added and no enzyme is added".

表９の結果から、Ｎｏ．１〜９の各抽出物が、エラスターゼ活性阻害作用を有することが確認された。

From the results in Table 9, No. It was confirmed that each of the extracts 1 to 9 has an elastase activity inhibitory action.

(Example 7)
<Estrogen-like action test>
No. Each extract of 1 to 9 was tested for estrogenic action by the following method.
First, a test was conducted according to the method of Thomas et al. (In Vitro Cell. Dev. Biol. 28A, 595-602, 1992) for examining the influence on the proliferation of estrogen-dependent cells.
MCF-7 cells derived from human breast cancer are cultured in a 75 cm ² flask until confluent, and the MCF-7 cells are collected by trypsin treatment. 10% FBS (activated carbon), 1% NEAA and 1 mM sodium pyruvate Was prepared to 3.3 × 10 ⁴ cells / mL using a MEM medium containing no phenol red (hereinafter sometimes referred to as “MEM medium”).
The prepared MCF-7 cells were seeded at a rate of 0.45 mL in a 48-well plate, and cultured at 37 ° C. under 5% CO ₂ -95% air to establish this. After 6 hours (Day 0), No. 2 prepared to 50 μg / mL with MEM medium. 50 μL of each of the extract solutions 1 to 9 was added to the plate, and the culture was continued.
On the sixth day from the start of the culture, the medium was replaced with a MEM medium containing 0.97 mmol / L of MTT, and after culturing for 2 hours, the medium was replaced with isopropanol, and blue formazan produced in the cells was extracted. For the isopropanol containing the eluted blue formazan, the absorbance at 570 nm where the absorption maximum of blue formazan is present was measured.
In order to correct the influence of adherent cells, the absorbance at 650 nm was also measured at the same time, and the difference between the two absorbances was taken as a value proportional to the amount of blue formazan produced (the absorbance in Equation 1 below is this corrected absorbance). As a positive control, 10 ⁻⁹ M β-estradiol was used. The strength of the estrogen-like action (estrogen-dependent proliferation action) was calculated by the following formula 1 with the absorbance when no sample was added as 100%. The results are shown in Table 10.
<Formula 1>
Estrogen-like action rate (%) = (A / B) × 100
However, in the said Numerical formula 1, A represents the light absorbency in the case of sample addition. B represents the absorbance when no sample is added.

表１０の結果から、Ｎｏ．１〜９の各抽出物が、エストロゲン様作用を有することが確認された。

From the results in Table 10, No. It was confirmed that each of the extracts 1 to 9 has an estrogenic effect.

(Formulation Example 1) -Emulsion-
An emulsion having the following composition was produced by a conventional method.
・ No. Water extract of 1 Murasaki Mokuwanju ... 0.01g
-Jojoba oil: 4.0 g
・ Placenta 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
・ Stearyl glycyrrhetinate ... 0.1g
・ 1,3-Butylene glycol ・ ・ ・ 3.0g
・ Hinokitiol 0.15g
・ Fragrance ... 0.05g
・ Purified water: remainder (the total amount is 100 g)

(Formulation Example 2) -Cream-
A cream having the following composition was produced by a conventional method.
・ No. 50% ethanol extract of 5 phyllisocinka ... 0.05g
・ Aloe extract ... 0.1g
-Liquid paraffin: 5.0 g
・ Salax beeswax ... 4.0g
・ Squalane ... 10.0g
・ Cetanol ... 3.0g
・ Lanoline ... 2.0g
・ Stearic acid: 1.0 g
・ Oleic acid polyoxyethylene sorbitan (20E.O) ... 1.5g
・ Glyceryl monostearate ... 3.0 g
・ Oil-soluble licorice extract ... 0.1g
・ 1,3-Butylene glycol ・ ・ ・ 6.0g
・ Methyl paraoxybenzoate 1.5g
・ Fragrance ... 0.1g
・ Purified water: remainder (the total amount is 100 g)

(Formulation Example 3) -Cosmetic liquid-
A serum having the following composition was produced by a conventional method.
・ No. 3 water extract of Akabanassoshinka ... 0.01g
-Chamomile extract ... 0.1g
・ Xanthan gum ・ ・ ・ 0.3g
・ Hydroxyethylcellulose ・ ・ ・ 0.1g
・ Carboxyvinyl polymer ... 0.1g
・ 1,3-Butylene glycol ・ ・ ・ 4.0g
・ Dipotassium glycyrrhizinate ... 0.1g
・ Glycerin ... 2.0g
・ Potassium hydroxide ... 0.25g
・ Perfume 0.01g
・ Preservative (methyl paraoxybenzoate) ... 0.15g
・ Ethanol ... 2.0g
・ Purified water: remainder (the total amount is 100 g)

(Formulation Example 4) -Pack-
A pack having the following composition was produced by a conventional method.
・ No. Eight Phyrisosinka ethanol extract ... 0.05g
・ Yokuinin extract ... 0.1g
・ Polyvinyl alcohol ... 15g
・ Polyethylene glycol 3g
・ Propylene glycol ・ ・ ・ 7g
・ Ethanol ... 10g
・ Methyl paraoxybenzoate 0.05g
・ Dipotassium glycyrrhizinate ... 0.1g
・ Fragrance ... 0.05g
・ Purified water: remainder (the total amount is 100 g)

(Formulation Example 5)-Lotion-
A lotion having the following composition was produced by a conventional method.
・ No. 6% 50% ethanol extract of Akabanassoshinka 0.05g
・ Lavender extract ... 0.1g
・ 1,3-Butylene glycol ・ ・ ・ 4.0g
・ Glycerin: 4.0g
・ Dipropylene glycol ... 2.0g
・ Polyoxyethylene polyoxypropylene decyl tetradecyl ether ・ ・ ・ 0.7g
・ Ethanol ... 3.0g
・ Dipotassium glycyrrhizinate ... 0.1g
・ Perfume 0.001g
・ Preservative (methyl paraoxybenzoate) ... 0.15g
・ Purified water: remainder (the total amount is 100 g)

  The anti-inflammatory agent and anti-aging agent of the present invention have excellent cyclooxygenase-2 (COX-2) inhibitory action, TNF-α production inhibitory action, cyclic AMP phosphodiesterase inhibitory action, type I collagen production promoting action, type IV collagen production Since it has at least one of promoting action, elastase activity inhibiting action, and estrogen-like action, for example, ointment, cream, emulsion, lotion, pack, jelly, lip balm, lipstick, bath preparation, tonic, rinse, shampoo It is preferably used as a skin external preparation such as astringent.

Claims (7)

Water extract of flowers of Bauhinia purpurea , hydrophilic organic solvent extract or mixed solvent extract of water and hydrophilic organic solvent , water extract of flowers of Bauhinia variegata , hydrophilic organic Solvent extract or mixed solvent extract of water and hydrophilic organic solvent , and water extract of flower of Bauhinia blackeana , hydrophilic organic solvent extract or mixed solvent extraction of water and hydrophilic organic solvent TNF-alpha production inhibitor characterized by containing at least one selected from the object. Water extract of flowers of Bauhinia purpurea , hydrophilic organic solvent extract or mixed solvent extract of water and hydrophilic organic solvent , water extract of flowers of Bauhinia variegata , hydrophilic organic Solvent extract or mixed solvent extract of water and hydrophilic organic solvent , and water extract of flower of Bauhinia blackeana , hydrophilic organic solvent extract or mixed solvent extraction of water and hydrophilic organic solvent cyclic AMP phosphodiesterase inhibitor characterized by containing at least one selected from the object. Bauhinia variega flower water extract, hydrophilic organic solvent extract or mixed solvent extract of water and hydrophilic organic solvent, and water extract of Bauhinia varkeana flower , hydrophilic organic A cyclooxygenase-2 (COX-2) inhibitor comprising at least one selected from a solvent extract or a mixed solvent extract of water and a hydrophilic organic solvent . Water extract of flowers of Bauhinia purpurea , hydrophilic organic solvent extract or mixed solvent extract of water and hydrophilic organic solvent , water extract of flowers of Bauhinia variegata , hydrophilic organic Solvent extract or mixed solvent extract of water and hydrophilic organic solvent , and water extract of flower of Bauhinia blackeana , hydrophilic organic solvent extract or mixed solvent extraction of water and hydrophilic organic solvent Elastase activity inhibitor characterized by containing at least 1 sort (s) selected from a thing . Bauhinia variega flower water extract, hydrophilic organic solvent extract or mixed solvent extract of water and hydrophilic organic solvent , and water extract of Bauhinia varkeana flower , hydrophilic organic An estrogenic agent comprising at least one selected from a solvent extract or a mixed solvent extract of water and a hydrophilic organic solvent . Bauhinia variega flower water extract, hydrophilic organic solvent extract or mixed solvent extract of water and hydrophilic organic solvent , and water extract of Bauhinia varkeana flower , hydrophilic organic A type I collagen production promoter comprising at least one selected from a solvent extract or a mixed solvent extract of water and a hydrophilic organic solvent . Bauhinia variega flower water extract, hydrophilic organic solvent extract or mixed solvent extract of water and hydrophilic organic solvent , and water extract of Bauhinia varkeana flower , hydrophilic organic A type IV collagen production promoter comprising at least one selected from a solvent extract or a mixed solvent extract of water and a hydrophilic organic solvent .