JP2006143676A - Degranuration inhibitor and skin preparation for external use containing the degranuration inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a degranulation inhibitor expressing continuous protection effect of skin and hair from inflammation damages caused by stimulants in the environment such as UV rays, house dusts and the like owing to having action suppressing release of chemical mediators from basophilic leukocytes and mast cells and inhibition action for generating inflammation-associated prostagrandin E2, while having little stimulation to the skin, excellent in living body stability and useful as an additional raw material for the skin preparation for external use, and provide a skin preparation for external use containing the degranulation inhibitor and protecting the skin from damages caused by oxidation reactions and maintaining or improving the skin in healthy and youthful conditions. <P>SOLUTION: The degranuration inhibitor contains an extract of a plant belonging to the genus Tabebuia, Bignoniaceae as an effective ingredient. The skin preparation for external use contains the degranuration inhibitor containing the extract of the plant belonging to the genus Tabebuia, Bignoniaceae as an effective ingredient. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a degranulation inhibitor comprising a plant extract as an active ingredient and a skin external preparation containing the same, and more particularly, whitening or anti-inflammatory / antiallergic activity through suppression of degranulation of basophils and mast cells. It functions as an ingredient and suppresses or improves skin pigmentation, rough skin, itching and pain caused by chemical mediators, keeps and improves skin and hair in a healthy and youthful state, and is derived from natural products Therefore, a novel degranulation inhibitor excellent in biological safety, and a skin external preparation containing the degranulation inhibitor and having excellent whitening / skinning, anti-inflammatory / antiallergic effects and high biological safety About.

The environment that surrounds us is surrounded by substances that can cause inflammation and allergies, such as house dust, exhaust gas, and mites. For the onset of inflammation and allergies caused by these antigens, antigens are stimulated by cross-linking the Fab chain of IgE antibody of basophils and mast cells, and histamine, serotonin, eosinophil migration factor, etc. It is known that the degranulation that is released is involved. Furthermore, when basophils and mast cells are stimulated by an antigen, the calcium channel of the cell membrane opens and calcium ions flow into the cell. As a result, phospholipase A2 is activated and an arachidonic acid cascade is formed, causing an inflammatory chemical. It is known that prostaglandins, which are mediators, are secreted and cause inflammation.
In addition, histamine, which is one of chemical mediators released by degranulation, is known to stimulate melanocytes and cause pigmentation through H2 receptors present in epidermal melanocytes in the skin ( Fragrance Journal Extra Number No. 18, pp. 22-29).

In addition to the above-mentioned antigens, UV exposure is particularly important in the development of pigmentation and inflammation in the skin. However, pigmentation and inflammation such as spots and freckles caused by UV exposure, and inflammation For the purpose of preventing pigmentation and improving symptoms based on the above, melanin production inhibitors such as ascorbic acid derivatives and hydroquinone derivatives and anti-inflammatory agents such as glycyrrhizic acid have been proposed, and skin external preparations containing these have been marketed. Yes.
However, in order to obtain a sufficient effect, the above melanin production inhibitor and anti-inflammatory agent must be mixed in a considerably high concentration. For this reason, there are problems in terms of safety and formulation stability, and there are currently no satisfactory ones in all aspects of safety, formulation stability and action effects.

Fragrance Journal Special Issue No. 18, pages 22-29

  As is clear from the above, external stimulating factors surrounding the environment invade the skin and become antigens to induce degranulation, or inflammation, itching, pigments caused by exposure of the skin to ultraviolet rays There is a need for an active ingredient that exhibits prevention or symptom improvement effects against deposition. For this reason, various investigations have been made for components for external preparation of skin having anti-inflammatory action, anti-allergic action, and even whitening action, but no satisfactory one has been obtained in terms of effectiveness and skin safety. However, the provision of such materials and raw materials remains a problem.

As a result of extensive studies to solve the above problems, the present inventors have found that the extract of the genus Tabebuia sp. Has a strong degranulation-inhibiting action and is derived from natural products. The present invention has been completed by finding that it is excellent in biological safety and useful as a degranulation inhibitor.
That is, the present invention first provides a degranulation inhibitor comprising, as an active ingredient, an extract of a plant of the genus Tabebuia.
Secondly, the present invention provides an external preparation for skin containing a degranulation inhibitor comprising, as an active ingredient, an extract of a plant of the genus Tabebuia.

For use as a skin external preparation compounding component of the plant of the genus Tabenia (hereinafter referred to as Tabbeia genus plant), a bath composition containing an extract of the bark of the plant in JP-A-5-17340, JP-A-11-180819 and JP-A-2001-55318 disclose an anti-androgen agent comprising a tabebuia plant extract as an active ingredient and a tooth having a heat-retaining effect, a cosmetic effect, and a deodorant effect. Although inventions of oral compositions for the prevention and treatment of peripheral diseases have been disclosed, respectively, the use of the tabebuia genus plant extract disclosed in JP-A-2001-55318 as an oral composition However, there is no disclosure of detailed data on anti-inflammation, but the mechanism of action is completely unknown. In the state.
Therefore, Tabebuia plant extracts inhibit the degranulation of basophils and mast cells caused by environmental stimulating factors, and also inhibit the activity of cyclooxynase in cells when exposed to ultraviolet light. This makes it possible to prevent and improve symptoms of skin inflammation, allergy and pigmentation caused by various stimulating factors. From the viewpoint of providing a whitening / skin-beautifying agent or anti-inflammatory / anti-allergic agent that is highly effective and safe, it is completely difficult to predict from these known facts, and is apparent only by the present invention. It is just now.

The degranulation inhibitor of the present invention comprising, as an active ingredient, an extract of a genus Tabbya is a basophil or mast cell produced by a substance that causes inflammation and allergies such as house dust, exhaust gas, and mites surrounding the environment. Inhibits the release of chemical mediators such as histamine, serotonin, and eosinophil migration factor, and further suppresses the activity of cyclooxygenase, thereby inhibiting the cyclic pathway of the arachidonic acid cascade and prosta, an inflammatory chemical mediator. By suppressing the production of glandin E2, it has the effect of suppressing inflammation, itching, and further pigmentation caused by inflammation occurring in the skin. Therefore, when this is used to protect against skin inflammatory damage caused by ultraviolet rays or the like, unlike conventional methods using anti-inflammatory agents, it suppresses the release of chemical mediators that cause inflammation, and further prevents the use of inflammatory chemical mediators. It also suppresses production itself, prevents skin roughness and gloss caused by inflammation, and prevents wrinkles, thereby preventing pigmentation. In addition, since the degranulation inhibitor of the present invention is composed of plant-derived components, it has little skin irritation and the like, and is extremely excellent in biological safety.
The topical skin preparation of the present invention comprising such a degranulation inhibitor can protect the skin from damage caused by an inflammatory reaction when applied to the skin, and the skin becomes healthy and youthful. It has the effect of maintaining or improving. In addition, the external preparation for skin of the present invention is highly safe, and there is no possibility of adversely affecting the skin even when used for a long time.

Hereinafter, the present invention will be described in detail.
Examples of the plant belonging to the genus Tabebuia used for the preparation of the degranulation inhibitor of the present invention include, for example, Tabebuia impetiginosa, Tabebuia rosea, Tabebuia carabia, Tabebaiabiae chrysantha], Tabebuia chrysotricha, and the like. In the present invention, the whole plant or bark (inner bark) of these genus Tabebuia is preferably used as a raw material for extraction.
Of these plants belonging to the genus Tabebuia, the use of tabebuia impetigenosa, particularly the use of internal bark, is most preferable from the viewpoint of the degranulation inhibitory action of the extract.
Tabebuia Impetiginosa is called Paudarco, Ipe, Iperoscio, Rapacho, Tahibo, etc. in Brazil, and synonyms include Tabebuia Avellaneda [T. Avellanedae], Tabebuaipe [T. ipe].

  Preparation of the extract of the plant of the genus Tabebuai is a suitable means such as a dipping method, a countercurrent extraction method, etc., after pre-washing the part to be extracted, for example, the inner bark, if necessary, preliminarily washed, dried, preferably further shredded or ground. By contacting with an extraction solvent.

  Extraction solvents include water; lower alcohols such as methanol, ethanol and propanol; higher alcohols such as oleyl alcohol, stearyl alcohol and octyldodecanol; and many other solvents such as ethylene glycol, propylene glycol, 1,3-butylene glycol and glycerin. Monohydric alcohols; esters such as ethyl acetate, butyl acetate, methyl propionate and glyceryl trioctanoate; ketones such as acetone and methyl ethyl ketone; ethers such as ethyl ether and isopropyl ether; carbonization such as n-hexane, toluene and chloroform Examples thereof include hydrogen-based solvents, which are used alone or in combination of two or more. Furthermore, it is preferable to use one kind of single solvent or two or more kinds of mixed solvents selected from water, lower alcohols and polyhydric alcohols from the viewpoint that they can be widely applied to cosmetics. Single use is most preferred.

  The mixing ratio in the case of using a mixed solvent is, for example, 1: 1 to 25: 1 by volume ratio (hereinafter the same) if the mixed solvent is water and ethyl alcohol, and 1: if the mixed solvent is water and glycerin. In the case of a mixed solvent of 1 to 20: 1, or water and 1,3-butylene glycol, it is preferably in the range of 1: 1 to 20: 1.

  In the preparation of the extract of the present invention, the pH of the extract is preferably maintained in the range of 4 to 8. In this sense, if necessary, the extraction solvent may be sodium hydroxide, sodium carbonate, potassium hydroxide. Alternatively, an alkaline adjusting agent such as arginine, an acidic adjusting agent such as citric acid, hydrochloric acid, phosphoric acid, sulfuric acid, or the like may be blended to adjust to a desired pH.

  In the case of the dipping method, the amount ratio of the extraction solvent to the substance to be extracted is generally in the range of 1: 1 to 1: 200 (weight ratio), preferably in the range of 1:15 to 1:35.

  Moreover, although extraction conditions, such as extraction temperature and time, also differ depending on the type of solvent used, the extraction site of the plant, and the degree of shredding, for example, in the case of the immersion method, the extraction temperature is generally 4 to 80 ° C., The temperature is preferably in the range of 40 ° C. or lower, and the extraction time is preferably about 1 hour to 1 week, particularly about 12 to 24 hours.

  The extract solution obtained here may generally be adjusted to a pH of 4 to 8 and adjusted to an appropriate concentration as it is or by dilution or concentration under reduced pressure, etc. Depending on the case, it may be pulverized according to a conventional method such as spray-drying method or freeze-drying method and blended into the external preparation for skin.

  The extract of the Tavebuia genus plant of the present invention prepared as described above has an action to suppress degranulation of basophils and a cyclooxygenase which is an important enzyme in the cyclic pathway of the arachidonic acid cascade, as shown in Test Examples later. It has an action of suppressing the activity of selenium, a function of suppressing the production of prostaglandin E2, and is excellent in biological safety such as low skin irritation, and is useful as a degranulation inhibitor for blending with an external preparation for skin.

  The external preparation for skin of the present invention containing such a degranulation inhibitor can be used as any of cosmetics, quasi-drugs, pharmaceuticals, etc., and the application site is particularly limited to skin in general including the scalp. There is no. The dosage forms include, for example, emulsions, creams, lotions, essences, ointments, packs, haps, skin cleansers (soaps, etc.), facial cleansers, hair tonics, hair shampoos, hair rinses, hair treatments, and various makeup cosmetics. (Lipsticks, foundations, makeup press powders, etc.), bath agents, etc. are mentioned, but of course not limited thereto.

  The blending amount of the degranulation inhibitor in the external preparation for skin of the present invention varies depending on the use, application site, etc. of the external preparation for skin, but is generally 0.00001 to as the solid content of the Tabebia plant extract as its active ingredient. It is preferable to mix in the range of 10% by weight, preferably 0.0001-5% by weight, particularly preferably 0.001-1% by weight.

In addition to the above-described degranulation inhibitor as an essential component, the external preparation for skin of the present invention includes components usually used in external preparations for skin, such as oil components, surfactants, moisturizers, thickeners, antiseptic / bactericides, A powder component, an ultraviolet absorber, an antioxidant, a pigment, a fragrance, and the like can be appropriately blended as necessary.
In addition, other physiologically active ingredients can be blended together as long as the effectiveness and features of the degranulation inhibitor of the present invention are not impaired.

  Here, as the oil component, for example, olive oil, jojoba oil, castor oil, soybean oil, rice oil, rice germ oil, palm oil, palm oil, cacao oil, meadow foam oil, sheer butter, tea tree oil, avocado oil, Oils derived from plants such as macadamia nut oil and plant-derived squalane; Fats derived from animals such as mink oil and turtle oil; waxes such as beeswax, carnauba wax, rice wax, lanolin; liquid paraffin, petrolatum, paraffin wax, squalane, etc. Hydrocarbons; fatty acids such as myristic acid, palmitic acid, stearic acid, oleic acid, isostearic acid, cis-11-eicosenoic acid; higher alcohols such as lauryl alcohol, cetanol, stearyl alcohol; isopropyl myristate, palmitic acid Isopropyl, me Butyl phosphate, 2-ethylhexyl glycerides, higher fatty acid octyldodecyl (octyl stearate dodecyl and the like), and the synthetic esters and synthetic triglycerides such like.

Examples of the surfactant include polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene Nonionic surfactants such as oxyethylene sorbitol fatty acid esters; fatty acid salts, alkyl sulfates, alkylbenzene sulfonates, polyoxyethylene alkyl ether sulfates, polyoxyethylene fatty amine sulfates, polyoxyethylene alkyl phenyl ether sulfates, Polyoxyethylene alkyl ether phosphates, α-sulfonated fatty acid alkyl ester salts, polyoxyethylene alkyl phenyl ether phosphates Quaternary ammonium salts, primary to tertiary fatty amine salts, trialkylbenzylammonium salts, alkylpyridinium salts, 2-alkyl-1-alkyl-1-hydroxyethylimidazolinium salts, N Cationic surfactants such as N, N-dialkylmorphonium salt, polyethylene polyamine fatty acid amide salt; N, N-dimethyl-N-alkyl-N-carboxymethylammoniobetaine, N, N, N-trialkyl-N- Amphoteric surfactants such as alkylene ammoniocarboxybetaine and N-acylamidopropyl-N ′, N′-dimethyl-N′-β-hydroxypropylammoniosulfobetaine can be used.
In addition, as emulsifiers or emulsifiers, stevia derivatives such as enzyme-treated stevia, lecithin and derivatives thereof, lactic acid bacteria fermented rice, lactic acid bacteria fermented rice, lactic acid bacteria fermented cereals (wheat, beans, millet, etc.), juzyiro (Rhamnaceae) ) An extract or the like can also be blended.

  Examples of the humectant include glycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol, polyethylene glycol, sorbitol, xylitol, sodium pyrrolidonecarboxylate, and sugars such as trehalose and maltose, lactic acid bacteria fermented rice, mucos Polysaccharides (eg, hyaluronic acid and its derivatives, chondroitin and its derivatives, heparin and its derivatives, etc.), elastin and its derivatives, collagen and its derivatives, hydrolyzed silk protein, NMF related substances, lactic acid, urea, higher fatty acid octyldodecyl Phytosterol, soybean phospholipid, cholesteryl isostearate, seaweed extract, seafood-derived collagen and its derivatives, various amino acids and their derivatives (for example, trimethylglycine) It is below.

  Examples of thickeners include, for example, brown algae such as alginic acid, agar, carrageenan, fucoidan, green algae or red algae-derived components, extract of sand cucumber, pectin, locust bean gum, polysaccharides such as aloe polysaccharide, xanthan gum, tragacanth gum, guar gum, etc. Synthetic polymers such as gums, cellulose derivatives such as carboxymethylcellulose, hydroxyethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, acrylic acid / methacrylic acid copolymer; hyaluronic acid and its derivatives, polyglutamic acid and its derivatives, etc. Is mentioned.

  Examples of the antiseptic / bactericidal agent include urea; paraoxybenzoates such as methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and butyl paraoxybenzoate; phenoxyethanol, dichlorophene, hexachlorophene, chlorhexidine hydrochloride, benzal chloride Luconium, salicylic acid, ethanol, undecylenic acid, phenols, jamal (imidazodenyl urea), 1,2-pentanediol, various essential oils, bark dry matter, and the like.

  Examples of powder components include sericite, titanium oxide, talc, kaolin, bentonite, zinc oxide, magnesium carbonate, magnesium oxide, zirconium oxide, barium sulfate, anhydrous silicic acid, mica, 6- or 12-nylon powder, polyethylene powder Silk powder, cellulosic powder, grains (rice, wheat, corn, millet, etc.) powder, beans (soybean, red beans, etc.) powder, and the like.

  Examples of the ultraviolet absorber include ethyl paraaminobenzoate, ethylhexyl paradimethylaminobenzoate, octyl paradimethylaminobenzoate, amyl salicylate and derivatives thereof, octyl salicylate, homomenthyl salicylate, 2-ethylhexyl paramethoxycinnamate, octyl paramethoxycinnamate, Octyl cinnamate, oxybenzone, 2,4-dihydroxybenzophenone, tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonate, 4-tertiarybutyl-4-methoxybenzoylmethane, 2- (2-hydroxy -5-methylphenyl) benzotriazole, urocanic acid, ethyl urocanate, aloe extract and the like.

  Antioxidants include, for example, butylhydroxyanisole, butylhydroxytoluene, propyl gallate, vitamin E and its derivatives, ubidecaquinone (ubiquinone), rutin, rutin glucoside, white coconut extract, rice extract, murasakikibu extract, birch extract Products, Hamelis extract, oolong tea extract and the like.

  Examples of physiologically active ingredients include whitening ingredients such as t-cycloamino acid derivatives, kojic acid and its derivatives, hydroquinone derivatives, ellagic acid and its derivatives, resorcinol derivatives, placenta extract, cysteine, Sakuhakhi extract, yukinoshita extract, rice bran Extract, rice bran extract hydrolyzate, lactic acid bacteria fermented rice, lactic acid bacteria fermented germinated rice, lactic acid bacteria fermented cereals (barley, beans, millet), white coconut hydrolyzed extract, murasakixikib extract, lotus seed ferment Extract, Pandanus amaryllifolius Roxb. Extract, Arcangelicia flava Merrilli extract, chamomile extract (trade name: chamomile ET), japonica extract Extracts of seaweeds such as licorice extract, sawably extract, licorice extract, licorice poppo extract, artea extract, genus shochu extract, cypress extract, jujube extract, peonies extract, suzuki extract, peach extract, kombu , Linoleic acid and its derivatives or processed products (such as liposomal linoleic acid), 2,5-dihydroxybenzoic acid derivatives, etc., as an anti-skin aging / beautifying component, animal or fish Collagen and its derivatives, elastin and its derivatives, intercellular lipids such as ceramide, placental extract, nicotinic acid and its derivatives, glycyrrhizic acid and its derivatives (dipotassium salt, etc.), t-cycloamino acid derivatives, vitamin A and its Derivatives, vitamin E and its derivatives, allantoin, α-hydroxy acids, Herbal extracts such as isopropylamine dichloroacetate, γ-amino-β-hydroxybutyric acid, gentian extract, licorice extract, pearl barley extract, chamomile extract, carrot extract, aloe extract, cuckoo extract, rice extract hydrolyzate, rice bran extract Hydrolyzate, rice fermentation extract, beetle extract, anaosa extract, seaweed extract such as sea ammo, soakakuhi extract, jiazeiro extract, beech extract, beetle aloe extract, mannenrou extract, ginkgo biloba extract , Horsetail extract, safflower extract, ginseng extract, carrot extract, elderberry extract, yeast extract, eggshell membrane extract protein, deoxyribonucleic acid potassium salt, etc. Azulene derivatives such as um, guaiazulene sulfonate, dipotassium glycyrrhizinate, glycyrrhizic acid derivatives such as stearyl glycyrrhizinate, allantoin, licorice extract, cucumber extract, peonies extract, button pi extract, forsythia extract, ryutan extract, There are eucalyptus extract, parsley extract, hypericum extract, broomtake extract, cassia extract and the like.

  Examples of the kojic acid derivatives include kojic acid esters such as kojic acid monobutyrate, kojic acid monocaprate, kojic acid monopalmitate, kojic acid dibutyrate, kojic acid ethers, kojic acid sugar derivatives such as kojic acid glucoside, etc. As the ascorbic acid derivatives, for example, L-ascorbic acid-2-phosphate sodium, L-ascorbic acid-2-phosphate magnesium, L-ascorbic acid-2-sulfate sodium, L-ascorbic acid-2 -Ascorbic acid ester salts such as magnesium sulfate, L-ascorbic acid-2-glucoside (2-O-α-D-glucopyranosyl-L-ascorbic acid), L-ascorbic acid-5-glucoside (5-O-α) -D-Glucopyranosyl-L-ascorbine Acid) ascorbic acid sugar derivatives, acylated 6-positions of these ascorbic acid sugar derivatives (acyl groups are hexanoyl, octanoyl, decanoyl, etc.), L-ascorbic acid tetraisopalmitate, L-ascorbic acid tetra L-ascorbic acid tetra-fatty acid esters such as lauric acid ester, 3-O-ethylascorbic acid, L-ascorbic acid-2-phosphate-6-O-palmitate sodium, etc. include arbutin (hydroquinone) -Β-D-glucopyranoside), α-arbutin (hydroquinone-α-D-glucopyranoside) and the like, and as the resorcinol derivative, for example, 4-n-butylresorcinol, 4-isoamylresorcinol and the like are 2,5-dihydroxybenzoic acid. Derivatives and For example, 2,5-diacetoxybenzoic acid, 2-acetoxy-5-hydroxybenzoic acid, 2-hydroxy-5-propionyloxybenzoic acid, etc., and nicotinic acid derivatives include, for example, nicotinic acid amide, benzyl nicotinate, etc. However, examples of vitamin E derivatives include vitamin E nicotinate and vitamin E linoleate, and examples of α-hydroxy acids include lactic acid, malic acid, succinic acid, citric acid, and α-hydroxyoctanoic acid.

  Next, although an Example, a test example, and a prescription example (Example of skin external preparation) are given and this invention is demonstrated further more concretely, this invention is not limited to them. In the following, all parts are parts by weight, and all% are% by weight.

Example 1. Preparation of degranulation inhibitor (1)
Purified water (1000 g) was mixed with 100 g of the internal bark of Tabebuia impetigenosa, and extracted at 4 ° C. for 24 hours, followed by filtration to obtain 650 g of a light brown transparent extract solution (solid content 1) .2%). This was diluted 6 times with purified water to obtain a pale yellow transparent degranulation inhibitor.

Example 2 Preparation of degranulation inhibitor (2)
Mixing 900 g of 9: 1 (weight ratio) of purified water and ethanol with 100 g of cuts of the internal bark of Tabebuia impetiginosa, extracting at 40 ° C. for 3 hours, filtering, and removing light brown transparent 720 g of a granule inhibitor was obtained (solid content concentration 1.9%).

Example 3 Preparation of degranulation inhibitor (3)
Purified water and 900 g of an 8-: 2 (weight ratio) mixture of 1,3-butylene glycol were mixed with 100 g of the internal bark of Tabebuia impetiginosa, and extraction was performed at 80 ° C. for 6 hours, followed by filtration. 460 g of a light brown transparent degranulation inhibitor was obtained (solid content concentration 2.0%).

Example 4 Preparation of degranulation inhibitor (4)
500 g of a light yellow transparent extract solution of tabebuia rosacea bark was obtained in the same manner as in Example 1 except that barbecue arrosea bark was used instead of tabebuia impetiginosa (solid content concentration 2.3%) ). This was diluted with 10 times purified water to obtain a pale yellow transparent degranulation inhibitor.

Embodiment 5 FIG. Preparation of degranulation inhibitor (5)
520 g of a pale yellow transparent extract solution was obtained in the same manner as in Example 1 except that leaves were used instead of the bark of Tabebuia impetigenosa (solid content concentration 1.0%).

Example 6 Preparation of degranulation inhibitor (6)
500 g of the tabebuia impetigenosa extract solution prepared in the same manner as in Example 1 was freeze-dried and then pulverized to obtain 12.0 g of a tan brown tabebuia impetigenosa extract powder.

Test Example 1 Degranulation Inhibition Test The extract solution (degranulation inhibitor) obtained in Example 1 was examined for degranulation inhibitory effect on basophils.
[Test method]
(A) Induction of degranulation into cell culture supernatant Rat basophil leukemia cells (RBL-2H3: Lot. 408828 (7)) were suspended in Eagle's minimum essential medium containing 10% (NCS) in a 96-well plate. 1 × 10 ⁵ seeds were inoculated and cultured at 37 ° C. for 24 hours. The confluent cells were released into a releasing buffer [117 mM NaCl, 5.4 mM KCl, 2.0 mM CaCl ₂ , 0.8 mM MgSO ₄ , 5.6 mM D-glucose, 25 mM HEPES (2- [4- (2-hydroxyethyl) -1-piperazinyl] ethanesulfonic acid), 1 mg / mL BSA / pH 7.7] After washing with 200 μL / well, the extract solution of Example 1 was added to the releasing buffer. In order to induce further degranulation, 200 μg / mL compound 48/80 (compound 48/80) / Add 100 μL of release buffer solution and incubate at 37 ° C. for 1 hour .
For comparison, two wells to which only the buffer solution was added instead of the releasing buffer solution containing the extract solution of Example 1 were provided, and one well (control) was used for degranulation as described above. Compound 48/80 / releasing buffer solution and 200 μL of releasing buffer alone were added to the other well (control), respectively, and incubated at 37 ° C. for 1 hour.
(B) Determination of degranulation rate by measuring β-hexosaminidase activity In order to measure the enzyme activity of beta-hexosaminidase released extracellularly after degranulation induction, 50 μL of cell supernatant was used. Sorted into another 96-well microplate.
The measurement of beta hexosaminidase activity was performed as follows.
50 μL of 5 mM paranitrophenyl-2-acetamido-2-deoxy-betaglucopyranoside (p-Nitrophenyl-2-acetamide-2-deoxy-s-D-glucopyranoside) was added as a substrate to 50 μL of each cell supernatant taken on a separate plate. For 30 minutes in a CO ₂ incubator at 37 ° C. Thereafter, 100 μL of 0.2 M glycine buffer (pH 10.7) was added to stop the reaction, and the absorbance at 415 nm was measured with an absorbance plate reader, which was used as an index of beta-hexosaminidase activity.

  [Results] are shown in FIG. As shown in FIG. 1, the Tavebuia impetiginosa extract (Extract solution of Example 1) of the plant of the genus Tabenia is remarkably suppressing the release (degranulation) of chemical mediators from basophils. Is recognized.

Test Example 2 Cyclooxygenase activity inhibition test The extract solution (degranulation inhibitor) obtained in Example 1 was examined for activity inhibition activity of cyclooxygenase, which is an enzyme involved in the cyclic pathway of the arachidonic acid cascade.
[Test method]
2.52 ml of 20 mM tryptophan / 0.2 M Tris-HCl (Tris-HCl) buffer (pH 8.0), 0.03 ml of 40 mM hemoglobin / 0.2 M Tris-HCl (Tris-HCL) buffer (pH 8.0) and implementation 0.15 ml of the solution obtained by diluting the extract solution of Example 1 with purified water to a concentration of 2.5% or 5.0% (as a solution) was mixed. After heating to 37 ° C., 0.1 ml of 2 mM arachidonic acid / 0.2 mM Tris-HCl (Tris-HCL) buffer (pH 8.0) and 0.2 ml of 250 unit / ml cyclooxygenase were mixed and stirred in a sealed state. Then, a cyclooxygenase enzyme reaction using arachidonic acid as a substrate was performed for 10 minutes.
During the course of the reaction, the dissolved oxygen concentration was measured every specified time using a biological oxygen monitor (YSI MODEL 5300), and the oxygen consumption rate over time was calculated with the dissolved oxygen concentration immediately before the reaction as 100%.
When the oxygen consumption rate at each time is χ%, the oxygen consumption amount in 3 ml of the sample solution is obtained by the following equation.
Oxygen consumption in sample solution (μl) = χ / 100 × 5.02 × 3
For comparison, also when 0.15 mL of purified water was mixed instead of the extract solution of Example 1 and when 0.15 mL of a 1 mM aqueous solution of indomethacin, a known anti-inflammatory drug, was mixed (positive control) A similar test was conducted.

[result]
The change in oxygen consumption over time is shown in FIG.
As is clear from the results of FIG. 2, the plant extract of the genus Tabenia of the present invention has a remarkable cyclooxygenase activity inhibitory effect and is useful as an anti-inflammatory agent.
Further, the cosmetic of the present invention, which is obtained by blending this plant extract of the genus Tabenia, exhibits an excellent effect for preventing skin aging due to the anti-inflammatory action of the extract.

Test Example 3 Prostaglandin E2 Production Inhibition Test With respect to the extract solution (degranulation inhibitor) obtained in Example 1, the production inhibitory action of prostaglandin E2 (PGE2) was examined using rabbit cornea-derived cells.
[Test method]
Rabbit cornea-derived cells (SIRC: Lot. 409916 (7)) are suspended in Eagle's minimum essential medium containing 10% (FBS) and seeded in a 96-well plate at 5.0 × 10 ³ cells at 37 ° C. for 3 days. After culturing, the extract solution of Example 1 was added to the medium so as to have a concentration of 5.0% or 10.0% (as a solution), and further cultured for 24 hours. As a control, purified water was added instead of the extract solution of Example 1 and cultured for 24 hours. Next, an ultraviolet B wave of 0.5 mW / cm ² was irradiated from the bottom of the incubator, and after further culturing for 2 days, the amount of PGE2 secreted into the culture supernatant was measured using a PGE2 measurement kit (manufactured by Cayman Caymic). Measured. As a positive control, indomethacin was used and added to the medium to a concentration of 10 μM.
In addition, the amount of PGE2 was also measured in the case of adding purified water instead of the extract solution of Example 1 and culturing for 24 hours and then irradiating ultraviolet rays (control).

[Results] The results are shown in FIG. As shown in FIG. 3, it was found that the barb extract of the genus Tabebia genus Tabebuia impetigenosa bark has a strong anti-inflammatory effect, with the suppression of PGE2 production equivalent to that of indomethacin, which is a strong acidic anti-inflammatory drug.

In order to confirm the safety of the extract solution obtained in Example 1, a skin primary irritation test was performed.
[Test method]
Five adult males aged 20 to 50 years were used as subjects, and the inner side of each upper arm was wiped with ethanol to remove sebum, and the extract solution of Example 1 and the control day were placed on the aluminum plate of the fin chamber. Each of 0.2 g of topical hydrophilic petrolatum was applied. After 24 hours, the fin chamber was removed, and the degree of skin irritation was determined by the method and criteria described below.
[Judgment]
After 1 hour, 24 hours and 48 hours after removing the patch, the state of erythema and edema at the applied site was visually determined based on the following “skin irritation criteria by dreze method”, and the average value of 5 subjects was calculated. Asked.
(Erythema)
Score Skin condition 0: No erythema 1: Extremely mild erythema 2: Clear erythema 3: Moderate to strong erythema 4: Light crust formation in strong crimson erythema (edema)
Score Skin condition 0: No edema 1: Extremely mild edema 2: Clear edema (clearly distinguishable from surroundings)
3: Moderate edema (swelling of 1 mm or more)
4: Strong edema (further spread around)

表１の結果から明らかな通り、ノウゼンカズラ科タベブイア属植物の抽出物を有効成分としてなる本発明の脱顆粒抑制剤は皮膚刺激が殆どなく、安全性に極めてすぐれている。 [result]
The results are shown in Table 1.

As is apparent from the results in Table 1, the degranulation inhibitor of the present invention comprising an extract of the plant belonging to the genus Tabebia belonging to the genus Candidaceae as an active ingredient has almost no skin irritation and is extremely excellent in safety.

Formulation Example 1 Cream [Component A] Liquid paraffin 5.0
Hexalan (Note 1) 4.0
Paraffin 5.0
Glyceryl monostearate 2.0
Polyoxyethylene (20) sorbitan monostearate 6.0
Butylparaben 0.1
(Note 1) Technoble Co., Ltd. glyceryl trioctanoate
[B component]
Degreasing inhibitor of Example 1 10.0
Glycerin 5.0
Methylparaben 0.1
Moiston C (Note 2) 1.0
Amount of purified water totaling 100 parts
(Note 2) NMF component manufactured by Technoble Co., Ltd.
[C component]
Perfume
The components A and B were each heated to 80 ° C. or higher and then mixed by stirring. After this was cooled to 50 ° C., component C was added and further stirred and mixed to obtain a cream.

Formulation Example 2 Cream A cream was obtained in the same manner as in Formulation Example 1 except that the degranulation inhibitor of Example 2 was used instead of the degranulation inhibitor of Example 1 in the B component of Formulation Example 1.

Formulation Example 3 Emulsion [component A] part liquid paraffin 6.0
Hexalan 4.0
Jojoba oil 1.0
Polyoxyethylene (20) sorbitan monostearate 2.0
Soy lecithin 1.5
Methylparaben 0.15
Ethylparaben 0.03
[B component]
Degreasing inhibitor of Example 1 10.0
Glycerin 3.0
1,3-butylene glycol 2.0
Carboxymethylcellulose 0.3
Sodium hyaluronate 0.01
Amount of purified water totaling 100 parts
[C component]
Perfume
The components A and B were each heated to 80 ° C. or higher and then mixed by stirring. After cooling this to 50 ° C., component C was added and further stirred and mixed to obtain an emulsion.

Formulation Example 4 Lotion [component] part degranulation inhibitor of Example 3 10.0
Ethanol 10.0
Glycerin 3.0
1,3-butylene glycol 2.0
Methylparaben 0.2
Citric acid 0.1
Sodium citrate 0.3
Carboxyvinyl polymer 0.1
Perfume
Potassium hydroxide appropriate amount Purified water Amount that makes 100 parts in total
The above ingredients were mixed to obtain a lotion.

Formulation Example 5 Lotion [component A] part olive oil 1.0
Polyoxyethylene (5.5) cetyl ether 0.5
Butylparaben 0.1
[B component]
Deagglomeration inhibitor of Example 4 10.0
Ethanol 5.0
Glycerin 5.0
1,3-butylene glycol 5.0
Methylparaben 0.1
Potassium hydroxide appropriate amount Purified water Amount that makes 100 parts in total
[C component]
Perfume
After each component A and component B was heated to 80 ° C. or higher, the component B was added to the component A and stirred, and further homogenized with Hiscotron (5000 rpm) for 2 minutes.
After cooling this to 50 degreeC, C component was added and stirred and mixed, and also it cooled to 30 degrees C or less, and the lotion was obtained.

Formulation Example 6 Emulsion An emulsion was obtained in the same manner as in Formulation Example 3 except that the degranulation inhibitor of Example 2 was used instead of the degranulation inhibitor of Example 1 in the B component of Formulation Example 3.

Formulation Example 7 Emulsion An emulsion was obtained in the same manner as in Formulation Example 3, except that the degranulation inhibitor of Example 3 was used instead of the degranulation inhibitor of Example 1 in the component B of Formulation Example 3.

Formulation Example 8 Emulsion An emulsion was obtained in the same manner as in Formulation Example 3, except that the degranulation inhibitor of Example 5 was used instead of the degranulation inhibitor of Example 1 in the component B of Formulation Example 3.

Formulation Example 9 Emulsion [component A] part liquid paraffin 6.0
Hexalan 4.0
Jojoba oil 1.0
Polyoxyethylene (20) sorbitan monostearate 2.0
Soy lecithin 1.5
Methylparaben 0.15
Ethylparaben 0.03
[B component]
Degreasing inhibitor of Example 1 10.0
L-Ascorbic acid-2-glucoside 2.0
Glycerin 3.0
1,3-butylene glycol 2.0
Carboxymethylcellulose 0.3
Sodium hyaluronate 0.01
Potassium hydroxide Appropriate amount Purified water Amount of 100 parts [C component]
Fragrance Appropriate amount Each of the above components A and B was heated to 80 ° C. or higher, and then mixed by stirring. After cooling this to 50 ° C., component C was added and further stirred and mixed to obtain an emulsion.

Formulation Example 10 Emulsion In addition to using 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 parts of potassium hydroxide in component B of Formulation Example 9, 2.0 parts of magnesium L-ascorbyl-2-phosphate is used. Gave a milky lotion in the same manner as in Formulation Example 9.

Formulation Example 11 Emulsion In addition to using 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 parts of potassium hydroxide in component B of Formulation Example 9, 2.0 parts of sodium L-ascorbic acid-2-phosphate is used. Gave a milky lotion in the same manner as in Formulation Example 9.

Formulation Example 12. Emulsion In the same manner as Formulation Example 9, except that 2.0 parts of arbutin is used instead of 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 part of potassium hydroxide in the B component of Formulation Example 9. Obtained.

Formulation Example 13 Emulsion In place of component B in Formulation Example 9, instead of 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 part of potassium hydroxide, a rice bran extract hydrolyzate (trade name “Grace Know” manufactured by Technoble Co., Ltd.) * Snow * HP ", solid content concentration 3.5%) An emulsion was obtained in the same manner as in Formulation Example 9, except that 5.0 parts were used.

Formulation Example 14. Latex In the B component of Formulation Example 9, in place of 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 part of potassium hydroxide, white seed (Brassica Alba) seed extract (trade name, manufactured by Technoble Co., Ltd.) An emulsion was obtained in the same manner as in Formulation Example 9 except that 5.0 parts of “Sinablanca-WH” (solid content concentration 1.0%) were used.

Formulation Example 15. Emulsion Formulation Example 9 except for using 1.0 part of γ-amino-β-hydroxybutyric acid instead of 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 part of potassium hydroxide in the B component of Formulation Example 9. In the same manner as in No. 9, an emulsion was obtained.

Formulation Example 16. Emulsion In place of the B component of Formulation Example 9, instead of 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 part of potassium hydroxide, a rice extract hydrolyzate (trade name “Orisenoble, manufactured by Technoble Co., Ltd.) A solid emulsion was obtained in the same manner as in Formulation Example 9 except that 5.0 parts of a solid content concentration of 1.5% was used.

Formulation Example 17. Lotion [component] part degranulation inhibitor 10.0 of Example 10.0
L-Ascorbic acid-2-glucoside 2.0
Ethanol 10.0
Glycerin 3.0
1,3-butylene glycol 2.0
Methylparaben 0.2
Citric acid 0.1
Sodium citrate 0.3
Sodium alginate 0.1
Potassium hydroxide appropriate amount Perfume appropriate amount
Amount of purified water totaling 100 parts
The above ingredients were mixed to obtain a lotion.

Formulation Example 18. Pressed powder [A component] Part Bengala 0.5
Yellow iron oxide 1.5
Black iron oxide 0.1
Titanium oxide 10.0
6-Nylon powder 4.0
Amount that makes 100 parts of sericite Mica 23.0
Talc 25.0
Degranulation inhibitor of Example 6 0.1
[B component]
Squalane 1.0
Methylpolysiloxane 4.0
Propylparaben 0.1
Dehydroacetic acid 0.1
Liquid paraffin 2.0
Perfume
The above A component and B component were mixed and stirred, mixed, then passed through a 200 mesh Tyler mesh sieve, and the resulting mixed powder was cast into a mold to obtain a pressed powder.

Formulation Example 19. Liquid foundation [component A] part Stearic acid 2.4
Propylene glycol monostearate 2.0
Cetostearyl alcohol 0.2
Liquid lanolin 2.0
Liquid paraffin 3.0
Isopropyl myristate 8.5
Propylparaben 0.05
[B component]
Degranulation inhibitor of Example 2 5.0
Sodium carboxymethylcellulose 0.2
Bentonite 0.5
Propylene glycol 4.0
Triethanolamine 1.1
Methylparaben 0.1
Purified water Amount that makes the total amount 100 parts [C component]
Titanium oxide 8.0
Talc 4.0
Coloring pigment appropriate amount The components A and B were heated and mixed and stirred. This was reheated, the above C component was added, poured into a mold, and stirred until it reached room temperature to obtain a liquid foundation.

Example 20. Cream foundation [component A] part Stearic acid 5.0
Cetanol 2.0
Glyceryl monostearate 3.0
Liquid paraffin 5.0
Squalane 3.0
Isopropyl myristate 8.0
Polyoxyethylene (20) glyceryl monostearate 2.0
Propylparaben 0.1
[B component]
De-granulation inhibitor of Example 1 5.0
Sorbitol 3.0
1,3-butylene glycol 5.0
Triethanolamine 1.5
Methylparaben 0.1
Purified water Amount of 100 parts [component C]
Titanium oxide 8.0
Talc 2.0
Kaolin 5.0
Bentonite 1.0
Coloring pigment appropriate amount [component D]
Fragrance 0.3
Component C was mixed and pulverized with a pulverizer. The component B was mixed, and the pulverized component C was added thereto and uniformly dispersed in a colloid mill. The components A and B and C dispersed uniformly were each heated to 80 ° C., and then the components A were added to the components B and C while stirring, and further homogenized with Hiscotron (5000 rpm) for 2 minutes. After cooling this to 50 degreeC, D component was added and stirred and mixed, and also it cooled to 30 degrees C or less, stirring, and obtained the cream foundation.

Formulation Example 21. Hair artic [component A] part ethanol 60.0
l-Menthol 0.5
Fragrance 0.1
Methylparaben 0.1
[B component]
Glycerin 2.0
1,3-butylene glycol 2.0
Deagglomeration inhibitor of Example 3 10.0
Purified water in an amount of 100 parts The above A component and B component were each dissolved at room temperature, then the B component was added to the A component with stirring and dissolved to obtain a hair-tonic.

Formulation Example 22. Hair treatment [ingredient] part stearyltrimethylammonium chloride 6.0
Polyvinylpyrrolidone 4.0
Glycerin 1.0
Ethylparaben 0.1
Degranulation inhibitor of Example 2 5.0
Purified water in a total amount of 100 parts The above ingredients were heated to 80 ° C and then mixed and stirred to obtain a hair treatment.
This product was also suitable as a hair pack.

Formulation Example 23. Hair shampoo [component A] part N-coconut oil fatty acid methyl taurine sodium 10.0
Polyoxyethylene (3) sodium alkyl ether sulfate 20.0
Lauryldimethylaminoacetic acid betaine 10.0
Palm oil fatty acid diethanolamide 4.0
Methylparaben 0.1
[B component]
Citric acid 0.1
Degranulation inhibitor of Example 2 5.0
1,3-butylene glycol 2.0
Purified water Amount to be 100 parts A component and B component are each heated to 80 ° C and dissolved uniformly, then B component is added to A component, and stirring is continued to cool to room temperature to obtain a hair shampoo It was.

Formulation Example 24. Hair rinse [component A] Part Polyoxyethylene (10) hydrogenated castor oil 1.0
Distearyldimethylammonium chloride 1.5
Stearyltrimethylammonium chloride 2.0
Glyceryl 2-ethylhexanoate 1.0
Cetanol 3.2
Stearyl alcohol 1.0
Methylparaben 0.1
[B component]
Degranulation inhibitor of Example 2 5.0
1,3-butylene glycol 5.0
Purified water Amount to be 100 parts A component and B component are each heated to 80 ° C and dissolved uniformly, then B component is added to A component and stirring is continued to cool to room temperature to obtain hair rinse It was.

Formulation Example 25. Body shampoo [component A] part N-lauroylmethylalanine sodium 25.0
Palm oil fatty acid potassium liquid (40%) 26.0
Palm oil fatty acid diethanolamide 3.0
Methylparaben 0.1
[B component]
Degreasing inhibitor of Example 2 10.0
1,3-butylene glycol 2.0
Purified water Amount to be 100 parts A component and B component are each heated to 80 ° C and dissolved uniformly, then B component is added to A component and stirring is continued to cool to room temperature to obtain a body shampoo It was.

Formulation Example 26. Soap [component A] part hardened castor oil 26.0
Coconut oil 10.0
Olive oil 4.0
[B component]
Sodium hydroxide 6.0
Sugar 10.0
Glycerin 5.0
Deagglomeration inhibitor of Example 6 0.5
Purified water Amount of 100 parts [component C]
Ethanol 20.0
Perfume Appropriate A component and B component were each heated to 80 ° C. and dissolved uniformly, and then B component was added to A component to saponify. This was cooled to 50 ° C. with stirring, and component C was added. This was poured into a mold and cooled, and then dried at room temperature for several days. A sufficiently dried product was taken out from the mold to obtain soap.

FIG. 1 is a graph showing the degranulation inhibitory effect in Test Example 1 (vertical axis: beta-hexosaminidase activity (ΔABS415)).

FIG. 2 is a graph showing the cyclooxygenase activity inhibitory effect in Test Example 2. The vertical axis represents the oxygen consumption rate (%), and the horizontal axis represents the reaction time (min.).

FIG. 3 is a graph showing the effect of suppressing the production of prostaglandin (PGE2) in Test Example 3. The vertical axis represents the amount of PGE2 produced (pg / mL).

Explanation of symbols

FIG.
A Control B Control C Addition of 2.5% of the extract solution of Example 1 D Addition of 5.0% of the extract solution of Example 1

FIG.
E Control F Add 2.5% solution of the extract solution of Example 1 G Add 5.0% solution of the extract solution of Example 1 H Add 1 mM solution of indomethacin (positive control)

FIG.
I Control J Control K 5.0% of the extract solution of Example 1 was added L 10.0% of the extract solution of Example 1 was added M 10 μM of indomethacin was added (positive control)

Claims (7)

A degranulation inhibitor comprising, as an active ingredient, an extract from a plant of the genus Tabebuia sp. The degranulation inhibitor according to claim 1, comprising an extract of bark of a Tabebuia sp. The degranulation inhibitor according to claim 1 or 2, wherein the Tabebuia sp. Plant is Tabebuia Impetiginosa. 4. The degranulation inhibitor according to claim 1, which has cyclooxygenase inhibitory activity. A skin external preparation containing the degranulation inhibitor according to claim 1. The skin external preparation according to claim 5, which is for whitening. The external preparation for skin according to claim 5, which is used for anti-inflammatory or anti-allergy.

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