JP2017190310A - OPH activity enhancer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel oxidized protein hydrolase (OPH) activity enhancer that allows an OPH active ingredient present in the stratum corneum to be purified and OPH-like activity enhancing components for various plant extracts to be searched, and can be suitably applied to cosmetics, etc.SOLUTION: According to the present invention, there is provided a cosmetic in which an extract from a plant is blended as an OPH activity enhancer. Here, the plant is at least one plant selected from Uncaria gambir, Scutellaria japonica, Geranium herb, rice bran, salvia, marjoram, aloe, Malva sylvestris, Trillium apetalon, Coptis rhizome, Ononis, rose hip, Gardenia Fruit, and Piper longum.SELECTED DRAWING: Figure 2

Description

  The present invention relates to an OPH activity enhancer that activates the action of oxidized protein hydrolase (OPH), which is an in vivo enzyme that degrades oxidized protein, and a cosmetic that contains the OPH activity enhancer.

  It has been clarified that protein saccharification in vivo is involved in aging-related functional deterioration and diseases such as skin aging, dementia, cancer, hypertension, and arteriosclerosis. For example, the protein turns brown due to the saccharification reaction, which causes dullness on the skin. Various studies have been conducted to inhibit the saccharification reaction, which is a cause of diseases and functional deterioration caused by such aging (Patent Document 1).

  In addition, protein oxidation has also attracted attention as another factor that causes aging-related diseases and functional decline. Examples of the effects on cells and tissues caused by protein oxidation in vivo include various diseases and functional deterioration such as age-related changes such as tissue collagen, Alzheimer's disease, cataracts, and skin aging.

  Oxidized protein produced by protein oxidation in vivo is decomposed and removed by an in vivo enzyme called oxidized protein hydrolase (hereinafter referred to as OPH). OPH is a kind of serine protease that is widely distributed in living tissues and preferentially degrades oxidized protein, and acylamino-acid-releasing enzyme: an enzyme that releases N-terminal acylated amino acids of proteins. AARE).

  The activity of OPH decreases with age. Therefore, the skin aging, disease, etc. as described above are brought about by the decrease in the activity. Therefore, studies have been made on agents that promote the activity of OPH in order to prevent diseases and aging (Patent Document 2).

  Research has also been conducted on active substances that can inhibit both glycation and oxidation of proteins or decompose any reaction product. The protein of OPH, an enzyme that degrades oxidized proteins, is also being studied. Several AGEs degradation activity enhancers of OPH have been proposed that show the presence of a degradation action on AGEs, which are the final product of the saccharification reaction, and activate the degradation action (Patent Document 3).

  In this way, oxidative proteolytic enzymes (OPHs) in the body have a degrading action on glycated proteins and glycated end products (AGEs) that are generated and accumulated due to increased glycation stress in the body and affect aging and disease progression. In addition, it has been suggested that it may work to control diabetes and aging.

Japanese Patent No. 4195840 International Publication Number WO2011 / 004733 JP 2014-118406 A

  Based on the technical background described above, the present inventors have found that OPH-like activity is present in the stratum corneum of the skin, purifies the OPH-like active ingredient in the stratum corneum, and is also OPH-like for various plant extracts. We searched for activity-enhancing ingredients and studied application to cosmetics. This invention makes it a subject to provide the new OPH activity enhancer which can be applied suitably for cosmetics etc.

  The present inventors have found that a specific plant extract (plant extract) that can be suitably used for cosmetics has an action of increasing OPH activity, in particular, increasing OPH-like activity in the human skin stratum corneum, The present invention has been reached.

That is, this invention relates to the OPH activity enhancer shown below.
1) Enhancing OPH activity comprising at least one plant extract selected from the group consisting of Acacia yak, Ogon, Genokosho, Rice bran, Salvia, Marjoram, Aloe, Usbenia, Enmeiso, Auren, Ononis, Rosehip, Sanshin, and Hibatsu Agent.

2) The OPH activity enhancer according to 1), wherein the plant extract is at least one selected from the group consisting of Ononis, Enmezo, Rice bran, Sancin and Hibatsu.
3) The OPH activity enhancer according to 1), wherein the plant extract is at least one selected from the group consisting of Enmezo, Rice bran, and Hibatsu.

4) A cosmetic comprising one or more OPH activity enhancers according to 1).
5) An external preparation for skin containing at least one OPH activity enhancer according to 1).

6) A food or drink containing one or more OPH activity enhancers according to 1).
7) A food additive containing one or more OPH activity enhancers according to 1).
8) A pharmaceutical comprising one or more OPH activity enhancers according to 1).
9) A quasi-drug containing one or more OPH activity enhancers according to 1).

  The OPH activity enhancer of the present invention is capable of enhancing OPH capable of preventing diseases and aging, particularly an OPH-like active ingredient in the human skin stratum corneum. Therefore, by blending the OPH activity enhancer of the present invention in cosmetics and skin external preparations, the OPH-like activity in the horny layer of the skin can be enhanced and the progress of skin aging can be suppressed.

It is a graph showing the OPH enzyme specific activity of the human skin stratum corneum extract of each part. It is a graph which shows the result of the OPH activity enhancement effect | action secondary screening of each plant extract. It is a graph which shows the relationship between a plant extract density | concentration and OPH activity rate. It is a graph which shows the relationship between an enamel extract concentration and a hi OPH activity enhancement rate.

  The OPH activity enhancer of the present invention is at least one kind of plant extract selected from the group consisting of Asenyaku, Ogon, Gennoshoko, Rice bran, Salvia, Marjoram, Aloe, Usbeneer, Oenothera, Auren, Ononis, Rosehip, Sancin, and Hihitsu Contains products (plant extracts).

(1) Plant extract Below, the plant used by this invention is demonstrated.
“Asenyaku” is a dry water extract obtained from leaves and young branches of Uncaria gambir Roxburgh (Rubiaceae; Rubiaceae).
“Ougon” is a dried root of the cut root of Scutellaria baicalensis Georgi (Labiatae).
"Ganoshoco" is the above-ground part of Geranium thunbergii Siebold et Zuccarini (Geraniaceae).
“Komenuka” Oryza sativa Linne (Gramineae) is the part of the pericarp, seed coat, germ, etc. that appears when rice of the grass family is refined.
“Salvia” Salvia officinalis Linne (Labiatae) is a Labiatae plant.
“Marjoram” Origanum majorana Linne (Labiatae) is a plant of the Labiatae family.
"Aloe" Aloe arborescens Miller is a plant of the lily family.
The "Usvenid mallow" Malva sylvestris Linne (Malvaceae) is a plant in the mallow family.
“Emisodia” Isodon japonicus Hara (Labiatae) is a Labiatae plant.
"Ouren" Coptis japonica Makino (Ranunculaceae) is a plant of the family Ranunculaceae.
"Ononis" Ononis spinosa (Leguminosae) is a legume plant.
"Rose hip" Rosa canina Linne (Rosaceae) is a plant of the Rosaceae family.
“Sansin” Gardenia jasminoides Ellis (Rubiaceae) is a plant of the Rubiaceae family.
“Hihatsu” Piper longum Linne is a plant belonging to the genus Pepperaceae.

  Among the above-mentioned plants, preferably at least one selected from the group consisting of Ononis, Enmeso, Rice bran, sancin and Hibatsu, more preferably at least one selected from the group consisting of Enniso, Koenuka and Hihatsu, especially Preferred is enamel.

  The plant extract used in the present invention may be extracted from any part of the plant described above, for example, extracted from whole grass, flowers, seeds, fruits, branches, stems, bark, roots, etc. It may be. Specifically, it is desirable to extract from the aerial part for enamel, from the root for onionis, from seed coat for rice bran, from fruit for sancin, and from fruit for jade. Further, the properties of the extract are not particularly limited, and may be any liquid or solid.

  A method for producing a plant extract, that is, a method for extracting an extract from a plant is not particularly limited, and a known method can be used. For example, extraction can be performed using a known extraction solvent such as water, alcohols such as ethanol, ethers, or a mixture thereof. More preferably, the method of extracting using water, ethanol, and the liquid mixture of water and ethanol is mentioned.

(2) Cosmetics or external preparation for skin OPH activity enhancer consisting of at least one (or one or a combination of two or more) extracts obtained from the above-described plants of the present invention is a cosmetic or It can be applied as an external preparation for skin.

  When blended in cosmetics, the blending ratio of the above-mentioned OPH activity enhancer can be appropriately selected according to the dosage form, application, use mode, etc., but preferably 0.001 to 10.0 wt. %, More preferably 0.01 to 5.0% by weight, particularly preferably about 0.1 to 1.0% by weight.

  The dosage form of the cosmetic is arbitrary, and any dosage form may be used as long as the effects of the present invention are not impaired. For example, it can be made into dosage forms such as lotions, emulsions, creams, ointments, packs, powders, aerosols and the like. Of these, preferred dosage forms are emulsions and creams.

  Moreover, the use of cosmetics is also arbitrary and may be any use as long as the effects of the present invention are not impaired. For example, cosmetics for skin care such as lotion, milky lotion, cream, sunscreen, makeup cosmetics such as makeup base, concealer, foundation, pressed powder and the like can be mentioned. In particular, those applied to the face cheek are preferred.

  In the cosmetic of the present invention, various optional components can be appropriately blended as necessary within a range not impairing the effects of the present invention. Examples of such optional components include solvents, colorants, preservatives, surfactants, fragrances, pigments, cooling agents, ultraviolet absorbers, thickeners, and the like.

  Such optional ingredients include, for example, macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, coconut oil, palm oil, liquid lanolin, hydrogenated coconut oil Oils such as hardened oil, mole, castor oil, beeswax, candelilla wax, carnauba wax, ibotarou, lanolin, reduced lanolin, hard lanolin, jojoba wax, mineral oil (mineral oil), waxes, liquid paraffin, squalane, pristane, Hydrocarbons such as ozokerite, paraffin, ceresin, petrolatum, microcrystalline wax;

  Cetyl isooctanoate, isopropyl myristate, hexyl decyl isostearate, diisopropyl adipate, di-2-ethylhexyl sebacate, cetyl lactate, diisostearyl malate, ethylene glycol di-2-ethylhexanoate, neopentyl glycol dicaprate, Di-2-heptylundecanoic acid glycerin, tri-2-ethylhexanoic acid glycerin, tri-2-ethylhexanoic acid trimethylolpropane, triisostearic acid trimethylolpropane, tetra-2-ethylhexanoic acid pentane erythritol, hydrogenated coco Esters such as glyceryl, polyglyceryl stearate, methyl paraoxybenzoate (methylparaben);

  Linear polysiloxanes such as dimethylpolysiloxane, methylphenylpolysiloxane, diphenylpolysiloxane, cyclic polysiloxanes such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexanesiloxane, amino-modified polysiloxane, polyether-modified poly Oil agents such as silicone oil such as siloxane, alkyl-modified polysiloxane, and modified polysiloxane such as fluorine-modified polysiloxane;

  Fatty acid soap (sodium laurate, sodium palmitate, etc.), anionic surfactants such as potassium lauryl sulfate, alkylsulfuric triethanolamine ether, cationic surfactants such as stearyltrimethylammonium chloride, benzalkonium chloride, laurylamine oxide , Imidazoline-based amphoteric surfactants (such as 2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt), betaine surfactants (such as alkylbetaines, amidebetaines, sulfobetaines), acyls Amphoteric surfactants such as methyl taurine, sorbitan fatty acid esters (such as sorbitan monostearate, sorbitan sesquioleate), glycerin fatty acids (such as glyceryl monostearate), propylene glycol Fatty acid esters (propylene glycol monostearate, etc.), hardened castor oil derivatives, glycerin alkyl ethers, sucrose fatty acid esters, surfactants such as nonionic surfactants such as alkyl glucoside;

Polyhydric alcohols such as polyethylene glycol, 1,3-butylene glycol and glycerin;
Higher fatty acids such as stearic acid;
Moisturizing ingredients such as sodium pyrrolidonecarboxylate, lactic acid, sodium lactate;

  Gua gum, quince seed, carrageenan, galactan, gum arabic, pectin, mannan, starch, curdlan, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, methylhydroxypropylcellulose, chondroitin sulfate, dermatan sulfate, glycogen, heparan sulfate, sodium hyaluronate, tragacanth gum , Keratan sulfate, chondroitin, mucoitin sulfate, hydroxyethyl guar gum, carboxymethyl guar gum, dextran, keratosulfate, locust bean gum, succinoglucan, carolinic acid, chitin, chitosan, carboxymethyl chitin, agar, polyvinyl alcohol, polyvinyl pyrrolidone, carboxy Polyacrylates such as vinyl polymer (carbomer) and sodium polyacrylate Le acid and / or salts thereof, polyethylene glycol, bentonite, thickeners such as particulate cellulose gel;

  Powders such as mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, anhydrous silicic acid (silica), aluminum oxide, barium sulfate, etc. which may be treated on the surface; may be treated on the surface Bengala, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen, zinc oxide inorganic pigments; surface treated pearlescent agents such as titanium mica, fish phosphorus foil, bismuth oxychloride; lake Red 202, red 228, red 226, yellow 4, blue 404, yellow 5, red 505, red 230, red 223, orange 201, red 213, Organic dyes such as yellow No. 204, yellow No. 203, blue No. 1, green No. 201, purple No. 201, red No. 204; polyethylene powder, polymethyl methacrylate, nylon powder, Organic powders such as organopolysiloxane elastomers;

  Paraaminobenzoic acid UV absorbers, anthranilic acid UV absorbers, salicylic acid UV absorbers, cinnamic acid UV absorbers, benzophenone UV absorbers, sugar UV absorbers, 2- (2'-hydroxy-5 ' UV absorbers such as -t-octylphenyl) benzotriazole, 4-methoxy-4'-t-butyldibenzoylmethane;

Lower alcohols such as ethanol and isopropanol;
Vitamin A or a derivative thereof, vitamin B6 hydrochloride, vitamin B6 tripalmitate, vitamin B6 dioctanoate, vitamin B2 or a derivative thereof, vitamin B such as vitamin B12, vitamin B15 or a derivative thereof, α-tocopherol, β-tocopherol, γ -Vitamin E such as tocopherol and vitamin E acetate, vitamin D, vitamin H, pantothenic acid, panthetin, pyrroloquinoline quinone and the like;

Also, menthol, cooling agents, etc. can be used as a cooling agent.
Further, as a whitening agent, L-ascorbic acid, sodium L-ascorbate, sodium ascorbate phosphate, magnesium ascorbate phosphate, sodium ascorbate sulfate, glyceryl ascorbate (polyglyceryl) ethers, glyceryl ascorbate ( Polyglyceryl) esters, ascorbic acid glucosides (glycosides), ascorbic acid alkyl esters, ascorbic acid alkyl ethers and other vitamin C and derivatives thereof, kojic acid, alptin, sulfur and the like can be used.

  When blended into a skin external preparation, the blending ratio of the OPH activity enhancer can be appropriately selected depending on the dosage form, application, use mode, etc., but preferably 0.001 to 10. It is 0% by weight, more preferably 0.01 to 5.0% by weight, particularly preferably about 0.1 to 1.0% by weight.

  Examples of the external preparation for skin include ointments, solutions, patches, sprays, liniments and the like, and the active ingredient can be absorbed into the body by transdermal administration.

  In the case of an ointment, as an optional component other than the above-mentioned OPH activity enhancer, those used in general ointments can be appropriately blended as necessary. For example, fat, fatty oil, lanolin, petrolatum as a base material , Waxes, resins, glycols, higher alcohols, glycerin, emulsifiers, suspending agents, and the like.

  In the case of a liquid agent, as an optional component other than the OPH activity enhancer, those used in general liquid agents can be appropriately blended as necessary. For example, a preservative (methyl paraoxybenzoate, propyl paraoxybenzoate) ), Sugars, sweeteners, ethanol, fatty oils, soap, glycerin, emulsifiers, suspending agents and the like.

  In the case of a patch, as an optional component other than the OPH activity enhancer, those used in general patches can be appropriately blended as necessary. For example, kaolin, essential oil components, menthol, mint oil, Eucalyptus oil, glycerin, propylene glycol, a suspending agent, an emulsifier, water and the like can be blended.

(3) Food / beverage products or food additives The OPH activity enhancer of the present invention can also be applied as food / beverage products or food additives containing one or more of these. Specific examples of food and drink include herbal tea and soft drinks. Specific examples of food additives include bread and confectionery.

  When blended in foods and drinks and food additives, the blending ratio of the OPH activity enhancer can be appropriately selected according to the application and use mode, but preferably 0.001 to 10.0 weight with respect to the total amount. %, More preferably 0.01 to 5.0% by weight, particularly preferably about 0.1 to 1.0% by weight.

(4) Drug or quasi-drug The OPH activity enhancer of the present invention can also be applied as a drug or quasi-drug containing one or more of these. Specific examples of pharmaceuticals include antidiabetic drugs. Specific examples of quasi drugs include whitening cosmetics.

  When blended in pharmaceuticals and quasi-drugs, the proportion of the OPH activity enhancer can be appropriately selected according to the application and usage, etc., but preferably 0.001 to 10.0 wt. %, More preferably 0.01 to 5.0% by weight, particularly preferably about 0.1 to 1.0% by weight.

Examples The present invention will be described below with reference to examples, but the present invention is not limited to these examples.
<Example 1>
(1) Extraction of OPH-like active ingredient in skin stratum corneum Hereinafter, a method for confirming the presence of OPH-like activity in the skin stratum corneum and purifying the OPH-like active ingredient in the skin stratum corneum will be shown.

  After applying a transparent adhesive tape (Nichibansello tape (CT-24): 24 mm x 80 mm) to the skin surface of each part of the upper arm inner part, lower arm outer part and face cheek part of one subject (male; 40s) Then, the stratum corneum was collected by peeling based on the tape stripping method. This was repeated three times at the same site, and the second (second layer) and third (third layer) were used. In addition, the test contents were fully explained to the subjects in advance, and the consent of the person's free intention was obtained.

  The cellophane tape from which the stratum corneum was collected was cut with scissors, and 2 mL of the stratum corneum extraction buffer was added and sonicated (40 KHz; 20 seconds × 4 times) to obtain a human skin stratum corneum extract. Here, the ultrasonic device used is a product name; US CREANER, manufactured by AS ONE. The stratum corneum extraction buffer used was Tris buffer (0.2M Tris-HCl Buffer; pH 7.4; containing 0.14M-NaCl, 0.1% -TritonX100) (manufactured by Wako Pure Chemical Industries, Ltd.).

(2) Measurement of specific activity of OPH enzyme The oxidative proteolytic enzyme (OPH) activity of the human skin stratum corneum extract obtained above was measured by the following method.

  A 96-well microplate (transparent) was injected with the human skin stratum corneum extract solution (180 μL) and then 50 mM-AAPA (acetyl-L-alanine p-nitroaniline) 50% -EtOH solution (20 μL) and incubated at 37 ° C. for 60 minutes. Incubation was performed to obtain a crude enzyme / substrate mixture. Before and after the incubation, the crude enzyme / substrate mixed solution was subjected to Abs. Absorbance at 405 nm was measured.

  The enzyme activity was calculated by a calibration curve using acylamino-acid-releasing enzyme (AARE; manufactured by Takara Bio Inc.) which is an OPH enzyme. On the other hand, the protein amount was measured by DC protein assay (lowry method), and OPH-like specific activity (μUnit / μg) was calculated.

  The results are shown in FIG. FIG. 1 is a graph showing the OPH enzyme specific activity of human skin stratum corneum extract at each site. According to this result, it can be seen that the OPH-like active ingredient in the human skin stratum corneum is contained especially in the face.

<Example 2: Primary screening for enhancing OPH activity by various plant extracts>
With respect to various plant extracts (hereinafter referred to as “plant extracts”), primary screening for an OPH activity enhancing effect was performed by the following method.

  In a 96-well microplate (black), Tris buffer (0.2 M Tris-HCl Buffer; pH 7.4) 150 to 240 μL, and then various plant extracts (1 mg / mL as a dry solid amount) in a 70% -EtOH solution; 10 μL and then AARE (0.5 U / mL); 10 μL and then AGE-HSA; 80 μL were injected and incubated at 37 ° C. for 18 hours to obtain an enzyme / substrate mixture.

  Here, the AGE-HSA (human serum albumin final glycation product) was mixed with 20 mL of a human serum albumin aqueous solution adjusted to a concentration of 40 mg / mL, 10 mL of 2 mol / L glucose, 0.1 M phosphate buffer (pH 7. 4) It was obtained by adding 50 mL and 20 mL of water and incubating at 60 ° C. for 40 hours.

  Fluorescence intensity (Ex; 370 nm, Em; 430 nm) of the enzyme / substrate mixture obtained after the incubation was measured with a fluorescence intensity measuring apparatus (manufactured by TECAN, product name: infinite F200PRO). The decrease rate increase rate when the plant extract was added when the fluorescence intensity decrease amount when the plant extract was not added was used as a reference (0%) was shown as the OPH activation rate. The results are shown in Table 1 <Results of primary screening for enhancing OPH activity of various plant extracts>.

<Example 3; Secondary screening for enhancing OPH activity>
As a plant extract, Asenyaku, Ogon, Genokosho, Rice bran, Salvia, Marjoram, Aloe, Usbeneer, Enmussel, Auren, Ononis, and Rosehip were selected.

  A mixture of enzyme and substrate was used in the same manner as in Example 2 except that each plant extract selected above, AGE-HSA, and Tris buffer were mixed, and finally AARE was added and incubated at 37 ° C. for 1 hour. Got.

  Fluorescence intensity was measured immediately after addition of AARE and after incubation for 1 hour at 37 ° C., and the activity enhancement rate was calculated when the OPH activity when no plant extract was added was taken as 100%. The results are shown in FIG. FIG. 2 is a graph showing the results of the secondary screening for enhancing the OPH activity of each plant extract.

<Example 4>
As a plant extract, Asenyaku, Rice bran, Enmiso and Hibatsu were selected.
In Example 2, each plant extract, AGE-HSA, and Tris buffer selected above were mixed, and finally AARE was added and incubated at 37 ° C. for 1 hour, followed by the same method as in Example 2. A saccharification product mixture was obtained. A saccharification product mixture in which the concentration (mg / mL) of each plant extract was changed was similarly prepared, and the OPH activity rate was measured. The OPH activity rate represents the rate of increase in the amount of decrease when the plant extract is added when the amount of decrease in fluorescence intensity when the plant extract is not added is 100%.

  The obtained results are shown in FIG. FIG. 3 is a graph showing the relationship between plant extract concentration and OPH activity rate. According to this, concentration dependency was confirmed in the yellow-necked peas, hihatsu and rice bran.

<Example 5>
An enamel was selected as a plant extract, and extracts having three concentrations of 25 μg / mL, 50 μg / mL, and 125 μg / mL (each as an amount of a solid product obtained by ignition) were prepared. In Example 3, it carried out similarly except having used the said three kinds of concentration of the Amesia extract as a plant extract, and the OPH activity enhancement rate was calculated | required. The results are shown in FIG. FIG. 4 is a graph showing the relationship between the concentration of enamel extract and the enhancement rate of HIOPH activity. According to this, it was confirmed that at least the enamel extract has an action of enhancing the OPH activity extracted from the horny layer of the skin.

The OPH-like active ingredient confirmed in the human skin stratum corneum is considered to have OPH present in the human skin stratum corneum since the active fraction coincided with the AARE which is OPH. In addition, it has been confirmed that a specific plant extract (plant extract) that can be suitably used for cosmetics has an effect of increasing OPH activity, and in particular, it increases OPH activity in human skin stratum corneum.
Therefore, the skin OPH activity enhancement by cosmetics and skin external preparations is promoted by incorporating the OPH activity enhancer containing the specific plant extract (plant extract) of the present invention into the cosmetics and skin external preparations, and the skin aging progresses. Can be suppressed.

Claims (9)

  An OPH activity potentiator comprising at least one plant extract selected from the group consisting of Acacia yak, Ogon, Genokosho, Rice bran, Salvia, Marjoram, Aloe, Usbenia, Enmeiso, Auren, Onis, rosehip, sancin, and baboon.   2. The OPH activity enhancer according to claim 1, wherein the plant extract is at least one selected from the group consisting of Ononis, Enmeso, Rice bran, Sancin and Hibatsu.   The OPH activity enhancer according to claim 1, wherein the plant extract is at least one selected from the group consisting of Cyprus, Rice bran, and Hibatsu.   A cosmetic comprising one or more OPH activity enhancers according to claim 1.   A skin external preparation containing one or more OPH activity enhancers according to claim 1.   A food or drink comprising at least one OPH activity enhancer according to claim 1.   A food additive comprising at least one OPH activity enhancer according to claim 1.   A pharmaceutical comprising at least one OPH activity enhancer according to claim 1. A quasi-drug containing one or more OPH activity enhancers according to claim 1.

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