JP2018184349A - Eyelid skin surface impression improver and screening method therefor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a component that improves an eyelid skin surface impression.SOLUTION: A component that improves an eyelid skin surface impression is searched for, with a fast muscle mass used as an index. A fast muscle enhancing component is used as an eyelid skin surface impression improver. Preferable examples of the fast muscle enhancing component include a combination of extract from Cydonia sp. plants and extract from Lilium sp. plants, or extract from Paeonia sp. plants.SELECTED DRAWING: None

Description

  The present invention relates to an eyelid skin surface impression improving agent and a screening method thereof.

The eyes are the parts that greatly affect the appearance of the face.
Since the skin of the eyes is thin and is frequently moved by blinking, aging symptoms are likely to appear, and there is a great interest in improving the symptoms. Conventionally, it has been proposed to eliminate typical aging symptoms such as wrinkles in the corners of the eyes and talmi (sagging) of the skin under the eyes by moisturizing or applying collagen.
In addition, as the skin ages, the eyelid skin is also denatured and altered, and it is not preferable because it loses its elasticity and feels like a shabby, has a rough surface and gives an impression of aging. However, no elucidation of the cause and sufficient improvement measures have been reported for such a relaxed state.

  By the way, it is known that certain plant extracts have an effect of strengthening muscles (Patent Documents 1 and 2). Moreover, various things other than a plant extract are reported as what strengthens a fast muscle among muscles (patent documents 3-5, nonpatent literature 1).

Japanese Patent Laying-Open No. 2015-157785 JP 2008-214315 A International Publication No. 2012/026575 Pamphlet Japanese Patent Laid-Open No. 2013-100302 JP 2002-053489 A

Jobgen W., et al., J. Nutr. 2009 Feb; 139 (2): 230-7

In recent years, due to increasing interest in anti-aging, there is a demand for countermeasures against old impressions caused by changes in the surface of the eyelid skin, but effective improvement measures are not yet known. The reason is that the cause of the change in the surface of the eyelid skin that causes such an impression is not clearly known.
In view of such circumstances, an object of the present invention is to establish a method for searching for a component that improves the eyelid skin surface impression, and to provide an effective eyelid skin surface impression improving agent.

As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that the decline of the ocular muscles (muscles around the eyes), which are facial muscles, is the cause of changing the impression of the eyelid skin surface. I found it. That is, when the ocular muscles decrease, the supported skin is denatured and deformed, and not only the dents and bulges of the eyelid skin change, but also a finer uneven shape is generated on the surface. It turns out that it gives the impression that it has lost its elasticity. Furthermore, the present inventors have found that when the fast muscles that occupy about 90% of the ocular muscles are strengthened, the ocular muscles are strengthened, the unevenness of the eyelid skin is reduced, and the smoldering impression is reduced. It was. The inventors have conceived that a fast muscle enhancing component can be an effective component of an eyelid skin surface impression improving agent, and have completed the present invention by searching for such component.

That is, the present invention is as follows.
[1] An eyelid skin surface impression improving agent comprising a fast muscle enhancing component.
[2] The fast muscle enhancing component is a combination of an extract of a genus Rosaceae (Cydonia sp.) And an extract of a lily family (Lilium sp.), Or a button family (Paeonia sp.). The eyelid skin surface impression improving agent according to [1], which is an extract of
[3] The eyelid skin surface impression improving agent according to [2], wherein the Rosaceae quince plant is quince (Cydonia oblonga).
[4] The eyelid skin surface impression-improving agent according to [2] or [3], wherein the lily family lily plant extract is an extract of roots of madonna lily (Lilium candidum).
[5] The eyelid skin surface impression improving agent according to [2], wherein the button family button genus plant is peony (Paeonia lactiflora).
[6] An anti-aging cosmetic comprising the eyelid skin surface impression improving agent according to any one of [1] to [5].
[7] The anti-aging cosmetic according to [6], which is for eyes.
[8] A screening method for an eyelid skin surface impression improving agent, characterized by using the amount of fast muscle as an index.
[9] The amount of fast muscle is a gene encoding myosin heavy chain protein 2 or the expression level of the protein, and the expression level in a cell to which a test substance is added is an expression level in a cell to which no test substance is added The method according to [8], wherein the test substance is determined to have an action to improve the eyelid skin surface impression when the test substance is larger than
[10] When the expression level in the cell to which the test substance is added is 120% or more of the expression level in the cell to which the test substance is not added, it is determined that the test substance has an eyelid skin surface impression improving effect. The method according to [9].

  According to the present invention, an eyelid skin surface impression improving agent suitable for inclusion in an anti-aging cosmetic is provided. Moreover, the screening method which can search an effective component as an eyelid skin surface impression improving agent is provided.

It is a drawing substitute photograph which shows that the change of the eyelid skin surface impression gives an old impression. (Left) Eyes that have elasticity, have a slick eyelid, and give a youthful impression. (Right) Gives the impression of aging, with an eyelid with fine irregularities on the surface, with a soft and soft impression.

<1> Eyelid skin surface impression improving agent The eyelid skin surface impression improving agent of the present invention comprises a fast muscle enhancing component.
The fast muscle enhancing component is a component that increases the amount of fast muscle, for example, a component that promotes the production of fast muscle, or a component that suppresses the degradation of fast muscle.
Such a fast muscle enhancement component increases the amount of ocular muscles that make up about 90% of the fast muscles, so that the skin dents and bulge changes supported by the fast muscles, and the uneven shape of the surface In addition, the stubborn impression and the non-harsh feel caused by these are improved, and the surface impression of the eyelid skin is comprehensively improved.

In the present specification, the “eyelid skin surface impression” means a change in the dent or bulge portion of the eyelid skin (position change or disappearance), resulting in fine irregularities on the surface, and shadows caused by these shapes. This refers to the impression of a sizzling appearance and / or a firm feeling when touching such a state (see the right side of FIG. 1). In general, it is distinguished from “tarmi / slack” which represents the drooping of the skin under the eyes.
The improvement in the eyelid skin surface impression is, for example, observing the appearance of the eyelid, preferably the upper eyelid, to determine whether the unevenness has disappeared or relaxed, or touching the eyelid, preferably the upper eyelid, It can be confirmed by determining whether or not there is a sense of touch and elasticity.

As the fast muscle enhancing component in the present invention, a combination of an extract of genus Rosaceae (Cydonia sp.) And an extract of Lilium sp. ) Is preferred.
Although it does not specifically limit as said Rosaceae quince plant, A quince (Cydonia oblonga) is mentioned preferably.
Although it does not specifically limit as said lily family Lily plant, Madonna lily (Lilium candidum) is mentioned preferably, The extract of the root is more preferable.
Although the said button family button genus plant is not specifically limited, Peonies (Paeonia lactiflora) are mentioned preferably.
The plant extract may be any extract that is usually used in cosmetics and pharmaceutical skin external preparations, and those extracted from a plant by a conventional method can be used.

The administration route of the eyelid skin surface impression improving agent of the present invention is not particularly limited, but is usually transdermal.
The dose is not particularly limited, but considering the desired effect and safety, for example, when the fast muscle enhancing component is a plant extract and is transdermally administered, it is 0.0002 to 0 in terms of solid matter. 0.05 mg / day is preferred.

  The eyelid skin surface impression-improving agent of the present invention can be contained in any composition, and is particularly preferably a composition for external use that can be expected to have an effect of percutaneous absorption. The form of the external composition for skin is not particularly limited as long as it is externally applied to the skin, but preferably includes cosmetics (including quasi-drugs) and pharmaceuticals, and cosmetics are more preferable. Aging cosmetics are more preferred. Furthermore, the anti-aging cosmetic is suitable for those applied to the eyes, particularly the eyelids.

  Examples of the dosage form of the composition for external skin include, but are not particularly limited to, a lotion dosage form, an emulsifier type such as emulsion and cream, an oil dosage form, a gel dosage form, a pack, and a cleaning agent.

  When the eyelid skin surface impression-improving agent of the present invention is contained in cosmetics, the total amount thereof is preferably 0.001% to 20% by mass, more preferably 0.01 to 10% by mass with respect to the total amount of cosmetics. %, More preferably 0.05 to 5% by mass, the desired effect can be easily obtained and the degree of freedom in formulating design can be ensured.

The cosmetics of the present invention can optionally contain, in addition to the eyelid skin surface impression improving agent, components that are blended in ordinary cosmetics as long as the effects of the present invention are not impaired.
Examples of such components include 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, and hardened oil. Oil, wax, oils, waxes; liquid paraffin, squalane, pristane, ozokerite, paraffin, ceresin, petrolatum, microcrystallin, oil, wax, oil, wax, wax candy, bean wax, candelilla wax, carnauba wax, ibotarou, lanolin, reduced lanolin Hydrocarbons such as wax; higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, undecylenic acid; cetyl alcohol, stearyl alcohol, isostearyl alcohol Alcohol, behenyl alcohol, octyldodecanol, higher alcohol such as myristyl alcohol, cetostearyl alcohol, etc .; cetyl isooctanoate, isopropyl myristate, hexyldecyl isostearate, diisopropyl adipate, di-2-ethylhexyl sebacate, cetyl lactate, apple Diisostearyl acid, ethylene glycol di-2-ethylhexanoate, neopentyl glycol dicaprate, glycerin di-2-heptylundecanoate, glycerin tri-2-ethylhexanoate, trimethylolpropane tri-2-ethylhexanoate, Synthetic ester oils such as trimethylolpropane triisostearate and pentane erythritol tetra-2-ethylhexanoate; dimethylpolysiloxane, methylphenylpolysiloxane Chain polysiloxanes such as diphenylpolysiloxane; cyclic polysiloxanes such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexanesiloxane; amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, Oil agents such as silicone oils such as modified polysiloxanes such as fluorine-modified polysiloxanes;

  Anionic surfactants such as fatty acid soap (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, alkylsulfuric acid triethanolamine ether; cationic surfactants such as stearyltrimethylammonium chloride, benzalkonium chloride, laurylamine oxide Class: imidazoline amphoteric surfactant (2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt, etc.), betaine surfactant (alkyl betaine, amidobetaine, sulfobetaine, etc.), acyl 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 (such as propylene glycol monostearate), hydrogenated castor oil derivative, glycerin alkyl ether, POE sorbitan fatty acid esters (such as POE sorbitan monooleate, polyoxyethylene sorbitan monostearate), POE sorbite fatty acid esters ( POE-sorbitol monolaurate, etc.), POE glycerin fatty acid esters (POE-glycerin monoisostearate, etc.), POE fatty acid esters (polyethylene glycol monooleate, POE distearate, etc.), POE alkyl ethers (POE2-octyldodecyl ether) Etc.), POE alkyl phenyl ethers (POE nonyl phenyl ether, etc.), Pluronic types, POE / POP alkyl ethers (POE / POP2-dec) Tetradecyl ether, etc.), Tetronics, POE castor oil / hardened castor oil derivatives (POE castor oil, POE hardened castor oil, etc.), nonionic surfactants such as sucrose fatty acid esters, alkyl glucosides; polyethylene glycol, glycerin 1,3-butylene glycol, erythritol, sorbitol, xylitol, maltitol, propylene glycol, dipropylene glycol, diglycerin, isoprene glycol, 1,2-pentanediol, 2,4-hexanediol, 1,2-hexanediol Polyhydric alcohols such as 1,2-octanediol;

Moisturizing components such as sodium pyrrolidone carboxylate, lactic acid, sodium lactate; mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, anhydrous silicic acid (silica), aluminum oxide, sulfuric acid, which may be treated on the surface Powders such as barium; inorganic pigments such as bengara, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen, titanium oxide, and zinc oxide that may be treated on the surface; even if the surface is treated Pale agents such as good mica titanium, fish phosphorus foil, bismuth oxychloride; red 202, red 228, red 226, yellow 4, blue 404, yellow, which may be laked No. 5, Red No. 505, Red No. 230, Red No. 223, Orange No. 201, Red No. 213, Yellow No. 204, Yellow No. 203, Blue No. 1, Green No. 201, Purple No. 201, Organic dyes such as color No. 204; organic powders such as polyethylene powder, polymethyl methacrylate, nylon powder, organopolysiloxane elastomer; paraaminobenzoic acid UV absorbers; anthranilic acid UV absorbers; salicylic acid UV absorbers Agent: Cinnamic acid UV absorber; Benzophenone UV absorber; Sugar UV absorber; 2- (2'-hydroxy-5'-t-octylphenyl) benzotriazole, 4-methoxy-4'-t-butyl UV absorbers such as dibenzoylmethane;

Lower alcohols such as ethanol and isopropanol; vitamin A or a derivative thereof, vitamin B ₆ hydrochloride, vitamin B ₆ tripalmitate, vitamin B ₆ dioctanoate, vitamin B ₂ or a derivative thereof, vitamin B ₁₂ , vitamin B ₁₅ or a derivative thereof Vitamin B such as α-tocopherol, β-tocopherol, γ-tocopherol, vitamin E acetate and other vitamin E, vitamin D, vitamin H, pantothenic acid, pantethenic acid, pyrroloquinoline quinone and the like; methyl paraben, Antibacterial agents (preservatives) such as ethyl paraben, butyl paraben and phenoxyethanol; anti-inflammatory agents such as glycyrrhizic acid derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, zinc oxide, allantoin; retinol, ascorbine Wrinkle improving agents such as acid, tocopherol, or farnesyl acetate; various extracts (eg, buckwheat, auren, shikon, peonies, assembly, birch, sage, loquat, carrot, aloe, mallow, iris, grape, yokinein, loofah, Saffron, senkyu, ginger cucumber, onionis, garlic, red pepper, chimney, red pepper, seaweed, etc.); activators such as royal jelly, photosensitizers, cholesterol derivatives, etc .; And anti-seborrheic agents such as thianthol; anti-inflammatory agents such as tranexamic acid, thiotaurine and hypotaurine; and water-soluble polymers such as collagen and hyaluronic acid.

In addition to the eyelid skin surface impression improving agent of the present invention, the cosmetic material of the present invention also contains components for the eyelid skin surface impression improving agent, components for preventing and improving skin aging such as tarmi and wrinkles on the eyes, etc. May be.
The cosmetic of the present invention can be produced without difficulty by treating and blending the above-mentioned components according to a conventional method. The dosage form is not particularly limited, such as a lotion form, an emulsifier form, and an oil form, and any form can be adopted.

<2> Screening method for eyelid skin surface impression improving agent The screening method of the present invention is a method for screening an eyelid skin surface impression improving agent, characterized by using the amount of fast muscle as an index.

  In a preferred embodiment of this method, the amount of fast muscle refers to the expression level of myosin heavy chain protein 2, more preferably myosin heavy chain protein IIx / d (MYH1), myosin heavy chain protein IIa (MYH2), myosin heavy chain The expression level of protein IIb (MYH4) or a gene encoding each protein, more preferably the expression level of the gene encoding MYH2 or the protein. In the present specification, the expression level refers to either the transcription level of mRNA of the gene or the translation level of the protein encoded by the gene.

  In a preferred embodiment of the screening method of the present invention, when the expression level of MYH1, MYH2, or MYH4 in the cell to which the test substance is added is larger than the expression level in the cell to which the test substance is not added, the test The substance is determined to have an effect of improving the eyelid skin surface impression.

In a more preferred embodiment of this method, the amount of slow muscle is also used as an index.
Here, the amount of slow muscle is usually the expression level of a gene encoding myosin heavy chain protein B (MYH7) or the protein.

In a more preferred embodiment of the screening method of the present invention, the expression level of MYH1, MYH2, or MYH4 in the cell to which the test substance is added is larger than the expression level in the cell to which the test substance is not added, and the test is performed. When the expression level of MYH7 in the cell to which the substance is added is not smaller than the expression level in the cell to which the test substance is not added, it is determined that the test substance has an eyelid skin surface impression improving effect.

The expression level of the gene can be measured using any method. For example, PCR is performed using a DNA fragment having a sequence that specifically binds to the sequence of the gene as a primer, and quantitative detection is performed. The human gene sequences encoding the above-described myosin are publicly disclosed, and those skilled in the art can design primers appropriately and use them for PCR.
In addition, for example, the intracellular expression level of the protein may be measured by a conventional method, for example, an immunological technique using an antibody or the like to obtain the gene expression level.

Although it does not specifically limit as a cell used for the screening method of this invention, Usually, a skeletal muscle cell or a skeletal muscle myoblast is used. In a more preferred embodiment, myotube-formed skeletal muscle cells or skeletal muscle myoblasts are used.
Cell culture conditions can be applied without particular limitation as long as the culture conditions do not hinder the execution of the screening method of the present invention, specifically the measurement of the expression level, in addition to the normal culture conditions. Can do.

The test substance targeted by the screening method of the present invention may be a pure substance, an extract derived from animals or plants, or a mixture thereof.
The extracts derived from animals and plants mean not only animal or plant-derived extracts themselves, but also generic names of extract fractions, purified fractions, extracts or fractions, solvent removal products of purified products, Examples of plant-derived extracts include native or grown plants, extracts that are sold as herbal medicine raw materials, commercially available extracts, and the like.
In addition to using the whole plant part of the plant, the plant part, the above-ground part, the rhizome part, the tree trunk part, the leaf part, the stem part, the flower, the floret, the fruit, etc. can be used. Or it is preferable to improve the extraction efficiency by chopping. Extraction solvents include water, alcohols such as ethanol, isopropyl alcohol and butanol, polyhydric alcohols such as 1,3-butanediol and polypropylene glycol, ketones such as acetone and methyl ethyl ketone, ethers such as diethyl ether and tetrahydrofuran. One or two or more selected from polar solvents such as the above can be exemplified as suitable ones. As a specific extraction method, for example, 1 to 30 parts by mass of a solvent is added to 1 part by mass of a part used for extraction of a plant or the like or a dried product thereof. For example, after immersion for several hours and cooling to room temperature, the insoluble matter and / or solvent may be removed if desired, followed by fractional purification by column chromatography or the like.

An example of the procedure in the screening method of the present invention is given below, but is not limited to the following contents without departing from the gist of the present invention, and can be implemented with appropriate modifications.
First, a test substance is added to skeletal muscle cells that have been myotube-formed and incubated for 24 hours. Thereafter, mRNA is extracted from the cells, and the expression level of a gene encoding a myosin heavy chain protein (MYH2, etc.) relating to the fast muscle as an indicator is subjected to RT-PCR using a primer that specifically detects the gene. Measure quantitatively. As a control, the expression level of the gene is also measured in cells to which no test substance was added. When the expression level of the gene in the cell to which the test substance is added is larger than the expression level (control) of the gene in the cell to which the test substance is not added, preferably 120% or more than the control When it is preferably 135% or more, more preferably 150% or more, it is determined that the test substance is a fast muscle enhancing component and has an effect of improving the eyelid skin surface impression.
When also measuring the expression level of a gene encoding a myosin heavy chain protein (MYH7, etc.) relating to the slow muscle, the expression level of the gene in the cell to which the test substance is added is equal to the gene in the cell to which the test substance is not added. The test substance is a component that does not reduce slow muscles when it becomes larger than the expression level (control), preferably 100% or more of the control, and screening using the fast muscle mass as an index It is determined that the fast muscle-enhancing component selected by the method does not prevent adoption of the eyelid skin surface impression improving agent.

  EXAMPLES Hereinafter, although an Example demonstrates this invention still in detail, this invention is not limited to a following example, unless the summary is exceeded.

<Example 1> Screening of eyelid skin surface impression improving agent The eyelid skin surface impression improving agent was screened by using the expression levels of MYH2 and MYH7 as indicators in the following procedure.
Human cultured skeletal muscle cells were seeded in a 96-well multiwell plate together with a growth medium, and then cultured until 60% confluent. Thereafter, the culture medium was changed to a differentiation medium, and cultured for 10 days while changing the differentiation medium every 3 days to form myotubes. The plant extract shown in Table 1 was added thereto as a test substance (1 μL / well), cultured for 24 hours, the medium was removed, and cDNA was obtained using FastLane Cell cDNA Kit (QIAGEN). Real-time PCR was performed using QuantTect Primer Assay, and the amounts of MYH2 and MYH7 mRNA were measured (n = 3). As an endogenous control, the amount of ACTB mRNA was also measured and analyzed by the ratio to the amount of ACTB mRNA. The primers listed in Table 2 (QIAGEN) were used. For comparison, the amount of mRNA (control) in skeletal muscle cells cultured in the same manner except that only the test substance dilution solvent was added was also measured.

  Table 2 shows the relative expression level when the control mRNA expression level is "1". When the combination of the quince extract and the Madonna lily root extract and the peony extract were added, an increase in the gene expression level of MYH2, which is an index of fast muscle mass, was observed. In the above case, no decrease in the gene expression level of MYH7, which is an indicator of slow muscle mass, was observed.

<Test Example 2> Evaluation of the effect of improving the eyelid skin surface impression by the fast muscle-enhancing component The eyelid skin surface impression was improved with respect to the plant extract that was found to increase the expression level of MYH2 mRNA in the above example by the following procedure. Evaluated.

  According to the formulation of Table 3, a skin external preparation (eye cream) containing a plant extract was prepared by a conventional method.

Thirty healthy 40-60 year old female panelists applied any of the above-prepared skin external preparations to the eyes (around both eyes) for 8 weeks every morning and evening (5 people in each group).
Eight weeks after the start of application, a skilled evaluator determined the appearance and feel of the upper and lower eyelids of the paneler according to the following criteria, and the average score of the five was used as the score for each external preparation for skin. The results are shown in Table 3.
(Appearance of upper and lower eyelids)
5: Conspicuous irregularities are conspicuous, accompanied by dents and bends 4: Concavities and convexities are connected and looks like wrinkled grooves 3: Irregularities are conspicuous and are recognized in the figure shape 2: Irregularities are observed 1: There are no irregularities 1: Flat and smooth Looks like (feeling of upper and lower eyelids)
5: There is no firmness and soft touch feeling 4: 3 Touch between 3 and 5 3: Soft feel without touch 2: 2 Touch between 2 and 1 1: There is firmness with bread and smooth touch

According to the present invention, an effective component as an eyelid skin surface impression improving agent can be searched, and an eyelid skin surface impression improving agent suitable for anti-aging cosmetics and the like is provided, which is very useful industrially.

Claims (10)

  An eyelid skin surface impression improving agent comprising a fast muscle enhancing component.   The fast muscle-enhancing component is a combination of an extract of the genus Rosaceae (Cydonia sp.) And an extract of the Lilium sp. (Lilium sp.), Or an extract of the Button genus Button (Paeonia sp.) The eyelid skin surface impression improving agent of Claim 1 which is a thing.   The eyelid skin surface impression improving agent of Claim 2 whose said Rosaceae quince plant is a quince (Cydonia oblonga).   The eyelid skin surface impression improving agent according to claim 2 or 3, wherein the lily family lily plant extract is an extract of roots of Lilium candidum.   The eyelid skin surface impression-improving agent according to claim 2, wherein the button family button genus plant is peony (Paeonia lactiflora).   An anti-aging cosmetic comprising the eyelid skin surface impression improving agent according to any one of claims 1 to 5.   The anti-aging cosmetic according to claim 6, wherein the cosmetic is for eyes.   A screening method for an eyelid skin surface impression improving agent, characterized by using fast muscle mass as an index. The amount of fast muscle is the gene encoding myosin heavy chain protein 2 or the expression level of the protein,
The test substance is judged to have an effect of improving the eyelid skin surface impression when the expression level in the cell to which the test substance is added is larger than the expression level in the cell to which the test substance is not added. The method described in 1.   When the expression level in the cells to which the test substance is added is 120% or more of the expression level in cells to which the test substance is not added, it is determined that the test substance has an eyelid skin surface impression improving effect. Item 10. The method according to Item 9.