Beauty treatment instrument

Abstract

To provide a method for improving aging by using a new mechanism different from agents for improving facial aging such as reduction of skin tension and skin looseness or known means for improving facial aging.SOLUTION: There is provided a beauty treatment method for improving skin looseness, wrinkles or facial leanness by focusing on a relation between skin looseness and arrector pili muscle and activating or proliferating arrector pili muscle cells.SELECTED DRAWING: Figure 15

Description

[Technical field]

[0001] The present invention relates to a beauty device that activates arrector pili muscle cells. [Background technology]

[0002] Sagging skin has a large impact on the appearance of age, and maintaining the firmness of the skin and improving sagging is a major cosmetic challenge. Loss of firmness of the skin leads to sagging, wrinkles, or sagging, which gives the impression of aging. Skin firmness is mainly due to the thickness of the dermis, and firm skin is rich in elastic fibers such as collagen and elastin that fill the dermis. It is known that the function of dermal fibroblasts decreases due to the influence of aging and exposure to ultraviolet rays, and matrix metalloproteinase is activated. As a result, the dermis layer becomes thinner due to the decrease in elastic fibers such as collagen and elastin, and the skin loses firmness, resulting in sagging, wrinkles, or sagging. On the other hand, the cause of the decrease in firmness of the skin is not necessarily only the thickness of the dermis layer, and it is also known that the loss of firmness due to the weakening of facial muscles and the increase in subcutaneous fat causes sagging, wrinkles, or sagging. Conventional cosmetic methods have focused on increasing collagen, elastic fibers, and the like by activating dermal fibroblasts or inhibiting the decomposition of collagen, elastic fibers, and the like in order to improve sagging. Components that have an effect of activating dermal fibroblasts, promoting collagen production, or inhibiting the decomposition of collagen have been discovered and are being applied to cosmetics. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] JP 2012-144499 A [Patent Document 2] JP 2013-014555 A Summary of the Invention [Problem to be solved by the invention]

[0004] To provide a method for improving sagging by utilizing a new mechanism different from the sagging mechanisms found so far. [Means for solving the problem]

[0005] The present inventors have conducted intensive research to identify the causes of facial aging, such as loss of firmness and sagging, and have surprisingly found a relationship between skin sagging and elasticity and the amount of arrector pili muscle. Furthermore, as a result of further research, they have found that stem cell-like cells exist in the arrector pili muscle, and that the stem cell-like cells proliferate when physical stimulation is applied. Furthermore, the inventors discovered that stem cell-like cells present in the arrector pili muscle express adrenergic receptors, and that stem cell-like cells can be activated and / or proliferated by activating the adrenergic receptors, leading to the present invention.

[0006] The present invention thus relates to: [1] A cosmetic method comprising activating and / or proliferating arrector pili muscle cells. [2] The cosmetic method described in item 1, which improves sagging, wrinkles, or sagging skin. [3] The cosmetic method according to item 1 or 2, wherein the arrector pili muscle cells proliferate in response to physical stimulation of the skin or stimulation via an adrenergic receptor in the arrector pili muscle cells. [4] The cosmetic method described in item 3, wherein the physical stimulation is a stretching stimulation in the direction of the arrector pili muscles. [5] The method according to item 3, wherein the stimulation of arrector pili muscle cells via adrenergic receptors is achieved by administering a catecholamine compound to the skin. [6] The method according to item 3, wherein the stimulation of arrector pili muscle cells via adrenergic receptors is stimulation by emotional stimulation-induced release of noradrenaline in vivo. [7] A method for screening treatments for improving sagging, wrinkles, or sagging skin, using the activity of stem cell-like cells present in the arrector pili muscle as an indicator. [8] The screening method described in Item 7, wherein the stem cell-like cells are CD34-positive cells. [9] The screening method comprises the steps of: performing skin organotypic culture; applying a candidate treatment to the skin organ; Measuring the activity of stem cell-like cells present in the arrector pili muscle; 9. The screening method according to item 7 or 8, comprising:

[10] The screening method of item 9, wherein the candidate treatment is culturing the skin organ in a solution containing a candidate drug.

[11] Culturing an adrenergic receptor-expressing cell in a solution containing a candidate drug; Measuring the activity of the adrenergic receptor expressing cells The present invention relates to a method for screening for an agent for activating sagging and arrector pili muscle cells, the method comprising the steps of:

[12] The method for screening an arrector pili cell activating agent according to Item 11, wherein the adrenergic receptor-expressing cells are selected from the group consisting of smooth muscle cells, cardiac muscle cells, nerve cells, and cells transfected with an adrenergic receptor gene.

[13] The screening method according to item 11 or 12, wherein the arrector pili muscle cell activator is an agent for improving sagging, wrinkles, or alopecia.

[14] The method according to item 12, wherein the smooth muscle cells are selected from the group consisting of vascular muscle cells, arrector pili muscle cells, and uterine muscle cells.

[15] A composition for stimulating smooth muscle cells, comprising licorice extract.

[16] The enhancer composition according to Item 15, further comprising raspberry extract.

[17] The stimulating composition according to item 15 or 16, wherein the smooth muscle cells are selected from the group consisting of vascular muscle cells, arrector pili cells, and uterine muscle cells.

[18] A composition for improving sagging, wrinkles, or sagging skin, comprising the composition for activating smooth muscle cells according to any one of items 15 to 17.

[19] A beauty device including an imaging unit, a probe unit having an extension direction adjustment mechanism, and an information processing unit, The information processing unit processes the image captured by the imaging unit to determine the hair flow; The information processing unit determines the extension direction based on the flow of the hair; The extension direction adjustment mechanism of the probe portion adjusts the angle of the probe portion in the determined extension direction. The beauty device comprising:

[20] An apparatus for determining skin stretch direction for massage, comprising: A photographing unit that takes facial images; An information processing unit that analyzes the captured facial image and determines the hair flow and / or the extension direction along the hair flow; and an output unit for displaying the hair flow and / or the direction of extension along the hair flow; The apparatus comprising:

[21] A program for controlling an apparatus for determining a skin stretching direction for a massage, the apparatus including an imaging unit, an information processing unit, and an output unit, A command to activate the information processing unit to analyze the face image captured by the imaging unit and determine the hair flow and / or the extension direction along the hair flow; A command to display on an output unit the determined hair flow and / or the extension direction along the hair flow. The program comprising: Effect of the Invention

[0007] By utilizing a new mechanism, it is possible to effectively improve facial aging, such as loss of firmness, sagging, wrinkles, and sunken skin. In addition, by focusing on the new mechanism, it is possible to provide a new screening method, and a new drug selected by the screening method is provided. [Brief description of the drawings]

[0008] [Figure 1] Figure 1 shows a cylindrical skin slice taken as is, or with pressure applied from the epidermal side, and then X-ray CT scan was performed. The 3D display of the skin slice with pressure applied shows the amount of movement as a heat map. [Diagram 2]Figure 2A shows the coordinates of a circular skin sample, Figure 2B shows pressure being applied from above the circular sample, and Figure 2C is a graph showing the resistance to vertical deformation of the skin of young and elderly subjects. [Diagram 3] Figure 3A shows a heat map of skin mobility when pressure is applied to a circular skin sample, and Figure 3B shows a heat map image of the circular sample with the structure within the circular sample overlaid. [Figure 4] FIG. 4 is a graph showing the deformation rate of each tissue in 3D reconstructed skin tissue before and after pressure. [Diagram 5] Figure 5A shows the arrector pili muscles present in a given skin area in samples from young and elderly subjects, and Figure 5B is a graph showing the amount of arrector pili muscles per given skin area in young and elderly subjects. [Figure 6] Figure 6 shows fluorescent micrographs of skin samples stained with the CD49f / CD34 markers. When comparing young subjects with elderly subjects, there were more CD49f / CD34 double positive cells in the young subjects. Figure 6B shows the density of CD49f / CD34 double positive cells (stem cell markers) in the young subjects and elderly subjects. [Figure 7] Figure 7 shows the change in CD34 (stem cell marker) positive cells in skin samples in which stretch stimulation was not applied and in which stretch stimulation was applied. Figure 7A shows the results of tissue staining, and Figure 7B shows the results of staining under a fluorescent microscope. [Figure 8] Figure 8A shows the relationship between the vellus hair follicle and the arrector pili muscle, which was reconstructed in 3D using X-ray CT. The orientation of the hair follicle and the arrector pili muscle is consistent, and the orientation of the arrector pili muscle is consistent with the hair flow. Figure 8B shows the hair flow on the human face. Figure 8C shows the difference in hair flow on the forehead and its proportion. [Figure 9] FIG. 9 is a schematic diagram showing the dynamic belt of the face. [Figure 10]FIG. 10 shows the percentage of improvement in sagging skin when it was classified into four levels: markedly effective, effective, moderately effective, and ineffective. [Figure 11] Figure 11A shows cells stained with CD49f / CD34 markers (stem cell markers) in cultured smooth muscle cells. Figure 11B shows cells stained with CD34, ADRA1 in cultured smooth muscle cells. Figure 11C shows cells stained with CD34, ADRA1 in skin samples. [Figure 12] Figure 12A shows CD49f / CD34 marker (stem cell marker) double positive cells in cultured smooth muscle cells with or without phenylephrine stimulation. Figure 12B shows the proliferation rate of CD49f / CD34 marker (stem cell marker) double positive cells depending on the concentration of phenylephrine. [Figure 13] FIG. 13 is a graph showing that licorice extract activates smooth muscle cells. [Figure 14] FIG. 14 is a graph showing that licorice extract activates smooth muscle cells, whereas raspberry extract does not (FIG. 14A), but that when licorice extract and raspberry extract are used in combination, raspberry extract does not inhibit the efficacy of licorice extract (FIG. 14B). [Figure 15] Fig. 15A is a schematic diagram of a beauty device 10 according to the present invention, and Fig. 15B is a block diagram showing the configuration of the beauty device 10 according to the present invention. [Figure 16] Fig. 16A shows a block diagram of a device for determining a skin stretching direction for a massage according to the present invention, and Fig. 16B shows a block diagram of a system in which information processing is performed in an external device connected to the Internet in the device. [Figure 17] FIG. 17 is a flow chart showing the process of the device for determining the skin stretch direction for massage. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] One aspect of the present invention relates to a cosmetic method comprising proliferating arrector pili muscle cells, and since sagging skin is improved by proliferating arrector pili muscle cells and activating arrector pili muscles, the cosmetic method of the present invention can be called a method for improving sagging. In addition, since sagging and reduced skin viscoelasticity are involved in reduced skin elasticity, wrinkles, or sagging, and give the impression of aging, the cosmetic method of the present invention can also be called a method for improving elasticity, wrinkles, or sagging, or a method for improving aging.

[0010] The arrector pili muscle is a type of smooth muscle that exists between the hair follicle and the upper layer of the dermis. The arrector pili muscle is controlled by the sympathetic nerve and contracts due to cold stress or emotional stress such as fear or surprise. The hair root grows obliquely to the skin surface, which creates the flow of hair. In addition, since the arrector pili muscle is oriented approximately parallel to the hair or hair follicle, the running direction of the hair or hair follicle can also be called the running direction of the arrector pili muscle. When the arrector pili muscle contracts, the hair root moves perpendicular to the skin surface, causing the hair to stand up, forming a condition known as goosebumps. A pressing test on a cylindrical skin sample by the present inventors has shown that the skin of the face has a directional resistance to deformation stimuli (Figure 2), and that the arrector pili muscle is involved in such resistance (Figure 3). The amount of arrector pili muscle correlates with the sagging or viscoelasticity of the skin (Example 2). Since arrector pili muscles decrease with age (Figure 5), increasing the mass of arrector pili muscles can improve phenomena related to skin sagging or viscoelasticity, such as firmness, wrinkles, or sagging.

[0011] Arrector pili muscle cells are muscle cells that constitute the arrector pili muscle. Arrector pili muscle cells are mononuclear cells. The present inventors have found that many cells expressing CD49f / CD34 markers are present in the cells contained in the arrector pili muscle (Figure 6). CD49f and CD34 markers are known as markers of smooth muscle stem cells present in smooth muscle, and in the present invention, CD49f and CD34 markers can also be referred to as stem cell markers. It has also been found that cells expressing stem cell markers exist in the arrector pili muscle of the skin, and it has been shown that stem cell-like cells exist in the arrector pili muscle. In the present invention, arrector pili muscle cells include arrector pili muscle cells and arrector pili muscle stem cells. In the arrector pili muscle, CD34-positive cells were also positive for the CD49f marker, so the CD34 marker alone can also be referred to as a stem cell marker, and CD34-positive arrector pili muscle cells are referred to as arrector pili muscle stem cells. The present inventors further found that the proportion of cells expressing CD34 increased by applying mechanical stimulation (Figure 7). It has been reported that CD34 is expressed in various somatic stem cells, including mesenchymal stem cells (Pediatric Cardiology and Cardiac Surgery (2015) 31(3): 80-87). In the arrector pili muscle before mechanical stimulation, CD34-positive cells were negative for αSMA, a smooth muscle cell marker. On the other hand, in the arrector pili muscle after mechanical stimulation, many of the CD34-positive cells were αSMA-positive cells (Figure 7B). Although not intending to be limited by theory, it is believed that the number of cells positive for both CD34 and αSMA increased as a result of the activation, proliferation, and further differentiation of the arrector pili muscle stem cells contained in the arrector pili muscle cells.

[0012] The present inventors have found that arrector pili muscle stem cells express α1 adrenergic receptor (ADRA1) like cardiac muscle cells and other smooth muscle cells (FIG. 11), and that administration of an agonist of the α1 adrenergic receptor causes proliferation of arrector pili muscle cells (FIG. 12). Therefore, arrector pili muscle cells can be proliferated via the α1 adrenergic receptor. Any compound known in the art is known as a substance that activates the α1 adrenergic receptor. For example, catecholamine compounds such as adrenaline, noradrenaline, and phenylephrine are known as agonists of the α1 adrenergic receptor. Therefore, by directly applying an agonist of the α1 adrenergic receptor to the skin, it acts on the arrector pili muscle cells to activate them, thereby inducing proliferation and differentiation into arrector pili muscle, thereby activating the arrector pili muscle, and thus providing a cosmetic method that improves sagging, sagging, and wrinkles. Therefore, an agonist of the α1 adrenergic receptor can be said to be an activator of arrector pili muscle cells, or an activator of stem cell-like cells present in the arrector pili muscle. In the present invention, activation means that the activity of cells is increased. By activating cells, for example, proliferation, metabolism, or differentiation can be promoted. The activation of the α1 adrenergic receptor can also be measured by measuring intracellular signal transduction by the α1 adrenergic receptor and the associated calcium influx.

[0013] Noradrenaline, an agonist of α1 adrenergic receptors, is a type of neurotransmitter, but it is also released into the bloodstream from the adrenal gland and acts as a hormone. Noradrenaline contributes to the activation of the autonomic nervous system, especially the sympathetic nervous system, by emotional stimulation. The arrector pili muscle contracts due to the action of noradrenaline, resulting in the phenomenon known as goosebumps. Goosebumps are caused by cold stress or fear, but also by emotional stimuli such as strong joy and emotion. Therefore, by providing an emotional stimulus, it is possible to activate the arrector pili muscle cells through the action of noradrenaline, which can lead to emotion and thus provide a beauty method that improves sagging, sagging, and wrinkles. Examples of emotional stimuli that induce emotion include stimuli of the five senses, such as sight, taste, hearing, touch, and smell. In particular, auditory stimuli from music, stimuli from a specific smell, and visual stimuli from images, color changes, videos, etc. are preferable as emotional stimuli that induce emotion. As an example, a cosmetic method is provided that uses a fragrance to induce emotional stimulation via the sense of smell and activate arrector pili muscle cells, thereby improving sagging, wrinkles, or moss. Examples of such fragrances include grapefruit, pepper, hyssop, sage, and the like. Such fragrances may be used as perfumes, aromas, and fragrances, or may be incorporated into cosmetics.

[0014] The physical stimulus refers to a mechanical stimulus given to the skin. For example, the mechanical stimulus can be given by contacting a roller or a probe with the skin. From the viewpoint of giving a stretching stimulus to the arrector pili muscle, it is preferable to apply a roller or a probe to cause the stretching of the skin and the stretching of the pores, leading to the stretching of the arrector pili muscle. Since the arrector pili muscle is present along the hair flow (FIG. 8A), the direction of the mechanical stimulus can be determined based on the hair flow (FIGS. 8B and 8C). The mechanical stimulus brings about deformation of the skin, and thus a stretching stimulus is given along the direction of the arrector pili muscle, that is, along the hair flow direction. Since the hair flow in the forehead in particular differs from person to person, an optimal massage can be provided by analyzing the hair flow for each individual. In a dynamic analysis of skin deformation in a 3D reconstructed skin, it has been shown that the anchoring part of the arrector pili muscle to the epidermis restricts the movement of the skin by a pressure stimulus, and it is thought that sagging is prevented by lifting the epidermis with the anchoring part. The orientation of the arrector pili muscles that improves sagging is called a dynamic belt, and applying a stretching stimulus along this orientation can activate the arrector pili muscle cells (Figure 9). From the viewpoint of applying a stretching stimulus to the arrector pili muscles present in the dermis layer, when applying mechanical stimulation to the cheek of the face, it is applied with a strength that brings about a deformation of 5% to 50%, preferably a deformation of 10% to 40%, and most preferably about 30%. The deformation can be determined by measuring the amount of deformation such as analyzing the photographed surface shape or actually measuring the surface shape, or by using a strain gauge or a force gauge. In addition, by determining the relationship between the amount of deformation and the stretching force in advance in a group of subjects, the deformation can be measured using the stretching force as an index.

[0015] The present specification relates to a cosmetic method for improving sagging, wrinkles, or sagging skin by activating arrector pili muscle cells, and can be distinguished from treatments performed by doctors or medical professionals. Such a cosmetic method may be performed individually or in a beauty salon, a cosmetics store, an esthetic salon, or the like.

[0016] Another aspect of the present invention relates to a method for screening for treatments for improving sagging, wrinkles, or sagging skin, using the activity of stem cell-like cells present in the arrector pili muscle as an index. More specifically, this screening method comprises the following steps: performing skin organotypic culture; administering a candidate treatment to the skin organ; Measuring the activity of stem cell-like cells present in the arrector pili muscle; Includes.

[0017] The method may further include a step of comparing the activity of stem cell-like cells present in the arrector pili muscle in a treatment group in which the candidate treatment has been performed with the activity of stem cell-like cells present in the arrector pili muscle in a control group that differs only in that the candidate treatment has not been performed. The experiment for the control group may be performed in parallel, or an experiment for the control group may be performed in advance. If the activity of stem cell-like cells present in the arrector pili muscle is increased compared to the activity of stem cell-like cells present in the arrector pili muscle of the control group, the candidate treatment can be screened as a treatment for improving sagging, wrinkles, or baldness.

[0018] In skin organ culture, it is preferable to culture an organ containing the arrector pili muscle. The culture step includes only the step of seeding the skin organ. The medium can be any medium normally used in skin organ culture, and for example, DMEM medium, MEM medium, etc. can be used. The candidate treatment can be any treatment expected to enhance the activity of stem cell-like cells present in the arrector pili muscle, and for example, it can be a physical stimulation treatment or a drug stimulation treatment. The physical stimulation is not limited to mechanical stimulation, and includes temperature stimulation, light stimulation, etc. The drug treatment includes a step of replacing the solution with a solution containing a candidate drug or adding a candidate drug and culturing. The drug treatment can be performed for, for example, 1 hour to 7 days. The activity of stem cell-like cells present in the arrector pili muscle can be determined by using a method known in the art, and for example, based on at least one of the following: the degree of reduction of the medium, the number of cells expressing CD34, the proliferation ability of the arrector pili muscle cells, and the shape of the arrector pili muscle cells.

[0019] Yet another embodiment relates to a method for screening for an arrector pili muscle activator using the activity of an adrenergic receptor-expressing cell as an index. More specifically, this screening method comprises the following steps: Culturing the adrenergic receptor-expressing cells in a solution containing a candidate drug; Measuring the activity of the adrenergic receptor expressing cells Includes.

[0020] The method may include a pre-culture step in a medium not containing the candidate drug before the step of culturing the adrenergic receptor-expressing cells in a solution containing the candidate drug. The method may further include a step of comparing the activity of the adrenergic receptor-expressing cells in a group in which the adrenergic receptor-expressing cells are cultured in a solution containing the candidate drug with the activity of the adrenergic receptor-expressing cells in a control group that differs only in that the adrenergic receptor-expressing cells do not contain the candidate drug. The experiment on the control group may be performed in parallel, or an experiment on the control group may be performed in advance. If the activity of the adrenergic receptor-expressing cells is increased compared to the activity of the adrenergic receptor-expressing cells in the control group, the candidate drug can be screened as an arrector pili muscle activator. The arrector pili muscle activator can activate arrector pili muscle cells or stem cells present in the arrector pili muscle through excitation of the adrenergic receptor. The stem cells proliferate and differentiate into arrector pili muscle cells, thereby increasing the amount of arrector pili muscle, which can improve sagging, wrinkles, or moss. Therefore, the arrector pili muscle activator screened by this method can also be called a sagging, wrinkle, or moss improving agent.

[0021] The solution containing the candidate drug may be any solution, but is preferably a culture medium. Any medium commonly used in skin organ culture can be used as the culture medium, and as an example, DMEM medium, MEM medium, etc. can be used. The step of culturing the adrenergic receptor-expressing cells in a solution containing the candidate drug can be performed by replacing the pre-culture medium with a solution containing the candidate drug, or by adding the candidate drug to the pre-culture medium and culturing. The culture period can be, for example, 1 hour to 7 days. The activity of the smooth muscle cells can be determined by using a method known in the art, and as an example, based on at least one of the degree of reduction of the medium, the number of cells expressing CD34, the proliferation ability of the adrenergic receptor-expressing cells, and the shape of the adrenergic receptor-expressing cells.

[0022] As the candidate drug, a drug contained in any drug library such as a cosmetic material, food material, or pharmaceutical material can be used. These drug libraries may be compound libraries or extract libraries. As a result of carrying out the screening method of the present invention using an extract library of a cosmetic material, it was possible to screen licorice extract as a drug that activates smooth muscle cells and as an agent for improving sagging, wrinkles, or moss (Figure 13). Note that, although raspberry extract does not activate smooth muscle cells, it did not interfere with the smooth muscle cell activation action of licorice extract when used in combination with licorice (Figure 14).

[0023] Adrenergic receptor-expressing cells may be any cells that express an adrenergic receptor, or may be cells that express an adrenergic receptor by gene transfer. Examples of adrenergic receptor cells include smooth muscle cells, cardiac muscle cells, and nerve cells. The smooth muscle cells may be any smooth muscle cells, and may be selected from the group consisting of vascular muscle cells, tracheal smooth muscle cells, arrector pili cells, and uterine muscle cells. These cells may be established cell lines, or may be cells that have been primarily cultured from a tissue sample or their progeny.

[0024] Licorice extract refers to an extract extracted from the plant body, particularly the roots and / or rhizomes, of licorice, a perennial plant of the genus Glycyrrhiza of the legume family that grows naturally in the Mediterranean region, Asia Minor, southern Russia, Central Asia, northern China, North America, etc. Any solvent, such as water, alcohol, such as ethanol, butylene glycol, or a mixture thereof, may be used for the extraction. For example, a 50% aqueous ethanol solution or a 50% aqueous butylene glycol solution may be used.

[0025] Rubus extract refers to an extract extracted from the plant body, especially the fruit, of the Rubus genus, which grows naturally in the cold to temperate zones of the Northern Hemisphere. Any solvent, such as water, alcohol, such as ethanol, butylene glycol, or a mixture thereof, may be used for the extraction. As an example, an extract extracted with butylene glycol may be used.

[0026] In another aspect of the present invention, the present invention relates to a composition for activating smooth muscle cells, which contains licorice extract. In yet another aspect, the present invention also relates to a composition for improving sagging, wrinkles, or moss, which contains licorice extract. The composition for improving sagging, wrinkles, or moss can be called an anti-aging agent. This composition for improving sagging can improve sagging, wrinkles, or moss on the skin through activation of smooth muscle cells, particularly arrector pili muscle cells. The composition for activating and / or the composition for improving sagging, wrinkles, or moss according to the present invention may be incorporated into cosmetics, medicines, or quasi-drugs, or may be incorporated into foods, such as nutritional supplements such as supplements. The amount of licorice extract and / or raspberry extract to be incorporated into cosmetics, medicines, or quasi-drugs can be selected arbitrarily within the range in which arrector pili muscle cells can be activated, and may be incorporated at, for example, 0.01 to 1%. From the viewpoint of activating arrector pili muscle cells, 0.01% or more is preferable, and 0.1% or more is even more preferable. From the viewpoint of not exerting side effects, 1% or less is preferable, and 0.3% or less is more preferable. Since arrector pili muscle cells are present around the pores of the skin, it is preferable to apply it percutaneously, and it is preferable to blend it into a cosmetic material to be applied to the skin. Examples of the cosmetic material to be blended include lotions, beauty essences, beauty creams, sunscreens, bath additives, massage creams, and makeup products, but it can be blended into any cosmetic material that is applied to the skin. Cosmetics and pharmaceuticals to which the composition for activating smooth muscle cells of the present invention and / or the composition for improving sagging, wrinkles, or moss of the present invention are blended can be blended with optional ingredients that are usually used as necessary. Examples of the optional ingredients include oils and fats, surfactants, powders, coloring materials, water, alcohols, thickeners, chelating agents, silicones, antioxidants, ultraviolet absorbers, moisturizers, fragrances, various medicinal ingredients, preservatives, pH adjusters, and neutralizers. Other medicinal ingredients, such as collagen production promoters, may be included.

[0027] In yet another aspect of the present invention, the present invention also relates to an application for sensing the flow of hair and instructing the application of stretching stimulation along the flow of hair, and further to a beauty tool 10 for applying stretching force along the flow of hair. To carry out such an application, the present invention relates to a device 30 for determining the skin stretching direction for massage, specifically A photographing unit 11 for photographing facial images; An information processing unit 13 that analyzes the captured face image and determines the hair flow and / or the extension direction along the hair flow; and an output unit 21 for displaying the hair flow and / or the extension direction along the hair flow; Such an apparatus 30 may store data of the captured face image and the determined hair flow and / or the extension direction along the hair flow in the memory unit 23. Yet another aspect may relate to a program for operating such an apparatus, such a program comprising: A command to operate the information processing unit to analyze the face image captured by the imaging unit 11 and determine the hair flow and / or the extension direction along the hair flow; A command to display the determined hair flow and / or the extension direction along the hair flow on the output unit 21. Furthermore, the program may include a command to operate the image capture unit 11 to capture a face image.

[0028] The device of the present invention may be a system 50 including an external device 40 in which an information processing unit 13 is externally disposed. Such a system includes a terminal device 31 and the external device 40, and the terminal device 31 has the following: A photographing unit 11 for photographing facial images; a communication unit 22 for transmitting the photographed data to an external device and receiving data on the hair flow and / or the extension direction along the hair flow; An output unit 21 that displays the hair flow and / or the extension direction along the hair flow The external device 40 includes: a communication unit 22 for receiving the photographed data and transmitting data on the determined hair flow and / or the extension direction along the hair flow; an information processing unit 13 that analyzes a facial image of the captured data and determines the hair flow and / or the extension direction along the hair flow; Yet another aspect may relate to a program for operating such a system, the program comprising: A command to activate the communication unit 22 and transmit the face image captured by the imaging unit 13; a command to activate the communication unit 22 to receive data on the hair flow and / or the extension direction along the hair flow; A command to cause the output unit 21 to display the hair flow and / or the extension direction along the hair flow; The program for operating the external device further comprises: A command to operate the communication unit 22 to receive the face image captured by the imaging unit 11; A command to operate the information processing unit 13 to analyze the face image captured by the image capturing unit 22 and determine the hair flow and / or the extension direction along the hair flow. A command to activate the communication unit 22 to transmit data on the hair flow and / or the extension direction along the hair flow; Includes.

[0029] The beauty tool 10 comprises an imaging unit 11 and a probe unit 12, and further comprises an information processing unit 13 (FIG. 15). The imaging unit 11 is a camera capable of imaging facial hair, preferably a microscope. The probe unit 12 is an extension probe equipped with an extension direction adjustment mechanism 15 capable of applying an extension force to the skin surface from any direction. The surface size of the skin contact portion 14 of the probe unit 12 can be determined arbitrarily, and can be set to any value within a range of 1 mm 2 ~100cm 2As an example, the extension direction adjustment mechanism 15 can adjust the probe to an arbitrary angle by using an angle adjustment mechanism 17 for adjusting the angle with respect to the base 19 and a rotation mechanism 18 for rotating the base 19. The angle adjustment mechanism may have one axis, but may have two or more axes. The extension force adjustment mechanism 16 can adjust the skin contact part 14 of the probe part 12 to apply an appropriate extension force to the skin by expanding and contracting. The image captured by the imaging part 11 is image-processed in the information processing part 13, and the flow of hair is determined. Based on the determined flow of hair, the extension direction and / or the extension force of the probe part 12 is adjusted. More specifically, the extension direction along the flow of hair can be determined in the information processing part 13. The extension mechanism direction adjustment mechanism 15 adjusts the angle of the probe part 12 with respect to the determined extension direction. As a result of the extension of the probe 12, when it is applied to the cheek of the face, it is deformed by, for example, 5% to 50%, preferably 10% to 40%, and most preferably about 30%. The deformation can be determined by analyzing the photographed surface morphology, measuring the deformation amount such as actual measurement of the surface morphology, or by a strain gauge or a force gauge. In addition, by determining the relationship between the deformation amount and the force in advance in a group of subjects, the deformation can be measured using the stretching stimulus (force) as an index. The beauty tool 10 may be equipped with multiple probe units 12. In this case, the photographing unit 11 may also be installed for each probe unit 12. Such a beauty tool may be equipped with any configuration that a facial beauty device normally has, such as a light irradiation unit, a temperature control mechanism, and a voltage application mechanism. Such a beauty tool 10 further includes an operation unit 20, which can be used to turn the power on / off and switch modes.

[0030] The storage unit 23 relates to any device that stores data, and examples of such devices include memory devices such as RAM, ROM, and flash memory, fixed disk devices such as hard disk drives, and portable storage devices such as flexible disks and optical disks. The storage unit 23 stores image data and instructions captured by the imaging unit 11, programs used for various computer processes, processing results by the information processing unit 13, databases, forms to be output to the output unit 21, and the like. The computer programs may be installed from computer-readable recording media such as CD-ROMs and DVD-ROMs, or via the Internet. The computer programs are installed in the storage unit 23 using a known setup program or the like.

[0031] The information processing unit 13 is any device that performs arithmetic processing, and typically has one or more processors or their peripheral circuits. The information processing unit 13 generally controls the overall operation of the device 30, and is, for example, a central processing unit (CPU). The information processing unit 13 executes various arithmetic processing according to a program stored in the storage unit 23. The arithmetic processing is performed by a processor included in the information processing unit 13. This processor includes a functional module that controls the imaging unit 11, the storage unit 23, and the output unit 21, and can perform various controls. Each of these units may be composed of an independent integrated circuit, microprocessor, firmware, or the like. The information processing unit 13 determines the flow of facial hair from image data captured by the imaging unit 11. By using image recognition technology, it is possible to determine the flow of hair on the entire face by recognizing each hair growing on the face and determining the flow from the pores to the tip of each hair. The information processing unit 13 further determines the extension direction along the hair flow based on the hair flow. The information regarding the hair flow and / or the extension direction along the hair flow determined by the information processing unit 13 may be temporarily stored in the storage unit 23.

[0032] The output unit 21 is any device capable of outputting the results of processing by the information processing unit 13, for example, a display device such as a liquid crystal display that directly displays the results, a printer, or other output means, and may include an interface. The output unit 21 outputs the results of processing by the information processing unit 13, i.e., the hair flow and / or the extension direction along the hair flow. At this time, the output unit 21 calls up a form or face image stored in the storage unit 23, and displays the hair flow and / or the extension direction along the hair flow by superimposing it on the form or face image.

[0033] The communication unit 22 may be connected to a communication unit for outputting via a network or an external storage device via an interface. The communication unit used in the photographing unit 11 and the output unit 14 relates to a communication interface such as a LAN or a port for connecting an information processing device to a network.

[0034] Counseling can be performed based on the resistance to skin aging output from the output unit 14. In the counseling, preventive treatment according to the resistance to skin aging can be provided. "According to the resistance to skin aging" means providing a treatment that can supplement the resistance when the resistance is low. The relationship between the resistance to skin aging and the preventive treatment may be stored in the memory unit 12 in advance, and the output unit 14 can output information on the preventive treatment together with the output of the resistance to skin aging. The preventive treatment may be a cosmetic treatment such as the frequency and method of use of cosmetics and ingredients, as well as a treatment to change lifestyle habits or the external environment.

[0035] All documents mentioned herein are incorporated by reference in their entirety.

[0036] The following examples of the present invention are for illustrative purposes only and do not limit the technical scope of the present invention. The technical scope of the present invention is limited only by the claims. The present invention can be modified, for example, by adding, deleting, and replacing the constituent elements of the present invention, without departing from the spirit of the present invention. EXAMPLES

[0037] Example 1: 3D analysis of arrector pili muscles X-ray CT observation Skin specimens were obtained from excess skin excised during plastic surgery. Cylindrical skin slices measuring several millimeters in diameter were cut from the skin specimens and subjected to X-ray CT imaging in a moist environment using an Xradia device (ZEISS). Observing the unfixed sections made it possible to observe the tissue in a deformed state. Even when the skin was deformed by pressure, the deformation returned to its original state when pressure was stopped. For the images obtained from the X-ray CT imaging, 3D reconstruction of the skin was performed using automatic classification technology by Dragonfly (Object Research Systems), an artificial intelligence-based deep learning system.

[0038] X-ray CT scans were taken while applying pressure vertically from the epidermis side, and 3D reconstruction was performed. Landmark points were densely placed on the surface of each 3D reconstructed tissue, and the amount of movement of the pore tissue structure before and during pressure application was analyzed. The amount of movement of each landmark is shown in a heat map in Figure 1. It was shown that pressure does not cause uniform deformation, and the amount of deformation varies depending on the tissue inside the skin.

[0039] X-ray CT scans were performed on skin samples from a young individual (14 years old) and an elderly individual (76 years old) to perform 3D reconstructions to show the arrector pili muscles (Figure 5A) and compare the amount of arrector pili muscles per given area of ​​skin (Figure 5B).

[0040] Skin slices subjected to pressure stimulation Vertical pressure was applied to cylindrical skin slices (young and old subjects) (Fig. 2A, B). When pressure was applied vertically, the skin of the old subjects stretched uniformly, while the skin of the young subjects stretched horizontally and resisted vertical stretching. The resistance to stretching was shown graphically (Fig. 2C). A heat map was shown of the mobility of the skin when pressure was applied from above the circular skin sample of the young subject (Fig. 3A). It was found that there were localized areas in the skin sample where the amount of movement was restricted (Fig. 3A). X-ray CT scans of the circular skin sample were performed and 3D reconstruction was performed, showing that the arrector pili muscles were present at the locations where the amount of movement was restricted (Fig. 3B). The arrector pili muscles, hair follicles, sweat glands, and sebaceous glands present in the circular skin samples were identified, and the amount of deformation due to pressure was compared (Fig. 4). It was shown that extension was suppressed in areas where the arrector pili muscles were present inside the skin.

[0041] Example 2: Correlation between arrector pili muscles and skin sagging or elasticity The skin viscoelasticity of the cheeks of the faces of 30 middle-aged subjects was measured using a Cutometer. The severity of skin sagging was also evaluated using photographs. The relationship between the amount of arrector pili muscle in the skin of the cheeks of the faces of each subject was analyzed. Statistical analysis was performed using Speaman's correlation coefficient for skin viscoelasticity and arrector pili muscle volume, and for the severity of skin sagging and arrector pili muscle volume. The results are shown in the table below. [Table 1] The results showed an inverse correlation between arrector pili muscle mass and the severity of sagging, as well as a correlation between arrector pili muscle mass and skin viscoelasticity. Therefore, the relationship between arrector pili muscle mass and sagging, wrinkles, and moss was demonstrated.

[0042] Example 3: Observation of skin sections Stem cell-like cells Skin samples from young and elderly subjects were immunostained according to standard methods. Labeling was performed using the CD49f / CD34 marker (Abcam). Nuclei were stained with DAPI and observed under a fluorescent microscope (Figure 6A). It was shown that the arrector pili muscle contains cells expressing the CD49f / CD34 marker (stem cell marker). When comparing skin samples from young and elderly subjects, the number of cells expressing the CD49f / CD34 marker (stem cell marker) was reduced in the elderly subjects (Figure 6B). It was shown that the arrector pili muscle mass also decreases due to the decrease in stem cells contained in the arrector pili muscle with age.

[0043] Organ culture experiments Cylindrical skin samples with a diameter of 10 mm were obtained. One was cultured without applying a stretching stimulus, while the other was stretched so that it deformed vertically by about 30%. The sample was then immersed in DMEM medium containing 10% FBS and incubated in 5% CO. 2 The cells were cultured at 37°C for 7 days.

[0044] staining Skin sections with and without stretch stimulation were stained with anti-CD34 antibody (Cell Signaling), then with 3,3-diaminobenzidine (DAB) using the Emvision system (DAKO) to stain CD34, followed by hematoxylin staining (Figure 7A). Nuclei were stained blue (indicated by black ovals or flat shapes in the figure), and the presence of CD34 was stained brown (indicated by arrows in the figure).

[0045] Fluorescent staining Immunostaining was performed according to standard methods on skin samples with and without stretch stimulation. Anti-CD34 antibody (Abcam) and anti-αSMA antibody (Abcam) were used, and labeling was performed with the corresponding fluorescently labeled secondary antibody, and the samples were observed under a fluorescent microscope (Figure 7B). When stretch stimulation was not applied, a small number of CD34-positive αSMA-negative cells were present in the arrector pili muscle (indicated by the white triangle in the figure). On the other hand, when stretch stimulation was applied, a large number of CD34αSMA double positive cells were present (indicated by the white arrow in the figure). From these results, it is thought that stretch stimulation activates and proliferates CD34-positive αSMA-negative stem cells, which then differentiate, resulting in an increase in CD34-αSMA double positive cells.

[0046] Example 4: Orientation of the arrector pili muscles in the face The relationship between the hair follicles that form vellus hair and the arrector pili muscle was investigated from facial skin specimens using X-ray CT imaging and 3D reconstruction (Figure 8A). For facial vellus hair, the orientation of the arrector pili muscle coincided with the orientation of the hair. Since hair flow occurs when hair grows in the direction of the hair follicle, the orientation of the arrector pili muscle can be determined by analyzing the hair flow. The hair orientation was analyzed from facial photographs of 62 female volunteers (Figure 8B). The hair flow on the face was consistent except for the forehead (Figure 8C).

[0047] Massage to the orientation of the arrector pili muscles Eight female volunteers (middle-aged) were given stretching stimulation in the direction of hair flow once a day for four weeks, and photographs were taken. Based on the photographs, the degree of improvement in lower eyelid sagging, for example, was classified into four levels: marked, effective, mild, and ineffective (Figure 10). Sagging was improved by applying stretching stimulation to the direction of the arrector pili muscles.

[0048] Example 5: Activation of stem cells via adrenergic receptor 1 (ADRA1) Expression of ADRA1 in stem cell-like cells Smooth muscle cells (PromoCel) were cultured in smooth muscle culture medium. Primary cultured smooth muscle cells were labeled with CD49f / CD34 markers (Abcam). Nuclei were further stained with DAPI and observed under a fluorescent microscope (Figure 11A). It was shown that primary smooth muscle cells also contain stem cell-like cells. Fixed primary cultured smooth muscle cells and skin sections were then labeled with anti-ADRA1 antibody (Abcam) and anti-CD34 antibody (Abcam). Nuclei were further stained with DAPI and observed under a fluorescent microscope. Similar to primary smooth muscle cells, stem cells in arrector pili muscles also expressed adrenergic receptors (Figures 11B and 11C).

[0049] Noradrenergic stimulation Smooth muscle cells were cultured for 48 hours in smooth muscle culture medium supplemented with phenylephrine (3 μM, 10 μM). After culture, the cells were labeled with the CD49f / CD34 marker (Abcam) and the corresponding fluorescently labeled secondary antibody according to standard methods and observed under a fluorescent microscope. CD49f / CD34 marker double positive cells were counted. Stem cell marker positive cells increased in a dose-dependent manner with phenylephrine (Figure 12A, B), suggesting that stem cell-like cells proliferated due to the action of phenylephrine.

[0050] Example 6: Measurement of smooth muscle cell activity Smooth muscle cells (Promo Cell) at 1×10 4 The cells were suspended in smooth muscle cell growth medium 2 (Promo Cell) at a density of 1 cell / well and seeded onto a 24-well plate. Licorice extract (Maruzen Pharmaceuticals) was added to a concentration of 0.1%, and 50% butylene glycol was added to the control group. Furthermore, Almar Blue (Invitrogen) was added to the medium to a concentration of 10%, and the cells were incubated at 37°C and 5% CO for 3 hours. 2 The cells were cultured under atmospheric conditions. The fluorescence intensity of the 24-well plate was measured using a fluorescence plate reader (Figure 13). The fluorescence increased in the licorice extract-added group compared to the control group, indicating increased cell activity.

[0051] Smooth muscle cells (Promo Cell) at 1×104 The cells were suspended in smooth muscle cell growth medium 2 (Promo Cell) at a density of 10 cells / well and seeded onto a 24-well plate. Licorice extract (Maruzen Pharmaceuticals) and raspberry extract (Maruzen Pharmaceuticals) were added to give a concentration of 0.1% to form the test group, while 50% butylene glycol was added to the control group. In addition, a test group was prepared to which both licorice extract (Maruzen Pharmaceuticals) and raspberry extract (Maruzen Pharmaceuticals) were added. Furthermore, Almar Blue (Invitrogen) was added to these media to give a concentration of 10%, and the cells were incubated at 37°C and 5% CO for 3 hours. 2 The cells were cultured under atmospheric conditions. The fluorescence intensity of the 24-well plate was measured using a fluorescent plate reader (Figure 14). Licorice extract had a smooth muscle cell activating effect, whereas the group to which raspberry extract was added had no cell activating effect. On the other hand, the groups to which liquorice extract and raspberry extract were added showed cell activating effects, indicating that raspberry extract does not interfere with the cell activating effect of liquorice extract. [Explanation of symbols]

[0052] 10 Beauty equipment 11. Photography Department 12 Probe section 13 Information Processing Section 14 Skin contact parts 15 Extension direction adjustment mechanism 16 Extension force adjustment mechanism 17 Angle adjustment mechanism 18 Rotation mechanism 19 Foundation 20 Control section 21 Output section 22 Communications Department 23 Memory section 30 equipment 31 Terminal Equipment 40 External device 50 Systems

Claims

1. A composition for stimulating smooth muscle cells, comprising licorice extract.

2. The enhancer composition according to claim 1, further comprising raspberry extract.

3. The stimulatory composition according to claim 1 or 2, wherein the smooth muscle cells are selected from the group consisting of vascular muscle cells, arrector pili muscle cells, and uterine muscle cells.

4. A composition for improving sagging, wrinkles, or sagging skin, comprising the composition for activating smooth muscle cells according to any one of claims 1 to 3.

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