WO2023022011A1 - 美容方法 - Google Patents
美容方法 Download PDFInfo
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- WO2023022011A1 WO2023022011A1 PCT/JP2022/029977 JP2022029977W WO2023022011A1 WO 2023022011 A1 WO2023022011 A1 WO 2023022011A1 JP 2022029977 W JP2022029977 W JP 2022029977W WO 2023022011 A1 WO2023022011 A1 WO 2023022011A1
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- WIPO (PCT)
- Prior art keywords
- skin
- cosmetic
- beauty
- cells
- stretching
- Prior art date
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61H—PHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY
- A61H15/00—Massage by means of rollers, balls, e.g. inflatable, chains, or roller chains
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
Definitions
- the present disclosure relates to a cosmetic method capable of improving sagging skin and the like.
- Patent Document 1 a process of massaging the scalp of the parietal region of a subject to whom a scalp cosmetic containing a seaweed extract is applied, a process of massaging the scalp of the temporal region, and pulling up the scalp of the temporal region, A cosmetic massage method is disclosed that includes the steps of maintaining the position for a few seconds and returning to the lifted position in that order.
- Patent Document 2 discloses a facial massage method using a cork ball, which includes (1) massage by reciprocating motion from the center of the jaw to the front of the ear, and (2) massage by reciprocating motion from the corner of the mouth to the front of the ear. and (3) a method of massaging the face, in which the center of the cheek and the recessed portion of the lower edge of the cheekbone are pressed, and then the temple is massaged by reciprocating motion at least once.
- Patent Document 3 a cosmetic containing at least one of a component that promotes blood circulation and a component that suppresses capillary formation is applied in combination with a massage method that imparts light stimulation to the skin surface around the eyes.
- a massage beauty method is disclosed.
- Patent Document 4 discloses a cosmetic method including activating and/or growing piloerection muscle cells.
- the firmness of the skin is mainly due to the thickness of the dermal layer, and firm skin is rich in elastic fibers such as collagen and elastin that fill the dermal layer.
- elastic fibers such as collagen and elastin that fill the dermal layer.
- the effects of aging or exposure to ultraviolet light decrease the function of dermal fibroblasts and activate matrix metalloproteinases.
- elastic fibers including collagen and elastin are reduced, resulting in thinning of the dermis layer.
- the skin loses firmness and becomes saggy, wrinkled, or moss.
- the decrease in skin firmness is also caused by, for example, weakening of facial muscles or an increase in subcutaneous fat.
- Patent Document 4 filed by the present inventor is a cosmetic method based on a new mechanism focusing on piloerection muscle cells, which is different from conventional cosmetic methods. There has been a demand for further improvements that can improve sagging skin and the like more efficiently and effectively.
- the subject of the present disclosure is to provide a beauty method that can improve sagging skin and the like more efficiently and effectively than conventional beauty methods.
- ⁇ Aspect 1> A cosmetic method comprising stretching the skin by pressing a part of the skin and moving another part of the skin.
- ⁇ Aspect 2> The cosmetic method according to aspect 1, comprising maintaining the stretched state of the skin for 1 second or more.
- the cosmetic method according to aspect 1 or 2 wherein the stretching of the skin is performed at a speed of 5 cm/sec or less.
- ⁇ Aspect 4> The cosmetic method according to any one of aspects 1 to 3, wherein the stretching of the skin is performed twice or more at the same site and/or different sites.
- the cosmetic method according to any one of aspects 1 to 4 wherein the stretching of the skin is carried out substantially parallel to the direction in which the pili muscles support the skin.
- ⁇ Aspect 10> The stretching of the skin is performed while applying a cosmetic to the skin, and The beauty device comprises the cosmetic, The cosmetic method according to aspect 9.
- ⁇ Aspect 11> The cosmetic method according to any one of aspects 1 to 10, which improves sagging, wrinkles, or moss.
- ⁇ Aspect 12> A cosmetic for a cosmetic method according to any one of aspects 1 to 11.
- the cosmetic according to aspect 12 or 13 comprising a licorice extract, or a licorice extract and a raspberry extract.
- ⁇ Aspect 15> A cosmetic device for the cosmetic method according to any one of aspects 1-11.
- ⁇ Aspect 16> 16 The beauty device according to aspect 15, housed in a container and/or package having a description that it is used for the cosmetic method according to any one of aspects 1 to 11.
- ⁇ Aspect 18> A sheet or display displaying the cosmetic method according to any one of aspects 1 to 11.
- FIG. 1 is a drawing for explaining a cosmetic method according to an embodiment of the present disclosure.
- FIG. 2 shows a heat map of the amount of movement in the three-dimensional representation of a skin section acquired in a cylindrical shape, which is subjected to X-ray CT imaging as it is or while pressure is applied from the epidermis side. This is an image.
- FIG. 3A shows the orientation of a circular sample obtained from facial skin.
- FIG. 3B is a diagram showing that pressure was applied to the circular sample from above.
- FIG. 3C is a graph showing the resistance to vertical deformation in the skin of subjects in their twenties (young subjects) and fifties (elderly subjects).
- FIG. 1 is a drawing for explaining a cosmetic method according to an embodiment of the present disclosure.
- FIG. 2 shows a heat map of the amount of movement in the three-dimensional representation of a skin section acquired in a cylindrical shape, which is subjected to X-ray CT imaging as it is or while pressure is applied from the epiderm
- FIG. 4A is a diagram showing, as a heat map, the amount of movement when pressure is applied from above to a circular sample obtained from facial skin.
- FIG. 4B is a heatmap image of a circular sample and an overlay of structures within the circular sample.
- FIG. 5 is a graph showing the deformation rate of each tissue in the three-dimensionally reconstructed skin tissue before and after pressing.
- FIG. 6A shows a sample obtained from a subject in his 20s (young subject) and a sample obtained from a subject in his 50s (elderly subject), which was subjected to X-ray CT and three-dimensionally reconstructed hair follicles. and prickly muscle, and the prickly muscle is indicated by an arrow in the figure.
- FIG. 6B is a diagram showing pili muscles present in certain skin areas in samples obtained from subjects in their twenties (young subjects) and in samples obtained from subjects in their fifties (elderly subjects).
- FIG. 6C is a graph showing the amount of pili muscle per constant skin area in subjects in their twenties (young subject) and subjects in their fifties (elderly subject).
- FIG. 7A shows fluorescence micrographs of co-stained skin samples with CD49f/CD34, showing that 20 subjects in their 20s (young subjects) were compared to subjects in their 50s (older subjects).
- FIG. 4 shows that there are many cells co-stained with CD49f/CD34 in older subjects (young subjects).
- FIG. 7B is a graph showing the density of cells co-stained with CD49f/CD34 in subjects in their twenties (young subjects) and subjects in their fifties (old subjects).
- FIG. 8 is a diagram showing changes in CD34-positive cells in skin samples to which stretching stimulation was not applied and skin to which stretching stimulation was applied
- FIG. 8A is the result of tissue staining
- FIG. 8B is fluorescence. The results of staining under the microscope are shown.
- FIG. 9A is a diagram showing the relationship between a hair follicle and a pili muscle of downy hair that has been three-dimensionally reconstructed by X-ray CT. indicates that it is consistent with the flow of FIG.
- FIG. 9B is a diagram showing the flow of hair (direction of pili muscles) on the human face.
- FIG. 9C shows the difference in the direction of muscles in the forehead and their ratio.
- FIG. 10 is a schematic diagram showing dynamic belts on the face.
- FIG. 11A is a photograph showing the degree of improvement in sagging before and after stretching stimulation to the lower eyelid.
- FIG. 11B shows the ratio when the degree of sagging improvement is classified into 4 stages of marked effect, effective effect, slow effect, and ineffective.
- FIG. 12A is a photograph showing cells stained with CD49f and CD34 in cultured smooth muscle cells.
- FIG. 12B is a photograph showing cells stained with ADRA1 and CD34 in cultured smooth muscle cells.
- FIG. 12C is a photograph showing ADRA1, CD34-stained cells in a skin sample.
- FIG. 13A is a diagram showing CD49f/CD34-positive cells in cultured smooth muscle cells with and without noradrenaline stimulation.
- FIG. 13B is a graph showing the number of CD49f/CD34-positive cells depending on the concentration of noradrenaline.
- FIG. 13C shows fluorescence micrographs of CD34/ ⁇ SMA co-staining of pili muscle in skin tissue cultures with and without noradrenergic stimulation.
- FIG. 14 is a graph showing that licorice extract proliferates smooth muscle cells.
- Figure 15 shows that licorice extract proliferates smooth muscle cells, while raspberry extract does not proliferate smooth muscle cells (Figure 15A).
- FIG. 15B is a graph showing no inhibition of potency.
- FIG. 16 is a graph showing the realization of effects when the skin is stretched while pressing the skin under the face line and when the skin is stretched without pressing the skin under the face line.
- FIG. 17A is a drawing for explaining how to perform a conventional facial muscle massage around the mouth and cheeks.
- FIG. 17B is a drawing for explaining a conventional facial muscle massage method around the eyes.
- FIG. 18A is a drawing for explaining how to apply the cosmetic method of the present disclosure to the left cheek.
- FIG. 18B is a drawing for explaining how to apply the cosmetic method of the present disclosure to the right cheek.
- FIG. 19 is a drawing for explaining a conventional hand stretching method.
- FIG. 20A is a graph relating to the feeling of effect when only facial muscle massage is performed.
- FIG. 20A is a graph relating to the feeling of effect when only facial muscle massage is performed.
- FIG. 20A is a graph relating to the feeling of effect when only facial muscle massage is performed
- FIG. 20B is a graph related to actual effects when the facial muscle massage and the beauty method (stretch beauty method) of the present disclosure are performed.
- FIG. 21 is a drawing relating to an embodiment of a sheet displaying a cosmetic method according to an embodiment of the present disclosure.
- FIG. 22 is a drawing relating to another embodiment of a sheet showing how to perform a cosmetic method according to one embodiment of the present disclosure.
- FIG. 23 is a drawing relating to a display displaying a beauty method according to an embodiment of the present disclosure.
- the cosmetic method of the present disclosure includes stretching the skin by pressing a part of the skin and moving another part of the skin.
- the “cosmetic method” means a method of beautifying the skin by holding a part of the skin while moving another part of the skin, and performing surgery, treatment, or diagnosis on humans. It does not include how to
- “cosmetic method” may be described as “massage”, but this "massage” also aims at beauty and does not include methods of surgery, treatment, or diagnosis of humans.
- the cosmetic method of the present disclosure is performed by pressing a portion of the skin while moving another portion of the skin.
- Such a beauty treatment may be performed by an individual, or may be performed by a professional practitioner in a beauty salon, cosmetics store, beauty salon, or the like.
- the subject of the beauty method of the present disclosure is not particularly limited, and can be a man or a woman, and can be, for example, people in their twenties and above.
- Subjects of such a generation (sometimes referred to as “elderly subjects”) have poor skin restoration power compared to young subjects in their twenties to thirties. For this reason, it was believed that stretching sagging skin, especially in elderly subjects, would cause the skin to stretch further, increasing sagging.
- the cosmetic method of the present disclosure can also be suitably used for such elderly subjects.
- the method of pressing the skin is not particularly limited. For example, as shown in FIG. A method of pressing the skin can be mentioned.
- a method of stretching the skin can typically be performed by pressing a portion of the skin while moving another portion of the skin away from the pressed site. Specifically, for example, No. in FIG. 1 to No. It can be carried out by sliding a hand or a cosmetic device or the like against the skin in the direction indicated by 3. Other than such a method, for example, a method of pinching the skin can also be adopted.
- the skin When the skin is stretched by the method of the present disclosure, it can exhibit an elongation rate of 10% or more, 11% or more, 12% or more, 13% or more, 14% or more, or 15% or more in the elongation rate test described later. .
- the upper limit of the elongation rate is not particularly limited, and can be, for example, 30% or less, 27% or less, 25% or less, 23% or less, or 20% or less. Stretching of the skin exhibiting such an elongation rate is preferably performed one or more times, two or more times, or three or more times, for example, at a site desired to obtain a cosmetic effect during the cosmetic method of the present disclosure.
- the upper limit of the number of times is not particularly limited, and may be, for example, 20 times or less, 15 times or less, 10 times or less, 8 times or less, or 6 times or less.
- such skin elongation may be performed so that the elongation rate is substantially constant during the treatment of the cosmetic method of the present disclosure, or may be performed so that the elongation rate is different for each part. good.
- the strength of stretching the skin there is no particular limitation on the strength of stretching the skin, and for example, it can be set as appropriate according to the user of the cosmetic method of the present disclosure.
- ⁇ Retention time of stretched skin> after stretching the skin, it is preferable to keep the stretched state of the skin for 1 second or more from the viewpoint of increasing the amount of piloerection muscles and improving the accompanying skin sagging.
- Such holding time can be, for example, 3 seconds or longer, 5 seconds or longer, 7 seconds or longer, or 10 seconds or longer.
- the upper limit of the retention time is not particularly limited, and may be, for example, 1 minute or less, 30 seconds or less, 15 seconds or less, or 10 seconds or less.
- the length of time that the skin is stretched may be kept substantially constant during the cosmetic method of the present disclosure, or may vary from site to site.
- ⁇ Skin elongation speed> The stretching of the skin, which is carried out by moving the other part of the skin while pressing the part of the skin, is preferably carried out at such a speed that the pectoralis pili muscles are stretched slowly and thoroughly.
- the piloerection muscles are favorably stretched, so that the amount of piloerection muscles increases, and the accompanying effect of improving skin sagging and the like can be enhanced.
- the movement speed of the hand or the beauty device when stretching the skin can be, for example, 5 cm/sec or less, 4 cm/sec or less, 3 cm/sec or less, or 2 cm/sec or less.
- the lower limit of the speed is not particularly limited, and can be, for example, 0.5 cm/sec or more, 1 cm/sec or more, or 1.5 cm/sec or more.
- the movement speed of the hand or the beauty tool when stretching the skin may be substantially constant during the treatment of the cosmetic method of the present disclosure, or may vary from part to part.
- the number of times the skin is stretched in one treatment of the cosmetic method of the present disclosure is not particularly limited, but from the viewpoint of efficient and effective cosmetic effects, for example, it is performed twice or more at the same site and/or different sites. preferably. Such number of times may be, for example, 3 or more, 4 or more, or 5 or more.
- the upper limit of the number of times is not particularly limited, and may be, for example, 20 times or less, 15 times or less, 10 times or less, 8 times or less, or 6 times or less.
- the term “beauty effect” is intended to mean the effect of improving sagging, wrinkles, or moss.
- the cosmetic method of the present disclosure is preferably performed at least once in a week, at least once in 5 days, or at least once in 3 days, and at least once daily. It is more preferable to implement
- Stretching the skin in the cosmetic method of the present disclosure may be performed by pressing a part of the skin and moving the other part of the skin away from the pressed area.
- the present inventors have found that when a physical stimulus, particularly a stretching stimulus, is applied to the skin, stem cell-like cells in the piloerection muscle proliferate and differentiate into piloerection muscle cells. , the amount of piloerection muscle increases, thereby improving the sagging of the skin. Therefore, it is preferable that the application direction for stretching the skin is substantially parallel to the direction in which the pili muscles support the skin. Specifically, the application direction of skin elongation can be, for example, within ⁇ 30°, within ⁇ 20°, or within ⁇ 10° with respect to the direction in which the pili muscle supports the skin. When the skin is stretched in such a direction, the piloerection muscles can be suitably stretched, and as a result, the sagging of the skin can be improved more efficiently and effectively.
- the cosmetic methods of the present disclosure can be performed on skin on any part of the body. For example, it can be performed on the skin surface of the head, face (eyes, cheeks, forehead, lips, nose, etc.), neck, ears, hands, arms, legs, feet, chest, abdomen, back, buttocks.
- the cosmetic method of the present disclosure can, for example, efficiently and effectively improve sagging, wrinkles, or moss on the skin. It is advantageous to perform the cosmetic method of the present disclosure on the skin of the hands.
- stretching the skin in the cosmetic methods of the present disclosure is performed while applying the cosmetic to the skin or after applying the cosmetic to the skin.
- Cosmetics may also be further applied to the skin after performing the cosmetic method of the present disclosure and any other cosmetic method.
- the cosmetics for the beauty method of the present disclosure are not particularly limited, and examples include skin care cosmetics such as serums, lotions, moisturizing gels, massage gels, milky lotions, and creams.
- Cosmetics can be used individually or in combination of 2 or more types. Moreover, you may use, for example, impregnating a face mask etc. with cosmetics.
- licorice extract can be used as an agent that can increase the activity of piloerection muscle cells and improve sagging, wrinkles, or moss, as described later. Therefore, it is preferable that the cosmetic contains a licorice extract, or a raspberry extract together with the licorice extract.
- Optional ingredients that are usually used in cosmetics can be appropriately blended as needed.
- optional ingredients include fats and oils, surfactants, powders, colorants, water, alcohols, thickeners, chelating agents, silicones, antioxidants, UV absorbers, moisturizers, fragrances,
- Various medicinal ingredients, preservatives, pH adjusters and neutralizers are included.
- other medicinal ingredients such as collagen production promoters may be included.
- the cosmetic can be stored in a container and/or package having a description that it is for the above-described beauty method of the present disclosure, so that the cosmetic used is the above-described beauty method of the present disclosure. It can be clearly stated that it is for Such writing may be on the exterior and/or interior of the container or package.
- the stretching of the skin in the cosmetic method of the present disclosure is performed by manually pressing a portion of the skin while moving another portion of the skin with a cosmetic device.
- a beauty tool for the beauty treatment method of the present disclosure there are no particular restrictions on the beauty tool for the beauty treatment method of the present disclosure, and for example, various commercially available beauty tools can be used.
- a beauty device having rollers that come into contact with the skin can be preferably used.
- the skin can be effectively stretched while reducing the friction on the skin compared to hands.
- a beauty device that includes a roller that contacts the skin and cosmetics can also be preferably used. With such a beauty device, the cosmetics are integrated into the beauty device, so the skin can be stretched while applying the cosmetics to the skin.
- the beauty device can be housed in a container and/or package having a description that it is for the above-described beauty method of the present disclosure, so that the beauty device to be used is the above-described beauty method of the present disclosure. It can be clearly stated that it is for Such writing may be on the exterior and/or interior of the container or package.
- the stretching of the skin in the cosmetic method of the present disclosure can use stretching by hand (sometimes referred to as "hand stretching") together with stretching by the above-described beauty equipment.
- the hand stretching at this time may be performed without pressing a part of the skin.
- Hand stretching may be performed before stretching with a beauty tool, or after stretching with a beauty tool.
- the cosmetic method of the present disclosure may be used in combination with a conventional cosmetic method.
- a beauty treatment method is not particularly limited, and examples thereof include methods for stimulating facial muscles, such as facial muscle massage for softening facial muscles and facial muscle exercises for strengthening facial muscles.
- the cosmetic method of the present disclosure can be performed before and/or after conventional cosmetic methods.
- facial muscle massage is used as a conventional beauty method
- facial muscle massage is performed after performing the beauty method of the present disclosure using the above-described beauty device, and then the above-described hand stretching is performed. preferably.
- the cosmetic effect can be further enhanced.
- a sheet displaying the cosmetic methods of the present disclosure as described above can be provided (FIGS. 21, 22).
- Such sheets are not particularly limited, and examples thereof include flyers, leaflets, instruction manuals, pamphlets, and catalogs. Since the sheet on which the beauty method of the present disclosure is displayed allows the user to accurately perform the method of the present disclosure while viewing it, sagging skin and the like can be improved more efficiently and effectively. .
- Such a sheet may be composed of one sheet, or may be composed of two or more sheets. Also, the sheet may be in a folded state.
- the shape of the sheet is not particularly limited, and examples include polygons (eg, triangles, squares, rectangles, rhombuses, pentagons, hexagons, octagons), circles, and ovals.
- the sheet shape may be an irregular shape.
- FIG. 22 shows an example of an irregularly-shaped sheet, and such a sheet can constitute a container capable of containing, for example, the above-described cosmetics or beauty tools.
- the indication of the cosmetic method of the present disclosure may be indicated on the inner and/or outer surface of the container, but from the viewpoint of designability of the appearance of the container, such indication is indicated on the inner surface of the container. preferably.
- a non-irregularly shaped sheet for example, a rectangular sheet as shown in FIG. can configure a package that allows
- the indication of the cosmetic method of the present disclosure may be indicated on the inner and/or outer surface of the package, but from the viewpoint of designability of the appearance of the package, such indication is indicated on the inner surface of the container. preferably.
- a display can be provided displaying the cosmetic methods of the present disclosure described above (FIG. 23).
- Such displays are not particularly limited, and examples thereof include various displays such as smartphones, mobile phones, tablet terminals, laptop computers, monitors, televisions, and goggle-type displays.
- the display on which the beauty method of the present disclosure is displayed also allows the user to accurately perform the method of the present disclosure while looking at it, so that sagging skin and the like can be improved more efficiently and effectively. .
- the content and display format of the beauty method of the present disclosure displayed on the display are not particularly limited, and the content of the beauty method described above can be displayed as still images (e.g., text, drawings, photographs) and/or moving images (e.g., animation). It can be displayed as appropriate through the image.
- a massage method can be practiced or instructed, and the beauty method of the present disclosure can be displayed.
- the means for providing images to the display there are no particular restrictions on the means for providing images to the display, and for example, monitor images, touch panel images, etc. can be adopted.
- the provision of images may be performed based on image information stored in the display, or may be performed through wired or wireless means.
- the display can also display, for example, how to operate the beauty equipment and the user's skin information.
- the present inventor conducted intensive research to find out the known causes of facial aging such as loss of firmness or sagging, and surprisingly found that there was a difference between skin sagging or elasticity and piloerection muscle mass. found a relationship between Furthermore, as a result of further research, it was found that stem cell-like cells exist in the arrector pili muscles, and that stem cell-like cells proliferate by applying physical stimulation. In addition, the present inventors have found that stem-like cells present in the pili muscle express adrenergic receptors and that activation of the adrenergic receptors can proliferate stem-like cells.
- the cosmetic method of the present disclosure can be referred to as a method for improving sagging because it can improve sagging of the skin by proliferating piloerection muscle cells.
- sagging or decreased skin viscoelasticity contributes to decreased skin firmness, wrinkles, or moss, giving an aged impression.
- the cosmetic method of the present disclosure can improve skin tone, wrinkles, or moss, it can also be referred to as a method for improving these or a method for improving aging.
- the pili muscle is a type of smooth muscle that exists between the hair follicle and the upper dermis.
- the arrector pili muscle is innervated by sympathetic nerves and contracts by cold stress and emotional stress such as fear and surprise. Hair roots grow diagonally to the surface of the skin, creating a flow of hair. Since the prickly pili muscle is oriented substantially parallel to the hair or hair follicle, the orientation (running direction) of the hair or hair follicle can also be referred to as the orientation (running direction) of the pili pili muscle. In addition, when the pili muscles contract, the hair roots move in a direction perpendicular to the skin surface, causing the hair to stand on end, forming a so-called goose bump.
- a piloerection muscle cell is a muscle cell that constitutes the piloerection muscle and is a mononuclear cell.
- the inventors found that many cells expressing the stem cell markers CD34 and CD49f exist among the cells contained in the pili muscle (Fig. 7).
- CD34 and CD49f are known as markers of smooth muscle stem cells present in smooth muscle, and it has been shown that stem cell-like cells also exist in arrector pili muscle. In the arrector pili muscle, the CD34-positive cells were also positive for CD49f, so the CD34-positive pili muscle stem cells are called arrector pili muscle stem cells.
- CD34 is known to be expressed in various somatic stem cells including mesenchymal stem cells.
- the CD34-positive cells were negative for ⁇ SMA, a smooth muscle cell marker.
- ⁇ SMA-positive cells were ⁇ SMA-positive cells (Fig. 8).
- piloerection muscle stem cells like cardiomyocytes and other smooth muscle cells, express the ⁇ 1 adrenergic receptor (ADRA1) (Fig. 12), and administration of an ⁇ 1 adrenergic receptor agonist Pili muscle cells were found to proliferate (Fig. 13). Therefore, piloerection muscle cells can be proliferated via ⁇ 1-adrenergic receptors.
- ADRA1 ⁇ 1 adrenergic receptor
- Any compound known in the technical field is known as a substance that activates ⁇ 1 adrenergic receptors.
- catecholamine compounds such as adrenaline and noradrenaline are known as ⁇ 1-adrenergic receptor agonists. Therefore, by directly applying an ⁇ 1 adrenergic receptor agonist to the skin, it can act on the piloerection muscle cells and activate the piloerection muscle cells. As a result, proliferation of piloerection muscle cells and differentiation into piloerection muscles can be induced, and sagging, moss, or wrinkles can be improved.
- agonists of ⁇ 1 adrenergic receptors can be referred to as activators of pili pili muscle cells, or activators of stem cell-like cells present in pili pili muscles.
- activation refers to promotion of proliferation, metabolism, or differentiation by increasing cell activity.
- Activation of ⁇ 1-adrenergic receptors can also be measured by measuring intracellular signal transduction by ⁇ 1-adrenergic receptors, calcium influx associated therewith, and the like.
- Noradrenaline an ⁇ 1 adrenergic receptor agonist
- Noradrenaline contributes to the activation of the autonomic nervous system, especially the sympathetic nerve, by emotional stimulation.
- the arrector pili muscles contract due to the action of noradrenaline, resulting in a phenomenon of so-called goosebumps.
- Goosebumps can also be caused by cold stress or emotional stimuli such as fear, intense joy, and excitement. Therefore, application of an emotional stimulus can evoke emotion and activate the piloerection muscle cells through the action of noradrenaline. As a result, sagging, moss, or wrinkles can be improved.
- Emotional stimuli that cause emotions include, for example, five senses such as sight, taste, hearing, touch, and smell.
- auditory stimuli such as music
- olfactory stimuli such as specific odors
- visual stimuli such as images, color changes, moving images, etc. are preferable as emotional stimuli that cause impression.
- Physical stimulation refers to mechanical stimulation given to the skin. Mechanical stimulation can be applied, for example, by bringing a roller or probe into contact with the skin.
- the mechanical stimulation to the pectoralis pili muscle is preferably a stimulation (stretching stimulation) that causes stretching of the skin or stretching of the pores by applying a roller or probe to lead to stretching of the pili pili muscle.
- the direction of mechanical stimulation can be determined based on the hair flow as shown in FIG. 9B.
- the direction of hair flow (direction of prickly pili muscle) can be determined, for example, by image analysis of a photograph of the skin.
- the mechanical stimulation results in deformation of the skin, thereby imparting a stretching stimulus along the direction of the erector pili muscle, ie along the long axis of the hair.
- the flow of hair on the forehead differs from person to person, so by analyzing the flow of hair on an individual basis, it is possible to provide an optimum beauty treatment method.
- ⁇ Screening method> The cosmetics described above can be blended with a drug capable of increasing the activity of piloerection muscle cells. Such agents can be screened using, for example, but not limited to, the screening methods described below.
- One embodiment includes a screening method for treatment to improve sagging, wrinkles, or moss, using the activity of stem cell-like cells present in the pili muscle as an index.
- this screening method includes the following steps: performing skin organ culture; applying a candidate treatment to the skin organ; A step of measuring the activity of stem cell-like cells present in the pili muscle.
- the step of comparing the activity of stem cell-like cells present in the pili pili muscle in the treatment group with the candidate treatment to the activity of the stem cell-like cells present in the pili pili muscle in the control group that differs only in that the candidate treatment is not applied. may contain. Experiments on the control group may be performed in parallel, or an experiment on the control group may be performed in advance. Candidate treatments are screened as sagging, wrinkle, or moss-improving treatments if the activity of stem-like cells present in the pectoralis pili muscle is increased compared to the activity of the stem-like cells present in the pectoralis pili muscle of the control group. be able to.
- the culturing step shall also include only the step of seeding the skin organs.
- Any medium commonly used for skin organ culture can be used as the medium, and examples thereof include DMEM medium and MEM medium.
- the candidate treatment may be any treatment that is expected to enhance the activity of the stem cell-like cells present in the pili muscle, and examples thereof include physical stimulation treatment or drug stimulation treatment.
- the physical stimulation treatment is not limited to mechanical stimulation treatment, but includes temperature stimulation, light stimulation, and the like.
- the drug stimulation treatment may include a step of substituting with a solution containing a candidate drug or adding a candidate drug and culturing.
- a drug stimulation treatment can be performed, for example, for 1 hour to 7 days.
- the activity of stem cell-like cells present in the arrector pili muscle can be measured using methods known in the art.
- the determination can be based on at least one of the cell shapes.
- Another embodiment includes a screening method for an activator of pectoralis pili muscle, using the activity of adrenergic receptor-expressing cells as an index.
- this screening method includes the following steps: culturing the adrenergic receptor-expressing cells in a solution containing the candidate agent; Measuring the activity of adrenergic receptor-expressing cells.
- a pre-culturing step in a medium that does not contain the candidate drug may be included before the step of culturing the adrenergic receptor-expressing cells in the solution containing the candidate drug. Comparing the activity of the adrenergic receptor-expressing cells in a group in which the adrenergic receptor-expressing cells were cultured in a solution containing the candidate agent with the activity of the adrenergic receptor-expressing cells in a control group that differed only in that they did not contain the candidate agent. may further include Experiments on the control group may be performed in parallel, or an experiment on the control group may be performed in advance.
- a candidate agent can be screened as a pili muscle activator if the activity of adrenergic receptor-expressing cells is increased compared to the activity of adrenergic receptor-expressing cells in a control group.
- the pili pectoralis muscle activator can activate pili pili muscle cells or stem cells present in the pili pili muscle through stimulation of adrenergic receptors. Stem cells proliferate and differentiate into piloerection muscle cells, thereby increasing the piloerection muscle mass and thereby improving sagging, wrinkles, or moss. Therefore, a pili pectoris activator screened by this method can also be referred to as a slackening, wrinkle, or moss-improving agent.
- a solution containing a candidate drug may be any solution, but is preferably a medium. Any medium commonly used for skin organ culture can be used as the medium, and examples thereof include DMEM medium and MEM medium.
- the step of culturing the adrenergic receptor-expressing cells in the solution containing the candidate drug can be performed by substituting the solution containing the candidate drug or by adding the candidate drug to the pre-culture medium and culturing.
- the culture period can be carried out, for example, from 1 hour to 7 days.
- the activity of smooth muscle cells can be measured by methods known in the art, and examples include the degree of reduction of medium, the number of cells expressing CD34, the proliferative capacity of adrenergic receptor-expressing cells, and the shape of adrenergic receptor-expressing cells. can be determined based on at least one of:
- drugs contained in any drug library such as cosmetic materials, food materials, and pharmaceutical materials
- drug libraries may be compound libraries or extract libraries.
- licorice extract can be screened as a drug that can improve sagging, wrinkles, or moss by increasing the activity of piloerection muscle cells. was made (Fig. 14).
- the raspberry extract did not increase the activity of the piloerection muscle cells, when used in combination with the licorice extract, it did not interfere with the activation effect of the licorice extract on the piloerection muscle cells (Fig. 15). .
- the adrenergic receptor-expressing cells may be any cells as long as they are cells that express adrenergic receptors, and may be cells that express adrenergic receptors through gene transfer.
- adrenergic receptor cells include smooth muscle cells, cardiomyocytes, and nerve cells.
- the smooth muscle cells may be any smooth muscle cells, and by way of example may be selected from the group consisting of vascular muscle cells, tracheal smooth muscle cells, piloerection muscle cells, and uterine muscle cells. These cells may be established cell lines, primary cultured cells from tissue samples, or progeny thereof.
- Glycyrrhiza extract is extracted from the plant body of Glycyrrhiza, a perennial herb of the genus Glycyrrhiza of the legume family, which grows naturally in the Mediterranean region, Asia Minor, southern Russia, Central Asia, northern China, North America, etc., especially from the root and/or rhizome.
- Any solvent such as water, alcohols such as ethanol, butylene glycol, or mixtures thereof may be used for the extraction.
- a 50% ethanol aqueous solution and a 50% butylene glycol aqueous solution are used.
- the raspberry extract refers to an extract extracted from plants, especially fruits, of the genus Rubus, which grows naturally in the cold to temperate zones of the northern hemisphere.
- Any solvent such as water, alcohols such as ethanol, butylene glycol, or mixtures thereof may be used for the extraction.
- an extract extracted with butylene glycol can be used.
- each of these agents independently contains 0.01% by mass or more, 0.05% by mass or more, or 0.05% by mass or more of the total amount of the cosmetic. .1% by mass or more, and preferably 1% by mass or less, 0.5% by mass or less, or 0.3% by mass or less.
- Example 1 Three-dimensional analysis of prickly muscle> (X-ray CT observation) Facial skin specimens were obtained from excess skin under excision during plastic surgery. A cylindrical skin section with a diameter of several millimeters was cut out from the skin sample and subjected to X-ray CT imaging under an unfixed, wet environment using an Xradia device (manufactured by ZEISS). Observation without fixation made it possible to observe the tissue with the skin deformed. Even when the skin was deformed by pressing, the deformation of the skin returned to its original state when the pressing was stopped. For the images obtained by X-ray CT imaging, three-dimensional reconstruction of the skin was performed using automatic classification technology by Dragonfly (manufactured by Object Research Systems), a deep learning system based on artificial intelligence (Fig. 2).
- An X-ray CT was taken while pressing vertically from the epidermis side, and a three-dimensional reconstruction was performed. Landmark points were densely arranged on the surface of each tissue that had been three-dimensionally reconstructed, and the amount of movement of the structure of the pore tissue before and during the application of pressure was analyzed. A heat map showing the amount of movement of each landmark shows that the deformation is not uniform due to pressure, and that the amount of deformation varies depending on the tissue inside the skin.
- a skin sample obtained from a young subject (20s) and a skin sample obtained from an elderly subject (50s) were subjected to X-ray CT imaging and three-dimensionally reconstructed to show the pili muscles and hair follicles.
- Fig. 6A In the image, the arrow indicates the pili muscle.
- the pili muscle in the skin of a certain area is similarly shown (Fig. 6B).
- Fig. 6C We compared the amount of prickly pili per skin.
- FIG. 3C The resistance to stretching was graphed and shown (Fig. 3C).
- Fig. 4A A heat map of the amount of deformation upon pressing of a circular skin sample from a young subject was presented (Fig. 4A).
- Fig. 4A A heat map of the amount of deformation upon pressing of a circular skin sample from a young subject was presented (Fig. 4A).
- Fig. 4A A heat map of the amount of deformation upon pressing of a circular skin sample from a young subject was presented.
- Fig. 4A We found that there were localized areas of restricted movement in the skin samples (Fig. 4A).
- Fig. 4B As a result of X-ray CT imaging and three-dimensional reconstruction of this circular skin sample, it was shown that there were pili muscles at positions where the amount of movement was restricted (Fig. 4B).
- Example 2 Correlation between erector pili muscle and skin sagging or elasticity>
- the skin viscoelasticity of the facial cheeks was measured using a cutometer.
- the degree of severity of skin sagging was evaluated by photography.
- Statistical analysis was performed using Spearman's correlation coefficient for skin viscoelasticity and piloerection muscle mass, as well as the severity of skin sagging and piloerection muscle mass. The results are shown in Table 1 below.
- Example 3 Observation of skin section> (stem cell-like cells) Skin samples obtained from young subjects and skin samples obtained from aged subjects were subjected to immunostaining according to a standard method. Anti-CD49f antibody (manufactured by Abcam) and anti-CD34 antibody (manufactured by Abcam) were used, and labeling was performed using the corresponding fluorescence-labeled secondary antibody. Nuclei were stained with DAPI and observed under a fluorescence microscope (Fig. 7A). The arrector pili muscle was shown to contain cells expressing the stem cell markers CD49f/CD34. When skin samples from young and aged subjects were compared, the number of cells expressing CD49f/CD34 was reduced in the aged subjects (Fig. 7B). It was shown that the stem cells contained in the piloerection muscle decrease with aging, and the piloerection muscle mass also decreases.
- a skin sample is obtained, one of which is cultured without applying a stretching stimulus, and the other is stretched so as to deform in the longitudinal direction (longitudinal direction) by about 30%, and is placed in DMEM containing 10% FBS.
- the cells were immersed in a medium and cultured for 7 days in an atmosphere of 5% CO 2 and 37°C.
- Orientation of piloerection muscles on the face> The relationship between the hair follicles forming the downy hair and the erector pili muscle was investigated from the facial skin sample by X-ray CT imaging and three-dimensional reconstruction (Fig. 9A). Regarding downy hair on the face, the orientation of the erector pili muscle was consistent with the orientation of the hair. Since hair flow occurs when the hair grows in the direction of the hair follicle, the orientation of the pili muscle can be determined by analyzing the hair flow. For 62 female volunteers (aged 20s-40s), hair orientation was analyzed from facial photographs (Fig. 9B). Facial hair flow was common except for the forehead (Fig. 9C).
- Activation of stem cells via adrenergic receptor 1 (ADRA1)> (Expression of ADRA1 in stem cell-like cells)
- Smooth muscle cells (Promo Cell) were cultured in smooth muscle culture medium.
- Primary cultured smooth muscle cells were labeled with anti-CD49f antibody (Abcam) and anti-CD34 antibody (Abcam) with the corresponding fluorescently labeled secondary antibodies.
- nuclei were stained with DAPI and observed under a fluorescence microscope (Fig. 12A).
- Primary smooth muscle cells were also shown to contain stem-like cells.
- the fixed primary cultured smooth muscle cells and the skin sections were labeled with an anti-ADRA1 antibody (Abcam) and an anti-CD34 antibody (Abcam).
- nuclei were stained with DAPI and observed under a fluorescence microscope. Similar to primary smooth muscle cells, stem cells in arrector pili muscle also expressed adrenergic receptors (FIGS. 12B, 12C).
- Example 6 Activity measurement of smooth muscle cells> Smooth muscle cells (manufactured by Promo Cell) were suspended in smooth muscle cell growth medium 2 (manufactured by Promo Cell) at a density of 1 ⁇ 10 4 cells/well and seeded in a 24-well plate. Glycyrrhiza extract (manufactured by Maruzen Pharmaceutical Co., Ltd.) was added to 0.1%, and 50% butylene glycol was added to the control group. Furthermore, Alamar Blue (manufactured by Invitrogen) was added to the medium to a concentration of 10%, and cultured for 3 hours at 37°C in a 5% CO2 atmosphere. The fluorescence intensity of the 24-well plate was measured using a fluorescence plate reader (Fig. 14). In the licorice extract-added group, the fluorescence increased compared to the control group, indicating that the cell activity was enhanced.
- Smooth muscle cells were suspended in smooth muscle cell growth medium (Promo Cell) at a density of 1 ⁇ 10 4 cells/well and seeded in 24-well plates.
- Glycyrrhiza extract manufactured by Maruzen Pharmaceutical Co., Ltd.
- raspberry extract manufactured by Maruzen Pharmaceutical Co., Ltd.
- 50% butylene glycol was added to the control group.
- a test group was prepared to which both licorice extract (manufactured by Maruzen Pharmaceutical Co., Ltd.) and raspberry extract (manufactured by Maruzen Pharmaceutical Co., Ltd.) were added.
- Alamar Blue (Invitrogen) was added to these media to a concentration of 10%, and the cells were cultured for 3 hours at 37° C. in a 5% CO 2 atmosphere.
- the fluorescence intensity of the 24-well plate was measured using a fluorescence plate reader (Fig. 15).
- the licorice extract had a smooth muscle cell activating effect, while the raspberry extract-added group did not have a cell activating effect.
- the groups added with the licorice extract and the raspberry extract exhibited a cell-activating effect, indicating that the raspberry extract does not interfere with the cell-activating effect of the licorice extract.
- Test method (1) While pressing the skin near the chin with a hand, the skin was stretched by pulling up the cheeks with a roller of a beauty tool. (2) Without pressing the skin near the chin with a hand, the skin was stretched by pulling up the cheeks with a roller of a beauty tool. (3) The skin was stretched by lifting the cheek with the hand without pressing the skin near the chin with the hand.
- evaluation item "it seems to be easier to create facial expressions” means, for example, that it becomes easier to create a smile, or that facial expressions become richer.
- evaluation criteria mean that the higher the score, the more effective (maximum: 5 points, minimum: 1 point).
- Example 8 Realization of effect when conventional facial muscle massage and beauty method of the present disclosure are used together
- a conventional facial muscle massage was performed, and then, according to the procedure of FIG. 19, the palm was moved so as to slide without pressing the skin near the chin.
- This series of procedures was performed once a day for 30 days.
- the feeling of effect after 1 day and 30 days was scored and evaluated according to the following evaluation criteria.
- a graph based on the average values of the evaluation results is shown in FIG. 20B.
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Abstract
Description
皮膚の一部を押さえつつ前記皮膚の他の一部を移動させることによって、前記皮膚を伸長させることを含む、美容方法。
〈態様2〉
前記皮膚を伸長させた状態を1秒以上保持することを含む、態様1に記載の美容方法。
〈態様3〉
前記皮膚の伸長が、5cm/秒以下の速度で実施される、態様1又は2に記載の美容方法。
〈態様4〉
前記皮膚の伸長が、同一の部位及び/又は異なる部位において、2回以上実施される、態様1~3のいずれかに記載の美容方法。
〈態様5〉
前記皮膚の伸長が、立毛筋が皮膚を支えている方向に対して略平行に実施される、態様1~4のいずれかに記載の美容方法。
〈態様6〉
前記皮膚の伸長が、化粧料を皮膚に適用しながら実施される、又は化粧料を皮膚に適用した後に実施される、態様1~5のいずれかに記載の美容方法。
〈態様7〉
前記化粧料が、カンゾウエキス、又はカンゾウエキス及びキイチゴエキスを含む、態様6に記載の美容方法。
〈態様8〉
前記皮膚が、顔、首、腕、又は手の皮膚である、態様1~7のいずれかに記載の美容方法。
〈態様9〉
前記皮膚の伸長が、前記皮膚の一部を手で押さえつつ、前記皮膚の他の一部を美容器具のローラーによって移動させることによって実施される、態様1~8のいずれかに記載の美容方法。
〈態様10〉
前記皮膚の伸長が、化粧料を皮膚に適用しながら実施され、かつ、
前記美容器具が、前記化粧料を備えている、
態様9に記載の美容方法。
〈態様11〉
たるみ、しわ、又はこけを改善する、態様1~10のいずれかに記載の美容方法。
〈態様12〉
態様1~11のいずれかに記載の美容方法のための化粧料。
〈態様13〉
態様1~11のいずれか一項に記載の美容方法のためのものである旨の記載を有する容器及び/又はパッケージに収容されている、態様12に記載の化粧料。
〈態様14〉
カンゾウエキス、又はカンゾウエキス及びキイチゴエキスを含む、態様12又は13に記載の化粧料。
〈態様15〉
態様1~11のいずれかに記載の美容方法のための美容器具。
〈態様16〉
態様1~11のいずれかに記載の美容方法のためのものである旨の記載を有する容器及び/又はパッケージに収容されている、態様15に記載の美容器具。
〈態様17〉
皮膚と接触するローラーを備える、態様15又は16に記載の美容器具。
〈態様18〉
態様1~11のいずれかに記載の美容方法を表示した、シート又はディスプレイ。
本開示の美容方法は、皮膚の一部を押さえつつ皮膚の他の一部を移動させることによって実施される。かかる美容方法は、個人的に行われてもよく、或いは、美容室、化粧品の販売店、エステサロンなどにおける専門の施術者によって実施されてもよい。
皮膚を押さえる方法としては特に制限はなく、例えば、図1に示されるように、手で直接的に皮膚を押さえる方法、或いは、タオル又はフェイスマスクなどの任意の部材を介して手で間接的に皮膚を押さえる方法を挙げることができる。
皮膚を伸ばす方法は、典型的には、皮膚の一部を押さえつつ、その押さえている部位から離れるように、皮膚の他の一部を移動させることによって実施され得る。具体的には、例えば、図1のNo.1~No.3と示されている方向に、皮膚に対して手又は美容器具などを滑らせるように移動させることで実施することができる。このような方法以外に、例えば、皮膚をつまむような方法も採用することができる。
いくつかの実施形態において、立毛筋量の増大、それに伴う肌のたるみ等の改善効果の観点から、皮膚を伸長させた後、その皮膚を伸長させた状態を1秒以上保持することが好ましい。かかる保持時間としては、例えば、3秒以上、5秒以上、7秒以上、又は10秒以上とすることができる。保持時間の上限値としては特に制限はなく、例えば、1分以下、30秒以下、15秒以下、又は10秒以下とすることができる。皮膚の伸長状態の保持時間は、本開示の美容方法の施術中において、略一定に実施されてもよく、或いは、部位ごとに異なっていてもよい。
皮膚の一部を押さえながら皮膚の他の一部を移動させて実施する皮膚の伸長は、立毛筋がゆっくりかつじっくりと伸ばされるような速度で実施することが好ましい。このような速度で皮膚が伸張されると、立毛筋が好適にストレッチ作用を受けるため、立毛筋量の増大、それに伴う肌のたるみ等の改善効果を向上させることができる。具体的には、皮膚を伸ばすときの手又は美容器具などの移動速度としては、例えば、5cm/秒以下、4cm/秒以下、3cm/秒以下、又は2cm/秒以下とすることができる。かかる速度の下限値としては特に制限はなく、例えば、0.5cm/秒以上、1cm/秒以上、又は1.5cm/秒以上とすることができる。皮膚を伸ばすときの手又は美容器具などの移動速度は、本開示の美容方法の施術中において、略一定に実施されてもよく、或いは、部位ごとに異なっていてもよい。
本開示の美容方法の一度の施術における皮膚の伸長回数としては特に制限はないが、効率的かつ効果的な美容効果の観点から、例えば、同一の部位及び/又は異なる部位において、2回以上実施することが好ましい。かかる回数としては、例えば、3回以上、4回以上、又は5回以上とすることができる。回数の上限値としては特に制限はなく、例えば、20回以下、15回以下、10回以下、8回以下、又は6回以下とすることができる。なお、本開示において単に「美容効果」と表記してある場合には、たるみ、しわ、又はこけの改善効果を意図する。
本開示の美容方法における皮膚の伸長は、皮膚の一部を押さえつつ、その押させている部位から離れるような方向に、皮膚の他の一部を移動させることによって実施すればよい。
本開示の美容方法は、体のあらゆる部分の皮膚に対して実施することができる。例えば、頭、顔(目元、頬、額、唇、鼻など)、首、耳、手、腕、脚、足、胸、腹、背中、臀部等の皮膚表面に対して実施することができる。本開示の美容方法は、例えば、肌における、たるみ、しわ、又はこけ等を効率的かつ効果的に改善することができるため、上述した皮膚の中でも、視認されやすい、顔、首、腕、又は手の皮膚に対して、本開示の美容方法を実施することが有利である。
いくつかの実施形態において、本開示の美容方法における皮膚の伸長は、化粧料を皮膚に適用しながら実施される、又は化粧料を皮膚に適用した後に実施される。化粧料を併用することで、美容効果をより向上させることができる。また、化粧料は、本開示の美容方法及び任意の他の美容方法を実施した後に、皮膚にさらに適用してもよい。
いくつかの実施形態において、本開示の美容方法における皮膚の伸長は、皮膚の一部を手で押さえつつ、この皮膚の他の一部を美容器具で移動させることによって実施される。本開示の美容方法のための美容器具としては特に制限はなく、例えば、市販されている種々の美容器具を使用することができる。なかでも、皮膚と接触するローラーを備える美容器具を好適に使用することができる。かかる美容器具を用いて本開示の美容方法を実施すると、手の場合に比べて皮膚に対する摩擦を低減しながら、皮膚を効果的に伸ばすことができる。さらに、皮膚と接触するローラーと化粧料とを備える美容器具も好適に使用することができる。かかる美容器具は、化粧料が美容器具に一体化されているため、化粧料を皮膚に適用しながら皮膚を伸ばすことができる。
本開示の美容方法は、従来の美容方法を併用してもよい。かかる美容方法としては特に制限はなく、例えば、表情筋の筋肉を和らげるような表情筋マッサージ、及び表情筋を鍛えるような表情筋エクササイズなどの表情筋を刺激する方法を挙げることができる。
いくつかの実施形態において、上述した本開示の美容方法を表示したシートを提供することができる(図21、22)。このようなシートとしては特に制限はなく、例えば、チラシ、能書き、取り扱い説明書、パンフレット、及びカタログを挙げることができる。本開示の美容方法が表示されたシートは、利用者がそれを見ながら本開示の方法を的確に実施することができるため、肌のたるみ等をより効率的かつ効果的に改善することができる。
いくつかの実施形態において、上述した本開示の美容方法を表示したディスプレイを提供することができる(図23)。このようなディスプレイとしては特に制限はなく、例えば、スマートフォン、携帯電話、タブレット端末、ノート型パソコン、モニター、テレビ、ゴーグル型ディスプレイなどの各種ディスプレイを挙げることができる。本開示の美容方法が表示されたディスプレイも、利用者がそれを見ながら本開示の方法を的確に実施することができるため、肌のたるみ等をより効率的かつ効果的に改善することができる。
次に、立毛筋細胞の活性化、及びそれに伴う美容効果等について以下に説明する。
上述した化粧料には、立毛筋細胞の活性を増大させ得る薬剤を配合することができる。このような薬剤は、次のものに限定されないが、例えば以下に示すスクリーニング方法を用いて選別することができる。
皮膚器官培養を行う工程;
皮膚器官に対し候補処理を行う工程;
立毛筋内に存在する幹細胞様細胞の活性を測定する工程。
候補薬剤を含む溶液中でのアドレナリン受容体発現細胞を培養する工程、
アドレナリン受容体発現細胞の活性を測定する工程。
〈実施例1:立毛筋の3次元解析〉
(X線CT観察)
形成手術中に切除下余剰皮膚から顔面皮膚標本を得た。皮膚標本から数ミリ径の円柱状皮膚切片を切り出し、Xradia装置(ZEISS社製)を用いて、未固定、湿潤環境下でX線CT撮影に供した。未固定での観察を行うことにより、皮膚を変形させた状態での組織の観察が可能になった。押圧により皮膚を変形させた場合も、押圧をやめると皮膚の変形も元に戻った。X線CT撮影に取得された画像について、人工知能に基づくディープラーニングシステムであるDragonfly(Object Research Systems社製)による自動分類技術を用いて皮膚の3次元再構築を行った(図2)。
円柱状に切り出された皮膚切片(若齢対象と及び高齢対象)に垂直方向から押圧を付与した(図3B)。垂直に圧力をかけた場合に、高齢対象の皮膚では一様に伸展したが、若齢対象の皮膚では水平方向に伸展する一方で、垂直方向に対して伸展に対し抵抗性であった。
30歳代~50歳代の被験者30名について、顔面の頬部の皮膚粘弾性を、Cutometerを用いて測定した。また、皮膚のたるみの重篤度を、写真評価した。各被験者における顔面の頬部の皮膚中の立毛筋量の関係性を解析した。皮膚粘弾性と立毛筋量及び皮膚のたるみの重篤度と立毛筋量について、Speaman’s correlation coefficientを用いて統計解析を行った。結果を下記の表1に示す。
(幹細胞様細胞)
若齢対象から得られた皮膚試料と、高齢対象から得られた皮膚試料について、定法に従い免疫染色を実施した。抗CD49f抗体(Abcam社製)と抗CD34抗体(Abcam社製)を用い、対応する蛍光標識二次抗体を用いて標識を行った。DAPIを用いて核を染色し、蛍光顕微鏡で観察した(図7A)。立毛筋には、幹細胞マーカーであるCD49f/CD34を発現する細胞が含まれていることが示された。若齢対象の皮膚試料と、高齢対象の皮膚試料を比較すると、高齢対象ではCD49f/CD34を発現する細胞数が減った(図7B)。加齢に伴い立毛筋に含まれる幹細胞が減少することで、立毛筋量も減少することが示された。
皮膚試料を取得し、一方については、伸展刺激を与えずに培養し、もう一方に対しては、30%程度縦方向(長さ方向)に変形するように伸展し、10%FBSを含むDMEM培地中に浸漬して、5%CO2、37℃雰囲気下で7日間培養した。
機械刺激を付与した皮膚切片と付与していない皮膚切片について、抗CD34抗体(セルシグナリング)を反応させ、次いでEmvision system(DAKO社製)にて3,3-ジアミノベンジジン(DAB)を反応させて、CD34を染色し、後染色として、ヘマトキシリン染色を行った(図8A)。核が青色(図中では黒色楕円~扁平形状で示される)に染色され、CD34の存在が茶色(図中白矢印で示す)に染色された。
伸展刺激を付与した皮膚試料と、付与していない皮膚試料について、定法に従い免疫染色を実施した。抗CD34抗体(Abcam社製)と抗αSMA抗体(Abcam社製)を用い、対応する蛍光標識二次抗体を用いて標識を行い、蛍光顕微鏡で観察した(図8B)。伸展刺激を付与していない場合には、立毛筋にはCD34陽性αSMA-陰性細胞が少量存在していた。一方、伸展刺激を付与することにより、CD34αSMA二重陽性細胞が大量に存在した。これらの結果から、伸展刺激を行うことで、CD34陽性αSMA-陰性の幹細胞が活性化されて増殖し、次いで分化することでCD34-αSMA二重陽性細胞が増加したと考えられる。
顔面皮膚標本から産毛を形成する毛包と立毛筋との関係を、X線CT撮影と、3次元再構築により調べた(図9A)。顔面の産毛については、立毛筋の配向と、毛の配向とが一致した。毛包の方向に毛が生えることで毛の流れが生じることから、毛の流れを解析することで、立毛筋の配向を決定することができる。62名の女性ボランティア(年齢20~40歳代)について、顔面の写真から毛の配向を分析した(図9B)。顔面の毛の流れは、額部を除き共通した(図9C)。
8名の女性ボランティア(年齢40歳代)について、下瞼に毛の流れ方向に逆らって、1日1回、4週間にわたり伸展刺激を付与し、写真を撮影した(図11A)。写真に基づいて、たるみの改善度を、著効、有効、緩効、無効と4段階に分類した(図11B)。立毛筋の配向に対し伸展刺激を行うことで、たるみが改善した。なお、ここでの伸展刺激は、皮膚の一部を押さえながら伸ばす方法ではない。
(幹細胞様細胞におけるADRA1の発現)
平滑筋細胞(Promo Cell社製)を平滑筋培養培地で培養した。初代培養平滑筋細胞を、抗CD49f抗体(Abcam社製)と抗CD34抗体(Abcam社製)を用い、対応する蛍光標識二次抗体を用いて標識を行った。さらにDAPIを用いて核を染色し、蛍光顕微鏡で観察した(図12A)。初代平滑筋細胞にも、幹細胞様細胞が含まれることが示された。次に、固定された初代培養平滑筋細胞及び皮膚切片について、抗ADRA1抗体(Abcam社製)と抗CD34抗体(Abcam社製)を用いて標識を行った。さらにDAPIを用いて核を染色し、蛍光顕微鏡で観察した。初代平滑筋細胞と同様に、立毛筋における幹細胞もアドレナリン受容体を発現した(図12B、12C)。
平滑筋細胞について、ノルアドレナリン添加平滑筋培養培地(3μM、10μM)中で48時間間培養した。培養後に、細胞を抗CD49f抗体(Abcam社製)と抗CD34抗体(Abcam社製)を用い、対応する蛍光標識二次抗体を用いて標識を行って蛍光顕微鏡で観察した。CD34及びCD49fの二重陽性細胞を計数した。ノルアドレナリンの用量依存的に、CD34及びCD49fの二重陽性細胞が増えており(図13A、B)、ノルアドレナリンの作用により幹細胞様細胞が増殖したと考えられる。皮膚試料について、ノルアドレナリン添加DMEM培地(100μM)中で7日間培養した。培養後に、細胞を、抗CD34抗体(Abcam社製)と抗αSMA抗体(Abcam社製)を用い、対応する蛍光標識二次抗体を用いて標識を行って蛍光顕微鏡で観察した。立毛筋中のCD34及びαSMA二重陽性細胞を矢印で示した(図13C)。ノルアドレナリンの作用により、立毛筋中に存在する幹細胞が活性化し、さらに平滑筋細胞へと分化したことが示された。
平滑筋細胞(Promo Cell社製)を1×104個/ウェルの密度で平滑筋細胞増殖培地2(Promo Cell社製)中に懸濁し、24穴プレートに播種した。0.1%となるようにカンゾウエキス(丸善製薬株式会社製)を添加し、対照群では50%ブチレングリコールを添加した。さらに培地中にAlmar Blue(Invitrogen社製)を10%となるように添加し、3時間、37℃5%CO2雰囲気下で培養した。24穴プレートを蛍光プレートリーダーで蛍光強度を測定した(図14)。カンゾウエキス添加群において対照群に比較して蛍光が増大し、細胞活性が高まっていることが示された。
〈皮膚を押さえることの有無に伴う皮膚の伸長率の差異〉
50歳代2名、30歳代1名の合計3名の被験者を対象にして、次の伸長率試験により、皮膚を押さえることの有無に伴う皮膚の伸長率の差異について検討した。
(1)手で顎付近の皮膚を押さえながら、美容器具のローラーで頬を引き上げるようにして皮膚を伸長させた。
(2)手で顎付近の皮膚を押さえることなく、美容器具のローラーで頬を引き上げるようにして皮膚を伸長させた。
(3)手で顎付近の皮膚を押さえることなく、手で頬を引き上げるようにして皮膚を伸長させた。
表2の結果から、皮膚を手で押さえながら伸ばすと、皮膚を手で押さえない場合に比べて、約2倍以上も皮膚を伸ばせることが確認できた。
50歳代3名、40歳代1名、20歳代1名の合計5名の被験者を対象にして、手で顎付近の皮膚を押さえながら、美容器具のローラーで頬を引き上げるようにして皮膚を伸長させたときと、手で顎付近の皮膚を押さえることなく、美容器具のローラーで頬を引き上げるようにして皮膚を伸長させたときにおける以下の評価項目に基づく効果実感を、以下の評価基準に従って点数化して評価した。その評価結果の平均値に基づくグラフを図16に示す。ここで、評価項目における「表情をつくりやすくなりそう」とは、例えば、笑顔が作りやすくなること、表情が豊かになることを意味する。また、評価基準は、点数が高いほど効果があることを意味する(最高:5点、最低:1点)。
(1)皮膚が伸びた感じがする。
(2)ハリが出そう。
(3)フェイスラインが引き締まりそう。
(4)ほおが引き締まりそう。
(5)目もとが引き締まりそう。
(6)表情を作りやすくなりそう。
(7)血行が良くなりそう。
(8)肌が明るくなりそう。
(9)頬につやが出そう。
(10)顔がすっきりしそう。
(11)たるみに効きそう。
(12)使い続けたら肌に嬉しい変化が出そう。
5点:とてもそう思う。
4点:そう思う。
3点:どちらともいえない。
2点:そう思わない。
1点:全くそう思わない。
図16の結果から、手で顎付近の皮膚を押さえながら、美容器具のローラーで頬を引き上げるようにして皮膚を伸長させた方が、全体的に効果実感が向上することが確認できた。なかでも、図16の破線の円内の項目に関しては、より顕著な効果実感が得られることが分かった。
(比較例3:従来の表情筋マッサージによる効果実感)
30~50歳代の合計15名の被験者を対象にして、皮膚を押さえずに実施する従来の表情筋マッサージを、図17A及びBの手順に従って、1日に1回、30日間にわたって実施した。1日後及び30日後の効果実感を、以下の評価基準に従って点数化して評価した。その評価結果の平均値に基づくグラフを図20Aに示す。ここで、評価基準は、点数が高いほど効果があることを意味する(最高:5点、最低:1点)。また、図中の「1D」及び「1M」は、1日後及び30日後を意味する。
30~50歳代の合計30名の被験者を対象にして、図18A及びBの手順に従って、手で顎付近の皮膚を押さえながら、美容器具のローラーで両頬を引き上げるようにして皮膚を伸長させ、次いで、図17A及びBの手順に従って、従来の表情筋マッサージを実施し、続いて、図19の手順に従って、手で顎付近の皮膚を押さえることなく、手のひらを滑らせるように移動させた。この一連の手順を、1日に1回、30日間にわたって実施した。1日後及び30日後の効果実感を、以下の評価基準に従って点数化して評価した。その評価結果の平均値に基づくグラフを図20Bに示す。
(1)ハリが出た。
(2)ほおが引き締まった。
(3)表情を作りやすくなった。
(4)血行が良くなった感じがする。
(5)肌が明るくなった。
(6)頬につやがでた。
(7)顔がすっきりした。
(8)たるみがなくなった。
5点:とてもそう思う。
4点:そう思う。
3点:どちらともいえない。
2点:そう思わない。
1点:全くそう思わない。
図20A及びBの結果から、皮膚を押さえない従来の表情筋マッサージのみの場合(図20A)に比べ、皮膚を押さえながら伸ばす本開示の美容方法を併用した場合(図20B)の方が、少なくとも図20Bの破線の円内の項目に関しては、より顕著な効果実感が得られることが分かった。これはすなわち、本開示の美容方法の方が、従来の美容方法に比べて、肌のたるみ等を効率的かつ効果的に改善できているといえる。
Claims (18)
- 皮膚の一部を押さえつつ前記皮膚の他の一部を移動させることによって、前記皮膚を伸長させることを含む、美容方法。
- 前記皮膚を伸長させた状態を1秒以上保持することを含む、請求項1に記載の美容方法。
- 前記皮膚の伸長が、5cm/秒以下の速度で実施される、請求項1又は2に記載の美容方法。
- 前記皮膚の伸長が、同一の部位及び/又は異なる部位において、2回以上実施される、請求項1~3のいずれか一項に記載の美容方法。
- 前記皮膚の伸長が、立毛筋が皮膚を支えている方向に対して略平行に実施される、請求項1~4のいずれか一項に記載の美容方法。
- 前記皮膚の伸長が、化粧料を皮膚に適用しながら実施される、又は化粧料を皮膚に適用した後に実施される、請求項1~5のいずれか一項に記載の美容方法。
- 前記化粧料が、カンゾウエキス、又はカンゾウエキス及びキイチゴエキスを含む、請求項6に記載の美容方法。
- 前記皮膚が、顔、首、腕、又は手の皮膚である、請求項1~7のいずれか一項に記載の美容方法。
- 前記皮膚の伸長が、前記皮膚の一部を手で押さえつつ、前記皮膚の他の一部を美容器具のローラーによって移動させることによって実施される、請求項1~8のいずれか一項に記載の美容方法。
- 前記皮膚の伸長が、化粧料を皮膚に適用しながら実施され、かつ、
前記美容器具が、前記化粧料を備えている、
請求項9に記載の美容方法。 - たるみ、しわ、又はこけを改善する、請求項1~10のいずれか一項に記載の美容方法。
- 請求項1~11のいずれか一項に記載の美容方法のための化粧料。
- 請求項1~11のいずれか一項に記載の美容方法のためのものである旨の記載を有する容器及び/又はパッケージに収容されている、請求項12に記載の化粧料。
- カンゾウエキス、又はカンゾウエキス及びキイチゴエキスを含む、請求項12又は13に記載の化粧料。
- 請求項1~11のいずれか一項に記載の美容方法のための美容器具。
- 請求項1~11のいずれか一項に記載の美容方法のためのものである旨の記載を有する容器及び/又はパッケージに収容されている、請求項15に記載の美容器具。
- 皮膚と接触するローラーを備える、請求項15又は16に記載の美容器具。
- 請求項1~11のいずれか一項に記載の美容方法を表示した、シート又はディスプレイ。
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JP2003183122A (ja) * | 2001-12-21 | 2003-07-03 | Ichimaru Pharcos Co Ltd | コラゲナーゼ活性阻害剤 |
JP2005314329A (ja) * | 2004-04-30 | 2005-11-10 | Kanebo Cosmetics Inc | 美容施術方法およびそれに用いる美容施術ツール |
JP2006028071A (ja) * | 2004-07-15 | 2006-02-02 | Nippon Menaade Keshohin Kk | プロテオグリカンの生成促進剤 |
JP2019097646A (ja) * | 2017-11-29 | 2019-06-24 | 三井化学株式会社 | 皮膚用マッサージ器具 |
JP2019108278A (ja) * | 2017-12-15 | 2019-07-04 | 丸善製薬株式会社 | しわ改善剤 |
WO2021167097A1 (ja) * | 2020-02-19 | 2021-08-26 | 株式会社 資生堂 | 立毛筋細胞の賦活化による老化改善方法 |
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JP2003183122A (ja) * | 2001-12-21 | 2003-07-03 | Ichimaru Pharcos Co Ltd | コラゲナーゼ活性阻害剤 |
JP2005314329A (ja) * | 2004-04-30 | 2005-11-10 | Kanebo Cosmetics Inc | 美容施術方法およびそれに用いる美容施術ツール |
JP2006028071A (ja) * | 2004-07-15 | 2006-02-02 | Nippon Menaade Keshohin Kk | プロテオグリカンの生成促進剤 |
JP2019097646A (ja) * | 2017-11-29 | 2019-06-24 | 三井化学株式会社 | 皮膚用マッサージ器具 |
JP2019108278A (ja) * | 2017-12-15 | 2019-07-04 | 丸善製薬株式会社 | しわ改善剤 |
WO2021167097A1 (ja) * | 2020-02-19 | 2021-08-26 | 株式会社 資生堂 | 立毛筋細胞の賦活化による老化改善方法 |
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