Needle beauty instrument, beauty kit, and beauty method

Abstract

Provided are a beauty instrument for improving the barrier function and / or the transparency of skin, a beauty instrument for promoting collagen production, and a beauty instrument for ameliorating sagging of the skin.　This needle beauty instrument has a part equipped with a needle-like projection and is used for improving the barrier function of skin, improving the transparency of the skin, promoting collagen production by the skin, or ameliorating sagging of the skin.

Description

Needle beauty device, beauty kit, and beauty method

[0001] A first aspect of the present invention relates to a beauty device and a beauty kit for improving the barrier function and / or clarity of the skin. A second aspect of the present invention also relates to a method for improving the barrier function and / or clarity of the skin.

[0002] A second aspect of the present invention relates to a needle cosmetic device and a cosmetic kit for promoting collagen production and / or reducing sagging skin. The second aspect of the present invention also relates to a method for promoting collagen production using the needle cosmetic device.

[0003] A third aspect of the present invention relates to a beauty tool, a beauty kit, and a beauty method using the same for use in a beauty method for improving the condition of the skin of a subject.

[0004] [Background Art of First Embodiment] Numerous beauty methods and beauty devices using microneedles have been developed to date.

[0005] For example, Patent Document 1 discloses a cosmetic method for brightening the overall facial tone by applying a microneedle sheet on which a plurality of microneedles are arranged to a part of the face.

[0006] Furthermore, Patent Document 2 reports a part with needle-like protrusions that can retain a liquid composition / liquid cosmetic, with any active ingredient, on the surface and inside of an object so as not to leak through gaps. The part with needle-like protrusions of Patent Document 2 can be attached to a fixed-needle injection device as a needle cosmetic tool and used.

[0007] [Background Technology of the Second Embodiment] Collagen is a type of protein and has various types, such as types I, II, III, IV, V, XII, and XIV. Of these, type I collagen accounts for 80% of the total and is known to be involved in skin elasticity and firmness. Furthermore, a decrease in type I collagen is one of the causes of wrinkles and sagging. Therefore, promoting the production of type I collagen is thought to be effective in preventing and improving wrinkles and sagging.

[0008] Many collagen production promoters have been developed to date.

[0009] For example, Patent Document 4 discloses a collagen production promoter comprising an essential oil obtained by steam distillation of one or more plants selected from thyme (scientific name: Thymus (vulgaris)) of the Lamiaceae family, elder (scientific name: Sambucus nigra) of the Caprifoliaceae family, and elemi (scientific name: Canarium izonicum) of the Burseraceae family.

[0010] Patent Document 2 discloses a part with needle-like protrusions that can retain a liquid composition / liquid cosmetic, with any active ingredient, on the surface and inside of an object so as not to leak through gaps. The part with needle-like protrusions of Patent Document 2 can be attached to a fixed-needle injection device as a needle cosmetic tool and used.

[0011] [Background Art of the Third Embodiment] Numerous beauty methods and beauty devices using microneedles have been developed to date.

[0012] For example, Patent Document 1 discloses a cosmetic method for brightening the overall facial tone by applying a microneedle sheet on which a plurality of microneedles are arranged to a part of the face.

[0013] Furthermore, Patent Documents 2 and 3 disclose parts with needle-like protrusions and needle beauty devices having such parts. For example, Patent Document 2 reports a part with needle-like protrusions that can retain a liquid composition / liquid cosmetic preparation, with any active ingredient, on the surface and inside of an object without leaking through gaps. Furthermore, the part with needle-like protrusions in Patent Document 2 can be attached to a fixed-needle injection device as a needle beauty device and used.

[0014] Japanese Patent Application Laid-Open No. 2020-164432 International Publication No. 2022 / 071322 International Publication No. 2023 / 190584 Japanese Patent Application Laid-Open No. 2006-232740

[0015] Skin Research and Technology 2009; 15: 299-305

[0016] [Problem in one aspect of the first invention] Currently, most microneedles commercially available for cosmetic use are composed mainly of hyaluronic acid. Therefore, the cosmetic effects of cosmetic methods and cosmetic devices using microneedles are thought to be mainly derived from hyaluronic acid, i.e., the moisturizing effect is mainly expected.

[0017] On the other hand, there is still room for improvement in beauty tools for improving the barrier function of the skin and beauty tools for improving the transparency of the skin.

[0018] According to a first aspect of the present invention, there is provided a beauty device and beauty kit for improving the barrier function and / or clarity of the skin.

[0019] According to one aspect of the first invention, there is also provided a method for improving the barrier function of skin and / or a method for improving skin clarity.

[0020] [Problems in one aspect of the second present invention] As described in Patent Document 4, various collagen production promoters have been developed, and there is also a need for the development of beauty devices and the like for promoting collagen production.

[0021] According to a second aspect of the present invention, a beauty device and a beauty kit for promoting collagen production are provided.

[0022] According to another aspect of the second invention, a method for promoting collagen production can be provided.

[0023] According to another aspect of the second invention, a beauty tool and a beauty kit for improving sagging skin can be provided.

[0024] According to another aspect of the second invention, there can be provided a method for improving sagging skin.

[0025] [Problem in the Third Aspect of the Invention] Currently, most microneedles commercially available for cosmetic use are composed mainly of hyaluronic acid. Therefore, the cosmetic effects of cosmetic methods and cosmetic devices using microneedles are thought to be mainly derived from hyaluronic acid, i.e., the moisturizing effect is mainly expected.

[0026] On the other hand, there is still room for improvement in beauty devices and the like for use in beauty methods for improving the skin condition of a subject, particularly in subjects who need to adjust the M1 / M2 balance or increase the number of muscle fiber cells.

[0027] According to a third aspect of the present invention, there is provided a method for improving the condition of a subject's skin, which may involve using, for example, a tool having a part with needle-like protrusions (sometimes referred to as a beauty tool or needle beauty tool).

[0028] According to a third aspect of the present invention, there can be provided an apparatus (which may be referred to as a beauty apparatus, needle beauty apparatus, etc.) for use in a beauty method for improving the condition of a subject's skin.

[0029] A first aspect of the present invention that achieves the above object is as follows.

[0030] <Aspect 1-1> A needle beauty device having a part with needle-like projections, and for improving the barrier function and / or transparency of the skin. <Aspect 1-2> The beauty device according to Aspect 1-1, wherein the part with needle-like projections has: a plate having an injection hole penetrating vertically; one or more minute needle-like projections protruding from one side of the plate; and a lip portion formed on the outer edge of one side of the plate. <Aspect 1-3> The beauty device according to Aspect 1-1, wherein the part with needle-like projections has: a plate; one or more pedestal portions protruding from one side of the plate; one or more minute needle-like projections protruding from the tip surface of each of the one or more pedestal portions; and a lip portion formed on the outer edge of the tip surface of the pedestal portion. <Aspect 1-4> The beauty device according to any one of Aspects 1-1 to 1-3, wherein a medicinal solution is injected into a target object via the part with needle-like projections. Aspect 1-5: A beauty kit for improving skin barrier function and / or clarity, comprising the beauty tool according to Aspect 1-4 and the medicinal solution. Aspect 1-6: A beauty kit according to Aspect 1-5, wherein the medicinal solution contains niacinamide. Aspect 1-7: A beauty kit according to Aspect 1-5 or 1-6, which can improve skin clarity in a shorter period of time than when the medicinal solution is applied to the skin. Aspect 1-8: A beauty kit according to any one of Aspects 1-5 to 1-7, which can improve skin barrier function, improve skin clarity, promote collagen production in the skin, or reduce sagging skin. Aspect 1-9: A method for improving skin barrier function and / or clarity, comprising applying the beauty tool according to any one of Aspects 1-1 to 1-4 to skin. Aspect 1-10: A method for improving skin barrier function and / or clarity, comprising applying the beauty tool to skin using the beauty kit according to any one of Aspects 1-5 to 1-8. Aspect 1-11: The method according to Aspect 1-9 or 1-10, comprising injecting a medicinal solution into the subject, and wherein the medicinal solution comprises niacinamide.Aspect 1-12: The method according to any one of Aspects 1-9 to 1-1-11, which can improve the skin's barrier function, improve skin clarity, promote collagen production in the skin, or reduce skin sagging. Aspect 1-13: The method according to any one of Aspects 1-9 to 1-12, which can improve skin clarity in a shorter period of time than when the medicinal liquid is applied to the skin.

[0031] A second aspect of the present invention that achieves the above object is as follows.

[0032] <Aspect 2-1> A needle beauty device having a part with needle-like projections and for promoting collagen production. <Aspect 2-2> A needle beauty device having a part with needle-like projections and for improving sagging skin. <Aspect 2-3> The beauty device according to Aspect 2-1 or 2-2, wherein the part with needle-like projections has: a plate formed with an outlet hole passing through in the vertical direction; one or more minute needle-like projections protruding from one side of the plate; and a lip portion formed on the outer edge of the one side of the plate. <Aspect 2-4> The beauty device according to Aspect 2-1 or 2-2, wherein the part with needle-like projections has: a plate; one or more pedestal portions protruding from one side of the plate; one or more minute needle-like projections protruding from the tip surface of each of the one or more pedestal portions; and a lip portion formed on the outer edge of the tip surface of the pedestal portion. <Aspect 2-5> The beauty tool according to any one of Aspects 2-1 to 2-4, which is for injecting a medicinal solution into a target object via the part with needle-like projections. <Aspect 2-6> A beauty kit for promoting collagen production, comprising the beauty tool according to Aspect 2-5 and the medicinal solution. <Aspect 2-7> The beauty kit according to Aspect 2-6, wherein the medicinal solution contains niacinamide. <Aspect 2-8> The beauty kit according to Aspect 2-6 or 2-7, which is capable of improving sagging skin, promoting collagen production in the skin, improving the skin's barrier function, or improving skin clarity. <Aspect 2-9> A method for promoting collagen production, which comprises applying the beauty tool according to any one of Aspects 2-1 to 2-5 to skin. <Aspect 2-10> A method for promoting collagen production, which comprises applying the beauty tool to skin using the beauty kit according to any one of Aspects 2-6 to 2-8. Aspect 2-11: The method for promoting collagen production according to Aspect 2-9 or 2-10, which comprises injecting a medicinal solution into a subject, and the medicinal solution contains niacinamide. Aspect 2-12: The method for promoting collagen production according to any one of Aspects 2-9 to 2-11, which is capable of improving sagging skin, promoting collagen production in the skin, improving the skin barrier function, or improving skin transparency.

[0033] A third aspect of the present invention that achieves the above object is as follows.

[0034] As described above, this embodiment provides, for example, a method for improving the skin condition of a subject. In the above method, for example, an instrument having a part with needle-like protrusions (sometimes referred to as a beauty instrument, needle beauty instrument, etc.) is used. In the above method, the effective puncture length of the needle-like protrusions into the skin may be 5 μm or more and 200 μm or less. This prevents the needle-like protrusions from reaching the dermis. As a result, damage to the skin can be reduced.

[0035] In the above method, the part with needle-like protrusions comprises, for example, a plate having a pouring hole formed therethrough in the vertical direction, and one or more minute needle-like protrusions protruding from one surface of the plate. The part with needle-like protrusions may further comprise a lip portion formed on the outer edge of one surface of the plate. In the part with needle-like protrusions, at least one of the one or more minute needle-like protrusions may be arranged inside the lip portion.

[0036] In the above method, the part with pin-like protrusions may, for example, comprise a plate, one or more base portions protruding from one side of the plate, and one or more minute pin-like protrusions protruding from the tip surface of each of the one or more base portions. The part with pin-like protrusions may further comprise a lip portion formed on the outer edge of the tip surface of the base portion. In the part with pin-like protrusions, at least one of the one or more minute pin-like protrusions may be arranged inside the lip portion.

[0037] The above method includes, for example, (i) a step of pressing the needle-shaped projections against the skin with a pressure of 50 to 1200 gf. This can have the effects of improving the skin's barrier function, improving skin clarity, promoting collagen production in the skin, and / or reducing skin sagging. The above method can have particularly significant effects when used in combination with a specific drug. The above pressure may be 100 to 1000 gf. This can suppress damage to the skin. The above pressure is preferably 300 to 900 gf. This can further suppress damage to the skin. As a result, for example, skin darkening can be suppressed.

[0038] The above method includes, for example, (ii) a step of pressing the acicular projections against the skin at least twice at a frequency of at least once every two days, or at least three times a week. This significantly improves the skin's barrier function, improves skin clarity, promotes collagen production in the skin, and / or reduces sagging skin, thereby improving the user experience.

[0039] According to this embodiment, there is provided a device (which may be referred to as a beauty device, needle beauty device, etc.) for use in a beauty method for improving the skin condition of a subject. The device has, for example, a part with needle-like protrusions. The device may be a needle beauty device. In the device, the part with needle-like protrusions may include needle-like protrusions. The effective puncture length of the needle-like protrusions into the skin is preferably a length that does not reach the dermis. The effective puncture length may be 5 μm or more and 200 μm or less. This can reduce damage to the skin.

[0040] For the above-described device, the cosmetic method includes, for example, (i) pressing the device against the skin with a pressure of 50 to 1200 gf. The cosmetic method includes, for example, (ii) pressing the device against the skin at least twice a day at a frequency of at least once every two days, or at least three times a week. This significantly improves the skin's barrier function, improves skin clarity, promotes collagen production, and / or reduces sagging skin. As a result, the user experience is improved.

[0041] The above method and / or device can adjust the M1 / M2 balance within the skin, and therefore, by applying the above method and / or device to a subject for whom adjustment of the M1 / M2 balance within the skin is desired, the M1 / M2 balance within the skin of the subject can be particularly improved.

[0042] The above method and / or the above device can increase the number of muscle fiber cells inside the skin. Therefore, when the above method and / or the above device are applied to a subject for whom an increase in the number of muscle fiber cells inside the skin is desired, the number of muscle fiber cells inside the skin of the subject can be particularly increased.

[0043] <Aspect 3-1> A device for use in a method for improving the skin condition of a subject, the device having a part with needle-like protrusions, the part with needle-like protrusions including needle-like protrusions, and the effective puncture length of the needle-like protrusions in the skin is a length that does not reach the dermis, the method comprising: (i) applying a pressing pressure of 50 to 1200 gf to the skin with the beauty device, and (ii) using the device at least twice a day and at least once every two days, or at least three times a week. <Aspect 3-2> The beauty device according to Aspect 3-1, wherein the subject needs to have the M1 / M2 balance adjusted. <Aspect 3-3> The beauty device according to Aspect 3-1, wherein the subject needs to have the number of muscle fiber cells increased. Aspect 3-4: The beauty tool according to any one of Aspects 3-1 to 3-3, wherein the part with needle-like projections comprises: a plate having a vertically penetrating outlet formed therein; one or more minute needle-like projections protruding from one surface of the plate; and a lip portion formed on the outer edge of one surface of the plate. Aspect 3-5: The beauty tool according to any one of Aspects 3-1 to 3-3, wherein the part with needle-like projections comprises: a plate; one or more pedestal portions protruding from one surface of the plate; one or more minute needle-like projections protruding from a tip surface of each of the one or more pedestal portions; and a lip portion formed on the outer edge of the tip surface of the pedestal portion. Aspect 3-6: The tool according to Aspect 3-1, which is used to improve the barrier function of the skin. Aspect 3-7: The tool according to Aspect 3-1, which is used to improve the transparency of the skin. Aspect 3-8: The tool according to Aspect 3-1, which is used to promote collagen production in the skin. <Aspect 3-9> The device according to Aspect 3-1, used to improve sagging skin. <Aspect 3-10> The device according to any one of Aspects 3-1 to 3-9, which is for injecting a medicinal solution into a subject via the part with needle-like projections. <Aspect 3-11> A beauty kit for improving the barrier function and / or transparency of the skin, comprising the device according to Aspect 3-10 and the medicinal solution. <Aspect 3-12> The beauty kit according to Aspect 3-10, wherein the medicinal solution contains niacinamide.<Aspect 3-13> The beauty kit according to Aspect 3-11 or 3-12, which can improve the transparency of the skin in a shorter period of time than when the medicinal liquid is applied to the skin. <Aspect 3-14> The beauty kit according to any one of Aspects 3-11 to 3-13, which can improve the skin's barrier function, improve the transparency of the skin, promote collagen production in the skin, or reduce sagging skin. <Aspect 3-15> A beauty method for improving the condition of a subject's skin, comprising: (i) applying a pressing pressure of 50 to 1200 gf with a beauty tool against the skin, and (ii) using the beauty tool at a frequency of at least once every two days and at least twice a week, or at least three times a week; and wherein the beauty tool is a needle beauty tool having a part with needle-like projections, the part with needle-like projections includes needle-like projections, and the effective puncture length of the needle-like projections in the skin is a length that does not reach the dermis. <Aspect 3-16> The cosmetic method according to Aspect 3-15, wherein the subject requires adjustment of the M1 / M2 balance. <Aspect 3-17> The cosmetic method according to Aspect 3-15, wherein the subject requires an increase in the number of muscle fiber cells. <Aspect 3-18> The cosmetic method according to any one of Aspects 3-15 to 3-17, wherein the purpose is to adjust the M1 / M2 balance of the subject and / or to increase the number of muscle fiber cells of the subject. <Aspect 3-19> A cosmetic kit for promoting collagen production, comprising the device according to any one of Aspects 3-1 to 3-10 and the medicinal solution. <Aspect 3-20> The cosmetic kit according to claim 3-19, wherein the medicinal solution contains niacinamide. <Aspect 3-21> The cosmetic kit according to Aspect 3-19 or 3-20, which is capable of improving sagging skin, promoting collagen production in the skin, improving the skin's barrier function, or improving skin clarity. <Aspect 3-22> A method for promoting collagen production, comprising applying to skin the tool according to any one of Aspects 3-1 to 3-10. <Aspect 3-23> A method for promoting collagen production, comprising applying to skin the beauty tool using the beauty kit according to any one of Aspects 3-19 to 3-21.<Aspect 3-24> The method for promoting collagen production according to Aspect 3-22 or 3-23, comprising injecting a medicinal solution into a subject, and the medicinal solution contains niacinamide. <Aspect 3-25> The method for promoting collagen production according to any one of Aspects 3-22 to 3-24, which is capable of improving sagging skin, promoting collagen production in the skin, improving the skin's barrier function, or improving skin clarity. <Aspect 3-26> The device according to any one of Aspects 3-1 to 3-10, wherein the effective puncture length of the needle-like projections into the skin is 5 μm or more and 200 μm or less. <Aspect 3-27> The beauty method according to Aspects 3-15 to 3-18, wherein the beauty device is the device according to any one of Aspects 3-1 to 3-10.

[0044] [Effects of the First Aspect of the Present Invention] According to the first aspect of the present invention, it is possible to provide a beauty tool for improving the barrier function and / or transparency of the skin.

[0045] According to one aspect of the first present invention, a beauty kit for improving the barrier function and / or clarity of the skin can also be provided.

[0046] Furthermore, according to one aspect of the first present invention, a method for improving the barrier function and / or clarity of the skin can be provided.

[0047] [Effect of the Second Aspect of the Present Invention] According to the second aspect of the present invention, a beauty tool for promoting collagen production can be provided.

[0048] According to the second aspect of the present invention, a beauty kit for promoting collagen production can also be provided.

[0049] Furthermore, according to a second aspect of the present invention, a method for promoting collagen production can be provided.

[0050] As described above, one aspect of the second present invention promotes collagen production by utilizing physical stimulation from a needle cosmetic device, and can achieve a collagen production promoting effect through a mechanism different from that of conventional topical skin preparations such as collagen production promoters.

[0051] According to a second aspect of the present invention, a needle cosmetic device for reducing sagging skin can be provided. According to a second aspect of the present invention, a cosmetic kit for reducing sagging skin can be provided. Furthermore, according to a second aspect of the present invention, a method for reducing sagging skin can be provided.

[0052] [Effects of the Third Aspect of the Present Invention] According to the third aspect of the present invention, it is possible to provide a beauty tool for use in a beauty method for improving the condition of the skin of a subject.

[0053] Furthermore, the subject of one aspect of the third present invention may be a subject in which the M1 / M2 balance needs to be regulated, or a subject in which the number of muscle fiber cells needs to be increased.

[0054] Therefore, according to the third aspect of the present invention, it is possible to adjust the M1 / M2 balance in the skin of a subject, and also to increase the number of muscle fiber cells in a subject.

[0055] FIG. 1 is a schematic diagram showing one embodiment of the acicular projection part according to the first, second and third aspects of the present invention. FIG. 2 is a schematic diagram showing a part of another embodiment of the acicular projection part according to the first and second aspects of the present invention. FIG. 3 is a schematic diagram showing one embodiment of a beauty tool comprising a acicular projection part and a fixing device. FIG. 4 is a diagram showing the intradermal distribution of the epidermal proliferation marker Ki-67 when Examples 1-1 and 1-2 are applied. FIG. 4-1 is a diagram showing the collagen production promoting effect of Examples 2-1 and 2-2. FIG. 5 is a diagram showing the density of epidermal proliferation marker Ki-67-positive cells in the skin (cells / mm ) when Examples 1-1 and 1-2 are applied. ２) and changes in the amount of α-SMA / Vimentin. Figure 5-1 shows the results of immunofluorescent staining of α-SMA / Vimentin and nuclei (Hoechst) in Example 2-3. Figure 5-2 is a graph showing the quantification of the stained image of Figure 5-1 in Example 2-3, using the image analysis software Image J, within 200 μm of the epidermal basement membrane, and counting the number of α-SMA / Vimentin positive cells (myofibroblasts) within that area. Figure 6 is an explanatory diagram showing the application site of Example 1-3. Figure 6-1 is a diagram showing the penetration-promoting effect of a niacinamide-containing solution using the second beauty device of the present invention. Figure 7 is a diagram showing the amount of skin water loss in Example 1-3. Figure 7 is a diagram showing the penetration-promoting effect of a medicinal solution containing a model drug (water-soluble fluorescent substance) using the second beauty device of the present invention. Figure 8 is a diagram showing the evaluation scale for evaluating transparency. Figure 8-1 is an explanatory diagram showing the application site of Example 2-5. FIG. 9 shows the improvement in skin clarity achieved by Example 1-4. FIG. 9-1 shows the change in facial line angle over time for subjects in Example 2-5. FIG. 10 shows the penetration-promoting effect of a niacinamide-containing solution achieved by the first beauty device of the present invention. FIG. 10-1 shows a 3D scan image of the lower jaw showing the sagging improvement effect of one subject in Example 2-5. FIG. 11 shows the penetration-promoting effect of a medicinal solution containing a model drug (water-soluble fluorescent substance) achieved by the first beauty device of the present invention. FIG. 11-1 shows the results of the volume change in the lower jaw for subjects in Example 2-6 and Comparative Example 2-1. FIG. 12 shows images of fresh skin photographed with a confocal microscope after fluorescent immunostaining using antibodies against the vascular endothelial cell marker CD31, the myofibroblast marker αSMA, and the fibroblast marker vimentin, and Hoechst for nuclear staining. Figure 13 is a graph showing the time course of counting myofibroblasts (α-SMA / vimentin positive cells) present in a range of 200 μm beneath the epidermal basement membrane using the image analysis software ImageJ based on the results of Figure 12. Figure 14 is a graph showing the time course of counting vascular endothelial cells (CD31 positive cells) present in a range of 200 μm beneath the epidermal basement membrane using the image analysis software ImageJ based on the results of Figure 12.Figure 15 shows fresh skin fluorescently stained with antibodies against the M1 macrophage marker CD86 and the macrophage marker CD68, and Hoechst stained for nuclei, followed by confocal microscopy. Figure 16 shows fresh skin fluorescently stained with antibodies against the M2 macrophage marker CD206 and the macrophage marker CD68, and Hoechst stained for nuclei, followed by confocal microscopy. Figure 17 shows a graph of the time course of the number of M1 macrophages present within 200 μm of the epidermal basement membrane, counted using image analysis software ImageJ based on the results of Figure 15. Figure 18 shows a graph of the time course of the number of M2 macrophages present within 200 μm of the epidermal basement membrane, counted using image analysis software ImageJ based on the results of Figure 16. Figure 19 is a graph showing the quantification of the M1 / M2 ratio based on the number of M1 macrophages and the number of M2 macrophages in Figures 17 and 18, and the time course of the quantification. Figure 20-1 shows the actual image and functional explanatory diagram of the manufactured Injectable-MN. a) is a top view and a side view of the PGA-MN, b) is a diagram of the Injectable-MN (PGA-MN connected to a knock-type pen), and c) is a functional diagram of the Injectable-MN. Figure 20-2 is a schematic diagram of the MN (array) structure. a) is a cross-sectional view, and b) is a top view of the MN array. Figure 20-3 shows the results of the puncture ability test. a) Puncture ability vs. MN length, b) Puncture ability vs. total length (MN + MN w / base), c) Puncture ability vs. a. Diameter of the base under the MN, d. Puncture rate of the arrayed MN, e. Puncture rate vs. Pitch between MNs on the array. Figure 20-4 shows a cross-sectional view of a PGA-MN-coated skin resin. Figure 20-5 shows the results of the penetration test. a. Quantitative analysis by fluorescence intensity quantification. b. Visualization of permeability by confocal Raman spectroscopy; color shading indicates niacinamide concentration. Data are shown ± SEM, and * indicates p<0.05. Figure 20-6 shows the results of RNA-seq.Figure 20-7 shows the difference in blood flow before and after application. Data are shown as ±SEM, with * indicating p<0.05 and ** indicating p<0.01. Figure 20-8 shows the results of a home-use human experiment. a. Graph of changes in wrinkle grade over time; b. Graph of changes in skin clarity grade over time; c. Graph of changes in skin softness sensation over time; d. Graph of changes in skin moisture sensation over time; e. Graph of changes in nasolabial fold grade over time; f. Graph of changes in marionette line grade over time; g. Graph of changes in face line grade over time; h. Graph of changes in chin volume over time; i. Photograph of subject's appearance: example of improvement in nasolabial folds; j. 20-9 is a graph showing the time course of TEWL. Data are shown as ±SEM, with * indicating p<0.05, ** indicating p<0.01, and *** indicating p<0.001. Figure 20-9 is a schematic diagram showing activation of whole skin cells by injectable MN (the synergistic effect of mechanobiological stimulation and effective nutrient delivery).

[0056] The present invention will be described below through embodiments of the invention, but the following embodiments do not limit the invention according to the claims. Furthermore, not all combinations of features described in the embodiments are necessarily essential to the solution of the invention. In this specification, when a numerical range is expressed as "A to B," this expression means A or more and B or less.

[0057] [First Present Invention] Hereinafter, a first embodiment of the present invention will be described in detail with reference to the drawings. For the sake of convenience, the same or corresponding parts in each drawing are designated by the same reference numerals, and duplicate explanations will be omitted. Furthermore, not all components of the embodiments are necessarily essential, and some components may be omitted. However, the first present invention is not limited to the following embodiments, and various modifications can be made within the scope of the invention.

[0058] <<Needle Beauty Device>> A needle beauty device according to a first embodiment of the present invention (hereinafter also simply referred to as the “beauty device of the first embodiment”) has parts with needle-like protrusions and is intended to improve the barrier function and / or transparency of the skin.

[0059] The "needle-shaped protrusion part" disclosed in Patent Document 2 can be used as the needle-shaped protrusion part of the beauty device of the first embodiment. Furthermore, the beauty device (apparatus) disclosed in Patent Document 2 can be used as the needle beauty device of the first embodiment. Note that Patent Document 2 does not disclose or suggest anything about the skin's barrier function, but rather describes the "needle-shaped protrusion part" as being intended to retain a liquid composition / liquid cosmetic, with any active ingredient, on the surface or inside of an object to prevent leakage through gaps. In this regard, considering that microneedles and the like puncture the skin, the effect of improving the skin's barrier function of the first embodiment is considered unexpected.

[0060] Through intensive research, the inventors have found that the barrier function of the skin can be improved by using the beauty device of the first embodiment that has such a part with needle-like projections.

[0061] Without being limited by theory, it is speculated that the application of the beauty device of the first embodiment to the skin with its needle-like protrusions causes punctures in the surface layer of the skin and large deformations that reach deep into the skin, stimulating cells and activating differentiation, thereby promoting cell turnover. It is speculated that the promotion of cell turnover leads to improvements in the skin's barrier function and / or transparency. Furthermore, it has been found that application of this beauty device has a transient blood flow promotion effect (data not shown), and it is speculated that the further promotion of cell turnover enhances the above-mentioned effects.

[0062] Furthermore, through extensive research by the present inventors, it has been found that the beauty device of the first embodiment has the effect of promoting epidermal cell proliferation, which is thought to lead to improvements in the barrier function and / or transparency of the skin.

[0063] In the first embodiment, the skin barrier function is a function performed by the stratum corneum and epidermis of the skin, which prevents the loss of water essential for the activity of cells and tissues constituting a living body, and prevents external stimuli and substances such as viruses and bacteria from entering the body. The skin barrier function is measured as the transepidermal water loss (TEWL) (g / m) under non-sweating conditions. ２ ・h) can be used as a unit of evaluation (Cosmetics Encyclopedia, edited by the Japan Society of Cosmetic Chemists, Maruzen Co., Ltd., 2005, pp. 83-84).

[0064] In the first embodiment, the transparency of the skin refers to a state in which the skin (particularly the entire face) appears clear and transparent.

[0065] The part with needle-like protrusions according to the first embodiment may have: a plate having an injection hole formed therein that penetrates vertically; one or more tiny needle-like protrusions protruding from one side of the plate; and a lip portion formed on the outer edge of one side of the plate; or may have: a plate; one or more base portions protruding from one side of the plate; one or more tiny needle-like protrusions protruding from the tip surface of each of the one or more base portions; and a lip portion formed on the outer edge of the tip surface of the base portion.

[0066] The beauty tool of the first embodiment may be used to inject a medicinal liquid into a target object via a part with needle-like projections.

[0067] In this case, the beauty tool of the first embodiment may be a beauty tool having a part with needle-like protrusions for injecting a medicinal solution into a target object, the part with needle-like protrusions having: a plate formed with an outlet hole passing through it vertically; one or more minute needle-like protrusions protruding from one surface of the plate; and a lip portion formed on the outer edge of one surface of the plate, and when the composition of the first embodiment is extruded from the outlet hole, the composition of the first embodiment spreads into the space formed between the target object, the lip portion, and one surface of the plate, and also enters the inside of the target object through the holes opened by the one or more needle-like protrusions, or a beauty tool having a part with needle-like protrusions for injecting the composition of the first embodiment into a target object, the part with needle-like protrusions having: a plate; one or more pedestal portions protruding from one surface of the plate; one or more minute needle-like protrusions protruding from the tip surface of each of the one or more pedestal portions; and a lip portion formed on the outer edge of the tip surface of the pedestal portion, The beauty device may be one in which the plate and one or more base parts are formed with a dispensing hole that penetrates vertically from another surface of the plate to the tip surface of the base part, and when the composition of the first embodiment is discharged from the dispensing hole, the composition of the first embodiment spreads into a space formed between the target object, the lip part, and the tip surface of the base part, and also enters the inside of the target object through holes formed by the one or more needle-like protrusions.

[0068] In the first embodiment and the second and third embodiments described below, the object (or subject) may be the skin of a mammal, preferably a human, or the skin of an animal or a plant. The part with needle-like protrusions may be an example of a needle beauty tool, a beauty tool, or a tool. The needle beauty tool may be an example of a beauty tool or a tool. As long as no technical contradiction occurs, the features of the first embodiment may be applied to the second and / or third embodiments, and the features of the second and / or third embodiments may be applied to the first embodiment.

[0069] Hereinafter, the parts with needle-like projections included in the needle cosmetic device of the first embodiment will be described as examples with reference to the drawings.

[0070] FIG. 1 is a schematic diagram showing one aspect of a part with needle-like projections according to the first embodiment.

[0071] Fig. 1 shows a state in which a part 100 with needle-like protrusions according to the first embodiment is puncturing a target object (skin) S. As shown in Fig. 1, the part 100 with needle-like protrusions has a plate 10 and an attachment frame 20. The plate 10 also has an outlet hole 10a that penetrates vertically, a plurality of minute needle-like protrusions 10b that protrude from one surface of the plate, and a lip portion 10c formed on the outer edge of one surface of the plate.

[0072] 1, the plate 10 has a plurality of minute needle-like projections 10b, but in the first embodiment, the number of such minute needle-like projections 10b may be one. Furthermore, in the first embodiment, such minute needle-like projections (also referred to as "microneedles" or "microneedles") need only have a certain degree of hardness so that they can be inserted into the skin and provide stimulation, and the material that constitutes them is not particularly limited. However, since they are inserted into the skin, the minute needle-like projections must be made of a biocompatible material, and may preferably be made of a material that can dissolve or swell in vivo. Examples of such materials include polyglycolic acid (PGA), polylactic acid (PLA), polylactic-co-glycolic acid (PLGA), hyaluronic acid, polysaccharides such as chitosan, maltose, alginate, amylose, and agarose, celluloses such as carboxymethyl cellulose and hydroxypropyl cellulose, and starch, and may be formed from a single material or a mixture of two or more materials. Of these materials, polyglycolic acid (PGA), polylactic acid (PLA), or polylactic-co-glycolic acid (PLGA) is particularly preferred. Alternatively, the minute needle-like projections may be formed from a resin or the like that does not dissolve or swell in the body and does not affect the body, and more specifically, they may be formed from, for example, polymethyl methacrylate, cellulose acetate, ethyl cellulose, polyethylene resin, polypropylene resin, ethylene-propylene copolymer, ethylene-vinyl acetate copolymer, vinyl chloride resin, vinylidene chloride resin, vinyl acetate-vinyl chloride copolymer, polyamide resin, polyester resin, ABS resin, SIS resin, SEBS resin, urethane resin, silicone resin, stainless steel, aluminum, magnesium, etc.

[0073] As shown in FIG. 1 , when the medicinal liquid C is extruded from the injection hole 10a, it spreads within the space formed between the target object S, the lip portion 10c, and one surface of the plate 10. The medicinal liquid C also penetrates into the target object S through the holes formed by the multiple needle-like protrusions 10b. That is, the medicinal liquid C can permeate through the gaps between the surface of the needle-like protrusions 10b and the target object S. The medicinal liquid C may be directly contained within the attachment tube 20b, or may be contained within a syringe barrel (not shown) and syringe tip 30a via a syringe. Note that in FIG. 1 , the syringe tip 30a is only a part of the syringe, and the entire syringe is not shown. The method for extruding the medicinal liquid C is not particularly limited. For example, when the needle-like protrusion part 100 is attached to a syringe, the extrusion may be performed using the syringe plunger. After injection, the needle-like protrusion part 100 may be maintained pressed against the target object S via the syringe for a predetermined time (less than 1 second to approximately 30 minutes, preferably several seconds to several minutes). Then, after a predetermined time has elapsed, the syringe may be removed from the subject S, thereby removing the needle-shaped projections 10b from the subject S. In this way, in the first embodiment, the medicinal solution C can be spread over the subject S inside the lip portion 10c, and can also permeate into the subject S through holes made by the needle-shaped projections 10b. Therefore, the medicinal solution C can permeate the subject S from both the outside and the inside. For example, if the subject S is human skin and the medicinal solution C contains a cosmetic substance, the cosmetic substance can permeate the skin from both the outside and the inside.

[0074] Although not shown in FIG. 1 , the pinned part 100 may be integrally formed with the plate 10 and the mounting frame 20. That is, the pinned part 100 may be integral. The integral pinned part 100 may be made of a biocompatible material, such as a biodegradable resin, for example, polyglycolic acid, polylactic acid, or polyglycolic acid-polylactic acid copolymer. More specifically, the integral pinned part 100 may be made of a thermoplastic resin, such as polypropylene (PP), polyethylene (PE), acrylonitrile butadiene styrene (ABS), polybutylene terephthalate (PBS), polyacetal (POM), polyethylene terephthalate (PET), polycarbonate (PC), or polyether ether ketone (PEEC).

[0075] Furthermore, the height of the needle-like protrusions 10b is not particularly limited, and the puncture depth from the tip of the needle-like protrusions 10b into the skin (i.e., the "effective puncture length of the needle-like protrusions") can be adjusted appropriately, for example, by designing the height of the lip portion 10c.

[0076] In order to maximize the effects of the third embodiment, it is preferable that the effective puncture length of the needle-like protrusions of the beauty device of the present invention is a length that does not reach the dermis. The depth from the surface of the skin to the dermis may vary or may be the same depending on the subject. Furthermore, even for the same subject, the depth from the surface of the skin to the dermis may vary or may be the same depending on the location on the skin. The depth from the surface of the skin to the dermis of the subject can be measured, for example, by preparing thin slices of excised skin and using a microscope.

[0077] Furthermore, in the third present invention, the specific value of the effective puncture length of the needle-like protrusions of the beauty device of the present invention into the skin is not particularly limited, and may be, for example, 5 μm or more, 10 μm or more, 20 μm or more, 30 μm or more, 40 μm or more, 50 μm or more, 60 μm or more, 70 μm or more, 80 μm or more, 90 μm or more, or 100 μm or more, or may be 200 μm or less, 180 μm or less, 170 μm or less, 160 μm or less, 150 μm or less, 140 μm or less, 130 μm or less, 120 μm or less, 110 μm or less, or 100 μm or less.

[0078] Furthermore, in FIG. 1, an example is described in which there is one central hole, which is the extraction hole 10a, but the hole does not have to be one, i.e., there may be two or more. The hole may be in the center, or not. Furthermore, while an example is shown in which the outer shape of the acicular projections 10b is conical, the acicular projections may be polygonal pyramid-shaped or other needle-like shapes (star-shaped, cross-shaped, etc.). Furthermore, hollow needle-shaped projections may be used instead of solid needle-shaped projections. Furthermore, the solid needle-shaped projections that constitute the acicular microprojections may have a diameter of the thickest part of the needle in the range of 2 to 5000 μm, more preferably in the range of 5 to 3000 μm.

[0079] FIG. 2 is a schematic view showing a part of another embodiment of the part with pin-like projections according to the first aspect of the present invention.

[0080] 2, a part of the part with needle-like protrusions has a plate 11, a plurality of pedestals 11d protruding from one side of the plate 11, a plurality of minute needle-like protrusions 11b protruding from the tip surface of each of the plurality of pedestals 11d, and a lip portion 11c formed on the outer edge of the tip surface of the pedestal portion 11d. In addition, the plate 11 and the plurality of pedestals 11d are formed with pouring holes 11a that penetrate vertically from the other side of the plate 11 to the tip surfaces of the pedestals 11d.

[0081] As shown in Figure 2, when the medicinal liquid C is discharged from the dispensing hole 11a, the medicinal liquid C spreads in the space formed between the object S and the tip surface of the lip portion 11c and the base portion 11d, and the medicinal liquid C can enter the inside of the object S through the hole opened by the needle-like protrusion 11b.

[0082] 2, the chemical solution C spreads over the object S on the inner circumferential side of the lip portion 11c on the contact surface CF2 of the base portion 11d, and can also permeate into the object S through the holes made by the needle-like projections 11b. Therefore, the chemical solution C can permeate the object S from both the outside and the inside.

[0083] Furthermore, in the first aspect of the present invention, because a puddle can be formed at the tip side of the pedestal portion 11d, the medicinal solution C can spread in the area inside the lip portion 11c of each pedestal portion 11d. This allows for pinpoint application of the medicinal solution C, for example, when the part with needle-like protrusions is large and the surface area of ​​the plate 11 is wide. Furthermore, in the first aspect of the present invention, the lip portion 11c connecting to the pedestal portion 11d can spread the object S over a narrow area to allow the needle-like protrusions 11b to puncture the object S, making it easier for the needle-like protrusions 11b to pierce the object S even when the surface of the object S is uneven or soft, making it possible to more reliably apply the medicinal solution C from both the outside and the inside. Furthermore, in the first aspect of the present invention, the lip portion 11c contacts the object S regardless of whether the needle-like projections 11b have punctured the object S, allowing injection pressure (resistance) to be uniformly applied to the inner peripheral region of the lip portion 11c, i.e., the entire tip portion. This has the advantage of reliably improving injectability. Furthermore, in the first aspect of the present invention, since the medicinal solution C can be more efficiently moved from the center to the outside in the gap between the plate 11 and the round plate on the top surface of the container, a band-shaped recess may be formed on the other surface F2 of the plate 11, with the shortest path for the liquid to flow from the center to the multiple injection holes 11a as a flow path. Furthermore, multiple needle-like projections 11b and / or multiple injection holes 11a may be provided on one base portion 11d. In this case, in each base portion 11d, the medicinal liquid C pushed out from the multiple injection holes 11a spreads over the object S on the inner side of the lip portion 11c on the contact surface CF2 of the base portion 11d, and can also penetrate into the inside of the object S through holes made by the multiple needle-shaped protrusions 11b.

[0084] Note that the part of the part with pin-like projections shown in FIG. 2, and the whole part (not shown), may have various forms and modifications, just like the pin-like projections part 100 described above.

[0085] Furthermore, the beauty tool of the first aspect of the present invention may further include, in addition to the above-described part with needle-like protrusions, a fixing device to which the part with needle-like protrusions can be attached. The fixing device can also contain a medicinal solution.

[0086] FIG. 3 is a schematic diagram showing one embodiment of a beauty tool including a part with needle-like projections and a fixing device.

[0087] As shown in FIG. 3 , the beauty tool 200 includes a needle-like protrusion part 101 and a syringe 30 as a fixing device to which the needle-like protrusion part 101 is attached. The needle-like protrusion part 101 includes a mounting frame 20 and a plate 10. The mounting frame 20 has a plate support part 20a and a mounting cylinder 20b. The plate 10 has an injection hole (not shown) penetrating vertically, one or more minute needle-like protrusions protruding from one side of the plate 10, and a lip part formed on the outer edge of one side of the plate 10. The syringe 30 includes a syringe barrel (main body) 30b and a plunger 30c. The needle-like protrusion part 101 is attached from the mounting cylinder 20b side of the mounting frame 20 to the syringe barrel tip 30a side of the syringe 30. The syringe barrel 30b contains medicinal solution C, and the plunger 30c is inserted into the syringe barrel 30b. When the pushing piece 30d at the rear end of the plunger 30c is pressed, the plunger 30c moves inside the syringe barrel 30b, releasing the medicinal solution C into the needle-like protrusion part 101 and allowing it to penetrate into the target object (not shown). In the first aspect of the present invention, the fixing device can be a syringe having a capacity of, for example, 1 mL, 2.5 mL, 5 mL, or 10 mL. Depending on the specific use of the needle-like protrusion part, the syringe may have a larger or smaller capacity.

[0088] In addition, in FIG. 3, the fixing device is depicted in the shape of a syringe 30, but it may be modified to have another shape as long as the effect of the first invention is not impaired.

[0089] Furthermore, the beauty tool of the first aspect of the present invention may optionally be provided with a cap (not shown), for example, on the side of the needle-like projections of the part with needle-like projections.

[0090] In the first invention and the second and third inventions described below, the pressure applied to press the beauty tool of the present invention is not particularly limited and may be, for example, 1200 gf or less, 1100 gf or less, 1000 gf or less, 900 gf or less, 800 gf or less, 700 gf or less, or 600 gf or less, or 50 gf or more, 100 gf or more, 200 gf or more, 300 gf or more, 400 gf or more, 500 gf or more, or 600 gf or more. From the viewpoint of further exerting the effects of the third invention, the pressure applied to press the beauty tool of the present invention is preferably, for example, 900 gf or less.

[0091] <<Cosmetic Kit of the First Invention>> The first invention also provides a cosmetic kit, particularly a cosmetic kit for improving the barrier function and / or clarity of skin. Preferably, the first invention provides a cosmetic kit for improving the barrier function and clarity of skin.

[0092] The beauty kit of the first invention includes the beauty tool of the first invention and a medicinal solution. For a detailed description of the beauty tool of the first invention, please refer to the description in the "Beauty Tool of the First Invention" section above.

[0093] In the first aspect of the present invention, the medicinal liquid is not particularly limited as long as it does not impair the effects of the first aspect of the present invention, and may be, for example, a cosmetic substance that provides some kind of cosmetic effect to the skin (e.g., moisturizing effect, firming effect, barrier function improving effect, blood flow enhancing effect, whitening effect, anti-blemish effect, anti-wrinkle effect, anti-acne effect, or anti-inflammatory effect, etc.). Specifically, the medicinal liquid may be, for example, a moisturizing agent, firming agent, barrier function improving agent, blood flow enhancing agent, whitening agent, anti-blemish agent, anti-wrinkle agent, anti-acne agent, or anti-inflammatory agent, and among these cosmetic substances, water-soluble cosmetic substances are particularly preferred. More specifically, examples of medicinal solutions include, but are not limited to, alkoxysalicylic acid and its salts, 1-piperidinepropionic acid and its salts, tranexamic acid and its salts, hyaluronic acid and its salts, vitamin A group and its derivatives, vitamin B group and its derivatives, vitamin C group and its derivatives, alkylene oxide derivatives, proteins and peptides such as collagen and EGF, amino acids, and polyhydric alcohols such as glycerin.

[0094] Through intensive research, the first inventors have found that the beauty device of the first invention can improve the permeability of niacinamide into the skin. Therefore, in the first invention, the medicinal solution preferably contains niacinamide.

[0095] Niacinamide, also known as nicotinamide or vitamin B3, is a coenzyme that is deeply involved in various biochemical reactions in the body, such as energy metabolism and oxidation-reduction. The structure of niacinamide is shown in the following formula.

[0096]

[0097] The first cosmetic device of the present invention can improve the skin barrier function in a shorter time when a medicinal solution containing niacinamide is injected into the subject via a part with needle-like protrusions, compared to when niacinamide is applied directly to the skin. Therefore, the first cosmetic device of the present invention can be a cosmetic device for improving the skin barrier function in a short time. Here, the short time period for improving the skin barrier function can be, for example, within 2 months, 8 weeks, 7 weeks, 6 weeks, 5 weeks, 4 weeks, 3 weeks, 2 weeks, or 1 week. The lower limit is not particularly limited, and can be, for example, 1 day or more, 2 days or more, 3 days or more, 4 days or more, 5 days or more, 6 days or more, or 1 week or more.

[0098] Furthermore, when the first cosmetic device of the present invention injects a medicinal solution containing niacinamide into a subject via a part with needle-like protrusions, it can improve skin clarity in a shorter period of time than when niacinamide is applied directly to the skin. Therefore, the first cosmetic device of the present invention may be a cosmetic device for improving skin clarity in a short period of time. Here, the short period of time for improving skin clarity may be, for example, within 2 months, 8 weeks, 7 weeks, 6 weeks, 5 weeks, 4 weeks, 3 weeks, 2 weeks, or 1 week. The lower limit of the period is not particularly limited, and may be, for example, 1 day or more, 2 days or more, 3 days or more, 4 days or more, 5 days or more, 6 days or more, or 1 week or more.

[0099] It is generally known that in order to give skin a translucent appearance, it is important to have a balance between moisture and oil and for skin turnover to occur smoothly. However, since the skin turnover cycle is usually about 30 days, it has been difficult to improve skin translucency in a period shorter than the turnover cycle.

[0100] In the first aspect of the present invention, the concentration of niacinamide in the medicinal solution is not particularly limited.From the viewpoint of more effectively and preferably more quickly promoting the improvement of the barrier function and / or transparency of the skin, the concentration of niacinamide is, for example, 0.10% by mass or more, 0.15% by mass or more, 0.20% by mass or more, 0.25% by mass or more, 0.30% by mass or more, 0.35% by mass or more, 0.40% by mass or more, 0.45% by mass or more, 0.50% by mass or more, 0.55% by mass or more, 0.60% by mass or more, 0.65% by mass or more, 0.70% by mass or more, 0.75% by mass or more, 0.80% by mass or more, 0.85% by mass or more, 0.90% by mass or more, 0.95 ... 0% by mass or more, 0.75% by mass or more, 0.80% by mass or more, 0.85% by mass or more, 0.90% by mass or more, 1.00% by mass or more, 1.10% by mass or more, 1.20% by mass or more, 1.30% by mass or more, 1.40% by mass or more, 1. 50% by mass or more, 1.60% by mass or more, 1.70% by mass or more, 1.80% by mass or more, 1.90% by mass or more, 2.00% by mass or more, 2.10% by mass or more, 2.20% by mass or more, 2.30% by mass or more, 2.40% by mass or more, 2. 50% by mass or more, 2.60% by mass or more, 2.70% by mass or more, 2.80% by mass or more, 2.90% by mass or more, 3.00% by mass or more, 3.50% by mass or more, 4.00% by mass or more, 4.50% by mass or more, 5.00% by mass or more, 6 .00 mass% or more, 7.00 mass% or more, 8.00 mass% or more, 9.00 mass% or more, 10.0 mass% or more, 11.0 mass% or more, 12.0 mass% or more, 13.0 mass% or more, 14.0 mass% or more, or 15.00 mass% or more Also, 30.0 mass% or less, 25.0 mass% or less, 20.0 mass% or less, 15.0 mass% or less, 14.0 mass% or less, 13.0 mass% or less, 12.0 mass% or less, 11.0 mass% or less, 10.0 mass% or less The content may be 9.00% by mass or less, 8.00% by mass or less, 7.00% by mass or less, 6.00% by mass or less, 5.00% by mass or less, 4.50% by mass or less, 4.00% by mass or less, 3.50% by mass or less, or 3.00% by mass or less.

[0101] The beauty kit of the first invention may optionally further include an instruction manual, which may describe how to set up the beauty tool of the first invention before use, how to hold it, how to use it, how often to use it, etc.

[0102] Regarding the method of using the beauty kit of the first aspect of the present invention, the description of FIG. 3 above may be referred to as appropriate. The number of times that the needle-shaped protrusion-equipped part of the beauty tool of the first aspect of the present invention is applied to a target object is not particularly limited, and the number of times may be increased as appropriate. For example, the medicinal solution may be released and penetrated into a single application site one or more times, three or more times, five or more times, ten or more times, fifteen or more times, twenty or more times, twenty or more times, thirty or more times, or thirty-five or more times. Alternatively, the medicinal solution may be released and penetrated into a single application site 100 or fewer times, 50 or fewer times, 10 or fewer times, seven or fewer times, six or fewer times, five or fewer times, four or fewer times, three or fewer times, or two or fewer times. The amount of medicinal liquid released per dose is not particularly limited and may be 0.1 μL or more, 0.2 μL or more, 0.3 μL or more, 0.4 μL or more, 0.5 μL or more, 0.6 μL or more, 0.7 μL or more, 0.8 μL or more, 0.9 μL or more, 1.0 μL or more, 1.1 μL or more, 1.2 μL or more, 1.3 μL or more, 1.4 μL or more, 1.5 μL or more, 1.6 μL or more, 1.7 μL or more, 1.8 μL or more, 1.9 μL or more, or 2.0 μL or more, or may be 10 μL or less, 5 μL or less, or 2 μL or less. The method of applying the cosmetic tool of the first present invention to the object is not particularly limited and, for example, the cosmetic tool may be applied while rotating or without rotating.

[0103] Furthermore, the frequency of use of the first beauty kit of the present invention is not particularly limited, and may be, for example, once per day, once per two days, or once per three days, or may be 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, or 6 or more times within a week, or 7 or less, 6 or less, 5 or less, 4 or less, 3 or less, or 2 or less times within a month, or even 7 or less, 6 or less, 5 or less, 4 or less, 3 or less, 2 or less, or 1 or less times within a week.

[0104] <<Method for Improving Skin Barrier Function and / or Transparency>> The first present invention also provides a method for improving skin barrier function and / or transparency. Preferably, the first present invention provides a method for improving skin barrier function and transparency.

[0105] The first method of the present invention for improving skin barrier function and / or clarity includes applying the above-described beauty device of the first present invention to skin. The first method of the present invention for improving skin barrier function and / or clarity preferably uses the beauty device of the first present invention in combination with a medicinal solution containing niacinamide. This is because the improvement of skin barrier function and / or clarity can be achieved in a shorter period of time than when using the beauty device of the first present invention alone or when applying niacinamide directly to the skin. Therefore, the first method of the present invention may be a method for improving skin barrier function and / or clarity in a short period of time.

[0106] In the method for improving the skin barrier function and transparency of the first invention, when a medicinal solution containing niacinamide is used, the method may include injecting the medicinal solution into the subject, applying the medicinal solution to the subject, or attaching a sheet mask containing the medicinal solution to the subject. In the latter case, the medicinal solution may be applied or the sheet mask may be attached to the subject before, after, or both before and after applying the cosmetic device of the first invention to the skin.

[0107] More preferably, the method for improving the barrier function and clarity of the skin of the first invention comprises injecting a medicinal solution into a subject, and the medicinal solution comprises niacinamide.

[0108] The method for improving the barrier function and transparency of the skin according to the first aspect of the present invention is strictly for cosmetic purposes and is not a so-called "medical procedure" such as a surgical procedure for humans or a treatment method for human illnesses.

[0109] Furthermore, in the first aspect of the present invention, the skin is not limited to mammalian skin (particularly human skin), but may also be animal skin, or the surface of a plant stem, trunk, or leaf, or the like.

[0110] [Second Present Invention] Hereinafter, a detailed description will be given of an embodiment of the second present invention with reference to the drawings. For the sake of convenience, the same or corresponding parts in each drawing are designated by the same reference numerals, and duplicate explanations will be omitted. Furthermore, not all of the components of the embodiment are necessarily essential, and some components may be omitted. However, the present invention is not limited to the following embodiment, and various modifications can be made within the scope of the invention.

[0111] The needle beauty device of the second present invention (hereinafter also referred to simply as the "beauty device of the second present invention") has parts with needle-like projections and is intended to promote collagen production. The beauty device of the second present invention may also have parts with needle-like projections and be intended to improve sagging skin.

[0112] The "needle-shaped protrusion part" disclosed in Patent Document 2 can be used as the needle-shaped protrusion part of the beauty tool of the second invention. The beauty tool (apparatus) disclosed in Patent Document 2 can be used as the needle-shaped protrusion part of the second invention. It should be noted that Patent Document 2 describes the "needle-shaped protrusion part" as a part that can retain a liquid composition / liquid cosmetic, with any active ingredient, on the surface or inside of an object to prevent leakage through gaps, but does not disclose or suggest anything about collagen production, improvement of sagging, or the like.

[0113] Through intensive research, the present inventors have found that collagen production can be promoted by using the cosmetic device of the second invention having such a part with needle-like projections. Furthermore, the cosmetic device of the second invention can also be used to improve sagging skin.

[0114] Without being limited by theory, it is speculated that the second beauty device of the present invention, when its needle-like protrusion parts are applied to the skin, causes significant deformation deep into the skin, thereby promoting blood flow and facilitating collagen production.

[0115] A part with needle-like protrusions according to the second aspect of the present invention may have: a plate having an injection hole formed therein that penetrates vertically; one or more tiny needle-like protrusions protruding from one side of the plate; and a lip portion formed on the outer edge of one side of the plate; or may have: a plate; one or more base portions protruding from one side of the plate; one or more tiny needle-like protrusions protruding from the tip surface of each of the one or more base portions; and a lip portion formed on the outer edge of the tip surface of the base portion.

[0116] The second beauty tool of the present invention may be for injecting a medicinal solution into a target object via a part with needle-like protrusions. The second beauty tool of the present invention may be the same as the "first beauty tool" described above. Therefore, the description of the "first beauty tool" described above can be referenced for the second beauty tool of the present invention, and the description thereof will be omitted here.

[0117] <<Cosmetic Kit of the Second Invention>> The second invention also provides a cosmetic kit, particularly a cosmetic kit for promoting collagen production.

[0118] The beauty kit of the second invention includes the beauty tool of the second invention and a medicinal solution. For a detailed description of the beauty tool of the second invention, please refer to the description of the "Beauty Tool of the First Invention" above.

[0119] In the second invention, the medicinal liquid is not particularly limited as long as it does not impair the effects of the second invention, and may be, for example, a cosmetic substance that provides some kind of cosmetic effect to the skin (e.g., moisturizing effect, firming effect, barrier function improving effect, blood flow enhancing effect, whitening effect, anti-blemish effect, anti-wrinkle effect, anti-acne effect, or anti-inflammatory effect, etc.). Specifically, the medicinal liquid may be, for example, a moisturizing agent, firming agent, barrier function improving agent, blood flow enhancing agent, whitening agent, anti-blemish agent, anti-wrinkle agent, anti-acne agent, or anti-inflammatory agent, and among these cosmetic substances, water-soluble cosmetic substances are particularly preferred. More specifically, examples of medicinal solutions include, but are not limited to, alkoxysalicylic acid and its salts, 1-piperidinepropionic acid and its salts, tranexamic acid and its salts, hyaluronic acid and its salts, vitamin A group and its derivatives, vitamin B group and its derivatives, vitamin C group and its derivatives, alkylene oxide derivatives, proteins and peptides such as collagen and EGF, amino acids, and polyhydric alcohols such as glycerin.

[0120] Through extensive research, the present inventors have found that the cosmetic device of the second invention can improve the permeability of niacinamide into the skin. Therefore, in the second invention, the medicinal solution preferably contains niacinamide.

[0121] Niacinamide is as explained above in the section "First Invention," and detailed explanation will be omitted here.

[0122] When the second beauty device of the present invention injects a medicinal solution containing niacinamide into the target object via a part with needle-like protrusions, it can promote collagen production more efficiently than when the second beauty device of the present invention is used alone (i.e., without using a medicinal solution) or when niacinamide is applied directly to the skin.

[0123] Furthermore, the cosmetic tool of the second invention can improve sagging skin when a medicinal solution containing niacinamide is injected into the target object via the part with needle-like projections.

[0124] It is known that sagging occurs with aging and can cause significant changes in facial appearance, such as loosening of the facial line and the appearance of nasolabial folds and marionette lines. Therefore, many people wish to improve this for anti-aging purposes.

[0125] However, improving sagging has not been easy. For example, wrinkles, a similar sign of aging, can sometimes be improved by working on the shallow layer of skin (epidermis), but the cause of sagging lies in the deeper layers of the skin (dermis, subcutaneous tissue, muscle), and it is thought that it is difficult to improve with mere cosmetics. Furthermore, as a means to improve sagging to this extent, treatments using physical energy such as HIFU (High Intensity Focused Ultrasound; also simply referred to as "HIFU") and surgical treatments such as thread lifts have been performed. However, these treatments are highly invasive, and many people are reluctant to undergo them. On the other hand, non-invasive methods include facial muscle training and massage, but these take time to produce results and it is difficult to publicize the appropriate techniques.

[0126] In response to these problems, the beauty kit of the second invention, particularly by using the beauty tool of the second invention in combination with a medicinal solution containing niacinamide, can achieve sagging improvement in a minimally invasive, quick, simple, and easy manner. Furthermore, it goes without saying that improving sagging using the beauty kit of the second invention is easier than the above-mentioned facial muscle training or massage, and can be performed more efficiently than, for example, applying niacinamide directly to the skin or applying the beauty tool of the second invention alone to the skin. Therefore, the beauty kit of the second invention may be used to improve sagging.

[0127] In the second aspect of the present invention, the concentration of niacinamide in the medicinal solution is not particularly limited. From the viewpoint of more effectively promoting collagen production or more effectively improving sagging, the concentration of niacinamide may be, for example, 0.10% by mass or more, 0.15% by mass or more, 0.20% by mass or more, 0.25% by mass or more, 0.30% by mass or more, 0.35% by mass or more, 0.40% by mass or more, 0.45% by mass or more, 0.50% by mass or more, 0.55% by mass or more, 0.60% by mass or more, 0.65% by mass or more, 0.70% by mass or more, or more. % by mass or more, 0.75 mass% or more, 0.80 mass% or more, 0.85 mass% or more, 0.90 mass% or more, 1.00 mass% or more, 1.10 mass% or more, 1.20 mass% or more, 1.30 mass% or more, 1.40 mass% or more, 1.50 Mass% or more, 1.60 mass% or more, 1.70 mass% or more, 1.80 mass% or more, 1.90 mass% or more, 2.00 mass% or more, 2.10 mass% or more, 2.20 mass% or more, 2.30 mass% or more, 2.40 mass% or more, 2.5 0% by mass or more, 2.60% by mass or more, 2.70% by mass or more, 2.80% by mass or more, 2.90% by mass or more, 3.00% by mass or more, 3.50% by mass or more, 4.00% by mass or more, 4.50% by mass or more, 5.00% by mass or more, 6. 00 mass% or more, 7.00 mass% or more, 8.00 mass% or more, 9.00 mass% or more, 10.0 mass% or more, 11.0 mass% or more, 12.0 mass% or more, 13.0 mass% or more, 14.0 mass% or more, or 15.00 mass% or more Also, 30.0 mass% or less, 25.0 mass% or less, 20.0 mass% or less, 15.0 mass% or less, 14.0 mass% or less, 13.0 mass% or less, 12.0 mass% or less, 11.0 mass% or less, 10.0 mass% or less The content may be 9.00% by mass or less, 8.00% by mass or less, 7.00% by mass or less, 6.00% by mass or less, 5.00% by mass or less, 4.50% by mass or less, 4.00% by mass or less, 3.50% by mass or less, or 3.00% by mass or less.

[0128] The beauty kit of the second invention may optionally further include an instruction manual, which may describe how to set up the beauty tool of the second invention before use, how to hold it, how to use it, how often to use it, etc.

[0129] For a method of using the beauty kit of the second aspect of the present invention, the description of FIG. 3 above may be referred to as appropriate. The number of times that the needle-shaped protrusion-equipped part of the beauty tool of the second aspect of the present invention is applied to a target object is not particularly limited, and the number of times may be increased as appropriate. For example, the medicinal solution may be released and penetrated into a single application site one or more times, three or more times, five or more times, ten or more times, fifteen or more times, twenty or more times, twenty-five or more times, thirty or more times, or thirty-five or more times. Alternatively, the medicinal solution may be released and penetrated into a single application site 100 or fewer times, 50 or fewer times, 10 or fewer times, seven or fewer times, six or fewer times, five or fewer times, four or fewer times, three or fewer times, or two or fewer times. The amount of medicinal liquid released per dose is not particularly limited and may be, for example, 0.1 μL or more, 0.2 μL or more, 0.3 μL or more, 0.4 μL or more, 0.5 μL or more, 0.6 μL or more, 0.7 μL or more, 0.8 μL or more, 0.9 μL or more, 1.0 μL or more, 1.1 μL or more, 1.2 μL or more, 1.3 μL or more, 1.4 μL or more, 1.5 μL or more, 1.6 μL or more, 1.7 μL or more, 1.8 μL or more, 1.9 μL or more, or 2.0 μL or more, or may be 10 μL or less, 5 μL or less, or 2 μL or less. The method of applying the cosmetic tool of the second present invention to the object is not particularly limited and, for example, the cosmetic tool may be applied while rotating or without rotating.

[0130] Furthermore, the frequency of use of the second beauty kit of the present invention is not particularly limited, and may be, for example, once per day, once per two days, or once per three days, or may be 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, or 6 or more times within a week, or 7 or less, 6 or less, 5 or less, 4 or less, 3 or less, or 2 or less times within a month, or even 7 or less, 6 or less, 5 or less, 4 or less, 3 or less, 2 or less, or 1 or less times within a week.

[0131] <<Method for Promoting Collagen Production>> The second present invention also provides a method for promoting collagen production. The method for promoting collagen production of the second present invention comprises applying the above-mentioned cosmetic device of the second present invention to skin.

[0132] The method for promoting collagen production of the second invention preferably uses the beauty tool of the second invention in combination with a medicinal solution containing niacinamide, because this method can promote collagen production more efficiently than using the beauty tool of the second invention alone or applying niacinamide directly to the skin.

[0133] In the second method of promoting collagen production of the present invention, when a medicinal solution containing niacinamide is used, the method may include injecting the medicinal solution into the subject, applying the medicinal solution to the subject, or attaching a sheet mask containing the medicinal solution to the subject. In the latter case, the medicinal solution may be applied or the sheet mask may be attached to the subject before, after, or both before and after applying the cosmetic device of the second present invention to the skin.

[0134] More preferably, the collagen production promoting method of the second present invention comprises injecting a medicinal solution into a subject, and the medicinal solution contains niacinamide.

[0135] Furthermore, the method for promoting collagen production according to the second invention can improve sagging. Therefore, the second invention can provide a method for improving sagging. The method for improving sagging according to the second invention can be carried out more efficiently than a method in which niacinamide is applied directly to the skin or a method in which the cosmetic device according to the second invention is applied alone to the skin.

[0136] The collagen production promoting method and the method for improving sagging skin of the second invention are strictly for cosmetic purposes and are not so-called "medical procedures" such as surgical procedures on humans or treatments for human illnesses.

[0137] As described above, the first and second aspects of the present invention can improve the barrier function of the skin, improve the transparency of the skin, promote collagen production in the skin, or improve sagging skin.

[0138] [Third Invention] Hereinafter, a detailed description will be given of an embodiment of the third invention with reference to the drawings. For the sake of convenience, the same or corresponding parts in each drawing are designated by the same reference numerals, and duplicate explanations will be omitted. Furthermore, not all of the components of the embodiments are necessarily essential, and some components may be omitted. However, the present invention is not limited to the following embodiments, and various modifications can be made within the scope of the invention.

[0139] <<Beauty Device>> A third beauty device of the present invention is a beauty device for use in a beauty method for improving the condition of the skin of a subject, wherein the beauty device is a needle beauty device having a part with needle-like protrusions, the part with needle-like protrusions includes needle-like protrusions, and the effective puncture length of the needle-like protrusions in the skin is a length that does not reach the dermis, and the beauty method includes: (i) applying a pressing pressure of 100 to 1200 gf to the skin with the beauty device, and (ii) using the beauty device at a frequency of once every two days or more and twice or more, or three times a week or more.

[0140] The third needle beauty device of the present invention (hereinafter also referred to simply as "the beauty device of the third invention") has a part with needle-like protrusions, the part with needle-like protrusions includes needle-like protrusions, and the effective puncture length of the needle-like protrusions into the skin is a length that does not reach the dermis.

[0141] The "needle-shaped protrusion part" disclosed in Patent Document 2 can be used as the needle-shaped protrusion part of the beauty tool of the third invention. The beauty tool (apparatus) disclosed in Patent Document 2 can be used as the needle-shaped protrusion part of the third invention. It should be noted that Patent Document 2 does not disclose or suggest anything about collagen production, improvement of sagging, etc., but rather that the "needle-shaped protrusion part" is used to retain a liquid composition / liquid cosmetic, with no particular active ingredient, on the surface or inside of an object so as to prevent leakage through gaps.

[0142] Through intensive research by the present inventors, it has been found that collagen production can be promoted by using the cosmetic device of the third aspect of the present invention having such a part with needle-like projections.

[0143] Without being limited by theory, the effective puncture length of the needle-like projections of the cosmetic device of the third invention is such that they do not reach the dermis, and therefore stimulates skin cells by pressure without damaging the dermis, and as a result, surprisingly, it is possible to regulate the M1 / M2 balance and increase the number of myofibroblasts.

[0144] Here, "M1 / M2 balance" refers to the relative balance between the numbers of M1 and M2 macrophages. The M1 / M2 balance is closely related to the control of skin immune responses and inflammation, and also affects wound healing, inflammatory diseases, and even beauty and skin aging. Therefore, "regulating the M1 / M2 balance" refers to increasing the ratio of M2 to M1. As a result of regulating the M1 / M2 balance, it is possible to achieve, for example, promotion of collagen production, immune induction, wound healing, etc.

[0145] "Myofibroblasts" are cells found primarily in the dermis and play an important role in wound healing and tissue repair. Myofibroblasts possess the properties of both normal fibroblasts and smooth muscle cells, and are activated during wound healing and tissue remodeling, playing an important role in repairing damaged skin. Perivascular myofibroblasts also play an important role in maintaining the vascular structure, and increasing their number affects the stabilization of the vascular structure. Therefore, increasing the number of myofibroblasts can result in, for example, collagen production promotion, immune induction, wound healing, and stabilization of the vascular structure.

[0146] Therefore, the subject of the third invention may be a subject in which the M1 / M2 balance needs to be adjusted.

[0147] Furthermore, the subject of the third aspect of the present invention may be a subject in need of increasing the number of muscle fiber cells.

[0148] A part with needle-like protrusions according to the third aspect of the present invention may have: a plate having an injection hole formed therein that penetrates vertically; one or more tiny needle-like protrusions protruding from one side of the plate; and a lip portion formed on the outer edge of one side of the plate; or may have: a plate; one or more base portions protruding from one side of the plate; one or more tiny needle-like protrusions protruding from the tip surface of each of the one or more base portions; and a lip portion formed on the outer edge of the tip surface of the base portion.

[0149] The third beauty tool of the present invention may be for injecting a medicinal solution into a target object via a part with needle-like protrusions. The third beauty tool of the present invention may be the same as the "first beauty tool" described above. Therefore, the description of the "first beauty tool" described above can be referenced for the third beauty tool of the present invention, and its description will be omitted here.

[0150] <<Cosmetic Kit of the Third Invention>> The third invention also provides a cosmetic kit, particularly a cosmetic kit for promoting collagen production.

[0151] The beauty kit of the third aspect of the present invention includes the beauty tool of the third aspect of the present invention and a medicinal solution. For a detailed description of the beauty tool of the third aspect of the present invention, please refer to the description of the "Beauty Tool of the First Aspect of the Present Invention" above.

[0152] In the third invention, the medicinal liquid is not particularly limited as long as it does not impair the effect of the third invention, and may be, for example, a cosmetic substance that provides some kind of cosmetic effect to the skin (e.g., moisturizing effect, firming effect, barrier function improving effect, blood flow enhancing effect, whitening effect, anti-blemish effect, anti-wrinkle effect, anti-acne effect, or anti-inflammatory effect, etc.). Specifically, the medicinal liquid may be, for example, a moisturizing agent, firming agent, barrier function improving agent, blood flow enhancing agent, whitening agent, anti-blemish agent, anti-wrinkle agent, anti-acne agent, or anti-inflammatory agent, and among these cosmetic substances, water-soluble cosmetic substances are particularly preferred. More specifically, examples of medicinal solutions include, but are not limited to, alkoxysalicylic acid and its salts, 1-piperidinepropionic acid and its salts, tranexamic acid and its salts, hyaluronic acid and its salts, vitamin A group and its derivatives, vitamin B group and its derivatives, vitamin C group and its derivatives, alkylene oxide derivatives, proteins and peptides such as collagen and EGF, amino acids, and polyhydric alcohols such as glycerin.

[0153] Through extensive research, the present inventors have found that the cosmetic device of the third aspect of the present invention can improve the permeability of niacinamide into the skin. Therefore, in the third aspect of the present invention, the medicinal solution preferably contains niacinamide.

[0154] Niacinamide is as explained above in the section "First Invention," and detailed explanation will be omitted here.

[0155] When the cosmetic device of the third invention injects a medicinal solution containing niacinamide into the target object via a part with needle-like protrusions, it can promote collagen production more efficiently than when the cosmetic device of the third invention is used alone (i.e., without using a medicinal solution) or when niacinamide is applied directly to the skin.

[0156] Furthermore, the cosmetic tool of the third aspect of the present invention can improve sagging skin when a medicinal solution containing niacinamide is injected into the target object via the part with needle-like projections.

[0157] It is known that sagging occurs with aging and can cause significant changes in facial appearance, such as loosening of the facial line and the appearance of nasolabial folds and marionette lines. Therefore, many people wish to improve this for anti-aging purposes.

[0158] However, improving sagging has not been easy. For example, wrinkles, a similar sign of aging, can sometimes be improved by working on the shallow layer of skin (epidermis), but the cause of sagging lies in the deeper layers of the skin (dermis, subcutaneous tissue, muscle), and it is thought that it is difficult to improve with mere cosmetics. Furthermore, as a means to improve sagging to this extent, treatments using physical energy such as HIFU (High Intensity Focused Ultrasound; also simply referred to as "HIFU") and surgical treatments such as thread lifts have been performed. However, these treatments are highly invasive, and many people are reluctant to undergo them. On the other hand, non-invasive methods include facial muscle training and massage, but these take time to produce results and it is difficult to publicize the appropriate techniques.

[0159] In response to these problems, the beauty kit of the third invention, particularly by using the beauty tool of the third invention in combination with a medicinal solution containing niacinamide, can achieve sagging improvement in a minimally invasive, quick, simple, and easy manner. Furthermore, it goes without saying that improving sagging using the beauty kit of the third invention is easier than the above-mentioned facial muscle training or massage, and can be performed more efficiently than, for example, applying niacinamide directly to the skin or applying the beauty tool of the third invention alone to the skin. Therefore, the beauty kit of the third invention may be used to improve sagging.

[0160] In the third aspect of the present invention, the concentration of niacinamide in the medicinal solution is not particularly limited. From the viewpoint of more effectively promoting collagen production or more effectively improving sagging, the concentration of niacinamide may be, for example, 0.10% by mass or more, 0.15% by mass or more, 0.20% by mass or more, 0.25% by mass or more, 0.30% by mass or more, 0.35% by mass or more, 0.40% by mass or more, 0.45% by mass or more, 0.50% by mass or more, 0.55% by mass or more, 0.60% by mass or more, 0.65% by mass or more, 0.70% by mass or more, or more. % by mass or more, 0.75 mass% or more, 0.80 mass% or more, 0.85 mass% or more, 0.90 mass% or more, 1.00 mass% or more, 1.10 mass% or more, 1.20 mass% or more, 1.30 mass% or more, 1.40 mass% or more, 1.50 Mass% or more, 1.60 mass% or more, 1.70 mass% or more, 1.80 mass% or more, 1.90 mass% or more, 2.00 mass% or more, 2.10 mass% or more, 2.20 mass% or more, 2.30 mass% or more, 2.40 mass% or more, 2.5 0% by mass or more, 2.60% by mass or more, 2.70% by mass or more, 2.80% by mass or more, 2.90% by mass or more, 3.00% by mass or more, 3.50% by mass or more, 4.00% by mass or more, 4.50% by mass or more, 5.00% by mass or more, 6. 00 mass% or more, 7.00 mass% or more, 8.00 mass% or more, 9.00 mass% or more, 10.0 mass% or more, 11.0 mass% or more, 12.0 mass% or more, 13.0 mass% or more, 14.0 mass% or more, or 15.00 mass% or more Also, 30.0 mass% or less, 25.0 mass% or less, 20.0 mass% or less, 15.0 mass% or less, 14.0 mass% or less, 13.0 mass% or less, 12.0 mass% or less, 11.0 mass% or less, 10.0 mass% or less The content may be 9.00% by mass or less, 8.00% by mass or less, 7.00% by mass or less, 6.00% by mass or less, 5.00% by mass or less, 4.50% by mass or less, 4.00% by mass or less, 3.50% by mass or less, or 3.00% by mass or less.

[0161] The beauty kit of the third invention may optionally further include an instruction manual, which may describe how to set up the beauty tool of the third invention before use, how to hold it, how to use it, how often to use it, etc.

[0162] For a method of using the beauty kit of the third aspect of the present invention, the description of FIG. 3 above may be referred to as appropriate. The number of times that the needle-shaped protrusion-equipped part of the beauty tool of the third aspect of the present invention is applied to a target object is not particularly limited, and the number of times may be increased as appropriate. For example, the medicinal solution may be released and penetrated into a single application site one or more times, three or more times, five or more times, ten or more times, fifteen or more times, twenty or more times, twenty-five or more times, thirty or more times, or thirty-five or more times. Alternatively, the medicinal solution may be released and penetrated into a single application site 100 or fewer times, 50 or fewer times, 10 or fewer times, seven or fewer times, six or fewer times, five or fewer times, four or fewer times, three or fewer times, or two or fewer times. The amount of medicinal liquid released per dose is not particularly limited and may be, for example, 0.1 μL or more, 0.2 μL or more, 0.3 μL or more, 0.4 μL or more, 0.5 μL or more, 0.6 μL or more, 0.7 μL or more, 0.8 μL or more, 0.9 μL or more, 1.0 μL or more, 1.1 μL or more, 1.2 μL or more, 1.3 μL or more, 1.4 μL or more, 1.5 μL or more, 1.6 μL or more, 1.7 μL or more, 1.8 μL or more, 1.9 μL or more, or 2.0 μL or more, or may be 10 μL or less, 5 μL or less, or 2 μL or less. The method of applying the cosmetic tool of the second present invention to the object is not particularly limited and, for example, the cosmetic tool may be applied while rotating or without rotating.

[0163] Furthermore, the frequency of use of the beauty kit of the third present invention is not particularly limited, and may be, for example, once per day, once per two days, or once per three days, or may be 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, or 6 or more times per week, or 7 or less, 6 or less, 5 or less, 4 or less, 3 or less, or 2 or less times per month, or may be 7 or less, 6 or less, 5 or less, 4 or less, 3 or less, 2 or less, or 1 or less times per week.

[0164] Furthermore, the frequency of use of the beauty tool or beauty kit of the third invention is preferably at least once every two days and at least two times, or preferably at least three times a week. The frequency of use of the beauty tool or beauty kit of the third invention is more preferably at least once every two days and at least three times, at least four times, at least five times, or at least six times, or more preferably at least four times, at least five times, at least six times, or at least seven times a week.

[0165] <<Cosmetic Method>> The third present invention can also provide a cosmetic method.

[0166] A third cosmetic method of the present invention is a cosmetic method for improving the condition of a subject's skin, comprising: (i) applying a pressing pressure of 100 to 1200 gf with a cosmetic tool against the skin; and (ii) using the cosmetic tool at a frequency of at least once every two days and at least twice a week, or at least three times a week; and wherein the cosmetic tool is a needle cosmetic tool having a part with needle-like protrusions, the part with needle-like protrusions includes needle-like protrusions, and the effective puncture length of the needle-like protrusions in the skin is a length that does not reach the dermis.

[0167] The beauty tool used here may be the "beauty tool of the third invention" described above. Therefore, for the beauty method of the third invention, reference can be made to the explanations of the "beauty tool of the third invention" and the "beauty kit of the third invention" described above.

[0168] Specifically, the pressing pressure applied to the skin by the beauty device may be, for example, 300 gf or more, 400 gf or more, 500 gf or more, or 600 gf or more, and may be 900 gf or less, 850 gf or less, 800 gf or less, 750 gf or less, 700 gf or less, or 650 gf or less.

[0169] The cosmetic method of the third invention may be for adjusting the M1 / M2 balance in a subject and / or for increasing the number of muscle fiber cells in the subject.

[0170] <<Method for Promoting Collagen Production>> The third present invention also provides a method for promoting collagen production. The method for promoting collagen production of the second present invention comprises applying the above-mentioned cosmetic device of the third present invention to skin.

[0171] The method for promoting collagen production of the third invention preferably uses the cosmetic tool of the third invention in combination with a medicinal solution containing niacinamide, because this method can promote collagen production more efficiently than using the cosmetic tool of the third invention alone or applying niacinamide directly to the skin.

[0172] In the method for promoting collagen production of the third aspect of the present invention, when a medicinal solution containing niacinamide is used, the method may include injecting the medicinal solution into the subject, applying the medicinal solution to the subject, or attaching a sheet mask containing the medicinal solution to the subject. In the latter case, the medicinal solution may be applied or the sheet mask may be attached to the subject before, after, or both before and after applying the cosmetic device of the third aspect of the present invention to the skin.

[0173] More preferably, the collagen production promoting method of the second present invention comprises injecting a medicinal solution into a subject, and the medicinal solution contains niacinamide.

[0174] Furthermore, the method for promoting collagen production according to the third aspect of the present invention can improve sagging. Therefore, the third aspect of the present invention can provide a method for improving sagging. The method for improving sagging according to the second aspect of the present invention can be carried out more efficiently than a method in which niacinamide is applied directly to the skin or a method in which the cosmetic device according to the second aspect of the present invention is applied solely to the skin.

[0175] The method for promoting collagen production and the method for improving sagging skin of the third aspect of the present invention are strictly for cosmetic purposes and are not so-called "medical procedures" such as surgical procedures for humans or treatments for human illnesses.

[0176] As described above, the first, second and third aspects of the present invention can improve the barrier function of the skin, improve the transparency of the skin, promote collagen production in the skin, or improve sagging skin.

[0177] [First Invention] The first invention will be described in more detail below with reference to examples, but the invention is not limited to these.

[0178] Examples 1-1 and 1-2 In Examples 1-1 and 1-2, epidermal cell proliferation promotion tests were conducted for the case where the first beauty tool of the present invention was used alone (Example 1-1), and for the case where the first beauty tool of the present invention was used in combination with a medicinal solution containing niacinamide (Example 1-2).

[0179] Specifically, fresh skin excised from the abdomen of a subject who provided informed consent was purchased and obtained. In Example 1-1, the first cosmetic device of the present invention was applied to freshly excised human skin 2 to 8 times with appropriate pressure, rotating the cosmetic device each time, and then cultured on a culture medium. In Example 2, a nonwoven fabric impregnated with a medicinal solution containing niacinamide was placed on ex vivo skin, applied so that it was in close contact with the skin, and left to stand for 5 minutes. After that, the nonwoven fabric was removed, and the cosmetic device was applied in the same manner as in Example 1-1, and then the nonwoven fabric was again applied for 5 minutes. As a control, the tissue was similarly cultured on a culture medium without these treatments (Examples 1-1 and 1-2). The culture medium was changed daily, and tissue fragments were collected on the 7th day. In addition, an antibody against Ki-67 (SP6) (Thermo Fisher Scientific, RM-9106-S, rabbit mouse monoclonal antibody) was used as a cell proliferation marker. The results obtained are shown in FIGS.

[0180] Fig. 4 shows the results of immunofluorescent staining of Ki-67 and nuclei (Hoechst). Fig. 5 is a graph showing the number of Ki-67-positive epidermal cells per length of epidermal basement membrane, which was determined by quantifying the length of the epidermal basement membrane using the image analysis software Image J for the stained image of Fig. 4.

[0181] The formulation of the medicinal solution containing niacinamide is as shown in Table 1-1 below:

[0182] Example 1-3 In Example 1-3, the first beauty tool of the present invention was set up with a metered dose dispenser (a pen-shaped cosmetic container with a volume of about several mL) containing a niacinamide-containing medicinal solution ("Solution A"), and the amount of skin moisture loss was measured up to 8 weeks after application to a subject once every two days. As a control, the first beauty tool of the present invention was not used, and the subject was given the same amount of Solution A as when using the beauty tool once every two days, and the amount of skin moisture loss was measured. The results are shown in Figure 7.

[0183] More specifically, the procedure was as follows: 1. Place the protruding surface flat against the subject's skin, press in, and then click once (press firmly enough to not cause pain). 2. Repeat the above step "1," applying the product while moving it little by little, referring to Figure 6. (Total of 50 clicks (25 clicks x left and right)) a: Smile lines, marionette lines 10 clicks x left and right b: Corners of the eyes to under the eyes 10 clicks x left and right c: Concerned areas on the cheeks (areas of concern such as dryness, pores, etc.) 5 clicks x left and right 3. Spread the liquid over the entire face and blend it in with the entire palm of your hand.

[0184] The subjects were 20 women aged 45 to 59, with a BMI of 18.5 to 25.0 and wrinkle grades of 3 to 5.

[0185] The formulation of "Medicinal Solution A" is as shown in Table 2 below:

[0186] The amount of skin moisture loss was measured by a transdermal evaporation method using a Vapometer (Delfin Technologies).

[0187] 7, it was found that the moisture content was significantly increased in Example 1-3 compared to the control about two weeks after application, suggesting that Example 1-3 can improve the skin barrier function in as short a period as two weeks.

[0188] Example 1-4 In Example 1-4, the first beauty tool of the present invention was combined with a metered dose dispenser (a pen-shaped cosmetic container with a volume of several mL) containing a niacinamide-containing medicinal solution ("Solution A"), and the subject was tested for skin clarity up to 8 weeks after application of the solution once every two days in the same manner as in Example 1-3. As a control, the first beauty tool of the present invention was not used, and the subject was tested for skin clarity after application of the same amount of Solution A as when using the beauty tool once every two days.

[0189] The skin transparency was evaluated by six expert evaluators using the method in Table 3 below, based on the evaluation scale shown in Figure 8. The evaluation was made based on the overall balance of the face. Therefore, "not noticeable" includes "absolutely no noticeable phenomenon" and "very slight noticeable phenomenon, but not noticeable when viewed from the face as a whole."

[0190]

[0191] The results obtained are shown in FIG.

[0192] As is clear from the results in FIG. 9, it was found that, compared to the control, Example 1-4 showed a high improvement effect on skin transparency from an earlier stage.

[0193] Furthermore, since Examples 1-4 and the control ultimately improved the transparency to similar levels (after 8 weeks), it was also suggested that the penetration speed and amount of niacinamide were increased in Examples 1-4 by the first cosmetic device of the present invention.

[0194] Reference Examples 1-1 and 1-2 The penetration-promoting effect of a niacinamide-containing solution ("Solution B") listed in Table 1-4 using the first beauty device of the present invention was confirmed by confocal micro-Raman spectroscopy (Reference Example 1-1). The penetration-promoting effect of a water-soluble fluorescent substance as a model drug was also confirmed by fluorescence intensity quantification (Reference Example 1-2). The respective results are shown in Figure 10 (Raman spectroscopy) and Figure 11 (fluorescence intensity). Note that Figure 10 is a three-dimensional image of the Raman intensity of niacinamide based on the spectral and spatial information obtained from confocal micro-Raman spectroscopy.

[0195] More specifically, the experimental method is as follows: (Confocal Raman Spectroscopy) - 5 μL of "Chemical Solution B" was applied to an excised human skin per square centimeter. - Then, the first beauty device of the present invention was applied to the excised human skin 50 times. - The fingerprint area (600-2200 cm) was measured. －１ The time-dependent change in the Raman spectrum of the compound was evaluated. As a control, 5 μL of "drug solution B" was simply applied to an excised human skin area per square centimeter.

[0196] (Fluorescence Intensity) The permeability of each composition was examined when it was applied to excised human skin (commercially available) via a cosmetic tool, and when it was applied directly to the skin without a cosmetic tool. More specifically, using a texture analyzer, a fine needle plate was pressed 50 times perpendicularly to the stratum corneum surface of the excised human skin, and then 5 μL of an aqueous solution containing 0.2% fluorescent dye (sodium fluorescein) was applied per square centimeter, and the excised skin was left standing at 37°C for 15 minutes. Next, the surface of the skin where each composition had been applied was cleaned, and the corresponding skin was cut into a circle with a diameter of 8 mm using a skin punch. The obtained skin was placed in an appropriate amount of extraction solvent and subjected to ultrasonic treatment to extract the fluorescent dye. The fluorescence intensity of the extracted sample was then measured using a spectrophotometer.

[0197] Control 1 shows autofluorescence from excised human skin, and Control 2 shows a case in which a solution containing 0.2% by mass of a fluorescent dye (sodium fluorescein) was simply applied to excised human skin at 5 μL per square centimeter and allowed to stand at 37° C. for 15 minutes.

[0198] The prescription for "Medicine Solution B" is as shown in Table 1-4 below:

[0199] The "model drug" used in Reference Example 1-2 had the same formulation as the above-mentioned "drug solution B," except that 0.2% by mass of sodium fluorescein was blended in place of 5.0% by mass of niacinamide, and the remaining amount was adjusted with water.

[0200] As is clear from FIG. 10, Reference Example 1-1 promoted the permeation of niacinamide in a much shorter time than the control.

[0201] Furthermore, as is clear from Figure 11, it was found that Reference Example 1-2 had a significantly improved penetration amount of the drug solution containing the model drug (water-soluble fluorescent substance) compared to both Controls 1 and 2.

[0202] [Second Invention] The second invention will be described in more detail below with reference to examples, but the second invention is not limited to these.

[0203] In each of the following experiments, unless otherwise specified, the second beauty device of the present invention used had a part with acicular protrusions that was circular and had a diameter of 15 mm, the effective puncture length of the acicular protrusions (i.e., needles) was 20 μm, and the number of acicular protrusions was 18.

[0204] Examples 2-1 and 2-2: The promotion of collagen production was evaluated when the second beauty device of the present invention was applied alone to freshly excised human skin (Example 1), and when the second beauty device of the present invention was applied in combination with 5% by mass of niacinamide solution (Example 2-2). Similar freshly excised human skin was used as a control. The results are shown in Figure 4-1.

[0205] Specifically, fresh skin excised from the abdomen of a subject who provided informed consent was purchased and obtained. In Example 2-1, the second cosmetic device of the present invention was applied to freshly excised ex vivo human skin 2 to 8 times with appropriate pressure, rotating the cosmetic device each time, and then cultured on a culture medium. In Example 2, a nonwoven fabric impregnated with a medicinal solution containing niacinamide was placed on the ex vivo skin, applied so that it was in close contact with the skin, and left to stand for 5 minutes. After that, the nonwoven fabric was removed, and the cosmetic device was applied in the same manner as in Example 2-1, and then the nonwoven fabric was again applied for 5 minutes. In the control, these treatments (Examples 2-1 and 2-2) were not performed and the skin was similarly cultured on a culture medium. In addition, after 24 hours of culture, the amount of procollagen gene (COL1A1) production was confirmed by RT-qPCR (Δ-ΔCT method) for the treated skin and the control skin, confirming the production of procollagen I. - Tests were performed 6 times each. - qPCR: n = 3

[0206] The formulation of the niacinamide solution (5% by mass) is as shown in Table 1-2 below:

[0207] As is clear from the results in Figure 4-1, it was found that the production amount of the procollagen gene (COL1A1) was significantly increased in Examples 2-1 and 2-2 compared to the control. In other words, it was suggested that the production of procollagen I was promoted by Examples 2-1 and 2-2.

[0208] Example 2-3 In Example 2-3, differentiation into myofibroblasts was confirmed when the beauty tool of the second aspect of the present invention was used alone.

[0209] In Example 2-3, the second cosmetic device of the present invention was applied to freshly excised human skin 2 to 8 times with appropriate pressure, rotating the cosmetic device each time, and then cultured on a medium. As a control, the tissue was cultured on the same dedicated medium without application of the second cosmetic device of the present invention, and the tissue explant was collected the next day. Furthermore, antibodies against α-SMA (α-Smooth Muscle Actin) and Vimentin were used as myofibroblast markers, and α-SMA / Vimentin co-positive cells were counted as myofibroblasts. The results obtained are shown in Figures 5-1 and 5-2.

[0210] Figure 5-1 shows the results of immunofluorescent staining of α-SMA (α-Smooth Muscle Actin) / Vimentin and nuclei (Hoechst). Figure 5-2 is a graph showing the number of α-SMA / Vimentin positive cells (myofibroblasts) counted within an area 200 μm below the epidermal basement membrane, quantified using the image analysis software Image J for the stained image of Figure 5-1.

[0211] As is clear from Figures 5-1 and 5-2, it was found that differentiation into α-SMA / Vimentin positive cells, i.e., myofibroblasts, was more induced in Example 2-3 than in the control. In other words, it was suggested that Example 2-3 promoted the production of procollagen I through differentiation into myofibroblasts.

[0212] Example 2-4 The penetration-promoting effect of a medicinal solution containing niacinamide ("Solution A") in Table 2-2 using the second beauty device of the present invention was confirmed by confocal micro-Raman spectroscopy (Example 2-4-1). The penetration-promoting effect of a water-soluble fluorescent substance as a model drug was also confirmed by fluorescence intensity quantification (Example 2-4-2). The respective results are shown in Figure 6-1 (Raman spectroscopy) and Figure 7-1 (fluorescence intensity). Note that Figure 6 is a three-dimensional image of the Raman intensity of niacinamide based on the spectral and spatial information obtained from confocal micro-Raman spectroscopy.

[0213] More specifically, the experimental method is as follows: (Confocal Raman Microspectroscopy) - "Chemical Solution A" was applied directly to an excised human skin at a rate of 5 μL per square centimeter. - Then, the second beauty device of the present invention was applied to the excised human skin 50 times. - The fingerprint area (600-2200 cm) was measured. －１ The time-dependent change in the Raman spectrum of the compound was evaluated. As a control, 5 μL of "Drug Solution A" was simply applied to an excised human skin.

[0214] (Fluorescence Intensity) The permeability of each composition was examined when it was applied to excised human skin (commercially available) via a cosmetic tool, and when it was applied directly to the skin without a cosmetic tool. More specifically, using a texture analyzer, a fine needle plate was pressed 50 times perpendicularly to the stratum corneum surface of the excised human skin, and then 5 μL of an aqueous solution containing 0.2% fluorescent dye (sodium fluorescein) was applied per square centimeter, and the excised skin was left standing at 37°C for 15 minutes. Next, the surface of the skin where each composition had been applied was cleaned, and the corresponding skin was cut into a circle with a diameter of 8 mm using a skin punch. The obtained skin was placed in an appropriate amount of extraction solvent and subjected to ultrasonic treatment to extract the fluorescent dye. The fluorescence intensity of the extracted sample was then measured using a spectrophotometer.

[0215] Control 1 shows autofluorescence from excised human skin, and Control 2 shows a case in which a solution containing 0.2% by mass of a fluorescent dye (sodium fluorescein) was simply applied to excised human skin at 5 μL per square centimeter and allowed to stand at 37° C. for 15 minutes.

[0216] The prescription for "Medicine Solution A" is as shown in Table 2-2 below:

[0217] The "model drug" used in Example 2-4-2 had the same formulation as the above-mentioned "drug solution A," except that 0.2% by mass of sodium fluorescein was blended instead of 5.0% by mass of niacinamide, and the remaining amount was adjusted with water.

[0218] As is clear from FIG. 6-1, Example 2-4-1 promoted the penetration of niacinamide in a much shorter time than the control.

[0219] Furthermore, as is clear from Figure 7-1, it was found that Example 2-4-2 had a significantly improved penetration amount of the drug solution containing the model drug (water-soluble fluorescent substance) compared to both Controls 1 and 2.

[0220] Example 2-5 In Example 2-5, the second beauty tool of the present invention was set up with a fixed-volume dispenser (a pen-shaped cosmetic container with a volume of about several mL) containing a liquid medicine containing niacinamide ("liquid medicine B"), and the effect of improving sagging skin after applying the liquid medicine to a subject once every two days was confirmed.

[0221] More specifically, the procedure was as follows: 1. The protruding surface was placed flat against the subject's skin, pressed in, and then clicked twice. 2. The above step "1." was repeated, moving the product slightly as shown in Figure 8. (50 sets in total, applied to only the designated side) a: Nasolabial folds 10 sets b: Corners of the eyes to under the eyes 10 sets c: Forehead, between the eyebrows 10 sets d: Entire side 20 sets (centered on cheeks) 3. The liquid was then lightly applied to the entire side of the face.

[0222] Thirty-four women aged 45 to 59 and with a BMI of 18.5 to 25.0 were recruited as subjects.

[0223] The formulation of "Medicinal Solution B" is as shown in Table 3 below:

[0224] The experiment was conducted on subjects for four consecutive weeks. The changes in face line angle before application, two weeks after application, and four weeks after application were measured using a 3D handheld scanner (a non-contact three-dimensional anthropometric measurement system). The results are shown in Figure 9-1. In addition, to show the face line angle, a 3D scan image of the lower jaw of one subject is shown in Figure 10-1.

[0225] As is clear from the results of Figures 9-1 and 10-1, it was found that in Example 2-5, the facial lines of the subjects were able to be sharpened in two weeks. In other words, it was suggested that in Example 2-5, sagging skin can be improved in as short a time as two weeks by using the second beauty device of the present invention in combination with a medicinal solution containing niacinamide.

[0226] Example 2-6 In Example 2-6, the second beauty tool of the present invention was set up with a fixed-dose dispenser container (a pen-shaped cosmetic container with a volume of about several mL) containing a medicinal solution containing niacinamide ("medical solution C"), and the test subject applied the solution once every two days to evaluate the effect of improving sagging skin, comparing it with the effect of simply applying a medicinal solution of the same formulation (Comparative Example 2-1).

[0227] More specifically, the procedure was as follows: 1. Place the protruding surface flat against the subject's skin, press in, and then click once (press firmly but not enough to cause pain). 2. Repeat the above step "1," applying the product while moving it little by little, referring to Figure 8-1. (Total of 50 clicks (25 clicks x left and right)) a: Smile lines, marionette lines 10 clicks x left and right b: Corners of the eyes to under the eyes 10 clicks x left and right c: Concerned areas on the cheeks (areas of concern such as dryness, pores, etc.) 5 clicks x left and right 3. Spread the liquid over the entire face and blend it in with the entire palm of your hand.

[0228] The subjects were 20 women aged 45 to 59, with a BMI of 18.5 to 25.0 and wrinkle grades of 3 to 5.

[0229] The formulation of "Medicine Solution C" is as shown in Table 4 below:

[0230] The experiment was conducted on subjects for two consecutive weeks. The volume of the mandible was measured using VECTRA H2 before and two weeks after application, and the change in volume before and after application was calculated. The results are shown in Figure 11-1.

[0231] As is clear from the results of Figure 11-1, it was found that Example 6 significantly reduced the overall volume of the subject's lower jaw, i.e., tightened it, in two weeks. On the other hand, in Comparative Example 2-1, in which medicinal solution C was simply applied, no change in volume occurred.

[0232] As described above, Examples 2-6 suggest that by using the second beauty device of the present invention in combination with a medicinal solution containing niacinamide, it is possible to improve sagging skin that cannot be improved by using ordinary cosmetics in a short period of two weeks.

[0233] Examples 2-7-1 to 2-7-3 In Examples 2-7-1 to 2-7-3, the effect of the concentration of niacinamide in the medicinal solution on improving sagging was confirmed.

[0234] Drug solutions containing different concentrations of niacinamide were prepared according to Tables 2-5 below.

[0235] More specifically, in each example, one panelist was asked to compare the sagging grades before and after one half of the face was injected with the second cosmetic device of the present invention (continuous use for one week) and the other half of the face was applied with the same formulation (continuous use for one week). Based on Non-Patent Document 1 (Skin Research and Technology 2009; 15: 299-305), the sagging grades were evaluated in increments of 0.5 for three areas: the upper cheek, the lower cheek, and the outer cheek. The evaluation criteria were as follows: (Evaluation Criteria) A change in the sagging grade of -0.5 or less before and after one week was evaluated as follows: 3 areas: "A" rating; 2 areas: "B" rating; 1 area: "C" rating; 0 areas: "D" rating. The evaluation results are shown in Table 6.

[0236] The more negative the change in the sagging grade, the greater the effect of improving sagging. Also, the more areas that have changed, the greater the effect of improving sagging can be evaluated. Therefore, an "A" rating is the most effective in improving sagging, with the effects decreasing in order from "B," "C," and "D."

[0237]

[0238] As is clear from the results in Table 2-6, when a medicinal solution containing niacinamide was injected using the second cosmetic device of the present invention in a short period of one week, the effect of improving sagging was greater than when the medicinal solution was applied alone.

[0239] Furthermore, even when the concentration of niacinamide in the solution was 0.1% by mass, it was found that injection using the second beauty device of the present invention was more effective in improving sagging than application alone.

[0240] Furthermore, when a medicinal solution containing niacinamide is injected using the cosmetic device of the second invention, it has been found that the effect of improving sagging skin gradually increases as the concentration of niacinamide in the medicinal solution increases.

[0241] [Third Invention] The third invention will be described in more detail below with reference to examples, but the second invention is not limited to these.

[0242] In each of the following experiments, unless otherwise specified, the third beauty device of the present invention used had a part with acicular protrusions that was circular and had a diameter of 15 mm, the effective puncture length of the acicular protrusions (i.e., needles) was 20 μm, and the number of acicular protrusions was 18.

[0243] Time-dependent changes in myofibroblast numbers and M1 / M2 macrophages (RNA-Seq) Fresh human abdominal skin (Genoskin, France) (n=4, 29-39 years old, mean=35.8 years) was air-shipped from France and organ cultured to maintain tissue equivalence throughout the study. Full-thickness skin, excised of subcutaneous fat, was used in all studies.

[0244] The microneedles were applied once every two days. The skin was placed on a cork board with the stratum corneum side facing up, and a pressure of 600 gf was applied vertically using an instrument (Pressure Instrument, Clinical & Derm, Inc.; description unnecessary, but if necessary, please provide it) for 10 seconds, followed by two more pressures, each time changing direction by 90°.

[0245] Skin samples were collected on days 1, 3, and 7 of culture. Total RNA was extracted from the epidermis and dermis of the isolated skin using a Qiagen RNeasy mini kit (Qiagen, The Netherlands).

[0246] RNA-seq analysis was performed using dermal RNA, as described in Reference 11 below. Lowly expressed genes with a median mapped read count of less than 1 were excluded from the analysis. Heat maps were drawn using heatmap 2 in the gplots package (version 3.1.3.1) (see Reference 12 below). Enrichment analysis of the biological functions of selected genes was performed using Metascape (see Reference 13 below).

[0247] (Paraffin block, section preparation) Fresh human abdominal skin was collected and fixed using cold acetone according to the AMeX method. After dehydration, the skin was replaced with acetone, methyl benzoate, and xylene in that order, and embedded in paraffin. Sections were prepared at a thickness of 4 μm for histological staining.

[0248] (Various Immunostaining) Paraffin sections prepared at a thickness of 4 μm were deparaffinized with xylene and then hydrated with EtOH. Fluorescent immunostaining was performed using antibodies against anti-alpha smooth muscle actin (αSMA) (ab7817, Abcam), vimentin (ab24525, Abcam), CD31 (AF806, R&D Systems), CD68 (ab955, Abcam), CD86 (AF141NA, R&D Systems), and CD206 (AF2534, R&D Systems). (Figures 12, 15, and 16)

[0249] Based on the results of the fluorescent immunostaining, the number of myofibroblasts (αSMA / vimentin positive cells) present in a region of 200 μm immediately below the epidermal basement membrane was counted using the image analysis software ImageJ, and the time-dependent changes were plotted as a graph ( FIG. 13 ).

[0250] Based on the results of the fluorescent immunostaining, myofibroblasts (CD31-positive cells) present within a range of 200 μm immediately below the epidermal basement membrane were counted using image analysis software ImageJ, and the changes over time were plotted as a graph ( FIG. 14 ).

[0251] 12 to 14, "MN" represents the results when the microneedles of the present invention were applied, and "Control" represents the control, i.e., the results when the microneedles were not applied. The same applies to the following figures.

[0252] Similarly, based on the results of the fluorescent immunostaining in Figures 15 and 16, the image analysis software ImageJ was used to count M1 macrophages (CD86 / CD68 dual-positive cells) and M2 macrophages (CD206 / CD68 dual-positive cells) present within a range of 200 µm immediately below the epidermal basement membrane, and the number of each and the M1 / M2 ratio were quantified and plotted as time-dependent graphs (Figures 17 to 19).

[0253] 12 to 14, it was found that the number of myofibroblasts increased over time in the skin to which the microneedles of the present invention were applied. Although the number of CD31-positive cells, which indicate blood vessels, did not change, it was suggested that the number of myofibroblasts around the blood vessels may have increased.

[0254] As is clear from the results of Figures 15 to 19, in the skin to which the microneedles of the present invention were applied, the ratio of M2 to M1 increased over time, i.e., the M1 / M2 ratio decreased over time.

[0255] [Supplementary explanation of the third invention] The innovative Skin Vitalizer, which activates all skin cells through mechanobiological stimulation and efficiently delivers nutrients, opens up a new dimension in skin care.

[0256] As an excellent transdermal or intradermal drug delivery system (DDS), microneedles (MNs) can bypass the skin's barrier function with a simple and elegant mechanism. However, existing MN technologies in the cosmetic field have difficulty controlling the puncture depth, making it difficult to simultaneously achieve safety and efficacy. For example, solid-MNs (solid-type microneedles) cause unacceptable levels of damage due to their excessive puncture depth, and dissolving-MNs (dissolving-type microneedles) are unable to deliver sufficient drug due to the fragility of their basic polymers. This disclosure solves this problem by developing a novel MN technology featuring a unique shape that artificially elongates the MN to control the puncture depth.

[0257] Several tests, including confocal Raman spectroscopy, demonstrated that the penetration depth remained within the stratum corneum (SC). Meanwhile, the unique shape of the MN ensured rapid delivery of large amounts of drug to the viable epidermis (VE), leading to the name "Injectable-MN." Furthermore, RNA-seq results suggested that Injectable-MN can induce skin regeneration similar to wound healing without causing damage. Finally, a home test using Injectable-MN supplemented with niacinamide showed significant improvements in sagging, wrinkles, skin clarity, and barrier function in just two weeks. In conclusion, our Injectable-MN is an extremely versatile DDS platform that can unlock the potential of functional skincare and deliver unprecedented results to consumers.

[0258] Keywords: drug delivery, microneedle, injection, mechanobiology, rejuvenation

[0259] Introduction MNs utilize a simple "puncture" mechanism to penetrate the SC barrier and achieve transdermal and intradermal drug delivery. Because of their simple mechanism, they can be combined with a variety of drugs and are easy to use. These advantages make MNs a highly versatile transdermal and intradermal DDS (References 1, 2, 3). The use of MNs is also increasing in the cosmetic field, with solid and soluble MNs becoming the mainstream among the several types of MNs (References 1, 2, 4, 5).

[0260] In particular, Solid-MN has gained popularity, especially for use in cosmetic procedures (References 2, 4, 6). The main idea behind this technology is to perforate the skin using a sharp, hard metal needle, which facilitates the penetration of drugs into the skin. Furthermore, the wound healing process caused by perforation of the dermis results in a remodeling effect on the dermal matrix structure. These two mechanisms are increasingly recognized as providing a highly rejuvenating effect. However, this procedure involves bleeding, downtime, and carries the risk of infection and scar formation. Products with such risks are not acceptable for consumers' daily skin care routines.

[0261] So, how can we achieve the high rejuvenating effects of Solid-MN while ensuring safety as a cosmetic?

[0262] To solve this challenge, we focus on the shape of the MN and develop a skin-depth-based approach.

[0263] Our first attempt addressed the fundamental challenge of controlling the penetration depth. Cosmetic applications require selective penetration of thin layers, such as the skin's SC and VE, but achieving the necessary fine control is extremely difficult (Ref. 2). According to Guang et al. (Ref. 8), only needles longer than 600 μm can reliably penetrate the skin's SC. This is because shorter needles are hindered by the skin's tough, shock-absorbing SC and viscoelastic properties, preventing MNs from penetrating the SC and remaining in the superficial layers.

[0264] On the other hand, MNs with needle lengths longer than 600 μm can reach the dermis, but may cause damage. Considering safety as a cosmetic product, they must be limited to a depth of approximately 200 μm, which is the epidermis. However, if the needle length is shortened to 200 μm or less, the needle will barely penetrate the skin when simply pressed with the pad of a finger (Reference 9).

[0265] To solve these problems, it is necessary to use a device that can apply MN at high speed (References 1, 2, 3, 9). However, such devices are expensive and are not widely used. Therefore, when considering the application of MN to cosmetics, the choice is between designing a device that will not puncture and prioritize safety, or prioritizing efficacy and ignoring safety. However, we took a new approach and attempted to simultaneously achieve two mechanisms: effective drug delivery and wound healing-like effects.

[0266] We hypothesized that we could achieve the following: First, we embedded a MN of the desired length into the stretched SC while significantly deforming the skin, reducing the shock absorption capacity of the skin's elasticity. At the same time, this large deformation itself allows access to the deeper layers of the skin.

[0267] To this end, we first fabricated MNs of various shapes and evaluated their puncture properties.

[0268] Furthermore, it became possible to inject medicinal solutions into the skin via these MNs. Using permeability evaluation methods such as confocal Raman microscopy, we verified whether this was possible with the MNs we created. Furthermore, using RNA-seq and blood flow observation, we verified the ability of the novel MNs to reach the deeper layers of the skin below the dermis, which was difficult with conventional cosmetics.

[0269] Finally, niacinamide, which is known to be involved in various functions in the body and to be beneficial to the skin (Reference 10), was included in a formulation used with MN to evaluate the changes it could make in home studies.

[0270] Experimental Materials and Methods

[0271] Materials Injectable-MN The Injectable-MN (the "instrument" or "beauty instrument" of the present invention) we developed consists of a PGA-MN (Figure 20-1-a, design details are described in the next section) that we designed and manufactured ourselves, connected to a knock-type pen-type package (Figure 20-1-b) that can deliver a fixed amount of liquid. By simply clicking the button on the back of the knock-type pen, the serum in the package can be ejected from the tip of the PGA-MN.

[0272] The PGA-MN is made of polyglycolic acid (PGA), a known biocompatible and biodegradable resin. The MNs are arranged at an appropriate pitch, and a base of appropriate shape is located below the MN to ensure that the puncture site remains within the SC. A close-up of the tip of the base reveals the solid MN, an independent liquid injection hole, and a surrounding protective ring (Figure 20-1, part a). The total length of the MN is 120 μm, and the surrounding protective ring controls the puncture depth, resulting in an effective puncture length of 20 μm, which remains within the SC. The PGA-MN receives drug solution from a connected syringe or other device, which is expelled from the liquid injection hole and fills the protective ring. When the PGA-MN is applied to the skin and injected through the SC, the drug solution penetrates into the skin due to capillary action in the gap between the skin and the MN and the injection pressure generated within the sealing ring (Figure 20-1, part c).

[0273] Microneedles MNs of various shapes were fabricated and used in the tests. A schematic diagram of the MN is shown in Figure 20-2. Each MN was fabricated by appropriately assigning the following geometric parameters: A. MN length (μm): 200-1,000 B. Base length (μm): 0-2,000 C. Total length (μm): 200-2,200 D. Apex diameter of base (μm): 150-1,000 E. Distance between MNs (μm): 2,000-5,000 F. Bottom diameter of MN (μm): 150-750 (depending on A.) G. Number of MNs arrayed: 1-19

[0274] The aspect ratio of the MN (A. length of MN / F. base diameter of MN) was maintained at 4 / 3 for all samples. All samples except the PGA-MN were made of medical-grade stainless steel (SUS), and only the PGA-MN was made of PGA. The geometric parameters of the PGA-MN were as follows: A. 20 μm* (effective puncture length), B. 2,100 μm, C. 2,120 μm, D. 520 μm, E. 3,000 μm, G. 18.

[0275] Chemical substances Reagents were purchased and used from commercial sources in Japan.

[0276] The serum formulation contained the following: 5 (w / v)% niacinamide, deionized water, ethanol, glycerol, DPG, xylitol, sodium hyaluronate, 4-methoxysalicylic acid, dipotassium glycyrrhizinate, citric acid, sodium citrate, EDTA, and phenoxyethanol.

[0277] For quantifying the fluorescence intensity, 0.02 (w / v)% sodium fluorescein (Flu-Na) was added, and niacinamide, 4-methoxysalicylic acid, and dipotassium glycyrrhizinate were omitted from the above formulation.

[0278] For the home human study, the above formula was used, but 4-methoxysalicylic acid was omitted.

[0279] Skin Samples: For puncture ability and penetration tests, frozen human dorsal skin (n = 3-4, 45-69 years old, mean = 60.0 years) was thawed and warmed to a surface temperature of 32°C. For RNA-seq, fresh human abdominal skin (Genoskin, France) (n = 4, 29-39 years old, mean = 35.8 years old) was air-shipped from France and organ cultured to maintain tissue equivalence throughout the study period. Full-thickness skin samples, excised of subcutaneous fat, were used in all tests.

[0280] Methods: Puncture Ability Test: Methylene Blue Staining. A MN was inserted into a skin specimen placed with the SC side facing up on a base adjusted to approximate the elasticity of human cheekbone skin. To insert the MN, a texture analyzer (TA.XTplusC, EKO INSTRUMENTS, Japan) was used as a manipulator. The MN was pressed vertically at a speed of 40 mm / sec under a load of 1 kgf, held for 10 seconds, and then withdrawn. The specimen was then immersed, SC side down, in a 1 mg / mL methylene blue solution for 20 minutes. The solvent on the surface was then wiped off, and the specimen was washed with purified water. Tape stripping was performed 5 to 10 times using a D-Squame® sampling disk (Clinical and Derm, USA). The specimen was observed under a digital microscope (Hirox, Japan) to assess whether it had been successfully punctured. Some specimens were embedded in OCT compound, frozen, and then thin sections were prepared. The cross sections were observed under a microscope (BX51, Olympus, Japan) to evaluate the penetration depth.

[0281] The puncture rate was calculated as follows:

[0282] The MN was inserted into the skin in the same manner as when using methylene blue staining. After that, the MN was fixed in 10% neutral buffered formalin solution while still inserted in the skin, and thin methyl methacrylate resin sections were prepared and stained with HE.

[0283] Permeation studies: Fluorescence intensity quantification Serum preparations (5 μl / cm ２ ) was applied to the skin using a pipette. Then, PGA-MN was used to press the skin 50 times at a pressure of 1 kgf. After leaving it for 15 minutes, the surface was wiped with PBS, and tape stripping was performed three times using a D-Squame® sampling disk. Flu-Na was then extracted from the crushed skin using Dulbecco's PBS (D-PBS) as a solvent. Finally, the fluorescence intensity of each sample was measured using a microplate reader (PerkinElmer Life and Analytical Sciences, Finland), and the amount of Flu-Na permeated into the skin was evaluated by subtracting the average value of skin autofluorescence.

[0284] Penetration study using confocal Raman spectroscopy. ２ ) was applied to the skin using a pipette, and then PGA-MN was pressed into the skin 50 times at a pressure of 1 kgf. As a control, a cosmetic serum (5 μl / cm ) was applied to the skin using a pipette without PGA-MN. ２ ) was applied to the skin. Then, the fingerprint area (600-2200 cm －１ The time change of the Raman spectrum of niacinamide (1042 cm) was evaluated. －１ The Raman intensity was calculated by normalizing it according to the laser intensity at each depth. The Raman intensity was measured intermittently from the SC to the VE in steps of 2 μm or 3 μm, and then measured at 4 or 6 μm. ２ The area was measured to a maximum depth of 30 μm or 60 μm. Finally, the 3D transmission images were visualized with ImageJ and Imaris software.

[0285] RNA-seq method: PGA-MN was applied once every two days. Skin samples were collected on days 1, 3, and 7 of incubation. Total RNA was extracted from the epidermis and dermis of the isolated skin using the Qiagen RNeasy mini kit (Qiagen, The Netherlands). RNA-seq analysis was performed using dermal RNA as previously reported

[11] . Low-expressing genes with a median mapped read count of less than 1 were excluded from the analysis. Heatmaps were generated using heatmap 2 in the gplots package (version 3.1.3.1) (Reference 12). Enrichment analysis of selected genes by biological function was performed using Metascape (Reference 13).

[0286] Blood flow: A half-face comparative evaluation was conducted on 24 men (aged 30 to 60). Injectable-MN (Figure 20-1), which contains a beauty serum, was applied to half of the face 50 times. The remaining beauty serum was then spread on the skin, and immediately afterwards, blood flow on both sides of the face was measured using an Omegazone laser speckle blood flow meter (Omegawave Japan).

[0287] Home-Based Human Study: A home-based before-and-after test was conducted on 45 women (aged 40-50) who met the screening criteria to assess the improvement in skin condition following application of "Injectable-MN" or the "serum." Wrinkles, sagging, and skin clarity were assessed on a scale before and after 2, 4, and 8 weeks of continuous use. Sagging was assessed based on the scoring system of Ezure et al. (Reference 14). Changes in mandibular volume were measured using a VECTRA H2 (Canfield Scientific, US) as previously reported (Reference 15). Transepidermal water loss (TEWL) was measured using a Vapometer (Delfin Technologies, Finland). A questionnaire survey was also conducted.

[0288] The "Injectable-MN" group was given Injectable-MN (Figure 20-1) containing a cosmetic serum, which they used only in the evenings every other day. For each treatment, 50 punctures and injections were performed in the nasolabial folds, around the eyes, and part of the cheek. The "Serum" group was given the same cosmetic serum without the "Injectable-MN" and instructed to apply the same amount as the "Injectable-MN" group every other day.

[0289] Compliance with ethical standards All studies were conducted in accordance with ethical considerations based on the World Medical Association Declaration of Helsinki. All studies using humans or human skin samples were approved by the Shiseido Human Research Ethics Committee.

[0290] Statistical Analysis For the puncture ability test, the data obtained were analyzed using Cochran's Q test and Steel-Dwass test. For the analysis of the home test questionnaire, Steel's multiple comparison test and Mann-Whitney U test were used. Data obtained other than those mentioned above were analyzed using Student's t-test, Dunnett's test, Tukey-Kramer's honestly significant difference (HSD) test, or analysis of variance (ANOVA). In all cases, p<0.05 was considered significant.

[0291] EdgeR (version 3.40.0) (Reference 16) was used to analyze differentially expressed genes from RNA-seq. Multiple testing was corrected using the Benjamini-Hochberg method, and genes with an adjusted p-value (FDR) < 0.05 were identified as differentially expressed genes.

[0292] Results Puncture ability test In Figure 20-3a, a simple single-needle MN was carved to examine the change in puncture ability due to differences in MN length. There was a tendency for the puncture success rate to differ depending on the MN length (p=0.079).

[0293] On the other hand, in Figure 20-3b, a base was added below the single needle MN with a fixed needle length of 200 μm to artificially lengthen the overall length, and the puncture success rate was compared depending on the length. Stable puncture was observed when the overall length was 600 μm or more, and a significant difference in the puncture success rate was observed between the groups at a risk rate of 0.5%.

[0294] In Figure 20-3c, the puncture performance was evaluated by changing the tip diameter of the base under the MN. It was found that puncture was successful when the tip diameter was 600 μm or less, and there was a significant difference in the puncture success rate with a risk rate of 1%. However, in tomographic images of frozen sections, punctures with a tip diameter of 200 μm or less failed to remain in the epidermis and reached the dermis (data not shown). Therefore, it was thought that the tip diameter needed to be set to 300 to 600 μm in order for the puncture to remain within the epidermis.

[0295] Subsequently, as shown in Figure 20-3d, a single-needle MN (MN) with a length of 200 μm, an array of 19 MNs of the same shape (MN Array), a single-needle MN (MN w / Base) with a length of 200 μm and a base length of 2,000 μm, and an array of 19 MNs of the same shape as the MN w / Base were fabricated, and their puncture performance was evaluated. The results showed that adding a base below the MN and simultaneously forming it into an array significantly improved the puncture rate.

[0296] Finally, in Figure 20-3e, the pitch between MNs was changed to evaluate the change in the puncture rate due to the arrangement of the array. Although no significant change was observed due to differences in pitch, a tendency for the puncture rate to decrease was observed when the pitch was 5 mm or more.

[0297] Based on these results, we developed a new type of MN (PGA-MN) that remains within the SC, as shown in Figure 20-1. Using PGA-MN, we verified whether the intended puncture was possible by methylene blue staining and resin section & HE staining. As a result, 17 of 18 MNs punctured up to the 5th layer of the SC, and 10 of those reached the 10th layer (data not shown).

[0298] Next, we evaluated the puncture depth using resin sections (Figure 20-4). Unfortunately, the MN tip hydrolyzed during fixation, making it impossible to simultaneously photograph the needle tip and skin. However, we were able to confirm that the MN puncture mark remained within the SC and that the MN puncture site had been significantly deformed down to the dermis.

[0299] Penetration Study The injectability of PGA-MN was evaluated by the penetration-enhancing effect of hydrophilic model drugs using fluorescence intensity quantification and confocal Raman microscopy.

[0300] The permeability of a model drug (Flu-Na) was evaluated using fluorometry. As a result, a significant increase in the amount of permeation was observed 15 minutes after application of Injectable-MN, approximately 2.9 times that observed with simple application (Fig. 20-5a).

[0301] Furthermore, confocal Raman spectroscopy was used to visualize the time-dependent intradermal penetration of a model drug (niacinamide). Simple application showed that even after 3 hours, the penetration depth remained at approximately 20 μm, the same as that of SC, whereas when Injectable-MN was used in combination, the penetration depth reached the same depth as that of VE after 30 minutes (Figure 20-5b).

[0302] RNA-seq analysis of the control group and the PGA-MN treatment group revealed significant changes in 11 genes on day 1, 5 genes on day 3, and 79 genes on day 7. A heat map showing differentially expressed genes is shown in Figure 20-6a. Green blocks indicate genes with decreased expression, and red blocks indicate genes with increased expression.

[0303] The enrichment analysis indicated that the functions of six gene clusters were significantly upregulated and the functions of 18 gene clusters were downregulated in PGA-MN compared to the control group (Fig. 20-6b). Among these, gene clusters related to NABA ECM regulators, vascular permeability regulators, and innate immune responses may be related to the improvements in blood flow, wrinkles, and sagging observed in the in vivo human studies described below.

[0304] Blood flow When blood flow was evaluated, a significant increase in blood flow was observed only on the side where Injectable-MN was applied (Figure 20-7).

[0305] Home-use human test Injectable-MN brought about a significant improvement in the grade of wrinkles two weeks after application, while in the control group (serum), improvement in wrinkles was observed from four weeks after application (Fig. 20-8a).

[0306] Furthermore, the skin clarity after two weeks of application was significantly improved compared to the serum group (Fig. 20-8b).

[0307] Furthermore, in the questionnaires given two and eight weeks later, significant improvements were observed in the items "skin became softer" and "skin became moist" (Fig. 20-8c, d).

[0308] Furthermore, significant changes were observed in the sagging grades of the nasolabial folds, marionette lines, and facial lines from the initial values ​​(Fig. 20-8 e, f, g). In the control group, no significant changes were observed in the improvement of sagging of the marionette lines and facial lines. Furthermore, only in the Injectable-MN group, the volume of the mandible significantly decreased after 2 and 8 weeks of continuous use compared to before use (Fig. 20-8 h). A visually obvious reduction in sagging was observed in some subjects (Fig. 20-8 i).

[0309] Barrier function also improved significantly in both groups after two weeks (Fig. 20-8j).

[0310] Furthermore, when asked whether the irritation caused by application of the test product was tolerable, 96% of the Injectable-MN group answered "yes," and no significant difference was observed between the group administered Injectable-MN and the control group (data not shown).

[0311] Discussion The conflicting issue of the length of the MN (if it is too long it will penetrate deeply, but if it is too short it will not penetrate the skin at all) was resolved by adding base parts that artificially lengthen the MN and arranging them at an appropriate pitch.

[0312] It was confirmed that the optimized PGA-MN remained in the target skin layer, SC or VE.

[0313] At the same time, when resin sections were examined under a microscope, significant deformation was observed in the deep epidermis.

[0314] This deformation is thought to have two functions: First, by compressing or stretching the skin, the shock absorption ability of the skin is reduced, allowing a short needle of 200 μm or less to be used to puncture the target area accurately.

[0315] The other is to apply mechanical stress, which contributes to the results of RNA-seq and blood flow assessment.

[0316] The injectability of hydrophilic model drugs was evaluated by their penetration-enhancing effect using fluorescence intensity quantification and confocal Raman microscopy. The results revealed that PGA-MN improved the skin permeability of the model drugs in terms of quantity, speed, and depth.

[0317] RNA-seq results indicated that PGA-MN pressure altered NABA ECM regulators, vascular permeability regulators, and innate immune responses. These genes included several commonly known to be regulated by mechanical stress, suggesting that PGA-MN may induce mechanobiological effects in the dermis. These changes likely contribute to ECM and vascular remodeling and may signal a transition from the inflammatory phase to the proliferative and remodeling phase.

[0318] Although it has been reported that the modulation of key genes, such as VEGF, during wound healing can cause significant damage

[17] , no such genes were altered in our results. Therefore, our hypothesis is that PGA-MN may promote a mild immune response, leading to skin improvement through remodeling of the dermal ECM and blood vessels via a wound healing-like mechanism, without causing significant skin damage.

[0319] In wound healing, both wound formation and mechanobiological effects are thought to contribute to the initiation of the process. However, the PGA-MN used in this study remains within the SC and does not form a wound. Therefore, it is speculated that the mild action of mechanobiological effects alone may be sufficient. In other words, we have discovered unique evidence that skin rejuvenation can be achieved without the risk of scar formation through invasive methods. Whether these changes in gene expression actually manifest as traits will be clarified using methods such as immunostaining.

[0320] Furthermore, this mechanical stress also had the immediate effect of improving blood flow. These results indicate that Injectable-MN has multiple effects on both the epidermis and dermis.

[0321] It was also revealed that sagging, wrinkles, skin clarity, and barrier function were significantly improved after two weeks of continuous use. These skin-beautifying effects exceeded those of conventional cosmetics and existing MN technology.

[0322] The effects of niacinamide on the appearance of skin texture and pigmentation are well known (Reference 10). However, when niacinamide was injected using Injectable-MN, significant improvements in wrinkles and skin clarity were observed in a short period of time compared to conventional methods. Furthermore, the improvement in skin softness and moisture in the Injectable-MN administration group was shown to exceed that observed with simple topical application.

[0323] Furthermore, it was found to have an effect of improving sagging skin in previously unknown areas such as nasolabial folds, marionette lines, and facial lines. This is thought to be due to a complex reaction that not only rapidly supplies large amounts of niacinamide to the deep skin, but also promotes metabolic reactions through mechanobiological effects caused by MN pressure and improved blood flow.

[0324] In addition, although injectable MN improves barrier function, its mechanism of action, "piercing the SC," actually tends to impair barrier function (Reference 18). This is because Injectable-MN remains within the SC at a precisely controlled puncture depth, preventing damage to the barrier function. We have discovered that Injectable-MN can regenerate skin and address serious aging concerns, such as sagging, without destroying the skin's barrier function. We have achieved an extremely high level of both safety and efficacy, something that neither cosmetics nor aesthetic medicine have been able to achieve.

[0325] Conclusion Injectable-MN is a groundbreaking technology that combines safety and unprecedented rejuvenating effects at a very high level, something that has not been achieved with existing cosmetics or cosmetic medicine.

[0326] Thanks to its unique shape, Injectable-MN has been shown to non-invasively provide effects that exceed those of conventional cosmetics. The mechanism of action is thought to be due to the combined effects of: 1) rapid, high-dose penetration of the drug into the epidermal layer achieved by precise puncture and injection, 2) remodeling of the dermal ECM and blood vessels through a mechanism similar to non-invasive wound healing, and 3) immediate increase in blood flow (Figure 20-9), resulting in activation of the entire skin cells.

[0327] Injectable-MN technology enables control of not only the amount of penetration but also the location and time, ushering functional cosmetics into a new dimension as a new DDS platform. Furthermore, the effects of non-invasive mechanobiology amplify the potential of this technology many times over. This will be a game-changer, freeing consumers from the limitations of existing cosmetic efficacy and the burdens imposed by aesthetic medicine.

[0328] List of References

[0329] REFERENCE SIGNS LIST 10, 11 Plate 10a, 11a Dispensing hole 10b, 11b Needle-shaped protrusion 10c, 11c Lip portion 11d Base portion 20 Mounting frame 20a Plate support portion 20b Mounting barrel 30 Syringe 30a Syringe barrel tip 30b Syringe barrel 30c Plunger 30d Pressing piece 100, 101 Part with needle-shaped protrusion 200 Beauty tool C Medicinal solution S Target (skin)

Claims

1. A device for use in a method for improving the condition of a subject's skin, said device having a part with needle-like protrusions, said part with needle-like protrusions including needle-like protrusions, and an effective puncture length of said needle-like protrusions in the skin is a length that does not reach the dermis, said method comprising: (i) applying a pressing pressure of 50 to 1200 gf of said cosmetic device to the skin; and (ii) using said device at least once every two days and at least twice a day, or using said device at least three times a week.

2. The apparatus of claim 1, wherein the subject is required to adjust M1 / M2 balance.

3. The device of claim 1, wherein the subject is in need of increasing muscle fiber cell numbers.

4. An apparatus according to any one of claims 1 to 3, wherein the part with needle-like protrusions comprises: a plate having an injection hole penetrating vertically; one or more tiny needle-like protrusions protruding from one side of the plate; and a lip portion formed on the outer edge of one side of the plate.

5. An instrument according to any one of claims 1 to 3, wherein the part with needle-like projections comprises: a plate; one or more base portions protruding from one side of the plate; one or more tiny needle-like projections protruding from the tip surface of each of the one or more base portions; and a lip portion formed on the outer edge of the tip surface of the base portion.

6. The device according to claim 1, which is used to improve the barrier function of the skin.

7. The device according to claim 1, which is used to improve the clarity of the skin.

8. The device according to claim 1, which is used to promote collagen production in the skin.

9. The device according to claim 1, which is used to improve sagging skin.

10. A needle beauty device having parts with needle-shaped protrusions and intended to improve the barrier function and / or transparency of the skin.

11. The beauty device according to claim 10, wherein the part with needle-like protrusions comprises: a plate having an outlet hole penetrating vertically; one or more tiny needle-like protrusions protruding from one side of the plate; and a lip portion formed on the outer edge of one side of the plate.

12. The beauty device according to claim 10, wherein the part with needle-like protrusions comprises: a plate; one or more base portions protruding from one side of the plate; one or more tiny needle-like protrusions protruding from a tip surface of each of the one or more base portions; and a lip portion formed on the outer edge of the tip surface of the base portion.

13. The device according to any one of claims 1 to 12, which is for injecting a medicinal liquid into a target object via the part with needle-like protrusions.

14. A beauty kit for improving the barrier function and / or transparency of the skin, comprising the beauty tool according to claim 13 and the medicinal solution.

15. The beauty kit of claim 14, wherein the medicinal solution includes niacinamide.

16. The beauty kit according to claim 14 or 15, which can improve the transparency of the skin in a shorter period of time than when the medicinal liquid is applied to the skin.

17. The beauty kit according to any one of claims 14 to 16, which is capable of improving the barrier function of the skin, improving the transparency of the skin, promoting collagen production in the skin, or improving sagging skin.

18. A cosmetic method for improving the condition of a subject's skin, comprising: (i) applying a pressing pressure of 50 to 1,200 gf with a cosmetic tool against the skin; and (ii) using the cosmetic tool at least once every two days and at least twice a day, or at least three times a week; and wherein the cosmetic tool is a needle cosmetic tool having a part with needle-like projections, the part with needle-like projections includes needle-like projections, and the effective puncture length of the needle-like projections in the skin is a length that does not reach the dermis.

19. The cosmetic method according to claim 18, wherein the subject needs to adjust the M1 / M2 balance.

20. The cosmetic method according to claim 18, wherein the subject is in need of increasing the number of muscle fiber cells.

21. The cosmetic method according to any one of claims 18 to 20, for adjusting the M1 / M2 balance of the subject and / or for increasing the number of muscle fiber cells of the subject.

22. A method for improving the barrier function and / or clarity of the skin, comprising applying a cosmetic device according to any one of claims 10 to 13 to the skin.

23. A method for improving the barrier function and / or clarity of the skin, comprising applying the beauty tool to the skin using the beauty kit according to any one of claims 14 to 17.

24. The method of claim 22 or 23, comprising injecting a medicinal solution into a subject, the medicinal solution comprising niacinamide.

25. The method according to any one of claims 22 to 24, which is capable of improving the barrier function of the skin, improving the transparency of the skin, promoting collagen production in the skin, or improving sagging skin.

26. The method according to any one of claims 22 to 25, which can improve the sense of transparency in a shorter period of time than when the medicinal liquid is applied to the skin.

27. A needle beauty device having parts with needle-shaped protrusions and intended to promote collagen production.

28. A needle beauty device having parts with needle-like protrusions and intended to improve sagging skin.

29. A beauty device as described in claim 27 or 28, wherein the part with needle-like protrusions comprises: a plate having an outlet hole penetrating vertically; one or more tiny needle-like protrusions protruding from one side of the plate; and a lip portion formed on the outer edge of one side of the plate.

30. A beauty device as described in claim 27 or 28, wherein the part with needle-like protrusions comprises: a plate; one or more base portions protruding from one side of the plate; one or more tiny needle-like protrusions protruding from the tip surface of each of the one or more base portions; and a lip portion formed on the outer edge of the tip surface of the base portion.

31. The device according to any one of claims 1 to 5 and 27 to 30, which is for injecting a medicinal liquid into a target object via the part with needle-like protrusions.

32. A beauty kit for promoting collagen production, comprising the beauty tool according to claim 31 and the medicinal liquid.

33. The beauty kit of claim 32, wherein the medicinal solution includes niacinamide.

34. The beauty kit according to claim 32 or 33, which is capable of improving sagging skin, promoting collagen production in the skin, improving the barrier function of the skin, or improving the transparency of the skin.

35. A method for promoting collagen production, comprising applying the cosmetic device according to any one of claims 27 to 31 to the skin.

36. A method for promoting collagen production, comprising applying the beauty tool to the skin using the beauty kit according to any one of claims 31 to 34.

37. A method for promoting collagen production according to claim 35 or 36, comprising injecting a medicinal solution into a subject, the medicinal solution including niacinamide.

38. A method for promoting collagen production according to any one of claims 35 to 37, which is capable of improving sagging skin, promoting collagen production in the skin, improving the barrier function of the skin, or improving the transparency of the skin.

39. A device according to any one of claims 1 to 13 and 27 to 31, wherein the effective puncture length of the needle-like projections into the skin is 5 μm or more and 200 μm or less.

40. A beauty method according to any one of claims 18 to 21, wherein the beauty tool is a tool according to any one of claims 1 to 13 and 27 to 31.

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