Needle beauty appliance, beauty kit and beauty method

Abstract

Provided are a cosmetic appliance for improving the barrier function and / or transparency of the skin, a cosmetic appliance for promoting collagen production, and a cosmetic appliance for improving the laxity of the skin. A needle cosmetic instrument has a member with needle-like protrusions, and is used to improve the barrier function of the skin, improve the transparency of the skin, promote collagen production of the skin, or improve the laxity of the skin.

Description

Technical Field

[0001] The first aspect of the present invention relates to beauty devices and beauty kits for improving the skin's barrier function and / or translucency. The second aspect of the present invention also relates to methods for improving the skin's barrier function and / or translucency.

[0002] A second aspect of the invention relates to a needle-shaped cosmetic device and beauty kit for promoting collagen production and / or improving skin laxity. The second invention also relates to a method for promoting collagen production using the needle-shaped cosmetic device.

[0003] The third aspect of the invention relates to beauty devices, beauty kits, and beauty methods for use in cosmetic methods for improving the skin condition of an object. Background Technology

[0004] [Background Art of the First Embodiment]

[0005] To date, a great deal of development has been carried out on beauty methods and devices that utilize microneedling.

[0006] For example, Patent Document 1 discloses a cosmetic method that brightens the overall tone of the face by attaching a microneedle sheet with multiple microneedles to a part of the face.

[0007] Furthermore, Patent Document 2 reports a component with needle-like protrusions that can retain liquid compositions / liquid cosmetics without limiting active ingredients on the surface and inside of an object in a manner that prevents leakage from gaps. Moreover, the component with needle-like protrusions of Patent Document 2 can be installed in a needle-fixed injection device used as a needle-type beauty device.

[0008] [Background Art of the Second Embodiment]

[0009] Collagen is a type of protein with various types, including type I, type II, type III, type IV, type V, XII, and XIV. Type I collagen is known to account for 80% of the total collagen and is related to skin elasticity and firmness. Furthermore, a decrease in type I collagen is cited as one of the causes of wrinkles and sagging. Therefore, promoting the production of type I collagen can be considered effective in preventing and improving wrinkles and sagging.

[0010] To date, a great deal of research has been conducted on collagen production promoters.

[0011] For example, Patent Document 4 discloses a collagen production promoter, characterized in that it is composed of essential oils, which are obtained by steam distillation of one or more plants selected from the Lamiaceae family, the Caprifoliaceae family, the Sambucus nigra family, and the Burseraceae family, the Olive genus, and the Canarium Iuzonicum family.

[0012] Furthermore, Patent Document 2 discloses a component with needle-like protrusions capable of retaining a liquid composition / liquid cosmetic without limiting the active ingredients on the surface and inside of an object in a manner that prevents leakage from gaps. Moreover, the component with needle-like protrusions of Patent Document 2 can be installed in a needle-fixing type injection device used as a needle-shaped beauty device.

[0013] [Background Art of the Third Embodiment]

[0014] To date, a great deal of development has been carried out on beauty methods and devices that utilize microneedling.

[0015] For example, Patent Document 1 discloses a cosmetic method that brightens the overall tone of the face by attaching a microneedle sheet with multiple microneedles to a part of the face.

[0016] Furthermore, Patent Documents 2 and 3 disclose components with needle-like protrusions and beauty device devices having such components. For example, Patent Document 2 reports a component with needle-like protrusions capable of leaving a liquid composition / liquid cosmetic without limiting active ingredients on the surface and inside of an object in a manner that prevents leakage from gaps. Moreover, the component with needle-like protrusions of Patent Document 2 can be installed in a needle-fixing injection device as a beauty device.

[0017] Existing technical documents

[0018] Patent documents

[0019] Patent Document 1: Japanese Patent Application Publication No. 2020-164432

[0020] Patent Document 2: International Publication No. 2022 / 071322

[0021] Patent Document 3: International Publication No. 2023 / 190584

[0022] Patent Document 4: Japanese Patent Application Publication No. 2006-232740

[0023] Non-patent literature

[0024] Non-patent literature 1: Skin Research and Technology 2009; 15: 299-305 Summary of the Invention

[0025] The problem that the invention aims to solve

[0026] [The problem in one aspect of the first invention]

[0027] Currently, most microneedles commercially available for cosmetic use are primarily composed of hyaluronic acid needles. Therefore, the cosmetic effects resulting from microneedling techniques and devices can be considered to mainly originate from hyaluronic acid, i.e., the primary expected effect is moisturizing.

[0028] On the other hand, there is still room for improvement regarding beauty devices used to improve the skin's barrier function and to improve the skin's transparency.

[0029] According to one aspect of the first invention, beauty devices and beauty kits are provided for improving the skin's barrier function and / or transparency.

[0030] Furthermore, according to one aspect of the first invention, a method for improving the skin's barrier function and / or a method for improving transparency is provided.

[0031] [A problem in one aspect of the second invention]

[0032] As described in Patent Document 4, various collagen production promoters have been developed, and there are also requests to develop beauty devices for promoting collagen production.

[0033] According to one aspect of the second invention, beauty devices and beauty kits for promoting collagen production are provided.

[0034] Furthermore, according to other aspects of the second invention, a method for promoting collagen production can be provided.

[0035] Furthermore, according to other aspects of the second invention, it is possible to provide beauty devices and beauty kits for improving skin laxity.

[0036] Furthermore, according to other aspects of the second invention, a method for improving skin laxity can be provided.

[0037] [A problem in one aspect of the third invention]

[0038] Currently, most microneedles commercially available for cosmetic use are primarily composed of hyaluronic acid needles. Therefore, the cosmetic effects resulting from microneedling techniques and devices can be considered to mainly originate from hyaluronic acid, i.e., the primary expected effect is moisturizing.

[0039] On the other hand, there is still room for improvement regarding beauty instruments used in cosmetic methods that improve the skin condition of the subject. In particular, there is still room for improvement regarding beauty instruments used on subjects who require adjustment of M1 / M2 balance or who require an increase in the number of myofibroblasts.

[0040] According to one aspect of the third invention, a method for improving the skin condition of an object can be provided. In the above method, for example, an instrument having a component with needle-like protrusions (sometimes referred to as a beauty instrument, needle beauty instrument, etc.) is used.

[0041] According to other aspects of the third invention, it is possible to provide an instrument (sometimes referred to as a beauty instrument, needle beauty instrument, etc.) for use in cosmetic methods for improving the skin condition of a subject.

[0042] Methods for solving problems

[0043] The first embodiment of the present invention that achieves the above-mentioned objective is described below.

[0044] <Option 1-1>

[0045] A needle-shaped beauty device has a component with needle-like protrusions, and

[0046] Used to improve the skin's barrier function and / or transparency.

[0047] <Options 1-2>

[0048] According to the beauty device described in Scheme 1-1, the component with needle-like protrusions has: A plate with liquid outlet holes running vertically through it. One or more tiny needle-like projections protruding from one side of the plate, and A lip formed on the outer edge of one side of the plate.

[0049] <Options 1-3>

[0050] According to the beauty device described in Scheme 1-1, the component with needle-like protrusions has: plate, One or more base parts protruding from one side of the plate One or more tiny needle-like protrusions protruding from the top surface of one or more base portions, and A lip is formed on the outer edge of the top surface of the base.

[0051] <Options 1-4>

[0052] The beauty device according to any one of Schemes 1-1 to 1-3 is an instrument for injecting a medicinal liquid into a target object via the aforementioned component with needle-like protrusions.

[0053] <Options 1-5>

[0054] A beauty kit for improving the skin's barrier function and / or translucency, comprising the beauty instruments described in schemes 1-4 and the aforementioned medicinal solution.

[0055] <Options 1-6>

[0056] According to the beauty kits described in schemes 1-5, the above-mentioned liquid contains niacinamide.

[0057] <Options 1-7>

[0058] The beauty kit described in schemes 1-5 or 1-6 can improve the transparency in a shorter period of time compared to applying the above-mentioned liquid to the skin.

[0059] <Options 1-8>

[0060] The beauty kit according to any one of Schemes 1-5 to 1-7 can improve the skin barrier function, improve the skin's transparency, promote collagen production, or improve skin laxity.

[0061] <Options 1-9>

[0062] A method for improving the skin's barrier function and / or transparency includes: applying the beauty device described in any one of Schemes 1-1 to 1-4 to the skin.

[0063] <Options 1-10>

[0064] A method for improving the skin's barrier function and / or translucency includes: applying the aforementioned beauty device to the skin using a beauty kit as described in any one of schemes 1-5 to 1-8.

[0065] <Option 1-11>

[0066] The method described according to schemes 1-9 or 1-10 includes injecting a drug solution into the target object, and

[0067] The above-mentioned liquid contains nicotinamide.

[0068] <Options 1-12>

[0069] The method according to any one of Schemes 1-9 to 1-1-11 can improve the skin barrier function, improve the skin transparency, promote the production of collagen in the skin, or improve skin laxity.

[0070] <Option 1-13>

[0071] The method according to any one of Schemes 1-9 to 1-12 can improve the transparency in a shorter period of time compared to applying the above-mentioned medicinal solution to the skin.

[0072] A second embodiment of the present invention that achieves the above-mentioned objective is described below.

[0073] <Option 2-1>

[0074] A needle-shaped beauty device having a component with needle-like protrusions and for promoting collagen production.

[0075] <Option 2-2>

[0076] A needle-shaped beauty device having a component with needle-like protrusions, and used to improve skin laxity.

[0077] <Option 2-3>

[0078] According to the beauty device described in Scheme 2-1 or 2-2, the component with needle-like protrusions has: A plate with liquid outlet holes running vertically through it. One or more tiny needle-like projections protruding from one side of the plate, and A lip formed on the outer edge of one side of the plate.

[0079] <Options 2-4>

[0080] According to the beauty device described in Scheme 2-1 or 2-2, the component with needle-like protrusions has: plate, One or more base parts protruding from one side of the plate One or more tiny needle-like protrusions protruding from the top surface of one or more base portions, and A lip is formed on the outer edge of the top surface of the base.

[0081] <Option 2-5>

[0082] The beauty device according to any one of Schemes 2-1 to 2-4 is an instrument for injecting a medicinal liquid into a target object via the aforementioned component with needle-like protrusions.

[0083] <Option 2-6>

[0084] A beauty kit for promoting collagen production, comprising the beauty instruments described in schemes 2-5 and the aforementioned medicinal solution.

[0085] <Option 2-7>

[0086] According to the beauty kit described in Scheme 2-6, the above-mentioned liquid contains niacinamide.

[0087] <Option 2-8>

[0088] The beauty kit described in schemes 2-6 or 2-7 can improve skin laxity, promote collagen production, improve skin barrier function, or improve skin transparency.

[0089] <Option 2-9>

[0090] A method for promoting collagen production includes: applying the beauty device described in any one of schemes 2-1 to 2-5 to the skin.

[0091] <Option 2-10>

[0092] A method for promoting collagen production includes: applying the beauty device to the skin using any one of the beauty kits described in Schemes 2-6 to 2-8.

[0093] <Option 2-11>

[0094] The collagen production promotion method according to schemes 2-9 or 2-10 includes injecting a drug solution into the target object, and

[0095] The above-mentioned liquid contains nicotinamide.

[0096] <Option 2-12>

[0097] The collagen production promotion method according to any one of Schemes 2-9 to 2-11 can improve skin laxity, promote skin collagen production, improve skin barrier function, or improve skin transparency.

[0098] A third embodiment of the present invention that achieves the above-mentioned objective is described below.

[0099] As described above, according to this embodiment, for example, a method for improving the skin condition of an object is provided. In this method, for example, an instrument (sometimes referred to as a beauty instrument, needle beauty instrument, etc.) having a component with needle-like protrusions is used. In this method, the effective puncture length of the needle-like protrusions into the skin can be 5 μm or more and 200 μm or less. This inhibits the needle-like protrusions from reaching the dermis. As a result, damage to the skin can be suppressed.

[0100] In the above method, the component with needle-like protrusions includes, for example, a plate with a liquid outlet hole extending vertically, and one or more minute needle-like protrusions protruding from one side of the plate. The component with needle-like protrusions may further include a lip formed at the outer edge of one side of the plate. In the component with needle-like protrusions, at least one of the minute needle-like protrusions may be disposed inside the lip.

[0101] In the above method, the component with needle-like protrusions includes, for example, a plate, one or more base portions protruding from one side of the plate, and one or more minute needle-like protrusions protruding from the top surface of each of the one or more base portions. The component with needle-like protrusions may further include a lip formed at the outer edge of the top surface of the base portion. In the component with needle-like protrusions, at least one of the one or more minute needle-like protrusions may be disposed inside the lip.

[0102] The above method includes, for example, a stage in which needle-like protrusions are pressed against the skin at a pressure of 50 to 1200 gf. This can improve the skin's barrier function, enhance skin transparency, promote collagen production, and / or reduce skin laxity. The method can achieve particularly significant effects when used in combination with specific pharmaceutical agents. The pressure can be 100 to 1000 gf. This can suppress skin damage. The pressure is preferably 300 to 900 gf. This can further suppress skin damage. As a result, for example, skin darkening can be suppressed.

[0103] The above method includes, for example, (ii) a stage where the needle-like protrusion is pressed onto the skin at a frequency of once or more every two days and at least twice, or a stage where the needle-like protrusion is pressed onto the skin at a frequency of three or more times per week. As a result, effects such as improving the skin barrier function, improving skin transparency, promoting collagen production, and / or improving skin laxity become significant. Consequently, the user experience is improved.

[0104] According to this embodiment, an instrument (sometimes referred to as a beauty instrument, needle beauty instrument, etc.) for use in a cosmetic method for improving the skin condition of a subject is provided. The instrument has, for example, a component with needle-like protrusions. The instrument can be a needle beauty instrument. In the instrument, the component 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 can be 5 μm or more and 200 μm or less. This suppresses damage to the skin.

[0105] In the aforementioned apparatus, the aforementioned beauty method includes, for example, a stage of pressing the apparatus onto the skin with a pressure of 50 to 1200 gf. The aforementioned beauty method includes, for example, a stage of pressing the apparatus onto the skin at a frequency of once or more every two days and at least twice, or a stage of pressing the apparatus onto the skin at a frequency of three or more times per week. As a result, effects such as improving the skin barrier function, improving skin transparency, promoting collagen production, and / or improving skin laxity become significant. Consequently, the user experience is improved.

[0106] According to the methods and / or the instruments described above, the M1 / M2 balance within the skin can be adjusted. Therefore, by applying the methods and / or the instruments described above to a subject for whom it is desired to adjust the M1 / M2 balance within the skin, it is particularly possible to improve the M1 / M2 balance within the skin of that subject.

[0107] According to the above method and / or the above apparatus, the number of myofibroblasts inside the skin can be increased. Therefore, by applying the above method and / or the above apparatus to a subject who desires to increase the number of myofibroblasts inside the skin, the number of myofibroblasts inside the skin of that subject can be increased.

[0108] <Option 3-1>

[0109] An instrument used in methods for improving the skin condition of an object. The aforementioned device has: a component with needle-like protrusions, The aforementioned component 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. The above methods include: (i) Apply the above-mentioned beauty device to the skin with an extrusion pressure of 50–1200 gf, and (ii) Using the above-mentioned appliance more than once every two days and using it more than twice, or using the above-mentioned appliance more than three times a week.

[0110] <Option 3-2>

[0111] According to the beauty tools described in Scheme 3-1, the above-mentioned objects need to be balanced by adjusting M1 / M2.

[0112] <Option 3-3>

[0113] According to the beauty device described in Scheme 3-1, the above-mentioned objects need to increase the number of myofibril cells.

[0114] <Options 3-4>

[0115] According to any one of Schemes 3-1 to 3-3, the beauty device with needle-like protrusions described above has: A plate with liquid outlet holes running vertically through it. One or more tiny needle-like projections protruding from one side of the plate, and A lip formed on the outer edge of one side of the plate.

[0116] <Options 3-5>

[0117] According to any one of Schemes 3-1 to 3-3, the beauty device with needle-like protrusions described above has: plate, One or more base parts protruding from one side of the plate One or more tiny needle-like protrusions protruding from the top surface of one or more base portions, and A lip is formed on the outer edge of the top surface of the base.

[0118] <Options 3-6>

[0119] The device described in Scheme 3-1 is used to improve the skin barrier function.

[0120] <Option 3-7>

[0121] The device described in Scheme 3-1 is used to improve the transparency of the skin.

[0122] <Option 3-8>

[0123] The device described in Scheme 3-1 is used to promote collagen production in the skin.

[0124] <Options 3-9>

[0125] The device described in Scheme 3-1 is used to improve skin laxity.

[0126] <Option 3-10>

[0127] The apparatus according to any one of Schemes 3-1 to 3-9 is an apparatus for injecting a liquid medicine into an object via the aforementioned component with needle-like protrusions.

[0128] <Option 3-11>

[0129] A cosmetic kit for improving the skin's barrier function and / or translucency, comprising the apparatus described in schemes 3-10 and the aforementioned medicinal solution.

[0130] <Option 3-12>

[0131] According to the beauty kit described in Scheme 3-10, the above-mentioned liquid contains niacinamide.

[0132] <Option 3-13>

[0133] The beauty kit described in schemes 3-11 or 3-12 can improve the transparency in a shorter period of time compared to applying the above-mentioned liquid to the skin.

[0134] <Option 3-14>

[0135] The beauty kit according to any one of Schemes 3-11 to 3-13 can improve the skin barrier function, improve the skin's transparency, promote collagen production, or improve skin laxity.

[0136] <Option 3-15>

[0137] A cosmetic method for improving the skin condition of a subject, comprising: (i) Apply the cosmetic device to the skin with an extrusion pressure of 50–1200 gf, and (ii) Using the above-mentioned beauty tools more than once every two days and for more than two times, or using them more than three times a week. and The aforementioned beauty device is a needle-type beauty device, which has a component with needle-like protrusions. The aforementioned component 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.

[0138] <Option 3-16>

[0139] According to the beauty method described in Scheme 3-15, the above-mentioned object needs to have its M1 / M2 balance adjusted.

[0140] <Option 3-17>

[0141] According to the cosmetic method described in Scheme 3-15, the above-mentioned object needs to increase the number of myofibril cells.

[0142] <Option 3-18>

[0143] The cosmetic method according to any one of Schemes 3-15 to 3-17 is used to adjust the M1 / M2 balance of the above-mentioned object and / or increase the number of myofibril cells of the above-mentioned object.

[0144] <Option 3-19>

[0145] A beauty kit for promoting collagen production, comprising the apparatus described in any one of schemes 3-1 to 3-10 and the aforementioned medicinal solution.

[0146] <Option 3-20>

[0147] According to the beauty kit described in Scheme 3-19, the above-mentioned liquid contains niacinamide.

[0148] <Option 3-21>

[0149] The beauty kit described in schemes 3-19 or 3-20 can improve skin laxity, promote collagen production, improve skin barrier function, or improve skin transparency.

[0150] <Option 3-22>

[0151] A method for promoting collagen production includes applying the apparatus described in any one of schemes 3-1 to 3-10 to the skin.

[0152] <Option 3-23>

[0153] A method for promoting collagen production includes: applying the beauty device to the skin using any one of the beauty kits described in Schemes 3-19 to 3-21.

[0154] <Option 3-24>

[0155] The collagen production promotion method according to scheme 3-22 or 3-23 includes injecting a drug solution into the target object, and

[0156] The above-mentioned liquid contains nicotinamide.

[0157] <Option 3-25>

[0158] The collagen production promotion method according to any one of Schemes 3-22 to 3-24 can improve skin laxity, promote skin collagen production, improve skin barrier function, or improve skin transparency.

[0159] <Option 3-26>

[0160] According to any one of the embodiments 3-1 to 3-10, the effective puncture length of the needle-like protrusion into the skin is more than 5 μm and less than 200 μm.

[0161] <Option 3-27>

[0162] According to the beauty methods described in schemes 3-15 to 3-18, the aforementioned beauty device is any one of the devices described in schemes 3-1 to 3-10.

[0163] The effects of the invention

[0164] [Effects of one aspect of the first invention]

[0165] According to one aspect of the first invention, a beauty device can be provided for improving the skin's barrier function and / or transparency.

[0166] Furthermore, according to one aspect of the first invention, a cosmetic kit for improving the skin's barrier function and / or transparency can also be provided.

[0167] Furthermore, according to one aspect of the first invention, a method for improving the skin's barrier function and / or transparency can also be provided.

[0168] [Effects of one aspect of the present invention]

[0169] According to one aspect of the second invention, a beauty device for promoting collagen production can be provided.

[0170] Furthermore, according to one aspect of the second invention, a beauty kit for promoting collagen production can also be provided.

[0171] Furthermore, according to one aspect of the second invention, a method for promoting collagen production can also be provided.

[0172] As described above, the second aspect of the present invention utilizes the physical stimulation provided by the needle beauty device to promote collagen production, and can achieve the collagen production promotion effect through a different action than conventional collagen production promoters and other topical skin agents.

[0173] Furthermore, according to one aspect of the second invention, a needle-shaped beauty device for improving skin laxity can be provided. Additionally, according to one aspect of the second invention, a beauty kit for improving skin laxity can also be provided. Furthermore, according to one aspect of the second invention, a method for improving skin laxity can also be provided.

[0174] [Effects of one aspect of the present invention]

[0175] According to one aspect of the third invention, a beauty device can be provided for use in a cosmetic method for improving the skin condition of an object.

[0176] Furthermore, the third embodiment of the present invention can be an object that needs to adjust the M1 / M2 balance, or an object that needs to increase the number of myofibril cells.

[0177] Therefore, according to one aspect of the third invention, the M1 / M2 balance of the skin of the object can be regulated. Furthermore, according to one aspect of the third invention, the number of myofibril cells in the object can be increased. Attached Figure Description

[0178] Figure 1 A schematic diagram showing one embodiment of the components with needle-like protrusions according to the present invention, namely the first, second and third embodiments.

[0179] Figure 2 A schematic diagram showing a portion of another embodiment of the component with needle-like protrusions according to the present invention, for the purposes of the first and second inventions.

[0180] Figure 3 A schematic diagram showing a design for a beauty device with components and fastening devices featuring needle-like protrusions.

[0181] Figure 4 A diagram showing the intradermal distribution of the epidermal proliferation marker Ki-67 when applied in Examples 1-1 and 1-2.

[0182] Figure 4-1 Graphs showing the collagen production promoting effects of Examples 2-1 and 2-2.

[0183] Figure 5 To demonstrate the density (cells / mm²) of Ki-67 positive epidermal proliferation markers in the skin during the applications of Examples 1-1 and 1-2. 2 A graph showing the changes in ( ).

[0184] Figure 5-1 The figure shows the results of immunofluorescence staining of α-SMA / Vimentin and the nucleus (Hoechst) in Examples 2-3.

[0185] Figure 5-2 To illustrate for Examples 2-3 Figure 5-1 The stained images were obtained by using the image analysis software ImageJ to quantify the area immediately below the epidermal basement membrane (200 μm) and count the α-SMA / Vimentin double-positive cells (myofibroblasts) in this area.

[0186] Figure 6 Explanatory diagrams showing the application locations of Examples 1-3.

[0187] Figure 6-1 A graph illustrating the penetration-enhancing effect of the nicotinamide-containing solution brought about by the beauty device of the second invention.

[0188] Figure 7 A graph showing the amount of skin moisture evaporation in Examples 1-3.

[0189] Figure 7-1 A graph illustrating the penetration-enhancing effect of a solution containing a model agent (water-soluble fluorescent substance) provided by the beauty device of the second invention.

[0190] Figure 8 A diagram showing the evaluation scale when assessing transparency.

[0191] Figure 8-1 Explanatory diagrams showing the application locations of Examples 2-5.

[0192] Figure 9 The figures illustrate the improved transparency achieved by Examples 1-4.

[0193] Figure 9-1 A graph showing the changes in facial contour angles of the subjects in Examples 2-5.

[0194] Figure 10 A graph illustrating the penetration-enhancing effect of a nicotinamide-containing solution brought about by the beauty device of the first invention.

[0195] Figure 10-1 A 3D scan image of the jawbone showing the relaxation improvement effect in one subject in Examples 2-5.

[0196] Figure 11 A graph illustrating the penetration-enhancing effect of a solution containing a model agent (water-soluble fluorescent substance) provided by the beauty device of the first invention.

[0197] Figure 11-1 A graph showing the results of the volume change of the mandible in the subjects of Examples 2-6 and Comparative Example 2-1.

[0198] Figure 12 The image was obtained by confocal microscopy after using Hoechst fluorescence immunostaining on fresh skin to detect antibodies against CD31 (a marker for vascular endothelial cells), αSMA (a marker for myofibroblasts), and vimentin (a marker for fibroblasts), as well as nuclear staining.

[0199] Figure 13 Based on Figure 12 The results were obtained by using the image analysis software ImageJ to count the myofibroblasts (αSMA / Vimentin double-positive cells) located in a region of 200 μm immediately below the epidermal basement membrane, and plotting the changes over time.

[0200] Figure 14 Based on Figure 12 The results were obtained by using the image analysis software ImageJ to count the vascular endothelial cells (CD31-positive cells) located in a region of 200 μm immediately below the epidermal basement membrane, and plotting the changes over time.

[0201] Figure 15 This image, taken using a confocal microscope, shows M1 macrophages (CD86 and CD68) present in a region approximately 200 μm below the epidermal basement membrane. It was created by applying antibodies against CD86 and CD68 to fresh skin and performing Hoechst fluorescence immunostaining.

[0202] Figure 16 Images obtained by confocal microscopy of fresh skin after applying antibodies against CD206 (a marker of M2 macrophages) and CD68 (a marker of macrophages), and after nuclear staining using Hoechst fluorescence immunostaining.

[0203] Figure 17 Based on Figure 15 The results were obtained by using the image analysis software ImageJ to count the number of M1 macrophages in the region immediately below the epidermal basement membrane and plotting the changes over time.

[0204] Figure 18 Based on Figure 16 The results were obtained by using the image analysis software ImageJ to count the number of M2 macrophages in the region immediately below the epidermal basement membrane and plotting the changes over time.

[0205] Figure 19 Based on Figure 17 and Figure 18 The number of M1 macrophages and M2 macrophages was used to quantify the M1 / M2 ratio, and the changes over time were plotted to obtain the graph.

[0206] Figure 20-1 The images and functional diagrams for the manufactured Injectable-MN are shown below. a is a top view and a side view of the PGA-MN, b is a diagram of the Injectable-MN (formed by connecting the PGA-MN to a push-button pen), and c is a functional diagram of the Injectable-MN.

[0207] Figure 20-2 This 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.

[0208] Figure 20-3 A graph showing the results of the puncture capability test. a. Puncture capability relative to the length of MN, b. Puncture capability relative to the total length (MN + MN w / Base), c. Puncture capability relative to the top diameter of the base under MN, d. Puncture rate of arrayed MNs, e. Puncture rate relative to the spacing between MNs in the array.

[0209] Figure 20-4 Cross-sectional view of the skin resin portion of PGA-MN.

[0210] Figure 20-5 Figures illustrating the results of the permeation test. a. Quantitative analysis using fluorescence intensity quantification method; b. Visualization of permeability using confocal Raman spectroscopy; color intensity indicates nicotinamide concentration. Data are expressed as ±SEM, * indicates p < 0.05.

[0211] Figure 20-6 Figures showing the results of RNA-seq. a is a heatmap of gene clusters with differential expression in dermal mRNA, and b is an enrichment analysis of gene clusters with differential expression in dermal RNA.

[0212] Figure 20-7 To illustrate the difference in blood flow before and after application. Data are expressed as ±SEM, * indicates p < 0.05, ** indicates p < 0.01.

[0213] Figure 20-8Figures illustrating the results of a home-based human trial. a. Time-varying changes in wrinkle severity, b. Time-varying changes in skin translucency, c. Time-varying changes in skin softness, d. Time-varying changes in skin moisture, e. Time-varying changes in nasolabial fold severity, f. Time-varying changes in marionette line severity, g. Time-varying changes in facial contour severity, h. Time-varying changes in jaw volume, i. Photographs of the subjects: examples of improved nasolabial folds, j. Time-varying changes in TEWL (transverse endothelial fold). Data are expressed as ±SEM, * indicates p < 0.05, ** indicates p < 0.01, *** indicates p < 0.001.

[0214] Figure 20-9 This is a schematic diagram illustrating the overall activation of skin cells using injectable MN (synergistic effect of mechanobiological stimulation and effective nutrient delivery). Detailed Implementation

[0215] The present invention will now be described through embodiments thereof, but these embodiments do not limit the invention as described in the claims. Furthermore, not all combinations of features described in the embodiments are necessarily necessary in 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.

[0216] [The first invention]

[0217] Hereinafter, the embodiments for carrying out the first invention will be described in detail with reference to the accompanying drawings. Furthermore, for ease of explanation, the same reference numerals are used for the same or equivalent parts in each figure, and repeated descriptions are omitted. In addition, not all constituent elements of the embodiments are necessarily necessary, and sometimes some constituent elements may be omitted. Of course, the first invention is not limited to the following embodiments, and can be implemented with various modifications within the scope of the inventive intent.

[0218] Needle Beauty Devices

[0219] The first embodiment of the present invention relates to a needle-shaped beauty device (hereinafter also referred to as "the beauty device of the first embodiment") having a component with needle-like protrusions, and is used to improve the skin's barrier function and / or transparency.

[0220] The beauty device of the first embodiment includes a component with needle-like protrusions, which can be, for example, the "component with needle-like protrusions" disclosed in Patent Document 2. Furthermore, the beauty device (device) disclosed in Patent Document 2 can also be used as the needle-shaped beauty device of the first embodiment. However, in Patent Document 2, the "component with needle-like protrusions" refers to a component capable of retaining a liquid composition / liquid cosmetic without limiting active ingredients on the surface and inside of the object in a manner that prevents leakage from gaps; no disclosure / disclosure is made regarding the skin barrier function. In this regard, considering skin punctures such as microneedles, the effect of the first embodiment in improving the skin barrier function can be considered unexpected.

[0221] Through in-depth research, the inventors discovered that by using a beauty device of the first embodiment having such a needle-like protrusion, the skin barrier function can be improved.

[0222] While not theoretically limited, it is speculated that the beauty device of the first embodiment, by applying the component with needle-like protrusions to the skin, causes puncture of the skin's surface and large deformation reaching the deeper layers, resulting in stimulated cell differentiation and activation, thereby promoting cell renewal. Furthermore, it is speculated that this promoted renewal can lead to improvements in the skin's barrier function and / or translucency. Moreover, it is known that the application of this beauty device provides a temporary blood flow promotion effect (data not published), and it is speculated that further promotion of renewal occurs, thereby enhancing the aforementioned effects.

[0223] Furthermore, through in-depth research, the inventors have discovered that the beauty device of the first embodiment has an epidermal cell proliferation-promoting effect. It can also be considered that this epidermal cell proliferation-promoting effect can lead to improvements in the skin's barrier function and / or transparency.

[0224] Furthermore, in the first embodiment, the so-called skin barrier function refers to the function undertaken by the stratum corneum and epidermis of the skin, which is to prevent the loss of water essential for the activities of cells and tissues that constitute an organism, and to prevent the invasion of external stimuli, viruses, bacteria, and other substances into the body. In addition, the skin barrier function can be measured by measuring transdermal epidermal loss (TEWL) under non-sweating conditions, expressed in g / m³. 2 •h) is used as a unit for evaluation (Japan Cosmetic Technicians Association, Cosmetic Encyclopedia, Maruzen Co., Ltd., 2005, pp. 83-84).

[0225] Furthermore, in the first embodiment, the so-called skin transparency refers to the skin (especially the entire face) appearing clear and translucent without dullness.

[0226] The component with needle-like protrusions according to the first embodiment may have: A plate with liquid outlet holes running vertically through it. One or more tiny needle-like projections protruding from one side of the plate, and A lip formed at the outer edge of one side of the plate. In addition, it can have: plate, One or more base parts protruding from one side of the plate One or more tiny needle-like protrusions protruding from the top surface of one or more base portions, and A lip is formed on the outer edge of the top surface of the base.

[0227] Furthermore, the beauty device of the first embodiment can be a beauty device for injecting a medicinal liquid into a target object via a component with needle-like protrusions.

[0228] In this case, the beauty device of the first embodiment can be

[0229] It has a component with needle-like protrusions for injecting liquid medicine into an object. Components with needle-like protrusions have A plate with liquid outlet holes running vertically through it. One or more tiny needle-like projections protruding from one side of the plate, and A lip formed at the outer edge of one side of the plate. and If the composition of the first embodiment is extruded from the liquid outlet, the composition of the first embodiment expands in the space formed between the object and one side of the lip and the plate, and the composition of the first embodiment enters the interior of the object through the hole opened by one or more needle-like protrusions. Or it could be A component with needle-like protrusions is provided for injecting the composition of the first embodiment into an object. Components with needle-like protrusions have plate, One or more base parts protruding from one side of the plate One or more tiny needle-like protrusions protruding from the top surface of one or more base portions, and A lip is formed on the outer edge of the top surface of the base. A liquid outlet hole is formed in the plate and one or more base portions, extending vertically from the other side of the plate to the top surface of the base portion, and If the composition of the first embodiment is discharged from the liquid outlet, the composition of the first embodiment expands in the space formed between the object and the top surface of the lip and the base, and at the same time, the composition of the first embodiment enters the beauty device inside the object through the hole opened by one or more needle-like protrusions.

[0230] Furthermore, in the first and subsequent second and third embodiments, the object (or subject) can be the skin of mammals, preferably humans, animals, or plants. Additionally, the component with needle-like protrusions can be an example of a needle-shaped beauty device, beauty device, or apparatus. A needle-shaped beauty device can be an example of a beauty device or apparatus. As long as there is no technical inconsistency, the matters relating to the first embodiment can be applied to the second and / or third embodiments, and the matters relating to the second and / or third embodiments can also be applied to the first embodiment.

[0231] Hereinafter, the component with needle-like protrusions included in the needle beauty container of the first embodiment will be described illustratively using the accompanying drawings.

[0232] Figure 1 A schematic diagram showing one embodiment of the component with needle-like protrusions according to the first embodiment.

[0233] exist Figure 1 The image shows the state in which the component 100 with needle-like protrusions according to the first embodiment punctures the object (skin) S. For example... Figure 1 As shown, the component 100 with needle-like protrusions has a plate 10 and a mounting frame 20. In addition, the plate 10 has a liquid outlet hole 10a that runs vertically through the plate, a plurality of tiny needle-like protrusions 10b that protrude from one side of the plate, and a lip 10c formed at the outer edge of one side of the plate.

[0234] In addition, Figure 1In the first embodiment, the plate 10 has multiple tiny needle-like protrusions 10b. Furthermore, in the first embodiment, these tiny needle-like protrusions (also called "microneedles" or "micro-needles") only need to have a certain degree of hardness to cause irritation when inserted into the skin; the material itself is not particularly limited. However, since they pierce the skin, the tiny needle-like protrusions need to be made of biocompatible materials, preferably materials that can dissolve or swell in vivo. Examples of such materials include polyglycolic acid (PGA), polylactic acid (PLA), polylactic-co-glycolic acid copolymer (PLGA), hyaluronic acid, deacetylated chitosan, maltose, alginate, amylose, agarose, and other polysaccharides, carboxymethyl cellulose, hydroxypropyl cellulose, starch, etc. These materials can be formed individually or as a mixture of two or more materials appropriately blended. Among these materials, polyglycolic acid (PGA), polylactic acid (PLA), or polylactic-glycolic acid copolymer (PLGA) are particularly preferred. Alternatively, the tiny needle-like protrusions can be formed from resins that do not dissolve or swell in vivo and do not affect the organism. More specifically, for example, they can be formed from polymethyl methacrylate, cellulose acetate, ethyl cellulose, polyethylene resin, polypropylene resin, ethylene-propylene copolymer, ethylene-vinyl acetate copolymer, vinyl chloride resin, 1,1-dichloroethylene 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.

[0235] like Figure 1 As shown, if liquid medicine C is squeezed out from the outlet 10a, liquid medicine C expands within the space formed between the object S and one surface of the lip 10c and the plate 10, and liquid medicine C enters the interior of the object S through holes opened by multiple needle-like protrusions 10b, that is, it can penetrate from the gap between the surface of the needle-like protrusions 10b and the object S. Alternatively, liquid medicine C can be directly contained in the mounting cylinder 20b, for example, it can be contained in the syringe barrel (not shown) and the syringe barrel tip 30a via a syringe. Furthermore, in Figure 1In this embodiment, the tip 30a of the syringe is part of the syringe, and the entire syringe is not shown. Furthermore, there are no particular limitations on the method for dispensing the liquid medicine C; for example, when the component 100 with needle-like protrusions is attached to the syringe, it can be done via the syringe plunger. Additionally, after injection, the state in which the component 100 with needle-like protrusions is pressed against the object S via the syringe can be maintained for a predetermined time (less than 1 second to about 30 minutes, preferably a few seconds to a few minutes). Then, after the predetermined time has elapsed, the syringe can be separated from the object S, thereby removing the needle-like protrusions 10b from the object S. Thus, in the first embodiment, the liquid medicine C can spread on the object S on the inside of the lip 10c, and simultaneously permeate into the inside of the object S through the hole opened by the needle-like protrusions 10b. Therefore, the liquid medicine C can permeate from both the outside and inside of the object S. For example, if the object S is human skin and the liquid medicine C contains a cosmetic substance, the cosmetic substance can permeate from both the outside and inside of the skin.

[0236] In addition, although Figure 1 Although not shown, the component 100 with needle-like protrusions can integrally include the plate 10 and the mounting frame 20. That is, the component 100 with needle-like protrusions can be a single piece. Furthermore, the single-piece component 100 with needle-like protrusions can be made of biocompatible materials, such as biodegradable resins like polyglycolic acid, polylactic acid, and polyglycolic acid-polylactic acid copolymers. More specifically, the single-piece component 100 with needle-like protrusions can be made of thermoplastic resins such as polypropylene (PP), polyethylene (PE), acrylonitrile / butadiene / styrene (ABS), polybutylene terephthalate (PBS), polyacetal (POM), polyethylene terephthalate (PET), polycarbonate (PC), and polyetheretherketone (PEEC).

[0237] Furthermore, the height of the needle-like protrusion 10b is not particularly limited. For example, the puncture depth from the tip of the needle-like protrusion 10b to the skin (i.e., the "effective puncture length of the needle-like protrusion") can be appropriately adjusted according to the design of the height of the lip 10c.

[0238] Furthermore, from the viewpoint of further enhancing the effects of the third embodiment, the effective puncture length of the needle-like protrusion of the beauty device of the present invention into the skin is preferably a length that does not reach the dermis. The depth from the skin surface to the dermis sometimes varies depending on the object, and sometimes it is the same. Moreover, even for the same object, the depth from the skin surface to the dermis sometimes varies depending on the location of the skin, and sometimes it is the same. The depth from the skin surface of the object to the dermis can be measured, for example, by removing the skin to make a thin section and using a microscope or the like.

[0239] Furthermore, in the third aspect of the present invention, the specific value of the effective puncture length of the needle-like protrusion of the beauty device of the present invention to the skin is not particularly limited. For example, it can be 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. Alternatively, it can 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.

[0240] Furthermore, in Figure 1 The example shown is a single central hole for the liquid outlet 10a, but there may be more than one hole, i.e., two or more. Furthermore, the hole may or may not be central. Additionally, an example of a needle-like protrusion 10b with a conical shape is shown, but the needle-like protrusion may be a pyramidal shape or other needle-like shapes (star-shaped, cross-shaped, etc.). Furthermore, a needle-like protrusion that is a hollow needle may be used instead of a solid needle-like protrusion. Moreover, the diameter of the solid needle-like protrusion constituting the needle-like micro-protrusion can be in the range of 2 to 5000 μm, more preferably in the range of 5 to 3000 μm, for the thickest part of the needle.

[0241] Figure 2 A schematic diagram showing a portion of another embodiment of the component with needle-like protrusions according to the first invention.

[0242] like Figure 2 As shown, a portion of the component with needle-like protrusions has a plate 11, a plurality of base portions 11d protruding from one side of the plate 11, a plurality of tiny needle-like protrusions 11b protruding from the top surfaces of each of the base portions 11d, and a lip 11c formed on the outer edge of the top surface of the base portion 11d. Furthermore, a liquid outlet hole 11a is formed on the plate 11 and the plurality of base portions 11d, extending vertically from the other surfaces of the plate 11 to the top surface of the base portion 11d.

[0243] like Figure 2 As shown, if liquid medicine C is discharged from the outlet hole 11a, liquid medicine C can expand in the space formed between the object S and the top surface of the lip 11c and the base 11d, and at the same time, liquid medicine C enters the interior of the object S through the hole opened by the needle-shaped protrusion 11b.

[0244] In addition, such as Figure 2 As shown, the liquid medicine C can spread on the object S on the inner circumference side of the lip 11c on the contact surface CF2 of the base portion 11d, and simultaneously penetrate into the inner side of the object S through the hole opened by the needle-like protrusion 11b. Therefore, the liquid medicine C can penetrate from both the outer and inner sides of the object S.

[0245] Furthermore, in the first invention, since liquid can be formed at the top of the base portion 11d, the medication C can be spread in the region inside the lip 11c of each base portion 11d. Therefore, for example, it is possible to apply the medication C in a dotted manner to the needle tip when the component with the needle-like protrusion is large and the area of ​​the plate 11 is wide. Further, in the first invention, the height difference between the base portion 11d and one surface F1 of the plate 11 allows the lip 11c connected to the base portion 11d to spread the object S within a narrow range so that the needle-like protrusion 11b can pierce it. Therefore, even when the surface of the object S is uneven or the object S is soft, the needle-like protrusion 11b can easily pierce the object S, allowing the medication C to be applied more reliably from both the outside and inside. Furthermore, in the first invention, the lip 11c contacts the object S regardless of whether the needle-like protrusion 11b punctures it, thus allowing injection pressure (resistance) to be uniformly applied to the inner circumferential region of the lip 11c, which constitutes the entire tip portion. This provides the advantage of reliably improving injection performance. Furthermore, in the first invention, to more efficiently move the liquid medicine C from the center outwards in the gap space between the plate 11 and the circular plate housing the top surface, a strip-shaped recess can be formed on the other side F2 of the plate 11, using the portion of the shortest path for the liquid to flow from the center to the plurality of outlet holes 11a as the flow path. Additionally, a plurality of needle-like protrusions 11b and / or a plurality of outlet holes 11a can be provided in a single base portion 11d. In this case, in each base portion 11d, the liquid medicine C squeezed out from the multiple liquid outlet holes 11a can spread on the object S on the inner circumferential side of the lip 11c on the contact surface CF2 of the base portion 11d, and at the same time, it can penetrate into the inner side of the object S through the holes opened by the multiple needle-like protrusions 11b.

[0246] in addition, Figure 2 The part and the whole of the component with needle-like protrusions shown (not shown) are the same as the component 100 with needle-like protrusions described above, and can be various designs, variations, etc.

[0247] Furthermore, the beauty device of the first invention may, in addition to the aforementioned component with needle-like protrusions, further include, for example, a fixing device capable of mounting the component with needle-like protrusions. Furthermore, the fixing device may contain a medicinal liquid.

[0248] Figure 3 A schematic diagram showing a design for a beauty device with components and fastening devices featuring needle-like protrusions.

[0249] like Figure 3As shown, the beauty device 200 includes a component 101 with needle-like protrusions and a syringe 30 serving as a fixing device for mounting the component 101 with needle-like protrusions. The component 101 with needle-like protrusions includes a mounting frame 20 and a plate 10. The mounting frame 20 also includes a plate support 20a and a mounting cylinder 20b. The plate 10 has a through-hole (not shown) extending vertically, one or more minute needle-like protrusions protruding from one surface of the plate 10, and a lip formed at the outer edge of one surface of the plate 10. The syringe 30 includes a syringe barrel (body) 30b and a plunger 30c. The component 101 with needle-like protrusions is mounted from the mounting cylinder 20b side of the mounting frame 20 towards the syringe barrel tip 30a side of the syringe 30. The syringe barrel 30b contains a liquid medicine C, and the plunger 30c is inserted into it. The plunger 30c is pushed by the rear-end pusher 30d and moves inside the syringe 30b, thereby releasing the drug solution C into the component 101 with needle-like protrusions, which then penetrates the target object (not shown). Furthermore, in the first invention, the fixing device can be, for example, a syringe with a volume of 1 mL, 2.5 mL, 5 mL, or 10 mL. Moreover, depending on the specific use of the component with needle-like protrusions, the syringe can have a larger or smaller volume.

[0250] In addition, Figure 3 In this invention, although the fixing device is depicted in the shape of a syringe 30, it can be deformed into other shapes as long as it does not impair the effect of the first invention.

[0251] Furthermore, the beauty device of the first invention can be arbitrary, for example, having a cap (not shown) on the needle-like protrusion side of the component with needle-like protrusions.

[0252] Furthermore, in the first invention and the second and third inventions described below, the pressure applied to the beauty device of the invention is not particularly limited. For example, it can be 1200gf or less, 1100gf or less, 1000gf or less, 900gf or less, 800gf or less, 700gf or less, or 600gf or less. Alternatively, it can be 50gf or more, 100gf or more, 200gf or more, 300gf or more, 400gf or more, 500gf or more, or 600gf or more. Moreover, from the viewpoint of further enhancing the effects of the third invention, the pressure applied to the beauty device of the invention is preferably, for example, 900gf or less.

[0253] The first invention, a beauty kit.

[0254] The first invention also provides beauty kits, particularly beauty kits for improving the skin's barrier function and / or translucency. Preferably, the first invention provides beauty kits for improving the skin's barrier function and translucency.

[0255] The beauty kit of the first invention includes the beauty device and the medicinal liquid described above. Further detailed descriptions relating to the beauty device of the first invention can be found in the description of the "beauty device of the first invention" item above.

[0256] In the first invention, the liquid is not particularly limited as long as it does not impair the effects of the first invention. For example, it can be a cosmetic substance that brings certain cosmetic effects to the skin (e.g., moisturizing effect, firming effect, barrier function improvement effect, blood flow enhancement effect, whitening effect, anti-spot effect, anti-wrinkle effect, anti-acne effect, or anti-inflammatory effect, etc.). Specifically, the liquid can be, for example, a moisturizer, a firming agent, a barrier function improver, a blood flow enhancer, a whitening agent, an anti-spot agent, an anti-wrinkle agent, an anti-acne agent, or an anti-inflammatory agent. Among these cosmetic substances, water-soluble cosmetic substances are particularly preferred. More specifically, examples of the liquid include, for example, alkoxysalicylic acid and its salts, 1-piperidinylpropionic acid and its salts, tranexamic acid and its salts, hyaluronic acid and its salts, vitamin A and its derivatives, vitamin B and its derivatives, vitamin C and its derivatives, oxidized olefin derivatives, collagen, EGF and other proteins / peptides, amino acids, and polyols such as glycerol, but it is not limited to these.

[0257] Through in-depth research, the inventors of the first invention have discovered that the beauty device of the first invention can improve the skin permeability of niacinamide. Therefore, in the first invention, the medicinal solution preferably contains niacinamide.

[0258] Nicotinamide, also known as nicotinamide or vitamin B3, is a coenzyme closely related to various biochemical reactions in the body, such as energy metabolism and redox reactions. The structure of nicotinamide is shown in the following formula.

[0259]

[0260] The beauty device of the first invention, when injecting a solution containing niacinamide into a target object via a component with needle-like protrusions, can improve the skin barrier function in a short period of time compared to applying niacinamide directly to the skin. Therefore, the beauty device of the first invention can be used to improve the skin barrier function in a short period of time. Here, the "short period" of 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. Furthermore, the lower limit is not particularly limited, and can be, for example, more than 1 day, more than 2 days, more than 3 days, more than 4 days, more than 5 days, more than 6 days, or more than 1 week.

[0261] Furthermore, when the beauty device of the first invention injects a solution containing niacinamide into the object via a component with needle-like protrusions, it can improve the skin's translucency in a shorter period compared to applying niacinamide directly to the skin. Therefore, the beauty device of the first invention can be a beauty device for improving the skin's translucency in a shorter period. Here, the "short period" in improving the skin's translucency can be, for example, within 2 months, within 8 weeks, within 7 weeks, within 6 weeks, within 5 weeks, within 4 weeks, within 3 weeks, within 2 weeks, or within 1 week. Moreover, there is no particular limitation on the lower limit value; for example, it can be more than 1 day, more than 2 days, more than 3 days, more than 4 days, more than 5 days, more than 6 days, or more than 1 week.

[0262] In addition, it is generally known that to give skin a translucent appearance, achieving a balance of moisture and oil, and ensuring smooth skin renewal, is important. However, the skin's renewal cycle is typically about 30 days, so until now it has been difficult to improve skin translucency in a short period of time compared to the renewal cycle.

[0263] In the first invention, the concentration of nicotinamide in the solution is not particularly limited. From the viewpoint of more effectively and preferably earlier promoting the improvement of skin barrier function and / or translucency, the concentration of nicotinamide relative to the total solution may, for example, be 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. ≥1.00%, ≥0.80%, ≥0.85%, ≥0.90%, ≥1.00%, ≥1.10%, ≥1.20%, ≥1.30%, ≥1.40%, ≥1.50%, ≥1.60%, ≥1.70%, ≥1.80%, ≥1.90%, ≥2.00%, ≥2.10%, ≥2.20%, ≥2.30%, ≥2.40%, ≥2.50% Quantity % or more, 2.60% or more, 2.70% or more, 2.80% or more, 2.90% or more, 3.00% or more, 3.50% or more, 4.00% or more, 4.50% or more, 5.00% or more, 6.00% or more, 7.00% or more, 8.00% or more, 9.00% or more, 10.0% or more, 11.0% or more, 12.0% or more, 13.0% or more, 14.0% or more, or 15.00% or more. More than 30.0% of mass, or less than 25.0% of mass, less than 20.0% of mass, less than 15.0% of mass, less than 14.0% of mass, less than 13.0% of mass, less than 12.0% of mass, less than 11.0% of mass, less than 10.0% of mass, less than 9.00% of mass, less than 8.00% of mass, less than 7.00% of mass, less than 6.00% of mass, less than 5.00% of mass, less than 4.50% of mass, less than 4.00% of mass, less than 3.50% of mass, or less than 3.00% of mass.

[0264] The beauty kit of the first invention may optionally include an instruction manual. The instruction manual may describe the setup method, handling method, usage method, and frequency of use of the beauty device of the first invention.

[0265] Here, as for the method of using the beauty kit of the first invention, please refer appropriately to the above. Figure 3The description continues. Furthermore, the number of times the needle-like protrusion component of the beauty device of the first invention is applied to the object is not particularly limited, and the number of applications can be appropriately increased. For example, the liquid can be released to one application site more than once, more than three times, more than five times, more than ten times, more than fifteen times, more than twenty times, more than twenty-five times, more than thirty times, or more than thirty-five times to allow penetration. Alternatively, it can be released to one application site less than 100 times, less than 50 times, less than 10 times, less than 7 times, less than 6 times, less than 5 times, less than 4 times, less than 3 times, or less than 2 times to allow penetration. Furthermore, the amount of medicine released per application is not particularly limited, and can 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. Alternatively, it can be less than 10 μL, less than 5 μL, or less than 2 μL. Furthermore, the method of applying the beauty device of the first invention to the object is not particularly limited; for example, it can be applied while rotating the beauty device, or it can be applied without rotating the beauty device.

[0266] Furthermore, the frequency of use of the beauty kit of the first invention is not particularly limited. For example, it can be used once a day, once every two days, or once every three days. Alternatively, it can be used more than once, more than twice, more than three times, more than four times, more than five times, or more than six times within a week. In addition, it can be used less than seven times, less than six times, less than five times, less than four times, less than three times, or less than two times each time. Further, it can be used less than seven times, less than six times, less than five times, less than four times, less than three times, less than two times, or less than once per week.

[0267] Methods to improve skin barrier function and / or radiance

[0268] The first invention also provides a method for improving the skin's barrier function and / or transparency. Preferably, the first invention provides a method for improving the skin's barrier function and transparency.

[0269] The method of the first invention for improving the skin's barrier function and / or translucency includes applying the aforementioned beauty device of the first invention to the skin. Particularly preferred in this method is the use of the beauty device of the first invention in combination with a solution containing niacinamide. This is because, compared to using the beauty device of the first invention alone, or applying niacinamide directly to the skin, improvement in the skin's barrier function and / or translucency can be achieved in a shorter period. Therefore, the method of the first invention can be used for improving the skin's barrier function and / or translucency in a short period.

[0270] In the method for improving the skin's barrier function and translucency according to the first invention, when using a medicinal solution containing niacinamide, the method may include injecting the medicinal solution into the object, applying the medicinal solution to the object, or attaching a sheet mask containing the medicinal solution to the object. In the latter case, the medicinal solution may be applied or the sheet mask may be attached to the object before, after, or before / after applying the beauty device of the first invention to the skin.

[0271] More preferably, the method of the first invention for improving the skin's barrier function and transparency includes injecting a medicinal solution into the object, wherein the medicinal solution contains niacinamide.

[0272] Furthermore, the method of the first invention for improving the skin's barrier function and transparency is for cosmetic purposes, not for surgical procedures or treatments for diseases, or other so-called "medical procedures".

[0273] Furthermore, in the first invention, the skin can be not only the skin of mammals (especially human skin), but also the skin of animals or the surface of the stems, trunks or leaves of plants.

[0274] [Second invention]

[0275] Hereinafter, the embodiments for carrying out the second invention will be described in detail with reference to the accompanying drawings. Furthermore, for ease of explanation, the same reference numerals are used for the same or equivalent parts in each figure, and repeated descriptions are omitted. In addition, not all constituent elements of the embodiments are necessarily necessary, and sometimes some constituent elements may be omitted. Of course, the present invention is not limited to the following embodiments, and various modifications can be made within the scope of the inventive intent.

[0276] Needle Beauty Devices

[0277] The second beauty device of the present invention (hereinafter also simply referred to as "the beauty device of the second invention") has a component with needle-like protrusions and is used to promote collagen production. Furthermore, the beauty device of the second invention may have a component with needle-like protrusions and be used to improve sagging skin.

[0278] As a component with needle-like protrusions in the beauty device of the second invention, the "component with needle-like protrusions" disclosed in, for example, Patent Document 2 can be used. Furthermore, as a needle-shaped beauty device of the second invention, the beauty device (device) disclosed in Patent Document 2 can be used. However, in Patent Document 2, the "component with needle-like protrusions" is used to leave a liquid composition / liquid cosmetic without specific active ingredients on the surface and inside of the object in a manner that prevents leakage from gaps; no disclosure / instruction is made regarding collagen production, relaxation improvement, etc.

[0279] Through in-depth research, the inventors discovered that a second beauty device of the present invention, having a component with needle-like protrusions, can be used to promote collagen production. Furthermore, the second beauty device of the present invention can also be used to improve skin laxity.

[0280] Although not limited by theory, it is speculated that the beauty device of the second invention, by applying the component with needle-like protrusions to the skin, causes the skin to deform significantly to the deep layers, resulting in improved blood flow and increased collagen production.

[0281] The second part of the present invention, which has needle-like protrusions, may have

[0282] A plate with liquid outlet holes running vertically through it. One or more tiny needle-like projections protruding from one side of the plate, and A lip formed at the outer edge of one side of the plate; In addition, it can have plate, One or more base parts protruding from one side of the plate One or more tiny needle-like protrusions protruding from the top surface of one or more base portions, and A lip is formed on the outer edge of the top surface of the base.

[0283] Furthermore, the second beauty device of the present invention can be used to inject a medicinal liquid into a target object via a component with needle-like protrusions. Additionally, the second beauty device of the present invention can be the same as the "first beauty device" described above. Therefore, the second beauty device of the present invention can be described with reference to the above description of the "first beauty device," and its description is omitted here.

[0284] The second invention, a beauty kit.

[0285] The second invention also provides beauty kits, particularly beauty kits for promoting collagen production.

[0286] The beauty kit of the second invention includes the beauty device and the medicinal liquid described above. Furthermore, detailed descriptions relating to the beauty device of the second invention can be found in the description of the "beauty device of the first invention" item above.

[0287] In the second invention, the liquid is not particularly limited as long as it does not impair the effects of the second invention. For example, it can be a cosmetic substance that brings certain cosmetic effects to the skin (e.g., moisturizing effect, firming effect, barrier function improvement effect, blood flow enhancement effect, whitening effect, anti-spot effect, anti-wrinkle effect, anti-acne effect, or anti-inflammatory effect, etc.). Specifically, the liquid can be, for example, a moisturizer, a firming agent, a barrier function improver, a blood flow enhancer, a whitening agent, an anti-spot agent, an anti-wrinkle agent, an anti-acne agent, or an anti-inflammatory agent. Among these cosmetic substances, water-soluble cosmetic substances are particularly preferred. More specifically, examples of the liquid include, for example, alkoxysalicylic acid and its salts, 1-piperidinylpropionic acid and its salts, tranexamic acid and its salts, hyaluronic acid and its salts, vitamin A complex and its derivatives, vitamin B complex and its derivatives, vitamin C complex and its derivatives, oxidized olefin derivatives, collagen, EGF and other proteins / peptides, amino acids, and polyols such as glycerol, but it is not limited to these.

[0288] Through in-depth research, the inventors have discovered that the beauty device of the second invention can enhance the permeability of niacinamide into the skin. Therefore, in the second invention, the solution preferably contains niacinamide.

[0289] In addition, as described in the above-mentioned "First Invention", detailed description of nicotinamide is omitted here.

[0290] When the beauty device of the second invention injects a solution containing niacinamide into the object via a component with needle-like protrusions, it can promote collagen production more efficiently than when the beauty device of the second invention is used alone (i.e., without using the solution) or when niacinamide is applied directly to the skin.

[0291] Furthermore, the beauty device of the second invention can improve relaxation when a solution containing nicotinamide is injected into the object via a component with needle-like protrusions.

[0292] Here, it is known that sagging occurs along with aging, and the loosening of facial contours and the prominent nasolabial folds / marionette lines bring significant changes to one's appearance. Therefore, many people hope to improve sagging in order to combat aging.

[0293] However, improving sagging skin is not simple. For example, wrinkles, a similar sign of aging, can sometimes be improved even when applied to the superficial layers of the skin (epidermis), but sagging skin originates deep within the skin (dermis, subcutaneous tissue, and muscles), making it difficult to improve with simple cosmetics. Furthermore, current methods for improving sagging skin include treatments using physical energy such as High Intensity Focused Ultrasound (HIFU) and surgical procedures like thread lifting. However, these treatments are highly invasive, and many people experience sensory resistance. On the other hand, non-invasive methods include facial muscle training and massage, but these take time to show results, and suitable methods are often difficult to identify.

[0294] To address these issues, the beauty kit of the second invention, in particular, by combining the beauty device of the second invention with a solution containing niacinamide, achieves improvement in skin laxity through a low-invasive, rapid, simple, and easy method. Furthermore, it goes without saying that the improvement in skin laxity brought about by the beauty kit of the second invention is easier than the aforementioned facial muscle training and massage; for example, it can be performed more efficiently even compared to applying niacinamide directly to the skin or applying the beauty device of the second invention alone to the skin. Therefore, the beauty kit of the second invention can be used for improving skin laxity.

[0295] Furthermore, in the second invention, the concentration of nicotinamide in the solution is not particularly limited. From the viewpoint of more effectively promoting collagen production or more effectively improving relaxation, the concentration of nicotinamide relative to the total solution can, for example, be 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 0.75% by mass or more. % or more, 0.80% or more by mass, 0.85% or more by mass, 0.90% or more by mass, 1.00% or more by mass, 1.10% or more by mass, 1.20% or more by mass, 1.30% or more by mass, 1.40% or more by mass, 1.50% or more by mass, 1.60% or more by mass, 1.70% or more by mass, 1.80% or more by mass, 1.90% or more by mass, 2.00% or more by mass, 2.10% or more by mass, 2.20% or more by mass, 2.30% or more by mass, 2.40% or more by mass, 2.50% or more by mass % or more, 2.60% or more, 2.70% or more, 2.80% or more, 2.90% or more, 3.00% or more, 3.50% or more, 4.00% or more, 4.50% or more, 5.00% or more, 6.00% or more, 7.00% or more, 8.00% or more, 9.00% or more, 10.0% or more, 11.0% or more, 12.0% or more, 13.0% or more, 14.0% or more, or 15.00% or more. More than 30.0% of mass, or less than 25.0% of mass, less than 20.0% of mass, less than 15.0% of mass, less than 14.0% of mass, less than 13.0% of mass, less than 12.0% of mass, less than 11.0% of mass, less than 10.0% of mass, less than 9.00% of mass, less than 8.00% of mass, less than 7.00% of mass, less than 6.00% of mass, less than 5.00% of mass, less than 4.50% of mass, less than 4.00% of mass, less than 3.50% of mass, or less than 3.00% of mass.

[0296] The beauty kit of the second invention may optionally include an instruction manual. The instruction manual may describe the setup method, handling method, usage method, and frequency of use of the beauty device of the second invention.

[0297] Here, the method of using the beauty kit of the second invention can be appropriately referred to the above description. Figure 3The description continues. Furthermore, the number of times the needle-like protrusion component of the beauty device of the second invention is applied to the object is not particularly limited, and the number of applications can be appropriately increased. For example, the liquid can be released to one application site more than once, more than three times, more than five times, more than ten times, more than fifteen times, more than twenty times, more than twenty-five times, more than thirty times, or more than thirty-five times to allow penetration. Alternatively, it can be released to one application site less than 100 times, less than 50 times, less than 10 times, less than 7 times, less than 6 times, less than 5 times, less than 4 times, less than 3 times, or less than 2 times to allow penetration. Furthermore, the amount of medicine released per application is not particularly limited, and can 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. Alternatively, it can be less than 10 μL, less than 5 μL, or less than 2 μL. Furthermore, the method of applying the beauty device of the second invention to the object is not particularly limited; for example, it can be applied while rotating the beauty device, or it can be applied without rotating the beauty device.

[0298] Furthermore, the frequency of use of the beauty kit of the second invention is not particularly limited. For example, it can be used once a day, once every two days, or once every three days. Or, within a week, it can be used more than once, more than twice, more than three times, more than four times, more than five times, or more than six times. In addition, it can be used less than seven times, less than six times, less than five times, less than four times, less than three times, or less than two times per month. Furthermore, it can be used less than seven times, less than six times, less than five times, less than four times, less than three times, less than two times, or less than once per week.

[0299] Methods to Promote Collagen Production

[0300] The second invention also provides a method for promoting collagen production. The method for promoting collagen production of the second invention includes applying the aforementioned beauty device of the second invention to the skin.

[0301] The collagen production promotion method of the second invention preferably combines the beauty device of the second invention with a solution containing niacinamide. This is because, compared with the method of using the beauty device of the second invention alone or the method of directly applying niacinamide to the skin, collagen production promotion can be performed more efficiently.

[0302] In the collagen production promotion method of the second invention, when using a solution containing nicotinamide, the method may involve injecting the solution into the target, applying the solution to the target, or attaching a sheet mask containing the solution to the target. In the latter case, the solution may be applied or the sheet mask may be attached to the target before, after, or before / after applying the beauty device of the second invention to the skin.

[0303] More preferably, the second method for promoting collagen production of the present invention includes injecting a drug solution into a target, wherein the drug solution contains nicotinamide.

[0304] Furthermore, the collagen production promotion method of the second invention can improve skin laxity. Therefore, the second invention can provide a method for improving skin laxity. The method for improving skin laxity of the second invention is also more efficient than methods of directly applying niacinamide to the skin or applying the beauty device of the second invention to the skin alone.

[0305] Furthermore, the collagen production promotion method and the method for improving sagging of the second invention are for cosmetic purposes, and are not so-called "medical procedures" such as surgical methods or treatments for human diseases.

[0306] As described above, the first and second inventions can improve the skin barrier function, improve skin transparency, promote collagen production, or improve skin laxity.

[0307] [The third invention]

[0308] Hereinafter, the embodiments for carrying out the third invention will be described in detail with reference to the accompanying drawings. Furthermore, for ease of explanation, the same reference numerals are used for the same or equivalent parts in each figure, and repeated descriptions are omitted. In addition, not all constituent elements of the embodiments are necessarily necessary, and sometimes some constituent elements may be omitted. Of course, the present invention is not limited to the following embodiments, and various modifications can be made within the scope of the inventive intent.

[0309] "Beauty Equipment"

[0310] The third beauty device of the present invention is a beauty device used in a cosmetic method for improving the skin condition of a subject. Beauty devices are needle-type beauty devices, featuring parts with needle-like protrusions. The component with needle-like projections includes needle-like projections, and the effective puncture length of the needle-like projections into the skin is a length that does not reach the dermis. Beauty methods include: (i) Apply the above-mentioned beauty device to the skin with an extrusion pressure of 100–1200 gf, and (ii) Using beauty tools more than once every two days and more than twice, or using them more than three times a week.

[0311] The third beauty device of the present invention (hereinafter also referred to as "the beauty device of the third invention") has a component with needle-like protrusions, the component 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.

[0312] As a component with needle-like protrusions in the beauty device of the third invention, the "component with needle-like protrusions" disclosed in, for example, Patent Document 2 can be used. Furthermore, as a needle-shaped beauty device of the third invention, the beauty device (device) disclosed in Patent Document 2 can be used. However, in Patent Document 2, the "component with needle-like protrusions" is used to leave a liquid composition / liquid cosmetic without specific active ingredients on the surface and inside of the object in a manner that prevents leakage from gaps; no disclosure / instruction is made regarding collagen production, relaxation improvement, etc.

[0313] Through in-depth research, the inventors discovered that a third beauty device of the present invention, having such a component with needle-like protrusions, can be used to promote collagen production.

[0314] Although not limited by theory, the beauty device of the third invention, because the effective puncture length of the needle-like protrusions into the skin is the length that does not reach the dermis, does not damage the dermis but provides stimulation to the skin cells caused by the pressure. Surprisingly, it can regulate the M1 / M2 balance and increase the number of myofibroblasts.

[0315] Here, the "M1 / M2 balance" refers to the relative balance between the M1 and M2 types of macrophages. The M1 / M2 balance is significantly related to the skin's immune response and inflammation control, and also affects wound healing, inflammatory diseases, cosmetic procedures, and skin aging. Therefore, "regulating the M1 / M2 balance" means increasing the ratio of M2 to M1. As a result of regulating the M1 / M2 balance, benefits can include, for example, increased collagen production, immune induction, and wound healing.

[0316] Furthermore, so-called "myofibroblasts" are cells primarily found in the dermis, specifically those that play a crucial role in wound healing and tissue repair. Myofibroblasts possess properties of both typical fibroblasts and smooth muscle cells, and are activated during wound healing and tissue remodeling, playing a vital role in repairing injured skin. Moreover, since perivascular myofibroblasts play a crucial role in maintaining vascular structure, an increase in their number affects vascular stability. Therefore, an increase in the number of myofibroblasts can result in benefits such as promoted collagen production, immune induction, wound healing, and vascular stabilization.

[0317] Therefore, the object of the third invention can be an object that requires adjustment of the M1 / M2 balance.

[0318] Furthermore, the third object of the present invention can be an object that requires an increase in the number of myofibril cells.

[0319] The third component of the present invention, which has needle-like protrusions, may have...

[0320] A plate with liquid outlet holes running vertically through it. One or more tiny needle-like projections protruding from one side of the plate, and A lip formed at the outer edge of one side of the plate; In addition, it can have plate, One or more base parts protruding from one side of the plate One or more tiny needle-like protrusions protruding from the top surface of one or more base portions, and A lip is formed on the outer edge of the top surface of the base.

[0321] Furthermore, the third beauty device of the present invention can be used to inject a medicinal liquid into a target object via a component with needle-like protrusions. Additionally, the third beauty device of the present invention can be the same as the "first beauty device" described above. Therefore, the third beauty device of the present invention can be described with reference to the above description of the "first beauty device," and its description is omitted here.

[0322] The third invention, a beauty kit.

[0323] The third invention also provides beauty kits, particularly beauty kits for promoting collagen production.

[0324] The beauty kit of the third invention includes the beauty device and the liquid described above. For further details regarding the beauty device of the third invention, please refer to the description of the "beauty device of the first invention" item above.

[0325] In the third invention, the liquid is not particularly limited as long as it does not impair the effects of the third invention. For example, it can be a cosmetic substance that brings certain cosmetic effects to the skin (e.g., moisturizing effect, firming effect, barrier function improvement effect, blood flow enhancement effect, whitening effect, anti-spot effect, anti-wrinkle effect, anti-acne effect, or anti-inflammatory effect, etc.). Specifically, the liquid can be, for example, a moisturizer, a firming agent, a barrier function improver, a blood flow enhancer, a whitening agent, an anti-spot agent, an anti-wrinkle agent, an anti-acne agent, or an anti-inflammatory agent. Among these cosmetic substances, water-soluble cosmetic substances are particularly preferred. More specifically, examples of the liquid include, for example, alkoxysalicylic acid and its salts, 1-piperidinylpropionic acid and its salts, tranexamic acid and its salts, hyaluronic acid and its salts, vitamin A complex and its derivatives, vitamin B complex and its derivatives, vitamin C complex and its derivatives, oxidized olefin derivatives, collagen, EGF and other proteins / peptides, amino acids, and polyols such as glycerol, but it is not limited to these.

[0326] Through in-depth research, the inventors have discovered that the beauty device of the third invention can enhance the permeability of niacinamide into the skin. Therefore, in the third invention, the medicinal solution preferably contains niacinamide.

[0327] In addition, as described in the above-mentioned "First Invention", detailed description of nicotinamide is omitted here.

[0328] When the beauty device of the third invention injects a solution containing niacinamide into the object via a component with needle-like protrusions, it can promote collagen production more efficiently than when the beauty device of the third invention is used alone (i.e., without using the solution) or when niacinamide is applied directly to the skin.

[0329] Furthermore, the beauty device of the third invention can improve sagging when a solution containing nicotinamide is injected into the object via a component with needle-like protrusions.

[0330] It is known that sagging occurs with aging, causing significant changes to one's appearance, such as loosening of facial contours and the prominent appearance of nasolabial folds / marionette lines. Therefore, many people want to improve sagging in order to combat aging.

[0331] However, improving sagging skin is not simple. For example, wrinkles, a similar sign of aging, can sometimes be improved even when applied to the superficial layers of the skin (epidermis), but sagging skin is caused by deeper layers (dermis, subcutaneous tissue, and muscles), making it difficult to improve with cosmetics alone. Furthermore, current methods for improving sagging skin include physical treatments such as High Intensity Focused Ultrasound (HIFU) and surgical procedures like thread lifting. However, these treatments are highly invasive and often cause sensory resistance. On the other hand, non-invasive methods include facial muscle training and massage, but these take time to show results, and suitable methods are often difficult to identify.

[0332] To address these issues, the beauty kit of the third invention, in particular, by combining the beauty device of the third invention with a medicinal solution containing niacinamide, achieves improvement in skin laxity through a low-invasive, rapid, simple, and easy method. Furthermore, it goes without saying that the improvement in skin laxity brought about by the beauty kit of the third invention is easier than the aforementioned facial muscle training and massage; for example, it can be performed more efficiently than applying niacinamide directly to the skin or applying the beauty device of the third invention alone to the skin. Therefore, the beauty kit of the third invention can be used to improve skin laxity.

[0333] Furthermore, in the third aspect of this invention, the concentration of nicotinamide in the solution is not particularly limited. From the viewpoint of more effectively promoting collagen production or more effectively improving relaxation, the concentration of nicotinamide relative to the overall solution may, for example, be 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 0.75% by mass. Above, 0.80% by mass, 0.85% by mass, 0.90% by mass, 1.00% by mass, 1.10% by mass, 1.20% by mass, 1.30% by mass, 1.40% by mass, 1.50% by mass, 1.60% by mass, 1.70% by mass, 1.80% by mass, 1.90% by mass, 2.00% by mass, 2.10% by mass, 2.20% by mass, 2.30% by mass, 2.40% by mass, 2.50% by mass ≥, 2.60% or more by mass, 2.70% or more by mass, 2.80% or more by mass, 2.90% or more by mass, 3.00% or more by mass, 3.50% or more by mass, 4.00% or more by mass, 4.50% or more by mass, 5.00% or more by mass, 6.00% or more by mass, 7.00% or more by mass, 8.00% or more by mass, 9.00% or more by mass, 10.0% or more by mass, 11.0% or more by mass, 12.0% or more by mass, 13.0% or more by mass, 14.0% or more by mass, or 15.00% by mass. % or more; in addition, it can be 30.0% or less, 25.0% or less, 20.0% or less, 15.0% or less, 14.0% or less, 13.0% or less, 12.0% or less, 11.0% or less, 10.0% or less, 9.00% or less, 8.00% or less, 7.00% or less, 6.00% or less, 5.00% or less, 4.50% or less, 4.00% or less, 3.50% or less, or 3.00% or less.

[0334] The beauty kit of the third invention may optionally include an instruction manual. The instruction manual may describe the setup method, handling method, usage method, and frequency of use of the beauty device of the third invention.

[0335] Here, the method of using the beauty kit of the third invention can be appropriately referred to the above description. Figure 3The description continues. Furthermore, the number of times the needle-like protrusion component of the beauty device of the third invention is applied to the object is not particularly limited, and the number of applications can be appropriately increased. For example, the liquid can be released to one application site more than once, more than three times, more than five times, more than ten times, more than fifteen times, more than twenty times, more than twenty-five times, more than thirty times, or more than thirty-five times to allow penetration. Alternatively, it can be released to one application site less than 100 times, less than 50 times, less than 10 times, less than 7 times, less than 6 times, less than 5 times, less than 4 times, less than 3 times, or less than 2 times to allow penetration. Furthermore, the amount of medicine released per application is not particularly limited, and can 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. Alternatively, it can be less than 10 μL, less than 5 μL, or less than 2 μL. Furthermore, the method of applying the beauty device of the second invention to the object is not particularly limited; for example, it can be applied while rotating the beauty device, or it can be applied without rotating the beauty device.

[0336] Furthermore, the frequency of use of the beauty kit of the third invention is not particularly limited. For example, it can be used once a day, once every two days, or once every three days, or more than once, twice, three times, four times, five times, or six times a week. Alternatively, it can be used less than seven times, six times, five times, four times, three times, or two times a month. Further, it can be used less than seven times, six times, five times, four times, three times, two times, or once a week.

[0337] Furthermore, the beauty device or beauty kit of the third invention is preferably used more than once every two days and more than twice, or preferably more than three times a week. More preferably, the beauty device or beauty kit of the third invention is used more than once every two days and more than three, four, five, or six times a week. Alternatively, more preferably, the beauty device or beauty kit of the third invention is used more than four, five, six, or seven times a week.

[0338] Beauty Methods

[0339] The third invention can also provide a cosmetic method.

[0340] The third cosmetic method of the present invention is a cosmetic method for improving the skin condition of a subject, comprising: (i) Applying the cosmetic device to the skin with an extrusion pressure of 100–1200 gf, and (ii) Using the aforementioned beauty tools more than once every two days for more than two times, or using them more than three times a week, and The aforementioned beauty device is a needle-type beauty device, which has a component with needle-like protrusions. The aforementioned component 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.

[0341] Here, the beauty device used can be the aforementioned "beauty device of the third invention". Therefore, the beauty method of the third invention can be described with reference to the above description of the "beauty device of the third invention" and the "beauty kit of the third invention".

[0342] In addition, the squeezing pressure of the beauty device applied to the skin can be, for example, 300gf or more, 400gf or more, 500gf or more, or 600gf or more. Alternatively, it can be 900gf or less, 850gf or less, 800gf or less, 750gf or less, 700gf or less, or 650gf or less.

[0343] The third cosmetic method of the present invention can be used to regulate the M1 / M2 balance of a subject and / or to increase the number of myofibril cells in the subject.

[0344] Methods to Promote Collagen Production

[0345] The third invention also provides a method for promoting collagen production. The method for promoting collagen production of the second invention includes applying the beauty device of the third invention described above to the skin.

[0346] The collagen production promotion method of the third invention preferably combines the beauty device of the third invention with a solution containing niacinamide. This is because, compared with the method of using the beauty device of the third invention alone or the method of directly applying niacinamide to the skin, collagen production promotion can be performed more efficiently.

[0347] In the collagen production promotion method of the third invention, when using a solution containing nicotinamide, the method may include injecting the solution into the target, applying the solution to the target, or attaching a sheet mask containing the solution to the target. In the latter case, the solution may be applied or the sheet mask may be attached to the target before, after, or before / after applying the beauty device of the third invention to the skin.

[0348] More preferably, the second method for promoting collagen production of the present invention includes injecting a drug solution into a target, wherein the drug solution contains nicotinamide.

[0349] Furthermore, the collagen production promotion method of the third invention can improve skin laxity. Therefore, the third invention can provide a method for improving skin laxity. The method for improving skin laxity of the second invention can also be performed more efficiently than methods of directly applying niacinamide to the skin or applying the beauty device of the second invention to the skin alone.

[0350] Furthermore, the collagen production promotion method and the method for improving sagging of the third invention are for cosmetic purposes, not so-called "medical procedures" such as surgical methods or treatments for human diseases.

[0351] As described above, the first, second and third inventions can improve the skin barrier function, improve the skin's transparency, promote collagen production in the skin or improve skin laxity.

[0352] Example

[0353] [The first invention]

[0354] The following examples illustrate the first invention in further detail, but the invention is not limited to these examples.

[0355] Examples 1-1 and 1-2

[0356] In Examples 1-1 and 1-2, epidermal cell proliferation promotion tests were conducted in the case of applying the beauty device of the first invention alone (Example 1-1) and in the case of applying the beauty device of the first invention in combination with a drug solution containing nicotinamide (Example 1-2).

[0357] Specifically, fresh skin was removed from the abdomen of subjects who had given informed consent. In Example 1-1, the beauty device of the first invention was applied to fresh removed human skin with appropriate pressure, rotating the device each time, 2-8 times, and then cultured on a culture medium. In Example 2, a nonwoven fabric impregnated with a solution containing nicotinamide was placed on the skin outside the organism, applied in a way that was in close contact with the skin, left to stand for 5 minutes, the nonwoven fabric was temporarily removed, and the beauty device was applied in the same manner as in Example 1-1, followed by application of the nonwoven fabric for another 5 minutes. For the control, these treatments were not performed (Examples 1-1, 1-2), and the tissue was cultured on a culture medium in the same way. The culture medium was changed daily, and tissue sections were recovered on day 7. In addition, an antibody (Thermo Fisher Scientific, RM-9106-S, rabbit mouse monoclonal antibody) against Ki-67 (SP6), a marker of cell proliferation, was used. The results are shown in... Figure 4 and Figure 5 middle.

[0358] in addition, Figure 4 The results of immunofluorescence staining for Ki-67 and the nucleus (Hoechst). Figure 5 To show the Figure 4 The staining images were analyzed using ImageJ image analysis software to quantify the length of the epidermal basement membrane, and the results of counting Ki-67 positive epidermal cells per unit length of the epidermal basement membrane were plotted.

[0359] In addition, the prescriptions for the nicotinamide-containing solutions here are as shown in Table 1-1 below.

[0360]

[0361] Examples 1-3

[0362] In Examples 1-3, the beauty device of the first invention and a dispensing device (a pen-shaped cosmetic container with a volume of about a few mL) containing a solution containing niacinamide ("solution A") were installed, and the amount of skin moisture evaporation was investigated for up to 8 weeks after application to subjects every 2 days. Additionally, as a control, the amount of skin moisture evaporation was investigated when subjects applied solution A every 2 days in the same amount as when using the beauty device, without using the beauty device of the first invention. The results are shown in... Figure 7 middle.

[0363] More specifically, it will be done as follows: 1. Press the protruding surface flat against the subject's skin and squeeze in once (squeeze in firmly without causing pain).

[0364] 2. Repeat the action in "1." above, while using... Figure 6 Use this as a reference to move the application a little bit at a time.

[0365] (A total of 50 presses (25 presses on each side))

[0366] a: Press the nasolabial folds and marionette lines 10 times on each side.

[0367] b: Press 10 times on each side from the outer corner of the eye to the lower part of the eye.

[0368] c: Press the affected areas on your cheeks (dryness / pore problems, etc.) 5 times on each side.

[0369] 3. Spread the liquid evenly over your face and use your palms to allow it to be absorbed.

[0370] In addition, 20 women aged 45–59 years, with a BMI of 18.5–25.0 and a wrinkle grade of 3–5 were selected as subjects.

[0371] The prescription for "Drug Solution A" is as shown in Table 2 below.

[0372]

[0373] In addition, the amount of skin moisture evaporation was measured using a Vapometer (Delfin Technologies) via the transdermal evaporation method.

[0374] Depend on Figure 7 The results clearly showed that, approximately two weeks after application, Examples 1-3 exhibited a significantly increased moisture content compared to the control. That is, Examples 1-3 demonstrate the ability to improve skin barrier function within a short period of two weeks.

[0375] Examples 1-4

[0376] In Examples 1-4, the beauty device of the first invention and a dispensing device (a pen-shaped cosmetic container with a volume of about a few mL) containing a solution containing nicotinamide ("solution A") were installed, and the procedure was performed in the same manner as in Examples 1-3 above. The skin transparency of the subjects was investigated up to 8 weeks after application every 2 days. Additionally, as a control, the skin transparency of the subjects was investigated when the beauty device of the first invention was not used, and the subjects applied solution A every 2 days in the same amount as when using the beauty device.

[0377] In addition, regarding the skin's translucency, it was assessed by six professional evaluators based on... Figure 8 The evaluation criteria shown were evaluated using the method described in Table 3 below. Furthermore, the evaluation was judged based on the overall balance within the face as a whole. Therefore, the condition "not perceptible" includes both "the phenomenon is completely absent" and "the phenomenon is so rare that it is not perceptible when observed as a whole of the face."

[0378]

[0379] The results are shown in Figure 9 middle.

[0380] Depend on Figure 9 The results clearly showed that, compared with the control, Examples 1-4 demonstrated a higher improvement in skin transparency from an earlier stage.

[0381] Furthermore, the fact that Examples 1-4 and the control ultimately (after 8 weeks) improved transparency to approximately the same level also suggests that the penetration rate and amount of nicotinamide were increased by the beauty device of the first invention in Examples 1-4.

[0382] (Refer to Examples 1-1 and 1-2)

[0383] The penetration-enhancing effect of the nicotinamide-containing solutions (“Solution B”) in Tables 1-4, resulting from the beauty device of the first invention, was confirmed by confocal micro-Raman spectroscopy (Reference Example 1-1). Furthermore, the penetration-enhancing effect of the water-soluble fluorescent substance used as a model agent was confirmed by fluorescence intensity quantification (Reference Example 1-2). The respective results are shown in… Figure 10 (Raman spectroscopy) and Figure 11 (Fluorescence intensity) is within range. Additionally... Figure 10 This is a three-dimensional image of the Raman intensity of nicotinamide based on spectral and spatial information obtained by confocal microRaman spectroscopy.

[0384] The more specific experimental methods are as follows: (Confocal Raman spectroscopy) - Apply "Drug B" at a rate of 5 μL per square centimeter to the removed human skin.

[0385] -Then, the first beauty device of the present invention is applied to remove human skin 50 times.

[0386] - The fingerprint region (600–2200 cm) was evaluated. -1 The time variation of the Raman spectrum of ).

[0387] In addition, the control group only applied "Drug B" at a rate of 5 μL per square centimeter to the removed human skin.

[0388] (Fluorescence intensity)

[0389] The permeability of each composition was investigated in cases where it was applied to excised human skin (commercially available) via a beauty device and in cases where it was applied directly to the skin without a beauty device. More specifically, using a texture analyzer, a microneedle plate was inserted 50 times by vertically applying appropriate weight to the stratum corneum of excised human skin. Then, an aqueous solution containing 0.2% fluorescein dye (sodium fluorescein) was applied at 5 μL per square centimeter and allowed to stand at 37°C for 15 minutes. Next, the surface of the skin at the site where each composition was applied was cleaned, and the skin portion was cut into 8 mm diameter circles using a dermal punch. The resulting skin was added to an appropriate amount of extraction solvent and subjected to ultrasonic treatment to extract the fluorescein dye. The fluorescence intensity of the extracted samples was then measured using a spectrophotometer.

[0390] Additionally, Control 1 showed autofluorescence derived from the removed human skin. Furthermore, Control 2 used an example where a solution containing only 0.2% by mass of fluorescent dye (sodium fluorescein) was applied at 5 μL per square centimeter to the removed human skin and left to stand at 37°C for 15 minutes.

[0391] The prescription for "Drug Solution B" is as shown in Table 1-4 below.

[0392]

[0393] In addition, regarding the “model reagent” used in Reference Examples 1-2, 0.2% sodium fluorescein was mixed in place of 5.0% nicotinamide, and the residual amount was adjusted with water. Otherwise, the formulation is the same as that of the above-mentioned “solution B”.

[0394] Depend on Figure 10 It is clearly known that, compared with the control, Reference Example 1-1 promoted the penetration of nicotinamide in a much shorter time.

[0395] In addition, by Figure 11 It was also clearly found that, compared with Controls 1 and 2, the penetration of the drug solution containing the model agent (water-soluble fluorescent substance) was significantly increased in Reference Examples 1-2.

[0396] [Second invention]

[0397] The following examples illustrate the second invention in further detail, but the second invention is not limited to these examples.

[0398] In addition, in the following experiments, unless otherwise specified, the device of the second invention used was a circular device with a diameter of 15 mm, an effective puncture length of 20 μm for the needle-like protrusions (i.e., needles), and 18 needle-like protrusions.

[0399] Examples 2-1 and 2-2

[0400] The effects of collagen production promotion were evaluated in cases where the second invention's beauty device was applied alone to fresh exfoliated human skin (Example 1) and in cases where the second invention's beauty device was used in combination with 5% by mass nicotinamide solution (Examples 2-2). Additionally, the same fresh exfoliated human skin was used as a control. The results are shown below. Figure 4-1 middle.

[0401] Specifically, fresh skin was removed from the abdomen of subjects who had given informed consent. In Example 2-1, the beauty device of the second invention was applied to freshly removed in vitro human skin 2-8 times with appropriate pressure while rotating the device each time, and then cultured on a culture medium. In Example 2, a nonwoven fabric impregnated with a solution containing nicotinamide was placed on the in vitro skin, applied in a way that ensured close contact with the skin, left to stand for 5 minutes, the nonwoven fabric was temporarily removed, and the beauty device was applied again in the same manner as in Example 2-1, followed by another 5 minutes of nonwoven fabric application. For the control, these treatments were not performed (Examples 2-1, 2-2), and the skin was cultured on a culture medium in the same way. Furthermore, after 24 hours of culture, the amount of procollagen gene (COL1A1) produced was confirmed by RT-qPCR (Δ-ΔCT method) relative to the treated skin and the control skin, confirming the production of procollagen I.

[0402] - Each experiment was conducted 6 times.

[0403] -qPCR: n=3

[0404] In addition, the formulation of nicotinamide liquid (5% by mass) is as shown in Table 1-2 below.

[0405]

[0406] Depend on Figure 4-1 The results clearly showed that, compared with the control, the production of the procollagen gene (COL1A1) was significantly increased in Examples 2-1 and 2-2. That is, Examples 2-1 and 2-2 indicate that the production of procollagen I was promoted.

[0407] Examples 2-3

[0408] In Examples 2-3, differentiation of myofibroblasts was confirmed when the beauty device of the second invention was used alone.

[0409] In Examples 2-3, the beauty device of the second invention was applied to freshly removed human skin 2-8 times with appropriate pressure while rotating the device each time, and then cultured on a culture medium. For the control group, the beauty device of the second invention was not applied, and the skin was cultured on the same dedicated culture medium; tissue sections were recovered the following day. Furthermore, α-SMA / vimentin double-positive cells were counted as myofibroblasts using antibodies against α-SMA (α-Smooth Muscle Actin) and vimentin, markers for myofibroblasts. The results are shown in… Figure 5-1 and Figure 5-2 middle.

[0410] Figure 5-1 The results of immunofluorescence staining for α-SMA (α-Smooth Muscle Actin) / Vimentin and the nucleus (Hoechst). Figure 5-2 To show the Figure 5-1 The stained images were obtained by using the image analysis software ImageJ to quantify the area immediately below the epidermal basement membrane (200 μm) and count the α-SMA / Vimentin double-positive cells (myofibroblasts) in this area.

[0411] Depend on Figure 5-1 and Figure 5-2 It was clearly observed that, compared to the control group, differentiation into α-SMA / vimentin double-positive cells, i.e., myofibroblasts, was further induced in Examples 2-3. That is, Examples 2-3 demonstrate the promotion of procollagen I production via differentiation into myofibroblasts.

[0412] Examples 2-4

[0413] The penetration-enhancing effect of the nicotinamide-containing solution (“Solution A”) in Table 2-2, resulting from the beauty device of the second invention, was confirmed by confocal micro-Raman spectroscopy (Example 2-4-1). Furthermore, the penetration-enhancing effect of the water-soluble fluorescent substance used as a model agent was 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) is within range. Additionally... Figure 6 This is a three-dimensional image of the Raman intensity of nicotinamide based on spectral and spatial information obtained by confocal microRaman spectroscopy.

[0414] The more specific experimental methods are described below: (Confocal Raman Spectroscopy) - Apply "Drug Solution A" directly to the skin of the person who has been removed, at a rate of 5 μL per square centimeter.

[0415] -Then, the beauty device of the second invention is applied to remove human skin 50 times.

[0416] - The fingerprint region (600–2200 cm) was evaluated. -1 The time variation of the Raman spectrum of ).

[0417] In addition, the control group only applied "Drug Solution A" at a rate of 5 μL per square centimeter to the removed human skin.

[0418] (Fluorescence intensity)

[0419] The permeability of each composition was investigated in cases where it was applied to excised human skin (commercially available) via a beauty device and in cases where it was applied directly to the skin without a beauty device. More specifically, using a texture analyzer, after applying appropriate vertical load to the stratum corneum of excised human skin and inserting a microneedle plate 50 times, an aqueous solution containing 0.2% fluorescein (sodium fluorescein) was applied at a rate of 5 μL per square centimeter and allowed to stand at 37°C for 15 minutes. Next, the surface of the skin at the site where each composition was applied was cleaned, and the skin portion was cut into 8 mm diameter circles using a dermal punch. The resulting skin was added to an appropriate amount of extraction solvent and subjected to ultrasonic treatment to extract the fluorescein. The fluorescence intensity of the extracted samples was then measured using a spectrophotometer.

[0420] Additionally, Control 1 showed autofluorescence derived from the removed human skin. Furthermore, Control 2 used an example where a solution containing only 0.2% by mass of fluorescent dye (sodium fluorescein) was applied at 5 μL per square centimeter to the removed human skin and left to stand at 37°C for 15 minutes.

[0421] The prescription for "Drug Solution A" is as shown in Table 2-2 below.

[0422]

[0423] In addition, regarding the “model reagent” used in Example 2-4-2, 0.2% sodium fluorescein was mixed in place of 5.0% nicotinamide, and the residual amount was adjusted with water. Otherwise, the formulation was the same as that of the above-mentioned “solution A”.

[0424] Depend on Figure 6-1 It is clearly known that Example 2-4-1 promoted nicotinamide penetration in a much shorter time compared to the control.

[0425] In addition, by Figure 7-1 It is also clear that, compared with controls 1 and 2, the penetration of the drug solution containing the model agent (water-soluble fluorescent substance) in Examples 2-4-2 was significantly increased.

[0426] Examples 2-5

[0427] In Examples 2-5, the second beauty device of the present invention and a dispensing container (a pen-shaped cosmetic container with a volume of about a few mL) containing a solution containing nicotinamide ("solution B") were installed, and the relaxation improvement effect was confirmed after the subject applied the solution once every 2 days.

[0428] More specifically, it will be done as follows: 1. The protruding surface was pressed into the subject's skin and then pressed twice.

[0429] 2. Repeat the action in "1." above, to... Figure 8 Use it as a reference, moving it little by little as you go.

[0430] (A total of 50 sets; additionally, only applicable to the designated side)

[0431] a: 10 groups of nasolabial folds

[0432] b: 10 groups from the outer corner of the eye to below the eye

[0433] c: Forehead, between the eyebrows (10 groups)

[0434] d: 20 groups on one side (cheek center)

[0435] 3. Then, gently allow the liquid to be absorbed onto one side of the face.

[0436] In addition, 34 women aged 45–59 years with a BMI of 18.5–25.0 were included as subjects.

[0437] The prescription for "Drug Solution B" is as shown in Table 3 below.

[0438]

[0439] The experiment was conducted on subjects for four consecutive weeks. Changes in facial contour angles were measured before application, two weeks after application, and four weeks after application using a 3D handheld scanner (non-contact method / 3D anthropometry system). The results are shown in... Figure 9-1 In addition, to illustrate facial contour angles, a 3D scan image of the jawline of one subject is shown. Figure 10-1 middle.

[0440] Depend on Figure 9-1 and Figure 10-1 The results clearly showed that, in Examples 2-5, the subjects' facial contours could be made more defined within 2 weeks. That is, Examples 2-5 suggest that by combining the second beauty device of the present invention with a solution containing nicotinamide, sagging can be improved in a short period of 2 weeks.

[0441] Examples 2-6

[0442] In Examples 2-6, the second beauty device of the present invention and a dispensing container (a pen-shaped cosmetic container with a volume of about a few mL) containing a solution containing nicotinamide ("solution C") were installed. The relaxation improvement effect after the subject applied the solution once every 2 days was evaluated by comparing it with the case of simply applying the solution of the same prescription (Comparative Example 2-1).

[0443] More specifically, it will be done as follows: 1. The protruding surface was pressed into the subject's skin and then pressed once (to ensure proper insertion without pain).

[0444] 2. Repeat the action in "1." above, to... Figure 8-1 Use it as a reference, moving it little by little as you go.

[0445] (A total of 50 presses (25 presses on each side))

[0446] a: Press the nasolabial folds and marionette lines 10 times on each side × (left and right).

[0447] b: Press 10 times on each side from the outer corner of the eye to below the eye × left and right.

[0448] c: Press the affected areas on your cheeks (dryness / pore problems, etc.) 5 times on each side.

[0449] 3. Spread the liquid evenly over your face and use your palms to allow it to be absorbed.

[0450] In addition, 20 women aged 45–59 years, with a BMI of 18.5–25.0 and a wrinkle grade of 3–5 were selected as subjects.

[0451] The prescription for "Drug Solution C" is as shown in Table 4 below.

[0452]

[0453] 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 volume change before and after application was calculated. The results are shown in... Figure 11-1 middle.

[0454] Depend on Figure 11-1 The results clearly showed that in Example 6, the overall volume of the subject's jawline significantly decreased, i.e., tightened, after 2 weeks. On the other hand, in Comparative Example 2-1, where only solution C was applied, no volume change occurred.

[0455] Thus, as illustrated in Examples 2-6, by combining the beauty device of the second invention with a medicated solution containing niacinamide, it is possible to improve sagging that cannot be improved by using conventional cosmetics within a short period of 2 weeks.

[0456] Examples 2-7-1 to 2-7-3

[0457] In Examples 2-7-1 to 2-7-3, the effect of the concentration of nicotinamide in the drug solution on relaxation improvement was confirmed.

[0458] Based on Table 2-5 below, prepare drug solutions containing different concentrations of nicotinamide.

[0459]

[0460] More specifically, in each embodiment, a reviewer compared the pre- and post-application relaxation levels of a patient who applied the medication to one side of the face using the beauty device of the second invention (for one week) and another patient who applied the same prescription medication to the opposite side of the face (for one week). The relaxation level was based on Non-Patent Literature 1 (Skin Research and Technology 2009; 15: 299-305), evaluating three areas: the upper cheek, lower cheek, and outer cheek, in units of 0.5. The evaluation criteria are as follows: (Evaluation Criteria) In the relaxation level, changes below -0.5 within a week are evaluated as follows: • 3 parts: "A" rating • Part 2: "B" rating Part 1: "C" rating • Part 0: "D" rating.

[0461] The evaluation results are shown in Table 6.

[0462] Furthermore, the more negative the change in the relaxation level, the greater the improvement in relaxation. Additionally, the more areas affected by the change, the greater the improvement in relaxation. Therefore, an "A" rating represents the highest level of effectiveness in relaxation improvement, with the effectiveness decreasing in the order of "B," "C," and "D."

[0463]

[0464] The results in Table 2-6 clearly show that, in a short period of one week, when the nicotinamide-containing solution was injected into the beauty device of the second invention, the relaxation improvement effect was greater compared to the application of the solution alone.

[0465] Furthermore, it was found that when the concentration of nicotinamide in the solution was 0.1% by mass, injection was also performed using the beauty device of the second invention, and a relaxation improvement effect was observed compared with the case of application alone.

[0466] It was further learned that when a solution containing nicotinamide was injected through the beauty device of the second invention, the relaxation and improvement effect gradually increased as the concentration of nicotinamide in the solution increased.

[0467] [The third invention]

[0468] The following examples illustrate the third invention in further detail, but the second invention is not limited to these examples.

[0469] In addition, in the following experiments, unless otherwise specified, the beauty device of the third invention used a circular part with needle-like protrusions having a diameter of 15 mm, an effective puncture length of 20 μm for the needle-like protrusions (i.e., needles), and a number of 18 needle-like protrusions.

[0470] Time-related changes in the number of myofibroblasts and the M1 / M2 macrophage ratio

[0471] (RNA Seq)

[0472] Fresh human abdominal skin (Genoskin, France) (n=4, 29–39 years old, mean = 35.8 years old) was airlifted from France and organ cultures were performed during the trials to maintain tissue homology. In all trials, skin of complete thickness with subcutaneous fat removed was used.

[0473] Microneedling was applied once every two days. On skin with the stratum corneum facing upward on a cork board, a pressure of 600 gf was applied vertically for 10 seconds using an instrument (Pressure Instrument, Clinical & Derm, although it is not considered necessary to record this but if necessary). The instrument was then inserted twice, changing the direction by 90° each time.

[0474] Skin samples were collected on days 1, 3, and 7 after culture. Total RNA was extracted from the epidermis and dermis of the isolated skin samples using the Qiagen RNeasy mini kit (Qiagen, Netherlands).

[0475] In addition, RNA-seq analysis was performed using dermal RNA, as described in Reference 11 below. Low-expression genes with a center value of less than 1 for mapped read count were excluded from the analysis. Heatmaps were plotted using heatmap 2 of the gplots package (version 3.1.3.1) (Reference 12 below). Enrichment analysis based on the biological function of selected genes was performed using Metascape (Reference 13 below).

[0476] (Prepared from paraffin blocks and slices)

[0477] Fresh human abdominal skin was recovered and dehydrated and fixed with cold acetone using the AMeX method. The skin was then replaced with acetone, methyl benzoate, and xylene in that order, and embedded in paraffin. Sections were prepared to a thickness of 4 μm for tissue staining.

[0478] (Various immunostaining methods)

[0479] Paraffin sections prepared to a thickness of 4 μm were deparaffinized with xylene and then hydrated with EtOH. Fluorescent immunostaining was performed using antibodies against α-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). Figure 12 , Figure 15 , Figure 16 ).

[0480] Based on the results of fluorescence immunostaining, the number of myofibroblasts (αSMA / vimentin double-positive cells) located in a region of 200 μm immediately below the epidermal basement membrane was counted using the image analysis software ImageJ, and the changes over time were plotted. Figure 13 ).

[0481] Based on the results of fluorescence immunostaining, myofibroblasts (CD31-positive cells) located within a 200 μm region immediately below the epidermal basement membrane were counted using the image analysis software ImageJ, and their changes over time were plotted. Figure 14 ).

[0482] In addition, Figures 12-14 In the text, "MN" indicates the result of applying the microneedles of the present invention, and "control" indicates the control, that is, the result without applying the microneedles. The same applies to the following figures.

[0483] Similarly, based on Figure 15 , Figure 16 The results of fluorescence immunostaining were used to count M1 macrophages (CD86 / CD68 double-positive cells) and M2 macrophages (CD206 / CD68 double-positive cells) located in a region of 200 μm immediately below the epidermal basement membrane using ImageJ image analysis software. The number of each macrophage and the M1 / M2 ratio were quantified, and the changes over time were plotted. Figures 17-19 ).

[0484] Depend on Figures 12-14 The results clearly showed that the number of myofibroblasts increased over time in the skin where the microneedles of the present invention were applied. While the number of CD31-positive cells in blood vessels remained unchanged, an increase in perivascular myofibroblasts was observed.

[0485] Depend on Figures 15-19 The results clearly show that in skin where the microneedles of the present invention are applied, the ratio of M2 to M1 increases over time, that is, the ratio of M1 / M2 decreases over time.

[0486] [Third Supplementary Description of the Invention]

[0487] A new concept in skin revitalizers, which activate skin cells holistically through mechanobiological stimulation and efficiently deliver nutrients, opens up a new dimension in skin care.

[0488] summary

[0489] As an excellent transdermal / intradermal drug delivery system (DDS), microneedles (MNs) can bypass the skin barrier function through a simple and well-defined mechanism. However, existing MN technologies in the cosmetic field are difficult to control in terms of puncture depth, making it challenging to simultaneously achieve safety and efficacy. For example, Solid-MNs cause unacceptable levels of damage due to excessively deep punctures, while Dissolving-MNs cannot achieve adequate drug delivery due to their reliance on the fragility of basic polymers. In this disclosure, this problem is solved by developing a novel MN technology characterized by a unique shape that pseudo-grows the MN in order to control puncture depth.

[0490] Several experiments, including confocal Raman spectroscopy, demonstrated that the puncture depth remained within the stratum corneum (SC). Furthermore, due to the unique shape of the MN, a large amount of medication was rapidly delivered to the living epidermis (VE), hence the name "Injectable-MN." Further, RNA-seq results indicated that Injectable-MN does not cause damage and can induce skin regeneration similar to wound healing. Finally, in home use tests using Injectable-MN with added niacinamide, significant improvements in sagging, wrinkles, skin radiance, and barrier function were observed in just two weeks. In conclusion, the company's Injectable-MN is a highly versatile DDS platform that unlocks the possibilities of functional skincare, delivering results to consumers never before seen.

[0491] Keywords: drug delivery, microneedles, injection, mechanobiology, rejuvenation

[0492] first

[0493] MN (Neuroplastic Injection) utilizes a simple "puncture" mechanism to overcome the barrier function of SC (Synthetic Catheter) and achieve transdermal / intradermal drug delivery. Due to its simple mechanism, it can be combined with various drugs and is easy to use. Considering these advantages, MN is a highly versatile transdermal / intradermal drug delivery system (DRS) (References 1, 2, 3). Furthermore, the use of MN in the cosmetic field is increasing, with solid MN and soluble MN becoming the mainstream among several types (References 1, 2, 4, 5).

[0494] In particular, Solid-MN is gaining popularity due to its use in cosmetic treatments (References 2, 4, 6). The main idea behind this technique is to use sharp, hard metal needles to puncture the skin, facilitating the penetration of the medication. Furthermore, the wound healing process caused by puncturing the dermis leads to the remodeling of the dermal matrix structure. It has been gradually recognized that high rejuvenating effects can be achieved through these two mechanisms. However, this technique carries risks such as bleeding, recovery time, potential infection, and scarring. Products with these risks are not acceptable to consumers for daily skincare.

[0495] So how can we achieve the same high level of rejuvenation as Solid-MN while ensuring its safety as a cosmetic product?

[0496] To address this challenge, we focused on the shape of the MN and developed a skin-depth-based approach.

[0497] Our initial attempts focused on the fundamental issue of controlling the puncture depth. In cosmetic applications, selective puncture of thin layers such as SC and VE is necessary, making the necessary fine control extremely difficult (Reference 2). According to Guang et al. (Reference 8), only needle lengths of 600 μm or longer can be reliably punctured. This is because short needles are hindered by the toughness and viscoelasticity of the skin's SC, which absorbs impact, and MN cannot penetrate the SC, remaining on the surface.

[0498] On the other hand, while needles longer than 600 μm can reach the dermis, they pose a risk of causing damage. Considering safety in cosmetic applications, a depth of around 200 μm is necessary, which is the depth of the epidermis. However, if the needle length is shortened to below 200 μm, it is almost impossible to pierce the skin if only the inside of the fingertip is used to push against it (Reference 9).

[0499] To address these issues, devices for high-speed application of MN are needed (references 1, 2, 3, 9). However, such devices are currently not used effectively due to their high cost. Therefore, considering the application of MN in cosmetics, a choice has been made between designs that prioritize safety over puncture and designs that prioritize efficacy over safety. However, we take a new perspective and attempt to achieve both effective drug delivery and wound-healing-like effects simultaneously.

[0500] We assume that we want to achieve the following goals.

[0501] First, by significantly deforming the skin, the impact absorption capacity due to the skin's elasticity is reduced while the target length MN is embedded into the extended SC. Simultaneously, this large deformation itself allows it to approach deeper into the skin.

[0502] Therefore, firstly, MNs of various shapes were fabricated, and their puncture characteristics were evaluated.

[0503] Furthermore, it is also possible to inject drugs into the skin via this MN. Transmittance evaluation methods, such as confocal Raman microscopy, were used to verify whether the fabricated MN could achieve the aforementioned injection. Further RNA-seq and blood flow observation were used to verify that the new MNs reached the deep skin layers below the dermis, which were previously difficult to reach with cosmetics.

[0504] Finally, nicotinamide (Reference 10), known to participate in various functions in the body and beneficial to the skin, was mixed with a formulation used with MN, and the effects were evaluated through home use trials.

[0505] experiment

[0506] Materials and methods

[0507] Material

[0508] Injectable-MN

[0509] Our developed Injectable-MN (the "device" or "beauty device" of this invention) is a push-button pen-shaped package capable of dispensing a precise amount of liquid. Figure 20-1 b) and the independently designed / manufactured PGA-MN ( Figure 20-1 -a, the design details are described below) are connected. The serum inside the package can be dispensed from the top of the PGA-MN simply by pressing the button located on the back of the push-button pen.

[0510] PGA-MN is made from polyglycolic acid (PGA), a resin known for its biocompatibility and biodegradability. The MNs are arranged at appropriate intervals, with a suitably shaped base beneath each MN so that the puncture site remains within the SC. It is known that if the top of the base is closed, a solid MN is formed, along with separate liquid injection holes and a protective ring surrounding them. Figure 20-1 (a) The total length of MN is 120 μm. The surrounding protective ring controls the puncture depth, so the effective puncture length is 20 μm, which remains within the SC. PGA-MN is supplied with medication from a connected syringe, etc., and is discharged from the liquid injection port, filling the protective ring. If PGA-MN is applied to the skin and injected through a puncture in the SC, the medication penetrates into the skin through capillary action between the skin and MN and the injection pressure generated within the sealing ring. Figure 20-1(c).

[0511] microneedles

[0512] Create MNs of various shapes for experimental purposes. A schematic diagram of an MN is shown below. Figure 20-2 In the middle, each MN is made by appropriately allocating the geometric parameters described below.

[0513] A. Length of MN (μm): 200-1,000

[0514] B. Length of the base portion (μm): 0-2,000

[0515] C. Total length (μm): 200-2,200

[0516] D. Top diameter of the base portion (μm): 150-1,000

[0517] Between E and MN (μm): 2,000-5,000

[0518] F.MN's base diameter (μm): 150–750 (according to A.)

[0519] G. Number of arrayed MNs: 1-19

[0520] The aspect ratio (A. length of MN / F. base diameter of MN) remained at 4 / 3 in all samples. All samples except PGA-MN were made of medical-grade stainless steel (SUS), with only PGA-MN being made of PGA. The geometric parameters of PGA-MN are 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.

[0521] chemical substances

[0522] The reagents were purchased and sold in Japan.

[0523] The beauty serum formula contains the following substances: 5 (w / v)% niacinamide, deionized water, ethanol, glycerin, DPG, xylitol, sodium hyaluronate, 4-methoxysalicylic acid, dipotassium glycyrrhizate, citric acid, sodium citrate, EDTA, and phenoxyethanol.

[0524] In the quantification of fluorescence intensity, 0.02 (w / v)% of fluorescein sodium (Flu-Na) is added to remove nicotinamide, 4-methoxysalicylic acid, and dipotassium glycyrrhizate from the above formulation before use.

[0525] In the home-based human trials, a formulation in which 4-methoxysalicylic acid was removed from the above prescription was used.

[0526] Skin (skin) sample

[0527] In puncture and penetration tests, frozen human back skin (n=3-4, 45-69 years old, mean = 60.0 years old) was thawed and warmed to a surface temperature of 32°C before use. In RNA-seq, fresh human abdominal skin (Genoskin, France) (n=4, 29-39 years old, mean = 35.8 years old) was airlifted from France, and organ cultures were performed during the experiments to maintain tissue isomorphism. Skin of complete thickness with subcutaneous fat removed was used in all experiments.

[0528] method

[0529] Puncture capability test with methylene blue staining

[0530] MN was inserted into a skin patch placed with the SC side facing upwards on a base adjusted to a level similar to the elasticity of human cheekbone skin. Insertion of MN was performed using a texture analyzer (TA.XTplusC, EKO INSTRUMENTS, Japan) as the manipulator, applying a 1 kgf load while vertically pushing MN at a speed of 40 mm / s, holding for 10 seconds before removal. Next, the SC side was immersed in a 1 mg / mL methylene blue aqueous solution for 20 minutes. After wiping off the surface solvent and washing with purified water, 5–10 peelings were performed using a D-Squame sampling tray (manufactured by Clinical and Derm, USA). The presence or absence of punctures was evaluated by observing the specimens under a digital microscope (Hirox, Japan). A portion of the specimen was embedded in an OCT complex, frozen, and thin sections were prepared; the cross-sections were observed under a microscope (BX51, Olympus, Japan) to evaluate the penetration depth.

[0531] The puncture rate is calculated as follows: .

[0532] Puncture capability test resin section and HE staining

[0533] Insertion of MN into the skin was performed using the same method as when methylene blue staining was used. Then, with the MN inserted into the skin, it was fixed in 10% neutral buffered formalin solution, and thin methyl methacrylate sections were prepared and stained with hematoxylin and eosin (HE).

[0534] Permeation study: Quantitative fluorescence intensity analysis

[0535] Serum preparation (5 μl / cm) 2Flu-Na was applied to the skin using a pipette. Then, PGA-MN was squeezed in 50 times at a pressure of 1 kgf. After 15 minutes, the surface was wiped with PBS, and the skin was peeled off three times using a D-Squame (registered trademark) sampling tray. Flu-Na was then extracted from the broken skin using Dalberg'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 average value of the skin's own fluorescence was subtracted to evaluate the permeability of Flu-Na to the skin.

[0536] Penetration Research Confocal Raman Spectroscopy

[0537] In the beauty serum (5μl / cm) 2 After applying the product to the skin using a pipette, PGA-MN was injected into the skin 50 times at a pressure of 1 kgf. As a control, without using PGA-MN, the beauty solution (5 μl / cm) was applied using a pipette. 2 Apply to the skin. Then, evaluate the fingerprint area (600-2200cm). -1 The time variation of the Raman spectrum of nicotinamide (1042 cm⁻¹) was calculated while normalizing according to the laser intensity at each depth. -1 The Raman intensity was measured intermittently from SC to VE in steps of 2 μm or 3 μm, and at 4 or 6 μm. 2 The measurements were taken in the area up to a maximum depth of 30 μm or 60 μm. Finally, the 3D transmission images were visualized using ImageJ and Imaris software.

[0538] RNA-seq method

[0539] PGA-MN was applied every two days. Skin samples were collected on days 1, 3, and 7 post-culture. Total RNA was extracted from the epidermis and dermis of the isolated skin samples using the Qiagen RNeasy mini kit (Qiagen, Netherlands). RNA-seq analysis was performed using dermal RNA as previously reported

[11] . Low-expression genes with a center value less than 1 for the mapped read count were excluded from the analysis. Heatmaps were plotted using heatmap 2 of the gplots package (version 3.1.3.1) (Reference 12). Enrichment analysis based on the biological function of the selected genes was performed using Metascape (Reference 13).

[0540] blood flow

[0541] A comparative evaluation of half of the face was conducted on 24 male subjects (aged 30-60). The beauty serum was mixed with Injectable-MN ( Figure 20-1 Apply the serum to one side of the face 50 times. Then, spread the remaining serum on the skin and immediately measure the blood flow on both sides of the face using an OMEGAZONE laser speckle flowmeter (manufactured by Omegawave, Japan).

[0542] Family-based personnel experiment

[0543] Forty-five women (aged 40-50) who met the review criteria were included in a pre- and post-treatment trial based on home use to investigate improvements in skin condition resulting from the application of "Injectable-MN" or "beauty serum." Evaluations of wrinkles, sagging, and skin radiance were conducted before continuous use, and at 2, 4, and 8 weeks after continuous use. Sagging was assessed using the scoring method of Ezure et al. (Reference 14). Changes in jaw 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.

[0544] In the "Injectable-MN" group, the beauty serum was mixed with Injectable-MN ( Figure 20-1 Use only in the evening, every other day. For one treatment, 50 punctures and injections were performed on the nasolabial folds, around the eyes, and a portion of the cheek. In the "Beauty Serum" group, the same beauty serum without "Injectable-MN" was dispensed, and the user was instructed to apply the same amount as used in the "Injectable-MN" group every other day.

[0545] Adherence to ethical standards

[0546] All experiments were conducted in accordance with ethical considerations based on the Declaration of Helsinki of the World Medical Association. All experiments using human or human skin samples were conducted with the approval of Shiseido's Human Research Ethics Committee.

[0547] Statistical analysis

[0548] For the puncture proficiency test, the obtained data were analyzed using the Cochran's Q test and the Steel-Dwass test. In the analysis of the questionnaire survey for the home use test, the Steel multiple comparison test and the Mann-Whitney U test were used. Other data obtained were analyzed using Student's t-test, Dunnett's test, Tukey-Kramer's honest significance test (HSD), or analysis of variance (ANOVA). In all cases, p < 0.05 was considered significant.

[0549] In the differential gene expression analysis using RNA-seq, edgeR (version 3.40.0) was used (reference 16). Multiple validation was performed using the Benjamini-Hochberg method, and genes with an adjusted p-value (FDR) < 0.05 were considered differentially expressed genes.

[0550] result

[0551] Puncture capability test

[0552] exist Figure 20-3 In case a, a simple single needle MN was sculpted, and the variation in puncture capability caused by different lengths of MN was investigated. The puncture success rate tended to vary with the length of MN (p = 0.079).

[0553] On the other hand, Figure 20-3 In group b, a base was set under a single needle MN with a fixed needle length of 200 μm to make the total length spuriously longer, and the puncture success rate caused by the different lengths was compared. Stable punctures were observed at a total length of over 600 μm, and significant differences in puncture success rate were confirmed in each group at a significance level of 0.5%.

[0554] exist Figure 20-3 In section c, the puncture success was compared by varying the tip diameter of the basal portion under MN. It was found that punctures with a tip diameter below 600 μm were successful, showing a significant difference in success rate at a 1% significance level. However, in tomographic images of frozen sections, punctures with a tip diameter below 200 μm failed to remain in the epidermis and reached the dermis (data not shown). Therefore, it is considered that to ensure punctures remain within the epidermis, the tip diameter needs to be set between 300 and 600 μm.

[0555] Then, in Figure 20-3In the d-test, single needles MN with a length of 200 μm (MN), an array of 19 MNs of the same shape (MN Array), single needles MN with a length of 200 μm and a base length of 2,000 μm (MN w / Base), and an array of 19 MNs of the same shape as MN w / Base (MN w / Base Array) were fabricated, and their puncture capabilities were evaluated. The results show that by adding a base under the MN and simultaneously arraying them, the puncture rate is significantly improved.

[0556] Finally, Figure 20-3 In the study, the changes in puncture rate caused by the array configuration were evaluated by varying the spacing between MNs. Although no significant changes were observed due to different spacings, a tendency for the puncture rate to decrease was observed when the spacing became greater than 5 mm.

[0557] Based on these results, we developed Figure 20-1 The structure shown is a new shaped MN (PGA-MN) remaining within the SC. The feasibility of the expected puncture was verified using PGA-MN by methylene blue staining and resin sectioning & HE staining. As a result, 17 out of 18 MNs were punctured to layer 5 of the SC, and 10 of them reached layer 10 (data not shown).

[0558] Next, the puncture depth was evaluated using resin sections. Figure 20-4 Unfortunately, the tip of the MN needle hydrolyzed during fixation, making it impossible to simultaneously photograph the needle tip and the skin. However, it was confirmed that MN puncture marks remained within the SC, and the MN puncture site was significantly deformed into the dermis.

[0559] Penetration survey

[0560] The injectability of PGA-MN was evaluated using quantitative fluorescence intensity and confocal Raman microscopy, with the penetration-promoting effect of the hydrophilic model drug being assessed.

[0561] The permeability of the model drug (Flu-Na) was evaluated using quantitative fluorescence spectroscopy. The results showed that, 15 minutes after application of Injectable-MN, a significant increase in permeability was observed, approximately 2.9 times that of simple application. Figure 20-5 (a).

[0562] Furthermore, confocal Raman spectroscopy was used to visualize the time-dependent intradermal penetration of the model drug (nicotinamide). The results showed that in simple application, even after 3 hours, it remained at a depth of approximately 20 μm, comparable to SC. In contrast, when combined with Injectable-MN, it reached a depth comparable to VE after 30 minutes. Figure 20-5 (b).

[0563] RNA-seq method

[0564] A comprehensive analysis comparing the control group and the PGA-MN application group revealed significant changes in 11 genes on day 1, 5 genes on day 3, and 79 genes on day 7. A heatmap showing differentially expressed genes will be displayed. Figure 20-6 In cell 'a', green blocks represent genes with decreased expression, and red blocks represent genes with increased expression.

[0565] The results of the condensation analysis indicated that, compared with the control group, the functions of 6 gene clusters were significantly upregulated and the functions of 18 gene clusters were downregulated in PGA-MN. Figure 20-6 (b). This suggests the possibility that NABA ECM regulators, vascular permeability regulators, and gene clusters involved in innate immune responses are associated with improvements in blood flow, wrinkles, and sagging observed in in vivo human trials described later.

[0566] blood flow

[0567] Blood flow was evaluated, and a significant increase in blood flow was confirmed only on the side where Injectable-MN was applied. Figure 20-7 ).

[0568] Family-based personnel experiment

[0569] While Injectable-MN significantly improved the severity of wrinkles after two weeks of application, in the control group (serum), improvement in wrinkles was observed starting four weeks after application. Figure 20-8 (a).

[0570] Furthermore, after two weeks of application, the skin's radiance was significantly improved compared to the serum group. Figure 20-8 (b).

[0571] Furthermore, significant improvements were confirmed in questionnaires conducted 2 weeks and 8 weeks later in categories such as "skin becomes softer" and "skin becomes more moisturized." Figure 20-8 (c, d).

[0572] Furthermore, regarding the degree of relaxation, significant changes from initial values ​​were observed in nasolabial folds, marionette lines, and facial contours. Figure 20-8 (e, f, g). In the control group, no significant changes were observed regarding improvements in marionette lines and facial contour laxity. Furthermore, only the Injectable-MN group showed a significant reduction in jaw volume compared to pre-use levels after 2 and 8 weeks of continuous use. Figure 20-8 (h). In a subset of subjects, a visually significant reduction in relaxation was observed (h). Figure 20-8(i).

[0573] Barrier function also improved significantly from 2 weeks onwards in both groups. Figure 20-8 (j).

[0574] Furthermore, the study explored whether the irritation caused by the application of the test product was tolerable. The results showed that 96% of the Injectable-MN treatment group answered "yes," and no significant difference was found between the group and the control group (data not shown).

[0575] discuss

[0576] The problem of conflicting lengths of MN (if too long, it penetrates deeply, but if too short, it fails to penetrate the skin at all) was solved by adding base components that make MN appear falsely long, arranged at appropriate intervals.

[0577] The optimized PGA-MN was confirmed to remain in the target skin layer, either SC or VE.

[0578] Meanwhile, the resin sections were observed under a microscope, and significant deformation was observed in the deeper epidermis.

[0579] This deformation can be considered to have two functions. One is that by compressing or stretching the skin, the skin's shock absorption capacity is reduced, allowing for accurate puncture of the target area with short needles less than 200μm.

[0580] Another method involves applying mechanical pressure, which contributes to the results of RNA-seq and blood flow assessment.

[0581] Injectability was evaluated using quantitative fluorescence intensity and confocal Raman microscopy, based on the penetration-enhancing effect of the hydrophilic model drug. The results showed that PGA-MN improved the skin permeability of the model drug in terms of quantity, rate, and depth.

[0582] RNA-seq results suggest that NABA ECM regulators, vascular permeability regulators, and innate immune responses are altered by PGA-MN pressure. Among these genes are several that are generally known to be controlled by mechanical stress, suggesting the possibility that PGA-MN induces mechanobiological effects in the dermis. These changes may contribute to ECM and vascular remodeling, potentially indicating a shift from the inflammatory phase to the proliferative and remodeling phases.

[0583] Generally, reports have indicated significant damage during wound healing due to dysregulation of important genes such as VEGF

[17] , but in this study, such genes remained unchanged. Therefore, our hypothesis is that PGA-MN promotes a mild immune response without causing severe skin damage, and improves skin through wound healing mechanisms via dermal ECM and vascular remodeling.

[0584] It is generally believed that both wound formation and mechanobiological effects contribute to the process of wound healing, but the PGA-MN used in this study did not form a wound because it remained within the SC. Therefore, it is speculated that the mild effects resulting from mechanobiological processes alone may be sufficient. In other words, unique evidence has been found that skin rejuvenation can be achieved without the risk of scar formation through invasive methods. Further investigation using methods such as immunostaining can clarify whether these changes in gene expression actually constitute trait expression.

[0585] Furthermore, this mechanical pressure also provides an immediate effect, such as improved blood flow.

[0586] These results demonstrate that Injectable-MN has a combined effect on both the epidermis and dermis.

[0587] Furthermore, it was clearly demonstrated that sagging, wrinkles, skin radiance, and barrier function were significantly improved after two weeks of continuous use. These skin-beautifying effects surpass those of previous cosmetics and existing MN technology.

[0588] Niacinamide's effects on skin texture and pigmentation are well-known (Reference 10), but when niacinamide is injected using Injectable-MN, significant improvements in wrinkles and skin translucency were observed in a short period compared to previous methods. Furthermore, the Injectable-MN treatment group showed greater improvements in skin softness and hydration than those treated with topical application alone.

[0589] Furthermore, the previously unknown effects on improving nasolabial folds, marionette lines, and facial contour laxity were clarified. This is attributed not only to the rapid delivery of large amounts of niacinamide deep into the skin, but also to a complex response including the mechanobiological effects of MN pressure and the promotion of metabolic responses due to improved blood flow.

[0590] Furthermore, while injectable MN improves barrier function, it also tends to impair it through its mechanism of action, such as "penetrating the skin's sac" (SC) (Reference 18). This is because injectable-MN, by remaining within the SC at a precisely controlled puncture depth, does not damage the barrier function. We have found that injectable-MN regenerates the skin without disrupting its barrier function, addressing serious signs of aging such as sagging. This achieves a level of safety and efficacy that is unattainable in cosmetics and medical aesthetics.

[0591] in conclusion

[0592] Injectable-MN is a groundbreaking technology that achieves a level of safety and rejuvenation that is currently unattainable with existing cosmetics and medical aesthetics, at a very high level.

[0593] Due to its unique shape, Injectable-MN is known to deliver effects beyond those of previous cosmetics non-invasively. Its mechanism can be attributed to: 1) rapid, high-volume penetration of the drug into the epidermis through precise puncture and injection; 2) dermal ECM and vascular remodeling resulting from a mechanism similar to non-invasive wound healing; and 3) an immediate increase in blood flow. Figure 20-9 The combined effects of these factors lead to the overall activation of skin cells.

[0594] Injectable-MN technology not only controls the "amount" of penetration but also its "location" and "time," ushering in a new dimension for functional cosmetics as a novel DDS platform. Furthermore, its non-invasive mechanobiological effects exponentially expand the technology's potential. This could be a groundbreaking advancement that frees consumers from the limitations of existing cosmetic effects and the burdens imposed by cosmetic medicine.

[0595] References list

[0596] Explanation of symbols

[0597] 10, 11 boards

[0598] 10a and 11a liquid outlet holes

[0599] 10b, 11b needle-like projections

[0600] 10c, 11c Lips

[0601] 11d base section

[0602] 20 Installation Frame

[0603] 20a Plate Support

[0604] 20b Mounting Cylinder

[0605] 30 syringes

[0606] 30a Injector tip

[0607] 30b syringe

[0608] 30c plunger

[0609] 30D push-press tablet

[0610] Components with needle-like protrusions (100, 101)

[0611] 200 beauty appliances

[0612] C medicine solution

[0613] S represents the object (skin).

Claims

1. An apparatus for use in a method for improving the skin condition of an object. The device has: a component with needle-like protrusions, The component with needle-like projections includes needle-like projections, and the effective puncture length of the needle-like projections into the skin is a length that does not reach the dermis. The method includes: (i) Apply the beauty device to the skin with an extrusion pressure of 50–1200 gf, and (ii) Using the appliance more than once every two days and using it more than twice, or using the appliance more than three times a week.

2. The appliance according to claim 1, wherein the object requires adjustment of the M1 / M2 balance.

3. The apparatus according to claim 1, wherein the object requires an increased number of myofibril cells.

4. The appliance according to any one of claims 1 to 3, wherein the component with the needle-like protrusion has: A plate with liquid outlet holes running vertically through it. One or more tiny needle-like protrusions protruding from one side of the plate, and A lip formed on the outer edge of one side of the plate.

5. The appliance according to any one of claims 1 to 3, wherein the component with the needle-like protrusion has: plate, One or more base parts protruding from one side of the plate One or more tiny needle-like protrusions protruding from the top surface of one or more base portions, and A lip is formed on the outer edge of the top surface of the base.

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

7. The device according to claim 1, used to improve the transparency of the skin.

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

9. The device according to claim 1, used to improve skin laxity.

10. A needle-shaped beauty device, having a component with needle-like protrusions, and Used to improve the skin's barrier function and / or transparency.

11. The beauty device according to claim 10, wherein the component with needle-like protrusions has: A plate with liquid outlet holes running vertically through it. One or more tiny needle-like projections protruding from one side of the plate, and A lip formed on the outer edge of one side of the plate.

12. The beauty device according to claim 10, wherein the component with needle-like protrusions has: plate, One or more base parts protruding from one side of the plate One or more tiny needle-like protrusions protruding from the top surface of one or more base portions, and A lip is formed on the outer edge of the top surface of the base.

13. The apparatus according to any one of claims 1 to 12 is an apparatus for injecting a liquid medicine into an object via the component with the needle-like protrusion.

14. A beauty kit for improving the skin's barrier function and / or translucency, comprising the beauty device of claim 13 and the liquid medicine.

15. The beauty kit of claim 14, wherein the liquid contains niacinamide.

16. The beauty kit according to claim 14 or 15 can improve the transparency in a shorter period of time compared to applying the liquid to the skin.

17. The beauty kit according to any one of claims 14 to 16 can improve the skin barrier function, improve the skin transparency, promote collagen production in the skin, or improve skin laxity.

18. A cosmetic method for improving the skin condition of an object, the cosmetic method comprising: (i) Apply the cosmetic device to the skin with an extrusion pressure of 50–1200 gf, and (ii) Using the beauty device more than once every two days and more than twice, or using the beauty device more than three times a week. and The aforementioned beauty device is a needle-shaped beauty device, having a component with needle-like protrusions. The component 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.

19. The cosmetic method according to claim 18, wherein the object needs to have its M1 / M2 balance adjusted.

20. The cosmetic method according to claim 18, wherein the subject requires an increased number of myofibril cells.

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

22. A method for improving the skin's barrier function and / or translucency, comprising: Apply the beauty device according to any one of claims 10 to 13 to the skin.

23. A method for improving the skin's barrier function and / or translucency, comprising: Using the beauty kit according to any one of claims 14 to 17, the beauty device is applied to the skin.

24. The method according to claim 22 or 23, comprising injecting a drug solution into the object, and The solution contains nicotinamide.

25. The method according to any one of claims 22 to 24 can improve the skin barrier function, improve the skin transparency, promote collagen production in the skin, or improve skin laxity.

26. The method according to any one of claims 22 to 25 can improve the transparency in a shorter period of time compared to applying the medicinal solution to the skin.

27. A needle-shaped beauty device having a component with needle-like protrusions and for promoting collagen production.

28. A needle-shaped beauty device having a component with needle-like protrusions, and for improving skin laxity.

29. The beauty device according to claim 27 or 28, wherein the component with the needle-like protrusions has: A plate with liquid outlet holes running vertically through it. One or more tiny needle-like projections protruding from one side of the plate, and A lip formed on the outer edge of one side of the plate.

30. The beauty device according to claim 27 or 28, wherein the component with needle-like protrusions has: plate, One or more base parts protruding from one side of the plate One or more tiny needle-like protrusions protruding from the top surface of one or more base portions, and A lip is formed on the outer edge of the top surface of the base.

31. The apparatus according to any one of claims 1 to 5 and 27 to 30 is an apparatus for injecting a liquid medicine into an object via the component with the needle-like protrusion.

32. A beauty kit for promoting collagen production, comprising the beauty device of claim 31 and the liquid solution.

33. The beauty kit of claim 32, wherein the liquid contains niacinamide.

34. The beauty kit according to claim 32 or 33 can improve skin laxity, promote collagen production, improve skin barrier function, or improve skin transparency.

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

36. A method for promoting collagen production, comprising: Using the beauty kit according to any one of claims 31 to 34, the beauty device is applied to the skin.

37. The collagen production promotion method according to claim 35 or 36, comprising injecting a drug solution into the object, and The solution contains nicotinamide.

38. The collagen production promotion method according to any one of claims 35 to 37 can improve skin laxity, promote collagen production in the skin, improve the skin barrier function, or improve skin transparency.

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

40. The beauty method according to any one of claims 18 to 21, wherein the beauty device is the instrument according to any one of claims 1 to 13 and 27 to 31.

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