WO2025094645A1 - Needle beauty instrument, beauty kit, and beauty method - Google Patents

Abstract

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

Description

Needle beauty tool, beauty kit, and beauty method

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

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

A third aspect of the present invention relates to a beauty device, a beauty kit, and a beauty method using the same for use in a beauty method for improving the condition of a subject's skin.

[Background Art of the First Embodiment]
To date, many beauty methods and devices using microneedles have been developed.

For example, Patent Document 1 discloses a beauty method for brightening the overall facial tone by attaching a microneedle sheet on which multiple microneedles are arranged to part of the face.

Patent Document 2 also reports a part with needle-like protrusions that can hold a liquid composition/liquid cosmetic, with no particular active ingredient, on the surface and inside of an object so that it does not leak through gaps. The part with needle-like protrusions in Patent Document 2 can be attached to a fixed-needle injection device as a needle cosmetic device and used.

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

　To date, many collagen production promoters have been developed.

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

Patent Document 2 discloses a part with needle-like protrusions that can hold a liquid composition/liquid cosmetic, with no particular active ingredient, on the surface and inside of an object so that it does not leak through gaps. The part with needle-like protrusions in Patent Document 2 can be attached to a fixed-needle injection device as a needle cosmetic device and used.

[Background Art of the Third Embodiment]
To date, many beauty methods and devices using microneedles have been developed.

For example, Patent Document 1 discloses a beauty method for brightening the overall facial tone by attaching a microneedle sheet on which multiple microneedles are arranged to part of the face.

Patent Documents 2 and 3 disclose parts with needle-like protrusions and needle beauty devices having said parts. For example, Patent Document 2 reports a part with needle-like protrusions that can retain a liquid composition/liquid cosmetic agent, with no particular active ingredient, on the surface and inside of an object so that it does not leak through gaps. The part with needle-like protrusions in Patent Document 2 can be attached to a fixed-needle injection device as a needle beauty device and used.

JP 2020-164432 A International Publication No. 2022/071322 International Publication No. 2023/190584 JP 2006-232740 A

Skin Research and Technology 2009; 15: 299-305

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

On the other hand, there is still room for improvement in beauty devices for improving the skin's barrier function and for improving skin clarity.

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

In addition, according to a first aspect of the present invention, a method for improving the barrier function of the skin and/or a method for improving transparency is provided.

[Problem in the second aspect of the present invention]
As described in Patent Document 4, various collagen production promoters are being developed, and there is also a demand for the development of beauty devices and the like for promoting collagen production.

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

In addition, according to another aspect of the second invention, a method for promoting collagen production can be provided.

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

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

[Problem in the third aspect of the present invention]
Currently, most microneedles commercially available for cosmetic purposes are composed mainly of hyaluronic acid. Therefore, the cosmetic effects of cosmetic methods and cosmetic devices using microneedles are thought to be mainly derived from hyaluronic acid, that is, the main moisturizing effect is expected.

On the other hand, there is still room for improvement in beauty devices and the like for use in beauty methods to improve the condition of a subject's skin. In particular, there is still room for improvement in beauty devices and the like for subjects who need to adjust the M1/M2 balance or increase the number of muscle fiber cells.

According to a third aspect of the present invention, a method for improving the condition of the skin of a subject can be provided. In the above method, for example, an instrument having a part with needle-like protrusions (sometimes called a beauty instrument, needle beauty instrument, etc.) is used.

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

The first aspect of the present invention that achieves the above objective is as follows:

<Aspect 1-1>
The present invention relates to a cosmetic that has a part with needle-like projections, and is intended to improve the barrier function and/or transparency of the skin.
Needle beauty tool.
<Aspect 1-2>
The part with needle-like projections is
A plate having a pouring hole extending vertically therethrough;
One or more minute needle-like projections protruding from one surface of the plate;
a lip portion formed on an outer edge of one surface of the plate;
The beauty device according to aspect 1-1, comprising:
<Aspect 1-3>
The part with needle-like projections is
Plate and
one or more pedestals protruding from one surface of the plate;
One or more minute needle-like projections protruding from a tip end surface of each of the one or more base portions;
A lip portion formed on an outer edge portion of a tip surface of the base portion;
The beauty device according to aspect 1-1, comprising:
<Aspect 1-4>
The beauty tool according to any one of Aspects 1-1 to 1-3, which is for injecting a medicinal solution into a target object via the part with needle-like projections.
<Aspect 1-5>
A beauty kit for improving the barrier function and/or transparency of the skin, comprising the beauty tool according to any one of aspects 1 to 4 and the medicinal solution.
<Aspect 1-6>
The cosmetic kit according to any one of the preceding aspects, wherein the medicinal solution comprises niacinamide.
<Aspect 1-7>
The beauty kit according to aspect 1-5 or 1-6, which can improve the transparency in a shorter period of time than when the medicinal liquid is applied to the skin.
<Aspect 1-8>
The beauty kit according to any one of Aspects 1-5 to 1-7, which is capable of improving the barrier function of the skin, improving the transparency of the skin, promoting collagen production in the skin, or improving sagging skin.
<Aspect 1-9>
A method for improving the barrier function and/or transparency of the skin, comprising applying the cosmetic device according to any one of Aspects 1-1 to 1-4 to the skin.
<Aspect 1-10>
A method for improving the barrier function and/or transparency of the skin, comprising applying the beauty tool to the skin using the beauty kit according to any one of Aspects 1-5 to 1-8.
<Aspect 1-11>
injecting a medicinal solution into a subject, the medicinal solution including niacinamide;
The method according to aspect 1-9 or 1-10.
<Aspect 1-12>
The method according to any one of Aspects 1-9 to 1-1-11, which can improve the barrier function of the skin, improve the transparency of the skin, promote collagen production in the skin, or improve sagging of the skin.
<Aspect 1-13>
The method according to any one of Aspects 1-9 to 1-12, wherein the transparency can be improved in a shorter period of time than when the drug solution is applied to the skin.

The second aspect of the present invention that achieves the above object is as follows:

<Aspect 2-1>
A needle beauty device having parts with needle-like protrusions and for promoting collagen production.
<Aspect 2-2>
A needle beauty device having parts with needle-like projections and intended to improve sagging skin.
<Aspect 2-3>
The part with needle-like projections is
A plate having a pouring hole extending vertically therethrough;
One or more minute needle-like projections protruding from one surface of the plate;
a lip portion formed on an outer edge of one surface of the plate;
The beauty device according to aspect 2-1 or 2-2,
<Aspect 2-4>
The part with needle-like projections is
Plate and
one or more pedestals protruding from one surface of the plate;
One or more minute needle-like projections protruding from a tip end surface of each of the one or more base portions;
A lip portion formed on an outer edge portion of a tip surface of the base portion;
The beauty device according to aspect 2-1 or 2-2,
<Aspect 2-5>
The beauty tool according to any one of Aspects 2-1 to 2-4, which is for injecting a medicinal solution into a target object via the part with needle-like protrusions.
<Aspect 2-6>
A beauty kit for promoting collagen production, comprising the beauty tool according to aspect 2-5 and the medicinal solution.
<Aspect 2-7>
The cosmetic kit according to any one of claims 2 to 6, wherein the medicinal solution comprises niacinamide.
<Aspect 2-8>
The cosmetic kit according to Aspect 2-6 or 2-7, which is capable of improving sagging skin, promoting collagen production in the skin, improving the barrier function of the skin, or improving the transparency of the skin.
<Aspect 2-9>
A method for promoting collagen production, comprising applying the cosmetic device according to any one of Aspects 2-1 to 2-5 to skin.
<Aspect 2-10>
A method for promoting collagen production, comprising applying the beauty tool to skin using the beauty kit according to any one of Aspects 2-6 to 2-8.
<Aspect 2-11>
injecting a medicinal solution into a subject, the medicinal solution including niacinamide;
A method for promoting collagen production according to Aspect 2-9 or 2-10.
<Aspect 2-12>
The method for promoting collagen production according to any one of Aspects 2-9 to 2-11, which is capable of improving sagging skin, promoting collagen production in the skin, improving the barrier function of the skin, or improving the transparency of the skin.

The third aspect of the present invention that achieves the above object is as follows:

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

In the above method, the part with needle-like protrusions comprises, for example, a plate with an injection hole penetrating vertically, and one or more minute needle-like protrusions protruding from one side of the plate. The above part with needle-like protrusions may further comprise a lip portion formed on the outer edge of one side of the plate. In the above part with needle-like protrusions, at least one of the one or more minute needle-like protrusions may be disposed inside the lip portion.

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

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

The above method includes, for example, (ii) a step of pressing the needle-shaped projections against the skin at least twice and at least once every two days, or a step of pressing the needle-shaped projections against the skin at least three times a week. This results in significant effects such as improvement of the skin's barrier function, improvement of skin transparency, promotion of collagen production in the skin, and/or improvement of sagging skin. As a result, the user experience is improved.

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

In the above-mentioned device, the above-mentioned cosmetic method includes, for example, (i) a step of pressing the above-mentioned device against the skin with a pressure of 50 to 1200 gf. The above-mentioned cosmetic method includes, for example, (ii) a step of pressing the above-mentioned device against the skin at least twice every two days, or at least three times a week. This results in significant effects such as improvement of the skin's barrier function, improvement of skin transparency, promotion of collagen production in the skin, and/or improvement of sagging skin. As a result, the user experience is improved.

The above method and/or the above device can adjust the M1/M2 balance inside the skin. Therefore, by applying the above method and/or the above device to a subject for whom adjustment of the M1/M2 balance inside the skin is desired, the M1/M2 balance inside the skin of the subject can be improved in particular.

The above method and/or the above device can increase the number of muscle fiber cells inside the skin. Therefore, by applying the above method and/or the above device to a subject in whom an increase in the number of muscle fiber cells inside the skin is desired, the number of muscle fiber cells inside the skin of the subject in particular can be increased.

<Aspect 3-1>
1. An apparatus for use in a method of improving the condition of the skin of a subject, comprising:
The device has a part with a needle-like projection,
the part with needle-like projections includes needle-like projections, and an effective puncture length of the needle-like projections into the skin is a length that does not reach the dermis,
The method,
(i) applying a pressing pressure of 50 to 1200 gf to the skin with the cosmetic device; and (ii) using the device at least once every two days and at least twice a day, or using the device at least three times a week.
<Aspect 3-2>
The beauty device according to aspect 3-1, wherein the subject needs to adjust the M1/M2 balance.
<Aspect 3-3>
The cosmetic device according to aspect 3-1, wherein the subject needs to increase the number of muscle fiber cells.
<Aspect 3-4>
The part with needle-like projections is
A plate having a pouring hole extending vertically therethrough;
One or more minute needle-like projections protruding from one surface of the plate;
a lip portion formed on an outer edge of one surface of the plate;
The beauty device according to any one of aspects 3-1 to 3-3, comprising:
<Aspect 3-5>
The part with needle-like projections is
Plate and
one or more pedestals protruding from one surface of the plate;
One or more minute needle-like projections protruding from a tip end surface of each of the one or more base portions;
A lip portion formed on an outer edge portion of a tip surface of the base portion;
The beauty device according to any one of aspects 3-1 to 3-3, comprising:
<Aspect 3-6>
The device according to Aspect 3-1, which is used for improving the barrier function of the skin.
<Aspect 3-7>
The device according to Aspect 3-1, which is used for improving skin clarity.
<Aspect 3-8>
The device according to Aspect 3-1, which is used for promoting collagen production in the skin.
<Aspect 3-9>
The device according to Aspect 3-1, which is used for improving sagging skin.
<Aspect 3-10>
The device according to any one of aspects 3-1 to 3-9, which is for injecting a medicinal solution into a target object via the part with a needle-like protrusion.
<Aspect 3-11>
A cosmetic kit for improving the barrier function and/or transparency of the skin, comprising the device according to any one of aspects 3 to 10 and the medicinal solution.
<Aspect 3-12>
The cosmetic kit according to any one of claims 3 to 10, wherein the medicinal solution comprises niacinamide.
<Aspect 3-13>
The beauty kit according to aspect 3-11 or 3-12, which can improve the transparency in a shorter period of time than when the medicinal liquid is applied to the skin.
<Aspect 3-14>
The beauty kit according to any one of Aspects 3-11 to 3-13, which is capable of improving a skin barrier function, improving skin transparency, promoting collagen production in the skin, or improving sagging skin.
<Aspect 3-15>
A cosmetic method for improving a skin condition of a subject, comprising:
(i) applying a pressure of 50 to 1200 gf to the skin with the beauty tool; and (ii) using the beauty tool at least once every two days and at least twice a day, or at least three times a week; and the beauty tool is a needle beauty tool having a part with a needle-like protrusion,
the part with needle-like protrusions includes needle-like protrusions, and the effective puncture length of the needle-like protrusions into the skin is a length that does not reach the dermis;
Beauty methods.
<Aspect 3-16>
The cosmetic method according to any one of Aspects 3 to 15, wherein the subject needs to adjust the M1/M2 balance.
<Aspect 3-17>
The cosmetic method according to any one of aspects 3 to 15, wherein the subject needs to increase the number of muscle fiber cells.
<Aspect 3-18>
The cosmetic method according to any one of Aspects 3-15 to 3-17, for adjusting the M1/M2 balance in the subject and/or for increasing the number of muscle fiber cells in the subject.
<Aspect 3-19>
A beauty kit for promoting collagen production, comprising the device according to any one of aspects 3-1 to 3-10 and the medicinal solution.
<Aspect 3-20>
The cosmetic kit of any one of claims 3 to 19, wherein the medicinal solution comprises niacinamide.
<Aspect 3-21>
The cosmetic kit according to Aspect 3-19 or 3-20, which is capable of improving sagging skin, promoting collagen production in the skin, improving the barrier function of the skin, or improving the transparency of the skin.
<Aspect 3-22>
A method for promoting collagen production, comprising applying the device according to any one of Aspects 3-1 to 3-10 to the skin.
<Aspect 3-23>
A method for promoting collagen production, comprising applying the beauty tool to skin using the beauty kit according to any one of Aspects 3-19 to 3-21.
<Aspect 3-24>
injecting a medicinal solution into a subject, the medicinal solution including niacinamide;
A method for promoting collagen production according to Aspect 3-22 or 3-23.
<Aspect 3-25>
The method for promoting collagen production according to any one of Aspects 3-22 to 3-24, which is capable of improving sagging skin, promoting collagen production in the skin, improving the barrier function of the skin, or improving transparency of the skin.
<Aspect 3-26>
The device according to any one of aspects 3-1 to 3-10, wherein the effective puncture length of the needle-like projections into the skin is 5 μm or more and 200 μm or less.
<Aspect 3-27>
The beauty method according to any one of aspects 3-15 to 3-18, wherein the beauty tool is the tool according to any one of aspects 3-1 to 3-10.

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

In addition, according to one aspect of the first invention, a beauty kit for improving the barrier function and/or transparency of the skin can be provided.

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

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

In addition, according to a second aspect of the present invention, a beauty kit for promoting collagen production can be provided.

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

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

Furthermore, according to a second aspect of the present invention, a needle beauty device for improving sagging skin can be provided. Further, according to a second aspect of the present invention, a beauty kit for improving sagging skin can be provided. Furthermore, according to a second aspect of the present invention, a method for improving sagging skin can be provided.

[Effect of the third aspect of the present invention]
According to a third aspect of the present invention, a beauty device for use in a beauty method for improving the condition of a subject's skin can be provided.

The subject of the third aspect of the present invention may be a subject in which the M1/M2 balance needs to be adjusted, or a subject in which the number of muscle fiber cells needs to be increased.

Accordingly, according to the third aspect of the present invention, it is possible to adjust the M1/M2 balance in the skin of a subject. Also, according to the third aspect of the present invention, it is possible to increase the number of muscle fiber cells in a subject.

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

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

[First aspect of the present invention]
Hereinafter, the first embodiment of the present invention will be described in detail with reference to the drawings. For convenience of explanation, the same or corresponding parts in each drawing are given the same reference numerals, and duplicate explanations are omitted. In addition, not all components of the embodiment are necessarily essential, and some components may be omitted. However, the first embodiment of the present invention is not limited to the following embodiment, and can be modified in various ways within the scope of the invention.

《Needle beauty equipment》
The needle beauty device according to the first embodiment of the present invention (hereinafter also simply referred to as the "beauty device of the first embodiment") has parts with needle-shaped protrusions and is intended to improve the barrier function and/or transparency of the skin.

The needle-shaped protrusion parts of the beauty device of the first embodiment can be, for example, the "needle-shaped protrusion parts" disclosed in Patent Document 2. The needle beauty device of the first embodiment can be the beauty device (apparatus) disclosed in Patent Document 2. Note that Patent Document 2 describes the "needle-shaped protrusion parts" as being for the purpose of retaining a liquid composition/liquid cosmetic, with no particular active ingredient, on the surface and inside of an object so as not to leak through gaps, and does not disclose or suggest anything about the barrier function of the skin. In this regard, considering that microneedles and the like puncture the skin, the effect of improving the barrier function of the skin of the first embodiment is unexpected.

Through intensive research, the inventors have discovered that the skin's barrier function can be improved by using the beauty device of the first embodiment, which has such parts with needle-like protrusions.

Without being limited to theory, it is speculated that the beauty device of the first embodiment, when its needle-like protrusion parts are applied to the skin, punctures the surface of the skin and causes large deformations that reach the deeper layers of the skin, stimulating cells to activate differentiation and thereby promoting cell turnover. It is speculated that the promotion of cell turnover leads to an improvement in the skin's barrier function and/or transparency. Furthermore, it is known that the application of this beauty device has a temporary blood flow promotion effect (data not shown), and it is speculated that the above-mentioned effects are enhanced as a result of further promotion of cell turnover.

Furthermore, through intensive research by the inventors, it has been found that the beauty device of the first embodiment has an effect of promoting the proliferation of epidermal cells. It is believed that this effect of promoting the proliferation of epidermal cells leads to an improvement in the barrier function and/or transparency of the skin.

In the first embodiment, the barrier function of the skin is a function performed by the stratum corneum and epidermis of the skin, which prevents the loss of moisture essential for the activity of cells and tissues that constitute a living body, and prevents external stimuli and substances such as viruses and bacteria from entering the body. The barrier function of the skin can be evaluated in units of (g/ ^m2 ·h) by measuring the transepidermal water loss (TEWL) under non-sweating conditions (Cosmetics Encyclopedia, edited by the Association of Japanese Cosmetic Engineers, Maruzen Co., Ltd., 2005, pp. 83-84).

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

The part with needle-like projections according to the first embodiment is
A plate having a pouring hole extending vertically therethrough;
One or more minute needle-like projections protruding from one surface of the plate;
a lip portion formed on an outer edge of one surface of the plate;
and a plate;
one or more pedestals protruding from one surface of the plate;
One or more minute needle-like projections protruding from a tip end surface of each of the one or more base portions;
A lip portion formed on an outer edge portion of a tip surface of the base portion;
[0043]

The beauty device of the first embodiment may be used to inject a medicinal liquid into a target object via a part with needle-like protrusions.

In this case, the beauty tool of the first embodiment has a part with needle-like protrusions for injecting a medicinal solution into a target object,
The needle-shaped protrusion parts are
A plate having a pouring hole extending vertically therethrough;
One or more minute needle-like projections protruding from one surface of the plate;
a lip portion formed on an outer edge of one surface of the plate;
and when the composition of the first embodiment is extruded from the spout hole, the composition of the first embodiment spreads into a space formed between the object, the lip portion, and one surface of the plate, and the composition of the first embodiment penetrates into the object through holes formed by one or more needle-like projections.
It may be a beauty device, or
A part with needle-like protrusions for injecting the composition of the first embodiment into an object,
The needle-shaped protrusion parts are
Plate and
one or more pedestals protruding from one surface of the plate;
One or more minute needle-like projections protruding from a tip end surface of each of the one or more base portions;
a lip portion formed on an outer edge portion of a tip surface of the base portion,
a pouring hole is formed in the plate and the one or more pedestals, penetrating vertically from another surface of the plate to a tip surface of the pedestal, and when the composition of the first embodiment is discharged from the pouring hole, the composition of the first embodiment spreads in a space formed between the target object, the lip portion, and the tip surface of the pedestal, and the composition of the first embodiment enters the inside of the target object through holes formed by the one or more needle-like projections;
It may be a beauty tool.

In the first embodiment, and in the second and third embodiments described below, the subject (or object) may be the skin of a mammal, preferably a human, or the skin of an animal or a plant. The part with needle-shaped protrusions may be an example of a needle beauty tool, beauty tool, or tool. The needle beauty tool may be an example of a beauty tool or tool. As long as there is no technical contradiction, the matters related to the first embodiment may be applied to the second and/or third embodiment, and the matters related to the second and/or third embodiment may be applied to the first embodiment.

Below, the parts with needle-shaped protrusions included in the needle cosmetic device of the first embodiment will be described as examples using the drawings.

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

In FIG. 1, a part with needle-like protrusions 100 according to the first embodiment is shown puncturing a target object (skin) S. As shown in FIG. 1, the part with needle-like protrusions 100 has a plate 10 and an attachment frame 20. The plate 10 also has an injection hole 10a that penetrates vertically, a number of tiny needle-like protrusions 10b that protrude from one side of the plate, and a lip portion 10c formed on the outer edge of one side of the plate.

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

As shown in FIG. 1, when the liquid medicine C is pushed out from the injection hole 10a, the liquid medicine C spreads in the space formed between the object S, the lip portion 10c, and one side of the plate 10, and also enters the inside of the object S through the holes opened by the multiple needle-like protrusions 10b, that is, it can permeate through the gap between the surface of the needle-like protrusions 10b and the object S. The liquid medicine C may be directly contained in the attachment tube 20b, or may be contained in a syringe (not shown) and a syringe tip 30a via a syringe, for example. In FIG. 1, the syringe tip 30a is a part of the syringe, and the entire syringe is not shown. The method of pushing out the liquid medicine C is not particularly limited, and for example, when the part 100 with needle-like protrusions is attached to a syringe, it can be done by using the plunger of the syringe. After the injection, the needle-shaped protrusion part 100 may be pressed against the object S via the syringe for a predetermined time (less than 1 second to about 30 minutes, preferably several seconds to several minutes). After the predetermined time has elapsed, the syringe may be removed from the object S to pull out the needle-shaped protrusions 10b from the object S. In this way, in the first embodiment, the drug solution C can be spread on the object S inside the lip portion 10c, and can also be permeated into the object S through the holes made by the needle-shaped protrusions 10b. Therefore, the drug solution C can be permeated from both the outside and the inside of the object S. For example, if the object S is human skin and the drug solution C contains a cosmetic substance, the cosmetic substance can be permeated from both the outside and the inside of the skin.

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

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

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

In addition, in the third invention, the specific value of the effective puncture length of the needle-like protrusions of the beauty device of the present invention into the skin is not particularly limited, and may be, for example, 5 μm or more, 10 μm or more, 20 μm or more, 30 μm or more, 40 μm or more, 50 μm or more, 60 μm or more, 70 μm or more, 80 μm or more, 90 μm or more, or 100 μm or more, and may also 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.

Furthermore, in FIG. 1, an example is described in which there is one central hole, which is the injection hole 10a, but the hole does not have to be one, i.e., there may be two or more holes. Also, the hole may be in the center, or not. Also, an example is shown in which the outer shape of the needle-like protrusion 10b is conical, but the needle-like protrusion may be in a polygonal pyramid shape or other needle-like shape (star-shaped, cross-shaped, etc.). Also, needle-like protrusions that are solid needles can be used as hollow needles. Furthermore, the needle-like protrusions that are solid needles that make up the needle-like fine protrusions may have a diameter of 2 to 5000 μm at the thickest part of the needle, more preferably in the range of 5 to 3000 μm.

FIG. 2 is a schematic diagram showing a portion of another embodiment of a part with needle-like protrusions according to the first aspect of the present invention.

2, a part of the part with needle-like protrusions has a plate 11, a number of base portions 11d protruding from one side of the plate 11, a number of tiny needle-like protrusions 11b protruding from the tip surface of each of the number of base portions 11d, and a lip portion 11c formed on the outer edge of the tip surface of the base portion 11d. In addition, the plate 11 and the number of base portions 11d are formed with an injection hole 11a that penetrates vertically from the other side of the plate 11 to the tip surface of the base portion 11d.

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

Also, as shown in Figure 2, the medicinal liquid C spreads over the object S on the inner circumferential side of the lip portion 11c on the contact surface CF2 of the base portion 11d, and can also permeate into the inside of the object S through the holes made by the needle-like protrusions 11b. Therefore, the medicinal liquid C can permeate the object S from both the outside and the inside.

In addition, in the first invention, since a puddle can be formed at the tip side of the base portion 11d, the medicinal liquid C can spread in the area inside the lip portion 11c of each base portion 11d. Therefore, for example, when the part with needle-like protrusions is large and the area of the plate 11 is wide, it is possible to apply the medicinal liquid C in a pinpoint manner. Furthermore, in the first invention, due to the step between the base portion 11d and one surface F1 of the plate 11, the lip portion 11c connected to the base portion 11d can spread the target S in a narrow range and puncture the needle-like protrusions 11b, so that even if the surface of the target S is uneven or the target S is soft, the needle-like protrusions 11b can easily pierce the target S, making it possible to more reliably apply the medicinal liquid C from the outside and inside. Furthermore, in the first invention, regardless of whether the needle-like projections 11b are pierced into the object S, the lip portion 11c contacts the object S, so that the injection pressure (resistance) can be uniformly applied to the inner peripheral area of the lip portion 11c, which is the entire tip portion. This has the advantage of reliably improving the injectability. Furthermore, in the first invention, since the drug solution C can be moved more efficiently from the center to the outside in the gap space between the plate 11 and the round plate of the storage top surface, a band-shaped recess may be formed on the other surface F2 of the plate 11, with the shortest path for the liquid to flow from the center to the multiple injection holes 11a as a flow path. In addition, multiple needle-like projections 11b and/or multiple injection holes 11a may be provided in one base portion 11d. In this case, in each base portion 11d, the medicinal liquid C pushed out from the multiple injection holes 11a spreads over the target object S on the inner periphery of the lip portion 11c on the contact surface CF2 of the base portion 11d, and can also penetrate into the inside of the target object S through holes made by the multiple needle-like protrusions 11b.

Note that the part with needle-like protrusions shown in FIG. 2, as well as the entire part (not shown), may have various configurations and modifications, just like the needle-like protrusion part 100 described above.

The first beauty tool of the present invention may further include, in addition to the above-mentioned part with needle-like protrusions, a fixing device to which the part with needle-like protrusions can be attached. The fixing device can also contain a medicinal liquid.

FIG. 3 is a schematic diagram showing one embodiment of a beauty device equipped with a part with needle-like protrusions and a fixing device.

As shown in FIG. 3, the beauty tool 200 includes a part 101 with needle-like protrusions and a syringe 30 as a fixing device to which the part 101 with needle-like protrusions is attached. The part 101 with needle-like protrusions includes an attachment frame 20 and a plate 10. The attachment frame 20 includes a plate support portion 20a and an attachment tube 20b. The plate 10 includes an injection hole (not shown) that penetrates vertically, one or more minute needle-like protrusions protruding from one side of the plate 10, and a lip portion formed on the outer edge portion of one side of the plate 10. The syringe 30 includes a syringe tube (main body) 30b and a plunger 30c. The part 101 with needle-like protrusions is attached from the attachment tube 20b side of the attachment frame 20 to the syringe tube tip 30a side of the syringe 30. The syringe tube 30b contains the medicinal liquid C, and the plunger 30c is inserted into the syringe tube 30b. When the rear end pressing piece 30d is pressed, the plunger 30c moves inside the syringe barrel 30b, and the medicinal liquid C is released into the needle-shaped protrusion part 101 and can penetrate into the target object (not shown). In the first invention, the fixing device can be a syringe having a volume of, for example, 1 mL, 2.5 mL, 5 mL, or 10 mL. Depending on the specific use of the needle-shaped protrusion part, the syringe may have a larger or smaller volume.

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

The first beauty tool of the present invention may also be optionally provided with a cap (not shown), for example, on the needle-like protrusion side of the part with needle-like protrusions.

In addition, in the first invention and the second and third inventions described below, the pressure with which the beauty tool of the present invention is pressed is not particularly limited, and may be, for example, 1200 gf or less, 1100 gf or less, 1000 gf or less, 900 gf or less, 800 gf or less, 700 gf or less, or 600 gf or less, or 50 gf or more, 100 gf or more, 200 gf or more, 300 gf or more, 400 gf or more, 500 gf or more, or 600 gf or more. In order to further exert the effect of the third invention, it is preferable that the pressure with which the beauty tool of the present invention is pressed is, for example, 900 gf or less.

<<Beauty kit according to the first aspect of the present invention>>
The first invention also provides a cosmetic kit, particularly a cosmetic kit for improving the barrier function and/or clarity of the skin. Preferably, the first invention provides a cosmetic kit for improving the barrier function and clarity of the skin.

The beauty kit of the first invention includes the above-mentioned beauty tool of the first invention and a medicinal solution. For a detailed explanation of the beauty tool of the first invention, please refer to the explanation in the above-mentioned "Beauty tool of the first invention".

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

The first inventors' intensive research has revealed that the beauty device of the first invention can improve the permeability of niacinamide into the skin. Therefore, in the first invention, it is preferable that the medicinal solution contains niacinamide.

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

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

Furthermore, when the first beauty device of the present invention injects a medicinal solution containing niacinamide into the subject via a part with needle-like projections, it can improve the transparency of the skin in a short period of time compared to when niacinamide is directly applied to the skin. Therefore, the first beauty device of the present invention may be a beauty device for improving the transparency of the skin in a short period of time. Here, a short period of time for improving the transparency of the skin may 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, within 1 week, and the lower limit is not particularly limited, and may be, for example, 1 day or more, 2 days or more, 3 days or more, 4 days or more, 5 days or more, 6 days or more, or 1 week or more.

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

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

The beauty kit of the first invention may optionally further include an instruction manual. The instruction manual may include instructions on how to set up the beauty tool of the first invention before use, how to hold it, how to use it, how often to use it, etc.

Here, the explanation regarding FIG. 3 above may be referred to as appropriate for the method of using the first beauty kit of the present invention. The number of times that the needle-shaped protrusion-equipped parts of the first beauty tool of the present invention are applied to the target object is not particularly limited, and the number of times may be increased as appropriate. For example, the medicinal liquid may be released and penetrated into one application site 1 or more times, 3 or more times, 5 or more times, 10 or more times, 15 or more times, 20 or more times, 25 or more times, 30 or more times, or 35 or more times, or may be released and penetrated into one application site 100 or less times, 50 or less times, 10 or less times, 7 or less times, 6 or less times, 5 or less times, 4 or less times, 3 or less times, or 2 or less times. The amount of medicinal liquid released each time is not particularly limited, and may be 0.1 μL or more, 0.2 μL or more, 0.3 μL or more, 0.4 μL or more, 0.5 μL or more, 0.6 μL or more, 0.7 μL or more, 0.8 μL or more, 0.9 μL or more, 1.0 μL or more, 1.1 μL or more, 1.2 μL or more, 1.3 μL or more, 1.4 μL or more, 1.5 μL or more, 1.6 μL or more, 1.7 μL or more, 1.8 μL or more, 1.9 μL or more, or 2.0 μL or more, and may be 10 μL or less, 5 μL or less, or 2 μL or less. The method of applying the first beauty tool of the present invention to the object is not particularly limited, and for example, the beauty tool may be applied while rotating or without rotating the beauty tool.

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

Method for improving skin barrier function and/or transparency
The first invention also provides a method for improving the barrier function and/or transparency of the skin. Preferably, the first invention provides a method for improving the barrier function and transparency of the skin.

The first method of the present invention for improving the barrier function and/or transparency of the skin includes applying the above-mentioned first cosmetic device of the present invention to the skin. In particular, the first method of the present invention for improving the barrier function and/or transparency of the skin preferably uses the first cosmetic device of the present invention in combination with a medicinal solution containing niacinamide. This is because the barrier function and/or transparency of the skin can be improved in a short period of time compared to the method of using the first cosmetic device of the present invention alone or the method of applying niacinamide directly to the skin. Therefore, the first method of the present invention may be a method for improving the barrier function and/or transparency of the skin in a short period of time.

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

More preferably, the first method of the present invention for improving the barrier function and transparency of the skin includes injecting a medicinal solution into a subject, and the medicinal solution includes niacinamide.

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

In addition, in the first aspect of the present invention, the skin may be not only mammalian skin (particularly human skin) but also animal skin, or the surface of a plant stem, trunk, or leaf, etc.

[Second aspect of the present invention]
Hereinafter, the second embodiment of the present invention will be described in detail with reference to the drawings. For convenience of explanation, the same or corresponding parts in each drawing are given the same reference numerals, and duplicate explanations are omitted. In addition, not all components of the embodiment are necessarily essential, and some components may be omitted. However, the present invention is not limited to the following embodiment, and various modifications can be made within the scope of the invention.

《Needle beauty equipment》
The needle cosmetic device of the second invention (hereinafter also simply referred to as the "beauty device of the second invention") has parts with needle-like projections and is intended to promote collagen production. The beauty device of the second invention may also have parts with needle-like projections and be intended to improve sagging.

The needle-shaped protrusion parts of the second beauty tool of the present invention may be, for example, the "needle-shaped protrusion parts" disclosed in Patent Document 2. The needle-shaped beauty tool of the second invention may be the beauty tool (apparatus) disclosed in Patent Document 2. Note that in Patent Document 2, the "needle-shaped protrusion parts" are intended to keep liquid compositions/liquid cosmetics, with no particular active ingredients, on the surface and inside of an object so that they do not leak through gaps, and there is no disclosure or suggestion regarding collagen production or improvement of sagging skin.

Through intensive research by the inventors, it was discovered that collagen production can be promoted by using the second beauty device of the present invention, which has such parts with needle-like protrusions. In addition, sagging skin can also be improved by using the second beauty device of the present invention.

Without being limited by theory, it is speculated that the second beauty device of the present invention, when its needle-like protrusion parts are applied to the skin, causes significant deformation deep into the skin, which in turn promotes blood flow and collagen production.

The part with needle-like projections according to the second aspect of the present invention comprises:
A plate having a pouring hole extending vertically therethrough;
One or more minute needle-like projections protruding from one surface of the plate;
a lip portion formed on an outer edge of one surface of the plate;
and a plate;
one or more pedestals protruding from one surface of the plate;
One or more minute needle-like projections protruding from a tip end surface of each of the one or more base portions;
A lip portion formed on an outer edge portion of a tip surface of the base portion;
[0043]

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

<<Beauty kit according to the second aspect of the present invention>>
The second invention also provides a cosmetic kit, particularly a cosmetic kit for promoting collagen production.

The beauty kit of the second invention includes the beauty tool of the second invention described above and a medicinal solution. For a detailed explanation of the beauty tool of the second invention, please refer to the explanation in the "Beauty tool of the first invention" section above.

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

Through intensive research by the inventors, it has been found that the beauty device of the second invention of the present invention can improve the permeability of niacinamide into the skin. Therefore, in the second invention of the present invention, it is preferable that the medicinal solution contains niacinamide.

Niacinamide is as explained in the "First Invention" section above, so a detailed explanation will be omitted here.

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

The second beauty device of the present invention can also improve sagging skin when a medicinal liquid containing niacinamide is injected into the target object via a part with needle-like projections.

It is known that sagging occurs with aging and can bring about major changes to facial appearance, such as loosening of the face line and the appearance of nasolabial folds and marionette lines. Therefore, many people wish to improve this for anti-aging purposes.

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

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

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

The beauty kit of the second invention may optionally further include an instruction manual. The instruction manual may include instructions on how to set up the beauty tool of the second invention before use, how to hold it, how to use it, how often to use it, etc.

Here, the explanation regarding FIG. 3 above may be referred to as appropriate for the method of using the second beauty kit of the present invention. The number of times that the needle-shaped protrusion-equipped parts of the second beauty tool of the present invention are applied to the target object is not particularly limited, and the number of times may be increased as appropriate. For example, the medicinal liquid may be released and penetrated into one application site 1 or more, 3 or more, 5 or more, 10 or more, 15 or more, 20 or more, 25 or more, 30 or more, or 35 or more times, or may be released and penetrated into one application site 100 or less, 50 or less, 10 or less, 7 or less, 6 or less, 5 or less, 4 or less, 3 or less, or 2 or less times. The amount of medicinal liquid released each time is not particularly limited, and may be, for example, 0.1 μL or more, 0.2 μL or more, 0.3 μL or more, 0.4 μL or more, 0.5 μL or more, 0.6 μL or more, 0.7 μL or more, 0.8 μL or more, 0.9 μL or more, 1.0 μL or more, 1.1 μL or more, 1.2 μL or more, 1.3 μL or more, 1.4 μL or more, 1.5 μL or more, 1.6 μL or more, 1.7 μL or more, 1.8 μL or more, 1.9 μL or more, or 2.0 μL or more, or may be 10 μL or less, 5 μL or less, or 2 μL or less. The method of applying the second beauty tool of the present invention to the object is not particularly limited, and may be, for example, applied while rotating the beauty tool, or may be applied without rotating the beauty tool.

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

Method for promoting collagen production
The second invention also provides a method for promoting collagen production, which comprises applying the above-mentioned cosmetic device according to the second invention to skin.

The collagen production promotion method of the second invention is preferably used in combination with a cosmetic device of the second invention and a medicinal solution containing niacinamide. This is because collagen production can be promoted more efficiently than when the cosmetic device of the second invention is used alone or when niacinamide is applied directly to the skin.

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

More preferably, the second collagen production promoting method of the present invention includes injecting a medicinal solution into a subject, and the medicinal solution includes niacinamide.

Furthermore, the collagen production promoting method of the second invention can improve sagging. Therefore, the second invention can provide a method for improving sagging. The method for improving sagging according to the second invention can be performed more efficiently than the method of applying niacinamide directly to the skin or the method of applying the beauty device of the second invention alone to the skin.

The collagen production promotion method and method for improving sagging according to the second aspect of the present invention are strictly for cosmetic purposes and are not so-called "medical procedures" such as surgical procedures for humans or treatments for human illnesses.

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

[Third aspect of the present invention]
Hereinafter, the third embodiment of the present invention will be described in detail with reference to the drawings. For convenience of explanation, the same or corresponding parts in each drawing are given the same reference numerals, and duplicate explanations will be omitted. In addition, not all components of the embodiment are necessarily essential, and some components may be omitted. However, the present invention is not limited to the following embodiment, and various modifications can be made within the scope of the invention.

《Beauty Equipment》
The beauty tool of the third aspect of the present invention is
1. A cosmetic device for use in a cosmetic method for improving a subject's skin condition, comprising:
The beauty tool is a needle beauty tool having a part with a needle-like protrusion,
the part 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 beauty method is
(i) applying a pressing pressure of 100 to 1200 gf to the skin with the beauty tool; and (ii) using the beauty tool at least once every two days and at least twice a day, or at least three times a week.
It is a beauty tool.

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

The needle-shaped protrusion parts of the third beauty tool of the present invention may be, for example, the "needle-shaped protrusion parts" disclosed in Patent Document 2. The needle-shaped beauty tool of the third invention may be the beauty tool (apparatus) disclosed in Patent Document 2. Note that in Patent Document 2, the "needle-shaped protrusion parts" are intended to keep liquid compositions/liquid cosmetics, with no particular active ingredients, on the surface and inside of an object so that they do not leak through gaps, and there is no disclosure or suggestion regarding collagen production or improvement of sagging, etc.

Through intensive research by the present inventors, it was discovered that collagen production can be promoted by using the third inventive beauty device having such a part with needle-like protrusions.

Without being limited by theory, the effective puncture length of the needle-like projections of the third beauty device of the present invention is such that it does not reach the dermis, so that it stimulates skin cells by pressure without damaging the dermis, and as a result, surprisingly, it is possible to adjust the M1/M2 balance and increase the number of myofibroblasts.

Here, "M1/M2 balance" refers to the balance between the relative numbers of M1 and M2 macrophages. The M1/M2 balance is closely involved in controlling immune responses and inflammation in the skin, and also affects wound healing, inflammatory diseases, and even beauty and skin aging. Therefore, "adjusting the M1/M2 balance" refers to increasing the ratio of M2 to M1. Adjusting the M1/M2 balance can result in, for example, promotion of collagen production, immune induction, wound healing, etc.

"Myofibroblasts" are cells found mainly in the dermis, and are particularly important in wound healing and tissue repair. Myofibroblasts have the properties of both normal fibroblasts and smooth muscle cells, and are activated during the process of wound healing and tissue remodeling, playing an important role in repairing damaged skin. In addition, myofibroblasts around blood vessels play an important role in maintaining the vascular structure, so an increase in their number has an impact on the stabilization of the vascular structure. Therefore, an increase in the number of myofibroblasts can result in, for example, the promotion of collagen production, immune induction, wound healing, and stabilization of the vascular structure.

The subject of the third invention may therefore be a subject in which the M1/M2 balance needs to be adjusted.

The subject of the third invention may be a subject in which it is necessary to increase the number of muscle fiber cells.

A part with needle-like projections according to the third aspect of the present invention comprises:
A plate having a pouring hole extending vertically therethrough;
One or more minute needle-like projections protruding from one surface of the plate;
a lip portion formed on an outer edge of one surface of the plate;
and a plate;
one or more pedestals protruding from one surface of the plate;
One or more minute needle-like projections protruding from a tip end surface of each of the one or more base portions;
A lip portion formed on an outer edge portion of a tip surface of the base portion;
[0043]

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

<<Third beauty kit of the present invention>>
The third invention also provides a cosmetic kit, particularly a cosmetic kit for promoting collagen production.

The beauty kit of the third invention includes the beauty tool of the third invention described above and a medicinal liquid. For a detailed explanation of the beauty tool of the third invention, please refer to the explanation in the "Beauty tool of the first invention" section above.

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

Through intensive research by the inventors, it has been found that the beauty device of the third invention of the present invention can improve the permeability of niacinamide into the skin. Therefore, in the third invention of the present invention, it is preferable that the medicinal solution contains niacinamide.

Niacinamide is as explained in the "First Invention" section above, so a detailed explanation will be omitted here.

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

The third beauty device of the present invention can improve sagging skin when a medicinal liquid containing niacinamide is injected into the target object via a part with needle-like projections.

It is known that sagging occurs with aging and can bring about major changes to facial appearance, such as loosening of the face line and the appearance of nasolabial folds and marionette lines. Therefore, many people wish to improve this for anti-aging purposes.

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

In response to these problems, the beauty kit of the third invention, particularly when used in combination with the beauty tool of the third invention and a medicinal liquid containing niacinamide, can improve sagging skin in a minimally invasive, rapid, simple, and easy manner. Furthermore, it goes without saying that improving sagging skin with the beauty kit of the third invention is easier than the facial muscle training and massage described above, and can be performed more efficiently than, for example, applying niacinamide directly to the skin or applying the beauty tool of the third invention alone to the skin. Therefore, the beauty kit of the third invention may be one for improving sagging skin.

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

The beauty kit of the third invention may optionally further include an instruction manual. The instruction manual may include instructions on how to set up the beauty tool of the third invention before use, how to hold it, how to use it, how often to use it, etc.

Here, the explanation regarding FIG. 3 above may be referred to as appropriate for the method of using the beauty kit of the third invention. The number of times that the needle-shaped protrusion-equipped parts of the beauty tool of the third invention are applied to the target object is not particularly limited, and the number of times may be increased as appropriate. For example, the medicinal liquid may be released and penetrated into one application site 1 or more times, 3 or more times, 5 or more times, 10 or more times, 15 or more times, 20 or more times, 25 or more times, 30 or more times, or 35 or more times, or may be released and penetrated into one application site 100 or less times, 50 or less times, 10 or less times, 7 or less times, 6 or less times, 5 or less times, 4 or less times, 3 or less times, or 2 or less times. The amount of medicinal liquid released each time is not particularly limited, and may be, for example, 0.1 μL or more, 0.2 μL or more, 0.3 μL or more, 0.4 μL or more, 0.5 μL or more, 0.6 μL or more, 0.7 μL or more, 0.8 μL or more, 0.9 μL or more, 1.0 μL or more, 1.1 μL or more, 1.2 μL or more, 1.3 μL or more, 1.4 μL or more, 1.5 μL or more, 1.6 μL or more, 1.7 μL or more, 1.8 μL or more, 1.9 μL or more, or 2.0 μL or more, or may be 10 μL or less, 5 μL or less, or 2 μL or less. The method of applying the second beauty tool of the present invention to the object is not particularly limited, and may be, for example, applied while rotating the beauty tool, or may be applied without rotating the beauty tool.

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

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

《Beauty Methods》
The third invention can also provide a cosmetic method.

The cosmetic method of the third invention of the present invention comprises:
A cosmetic method for improving a skin condition of a subject, comprising:
(i) applying a pressure of 100 to 1200 gf to the skin with a beauty tool; and (ii) using the beauty tool at least once every two days and at least twice a day, or at least three times a week; and the beauty tool is a needle beauty tool having a part with a needle-like protrusion,
the part with needle-like protrusions includes needle-like protrusions, and the effective puncture length of the needle-like protrusions into the skin is a length that does not reach the dermis;
It is a beauty method.

The beauty tool used here may be the "third beauty tool of the present invention" described above. Therefore, for the beauty method of the third invention, the explanation of the "third beauty tool of the present invention" and the "third beauty kit of the present invention" described above can be referred to.

The pressure with which the beauty tool is pressed against the skin may be, for example, 300 gf or more, 400 gf or more, 500 gf or more, or 600 gf or more, and may be 900 gf or less, 850 gf or less, 800 gf or less, 750 gf or less, 700 gf or less, or 650 gf or less.

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

Method for promoting collagen production
The third invention also provides a method for promoting collagen production. The method for promoting collagen production of the second invention comprises applying the above-mentioned cosmetic device of the third invention to skin.

The collagen production promotion method of the third invention is preferably performed by using the beauty device of the third invention in combination with a medicinal solution containing niacinamide. This is because collagen production can be promoted more efficiently than by using the beauty device of the third invention alone or by applying niacinamide directly to the skin.

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

More preferably, the second collagen production promoting method of the present invention includes injecting a medicinal solution into a subject, and the medicinal solution includes niacinamide.

Furthermore, the collagen production promoting method of the third invention can improve sagging. Therefore, the third invention can provide a method for improving sagging. The method for improving sagging according to the second invention can be performed more efficiently than the method of applying niacinamide directly to the skin or the method of applying the beauty device of the second invention alone to the skin.

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

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

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

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

Specifically, fresh skin excised from the abdomen of a subject who had given informed consent was purchased and obtained. In Example 1-1, the first beauty device of the present invention was applied to freshly excised human skin 2 to 8 times with appropriate pressure, rotating the beauty device each time, and then cultured on a medium. In Example 2, a nonwoven fabric impregnated with a drug solution containing niacinamide was placed on the ex vivo skin and applied so as to be in close contact with the skin, and left to stand for 5 minutes, after which the nonwoven fabric was removed once, the beauty device was applied as in Example 1-1, and the nonwoven fabric was applied again for 5 minutes. In the control, these treatments (Examples 1-1 and 1-2) were not performed and the tissue was similarly cultured on a medium. The medium was replaced every day, and tissue pieces were collected on the 7th day. In addition, an antibody against Ki-67 (SP6) (Thermo Fisher Scientific, RM-9106-S, rabbit mouse monoclonal antibody) was used as a cell proliferation marker. The results are shown in Figures 4 and 5.

Figure 4 shows the results of immunofluorescent staining of Ki-67 and nuclei (Hoechst). Figure 5 is a graph showing the results of quantifying the length of the epidermal basement membrane using the image analysis software Image J for the stained image in Figure 4, and counting the number of Ki-67 positive epidermal cells per length of the epidermal basement membrane.

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

Example 1-3
In Example 1-3, the first beauty tool of the present invention was set up with a constant-volume dispenser (a pen-shaped cosmetic container with a volume of about several mL) containing a liquid medicine ("liquid medicine A") containing niacinamide, and the amount of water evaporation from the skin was examined for up to 8 weeks after application to a subject once every two days. As a control, the first beauty tool of the present invention was not used, and the amount of water evaporation from the skin was examined when the subject applied the same amount of liquid medicine A to the subject once every two days as when using the beauty tool. The results are shown in FIG. 7.

More specifically, the following was done:
1. The protruding surface was placed flat against the subject's skin, pressed in, and then clicked once (pressed firmly but not to the point of causing pain).
2. The above step "1." was repeated, and the movement was applied little by little while referring to FIG.
(Total 50 clicks (25 clicks x left and right))
a: Nasolabial folds, marionette lines 10 clicks x left and right b: Corners of the eyes to under the eyes 10 clicks x left and right c: Cheeks (problem areas for dryness, pores, etc.) 5 clicks x left and right 3. Spread the liquid over the entire face and blend with the entire palm of your hand.

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

The formulation of "Chemical Solution A" is as shown in Table 2 below:

The amount of water lost from the skin was measured by the transdermal evaporation method using a Vapometer (Delfin Technologies).

As is clear from the results in Figure 7, it was found that within about two weeks of application, Example 1-3 showed a significant increase in moisture content compared to the control. In other words, it was suggested that Example 1-3 can improve the skin's barrier function in as short a period as two weeks.

Example 1-4
In Example 1-4, the first beauty tool of the present invention was set up with a constant-volume dispenser (a pen-shaped cosmetic container with a volume of about several mL) containing a niacinamide-containing liquid ("liquid A"), and the skin transparency was examined for up to 8 weeks after application to a subject once every two days in the same manner as in Example 1-3 described above. As a control, the first beauty tool of the present invention was not used, and the skin transparency was examined when the subject was applied with the same amount of liquid A as when using the beauty tool once every two days.

Six expert evaluators evaluated the transparency of the skin using the method in Table 3 below, based on the evaluation scale shown in Figure 8. The evaluation is judged based on the overall balance of the face. Therefore, "not felt" includes "absent at all" and "very slight, but not felt when looking at the face as a whole."

The results are shown in Figure 9.

As is clear from the results in Figure 9, compared to the control, Examples 1-4 showed a greater improvement in skin transparency from an earlier stage.

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

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

More specifically, the experimental method is as follows:
(Confocal Raman Spectroscopy)
"Chemical Solution B" was applied to excised human skin at 5 μL per square centimeter.
The first cosmetic device of the present invention was then applied 50 times to excised human skin.
The time-dependent change in the Raman spectrum in the fingerprint region (600-2200 cm ^-1 ) was evaluated.
As a control, "medicinal solution B" was simply applied to an excised human skin at 5 μL per square centimeter.

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

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

The formulation of "Chemical Solution B" is as shown in Table 1-4 below:

The "model drug" used in Reference Example 1-2 has the same formulation as "Chemical Solution B" above, except that 0.2% by mass of sodium fluorescein was added instead of 5.0% by mass of niacinamide, and the remaining amount was adjusted with water.

As is clear from Figure 10, Reference Example 1-1 promoted the penetration of niacinamide in a much shorter time than the control.

As is also clear from Figure 11, Reference Example 1-2 showed a significantly improved penetration amount of the drug solution containing the model drug (water-soluble fluorescent substance) compared to both Controls 1 and 2.

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

In each of the following experiments, unless otherwise specified, the second beauty device of the present invention used had a circular part with needle-like protrusions having a diameter of 15 mm, an effective puncture length of the needle-like protrusions (i.e., needles) of 20 μm, and 18 needle-like protrusions.

Example 2-1 and Example 2-2
The collagen production promotion was evaluated when the second beauty device of the present invention was applied alone to freshly excised human skin (Example 1), and when the second beauty device of the present invention was applied in combination with 5% by mass of niacinamide solution (Example 2-2). As a control, a similar freshly excised human skin was used. The obtained results are shown in FIG. 4-1.

Specifically, fresh skin excised from the abdomen of a subject who had given informed consent was purchased and obtained. In Example 2-1, the second beauty tool of the present invention was applied to fresh excised human skin ex vivo 2 to 8 times with an appropriate pressure while rotating the beauty tool each time, and then cultured on a medium. In Example 2, a nonwoven fabric impregnated with a drug solution containing niacinamide was placed on the ex vivo skin and applied so as to be in close contact with the skin, and left to stand for 5 minutes, after which the nonwoven fabric was removed once, the beauty tool was applied in the same manner as in Example 2-1, and the nonwoven fabric was applied again for 5 minutes. In the control, these treatments (Examples 2-1 and 2-2) were not performed and the skin was similarly cultured on a medium. In addition, the amount of procollagen gene (COL1A1) produced was confirmed by RT-qPCR (Δ-ΔCT method) for the treated skin and the control skin after 24 hours of culture, and the production of procollagen I was confirmed.
- Each test was carried out six times.
- qPCR: n=3

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

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

Example 2-3
In Example 2-3, differentiation into myofibroblasts was confirmed when the second beauty device of the present invention was used alone.

In Example 2-3, the second beauty tool of the present invention was applied to freshly excised human skin 2 to 8 times with appropriate pressure, rotating the beauty tool each time, and then cultured on a medium. As a control, the second beauty tool of the present invention was not applied, but the tissue was cultured on a similar dedicated medium, and the tissue fragment was collected the next day. In addition, antibodies against α-SMA (α-Smooth Muscle Actin) and Vimentin were used as markers for myofibroblasts, and α-SMA/Vimentin positive cells were counted as myofibroblasts. The results obtained are shown in Figures 5-1 and 5-2.

Figure 5-1 shows the results of immunofluorescence staining of α-SMA (α-Smooth Muscle Actin)/Vimentin and nuclei (Hoechst). Figure 5-2 is a graph showing the quantification of the stained image in Figure 5-1 using the image analysis software Image J, 200 μm below the epidermal basement membrane, and the count of α-SMA/Vimentin positive cells (myofibroblasts) within that area.

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

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

More specifically, the experimental method is as follows:
(Confocal Raman Microscopy)
"Chemical solution A" was applied directly to excised human skin at 5 μL per square centimeter.
-The second inventive cosmetic device was then applied 50 times to excised human skin.
The time-dependent change in the Raman spectrum in the fingerprint region (600-2200 cm ^-1 ) was evaluated.
As a control, "medicinal solution A" was simply applied to an excised human skin at 5 μL per square centimeter.

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

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

The prescription for "Chemical Solution A" is as shown in Table 2-2 below:

The "model drug" used in Example 2-4-2 was similar to the above-mentioned "medicinal solution A" except that 0.2% by mass of sodium fluorescein was added instead of 5.0% by mass of niacinamide, and the remaining amount was adjusted with water.

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

As is also clear from Figure 7-1, Example 2-4-2 showed a marked improvement in the amount of penetration of the drug solution containing the model drug (water-soluble fluorescent substance) compared to both Controls 1 and 2.

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

More specifically, the following was done:
1. The protruding surface was placed flat against the subject's skin, pressed in, and then clicked twice.
2. The above operation "1." was repeated, and the operation was applied while moving it little by little with reference to FIG.
(50 sets in total, only applicable to the specified side)
a: Nasolabial folds 10 sets b: Eye corners to under eyes 10 sets c: Forehead, between the eyebrows 10 sets d: Entire side 20 sets (centered on cheeks)
3. After that, I lightly applied the liquid to one side of my face.

The subjects were 34 women aged 45-59 and with a BMI of 18.5-25.0.

The formulation of "Chemical Solution B" is as shown in Table 3 below:

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

As is clear from the results of Figures 9-1 and 10-1, in Example 2-5, it was found that the subject's facial line was able to be sharpened in two weeks. In other words, in Example 2-5, it was suggested that by using the second beauty device of the present invention in combination with a medicinal solution containing niacinamide, it is possible to improve sagging in the short period of two weeks.

Example 2-6
In Example 2-6, the second beauty tool of the present invention was set up with a fixed-volume dispenser (a pen-shaped cosmetic container having a volume of about several mL) containing a liquid medicine containing niacinamide ("liquid medicine C"), and the test subject was given the liquid medicine once every two days. The effect of improving sagging skin after the application was evaluated in comparison with the case where the liquid medicine of the same formulation was simply applied (Comparative Example 2-1).

More specifically, the following was done:
1. The protruding surface was placed flat against the subject's skin, pressed in, and then clicked once (pressed firmly but not to the point of causing pain).
2. Repeat the above step 1, moving it little by little while referring to Figure 8-1.
(Total 50 clicks (25 clicks x left and right))
a: Nasolabial folds, marionette lines 10 clicks x left and right b: Corners of the eyes to under the eyes 10 clicks x left and right c: Cheeks (problem areas for dryness, pores, etc.) 5 clicks x left and right 3. Spread the liquid over the entire face and blend with the entire palm of your hand.

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

The formulation of "Chemical Solution C" is as shown in Table 4 below:

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

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

In this way, Examples 2-6 suggest that by using the second beauty device of the present invention in combination with a medicinal solution containing niacinamide, it is possible to improve sagging skin that cannot be improved by using regular cosmetics in the short period of two weeks.

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

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

More specifically, in each example, one panel member was given a second cosmetic device of the present invention to inject the liquid into one half of the face (one week of continuous use), and the other half of the face was given the same liquid formulation (one week of continuous use). The sagging grade was evaluated by one evaluator before and after each treatment. The sagging grade was evaluated in increments of 0.5 for three areas: upper cheek, lower cheek, and outer cheek, based on Non-Patent Document 1 (Skin Research and Technology 2009; 15: 299-305). The evaluation criteria were as follows:
(Evaluation Criteria)
In terms of sagging grade, the change in the grade is -0.5 or less in about a week.
3 sites: Graded A 2 sites: Graded B 1 site: Graded C 0 sites: Graded D The evaluation results are shown in Table 6.

The more negative the change in the sagging grade, the greater the effect of improving sagging. Also, the more areas that change, the greater the effect of improving sagging. Therefore, an "A" rating is the most effective in improving sagging, followed by "B," "C," and "D," in that order.

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

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

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

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

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

<Changes in myofibroblast numbers and M1/M2 macrophages over time>
(RNA Seq)
Fresh human abdominal skin (Genoskin, France) (n=4, 29-39 years, mean=35.8 years) was flown from France and organ cultured to maintain tissue equivalence for the duration of the study. Full thickness skin, excised of subcutaneous fat, was used in both studies.

The microneedles were applied once every two days. The skin was placed on a corkboard with the stratum corneum side facing up, and a pressure of 600 gf was applied vertically using an instrument (Pressure Instrument, Clinical & Derm Inc.; no need to specify, but please use if necessary) for 10 seconds, after which the direction was changed by 90° and the needles were pressed twice more.

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

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

(Paraffin block, sectioning)
Fresh human abdominal skin was dehydrated and fixed using cold acetone according to the AMeX method, then substituted with acetone, methyl benzoate, and xylene, and embedded in paraffin. Sections were made at a thickness of 4 μm, and sections for histological staining were prepared.

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

Based on the results of the fluorescent immunostaining, the image analysis software ImageJ was used to count myofibroblasts (αSMA/vimentin positive cells) present within a range of 200 μm directly below the epidermal basement membrane, and the changes over time were plotted as a graph (Figure 13).

Based on the results of the fluorescent immunostaining, the image analysis software ImageJ was used to count myofibroblasts (CD31 positive cells) present within a range of 200 μm just below the epidermal basement membrane, and the changes over time were plotted as a graph (Figure 14).

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

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

As is clear from the results of Figures 12 to 14, it was found that the number of myofibroblasts increased over time in the skin to which the microneedles of the present invention were applied. The number of CD31-positive cells, which indicate blood vessels, did not change, but it was suggested that the myofibroblasts around the blood vessels may have increased.

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

[Supplementary explanation of the third invention]
This new concept skin vitalizer uses mechanobiological stimulation to activate skin cells and efficiently deliver nutrients, opening up a new dimension in skin care.

Overview As an excellent transdermal and intradermal drug delivery system (DDS), microneedles (MN) can circumvent the skin barrier function with a simple and sophisticated mechanism. However, with existing MN technologies in the cosmetic field, it is difficult to control the puncture depth, making it difficult to achieve safety and efficacy at the same time. For example, Solid-MN (solid-type microneedle) causes unacceptable levels of damage due to its excessive puncture depth, and Dissolving-MN (dissolving type microneedle) cannot deliver sufficient drug due to its fragility dependent on basic polymers. In this disclosure, this problem has been solved by developing a novel MN technology featuring a unique shape that pseudo-lengthens MN to control the puncture depth.

Several tests, including confocal Raman spectroscopy, proved that the puncture depth remained within the stratum corneum (SC). Meanwhile, the unique shape of the MN ensured that a large amount of the drug was rapidly delivered to the viable epidermis (VE), which is why it was named "Injectable-MN". Furthermore, the RNA-seq results suggested that Injectable-MN could induce skin regeneration similar to wound healing without causing any damage. Finally, a home test using Injectable-MN supplemented with niacinamide showed significant improvements in sagging, wrinkles, skin clarity, and barrier function in just two weeks. In conclusion, our Injectable-MN is an extremely versatile DDS platform that can unlock the potential of functional skin care and bring unprecedented results to consumers.

Keywords: drug delivery, microneedle, injection, mechanobiology, rejuvenation

Introduction MN uses a simple "puncture" mechanism to break through the barrier function of the SC and realize transdermal and intradermal delivery of drugs. Because of its simple mechanism, it can be combined with various drugs and is easy to use. Due to these advantages, MN is a highly versatile transdermal and intradermal DDS (References 1, 2, 3). The use of MN is also increasing in the cosmetic field, and among the several types of MN, solid MN and soluble MN are the mainstream (References 1, 2, 4, 5).

In particular, Solid-MN has become popular, especially for use in cosmetic procedures (References 2, 4, 6). The main idea behind this technique is to use a sharp, hard metal needle to perforate the skin, helping drugs penetrate the skin. In addition, the wound healing process caused by the perforation of the dermis has a remodeling effect on the dermal matrix structure. These two mechanisms are increasingly recognized to provide a high rejuvenation effect. However, this procedure involves bleeding, downtime, and risks such as induction of infection and scar formation. Products with such risks are not acceptable for consumers' daily skin care.

So how can we achieve the same high rejuvenating effects as Solid-MN while still ensuring its safety as a cosmetic?

To solve this difficult problem, we focused on the shape of the MN and developed an approach based on skin depth.

Our first attempt addressed the fundamental challenge of controlling the penetration depth. Cosmetic applications require selective penetration of thin layers such as the SC and VE, but obtaining the fine control required for this is extremely difficult (Reference 2). According to Guang et al. (Reference 8), only needle lengths of 600 μm or more can be reliably penetrated, because short needles are hindered by the tough SC and viscoelasticity of the skin, which absorbs shock, and the MN cannot penetrate the SC and remains in the superficial layers.

On the other hand, MN needles with a length of more than 600 μm can reach the dermis, but there is a possibility of causing damage. Considering safety as a cosmetic product, it is necessary to limit the depth to about 200 μm, which is the depth of the epidermis. However, if the needle length is shortened to 200 μm or less, the needle will hardly penetrate the skin when simply pressed against the skin with the pad of a finger (Reference 9).

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

Our hypothesis was to achieve the following:
First, the skin was deformed significantly to reduce the shock absorption capacity of the skin, while the MN of the desired length was embedded in the stretched SC. At the same time, this large deformation itself allowed access to the deeper part of the skin.

To achieve this, we first created MNs of various shapes and evaluated their puncture properties.

It has also become possible to inject medicinal liquids into the skin via this MN. Using permeability evaluation methods such as confocal Raman microscopy, it was verified whether this was possible with the MN that was created. Furthermore, using RNA-seq and blood flow observation, it was verified that the new MNs could reach the deep layers of the skin below the dermis, which was difficult to do with conventional cosmetics.

Finally, niacinamide (Reference 10), which is known to be involved in various functions in the body and to be beneficial for the skin, was added to a formulation used with MN and evaluated in a home study to see what changes it could make.

Experimental Materials and Methods

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

The PGA-MN is made of polyglycolic acid (PGA), which is known as a resin with biocompatibility and biodegradability. The MNs are arranged at an appropriate pitch, and there is a base of an appropriate shape under the MN so that the puncture part remains within the SC. A close-up of the tip of the base shows that a solid MN, an independent liquid injection hole, and a protective ring surrounding them are formed (Figure 20-1, a). The total length of the MN is 120 μm, and since the surrounding protective ring plays the role of controlling the puncture depth, the effective puncture length is 20 μm, which remains within the SC. The PGA-MN is supplied with a drug solution from a connected syringe or the like, which is discharged from the liquid injection hole and fills the inside of the protective ring. When the PGA-MN is applied to the skin and punctured from the SC and injected, the drug solution penetrates into the skin due to the capillary action in the gap between the skin and the MN and the injection pressure generated within the sealing ring (Figure 20-1, c).

Microneedle MNs of various shapes were fabricated and used in the test. A schematic diagram of the MN is shown in Figure 20-2. Each MN was fabricated by appropriately assigning the geometric parameters described below.
A. MN length (μm): 200-1,000
B. Length of base portion (μm): 0 to 2,000
C. Total length (μm): 200 - 2,200
D. Diameter of the top of the base (μm): 150 - 1,000
E. Between MN (μm): 2,000 - 5,000
F. MN bottom diameter (μm): 150-750 (depending on A.)
G. Number of MNs in the array: 1-19

The aspect ratio of the MN (A. length of MN/F. base diameter of MN) was kept at 4/3 for all samples. All samples except the PGA-MN were made of medical grade stainless steel (SUS), only the PGA-MN was made of PGA. The geometric parameters of the 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.

Chemical substances The reagents used were purchased from commercial sources in Japan.

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

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

For home human testing, the above formula was used, but without 4-methoxysalicylic acid.

Skin samples For the puncture ability and penetration force tests, frozen human dorsal skin (n=3-4, 45-69 years, mean=60.0 years) was used after thawing and warming to a surface temperature of 32°C. For RNA-seq, fresh human abdominal skin (Genoskin, France) (n=4, 29-39 years, mean=35.8 years) was air-shipped from France and organ-cultured to maintain tissue equivalence during the study period. Full thickness skin with subcutaneous fat removed was used in all tests.

Methods Puncture Ability Test Methylene Blue Staining MN was inserted into a skin piece set with the SC side facing up on a base adjusted to approximate the elasticity of human cheekbone skin. MN was inserted by pressing the MN vertically at a speed of 40 mm/sec while applying a load of 1 kgf using a texture analyzer (TA.XTplusC, EKO INSTRUMENTS, Japan) as a manipulator, and then pulling it up after holding it for 10 seconds. Next, the MN was immersed in a 1 mg/mL methylene blue aqueous solution with the SC side facing down for 20 minutes. Next, the solvent on the surface was wiped off, and the sample was washed with purified water, after which tape stripping was performed 5 to 10 times using a D-Squame® sampling disk (Clinical and Derm, USA). The presence or absence of puncture was evaluated by observing the specimen with a digital microscope (Hirox, Japan). Some of the specimens were embedded in OCT compound, frozen, and then thin sections were prepared. The cross sections were observed under a microscope (BX51, Olympus, Japan) to evaluate the penetration depth.

The puncture rate was calculated as follows:

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

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

Penetration Study Confocal Raman Spectroscopy The serum (5 μl/cm ² ) was applied to the skin with a pipette, and then the PGA-MN was pressed into the skin 50 times with a pressure of 1 kgf. As a control, the serum (5 μl/cm ² ) was applied to the skin with a pipette without the PGA-MN. Then, the time evolution of the Raman spectrum in the fingerprint region (600-2200 ^{cm −1} ) was evaluated. The Raman intensity of niacinamide (1042 cm ⁻¹ ) was calculated while being standardized according to the laser intensity at each depth. The Raman intensity was measured intermittently from the SC to the VE in 2 μm or 3 μm steps, and was measured in an area of 4 or 6 μm ² up to a maximum depth of 30 μm or 60 μm. Finally, the 3D transmission images were visualized with ImageJ and Imaris software.

RNA-seq method PGA-MN was applied once every 2 days. Skin samples were collected on days 1, 3, and 7 after incubation. Total RNA was extracted from the epidermis and dermis of the isolated skin using the Qiagen RNeasy mini kit (Qiagen, Netherlands). RNA-seq analysis was performed using dermal RNA as previously reported [11]. Low-expressing genes with a median mapped read count of less than 1 were excluded from the analysis. Heatmaps were drawn using heatmap 2 of the gplots package (version 3.1.3.1) (Reference 12). Enrichment analysis of selected genes by biological function was performed using Metascape (Reference 13).

Blood flow A half-face comparative evaluation was conducted on 24 men (30s to 60s). Injectable-MN (Figure 20-1) containing beauty essence was applied 50 times to half of the face. The remaining beauty essence was then spread on the skin, and immediately after that, the blood flow on the left and right sides of the face was measured using an Omega Zone Laser Speckle Blood Flow Meter (Omega Wave Japan).

Home-use human test A home-use before-and-after test was conducted on 45 women (aged 40-50) who met the screening criteria to evaluate the improvement of skin condition by applying "Injectable--MN" or "Serum". Wrinkles, sagging, and skin clarity were graded before and after continuous use for 2, 4, and 8 weeks. Sagging was scored based on the scoring method of Ezure et al. (Reference 14). Changes in mandibular volume were measured using 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.

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

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

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

EdgeR (version 3.40.0) (Reference 16) was used for RNA-seq differential expression gene analysis. Multiple testing correction was performed using the Benjamini-Hochberg method, and genes with an adjusted p-value (FDR) < 0.05 were defined as differentially expressed genes.

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

On the other hand, in Figure 20-3b, a base was placed under the single needle MN with a fixed needle length of 200 μm to artificially lengthen the overall length, and the puncture success rate due to differences in length was compared. Stable puncture was observed when the overall length was 600 μm or more, and a significant difference was observed in the puncture success rate of each group at a risk rate of 0.5%.

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

Then, in Fig. 20-3d, a single-needle MN (MN) with an MN length of 200 μm, an array of 19 MNs of the same shape (MN Array), a single-needle MN with an MN 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 the MN w/ Base (MN w/ Base Array) were fabricated and their puncture capabilities were evaluated. As a result, it was shown that the puncture rate was significantly improved by adding a base under the MN and forming it into an array at the same time.

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

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

Next, the puncture depth was evaluated using resin sections (Figure 20-4). Unfortunately, the MN tip was hydrolyzed during fixation, and it was not possible to simultaneously photograph the needle tip and the skin. However, it was possible to confirm that the MN puncture mark remained within the SC and that the MN puncture site had been significantly deformed down to the dermis.

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

The permeability of the model drug (Flu-Na) was evaluated using a fluorescence quantification method. As a result, a significant increase in the amount of penetration was observed 15 minutes after application of Injectable-MN, approximately 2.9 times that of simple application (Figure 20-5a).

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

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

The results of the enrichment analysis suggested that, compared to the control group, PGA-MN significantly upregulated the functions of six gene clusters and downregulated the functions of 18 gene clusters (Figure 20-6b). Of these, it was suggested that gene clusters involved in NABA ECM regulators, vascular permeability regulators, and natural immune responses may be related to the improvements in blood flow, wrinkles, and sagging observed in the in vivo human tests described below.

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

In the home human test, Injectable-MN brought about a significant improvement in the grade of wrinkles after two weeks of application, whereas in the control group (serum), improvement in wrinkles was observed from four weeks after application (FIG. 20-8a).

Furthermore, skin clarity two weeks after application was significantly improved compared to the serum group (Figure 20-8b).

Furthermore, questionnaires taken two and eight weeks later showed significant improvements in the categories of "skin became softer" and "skin became moist" (Fig. 20-8 c and d).

Furthermore, regarding the grade of sagging, significant changes from the initial values were observed in the nasolabial folds, marionette lines, and face line (Fig. 20-8 e, f, g). In the control group, no significant changes were observed in the improvement of sagging in the marionette lines and face line. Furthermore, only in the Injectable-MN group, the volume of the lower jaw was significantly reduced after 2 and 8 weeks of continuous use compared to before use (Fig. 20-8 h). In some subjects, a visually obvious reduction in sagging was observed (Fig. 20-8 i).

Barrier function also improved significantly in both groups after two weeks (Figure 20-8j).

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

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

The optimized PGA-MN was confirmed to remain in the target skin layers, SC or VE.

At the same time, when the resin slices were examined under a microscope, significant deformation was observed in the deeper epidermis.

This deformation is thought to have two functions. First, by compressing and stretching the skin, the shock absorption ability of the skin is reduced, making it possible to puncture the targeted area precisely with a short needle of less than 200 μm.

The other is to apply mechanical stress, which will contribute to the results of RNA-seq and blood flow assessment.

The injectability was evaluated from the penetration-enhancing effect of a hydrophilic model drug using fluorescence intensity quantification and confocal Raman microscopy. The results showed that PGA-MN improved the skin permeability of the model drug in terms of amount, speed, and depth.

The results of RNA-seq suggested that NABA ECM regulators, vascular permeability regulators, and innate immune responses were altered by PGA-MN compression. These genes included several genes commonly known to be regulated by mechanical stress, suggesting that PGA-MN may induce mechanobiological effects in the dermis. These changes likely contribute to ECM and vascular remodeling and may indicate a transition from the inflammatory phase to the proliferation and remodeling phase.

It has been reported that the modulation of important genes such as VEGF during wound healing can cause serious damage [17], but in the present study, no such genes were altered. Therefore, our hypothesis is that PGA-MN may promote a mild immune response, leading to skin improvement through remodeling of the dermal ECM and blood vessels by a wound healing-like mechanism, without causing serious damage to the skin.

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

Moreover, this mechanical stress had the immediate effect of improving blood flow.
These results demonstrated that Injectable-MN has a complex effect on both the epidermis and dermis.

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

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

Furthermore, it was found to have an effect of improving sagging in the nasolabial folds, marionette lines, and face lines, which was previously unknown. This is thought to be due to a complex reaction that not only allows large amounts of niacinamide to be rapidly delivered deep into the skin, but also has a mechanobiological effect due to MN pressure and promotes metabolic reactions due to improved blood flow.

In addition, although injectable MN improves barrier function, MN's mechanism of action, "breaking through the SC," actually tends to impair barrier function (Reference 18). This is because Injectable-MN remains within the SC at a precisely controlled puncture depth and does not damage the barrier function. We have discovered that Injectable-MN can regenerate skin and address serious aging concerns such as sagging skin without destroying the skin's barrier function. We have achieved an extremely high level of both safety and efficacy that neither cosmetics nor cosmetic medicine have been able to achieve.

Conclusion Injectable-MN is a groundbreaking technology that combines an extremely high level of safety with unprecedented rejuvenating effects, something that has not been achieved with existing cosmetics or cosmetic medicine.

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

Injectable-MN technology allows control of not only the amount of penetration but also the location and time, and as a new DDS platform, it will take functional cosmetics to a new dimension. Not only that, but the effects of non-invasive mechanobiology will amplify the potential of this technology many-fold. This will be a game changer that will free consumers from the limitations of the effectiveness of existing cosmetics and the burdens imposed by aesthetic medicine.

List of references

REFERENCE SIGNS LIST 10, 11 Plate 10a, 11a Injection hole 10b, 11b Needle-shaped protrusion 10c, 11c Lip portion 11d Base portion 20 Mounting frame 20a Plate support portion 20b Mounting tube 30 Syringe 30a Syringe tip 30b Syringe 30c Pusher 30d Pressing piece 100, 101 Part with needle-shaped protrusion 200 Beauty tool C Medicinal liquid S Target (skin)

Claims (40)

1. An apparatus for use in a method of improving the condition of the skin of a subject, comprising:
The device has a part with a needle-like protrusion,
the part with needle-like projections includes needle-like projections, and an effective puncture length of the needle-like projections into the skin is a length that does not reach the dermis,
The method,
(i) applying a pressing pressure of 50 to 1200 gf to the skin with the cosmetic device; and (ii) using the device at least once every two days and at least twice a day, or using the device at least three times a week. The device of claim 1, in which the subject needs to adjust M1/M2 balance. The device of claim 1, wherein the subject is in need of increasing muscle fiber cell count. The part with needle-like projections is
A plate having a pouring hole extending vertically therethrough;
One or more minute needle-like projections protruding from one surface of the plate;
a lip portion formed on an outer edge of one surface of the plate;
The device according to any one of claims 1 to 3, comprising: The part with needle-like projections is
Plate and
one or more pedestals protruding from one surface of the plate;
One or more minute needle-like projections protruding from a tip end surface of each of the one or more base portions;
A lip portion formed on an outer edge portion of a tip surface of the base portion;
The device according to any one of claims 1 to 3, comprising: The device according to claim 1, which is used to improve the barrier function of the skin. The device according to claim 1, which is used to improve skin clarity. The device according to claim 1, which is used to promote collagen production in the skin. The device according to claim 1, which is used to improve sagging skin. The present invention relates to a cosmetic that has a part with needle-like projections, and is intended to improve the barrier function and/or transparency of the skin.
Needle beauty tool. The part with needle-like projections is
A plate having a pouring hole extending vertically therethrough;
One or more minute needle-like projections protruding from one surface of the plate;
a lip portion formed on an outer edge of one surface of the plate;
The cosmetic device according to claim 10, comprising: The part with needle-like projections is
Plate and
one or more pedestals protruding from one surface of the plate;
One or more minute needle-like projections protruding from a tip end surface of each of the one or more base portions;
A lip portion formed on an outer edge portion of a tip surface of the base portion;
The cosmetic device according to claim 10, comprising: The device according to any one of claims 1 to 12, which is for injecting a medicinal solution into a target object via the part with the needle-like protrusion. A beauty kit for improving the barrier function and/or transparency of the skin, comprising the beauty device according to claim 13 and the medicinal solution. The beauty kit according to claim 14, wherein the medicinal solution contains niacinamide. The beauty kit according to claim 14 or 15, which can improve the transparency of the skin in a shorter period of time than when the medicinal liquid is applied to the skin. The beauty kit according to any one of claims 14 to 16, which can improve the barrier function of the skin, improve the clarity of the skin, promote collagen production in the skin, or improve sagging skin. A cosmetic method for improving a skin condition of a subject, comprising:
(i) applying a pressure of 50 to 1200 gf to the skin with the beauty tool; and (ii) using the beauty tool at least once every two days and at least twice a day, or at least three times a week; and the beauty tool is a needle beauty tool having a part with a needle-like protrusion,
the part with needle-like protrusions includes needle-like protrusions, and the effective puncture length of the needle-like protrusions into the skin is a length that does not reach the dermis;
Beauty methods. The cosmetic method according to claim 18, wherein the subject needs to adjust the M1/M2 balance. The cosmetic method according to claim 18, wherein the subject needs to increase the number of muscle fiber cells. The cosmetic method according to any one of claims 18 to 20, for adjusting the M1/M2 balance of the subject and/or for increasing the number of muscle fiber cells of the subject. A method for improving the barrier function and/or transparency of the skin, comprising applying the cosmetic device according to any one of claims 10 to 13 to the skin. A method for improving the barrier function and/or clarity of the skin, comprising applying the beauty tool to the skin using the beauty kit according to any one of claims 14 to 17. injecting a medicinal solution into a subject, the medicinal solution including niacinamide;
24. The method of claim 22 or 23. The method according to any one of claims 22 to 24, which can improve the barrier function of the skin, improve the clarity of the skin, promote collagen production in the skin, or improve sagging skin. The method according to any one of claims 22 to 25, which can improve the sense of transparency in a shorter period of time than when the drug solution is applied to the skin. A needle beauty device that has parts with needle-like protrusions and is designed to promote collagen production. A needle beauty device that has parts with needle-like protrusions and is designed to improve sagging skin. The part with needle-like projections is
A plate having a pouring hole extending vertically therethrough;
One or more minute needle-like projections protruding from one surface of the plate;
a lip portion formed on an outer edge of one surface of the plate;
29. The cosmetic device according to claim 27 or 28, comprising: The part with needle-like projections is
Plate and
one or more pedestals protruding from one surface of the plate;
One or more minute needle-like projections protruding from a tip end surface of each of the one or more base portions;
A lip portion formed on an outer edge portion of a tip surface of the base portion;
29. The cosmetic device according to claim 27 or 28, comprising: The device according to any one of claims 1 to 5 and 27 to 30, which is for injecting a medicinal solution into a target object via the part with the needle-like protrusion. A beauty kit for promoting collagen production comprising the beauty tool according to claim 31 and the medicinal solution. The beauty kit of claim 32, wherein the medicinal solution contains niacinamide. The beauty kit according to claim 32 or 33, which can improve sagging skin, promote collagen production in the skin, improve the barrier function of the skin, or improve the clarity of the skin. A method for promoting collagen production, comprising applying the beauty device according to any one of claims 27 to 31 to the skin. A method for promoting collagen production, comprising applying the beauty tool to the skin using the beauty kit according to any one of claims 31 to 34. injecting a medicinal solution into a subject, the medicinal solution including niacinamide;
A method for promoting collagen production according to claim 35 or 36. The method for promoting collagen production according to any one of claims 35 to 37, which can improve sagging skin, promote collagen production in the skin, improve the barrier function of the skin, or improve the transparency of the skin. The device according to any one of claims 1 to 13 and 27 to 31, wherein the effective puncture length of the needle-like projections into the skin is 5 μm or more and 200 μm or less. The beauty method according to any one of claims 18 to 21, wherein the beauty tool is a tool according to any one of claims 1 to 13 and 27 to 31.

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