Ultrafine bubble-containing composition

Abstract

The object of the present invention is to provide an ultrafine bubble-containing composition that is excellent at promoting the penetration of water-soluble components into the skin. [Solution] The means for solving the above problem comprises ultrafine bubbles, a water-soluble component, and water. The concentration of the ultrafine bubbles is 1 × 10 8 It is more than one cell / mL. This is an ultrafine bubble-containing composition for topical application to the skin.

Description

[Technical Field]

[0001] This invention relates to an ultrafine bubble-containing composition. [Background technology]

[0002] Due to their small size and high specific surface area, ultrafine bubbles are expected to have applications in many industries. Furthermore, their use in the medical and cosmetics industries is being researched. The skin penetration effect of ultrafine bubbles is already known (Patent Document 1). However, Patent Document 1 did not investigate the conditions under which compositions containing ultrafine bubbles exhibit superior skin penetration.

[0003] Furthermore, as prior art, Patent Document 2 describes a skin penetration enhancer that uses an aloe-derived component as an active ingredient. In Patent Document 2, the skin penetration effect of the active ingredient (water-soluble component) is investigated using the skin penetration enhancing effect of calcein sodium. [Prior art documents] [Patent Documents]

[0004] [Patent Document 1] International Publication 2021 / 085633 Brochure [Patent Document 2] Patent No. 6879734 [Overview of the project] [Problems that the invention aims to solve]

[0005] As a result of diligent research by the inventors, we have discovered a composition containing ultrafine bubbles that is excellent at promoting the penetration of water-soluble components into the skin. In other words, the present invention aims to provide an ultrafine bubble-containing composition that is excellent at promoting the penetration of water-soluble components into the skin. [Means for solving the problem]

[0006] The present invention, which solves the above problems, is as follows.

[0007] [1] Contains ultrafine bubbles, water-soluble components, and water. The concentration of the ultrafine bubbles is 1 × 10 8 It is more than one cell / mL. A composition containing ultrafine bubbles for topical application to the skin.

[0008] [2] The topical skin composition containing ultrafine bubbles as described in [1], wherein the pH is 3 or higher.

[0009] [3] The water-soluble component is an ionizable water-soluble component, as described in [1] or [2], an ultrafine bubble-containing composition for external use on the skin.

[0010] [4] The water-soluble component is a water-soluble component that can be negatively charged, as described in [3], an ultrafine bubble-containing composition for external use on the skin.

[0011] [5] The concentration of the ultrafine bubbles is measured with NanoSight NS300. The topical ultrafine bubble-containing composition for skin application according to any one of [1] to [4]. A composition containing ultrafine bubbles for topical application to the skin.

[0012] [6] A cosmetic or quasi-drug composition containing ultrafine bubbles for external use on the skin, as described in any of [1] to [5].

[0013] [7] Contains ultrafine bubbles, water-soluble components, and water. The concentration of the ultrafine bubbles is 1 × 10 8 It is more than one cell / mL. A composition for assisting the penetration of water-soluble components into the skin.

[0014] [8] A composition for assisting the penetration of water-soluble components into the skin as described in [7], wherein the pH is 3 or higher.

[0015] [9] Comprising ultra-fine bubbles, a water-soluble component, and water, where the concentration of the ultra-fine bubbles is 1×10 8 or more per mL, A method of promoting the penetration of the water-soluble component into the skin by applying a skin-external-use ultra-fine bubble-containing composition.

[0016]

[10] The method for promoting the penetration of the water-soluble component into the skin according to [9], wherein the pH of the skin-external-use ultra-fine bubble-containing composition is 3 or more.

[0017]

[11] Including a preparation step of preparing a solution containing ultra-fine bubbles, water, and a water-soluble component, where the concentration of the ultra-fine bubbles in the solution obtained by the preparation step is 1×10 8 or more per mL, A method for producing a skin-external-use ultra-fine bubble-containing composition.

[0018]

[12] The method for producing a skin-external-use ultra-fine bubble-containing composition according to

[11] , wherein the pH of the skin-external-use ultra-fine bubble-containing composition is 3 or more.

[0019]

[13] The method for producing a skin-external-use ultra-fine bubble-containing composition according to

[11] or

[12] , wherein the preparation step includes a concentration operation of concentrating the solution obtained by the preparation step. [Advantages of the Invention]

[0020] According to the present invention, an ultra-fine bubble-containing composition excellent in promoting the permeation of a water-soluble component into the skin can be provided. [Brief Description of the Drawings]

[0021] [Figure 1] It is a graph showing the cumulative permeation amount of sodium fluorescein salt at 0h - 24h in Test Example 1. [Figure 2]This graph shows the cumulative permeation of sodium calcein salt at the 4-hour mark in Test Example 1. [Figure 3] This graph shows the cumulative permeation of sodium calcein salt under acidic conditions in Test Example 2. [Figure 4] This graph shows the cumulative permeation of sodium calcein salt under neutral conditions in Test Example 2. [Figure 5] This figure shows tissue sections of a three-dimensional cultured epidermal model after being treated for 4 hours with polyglyceryl-10 laurate (containing sodium calcein), an aqueous solution of sodium calcein, and an aqueous solution of sodium calcein containing ultrafine bubbles, in Test Example 3. [Modes for carrying out the invention]

[0022] <1> Ultrafine bubble-containing composition The ultrafine bubble-containing composition of the present invention comprises at least ultrafine bubbles and a water-soluble component.

[0023] Furthermore, the ultrafine bubble-containing composition of the present invention is characterized by containing water.

[0024] Furthermore, the ultrafine bubble-containing composition of the present invention has an ultrafine bubble concentration of 1 × 10⁻⁶ 8 It is characterized by having more than 1 / mL. The ultrafine bubble-containing composition in the above form exhibits excellent ability to promote the penetration of water-soluble components into the skin.

[0025] Preferred embodiments of the present invention will be described in detail below.

[0026] (1) Preferred embodiment of ultrafine bubbles The concentration of ultrafine bubbles in the ultrafine bubble-containing composition is preferably 1 × 10⁻⁶. 8 cells / mL or more, preferably 1.1 × 10 8 cells / mL or more, more preferably 1.2 × 108 more than [number] / mL, more preferably 1.25 × 10 8 more than [number] / mL, more preferably 1.3 × 10 8 / mL or more. The ultrafine bubble-containing composition in the above form is excellent in the effect of promoting the penetration of water-soluble components into the skin.

[0027] In addition, the concentration of ultrafine bubbles in the ultrafine bubble-containing composition is preferably 1 × 10 10 / mL or less, more preferably 5 × 10 9 / mL or less, still more preferably 2 × 10 9 / mL or less. The ultrafine bubble-containing composition in the above form is excellent in the effect of promoting the penetration of water-soluble components into the skin.

[0028] For the concentration of ultrafine bubbles in the ultrafine bubble-containing composition, the value measured by NanoSight NS300 (manufactured by Malvern) can be used. In particular, the value measured by the software with Concentration upgrade of NanoSight NS300 (manufactured by Malvern) can preferably be used.

[0029] In addition, the gas in the ultrafine bubbles in the present embodiment may be any of air, hydrogen, oxygen, carbon dioxide, nitrogen, and noble gases. Here, examples of noble gases include helium (He) and argon (Ar). In the present example, the gas in the ultrafine bubbles is preferably air, nitrogen, or a gas containing 70% or more of nitrogen. The ultrafine bubble-containing composition in the above form is excellent in the effect of promoting the penetration of water-soluble components into the skin.

[0030] (2) Water-soluble component In the present embodiment, the ultrafine bubble-containing composition contains a water-soluble component. Water-soluble components refer to components that dissolve in water at least partially after being suspended in water at 25-65°C and allowed to stand for one hour (excluding surfactants).

[0031] The water-soluble component is preferably a water-soluble component that has medicinal effects and / or improves skin condition. Here, examples of ingredients that have medicinal effects and / or improve skin condition include pigmentation-improving ingredients, blemish-improving ingredients, wrinkle-improving ingredients, moisturizing ingredients, UV-absorbing ingredients, anti-inflammatory ingredients, and wound-healing ingredients.

[0032] In this case, the water-soluble component is preferably an ionizable water-soluble component.

[0033] Furthermore, the water-soluble component is preferably a water-soluble component that can be negatively charged.

[0034] As shown in the examples described later, the ultrafine bubble-containing composition of this embodiment promotes the penetration of a negatively chargeable water-soluble component (calcein sodium salt) into the skin.

[0035] The following explains how including a negatively chargeable water-soluble component in the ultrafine bubble-containing composition results in a superior effect of promoting penetration into the skin. First, ultrafine bubbles are negatively charged. Here, because the water-soluble component is a component that can be negatively charged, electrostatic repulsion occurs in the base with the negatively charged ultrafine bubbles, which can further reduce the relative affinity between the base and the water-soluble component. Furthermore, high concentrations of ultrafine bubbles enhance the affinity between the base (corresponding to water in this invention) and the skin, thereby relatively reducing the affinity between the base and the water-soluble components. The synergistic effect of these actions makes it more difficult for negatively charged water-soluble components to remain on the base, improving transdermal absorption. Therefore, the ultrafine bubble-containing composition has an ultrafine bubble concentration of 1 × 10 8Having a concentration of ions / mL or more, and being in a form that contains at least a negatively chargeable water-soluble component and water, makes it possible to further enhance the skin penetration-promoting effect of the negatively chargeable water-soluble component (calcein sodium salt).

[0036] Here, the water-soluble component that can be negatively charged is preferably one that has a functional group that can be negatively charged. Examples of negatively chargeable functional groups include, for example, carboxyl groups, amino groups which may have alkyl groups, sulfonic acid residues, and hydroxyl groups. An ultrafine bubble-containing composition containing a negatively chargeable water-soluble component in the above form exhibits excellent ability to promote the penetration of water-soluble components into the skin.

[0037] Examples of water-soluble components include dipotassium glycyrrhizinate, ascorbic acid, and sodium calceinate.

[0038] Furthermore, examples of water-soluble components include natural water-soluble polymers such as plant-derived polymers (e.g., gum arabic, tragacanth gum, galactan, guar gum, carob gum, karaya gum, carrageenan, pectin, agar, quince seed (quince), algae colloid (cassia extract), starch (rice, corn, potato, wheat), glycyrrhizic acid); microbial polymers (e.g., xanthan gum, dextran, succinoglucan, pullulan, etc.); and animal-derived polymers (e.g., collagen, casein, albumin, gelatin, etc.). Furthermore, examples of water-soluble components include semi-synthetic water-soluble polymers such as starch-based polymers (e.g., carboxymethyl starch, methylhydroxypropyl starch, etc.); cellulose-based polymers (hydroxypropyl methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxypropyl methylcellulose stearoxy ether, sodium cellulose sulfate, carboxymethylcellulose, sodium carboxymethylcellulose, crystalline cellulose, cellulose powder, etc.); and alginate-based polymers (e.g., sodium alginate, propylene glycol alginate ester, etc.).

[0039] In this invention, a preferred water-soluble component is sodium calceinate.

[0040] Furthermore, the total amount of water-soluble components in the ultrafine bubble-containing composition is preferably 0.2 w / v% or more, more preferably 0.3 w / v% or more, even more preferably 0.4 w / v% or more, and even more preferably 0.45 w / v% or more.

[0041] Furthermore, the total amount of water-soluble components in the ultrafine bubble-containing composition is preferably 15 w / v% or less, more preferably 10 w / v% or less, even more preferably 5 w / v% or less, and even more preferably 1 w / v% or less.

[0042] Furthermore, the content of water-soluble components in the total amount of the ultrafine bubble-containing composition is preferably 1 mM or more, more preferably 3 mM or more, even more preferably 5 mM or more, and even more preferably 7 mM or more.

[0043] Furthermore, the content of water-soluble components in the total amount of the ultrafine bubble-containing composition is preferably 20 mM or less, more preferably 15 mM or less, even more preferably 10 mM or less, and even more preferably 8 mM or less.

[0044] By having the water-soluble component of the ultrafine bubble-containing composition in the above-described form, it is possible to provide an ultrafine bubble-containing composition that exhibits even better effects.

[0045] Furthermore, the total amount of water-soluble components in the ultrafine bubble-containing composition is 1 x 10⁻⁶ of ultrafine bubbles. 8 The amount per unit is preferably 0.2 mg or more, more preferably 0.3 mg or more, even more preferably 0.4 mg or more, and even more preferably 0.45 mg or more.

[0046] Furthermore, the total amount of water-soluble components in the ultrafine bubble-containing composition is 1 x 10⁻⁶ of ultrafine bubbles. 8 The amount per unit is preferably 15 mg or less, more preferably 10 mg or less, even more preferably 5 mg or less, and even more preferably 1 mg or less.

[0047] By having the water-soluble component of the ultrafine bubble-containing composition in the above-described form, it is possible to provide an ultrafine bubble-containing composition that exhibits even better effects.

[0048] (3) pH of the ultrafine bubble-containing composition The liquid properties of the ultrafine bubble-containing composition may be weakly acidic, neutral, weakly alkaline, or strongly alkaline.

[0049] Furthermore, in this embodiment, the pH of the ultrafine bubble-containing composition is preferably 3 or higher, more preferably 3.5 or higher, more preferably 4 or higher, and even more preferably 5 or higher.

[0050] In this embodiment, the pH of the ultrafine bubble-containing composition is preferably 9 or less, more preferably 8 or less, and more preferably 7 or less.

[0051] As shown in the examples described later, the above-mentioned pH ultrafine bubble-containing composition is excellent at promoting the penetration of water-soluble components into the skin. In particular, by ensuring that the pH of the ultrafine bubble-containing composition is above the above lower limit, it is possible to provide an ultrafine bubble-containing composition that has a continuous effect of promoting the permeation of water-soluble components into the skin. Furthermore, when the pH of the ultrafine bubble-containing composition is above the above lower limit, the charged state and particle size of the ultrafine bubbles change, and the effect of promoting the penetration of water-soluble components into the skin is strengthened.

[0052] By having the pH of the ultrafine bubble-containing composition in the above form, it is possible to provide an ultrafine bubble-containing composition that exhibits even better effects.

[0053] Here, the pH of the ultrafine bubble-containing composition can be adjusted using any pH adjusting agent.

[0054] (4) Preferred embodiments of the ultrafine bubble-containing composition The ultrafine bubble-containing composition of the present invention is preferably a topical skin preparation. Here, suitable examples of topical skin preparations include cosmetics, quasi-drugs, and pharmaceuticals. Among these, the ultrafine bubble-containing composition of the present invention is more preferably used as a cosmetic or quasi-drug.

[0055] Examples of the aforementioned cosmetics include skin cosmetics. Examples of the aforementioned skin cosmetics include cosmetics, lotions, emulsions, serums, creams, face masks, foundations, essences, eye creams, etc.

[0056] The optional components of the ultrafine bubble-containing composition in the present invention are not particularly limited and include components commonly used in cosmetics. Examples of such components include surfactants, oils, powders (pigments, dyes, resins), thickeners, resins, fragrances, ultraviolet absorbers (including organic and inorganic types; they may correspond to either UV-A or UV-B), natural plant extracts, seaweed extracts, herbal medicine components, amino acids, whitening agents, blood circulation promoters, anti-inflammatory agents, bactericides, cooling agents, antiperspirants, salts, antioxidants, skin activators, dyes, vitamins, neutralizing agents, and pH adjusters. These agents are not limited to their individual uses and can be repurposed for other uses depending on the purpose; for example, vitamins can be used as antioxidants, or they can be used in combination with other uses; for example, surfactants can be used to stabilize microbubbles. Furthermore, the examples are not limited to those listed above, and any agent commonly used by those skilled in the art can be used.

[0057] Here, the water content of the ultrafine bubble-containing composition is preferably 60% by mass or more, more preferably 70% by mass or more, more preferably 80% by mass or more, and more preferably 90% by mass or more. Furthermore, the water content of the ultrafine bubble-containing composition is preferably 99% by mass or less, more preferably 96% by mass or less, and more preferably 93% by mass or less.

[0058] <2> Composition for aiding penetration of water-soluble ingredients As shown in the examples described later, the aforementioned ultrafine bubble-containing composition also excels at promoting the penetration of water-soluble components into the skin. Therefore, the present invention comprises ultrafine bubbles, water-soluble components, and water, wherein the concentration of the ultrafine bubbles is 1 × 10⁻⁶ 8 It can also be used as a composition to assist the penetration of water-soluble components into the skin, with a concentration of ions / mL or more. Here, a preferred embodiment of the composition for assisting the penetration of water-soluble components is: <1> The contents of the ultrafine bubble-containing composition can be used as a reference.

[0059] <3> Methods to promote the penetration of water-soluble components into the skin As shown in the examples described later, the aforementioned ultrafine bubble-containing composition also excels at promoting the penetration of water-soluble components into the skin. Therefore, the present invention comprises ultrafine bubbles, water-soluble components, and water, wherein the concentration of the ultrafine bubbles is 1 × 10⁻⁶ 8 It can also be used as a method to promote the penetration of the water-soluble component into the skin by applying an ultrafine bubble-containing composition for topical use that has a concentration of ions / mL or more. Here, a preferred embodiment of a method for promoting the penetration of water-soluble components into the skin is: <1> The contents of the ultrafine bubble-containing composition can be used as a reference.

[0060] Herein, the method for promoting the penetration of the water-soluble component of the present invention into the skin does not involve medical procedures. More specifically, the method for promoting the penetration of the water-soluble component of the present invention into the skin is a non-therapeutic method.

[0061] <4> Method for producing an ultrafine bubble-containing composition for topical application to the skin. Furthermore, the present invention includes a preparation step of preparing a solution containing ultrafine bubbles, water, and a water-soluble component, wherein the concentration of the ultrafine bubbles in the solution obtained by the preparation step is 1 × 10⁻⁶ 8 This method also provides a method for producing an ultrafine bubble-containing composition for topical application that has a concentration of 1 / mL or more.

[0062] Here, the preparation step includes either a method of preparing a solution by mixing water containing ultrafine bubbles with a water-soluble component, or a method of preparing a solution by generating ultrafine bubbles in a liquid containing water and a water-soluble component.

[0063] In this context, the method for producing the topical ultrafine bubble-containing composition preferably includes a concentration step in which the solution obtained by the preparation step is concentrated. A preferred embodiment of the method for producing an ultrafine bubble-containing composition for topical application to the skin is: <1> The contents of the ultrafine bubble-containing composition can be used as a reference. [Examples]

[0064] [Test Example 1] In Test Example 1, the permeation-enhancing effect of a high-concentration UFB sample, which contains concentrated ultrafine bubbles (hereinafter also referred to as UFB), was verified.

[0065] (1) Preparation of test samples The test samples shown below were prepared. Here, sodium calcein salt was used as the water-soluble component.

[0066] [Table 1]

[0067] In Example 1, after generating ultrafine bubbles in the base material, the sample was concentrated twice using an evaporator under the conditions of 80°C, 100 hPa, and 30 min in order to increase the final concentration.

[0068] Furthermore, the final concentration of ultrafine bubbles was measured using NanoSight NS300 (with concentration upgraded software).

[0069] (2) Exam Content After delivery of the three-dimensional cultured skin model (LabCyte EPI-MODEL24 (J-TEC, 401124)), the culture cups were transferred to a 24-well plate with assay medium and pre-cultured overnight in a CO2 incubator. The following day, the culture cups were transferred to a PBS-containing sample vial that had been previously stored in a 32°C constant temperature bath, 200 μL of PBS was added, and the mixture was hydrated for 30 minutes to 1 hour. The PBS was then removed using a micropipette. 500 μL of the above sample, the same volume as in each test, was added to the hydrated three-dimensional cultured skin model. After adding the sample, 500 μL was taken from the receiver solution in the glass vial at 4, 6, 8, and 24 hours, and the sampled amount of PBS was replenished into the glass vial. The fluorescence intensity of the obtained samples was measured (490 nm, 535 nm, 0.1 s), and the cumulative transmission amount of sodium calcein salt was calculated from the obtained fluorescence intensity. The results are shown in Figure 1 (cumulative permeation of sodium calcein salt from 0h to 24h) and Figure 2 (cumulative permeation of sodium calcein salt at 4 hours).

[0070] As shown in Figures 1 and 2, it was found that Example 1 had a higher cumulative permeation amount of sodium calcein salt compared to Comparative Example 1. In other words, the concentration of ultrafine bubbles is 1 × 10 8 It was found that a concentration of 1 / mL or higher resulted in superior efficacy in promoting the penetration of water-soluble components into the skin.

[0071] [Test Example 2] In Test Example 2, the effect of the pH of an ultrafine bubble-containing composition on its ability to promote skin penetration was investigated.

[0072] (1) Preparation of test samples The test samples shown below were prepared. Calcein sodium salt was used as the water-soluble component. Water was used as the base in each test.

[0073] [Table 2]

[0074] Specifically, a 2% sodium calcein salt solution was diluted fourfold with ultrapure water (UFB) to prepare a 0.5% sodium calcein salt solution. pH adjustment was performed at the stage of the 2% sodium calcein salt solution. The pH of the 2% sodium calcein salt solution used in the samples of Reference Example 2-1 and Example 2-1 was 3.23, and the pH of the 2% sodium calcein salt solution used in the samples of Reference Example 2-2 and Example 2-2 was 5.96. pH adjustment was performed using 0.1N NaOH, which was obtained by diluting 5N NaOH (Wako, 194-05371).

[0075] (2) Exam Content The same amount of each sample was added to a three-dimensional cultured skin model (LabCyte EPI-MODEL24 (J-TEC, 401124)) that had been hydrated with PBS. After adding the sample, 500 μL was taken from the receiver solution in the glass vial at 4, 6, 8, and 24 hours, and the sampled amount of PBS was replenished into the glass vial. The fluorescence intensity of the obtained samples was measured (490 nm, 535 nm, 0.1 s), and the cumulative transmission amount of sodium calcein salt was calculated from the obtained fluorescence intensity. The measurement results were compared with test examples without ultrafine bubbles (each example being a reference example).

[0076] The results are shown in Table 3 and Figure 3. Table 3 below shows the [cumulative permeation amount of water-soluble components in the example (UFB) / cumulative permeation amount of water-soluble components in the reference example (negative control)] at each measurement point.

[0077] [Table 3]

[0078] As shown in Table 3 and Figures 3 and 4, it was found that in both Example 2-1 and Example 2-2, including ultrafine bubbles increased the cumulative permeation amount of water-soluble components. In other words, it was found that the cumulative permeation of water-soluble components increases when the pH of the ultrafine bubble-containing composition is 3.5 or higher.

[0079] Furthermore, a comparison of Examples 2-1 and 2-2 revealed that continuous cumulative permeation of water-soluble components can be achieved when the pH is 5 or higher. In other words, it was found that when the pH of the ultrafine bubble-containing composition is 5 or higher, it is more effective in promoting the penetration of water-soluble components into the skin.

[0080] [Test Example 3] In Test Example 3, the effects of an ultrafine bubble-containing composition with a high concentration of ultrafine bubbles on skin tissue were investigated.

[0081] <1> Preparation of an ultrafine bubble-containing composition A sodium calcein salt aqueous solution (solvent: ultrapure water) was prepared to achieve a final concentration of 0.1%.

[0082] Specifically, a 2% sodium calcein solution was diluted with ultrapure water-UFB to prepare a 0.1% sodium calcein solution. The final UFB concentration was approximately 137.1 million particles / mL. The number concentration of UFB in the solution was measured using a Malvern Panalytical nanoparticle analyzer (NanoSight NS300).

[0083] <2> Evaluation of ultrafine bubble-containing compositions The effects of each sample (polyglyceryl-10 laurate, UFB-containing composition) on three-dimensional cultured epidermis were observed. A sample containing sodium calcein salt (Figure 5) was prepared to demonstrate the penetration of the components. The specific procedure is described below.

[0084] <Sample Processing> (1) Culture cups containing a three-dimensional cultured skin model (LabCyte EPI-MODEL24 (J-TEC, 401124)) were transferred to a 24-well plate containing assay medium, and pre-cultured overnight in a CO2 incubator. (2) The following day, the culture cup was transferred to a sample vial containing PBS that had been stored in a 32°C constant temperature bath, 200 μL of PBS was added and hydrated for 30 minutes to 1 hour, and then the PBS was removed with a micropipette. (3) 500 μL of each test sample was added to a hydrated three-dimensional cultured skin model and treated for 4 hours.

[0085] <Frozen Section Protocol> (1) After adding each sample and treating the culture cups for 4 hours, they were washed with PBS and fixed by immersion in 10% neutral buffered formalin (Wako, 062-01661). (2) The fixed specimens were washed three times with Dulbecco's Phosphate-Buffered Saline (DPBS, MatTek, TC-PBS), then immersed in a 10% sucrose solution and left to stand at 4°C for 2 hours. (3) After that, the samples were immersed in a 20% sucrose solution and left to stand again at 4°C for 2 hours. (4) Using a disposable scalpel, the tissue was cut out from the culture cup and embedded in OCT compound. (5) After the embedded specimens were cooled to -30°C using a cryostat, sections were prepared. (6) Subsequently, the sections were nuclear-stained and mounted on slides using DAPI-Fluoromount-G (registered trademark, SBA, 0100-20) for novel nuclear staining.

[0086] <2> Tissue section observation results Each stained section was observed using a confocal laser scanning microscope (KEYENCE BZ-X800) (magnification 10x and 20x). The results are shown in Figure 5.

[0087] In samples treated with polyglyceryl-10 laurate (Figure 5: polyglyceryl-10 laurate), it was confirmed that the structure of the entire epidermis, not just the stratum corneum, was significantly disrupted.

[0088] On the other hand, in samples treated with an aqueous solution of sodium calcein salt (Figure 5: ultrapure water) and an aqueous solution of sodium calcein salt containing UFB (Figure 5: water containing UFB), almost no structural changes in the stratum corneum were observed, confirming that the tissue was maintained in a normal state. As described above, it contains ultrafine bubbles, water-soluble components, and water, and the concentration of the ultrafine bubbles is 1 × 10⁻⁶ 8 It has been found that topical ultrafine bubble-containing compositions with a concentration of 1 / mL or more effectively suppress the breakdown of the stratum corneum structure while promoting the penetration of water-soluble components into the skin. [Industrial applicability]

[0089] According to the present invention, an ultrafine bubble-containing composition can be provided.

Claims

1. Contains ultrafine bubbles, water-soluble components, and water. The concentration of the ultrafine bubbles is 1 × 10 ８ It is more than one cell per mL. A composition containing ultrafine bubbles for topical application to the skin.

2. The pH is 3 or higher. The ultrafine bubble-containing composition for external skin application according to claim 1.

3. The aforementioned water-soluble component is an ionizable water-soluble component. The ultrafine bubble-containing composition for external skin application according to claim 1 or 2.

4. The aforementioned water-soluble component is a water-soluble component that can be negatively charged. The ultrafine bubble-containing composition for external skin application according to claim 3.

5. The ultrafine bubble-containing composition for topical use on the skin according to claim 1 or 2, wherein the concentration of the ultrafine bubbles is measured using NanoSight NS300.

6. It is a cosmetic or quasi-drug. The ultrafine bubble-containing composition for external skin application according to claim 1 or 2.

7. Contains ultrafine bubbles, water-soluble components, and water. The concentration of the ultrafine bubbles is 1 × 10 ８ It is more than one cell per mL. A composition for assisting the penetration of water-soluble components into the skin.

8. The pH is 3 or higher. The composition for assisting the penetration of water-soluble components into the skin according to claim 7.

9. Contains ultrafine bubbles, water-soluble components, and water. The concentration of the ultrafine bubbles is 1 × 10 ８ It is more than one cell per mL. A method for promoting the penetration of the water-soluble component into the skin by applying an ultrafine bubble-containing composition for external use to the skin.

10. The pH of the aforementioned topical skin composition containing ultrafine bubbles is 3 or higher. A method for promoting the penetration of the water-soluble component into the skin according to claim 9.

11. The process includes a preparation step of preparing a solution containing ultrafine bubbles, water, and water-soluble components. The concentration of the ultrafine bubbles in the solution obtained by the above preparation step is 1 × 10 ８ It is more than one cell per mL. A method for producing an ultrafine bubble-containing composition for topical application to the skin.

12. The pH of the aforementioned topical skin composition containing ultrafine bubbles is 3 or higher. A method for producing the ultrafine bubble-containing composition for external use on the skin according to claim 11.

13. The preparation step includes a concentration step of concentrating the solution obtained by the preparation step. A method for producing an ultrafine bubble-containing composition for external use on the skin according to claim 11 or 12.

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