Cosmetic material for skin penetration of hyaluronate

Abstract

Provided is a hyaluronic acid salt skin permeation cosmetic that does not require a complicated process such as complexation of hyaluronic acid salt, and that allows the hyaluronic acid salt to permeate the skin. The hyaluronic acid salt skin permeation cosmetic of the present disclosure contains hyaluronic acid salt and an amphoteric surfactant.

Description

Technical Field

[0001] This disclosure relates to skin-penetrating cosmetics containing hyaluronic acid. Background Technology

[0002] For example, hyaluronic acid salts with moisturizing properties are used in cosmetics and other fields to moisturize the skin.

[0003] Patent Document 1 discloses a cosmetic containing hyaluronic acid-loaded nanoparticles, wherein at least one of the nanoparticles formed from any of polylactic acid, polyglycolic acid, and lactic acid / glycolic acid copolymers is loaded with hyaluronic acid.

[0004] Patent document 2 discloses a topical skin preparation containing composite nanoparticles comprising (A) hyaluronic acid and (B) a zwitterionic compound, with a particle size of less than 100 nm.

[0005] Existing technical documents

[0006] Patent documents

[0007] Patent Document 1: Japanese Patent Application Publication No. 2010-150151

[0008] Patent Document 2: International Publication No. 2018 / 182003 Summary of the Invention

[0009] The problem that the invention aims to solve

[0010] For example, the stratum corneum, the outermost layer of the skin, acts as a barrier to prevent foreign substances from penetrating the skin, thus making it difficult for active ingredients applied to the skin to penetrate deep into the skin. Therefore, by simply applying hyaluronic acid ingredients such as hyaluronic acid salts to the skin, the moisturizing effect of hyaluronic acid tends to remain on the skin surface, providing only a short-term moisturizing effect. As a result, to improve skin wrinkles and other conditions, frequent and long-term continuous application of hyaluronic acid is required.

[0011] The technologies described in Patent Documents 1 and 2 involve loading hyaluronic acid onto supporting materials such as polylactic acid, or combining hyaluronic acid with other materials (polyionic compounding), and the nanoparticle-based processing of hyaluronic acid is essential. All of these require complex processes such as ultracentrifugation during the production of cosmetics.

[0012] Therefore, the subject of this disclosure is to provide a skin-penetrating cosmetic containing hyaluronic acid salts that allows hyaluronic acid salts to penetrate the skin without undergoing complex processes such as compounding with hyaluronic acid components.

[0013] Methods for solving problems

[0014] <Option 1>

[0015] A skin-penetrating cosmetic containing hyaluronic acid salts, comprising hyaluronic acid salts and amphoteric surfactants.

[0016] Option 2

[0017] The cosmetic material according to Scheme 1 contains salt at a concentration with an ionic strength of 0.05 or higher.

[0018] Option 3

[0019] According to Scheme 1 or 2, the content of the above-mentioned amphoteric surfactant is 0.01% by mass or more relative to the total amount of the cosmetic.

[0020] Option 4

[0021] According to any one of Schemes 1 to 3, the amphoteric surfactant is selected from at least one of betaine-type amphoteric surfactants, amino acid-type amphoteric surfactants, sulfonic acid-type amphoteric surfactants, sulfate-ester-type amphoteric surfactants, and lecithin.

[0022] Option 5

[0023] The cosmetic according to any one of Schemes 2 to 4 contains a salt at a concentration of 0.05 or higher ionic strength, wherein the salt is at least one selected from monovalent, divalent, and trivalent salts.

[0024] <Option 6>

[0025] The cosmetic according to any one of Schemes 2 to 4 contains a salt at a concentration of ionic strength of 0.05 or higher, wherein the salt is at least one selected from sodium salts and magnesium salts.

[0026] <Option 7>

[0027] According to the cosmetic material described in Scheme 6, the sodium salt is sodium chloride and the magnesium salt is magnesium chloride.

[0028] <Option 8>

[0029] The cosmetic material according to any one of Schemes 1 to 7 comprises at least one moisturizer selected from propylene glycol, dipropylene glycol, and PEG / PPG-17 / 4 dimethyl ether.

[0030] <Option 9>

[0031] The cosmetic material according to Scheme 8 contains sodium chloride.

[0032] The effects of the invention

[0033] According to this disclosure, a skin-penetrating cosmetic containing hyaluronic acid salts can be provided, which enables the hyaluronic acid salts to penetrate the skin without undergoing complex processes such as compounding hyaluronic acid components. Attached Figure Description

[0034] Figure 1 This is a graph showing the amount of hyaluronic acid salts penetrating into simulated skin when various surfactants are used.

[0035] Figure 2 A graph showing the permeation of hyaluronic acid salts mixed with sodium chloride into simulated skin without the use of amphoteric surfactants.

[0036] Figure 3 A graph showing the penetration amount of hyaluronic acid salts mixed with sodium chloride or magnesium chloride into simulated skin when using amphoteric surfactants.

[0037] Figure 4 This is a graph showing the penetration amount of hyaluronic acid salts mixed with magnesium chloride into human skin when using amphoteric surfactants.

[0038] Figure 5 This is a graph showing the amount of hyaluronic acid salts penetrating into simulated skin when used in combination with various moisturizers along with amphoteric surfactants.

[0039] Figure 6 A graph showing the penetration amount of hyaluronic acid salts into simulated skin when used in combination with an amphoteric surfactant and a moisturizer (dipropylene glycol), accompanied by a mixture of sodium chloride or magnesium chloride. Detailed Implementation

[0040] The embodiments of this disclosure will now be described in detail. This disclosure is not limited to these embodiments, and various modifications can be made within the scope of the spirit of the invention.

[0041] The disclosed hyaluronic acid skin-penetrating cosmetic contains hyaluronic acid and an amphoteric surfactant.

[0042] Although not limited by principle, it can be considered that the cosmetic material disclosed herein contains amphoteric surfactants together with hyaluronic acid salts, thereby enabling hyaluronic acid salts to easily penetrate the skin, and the mechanism of action is as follows.

[0043] Hyaluronic acid molecules are typically large in molecular weight and exist in cosmetics in a filamentous, expanded state. Therefore, even when cosmetics containing hyaluronic acid in this state are applied to the skin, the hyaluronic acid molecules do not penetrate into the skin but tend to remain on the skin's surface.

[0044] The inventors have discovered that even without performing complexation processes such as ultracentrifugation as described in Patent Documents 1 and 2 to nanoparticle hyaluronic acid salts, hyaluronic acid salts can easily penetrate into the skin simply by mixing them with amphoteric surfactants in cosmetics.

[0045] One reason why hyaluronic acid salts can easily penetrate the skin is that amphoteric surfactants, for example, act on the intercellular lipids of the skin. That is, amphoteric surfactants can form tiny pores or cracks in the intercellular lipids of the skin, allowing hyaluronic acid salts to easily pass through these pores or cracks and penetrate the skin. Furthermore, it can be argued that at this time, near the skin, the positive charge of the amphoteric surfactant forms an ionic bond with the negative charge of the hyaluronic acid salt, causing a change in the polarity of the hyaluronic acid salt (apparently, increased hydrophobicity). Therefore, even without nanoparticle formation, hyaluronic acid salts can easily penetrate the highly hydrophobic stratum corneum.

[0046] Cosmetics for Skin Penetration

[0047] The cosmetic ingredient disclosed herein contains hyaluronic acid salts and amphoteric surfactants, which enhance the permeability of hyaluronic acid salts to the skin.

[0048] Hyaluronic acid salts

[0049] There are no particular limitations on the hyaluronic acid salts that can be blended into the cosmetics disclosed herein. Generally speaking, hyaluronic acid salts refer to linear polymeric salts formed by alternating N-acetyl-D-glucosamine residues and D-glucuronic acid residues. Such hyaluronic acid salts can be obtained, for example, by isolation and extraction from rooster combs or other animal tissues, or by fermentation using microorganisms such as Streptococcus.

[0050] Hyaluronic acid salts can be metal salts of hyaluronic acid such as sodium hyaluronate, potassium hyaluronate, magnesium hyaluronate, calcium hyaluronate, and aluminum hyaluronate. Furthermore, derivatives of hyaluronic acid salts obtained by etherifying, esterifying, amidating, acetylifying, acetalizing, or ketalizing the hydroxyl or carboxyl groups of hyaluronic acid if the residues contain a carboxyl group can be used. Here, the concept of "hyaluronic acid salts" in this disclosure can include hyaluronic acid salts and their derivatives.

[0051] There are no particular limitations on the weight-average molecular weight of hyaluronic acid salts; for example, it can be below 10,000,000. Not limited to hyaluronic acid salts, it is generally considered that low molecular weight agents easily penetrate the skin. Although amphoteric surfactants can also improve the skin penetration of low molecular weight hyaluronic acid salts, their moisture retention properties are inferior to those of high molecular weight hyaluronic acid salts because they do not easily remain within the skin, thus sometimes making it difficult to maintain a long-term moisturizing effect within the skin. Therefore, using high molecular weight hyaluronic acid salts is advantageous when a long-term moisturizing effect within the skin is desired. From the perspective of skin moisture retention, the weight-average molecular weight of hyaluronic acid salts can be, for example, 500 or more, 1,000 or more, 5,000 or more, 10,000 or more, 50,000 or more, 100,000 or more, 300,000 or more, 500,000 or more, 800,000 or more, or 1,000,000 or more. Alternatively, it can be less than 10,000,000, less than 8,000,000, less than 5,000,000, less than 3,000,000, less than 2,000,000, or less than 1,500,000. Here, the weight-average molecular weight refers to the weight-average molecular weight converted from polystyrene in gel permeation chromatography.

[0052] Hyaluronic acid salts can be used alone or in combination of two or more hyaluronic acid salts and their derivatives. Furthermore, the molecular weights of the hyaluronic acid salts and their derivatives used can be the same or different.

[0053] Hyaluronic acid salts can be commercially available. Examples of commercially available hyaluronic acid salts include HA-LQ hyaluronic acid (manufactured by Kuppy Co., Ltd.), FCH hyaluronic acid (manufactured by Kipkoman Bio-Okemifa Co., Ltd.), and HA12N bio-hyaluronic acid sodium (manufactured by Shiseido Co., Ltd.).

[0054] In several embodiments, the hyaluronic acid salt contained in the cosmetic of this disclosure does not need to be composite nanoparticle-sized as described in Patent Documents 1 and 2, so the hyaluronic acid salt-containing ingredients that penetrate into the skin can maintain a high concentration of hyaluronic acid salt in the ingredient.

[0055] However, hyaluronic acid-containing ingredients that penetrate the skin may contain other polymeric components besides hyaluronic acid, provided that they do not adversely affect moisturizing properties. The proportion of these other polymeric components, relative to the total polymer content in the hyaluronic acid-containing ingredient, may, for example, be less than 50% by mass, less than 40% by mass, less than 30% by mass, less than 20% by mass, less than 10% by mass, less than 5% by mass, less than 3% by mass, or less than 1% by mass. Here, the proportion of hyaluronic acid in the hyaluronic acid-containing ingredient can be determined, for example, using an ELISA method.

[0056] In several embodiments, the cosmetics disclosed herein do not contain composite nanoparticles with a particle size of less than 100 nm comprising hyaluronic acid salts and zwitterionic compounds.

[0057] The amount of hyaluronic acid salt in a cosmetic, from the perspective of moisturizing properties and cost, can be 0.005% by mass or more, 0.01% by mass or more, 0.05% by mass or more, 0.10% by mass or more, 0.15% by mass or more, 0.20% by mass or more, or 0.25% by mass or more, relative to the total amount of the cosmetic. Alternatively, it can be 1.0% by mass or less, 0.80% by mass or less, 0.60% by mass or less, 0.50% by mass or less, or 0.45% by mass or less. As described above, the hyaluronic acid salt contained in the cosmetic of this disclosure maintains a high concentration of hyaluronic acid salt in the hyaluronic acid salt-containing ingredients. The simultaneous mixing with amphoteric surfactants allows the hyaluronic acid salt to penetrate appropriately into the skin, thus providing sufficient moisturizing effects even when the content of hyaluronic acid salt in the cosmetic is relatively low.

[0058] Amphoteric Surfactants

[0059] In addition to hyaluronic acid salts, the cosmetic ingredients disclosed herein also contain amphoteric surfactants. Amphoteric surfactants can be used alone or in combination of two or more.

[0060] There are no particular limitations on the amphoteric surfactant, and examples include at least one selected from betaine-type amphoteric surfactants, amino acid-type amphoteric surfactants, sulfonic acid-type amphoteric surfactants, sulfate ester-type amphoteric surfactants, and lecithin. Among these, betaine-type amphoteric surfactants and lecithin are preferred from the viewpoint of the permeability of hyaluronic acid salts to the skin, and lecithin is particularly preferred. Hydrogenated lecithin can be used as the lecithin.

[0061] Examples of betaine-type amphoteric surfactants include alkyl betaine-type amphoteric surfactants, amide betaine-type amphoteric surfactants, and imidazoline-type amphoteric surfactants. Betaine-type amphoteric surfactants and sulfobetaine-type amphoteric surfactants. Examples of particularly suitable betaine-type amphoteric surfactants include lauryl betaine and imidazoline. Betaine, and cocamidopropyl betaine.

[0062] Examples of amino acid-type amphoteric surfactants include, for example, alkyl amino acids having an alkyl group having 6 to 18 carbon atoms. Specifically, examples include, for example, N-lauryl-β-alanine, N-stearyl-β-alanine, lauryl diaminoethyl glycine, and N-[3-alkyl(12,14)oxy-2-hydroxypropyl]-L-arginine hydrochloride.

[0063] Examples of sulfonic acid-type amphoteric surfactants include, for example, alkylaminosulfonic acids and alkylimidazoline sulfonic acids. Specifically, examples include, for example, decyl dimethylaminopropylsulfonic acid, lauryl dimethylaminopropylsulfonic acid, palmityl dimethylpropyl sulfonic acid, lauryl di-n-propylaminopropylsulfonic acid, and 2-undecylimidazoline-N-ethylsulfonic acid.

[0064] Examples of sulfate ester-type amphoteric surfactants include, for example, alkylaminosulfuric acid and alkylimidazoline sulfuric acid. Specifically, examples include, for example, decyl dimethylaminopropyl sulfuric acid, lauryl dimethylaminopropyl sulfuric acid, palmityl dimethylaminopropyl sulfuric acid, lauryl di-n-propylaminopropyl sulfuric acid, and 2-undecylimidazoline-N-ethyl sulfuric acid.

[0065] Regarding the mixing amount of amphoteric surfactants, for example, from the viewpoint of the permeability of hyaluronic acid salts to the skin, relative to the total amount of cosmetics, it can be 0.01% by mass or more, 0.03% by mass or more, 0.05% by mass or more, 0.07% by mass or more, 0.10% by mass or more, 0.13% by mass or more, 0.15% by mass or more, 0.17% by mass or more, or 0.20% by mass or more. In addition, it can be 5.0% by mass or less, 4.0% by mass or less, 3.0% by mass or less, or 2.0% by mass or less.

[0066] <Water-based media>

[0067] The cosmetics disclosed herein typically contain an aqueous medium. There are no particular limitations on the aqueous medium used in cosmetics, pharmaceuticals, etc. Examples of suitable aqueous media include ion-exchanged water, distilled water, ultrapure water, tap water, and buffer solutions. The aqueous medium can be used alone or in combination of two or more.

[0068] Examples of buffer solutions include citrate buffer, lactate buffer, phosphate buffer, acetate buffer, tartrate buffer, borate buffer, and Tris buffer. From the viewpoint of high buffering capacity, citrate buffer, lactate buffer, and phosphate buffer are preferred, and citrate buffer is more preferred.

[0069] The pH of the buffer solution can be below 7.0, below 6.8, or below 6.5. There is no particular limitation on the lower limit of the pH of the buffer solution, but from the viewpoint of skin irritation, it is preferable to be above 4.5, above 5.5, or above 6.0.

[0070] <Any Component>

[0071] The cosmetic ingredients disclosed herein can be appropriately blended with various ingredients to the extent that they do not adversely affect the effects of the present invention. Examples of such ingredients include, for instance, water-soluble agents applicable in pharmaceuticals, quasi-pharmaceuticals, cosmetics, etc., such as salts, moisturizers, skin or hair nutrients, vitamins, pharmaceuticals, quasi-pharmaceuticals, and cosmetics; ultraviolet absorbers; antioxidants; preservatives; antioxidant auxiliaries; thickeners; pigments; dyes; colorants; and fragrances. Any ingredient can be used alone or in combination of two or more.

[0072] (Salt)

[0073] The cosmetics disclosed herein may contain salts. Cosmetics containing hyaluronic acid salts, if containing salts, are as follows: Figure 2 As shown, the penetration of hyaluronic acid (HA) into the skin can sometimes be reduced. However, the cosmetics of this disclosure contain an amphoteric surfactant along with the hyaluronic acid, thus enabling good penetration of the hyaluronic acid into the skin even when salts are present. Salts can be used alone or in combination of two or more. Here, the term "salt" in this disclosure does not include hyaluronic acid.

[0074] There are no particular limitations on the salts that can be mixed in cosmetics, and examples include at least one salt selected from inorganic salts and organic acid salts. Considering its use as a cosmetic, among inorganic salts and organic acid salts, salts that are less likely to cause adverse effects on the skin are preferred. Here, "inorganic salt" refers to a salt composed solely of inorganic components, or in other words, a salt composed of ions generated by inorganic acids and inorganic bases. Furthermore, "organic acid salt" refers to a salt formed by the bonding of an organic acid with a metal ion. Additionally, salts in cosmetics generally exist in the form of ions derived from the salt. Therefore, in this disclosure, for example, "cosmetics containing salt" refers to salts contained in such ionic form. Furthermore, ionic surfactants are not included in the "salts" of this disclosure.

[0075] As a salt, at least one selected from, for example, monovalent, divalent, and trivalent salts can be used.

[0076] As an inorganic salt, it is preferably selected from at least one of sodium salts, potassium salts, calcium salts, magnesium salts, and aluminum salts, and more preferably from at least one of sodium salts and magnesium salts.

[0077] Specifically, examples of inorganic salts include sodium nitrate, sodium sulfate, sodium chloride, potassium nitrate, potassium sulfate, potassium chloride, calcium nitrate, calcium sulfate, calcium chloride, magnesium nitrate, magnesium sulfate, magnesium chloride, aluminum nitrate, aluminum sulfate, and aluminum chloride. Among these, sodium chloride and magnesium chloride are preferred, and sodium chloride is more preferred.

[0078] Examples of organic acid salts include, for instance, citrates, acetates, lactates, tartrates, succinates, malates, glycolates, salicylates, and pyrrolidone carboxylates. Specifically, examples include salts formed by organic acids such as citric acid, acetic acid, lactic acid, tartaric acid, succinic acid, malic acid, glycolic acid, salicylic acid, and pyrrolidone carboxylates bonded to metal ions such as sodium, potassium, calcium, magnesium, and aluminum ions.

[0079] The cosmetic disclosed herein can enhance the skin permeability of hyaluronic acid salts by mixing with amphoteric surfactants, thus allowing for the high concentration of salts in the cosmetic. The ionic strength of the salts in the cosmetic can be, for example, 0.05 or higher, 0.06 or higher, 0.07 or higher, or 0.08 or higher; and can also be 5.0 or lower, 4.0 or lower, 3.0 or lower, 2.0 or lower, 1.0 or lower, 0.7 or lower, 0.5 or lower, 0.4 or lower, or 0.3 or lower.

[0080] Here, for example, in the case of preparing cosmetics by adding salt to a buffer solution, the ionic strength of the salt is calculated based on the total salt content, including the salt content contained in the buffer solution itself and the salt content added separately to the buffer solution.

[0081] (Moisturizer)

[0082] The cosmetic ingredients disclosed herein may contain moisturizers. Moisturizers may be used alone or in combination of two or more. Furthermore, the moisturizers described herein do not contain hyaluronic acid salts.

[0083] In the moisturizer, at least one selected from propylene glycol, dipropylene glycol, and PEG / PPG-17 / 4 dimethyl ether is preferred. The skin penetration of hyaluronic acid salts can be further enhanced when these moisturizers are used in combination with hyaluronic acid salts and amphoteric surfactants. Furthermore, the skin penetration of hyaluronic acid salts can be further enhanced when magnesium chloride and / or sodium chloride, especially sodium chloride, are used in combination with these moisturizers, hyaluronic acid salts, and amphoteric surfactants.

[0084] The amount of hyaluronic acid salts used as a moisturizer in cosmetics can be 1.0% or more by mass, 3.0% or more by mass, 5.0% or more by mass, or 7.0% or more by mass, or less than 30.0% by mass, less than 25.0% by mass, less than 20.0% by mass, or less than 15.0% by mass, from the perspective of skin permeability.

[0085] <The permeability of cosmetics>

[0086] The permeability of the hyaluronic acid salts in the cosmetics of this disclosure can be evaluated, for example, by using a permeability test 1 (described later) on simulated skin. In such a permeability test, the cosmetics of this disclosure can achieve a hyaluronic acid salt concentration of 500 ng / cm³ in simulated skin. 2 Above, 1,000 ng / cm 2 Above, or 1,500 ng / cm 2 That's all. There is no particular limit to the upper limit of such hyaluronic acid content; for example, it can be 20,000 ng / cm³. 2 Below, 18,000 ng / cm 2 Below, 15,000 ng / cm 2 Below, or 12,000 ng / cm 2 the following.

[0087] Methods for preparing cosmetic ingredients

[0088] The cosmetic material disclosed herein can be formulated using, for example, the following method. Furthermore, various materials such as hyaluronic acid salts, amphoteric surfactants, water, and any ingredients (e.g., salts and moisturizers) can be used in the cosmetic material formulation method.

[0089] A solution can be prepared by mixing amphoteric surfactants, as well as salts and / or moisturizers as needed, in water or buffer solution and stirring to dissolve hyaluronic acid salts in the solution.

[0090] Alternatively, hyaluronic acid salts can be mixed with water or buffer solution, stirred to dissolve the hyaluronic acid salts, and then mixed with amphoteric surfactants, as well as salts and / or moisturizers as needed, and stirred to prepare cosmetics.

[0091] Application Areas of Cosmetics

[0092] The disclosed cosmetic can be applied to all parts of the body, for example, it can be applied to any location on the surface of the skin (body surface). Specifically, for example, it can be appropriately applied to the skin surface of the face (lips, around the eyes, eyelids, cheeks, forehead, between the eyebrows, nose, etc.), head (scalp), ears, hands, arms, neck, feet, legs, chest, abdomen, back, etc. Here, the skin also includes nails and other hardened parts of the skin's epidermis due to changes in keratinization.

[0093] Thus, the cosmetic material disclosed herein can be suitably used as a skin-penetrating cosmetic material for hyaluronic acid salts.

[0094] Beauty methods that use cosmetics

[0095] The beauty method using the cosmetic material disclosed herein includes applying the cosmetic material to the skin surface. Furthermore, the term "beauty method" in this disclosure refers to a method of applying the cosmetic material disclosed herein to the skin surface to improve and beautify the skin's condition, which differs from methods of performing surgery, treatment, or diagnosis on humans.

[0096] Generally speaking, skin exposed to dryness loses moisture without the skin realizing it, resulting in a state where the skin's surface moisture is not retained. For example, if the skin's surface moisture is insufficient, the skin's own moisturizing components (natural moisturizing factor (NMF)) cannot be produced effectively. As a result, due to the reduced barrier and moisturizing functions of the skin's surface, the skin is more susceptible to damage, thus losing moisture and causing wrinkles, rough skin, and other problems.

[0097] The cosmetic material disclosed herein enables hyaluronic acid salts to penetrate the skin effectively, thus providing excellent skin hydration. As a result, for example, the skin's own ability to produce moisturizing ingredients is improved, and the sluggish renewal of the stratum corneum is also improved, making it less likely for problems such as rough skin to occur, thereby enhancing the cosmetic effect.

[0098] There are no particular restrictions on the method of applying cosmetics to the skin. For example, it can be done by applying cosmetics to the skin. As a method of applying cosmetics to the skin, for example, it can be done by using a spray container containing cosmetics to spread it on the skin, or by adding cosmetics to a container without a spray function, taking an appropriate amount of cosmetics from such a container with fingers or palms, and spreading it on the skin.

[0099] Example

[0100] The following test examples and embodiments further illustrate the present invention in detail, but the invention is not limited to them. Furthermore, unless otherwise specified, the mixing amount is expressed as mass percent (%).

[0101] Experimental Examples 1-6

[0102] <Evaluation of Cosmetic Materials>

[0103] The various evaluations shown below were performed using cosmetic materials obtained through the manufacturing methods described below, and the results are summarized in Tables 1-6. Figures 1-6 Additionally, in the table and figure, "HA" refers to hyaluronic acid salt, "LB" refers to lauryl betaine, "PG" refers to propylene glycol, "BG" refers to butylene glycol, and "DPG" refers to dipropylene glycol.

[0104] (Permeability Test 1: Evaluation of the permeability of hyaluronic acid to simulated skin)

[0105] As a simulated skin, a Strat-M (trademark) film (manufactured by Merck Millipore) was used, and a diffusion cell array system (manufactured by Ikeda Rika Co., Ltd.) with a supply section and a receiving section was also used.

[0106] The Strat-M (trademark) film is positioned between the supply and receiving sections of the diffusion cell array system. The effective diffusion area of ​​the Strat-M (trademark) film is 0.785 cm². 2 Fill the receiving section with 2 ml of receiving solution (PBS solution) and continue stirring the receiving solution with a stirrer. Set the surface of the Strat-M (trademark) film to 32°C and apply 10 μL / cm of cosmetic to the supply section. 2 Twenty-four hours later, the Strat-M (trademark) film was removed, and its surface was washed with a soap solution and purified water. The film was then immersed in purified water and subjected to ultrasonic treatment for 20 minutes. Further extraction was performed overnight in a 37°C constant temperature bath, and hyaluronic acid was quantified by ELISA. The values ​​in the table and figures are the average values ​​of hyaluronic acid levels measured in 3-4 tests. Furthermore, regarding Test Example 6, Reference Example 3 and Examples 12-14, a cosmetic agent of 10 μL / cm was applied to the supply area. 2 Six hours later, the Strat-M (trademark) film was removed and the same procedure was performed.

[0107] (Permeability Test 2: Evaluation of the permeability of hyaluronic acid to human skin)

[0108] Hyaluronic acid salts were recovered from the stratum corneum after stripping using a stripping method, following steps (1) to (7) below. The permeability of the hyaluronic acid salts was evaluated based on the amount recovered. Furthermore, this evaluation test was conducted on six reviewers in their 20s, and their average values ​​are shown in the table and figure:

[0109] (1) The inside of the judge's forearm was washed with soap.

[0110] (2) Apply approximately 10 μl / cm to the inside of the reviewer's washed forearm. 2 The cosmetic was applied in a specific ratio.

[0111] (3) The reviewers waited for 4 hours.

[0112] (4) The inside of the reviewer's forearm was washed with purified water.

[0113] (5) The stratum corneum of the area where the cosmetic was applied was peeled 10 times.

[0114] (6) The stratum corneum attached to the band was soaked in purified water and hyaluronic acid was extracted by ultrasonic treatment.

[0115] (7) The extract was analyzed by ELISA to quantify the amount of hyaluronic acid in the extract.

[0116] <Experimental Example 1: Various Surfactants>

[0117] In Experimental Example 1, the effects of various surfactants mixed with hyaluronic acid salts were investigated. The results are shown in Tables 1-2 and... Figure 1 In the middle. Here, Tables 1-2 and... Figure 1 The terms "nonionic surfactant," "amphoteric surfactant," and "anionic surfactant" refer to nonionic surfactants, amphoteric surfactants, and anionic surfactants, respectively.

[0118] (Comparative Example 1)

[0119] Hyaluronic acid salts (manufactured by Shiseido Co., Ltd., Bio-Hyarol 12: weight-average molecular weight 1.2 million) were added to ion-exchanged water at a concentration of 0.3% by mass, and the solution was prepared by stirring with a stirrer. To this solution, POE(20) benzyl ether, a nonionic surfactant, was added at a concentration of 0.7% by mass, and the solution was stirred with a stirrer to prepare the test sample.

[0120] (Comparative Examples 2-10 and Examples 1-5)

[0121] The surfactants in Tables 1-2 were changed, and the test samples of Comparative Examples 2-10 and Examples 1-5 were prepared by operating in the same manner as Comparative Example 1.

[0122] (Refer to Example 1)

[0123] As the test sample (control sample) for Reference Example 1, the solution containing hyaluronic acid salts from Comparative Example 1 was used.

[0124] Table 1

[0125]

[0126] Nonionic surfactant 1: POE(20) benzyl ether

[0127] Nonionic surfactant 2: POE(30) benzyl ether

[0128] Nonionic surfactant 3: PEG-60 isostearate glyceryl ester

[0129] Nonionic surfactant 4: PEG-20 isostearate

[0130] Nonionic surfactant 5: POE(60) hardened castor oil

[0131] Nonionic surfactant 6: PPG-13 Decyltetradecyl alcohol polyether-24

[0132] Nonionic surfactant 7: PEG-2 laurate

[0133] Table 2

[0134]

[0135] Amphoteric agent 1: Cocamidopropyl betaine

[0136] Amphoteric agent 2: lauryl betaine

[0137] Amphoteric agent 3: Myristyl sulfobetaine

[0138] Amphoteric agent 4: A mixture of hydrogenated lecithin and ethanol

[0139] Amphoteric agent 5: imidazoline betaine

[0140] Anionic surfactant 1: Stearoyl glutamic acid Na

[0141] Anionic surfactant 2: Na methyl taurate

[0142] Anionic surfactant 3: Na stearoylmethyl taurate

[0143] (result)

[0144] From Tables 1-2 and Figure 1 The results clearly confirm that the permeability of hyaluronic acid salts is improved by mixing amphoteric surfactants.

[0145] <Experimental Example 2: The Effect of Salt Concentration Without Amphoteric Surfactants>

[0146] In Experiment 2, for reference, the effect of salt concentration without amphoteric surfactants on the permeability of hyaluronic acid salts was investigated. The results are shown below. Figure 2 middle.

[0147] (Preparation method of the test sample)

[0148] Hyaluronic acid salts (manufactured by Shiseido Co., Ltd., Bio-Hyaluronic 12: weight-average molecular weight 1.2 million) were added to ion-exchanged water at a concentration of 0.3% by mass, and the solution was stirred to prepare a solution containing hyaluronic acid salts. Sodium chloride was added to the separated solutions at concentrations of 0.05, 0.1, 0.2, and 0.5 ionic strengths, and the solutions were stirred to prepare the test samples.

[0149] (result)

[0150] Depend on Figure 2 The results clearly confirm that if the cosmetic does not contain amphoteric surfactants, the permeability of hyaluronic acid salts decreases with increasing salt concentration.

[0151] <Experimental Example 3: The Effect of Salt Concentration on the Inclusion of Amphoteric Surfactants>

[0152] In Experiment 3, the effect of salt concentration containing an amphoteric surfactant on the permeability of hyaluronic acid salts was investigated. The results are shown in Table 3 and... Figure 3 middle.

[0153] (Example 2)

[0154] The test sample of Example 2 of Test Example 1 above was used. Here, the test sample of Example 2 was prepared as follows. Hyaluronic acid salt (manufactured by Shiseido Co., Ltd., VioHyarol 12: weight average molecular weight 1.2 million) was added to ion-exchanged water at a content of 0.3% by mass, and the solution containing hyaluronic acid salt was prepared by stirring with a stirrer. To this solution, lauryl betaine, as an amphoteric surfactant, was added at a content of 0.7% by mass, and the solution was stirred with a stirrer to prepare the test sample.

[0155] (Example 6)

[0156] Sodium chloride was added to the test sample of Example 2 at a concentration of 0.1 ionic strength, and the mixture was stirred and mixed using a vortex mixer to prepare the test sample of Example 6.

[0157] (Example 7)

[0158] Magnesium chloride was added to the test sample of Example 2 at a concentration of 0.21 ionic strength, and the mixture was stirred and mixed using a vortex mixer to prepare the test sample of Example 7.

[0159] (Comparative Example 11)

[0160] As a test sample for Comparative Example 11, a solution containing hyaluronic acid salts from Example 2, which does not contain amphoteric surfactants and salts, was used.

[0161] (Comparative Example 12)

[0162] Sodium chloride was added to the solution containing hyaluronic acid salt in Example 2 at a concentration of 0.1 ionic strength, and the mixture was stirred with a stirrer to prepare the test sample of Comparative Example 12.

[0163] (Comparative Example 13)

[0164] Magnesium chloride was added to the solution containing hyaluronic acid salt in Example 2 at a concentration of 0.21 ionic strength, and the mixture was stirred with a stirrer to prepare the test sample of Comparative Example 13.

[0165] Table 3

[0166]

[0167] (result)

[0168] It can be seen that the cosmetics containing amphoteric surfactants in Examples 2, 6 and 7, compared with the cosmetics in Comparative Examples 11 to 13 that do not contain amphoteric surfactants, have improved permeability of hyaluronic acid salts even when salts are present.

[0169] <Experimental Example 4: Properties on Human Skin>

[0170] In Experiment 4, the permeability of hyaluronic acid salts containing amphoteric surfactants to human skin was investigated. The results are shown in Table 4 and... Figure 4 middle.

[0171] (Example 8)

[0172] Hyaluronic acid salts (manufactured by Shiseido Co., Ltd., Bio-Hyarol 12: weight-average molecular weight 1.2 million) were added to ion-exchanged water at a concentration of 0.5% by mass, and the mixture was stirred to prepare a solution containing hyaluronic acid salts. To this solution, lauryl betaine, an amphoteric surfactant, was added at a concentration of 0.1% by mass. Furthermore, magnesium chloride was added at a concentration with an ionic strength of 0.21, and the mixture was stirred to prepare the test sample.

[0173] (Comparative Example 14)

[0174] As a test sample for Comparative Example 14, a solution containing hyaluronic acid salts from Example 8, which does not contain amphoteric surfactants and salts, was used.

[0175] Table 4

[0176]

[0177] (result)

[0178] It can be confirmed that cosmetics containing amphoteric surfactants along with hyaluronic acid salts can improve the permeability of hyaluronic acid salts even on human skin.

[0179] <Experimental Example 5: Various Moisturizers>

[0180] In Experiment 5, the effects of various humectants mixed with hyaluronic acid salts and amphoteric surfactants were investigated. The results are shown in Table 5 and... Figure 5 In Table 5, although the examples listed are Comparative Examples 15-17, they are examples used for comparison with the results of Examples 9-11. That is, the test samples of Comparative Examples 15-17 also contain amphoteric surfactants, and since they exhibit the same performance as Reference Example 2, the test samples of Comparative Examples 15-17 can be considered examples when compared with test samples that do not contain amphoteric surfactants (such as the test sample of Comparative Example 1 in Table 1).

[0181] (Comparative Example 15)

[0182] Hyaluronic acid salts (manufactured by Shiseido Co., Ltd., Bio-Hyarol 12: weight-average molecular weight 1.2 million) were added to ion-exchanged water at a concentration of 0.3% by mass, and the mixture was stirred with a stirrer to prepare a solution containing hyaluronic acid salts. To this solution, lauryl betaine, an amphoteric surfactant, was added at a concentration of 0.7% by mass, and glycerin, a humectant, was added at a concentration of 10% by mass. Furthermore, sodium chloride was added at an ionic strength of 0.1, and the mixture was stirred with a stirrer to prepare the test sample.

[0183] (Examples 9-11 and Comparative Examples 16-17)

[0184] The humectant was changed to the one listed in Table 5. Otherwise, the test samples of Examples 9-11 and Comparative Examples 16-17 were prepared by operating in the same manner as Comparative Example 15.

[0185] (See Example 2 for reference)

[0186] The test sample (control sample) of Reference Example 2 was prepared in the same manner as Comparative Example 15, without containing any moisturizing agent.

[0187] Table 5

[0188]

[0189] (result)

[0190] It is known that when propylene glycol, dipropylene glycol, and PEG / PPG-17 / 4 dimethyl ether are used as moisturizers, the permeability of hyaluronic acid salts can be further improved compared with cosmetics that do not contain moisturizers and cosmetics that contain other moisturizers.

[0191] <Experimental Example 6: Synergistic Effects of Using Moisturizers or Moisturizers and Salts in Concomitant with Amphoteric Surfactants>

[0192] In Experiment 6, the synergistic effects of using humectants or humectants and salts in combination with amphoteric surfactants were investigated. The results are shown in Table 6 and... Figure 6 In the middle. Here, in Table 6 and Figure 6 The results of Comparative Examples 11 and 13 are also recorded in the report. Furthermore, the results of the permeability test 1 in Comparative Examples 11 and 13 show that when 10 μL / cm of cosmetic was applied to the supply section… 2 The results after 24 hours, in contrast to the results of permeability test 1 in Reference Example 3 and Examples 12-14, showed that when 10 μL / cm of cosmetic was applied to the supply area... 2 The results were obtained 6 hours later.

[0193] (Example 12)

[0194] Hyaluronic acid salts (manufactured by Shiseido Co., Ltd., Bio-Hyarol 12: weight-average molecular weight 1.2 million) were added to ion-exchanged water at a concentration of 0.3% by mass, and the mixture was stirred with a stirrer to prepare a solution containing hyaluronic acid salts. To this solution, lauryl betaine, an amphoteric surfactant, was added at a concentration of 0.1% by mass, and dipropylene glycol, a humectant, was added at a concentration of 9% by mass. The mixture was then stirred with a vortex mixer to prepare the test sample.

[0195] (Example 13)

[0196] Hyaluronic acid salts (manufactured by Shiseido Co., Ltd., Bio-Hyarol 12: weight-average molecular weight 1.2 million) were added to ion-exchanged water at a concentration of 0.3% by mass, and the solution was prepared by stirring with a stirrer. To this solution, lauryl betaine, an amphoteric surfactant, was added at a concentration of 0.1% by mass, and dipropylene glycol, a humectant, was added at a concentration of 9% by mass. Furthermore, magnesium chloride was added at an ionic strength of 0.21, and the mixture was stirred with a vortex mixer to prepare the test sample.

[0197] (Example 14)

[0198] Instead of magnesium chloride, sodium chloride was added at a concentration of 0.1 ionic strength. Otherwise, the test sample of Example 14 was prepared in the same manner as in Example 13.

[0199] (Refer to Example 3)

[0200] Without using a humectant, the test sample of Reference Example 3 was prepared in the same manner as in Example 12.

[0201] Table 6

[0202]

[0203] (result)

[0204] A comparison of Reference Example 3 with Example 12 clearly shows that the permeability of hyaluronic acid salts is improved when used in combination with dipropylene glycol as a moisturizer, along with an amphoteric surfactant.

[0205] Furthermore, it is known that the permeability of hyaluronic acid salts is further enhanced when salts, especially sodium chloride, are used in combination with dipropylene glycol. The effect of this salt addition is predicted to be similar to that of other humectants (propylene glycol, PEG / PPG-17 / 4 dimethyl ether) that enhance the permeability of hyaluronic acid salts through combination with amphoteric surfactants.

Claims

1. A skin-penetrating cosmetic containing hyaluronic acid, comprising hyaluronic acid, Amphoteric surfactants At least one humectant selected from propylene glycol, dipropylene glycol, and PEG / PPG-17 / 4 dimethyl ether, and Salts with an ionic strength greater than 0.05 The amphoteric surfactant comprises at least one selected from betaine-type amphoteric surfactants, sulfonic acid-type amphoteric surfactants, and lecithin. The salt contains at least one selected from sodium chloride and magnesium chloride.

2. The cosmetic according to claim 1, wherein the content of the amphoteric surfactant is 0.01% by mass or more relative to the total amount of the cosmetic.

3. The cosmetic material according to claim 1 or 2, comprising sodium chloride.

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