Hyaluronate skin-penetrating cosmetic

Abstract

Provided is a hyaluronate skin-penetrating cosmetic that allows hyaluronate to penetrate the skin without undergoing complicated processes such as conjugation. 　This hyaluronate skin-penetrating cosmetic includes hyaluronate and an amphoteric surfactant.

Description

Hyaluronic acid salt skin-penetrating cosmetics

[0001] The present disclosure relates to a cosmetic preparation for skin penetration of a hyaluronic acid salt.

[0002] For example, hyaluronic acid salts having moisturizing properties are used in the field of cosmetics and the like to keep the skin moist.

[0003] Patent Document 1 discloses a cosmetic preparation containing hyaluronic acid-loaded nanoparticles in which hyaluronic acid is loaded on at least one of the interior and surface of nanoparticles formed from either polylactic acid, polyglycolic acid, or lactic acid / glycolic acid copolymer.

[0004] Patent Document 2 discloses an external skin preparation that contains composite nanoparticles that contain (A) hyaluronic acid and (B) an amphoteric compound and have a particle size of 100 nm or less.

[0005] JP 2010-150151 A International Publication No. 2018 / 182003

[0006] For example, the stratum corneum, which is located in the outermost layer of the skin, has a barrier function to prevent foreign substances from entering from the outside, so that the active ingredient applied to the skin is difficult to penetrate into the inside of the skin.Therefore, if hyaluronic acid components such as hyaluronate are simply applied to the skin, the moisturizing effect of the hyaluronic acid components tends to remain on the surface of the skin, and can only exert a short-term moisturizing effect.As a result, when improving skin wrinkles, it is necessary to apply the hyaluronic acid components frequently and continuously for a long period of time.

[0007] The techniques described in Patent Documents 1 and 2 require the conversion of hyaluronic acid into nanoparticles by supporting hyaluronic acid on a support material such as polylactic acid, or by combining hyaluronic acid with other materials (forming a polyion complex), and both of these techniques require complex processes such as ultracentrifugation when producing the cosmetic.

[0008] Therefore, the subject of the present disclosure is to provide a cosmetic preparation for skin penetration of hyaluronic acid salt, which can allow hyaluronic acid salt to penetrate the skin without undergoing complicated processes such as complexing of hyaluronic acid components.

[0009] <Aspect 1> A cosmetic preparation for skin penetration of hyaluronate, comprising hyaluronate and an amphoteric surfactant. <Aspect 2> The cosmetic preparation according to Aspect 1, comprising a salt at a concentration having an ionic strength of 0.05 or greater. <Aspect 3> The cosmetic preparation according to Aspect 1 or 2, wherein the content of the amphoteric surfactant is 0.01% by mass or greater relative to the total amount of the cosmetic preparation. <Aspect 4> The cosmetic preparation according to any one of Aspects 1 to 3, wherein the amphoteric surfactant is at least one selected from the group consisting of betaine-type amphoteric surfactants, amino acid-type amphoteric surfactants, sulfonic acid-type amphoteric surfactants, sulfate ester-type amphoteric surfactants, and lecithin. <Aspect 5> The cosmetic preparation according to any one of Aspects 2 to 4, comprising a salt at a concentration having an ionic strength of 0.05 or greater, wherein the salt is at least one selected from the group consisting of monovalent salts, divalent salts, and trivalent salts. Aspect 6: The cosmetic preparation according to any one of Aspects 2 to 4, comprising a salt at a concentration having an ionic strength of 0.05 or greater, wherein the salt is at least one selected from the group consisting of sodium salts and magnesium salts. Aspect 7: The cosmetic preparation according to Aspect 6, wherein the sodium salt is sodium chloride and the magnesium salt is magnesium chloride. Aspect 8: The cosmetic preparation according to any one of Aspects 1 to 7, comprising at least one moisturizer selected from the group consisting of propylene glycol, dipropylene glycol, and PEG / PPG-17 / 4 dimethyl ether. Aspect 9: The cosmetic preparation according to Aspect 8, comprising sodium chloride.

[0010] According to the present disclosure, it is possible to provide a cosmetic preparation for skin penetration of hyaluronic acid salt, which can allow hyaluronic acid salt to penetrate the skin without undergoing complicated processes such as complexing of hyaluronic acid components.

[0011] 1 is a graph showing the amount of hyaluronate permeated into simulated skin when various surfactants are used. 2 is a graph showing the amount of hyaluronate permeated into simulated skin when sodium chloride is added when no amphoteric surfactant is used. 3 is a graph showing the amount of hyaluronate permeated into simulated skin when sodium chloride or magnesium chloride is added when an amphoteric surfactant is used. 4 is a graph showing the amount of hyaluronate permeated into human skin when magnesium chloride is added when an amphoteric surfactant is used. 5 is a graph showing the amount of hyaluronate permeated into simulated skin when various moisturizers are used in combination with an amphoteric surfactant. 6 is a graph showing the amount of hyaluronate permeated into simulated skin when sodium chloride or magnesium chloride is added when an amphoteric surfactant and a moisturizer (dipropylene glycol) are used in combination.

[0012] The present disclosure is not limited to the following embodiments, and various modifications can be made within the scope of the present invention.

[0013] The hyaluronate cosmetic composition for skin penetration of the present disclosure contains a hyaluronate and an amphoteric surfactant.

[0014] Without being limited by the theory, it is believed that the principle of action by which the cosmetic composition of the present disclosure, which contains an amphoteric surfactant together with hyaluronate, allows the hyaluronate to more easily penetrate the skin is as follows.

[0015] Hyaluronate molecules typically have a large molecular weight and exist in a thread-like state in cosmetics. Therefore, even if a cosmetic containing hyaluronate in this state is applied to the skin, the hyaluronate molecules do not penetrate into the skin and tend to remain on the surface of the skin.

[0016] The present inventors have discovered that hyaluronate can be more easily penetrated into the skin by simply blending an amphoteric surfactant with hyaluronate in a cosmetic product, without having to carry out a complexing process such as ultracentrifugation as described in Patent Documents 1 and 2 to turn the hyaluronate into nanoparticles.

[0017] It is believed that the reason why hyaluronate can penetrate into skin easily is that amphoteric surfactant acts on the intercellular lipid of skin.In other words, it is believed that amphoteric surfactant can form micropores or cracks in the intercellular lipid of skin, and thus hyaluronate can penetrate into skin easily through these holes or cracks.In addition, at this time, near skin, the positive charge of amphoteric surfactant and the negative charge of hyaluronate form ionic bond, and the polarity of hyaluronate changes (apparently, hydrophobicity increases), so that even without nanoparticle formation, hyaluronate can penetrate into the stratum corneum with high hydrophobicity.

[0018] <<Cosmetic Preparation for Skin Penetration>> The cosmetic preparation of the present disclosure contains a hyaluronate and an amphoteric surfactant, and has the effect of improving the permeability of the hyaluronate into the skin.

[0019] <Hyaluronic Acid Salt> There are no particular limitations on the hyaluronic acid salt that can be incorporated into the cosmetic composition of the present disclosure. Generally, hyaluronic acid salt refers to a salt of a linear polymer in which N-acetyl-D-glucosamine residues and D-glucuronic acid residues are alternately bonded. Such hyaluronic acid salt can be obtained, for example, by isolation and extraction from chicken combs or other animal tissues, or by fermentation using microorganisms such as Streptococcus.

[0020] As hyaluronic acid salt, metal hyaluronic acid salt such as sodium hyaluronate, potassium hyaluronate, magnesium hyaluronate, calcium hyaluronate, aluminum hyaluronate can be used.In addition, if it has carboxyl group residue, it can be used the derivative of hyaluronic acid salt obtained by etherifying, esterifying, amidating, acetylating, acetalizing or ketalizing the hydroxyl group, carboxyl group, etc. of hyaluronic acid.Here, " hyaluronic acid salt " in the present disclosure can include the concept of hyaluronic acid salt and its derivative.

[0021] The weight-average molecular weight of hyaluronate is not particularly limited, and can be, for example, below 10,000,000.Not only hyaluronate, but generally low molecular weight drugs are considered to be easy to penetrate into skin.Amphoteric surfactant can also improve the skin permeability of low molecular weight hyaluronate, but low molecular weight hyaluronate is difficult to stay in the inside of skin, and its water retention performance is inferior to that of high molecular weight hyaluronate, so it may be difficult to maintain the moisturizing effect in the inside of skin for a long time.Therefore, when maintaining the moisturizing effect in the inside of skin for a long time, it is advantageous to use high molecular weight hyaluronate. From the viewpoint of moisture retention performance inside skin, the weight-average molecular weight of hyaluronate can be, for example, above 500, above 1,000, above 5,000, above 10,000, above 50,000, above 100,000, above 300,000, above 500,000, above 800,000 or above 1,000,000, and can be below 10,000,000, below 8,000,000, below 5,000,000, below 3,000,000, below 2,000,000 or below 1,500,000.Here, weight-average molecular weight refers to the weight-average molecular weight measured by gel permeation chromatography in terms of polystyrene.

[0022] The hyaluronic acid salt and its derivatives can be used alone or in combination of two or more kinds. The molecular weights of the hyaluronic acid salt and its derivatives used may be the same or different.

[0023] Commercially available hyaluronates may be used, such as hyaluronic acid HA-LQ (manufactured by Kewpie Corporation), hyaluronic acid FCH (manufactured by Kikkoman Biochemifa Corporation), and biosodium hyaluronate HA12N (manufactured by Shiseido Co., Ltd.).

[0024] In some embodiments, the hyaluronate contained in the cosmetic composition of the present disclosure does not need to be formed into composite nanoparticles as described in Patent Documents 1 and 2, and therefore the hyaluronate-containing component that penetrates into the skin can maintain a high concentration of hyaluronate.

[0025] However, the hyaluronate-containing component that penetrates into skin can contain other polymer components other than hyaluronate, as long as it does not cause problems in moisturizing performance etc. The content ratio of other polymer components can be, for example, less than 50% by mass, 40% by mass or less, 30% by mass or less, 20% by mass or less, 10% by mass or less, 5% by mass or less, 3% by mass or less, or 1% by mass or less, relative to the total polymer amount in hyaluronate-containing component.Here, the content ratio of hyaluronate in hyaluronate-containing component can be measured for example by ELISA method.

[0026] In some embodiments, the cosmetic preparation of the present disclosure does not contain composite nanoparticles having a particle size of 100 nm or less, which contain hyaluronate and a zwitterionic compound.

[0027] The amount of hyaluronate in the cosmetic preparation can be, for example, from the viewpoints of moisturizing property, cost, etc., 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, and 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, based on the total amount of the cosmetic preparation. As described above, the hyaluronate contained in the cosmetic preparation of the present disclosure can maintain a high concentration of hyaluronate in the hyaluronate-containing component, and the amphoteric surfactant simultaneously incorporated can allow the hyaluronate to penetrate into the skin favorably, so that sufficient moisturizing effect can be provided even when the content of hyaluronate in the cosmetic preparation is relatively low.

[0028] <Amphoteric Surfactant> The cosmetic preparation of the present disclosure contains an amphoteric surfactant in addition to a hyaluronate. The amphoteric surfactants can be used alone or in combination of two or more.

[0029] Amphoteric surfactant is not particularly limited, and for example, can be at least one selected from the group consisting of betaine type amphoteric surfactant, amino acid type amphoteric surfactant, sulfonic acid type amphoteric surfactant, sulfate ester type amphoteric surfactant and lecithin.Among them, from the viewpoint of the permeability of hyaluronate into skin, betaine type amphoteric surfactant and lecithin are preferred, and lecithin is particularly preferred.As lecithin, hydrogenated lecithin can also be used.

[0030] Examples of betaine-type amphoteric surfactants include alkyl betaine-type amphoteric surfactants, amido betaine-type amphoteric surfactants, imidazolinium betaine-type amphoteric surfactants, and sulfobetaine-type amphoteric surfactants. Particularly suitable betaine-type amphoteric surfactants include lauryl betaine, imidazolinium betaine, and cocamidopropyl betaine.

[0031] Examples of amino acid-type amphoteric surfactants include alkylamino acids having an alkyl group with 6 to 18 carbon atoms, such as N-lauryl-β-alanine, N-stearyl-β-alanine, lauryldiaminoethylglycine, and N-[3-alkyl(12,14)oxy-2-hydroxypropyl]-L-arginine hydrochloride.

[0032] Examples of sulfonic acid type amphoteric surfactants include alkylaminosulfonic acids and alkylimidacillin sulfonic acids, specifically decyldimethylaminopropylsulfonic acid, lauryldimethylaminopropylsulfonic acid, palmityldimethylpropylsulfonic acid, lauryldipropylaminopropylsulfonic acid, and 2-undecylimidacillin-N-ethylsulfonic acid.

[0033] Examples of sulfate ester-type amphoteric surfactants include alkylaminosulfuric acids and alkylimidacillin sulfates, specifically decyldimethylaminopropyl sulfate, lauryldimethylaminopropyl sulfate, palmityldimethylaminopropyl sulfate, lauryldi-n-propylaminopropyl sulfate, and 2-undecylimidacillin-N-ethyl sulfate.

[0034] From the viewpoint of the penetration of the hyaluronate into the skin, the amount of amphoteric surfactant may be, for example, 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 relative to the total amount of the cosmetic, and may 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.

[0035] <Aqueous Medium> The cosmetic preparation of the present disclosure may typically contain an aqueous medium. There are no particular limitations on the aqueous medium, and aqueous media used in cosmetics, quasi-drugs, etc. can be used. For example, ion-exchanged water, distilled water, ultrapure water, tap water, buffer solution, etc. can be used. The aqueous medium can be used alone or in combination of two or more types.

[0036] Examples of the buffer solution include citrate buffer, lactate buffer, phosphate buffer, acetate buffer, tartrate buffer, borate buffer, and Tris buffer. From the viewpoint of high buffer capacity, citrate buffer, lactate buffer, and phosphate buffer are preferred, and citrate buffer is more preferred.

[0037] The pH of the buffer solution can be 7.0 or less, 6.8 or less, or 6.5 or less. The lower limit of the pH of the buffer solution is not particularly limited, but is preferably 4.5 or more, 5.5 or more, or 6.0 or more, for example, from the viewpoint of skin irritation.

[0038] <Optional Components> The cosmetic composition of the present disclosure may contain various components as appropriate, provided that they do not adversely affect the effects of the present invention. Examples of such components include salt, moisturizers, skin or hair nutrients, vitamins, water-soluble agents applicable to pharmaceuticals, quasi-drugs, cosmetics, etc., UV absorbers, antioxidants, preservatives, antioxidant aids, thickeners, pigments, dyes, coloring agents, and fragrances. Optional components may be used alone or in combination of two or more.

[0039] (Salt) The cosmetic preparation of the present disclosure may contain a salt. When a cosmetic preparation containing hyaluronate contains a salt, the amount of hyaluronate (HA) that penetrates into the skin may decrease, as shown in FIG. 2. However, since the cosmetic preparation of the present disclosure contains an amphoteric surfactant along with hyaluronate, even if a salt is contained, the hyaluronate can penetrate well into the skin. The salt may be used alone or in combination of two or more types. Here, the "salt" in the present disclosure does not include hyaluronate.

[0040] There are no particular limitations on the salts that can be incorporated into cosmetics, and examples include at least one salt selected from the group consisting of inorganic salts and organic acid salts. Considering use as cosmetics, among inorganic salts and organic acid salts, salts that are less likely to have adverse effects on the skin are preferred. Here, "inorganic salt" refers to a salt composed only of inorganic components, and can also be rephrased as a salt composed of ions derived from an inorganic acid and an inorganic base. Furthermore, "organic acid salt" refers to a salt formed by the combination of an organic acid and a metal ion. Note that salts generally exist in cosmetics in the form of ions derived from salts. Therefore, in the present disclosure, for example, "cosmetics containing salts" refers to salts contained in such ionic form. Furthermore, ionic surfactants are not included in the "salt" of the present disclosure.

[0041] As the salt, for example, at least one selected from the group consisting of a monovalent salt, a divalent salt, and a trivalent salt can be used.

[0042] The inorganic salt is preferably at least one selected from the group consisting of sodium salts, potassium salts, calcium salts, magnesium salts, and aluminum salts, and more preferably at least one selected from the group consisting of sodium salts and magnesium salts.

[0043] Specific 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. Of these, sodium chloride and magnesium chloride are preferred, and sodium chloride is more preferred.

[0044] Specific examples of organic acid salts include citrates, acetates, lactates, tartrates, succinates, malates, glycolates, salicylates, and pyrrolidone carboxylates. Specific examples include salts of organic acids such as citric acid, acetic acid, lactic acid, tartaric acid, succinic acid, malic acid, glycolic acid, salicylic acid, and pyrrolidone carboxylate bound to metal ions such as sodium ions, potassium ions, calcium ions, magnesium ions, and aluminum ions.

[0045] The cosmetic preparation of the present disclosure can improve the permeability of the hyaluronate salt into the skin by incorporating an amphoteric surfactant, and therefore can incorporate a high concentration of salt into the cosmetic preparation.The ionic strength of the salt in the cosmetic preparation can be, for example, 0.05 or more, 0.06 or more, 0.07 or more, or 0.08 or more, and can be 5.0 or less, 4.0 or less, 3.0 or less, 2.0 or less, 1.0 or less, 0.7 or less, 0.5 or less, 0.4 or less, or 0.3 or less.

[0046] Here, for example, when a cosmetic preparation is prepared by adding a salt to a buffer solution, the ionic strength of the salt is calculated based on all salt components, including salt components contained in the buffer solution itself and salt components added separately to the buffer solution.

[0047] (Moisturizing Agent) The cosmetic preparation of the present disclosure may contain a moisturizing agent. The moisturizing agents may be used alone or in combination of two or more. Note that the moisturizing agent referred to here does not include hyaluronate.

[0048] Among the moisturizing agents, at least one selected from the group consisting of propylene glycol, dipropylene glycol, and PEG / PPG-17 / 4 dimethyl ether is preferred. When these moisturizing agents are used in combination with hyaluronic acid salts and amphoteric surfactants, the permeability of the hyaluronic acid salts into the skin can be further improved. Furthermore, when these moisturizing agents, hyaluronic acid salts, and amphoteric surfactants are used in combination with the above-mentioned magnesium chloride and / or sodium chloride, especially sodium chloride, the permeability of the hyaluronic acid salts into the skin can be further improved.

[0049] The amount of moisturizer in the cosmetic composition may be 1.0% by mass or more, 3.0% by mass or more, 5.0% by mass or more, or 7.0% by mass or more, from the viewpoint of the permeability of the hyaluronate salt into the skin, and may be 30.0% by mass or less, 25.0% by mass or less, 20.0% by mass or less, or 15.0% by mass or less.

[0050] <Penetration of Cosmetics> The penetration of the hyaluronate in the cosmetic of the present disclosure can be evaluated, for example, by the below-described Penetration Test 1 using simulated skin. In such a penetration test, the cosmetic of the present disclosure has a hyaluronate content of 500 ng / cm in the simulated skin. ２ Above, 1,000ng / cm ２ or more, or 1,500 ng / cm ２ There is no particular upper limit to the amount of hyaluronate, and it can be, for example, 20,000 ng / cm ２ Below, 18,000ng / cm ２ Below, 15,000ng / cm ２ or less, or 12,000 ng / cm ２ It can be as follows:

[0051] <<Method for Preparing Cosmetics>> The cosmetics of the present disclosure can be prepared, for example, by the following method. Note that the various materials that can be used in the method for preparing cosmetics, such as hyaluronate, amphoteric surfactant, water, and optional components (e.g., salt and moisturizer), can be the same as those described above.

[0052] A cosmetic can be prepared by blending an amphoteric surfactant, and optionally a salt and / or a moisturizing agent, into water or a buffer solution, stirring and mixing to prepare a solution, blending a hyaluronate into this solution, and dissolving the hyaluronate while stirring and mixing.

[0053] Alternatively, the hyaluronic acid salt can be blended with water or a buffer solution, stirred and mixed to dissolve the hyaluronic acid salt, and then an amphoteric surfactant, and optionally a salt and / or a moisturizer, can be blended therein, stirred and mixed to prepare the cosmetic.

[0054] <<Application Area of ​​Cosmetic>> The cosmetic of the present disclosure can be applied to any part of the body, for example, any part of the skin surface (body surface). Specifically, it can be applied appropriately to the skin surface of, for example, the face (lips, eyes, eyelids, cheeks, forehead, between the eyebrows, nose, etc.), head (scalp), ears, hands, arms, neck, legs, feet, chest, abdomen, back, etc. Here, skin also includes nails, which are hardened due to changes in the keratin layer of the skin epidermis.

[0055] In this way, the cosmetic material of the present disclosure can be suitably used as a cosmetic material for skin penetration of hyaluronate.

[0056] A cosmetic method using the cosmetic of the present disclosure includes applying the cosmetic to a body surface. Note that in this disclosure, the term "cosmetic method" refers to a method of applying the cosmetic of the present disclosure to a body surface to improve and beautify the condition of the skin, and is different from methods of surgery, treatment, or diagnosis for humans.

[0057] Generally, when skin is exposed to dryness, moisture is robbed without us even realizing it, and the skin's surface moisture level is not maintained. For example, when the skin surface lacks moisture, the skin's own moisturizing components (natural moisturizing factors (NMF)) are not produced properly. As a result, the barrier function and moisturizing function of the skin surface are weakened, making the skin more susceptible to damage, which is thought to cause a loss of moisture and lead to wrinkles, rough skin, etc.

[0058] The cosmetic preparation of the present disclosure can effectively penetrate the hyaluronate into the skin, thereby effectively moisturizing the skin. As a result, for example, the function of producing moisturizing components produced by the skin itself is improved, and the turnover in the stratum corneum is also improved, thereby reducing the occurrence of skin problems such as rough skin, and improving the cosmetic effect.

[0059] The means for applying the cosmetic to the body surface is not particularly limited, and can be, for example, by spreading the cosmetic on the body surface. The means for applying the cosmetic to the body surface can be, for example, by spraying the cosmetic onto the skin using a spray container containing the cosmetic, or by putting the cosmetic into a container without a spray function, and then collecting an appropriate amount of the cosmetic from the container on a finger or the palm, and spreading it over the body surface.

[0060] The present invention will be described in more detail below with reference to test examples and examples, but the present invention is not limited thereto. Unless otherwise specified, the blending amounts are expressed in mass %.

[0061] Test Examples 1 to 6 Evaluation of Cosmetics The following various evaluations were carried out using each cosmetic obtained by the manufacturing method described below, and the results are summarized in Tables 1 to 6 and Figures 1 to 6. In the tables and figures, "HA" means hyaluronate, "LB" means lauryl betaine, "PG" means propylene glycol, "BG" means butylene glycol, and "DPG" means dipropylene glycol.

[0062] (Penetration Test 1: Evaluation of the amount of hyaluronate permeated into artificial skin) Strat-M (trademark) membrane (manufactured by Merck Millipore) was used as the artificial skin, and a diffusion cell array system (manufactured by Ikeda Rika Co., Ltd.) having a donor section and a receptor section was also used.

[0063] The Strat-M™ membrane was placed between the donor and receptor sections of the diffusion cell array system. The effective diffusion area of ​​the Strat-M™ membrane was 0.785 cm ２ The receptor part was filled with 2 ml of receptor solution (PBS solution), and the receptor solution was continuously stirred with a stirrer. The surface of the Strat-M (trademark) membrane was set to 32°C, and the cosmetic was applied to the donor part at 10 μL / cm ２ 24 hours after application, the Strat-M (trademark) membrane was removed, and the surface was washed with a soapy water solution and purified water. The membrane was then immersed in purified water and subjected to ultrasonic treatment for 20 minutes. It was then extracted overnight in a 37°C thermostatic bath, and the amount of hyaluronate was quantified by ELISA. The values ​​in the table and figure are the average values ​​of the amount of hyaluronate measured three to four times. Furthermore, for Reference Example 3 and Examples 12 to 14 of Test Example 6, the cosmetic was applied to the donor area at 10 μL / cm ２ Six hours after application, the Strat-M™ membrane was removed and the same procedure was carried out.

[0064] (Penetration Test 2: Evaluation of the Amount of Hyaluronate Permeated into Human Skin) The permeability of hyaluronate was evaluated based on the amount of hyaluronate recovered from the stratum corneum peeled with tape using the tape stripping method, following the procedures (1) to (7) below. This evaluation test was conducted on six panels in their twenties, and the average values ​​are shown in the tables and figures: (1) The inner forearm of the panel was washed with soap. (2) Approximately 10 μl / cm of cosmetic was applied to the inner forearm of the panel that had been washed. ２The cosmetic was applied at a ratio of 0.01 to 0.01. (3) The panel was left to stand for 4 hours. (4) The inner forearm of the panel was washed with purified water. (5) The stratum corneum in the area where the cosmetic was applied was tape-stripped 10 times. (6) The stratum corneum adhering to the tape was immersed in purified water, and hyaluronate was extracted by ultrasonic treatment. (7) The extract was analyzed by ELISA, and the amount of hyaluronate in the extract was quantified.

[0065] Test Example 1: Various Surfactants In Test Example 1, the effects of various surfactants formulated together with hyaluronate were investigated. The results are shown in Tables 1 and 2 and Figure 1. Here, "nonionic surfactant," "amphoteric surfactant," and "anionic surfactant" in Tables 1 and 2 and Figure 1 refer to nonionic surfactants, amphoteric surfactants, and anionic surfactants.

[0066] (Comparative Example 1) Hyaluronic acid salt (Shiseido Co., Ltd., Biohyalo 12: weight average molecular weight 1,200,000) is added in ion-exchanged water so as to be contained in 0.3% by weight, and is stirred and mixed with a stirrer to prepare the solution containing hyaluronic acid salt.Into this solution, the nonionic surfactant POE (20) behenyl ether is added so as to be contained in 0.7% by weight, and is stirred and mixed with a stirrer to prepare test sample.

[0067] (Comparative Examples 2 to 10 and Examples 1 to 5) Test samples of Comparative Examples 2 to 10 and Examples 1 to 5 were prepared in the same manner as Comparative Example 1, except that the surfactants were changed to those shown in Tables 1 and 2.

[0068] Reference Example 1 As a test sample (control sample) for Reference Example 1, the hyaluronate-containing solution of Comparative Example 1 was used.

[0069]

[0070]

[0071] (Results) As is clear from the results in Tables 1 and 2 and FIG. 1, it was confirmed that the permeability of hyaluronate was improved by adding an amphoteric surfactant.

[0072] Test Example 2: The influence of salt concentration when no amphoteric surfactant is contained In Test Example 2, for reference, the influence of salt concentration on the permeability of hyaluronate when no amphoteric surfactant is contained is examined.The results are shown in Figure 2.

[0073] (Preparation method of test sample) Hyaluronic acid salt (Shiseido Co., Ltd., Biohyalo 12: weight average molecular weight 1.2 million) is added in ion-exchanged water so that the content is 0.3% by mass, and is mixed and stirred with stirrer to prepare the solution containing hyaluronic acid salt.Add sodium chloride to each solution that is taken out with the concentration that ionic strength is 0.05, 0.1, 0.2 and 0.5, and is mixed and stirred with stirrer to prepare test sample.

[0074] (Results) As is clear from the results in Figure 2, it was confirmed that when the cosmetic preparation does not contain an amphoteric surfactant, the permeability of the hyaluronate decreases as the salt concentration increases.

[0075] Test Example 3: Effect of salt concentration when amphoteric surfactant is included In Test Example 3, the effect of salt concentration on the permeability of hyaluronate when amphoteric surfactant is included was investigated. The results are shown in Table 3 and Figure 3.

[0076] (Example 2) The test sample of Example 2 of Test Example 1 described above is used. Here, the test sample of Example 2 is prepared as follows. Hyaluronic acid salt (Shiseido Co., Ltd., Biohyalo 12: weight average molecular weight 1.2 million) is added to ion-exchanged water so that the content is 0.3 mass%, and then stirred and mixed with a stirrer to prepare a hyaluronic acid salt-containing solution. To this solution, lauryl betaine, which is an amphoteric surfactant, is added so that the content is 0.7 mass%, and then stirred and mixed with a stirrer to prepare a test sample.

[0077] Example 6 A test sample of Example 6 was prepared by adding sodium chloride to the test sample of Example 2 at a concentration of 0.1 ionic strength and mixing the mixture with a vortex mixer.

[0078] Example 7 A test sample of Example 7 was prepared by adding magnesium chloride to the test sample of Example 2 at a concentration of 0.21 ionic strength and mixing the mixture with a vortex mixer.

[0079] Comparative Example 11 As a test sample for Comparative Example 11, the hyaluronate-containing solution of Example 2, which did not contain an amphoteric surfactant or a salt, was used.

[0080] Comparative Example 12 A test sample of Comparative Example 12 was prepared by adding sodium chloride to the hyaluronate-containing solution of Example 2 at a concentration of 0.1 ionic strength and mixing the solution with a stirrer.

[0081] Comparative Example 13 A test sample of Comparative Example 13 was prepared by adding magnesium chloride to the hyaluronate-containing solution of Example 2 at a concentration of 0.21 ionic strength and mixing with a stirrer.

[0082]

[0083] (Results) It was found that the cosmetics of Examples 2, 6 and 7, which contained an amphoteric surfactant, had improved penetration of hyaluronate, even though they contained salt, compared to the cosmetics of Comparative Examples 11 to 13, which did not contain an amphoteric surfactant.

[0084] Test Example 4: Performance on human skin In Test Example 4, the permeability of hyaluronate into human skin when containing an amphoteric surfactant was investigated. The results are shown in Table 4 and FIG.

[0085] (Example 8) Hyaluronic acid salt (Shiseido Co., Ltd., Biohyalo 12: weight average molecular weight 1,200,000) is added in ion-exchanged water so that the content is 0.5% by mass, and is mixed and stirred with a stirrer to prepare the solution containing hyaluronic acid salt.Into this solution, the lauryl betaine of amphoteric surfactant is added so that the content is 0.1% by mass, and further, magnesium chloride is added with the concentration of ionic strength 0.21, and is mixed and stirred with a stirrer to prepare test sample.

[0086] Comparative Example 14 As a test sample for Comparative Example 14, the hyaluronate-containing solution of Example 8, which did not contain any amphoteric surfactant or salt, was used.

[0087]

[0088] (Results) It was confirmed that a cosmetic preparation containing an amphoteric surfactant together with hyaluronate can improve the permeability of hyaluronate into human skin.

[0089] Test Example 5: Various Moisturizing Agents In Test Example 5, the effects of various moisturizing agents blended with hyaluronate and amphoteric surfactant were investigated. The results are shown in Table 5 and FIG. 5. Here, Table 5 lists Comparative Examples 15 to 17, which are examples for comparison with the results of Examples 9 to 11. In other words, the test samples of Comparative Examples 15 to 17 also contain an amphoteric surfactant and exhibit performance equivalent to that of Reference Example 2. Therefore, when compared with a test sample that does not contain an amphoteric surfactant (for example, the test sample of Comparative Example 1 in Table 1), the test samples of Comparative Examples 15 to 17 can be considered examples.

[0090] (Comparative Example 15) Hyaluronate (Shiseido Co., Ltd., Biohyalo 12: weight-average molecular weight 1,200,000) is added in ion-exchanged water so that the content is 0.3% by mass, and is mixed and stirred with stirrer to prepare the solution containing hyaluronate.In this solution, amphoteric surfactant lauryl betaine is added so that the content is 0.7% by mass, moisturizing agent glycerin is added so that the content is 10% by mass, and sodium chloride is added with the concentration of ionic strength 0.1, and is mixed and stirred with stirrer to prepare test sample.

[0091] Examples 9 to 11 and Comparative Examples 16 to 17 Test samples of Examples 9 to 11 and Comparative Examples 16 to 17 were prepared in the same manner as in Comparative Example 15, except that the moisturizers were changed to those shown in Table 5.

[0092] Reference Example 2 A test sample (control sample) of Reference Example 2 was prepared in the same manner as in Comparative Example 15, except that no moisturizing agent was included.

[0093]

[0094] (Results) It was found that when propylene glycol, dipropylene glycol, and PEG / PPG-17 / 4 dimethyl ether were used as moisturizers, the permeability of hyaluronate could be improved more than when cosmetics containing no moisturizer or other moisturizers were used.

[0095] Test Example 6: Synergistic effect of combined use of moisturizer or moisturizer and salt with amphoteric surfactant In Test Example 6, the synergistic effect of combined use of moisturizer or moisturizer and salt with amphoteric surfactant was investigated. The results are shown in Table 6 and Figure 6. Table 6 and Figure 6 also show the results of Comparative Examples 11 and 13 described above. The results of Penetration Test 1 in Comparative Examples 11 and 13 were obtained by applying a cosmetic to the donor area at a concentration of 10 μL / cm ２ The results are from 24 hours after application, whereas the results of the penetration test 1 in Reference Example 3 and Examples 12 to 14 were obtained by applying the cosmetic to the donor area at a rate of 10 μL / cm ２ The results are shown 6 hours after application.

[0096] (Example 12) Hyaluronic acid salt (Shiseido Co., Ltd., Biohyalo 12: weight average molecular weight 1,200,000) is added in ion-exchanged water so as to be contained in 0.3% by mass, and is mixed and stirred with a stirrer to prepare the solution containing hyaluronic acid salt.Into this solution, amphoteric surfactant lauryl betaine is added in such as to be contained in 0.1% by mass, moisturizing agent dipropylene glycol is added in such as to be contained in 9% by mass, and is mixed and stirred with a vortex mixer to prepare test sample.

[0097] (Example 13) Hyaluronic acid salt (Shiseido Co., Ltd., Biohyalo 12: weight-average molecular weight 1,200,000) is added in ion-exchanged water so that the content is 0.3% by mass, and is mixed by stirring with a stirrer to prepare the solution containing hyaluronic acid salt.In this solution, amphoteric surfactant lauryl betaine is added so that the content is 0.1% by mass, moisturizing agent dipropylene glycol is added so that the content is 9% by mass, and further, magnesium chloride is added with the concentration of ionic strength 0.21, and is mixed by stirring with a vortex mixer to prepare test sample.

[0098] Example 14 A test sample of Example 14 was prepared in the same manner as in Example 13, except that sodium chloride was added in place of magnesium chloride at a concentration of 0.1 ionic strength.

[0099] Reference Example 3 A test sample of Reference Example 3 was prepared in the same manner as in Example 12, except that no moisturizing agent was used.

[0100]

[0101] (Results) As is clear from a comparison between Reference Example 3 and Example 12, it was found that the penetration of hyaluronate was improved when dipropylene glycol, a moisturizing agent, was used in combination with an amphoteric surfactant.

[0102] Furthermore, it was found that the use of dipropylene glycol in combination with salt, especially sodium chloride, further improved the permeability of hyaluronate.It is expected that the effect of adding this salt will also be achieved with other moisturizers (propylene glycol, PEG / PPG-17 / 4 dimethyl ether) that have been shown to improve the permeability of hyaluronate in combination with amphoteric surfactants.

Claims

1. A cosmetic preparation for skin penetration of hyaluronate, comprising hyaluronate and an amphoteric surfactant.

2. The cosmetic preparation according to claim 1 , comprising a salt at a concentration having an ionic strength of 0.05 or more.

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

4. 3. The cosmetic preparation according to claim 1, wherein the amphoteric surfactant is at least one selected from the group consisting of betaine-type amphoteric surfactants, amino acid-type amphoteric surfactants, sulfonic acid-type amphoteric surfactants, sulfate ester-type amphoteric surfactants, and lecithin.

5. The cosmetic preparation described in claim 2, wherein the salt is at least one selected from the group consisting of monovalent salts, divalent salts, and trivalent salts.

6. The cosmetic preparation described in claim 2, wherein the salt is at least one selected from the group consisting of sodium salts and magnesium salts.

7. The cosmetic preparation according to claim 6, wherein the sodium salt is sodium chloride and the magnesium salt is magnesium chloride.

8. 3. The cosmetic preparation according to claim 1, further comprising at least one moisturizing agent selected from the group consisting of propylene glycol, dipropylene glycol, and PEG / PPG-17 / 4 dimethyl ether.

9. The cosmetic preparation according to claim 8, comprising sodium chloride.